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High oocyte retrieval rates using transvaginal follicular aspiration for single follicles and improved laboratory techniques have engendered renewed interest in natural-cycle in vitro fertilization (IVF). To assess analgesia requirements during single-follicle aspiration, a double-blind study was set up in 30 patients comparing intraprocedure intravenous fentanyl with normal saline as a placebo. Analysis of pain perception using visual analogue scoring showed a similar pain tolerance in both groups for the procedures of vaginal ultrasound scanning, needle insertion, and follicular aspiration. A correlation between each patient's tolerance of common pain-producing experiences with that for the procedure was not well defined (r = 0.5). We conclude that one of the benefits of natural-cycle IVF using transvaginal single-follicle aspiration is that it can be performed without analgesia.

OBJECTIVE: Three indices, the SLE Disease Activity Index (SLEDAI), the Systemic Lupus Activity Measure (SLAM) and the British Isles Lupus Assessment Group (BILAG), have been found to be reliable and valid measures of disease activity in patients with systemic lupus erythematosus (SLE). Our aim was to investigate their use and comparative ability to assess change in disease activity over time.METHODS: Clinical and laboratory features of 8 patients with SLE on each of 3 consecutive visits were abstracted and sent in 3 separate packages to physicians from 8 centers. The order of the patient visit summaries was randomized, and the 3 indices rated in one of 6 specific sequences.RESULTS: The 3 indices were significantly (p < 0.01) correlated: SLEDAI/SLAM = 0.61, BILAG/SLAM = 0.55, SLEDAI/BILAG = 0.35. The sequence presented, the order of patients and order of index scoring did not contribute significantly (p > 0.05) to the variation of any of the 3 indices. All 3 indices detected differences among patients (p < 0.01). Differences between visits were detectable with SLEDAI (p = 0.04) but not with SLAM or BILAG:CONCLUSION: Our study confirms that the SLEDAI, SLAM and BILAG are comparable disease activity measures. SLEDAI appears to be sensitive to change in disease activity over time.

Urothelial carcinoma is the most common form of bladder cancer, but pathway changes that occur with stage-wise progression have not been well defined. We used a metabolomics approach to identify potential metabolic pathways uniquely altered in normal urothelium, nonmuscle-invasive bladder cancer (NMIBC), and muscle-invasive bladder cancer (MIBC). We performed global metabolomic profiling using GC-mass spectrometry (MS) and LC-MS platforms to identify metabolite signatures between normal urothelium and high-grade urothelial carcinoma of different stages. Pathways globally dysregulated in cancer relative to normal urothelium included glucose, tricarboxylic acid (TCA) cycle, lipid, amino acid, and nucleotide pathways. Urothelial carcinoma showed elevated glucose utilization for glycolysis and increased sorbitol pathway intermediates, consistent with Warburg effect. Anaplerosis to sustain energy production suggested by increased late TCA cycle intermediates, amino acids, and dipeptides occurs in bladder cancer. Urothelial carcinoma also shows altered membrane lipid membrane metabolism and differential derivation of nucleic acid components pyrimidine and purine. In stage comparison, MIBC appears to preferentially enhance cyclooxygenase (COX) and lipoxygenase (LOX) signaling, increase heme catabolism, and alter nicotinamide adenine dinucleotide (NAD+) synthesis with a possible influence from associated inflammatory cells. We identify numerous metabolomic alterations in NMIBC and MIBC that likely reflect underlying pathway changes. Differential pathway activity may have value in designing stage-specific novel therapeutics in urothelial carcinoma.

Histone modifications play critical roles in the progression of non-small cell lung cancer (NSCLC), which accounts for almost 85% of all diagnosed lung cancers. Magnolol and polyphenol mixture (PM) derived from Magnolia officinalis exhibited remarkable antitumor activities in lung cancer. However, the epigenetic effects and molecular mechanisms of magnolol and PM in NSCLC have yet to be reported. In this study, the epigenetic effects of magnolol and PM in NSCLC were examined in vitro and in vivo. Results revealed that magnolol and PM significantly suppressed the expression levels and function of class I histone deacetylases (HDACs). In A549 and H1299 cells, magnolol and PM remarkably induced cell apoptosis by arresting the cell cycle in the G0/G1 phase while simultaneously activating various pro-apoptotic signals, including TRAIL-R2 (DR5), Bax, caspase 3, cleaved caspase 3, and cleaved PARP. However, these apoptosis-promoting effects could be attenuated by TSA, which is a specific class I HDACs inhibitor. ChIP assays also demonstrated that magnolol and PM significantly enriched the histone acetyl mark (H3K27ac) in the promoter region of DR5. In A549 xenograft model, magnolol and PM notably reduced tumor growth by 44.40% and 35.40%, respectively. Therefore, magnolol and PM, as potential inhibitors of class I HDACs, induced tumor cell apoptosis and suppressed tumor growth partially by epigenetically activating DR5, which is a key protein in death receptor signaling pathway.

OBJECTIVE: This study examined the influence of the Promote Children's Growth and Development (PCGD) intervention on children's growth and development in rural areas in Indonesia.DESIGN AND SAMPLE: A community-based nonblinded cluster randomized controlled trial was conducted. Twelve clusters of villages were matched based on population and randomly assigned to intervention group (six clusters and 72 caregivers dyads) or control group (six clusters and 72 caregivers dyads) with inclusion criteria age 0-72 months and attending integrated health centers (Posyandu). The intervention was conducted for 14 weeks with caregivers.MEASURES: The weight-for-age Z-score (WAZ), height-for-age Z-score (HAZ), weight-for-height Z-score (WHZ), and body mass index-for-age Z-score (BAZ) were calculated using World Health Organization Anthro-Plus version 1.0.3. A prescreening developmental questionnaire (PSDQ) measured the development of children before and after the intervention.RESULTS: The proportion of stunting of HAZ, wasting of WHZ, and deviation development of PSDQ were higher in the control group compared to the intervention group, respectively (22.2% vs. 37.5%), (9.7% vs. 4.2%), and (12.5% vs. 2.8%). Caregivers were more confident promoting children's growth and development after attending 12 sessions of the PCGD intervention.CONCLUSION: The 12 session PCGD intervention is effective for promoting the growth and development of children of 0-72 months. The PCGD could be considered for implementation in community health centers.

Zinc (Zn) and Zn-transcription Factors regulate the metabolic pathways of lipids and glucose, consequently nutritional zinc deficiency or excess, activates stress pathways and deranges the hepatic metabolism of lipids. High fat diet (HFD) also leads to lipids' profile disorders as well as to intracellular free radicals (FR) accumulation and finally to metabolic stress-syndrome. Study of nutritional Zn effects on the lipidome of plasma lipoproteins and liver, in HFD-mice, was the aim of the present research. Three Zn enriched HF-Diets as follows, 3 mg/kg feed (Zn deficient diet), 30 mg/kg feed (Zn sufficient diet), 300mgZn /kg feed (Zn excess diet) (Mucedola s.r.l Italy-55% cal) were applied respectively to three groups of male wild type (wt) mice (Hybrid F1/F1),C57Bl/6xCBA, one month old, for 10 weeks. Accordingly, mice body weight rate and 1H-NMR spectrum analysis of liver extracts and plasma HDL and non-HDL lipoproteins were evaluated at the end of the experimental period. It is concluded that Zn sufficient diet (30 mg/Kg Feed) creates a highly protective lipidomic profile on plasma and liver lipoproteins of HFD-mice, related to significantly increased antiatherogenic indicators in lipids' composition, compared to mice in nutritional Zn deficiency or excess.

Adeno-associated virus (AAV) is gaining momentum as a gene therapy vector for human applications. However, there remain impediments to the development of this virus as a vector. One of these is the incomplete understanding of the biology of the virus, including nuclear targeting of the incoming virion during initial infection, as well as assembly of progeny virions from structural components in the nucleus. Toward this end, we have identified four basic regions (BR) on the AAV2 capsid that represent possible nuclear localization sequence (NLS) motifs. Mutagenesis of BR1 ((120)QAKKRVL(126)) and BR2 ((140)PGKKRPV(146)) had minor effects on viral infectivity ( approximately 4- and approximately 10-fold, respectively), whereas BR3 ((166)PARKRLN(172)) and BR4 ((307)RPKRLN(312)) were found to be essential for infectivity and virion assembly, respectively. Mutagenesis of BR3, which is located in Vp1 and Vp2 capsid proteins, does not interfere with viral production or trafficking of intact AAV capsids to the nuclear periphery but does inhibit transfer of encapsidated DNA into the nucleus. Substitution of the canine parvovirus NLS rescued the BR3 mutant to wild-type (wt) levels, supporting the role of an AAV NLS motif. In addition, rAAV2 containing a mutant form of BR3 in Vp1 and a wt BR3 in Vp2 was found to be infectious, suggesting that the function of BR3 is redundant between Vp1 and Vp2 and that Vp2 may play a role in infectivity. Mutagenesis of BR4 was found to inhibit virion assembly in the nucleus of transfected cells. This affect was not completely due to the inefficient nuclear import of capsid subunits based on Western blot analysis. In fact, aberrant capsid foci were observed in the cytoplasm of transfected cells, compared to the wild type, suggesting a defect in early viral assembly or trafficking. Using three-dimensional structural analysis, the lysine- and arginine-to-asparagine change disrupts hydrogen bonding between these basic residues and adjacent beta strand glutamine residues that may prevent assembly of intact virions. Taken together, these data support that the BR4 domain is essential for virion assembly. Each BR was also found to be conserved in serotypes 1 to 11, suggesting that these regions are significant and function similarly in each serotype. This study establishes the importance of two BR motifs on the AAV2 capsid that are essential for infectivity and virion assembly.

Exposure to certain environmental chemicals in human and animals has been found to cause cellular damage of the pancreatic â cells which will lead to the development of type 2 diabetes mellitus (T2DM). Although the mechanisms for the chemical-induced â cell damage were unclear and likely to be complex, one recurring finding is that these chemicals induce oxidative stress leading to the generation of excessive reactive oxygen species (ROS) which induce damage to the â cell. To identify potential diabetogenic environmental chemicals, we isolated pancreatic islet cells from C57BL/6 mice and cultured islet cells in 96-well cell culture plates; then, the islet cells were dosed with chemicals and the ROS generation was detected by 2',7'-dichlorofluorescein (DCFH-DA) fluorescent dye. Using this method, we found that bisphenol A (BPA), Benzo[a]pyrene (BaP), and polychlorinated biphenyls (PCBs), could induce high levels of ROS, suggesting that they may potentially induce damage in islet cells. This method should be useful for screening diabetogenic xenobiotics. In addition, the cultured islet cells may also be adapted for in vitro analysis of chemical-induced toxicity in pancreatic cells.

OBJECTIVES: Although emotional cues like facial emotion expressions seem to be important in social interaction, there is no specific training about emotional cues for psychiatrists. Here, we aimed to investigate psychiatrists' ability of facial emotion recognition and relation with their clinical identification as psychotherapy-psychopharmacology oriented or being adult and childhood-adolescent psychiatrist.METHODS: Facial Emotion Recognition Test was performed to 130 psychiatrists that were constructed by a set of photographs (happy, sad, fearful, angry, surprised, disgusted and neutral faces) from Ekman and Friesen's.RESULTS: Psychotherapy oriented adult psychiatrists were significantly better in recognizing sad facial emotion (p=.003) than psychopharmacologists while no significant differences were detected according to therapeutic orientation among child-adolescent psychiatrists (for each, p>.05). Adult psychiatrists were significantly better in recognizing fearful (p=.012) and disgusted (p=.003) facial emotions than child-adolescent psychiatrists while the latter were better in recognizing angry facial emotion (p=.008).CONCLUSION: For the first time, we have shown some differences on psychiatrists' facial emotion recognition ability according to therapeutic identification and being adult or child-adolescent psychiatrist. It would be valuable to investigate how these differences or training the ability of facial emotion recognition would affect the quality of patient-clinician interaction and treatment related outcomes.

The copy number of mitochondrial DNA (mtDNA) is decreased in most cancer types, including hepatocellular carcinoma (HCC), compared to normal counterparts. However, a decrease in mtDNA usually leads to defects in cell proliferation, which contradicts the robustness of cancer cell proliferation. In this study, we found that four out of seven HCC cell lines were of the mtDNA-less type. Interestingly, FOXM1, a member of the FOX transcription factor family, was highly expressed in a subset of them with proliferative potential maintained. B-MYB, a partner of FOXM1, was also expressed in the same cell lines. RNAi-mediated experiments demonstrated that when FOXM1/B-MYB was silenced in the cell lines, cell cycle-related genes were downregulated, while p21Cip1 was induced with senescence-associated â-galactosidase, resulting in G1/S cell cycle arrest. These results suggest that high expression of FOXM1/B-MYB is critical for sustaining cell proliferation in mtDNA-less cells. In addition, we found that high expression of FOXM1 was mediated by the deubiquitinating enzyme, OTUB1, in one cell line. Thus, interference with FOXM1/B-MYB expression, such as through OTUB1 inhibition, may induce a dormant state of senescence-like proliferation arrest in mtDNA-less cancer cells. This finding may be utilized for the development of precision medicine for relevant cancers.

BACKGROUND: This prospective study explores the incidence of preoperative deep venous thrombosis (DVT) in a group of patients with hip and femur fracture who for various reasons experienced a delay of >24 hours from the time of injury until time of surgery. We also evaluated the results of preoperative treatment with inferior vena cava (IVC) filter.METHODS: There were 101 consecutive patients with a mean age of 75.8 years. The mean time to surgery from injury was 3.5 days. All patients were evaluated for signs and symptoms of DVT and underwent Doppler ultrasound before surgery. All patients received preoperative prophylactic anticoagulation. Those patients with DVT underwent IVC filter insertion before surgical intervention.RESULTS: No patient exhibited signs or symptoms of DVT; however, preoperative ultrasound detected DVT in 10 patients. Despite negative ultrasound, two additional patients developed pulmonary embolus preoperatively for an overall incidence of thromboembolic disease of 11.9%. The average delay in surgery was 5.7 days for patients with DVT versus 3.2 days for those without (p = 0.021). The incidence increased each day from 14.5% if surgery was delayed >1 day to 33.3% if surgery was delayed >7 days. Relative risk increased from 2.32 to 3.71 over the same period. There were no postoperative thromboembolic complications or complications related to IVC filter placement in these patients.DISCUSSION: In this prospective study, we observed that patients experiencing a delay in surgical care for an acute hip or femur fracture are at a relatively high risk for development of thromboembolic disease despite prophylactic anticoagulation. There was a direct correlation between the period of delay and the incidence of thromboembolism. Clinical examination in this setting is unreliable as none of these patients had signs or symptoms suggestive of DVT. We suggest that all patients with delayed (>24 hours) surgical intervention undergo preoperative Doppler ultrasound to rule out DVT. Appropriate measures such as placement of an IVC filter and aggressive postoperative anticoagulation should then be implemented for those with DVT and/or pulmonary embolus.

The objective of the present study was to improve the quality and efficacy of the surgical treatment of chronic otitis media including the plastic correction of total and subtotal tympanic defects by fixing a many-layer chondro-perichondrial autograft with the use of a latex tissue glue. Twenty seven patients presenting with total and subtotal defects of the tympanic membrane underwent surgical intervention in the lateral position. The multilayer transplants composed of a thinned cartilage, fascia, and transposed circular cutaneous graft on the feeding pedicle were fixed using the latex tissue glue. The morphological and functional results of the treatment were estimated one year after surgery. It was shown that the use of the latex tissue glue for the fixation of many-layer autografts during myringoplasty made it possible to decrease the duration of the hospital stay of the patients, reduce to a minimum manifestations of negative subjective feelings, and ensure the reliable clinico-morphological and functional outcome of the treatment.

BACKGROUND: Small RNA molecules, called microRNAs, freely circulate in human plasma and correlate with varying pathologies. In this study, we explored their diagnostic potential in a selection of prevalent cardiovascular disorders.METHODS AND RESULTS: MicroRNAs were isolated from plasmas from well-characterized patients with varying degrees of cardiac damage: (1) acute myocardial infarction, (2) viral myocarditis, (3) diastolic dysfunction, and (4) acute heart failure. Plasma levels of selected microRNAs, including heart-associated (miR-1, -133a, -208b, and -499), fibrosis-associated (miR-21 and miR-29b), and leukocyte-associated (miR-146, -155, and -223) candidates, were subsequently assessed using real-time polymerase chain reaction. Strikingly, in plasma from acute myocardial infarction patients, cardiac myocyte-associated miR-208b and -499 were highly elevated, 1600-fold (P<0.005) and 100-fold (P<0.0005), respectively, as compared with control subjects. Receiver operating characteristic curve analysis revealed an area under the curve of 0.94 (P<10(-10)) for miR-208b and 0.92 (P<10(-9)) for miR-499. Both microRNAs correlated with plasma troponin T, indicating release of microRNAs from injured cardiomyocytes. In viral myocarditis, we observed a milder but significant elevation of these microRNAs, 30-fold and 6-fold, respectively. Plasma levels of leukocyte-expressed microRNAs were not significantly increased in acute myocardial infarction or viral myocarditis patients, despite elevated white blood cell counts. In patients with acute heart failure, only miR-499 was significantly elevated (2-fold), whereas no significant changes in microRNAs studied could be observed in diastolic dysfunction. Remarkably, plasma microRNA levels were not affected by a wide range of clinical confounders, including age, sex, body mass index, kidney function, systolic blood pressure, and white blood cell count.CONCLUSIONS: Cardiac damage initiates the detectable release of cardiomyocyte-specific microRNAs-208b and -499 into the circulation.

The development of an infection is a major complication for some patients with implanted biomaterials. Whether the material or surface composition of the used biomaterial influences infection has not been directly compared for key biomaterials currently in use in human patients. We conducted a thorough in vitro and in vivo investigation using titanium (Ti) and polyether-ether-ketone (PEEK) as both commercially available and as modified equivalents (surface polished Ti, and oxygen plasma treated PEEK). Complement activation and cytokine secretion of cell of the immune system was assessed in vitro for all materials in the absence and presence of bacterial stimulants. In a follow-up in vivo study, we monitored bacterial infection associated with clinically available and standard Ti and PEEK inoculated with Staphylococcus aureus. Complement activation was affected by material choice in the absence of bacterial stimulation, although the material based differences were largely lost upon bacterial stimulation. In the in vivo study, the bacterial burden, histological response and cytokine secretion suggests that there is no significant difference between both PEEK and Ti. In conclusion, the underlying material has a certain impact in the absence of bacterial stimulation, however, in the presence of bacterial stimulation, bacteria seem to dictate the responses in a manner that overshadows the influence of material surface properties. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1095-1106, 2019.

BACKGROUND: Chemotherapeutic drugs like Adriamycin (ADR) induces apoptosis or senescence in cancer cells but these cells often develop resistance and generate responses of short duration or complete failure. The methylxantine drug Pentoxifylline (PTX) used routinely in the clinics setting for circulatory diseases has been recently described to have antitumor properties. We evaluated whether pretreatment with PTX modifies apoptosis and senescence induced by ADR in cervix cancer cells.METHODS: HeLa (HPV 18+), SiHa (HPV 16+) cervix cancer cells and non-tumorigenic immortalized HaCaT cells (control) were treated with PTX, ADR or PTX + ADR. The cellular toxicity of PTX and survival fraction were determinated by WST-1 and clonogenic assay respectively. Apoptosis, caspase activation and ADR efflux rate were measured by flow cytometry, senescence by microscopy. IkappaBalpha and DNA fragmentation were determinated by ELISA. Proapoptotic, antiapoptotic and senescence genes, as well as HPV-E6/E7 mRNA expression, were detected by time real RT-PCR. p53 protein levels were assayed by Western blot.RESULTS: PTX is toxic (WST-1), affects survival (clonogenic assay) and induces apoptosis in cervix cancer cells. Additionally, the combination of this drug with ADR diminished the survival fraction and significantly increased apoptosis of HeLa and SiHa cervix cancer cells. Treatments were less effective in HaCaT cells. We found caspase participation in the induction of apoptosis by PTX, ADR or its combination. Surprisingly, in spite of the antitumor activity displayed by PTX, our results indicate that methylxantine, per se does not induce senescence; however it inhibits senescence induced by ADR and at the same time increases apoptosis. PTX elevates IkappaBalpha levels. Such sensitization is achieved through the up-regulation of proapoptotic factors such as caspase and bcl family gene expression. PTX and PTX + ADR also decrease E6 and E7 expression in SiHa cells, but not in HeLa cells. p53 was detected only in SiHa cells treated with ADR.CONCLUSION: PTX is a good inducer of apoptosis but does not induce senescence. Furthermore, PTX reduced the ADR-induced senescence and increased apoptosis in cervix cancer cells.

The purpose of this study was to increase our knowledge of the condition of Icelandic women aged 29 to 40 years during the premenstrual phase of the menstrual cycle. Premenstrual symptoms were measured by a retrospective instrument adapted from Halbreich and colleagues' Premenstrual Assessment Form. Our findings showed that Icelandic women experience premenstrual changes as do their peers in other countries. The most common symptoms were bloating, mood swings, irritability, abdominal discomfort-pain, and intolerance-impatience. Women who were symptomatic in the week before menses tended to manifest more symptoms at other times as well. In general, women responded to their symptoms by taking some time to relax, take pain medication, or seek support. Women experiencing more severe symptoms were more likely to seek support from a partner, relative, or friend. More than 40% of the sample reported that they perceived the symptoms as having negative effects on their relationships with their partners and children, and those experiencing more severe symptoms were more likely to report these perceptions.

OBJECTIVES: The standard surgical treatment for patients with non-small-cell lung cancer (NSCLC) is lobectomy with systematic nodal dissection (SND). Lobe-specific patterns of nodal metastases have been recognized, and lobe-specific SND (L-SND) has been reported. We performed L-SND depending on patient-related factors, such as age or the presence of diabetes or respiratory dysfunction, or in the context of specific tumour-related factors, such as the presence of a tumour with a wide area of ground-glass opacity.METHODS: Between September 2002 and December 2008, 335 consecutive patients with clinical and intraoperative N0 NSCLC underwent curative lobectomies at Shizuoka Cancer Center Hospital. Among these 335 patients, 206 underwent SND (Group A) and 129 underwent L-SND. Of the 129 patients undergoing L-SND, 98 underwent L-SND due to patient-related factors (Group B) and 31 underwent L-SND due to tumour-related factors (Group C).RESULTS: There were no significant differences in morbidity or blood loss between patients undergoing SND or L-SND, but there was a significant difference in the mean operative times. The 5-year disease-free survival (5-DFS) and 5-year overall survival (5-OS) of patients in Group C were 100%. Although the patients in Group B showed no significant difference in 5-DFS and 5-OS compared with Group A, patients in Group B had significantly more initial recurrence of mediastinal node cancer than did the Group A patients (P = 0.0050).CONCLUSIONS: The recurrence of mediastinal node cancer in patients undergoing L-SND was significantly greater than that in those undergoing SND.

Epithelial cell adhesion molecule (EpCAM) is overexpressed in most solid cancers and is an ideal antigen for clinical applications in cancer diagnosis, prognosis, imaging, and therapy. Currently, most of the EpCAM-based diagnostic, prognostic, and therapeutic strategies rely on the anti-EpCAM antibody. However, the use of EpCAM antibody is restricted due to its large size and instability. In this study, we have successfully identified DNA aptamers that selectively bind human recombinant EpCAM protein. The aptamers can specifically recognize a number of live human cancer cells derived from breast, colorectal, and gastric cancers that express EpCAM but not bind to EpCAM-negative cells. Among the aptamer sequences identified, a hairpin-structured sequence SYL3 was optimized in length, resulting in aptamer sequence SYL3C. The Kd values of the SYL3C aptamer against breast cancer cell line MDA-MB-231 and gastric cancer cell line Kato III were found to be 38 ± 9 and 67 ± 8 nM, respectively, which are better than that of the full-length SYL3 aptamer. Flow cytometry analysis results indicated that the SYL3C aptamer was able to recognize target cancer cells from mixed cells in cell media. When used to capture cancer cells, up to 63% cancer cell capture efficiency was achieved with about 80% purity. With the advantages of small size, easy synthesis, good stability, high binding affinity, and selectivity, the DNA aptamers reported here against cancer biomarker EpCAM will facilitate the development of novel targeted cancer therapy, cancer cell imaging, and circulating tumor cell detection.

Lactococcus lactis is a widely used bacteria in dairy industry, specially in cheese ripening. Numerous lactococcal enzymes and proteins are involved in this process. Proteomics makes it possible to deal with a high number of proteins and identify modification of their patterns in two-dimensional (2-D) gels. However, an annotated reference map is necessary prior to analyzing protein variations. We have begun to construct such a map in easily reproducible conditions and identify proteins.

BACKGROUND/OBJECTIVES: CD36 is known to be an orosensory receptor for dietary long-chain fatty acids, as well as being involved in the chemosensory mechanisms within the human gut. Recent data have demonstrated an association between CD36 single-nucleotide polymorphisms (SNPs) and lipid consumption behaviours in humans. This study aimed to test for associations between CD36 SNPs and response to a high-fat meal in a young healthy Australian cohort. Secondary associations were tested between CD36 gene variants and fasting lipid parameters, body composition, cardiovascular disease (CVD) risk factors and measures of oral fat preference.SUBJECTS/METHODS: Two SNPs (rs1527479 and rs1984112) were assessed for associations with response to a 75 g saturated fat oral fat tolerance test (OFTT), whole-body substrate oxidation, fasting plasma lipids, CVD risk factors and self-reported habitual diet questionnaires. Genotyping was performed using real-time polymerase chain reaction.RESULTS: Cross-sectional data were collected on 56 individuals (28 m, 28 f; 24.9±3.3 years), with 42 completing participation in a high-fat OFTT. No genotypic associations were evident in anthropometric data or self-reported fat preference measures. AA SNP carriers at rs1984112 exhibited significantly elevated fasting triglyceride when compared with non-carriers (P=0.024). This group also tended to have an elevated response to a high-fat meal (P=0.078).CONCLUSIONS: Although these data show the potential pleiotropic influence of CD36 SNP rs1984112 on lipoprotein accumulation in a young healthy cohort, further assessment in a larger cohort is warranted.

The present study was designed to investigate the effects of low-dose ketanserin on BPV (blood pressure variability), BRS (baroreflex sensitivity) and organ damage in SHR (spontaneously hypertensive rats). Ketanserin was mixed in rat chow at an estimated dose of 0.1 mg.kg(-1) of body weight.day(-1). SHR were treated for 4 months. BP (blood pressure) was then recorded continuously for 24 h in a conscious state. After determination of BRS, rats were killed for organ damage evaluation. It was found that long-term treatment with low-dose ketanserin did not lower BP levels, but significantly decreased BPV, enhanced BRS and reduced organ damage in SHR. Multiple regression analysis showed that the decrease in left ventricular hypertrophy was most closely correlated (or associated) with the increase in BRS, whereas the decrease in aortic hypertrophy was most closely associated with the decrease in diastolic BPV and the amelioration in renal lesion, with the increase in BRS and the decrease in diastolic BPV. In conclusion, low-dose ketanserin produces organ protection independently of its BP-lowering action in SHR, and this organ protection was importantly attributable to the enhancement of BRS and decrease in BPV.

Serum 25-hydroxyvitamin D (25OHD) is the main circulating form of vitamin D in the blood. Vitamin D status in adults is determined by numerous factors such as oral intake, skin generation, and body composition. However, there is limited understanding regarding determinants of 25OHD in young children. The aim of this study was to identify modifiable factors that may act as determinants of 25OHD at five years of age. Analysis conducted on 79 children from the ROLO Kids study. Dietary intakes and dietary habits were measured using a food frequency questionnaire and levels of sun exposure were assessed using a lifestyle questionnaire, both completed by the mother. Child weight, height, and skinfolds were measured. Vitamin D status was sufficient (25OHD > 50 nmol/L) in 61% of the participants. Neither reported dietary vitamin D nor calcium intake was significantly associated with 25OHD. Intakes of standard milk, eggs, and oily fish were not associated with 25OHD. However, reported consumption of fortified milk, and more than 7 bowls of cereal a week were independently associated with higher 25OHD (p < 0.001 and p = 0.049, respectively). Sun exposure (measured as obtaining at least half an hour of sun per day) was not significantly associated with 25OHD, but reported use of sunscreen was associated with higher 25OHD (p = 0.016). There was no association of body composition with 25OHD. These findings suggest the primacy of dietary and lifestyle habits as indicators of 25OHD in early childhood. This may have utility in identifying at-risk individuals for public health campaigns about education surrounding dietary habits, which may be useful to ensure sufficient vitamin D status within this age group.

Rice bran wax (RBX) obtained during rice bran oil purification can form organogels in edible oils. The kinetics of crystallization and the viscous properties of RBX organogels were studied using differential scanning calorimetry (DSC), viscosity changes with varying temperature, hardness measurements by penetrometry, and synchrotron radiation X-ray diffraction (SR-XRD). The organogels were prepared by RBX in concentrations of 1%, 3%, 6%, and 10% on a weight basis in salad oil, olive oil, and camellia oil. The liquid oil type had no significant effect on the melting and crystallization temperatures of the RBX. However, the viscosity and the texture of the organogels differed with liquid oil type, temperature, and RBX concentration. Changes in the viscosity of the RBX organogels were monitored during cooling from 80°C to 20°C. Drastic viscosity changes occurred in accordance with the onset of crystallization in DSC thermographs obtained at a rate of 5°C/min. RBX in the olive oil and camellia oil mixtures had higher viscosity than RBX in the salad oil mixture, which correlates with the hardness obtained in texture measurements at 20°C. SR-XRD was used to clarify the crystal structures of the building blocks of the RBX organogels in salad oil. It was found that the RBX formed crystals with a long spacing of 7.3 ± 1 nm and short spacings of 0.41 ± 1 nm and 0.37 ± 1 nm. The intensity of the long-spacing pattern was remarkably weaker than that of the short-spacing patterns, which demonstrated strong anisotropy in the crystal growth of RBX crystal particles.

BACKGROUND: Rectovaginal fistula is defined as a result of an abnormal connection between the rectum and vagina. It is often a result of inflammatory bowel disease, iatrogenic illness, malignancy or trauma. Rectovaginal fistula treatment is dependent on the classification of the fistula (simple or complex). There are few reports on transposition of gracilis muscle as a feasible option for treatment of rectal, vaginal and urethral fistula.CLINICAL CASES: We present the first three case experiences from the Instituto Nacional de Ciencias Medicas y Nutricion "Salvador Zubiran," a tertiary-care medical center in Mexico City.CONCLUSIONS: Gracilis muscle transposition is a feasible procedure in our population for treatment of recurrent rectovaginal and anorectal fistulas.

OBJECTIVE: Cerebral infarction, a common acute cereovascular disease, is one of the main complications of type 2 diabetes mellitus (DM). This paper is to explore the risk factors of cerebral infarction among type 2 DM patients.METHODS: A pair-matched case-control study was carried out. Data was analyzed with conditional logistic regression.RESULTS: One hundred and ten type 2 DM patients with cerebral infarction and controls were selected respectively. Results showed that higher educational level and physical exercises lowered the risk of cerebral infarction among type 2 DM patients. Higher HDL-C and blood sugar under control could also lower the risk of developing cerebral infarction among type 2 DM patients. The above factors seemed to have protective functions. Excessive salt intake and snoring increased the risks of cerebral infarction development among type 2 DM patients. Hypertension served as an independent risk factor while atrial fibrillation and hyperinsulinemia were important risk factors. High LDL-C, Apo-A, Lp(a), Fg increased the risk of cerebral infarction among type 2 DM patients. The study did not discover the relationship of smoking, drinking, oral contraception, menstrual and obstetrical history, TC, TG, Apo-A and cerebral infarction among type 2 DM patients.CONCLUSION: To prevent cerebral infarction among type 2 DM, measures need to be taken as control of salt intake; eating more vegetables; regular physical exercises; control of blood sugar, blood pressure and Hyperinsulinemia.

Using photoemission spectroscopy techniques, we show that oxygen intercalation is achieved on an extended layer of epitaxial graphene on Ir(111), which results in the "lifting" of the graphene layer and in its decoupling from the metal substrate. The oxygen adsorption below graphene proceeds as on clean Ir(111), giving only a slightly higher oxygen coverage. Upon lifting, the C 1s signal shows a downshift in binding energy, due to the charge transfer to graphene from the oxygen-covered metal surface. Moreover, the characteristic spectral signatures of the graphene-substrate interaction in the valence band are removed, and the spectrum of strongly hole-doped, quasi free-standing graphene with a single Dirac cone around the K point is observed. The oxygen can be deintercalated by annealing, and this process takes place at around T = 600 K, in a rather abrupt way. A small amount of carbon atoms is lost, implying that graphene has been etched. After deintercalation graphene restores its interaction with the Ir(111) substrate. Additional intercalation/deintercalation cycles readily occur at lower oxygen doses and temperatures, consistently with an increasingly defective lattice. Our findings demonstrate that oxygen intercalation is an efficient method for fully decoupling an extended layer of graphene from a metal substrate, such as Ir(111). They pave the way for the fundamental research on graphene, where extended, ordered layers of free-standing graphene are important and, due to the stability of the intercalated system in a wide temperature range, also for the advancement of next-generation graphene-based electronics.

PURPOSE: To investigate whether dynamic contrast -enhanced MRI (DCE-MRI) can distinguish the type of liver nodules in a rat model with N-nitrosodiethylamine- induced cirrhosis.METHODS: Liver nodules in cirrhosis were induced in 60 male Wistar rats via 0.01 % N-nitrosodiethylamine in the drinking water for 35-100 days. The nodules were divided into three groups: regenerative nodule (RN), dysplastic nodule (DN), and hepatocellular carcinoma (HCC). DCE-MRI was performed, and parameters including transfer constant (Ktrans), rate constant (Kep), extravascular extracellular space volume fraction (Ve), and initial area under the contrast concentration versus time curve (iAUC) were measured and compared.RESULTS: The highest Ktrans and iAUC values were seen in HCC, followed by DN and RN (all P < 0.05). The area under the receiver operating characteristic curve (AUROC) for DN and HCC were 0.738 and 0.728 for Ktrans and iAUC, respectively. The AUROC for HCC were 0.850 and 0.840 for Ktrans and iAUC, respectively. Ordinal logistic regression analysis showed that Ktrans had a high goodness of fit (0.970, 95 % confidence interval, 13.751-24.958).CONCLUSION: DCE-MRI is a promising method to differentiate of liver nodules. Elevated Ktrans suggested that the nodules may be transformed into HCC.KEY POINTS: • DCE-MRI is promising for differentiating among RN, DN, and HCC • K trans and iAUC positively correlated with malignancy degree of liver nodules • Elevated K trans suggests that the nodules may be transformed into HCC.

BACKGROUND: HLA-DRB3, DRB4 and DRB5 (DRB3/4/5) are paralogues of HLA-DRB1. They have important roles in transplantation and have been reported to be related to many diseases. HLA typing methods for DRB3/4/5 based on NGS data have many limitations now, such as need of polymerase chain reaction (PCR) or low accuracy.MATERIALS AND METHODS: We present a HLA typing method for DRB3/4/5 based on read mapping and haplotype assembly from NGS data. Also, copy number of DRB3/4/5 is determined by a k-means clustering method according to ratio of sequencing depth between DRB3/4/5 and DRB1.RESULTS: We achieved 100%, 100%, 100% accuracy on simulated data and 95.88%, 98.89%, 99.34% accuracy on MHC capture Illumina sequencing data at 4-digit resolution with 30-fold coverage for DRB3/4/5 separately. We also explored the DRB3/4/5 profiles in five continental populations through low coverage WGS data generated by the 1000 Genome Project. We found that frequency of DRB4 in African were significantly lower than that in all other populations.CONCLUSION: Our method for DRB3/4/5 typing has high accuracy. It is a good supplement to regular HLA typing and could help in disease studies, medical applications and human population diversity studies.

Several studies have identified two types of sleep spindles: fast (13-15 Hz) centroparietal and slow (11-13 Hz) frontal spindles. Alterations in spindle activity have been observed in Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI). Only few studies have separately assessed fast and slow spindles in these patients showing a reduction of fast spindle count, but the possible local specificity of this phenomenon and its relation to cognitive decline severity are not clear. Moreover, fast and slow spindle density have never been assessed in AD/MCI. We have assessed fast and slow spindles in 15 AD patients, 15 amnesic MCI patients, and 15 healthy elderly controls (HC). Participants underwent baseline polysomnographic recording (19 cortical derivations). Spindles during nonrapid eye movements sleep were automatically detected, and spindle densities of the three groups were compared in the derivations where fast and slow spindles exhibited their maximum expression (parietal and frontal, resp.). AD and MCI patients showed a significant parietal fast spindle density decrease, positively correlated with Minimental State Examination scores. Our results suggest that AD-related changes in spindle density are specific for frequency and location, are related to cognitive decline severity, and may have an early onset in the pathology development.

OBJECTIVE: The surgical treatment of extensive diffuse pigmented villonodular synovitis (PVNS) of large joints alone is unsatisfactory, with high rates of local recurrence. Post-synovectomy adjuvant treatment with external beam radiation therapy or intra-articular injection of yttrium 90 (90Y) yielded better results. We report our experience with 10 cases treated with debulking surgery followed by intra-articular injection of 90Y.PATIENTS AND METHODS: Between January 1989 and June 1998, 10 patients (eight males and two females aged 15-49 yr) with extensive diffuse PVNS were treated. In six patients the knee joint, in three patients the ankle joint, and in one patient the hip joint were involved. The 10 patients underwent 15 operations, one patient had three surgical procedures, and three patients underwent two surgeries (the intervals between re-operations for local recurrence were 2-4 yr). All patients had an intra-articular injection of 15-25 mCi (555-925 MBq) 90Y, 6-8 weeks after the last surgery.RESULTS: Mean follow-up time was 6 yr (range 2.5-12 yr). All patients were followed using repeated computerized tomography (CT) scans, magnetic resonance imaging (MRI), plain X-ray films and bone scans semi-annually. In nine patients, neither evidence of disease nor progression of bone or articular destruction were noted. In one patient, stabilization of disease was achieved with no further evidence of bony or articular damage. No complications were noticed after surgery or after the intra-articular 90Y injection.CONCLUSION: A combination of debulking surgery with intra-articular injection of 90Y for extensive diffuse PVNS of major joints is a reliable treatment method, with good results.

Pituitary adenoma cells from a mammosomatotroph adenoma obtained from a 21-year-old female presenting with acromegaly and amenorrhea were investigated by sandwich cell immunoblot assay, immunohistochemistry, and electron microscopy. The new, simple technique of sandwich cell immunoblot assay could detect two hormones secreted in the same one cell, and found that 89% of mammosomatotrophs secreted both growth hormone (GH) and prolactin (PRL). Immunohistochemistry showed that the tumor cells were positive for both GH and PRL. Electron microscopy showed cells contained granules ranging in size form 150 to 500 nm. This is the first demonstration of both GH and PRL in the same mammosomatotroph cell. Sandwich cell immunoblot assay can measure the amount of secreted hormone, allowing a new approach to the investigation of mammosomatotroph adenomas.

Ocean acidification is predicted to affect a wide diversity of marine organisms. However, no studies have reported the effects of ocean acidification on Indian Ocean fish. We have used the Indian Ocean medaka (Oryzias melastigma) as a model species for a marine fish that lives in coastal waters. We investigated the impact of ocean acidification on the embryonic development and the stereotyped escape behavior (mediated by the Mauthner cell) in newly hatched larvae. Newly fertilized eggs of medaka were reared in seawater at three different partial pressures of carbon dioxide (pCO2): control at 450 ìatm, moderate at 1160 ìatm, and high at 1783 ìatm. Hatch rates, embryonic duration, and larval malformation rates were compared and were not significantly different between the treatments and the control. In the high pCO2 group, however, the yolks of larvae were significantly smaller than in the control group, and the newly hatched larvae were significantly longer than the larvae in the control. In the moderate pCO2 group, the eye distance decreased significantly. No significantly negative growth effects were observed in the larvae when exposed to pCO2 levels that are predicted as a result of ocean acidification in the next 100-200 years. Larvae reared under control conditions readily produced C-start escape behavior to mechanosensory stimuli; however, in the moderate and high pCO2 experimental groups, the probabilities of C-start were significantly lower than those of the control group. Therefore, the sensory integration needed for the C-start escape behavior appears to be vulnerable to ocean acidification. Altered behavior in marine larval fish, particularly behaviors involved in escape from predation, could have potentially negative implications to fish populations, and, further, to the marine ecosystems at the levels of CO2 projected for the future.

OBJECTIVES: Sexually transmitted and blood-borne infections (STBBIs) are associated with stigmatizing attitudes and beliefs, which can affect the quality of and access to health care, as well as mental health and quality of life. The current study describes the adaptation from an HIV-related stigma scale and pilot testing of a new STBBI Stigma Scale, assessing the stigmatizing attitudes and beliefs of health and social service providers in Canada.METHODS: 144 health and social service providers from across Canada completed the newly adapted scale assessing stigma associated with HIV, hepatitis C, other viral STBBIs and bacterial STBBIs, as well as demographic information, a scale of social desirability and measures of convergent and divergent validity. Participants were recruited through listservs and completed the scale online.RESULTS: The new scale, consisting of 21 items for each category, demonstrated excellent internal consistency, reliability, and convergent and divergent validity. The factor structure of the scale supports a tripartite model of stigma consisting of stereotyping, prejudice and discrimination. Stereotyping had the highest relative scores on the subscales, and attitudes regarding other viral STBBIs differed significantly from the other STBBI categories.CONCLUSION: The new scale provides a contextually relevant and applicable psychometrically valid tool to assess STBBI-related stigma among health and social service providers in Canada. The tool can be used to assess attitudes and beliefs, as well as guide self-assessment and possible trainings for providers.

Human herpesvirus-6 (HHV-6), a ubiquitous virus that causes exanthem subitum and occasional cases of infectious mononucleosis, hepatitis and other viral syndromes, has also been associated with acute lymphocytic leukemia (ALL) in children. To further investigate this association, we obtained sera from 50 patients with ALL and 50 age-sex matched controls. Antibodies to HHV-6 were determined using ELISA and indirect immunofluorescent antibody (IFA) tests. No significant difference between antibody titers in the cases and controls was observed. Since seroepidemiologic studies have demonstrated higher HHV-6 antibody titers in young children than in adults, this serologic study suggests that the previous association reported for HHV-6 and ALL was a result of the age of the population rather than a relationship between the virus and the disease.

Irritable bowel syndrome (IBS) is characterized by visceral hypersensitivity likely related to altered processing of sensory stimuli along the brain-gut axis. Previous neuroimaging studies demonstrated structural and functional alteration of several brain areas involved in bodily representation, e.g. the insula, in patients with IBS. By means of resting-state functional magnetic resonance imaging (rs-fMRI) we searched for alteration of functional connectivity within the network involved in self-bodily consciousness. We found significant inverse correlation between hypochondriasis assessed through a clinical questionnaire and connectivity between posterior cingulate cortex and left supramarginal gyrus, extending into the adjacent superior temporal gyrus. Moreover, we observed a significant and positive correlation between a clinical questionnaire assessing interoception and connectivity between left anterior ventral insula and two clusters located in supramarginal gyrus bilaterally.Our findings highlight an "abnormal network synchrony" reflecting functional alteration, in the absence of structural and micro-structural changes, which might represent a possible therapeutic target for Irritable Bowel Syndrome.

OBJECTIVES: We studied the unilateral nodal yields for procedures reported as standard or modified radical neck dissection (RND) to determine their applicability in outcomes research.METHODS: We analyzed the unilateral nodal yields for all procedures reported as RND for carcinoma of the oral cavity, pharynx, and larynx at our institution from 1985 to 1997 (n = 64, no prior treatment). These included both standard and modified techniques, encompassing levels I through V of the neck. Each side of a bilateral RND was treated as a separate case. This sample was compared with a similar population from the National Cancer Institute's Surveillance, Epidemiology, and End-Results (SEER) registry. Nodal yield was obtained for RND alone and for unspecified neck dissection with primary excision for the same diseases and time period (n = 1499).RESULTS: The mean nodal yield from 64 RND was 30 vs 27 in the SEER data. The standard deviation was 14.7 compared with 17.2 in the SEER data. Values ranged from 7 to 66 nodes whereas the SEER range was from 1 to 97 nodes. Although the SEER data contain nodal yields from regional or selective neck dissection, we corroborate our findings of large variance in nodal yield from our RND sample.CONCLUSIONS: Large variance in nodal yields from RND may have undefined effects on quality of life, cure rate, and survival. Until correlation of nodal yields with outcomes is examined, we cannot know how to relate RND to outcomes.

Results from vessel bioassays have provided the foundation for much of our understanding of the mechanisms that control vascular homeostasis and blood flow. The seminal observations that led to the discovery that nitric oxide (NO) is a critical mediator of vascular relaxation were made with the use of such methodology, and many studies have used NO-dependent vessel relaxation as an experimental readout for understanding mechanisms that regulate vascular NO function. Studies have coupled controlling oxygen tensions within vessel bioassay chambers to begin to understand how oxygen-specifically hypoxia-regulate NO function, and this context has identified red cells-specifically hemoglobin within-as critical modulators. Alone, vessel bioassays or measuring oxygen partial pressures (pO2) is relatively straightforward, but the combination necessitates consideration of several factors. We use the example of deoxygenated red cells/hemoglobin-dependent potentiation of nitrite-dependent dilation to illustrate the salient factors that are critical to consider in designing and interpreting experiments aimed at understanding the interplay between oxygen and NO function in the vasculature.

Measuring attachment behaviors is relevant to creating secure couple relationships. This article seeks to test and examine the reliability and validity of the Brief Accessibility, Responsiveness, and Engagement (BARE) Scale-a practical measure of couple attachment-in a clinical sample. Couples took the BARE and other assessments measuring relationship functioning (self and partner reports of relationship satisfaction, relationship stability, positive and negative communication, and attachment styles). Results suggest that the BARE appears to be a reliable and valid tool for assessing couple attachment and can accurately predict and classify whether the couples belong in the clinical or nonclinical group, as well as their level of relationship satisfaction. Results also indicate attachment behaviors are related to relationship outcomes.

Six novel bacterial strains were isolated from the environment which can oxidize arsenite [As(III)] to the less mobile form arsenate [As(V)] coupled to CO(2) fixation under either aerobic or denitrifying conditions. PCR primers were designed to the conserved molybdopterin domain of the large subunit of arsenite oxidase in order to identify the arsenite oxidase genes from these isolates. The amino acid sequences for the arsenite oxidases reported here were 72-74% identical to that of strain NT-26, the only previously reported autotrophic arsenite oxidizer. Indeed the autotrophic arsenite oxidase genes form a distinct phylogenetic group, separated from previously described heterotrophic arsenite oxidase genes, with the exception of the heterotroph Agrobacterium tumefaciens. The arsenite oxidase primers described here represent a powerful culture-independent tool to assess the diversity of arsenite oxidase genes in environmental bacteria.

O(6)-Cyclohexylmethylguanine (NU2058) was developed as an inhibitor of CDK2 and was previously shown to potentiate cisplatin cytotoxicity in vitro. The aim of this study was to investigate the mechanism of cisplatin potentiation by NU2058. SQ20b, head and neck cancer cells were treated for 2h with NU2058 (100 microM) and then for a further 2h with cisplatin and NU2058. NU2058 increased cisplatin cytotoxicity, by clonogenic assay, with a dose modification factor (DMF) of 3.1. NU2058 increased total intracellular platinum levels 1.5-fold, and platinum-DNA adduct levels twofold. Furthermore, the cisplatin-DNA adducts formed were more toxic in the presence of NU2058. To investigate whether the effects of NU2058 on cisplatin adduct levels and toxicity were dependent on CDK2 activity, additional CDK2 inhibitors were tested. NU6230 (CDK2 IC(50) 18 microM) was equipotent to NU2058 (CDK2 IC(50) 17 microM) as a CDK2 inhibitor in cell-free and cell-based assays, yet did not potentiate cisplatin cytotoxicity. Furthermore, NU6102 was >1000-fold more potent than NU2058 as a CDK2 inhibitor (CDK2 IC(50) 5 nM) yet was no more active than NU2058 in potentiating cisplatin. NU2058 also potentiated melphalan (DMF 2.3), and monohydroxymelphalan (1.7), but not temozolomide or ionising radiation. Whilst NU2058 increased melphalan cytotoxicity, it did not increase melphalan-DNA adduct formation. These studies demonstrate that NU2058 alters the transport of cisplatin, causing more Pt-DNA adducts, as well as sensitizing cells to cisplatin- and melphalan-induced DNA damage. However, the effects of NU2058 are independent of CDK2 inhibition.

Studies of temporal behaviors of protein association in living cells are crucially important for elucidating the fundamental roles and the mechanism of interactive coordination for cell activities. We developed a method for investigating the temporal alternation of a particular protein assembly using monomeric fluorescent proteins, fluorescent timers (FTs), of which the fluorescent color changes from blue to red over time. We identified a dissection site of the FTs, which allows complementation of the split FT fragments. The split fragments of each FT variant recovered their fluorescence and maintained inherent rates of the color changes upon the reassembly of the fragments in vitro. We applied this method to visualize the aggregation process of á-synuclein in living cells. The size of the aggregates with the temporal information was analyzed from ratio values of the blue and red fluorescence of the reconstituted FTs, from which the aggregation rates were evaluated. This method using the split FT fragments enables tracing and visualizing temporal alternations of various protein associations by single fluorescence measurements at a given time point.

Comparisons of DNA from archaic and modern humans show that these groups interbred, and in some cases received an evolutionary advantage from doing so. This process-adaptive introgression-may lead to a faster rate of adaptation than is predicted from models with mutation and selection alone. Within the last couple of years, a series of studies have identified regions of the genome that are likely examples of adaptive introgression. In many cases, once a region was ascertained as being introgressed, commonly used statistics based on both haplotype as well as allele frequency information were employed to test for positive selection. Introgression by itself, however, changes both the haplotype structure and the distribution of allele frequencies, thus confounding traditional tests for detecting positive selection. Therefore, patterns generated by introgression alone may lead to false inferences of positive selection. Here we explore models involving both introgression and positive selection to investigate the behavior of various statistics under adaptive introgression. In particular, we find that the number and allelic frequencies of sites that are uniquely shared between archaic humans and specific present-day populations are particularly useful for detecting adaptive introgression. We then examine the 1000 Genomes dataset to characterize the landscape of uniquely shared archaic alleles in human populations. Finally, we identify regions that were likely subject to adaptive introgression and discuss some of the most promising candidate genes located in these regions.

Physician study groups or task forces based at the local or state level can play an important role in monitoring and disseminating outcome data. Twelve states already have begun pilot projects to look at data on practice variations.

The aim of this study carried out in 6 commercial layer houses was to examine the effect of litter management on water content, helminth egg count and litter infectiousness with the intestinal nematodes Ascaridia galli, Heterakis gallinarum, and Capillaria spp. Three types of litter management were established in each layer house in parallel: in compartment A, litter was left undisturbed, in compartment B, wet litter was replaced and in compartment C, new litter material was added weekly. Dry matter (DM) contents of the litter and parasitological parameters (helminth egg concentration in litter samples, faecal egg counts (FECs) in the permanent layer flocks, helminth prevalence and burdens in two series of tracer animals) were determined every 4 weeks during the first 32 weeks of one laying period. DM contents of the litter varied in a broad range (48-95%); 8 weeks after onset of the study, there were significant differences between sites (P<0.001) but not between management regimes. A. galli/H. gallinarum eggs were isolated from 91% of the litter samples, whereas eggs of Capillaria spp. were only extracted from 13% of the samples. Egg concentrations in litter remained at a similar level during the observation period. Neither management regime reduced helminth egg concentrations in the litter compared to the unmanaged regime. Laying hens started excreting helminth eggs 8 weeks after introduction to the layer house. In treatment C (litter added) FECs were lower than in the unmanaged treatment A in weeks 8 (P<0.0001), 20, and 28 (both P<0.1). There was no correlation between the concentration of helminth eggs in the litter and the FECs of the layer flocks. The prevalence of A. galli in tracer animals was lower (<10%) than the prevalences of H. gallinarum (68-80%) and Capillaria spp. (30-58%). Prevalences and H. gallinarum burdens did not differ significantly between management regimes. Although high helminth egg concentrations were found in litter, the prevalence and worm burdens in tracer animals were low compared to a similar study with tracers kept in poultry runs. The reasons for this may be that poultry litter negatively affects viability and infectiousness of helminth eggs. However, underlying mechanisms need to be clarified.

Calmodulin is a calcium transducer that activates key regulatory and structural proteins through calcium-induced binding to the target proteins. A fluorescent analog of calmodulin in conjunction with ratio imaging, relative to a volume indicator, has demonstrated that calmodulin is uniformly distributed in serum-deprived fibroblasts and there is no immediate change in the distribution upon stimulation with complete serum. The same fluorescent analog of calmodulin together with steady state fluorescence anisotropy imaging microscopy has been used to define the temporal and spatial changes in calmodulin binding to cellular targets during stimulation of serum-deprived fibroblasts and in polarized fibroblasts during wound healing. In serum-deprived fibroblasts, which exhibit a low free calcium ion concentration, a majority of the fluorescent analog of calmodulin remained unbound (fraction bound, fB < 10%). However, upon stimulation of the serum-deprived cells with complete serum, calmodulin binding (maximum fB approximately 95%) was directly correlated with the time course of the elevation and decline of the free calcium ion concentration, while the contraction of stress fibers continued for an hour or more. Calmodulin binding was also elevated in the leading lamellae of fibroblasts (maximum FB approximately 50%) during the lamellar contraction phase of wound healing and was spatially correlated with the contraction of transverse fibers containing myosin II. Highly polarized and motile fibroblasts exhibited the highest anisotropy (calmodulin binding) in the retracting tails and in association with contracting transverse fibers in the cortex of the cell. These results suggest that local activation of myosin II-based contractions involves the local binding of calmodulin to target proteins. The results also demonstrate a powerful yet simple mode of light microscopy that will be valuable for mapping molecular binding of suitably labeled macromolecules in living cells.

Pulmonary tuberculosis has long been associated with the formation of cavities in the lung. Many reports in the literature indicate that the occurrence of air-fluid levels in tuberculosis is unusual. The authors present 18 cases of proved active cavitary tuberculosis where air-fluid levels occurred during the active phase of the disease. The consideration of tuberculosis in the differential diagnosis of an air-fluid containing pulmonary cavity is emphasized and the pathogenesis of cavity formation is discussed.

One of the fish species with the highest potential for aquaculture is the sharpsnout seabream, Diplodus puntazzo Cetti. Among other aspects, the development of new fish cultures requires studies of potential pathogens that may compromise survival of the fish in captivity. Moreover, both cultured and wild fish can act as sources or reservoirs of pathogens which may negatively affect other well-established cultures. We have studied the parasite fauna of the wild sharpsnout seabream, and monitored the survival of the parasites in culture conditions. The sharpsnout seabream was sampled from two different Spanish localities and examined for parasites. Additionally, 20 fish were maintained in captivity. Ten of them were examined for parasites after a period of 10 days and a further ten fish after another 10 days. All fish were parasitized with at least four species, with 19 parasite species being identified, seven of which were recorded for the first time in the sharpsnout seabream. These included Microcotyle sp., Magnibursatus bartolii, Steringotrema pagelli, Galactosomum sp., Cardiocephaloides longicollis, Caligus ligusticus and Gnathia vorax. We also report the first records of two parasite species in the wild sharpsnout seabream, the polyopisthocotylean monogeneans Atrispinum seminalis and Sparicotyle chrysophrii. Previously, these parasites had only been recorded in farmed sharpsnout seabream. Most parasites in the skin, gills and alimentary tract disappeared under the conditions of captivity, with the exception of the monogeneans of the genus Lamellodiscus. The information provided about the sharpsnout seabream parasite fauna will be useful to prevent possible problems in fish farms due to some parasite species. Many parasites of the sharpsnout seabream recorded in the present study are shared by the main fish species in Mediterranean aquaculture, the gilthead seabream, thus suggesting the possibility of cross-infections.

PURPOSE: To evaluate the prevalence and radiologic findings of annular tear (especially of contrast material enhancement), bulging disk, and disk herniation on T2-weighted and gadolinium-enhanced T1-weighted magnetic resonance (MR) images in people without low back pain (LBP) or sciatica.MATERIALS AND METHODS: Thirty-six volunteers without LBP and/or sciatica (18 with no symptoms in their lifetime and 18 who were pain free for at least 6 months) were examined with sagittal and axial T2-weighted fast spin-echo (SE) and sagittal gadolinium-enhanced T1-weighted fast SE imaging. The prevalence and MR findings of bulging disk, focal protrusion, extrusion, and nonenhancing or enhancing annular tears were assessed.RESULTS: The prevalence of bulging disk and focal disk protrusion was 81% (29 volunteers) and 33% (12 volunteers), respectively. There were no extrusions. Twenty-eight annular tears were found in 20 patients (56%); 27 tears (96%) also showed contrast enhancement.CONCLUSION: Annular tears and focal disk protrusions on MR images, with or without contrast enhancement, are frequently found in an asymptomatic population. Extruded disk herniation, displacement of nerve root, and interruption of annuloligamentous complex are unusual findings in an asymptomatic population and can be more closely related to patients with LBP or sciatica.

The excessive use of nitrogen (N) fertilizers in sustaining high rice yields due to N dynamics in tropical acid soils not only is economically unsustainable but also causes environmental pollution. The objective of this study was to coapply biochar and urea to improve soil chemical properties and productivity of rice. Biochar (5 t ha(-1)) and different rates of urea (100%, 75%, 50%, 25%, and 0% of recommended N application) were evaluated in both pot and field trials. Selected soil chemical properties, rice plants growth variables, nutrient use efficiency, and yield were determined using standard procedures. Coapplication of biochar with 100% and 75% urea recommendation rates significantly increased nutrients availability (especially P and K) and their use efficiency in both pot and field trials. These treatments also significantly increased rice growth variables and grain yield. Coapplication of biochar and urea application at 75% of the recommended rate can be used to improve soil chemical properties and productivity and reduce urea use by 25%.

Learn the latest updates to JCAHO's environment of care standards.

BACKGROUND: The rhesus (Rh) system is the second most important blood group system after ABO, with highly immunogenic antigens. Although the anti-E Rh antibody has been reported to cause hemolytic disease of the newborn and delayed hemolytic transfusion reactions, acute hemolytic transfusion reactions (AHTR) have been rarely reported.METHODS: Peripheral blood (PB) samples were screened for irregular antibodies using a commercial ID-Diacell I - II antibody screening Panel (Bio-Rad Laboratories, Glattbrugg, Switzerland) and ID-cards "LISS/Coombs" (Bio-Rad, Switzerland). The antibody was confirmed using ID DiaPanel, an antibody identification panel (Bio-Rad, Switzerland). Rh phenotyping was performed for RhC/c and RhE/e antigens using an immediate-spin tube test with monoclonal anti-C, -c, -E, and -e (OrthoClinical Diagnostics, High Wycombe, UK) in saline-filled test-tubes.RESULTS: The patient was negative for antibody screening test before transfusion. After receiving a total of 6 units of cross-matching negative RBC transfusion, the antibody screening test result increased to 2+ after showing traces and the antibody was confirmed as anti-E Rh antibody. The Rh phenotype of the patient was C (+), c (+), E (-), and e (+). In addition, we verified that all the six units of RBCs transfused were E (+) except for the two units transfused before surgery.CONCLUSIONS: Here is an unusual case of an AHTR due to the anti-E Rh antibody after E-positive RBC transfusion in a patient with Crohn's disease. Because anemia is common in patients with Crohn's disease, it is important to determine the cause of the anemia and necessary to examine the Rh phenotype before transfusions because of the high need for transfusion due to any cause. Awareness of this possibility will ensure safe blood transfusion with special care to screen for antibodies and perform Rh phenotyping, thereby minimizing morbidity and preventing potential mortality.

Inflammation is a normal host defense reaction to infections and tissue injury. In pathology, the process of inflammation is deregulated by various environmental factors, prolonged activation of Toll-like receptors (TLRs), induction of epigenetic machinery or expression of receptors for advanced glycation end-products (RAGE). In the present study, we examined immunoexpression of proteins participating in the above-mentioned mechanisms, in the brain of patients with viral meningoencephalitis. The results showed that depending on the period of the disease, the process of inflammation is deregulated in different ways. In an early period of viral meningoencephalitis, we found numerous so-called microglial nodules which were strongly immunopositive to methyl-CpG protein 2 (MeCP2). This protein is an epigenetic factor important for methylation of DNA; therefore, our results suggest that cells collected in the nodules may participate in modification of the host defense reaction. Moreover, in the early period of viral meningoencephalitis, we found that Purkinje cells of the cerebellum contain TLR3 or TLR9 receptors that can recognize viral pathogens and may activate a self-destructive mechanism in these neurons. In the later (advanced) period of viral meningoencephalitis, despite some of the above observations, RAGE protein was detected in the brain of adult and aging patients. It means that in this period of the disease, the inflammatory process may be deregulated by numerous post-translationally modified proteins that are transported to the brain after binding with activated RAGE. In addition, young patients appeared more susceptible to viral infections than adult and aging patients, because most of them died during the early period of meningoencephalitis.

BACKGROUND: In the Neotropics, nearly 35% of amphibian species are threatened by habitat loss, habitat fragmentation, and habitat split; anuran species with different developmental modes respond to habitat disturbance in different ways. This entails broad-scale strategies for conserving biodiversity and advocates for the identification of high conservation-value regions that are significant in a global or continental context and that could underpin more detailed conservation assessments towards such areas.METHODOLOGY/PRINCIPAL FINDINGS: We identified key ecoregion sets for anuran conservation using an algorithm that favors complementarity (beta-diversity) among ecoregions. Using the WWF's Wildfinder database, which encompasses 700 threatened anuran species in 119 Neotropical ecoregions, we separated species into those with aquatic larvae (AL) or terrestrial development (TD), as this life-history trait affects their response to habitat disturbance. The conservation target of 100% of species representation was attained with a set of 66 ecoregions. Among these, 30 were classified as priority both for species with AL and TD, 26 were priority exclusively for species with AL, and 10 for species with TD only. Priority ecoregions for both developmental modes are concentrated in the Andes and in Mesoamerica. Ecoregions important for conserving species with AL are widely distributed across the Neotropics. When anuran life histories were ignored, species with AL were always underrepresented in priority sets.CONCLUSIONS/SIGNIFICANCE: The inclusion of anuran developmental modes in prioritization analyses resulted in more comprehensive coverage of priority ecoregions-especially those essential for species that require an aquatic habitat for their reproduction-when compared to usual analyses that do not consider this life-history trait. This is the first appraisal of the most important regions for conservation of threatened Neotropical anurans. It is also a first endeavor including anuran life-history traits in priority area-selection for conservation, with a clear gain in comprehensiveness of the selection process.

Contractile responses of aortas and mesenteric arteries from control and 3 month streptozotocin-diabetic rats to alpha-adrenoceptor agonists were compared in the presence and absence of endothelium. In the presence of endothelium, responses of both arteries from diabetic animals to norepinephrine and methoxamine were enhanced compared to control, although no response to clonidine could be detected in arteries from either control or diabetic animals. Following endothelium removal, no significant differences were found between control and diabetic arteries in maximum contractile responses to noradrenaline or methoxamine. However, the sensitivity (pD2) of diabetic aortas to these two agonists was significantly increased, while maximum responses of diabetic aortas and mesenteric arteries to clonidine were much greater than control. In addition, no differences between control and diabetic aortas were detected when cGMP levels were measured in the absence and presence of acetylcholine. These results suggest that enhanced responsiveness of arteries from diabetic animals to alpha-adrenoceptor stimulation is not the result of a decrease in endothelium-derived relaxing factor (EDRF) release in diabetic blood vessels.

There are now many injectable implants for face remodeling since the first product appeared in Europe in 1984. The treatment regions most in demand are the cheeks, jaws, lips, and the oval of the face. The aging process is due to fat resorption over the upper two thirds of the face, in addition to the loss of elasticity. Weakness in the skin and subcutaneous fascia becomes more apparent over the lower third of the face. The fat loss together with the slack skin gives the impression of gauntness and loss of volume under the eyes (i.e., the zygomatic and palpebral areas). Treating the zygomatic bone area and subcutaneous tissue by injecting filler products will increase volume around the zygomatic malar bone and subcutaneous area. To choose an implant, we must take into account the patient's wishes, hopes (whether temporary or long-lasting effects are required), age, skin type (dry, moist, greasy, thick, or thin), and the patient's medical history to prevent obvious contraindications in the choice of implant due to type of product, especially in the case of allergies, inflamed areas, or any suspicion of autoimmune disease or recent infection.

The periphery of the vitreous body contains a population of cells termed hyalocytes. Despite the existence for more than one century of publications devoted to the pecten oculi, a convoluted coil of blood vessels that seems to be the primary source of nutrients for the avian avascular retina, little information can be found concerning the pecteneal hyalocytes. These cells are situated on the inner limiting membrane in close relationship with the convolute blood vessels. To characterize the origin and macrophagic activity of pecteneal hyalocytes, we have analysed two different stages of quail eye development using histochemistry and immunohistochemistry. Pecteneal hyalocytes express the QH1 epitope and cKit, confirming that these cells belong to the haematopoietic system. They also express vimentin, an intermediate filament protein present in cells of mesenchymal origin and very important for differentiation of fully active macrophages. However, similarly as described in porcine hyalocytes, pecteneal hyalocytes express the glial fibrillary acidic protein, a recognized neuroglial marker. Pecteneal hyalocytes did not express other neuroglial markers, such as glutamine synthetase or S100. Acidic phosphatase was activated and Lep100 was found in secondary lysosomes, confirming phagocytic activity of pecteneal hyalocytes during ocular development. Pecteneal hyalocytes strongly react with RCA-I, WFA, WGA, PNA, SNA, LEA and SBA lectins, whereas other avian macrophages from thymus and the bursa of Fabricius did not bind PNA, SNA and LEA lectins. Interestingly, WGA lectin reacts with all kinds of avian macrophages, including pecteneal hyalocytes, probably reflecting the specific binding of WGA to components of the phagocytic and endocytic pathways. In conclusion, pecteneal hyalocytes are a special subtype of blood-borne macrophages that express markers not specifically associated with the haematopoietic system.

Ochratoxins are fungal secondary metabolites that may contaminate a broad variety of foodstuffs, such as grains, vegetables, coffee, dried fruits, beer, wine and meats. Ochratoxins are nephrotoxins, carcinogens, teratogens and immunotoxins in rats and are also likely to be in humans. In 2009/2010, a survey of the presence of Ochratoxin A (OTA) in regularly hunted wild boars in the Calabria region of southern Italy detected OTA in 23 animals in the kidney, urinary bladder, liver and muscles: 1.1 &#177; 1.15, 0.6 &#177; 0.58, 0.5 &#177; 0.54 and 0.3 &#177; 0.26 &#956;g/kg, respectively. Twelve tissue samples showed levels of OTA higher than the guideline level (1 &#956;g/kg) established by the Italian Ministry of Health. In five wild boars, gross-microscopic lesions were described for the organs displaying the highest concentrations of OTA determined by HPLC-FLD analysis, i.e., the kidney, liver and urinary bladder.

In this paper, a cellulose-based Electro-Active Paper (EAPap) energy scavenging transducer is presented. Cellulose is proven as a smart material, and exhibits piezoelectric effect. Specimens were prepared by coating gold electrodes on both sides of cellulose film. The fabricated specimens were tested by a base excited aluminum cantilever beam at resonant frequency. Different tests were performed with single and multiple parallel connected electrodes coated on the cellulose film. A maximum of 131 mV output voltage was measured, when three electrodes were connected in parallel. It was observed that voltage output increases significantly with the area of electrodes. From these results, it can be concluded that the piezoelectricity of cellulose-based EAPap can be used in energy transduction application.

Paragonimus westermani is a lung fluke of humans that is usually found in the lungs but may be found elsewhere in many unusual locations. A case of pelvic paragonimiasis was found incidentally by surgical intervention of inflammatory disease and myoma uteri. She was a 51-year-old Korean woman complaining of lower abdominal pain and intermittent vaginal spotting. Numerous Paragonimus ova were observed in the resected omentum in the pelvis after total abdominal hysterectomy. It is suggested that pelvic paragonimiasis may be one of causative agents of pelvic inflammatory disease.

The effect of exercise on mare reproductive efficiency was evaluated by comparing rates of embryo recovery from mares assigned to either an exercise regimen or a non-exercise (control) regimen. Exercised mares were worked daily for 30 min under average ambient conditions of >30 degrees C and >50% humidity. Mares were inseminated during estrus and subjected to uterine flush for embryo recovery on d 7 after ovulation for two consecutive cycles. After this, mares were allocated to the opposite group and allowed an estrous cycle without reproductive manipulation; then insemination and uterine flushing were conducted on two more consecutive cycles. Prostaglandin F(2alpha) was administered on the day of uterine flush. Mare rectal temperature increased during exercise from a mean of 38 degrees C to a mean of 39.9 degrees C. Mares had ovulations from smaller follicles when exercised than they did under control conditions (39.8+/-0.5 compared with 41.5+/-0.5mm diameter; P<0.05), and had an increased time from PGF(2alpha) administration to subsequent ovulation (8.47+/-0.337 compared with 9.27+/-0.294 d; P<0.05). Embryo recovery from control mares was 22 of 35 (63%). Fewer embryos were recovered from exercised mares (11 of 32, 34%; P<0.05). The proportion of embryos classified as Grade 1 tended to be less in exercised than in non-exercised mares (4 of 11, 36% compared with 16 of 22, 73%; P=0.051). These data indicate that exercising mares in a hot and humid environment are associated with changes in ovarian follicle development and ovulation, and a reduction in embryo recovery.

Thermoneutral water immersion increases cardiac preload and changes the neuroendocrine settings of blood volume regulation. The resulting marked diuresis may lead to significant haemodynamic changes after the end of a prolonged water immersion. Ten volunteers underwent 6 h of complete thermoneutral water immersion. Changes in cardiovascular status were assessed 1 h and 16 h after water immersion. Haemodynamic changes were assessed by Doppler echocardiography. Arterial wall distensibility was estimated by pulse wave velocity analysis. One hour after water immersion, mean weight loss was 1.78 kg and urine volume amounted to 1.5 litres. Echocardiographic measurements evidenced a significant decrease in dimensions of the left cardiac chambers and inferior vena cava. The decreased cardiac preload was paralleled by a lower stroke volume and cardiac output. A peripheral vasoconstriction associated with a relative decrease in the lower limb blood flow was evidenced by an increase in carotid-pedal pulse wave velocity and by a decrease in ankle brachial index. Sixteen hours after water immersion, cardiac preload and cardiac output remained below baseline values and peripheral vascular tone was still higher than at baseline. Marked haemodynamic changes had not returned to baseline 16 h after water immersion. There is a need to design fluid-replacement protocols to improve this recovery.

The aim of the study was the evaluation of the efficiency of Western blot (EcoLine) test detecting simoultanous presence of IgM and IgG antibodies against B. burgdorferi in diagnosis of early and late stage of Lyme borreliosis. The comparison of results achieved by performing test Western-blot, ELISA (based on recombinant antigens of three genospecies of Borrelia) and EIA (based on antigens of one B. burgdorferi genospecies). The tests Western blot: EcoLine (Virotech) with antygens "in vivo", ELISA Borrelia IgM, IgG recombinant (Biomedica), EIA: B. b. ss. IgG, EIA B. garinii IgG, EIA B. afzelii IgG (TestLine) were used. Results showed efficacy of detecting IgM, IgG antibodies against VlsE simultanously and IgG antibodies against "in vivo" antigens in diagnosis of early stages of Lyme disease when atypical picture skin lessions arise diagnostic doubts and in discerning early and late stage of disease. The EIA tests based on one B. burgdoreferi genospecies seem less effective in comparison to ELISA tests based on 3 genospecies antigens.

BACKGROUND AND STUDY AIMS: This was to determine whether intervention based on additional capnographic monitoring reduces the incidence of hypoxemia during midazolam and propofol sedation for endoscopic retrograde cholangiopancreatography (ERCP).METHODS: Patients (American Society of Anesthesiologists [ASA] I – IV) scheduled for ERCP under midazolam and propofol sedation were randomly assigned to a control arm with standard monitoring or an interventional arm with additional capnographic monitoring. In both arms detection of apnea prompted withholding of propofol administration, stimulation of the patient, insertion of a nasopharyngeal tube, or further measures. The primary study end point was incidence of hypoxemia (oxygen saturation [Sao 2] below 90 %); secondary end points included occurrences of severe hypoxemia (Sao 2 ? 85 %), bradycardia, and hypotension, and sedation quality (patient cooperation and satisfaction).RESULTS: 242 patients were enrolled at three German endoscopy centers. Intention-to-treat analysis revealed no significant reduction in hypoxemia incidence in the capnography arm compared with the standard arm (38.0 % vs. 44.4 %, P = 0.314). Apnea was more frequently detected in the capnography arm (64.5 % vs. 6.0 %, P < 0.001). There were no differences regarding rates of bradycardia and hypotension. Per-protocol analysis showed lower incidence of hypoxemia in the capnography arm compared with the standard arm (31.5 % vs. 44.8 %, P = 0.048). There was one death related to sedation in the standard arm. Sedation quality was similar in the two groups.CONCLUSION: Intention-to-treat analysis showed hypoxemia incidence was not significantly lower in the additional capnography arm compared with standard monitoring. Additional capnographic monitoring of ventilatory activity resulted in improved detection of apnea.

Hyperandrogenemia in postmenopausal women requires an evaluation to exclude pathologic ovarian or adrenal causes. Our patient exhibited no signs of hypercortisolism, congenital adrenal hyperplasia, or adrenal or ovarian neoplasia based on biochemical testing and pelvic sonography. We hypothesized that unexplained androgen excess in our patient was due to the development of gonadotropin-dependent excess ovarian stromal androgen production. This syndrome may be comparable to gestational hyperreactio luteinalis where elevated gonadotropins stimulate ovarian stromal androgen production. If tumor can confidently be excluded, such women may benefit from gonadotropin suppression with long-acting GnRH-a.

In this study we examined the correlations of actual pre-morbid IQ scores (obtained from routine educational assessments) and estimated current IQ scores in 27 treatment-resistant schizophrenia patients. Pre-morbid (mean = 93) and current (mean = 83) IQ scores were significantly correlated (r = 0.807, P < 0.0001), while duration of illness (10-40 years) was unrelated to the magnitude of IQ score decline (r = -0.103, P = 0.575). These data suggest that pre-morbid IQ test scores are highly predictive of post-morbid scores.

Using the islet perifusion preparation and the isolated rat pancreas in situ perfusion preparation, the effects of disopyramide (Diso) on insulin secretion were studied. In an isolated pancreatic islet perifusion experiment, Diso (300 micrograms/ml) produced a significant increase in the immunoreactive insulin (IRI) level in the perfusate. The Diso-induced IRI rise was not affected by pretreatment with various autonomic blocking agents, such as propranolol, phentolamine or atropine. In an isolated rat pancreas in situ perfusion experiment, the IRI level in the perfusate increased significantly after the administration of Diso (300 micrograms/0.1 ml) under the perfusion of Krebs-Ringer bicarbonate buffer solution containing 0.3% glucose (0.3% glucose buffer), but not under the perfusion of Krebs-Ringer bicarbonate buffer solution containing 0.1% glucose (0.1% glucose buffer). The Diso-induced IRI rise was not affected by pretreatment with the autonomic blocking agents. Diso suppressed the IRI rise which was induced by additional glucose application (25%, 0.2 ml) under the perfusion of 0.1% glucose buffer, but not under the perfusion of 0.3% glucose buffer. Furthermore, Diso also suppressed the hypersecretion of insulin induced by increasing the glucose concentration from 0.1% to 0.3% in the perfusion fluid. The suppressing action of Diso on glucose-stimulated insulin secretion was partially recovered after pretreatment with propranolol or phentolamine. These findings show that Diso has both stimulatory and inhibitory effects on insulin secretion processes, and that the inhibitory action of Diso is suppressed by high glucose solution.

Smoking and alcohol consumption are important risk factors for pulmonary tuberculosis (PTB). A cross-sectional survey was undertaken among the Gond tribe in Jabalpur district of Madhya Pradesh, and information on smoking and alcohol consumption was collected. As compared to females, males had an increased odds for PTB prevalence (odds ratio (OR) 3.2; 95% CI 486.4-1358.4; p=0.01). Similarly smokers and alcohol consumers had an increased odds for PTB compared to non-smokers and non-alcohol consumers, respectively [(OR 3.2; 95% CI 516.4-1986.4; p=0.003); (OR 3.2; 95% CI 480.8-2254.8; p=0.009)]. Persons who were both smokers and alcohol consumers had an equally increased odds of PTB than those who did not smoke and consumed alcohol (OR 4.1; 95% CI 477.6-2581.6; p=0.001). The study findings highlight the need to develop and implement culturally appropriate awareness raising activities among the tribal community to support TB control efforts.

Corticospinal tract (CST) axons from one hemisphere normally extend and terminate predominantly in the contralateral spinal cord. We previously showed that deleting the gene phosphatase and tensin homolog (PTEN) in the sensorimotor cortex enables CST axons to regenerate after spinal cord injury and that some regenerating axons extend along the "wrong" side. Here, we characterize the degree of specificity of regrowth in terms of laterality. PTEN was selectively deleted via cortical adeno-associated virus (AAV)-Cre injections in neonatal PTEN-floxed mice. As adults, mice received dorsal hemisection injuries at T12 or complete crush injuries at T9. CST axons from one hemisphere were traced by unilateral biotinylated dextran amine (BDA) injections in PTEN-deleted mice with spinal cord injury and in noninjured PTEN-floxed mice that had not received AAV-Cre. In noninjured mice, 97.9 ± 0.7% of BDA-labeled axons in white matter and 88.5 ± 1.0% of BDA-labeled axons in gray matter were contralateral to the cortex of origin. In contrast, laterality of CST axons that extended past a lesion due to PTEN deletion varied across animals. In some cases, regenerated axons extended predominantly on the ipsilateral side; in other cases, axons extended predominantly contralaterally, and in others, axons were similar in numbers on both sides. Similar results were seen in analyses of cases from previous studies using short hairpin (sh)RNA-mediated PTEN knock-down. These results indicate that CST axons that extend past a lesion due to PTEN deletion or knock-down do not maintain the contralateral rule of the noninjured CST, highlighting one aspect of how the resultant circuitry from regenerating axons may differ from that of the uninjured CST. J. Comp. Neurol. 524:2654-2676, 2016. © 2016 Wiley Periodicals, Inc.

Cerivastatin is a new but structurally distinct 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor ("statin"). It effectively decreases low-density lipoprotein (LDL) cholesterol at 1% of the doses of other currently available statins. The toxicology of cerivastatin was evaluated in a comprehensive program of studies including: (1) single- and multiple-dose toxicity studies in rats, mice, minipigs, dogs, and monkeys; (2) reproductive toxicity studies in rats and rabbits; (3) in vitro and in vivo mutagenicity assays in rats and mice; and (4) carcinogenicity studies in rats and mice. In addition, studies were undertaken to investigate the effects of cerivastatin on lens opacity, testicular tissue, and hemorrhage in dogs. Oral administration of single and multiple doses of cerivastatin over periods ranging from 4 weeks to 24 months was generally well tolerated. Adverse effects were similar to those observed with other statins and primarily involved the liver and muscle tissue. At the high doses used in the toxicologic studies, cerivastatin caused elevations in serum transaminases and creatine phosphokinase levels as well as some degeneration of muscle fibers in rats, mice, dogs, and minipigs. In dogs, the species most sensitive to statins, cerivastatin caused erosions and hemorrhages in the gastrointestinal tract, bleeding in the brain stem with fibroid degeneration of vessel walls in the choroid plexus, and lens opacity. Apart from minor morphologic changes in the testicular tissue of dogs--the only organ for which a comparably low margin of safety was observed--cerivastatin had no significant effects on the male or female reproductive system. Cerivastatin also caused no primary embryotoxic or teratogenic effects. With the exception of cerivastatin-induced effects on the eyes and testicles, administration of mevalonic acid reversed the toxicologic effects of cerivastatin, indicating that the toxic effects were related to its mode of action and not to any intrinsic toxicity of the molecule itself. There was no evidence that cerivastatin had any mutagenic effects and, in contrast to other statins, high doses of cerivastatin did not induce tumors in rats. The main metabolite of cerivastatin was well tolerated systemically in all animals, including dogs. Overall, cerivastatin has a similar toxicologic profile to other statins and is a well-tolerated HMG-CoA reductase inhibitor.

BACKGROUND: The authors report the long-term treatment results for advanced stage base of tongue (BOT) and tonsillar fossa (TF) carcinomas treated with surgery and postoperative radiation therapy (RT) at Memorial Sloan-Kettering Cancer Center.METHODS: Between 1973 and 1986, 51 patients with squamous cell carcinoma of the BOT (n = 31 patients) and TF (n = 20 patients) were treated with surgery plus RT. Indication(s) for RT included: advanced disease (Stage T3/T4, 34 patients [66%]); close or positive margins (33 patients, 64%) and multiple positive neck nodes (43 patients, 84%).RESULTS: The 7-year actuarial local control rates for BOT and TF lesions were 81% and 83%, respectively. Local control was achieved in 17 of 18 (94%) patients with T3 lesions, and 12 of 16 (75%) patients with T4 lesions. Among patients with positive or close margins who received postoperative doses of 60 Gy or more, the long-term control rate was 93%. The presence of a treatment interruption had a negative effect on the local control rates. The actuarial control among patients who required a treatment break was 64%; for those not requiring interruption of their treatment, the actuarial control was 93% (P = 0.05). At 7 years, the overall survival for all patients was 52%, and the disease-free survival was 64%. The actuarial incidence of neck failure was 21% and 18% for BOT and TF, respectively. The likelihood of having distant metastasis at 7 years for all patients was 30%. The actuarial incidence of having a second malignancy was 35% for patients with BOT disease. Second malignancy was not observed among patients with TF lesions.CONCLUSIONS: The authors conclude that surgery and postoperative RT can provide excellent long-term, disease-control rates for patients with advanced BOT and TF tumors. However, current strategies for BOT lesions have been directed at tongue preservation without surgery.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of at the request of the Editors-in-Chief. After a thorough investigation, the Editors have concluded that the acceptance of this article was partly based upon the positive advice of three illegitimate reviewer reports. The reports were submitted from email accounts which were provided by the corresponding author C.A. Damalas as suggested reviewers during the submission of the article. Although purportedly real reviewer accounts, the Editors have concluded that these were not of appropriate, independent reviewers. This manipulation of the peer-review process represents a clear violation of the fundamentals of peer review, our publishing policies, and publishing ethics standards. Apologies are offered to the reviewers whose identity was assumed and to the readers of the journal that this deception was not detected during the submission process.

The karyotype of specimens identified as Calomys lepidus, trapped at 3600 m above sea level in the Puna region, northwestern Argentina, was studied. All specimens analysed showed a 2n = 44 (NF(a) = 68) asymmetrical karyotype with 13 pairs of metacentric/submetacentric autosomes and 7 pairs of telocentric chromosomes. The X was a medium-sized submetacentric and the Y a small submetacentric chromosome. This karyotype was quite different from that previously described for C. lepidus from Peru (2n = 36, NF(a) = 68). However, both karyotypes may be easily interrelated by means of four centric fusions, and the chromosome complement of Punian C. lepidus fitted into a previously proposed chromosomal phylogeny of the genus. In addition, the spermatozoa of specimens corresponded to a morphological pattern previously described for other species of Calomys.

In a prospective epidemiological longitudinal study of children (n = 399) from age 8 to 18 years, children with specific reading retardation (n = 37) were identified by the modified Research Diagnostic Criteria of ICD-10. The group with specific reading retardation was compared with a group with other specific developmental disorders (n = 62), a group of children with normal intelligence (n = 285) and a group of children with below average intelligence (n = 15). No correlation was found between reading retardation and pre- and perinatal complications. Children with reading retardation suffered from environment-related stress factors in early childhood and adverse familial conditions at 8 years and the educational level of the mother was significantly lower. The number of additional psychiatric symptoms was increased at ages 8, 13 and 18. Conduct disorders, in particular, were more frequent in children with specific reading retardation and the rate of juvenile delinquency was increased (25%). The non-verbal intelligence remained constant between ages 8 and 13, and spelling performance developed parallel to the control group with normal intelligence. Only one out of three showed a significant improvement in spelling ability.

INTRODUCTION: Considering a poorer diagnostic accuracy of exercise stress test in women, echocardiographic stress tests are often recommended for the diagnosis of coronary artery disease (CAD) in this patient group.OBJECTIVES: The aim of the study was to compare the diagnostic value of a modified protocol of dobutamine-atropine stress echocardiography between men and women.PATIENTS AND METHODS: This was a prospective study including 250 patients with symptoms suggesting CAD. Coronary anatomy was examined in 248 subjects, and 1 female patient was excluded owing to coronary anomaly. We analyzed the results of dobutamine stress echocardiography with early atropine administration separately for patients with a history of myocardial infarction (109 women and 138 men; mean age, 62 ±9 years; group A) and patients without such history (72 women and 71 men; mean age, 62 ±9 years; group B). Atropine at a dose of up to 2 mg was administered after dobutamine infusion of 20 ìg/kg/min. Coronary luminal stenosis of 50% or more in diameter in the left main coronary artery and of 70% and more in the other arteries was considered significant.RESULTS: In group A, echocardiography had higher specificity and negative predictive value in women compared with men (84.5% vs. 64.4%, P = 0.001, and 92.3% vs. 64.4%, P <0.0001, respectively). The accuracy was 85.3% and 76.8% in women and men, respectively (P = 0.03). In group B, a higher specificity was observed in women compared with men (82.6% vs. 60%, P = 0.01), but the accuracy was similar between the sexes.CONCLUSIONS: Dobutamine stress echocardiography with early atropine administration offers a higher diagnostic value in women, especially with regard to specificity.

Nano-silver colloid was synthesized by using microwave method on the mixtures of sodium citrate solution and silver nitrate solution. The method has advantages of fast heating speed, uniform temperature distribution and easily controlled reaction conditions. The sizes and size distributions of the silver particles were characterized by means of quasi-elastic laser scattering (QLS). The average particles size was (53.27 +/- 2.65) nm and the size of the particles was mainly distributed around 56 nm. Surface-enhanced Raman spectra of the degradation products from goat horn were obtained with silver colloid as active substrate. It was observed that the Raman signal of SERS was enhanced significantly compared with that of regular Raman spectrum, especially at the Raman bands of 659, 830, 850, 929, 999, 1 028, 1 280, 1 439 and 1 599 cm(-1) which reflect the biochemical components in degradation products. The characteristic Raman bands of degradation products from goat horn were preliminary assigned. The assignments showed that the main constituents of the degradation products from goat horn were amino acids and polypeptides. It was for the first time that Surface-enhanced Raman spectroscopy was used to detect trace degradation products from the horns. Raman signal enhancement can be obtained with high sensitivity for the trace concentrations as low as ppm level. It is concluded that surface-enhanced Raman spectroscopy can provide a fast, direct and precise detecting method for the detection of trace degradation solution from horns.

A subdural haematoma is described in which a definite computed tomographic (CT) scan diagnosis was made only after contrast enhancement had been achieved by the inhalation of xenon. The different types of enhancement obtained with iodide containing contrast media and with xenon are discussed. The use of xenon to obtain further information in conditions which are inadequately elucidated by conventional CT must be balanced against its anaesthetic effects and relatively high cost.

RFamide-related peptide (RFRP-3) is a regulator of GnRH secretion from the brain, but it can also act in human ovary to influence steroidogenesis. We aimed to study the putative local role of RFRP-3 in the ovary and its potential participation in the development of a polycystic ovary phenotype induced by chronic sympathetic stress (cold stress). We used adult Sprague–Dawley rats divided into control and stressed groups. In both groups, we studied the effect of intraovarian exposure to RFRP-3 on follicular development and plasma ovarian steroid concentrations. We also tested the effect of RFRP-3 on ovarian steroid production in vitro. Chronic in vivo intraovarian exposure to RFRP-3 decreased basal testosterone concentrations and cold stress-induced progesterone production by the ovary. In vitro, RFRP-3 decreased hCG-induced ovarian progesterone and testosterone secretion. Immunohistochemistry and mRNA expression analysis showed a decrease in Rfrp and expression of its receptor in the ovary of stressed rats, a result which is in line with the increased testosterone levels found in stressed rats. In vivo application of RFRP-3 recovered the low levels of secondary and healthy antral follicles found in stressed rats. Taken together, our data indicate a previously unknown response of hypothalamic and ovarian RFRP-3 to chronic cold stress, influencing ovarian steroidogenesis and follicular dynamics. Thus, it is likely that RFRP-3 modulation in the ovary is a key component of development of the polycystic ovary phenotype.

Although estrogens exert many functions on vertebrate brains, there is little information on the relationship between brain aromatase and estrogen receptors. Here, we report the cloning and characterization of two estrogen receptors, alpha and beta, in pejerrey. Both receptors' mRNAs largely overlap and were predominantly expressed in the brain, pituitary, liver, and gonads. Also brain aromatase and estrogen receptors were up-regulated in the brain of estradiol-treated males. In situ hybridization was performed to study in more detail, the distribution of the two receptors in comparison with brain aromatase mRNA in the brain of adult pejerrey. The estrogen receptors' mRNAs exhibited distinct but partially overlapping patterns of expression in the preoptic area and the mediobasal hypothalamus, as well as in the pituitary gland. Moreover, the estrogen receptor alpha, but not beta, were found to be expressed in cells lining the preoptic recess, similarly as observed for brain aromatase. Finally, it was shown that the onset expression of brain aromatase and both estrogen receptors in the head of larvae preceded the morphological differentiation of the gonads. Because pejerrey sex differentiation is strongly influenced by temperature, brain aromatase expression was measured during the temperature-sensitive window and was found to be significantly higher at male-promoting temperature. Taken together these results suggest close neuroanatomical and functional relationships between brain aromatase and estrogen receptors, probably involved in the sexual differentiation of the brain and raising interesting questions on the origin (central or peripheral) of the brain aromatase substrate.

INTRODUCTION: Delayed gastric emptying and feed intolerance occur frequently in the critically ill. In these patients, gastric motor responses to nutrients are disturbed. Peptide YY (PYY) slows gastric emptying. The aim of this study was to determine fasting and nutrient-stimulated plasma PYY concentrations and their relationship to cholecystokinin (CCK) in critically ill patients.METHODS: Studies were performed in 19 unselected mechanically ventilated critically ill patients (12 males; 48 +/- 7 years old) in a randomised, single-blind fashion. Subjects received a 60-minute duodenal infusion of Ensure at either 1 or 2 kcal/minute. Blood samples were collected at baseline and at 20, 40, 60, and 180 minutes following commencement of the nutrient infusion for the measurement of plasma PYY and CCK concentrations (using radioimmunoassay). Patient data were compared to 24 healthy subjects (17 males; 43 +/- 2 years old).RESULTS: Fasting PYY concentration was higher in patients (P < 0.05), particularly in those with feed intolerance (P < 0.05). Plasma PYY concentrations were higher in patients during nutrient infusion (area under the curve [AUC] at 1 kcal/minute: 2,265 +/- 718 versus 1,125 +/- 138 pmol/l.min, P < 0.05; at 2 kcal/minute: 2,276 +/- 303 versus 1,378 +/- 210 pmol/l.min, P = 0.01) compared to healthy subjects. The magnitude of PYY elevation was greater in patients during the 1 kcal/minute infusion (AUC: 441 +/- 153 versus 186 +/- 58 pmol/l.min, P < 0.05), but not the 2 kcal/minute infusion. Fasting and nutrient-stimulated plasma CCK concentrations were higher in patients (P < 0.05). There was a relationship between plasma PYY and CCK concentrations during fasting (r = 0.52, P < 0.05) and nutrient infusion (r = 0.98, P < 0.0001).CONCLUSION: In critical illness, both fasting and nutrient-stimulated plasma PYY concentrations are elevated, particularly in patients with feed intolerance, in conjunction with increased CCK concentrations.

Heart hexokinase monomer has a molecular weight of 97000 and so20,w 5.2 S. It exists in equilibrium with dimer of 194000 molecular weight and so20,w 8.1 S. The proportions of monomer and dimer presence of added ligands are 91% and 9% respectively. The existence of these forms may be demonstrated by separation on electrophoresis or chromatography. In the presence of the regulatory molecule glucose 6-phosphate, the dimer form of the enzyme is favoured. The glucose 6-phosphate mediated dimerisation is abolished in the presence of phosphate or ATP-Mg and less effectively by free ATP. Glucose has no effect on the manomer-dimer equilibrium. On prolonged storage of hexokinase in glucose 6-phosphate polymers are also formed and polymerisation is further enhanced by removal of the ligand.

PURPOSE: To describe a modified technique of parotidectomy using face-lift approach and sternocleidomastoid flap.METHODS: Forty-six patients were divided into two groups; group 1 (23 cases) using veiled incision and sternocleidomastoid flap, group 2 (23 cases) using traditional incision (Blair's approach) without sternocleidomastoid flap. Postoperative complications included temporary facial paralysis and salivary fistula. The follow-up period was 2 years, oncological recurrence was compared between the two groups. The incidence of Frey's syndrome and the feeling of the region around the auricular lobule were evaluated. The data was analyzed using SPSS10.0 software package with Student's t test and Chi-square test.RESULTS: During the follow up period, the patients in the group 1 showed better aesthetic results than those in the group 2 and without obvious scar and deformity. There was no significant difference between these two groups in temporary facial paralysis, salivary fistula, tumor recurrence, Frey's syndrome, the feeling of the region around the auricular lobule.CONCLUSION: The modified technique of parotidectomy using veiled incision and sternocleidomastoid flap greatly reduces the disadvantages of traditional parotidectomy and provides better aesthetic results.

Cryopreservation is one of the key enabling technologies for tissue engineering and regenerative medicine, which can provide reliable long-term storage of engineered tissues (ETs) without losing their functionality. However, it is still extremely difficult to design and develop cryopreservation protocols guaranteeing the post-thaw tissue functionality. One of the major challenges in cryopreservation is associated with the difficulty of identifying effective and less toxic cryoprotective agents (CPAs) to guarantee the post-thaw tissue functionality. In this study, thus, a hypothesis was tested that the modulation of the cytoskeletal structure of cells embedded in the extracellular matrix (ECM) can mitigate the freezing-induced changes of the functionality and can reduce the amount of CPA necessary to preserve the functionality of ETs during cryopreservation. In order to test this hypothesis, we prepared dermal equivalents by seeding fibroblasts in type I collagen matrices resulting in three different cytoskeletal structures. These ETs were exposed to various freeze/thaw (F/T) conditions with and without CPAs. The freezing-induced cell-fluid-matrix interactions and subsequent functional properties of the ETs were assessed. The results showed that the cytoskeletal structure and the use of CPA were strongly correlated to the preservation of the post-thaw functional properties. As the cytoskeletal structure became stronger via stress fiber formation, the ET's functionality was preserved better. It also reduced the necessary CPA concentration to preserve the post-thaw functionality. However, if the extent of the freezing-induced cell-fluid-matrix interaction was too excessive, the cytoskeletal structure was completely destroyed and the beneficial effects became minimal.

OBJECTIVE: To analyze the prevalence of pressure injuries, diabetic and vasculogenic ulcers and associated factors in older adults attended in primary care.METHOD: A cross-sectional, analytical study with older adults attended in the Family Health Strategy in a Brazilian municipality. Data collection was performed from January to March 2016 using interviews and evaluations of injuries. The variables were submitted to the multivariate logistic regression model using the odds ratio, with their respective 95% confidence intervals and significance set at <0.05.RESULTS: 339 older adults participated in the study. The mean age was 71.1 years, 67.3% were female, 44% were illiterate, 85% had low family income, 91.7% had underlying diseases, 37.2% had dietary restrictions, and 76.1% did not practice physical activity. The prevalence of pressure injury was 5.0%, diabetic ulcer 3.2%, and vasculogenic ulcer 2.9%. Not working and not regularly practicing physical activity increased the chances of presenting these injuries by 1.5 and 2.3 times, respectively. Being actively mobility and not having dietary restrictions were protective factors for not developing chronic wounds.CONCLUSION: The prevalence of injuries among older adults was high, and its occurrence is associated with socioeconomic and clinical characteristics.

We have prepared a magnetite encapsulated polymer nanocomposite (MEPN) by an emulsification-diffusion technique and found that the encapsulation efficiency could be precisely controlled according to the portion of magnetite and the capping ligand that covers the surface of the magnetite nanoparticles. The field-dependence and temperature dependence on magnetization, measured by a superconducting quantum interference device, demonstrate that there was no size effect of the magnetite nanoparticles on the encapsulation behavior. The size distribution and T2 relaxivity of prepared MEPNs were measured using magnetic resonance imaging for analysis of the effect of aggregation and it was verified that aggregates of the magnetite nanoparticles provide enhanced relaxation ability.

The treatment of anxiety disorders has considerably improved and become more precise over the last two decades, on the basis of empirical results. The evidence of their efficacy is best established for panic disorder, obsessive-compulsive disorder and social phobia. The pharmacological treatment and the psychotherapeutical approaches of these three categories will be briefly reviewed, using data from well conceived studies and recommendations of experts. Thus, for each of these disorders, this article attempts to provide the physician with practical treatment guidelines.

Abstract Esthesioneuroblastoma, also known as olfactory neuroblastoma, is an uncommon malignant neoplasm arising from the olfactory epithelium in the roof of the nasal cavity. There are very few case reports published worldwide. The common presenting symptoms of Esthesioneuroblastoma are unilateral nasal obstruction (70%), epistaxis (50%), anosmia, rhinorrhoea, facial pain, headache, excessive lacrimation and rarely proptosis and visual disturbance. Apart from being locally aggressive, it metastasizes by haematogenous and lymphatic routes. We report an extremely rare case of esthesioneuroblastoma in a 20-year-old man with orbital involvement presenting as dystopia. This rare tumour should be considered in the differential diagnosis for young patients presenting to ophthalmic outpatient department with dystopia.

Non-invasive respiratory support is increasingly popular but is associated with complications including nasal trauma. The present report describes a novel method of oral continuous positive airway pressure (CPAP) delivery in an extremely premature infant with severe nasal septum erosion. The distal end of a cut down endotracheal tube was passed through a small hole made in the teat of a dummy (infant pacifier) and sutured in place. The dummy was secured in the infant's mouth and CPAP was delivered to the pharynx. The device was well tolerated and the infant was successfully managed using this technique for 48 days, avoiding endotracheal intubation and ventilation.

Anthropogenic noise is prevalent across the globe and can exclude birds from otherwise suitable habitat and negatively influence fitness; however, the mechanisms responsible for species' responses to noise are not always clear. One effect of noise is a reduction in effective acoustic communication through acoustic masking, yet some urban songbirds may compensate for masking by noise through altering their songs. Whether this vocal flexibility accounts for species persistence in noisy areas is unknown. Here, we investigated the influence of noise on habitat use and vocal frequency in two suboscine flycatchers using a natural experiment that isolated effects of noise from confounding stimuli common to urban habitats. With increased noise exposure, grey flycatcher (Empidonax wrightii) occupancy declined, but vocal frequency did not change. By contrast, ash-throated flycatcher (Myiarchus cinerascens) occupancy was uninfluenced by noise, but individuals in areas with greater noise amplitudes vocalized at a higher frequency, although the increase (?200 kHz) may only marginally improve communication and may represent a secondary effect from increased vocal amplitude. Even so, the different flycatcher behavioural responses suggest that signal change may help some species persist in noisy areas and prompt important questions regarding which species will cope with an increasingly noisy world.

The aim of this study was to determine the effect of starvation on the transport of sodium and chloride ions in the epithelium of rabbit caecum. The experiment consisted in measuring transepithelial electrical potential (PD in mV) and the transepithelial electrical potential difference (dPD in mV) of an isolated fragment of rabbit caecum, before and after 4-day-long starvation. The studied tissue was incubated in Ringer solution and subsequently ion transport was modified through incubation in the Ringer solution supplemented with amiloride or/and bumetanide. It was demonstrated that the values of electrophysiological parameters of the tissue fragments of caecum from starved rabbits were substantially lower than the values for the fragments of control caecum. A similar relationship was observed also in the reaction of this tissue to mechanical stimuli. After the incubation of the caecum tissue fragments in the presence of amiloride or/and bumetanide, the value of transepithelial electrical potential and the sensitivity to mechanical stimuli decreased in both groups studied. Experimental data presented in this paper indicate that the starvation process has effect on lowering sodium and chloride ion transport and decreasing sensitivity of the epithelium of the caecum to mechanical stimuli.

We have previously shown that high human papillomavirus (HPV) 16 load in Papanicolaou smears negative for dysplasia is strongly associated with risk for carcinoma in situ (CIS) of the cervix. Here we study the amount of HPV DNA for some of the most frequent high-risk HPV types as determinants of progression to cervical CIS. Real-time PCR is used to estimate the normalized viral load of HPV 16, 18, 31, 33, 35, 39, 45, 52, 58 and 67 in 457 cases of cervical CIS and 552 matched population controls. A total of 2,747 archival Pap smears from gynecologic health examinations, collected over a period of up to 26 years, were analyzed to assess viral load during the infection history. Cervical smear samples differ widely in amount of DNA, underscoring the need for normalization of HPV load to number of cells in the sample. The risk of developing cervical CIS increases with higher viral load for most of the HPV types studied. The range of copy numbers per cell does not differ between HPV types but the odds ratio for CIS in the percentile with highest viral load is substantially higher for HPV 16 (OR = 36.9; 95% CI = 8.9-153.2) than for HPV 31 (OR = 3.2; 95% CI = 1.1-9.1) or HPV 18/45 (OR = 2.6; 95% CI = 1.0-6.4). Therefore, HPV viral load may be predictive of future risk of cervical CIS at a stage when smears are negative for squamous abnormalities, but differences between HPV types need closer attention.

Atomic boundaries are defined within the topological theory of atoms in molecules as zero-flux surfaces in the gradient of electron density. The so-defined atomic surfaces often have quite complicated shapes that reflect the local characteristics of the electron distribution. A highly portable computer visualization program, called RhoScope, that displays the zero-flux atomic surfaces is described in this article. Examples of atomic surfaces in the C60 cluster and the C2H2LiCl carbenoid, rendered with the help of RhoScope, are presented.

Henna is a traditional cosmetic agent and is used worldwide. It is used worldwide not only as a cosmetic agent to stain the hair, skin and nails but also is applied to the body on lesions in the treatment of seborrheic dermatitis or fungal infections. Different pathologies have been described as caused by henna. The aim of this study is to draw attention to the adverse effects of henna, applied over the whole body, observed in glucose-6-phosphate dehydrogenase (G6PD) enzyme deficient siblings. In the present paper, we report on two siblings with G6PD deficiency who developed haemolytic anaemia following topical application of henna to their whole body to treat skin lesions. Their parents were also found to be G6PD deficient. Even though anti-inflammatory, analgesic and antipyretic effects of henna have been shown, it may cause severe side-effects in some cases. For this reason, especially, in the regions where G6PD enzyme deficiency is common, people should be informed about the side-effects of topical henna application and clinicians should be aware of these manifestations.

Growth on media containing 1.5% NaCl is one of the criteria for phenotypical differentiation of Campylobacter laridis from other thermophilic Campylobacter spp. Campylobacter isolates from birds and Campylobacter type strains could be adapted to growth at 3% NaCl within 19 to 72 subsequent passages on nutrient agar with increasing salt contents. The acquisition of salt-tolerance was stable after ten passages on media without salt and did not induce changes in other phenotypical characteristics. The results of slide agglutination demonstrate changes in the antigenic pattern of the Campylobacter strains after growth in salt. Heat-labile and heat-stable antigens of the salt-tolerant variants of Campylobacter type strains differed from those of the parent strains.

In the paper an attempt is made to describe important features in the anatomy and pathology of the Alsation's dentition and how if differs from the human, thus leading to other therapeutic measures. The experience of the author is based upon examination and treatment of 80 institutionalized Alsations bred at the school of dogs in the Royal Danish Air Force, Karup. The dogs are submitted to regular veterinary control every 3 months. Two case reports describe typical treatments performed at the Infirmary for dogs.

PURPOSE: The successful use of fondaparinux in a hemodialysis patient with heparin-induced thrombocytopenia type II (HIT II) is reported.SUMMARY: An 85-year-old, 68-kg Caucasian woman came to the emergency department with shortness of breath and exertional chest pain radiating to the neck. Testing revealed non-ST-segment elevation myocardial infarction, severe coronary artery disease, mitral regurgitation, left ventricular dysfunction, an ejection fraction of 25-30%, and pulmonary arterial hypertension. I.V. unfractionated heparin was given for therapeutic anticoagulation per hospital protocol and discontinued on hospital day 3 before mitral valve repair and coronary bypass procedure. Postoperatively unfractionated heparin and low-molecular-weight heparin were avoided because of a reduction in the platelet count and suspicion of HIT. Instead, the patient was placed on sequential compression devices in addition to aspirin for prophylaxis of deep venous thrombosis. By postoperative day 6, the patient's platelet count dropped 76% from baseline, and the patient was found to have heparin-dependent platelet factor 4 antibodies. Argatroban infusion was initiated but discontinued after 2 days due to bleeding. Fondaparinux was ordered for anticoagulation therapy. By hospital day 8, the patient developed renal insufficiency requiring hemodialysis and adjustment of the fondaparinux regimen. During the 30-day course of fondaparinux, the patient did not experience thromboembolic events or bleeding and did not require transfusions. There was no clotting within hemodialysis membranes, and her hepatic function improved by the time of her discharge.CONCLUSION: Fondaparinux was used in a hemodialysis patient with HIT II without the development of thromboembolic, hemodialysis-clotting, thrombocytopenic, or hemorrhagic complications. The patient's platelet count remained in the normal range during the 30-day course of fondaparinux.

AIM: Steroid-sparing effect of sublingual immunotherapy (SLIT) in mono/polisensitized asthmatic children were evaluated.MATERIALS AND METHODS: Children undergoing allergen-specific SLIT between 2010 and 2014 were included. Asthma control and usage/dose of inhaled corticosteroid (ICS) in the previous year was determined. Asthma control without ICS need ?6 months was defined as 'ICS avoidance'.RESULTS: 90 children (mean ± SD age 8.92 ± 4.17 years) were enrolled, 56.7% (n = 60) being polysensitized. Mono, 2-simultaneous and multiple-pollen-mix allergen SLIT were prescribed in 84.4, 17.8 and 7.8%, respectively. ICS was avoided in 70%, with no significant difference in mono- versus poly-sensitized patients. ICS-avoidance rates in mono-allergen, pollen-mixture and 2-simultaneous-allergen SLIT were 93.6, 83.3 and 73.7%, respectively. Longer-duration SLIT resulted in significantly more ICS-avoidance (p:0.0001).CONCLUSION: SLIT with mono/multiple-mixed/simultaneous allergens in childhood asthma resulted in retained-avoidance of ICS. Steroid-sparing effect of SLIT in polysensitized children warrants further investigation.

The efficacy of amlodipine (AML) was tested in hypertensive cats in a placebo-controlled, randomized, blinded clinical trial. Five cats were randomized to receive 0.625 mg AML once daily and 4 cats to receive placebo (PLA) once daily. The average systolic blood pressure (SBP) recorded by the Doppler method on day 0 was 212 +/- 21 mm Hg in the AML group and 216 +/- 32 mm Hg in the PLA group. On day 7, the cats receiving AML had a significantly lower average daily SBP (160 +/- 30 mm Hg) but SBP in the PLA group was unchanged (207 +/- 31 mm Hg). On day 7, all cats receiving PLA and one cat receiving AML were crossed over to the other group because of inadequate response. Blood pressure did not decrease adequately in 3 cats by day 14 (7 days of PLA and 7 days AML) and the treatment code was broken. Each of these cats was subsequently administered 1.25 mg AML daily. Cats requiring 1.25 mg AML once daily (6.1 kg +/- 0.7 kg) weighed significantly more than cats that responded to 0.625 mg AML once daily (4.1 +/- 0.7 kg). The average daily SBP recorded in the 6 cats that completed the study was significantly lower after 16 weeks of treatment (152 +/- 14 mm Hg) compared to day 0 (221 +/- 24 mm Hg). Three cats were euthanized before completion of the study. All 3 cats were responders to AML on day 7. SBPs measured 24 hours after AML administration were similar to the average daily SBP, suggesting that AML effectively controlled SBP for a 24-hour period. AML was shown to be an effective once-daily antihypertensive agent when administered to cats at a dosage of 0.18 +/- 0.03 mg/kg sid.

Forty-eight patients complaining of insomnia were studied at two sleep laboratories using an identical protocol to evaluate hypnotic efficacy. All met the screening requirement of a mean sleep latency of 30 min or greater on 3 laboratory nights following an adaptation night. Of these patients 34 still complaining of insomnia were screened a second time 2 to 6 months later. Sixteen of the 34 failed the second screen. Sleep parameters for the 34 on screen 1 compared with screen 2 were the same except for sleep latency (the eligibility criteria), which was significantly shorter. There was no evidence of a systematic difference between laboratories, a change in procedure from screen 1 to 2, or a systematic loss of patients from screen 1 to 2. The data show that the statistical phenomenon of regression toward the mean must be considered in designing hypnotic efficacy studies.

PURPOSE: We report two cases of ileoanal J-pouch rupture after rapid consumption of high-fiber, high-calorie meals.METHOD: We review the food intake, presentation, laboratory and radiographic data, and course of two patients who developed ileoanal J-pouch perforation after rapid consumption of meals rich in fiber or calories or both. The potential association between food consumption and rupture is explored.RESULTS: The authors propose that the rapid ingestion of a high-fiber, high-calorie meal may lead to an acute intraluminal pressure elevation or a closed-loop obstruction. These effects may be the basis for an association between food ingestion patterns and perforation at the distal transection site in an ileoanal J-pouch.CONCLUSION: The authors hypothesize that the rapid ingestion of a high-fiber, high-calorie meal may be associated with J-pouch perforation. Further investigative efforts are needed to confirm this association and to evaluate whether a causal relationship is present. If causality is established, physicians may develop a higher index of suspicion for pouch rupture in patients who present with abdominal disturbances after the rapid ingestion of a high-fiber, high-calorie meal.

BACKGROUND: Children with cow's milk allergy (CMA) have an increased risk of other allergic manifestations (AMs).OBJECTIVE: We performed a parallel-arm randomized controlled trial to test whether administration of an extensively hydrolyzed casein formula (EHCF) containing the probiotic Lactobacillus rhamnosus GG (LGG) can reduce the occurrence of other AMs in children with CMA.METHODS: Children with IgE-mediated CMA were randomly allocated to the EHCF or EHCF+LGG groups and followed for 36 months. The main outcome was occurrence of at least 1 AM (eczema, urticaria, asthma, and rhinoconjunctivitis). The secondary outcome was tolerance acquisition, which was defined as the negativization of a double-blind food challenge results at 12, 24, and 36 months. AMs were diagnosed according to standardized criteria. Tolerance acquisition was evaluated every 12 months.RESULTS: A total of 220 children (147 boys [67%]) with a median age of 5.0 months (interquartile range, 3.0-8.0 months) were randomized; 110 children were placed in the EHCF group, and 110 children were placed in the EHCF+LGG group. In the complete case analysis the absolute risk difference for the occurrence of at least 1 AM over 36 months was -0.23 (95% CI, -0.36 to -0.10; P < .001), and the absolute risk difference for the acquisition of cow's milk tolerance was 0.20 (95% CI, 0.05-0.35; P < .01) at 12 months, 0.24 (95% CI, 0.08-0.41; P < .01) at 24 months, and 0.27 (95% CI, 0.11-0.43; P < .001) at 36 months. In the sensitivity analysis the effect size of the main outcome was virtually unchanged when the occurrence of AMs was assigned to all 27 missing children.CONCLUSIONS: EHCF+LGG reduces the incidence of other AMs and hastens the development of oral tolerance in children with IgE-mediated CMA.