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Is progression of cervical dilatation in normal human labor unpredictable? The aim of this study was to analyze how the progression of cervical dilatation in active labor can be predicted by digital assessment in low-risk pregnant women, in spontaneous labor at term. This prospective observational study was performed on 328 women with singleton term gestations experiencing midwife-led labor according to local protocols, progressing to full dilatation and spontaneous delivery without any medical intervention. Mixed nonlinear models were adopted to (i) model individual cervical data into centile curves and (ii) calculate the time needed to gain 1 cm in cervical dilatation (TNG1cm ) modeled as a function of current dilatation. We correlated the first and the last TNG1cm on parturients with at least four cervical data points. TNG1cm showed large variations, both before and after 6 cm. This variability of natural progression of cervical curves described by the 10th and 90th centiles exceeded the differences observed in published curves from cohorts homogeneous for parity, weight and ethnicity. There was no significant correlation between the first and the last TNG1cm . Neonatal base excess was not significantly different in women with TNG1cm <10th centile and >90th centile.

The rate of cervical dilatation, traced by parsimonious nonlinear mixed models, is largely unpredictable in the case of spontaneous naturally progressing labor, even when possible larger individual variability is excluded by prudent clinical rules. Future research in labor and delivery should be focused on the diagnosis of the causes that lie behind apparently erratic cervical changes.

Is overexpression of members of the microRNA-183 family a risk factor for lung cancer : a case control study? Lung cancer is the leading cause of cancer-related deaths worldwide. Early detection is considered critical for lung cancer treatment. MicroRNAs (miRNAs) have shown promise as diagnostic and prognostic indicators. This study was to identify specific miRNAs with diagnostic and prognostic value for patients with lung cancer, and to explore the correlation between expression profiles of miRNAs and patient survival. Gene expression of members of the miR-183 family (miR-96, miR-182, and miR-183) were examined in 70 paired samples from lung cancer patients (primary cancer and non-cancerous tissues and sera), as well as 44 serum samples from normal volunteers and lung cancer cell lines by quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR). The correlation between the expression of miRNAs in tissues, sera, and patient overall survival were also examined by log-rank and Cox regression analysis. Expression levels of members of the miR-183 family in lung cancer tumor and sera were higher than that of their normal counterparts. The miR-96 expression in tumors was positively associated with its expression in sera. Log-rank and Cox regression analyses demonstrated that high expression of tumor and serum miRNAs of the miR-183 family were associated with overall poor survival in patients with lung cancer.

Our results suggest that the expressions of miR-96, miR-182, and miR-183 in tumor and sera may be considered potential novel biomarkers for the diagnosis and prognosis of lung cancer.

Does hospital-level variability in incisional hernia repair technique affect patient outcomes? Mesh placement during ventral incisional hernia repair has been shown to result in superior outcomes; however, significant variation persists in the adoption of this technique. We performed a multi-institutional study to understand how variation in surgical technique influences outcomes. This study is a retrospective, facility-level analysis of incisional hernia repairs performed at 16 veteran's administration medical centers between 1997 and 2002. Operative notes and a postoperative course were physician-abstracted from the medical record. Hospital rates for the type of hernia repair, mesh placement, and recurrence were calculated. Spearman's correlation and generalized linear models were performed. A total of 1,612 incisional hernia repairs with a median follow-up of 66.2 months were included in the study. The mean rate of mesh implantation was 63.7% but ranged from 37.5% to 90%. The 5-year recurrence rate was 25.6% and ranged from 16.0% to 38.4%. The rate of mesh use for the incisional hernia repair at the hospital level was associated significantly with the hospital recurrence rate for all cases (R(2) = .27; P = .04) and elective cases (R(2) = .31; P = .02). For every 10% increase in the rate of mesh placement, a corresponding 3.1% decrease was noted in the recurrence rates (P = .001). The hospital rate of mesh use was not associated significantly with rates of complications or patient satisfaction.

Hospitals that adopted a higher rate of mesh repair for incisional hernia repairs had lower recurrence rates. These data support that the efficacy of mesh repair previously proven in clinical trials is highly translatable to effective practice in the field. Continued studies on the attributable risk of complications to mesh placement are ongoing.

Does level of use of 3,4-methylenedioxymethamphetamine ( MDMA or Ecstasy ) in humans correlate with EEG power and coherence? Despite animal studies implicating 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) in serotonergic neurotoxicity, there is little direct evidence of changes in neural function in humans who use MDMA as a recreational drug. The present study investigated whether there is a correlation between quantitative EEG variables (spectral power and coherence) and cognitive/mood variables, and level of prior use of MDMA. Twenty-three recreational MDMA users were studied. Resting EEG was recorded with eyes closed, using a 128-electrode geodesic net system, from which spectral power, peak frequency and coherence levels were calculated. Tests of intelligence (NART), immediate and delayed memory, frontal function (card sort task), and mood (BDI and PANAS scales) were also administered. Pearson correlation analyses were used to examine the relationship between these measures and the subject's consumption of MDMA during the previous 12-month period. Partial correlation was used to control for the use of other recreational drugs. MDMA use was positively correlated with absolute power in the alpha (8-12 Hz) and beta (12-20 Hz) frequency bands, but not with the delta (1-3 Hz) or theta (4-7 Hz) bands. MDMA use was negatively correlated with EEG coherence, a measure of synchrony between paired cortical locations, in posterior brain sites thought to overly the main visual association pathways of the occipito-parietal region. MDMA use did not correlate significantly with any of the mood/cognitive measures except the card sort task, with which it was weakly negatively correlated.

Alpha power has been shown to be inversely related to mental function and has been used as an indirect measure of brain activation in both normal and abnormal states. Reduced coherence levels have been associated with dysfunctional connectivity in the brain in disorders such as dementia, white-matter disease and normal aging. Our results may indicate altered brain function correlated with prior MDMA use, and show that electroencephalography may be a cheap and effective tool for examining neurotoxic effects of MDMA and other drugs.

Does femoral artery ligation stimulate capillary growth and limits training-induced increases in oxidative capacity in rats? The purpose of this study was to assess the interaction of arterial insufficiency and exercise training on soleus and plantaris muscle capillarity and oxidative capacity in adult rats. Arterial insufficiency was created by ligation (LIG) of the right femoral artery, and exercise training (TR) was performed on a rodent treadmill. The left hindlimb served as a normally (NORM) perfused control. Capillary:fiber ratio number of capillary contacts per fiber, and citrate synthase activity (CS) were evaluated in the plantaris (Plant) and soleus (Sol) muscles. In sedentary rats, CS was similar between LIG and NORM (Plant: 24.4 vs. 24.3 mumol.min-1.g-1; Sol: 16.6 vs. 16.9 mumol.min-1.g-1), but capillaries per fiber and capillary contacts per fiber were significantly elevated in the plantaris muscle of LIG (2.46 vs. 2.10 caps/fiber, 5.78 vs. 5.03 capillary contacts). CS was elevated in both limbs of TR but was lower in LIG than in NORM (Plant: 28.5 vs. 32.4 mumol.min-1.g-1; Sol: 21.1 vs. 24.9 mumol.min-1.g-1). Treadmill training did not significantly affect capillarity in NORM. However, muscles in the ligated limb of TR tended to have greater capillarity than comparable muscles in either NORM of TR of LIG in SED.

These results demonstrate capillary proliferation in the plantaris but not soleus muscle of rat hindlimbs with femoral artery ligation. Capillarity and CS adaptations were not obligatorily related in LIG, and femoral artery ligation and exercise training appeared to have interactive effects on skeletal muscle capillarity.

Is high serum C-reactive protein level an independent predictor for stroke : the Rotterdam Study? Current guidelines recommend the assessment of C-reactive protein (CRP) levels with a high-sensitivity assay in cardiovascular risk prediction. Recent studies have put forward that although elevated CRP is a risk factor for cardiovascular disease, it is not helpful in the prediction of cardiovascular disease risk. We studied the importance of CRP as a risk factor and as a risk predictor of future stroke. The present study was based on 6430 participants of the Rotterdam Study who at baseline (1990-1993) were > or = 55 years of age, were stroke free, and had blood taken. Strokes were classified as hemorrhagic, ischemic, or unspecified. Ischemic strokes were further subclassified. Whether stroke risk varied with baseline CRP serum levels was assessed with Cox proportional hazards models. Whether CRP was helpful in the prediction of individual stroke risk was assessed with receiver operating characteristic curves and by comparing the distribution of strokes between predicted risk strata. During an average of 8.2 years of follow-up, 498 first-ever strokes occurred. High CRP levels were significantly associated with risk of any stroke (age- and sex-adjusted hazard ratio per SD, 1.14; 95% confidence interval, 1.04 to 1.24) and risk of ischemic stroke (age- and sex-adjusted hazard ratio per SD, 1.17; 95% confidence interval, 1.04 to 1.32). Taking CRP levels into account did not improve the individual stroke risk prediction, however, regardless of whether it was based on the Framingham stroke risk score or on age and sex only.

Although CRP levels are associated with stroke risk, their use in the assessment of individual stroke risk seems limited.

Does weekly dose-dense cisplatin-epirubicin-paclitaxel administration with granulocyte colony-stimulating factor support substantially improve prognosis in extensive disease small-cell lung cancer . A SICOG phase II study? The present study was aimed at defining the antitumor activity of the cisplatin-epirubicin-paclitaxel (PET) weekly administration with granulocyte colony-stimulating factor (G-CSF) support in chemonaive small-cell lung cancer patients with extensive disease (ED-SCLC). Chemonaive ED-SCLC patients received cisplatin 30 mg/sqm, epirubicin 50 mg/sqm and paclitaxel 120 mg/sqm, weekly, with G-CSF (5 microg/kg from day 3 to 5) support, for a maximum of 12 weeks. Thirty-nine patients were treated, for a total of 354 cycles delivered. Eight complete (21%), and 22 partial responses (56%) were recorded, giving a 77% (95% CI = 61-89%) objective response rate (ORR). After 14 (range, 7-28)-month median follow-up, 24 deaths have occurred. Median progression-free and overall survival were 7 months and 11 months, with 1- and 2-year projected survivals of 45 and 24%, respectively. No toxic deaths occurred. Grade 4 neutropenia and thrombocytopenia occurred in 4 (10%) and 1 (3%) patients, respectively. Only one case of neutropenic sepsis was recorded, while hemorrhagic thrombocytopenia was never observed. Emesis, loss of appetite, mucositis and fatigue were the main nonhematological toxicities, being severe in 9, 8, 4 and 7 patients, respectively.

The weekly PET combination with G-CSF support represents an active therapeutic approach in chemonaive ED-SCLC patients. However, both ORR and median survival does not seem substantially better than those achievable with a standard regimen. In view of that, and in consideration of the relevant nonhematological toxicity, this approach should not be pursued outside clinical trials.

Does web course on medication administration strengthen nursing students ' competence prior to graduation? Nursing students' competence has been found inadequate in mastering of pharmacotherapy regulations and prescriptions, pharmacology, medical calculations, fractional and decimal numbers, and mathematics on the whole. The study investigated the efficacy of an additional medication administration web course in increasing nursing students' self-evaluated competence on medication administration. Finnish nursing students self-evaluated their medication administration competence before and after the web-based medication course. Design was quasi-experimental. 244 students answered the questionnaire before and 192 after the web course. An online self-evaluation questionnaire was developed to measure students' competence on basic pharmacotherapy, intravenous medication and infusion, blood transfusion and epidural medication. The data was analysed with SPSS 18.0 software using descriptive analyses and comparing sum variables with Man-Whitney U-test. The medication administration web course, which took 8 h on average, significantly improved self-evaluated competence of nursing students in all the fields. Prior to the education most defects were found in matters concerning compatibility and adverse effects of pharmaceuticals and solutions and in epidural medication competency. The education strengthened all these competencies.

It is necessary to revise medication administration before graduation and web-based learning can be used in it.

Is pancreaticobiliary anomalies the leading cause of childhood recurrent pancreatitis? To explore the etiology, age and gender distribution, complications, and prognosis of recurrent pediatric pancreatitis. Between 1993 and 2005, 92 children were hospitalized at the National Taiwan University Hospital with pancreatitis. Only 25 diagnosed with recurrent pancreatitis, based on two or more episodes of pancreatitis, elevated serum amylase and/or lipase levels > or = 3 times the upper limit of normal, radiographic evidence, and clinical symptoms, were enrolled. A total of 85 episodes of pancreatitis in 25 patients (16 girls, 9 boys; mean age, 9.5 +/- 4.4 years; 3.4 +/- 1.9 episodes per person) were documented. The recurrence rate of pediatric pancreatitis was 27.2%. Recurrent pancreatitis was associated with pancreaticobiliary structural anomalies (n = 7), biliary stones or sludge (n = 4), hyperlipidemia (n = 3), pseudopapillary tumor of the pancreas (n = 2), trauma (n = 2), hypoxic encephalopathy with recurrent bacteremia and sepsis (n = 1), and idiopathic (n = 6). The age and gender distribution according to etiologies were not different (p = 0.301 for age, p = 0.137 for gender). Complications included cholangitis or cholestasis (16%), pancreatic necrosis (16%), pseudocyst formation (12%), shock (8%), hemorrhagic pancreatitis (4%), and diabetes mellitus (4%). No patient died of recurrent pancreatitis. Long-term morbidity after recurrent pancreatitis presented as gout, diabetes mellitus, non-alcoholic steatohepatitis, and chronic pancreatitis.

For children who suffer from recurrent pancreatitis, pancreaticobiliary structural anomalies should be considered first.

Does biomechanical comparison of 3 ankle brace with and without free rotation in the sagittal plane? Various designs of braces including hinged and nonhinged models are used to provide external support of the ankle. Hinged ankle braces supposedly allow almost free dorsiflexion and plantar flexion of the foot in the sagittal plane. It is unclear, however, whether this additional degree of freedom affects the stabilizing effect of the brace in the other planes of motion. To investigate the dynamic and passive stabilizing effects of 3 ankle braces, 2 hinged models that provide free plantar flexion-dorsiflexion in the sagittal plane and 1 ankle brace without a hinge. Crossover study. University Movement Analysis Laboratory. Seventeen healthy volunteers (5 women, 12 men; age = 25.4 ± 4.8 years; height = 180.3 ± 6.5 cm; body mass = 75.5 ± 10.4 kg). We dynamically induced foot inversion on a tilting platform and passively induced foot movements in 6 directions via a custom-built apparatus in 3 brace conditions and a control condition (no brace). Maximum inversion was determined dynamically using an in-shoe electrogoniometer. Passively induced maximal joint angles were measured using a torque and angle sensor. We analyzed differences among the 4 ankle-brace conditions (3 braces, 1 control) for each of the dependent variables with Friedman and post hoc tests (P < .05). Each ankle brace restricted dynamic foot-inversion movements on the tilting platform as compared with the control condition, whereas only the 2 hinged ankle braces differed from each other, with greater movement restriction caused by the Ankle X model. Passive foot inversion was reduced with all ankle braces. Passive plantar flexion was greater in the hinged models as compared with the nonhinged brace.

All ankle braces showed stabilizing effects against dynamic and passive foot inversion. Differences between the hinged braces and the nonhinged brace did not appear to be clinically relevant.

Is baroreflex sensitivity impaired in bilateral carotid atherosclerosis? The arterial baroreflex is an important determinant of the short-term regulation of blood pressure and cardiovascular variability. The purpose of our study was to determine whether baroreflex sensitivity (BRS) and heart rate (HR) variability are altered in patients with carotid atherosclerosis (CA) and to assess the impact of characteristics of CA on BRS. BRS and HR variability were prospectively evaluated in 75 consecutive patients undergoing carotid duplex examination in our neurosonology unit. Resting BRS was measured with the sequence method. HR variability was evaluated using spectral analysis. BRS was significantly reduced in patients with bilateral CA compared with patients without CA (P=0.015) and patients with unilateral CA (P=0.045). BRS was unaltered in patients with unilateral CA compared with patients with no CA. BRS was already reduced in mild (stenosis <50%), bilateral CA and was not further impaired in more severe CA. The association of BRS impairment with bilateral CA remained significant after adjustment for age, hypertension, and a history of stroke or transient ischemic attack. The study of HR variability demonstrated a reduction in the power of high-frequency band in patients with bilateral CA compared with patients with unilateral CA or without CA (P=0.015).

Bilateral CA is associated with an impairment of BRS and a shift of the sympathovagal balance toward a relative decrease of the parasympathetic component of HR variability. These changes are already present in mild, bilateral CA.

Is sFRS7-mediated splicing of tau exon 10 directly regulated by STOX1A in glial cells? In this study, we performed a genome-wide search for effector genes bound by STOX1A, a winged helix transcription factor recently demonstrated to be involved in late onset Alzheimer's disease and affecting the amyloid processing pathway. Our results show that out of 218 genes bound by STOX1A as identified by chromatin-immunoprecipitation followed by sequencing (ChIP-Seq), the serine/arginine-rich splicing factor 7 (SFRS7) was found to be induced, both at the mRNA and protein levels, by STOX1A after stable transfection in glial cells. The increase in SFRS7 was followed by an increase in the 4R/3R ratios of the microtubule-associated protein tau (MAPT) by differential exon 10 splicing. Secondly, STOX1A also induced expression of total tau both at the mRNA and protein levels. Upregulation of total tau expression (SFRS7-independent) and tau exon 10 splicing (SFRS7-dependent), as shown in this study to be both affected by STOX1A, is known to have implications in neurodegeneration.

Our data further supports the functional importance and central role of STOX1A in neurodegeneration.

Does brief wakeful response to command indicate wakefulness with suppression of memory formation during surgical anesthesia? In a previous study of patients emerging from anesthesia following surgery, we found that a brief wakeful response to command of an eye opening or single hand squeeze or count was not associated with memory formation, while the response of four hand squeezes or counts was associated with memory. We wanted to determine the anesthetic requirements for obtaining this brief wakeful response endpoint during surgery and to determine if memory occurred at this endpoint during surgical anesthesia. Six different combinations of isoflurane, 70% N2O, and fentanyl were administered to 326 patients undergoing pelvic laparoscopy. After insertion of the trocar, anesthesia was reduced while patients were given verbal commands, and they were observed for movement responses to surgery and to command. Patients were classified as either not arousing, arousing with a movement response to surgery, or arousing with a wakeful response to command. For the patients who aroused, we calculated the percentage of arousal responses that were wakeful responses to command. The effect of fentanyl dosage upon the percentage of arousal responses that were wakeful responses to command was determined by using a Mann-Whitney test to compare a group of patients receiving fentanyl 2 micrograms/kg or less, with a group receiving fentanyl 4 micrograms/kg. In a subset of 39 patients, the potential for memory formation was evaluated by presenting a target sound to 29 patients during a period of either no arousal, movement response to surgery, or wakeful response to command; for a control group of 10 patients, no target sound was presented. All 39 patients were tested for memory of the target sound; the results from each group receiving a target sound were compared with the results of the control group, using a Mann-Whitney test. A total of 68 patients aroused with either a movement response or a wakeful response to command. Wakeful responses occurred with only 1 of 39 patients (3%) receiving fentanyl 2 micrograms/kg or less; but, wakeful responses occurred with 17 of 29 patients (59%) receiving fentanyl 4 micrograms/kg. The difference between the groups was significant at p = 0.01. None of the 68 patients had recall of intraoperative events or unpleasant dreams. None of these patients who were in the multiple-choice memory subset recalled the target sound. There were no statistically significant differences on the multiple-choice memory test between the groups presented with the target sound and the control group. Patient anecdotes suggested that some patients may have had memory of the target sound; but, memory was no more likely in patients with a brief wakeful response to command than in those who responded with a movement to surgical stimulation or those who did not have an arousal response.

A brief wakeful response to a command of opening the eyes or squeezing the hand was not associated with increased memory formation during surgery. A brief wakeful response to command was found during surgery when patients received fentanyl 4 micrograms/kg; but it was rarely found at fentanyl dosages of 2 micrograms/kg or less.

Do the influence of gaze stabilization and fixation on stepping reactions in younger and older adults? To date, there has been little evidence to suggest the importance of foveal viewing versus peripheral retina viewing when trying to recover from a perturbation. The purposes of this investigation were to (1) determine whether a visual target can be stabilized on the fovea during a perturbation, (2) determine whether stepping responses following a perturbation are influenced by foveal fixation, and (3) compare gaze stability and stepping responses between young and aging adults. Ten young adults and 10 aging adults were asked to wear an eye-tracking device linked to a kinematic tracking system during perturbations. Perturbations were delivered under 2 conditions: control (no instructions regarding gaze location were given) and earth-fixed (EF) (subjects were asked to fixate gaze on an EF target). Stepping responses were recorded via force plates. Gaze stability, reported as percent foveal fixation (% FF), was calculated from eye-tracking data. Step latencies (SLs) were computed from force plate data. A 2 x 2 analysis of variance was used to assess statistical significance between groups. For the young and aging adults, linear correlations were made to identify relationships between % FF and SL. For each condition, aging adults took longer to initiate a step (control, P = .002; EF, P = .003). Young adults were better at maintaining gaze fixation than older adults (P = .0045). Linear correlations demonstrated significant negative relationships between SL and % FF for young (r = -0.76, P = .001) and older (r = -0.87, P = .0001) adults. As % FF increased, SL decreased.

The ability to maintain gaze fixation of an EF target may be important in reducing SL following a perturbation. Older adult subjects demonstrated a decreased ability to fixate a target during balance tasks while also displaying longer SLs.

Does pDGF receptor alpha inhibition induce apoptosis in glioblastoma cancer stem cells refractory to anti-Notch and anti-EGFR treatment? Cancer stem cells (CSC) represent a rare fraction of cancer cells characterized by resistance to chemotherapy and radiation, therefore nowadays there is great need to develop new targeted therapies for brain tumors and our study aim to target pivotal transmembrane receptors such as Notch, EGFR and PDGFR, which are already under investigation in clinical trials setting for the treatment of Glioblastoma Multiforme (GBM). MTS assay was performed to evaluate cells response to pharmacological treatments. Quantitative RT-PCR and Western blots were performed to state the expression of Notch1, EGFR and PDGFRα/β and the biological effects exerted by either single or combined targeted therapy in GBM CSC. GBM CSC invasive ability was tested in vitro in absence or presence of Notch and/or EGFR signaling inhibitors. In this study, we investigated gene expression and function of Notch1, EGFR and PDGFR to determine their role among GBM tumor core- (c-CSC) vs. peritumor tissue-derived cancer stem cells (p-CSC) of six cases of GBM. Notch inhibition significantly impaired cell growth of c-CSC compared to p-CSC pools, with no effects observed in cell cycle distribution, apoptosis and cell invasion assays. Instead, anti-EGFR therapy induced cell cycle arrest, sometimes associated with apoptosis and reduction of cell invasiveness in GBM CSC. In two cases, c-CSC pools were more sensitive to simultaneous anti-Notch and anti-EGFR treatment than either therapy alone compared to p-CSC, which were mostly resistant to treatment. We reported the overexpression of PDGFRα and its up-regulation following anti-EGFR therapy in GBM p-CSC compared to c-CSC. RNA interference of PDGFRα significantly reduced cell proliferation rate of p-CSC, while its pharmacological inhibition with Crenolanib impaired survival of both CSC pools, whose effects in combination with EGFR inhibition were maximized.

We have used different drugs combination to identify the more effective therapeutic targets for GBM CSC, particularly against GBM peritumor tissue-derived CSC, which are mostly resistant to treatments. Overall, our results provide the rationale for simultaneous targeting of EGFR and PDGFR, which would be beneficial in the treatment of GBM.

Does azelastine eye drop reduce and prevent allergic conjunctival reaction and exert anti-allergic activity? Azelastine is a selective H1-receptor antagonist, which has previously been demonstrated to be effective in the treatment of allergic rhinitis. We have recently demonstrated that nasal azelastine inhibits the clinical and inflammatory events following nasal allergen challenge. Particularly, we focused our attention on ICAM-1 expression on epithelial cells, since it is the natural ligand of LFA-1, an adhesion molecule expressed by leucocytes, including eosinophils. Since azelastine ocular drops are now available, the aim of the present study was the evaluation of the anti-allergic activity in the model of allergen specific conjunctival challenge (ASCC). Twenty outpatients with allergic rhinoconjunctivitis due to Parietaria Judaica (Wall Parietary) were included outside the pollen season. The study was designed as randomized, placebo-controlled, double-blind and parallel group, developed in two parts. The former investigated the onset of effect of a single dose of azelastine eye drops administered 20 min after clinical response due to ASCC. The latter evaluated the clinical and inflammatory parameters following ASCC after 7-days treatment with azelastine. Clinical parameters (hyperaemia, itching, lacrimation and eyelid swelling) were evaluated at baseline, 5, 10, 20 and 30 min (i.e. early phase reaction-EPR) and 6 h (i.e. late phase reaction-LPR) after ASCC. Cytological assessment (number of neutrophils, eosinophils. monocytes and lymphocytes) and ICAM-1 expression on conjunctival epithelial cells were evaluated at baseline, 30 min (i.e. early phase reaction-EPR) and 6 h (i.e. late phase reaction-LPR) after ASCC. When administered 30 min after ASCC, azelastine produced a clinical effect ranging between 10 and 20 min after eye drops administration (P < 0.01). After 7 days of treatment, 30 min after ASCC, azelastine induced a reduction of symptom scores during EPR and LPR (P < 0.01), a reduction of inflammatory cell infiltration during both EPR (P < 0.01) and LPR (P < 0.01), and a reduction of ICAM-1 expression during EPR and LPR (both P < 0.01). Placebo did not modify any of the studied parameters.

Azelastine eye drops exert anti-allergic activity, inducing a rapid improvement of clinical events when administered after ASCC, and reducing both symptoms and cellular infiltration when administered before ASCC. Finally, azelastine down-regulates ICAM-1 expression on epithelial conjunctival cells, confirming the results obtained at nasal level.

Is early gastrointestinal regulatory peptide response to intestinal resection in the rat stimulated by enteral glutamine supplementation? Intestinal resection stimulates the synthesis and release of gastrointestinal peptides that regulate the growth and adaptation of the mucosa. Luminal nutrients are necessary for optimal proliferation and glutamine is the preferential nutrient to the small bowel. The interplay between glutamine and regulatory peptides could be important in treating short bowel syndrome. 63 Sprague-Dawley rats were divided into 3 groups: resection; transection, or controls. After intestinal resection animals were orally fed either a diet without glutamine or a glutamine-supplemented diet for 2 days. Transected animals and controls without prior surgery were fed the same two diets. Epidermal growth factor (EGF), transforming growth factor-alpha, insulin-like growth factors I and II (IGF-I and IGF-II), peptide YY (PYY), and enteroglucagon were analyzed in mucosa from the proximal jejunum, distal ileum as well as in portal plasma when the animals were euthanized 72 h after surgery. Intestinal resection resulted in an early increase in portal plasma concentrations of PYY, EGF, enteroglucagon, and mucosal IGF-II and EGF content that were significant in glutamine-treated animals. Glutamine significantly increased PYY in portal blood after resection (p < 0.05).

Glutamine could be of importance for the functional adaptation of residual small bowel mucosa by increasing PYY release.

Do older age and greater carotid intima-media thickness predict ischemic events associated with carotid-artery stenting? Carotid-artery stenting (CAS) may be complicated by stroke. We aimed to determine predictors of procedure-related ischemic events. We analyzed new ischemic lesions in diffusion-weighted MRI (DWI) after CAS in 147 patients with symptomatic high-grade carotid stenosis. Nine covariates were assessed as potential risk factors for new lesions in DWI: age, gender, hypertension, diabetes, dyslipidemia, smoking status, severity of stenosis, side of intervention and carotid intima-media thickness (IMT). From the nine covariates assessed, only age and IMT were independently associated with new DWI lesions. An age of 68 years and an IMT of 1.5 mm gave the best separation between high- and low-risk populations. The subgroup of patients <68 years who had an IMT ≤1.5 mm had the lowest rate of new DWI lesions (11.3%). This rate was greater in patients ≥68 years (30.0%; odds ratio, OR, 3.4; 95% confidence interval, CI, 1.1-10.8) and in patients with an IMT >1.5 mm (36.4%; OR 4.5; 95% CI 1.2-17.0) and was particularly high in patients aged ≥68 years with IMT >1.5 mm (69.6%; OR 18.0; 95% CI 4.8-71.9).

Older age and greater IMT are independently associated with the risk of CAS-related ischemic events. This risk is particularly high in those patients in whom older age and greater IMT coincide.

Is oral flecainide effective in management of refractory tachycardia in infants? Propranolol and digoxin have been used as first line drugs for treatment of supraventricular tachycardia (SVT) in infants. Flecainide and other drugs have been effective as a second line treatment for controlling refractory SVT. This is a prospective study without randomization and control. The inclusion criteria were: infants (≤12 months) with tachyarrhythmia who failed to respond to first line drugs. Patients having post-surgical arrhythmias were excluded from the study. A total of 8 infants were treated with flecainide for refractory tachyarrhythmia's. Diagnosis on electrocardiogram (ECG) was atrioventricular reentry tachycardia (AVRT) in 5, atrial ectopic tachycardia (AET) in 2, a combination of AVRT and atrioventricular nodal reentry tachycardia (AVNRT) in 1. All patients had failed trial of antiarrhythmic drugs prior to presentation: digoxin and propranolol in 7, amiodarone in 3, cardioversion in 1. Flecainide (80-130 mg/m(2) orally) resulted in termination of the tachycardia in all 8 patients. Acute pharmacological termination of arrhythmia occurred with oral flecainide loading in 1 and temporarily with intravenous esmolol loading in 1 patient. Adjuvant therapy in form of propranolol was used in 5 and digoxin in 2. There were no side effects noted. Four episodes of recurrence were noted in 3 patients over 2 years, all of which responded to dose increase. Mean follow up time is 24.75 months.

This small case series indicates that flecainide is an effective antiarrhythmic agent, free of side effects and when used orally is capable of terminating and controlling relatively resistant supraventricular tachycardia in children.

Do the impact of fair colonoscopy preparation on colonoscopy use and adenoma miss rates in patients undergoing outpatient colonoscopy? The impact of fair bowel preparation on endoscopists' recommendations and adenoma miss rates in average-risk patients undergoing colonoscopy is unknown. To assess the impact of fair bowel preparation on endoscopists' interval colonoscopy recommendations and miss rates in colonoscopies performed within 3 years of the index colonoscopy in average-risk patients undergoing colorectal cancer screening. Retrospective chart review. Tertiary-care center. Average-risk patients undergoing index colonoscopy for colorectal cancer screening between 2004 and 2006. Colonoscopy. Endoscopists' interval recommendations, adenoma miss rates. A total of 16,251 colonoscopy records were reviewed over a 2-year period. Of these cases, 1943 colonoscopies were performed for the sole indication of average risk or screening. Of these, fair bowel preparation was reported in 619 patients (31.9%). A repeat colonoscopy within 5 years was recommended in 70.4% of patients. The follow-up colonoscopy compliance rate within 3 years was 55.9%. Adenoma detection rates at index and follow-up colonoscopy were 20.5% and 28.2%, respectively. Of the 39 patients with follow-up colonoscopy within 3 years, the overall adenoma miss rate was 28%. Of the patients with an adenoma identified on follow-up colonoscopy, 13.6% had normal colonoscopy results on index examination.

Retrospective design.

Are temporal bone thickness and texture major determinants of the high rate of insonation failures of transcranial Doppler in Amerindians ( the Atahualpa Project )? To assess the role of temporal bone characteristics in transcranial Doppler (TCD) insonation failures in Amerindians living in rural Ecuador. We evaluated thickness and texture of temporal bones in community-dwelling Amerindians ≥65 years old undergoing TCD. Using receiver operator characteristics curve analysis and generalized estimating equations, we investigated factors associated with insonation failures. Of 65 participants (mean age 74.7 ± 6.7 years, 60% women), 32 (49%) had uni- or bilateral insonation failure through temporal windows. Considering temporal bones independently, 57 of 130 (44%) had poor insonation. Mean thickness was higher (4.7 ± 1.2 versus 2.7 ± 0.9, p < 0.0001), and texture more often heterogeneous (93% versus 22%, p < 0.0001) in bones with poor acoustic windows. Thickness, better predicting poor insonation, was ≥3.6 mm if used alone, and ≥2.7 mm if used together with heterogeneous texture. For every millimeter of increase in thickness, subjects were 2.9 times more likely to have insonation failures. Per se, heterogeneous texture increased by 3.2 times the odds for poor insonation. In all models, being woman increased the odds for poor insonation by six to nine times.

Temporal bone thickness and texture are independent predictors of TCD insonation failure in Amerindians.

Do caloric restriction and body weight independently affect longevity in Wistar rats? To evaluate the independent effects of caloric restriction (CR) and body weight (BW) on mortality rate (MR) and the extent to which BW may mediate the effect of CR on MR. Data were from the Biosure Study, a randomized, controlled, prospective intervention study of diet regimens in 1200 Wistar rats. Animals were followed until they died spontaneously, were euthanized because of illness, or reached age 30 months. Cox regression was performed to evaluate the effects of CR and BW on MR. Bootstrap procedures were used to test the contribution of BW to the effect of CR on MR. CR initiated after age 13 weeks decreased the rate of subsequent mortality. The MR increased with higher BW in early adulthood (21 weeks) and this effect persisted even after adjustment for CR. After adjustment for BW in early adulthood, we did not find a similar relation between mortality and BW in late adulthood (105 weeks). Mediation analysis indicated that low BW associated with CR appeared to mediate some of the mortality-reducing effects of CR, but CR clearly had effects independent of BW. The reductions in BW appeared to account for approximately 11% of the effect of CR.

CR and BW have independent effects on MR in Wistar rats. BW may mediate a small part of the CR effects on MR.

Does lA sprout randomized controlled nutrition and gardening program reduces obesity and metabolic risk in Latino youth? To assess the effects of a 12-week gardening, nutrition, and cooking intervention ("LA Sprouts") on dietary intake, obesity parameters, and metabolic disease risk among low-income, primarily Hispanic/Latino youth in Los Angeles. The randomized controlled trial involved four elementary schools [two schools randomized to intervention (172 third-through fifth-grade students); two schools randomized to control (147 third-through fifth-grade students)]. Classes were taught in 90-minute sessions once a week to each grade level for 12 weeks. Data collected at pre- and postintervention included dietary intake via food frequency questionnaire (FFQ), anthropometric measures [BMI, waist circumference (WC)], body fat, and fasting blood samples. LA Sprouts participants had significantly greater reductions in BMI z-scores (0.1-vs. 0.04-point decrease, respectively; P = 0.01) and WC (-1.2 cm vs. no change; P < 0.001). Fewer LA Sprouts participants had the metabolic syndrome (MetSyn) after the intervention than before, while the number of controls with MetSyn increased. LA Sprouts participants had improvements in dietary fiber intake (+3.5% vs. -15.5%; P = 0.04) and less decreases in vegetable intake (-3.6% vs. -26.4%; P = 0.04). Change in fruit intake before and after the intervention did not significantly differ between LA Sprouts and control subjects.

LA Sprouts was effective in reducing obesity and metabolic risk.

Do differences in adhesion and protrusion properties correlate with differences in migration speed under EGF stimulation? Cell migration plays an essential role in many biological processes, such as cancer metastasis, wound healing and immune response. Cell migration is mediated through protrusion and focal adhesion (FA) assembly, maturation and disassembly. Epidermal growth factor (EGF) is known to enhance migration rate in many cell types; however it is not known how FA maturation, FA dynamics and protrusion dynamics are regulated during EGF-induced migration. Here we use total internal reflection fluorescence (TIRF) microscopy and image analysis to quantify FA properties and protrusion dynamics under different doses of EGF stimulation. EGF was found to broaden the distribution of cell migration rates, generating more fast and slow cells. Furthermore, groups based on EGF stimulation condition or cell migration speed were marked by characteristic signatures. When data was binned based on EGF stimulation conditions, FA intensity and FA number per cell showed the largest difference among stimulation groups. FA intensity decreased with increasing EGF concentration and FA number per cell was highest under intermediate stimulation conditions. No difference in protrusion behavior was observed. However, when data was binned based on cell migration speed, FA intensity and not FA number per cell showed the largest difference among groups. FA intensity was lower for fast migrating cells. Additionally, waves of protrusion tended to correlate with fast migrating cells.

Only a portion of the FA properties and protrusion dynamics that correlate with migration speed, correlate with EGF stimulation condition. Those that do not correlate with EGF stimulation condition constitute the most sensitive output for identifying why cells respond differently to EGF. The idea that EGF can both increase and decrease the migration speed of individual cells in a population has particular relevance to cancer metastasis where the microenvironment can select subpopulations based on some adhesion and protrusion characteristics, leading to a more invasive phenotype as would be seen if all cells responded like an "average" cell.

Do proteasome inhibitors act as bifunctional antagonists of human immunodeficiency virus type 1 latency and replication? Existing highly active antiretroviral therapy (HAART) effectively controls viral replication in human immunodeficiency virus type 1 (HIV-1) infected individuals but cannot completely eradicate the infection, at least in part due to the persistence of latently infected cells. One strategy that is being actively pursued to eliminate the latent aspect of HIV-1 infection involves therapies combining latency antagonists with HAART. However, discordant pharmacokinetics between these types of drugs can potentially create sites of active viral replication within certain tissues that might be impervious to HAART. A preliminary reverse genetic screen indicated that the proteasome might be involved in the maintenance of the latent state. This prompted testing to determine the effects of proteasome inhibitors (PIs) on latently infected cells. Experiments demonstrated that PIs effectively activated latent HIV-1 in several model systems, including primary T cell models, thereby defining PIs as a new class of HIV-1 latency antagonists. Expanding upon experiments from previous reports, it was also confirmed that PIs inhibit viral replication. Moreover, it was possible to show that PIs act as bifunctional antagonists of HIV-1. The data indicate that PIs activate latent provirus and subsequently decrease viral titers and promote the production of defective virions from activated cells.

These results represent a proof-of-concept that bifunctional antagonists of HIV-1 can be developed and have the capacity to ensure precise tissue overlap of anti-latency and anti-replication functions, which is of significant importance in the consideration of future drug therapies aimed at viral clearance.

Does adrenergic-cholinergic interaction that modulate repolarization in the atrium is altered with aging? Aging is associated with involution of both limbs of the autonomic nervous system, and the prejunctional and postjunctional effects of adrenergic and cholinergic stimulation are altered with senescence. Hence, postjunctional age-related changes in adrenergic-cholinergic interaction are a likely occurrence and may contribute to an altered substrate for arrhythmias. Microelectrode techniques were used to record action potentials from epicardial slices of Bachmann's bundles of dogs aged 3 to 5 years (adult) and 8 to 12 years (old) in the absence or presence of acetylcholine and isoproterenol (separately and in combination). In control, action potential duration to 90% repolarization (APD) was longer in old atria. Acetylcholine (10(-8) to 10(-5) mol/L) in a concentration-dependent manner hyperpolarized and shortened APD in both tissues, with more prominent effects in the old. The effects of isoproterenol (10(-9) to 10(-6) mol/L) to elevate the plateau and shorten APD were about the same in both adult and old tissues. In adults, low concentrations of isoproterenol (10(-9) and 10(-8) mol/L) significantly prolonged APD, which had been first shortened by acetylcholine. This effect of isoproterenol was decreased in old atrial tissue, resulting in shorter APD in old than adult atria in the combined presence of beta-adrenergic and muscarinic agonists.

In adult Bachmann's bundle, beta-adrenergic stimulation effectively operates as a "brake" to decrease the extent of cholinergic-induced APD shortening. The action of beta-adrenergic stimulation to antagonize acetylcholine-induced acceleration of repolarization declines with age, which may contribute to an altered arrhythmogenic substrate.

Do proteasome inhibitors abolish cell death downstream of caspase activation during anti-microtubule drug-induced apoptosis in leukemia cells? Anti-microtubule drugs and proteasome inhibitors are currently among the most intensively studied anti-tumor agents, however little is known about their pharmacological interactions at the cellular level. The human promyelocytic leukemia cell line, HL-60, was exposed to nocodazole or etoposide in combination with proteasome or caspase inhibitors. Apoptotic cell death was detected by flow cytometry as sub-G1 population. Caspase and proteasome activities were monitored by the fluorogenic substrates Ac-DEVD-AMC and Suc-LLVY-AMC, respectively, in cell lysate. Heat shock protein 70 (HSP70) expression was determined by Western blotting. Nocodazole, a microtubule inhibitor, induced caspase-dependent apoptosis in the HL-60 cell line. At sub-cytotoxic concentrations, proteasome inhibitors, including MG-132 or clasto-beta-lactone, decreased nocodazole-induced apoptotic DNA fragmentation without affecting the induction of caspase-3 activity. In contrast, MG-132 decreased both DNA fragmentation and caspase activation induced by etoposide, a topoisomerase-II inhibitor. HSP70 had previously been found to inhibit apoptosis independently from caspase activation. In this study, MG-132 up-regulated HSP70 protein expression, both in the presence or absence of nocodazole.

Proteasome inhibitors decreased anti-microtubule agent-induced apoptotic DNA fragmentation downstream of caspase-3 activation, possibly due to increased HSP70 expression. The results indicate that combination treatment with these novel anti-tumor agents in leukemia requires careful evaluation of their molecular interaction at the level of apoptosis induction.

Does lGE provide Incremental Prognostic Information Over Serum Biomarkers in AL Cardiac Amyloidosis? This study sought to determine the prognostic value of cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) in amyloid light chain (AL) cardiac amyloidosis. Cardiac involvement is the major determinant of mortality in AL amyloidosis. CMR LGE is a marker of amyloid infiltration of the myocardium. The purpose of this study was to evaluate retrospectively the prognostic value of CMR LGE for determining all-cause mortality in AL amyloidosis and to compare the prognostic power with the biomarker stage. Seventy-six patients with histologically proven AL amyloidosis underwent CMR LGE imaging. LGE was categorized as global, focal patchy, or none. Global LGE was considered present if it was visualized on LGE images or if the myocardium nulled before the blood pool on a cine multiple inversion time (TI) sequence. CMR morphologic and functional evaluation, echocardiographic diastolic evaluation, and cardiac biomarker staging were also performed. Subjects' charts were reviewed for all-cause mortality. Cox proportional hazards analysis was used to evaluate survival in univariate and multivariate analysis. There were 40 deaths, and the median study follow-up period was 34.4 months. Global LGE was associated with all-cause mortality in univariate analysis (hazard ratio = 2.93; p < 0.001). In multivariate modeling with biomarker stage, global LGE remained prognostic (hazard ratio = 2.43; p = 0.01).

Diffuse LGE provides incremental prognosis over cardiac biomarker stage in patients with AL cardiac amyloidosis.

Is dOCK10-mediated Cdc42 activation necessary for amoeboid invasion of melanoma cells? Tumor cells can move in a three-dimensional (3D) environment in either mesenchymal-type or amoeboid modes. In mesenchymal-type movement, cells have an elongated morphology with Rac-induced protrusions at the leading edge. Amoeboid cells have high levels of actomyosin contractility, and movement is associated with deformation of the cell body through the matrix without proteolysis. Because signaling pathways that control the activation of GTPases for amoeboid movement are poorly understood, we sought to identify regulators of amoeboid movement by screening an siRNA library targeting guanine nucleotide exchange factors (GEFs) for Rho-family GTPases. We identified DOCK10, a Cdc42 GEF, as a key player in amoeboid migration; accordingly, we find that expression of activated Cdc42 induces a mesenchymal-amoeboid transition and increases cell invasion. Silencing DOCK10 expression promotes conversion to mesenchymal migration and is associated with decreased MLC2 phosphorylation and increased Rac1 activation. Consequently, abrogating DOCK10 and Rac1 expression suppresses both amoeboid and mesenchymal migration and results in decreased invasion. We show that the Cdc42 effectors N-WASP and Pak2 are required for the maintenance of the rounded-amoeboid phenotype. Blocking Cdc42 results in loss of mesenchymal morphology, arguing that Cdc42 is also involved in mesenchymal morphology through different activation and effector pathways.

Previous work has identified roles of Rho and Rac signaling in tumor cell movement, and we now elucidate novel roles of Cdc42 signaling in amoeboid and mesenchymal movement and tumor cell invasion.

Is medicaid status associated with higher surgical site infection rates after spine surgery? The Spine End Results Registry (2003-2004) is a registry of prospectively collected data of all patients undergoing spinal surgery at the University of Washington Medical Center and Harborview Medical Center. Insurance data were prospectively collected and used in multivariate analysis to determine risk of perioperative complications. Given the negative financial impact of surgical site infections (SSIs) and the higher overall complication rates of patients with a Medicaid payer status, we hypothesized that a Medicaid payer status would have a significantly higher SSI rate. The medical literature demonstrates lesser outcomes and increased complication rates in patients who have public insurance than those who have private insurance. No one has shown that patients with a Medicaid payer status compared with Medicare and privately insured patients have a significantly increased SSI rate for spine surgery. The prospectively collected Spine End Results Registry provided data for analysis. SSI was defined as treatment requiring operative debridement. Demographic, social, medical, and the surgical severity index risk factors were assessed against the exposure of payer status for the surgical procedure. The population included Medicare (N = 354), Medicaid (N = 334), the Veterans' Administration (N = 39), private insurers (N = 603), and self-pay (N = 42). Those patients whose insurer was Medicaid had a 2.06 odds (95% confidence interval: 1.19-3.58, P = 0.01) of having a SSI compared with the privately insured.

The study highlights the increased cost of spine surgical procedures for patients with a Medicaid payer status with the passage of the Patient Protection and Affordable Care Act of 2010. The Patient Protection and Affordable Care Act of 2010 provisions could cause a reduction in reimbursement to the hospital for taking care of patients with Medicaid insurance due to their higher complication rates and higher costs. This very issue could inadvertently lead to access limitations.

Is mutation frequency of cystic fibrosis transmembrane regulator increased in oligozoospermic male candidates for intracytoplasmic sperm injection? To examine the frequency of anomalies of the vas deferens and the frequency of mutations of the cystic fibrosis transmembrane regulator (CFTR) gene in male candidates for intracytoplasmic sperm injection (ICSI) who had severe oligoasthenoteratozoospermia. The clinical data for male candidates for ICSI were studied. The three most frequent cystic fibrosis (CF)-causing CFTR mutations in the Dutch population (deltaF508, A455E, and G542X) and the three most frequent CFTR mutations potentially causing congenital bilateral absence of the vas deferens (CBAVD) in the Dutch population (deltaF508, R117H, and IVS8-5T) were analyzed. Delta I507 is also detected by the deltaF508 test. Samples of DNA from patients identified as CFTR mutation carriers were subjected to denaturing gradient gel electrophoresis analysis with use of a two-dimensional electrophoretic technique. University-based center for reproductive medicine and clinical genetics. Male candidates for ICSI who had oligoasthenoteratozoospermia and no history of operative sterilization and refertilization. Males with a chromosomal aberration or a Y-chromosome microdeletion were excluded. Semen and blood samples were collected from the patients at their first visit to the clinic. Frequency of anomalies of the vas deferens and frequency of mutations of the CFTR gene in male candidates for ICSI who had oligoasthenoteratozoospermia. None of the patients had abnormalities of the vas deferens at physical examination. In 4 of the 150 chromosomes (75 patients), a CFTR mutation was found, yielding a CFTR mutation frequency of 2.7% (95% confidence interval, 1.0-6.7%). None of the patients had two CFTR mutations.

The frequency of congenital abnormalities of the vas deferens in patients with oligoasthenoteratozoospermia is low. The frequencies of the CFTR mutations identified in this cohort did not differ significantly from the frequencies found in the normal Dutch population.

Does magnetic resonance spectroscopy suggest key differences in the metastatic behaviour of medulloblastoma? Metastatic medulloblastoma has a poorer prognosis than localised disease in part due to inherent properties of the tumour. 1H magnetic resonance spectroscopy (MRS) provides a powerful method for investigating tumour metabolism in vivo. Magnetic resonance imaging and short echo time (Te 30 ms) single voxel MRS were performed on the primary tumour of 16 children with medulloblastoma prior to surgical resection. Tumour volumes were calculated using a segmentation technique and the MRS was analysed using LCModel. Patients with metastatic disease had primary tumours which were smaller (p=0.01), had higher levels of total choline (p=0.03) and lower levels of mobile lipids (p=0.04).

Metastatic medulloblastomas have metabolite profiles indicative of increased cell growth and decreased cell death compared with localised tumours reflecting intrinsic differences in underlying biology. Localised tumours with an MRS metabolite profile similar to those with metastatic disease may be at increased risk of metastatic relapse.

Is p50 sensory gating a trait marker of the bipolar spectrum? Sensory gating deficit, assessed by a paired auditory stimulus paradigm (P50), has been reported as a stable marker of schizophrenia. The aim of this study was to explore if this neurophysiological disturbance also fulfilled stability criteria in the bipolar disorder (BD) spectrum bipolar, as state independence is one of the main points to be considered as a potential endophenotype of the illness. The P50 evoked potential was studied in 95 healthy controls and 126 bipolar euthymic patients. Euthymia was established according to Van Gorp's criteria. Bipolar I and II subtypes were analyzed separately. The influence of a lifetime history of psychoses was also evaluated in the clinical sample. P50 gating was deficitary in all the subsamples of patients relative to healthy comparison subjects. Bipolar I patients with and without a history of psychosis showed higher P50 ratios than the other subgroups of patients, although these differences were not significant. P50 alterations were mainly due to a deficit in the inhibition of the second wave (test wave or S2) amplitude.

The findings suggest that this inhibitory deficit can be considered characteristic of the illness and that the intensity of the gating abnormality varies according to the severity of BD.

Does painful conditioning stimuli of the craniofacial region evoke diffuse noxious inhibitory controls in men and women? To compare the modulatory effects of tonic mechanical or thermal craniofacial painful conditioning stimuli on pain sensitivity in craniofacial and spinal test sites in healthy men and women. Mechanical and cold headbands were developed and tested on 12 healthy men and 12 age-matched women (mean +/- SEM: 27 +/- 1.5 years). The pressure applied by the mechanical headband around the skull above the eyebrows could be adjusted over time via feedback from a 0 to 10 electronic visual analog scale (VAS) to maintain the pain intensity at a given level for 10 minutes (3 to 7 on VAS). The cold headband consisted of a series of plastic bags filled with antifreeze water having a temperature of approx 3 degrees C. During the 10 minutes of application, the subjects were asked to rate the pain intensity on a 10-cm VAS. Pressure pain thresholds (PPT) were recorded over the right and left masseter muscles (MAR, MAL), right splenius muscle (neck), right elbow (elbow), and right middle finger (finger) by a pressure algometer (1-cm2 area probe). The PPTs at each of the five sites were determined at baseline and during the mechanical or cold-induced pain. The two sessions with mechanical or cold headbands were performed at an interval of 30 minutes. Women had significantly lower absolute PPT values than men at most test sites (Unpaired t-test: P < .027). The mechanical headband caused pain in both men (peak pain mean +/- SEM: 4.7 +/- 0.4 cm) and women (4.9 +/- 0.4 cm) (P = .455). A significant PPT elevation was found at MAR, MAL, neck, and finger in men (11% to 17%; P < .031) and at MAR, MAL, and neck in women (15% to 22%; P < .020) during the mechanical-induced pain. The cold headband caused pain in both men (4.0 +/- 0.4 cm) and women (4.5 +/- 0.4 cm) (P = .285). During the cold-induced pain, a significant PPT elevation was found at all test sites in men (P < .023) and at all sites (P < .021) except for the finger in women. The relative changes in PPT values were not significantly different between men and women at any test site (unpaired t-test: P > .446).

This study has documented that mechanical and thermal painful tonic stimuli applied to the craniofacial region can evoke diffuse noxious inhibitory control (DNIC)-like effects in the craniofacial region as well as spinally innervated areas, but without sex differences.

Does mithramycin target sp1 and the androgen receptor transcription level-potential therapeutic role in advanced prostate cancer? Multiple lines of evidence implicate over-expression and activation of the androgen receptor (AR) in the progression of prostate cancer (PC) to androgen-independence (AI) and resistance to therapy. The mechanisms leading to AR over-expression are not fully understood but binding of Sp1 to specific Sp1-binding sites in the AR promoter and 5'-untranslated region (5'-UTR) was shown to up-regulate AR transcription. In this work, we further characterized the role of Sp1 in the control of AR transcription and explored its potential as a therapeutic target in androgen-dependent (AD) and independent (AI) LNCaP cells. We identified a pair of new Sp1-binding site in the 5'-UTR of AR which we named ARSp1-3. ARSp1-3 binds Sp1 with higher affinity than other known Sp1-binding sites in the promoter/5'-UTR and in transfection experiments, the ARSp1-3 reporter showed higher transcriptional activity in AI than in AD cells. Treatment of these cells with nanomolar concentrations of Mithramycin inhibited binding of Sp1 to its binding sites in the promoter/5'-UTR of the AR gene but more specifically the binding of ARSp1-3 while other regulatory elements of the AR promoter were not affected. Inhibition of Sp1 binding by Mithramycin decreased the AR transcription and transactivation of PSA reporter constructs. At the lowest concentrations, Mithramycin decreased endogenous AR protein and proliferation of AD and AI LNCaP cells. The combinations of Mithramycin with either paclitaxel or bicalutamide were highly synergistic.

Sp1 binding induces AR transcription in LNCaP cells. The higher affinity of ARSp1-3 for Sp1 may support higher AR mRNA levels in AI than AD LNCaP cells. Mithramycin is a potent and specific inhibitor of Sp1 and AR transcription with potential, at very low concentrations, to enhance the efficacy of hormones or taxane based therapy in patients with recurrent or androgen-independent progression that sustain AR expression.

Are neopterin and quinolinic acid surrogate measures of disease activity in the juvenile idiopathic inflammatory myopathies? We evaluated the utility of neopterin and quinolinic acid (QUIN) as surrogate measures of disease activity in juvenile idiopathic inflammatory myopathies (IIMs). Plasma and first morning void urine samples were measured for neopterin and QUIN using commercial ELISA, HPLC, or gas chromatography-mass spectrometry in 45 juvenile IIM patients and 79 healthy controls. Myositis disease activity assessments were obtained. Plasma and urine neopterin and QUIN concentrations were increased in juvenile IIM patients compared with healthy controls (P <0.017). Urine neopterin and QUIN highly correlated with each other (r(s) = 0.73; P <0.0001). Urine neopterin and QUIN correlated moderately with myositis disease activity assessments, including physician and parent global activity assessments, muscle strength testing, functional assessments (Childhood Myositis Assessment Scale, Childhood Health Assessment Questionnaire), skin global activity, and edema on magnetic resonance imaging (r(s) = 0.42-0.62; P <0.05), but generally not with muscle-associated enzymes in serum. Urine neopterin or QUIN, in combination with either serum lactate dehydrogenase (LD) or aspartate aminotransferase (AST), significantly predicted global disease activity (R(2) =0.40-0.56; P <0.002), and both were more sensitive to change than these serum enzymes (standardized response means, -0.41 to -0.48).

Urinary neopterin and QUIN are candidate measures of disease activity in juvenile IIM patients and add significantly to the prediction of global disease activity in combination with serum LD or AST values. Measurement of these markers in first morning void urine specimens appears to be as good as, or possibly better than, measurements of their concentrations in plasma.

Does a temporary immersion system improve in vitro regeneration of peach palm through secondary somatic embryogenesis? Secondary somatic embryogenesis has been postulated to occur during induction of peach palm somatic embryogenesis. In the present study this morphogenetic pathway is described and a protocol for the establishment of cycling cultures using a temporary immersion system (TIS) is presented. Zygotic embryos were used as explants, and induction of somatic embryogenesis and plantlet growth were compared in TIS and solid culture medium. Light microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to describe in vitro morphogenesis and accompany morpho-histological alterations during culture. The development of secondary somatic embryos occurs early during the induction of primary somatic embryos. Secondary somatic embryos were observed to develop continually in culture, resulting in non-synchronized development of these somatic embryos. Using these somatic embryos as explants allowed development of cycling cultures. Somatic embryos had high embryogenic potential (65·8 ± 3·0 to 86·2 ± 5·0 %) over the period tested. The use of a TIS greatly improved the number of somatic embryos obtained, as well as subsequent plantlet growth. Histological analyses showed that starch accumulation precedes the development of somatic embryos, and that these cells presented high nucleus/cytoplasm ratios and high mitotic indices, as evidenced by DAPI staining. Morphological and SEM observations revealed clusters of somatic embryos on one part of the explants, while other parts grew further, resulting in callus tissue. A multicellular origin of the secondary somatic embryos is hypothesized. Cells in the vicinity of callus accumulated large amounts of phenolic substances in their vacuoles. TEM revealed that these cells are metabolically very active, with the presence of numerous mitochondria and Golgi apparatuses. Light microscopy and TEM of the embryogenic sector revealed cells with numerous amyloplasts, large nuclei and nucleoli, and numerous plasmodesmata. Plantlets were obtained and after 3 months in culture their growth was significantly better in TIS than on solid culture medium. However, during acclimatization the survival rate of TIS-grown plantlets was lower.

The present study confirms the occurrence of secondary somatic embryos in peach palm and describes a feasible protocol for regeneration of peach palm in vitro. Further optimizations include the use of explants obtained from adult palms and improvement of somatic embryo conversion rates.

Does graphic reanalysis of the two NINDS-tPA trials confirm substantial treatment benefit? Multiple statistical analyses of the 2 NINDS-tPA trials have confirmed study findings of benefit of fibrinolytic therapy. A recent graphic analysis departed from best practices in the visual display of quantitative information by failing to take into account the skewed functional importance of NIH Stroke Scale raw scores and by scaling change axes at up to 20 times the range achievable by individual patients. Using the publicly available datasets of the 2 NINDS-tPA trials, we generated a variety of figures appropriate to the characteristics of acute stroke trial data. A diverse array of figures all visually delineated substantial benefits of fibrinolytic therapy, including: bar charts of normalized gain and loss; stacked bar, bar, and matrix plots of clinically relevant ordinal ranks; a time series stacked line plot of continuous scale disability weights; and line plot, bubble chart, and person icon array graphs of joint outcome table analysis. The achievable change figure showed substantially greater improvement among tPA than placebo patients, median 66.7% (interquartile range, 0 to 92.0) versus 50.0% (interquartile range, -7.1 to 80.0), P=0.003.

On average, under 3 hour patients treated with tPA recovered two-thirds while placebo patients improved only half of the way toward fully normal. Graphical analyses of the 2 NINDS-tPA trials, when performed according to best practices, is a useful means of conveying details about patient response to therapy not fully delineated by summary statistics, and confirms a valuable treatment benefit of under 3 hour fibrinolytic therapy in acute stroke.

Do assessment of dynamic mechanical properties of the respiratory system during high-frequency oscillatory ventilation*? 1) To investigate the possibility of estimating respiratory system impedance (Zrs, forced oscillation technique) by using high-amplitude pressure oscillations delivered during high-frequency oscillatory ventilation; 2) to characterize the relationship between Zrs and continuous distending pressure during an increasing/decreasing continuous distending pressure trial; 3) to evaluate how the optimal continuous distending pressure identified by Zrs relates to the point of maximal curvature of the deflation limb of the quasi-static pressure-volume curve. Prospective laboratory animal investigation. Experimental medicine laboratory. Eight New Zealand rabbits. The rabbits were ventilated with high-frequency oscillatory ventilation. Zrs was measured while continuous distending pressure was increased and decreased between 2 and 26 cm H2O in 1-minute steps of 4 cm H2O. At each step, a low-amplitude (6 cm H2O) sinusoidal signal was alternated with a high-amplitude (18 cm H2O) asymmetric high-frequency oscillatory ventilation square pressure waveform. Pressure-volume curves were determined at the end of the continuous distending pressure trial. All measurements were repeated after bronchoalveolar lavage. Zrs was estimated from flow and pressure measured at the inlet of the tracheal tube and expressed as resistance (Rrs) and reactance (Xrs). Linear correlation between the values, measured by applying the small-amplitude sinusoidal signal and the ventilator waveform, was good for Xrs (r = 0.95 ± 0.04) but not for Rrs (r = 0.60 ± 0.34). Following lavage, the Xrs-continuous distending pressure curves presented a maximum on the deflation limb, identifying an optimal continuous distending pressure that was, on average, 1.1 ± 1.7 cm H2O below the point of maximal curvature of the deflation limb of the pressure-volume curves.

Xrs can be accurately measured during high-frequency oscillatory ventilation without interrupting ventilation and/or connecting additional devices. An optimal continuous distending pressure close to the point of maximal curvature of the deflation limb of quasi-static pressure-volume curve can be identified by measuring Zrs during a decreasing continuous distending pressure trial. Zrs might constitute a useful bedside tool for monitoring lung mechanics and improving the continuous distending pressure optimization during high-frequency oscillatory ventilation.

Does adenoviral-mediated gene transfer of ICP47 inhibit major histocompatibility complex class I expression on vascular cells in vitro? Many viruses have evolved mechanisms to evade detection by the host immune system. The herpes simplex gene ICP47 encodes a protein that binds to the host antigen-processing transporter, inhibiting the formation of major histocompatibility complex class I (MHC-I) antigens in infected cells. MHC-I antigen expression is also important in acute allograft rejection. This study was designed to quantitate the effect of adenoviral-mediated gene transfer of ICP47 on MHC-I cell surface expression of human vascular cells. We hypothesized that the transduction of vascular cells with a replication-incompetent adenoviral vector that was expressing ICP47 (AdICP47) would inhibit constitutive and inducible MHC-I expression and thereby reduce the rate of cytolysis of ICP47-transduced vascular cells by sensitized cytotoxic T lymphocytes (CTL). A replication-incompetent adenoviral vector, AdICP47, was created to express ICP47 driven by the cytomegalovirus immediate early promoter. Cultured human vascular endothelial and smooth muscle cells and human dermal fibroblasts were transduced with either AdICP47 or the control empty vector AddlE1. Cell surface constitutive and gamma-interferon-induced MHC-I expression were quantitated by flow cytometry. A standard 4-hour chromium release cytotoxicity assay was used to determine the percent cytolysis of transduced and nontransduced endothelial cells by sensitized CTL. Finally, to quantitate the specificity of the effect of ICP47 on MHC-I expression, adhesion molecule expression was quantitated in both transduced and nontransduced cells. Constitutive MHC-I expression in AdICP47-transduced endothelial cells was inhibited by a mean of 84% +/- 5% (SEM) in five experiments. After 48 hours of exposure to gamma-interferon, AdICP47-transduced cells exhibited a mean of 66% +/- 8% lower MHC-I expression than nontransduced cells. Similar inhibition in MHC-I expression was achieved in AdICP47-transduced vascular smooth muscle cells and dermal fibroblasts. Percent cytolysis of AdICP47-transduced endothelial cells by CTL was reduced by 72%. Finally, the specificity of the effect of transduction of ICP47 on vascular cell MHC-I expression was confirmed by a lack of significant change in either constitutive or tumor necrosis factor-induced vascular cell adhesion molecule/intercellular adhesion molecule expression.

Transduction of vascular cells with AdICP47 strongly inhibits both constitutive and inducible MHC-I expression in human vascular cells. AdICP47-transduced cells exhibited a substantial reduction in cytolysis by CTL. Thus AdICP47 transduction holds promise as a technique to characterize the role of MHC-I expression in acute vascular allograft rejection in vivo and as a potential therapeutic intervention.

Do harris-Benedict equations adequately predict energy requirements in elderly hospitalized African Americans? Malnutrition, associated with poor outcome in the elderly, may be exacerbated by weight loss during hospitalization. Accurate estimation of energy requirements is important, particularly if predictions are applied to caloric supply. Because data on energy requirements for the elderly are limited, particularly for African-American patients, predictions are commonly made with equations derived from a younger, caucasian, cohort from 80 years ago. To compare measured resting metabolic rate (RMR) in a hospitalized elderly African-American cohort in an urban community hospital during 1998 with Harris-Benedict predictions of basal energy expenditure (BEE). Energy expenditure was measured by a strict protocol with a portable metabolic cart, and height and weight were measured standardly and used to calculate BEE and body mass index (BMI). In 61 subjects, aged 79.6+/-8.9 years, measured RMR was significantly greater than predicted BEE (p=0.001, t-test). Caloric expenditure averaged 24.7+/-5 kcal/kg/day, but the range was broad (14-39 kcal/kg/day). The BEE prediction was 20.3+/-2.4 kcal/kg/day.

In elderly hospitalized African-American patients, the Harris-Benedict equation significantly underestimated energy requirements. Given the link between unintentional weight loss and increased mortality on the one hand and potential clinical complications of overfeeding on the other, measurement of energy expenditure is warranted.

Are italian air force acrobatic pilots protected against flight-induced oxidative stress? The purpose of this study was to assess the oxidative stress of aircraft pilots by evaluating different markers of oxidative stress and any imbalance between free radicals and antioxidants in plasma. A group of 13 supersonic aircraft pilots, following regular exercise and personalized diet, were compared with a group of 40 healthy controls. Oxidative stress indicators, such as reactive oxidative metabolites, carbonyl proteins, 8-hydroxy-2-deoxyguanosine and total antioxidant status, were evaluated after three months of intense flight. Reactive oxygen metabolites, carbonyl protein and 8-hydroxy-2-deoxyguanosine plasma levels did not differ in supersonic aircraft pilots and healthy controls. The two groups also had similar total antioxidant status levels.

We suggest that supersonic aircraft pilots working at high altitude, even if exposed to physiological stresses, can, with proper diet, regular exercise and periodical medical examinations, maintain a healthy balance between oxidant and antioxidant status.

Does short-term anti-vascular endothelial growth factor treatment elicit vasculogenic mimicry formation of tumors to accelerate metastasis? Antiangiogenic therapy is one of the most significant advances in anticancer treatment. The benefits of antiangiogenic therapies of late-stage cancers have been investigated but are still too limited. We used an ovarian cancer model to test the effect of short-term bevacizumab treatment on metastasis as measured by bioluminescence. Western blotting and CD34-PAS dual staining were performed to assess hypoxia-inducible transcription factor-1α (HIF-1α) expression and vasculogenic mimicry(VM) formation. Cell viability was examined by a CCK8 assay. Bevacizumab demonstrated antitumor effects in models of ovarian cancer, but also accelerated metastasis together, with marked hypoxia and VM formation in mice receiving short-term therapy. Bevacizumab treatment did not affect SKOV3 cell viability and the amount of VM in three-dimensional culture.

These results suggest that antiangiogenic therapy may potentially influence the progression of metastatic disease, which has been linked to the hypoxic response and VM formation.

Does adjuvant Radiation improve Survival in Older Women Following Breast-Conserving Surgery for Estrogen Receptor-Negative Breast Cancer? Published prospective trials have questioned the role of post-lumpectomy radiotherapy in older women with early-stage, estrogen receptor-positive (ER The Surveillance, Epidemiology, and End Results database was queried from 1998 to 2011 for patients age ≥ 70 years receiving breast-conserving surgery for T1, ER Overall, 3685 patients received radiation and 1493 patients received lumpectomy alone. Patients treated with adjuvant radiation were younger (median age 76 vs. 78 years, P < .0001). Patients who received radiation had improved overall survival, with 5-year survival rates of 81.0% versus 61.7% without radiation (P < .0001). Cancer-specific survival was also improved with radiotherapy, with 5-year cancer-specific survival rates of 93.1% versus 85.0% (P < .0001).

This analysis of the SEER database demonstrates that women ages 70 and older treated with lumpectomy and radiotherapy for ER

Does oxytocin improve cytological and histological profiles of vaginal atrophy in postmenopausal women? To investigate if topical oxytocin can reverse vaginal atrophy, as assessed by cytological and histological examination of the vaginal mucosal epithelium, in postmenopausal women after 12 weeks of treatment as compared to placebo. Sixty-eight postmenopausal women diagnosed with vaginal atrophy were randomized for this multicenter, double-blinded, placebo-controlled trial. Thirty-three women received 600 IU vagitocin, an oxytocin containing gel, and 35 women received a placebo gel intravaginally. The dose was 600 IU daily for the first two weeks and thereafter 600 IU twice a week for 10 weeks. All participant women underwent four visits and a subgroup of 20 women had a further fifth visit. Vaginal smears for cytological evaluation were collected at all visits. Vaginal biopsies were taken in 20 women before and after 12 weeks of treatment for histological analysis. In these women a vaginal smear was also collected after 14 weeks. The increase in the percentage of superficial cells between 0 and 2 weeks was significantly greater after treatment with vagitocin in comparison with placebo (p = 0.04). The difference in the maturation value between 0 and 12 weeks was significantly higher in the vagitocin than in the placebo group (p = 0.01). The reduction in the scores of atrophy was according to the histological investigation significantly greater in the vagitocin group than in the placebo group at 12 weeks (p < 0.04).

Daily intravaginal treatment with vagitocin 600 IU improves expressions of vaginal atrophy as recorded by cytological investigation of vaginal smears and histological analysis of vaginal biopsies. Treatment twice weekly seems to be less effective regarding the increase in superficial cells.

Does gonadotropin-releasing hormone agonist administration affect the thymopoiesis in adult female rats independently on gonadal hormone production? In addition to having an indirect effect on the T-cell development by controlling the production of ovarian steroids, an accumulating body of evidence suggest that GnRH analogue (GnRH-A) administration may exert a thymopoietic regulatory effect that is not mediated by ovarian hormones. In non-ovariectomized (non-OVX) and OVX adult female AO rats treated s.c. with GnRH-A or saline (controls), over 14 days, were estimated the thymic cellularity and thymocyte expression of CD4/CD8/TCRalphabeta by stereological analysis and three-color flow cytometry, respectively. GnRH-A in both groups of rats diminished the thymic cellularity. In non-OVX rats GnRH-A increased the relative numbers of immature cells (CD4-8-TCRalphabeta(-), CD4-8-TCRalphabeta(low) and CD4+8-TCRalphabeta(low)), and reduced those of positively selected CD4+8+TCRalphabeta(high) and mature (CD4-8+TCRalphabeta(high), CD4(+8)-TCRalphabeta(high)) cells, suggesting decelerated expression of TCRalphabeta followed by less efficient positive selection and further maturation of the selected cells. Differently, in OVX rats GnRH-A decreased the percentage of immature (CD4-8-TCRalphabeta(-), CD4+8+ TCRalphabeta(-)) cells and increased those of all TCRalphabeta(high) subsets, suggesting an increased rate of early thymocyte differentiation, more efficient positive selection and further maturation of the selected cells.

The effect of GnRH-A administration is affected by the presence of ovarian steroids.

Does hippocampal atrophy confound template-based functional MR imaging measures of hippocampal activation in patients with mild cognitive impairment? Functional MR imaging has been used to study patterns of hippocampal activation that distinguish pathologic from normal memory loss in the elderly population. Our objective was to assess whether hippocampal atrophy confounds measurements of hippocampal activation in subjects with mild cognitive impairment (MCI). Twenty subjects with MCI and 20 elderly control subjects with objectively normal memory were studied at 4T during a face-name paradigm designed to activate the hippocampus. Hippocampal activation was measured using 2 separate approaches: applying a preset region of interest (ROI) in standardized template space and applying a manually drawn ROI in native subject space. Pearson correlation coefficients were calculated to compare group-dependent relationships between hippocampal volume and activation. Analysis of covariance (ANCOVA) was performed to assess group differences in hippocampal activation during encoding and retrieval. Age and hippocampal volume were included as covariates, as was a term for the interaction between hippocampal volume and group. When hippocampal activation was measured by the template-based method, the correlation coefficient in the right hippocampus of subjects with MCI but not control subjects during retrieval differed significantly from zero. There was a significant (P < .05) group-by-volume interaction in the ANCOVA model. No significant correlations or interactions were demonstrated when activation was measured in native subject space with manually drawn ROIs.

Our findings suggest a potential confounding relationship between hippocampal volume and activation for subjects with MCI in template-based analyses. Template-based measures of hippocampal activation that do not adequately account for hippocampal atrophy should be used with caution in patients with MCI.

Does cXCL12 impair the acquisition and extinction of auditory fear conditioning in rats via crosstalk with GABAergic system? Chemokines, such as CXCL12, are signaling molecules playing an important role in immune regulations. Chemokine upsurge has also been associated with neuroinflammatory conditions characterized with cognitive impairments. Recently, some in-vitro data suggests that CXCL12 is a potential neuromodulator and interacts with GABAergic system, but, so far, whether these effects translate into alterations in neural and behavioral functions has not been investigated. In the present study, we used auditory fear conditioning as a model to define the contribution of CXCL12/CXCR4 on fear-related cognitive disorders. We microinjected different dosages of CXCL12 into the bilateral amygdala of rats to investigate their behavioral effects on the acquisition and extinction of conditioned fear memory. Moreover, we pretreated the rats with the selective CXCR4 receptor antagonist (AMD3100), GABAA antagonist (bicuculline) and GABAB antagonist (CGP55845) to examine whether the CXCL12 induced changes could be reversed. We found that intra-amygdala infusion of CXCL12 impaired the acquisition and extinction of conditioned fear response. Pretreatment with AMD3100, rescued the CXCL12 induced impairments, indicating that CXCL12 produced the effects by activating CXCR4 receptors. Furthermore, both bicuculline and CGP55845 prevented CXCL12 from impairing the rat's ability of conditioned learning, indicating a crosstalk between CXCL12/CXCR4 and GABAergic system.

Our data suggest that the chemokine CXCL12 is able to regulate neurotransmitter mechanisms involved in associative learning functions, and the effect of GABAergic agents on CXCL12/CXCR4 may be new therapeutic potentials for neuroinflammatory diseases.

Does lifestyle mediate seasonal changes in metabolic health among the yakut ( sakha ) of northeastern siberia? Among indigenous circumpolar populations, extreme seasonality influences food availability and energy metabolism. Furthermore, subsistence patterns and wage labor opportunities shift with season. Thus, health measures among circumpolar populations likely exhibit seasonal changes that are influenced by lifestyle factors. This study examines how markers of cardio-metabolic health vary between summer and winter as a function of an individual's lifestyle and sex among the Yakut of northeastern Siberia. Anthropometric dimensions, serum lipids and glucose levels, blood pressure, and lifestyle data were collected for a sample of 115 Yakut participants (71 women, 44 men) in Berdygestiakh, Sakha Republic, Russia in the summer of 2009 and winter of 2011. Men and women experienced significant increases in total and HDL cholesterol and triglyceride levels from summer to winter. Women exhibited winter-time increases in adiposity and glucose levels. Men who reported greater market integration were more likely to have lower winter blood pressure levels. Additionally, time spent fishing was associated with lower winter-time LDL cholesterol, while foraging time was associated with higher HDL cholesterol.

While seasonal changes in anthropometric dimensions were modest, Yakut men and women experienced significant increases in total cholesterol and HDL cholesterol from summer to winter. These results also suggest that while Yakut individuals with greater subsistence participation are more buffered from adverse seasonal changes in cholesterol levels, they may be at a greater risk for winter increases in blood pressure. Furthermore, the interactions between lifestyle and seasonal change in metabolic health appear to differ between Yakut women and men. Am. J. Hum. Biol. 28:868-878, 2016. © 2016Wiley Periodicals, Inc.

Do pSD95 gene specific siRNAs attenuate neuropathic pain through modulating neuron sensibility and postsynaptic CaMKIIα phosphorylation? To observe the effects of PSD95 gene specific siRNAs on neuropathic pain relief, neuron viability, and postsynaptic calcium/calmodulin-dependent protein kinase IIα (CaMKIIα) phosphorylation in vitro and in vivo. Gene-specific siRNAs of rat PSD95 were synthesized chemically for transfection. Adult male Sprague-Dawley (SD) rats were randomly divided into 3 groups: naïve group (n=6), sham group (n=6), and sciatic nerve chronic constriction injury (CCI) group (n=24). The CCI group was further divided into 4 groups (n=6 in each group), which were pretreated with normal saline, transfection vehicle, negative control siRNAs, and PSD95 gene specific siRNAs respectively. All the subgroups received corresponding agents intrathecally for 3 days, started one day before the CCI of sciatic nerve. Both mechanical allodynia and thermal hyperalgesia were measured on post-operative day 3 and 7. PSD95 gene silenced NG108-15 cells were further stimulated by glutamate, with the cell viability and the expression/phosphorylation of CaMKIIα measured by MTT cell proliferation assay and Western blot, respectively. The siRNAs decreased PSD95 mRNA level significantly both in vivo and in vitro. Neuropathic pain rats pretreated with PSD95 gene specific siRNAs exhibited significant elevation in the mechanical withdrawal threshold and paw withdrawal thermal latency, without affecting the baseline nociception. PSD95 gene silencing enhanced neuronal tolerance against the glutamate excitotoxicity, meanwhile the phosphorylation of CaMKIIα Thr286 was attenuated.

Pre-emptive administration of PSD95 gene specific siRNAs may attenuate the central sensitization CaMKIIα-related signaling cascades, leading to the relief of neuropathic pain.

Does the addition of synchronous whole-body vibration to battling rope exercise increase skeletal muscle activity? To evaluate the effects of performing battling rope exercise with and without the addition of whole-body vibration (WBV) on muscle activity of the leg, trunk, and upper body. Twenty-eight recreationally active university students completed 20-s of battling rope undulation for 6 separate conditions: 1) alternating arm motion no WBV -Alt_NoWBV; 2) alternating arm motion 30 Hz low amplitude WBV -Alt_30 Hz-L; 3) alternating arm motion 50 Hz high amplitude -Alt_50 Hz-H; 4) double arm motion no WBV -Double_NoWBV; 5) double arm motion 30Hz low amplitude WBV -Double_30Hz-L; 6) double arm motion 50 'Hz high amplitude -Double_50 Hz-H. Electromyography (EMG) was measured for the gastrocnemius medialis (GM), vastus medialis oblique (VMO), vastus lateralis (VL), rectus abdominis (RA), multifidus (MF), biceps brachii (BB), and triceps brachii (TB) muscles. The double arm motion during undulation resulted in greater (p<0.05) muscle activity in the VMO, VL, RA, and MF muscles while the GM was more active during the alternating arm motion. WBV at 50Hz increased EMG in all muscles measured vs NoWBV and the 30 Hz condition.

These results are the first to demonstrate that the exercise stimulus of performing battling rope exercise can be augmented by completing the exercise while being exposed to WBV from a ground-based platform.

Is balance of unsaturated fatty acids important to a cholesterol-lowering diet : comparison of mid-oleic sunflower oil and olive oil on cardiovascular disease risk factors? To evaluate the effects of a trans fat-free monounsaturated fatty acid-rich vegetable oil (NuSun sunflower oil, National Sunflower Association, Bismark, ND) that is a good source of polyunsaturated fatty acids (PUFA) and low in saturated fatty acids on lipid and lipoprotein levels and oxidative stress. A double-blinded, randomized, three period crossover, controlled feeding study. Thirty-one men (n=12) and women (n=19) with moderate hypercholesterolemia who were 25 to 64 years of age. Experimental diets provided 30% fat (olive oil or NuSun sunflower oil contributed one half of the total fat), 8.3% vs 7.9% saturated fatty acid, 17.2% vs 14.2% monounsaturated fatty acid, and 4.3% vs. 7.7% PUFA (olive oil and NuSun sunflower oil, respectively), and 294 mg cholesterol. The control diet was an average American diet (34% fat, 11.2% saturated fatty acid, 14.9% monounsaturated fatty acid, 7.8% PUFA). Subjects consumed each diet for 4 weeks with a 2-week compliance break before crossing over to another diet. Lipid and lipoprotein levels were measured, and measures of oxidative stress, including lag time, rate of oxidation, total dienes, and lipid hydroperoxides, were assessed. The mixed model procedure was used to test for main effects of diet, feeding period, and order of diets. Tukey-Kramer adjusted P values were used to determine diet effects. The NuSun sunflower oil diet decreased both total and low-density lipoprotein cholesterol levels compared with the average American diet and the olive oil diet. There was no effect of the olive oil diet compared with the average American diet. Total cholesterol decreased 4.7% and low-density lipoprotein cholesterol decreased 5.8% on the NuSun sunflower oil diet vs the average American diet. There was no effect of the experimental diets on triglyceride levels, rate of oxidation, total dienes, lipid hydroperoxides, or alpha-tocopherol. Lag time was the longest following the olive oil diet and shortest following the NuSun sunflower oil diet.

The higher PUFA content appeared to account for the greater total and low-density lipoprotein cholesterol lowering and reduction in lag time of the NuSun sunflower oil diet. However, the fact that there were no differences in the resulting oxidation products suggests there were no adverse effects on low-density lipoprotein oxidation. Since PUFAs are important for cholesterol lowering, foods that replace saturated fatty acids should include a balance of unsaturated fatty acids.

Is oxLDL-dependent activation of arginase II dependent on the LOX-1 receptor and downstream RhoA signaling? Arginase II regulates NOS activity by competing for the substrate l-arginine. Oxidized LDL (OxLDL) is a proatherogenic molecule that activates arginase II. We tested the hypotheses that OxLDL-dependent arginase II activation occurs through a specific receptor, and via a Rho GTPase effector mechanism that is inhibited by statins. Arginase II activation by OxLDL was attenuated following preincubation with the LOX-1 receptor-blocking antibody JTX92. This also prevented the dissociation of arginase II from microtubules. LOX-1(-/-) mice failed to exhibit the increased arginase II activity seen in WT mice fed a high cholesterol diet. Furthermore, endothelium from LOX-1(-/-) mice failed to demonstrate the diet-dependent reduction in NO and increase in ROS that were observed in WT mice. OxLDL induced Rho translocation to the membrane and Rho activation, and these effects were inhibited by pretreatment with JTX92 or statins. Transfection with siRNA for RhoA, or inhibition of ROCK both decreased OxLDL-stimulated arginase II activation. Preincubation with simvastatin or lovastatin blocked OxLDL-induced dissociation of arginase II from microtubules and prevented microtubule depolymerization.

This study provides a new focus for preventive therapy for atherosclerotic disease by delineating a clearer path from OxLDL through the endothelial cell LOX-1 receptor, RhoA, and ROCK, to the activation of arginase II, downregulation of NO, and vascular dysfunction.

Does the cerebellar nodulus/uvula integrate otolith signals for the translational vestibulo-ocular reflex? The otolith-driven translational vestibulo-ocular reflex (tVOR) generates compensatory eye movements to linear head accelerations. Studies in humans indicate that the cerebellum plays a critical role in the neural control of the tVOR, but little is known about mechanisms of this control or the functions of specific cerebellar structures. Here, we chose to investigate the contribution of the nodulus and uvula, which have been shown by prior studies to be involved in the processing of otolith signals in other contexts. We recorded eye movements in two rhesus monkeys during steps of linear motion along the interaural axis before and after surgical lesions of the cerebellar uvula and nodulus. The lesions strikingly reduced eye velocity during constant-velocity motion but had only a small effect on the response to initial head acceleration. We fit eye velocity to a linear combination of head acceleration and velocity and to a dynamic mathematical model of the tVOR that incorporated a specific integrator of head acceleration. Based on parameter optimization, the lesion decreased the gain of the pathway containing this new integrator by 62%. The component of eye velocity that depended directly on head acceleration changed little (gain decrease of 13%). In a final set of simulations, we compared our data to the predictions of previous models of the tVOR, none of which could account for our experimental findings.

Our results provide new and important information regarding the neural control of the tVOR. Specifically, they point to a key role for the cerebellar nodulus and uvula in the mathematical integration of afferent linear head acceleration signals. This function is likely to be critical not only for the tVOR but also for the otolith-mediated reflexes that control posture and balance.

Does sumoylation of FOXP2 regulate Motor Function and Vocal Communication Through Purkinje Cell Development? Mutations in the gene encoding the transcription factor forkhead box P2 (FOXP2) result in brain developmental abnormalities, including reduced gray matter in both human patients and rodent models and speech and language deficits. However, neither the region-specific function of FOXP2 in the brain, in particular the cerebellum, nor the effects of any posttranslational modifications of FOXP2 in the brain and disorders have been explored. We characterized sumoylation of FOXP2 biochemically and analyzed the region-specific function and sumoylation of FOXP2 in the developing mouse cerebellum. Using in utero electroporation to manipulate the sumoylation state of FOXP2 as well as Foxp2 expression levels in Purkinje cells of the cerebellum in vivo, we reduced Foxp2 expression approximately 40% in the mouse cerebellum. Such a reduction approximates the haploinsufficiency observed in human patients who demonstrate speech and language impairments. We identified sumoylation of FOXP2 at K674 (K673 in mice) in the cerebellum of neonates. In vitro co-immunoprecipitation and in vivo colocalization experiments suggest that PIAS3 acts as the small ubiquitin-like modifier E3 ligase for FOXP2 sumoylation. This sumoylation modifies transcriptional regulation by FOXP2. We demonstrated that FOXP2 sumoylation is required for regulation of cerebellar motor function and vocal communication, likely through dendritic outgrowth and arborization of Purkinje cells in the mouse cerebellum.

Sumoylation of FOXP2 in neonatal mouse cerebellum regulates Purkinje cell development and motor functions and vocal communication, demonstrating evidence for sumoylation in regulating mammalian behaviors.

Is broad-based general surgery training a model of continued utility for the future? Our program has emphasized broad-based training that potentially allows residents to pursue a variety of career paths, with or without additional surgical training. Diverse experiences have emphasized a variety of rotations, including a university hospital with a large trauma service, several tertiary private institutions, and suburban and rural experiences with private practitioners. Our faculty includes surgeons with both broad-based and narrowly focused practices. In light of duty-hour restrictions and proposed changes in surgical training, we assessed the results of this model over an extended period. The case volume from the Residency Review Committee (RRC) operative logs, ABSITE scores, ABS performance, fellowship training, and subsequent career choices were examined for all graduating chief residents in general surgery from our program over the past 17 years. The impact of specialty faculty was assessed and data from 5 index (aortic, major esophagogastric, liver, pancreatic, and pelvic resections) cases were also abstracted from the logs. A survey was then sent to all 208 of the 212 surgeons who had completed the program since 1971. Of the 115 residents who completed training in the last 17 years, 60 pursued fellowship training and 55 went directly into general surgical practice in 20 states. Fifteen of the 29 residents who had an elective laboratory experience were among the 23 who remained in academic careers. The operative experience has been excellent (1090 +/- 42 total major; 240 +/- 21 surgeon chief). Experience did not vary, even though the number of graduating chiefs ranged from 5 to 8 per year, and there have been no deficiencies in RRC index cases. The addition of specialty faculty (n = 5) at various intervals promptly increased the volume of complex cases in pelvic, liver, pancreas, and vascular surgery. Since all residents promptly passed the ABS examinations, it was not possible to discern factors associated with Board performances other than broad-based training. The survey demonstrated that most continued to practice broad-based general surgery and believed that such training was highly relevant to their current practice.

The provision of broad-based training with generalists and specialty faculty has allowed for excellent breadth and depth in case volume. While many residents pursued fellowships, those who did not have indeed achieved successful careers. Most continue to practice general surgery, indicating the value of complete training in this field. It will be important to monitor these outcomes as changes in residency training occur.

Is prehypertension associated with atherosclerosis in Type 2 diabetes? Prehypertension is a risk factor for hypertension, diabetes, and cardiovascular diseases. However, the association between prehypertension and atherosclerosis in Type 2 diabetes mellitus (T2DM) has not been evaluated. In the present study, we investigated the impact of prehypertension on atherosclerosis in T2DM. Patients (n=930) with T2DM were recruited for the present study from the outpatient clinic of Shanghai Ruijin Hospital. The intima-media thickness (IMT) of the common carotid artery (CCA) was determined using ultrasound and brachial-ankle pulse wave velocity (baPWV) was determined by volume plethysmography to assess atherosclerosis. Of the 930 patients with T2DM (mean age of 59 years), 167 were categorized as normotensive, 213 were prehypertensive, and 550 were hypertensive. Diabetic subjects with prehypertension had significantly higher CCA-IMT and baPWV than those with normal blood pressure after adjustment for age and gender. Multiple logistic regression analysis revealed that, compared with normotension, prehypertension was a significant independent determinant of atherosclerosis (for maximum IMT ≥1.1 mm, odds ratio (OR) 2.10 and 95% confidence interval (CI) 1.28-3.44; for baPWV ≥1400 cm/s, OR 3.09 and 95% CI 1.78-5.36).

Prehypertension is associated with atherosclerosis independent of conventional cardiovascular risk factors in T2DM patients. We speculate that maintenance of systolic blood pressure <120 mmHg and diastolic blood pressure <80 mmHg may reduce the risk of atherosclerosis in T2DM.

Does bovine glycomacropeptide ameliorate experimental rat ileitis by mechanisms involving downregulation of interleukin 17? Bovine glycomacropeptide (BGMP) is an inexpensive, non-toxic milk peptide with anti-inflammatory effects in rat experimental colitis but its mechanism of action is unclear. It is also unknown whether BGMP can ameliorate inflammation in proximal regions of the intestine. Our aim was therefore two-fold: first, to determine the anti-inflammatory activity of BGMP in the ileum; second, to characterise its mechanism of action. We used a model of ileitis induced by trinitrobenzenesulphonic acid in rats. Rats were treated orally with BGMP and its efficacy compared with that of oral 5-aminosalicylic acid or vehicle, starting 2 days before ileitis induction. BGMP pretreatment (500 mg kg(-1) day(-1)) resulted in marked reduction of inflammatory injury, as assessed by lower extension of necrosis and damage score, myeloperoxidase, alkaline phosphatase, inducible nitric oxide synthase, interleukin 1beta, tumour necrosis factor and interleukin 17. These effects were generally comparable to those of 5-aminosalicylic acid (200 mg kg(-1) day(-1)). Neither compound affected the production of interferon gamma, tumour necrosis factor and interleukin 2 by mesenteric lymph node cells isolated from animals with ileitis. The expression of Foxp3 was increased in ileitis and not reduced significantly by BGMP or aminosalicylate treatment.

These results demonstrate that BGMP has anti-inflammatory activity in the ileum with similar efficacy to 5-aminosalicylic acid. The mechanism of action may involve Th17 and regulatory T cells and perhaps macrophages but probably not Th1 lymphocytes. Patients with Crohn's ileitis may benefit from treatment with BGMP.

Does assessment of basic human performance resources predict performance of ureteroscopy? Our objective was to predict endoscopic performance in a cadaver model using basic performance resources (BPRs) measurements. Medical students (n = 16) underwent intense ureteroscopic training on a virtual reality ureteroscopy trainer and were rated on performing ureteroscopy on a cadaver. The medical students also underwent 13 validated BPR measurements. Urology residents also performed cadaveric ureteroscopy and BPRs. A predictive model built from urology residents' (n = 16) BPRs and performance assessment was used to predict medical student cadaveric ureteroscopy performance based on their BPRs alone. The predictive model built with urology residents predicted the ureteroscopic performance of 10 of 16 medical students within 15% of their rated ureteroscopic performance on the cadaver.

A predictive model built with urology residents can moderately predict the ureteroscopic performance of medical students from BPRs. Additional in vivo evaluation is required.

Is myocardial phosphocreatine-to-ATP ratio a predictor of mortality in patients with dilated cardiomyopathy? In patients with heart failure due to dilated cardiomyopathy, cardiac energy metabolism is impaired, as indicated by a reduction of the myocardial phosphocreatine-to-ATP ratio, measured noninvasively by 31P-MR spectroscopy. The purpose of this study was to test whether the phosphocreatine-to-ATP ratio also offers prognostic information in terms of mortality prediction as well as how this index compares with well-known mortality predictors such as left ventricular ejection fraction (LVEF) or New York Heart Association (NYHA) class. Thirty-nine patients with dilated cardiomyopathy were followed up for 928+/-85 days (2.5 years). At study entry, LVEF and NYHA class were determined, and the cardiac phosphocreatine-to-ATP ratio was measured by localized 31P-MR spectroscopy of the anterior myocardium. During the study period, total mortality was 26%. Patients were divided into two groups, one with a normal phosphocreatine-to-ATP ratio (>1.60; mean+/-SE, 1.98+/-0.07; n=19; healthy volunteers: 1.94+/-0.11, n=30) and one with a reduced phosphocreatine-to-ATP ratio (<1.60; 1.30+/-0.05; n=20). At re-evaluation (mean, 2.5 years), 8 of 20 patients with reduced phosphocreatine-to-ATP ratios had died, all of cardiovascular causes (total and cardiovascular mortality, 40%). Of the 19 patients with normal phosphocreatine-to-ATP ratios, 2 had died (total mortality, 11%), one of cardiovascular causes (cardiovascular mortality, 5%). Kaplan-Meier analysis showed significantly reduced total (P=.036) and cardiovascular (P=.016) mortality for patients with normal versus patients with low phosphocreatine-to-ATP ratios. A Cox model for multivariate analysis showed that the phosphocreatine-to-ATP ratio and NYHA class offered significant independent prognostic information on cardiovascular mortality.

The myocardial phosphocreatine-to-ATP ratio, measured noninvasively with 31P-MR spectroscopy, is a predictor of both total and cardiovascular mortality in patients with dilated cardiomyopathy.

Is volume of the amygdala reduced in patients with narcolepsy - a structural MRI study? Based on the clinical observation that patients suffering from narcolepsy with cataplexy (NC) have cataplectic attacks when they experience positive emotions, it is therefore hypothesised that the abnormal processing of external emotional input through the limbic system, or motor dysregulation induced by emotions, takes place during these episodes. To date, imaging studies have failed to reveal consistent brain abnormalities in NC patients. Considering the discrepancies in reported structural or functional abnormalities of the hypothalamus, amygdala, and nucleus accumbens, we used the MRI volumetry to determine the volumes of the amygdala and nucleus accumbens in a group of eleven patients with NC (5 males and 6 females, mean age 41.7 years ± 17.7). This data was compared to an equal number of examinations in healthy volunteers matched for age and gender. We found a decrease in the amygdalar volume of NC patients in both raw (p<0.001) and relative (p<0.01) data sets. The difference in amygdalar volume between healthy volunteers and NC patients was about 17%. In contrast to the amygdala, we did not find any differences in the volumes of nucleus accumbens.

In the present MRI volumetric study, we found bilateral gray matter loss in the amygdala only.

Does unmet health services need experienced by Puerto Rican OEF/OIF veterans and families post deployment? This study examined perceptions of unmet health services needs among native Puerto Rican Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF) Veterans and family members (FMs) post deployment. Investigators used qualitative methods to collect and analyze data from 8 veterans and 8 FMs (N = 16). All participants were native-born residents of Puerto Rico. Investigators conducted single, in-depth interviews with participants. They conducted 13/16 interviews in Spanish. Puerto Rican-Spanish speakers transcribed audio-taped interviews verbatim and then translated them into English for coding. Veterans' unmet needs included psychological evaluations, mental health services, support groups, medical evaluations, and pain treatment. Denial and stigma emerged as factors that deter Veterans from seeking mental health treatment. The need for family support groups also emerged from the data.

Native Puerto Rican Veterans and FMs identified several gaps in health services. Findings suggest the need for studies comparing the health services needs of Puerto Rican versus mainland OEF/OIF Veterans and families.

Does siRNA inhibition of ER-alpha expression reduce KGF-induced proliferation of breast cancer cells? Keratinocyte growth factor (KGF) produces a rapid increase in the proliferation and motility of estrogen receptor (ER)-positive breast cancer cells which is abolished by estrogen deprivation and/or anti-estrogen treatment. The present study examined the hypothesis that ER-alpha is involved in the KGF proliferation in MCF-7 cancer cells using small interfering RNA (siRNA) to selectively inhibit ER-alpha expression. At 48 hours following ER-alpha siRNA transfection, the MCF-7 cells were treated with KGF (50 ng/ml) or vehicle for 24 hours. Cell proliferation was measured using a MTT assay. ER-alpha protein levels were quantified by Western blotting. ER-alpha siRNA transfection significantly reduced ER-alpha expression and MCF-7 cell proliferation. KGF-mediated enhancement of cell proliferation and motile cell morphology were reduced or absent in the siRNA transfected MCF-7 cells.

ER-alpha expression is associated with KGF-induced proliferation of breast cancer cells.

Is hAART neuroprophylactic in HIV-1 infection? To find out about the prophylactic value of antiretroviral therapy on HIV-1-associated subclinical and clinical psychomotor slowing as one marker of HIV-1-associated CNS disease. Prospective study with regular clinical and neurophysiologic examination every three months of 1482 consecutive HIV-1-seropositive and AIDS patients seen at our department till June 30, 1999. Antiretroviral therapy has a significant prophylactic value over an individual observation period of ten years with regard to the first, potentially transient manifestation of HIV-1-associated subclinical psychomotor slowing and with regard to the clinical manifestation of motor signs. However, a subgroup of patients is characterized through a second, more sustained manifestation of subclinical psychomotor slowing which cannot be prevented by any type of currently available antiretroviral therapy.

These findings suggest the existence of different pathomechanisms underlying HIV-1-associated brain disease which may in part be effectively prevented, but which in part also escape all antiretroviral treatment strategies in use today.

Does platelet aggregation promoted by biofilms of oral bacteria and the effect of mouth rinse in vitro? The purpose of this study was to observe platelet aggregation promoted by biofilms of Streptococcus sanguinis and Porphyromonas gingivalis and to evaluate the effect of two different mouth rinses on this process. In the first experiment, the same amount of S. sanguinis, P. gingivalis, and the S. sanguinis + P. gingivalis mixed solution was added to an equivalent amount of platelet-rich plasma (PRP). Aggregation was measured using a recording platelet aggregometer. In the second experiment, S. sanguinis, P. gingivalis, S sanguinis + P. gingivalis mixed solutions were pretreated with either Listerine antiseptic mouth rinse or Xipayi mouth rinse for 3 minutes, 6 minutes, and 10 minutes, respectively. The same amount of solution was added to the PRP, and the inhibition of aggregation was measured. In the first experiment, S. sanguinis and P. gingivalis were able to induce platelet aggregation. The aggregation rate of S. sanguinis + P. gingivalis was significantly lower than that of either S. sanguinis or P. gingivalis. In the second experiment, when S. sanguinis, P. gingivalis, and the S. sanguinis + P. gingivalis mixed solutions were pretreated with Listerine antiseptic mouth rinse for 3 minutes and Xipayi mouth rinse for 10 minutes, there was no significant platelet aggregation.

Platelets could adhere to S. sanguinis or P. gingivalis, but when S. sanguinis was mixed with P. gingivalis, the aggregation rate was reduced significantly. Treatment with Listerine antiseptic mouth rinse or Xipayi mouth rinse inhibited the ability of the bacteria to induce platelet aggregation.

Does awareness of memory impairment increase the adherence to immunosuppressants in kidney transplant recipients? Nonadherence to immunosuppressive drugs is a concern among kidney transplantation recipients (KTRs). The adverse effects of immunosuppressive drugs can trigger nonadherence and lead to a great impact on the allograft survival. The aim of this prospective controlled study is to determine the major adverse effects of immunosuppressive drugs and their correlation with the nonadherence in kidney transplantation recipients. All data were collected from medical and pharmacy records. We use modified Immunosuppressant Therapy Adherence Scale combined with Modified Transplant Symptom Occurrence and Symptom Distress scale to explore the relationship between symptom experience related to side effects of immunosuppressants and adherence. The risk of nonadherence was estimated by stepwise logistic regression while controlling for age, gender, education, and immunosuppressive medications. Multivariable analysis was performed using a single random effect of P < .2. In total, 412 KTRs completed the structured self-report instrument. The weekly pill counts were 84.2 ± 39.8. Overall, 21.4% of patients were nonadherent to immunosuppressive drugs. The most common adverse effects of immunosuppressive drugs were memory impairment (28.4%), insomnia (26.0%), gastrointestinal discomfort (21.4%), easy fatigue (22.1%), hand tremor (23.8%), and vision variation (29.1%). Multivariate analysis revealed that the adherence increased in patients with awareness of memory impairment (odds ratio 2.320, 95% confidence interval: 1.259-4.274, P = .007). There was no significant difference in the incidence of acute rejection, gender, age, and education between adherent and nonadherent patients.

In summary, these results indicate a significant prevalence of nonadherence to immunosuppressive drugs in kidney transplantation recipients. Awareness of memory impairment significantly affected adherence to immunosuppressive drugs.

Do saccadic eye movement abnormalities in autism spectrum disorder indicate dysfunctions in cerebellum and brainstem? Individuals with autism spectrum disorder (ASD) show atypical scan paths during social interaction and when viewing faces, and recent evidence suggests that they also show abnormal saccadic eye movement dynamics and accuracy when viewing less complex and non-social stimuli. Eye movements are a uniquely promising target for studies of ASD as their spatial and temporal characteristics can be measured precisely and the brain circuits supporting them are well-defined. Control of saccade metrics is supported by discrete circuits within the cerebellum and brainstem - two brain regions implicated in magnetic resonance (MR) morphometry and histopathological studies of ASD. The functional integrity of these distinct brain systems can be examined by evaluating different parameters of visually-guided saccades. A total of 65 participants with ASD and 43 healthy controls, matched on age (between 6 and 44-years-old), gender and nonverbal IQ made saccades to peripheral targets. To examine the influence of attentional processes, blocked gap and overlap trials were presented. We examined saccade latency, accuracy and dynamics, as well as the trial-to-trial variability of participants' performance. Saccades of individuals with ASD were characterized by reduced accuracy, elevated variability in accuracy across trials, and reduced peak velocity and prolonged duration. In addition, their saccades took longer to accelerate to peak velocity, with no alteration in the duration of saccade deceleration. Gap/overlap effects on saccade latencies were similar across groups, suggesting that visual orienting and attention systems are relatively spared in ASD. Age-related changes did not differ across groups.

Deficits precisely and consistently directing eye movements suggest impairment in the error-reducing function of the cerebellum in ASD. Atypical increases in the duration of movement acceleration combined with lower peak saccade velocities implicate pontine nuclei, specifically suggesting reduced excitatory activity in burst cells that drive saccades relative to inhibitory activity in omnipause cells that maintain stable fixation. Thus, our findings suggest that both cerebellar and brainstem abnormalities contribute to altered sensorimotor control in ASD.

Does genome-wide association scan in north Indians reveal three novel HLA-independent risk loci for ulcerative colitis? Over 100 ulcerative colitis (UC) loci have been identified by genome-wide association studies (GWASs) primarily in Caucasians (CEUs). Many of them have weak effects on disease susceptibility, and the bulk of the heritability cannot be ascribed to these loci. Very little is known about the genetic background of UC in non-CEU groups. Here we report the first GWAS on UC in a genetically distinct north Indian (NI) population. A genome-wide scan was performed on 700 cases and 761 controls. 18 single-nucleotide polymorphisms (SNPs) (p<5×10(-5)) were genotyped in an independent cohort of 733 cases and 1148 controls. A linear mixed model was used for case-control association tests. Seven novel human leucocyte antigen (HLA)-independent SNPs from chromosome 6, located in 3.8-1, BAT2, MSH5, HSPA1L, SLC44A4, CFB and NOTCH4, exceeded p<5×10(-8) in the combined analysis. To assess the independent biological contribution of such genes from the extended HLA region, we determined the percentage alternative pathway activity of complement factor B (CFB), the top novel hit. The activity was significantly different (p=0.01) between the different genotypes at rs12614 in UC cases. Transethnic comparisons revealed a shared contribution of a fraction of UC risk genes between NI and CEU populations, in addition to genetic heterogeneity.

This study shows varying contribution of the HLA region to UC in different populations. Different environmental exposures and the characteristic genetic structure of the HLA locus across ethnic groups collectively make it amenable to the discovery of causative alleles by transethnic resequencing. This may lead to an improved understanding of the molecular mechanisms underlying UC.

Does low junctional adhesion molecule A expression correlate with poor prognosis in gastric cancer? The aberrant expression of junctional adhesion molecule A (JAM-A), which has a close correlation with the development, progression, metastasis, and prognosis of cancer, has been frequently reported. However, neither JAM-A expression nor its correlation with clinicopathologic variables and patient survival has been defined in gastric cancers. Moreover, little is known about the role of JAM-A in gastric cancer progression. We carried out the present study to investigate the prognostic value of JAM-A expression in gastric cancer patients. Furthermore, the biological roles of JAM-A in gastric cancer progression were also investigated. We determined JAM-A expression in 167 primary gastric cancer tissues and 94 matched adjacent non-tumor tissues by immunohistochemistry. Transwell migration assays and matrigel invasion assays were used to explore the role of JAM-A in gastric cancer cells migration and invasion. CCK-8 assays were used to examine the effect of JAM-A on the proliferation of gastric cancer cells. JAM-A was downregulated in gastric cancer tissues. Low JAM-A expression was significantly associated with tumor size, lymphatic vessel invasion, lymph node metastasis, and TNM stage. Low JAM-A expression was also significantly associated with poor disease-specific survival in gastric cancer patients. Multivariate analysis demonstrated low JAM-A expression as an independent factor predicting poor survival. In addition, JAM-A had the effect on inhibition of gastric cancer cells migration and invasion. However, JAM-A had no significant effects on proliferation of gastric cancer cells.

Low JAM-A expression correlates with poor clinical outcome and promotes cell migration and invasion in gastric cancer.

Does ranitidine affect psoriasis : a multicenter , double-blind , placebo-controlled study? Data from open studies suggest that ranitidine has a beneficial effect on psoriasis and is well tolerated. Our purpose was to determine the effectiveness of ranitidine in a 24-week, multicenter, double-blind, placebo-controlled, dose-comparing study of 201 patients with psoriasis. Patients with moderate to severe psoriasis who had stopped systemic antipsoriatic therapy, including PUVA and UVB, for at least 10 weeks were included. After a washout period of 2 weeks, patients were randomly allocated to use either ranitidine, 150 mg twice a day; ranitidine, 300 mg twice a day; or placebo for up to 24 weeks. Assessment with the Psoriasis Area and Severity Index was performed at weeks 3, 6, 9, 12, 18, and 24 after randomization. Reduction of the Psoriasis Area and Severity Index score by 70% at the completion of the study was considered a treatment success. The success rates at week 24 in the 300 mg, 600 mg, and placebo groups were 11%, 5%, and 12%, respectively. No significant differences were observed between the three treatment groups at any stage of the study.

This study provides strong evidence that ranitidine does not affect the skin disease in patients with psoriasis.

Does the soluble guanylyl cyclase activator bay 58-2667 selectively limit cardiomyocyte hypertrophy? Although evidence now suggests cGMP is a negative regulator of cardiac hypertrophy, the direct consequences of the soluble guanylyl cyclase (sGC) activator BAY 58-2667 on cardiac remodeling, independent of changes in hemodynamic load, has not been investigated. In the present study, we tested the hypothesis that the NO(•)-independent sGC activator BAY 58-2667 inhibits cardiomyocyte hypertrophy in vitro. Concomitant impact of BAY 58-2667 on cardiac fibroblast proliferation, and insights into potential mechanisms of action, were also sought. Results were compared to the sGC stimulator BAY 41-2272. Neonatal rat cardiomyocytes were incubated with endothelin-1 (ET(1), 60nmol/L) in the presence and absence of BAY 41-2272 and BAY 58-2667 (0.01-0.3 µmol/L). Hypertrophic responses and its triggers, as well as cGMP signaling, were determined. The impact of both sGC ligands on basal and stimulated cardiac fibroblast proliferation in vitro was also determined. We now demonstrate that BAY 58-2667 (0.01-0.3 µmol/L) elicited concentration-dependent antihypertrophic actions, inhibiting ET(1)-mediated increases in cardiomyocyte 2D area and de novo protein synthesis, as well as suppressing ET(1)-induced cardiomyocyte superoxide generation. This was accompanied by potent increases in cardiomyocyte cGMP accumulation and activity of its downstream signal, vasodilator-stimulated phosphoprotein (VASP), without elevating cardiomyocyte cAMP. In contrast, submicromolar concentrations of BAY 58-2667 had no effect on basal or stimulated cardiac fibroblast proliferation. Indeed, only at concentrations ≥10 µmol/L was inhibition of cardiac fibrosis seen in vitro. The effects of BAY 58-2667 in both cell types were mimicked by BAY 41-2272.

Our results demonstrate that BAY 58-2667 elicits protective, cardiomyocyte-selective effects in vitro. These actions are associated with sGC activation and are evident in the absence of confounding hemodynamic factors, at low (submicromolar) concentrations. Thus this distinctive sGC ligand may potentially represent an alternative therapeutic approach for limiting myocardial hypertrophy.

Does supplementation with Pycnogenol® improves sign and symptoms of menopausal transition? The aim of this study was to evaluate the efficacy of Pycnogenol® standardized pine bark extract for alleviation of signs and symptoms associated with menopausal transition. Pycnogenol® was used by 38 women as daily supplement in a dosage of 100 mg over an eight week period and menopausal symptoms were evaluated by means of a scoring system, based on a total number of 33 common signs and symptoms. A parallel control group of 32 comparable women was also followed up for the same period. Pycnogenol® was well tolerated, no side effects were reported and the compliance was very good with 98.6% of tablets used as prescribed. A range of 33 menopausal symptoms were evaluated using a scoring system with values ranging from zero (absent) to maximum 4 (very serious). A subset of six most common symptoms comprising hot flushes, night sweats, mood swings, irregular periods, loss of libido and vaginal dryness showed a decrease from average 2.67/4 to 1.45/4 after 8 weeks supplementation with Pycnogenol®. The control group of women showed no change from initial average 2.72/4 to 2.73/4 after eight weeks. The improvement of symptoms was statistical significant compared to the control group. Further symptoms related to fatigue, sleeping disorders, concentration and memory problems, dizziness, depression and irritability all improved significantly with Pycnogenol® compared to baseline values but did not reach statistical significance compared to the control group of women. The sensation of pain related to headaches, breast pain, the feeling of "electric shocks", tingling extremities, burning tongue and itchy skin all improved significantly after intake of Pycnogenol® for eight weeks compared to baseline. Specifically the sensation of "electric shocks" and digestive problems improved significantly with Pycnogenol® as compared to women in the control group. The presence of elevated oxidative stress in women was investigated measuring capillary blood plasma free radicals. Oxidative stress was significantly lowered after four weeks (P<0.05) and eight weeks (P<0.022) in the Pycnogenol® group while no significant changes were observed in the control group at any time.

Pycnogenol® significantly contributed to reduce signs and symptoms associated with menopausal transitions in women investigated in this study. Furthermore, Pycnogenol® improved the quality of life of most women and these benefits may be at least in part attributed to decreased oxidative stress levels.

Is bronchial hyperresponsiveness a common feature in patients with chronic urticaria? Chronic urticaria (CU) is a skin disorder characterized by long-lasting release of histamine, and sometimes leukotrienes, from both mast cells and basophils. Although both these substances are potent inductors of contraction of airway smooth muscle, pulmonary function and airway hyperresponsiveness have not been systematically investigated in patients with CU. To assess pulmonary function and airway hyperresponsiveness in patients with CU. Twenty-six clinically well-characterized adult patients with CU (M/F 8/18; mean age 47 years) underwent pulmonary function tests and methacholine provocation during a phase of moderate activity of their disease. Twenty-six adult asthmatic patients submitted to methacholine provocation were used as controls. Two patients (8%) had overt asthma on baseline pulmonary function tests. Twenty (77%) patients with a normal baseline pulmonary function showed significant bronchial hyperresponsiveness on methacholine provocation. Altogether, 22/26 (85%) patients had asthma or abnormal bronchial reactivity. Airway hyperresponsiveness was not associated with gender, disease duration, intolerance to NSAID, positive autologous serum skin test or respiratory allergy. On average, asthmatic controls showed a much severer airway hyperresponsiveness than urticaria patients (p < 0.01).

Patients with CU frequently show bronchial hyperresponsiveness. Prospective studies are needed to assess whether they are at risk for bronchial asthma.

Do differentiation of calcification from chronic hemorrhage with corrected gradient echo phase imaging? The purpose of the current study was to prospectively evaluate the role of corrected gradient echo phase imaging in differentiation of calcified granuloma from chronic hemorrhage. Eighty-five patients with single/multiple calcifications and hemorrhages irrespective of their location were studied with corrected gradient echo phase imaging. In all the cases, CT was used as the gold standard for the presence/absence of calcification. All calcified lesions showed positive phase, whereas chronic hemorrhages showed negative phase in all cases. Five calcified lesions showed no phase shift at TE =15 ms and positive shift at TE = 35 ms. Heterogeneous phase shift was observed in three calcified lesions at TE = 35 ms; all three lesions showed positive phase shift at TE = 15 ms. There was no site-specific problem in differentiation of calcification from chronic hemorrhage including in the basal ganglia.

We conclude that calcified granuloma can be easily differentiated from chronic hemorrhage with corrected gradient echo phase imaging, which may obviate the need for CT for its confirmation.

Does prior meal enhance the plasma glucose lowering effect of exercise in type 2 diabetes? To compare the changes in plasma glucose and insulin levels in response to 1 h of exercise performed at 60% of VO(2peak) either in the fasted state or 2 h after a standardized breakfast in subjects with type 2 diabetes. Ten sedentary men with type 2 diabetes treated with oral agents and not under strict metabolic control were tested on two occasions (fasted and fed state) in a random order at a 1-wk interval. Plasma glucose was slightly but not significantly higher at the beginning of exercise performed in the fed state versus the fasted state (12.4 +/- 1.3 vs 11.1 +/- 1.1 mmol x L(-1) respectively; mean +/- SE, P = 0.06). However, after exercise, plasma glucose levels were much lower in the fed state (7.6 +/- 1.1 mmol x L(-1)) compared with the fasted state (10.0 +/- 1.0 mmol x L(-1); P = 0.009). Insulin levels were higher at the beginning of the exercise bout performed in the fed state (177 +/- 26 vs 108 +/- 19 pmol x L(-1); P < 0.05) and during exercise. Similar respiratory exchange ratio at identical workload indicated that the difference in glycemic response was not due to differences in whole body substrate utilization. Plasma concentrations of free fatty acids, glucagon, epinephrine, and norepinephrine were also similar during both experiments.

One hour of aerobic exercise has a minimal impact on plasma glucose level when performed in fasted moderately hyperglycemic men with type 2 diabetes but induces an important decrease in plasma glucose level when performed 2 h after breakfast. Because glucose utilization increased similarly during exercise in both conditions, the higher insulin levels after the meal might have blunted glucose production, creating an imbalance between total glucose production and total peripheral utilization in the fed state in contrast to the fasted state.

Is aF10-dependent transcription enhanced by its interaction with FLRG? FLRG (follistatin-related gene) is a secreted glycoprotein which is very similar to follistatin. As observed for follistatin, FLRG is involved in the regulation of various biological processes through its binding to members of the TGFbeta (transforming growth factor beta) superfamily, activin, BMPs (bone morphogenetic proteins) and myostatin. Unlike follistatin, FLRG has been found to be both secreted and localized within the nucleus of many FLRG-producing cells, suggesting the existence of specific intracellular functions of the protein. In order to analyse the function of the nuclear form of FLRG, we performed a yeast two-hybrid screen, in which we identified AF10 [ALL1 (acute lymphoblastic leukaemia) fused gene from chromosome 10], a translocation partner of the MLL (mixed-lineage leukaemia) oncogene in human leukaemia, as a FLRG-interacting protein. This interaction was confirmed by far-Western-blot analysis and co-immunoprecipitation with transfected COS-7 cells. The N-terminal region of AF10, including the PHD (plant homeodomain), is sufficient to mediate this interaction, and has been shown to be involved in AF10 homo-oligomerization. By immunoprecipitation experiments, we showed that FLRG enhances the homo-oligomerization of AF10. Functional studies demonstrated that FLRG enhances the transactivation properties of the AF10 protein fused to Gal4 DNA-binding domains in transient transfection assays.

Our present study provides novel insights into the function of the nuclear form of the FLRG protein, which is revealed as a novel regulator of transcription. The nuclear isoform of FLRG lacks an intrinsic transactivation domain, but enhances AF10-mediated transcription, probably through promoting the homo-oligomerization of AF10, thus facilitating the recruitment of co-activators.

Does plasma oxidized low density lipoprotein cholesterol correlate inversely with testosterone in young adult male smokers? There are indications that oxidized low density lipoprotein cholesterol (Ox-LDLC) may play an important role in cardiovascular disease (CVD) events. In most developing countries, the interplay between the different lipid fractions and cigarette smoking has not been studied. This study assessed the effect of cigarette smoking on the alterations in plasma lipid fractions and their associations with the gonadal hormone, testosterone (T). One hundred and sixty male participants, consisting of eighty smokers and eighty apparently healthy non-smokers were recruited. Anthropometric indices and biochemical parameters were determined using standard procedures. Significant increases were obtained in plasma total cholesterol (TC), triglyceride (TG), oxidized low density lipoprotein (Ox-LDLC) and Ox-LDLC/TT ratio (p<0.001) in smokers compared with the non-smokers. Plasma high density cholesterol (HDLC) (p<0.001) was significantly reduced in smokers compared with the non-smokers. The plasma mean T result was not significantly different from the non-smokers, but inversely correlated with Ox-LDLC and significantly correlated with the lipids and lipoproteins. Significantly high plasma TC, TG and LDLC (p<0.001) and low HDLC (p<0.001) were also obtained in smokers when co-founding factors such as duration and number of cigarette smoked per day were applied.

This study showed an inverse correlation between Ox-LDLC and testosterone as well as strong association between the number of tobacco and cigarettes usage per day. These changes in part, could be major causes of premature CVD and decreased fertility in young adults.

Does zinc deficiency lead to lipofuscin accumulation in the retinal pigment epithelium of pigmented rats? Age-related macular degeneration (AMD) is associated with lipofuscin accumulation whereas the content of melanosomes decreases. Melanosomes are the main storage of zinc in the pigmented tissues. Since the elderly population, as the most affected group for AMD, is prone to zinc deficit, we investigated the chemical and ultrastructural effects of zinc deficiency in pigmented rat eyes after a six-month zinc penury diet. Adult Long Evans (LE) rats were investigated. The control animals were fed with a normal alimentation whereas the zinc-deficiency rats (ZD-LE) were fed with a zinc deficient diet for six months. Quantitative Energy Dispersive X-ray (EDX) microanalysis yielded the zinc mole fractions of melanosomes in the retinal pigment epithelium (RPE). The lateral resolution of the analysis was 100 nm. The zinc mole fractions of melanosomes were significantly smaller in the RPE of ZD-LE rats as compared to the LE control rats. Light, fluorescence and electron microscopy, as well as immunohistochemistry were performed. The numbers of lipofuscin granules in the RPE and of infiltrated cells (Ø>3 µm) found in the choroid were quantified. The number of lipofuscin granules significantly increased in ZD-LE as compared to control rats. Infiltrated cells bigger than 3 µm were only detected in the choroid of ZD-LE animals. Moreover, the thickness of the Bruch's membrane of ZD-LE rats varied between 0.4-3 µm and thin, rangy ED1 positive macrophages were found attached at these sites of Bruch's membrane or even inside it.

In pigmented rats, zinc deficiency yielded an accumulation of lipofuscin in the RPE and of large pigmented macrophages in the choroids as well as the appearance of thin, rangy macrophages at Bruch's membrane. Moreover, we showed that a zinc diet reduced the zinc mole fraction of melanosomes in the RPE and modulated the thickness of the Bruch's membrane.

Is ectopic expression of CXCL13 , BAFF , APRIL and LT-β associated with artery tertiary lymphoid organs in giant cell arteritis? To investigate whether artery tertiary lymphoid organs (ATLOs) are present in giant cell arteritis (GCA) and that their formation is associated with the ectopic expression of constitutive lymphoid tissue-homing chemokines. Reverse transcriptase PCR, immunohistochemical and immunofluorescence analysis were used to determine the presence of ectopic ATLOs in GCA and the expression of chemokines/chemokine receptors and cytokines involved in lymphoneogenesis in the temporal artery samples obtained from 50 patients with GCA and 30 controls. The presence of lymphatic conduits, of follicular dendritic cells (FDCs) precursors and lymphoid tissue inducer cells was also investigated. Finally, expression of CXCL13, B cell activating factor (BAFF), a proliferation-inducing ligand (APRIL) and CCL21 by isolated myofibroblasts was evaluated before and after stimulation with Toll-like receptors (TLRs) agonists and cytokines. ATLOs were observed in the media layer of 60% of patients with GCA in close proximity to high endothelial venules and independently by the age of patients and the presence of atherosclerosis. ATLO formation was also accompanied by the expression of CXCL13, BAFF, a proliferation-inducing ligand (APRIL), lymphotoxin (LT)-β, interleukin (IL)-17 and IL-7, the presence of FDC precursors and of lymphoid conduits. Stimulation of myofibroblasts with TLR agonists and cytokines resulted in the upregulation of BAFF and CXCL13.

ATLOs occur in the inflamed arteries of patients with GCA possibly representing the immune sites where immune responses towards unknown arterial wall-derived antigens may be organised.

Does serum sodium based modification of the MELD improve prediction of outcome in acute liver failure? Acute liver failure (ALF) is a devastating clinical syndrome with a high mortality rate. The MELD score has been implied as a prognostic tool in ALF. Hyponatremia is associated with lethal outcome in ALF. Inclusion of serum sodium (Na) into the MELD score was found to improve its predictive value in cirrhotic patients. Therefore the aim of this study was to determine whether inclusion of serum Na improves the predictive value of MELD in ALF compared to established criteria. In a prospective single center study (11/2006-12/2010), we recruited 108 consecutive ALF patients (64% females / 36% males), who met the criteria defined by the "Acute Liver Failure Study Group Germany". Upon admission, clinical and laboratory data were collected, King's College Criteria (KCC), Model of End Stage Liver Disease score (MELD), and serum sodium based modifications like the MELD-Na score and the United Kingdom Model of End Stage Liver Disease score (UKELD) were calculated and area under the receiver operating characteristic curve analyses were performed regarding the prediction of spontaneous recovery (SR) or non-spontaneous recovery (NSR; death or transplantation). Serum bilirubin was of no prognostic value in ALF, and Na also failed to predict NSR in ALF. The classical MELD score was superior to sodium-based modifications and KCC.

We validated the prognostic value of MELD-Na and UKELD in ALF. Classic MELD score calculations performed superior to KCC in the prediction of NSR. Serum Na and Na-based modifications of MELD did not further improve its prognostic value.

Does genomic Integrity be Favourably Affected by High-Intensity Interval Training in an Animal Model of Early-Stage Chronic Kidney Disease? Chronic kidney disease (CKD) is an irreversible disease that diminishes length and quality of life. Emerging evidence suggests CKD progression and genomic integrity are inversely and causally related. To reduce health complications related to CKD progression, chronic aerobic exercise is often recommended. To date, appraisals of differing modes of exercise, along with postulations regarding the mechanisms responsible for observed effects, are lacking. In order to examine the ability of aerobic exercise to encourage improvements in genomic integrity, we evaluated the effects of 8 weeks of high-intensity interval training (HIIT; 85 % VO To assess genomic integrity, we examined kidney-specific messenger RNA (mRNA) expression of genes related to genomic repair and stability: Fan1, Mre11a, and telomere length as measured by T/S ratio. Following HIIT, mRNA expression of Fan1 was significantly up-regulated, compared to SED (p = 0.026) and T/S ratio was significantly increased, compared to SED (p < 0.001) and LIT (p = 0.002).

Our results suggest that HIIT is superior to SED and LIT as HIIT beneficially influenced the expression of genes related to genomic integrity.

Is chitotriosidase a biomarker for the resistance to World Trade Center lung injury in New York City firefighters? World Trade Center (WTC) exposure caused airflow obstruction years after exposure. Chitinases and IgE are innate and humoral mediators of obstructive airway disease. We investigated if serum expression of chitinases and IgE early after WTC exposure predicts subsequent obstruction. With a nested case-control design, 251 FDNY personnel had chitotriosidase, YKL-40 and IgE measured in serum drawn within months of 9/11/2001. The main outcome was subsequent Forced Expiratory Volume after 1 second/Forced Vital Capacity (FEV1/FVC) less than the lower limit of normal (LLN). Cases (N = 125) had abnormal FEV1/FVC whereas controls had normal FEV1/FVC (N = 126). In a secondary analysis, resistant cases (N = 66) had FEV1 (≥107%) one standard deviation above the mean. Logistic regression adjusted for age, BMI, exposure intensity and post-exposure FEV1/FVC modeled the association between early biomarkers and later lung function. Cases and Controls initially lost lung function. Controls recovered to pre-9/11 FEV1 and FVC while cases continue to decline. Cases expressed lower serum chitotriosidase and higher IgE levels. Increase in IgE increased the odds of airflow obstruction and decreased the odds of above average FEV1. Alternately, increasing chitotriosidase decreased the odds of abnormal FEV1/FVC and increased the odds of FEV1 ≥ 107%. Serum YKL-40 was not associated with FEV1/FVC or FEV1 in this cohort.

Increased serum chitotriosidase reduces the odds of developing obstruction after WTC-particulate matter exposure and is associated with recovery of lung function. Alternately, elevated IgE is a risk factor for airflow obstruction and progressive lung function decline.

Is less expression of prohibitin associated with increased caspase-3 expression and cell apoptosis in renal interstitial fibrosis rats? Prohibitin (PHB), a ubiquitous protein, is involved in a variety of molecular functions. Renal interstitial fibrosis (RIF) is a hallmark of common progressive chronic diseases that lead to renal failure. This study was performed to investigate whether PHB was associated with caspase-3 expression/cell apoptosis in RIF rats. Twenty-four male Wistar rats were randomly divided into two groups: sham operation group (SHO) and model group subjected to unilateral ureteral obstruction (GU), n = 12, respectively. The model was established by left ureteral ligation. Renal tissues were collected at 14 days and 28 days after surgery. RIF index, cell apoptosis index, protein expression of PHB, transforming growth factor-βl (TGF-β1), collagen-IV (Col-IV), fibronectin (FN) or caspase-3 in renal interstitium, and mRNA expression of PHB in renal tissue were detected. Compared with that in the SHO group, the PHB expression (mRNA and protein) was significantly reduced (P < 0.01). Protein expressions of TGF-β1, Col-IV, FN and caspase-3, and RIF index or cell apoptosis index in GU group were markedly elevated compared with those in SHO group (all P < 0.01). The protein expression of PHB had a negative correlation with the protein expression of TGF-β1, Col-IV, FN or caspase-3, and RIF index or cell apoptosis index (each P < 0.01).

Less expression of PHB is associated with increased caspase-3 expression/cell apoptosis in RIF rats. However, further research is needed to determine the effect of PHB on caspase-3 expression/cell apoptosis and to determine the potential of PHB as a therapeutic target.

Is anemia an independent predictor of mortality after percutaneous coronary intervention? The aim of the present study was to assess whether anemia is a marker of increased risk during interventional procedure and poor midterm survival after percutaneous coronary intervention (PCI). Anemia is associated with increased risk of mortality in patients with heart failure and myocardial infarction (MI). We examined the outcomes of 6,116 consecutive PCI patients based on the hemoglobin (Hb) value before the interventional procedure. Patients were divided into three groups based on the baseline Hb level (g/l): Hb <10 = severe anemia; Hb 10 to 12 = mild anemia; Hb >12 = no anemia. The presence of anemia is associated with higher 30-day major adverse cardiac events, post-PCI peak troponin and creatine kinase-MB fraction, and a longer length of stay. After controlling for multiple covariates, significant difference in one-year survival was noted in the anemic groups compared with no anemia group (adjusted hazard ratio for Hb 10 to 12: 1.5 [95% confidence interval 1.3 to 1.8]; for Hb <10: 1.8 [95% confidence interval 1.3 to 2.3]; p = 0.004.) This adverse effect of anemia on survival was noted in all three presenting clinical syndromes (stable angina, unstable angina, and MI).

Anemia is an independent predictor of mortality after PCI and is associated with higher short-term adverse procedural events.

Is pachydermia diagnostic of active laryngopharyngeal reflux disease? To determine the change in pachydermia/posterior commissure hypertrophy in patients with laryngopharyngeal reflux disease (LPR) on long-term acid-suppressive therapy. Retrospective chart review. Seventeen patients with LPR who were compliant with long-term acid-suppressive treatment and had good control of their symptoms for at least 20 months were examined. Pre- and posttreatment still laryngeal images from these patients were analyzed by five otolaryngologists blinded to patient information and were scored for pachydermia/posterior commissure hypertrophy according to the Reflux Finding Score (RFS) subset. Test-retest intraobserver reliability, intergrader correlations, as well as a paired t test for means of the data sets were then calculated. There was no significant difference in the grading scores between the pre- and posttreatment group for degree of pachydermia/posterior commissure hypertrophy despite a prolonged treatment interval (mean = 32 months) (P = .25).

There is no statistically significant difference in the degree of pachydermia/posterior commissure hypertrophy found at diagnosis and after long-term acid suppressive therapy in patients with LPR. Therefore, it appears that pachydermia, as an isolated finding, is unreliable in determining the presence of active LPR.

Do synthetic complementary peptides inhibit a neutrophil chemoattractant found in the alkali-injured cornea? We have previously presented evidence that the neutrophil chemoattractant, N-acetyl-proline-glycine-proline (N-acetyl-PGP), triggers the initial polymorphonuclear leukocyte (PMN) invasion into the alkali-injured eye. In this study, sense-antisense methodology was used to develop novel complementary peptides to be potential inhibitors of N-acetyl-PGP. The polarization assay was used to measure the potential chemotactic response of PMNs to synthetic N-acetyl-PGP, the ultrafiltered tripeptide chemoattractants obtained from alkali-degraded rabbit corneas, or leukotriene B4 (LTB4). Inhibition was expressed as the peptide concentration producing 50% inhibition (ID50) of polarization. Five complementary peptides were tested as potential inhibitors of N-acetyl-PGP: arginine-threonine-arginine (RTR), RTR-glycine-glycine (RTRGG), RTR dimer, RTR tetramer, and alanine-serine-alanine (ASA) tetramer. In addition, the RTR tetramer and both monomeric peptides (RTR and RTRGG) were separately tested for inhibition of the ultrafiltered tripeptide chemoattractants or LTB4. The complementary RTR tetrameric peptide was a powerful antagonist of N-acetyl-PGP-induced PMN polarization (ID50 of 200 nM). The RTR dimer was much less potent (ID50 of 105 microM). Both monomeric peptides, RTR and RTRGG, were only antagonistic at millimolar concentrations. The ASA tetramer showed no capacity to inhibit N-acetyl-PGP. The RTR tetramer also inhibited PMN activation by the ultrafiltered tripeptide chemoattractants (ID50 of 30 microM) but had no effect on LTB4.

A complementary peptide (RTR) was designed which is an effective inhibitor of the neutrophil chemoattractant, N-acetyl-PGP. The potency of the RTR complementary peptide is dramatically enhanced by tetramerization. Inhibition of N-acetyl-PGP by complementary peptides offers great promise for control of the inflammatory response in the alkali-injured eye.

Do multiple polymorphisms affect expression and function of the neuropeptide S receptor ( NPSR1 )? neuropeptide S (NPS) and its receptor NPSR1 act along the hypothalamic-pituitary-adrenal axis to modulate anxiety, fear responses, nociception and inflammation. The importance of the NPS-NPSR1 signaling pathway is highlighted by the observation that, in humans, NPSR1 polymorphism associates with asthma, inflammatory bowel disease, rheumatoid arthritis, panic disorders, and intermediate phenotypes of functional gastrointestinal disorders. Because of the genetic complexity at the NPSR1 locus, however, true causative variations remain to be identified, together with their specific effects on receptor expression or function. To gain insight into the mechanisms leading to NPSR1 disease-predisposing effects, we performed a thorough functional characterization of all NPSR1 promoter and coding SNPs commonly occurring in Caucasians (minor allele frequency >0.02). we identified one promoter SNP (rs2530547 [-103]) that significantly affects luciferase expression in gene reporter assays and NPSR1 mRNA levels in human leukocytes. We also detected quantitative differences in NPS-induced genome-wide transcriptional profiles and CRE-dependent luciferase activities associated with three NPSR1 non-synonymous SNPs (rs324981 [Ile107Asn], rs34705969 [Cys197Phe], rs727162 [Arg241Ser]), with a coding variant exhibiting a loss-of-function phenotype (197Phe). Potential mechanistic explanations were sought with molecular modelling and bioinformatics, and a pilot study of 2230 IBD cases and controls provided initial support to the hypothesis that different cis-combinations of these functional SNPs variably affect disease risk.

these findings represent a first step to decipher NPSR1 locus complexity and its impact on several human conditions NPS antagonists have been recently described, and our results are of potential pharmacogenetic relevance.

Is glucose but not insulin or insulin resistance associated with memory performance in middle-aged non-diabetic women : a cross sectional study? Elevated concentrations of plasma glucose appear to play a role in memory impairment, and it has been suggested that insulin might also have a negative effect on cognitive function. Our aim was to study whether glucose, insulin or insulin resistance are associated with episodic or semantic memory in a non-diabetic and non-demented population. We linked and matched two population-based data sets identifying 291 participants (127 men and 164 women, mean age of 50.7 ± 8.0 years). Episodic and semantic memory functions were tested, and fasting plasma insulin, fasting plasma glucose, and 2-hour glucose were analysed along with other potential influencing factors on memory function. Since men and women display different results on memory functions they were analysed separately. Insulin resistance was calculated using the HOMA-IR method. A higher fasting plasma glucose concentration was associated with lower episodic memory in women (r = -0.08, 95% CI -0.14; -0.01), but not in men. Plasma insulin levels and insulin resistance were not associated with episodic or semantic memory in women or in men after adjustments for age, fasting glucose, 2-hour glucose, BMI, education, smoking, cardiovascular disease, hypertension, cholesterol, and physical activity.

This indicates that fasting glucose but not insulin, might have impact on episodic memory in middle-aged women.

Does remote ischemic pre-conditioning alleviate contrast-induced acute kidney injury in patients with moderate chronic kidney disease? Although remote ischemic preconditioning (RIPC) is shown to preserve kidney function in patients at high risk of contrast-induced acute kidney injury (CI-AKI), the effect in patients at low-moderate risk remains unknown. The preventive effects of RIPC in patients not at high risk of CI-AKI were examined, and biomarkers with anticipated roles in renal protection via RIPC investigated. Sixty patients who had moderate chronic kidney disease and who underwent angiography were randomly assigned to the control (n=30) or RIPC (intermittent arm ischemia, n=30) group. The baseline characteristics in the 2 groups did not differ significantly. CI-AKI was evaluated by measuring urinary liver-type fatty acid-binding protein (L-FABP). Biomarkers were measured before and 24 and 48 h after angiography. Twenty-four hours after angiography, the percent change in urinary L-FABP level in the RIPC group was significantly smaller than in the control group (41.3±15.6 vs. 159±34.1%, P=0.003). L-FABP-based CI-AKI developed in 8 control patients (26.9%) vs. only 2 patients in the RIPC group (7.7%), suggesting that RIPC prevents CI-AKI. Factors contributing to CI-AKI were analyzed. Neither high-sensitivity C-reactive protein nor pentraxine-3 level differed significantly between the 2 groups, while the percent change in asymmetrical dimethy larginine (ADMA) level and blood derivatives of reactive oxidative metabolite levels were significantly smaller in the RIPC group.

RIPC alleviates CI-AKI in patients at low-moderate risk. This effect might be mediated partly by decreasing oxidative stress and plasma ADMA level.

Is the Asp727Glu polymorphism in the TSH receptor associated with insulin resistance in healthy elderly men? Variations in thyroid function within the normal range are associated with differences in metabolism and body composition. For instance, TSH is positively associated with body mass index (BMI). This could be due to alterations in thyroid hormone activity, or to direct effects of TSH, as the TSH receptor (TSHR) is also expressed in adipose tissue. The TSHR-Asp727Glu polymorphism is associated with lower serum TSH levels in vivo. In this study, we analysed whether serum thyroid parameters and the TSHR-Asp727Glu polymorphism were associated with glucose metabolism and insulin resistance. In addition, we analysed the Thr92Ala polymorphism in the type 2 deiodinase (D2), which was recently associated with insulin resistance. Genotypes were determined in a population of 349 elderly men (age 77.7 +/- 3.5 years), for whom serum thyroid parameters and data on insulin resistance, such as fasting blood glucose, serum insulin and homeostasis model assessment (HOMA) values, were available. In nondiabetic, euthyroid subjects, TSH was positively associated with leptin levels, whereas FT4 and rT3 were significantly negatively correlated with insulin and HOMA. Carriers of the TSHR-Glu727 allele had a significantly higher glucose (P = 0.01), insulin (P = 0.001), glycated haemoglobin (HbA1c) (P = 0.002), HOMA (P = 0.001) and leptin (P = 0.008). The D2-Ala(92) allele showed a trend towards higher levels of insulin (P = 0.07) and a higher HOMA (P = 0.09).

In this population of nondiabetic elderly men, serum thyroid parameters and the TSHR-Asp727Glu polymorphism were associated with relative insulin resistance. Our study suggests that genetic variation in TSHR plays a role in insulin resistance and thereby influences glucose metabolism.

Does intraoperative recruitment maneuver reverse detrimental pneumoperitoneum-induced respiratory effects in healthy weight and obese patients undergoing laparoscopy? Pulmonary function is impaired during pneumoperitoneum mainly as a result of atelectasis formation. We studied the effects of 10 cm H2O of positive end-expiratory pressure (PEEP) and PEEP followed by a recruitment maneuver (PEEP+RM) on end-expiratory lung volume (EELV), oxygenation and respiratory mechanics in patients undergoing laparoscopic surgery. Sixty consecutive adult patients (30 obese, 30 healthy weight) in reverse Trendelenburg position were prospectively studied. EELV, static elastance of the respiratory system, dead space, and gas exchange were measured before and after pneumoperitoneum insufflation with zero end-expiratory pressure, with PEEP alone, and with PEEP+RM. Results are presented as mean ± SD. Pneumoperitoneum reduced EELV (healthy weight, 1195 ± 405 vs. 1724 ± 774 ml; obese, 751 ± 258 vs. 886 ± 284 ml) and worsened static elastance and dead space in both groups (in all P < 0.01 vs. zero-end expiratory pressure before pneumoperitoneum) whereas oxygenation was unaffected. PEEP increased EELV (healthy weight, 570 ml, P < 0.01; obese, 364 ml, P < 0.01) with no effect on oxygenation. Compared with PEEP alone, EELV and static elastance were further improved after RM in both groups (P < 0.05), as was oxygenation (P < 0.01). In all patients, RM-induced change in EELV was 16% (P = 0.04). These improvements were maintained 30 min after RM. RM-induced changes in EELV correlated with change in oxygenation (r = 0.42, P < 0.01).

RM combined with 10 cm H2O of PEEP improved EELV, respiratory mechanics, and oxygenation during pneumoperitoneum whereas PEEP alone did not.

Is 0.03 % Tacrolimus ointment applied once or twice daily more efficacious than 1 % hydrocortisone acetate in children with moderate to severe atopic dermatitis : results of a randomized double-blind controlled trial? Topical corticosteroids are the usual treatment for atopic dermatitis (AD) in children but can have side-effects. This study compared the efficacy and safety of 0.03% tacrolimus ointment applied once or twice daily over a 3-week period with the twice daily application of 1% hydrocortisone acetate (HA) ointment in children with moderate to severe AD. Patients applied ointment daily to all affected body surface areas. The primary study endpoint was the percentage change in the modified Eczema Area and Severity Index (mEASI) between baseline and treatment end. Six hundred and twenty-four patients, aged 2-15 years, applied 0.03% tacrolimus ointment once daily (n = 207), twice daily (n = 210) or 1% HA twice daily (n = 207). By the end of treatment, application of 0.03% tacrolimus ointment both once or twice daily resulted in significantly greater median percentage decreases in mEASI (66.7% and 76.7%, respectively) compared with 1% HA (47.6%; P < 0.001). Furthermore, the median percentage decrease in mEASI was significantly greater for patients applying 0.03% tacrolimus twice daily compared with once daily (P = 0.007). Patients with severe AD benefited especially from twice daily application of 0.03% tacrolimus ointment compared with once daily application (P = 0.001). Transient mild to moderate skin burning occurred significantly more often in the 0.03% tacrolimus groups (P = 0.028) but resolved in most cases within 3-4 days. Laboratory parameters showed no clinically relevant changes.

0.03% tacrolimus ointment applied once or twice daily is significantly more efficacious than 1% HA in treating moderate-severe AD in children. Twice daily application of 0.03% tacrolimus ointment results in the greatest improvement in mEASI, and is especially effective in patients with severe baseline disease.

Does cyclooxygenase-2 promote hepatocellular apoptosis by interacting with TNF-α and IL-6 in the pathogenesis of nonalcoholic steatohepatitis in rats? The underlying mechanisms of nonalcoholic steatohepatitis (NASH) are poorly understood, and little is known about hepatocellular apoptosis in NASH. Cyclooxygenase (COX)-2, the key enzyme in eicosanoid metabolism, is highly expressed in NASH. COX-2 can also regulate the release of mediators of inflammation, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6. The aim of our study was to evaluate the effects of COX-2 on hepatocellular apoptosis and the mechanism of the action in the pathogenesis of NASH in rats. Sprague-Dawley rats were fed a high-fat diet (HFD) or standard diet for 8 and 12 weeks. COX-2 and cytokines expression in hepatic tissue and TNF-α and IL-6 levels in serum were measured at 8 and 12 weeks. Moreover, celecoxib (10 mg/kg body weight once a day) was administered to rats for 4 weeks to inhibit the expression of COX-2. Liver pathology was assessed by hematoxylin and eosin (H&E) stain and electron microscopy. Hepatocyte apoptosis was evaluated by TUNEL staining. COX-2 messenger RNA and protein were highly expressed in livers of HFD rats and were correlated with the severity of steatohepatitis (R = 0.82, p < 0.01). COX-2 upregulation was preceded by increases in TNF-α and IL-6. The level of hepatocellular apoptosis was significantly higher in HFD rats than in the control rats. The hepatocellular apoptosis was suppressed by the inhibition of COX-2.

COX-2 may promote hepatocellular apoptosis by interacting with TNF-α and IL-6 in NASH in rats.

Do urine neutrophil gelatinase-associated lipocalin and interleukin-18 predict acute kidney injury after cardiac surgery? About 30-50% patients develop acute kidney injury (AKI) after cardiac surgery, which is still diagnosed by serum creatinine on clinic. However, the increase of serum creatinine is insensitive and delayed. The aim of this study is to test the hypothesis that neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) are early biomarkers for AKI in patients after cardiac surgery. Thirty-three cases undergoing cardiac surgery were classified into an AKI group and non-AKI group, according to the AKI definition (> 26.5 micromol/L increase of serum creatinine, more than or equal to 50% increase of serum creatinine within 48 h, or a reduction in urine output < 0.5 mL/Kg per hour for more than six hours). The concentrations of serum NGAL, urine NGAL, and urine IL-18 at different time-points were measured. Nine cases (27.27%) developed postoperative AKI, but diagnosis with serum creatinine was 12-48 h postoperation. The concentrations of serum NGAL were not significantly increased postoperation. The concentrations of urine NGAL and IL-18 were significantly increased in the AKI group, which reached the peak at 2-4 h postoperation, and a more significant difference could be seen after correction for urine creatinine. The concentrations of urine NGAL and IL-18 2 h postoperation, either corrected for urine creatinine or not, showed good sensitivity and specificity. Increased levels of urine NGAL and IL-18 2 h postoperation were significantly correlated with increased level of serum creatinine 12 h postoperation. Logistic regression analysis showed that urine NGAL corrected for urine creatinine 2 h postoperation and urine IL-18 2 h postoperation emerged as powerful independent predictors of AKI after cardiac surgery.

The concentrations of urine NGAL and IL-18 could be useful biomarkers for AKI in patients after cardiac surgery, especially after correction for urine creatinine.

Do changes in activated T cells in the blood correlate with disease activity in multiple sclerosis? To determine whether changes in activation markers on peripheral blood T cells correlate with disease activity in patients with multiple sclerosis. In a prospective longitudinal study during 1 year, we analyzed the change in percentage of activated T lymphocytes in the peripheral blood of 40 patients with multiple sclerosis in relation to clinical findings and changes on brain magnetic resonance imaging (MRI) scans. The patients underwent repeated imaging of the brain (mean number of MRIs for each patient, 22) at the time blood samples were obtained as well as at monthly neurological examinations, and at the time of scoring on the Kurtzke Expanded Disability Status Scale (EDSS) and ambulation index scale. A change in the percentage of cells expressing the activation markers interleukin 2 receptor (CD25), class II major histocompatibility complex (MHC) (I3) or surface dipeptidyl peptidase (CD26) correlated significantly with a change in lesion volume or a change in number of gadolinium-enhancing lesions as detected on MRI. Changes in CD25( +) cells and in CD4(+) cells expressing class II MHC also correlated with changes in disability as measured by EDSS in patients with relapsing-remitting disease, and changes in CD4(+)CD25(+) cells correlated with the occurrence of attacks in patients with relapsing-remitting disease. These correlations are dependent on measurement of changes between time points sampled at 1- or 2-week intervals.

There is a linkage between peripheral T-lymphocyte activation as measured by cell surface markers and disease activity in patients with multiple sclerosis. Arch Neurol. 2000;57:1183-1189

Is ischemic stroke subtype associated with outcome in thrombolyzed patients? The impact of ischemic stroke subtype on clinical outcome in patients treated with intravenous tissue-type plasminogen activator (IV-tPA) is sparsely examined. We studied the association between stroke subtype and clinical outcome in magnetic resonance imaging (MRI)-evaluated patients treated with IV-tPA. We conducted a single-center retrospective analysis of MRI-selected stroke patients treated with IV-tPA between 2004 and 2010. The Trial of ORG 10172 in Acute Stroke Treatment criteria were used to establish the stroke subtype by 3 months. The outcomes of interest were a 3-month modified Rankin Scale score of 0-1 (favorable outcome), and early neurological improvement defined as complete remission of neurological deficit or improvement of ≥4 on the National Institute of Health Stroke Scale at 24 h. The outcomes among stroke subtypes were compared with multivariable logistic regression. Among 557 patients, 202 (36%) had large vessel disease (LVD), 153 (27%) cardioembolic stroke (CE), 109 (20%) small vessel disease, and 93 (17%) were of other or undetermined etiology. Early neurological improvement was present in 313 (56.4%) patients, and 361 (64.8%) patients achieved a favorable outcome. Early neurological improvement and favorable outcome were more likely in CE patients compared with LVD patients (odds ratio (OR), 2.1 (95% confidence interval, 1.4-3.3), and 2.0 (95% confidence interval, 1.2-3.3), respectively).

Cardioembolic stroke patients were more likely to achieve early neurological improvement and favorable outcome compared with LVD stroke following MRI-based IV-tPA treatment. This finding may reflect a difference in the effect of IV-tPA among stroke subtypes.

Are marine mimivirus relatives probably large algal viruses? Acanthamoeba polyphaga mimivirus is the largest known ds-DNA virus and its 1.2 Mb-genome sequence has revealed many unique features. Mimivirus occupies an independent lineage among eukaryotic viruses and its known hosts include only species from the Acanthamoeba genus. The existence of mimivirus relatives was first suggested by the analysis of the Sargasso Sea metagenomic data. We now further demonstrate the presence of numerous "mimivirus-like" sequences using a larger marine metagenomic data set. We also show that the DNA polymerase sequences from three algal viruses (CeV01, PpV01, PoV01) infecting different marine algal species (Chrysochromulina ericina, Phaeocystis pouchetii, Pyramimonas orientalis) are very closely related to their homolog in mimivirus.

Our results suggest that the numerous mimivirus-related sequences identified in marine environments are likely to originate from diverse large DNA viruses infecting phytoplankton. Micro-algae thus constitute a new category of potential hosts in which to look for new species of Mimiviridae.

Is red light phototherapy alone effective for acne vulgaris : randomized , single-blinded clinical trial? Recently, a demand for safe and effective treatment of acne has been increasing. Although visible light has attracted attention as a new option, the effect of red light alone has not yet been evaluated. The objective was to assess the efficacy of red light phototherapy with a portable device in acne vulgaris. Twenty-eight volunteers with mild to moderate acne were treated with portable red light-emitting devices in this split-face randomized trial. The right or left side of the face was randomized to treatment side and phototherapy was performed for 15 minutes twice a day for 8 weeks. Clinical photographs, lesion counts, and a visual analog scale (VAS) were used to assess each side of the face at baseline and Weeks 1, 2, 4, and 8, and a split-face comparison was performed. The percent improvement in noninflammatory and inflammatory lesion counts of the treated side was significant compared to the control side (p<.005). VAS decreased from 3.9 to 1.9 on the treatment side and the difference between the treatment and control sides was significant at Week 8 (p<.005).

This study shows that red light phototherapy alone can be a new therapeutic option for acne vulgaris.

Is loneliness in the elderly associated with the use of psychotropic drugs? The aim of this study was to evaluate the association between loneliness in elderly people with the use of psychotropic drugs. A subsample of 3111 participants (ages 55-85) of the large population-based German ESTHER study was included in the study. Loneliness was measured by using a three-item questionnaire. Two subgroups were defined according to their degrees of loneliness. Psychotropic drugs were categorized by study doctors. Logistic regression analyses were conducted to determine the association between loneliness subgroups and the use of psychotropic drugs adjusted for psychosocial variables, multimorbidity, depression, anxiety, and somatic symptom severity. Of the participants 14.1% (95%-CI = [12.9; 15.4]) were estimated to have a high degree of loneliness (women > men); 19% (95%-CI = [17.6; 20.4]) of the participants used psychotropic drugs, 8.4% (95%-CI = [7.5; 9.5]) antidepressants. Logistic regression analysis showed that more lonely participants had significantly higher odds for using psychotropic drugs (OR: 1.495; 95%-CI = [1.121; 1.993]). Depression severity, somatic symptom severity, and female gender were also positively associated with the use of psychotropic drugs.

A high degree of subjective loneliness in the elderly is associated with the use of psychotropic drugs, even after adjustment for somatic and psychological comorbidities and psychosocial variables.

Does psychological impact of positive cervical cancer screening result among Japanese women? While cervical cancer screening is useful for detecting and then treating the disease at an early stage, most women with screen-positive results are free from cervical cancer but nevertheless subject to the unnecessary worry entailed in receiving such results. The purpose of this study was to examine whether receiving a screen-positive result was actually related to psychological distress among Japanese women who underwent cervical cancer screening. We conducted a questionnaire survey at health facilities in a semiurban city of Ibaraki prefecture, involving 1744 women who underwent cervical cancer screening and 72 who received screen-positive results and then underwent further testing. We used the K6 scale to assess their psychological distress (K6 score ≥5) and performed multiple logistic regression analyses to estimate the relative effect of receiving screen-positive results on psychological distress. Psychological distress was more prevalent among women with screen-positive results (OR 2.22; 95 % CI 1.32-3.74), while it was also related to history of mental health consultation (OR 2.26; 95 % CI 1.69-3.01) and marital status (OR 1.32; 95 % CI 1.02-1.70).

Receiving a positive cervical cancer screening result was associated with psychological distress. To alleviate this psychological impact, the current form of communicating the screening results should be reconsidered.