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OBJECTIVE: The present study aimed to establish a cerebral schistosomiasis model in rabbits, to provide a valuable tool for morphological analysis, clinical manifestation observation, as well as investigations into immunological reactions and pathogenesis of focal inflammatory reaction in neuroschistosomiasis (NS).METHODS: Sixty New Zealand rabbits were randomly assigned into operation, sham-operation and normal groups. Rabbits in the operation group received direct injection of dead schistosome eggs into the brain, while their counterparts in the sham-operation group received saline injection. Rabbits in the normal group received no treatment. Base on the clinical manifestations, rabbits were sacrificed on days 3, 5, 7, 10, 20, and 30 post injection, and brain samples were sectioned and stained with hematoxylin-eosin. Sections were observed under the microscope.RESULTS: The rabbits in the operation group exhibited various neurological symptoms, including anorexy, partial and general seizures, and paralysis. The morphological analysis showed several schistosome eggs in the nervous tissue on day 3 post operation, with very mild inflammation. On days 7-10 post operation, several schistosome eggs were localized in proximity to red blood cells with many neutrophilic granulocytes and eosinophilic granulocytes around them. The schistosome eggs developed into the productive granuloma stage on days 14-20 post operation. On day 30, the schistosome eggs were found to be in the healing-by-fibrosis stage, and the granuloma area was replaced by fibrillary glia through astrocytosis. The sham-operation group and the normal group showed negative results.CONCLUSION: This method might be used to establish the cerebral schistosomiasis experimental model. Several factors need to be considered in establishing this model, such as the antigenic property of eggs, the time of scarification, and the clinical manifestations.

A 70-year-old man showed Balint's syndrome and other signs of bilateral posterior-hemisphere dysfunction of acute onset without initial unconsciousness. A computerized tomographic scan showed bilateral infarcts in the posterior arterial border-zone areas. Clinical evidence suggests that hypotension at the onset of atrial fibrillation caused these infarcts. There was a marked difference in the time course of recovery between the left and the right infarct which demonstrated that the elements of Balint's syndrome disappeared together with the left-hemisphere symptoms while the right-hemisphere symptoms were still present.

There is increasing evidence of a topographic organization within the human cerebellar cortex for motor and non-motor functions. Likewise, a subdivision of the dentate nucleus in a more dorsal and rostral motor domain and a more ventral and caudal non-motor domain has been proposed by Dum and Strick (2003) based on anatomical studies in monkey. In humans, however, very little is known about topographic organization within the dentate nucleus. Activation of the dentate nucleus in a verb generation task was examined in young and healthy subjects using ultra-highfield 7T functional magnetic resonance imaging (fMRI) with its increase in signal-to-noise ratio. Data of 17 subjects were included in statistical analysis. Subjects were asked to (i) read words (nouns) aloud presented on a screen, (ii) silently read the same nouns, (iii) silently generate the appropriate verbs to the same nouns and (iv) to silently repeat the names of the months. A block design was used. For image processing, a recently developed region of interest (ROI) driven normalization method of the dentate nuclei was applied. Activation related to motor speech (contrast aloud reading minus silent reading) was strongest in the rostral parts of the dentate nucleus. Dorsorostral activations were present bilaterally. Activation related to verb generation (contrast verb generation minus silent reading) was found in the ventrocaudal parts of the dentate nucleus on the right. The present findings are in good accordance with the anatomical data in monkeys and suggest that the human dentate nucleus can be subdivided into a rostral and more dorsal motor domain and a ventrocaudal non-motor domain.

3-Hydroxyisobutyryl-CoA hydrolase (HICH), a member of the enoyl-CoA (crotonase) superfamily, catalyzes the hydrolysis of 3-hydroxyisobutyryl-CoA to 3-hydroxyisobutyrate. Like other members of the superfamily, the sequence of HICH contains conserved sequences for an oxyanion hole that stabilizes anionic intermediates. In contrast to most members of the superfamily, the reaction catalyzed by HICH does not proceed via formation of a thioester enolate anion; instead, evidence based on substrate deuterium isotope effects, the reactivity of substrate analogues that cannot form thioester enolate anions, single-turnover experiments in H218O, and the kinetic phenotypes of site-directed mutants provide evidence for a mechanism involving the formation of an anhydride intermediate involving Glu143 in the active site. In the reactions catalyzed by many members of the superfamily, homologues of Glu143 abstract the alpha proton of the thioester substrate to generate the thioester enolate anion intermediate. Presumably, one or more of the anionic tetrahedral intermediates on the HICH reaction coordinate are stabilized by the oxyanion hole. Thus, we conclude that the conserved oxyanion hole in this superfamily can be used to stabilize a variety of anionic intermediates.

OBJECTIVES: We sought to determine the indications, type, and outcomes of reoperations on the aortic root after repair of tetralogy of Fallot (TOF).METHODS: Eleven centers belonging to the European Congenital Heart Surgeons Association contributed to the data collection process. We included 36 patients who underwent surgical procedures on the aortic root, including surgery on the aortic valve and ascending aorta, between January 1975 and December 2017. Original diagnoses included TOF-pulmonary stenosis (n = 18) and TOF-pulmonary atresia (n = 18). The main indications for reoperation were aortic insufficiency (n = 19, 53%), aortic insufficiency and dilatation of the ascending aorta (n = 10, 28%), aortic root dilatation (n = 4, 11%), and ascending aorta dilatation (n = 3, 8%).RESULTS: The median age at reoperation was 30.4 years (interquartile range 20.3-45.3 years), and mechanical aortic valve replacement was the most common procedure performed. Five patients died early after reoperation (14%), and larger ascending aorta diameters were associated with early mortality (P = .04). The median age at the last follow-up was 41.4 years (interquartile range 24.5-51.6 years). Late death occurred in five patients (5/31, 16%). Most survivors (15/26, 58%) were asymptomatic at the last clinical examination (New York Heart Association, NYHA class I). The remaining patients were NYHA class II (n = 7) and III (n = 3). The most common symptoms were fatigue (n = 5), dyspnea (n = 4), and exercise intolerance (n = 3).CONCLUSIONS: Reoperations on the aortic root are infrequent but may become necessary late after TOF repair. The main indications for reoperation are aortic insufficiency, either isolated or associated with a dilatation of the ascending aorta. The surgical risk at reoperation was high and the presence of ascending aorta dilation is related to higher mortality.

We used an error detection paradigm to examine the effects of skill on young (M = 23.74) and old (M = 68.87) adults' self-judged comprehension of texts. Skill was defined as the ability to evaluate comprehension by detecting text problems. Multiple regression results indicated that problematic texts produced lower comprehension judgments for older readers, regardless of level of skill, than for younger readers. Only more skilled younger readers tended to lower their comprehension judgments for problematic text. Younger adults who were less skilled at evaluating their comprehension assessed their comprehension as superior to their more skilled peers. Less skilled older adults appear to know, better than less skilled younger adults, when they do not comprehend a text. Research is needed to examine older adults' perceived self-efficacy and use of regulation strategies to resolve comprehension failures.

Adjuvant arthritis in rats is induced by a T cell clone specific for amino acids 180-188 of the mycobacterial 65-kD heat-shock protein, and synovial T cell responses to this same Ag have been noted in human arthritis. We have isolated 65-kD Ag-specific T cell clones from synovial fluid mononuclear cells of a patient with acute arthritis, which, unlike the corresponding PBMC, showed a marked proliferative response to the 65-kD Ag. Using synthetic peptides corresponding to the whole sequence of the 65-kD Ag, all the clones were shown to recognize an epitope present in the first NH2-terminal peptide (amino acids 1-15), with no response to the adjacent peptide (amino acids 6-22) or to any other peptide. The complete dominance of this epitope in the response to the 65-kD Ag was shown by documenting responses to the peptide in PBMC obtained after recovery from the arthritis. This epitope, like that recognized by the rat arthritogenic T cell clone, is in a portion of the 65-kD sequence that is not conserved between bacteria and eukaryotes, so that in this case, joint inflammation could not be attributed to bacteria-induced T cell clones cross-reacting with the self 65-kD Ag.

PURPOSE: To identify factors associated with success of Market Authorisation Applications (MAAs) for pharmaceutical drugs submitted to the European Medicines Agency (EMEA), with an emphasis on the Scientific Advice (SA) given by the Committee for Human Medicinal Products (CHMP).METHODS: MAAs with a CHMP decision (outcome) between 1 January 2004 and 31 December 2007 were included in the analysis. Factors evaluated were: company size, orphan drug (OD) status, product type, existence of SA, compliance with SA, therapeutic area and year of outcome. Compliance with SA was retrospectively assessed with reference to three critical clinical variables in pivotal studies: choice of primary endpoint, selection of control and statistical methods.RESULTS: Of 188 MAAs with an outcome, 137 (72.9%) were approved, whereas 51 (27.1%) were not approved or were withdrawn by the company. In the simple logistic regression analysis, company size [odds ratio (OR) 2.96, 95% confidence interval (CI) 1.92; 4.56, p < 0.0001) was positively correlated with a positive outcome, whereas OD status (OD vs. non-OD: OR 0.38, 95% CI 0.19; 0.77, p = 0.0067) was negatively correlated. A total of 59 (31.4%) MAAs had obtained SA related to one or more of the three critical variables. Thirty-nine of these were assessed as being compliant with SA. Obtaining an SA per se was not associated with outcome (SA vs. no-SA: OR 0.96, 95% CI 0.49; 1.88, p = 0.92), but complying with SA was significantly associated with positive outcome (compliant with SA vs. no-SA: OR 14.71, 95% CI 1.95; 111.2; non-compliant with SA vs. no-SA: OR 0.17, 95% CI 0.06; 0.47, p < 0.0001). Stepwise regression analysis revealed that company size and SA compliance were independent predictors of outcome. The proportion of the MAAs that had received SA increased from 22% in 2004 to 47% in 2007. Company size and product type were associated with the frequency of requesting SA (26, 33 and 46% for small, medium-sized and large companies, respectively; 16, 39 and 48% for known chemical substances, new chemical substances and biologics, respectively). Factors related to compliance with SA were company size and OD status (25, 60 and 84% for small, medium-sized, and large companies, respectively; 77 and 38% for non-OD and OD status, respectively).CONCLUSIONS: The strong association between company size and outcome suggests that resources and experience in drug development and obtaining regulatory approval are critical factors for a successful MAA. In addition, obtaining and complying with SA appears to be a predictor of outcome. Based on this analysis, companies, particularly smaller ones and those developing orphan drugs, are recommended to engage in a dialogue with European regulators via the SA procedure. Obtaining SA early in development and at major transition points as well as compliance with the advice given by the CHMP are recommended.

PURPOSE: Oxytocin (OT) was reported to inhibit the proliferation of various neoplastic tissues and cells, however, the regulation system remains unclear. This study examined the role of OT and its regulatory ability in endometrial adenocarcinoma.EXPERIMENTAL DESIGN: To investigate the possible function of placental leucine aminopeptidase (P-LAP) in endometrial adenocarcinoma, we transfected P-LAP cDNA into A-MEC cells, showing the lowest enzyme activity of P-LAP. Also we examined P-LAP protein expression in human endometrial adenocarcinoma.RESULTS: We demonstrated the presence of P-LAP, which is identical to cystine aminopeptidase as oxytocinase, in human endometrial adenocarcinoma tissues and found that the expression of P-LAP increase with advances in the grade. Exposure of endometrial adenocarcinoma cell lines to OT caused dose- and time-dependent inhibition of growth. Treatment with 10(-7) M OT for 72 h reduced cell growth by 62, 25, and 30% in A-MEC, HEC1A, and Ishikawa cells, respectively. P-LAP-transfectant cells not only partially recovered from OT-induced growth inhibition but also showed a higher growth rate than parental cells under condition without OT. An OT receptor antagonist and a protein kinase A inhibitor blocked OT-induced growth inhibition in A-MEC and A-MEC-pc cells but not in A-MEC-LAP cells.CONCLUSIONS: These findings suggested that P-LAP might be functionally positive on carcinoma cell growth by degrading suppressive peptides such as OT.

Four biogenetically related benzophenones have been isolated from the Fijian Garcinia pseudoguttifera. They are: 6-hydroxy-2,4-dimethoxy-3,5-bis(3-methyl-2-butenyl)benzophenone (myrtiaphenone-A); 2,2-dimethyl-8-benzoyl-7-hydroxy-5-methoxy-6-(3-methyl-2-butenyl)benzopy ran (myrtiaphenone-B); 2,6-dihydroxy-4-methoxy-3,5-bis(3-methyl-2-butenyl)benzophenone (vismiaphenone-C) and a new benzophenone, 2,2-dimethyl-8-benzoyl-3,7-dihydroxy-5-methoxy- 6-(3-methyl-2-butenyl)-3,4-dihydrobenzopyran (pseudoguttiaphenone-A). Pseudoguttiaphenone-A could be biogenetically derived from vismiaphenone-C. The major component of G. pseudoguttifera was identified as eupha-8,24-dien-3 beta-ol.

HIF (hypoxia-inducible factor) is the main transcription factor activated by low oxygen tensions. HIF-1alpha (and other alpha subunits) is tightly controlled mostly at the protein level, through the concerted action of a class of enzymes called PHDs (prolyl hydroxylases) 1, 2 and 3. Most of the knowledge of HIF derives from studies following hypoxic stress; however, HIF-1alpha stabilization is also found in non-hypoxic conditions through an unknown mechanism. In the present study, we demonstrate that NF-kappaB (nuclear factor kappaB) is a direct modulator of HIF-1alpha expression. The HIF-1alpha promoter is responsive to selective NF-kappaB subunits. siRNA (small interfering RNA) studies for individual NF-kappaB members revealed differential effects on HIF-1alpha mRNA levels, indicating that NF-kappaB can regulate basal HIF-1alpha expression. Finally, when endogenous NF-kappaB is induced by TNFalpha (tumour necrosis factor alpha) treatment, HIF-1alpha levels also change in an NF-kappaB-dependent manner. In conclusion, we find that NF-kappaB can regulate basal TNFalpha and, in certain circumstances, the hypoxia-induced HIF-1alpha.

Electromagnetic radiation emitted by earphones is a potential source of contamination of auditory evoked potentials, particularly when long-duration stimuli are used to evoke the response. One practical solution to this problem would be to estimate the magnitude and characteristics of this earphone radiation so that an appropriate choice of earphone is made. With this aim, earphone radiation measures obtained from a resistor network simulator laid out over the dimensions of an average head were compared with those obtained from three hearing impaired subjects to determine the efficacy of the simulator in estimating the magnitude of this radiation. Results indicated a close agreement between these measures suggesting that the simulator measures are realistic. It was shown that the earphone radiation (i) increases linearly with stimulus intensity; (ii) varies systematically as a function of recording configuration; and (iii) recorded in the simulator can be used to subtract out earphone radiation contaminating evoked responses recorded from subjects using unshielded earphones. Based on these results it was concluded that the simulator provides a practical means to simulate real recordings, at least for the purposes of estimating stimulus artifact that may contaminate auditory evoked potentials to sustained stimuli.

OBJECTIVE: To estimate the economic consequences in the United States of routine childhood immunization of children younger than 1 year of age with a rotavirus (RV) vaccine.DESIGN: Cost-effectiveness analysis of a national RV immunization program from the perspective of the health care system and the perspective of society. Estimates of disease incidence, medical expenditures, productivity costs, vaccine efficacy, and vaccine coverage rates were derived from published literature and unpublished vaccine trial reports. The impact of changes in estimates of vaccine efficacy and medical costs was determined by sensitivity analysis.MAIN OUTCOME MEASURES: Incremental cost effectiveness, expressed as savings per case of RV diarrhea prevented.RESULTS: Given a vaccine efficacy rate of 50% and a vaccine cost of $30 per dose, an RV immunization program would prevent more than 1 million cases of RV diarrhea, 58,000 hospitalizations, and 82 deaths per year. A vaccine program would cost $243 million per year but would yield net savings of $79 million from the perspective of the health care system and $466 million from the perspective of society. The incremental cost effectiveness was a savings of $459 per case prevented from the societal perspective and $78 per case prevented from the health care system perspective. Sensitivity analyses substantiated net savings over a wide range of variables, and cost effectiveness increased with greater vaccine efficacy or decreased vaccine cost.CONCLUSIONS: Economic and disease reduction benefits would be realized from the use of an RV vaccine that is partially protective against severe RV diarrhea. These findings suggest that immunization with an RV vaccine would be cost effective and cost saving.

We study cavitation dynamics when focusing ring-shaped femtosecond laser beams in water. This focusing geometry reduces detrimental nonlinear beam distortions and enhances energy deposition within the medium, localized at the focal spot. We observe remarkable postcollapse dynamics of elongated cavitation bubbles with high-speed ejection of microbubbles out of the laser focal region. Bubbles are ejected along the laser axis in both directions (away and towards the laser). The initial shape of the cavitation bubble is also seen to either enhance or completely suppress jet formation during collapse. In the absence of jetting, microbubble ejection occurs orthogonal to the laser propagation axis.

Human group A rotaviruses (RVAs) possess a large genetic diversity and new RVA strains and G/P genotype combinations are been identified frequently. Only a few studies reporting the distribution and co-circulation of RVA G and P genotypes are available for Pakistan. This hospital based study showed a RVA prevalence rate of 23.8%, which is similar to RVA detection rates estimated in other Eastern Mediterranean countries. During 2010, the following RVA strains were found to co-circulate: G1P[8] and G2P[4] (both 24.3%), G1P[6] (12.1%), G9P[8] (10.8%), G9P[6] (5.4%), G12P[6] (6.7%), G6P[1] (2.7%) and mixed infections (6.7%). Sequence analyses of selected G1, G2, G9 and G12 RVA strains revealed a close evolutionary relationship with typical human RVA strains. Sequence identities among the Pakistani VP7 RVA genes encoding G1, G2, G9 and G12 ranged between 91.5-98.7%, 99.6-98.9%, 97.7-99.5% and 99.2-99.9%, respectively. Analysis of the VP4 genes revealed co-prevalence of distinct lineages of the P[8] genotype. P[6] and P[4] showed a close relationship with typical human RVA strains detected in several Asian countries. The two G6P[1] RVA strains were closely related to typical bovine RVA strains, suggesting one or multiple interspecies transmission events. Our data provide important baseline data on the burden of RVA disease and genotype distribution in Rawalpindi, Pakistan, which is important with respect to vaccine introduction in national immunization programs.

A range of bright and photostable rhodamines and carbopyronines with absorption maxima in the range of ë=500-630 nm were prepared, and enabled the specific labeling of cytoskeletal filaments using HaloTag technology followed by staining with 1 ìm solutions of the dye-ligand conjugates. The synthesis, photophysical parameters, fluorogenic behavior, and structure-property relationships of the new dyes are discussed. Light microscopy with stimulated emission depletion (STED) provided one- and two-color images of living cells with an optical resolution of 40-60 nm.

Colonies of the Caribbean gorgonian Pseudopterogorgia elisabethae release eggs that are retained on the colony surface where they are fertilized and then develop. In December 2001, spawning on San Salvador Island, Bahamas, occurred over 6 d, with spawning by any one colony limited to 1-3 d. With the exception of the first and last days of the spawning period, fertilization success was high, often greater than 90%. Eggs collected in December 2001 had an overall fertilization success of more than 66%. At one site, the increase in fertilization after the first day of spawning correlated with male spawning, but male gonad index was a poor predictor of fertilization success. The number of male colonies close to a female was not correlated with fertilization success. Surface brooding is an efficient mechanism for "harvesting" sperm released upstream of female colonies. By maintaining their eggs at a single location, surface-brooding species can extend the period over which eggs are likely to encounter sperm. As a result, fertilization success is summed across the temporal variance in sperm availability, and the need for very high densities of sperm, with its concomitant risk of polyspermy, may be reduced.

Enlarged vestibular aqueduct (EVA) is a malformation in the inner ear and occurs in approximately 1-12% of the hearing-impaired individuals. A ten-year-old girl was seen at the emergency room (ER) because of sudden hearing loss on the right ear. The patient was known with sudden deafness on the left ear. In the ER she appeared completely deaf. A head CT-scan showed EVA, and she was treated with cochlear implant. This case report illustrates the importance of performing MR- or CT-scan, especially when diagnosing children with sudden hearing loss after a head injury.

Collagen type II (CII)-induced arthritis (CIA) can be induced in 78% of B10.RIII mice (H2r) by intradermal (id) immunization with CII of bovine origin in complete Freund's adjuvant (CFA), whereas immunization with CII of chick origin induces arthritis in less than 5% of these mice. Nevertheless, tolerization of B10.RIII mice with intravenously injected chick CII renders the animals resistant to induction of CIA by immunization with bovine CII. Such tolerization can be achieved either by intravenous injection of 500 micrograms chick CII 1 week prior to immunization with bovine CII in CFA or by such an intravenous injection of chick CII 2 weeks after immunization with bovine CII in CFA. Postimmunization treatment results in a significant decrease in the concentration of antibody to bovine CII. Preimmunization administration of chick CII causes a marked decrease in the antibody reactive with chick CII without a significant effect on the anti-bovine CII antibody concentration. In DBA/1 mice, a strain in which both bovine CII and chick CII can induce a high incidence of the disease, intravenous injection of bovine CII can also prevent arthritis induced by chick CII, even when given 7 or 14 days after immunization. The fact that chick CII as tolerogen is quite effective in preventing arthritis in B10.RIII mice, while as immunogen it is very ineffective in inducing arthritis in this strain, may be interpreted as evidence for interaction between different epitopes on CII in the pathogenesis of CIA.

Carvedilol and nitrendipine were given for 12 weeks in a double-blind study to 81 elderly patients (greater than or equal to 60 years) with essential hypertension. The effects on blood pressure were measured (Riva Rocci) before medication and after 2 h with the patient in a lying and standing position after 4 weeks of placebo therapy as well as after 4, 8 and 12 weeks of treatment. Carvedilol (25 mg/o.d.) reduced blood pressure measured in the supine and erect position very successfully, similar to the reduction achieved with nitrendipine (20 mg/o.d.), without influencing the pulse rate. Both substances were well tolerated. Carvedilol is an alternative substance for lowering high blood pressure in elderly hypertensive patients.

PURPOSE: Osteoblasts and their precursors support hematopoiesis in the bone marrow. We hypothesized that declines in Hgb levels are associated with bone mineral density (BMD).METHODS: The Cardiovascular Health Study is a prospective longitudinal study that enrolled 5888 community-dwelling adults aged >65 years and measured hemoglobin twice, in 1989-90 and 1992-93, as well as BMD by dual-energy X-ray absorptiometry (DXA) in 1994-95. In a subset of 1513 men and women with a Hgb in 1992-93 and BMD, we used linear regression to estimate associations of Hgb (per standard deviation (SD)) with total hip (TH), lumbar spine (LS) and total body (TB) BMD, and used Poisson regression to estimate associations of anemia (in 1992-93; Hgb <13 g/dL in men; <12 g/dL in women) with "low BMD" defined as T-score less than -1 at the TH. In 1277 participants with Hgb measured on average 2.9 years apart and BMD, we used linear regression to estimate the associations of annualized change in Hgb with TH, LS and TB BMD. All models included age, sex, study-site, race, smoking, alcohol use, weight, height, steroid use, physical activity score, self-reported health, previous cardiovascular disease and prior anti-fracture medication use.RESULTS: No significant association was observed between Hgb, measured a mean 2.2 years prior to BMD, and BMD at the TH and LS in men (TH beta = -0.60 [x 10-2 g/cm2per 1.1 g/dL Hgb], 95% CI: -1.88 to 0.68; LS beta = -1.69, 95% CI: -3.83 to 0.45) or women (TH beta = -0.49 [x 10-2 g/cm2per 1.3 g/dL Hgb], 95% CI: -1.57 to 0.59; LS beta = -0.40, 95% CI: -2.57 to 1.76). Anemia was not observed to be significantly associated with low BMD in men (RR = 0.99, 95% CI: 0.72-1.40) nor women (RR = 0.98, 95% CI: 0.82-1.17). The mean change in Hgb was a loss of 0.06 g/dL/year (SD = 0.32). Change in Hgb was not observed to be significantly associated with BMD in men (TH beta = -0.55[x 10-2 g/cm2per 1 g/dL annualized Hgb change], 95% CI: -4.28 to 3.19; LS beta = 0.63, 95% CI: -5.38 to 6.65) or women (TH beta = 0.92, 95% CI: -1.96 to 3.79; LS beta = -1.77, 95% CI: -7.52 to 3.98). No significant association was observed between anemia and low bone density by T-score in men and women.CONCLUSIONS: These findings support neither the hypothesis that low Hgb prior to bone density or decreases in Hgb are associated with bone density in older community-dwelling adults nor the use of Hgb level as a case-finding tool to prompt BMD measurement.

Two thousand seventy-seven women attending a university-based prenatal clinic were screened for gestational diabetes. The patients were divided into two groups. Group 1 consisted of 959 patients with historic or clinical factors traditionally employed to identify patients as being at high risk for the occurrence of gestational diabetes. Group 2 consisted of the remaining 1118 patients. The O'Sullivan 50-g 1-h test, with an upper limit of normal for serum glucose of 150 mg/dl, was employed as the initial screening procedure. Patients with an abnormal screening test underwent a 3-h oral glucose tolerance test (GTT) with a 100-g load. The values recommended by the First American Diabetes Association Workshop-Conference on Gestational Diabetes were employed for interpretation. Group 1 patients underwent screening at their initial visit and again at 28 wk gestation. Group 2 patients underwent an identical screening sequence between 28 and 32 wk gestation. Cost analysis was performed. The prevalences of positive screening tests were 7.2% and 6.1%, and the frequencies of abnormal GTTs were 1.5% and 1.4% among group 1 and group 2 patients, respectively. These rates were not statistically significantly different. Overall, 46.7% and 53.5% of the cases of gestational diabetes were identified among the patients with and without risk factors, respectively. The total cost of the screening program was +9869.00. The cost per patient screened and the cost per case of gestational diabetes identified were +4.75 and +328.96, respectively. These results reemphasize the inadequacy of screening only those patients with traditional risk factors for gestational diabetes and demonstrate the feasibility of implementing a program of universal glucose screening among a large obstetric population.(ABSTRACT TRUNCATED AT 250 WORDS)

The in vitro effects of ZK 36 374, a new chemically stable prostacyclin (PGI2) analog, on platelet aggregation were studied and compared to those of PGI2. Significantly lower concentrations of ZK 36 374, versus prostacyclin, were required to inhibit collagen and epinephrine-induced aggregation in human platelet-rich plasma. In contrast, in rat and rabbit platelet rich plasma, PGI2 was more effective than ZK 36 374 in inhibiting the aggregation elicited by ADP and collagen. It is concluded that ZK 36 374 is a potent antiaggregatory compound and may be useful in the prevention of cardiovascular disorders.

Deficiency of 21-hydroxylase provides an in vivo model of intrauterine induction of enzymes participating in steroid anabolism and catabolism. Quantitative data for 93 steroid metabolites in urine from 111 patients and 7 controls (25 samples) were compared over the first six weeks of life. Net flux through the key anabolic enzymes was examined by comparison of the totals of steroids derived from the intermediates prior to and following each enzymatic step. Metabolic relationships were established on structural grounds and by Pearson correlation. The relative importance of each catabolic route was evaluated after summing metabolites classified according to their structure as fetal, neonatal, and classical (adult) type. Hierarchical cluster analysis identified the structure at C3-C5 as a key distinguishing feature of the major catabolic streams and demonstrated a split point in metabolic pattern in patients at 7 days. Changes with time in steroid metabolism, larger in patients than in controls, could be interpreted as reflecting increased cortisol demand post partum, the clinical onset of salt-wasting and a transition in catabolism from fetal to postnatal life. Faster involution of the fetal zone and pronounced enhancement of steroid production in zona fasciculata and zona glomerulosa were indicated in patients. Predominant at birth were 'planar' fetal-type 5á-reduced metabolites, adapted to placental excretion, which gave way to additionally hydroxylated neonatal-type metabolites, facilitating renal excretion. Classical metabolism made gains over the study period. Overproduction of steroids in utero in 21-hydroxylase deficiency would have induced fetal catabolic pathways dependent on 5á-reduction. A progressive increase of steroids likely to arise from 5á-reductase type 2 activity, again more distinct in disease, was observed. We demonstrate that the key intermediates in the hypothetical 'backdoor' pathway of androgen synthesis are part of a broader catabolic network and should not be examined in isolation.

PURPOSE: To estimate the prevalence of dry eye disease in the normal non-complaining population.METHODS: Prospective systematic random sampling study of 251 subjects who accompanied patients with appointments to the eye clinic. Interviewers administered a dry eye symptoms and risk factor questionnaire. Tear film break up time, fluorescein corneal staining and Schirmer's test were performed. Slit lamp examination to evaluate the lid margins, Meibomian glands and ocular surface structures was also performed.RESULTS: Dry eye was diagnosed in 234 (93.2%) subjects on the basis of presence of one or more symptoms occurring often or most of the time, together with one or more of the following signs: tear film break up time < or = 10 seconds, fluorescein corneal staining > or = grade 1 and Schirmer test score < or = 5 mm. There was no statistically significant association between dry eye with advancing age or gender. Blepharitis was detected in 215 (91.9%) of the dry eye cases. Smoking was found to be the second most common risk factor as 18.8% of the dry eye cases were smokers. Sicca syndrome was found in 24.4% of the subjects.CONCLUSION: Dry eye is very prevalent disease. Blepharitis was found to be very common among dry eye cases. There was no statistically significant association between dry eye and age or gender in our study population.

1. Sixteen neurosurgical patients received (oral) beta-adrenoreceptor-blocking agents (beta-receptor blockers) for 3-22 days. 2. Lipophilic beta-receptor blockers (propranolol) and metoprolol appeared in cerebrospinal fluid at concentrations similar to the free drug plasma concentration. 3. Cerebrospinal fluid concentrations of beta-receptor blockers were poor predictors of brain concentrations. 4. Both lipophilic beta-receptor blockers appeared in high concentrations in the brain: the brain/plasma ratio was approximately 15:1. 5. Hydrophilic atenolol appeared at low concentrations in brain tissue (about 20 times lower than the lipophilic beta-receptor blockers): the brain/plasma ratio was approximately 0.1:1. 6. Central nervous system-related side effects associated mainly with lipophilic beta-receptor blockers possibly result from high brain tissue concentrations.

The study evaluated the effect of DHA 625 mg in women who experience menopausal symptoms, on sexuality and quality of life (QoL), and on the auditory brainstem response (ABR). Forty-two perimenopausal women were enrolled. The Kupperman Index (KI) was used to evaluate menopause symptoms. The Short Form-36 (SF-36), Female Sexual Function Index (FSFI), and the Female Sexual Distress Scale (FSDS) were used to assess QoL, sexual function, and sexual distress, respectively. Auditory evoked potentials to measure the ABR. The study had one follow-up at 6 months. The women reported an improvement in the KI total score (p < .001). Moreover, women reported QoL improvements in all the psychological categories (p < .001), but not in physical categories (p = NS). FSFI and FSDS total scores increased (p < .01) and the FSDS score decreased (p < .01), mainly due to arousal (p < .03) and lubrication (p < .05) sexual aspects. The ABR wave latencies were lower than the baseline values (p < .05). DHA could be effective in modulating some perimenopausal symptoms in women and, consequently could contribute to improve their QoL and sexual life. Finally, DHA seems to have a direct activity on the neuronal conduction time into the audiological system.

BACKGROUND: We assessed whether there was a difference in attenuation measurements (in Hounsfield units - HU) and geometric distribution of HU between femora with metastatic lesions that fracture, and metastatic lesions that did not fracture nor underwent prophylactic fixation.METHODS: Nine patients with femoral metastases who underwent CT and developed a pathological fracture were matched to controls. All femora were delineated in axial CT slices using a region of interest (ROI) tool; the HU within these ROIs were used to calculate: (1) the cumulative HU of the affected over the nonaffected side per slice and presented as a percentage, and (2) the cumulative HU accounting for geometric distribution (polar moment of HU). We repeated the analyses including cortical bone only (HU of 600 and above).RESULTS: CT-based calculations did not differ between patients with a lesion that fractured and those that did not fracture nor underwent prophylactic fixation when analyzing all tissue. However, when including cortical bone only, the pathological fracture group had a lower cumulative HU value compared to the no fracture and no fixation group for the weakest cross-sectional CT image (pathological fracture group, mean: 71, SD: 23 and no fracture and no prophylactic fixation group, mean: 85, SD: 18, p = 0.042) and the complete lesion analysis (pathological fracture group, mean: 78, SD: 21 and no fracture and no prophylactic fixation group, mean: 92, SD: 15, p = 0.032).CONCLUSION: The demonstrated CT-based algorithms can be useful for predicting pathological fractures in metastatic lesions.

STUDY DESIGN: A case of bilateral symptomatic facet joint synovial cysts arising in association with calcium pyrophosphate deposition disease is reported.OBJECTIVE: To present a previously unreported cause for symptomatic synovial cysts of the lumbar spine.SUMMARY OF BACKGROUND DATA: Synovial cysts of the facet joints occur most commonly in association with degenerative disease of the spine in older individuals. The association of these cysts with trauma, rheumatoid arthritis, spondylolysis, and kissing spinous processes also has been reported. These cysts can cause symptoms and signs from direct compression of the dura. Chondrocalcinosis has not been previously reported to cause symptomatic synovial cysts.METHODS: A 67-year-old woman presented with right lower limb sciatica caused by a right L4-L5 facet joint cyst, which resolved after surgical decompression. A year later, she presented with left lower limb sciatica caused by development of a new L4-L5 facet joint cyst, which also resolved after surgical decompression.RESULTS: Histopathologic examination of each cyst showed a cyst wall of fibrous tissue with synovial lining, inflammation, and granulation tissue. Examination of the tissue under polarized light showed positively birefringent, short blunt crystals of calcium pyrophosphate dihydrate.CONCLUSIONS: In patients with a history of gout or pseudogout, a rare possibility of a synovial cyst should be considered in the differential diagnosis during investigation for the cause of neural compression resulting in sciatic syndrome.

BACKGROUND: The etiology of secondary cancer in childhood cancer survivors is largely unclear. Exposure of normal somatic cells to radiation and/or chemotherapy can damage DNA and if not all DNA lesions are properly fixed, the mis-repair may lead to pathological consequences. It is plausible to assume that genetic differences, i.e. in the pathways responsible for cell cycle control and DNA repair, play a critical role in the development of secondary cancer.METHODOLOGY/FINDINGS: To identify factors that may influence the susceptibility for second cancer formation, we recruited 20 individuals who survived a childhood malignancy and then developed a second cancer as well as 20 carefully matched control individuals with childhood malignancy but without a second cancer. By antibody microarrays, we screened primary fibroblasts of matched patients for differences in the amount of representative DNA repair-associated proteins. We found constitutively decreased levels of RAD9A and several other DNA repair proteins in two-cancer patients, compared to one-cancer patients. The RAD9A protein level increased in response to DNA damage, however to a lesser extent in the two-cancer patients. Quantification of mRNA expression by real-time RT PCR revealed lower RAD9A mRNA levels in both untreated and 1 Gy ã-irradiated cells of two-cancer patients.CONCLUSIONS/SIGNIFICANCE: Collectively, our results support the idea that modulation of RAD9A and other cell cycle arrest and DNA repair proteins contribute to the risk of developing a second malignancy in childhood cancer patients.

Non-melanoma skin cancer (NMSC) has a high and increasing incidence all over the world. Solar radiation is the main aetiology for humans. Although most research into photocarcinogenesis uses UVB as a source of radiation, UVA is also carcinogenic in long term. Pomegranate (PGE) and cocoa (CE) extracts have been used for medicinal purposes for time immemorial. Recently, it has been claimed that some of their properties may be an effective preventative measure against photocarcinogenesis and photoaging, but to date in vivo models have not been tested using RUVA, the objective of the present work. A lower incidence of lesions was observed in SKH-1 mice treated with PGE (p<0.001), and lower incidence of invasive squamous carcinoma in both treatment groups (p<0.001 for PGE and p<0.05 for CE); the PGE group also showed a lower level of cell proliferation than the control group (p<0.001). Significantly greater p53 alteration was observed in the control group than the treatment groups (p<0.001 for PGE and p = 0.05 for CE). No significant differences were found in relation to TIMP-1 and MMP-9. Taken together, the results suggest that oral feeding of PGE and CE to SKH-1 mice affords substantial protection against the adverse effects of RUVA, especially PGE.

The M. longissimus dorsi of 171 pigs were histologically examined for pathological signs. Acute hyaline-plaque degenerations and necrosis (hsD/N) in various degrees of manifestation were recorded from 42.7 and hyaline transverse ligaments (hQb) from 22.8 per cent of all cases. The occurrence of hsD/N following container transport was lower with significance (33.3 per cent) than that following lorry transport (50.5 per cent). The form of transport failed to have any substantive effect on the occurrence of hQb, the figures being 20.5 per cent for container and 24.7 per cent for lorry. Short resting periods, between 0.5 and 1.2 hours, were followed with significantly higher occurrence of hsD/N, as compared to longer resting periods, between five and eight or 23 hours. These pathological findings were not further reduced by extending the resting period from something between five and eight to 20 hours. The pathological hsD/N and hQb findings were recordable from both PSE pork (hsD/N = 51.4 per cent, hQb = 25.7 per cent) and from pork without any quality shortcomings (hsD/N = 39.7 per cent, hQb = 22.1 per cent), but the number of hsD/N cases in the context of PSE pork tended to be higher than that in high-quality pork. No sex dependence was established. The results are discussed under the aspect of aetiopathogenesis of stress-borne myopathy.

In this study, we examined the interaction of 5-HT1A and 5-HT2A receptors in the rat medial prefrontal cortex (mPFc) using the techniques of extracellular single unit recording and microiontophoresis. The iontophoresis of the selective 5-HT1A receptor agonist (+-)-8-hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT) produced a current-dependent suppression (2.5-20 nA) of the basal firing rate of spontaneously active mPFc cells. The iontophoretic (5-10 nA) and systemic administration (0.1-0.5 mg/kg, i.v.) of the 5-HT2A/5-HT2C receptor antagonist ritanserin and the selective 5-HT2A receptor antagonist MDL 28727 significantly potentiated and prolonged 8-OHDPAT's suppressant action. In addition, the systemic administration of another selective 5-HT2A antagonist MDL 100907, but not its less active enantiomer MDL 100009, also potentiated and prolonged 8-OHDPAT's action. The potentiating effect of the 5-HT2A receptor antagonists on the action of 8-OHDPAT is specific in that neither the iontophoresis of ritanserin nor MDL 28727 altered the suppressant action produced by the iontophoresis of the 5-HT3 receptor agonist 2-methylserotonin onto mPFc cells. Moreover, the suppressant action of 8-OHDPAT was not altered by the systemic administration of the selective 5-HT3 receptor antagonist granisetron (0.1-0.5 mg/kg, i.v.). On the other hand, the iontophoresis of a low current (0.5 nA) of the 5-HT2A,2C receptor agonist (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) potentiated the excitation induced by the iontophoresis of l-glutamate on quiescent mPFc cells.(ABSTRACT TRUNCATED AT 250 WORDS)

An image processing technique with associated hardware was developed to quantitatively extract hyoid bone motion from realtime submandibular ultrasound images recorded during the swallowing act. Videofluorographic imaging, the "gold standard" of swallowing studies, was recorded simultaneously and synchronized to the ultrasound. Hyoid position obtained from the ultrasound was validated based on the videofluorography using personal computer-based image processing methods.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is the most common form of spinal deformity, affecting up to 4% of children worldwide. Familial inheritance of AIS is now recognised and several potential candidate loci have been found.METHODS: We studied 25 multi-generation AIS families of British descent with at least 3 affected members in each family. A genomewide screen was performed using microsatellite markers spanning approximately 10-cM intervals throughout the genome. This analysis revealed linkage to several candidate chromosomal regions throughout the genome. Two-point linkage analysis was performed in all families to evaluate candidate loci. After identification of candidate loci, two-point linkage analysis was performed in the 10 families that segregated, to further refine disease intervals.RESULTS: Significant linkage was obtained in a total of 10 families: 8 families to the telomeric region of chromosome 9q, and 2 families to the telomeric region of 17q. A significant LOD score was detected at marker D9S2157 Z(max) = 3.64 ( theta= 0.0) in a four-generation family (SC32). Saturation mapping of the 9q region in family SC32 defined the critical disease interval to be flanked by markers D9S930 and D9S1818, spanning approximately 21 Mb at 9q31.2-q34.2. In addition, seven other families segregated with this locus on 9q. In two multi-generation families (SC36 and SC23) not segregating with the 9q locus, a maximum combined LOD score of Z(max) = 4.08 ( = 0.0) was obtained for marker AAT095 on 17q. Fine mapping of the 17q candidate region defined the AIS critical region to be distal to marker D17S1806, spanning approximately 3.2 Mb on chromosome 17q25.3-qtel.CONCLUSION: This study reports a common locus for AIS in the British population, mapping to a refined interval on chromosome 9q31.2-q34.2 and defines a novel AIS locus on chromosome 17q25.3-qtel.

Polyhooks were isolated from Salmonella SJW880, a non-flagellated mutant, and purified by cesium chloride density gradient centrifugation. The polyhooks were disintegrated into protein subunits (monomer) by heat in the absence of salt. The monomer was repolymerized in the presence of moderately high concentrations of sodium citrate at neutral pH. Three types of polymer were produced. One type of polymer, produced at room temperature and at citrate concentrations less than 0.3 M, had no regular shape and no definite thickness. Another type of polymer, produced at room temperature and at citrate concentrations greater than 0.4 M, had a straight shape and a similar thickness to that of polyhook but was easily dissociated into monomer in the absence of salt. A third type of polymer was produced at low temperature, independently of the concentration of citrate, and seemed to be a tubular polymer with a thickness similar to that of polyhook but had no helical curvature. However, this type of polymer was shown to have a structure locally the same as that of polyhook by electron microscopic observation, optical diffraction and circular dichroism measurements.

A number of natural products with interesting biological properties are based on a diketopiperazine scaffold. In this context, we have developed a diversity oriented and efficient synthetic strategy to highly functionalized proline-based diketopiperazines. In this paper we describe the stereoselective synthesis of various scaffolds resembling abundant natural product core structures. These scaffolds can be conjugated to a solid phase and are thus platforms for the construction of small compound libraries and the synthesis of natural products with diketopiperazine cores.

A 13-year-old Hispanic female presented with symptoms of abdominal pain, amenorrhea, and unintentional weight loss of 11 kg. Preliminary investigation yielded no immediate causes, and an initial differential included inflammatory bowel disease (IBD), celiac disease, as well as viral, bacterial, or parasitic gastrointestinal infection. Evaluation of these potential diagnoses yielded negative results; thus, the team thought that the patient may be suffering from anorexia nervosa. The patient was discharged to outpatient care, and was treated in our adolescent health clinic, where repeat laboratory testing yielded a positive Giardia-antigen test. The patient was placed on metronidazole, rapidly gained weight, and resumed menstruation soon after. The final diagnosis was chronic giardiasis. Chronic giardiasis is a rare and enigmatic disease that presents with many symptoms similar to chronic gastrointestinal disorders (e.g. IBD and celiac disease) and anorexia nervosa. Practitioners involved in the diagnosis and treatment of anorexia nervosa should be aware of this disorder and include it in differential diagnoses of patients presenting with anorexia nervosa symptoms.

In this short discussion, we point out that it is apparently as easy to be fooled by robustness as it is to be fooled by randomness. Our objective is to bring to the attention of applied ecologists that radius-of-stability robustness models are models of local robustness. As such, these models are utterly unsuitable for the treatment/management of a severe uncertainty characterized by a vast uncertainty space and a likelihood-free quantification of the uncertainty. This observation is particularly pertinent to applications of info-gap decision theory in ecology, conservation biology, and environmental management, where the objective is to identify decisions that are robust against a severe uncertainty of this type.

BACKGROUND: Leukoencephalopathy with Vanishing White Matter (VWM) is an autosomal recessive disorder caused by germline mutations in the genes EIF2B1-5, which encode the 5 subunits of the eukaryotic translation initiation factor eIF2B. To date, analysis of the biochemical effects of mutations in the EIF2B2-5 genes has been carried out, but no study has been performed on mutations in the EIF2B1 gene. This gene encodes eIF2Bá, the smallest subunit in eIF2B which has an important role in both the structure and regulation of the eIF2B complex.METHODS: eIF2B subunits were overexpressed in HEK293 cells and isolated from the resulting cell lysates by affinity chromatography. Formation of the eIF2B complex and binding of its substrate, eIF2, was assessed by western blot. Assays of the guanine nucleotide exchange (GEF) activity were also carried out.RESULTS: Of the 5 eIF2Bá mutations studied, we found 3 that showed loss or reduction of binding of eIF2Bá to the rest of the complex, one with increased GEF activity, and one where no effects on activity or complex formation were observed.CONCLUSIONS: This is the first study on eIF2Bá VWM mutations. We show that some mutations cause expected decreases in GEF activity or complex formation, similar to a majority of observed VWM mutations. However, we also observe some unexpected changes which hint at other effects of these mutations on as yet undescribed functions of eIF2B.

INTRODUCTION: Paragangliomas are rare endocrine tumors that arise from the extra-adrenal autonomic paraganglia and sympathetic paragangliomas usually secret catecholamines and are located in the sympathetic paravertebral ganglia of thorax, abdomen, and pelvis. In contrast, most parasympathetic paragangliomas are nonfunctional and located along the glossopharyngeal and vagal nerves in the neck and at the base of the skull. Such neoplasms, although rare, are clinically important because they may recur after surgical resection and 10% of them give rise to metastases causing death with the lymphatic nodes, bones, liver, and lungs being the most common locations.CASE PRESENTATION: We present a case of a 26-year-old male patient that was diagnosed with paraganglioma of the right-frontal lobe infiltrating the falx and frontal bone which was diagnosed after suffering from a headache and abnormal vision. On initial work-up he was found to have right pulmonary nodules that increased in size after follow up and other nodules appeared in the contralateral lung. He underwent subtotal resection of the brain tumor and complete resection of the bilateral pulmonary nodules.CONCLUSION: To our knowledge, paraganglioma is considered to be a rare entity in the central nervous system with very few cases being reported in the supratentorial region and no cases were reported of metastatic such paraganglioma to the lung.

Diffusional (Pw) and osmotic (Pf) water permeability coefficients were determined for the syncytial epithelium of larval Echinococcus granulosus. Pw was calculated from simultaneous influx measurements of tritiated water and n-[14C]butanol through the hydatid cyst wall. The total diffusional water permeability coefficient, P'w, was found to be 2.2 X 10(-4) cm s-1; which is similar to that previously reported by Rotunno et al. (1974, J. Parasitol. 60, 13-620). Nevertheless, when P'f is corrected for the unstirred water layer effects, a Pw value of 6.2 X 10(-4) cm s-1 is obtained. Thus, the unstirred water layer effects have a very important contribution to P'w. Total steady state osmotic permeability coefficient, P'f, was bound to be about 15 X 10(-4) cm s-1 and it is scarcely affected by those mechanisms that tend to distort the evaluation of Pf. The experimentally determined osmotic coefficient differs from the corrected Pf by only 6%. The Pf/Pw ratio was found to be 2.4. The present study clearly confirms that syncytial membranes can be highly permeable to water, in spite of the fact that they lack tight junctions. Thus, water permeability through epithelial syncytium must be exclusively controlled by the permeability of the apical and/or basocellular membranes.

When SV40 tumor cells (F5-1) in culture were treated with dibutyryl cyclic adenylic acid (DbcAMP),marked alterations occurred in their growth and morphology. Additionally, the incorporation or uptake of labeled thymidine, uridine, phenylalanine, and choline were reduced by this treatment. These modifications with DbcAMP exposure produced conditions simulating those of a contact-inhibited state. The immunization of hamsters with X-irradiated tumor cells previously cultured in the presence of DbcAMP indicated that the tumor-specific transplantation antigens and/or fetal antigens were altered during short-term expsoure to DbcAMP. Further examination of membrane antigens of SV40 tumor cells using the isotopic antiglobulin technique demonstrated a significant reduction in the tumor membrane antigen on cells cultured with DbcAMP.

We examined local anesthetic effects of clonidine and its interaction with lidocaine with regard to tonic inhibition of the C-fiber action potential (AP) on the isolated, desheathed rabbit vagus nerve by the sucrose gap method. Clonidine and lidocaine at 500 microM concentrations caused a comparable degree of C-fiber inhibition, corresponding to an AP area under the curve of 75.8% +/- 9.4% (mean +/- SE) and 82.2% +/- 5.9% of control, respectively. Concentrations of clonidine less than 500 microM did not inhibit C-fiber AP. Clonidine, added in concentrations of 500 nM, 500 microM, and 5 mM to a 500 microM lidocaine perfusion, caused a significant decrease in fiber blockade of 18%, 20%, and 54%, respectively, as compared with clonidine added to Locke perfusion (P less than 0.05). The sodium channel blocker tetrodotoxin (3 microM) decreased the AP area to 9.3% +/- 1.3% of control. The remaining tetrodotoxin-resistant AP was almost completely blocked by clonidine (500 microM) and lidocaine (500 microM), indicating a higher susceptibility of tetrodotoxin-resistant fibers to the two drugs than the C-fiber population as a whole. The enhancing effect of a low dose of clonidine (500 nM) on lidocaine-induced (500 microM) inhibition of C-fiber AP might explain the clinical observation that clonidine, at approximately 1000-fold lower concentrations than lidocaine, prolongs the action of lidocaine in peripheral nerve block.

This study was conducted to assess trauma scores and posttraumatic stress symptoms among Kurdistanian refugee children and their parents in Sweden and a comparable group of Swedish children and their parents. Comparative Kurdistanian and Swedish samples composed of 32 children each and their parents were interviewed by means of a specially devised trauma instrument (HUTQ-C), to identify traumatic events and to measure trauma scores, and with (PTSS-C) and (HTQ) to diagnose posttraumatic stress syndrome (PTSD) among children and adults, respectively. Although Kurdistanian parents reported considerably more traumatic events than Swedish parents, children in both samples showed more similarities than differences, both with regard to types and levels of traumatic events. Kurdistanian parents showed higher PTSD frequencies than Swedish parents. However, these differences proved to be significant with regard to both the mother's and the father's lifetime and current PTSD symptom scores. Kurdistanian parents have experienced more war traumas and differ with regard to trauma exposure and its consequences when compared with Swedish parents. Children from the two samples showed more similarities than differences with regard to reported trauma and PTSD-related symptoms. These results underline the significance of child-specific factors in trauma and PTSD.

PURPOSE: This study aims to describe the process of conducting a randomized clinical trial of elderly with chronic dizziness subjected to vestibular rehabilitation (VR) and to verify its effectiveness on dizziness intensity.METHODS: Older adults (?65 years) with chronic dizziness from vestibular disorders referred to VR were enrolled to the trial. The control group (n=40) was submitted to the Cawthorne & Cooksey protocol and the experimental group (n=42) to the modified Cawthorne & Cooksey protocol which included multiple components. Protocols were performed during individual 50-minute sessions, twice-weekly, for eight weeks. Main measures were: recruitment data (refusal and eligibility), baseline characteristics, dropout rate, session attendance, protocol adherence, adverse effects, exercise adaptation and follow-up events. The Visual Analog Scale (VAS) was used to measure dizziness intensity.RESULTS: 144 elderly were referred to VR, 26.4% declined to participate and 16.7% were ineligible. There were 51 session non-attendances, with disease being the most frequent reason. Regardless of VR protocol, VAS dizziness intensity diminished along sessions (p<0.001). 88.6% of the participants reported improvement after treatment, and 22.9% mentioned an increase in dizziness on follow-up. Home exercises were no longer being performed by 21.4% of the subjects after 3 months from discharge. The final dropout rate was 14.6%. There were no differences between VR protocols on recruitment, dropout, session's attendance, adherence to protocol and treatment effects.CONCLUSIONS: Our results revealed many challenges in conducting a rehabilitation trial with an elderly sample. The VR protocols showed to be feasible and suitable to reduce dizziness in older adults.

BACKGROUND: New Zealand is a developed country with high incidence of bacterial infections and postinfectious sequelae including rheumatic heart disease. We sought to describe the clinical and microbiology features of children with infective endocarditis (IE) between 1994 and 2012.METHODS: Retrospective review of patients <16 years identified from hospital records.RESULTS: In total 85 episodes occurred in 82 children and 68 (80%) were classified as Definite IE and 17 as Possible IE according to modified Duke criteria. From Pacific Island countries, 13 cases were referred. There were 72 children who originated in New Zealand, of whom 52% were either indigenous New Zealand Maori or Pacific migrants. The median age at diagnosis was 7 (0-15) years. Of the 85 cases, 51 (60%) had congenital heart disease 10 children with rheumatic heart disease developed IE. Of the 85 cases, 35 (41%) met our criteria for healthcare-associated IE. 39/85 underwent surgery for IE. As direct result of IE, 4 (4.7%) children died and 9% of survivors had neurologic sequelae. Attributable in-hospital mortality was 4.7%. Staphylococcus aureus was the most common organism, accounting for 26 episodes (30.6%). Other notable pathogens included Corynebacterium diphtheriae (10 cases, 11.8%) and Streptococcus pyogenes (7 cases, 8.2%). In 6 episodes, the microbiologic diagnosis was made by 16S ribosomal RNA testing of excised cardiac tissue.CONCLUSIONS: Congenital heart disease was the major risk factor for IE; however, rheumatic heart disease is also an important risk factor in New Zealand, with implications for local endocarditis prophylaxis recommendations. In addition to a high burden of healthcare-associated and staphylococcal IE, pathogens such as C. diphtheriae and S. pyogenes occurred. 16S ribosomal RNA testing is a useful tool to determine the etiologic agent in culture-negative IE.

BACKGROUND: Inflammation plays an important role in formation and rupture of intracranial aneurysms. Expression of microsomal prostaglandin E2 (PGE2) synthase type 1 (mPGES-1) is increased in the wall of intracranial aneurysms in humans. PGE2, a by-product of mPGES-1, is associated with inflammation and cerebrovascular dysfunction.OBJECTIVE: To test the hypothesis that deletion of mPGES-1 decreases the formation and rupture of intracranial aneurysms in a murine model.METHODS: Intracranial aneurysms were induced in wild-type and mPGES-1 knockout (mPGES-1 KO) mice by using a combination of deoxycorticosterone acetate-salt-induced hypertension and intracranial injection of elastase in the basal cistern. Prevalence of aneurysms, subarachnoid hemorrhage, and mortality were assessed. We also tested the effects of administration of aspirin (6 mg/kg/d) by gavage and PGE2 (1 mg/kg/d) by subcutaneous infusion.RESULTS: Systolic blood pressure and prevalence of aneurysm were similar in wild-type and mPGES-1 KO mice. However, mortality and the prevalence of subarachnoid hemorrhage were markedly increased in mPGES-1 KO mice (P < .05). Bone marrow reconstitution studies suggest that mPGES-1 derived from leukocytes does not appear to increase rupture of intracranial aneurysms. Aspirin, but not PGE2, attenuated the increased mortality in mPGES-1 KO mice (P < .05).CONCLUSION: Vascular mPGES-1 plays a protective role in blood vessels and attenuates rupture of cerebral aneurysms. In contrast to effects on abdominal aneurysms, mPGES-1 deficiency is associated with an increase in rupture of cerebral aneurysms and mortality, which are attenuated by low-dose aspirin.

OBJECTIVE: Unstable angina (UA) is characterized by a state of coronary artery vascular inflammation and endothelial dysfunction. Statins mitigate inflammation and endothelial dysfunction and decrease mortality associated with percutaneous interventions for UA. We determined whether preoperative statin use is associated with decreased mortality and morbidity following coronary artery bypass+/-valve surgery for UA.METHODS: Patients with CCS Class IV angina having CABG+/-valve surgery were identified (n=1706). A logistic regression model determined the association of preoperative statin use with in-hospital mortality (IHM). Propensity score analysis was used to match two sub-groups of patients (GrpI, on statins, n=534; GrpII, not on statins, n=534) on factors known to affect outcomes. Outcomes were IHM, intra-aortic balloon pump (IABP) use, perioperative myocardial infarction (PMI), prolonged (>24 h) ventilation (p-vent), stroke, and a composite outcome (comp) defined as any one or more of the above.RESULTS: Of the 1706 patients, 1075 were on statins and 631 were not. Patients on statins were more likely to have isolated CABG, EF>40%, and be on a beta-blocker (P=0.0001); and less likely to have renal failure, MI<7 days, CHF, and undergoing urgent/emergent surgery (P=0.0001). Unadjusted rates of IHM (9 vs. 5%, P=0.001), stroke (4.4 vs. 2.3%, P=0.015), p-vent (28.4 vs. 19%, P=0.0001), and comp (32.5 vs. 22.8%, P=0.0001) were lower in patients receiving statins. After adjustment, statin use was not associated with a reduction in IHM (OR=1.0, 95% CI=0.6-1.5, P=0.85) or comp (OR=1.1, 95% CI=0.8-1.4, P=0.69). No significant differences were found in any of the propensity-adjusted outcomes for GrpI vs. GrpII: IHM (7.1 vs. 6.4%), PMI (2.8 vs. 1.7%), IABP use (3 vs. 3.8%), stroke (3.8 vs. 3.9%), p-vent (26.4 vs. 23.8%), comp (31.5 vs. 27.5%).CONCLUSIONS: Preoperative statin use is not associated with a reduction in IHM or major morbidity following CABG+/-valve surgery in patients with UA.

AIM: Polymicrogyria (PMG) is one of the most common forms of cortical malformation yet the mechanism of its development remains unknown. This study describes the histopathological aspects of PMG in a large series including a significant proportion of fetal cases.METHOD: We have reviewed the neuropathology and medical records of 44 fetuses and 27 children and adults in whom the cortical architecture was focally or diffusely replaced by one or more festooning bands of neurons.RESULTS: The pial surface of the brain overlying the polymicrogyric cortex was abnormal in almost 90% of cases irrespective of the aetiology. This accords with animal studies indicating the importance of the leptomeninges in cortical development. The aetiology of PMG was highly heterogeneous and there was no correlation between cortical layering patterns and aetiology. PMG was almost always associated with other brain malformations.INTERPRETATION: The inclusion of many fetal cases has allowed us to examine the early developmental stages of PMG. The study indicates the significance of surface signals responsible for human corticogenesis and the complex interaction between genetic and environmental factors leading to this common endpoint of cortical maldevelopment.

In this paper we report the amino acid sequence of pyruvate phosphate dikinase (PPDK) from Bacteroides symbiosus as determined from the nucleotide sequence of the PPDK gene. Comparison of the B. symbiosus PPDK amino acid sequence with that of the maize PPDK [Matsuoka, M., Ozeki, Y., Yamamoto, N., Hirano, H., Kamo-Murakami, Y., & Tanaka, Y. (1988) J. Biol. Chem. 263, 11080] revealed long stretches of homologous sequence (greater than 70% identity), which contributed to an overall sequence identity of 53%. The circular dichrosim spectra, hydropathy profiles, and calculated secondary structural elements of the two dikinases suggest that they may have very similar tertiary structures as well. A comparison made between the amino acid sequence of the maize and B. symbiosus dikinase with other known protein sequences revealed homology, concentrated in three stretches of sequences, to a mechanistically related enzyme, enzyme I of the Escherichia coli PEP: sugar phosphotransferase system [Saffen, D. W., Presper, K. A., Doering, T. L., Roseman, S. (1987) J. Biol. Chem. 262, 16241]. It is proposed that (i) these three stretches of sequence constitute the site for PEP binding and catalysis and a possible site for the regulation of enzymatic activity and (ii) the conserved sequences exist in a third mechanistically related enzyme, PEP synthase.

OBJECTIVE: Subarachnoid hemorrhage (SAH) is associated with cardiac injury and dysfunction. Whether aneurysm clipping versus coiling has a differential effect on the risk of troponin release and left ventricular (LV) dysfunction after SAH is unknown. It is hypothesized that aneurysm treatment does not affect the risk of developing cardiac injury and dysfunction.METHODS: The study included 172 consecutive SAH patients who underwent clipping (n = 109) or coiling (n = 63) aneurysm therapy. Hemodynamic data were collected, cardiac troponin I was measured, and echocardiography was performed on the 1st, 3rd, and 6th days after enrollment. A cardiac troponin I measurement of more than 1.0 microg/L was considered abnormal. For each echocardiographic examination, a blinded observer measured LV ejection fraction (abnormal if <50%) and quantified LV regional wall motion abnormalities. The incidence of cardiac outcomes in the treatment groups was compared using odds ratios (ORs).RESULTS: The coiled patients were older than the clipped patients (mean age, 59 +/- 13 yr versus 53 +/- 12 yr; t test, P < 0.001) and were more likely to have posterior aneurysms (33% versus 18%; chi(2) test, P = 0.019). There were no significant between-group differences in the risk of cardiac troponin I release (coil 21% versus clip 19%; OR = 0.89, P = 0.789), regional wall motion abnormalities (33% versus 28%; OR = 0.76, P = 0.422), or LV ejection fraction lower than 50% (16% versus 17%; OR = 1.06, P = 0.892). No patient died of cardiac causes (heart failure, myocardial infarction, or arrhythmia).CONCLUSION: Surgical and endovascular aneurysm therapies were associated with similar risks of cardiac injury and dysfunction after SAH. The presence of neurocardiogenic injury should not affect aneurysm treatment decisions.

Accumulation of amyloid-â (Aâ) peptide in the brain is the first critical step in the pathogenesis of Alzheimer's disease (AD). Studies in humans suggest that Aâ clearance from the brain is frequently impaired in late-onset AD. Aâ accumulation leads to the formation of Aâ aggregates, which injure synapses and contribute to eventual neurodegeneration. Cell surface heparan sulfates (HSs), expressed on all cell types including neurons, have been implicated in several features in the pathogenesis of AD including its colocalization with amyloid plaques and modulatory role in Aâ aggregation. We show that removal of neuronal HS by conditional deletion of the Ext1 gene, which encodes an essential glycosyltransferase for HS biosynthesis, in postnatal neurons of amyloid model APP/PS1 mice led to a reduction in both Aâ oligomerization and the deposition of amyloid plaques. In vivo microdialysis experiments also detected an accelerated rate of Aâ clearance in the brain interstitial fluid, suggesting that neuronal HS either inhibited or represented an inefficient pathway for Aâ clearance. We found that the amounts of various HS proteoglycans (HSPGs) were increased in postmortem human brain tissues from AD patients, suggesting that this pathway may contribute directly to amyloid pathogenesis. Our findings have implications for AD pathogenesis and provide insight into therapeutic interventions targeting Aâ-HSPG interactions.

We examined the stimulatory state of peritoneal macrophages (M phi) in caerulein-induced pancreatitis. Edematous pancreatitis was developed by the intravenous continuous injection of caerulein (5 micrograms/kg/hr) for 4 hr. Thereafter peritoneal M phi were collected and the activity for free radical production was measured by the reduction of nitro blue tetrazorium in the presence of phorbol myristate acetate. The increase in free radical production reached a statistical significance at 12 hr and a maximum at 20 hr after the beginning of caerulein infusion. These results suggested that the peritoneal M phi are activated even in mild edematous pancreatitis, and that their activation is involved into the mechanism of the development of remote organ failure in acute pancreatitis.

BACKGROUND: The improvement of feed efficiency is a key economic goal within the pig production industry. The objective of this study was to examine transcriptomic differences in both the liver and muscle of pigs divergent for feed efficiency, thus improving our understanding of the molecular mechanisms influencing feed efficiency and enabling the identification of candidate biomarkers. Residual feed intake (RFI) was calculated for two populations of pigs from two different farms of origin/genotype. The 6 most efficient (LRFI) and 6 least efficient (HRFI) animals from each population were selected for further analysis of Longissimus Dorsi muscle (n = 22) and liver (n = 23). Transcriptomic data were generated from liver and muscle collected post-slaughter.RESULTS: The transcriptomic data segregated based on the RFI value of the pig rather than genotype/farm of origin. A total of 6463 genes were identified as being differentially expressed (DE) in muscle, while 964 genes were identified as being DE in liver. Genes that were commonly DE between muscle and liver (n = 526) were used for the multi-tissue analysis. These 526 genes were associated with protein targeting to membrane, extracellular matrix organisation and immune function. In the muscle-only analysis, genes associated with RNA processing, protein synthesis and energy metabolism were down regulated in the LRFI animals while in the liver-only analysis, genes associated with cell signalling and lipid homeostasis were up regulated in the LRFI animals.CONCLUSIONS: Differences in the transcriptome segregated on pig RFI value rather than the genotype/farm of origin. Multi-tissue analysis identified that genes associated with GO terms protein targeting to membrane, extracellular matrix organisation and a range of terms relating to immune function were over represented in the differentially expressed genes of both liver and muscle.

We studied the effect of antioxidants such as N-acetylcysteine (NAC, 10 mM) and alpha-lipoic acid (ALA, 1.25 mM) and of the hormone melatonin (1 microM) on the ability of murine hepatoma cells MH22a to develop tumors in syngenic mice (C3HA) after subsutaneous injection. Tumor formation and development slowed down and mouse mortality decreased when the injected cells were pretreated by NAC, ALA or melatonin during 20 h. Melatonin had the most marked effect. Tumors appeared in 100 % cases after 10 days in control mice when untreated cells had been injected; injection of cells pretreated by NAC or ALA resulted in tumor formation only in 40 and 53 % of mice, respectively. When cells were pretreated with melatonin the tumors appeared only in 18-20 days after injection. Until the end of the observation (36 days) 67 % of control mice died, but when the cells were pretreated by NAC or ALA mouse death-rate was 20 and 53 %, respectively. In the case of melatonin we did not observed any dead mice at all. We showed that treatment by antioxidants delayed (NAC) or completely inhibited (ALA) cell cycle of hepatoma cells. Cell cycle was restored after removal of the antioxidants. Melatonin did not change cell cycle phase distribution. We conclude that there is no direct correlation between loss of tumorigenic properties and changing of proliferative activity of hepatoma cells. Different mechanisms of antioxidants and melatonin action resulting in transient tumor phenotype normalization are discussed.

BACKGROUND: To compare the retinal nerve fiber layer (RNFL) in eyes of patients with relapsing remitting multiple sclerosis (RRMS), neuromyelitis optica (NMO) and chronic relapsing inflammatory optic neuritis (CRION).METHODS: Evaluation of 62 patients with RRMS, NMO, and CRION in a cross-sectional study with spectral domain optical coherence tomography.RESULTS: A total of 124 eyes were evaluated (96 RRMS, 18 NMO, and 10 CRION). Frequency of optic neuritis for each disease was: 34% for RRMS, 84% for NMO, and 100% for CRION. Visual acuity and RNFL thickness were significantly worse in NMO and CRION eyes than in RRMS, but there were no differences between NMO and CRION eyes. A RNFL of 41 ìm was 100% specific for optic neuritis associated with NMO and CRION when compared to RRMS.CONCLUSION: This study established RNFL values to differentiate optic neuritis of RRMS from NMO and CRION. Although similarities observed between NMO and CRION eyes might suggest that they are within the same disease spectrum, it is still recommended that these 2 conditions be differentiated on clinical grounds. Optical coherence tomography serves as an additional diagnostic tool and can be used to monitor disease progression.

OBJECTIVES: The goal of this work was to investigate the volume development of the mandible in growing rabbits with bilaterally induced temporomandibular joint (TMJ) arthritis that was either left untreated or treated with the tumor necrosis factor-alpha (TNF-á) antagonist etanercept.METHODS: A total of 18 New Zealand White rabbits aged 8 weeks were randomized to three groups of 6 animals each. Two of these groups were used as arthritis groups by sensitizing the 12 animals to ovalbumin (OA) at 10 weeks, followed by intraarticular OA injections to induce bilateral TMJ arthritis and repeating these injections every 3 weeks to maintain the inflammation. One of the two arthritis groups was treated by weekly subcutaneous etanercept injections, whereas the other group was left untreated. The remaining 6 animals served as controls. Maxillofacial CT scans were obtained at 3-week intervals (from week 10 of the rabbits' lives to the end of the experiment at 22 weeks) to volumetrically track the development of the mandibles after segmentation.RESULTS: The mandibles did not grow at a continuous rate, but the rate of development was found to decrease in all groups over the course of the study (weeks 10-22). The most extensive volume increases were noted during weeks 10-13. Severe growth deficiencies, especially of the condylar processes, were observed in the arthritis group not receiving treatment. The arthritis group treated with etanercept showed better rates of growth without, however, reaching the normal range of the control group.CONCLUSION: Antigen-induced TMJ arthritis was found to involve severe problems of growth similar to those in juvenile idiopathic arthritis. Etanercept can improve the volume development but does not reestablish an entirely normal rate of growth.

Perfluorooctanoic acid (PFOA) is extremely persistent and bioaccumulative in the environment; thus, it is very urgent to investigate an effective and moderate technology to treat the pollution of PFOA. In this study, a process combined iron and granular activated carbon (Fe(0)/GAC) micro-electrolysis with VUV-Fenton system is employed for the remediation of PFOA. Approximately 50 % PFOA (10 mg L(-1)) could be efficiently defluorinated under the following conditions: pH 3.0, dosage of Fe 7.5 g L(-1), dosage of GAC 12.5 g L(-1), and concentration of H2O2 22.8 mmol L(-1). Meanwhile, during the process, evident defluorination was observed and the concentration of fluoride ion was eventually 3.23 mg L(-1). The intermediates including five shorter-chain perfluorinated carboxylic acids (PFCAs), i.e., C7, C6, C5, C4, and C3, were also analyzed by high-performance liquid chromatography tandem mass spectrometry (HPLC/MS/MS) and defluorination mechanisms of PFOA was proposed, which involved photochemical of OH·, direct photolysis (185-nm VUV), and photocatalytic degradation of PFOA in the presence of Fe(3+) (254-nm UV).

Kisspeptin (KP) plays a key role in the regulation of the hypothalamic-pituitary-gonadal axis via the release of GnRH. As normal KP signaling is essential for reproductive function, it could be an interesting new target for therapeutic interventions, e.g., nonsurgical contraception in dogs. The aims of the present study were to investigate the effect of KP-10 administration on plasma LH concentration in different stages of the reproductive cycle and to investigate the suitability of p271 as KP antagonist in the bitch. Two groups of six adult Beagle bitches were used. In one group, plasma LH concentration was determined before (40 and 0 minutes) and 10, 20, 40, and 60 minutes after the intravenous administration of 0.5-ìg/kg body weight (BW) canine KP-10. In the other group, the bitches received a continuous intravenous infusion with p271 (50 ìg/kg BW/h) for 3 hours, and 0.5-ìg/kg BW canine KP-10 was administered intravenously 2 hours after the start of the p271 infusion. Their plasma LH concentration was determined before (-40 and 0 minutes) and 30, 60, 90, 120, 130, 140, 160, and 180 minutes after the start of the p271 infusion. In both groups, the experiments were performed during the follicular phase, the first and second half of the luteal phase, and during anestrus. Canine KP-10 induced an increase of plasma LH concentration during all estrous cycle stages and anestrus. There was no difference in LH response between the two groups. The lowest LH response was seen during the follicular phase and the highest response during anestrus. The area under the curve (AUC) for LH and LH increment in the follicular phase were lower than those in anestrus. The AUC LH and LH increment in the first half of the luteal phase were lower than those in the second half of the luteal phase and anestrus. The AUC LH and LH increment in the second half of the luteal phase were not different from those in anestrus. Continuous administration of the antagonist p271 did not alter basal plasma LH concentration and could not prevent or lower the LH response to KP-10 in any of the cycle stages and anestrus. It can be concluded that the LH response to KP-10 is dependent on estrous cycle stage and that peripheral administrated p271 cannot be used as KP antagonist in the dog. This provides new insight in reproductive endocrinology of the bitch, which is important when KP signaling is considered for therapeutic interventions, such as for estrus induction or nonsurgical contraception in the bitch.

To enhance the shelf life of edible mature mushrooms, Agaricus bisporus, 2 kGy ionizing treatments were applied at two different dose rates: 4.5 kGy/h (I(-)) and 32 kGy/h (I(+)). Both I(+) and I(-) showed a 2 and 4 day shelf-life enhancement compared to the control (C). Before day 9, no significant difference (p>0.05) in L value was detected in irradiated mushrooms. However, after day 9, the highest observed L value (whiteness) was obtained for the mushrooms irradiated in I(-). Analyses of phenolic compounds revealed that mushrooms in I(-) contained more phenols than I(+) and C, the latter containing the lower level of phenols. The fluctuation of the precursors of glutaminyl-4-hydroxyaniline (GHB) was less in I(-) than in I(+). The polyphenol oxidase (PPO) activities of irradiated mushrooms, analyzed via catechol oxidase, dopa oxidase, and tyrosine hydroxylase substrates, were found to be significantly lowered (p = 0.05) compared to C, with a further decrease in I(+). Analyses of the enzymes indicated that PPO activity was lower in I(+), contrasting with its lower phenols concentration. The observation of mushrooms' cellular membranes, by electronic microscopy, revealed a better preserved integrity in I(-) than in I(+). It is thus assumed that the browning effect observed in I(+) was caused by both the decompartmentation of vacuolar phenol and the entry of molecular oxygen into the cell cytoplasm. The synergetic effect of the residual active PPO and the molecular oxygen, in contact with the phenols, allowed an increased oxidation rate and, therefore, a more pronounced browning I(+) than in I(-).

Background: In Japan, there has been a lot of reports showing an association between facial flushing after light alcohol consumption and heterozygosity for inactive aldehyde dehydrogenase-2 (ALDH2). Persons with inactive ALDH2 may have a higher risk of alcohol-related oral, pharyngeal and esophageal cancers, compared with those with wild-type ALDH2. The purpose of this study was to examine whether flushers with oral or pharyngeal squamous cell carcinoma have an increased risk of synchronous or metachronous cancer of the upper gastrointestinal (UGI) tract.Methods: A retrospective study was performed by medical chart review and through a questionnaire sent to 285 patients treated for oral and pharyngeal cancer. Responses were obtained from 150 patients (52.6%), who were classified as flushers or non-flushers, smokers (?20 pack-year; 1 pack-years = number of cigarettes/20 per day) or non-smokers, and drinkers (?14 units of alcohol consumption per week; 1 unit = 22 g) or non-drinkers. Relationships of these factors with occurrence of second primary cancers (SPCs) in the UGI tract were investigated.Results: In Kaplan-Meier analysis, there was a significantly higher rate of SPC at 5 years in flushers and drinkers, but no relationship with smoking. In multivariate analyses, a history of flushing was significantly associated with SPC in the UGI tract (HR 2.64, 95% CI 1.25-5.52, P = 0.0109), but not with smoking or alcohol consumption.Conclusions: A simple interview on history of facial flushing after alcohol intake can be useful for identifying patients at high risk for synchronous or metachronous cancers of the UGI tract.

The mechanism of uveitis following cataract surgery, which is mediated in part by the cyclooxygenase pathway, is complex, the complexity of which is likely to be due to several factors. We investigated the possible local involvement of interleukin 6 (IL-6) in this response. Using a specific bioassay, we showed a dramatic increase of IL-6 levels (> 4 x 10(3) times) in all of the aqueous humors of 12 patients following cataract surgery. The IL-6 levels in serum samples were below detection limits, indicating a local production of this cytokine. In addition, the injection of highly purified recombinant interleukin 6 in the anterior chamber of the eye in rabbits resulted in an inflammatory response. These observations suggest that IL-6 may play a crucial role in the occurrence of inflammation after cataract surgery, and it may lead to new therapeutic approaches to this problem.

UNLABELLED: Transsexualism is one of the gender identity disorders where psychological sex is opposed to anatomical sex. This disorder leads to a discrepancy between the preferred social gender and the biological sex.AIM: The aim of this research is to compare knowledge and attitude toward transsexualism in student's opinion, coming from three universities in L?d?.METHOD: The questionnaire study was performed in the group of 300 students from three universities in L?d?: Technical University of L?d?, University of L?d?, Medical University of L?d?. The questionnaire contained 30 questions related to respondent's sex, birthplace, knowledge about definition and aetiology of transsexualism and also rights which students would grant to transsexuals.RESULTS: The right definition of transsexualism was pointed by 64% of students from Medical University, 57% from Technical University and 40% from University of L?d?. The right to surgical sex change for transsexuals would be granted by 87% of students from the Medical University, 69% from the University of L?d? and 40% from the Technical University. Majority of medical students (90%) and respectively 78% and 57% from the University of L?d? and Technical University would accept a transsexual as his/her co-worker.CONCLUSIONS: Student's knowledge about transsexualism is similar and does not differ from a foreign student's knowledge. Students from natural science studies (medicine and biology) are the most tolerant towards transsexuals.

OBJECTIVE: To understand status of health literacy among diabetics and their health management behaviors, and analyze the relationship of health literacy and health management.METHODS: A two-staged cluster randomized sampling method was used to investigate 1 130 diabetics in Beijing, Ningbo and Xiamen from October to November in 2012. All participants should be diagnosed by primary hospital and above and have lived in the community over six months. Diabetic patients who indicated that they had severely impaired vision or cognitive disorder, or had severe physical deterioration, or did not live in the address provided were excluded. A total of 1 130 questionnaires were sent out and 1 083 eligible questionnaires were taken back, accounting for 96.87%. Multivariate logistic regression was adopted to analyze the association between health literacy and health management behaviors and blood glucose level.RESULTS: Among those participants, 47.7% (517) were men, 52.3% (566) were women, the age was (67.0 ± 9.5). According to diabetes health literacy scores, 73.7% (798/1 083) of them were classified as poor health literacy and 26.1% (283/1 083) as essential health literacy. Health literacy was associated with health management behaviors independently, demonstrating that the probability of utilizing health education, free physical examination, lifestyle guidance, monitoring blood glucose on their own, measuring blood glucose more than once a week and taking hypoglycemic agent regularly among diabetics with essential health literacy were 1.40 (95%CI:1.03-1.91), 1.65 (95%CI: 1.19-2.28), 2.70 (95%CI:1.98-3.69), 2.05 (95%CI:1.34-3.15), 2.56 (95%CI:1.85-3.56) , 1.48 (95%CI:1.07-2.06) times of those in diabetics with poor health literacy (P < 0.05).CONCLUSION: Health literacy may affect health management behaviors among diabetics. More activities targeted on diabetics with low health literacy were suggested to improve their' health literacy and their skills about diabetes mellitus management.

The toxicity of genistein, an inhibitor of tyrosine kinases and topoisomerase-II, on human thymocytes was investigated. Genistein induced marked chromatin fragmentation indicative of apoptosis in human thymocyte cultures. Genistein-induced thymocyte apoptosis is unlikely due to an inhibition of basal tyrosine kinase activity, since another tyrosine kinase inhibitor, herbimycin A, does not induce thymocyte apoptosis, whereas other topoisomerase-II inhibitors do. The thymocyte subpopulation most sensitive to genistein-induced apoptosis exhibited a CD3-CD4+CD8+ phenotype. This subpopulation of thymocytes is also sensitive to glucocorticoid-induced apoptosis; however, differences between genistein- and glucocorticoid-induced apoptosis were noted. In particular, unlike glucocorticoid-induced apoptosis, genistein-induced apoptosis does not involve changes in [Ca2+]i and cannot be blocked by activation of protein kinase C.

Diffuse pulmonary arteriovenous malformation is a rare entity, the exact incidence of which is unknown. It can be limited to a single lobe, or it can diffusely involve one or both the lungs. Early diagnosis and treatment is crucial, as it is associated with increased frequency of thoracic and neurologic complications. Different diagnostic modalities offer some advantages over the others. None of the reported cases in the literature have associated stenosis of any major artery. We describe a rare case of diffuse pulmonary arteriovenous malformation limited to a lobe associated with descending pulmonary artery stenosis.

The aim of the present investigation was to compare the costs for the use of patellar tendon versus hamstring tendons as grafts for anterior cruciate ligament (ACL) reconstruction including the different fixation methods. The background is that during recent years there has been a dramatic shift from patellar tendon to hamstring tendons in ACL reconstructions in Sweden. All our patients with ACL reconstructions performed during 1 year (2004) were included. Knee joints numbering 440 in 439 patients were primary ACL reconstructions. A hamstring graft was used in 345 knee joints (78.4%) and a patellar tendon graft in 95 (21.6%) of the patients (Table 2). On average 34 (SD 12.9; range 14-63) ACL reconstructions per surgeon were performed by a total of 14 surgeons. The average cost for patellar tendon procedure was 197 euros compared to 436 euros for the hamstring procedure. Mean time for surgery in primary reconstructions was 11.5 min shorter (P<0.001) for patellar tendon reconstructions (71.3+/-31 min) compared to hamstring reconstructions (83.2+/-27 min). This means a difference in cost of 90 euros. The total additional cost (fixation and surgery time) for the hamstring method compared to the patellar tendon method was on an average 329 euros. From a strict economic point of view we therefore recommend or at least consider the use of the patellar tendon as a graft in ACL reconstructions.

Sleep deprivation (SD) consistently degrades performance in tasks requiring sustained attention, resulting in slower and more variable response times that worsen with time-on-task. Loss of motivation to exert effort may exacerbate performance degradation during SD. To test this, we evaluated sustained performance on a vigilance task, combining this with an effort-based decision-making task and pupillometry. Vigilance was tested at rest and after sleep deprivation, under different incentive conditions (1, 5 or 15 cents for fast responses). Subsequently, preference measures were collected from an effort-discounting task, in which a commensurate reward was offered for maintaining attentional performance for different durations (1, 5, 10, 20 or 30 min). Vigilance was impaired during SD, in a manner modulated by reward value. Preference metrics showed that the value of available rewards was discounted by task duration, an effect compounded by SD. Pupillometry revealed that arousal was modulated during SD in a value-based manner, and moment-to-moment fluctuations in pupil diameter were directly predictive of performance. Together, these data demonstrate that attentional performance can be interpreted within a value-based effort allocation framework, such that the perceived cost of attentional effort increases after sleep deprivation.

China has 800,000 villages-one person out of seven on the globe is living in a Chinese rural settlement. Yet the global discussions about the situation in China is currently characterised by a disproportionate focus on the development of towns and until now circumstances have generally been neglected in the rural areas, where 70% of the Chinese population is still living. Within the 5 years of the SUCCESS project research, this set of actual problems has been considered and analysed under the principle of sustainability: "What to maintain?" "What to change?" were the overall research questions asked in the SUCCESS project; the researchers were looking for answers under a sustainability regime, respecting the need to raise the quality of life in the villages. Several interweaving processes were used to achieve results: the inter-disciplinary research process between many areas of expertise, the trans-disciplinary process between the researchers and the Chinese villagers, and a negotiation process that made the connection between these two processes. The introduction describes the basic sustainability definition that was orienting the whole study. The innovation lays mostly in the methodology: the inter-disciplinary research co-operation related to practice and to involving the affected communities is needed to manage the significant and growing imbalances between urban and rural areas regarding their sustainability. In the transdisciplinary work, the project developed "village future sentences" that describe the local outcome of the research as one step towards better theoretical understanding of the mechanisms that could lead to a sustainable future, and they also managed to start sustainability processes in the case study sites. The integrated approach of the project helped generating future scenarios for these villages covering all aspects of their development, including urban design issues. Out of these scenarios, the villages developed small projects that could be implemented during the research period. This work made an important impact on community thinking within these villages. However, it can also be seen as contributing to the dramatically changing development process in China, by finding a balance between traditional and contemporary approaches. In particular, the approach demonstrated a new, inter-disciplinary and trans-disciplinary negotiation processes whereby the local knowledge and the expert knowledge find common ground and outcomes. The article follows the hypothesis that only comprehensive concepts can contribute to an upgraded living standard, where living spaces and rural life should be recognised and esteemed in the future as a complement to urban lifestyles within the Chinese society. Innovative knowledge generation-such as the "systemic structure constellation" technique or the systems model approach-helped to bring out latent needs, hopes and potential of the villagers. Besides the practical usage of these implemented projects, the process leading there showed the stakeholders their own fields of action. One major impact of these projects is the visibility of the results, which is crucial for villagers' awareness, their self-confidence and their experience with a successful participation in decision-making processes. Another impact is the potential for replicating results of sustainability-oriented patterns throughout China, especially as three of the villages have been nominated official model villages. Scenarios of a sustainable future for Chinese villages were the objective of the SUCCESS project. The first condition for this future is the question whether they can persist into the future-and to picture the importance of the rural environment and living space as a relevant element of Chinese life that needs to get a better image and more attention from the authorities and from the public opinion. Therefore, the final sentence that the whole research consortium, composed of 17 scientific institutions from European Union and China, agreed upon as a common result for the SUCCESS project, is as follows: "China is composed of a rich diversity of villages with many attractive qualities and essential resources for the future growth of the whole country; we recommend that policy makers cherish the human and natural potential of the rural economy and environment so that villages provide the foundation for sustainable development of this progressive nation" [Dumreicher, H., 2006. SUCCESS-a sustainable future for Chinese villages. International Symposium "Chinese Villages and their Sustainable Future", University of Natural Resources and Applied Life Sciences, Vienna, January 16]. This sentence was used in papers that where sent to different Chinese authorities by the Chinese partners and found its way, as a sort of "unofficial Charta", towards governmental agencies at national and provincial levels. The team carried out a 5-year-research study in rural China, aiming at establishing future images under the premises of sustainability. But the basic topic that needed to be tackled with was the question whether at all those villages could persist in the coming decades of rapid development. Therefore, the first aim of the study was to establish the importance of the rural environment and living space as a basis for the future of China.

The generation of oxidative stress, characterized by enhanced reactive oxygen species (ROS) formation, has been found in obesity. ROS production was increased during the differentiation of 3T3-L1 cells into adipocytes. We previously reported that caffeic acid phenethyl ester (CAPE) suppresses 3T3-L1 differentiation to adipocytes through the inhibition of peroxisome proliferator-activated receptor ã. In this study, the preventive effect of CAPE on oxidative stress in 3T3-L1 cells was observed. The results were as follows: (1) ROS production during 3T3-L1 cell differentiation to adipocytes was significantly (p < 0.05) suppressed by CAPE treatment in a concentration-dependent manner, (2) with CAPE treatment, the extracellular superoxide dismutase mRNA expression level significantly increased, but the NOX4 mRNA expression level did not change, and (3) CAPE treatment significantly increased superoxide dismutase (SOD) activity in 3T3-L1 cells. From these results, we suggest that the increased oxidative stress in 3T3-L1 differentiation to adipocytes is attenuated by CAPE treatment. This attenuation may be partly caused by increased SOD production.

Application of pancreatic digestive enzymes is indicated in cases of a quantitatively decreased exogenous secretion or an asynchronous secretion of enzymes with regard to the duodenal passage of chyme. A clear indication for therapy is a proven steatorrhea, a relative indication loss weight of and/or uncharacteristic abdominal discomfort in patients with proven pancreatic disease, i.e. chronic pancreatitis. Uncharacteristic abdominal discomfort alone, which is regarded as a consequence of 'maldigestion' without proven pancreatic disease, is not an indication for therapy. To prevent a destruction of exogenously applied lipase by gastric acid and to enable a synchronous gastroduodenal passage of the enzymes together with food, acid-protected micropellets or -tablets with an ideal diameter around 1.4 mm containing high amounts of lipase are requested. In cases of anacidity i.e. gastrectomy or type-A gastritis, lipase rich 'conventional' enzymes applied as granulate are sufficient. Combinations (pancreatic enzymes with bile acids) or fungal lipases have either more side effects (diarrhea) or are less efficient when compared to porcine enzymes. Acid-resistant microbial lipases may be useful in the near future. Application of pure proteases or pancreatic enzymes with high concentrations of proteases as treatment of pain in chronic pancreatitis ('negative feedback regulation') are a rather expensive form of treatment when compared to analgetics and are probably ineffective.

To determine whether hormone analysis could be used for accurate determination of fetal sex, we measured testosterone (T) and follicle-stimulating hormone (FSH) in 130 amniotic fluid samples at midgestation. The mean unconjugated T in amniotic fluid of 73 patients carrying male fetuses was 202 pg. per milliliter (95 per cent confidence limits [CL]: 70 to 580) and all but three had levels higher than 90 pg. per milliliter. The mean amniotic fluid unconjugated T for 49 patients carrying female fetuses of 41 pg. per milliliter (95 per cent CL: 11 TO 125) was fivefold lower than that for the male fetuses and all but three patients carrying female fetuses had amniotic fluid T levels of 90 pg. per milliliter or lower. The mean amniotic fluid FSH of 0.7 ml. U. per milliliter (95 per cent CL: less than 0.5 to 3.4) for subjects with male fetuses was tenfold lower than that for patients with female fetuses. Amniotic fluid FSH levels less than 2.0 ml. U. per milliliter were found in 88 per cent of patients carrying male fetuses and in only one patient with a female fetus, and levels greater than 10 ml. U. per milliliter were found in those with female fetuses only. In eight patients (7 per cent of cases), neither amniotic fluid T nor FSH determinations were indicative of fetal sex. Measurement of unconjugated T and FSH in amniotic fluid may be an adjunct to other methods of determining fetal sex.

BACKGROUND: During long-term in vitro heart preservation and subsequent reperfusion, irreversible tissue damage occurs in part due to reactive oxygen species. Therefore, inhibition of generation of oxygen-derived free radicals and the related oxidative damage of ischemic tissue may be useful in maintaining heart function after long-term preservation. Complexes of Cu(II) may cause disproportionation of superoxide and thus may function as an inhibitor of the effects of oxygen-derived free radicals.METHODS: In this study, 24-h preservation of isolated rat hearts was performed. Using the Langendorff technique, hearts were perfused for 24 h with a hypothermic, moderately hyperkalemic (15 mM KCl) solution containing various metabolic and membrane-stabilizing additives at constant low pressure. In addition, the potential benefit of the addition of two Cu(II) compounds (Cu(II) Cl2 and Cu(II)2Asp4) to the perfusion solution was examined.RESULTS: The Cu(II)Cl2-treated hearts were significantly better preserved than control hearts after 24 h of preservation with regard to recovery of systolic pressure, coronary flow, max +dP/dt, and max -dP/dt. Lipid peroxidation as estimated by myocardial malonaldehyde (both P < 0. 001) and myocardial creatine kinase release (both P < 0.05 vs control) were significantly reduced in the Cu(II)Cl2 and Cu(II)2Asp4 groups. Overall, Cu(II)Cl2 best preserved the heart after 24 h of cold preservation with respect to indices of functional recovery, whereas Cu(II)2Asp4 did not significantly improve functional recovery compared to control.CONCLUSION: Low-pressure, cold perfusion with an enhanced solution is a potential method to preserve donor hearts in preparation for transplantation. The beneficial effect of Cu(II)Cl2 was attributed to (i) SOD activity of the Cu2+ species and/or (ii) termination of chain carriers in the lipid peroxidations by aqueous Cu2+ and Cu+ species. The negation of some of the positive effects of Cu2+ species by the introduction of acetylsalicylate was tentatively assigned to potentiation of the Ca2+ modality for reperfusion injury.

An analog model of the part of a patient's body containing a tumor is constructed by drawing anatomical contours obtained from computed tomograms on a set of transparent plastic sheets. The coverage of radiotherapy fields in the patient is visualized in three dimensions using the model and the light beam from the radiotherapy machine or a simulator. A clinical example is presented.

An experimental model of Taenia crassiceps intraocular cysticercosis was developed in rabbits. The objectives of this study were to analyze the pathophysiology of this parasitic infection and to evaluate the humoral immune response. Cysticerci, inoculated in the anterior chamber of the eye, were able to grow; no inflammatory changes in the eye or anticysticercus antibodies in serum or in aqueous humor were detected during the 12-day period. In contrast, rabbits that had previously been either infected intraperitoneally with living T. crassiceps cysts or immunized intramuscularly with T. crassiceps antigenic extract developed an intense inflammatory reaction in the eye and high levels of antibodies were detected in serum and aqueous humor even before the intraocular inoculation of parasites. Furthermore, intraocular cysticerci showed minimal growth and some were eliminated. These findings support the concept that the eye is an immunologically privileged site in the nonimmunized host and the importance of the immune response in the elimination of this parasitic infection.

The Duffy Antigen Receptor for Chemokines (DARC) belongs to a family of erythrocyte chemokine receptors that bind C-X-C and C-C chemokines such as interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1) and regulated-on-activation, normal T cell-expressed and -secreted (RANTES), but not macrophage inflammatory protein 1 alpha (MIP-1 alpha) or MIP-1 beta. DARC has also been identified to a receptor for malaria parasites Plasmodium vivax and Plasmodium knowlesi. In the present study, we show that HIV-1 binds to RBCs from Caucasian individuals via DARC making RBCs able to transmit HIV to peripheral blood mononuclear cells (PBMCs). Furthermore, binding of HIV-1 particles to RBCs is inhibited by treating these cells with recombinant RANTES, but not with recombinant MIP-1 alpha prior to their incubation with HIV-1. This finding suggests that RBCs may function as a reservoir for HIV-1 or as a receptor for the entry of HIV-1 into CD4-cell subsets as well as neurons or endothelial cells.

We located a novel binding site for grayanotoxin on the cytoplasmic linkers of voltage-dependent cardiac (rH1) or skeletal-muscle (mu 1) Na(+) channel isoforms (segments S4-S5 in domains D1 and D4), using the alanine scanning substitution method. GTX-modification of Na(+) channels, transiently expressed in HEK 293 cells, was evaluated under whole-cell voltage clamp, from the ratio of maximum chord conductance for modified and unmodified Na(+) channels. In mu 1, mutations K237A, L243A, S246A, K248A, K249A, L250A, S251A, or T1463A, caused a moderate, but statistically significant decrease in this ratio. On making corresponding mutations in rH1, only L244A dramatically reduced the ratio. Because in mu 1, the serine at position 251 is the only heterologous residue with respect to rH1 (Ala-252), we made a double mutant L243A&S251A to match the sequence of mu 1 and rH1 in S4-S5 linkers of both domains. This double mutation resulted in a significant decrease in the ratio, to the same extent as L244A substitution in rH1 did, indicating that the site at Leu-244 in rH1 or at Leu-243 in mu 1 is a novel one, exhibiting a synergistic effect of grayanotoxin.

Dynamic acousto-elastic testing (DAET) is based on the coupling of a low-frequency (LF) acoustic wave and high-frequency ultrasound (US) pulses (probing wave). It was developed to measure US viscoelastic and dissipative non-linearity in trabecular bone. It is well known that this complex biphasic medium contains microdamage, even when tissues are healthy. The purpose of the present study was to assess the sensitivity of DAET to monitor microdamage in human calcanei. Three protocols were therefore performed to investigate the regional heterogeneity of the calcaneus, the correlation between DAET measurements and microdamage revealed by histology, and DAET sensitivity to mechanically induced fatigue microdamage. The non-linear elastic parameter beta was computed for all these protocols. The study demonstrated the presence of high viscoelastic and dissipative non-linearity only in the region of the calcaneus close to the anterior talocalcaneal articulation (region of high bone density). Protocols 1 and 2 also showed that most unsorted calcanei did not naturally exhibit high non-linearity, which is correlated with a low level of microcracks. Nevertheless, when microdamage was actually present, high levels of US non-linearity were always found, with characteristic non-linear signatures such as hysteresis and tension/compression asymmetry. Finally, protocol 3 demonstrated the high sensitivity of DAET measurement to fatigue-induced microdamage.

Sarcoidosis (SA) is an immune-mediated multisystemic disorder of unknown etiology characterized by the accumulation of lymphocytes, mononuclear phagocytes and epithelioid cell granulomas involved in different organs and tissues. The belief that genetics contribute to SA etiology is supported by twin studies, disease clustering in families and racial differences in incidence rates. Involvements of SLC11A1 in macrophage function and activation, makes it an attractive candidate gene for immune-mediated and infectious diseases. We investigated the association between SA and four polymorphisms of the SLC11A1 gene, including a single nucleotide change in intron 4 (INT4); a nonconservative single-base substitution at codon 543 (D543N); a TGTG deletion in the 3' untranslated region; and the functional (GT)(n) repeat polymorphism in the 5' region, in 95 Turkish SA patients and 150 healthy controls, by using amplification refractory mutation system-polymerase chain reaction and sequencing. We found significant association between SA and INT4 G/C allele frequency (P = 0.0000; odds ratio 2.75; 95% confidence interval 1.68-4.52) and 5'(GT)(n) allele 2/3 frequency (P = 0.0000; odds ratio 2.69; 95% confidence interval 1.61-4.47) suggesting that SLC11A1 might be a plausible candidate gene for SA.

BACKGROUND: Pregnancy in patients with kidney grafts is considered high-risk.OBJECTIVES: Determine perinatal complications in women with kidney transplants treated by our hospital and compare them with complications reported in national and international literature.MATERIAL AND METHOD: We studied perinatal complications in 18 patients with renal transplantation who delivered 19 newborns and were treated between 1 January 2009 and 31 December 2010. Results were compared with previous reports.RESULTS: Maternal age: 28.27 ± 4.70 years old, parity: 2, interval from transplant to conception: 7.52 ± 6.20 years, first prenatal visit 14.35 ± 6.74 weeks, prenatal care: 18.88 ± 9.18 weeks, 6 prenatal visits, gestational age at birth: 33.11 ± 8.72 weeks. Maternal complications: cesarean section: 88.88%, blood transfusion: 38.88%, anaemia: 33.33%, premature rupture of membranes: 22.22%, preterm delivery: 22.22%, urinary tract infection: 16.66%, preeclampsia: 11.11%, uncontrolled hypertension: 11.11%, miscarriage: 11.11%, uterine antony: 5.55%, gestational diabetes: 0%, and mortality: 0%. Foetal complications: premature birth: 52.63%, mortality: 21.05%, intensive care: 21.05%, and low birth weight due to growth restriction: 10.52%. Transplantation complications: filtration impairment without need for dialysis: 5.55%, graft rejection: 0%, and graft loss: 0%.CONCLUSIONS: The frequency of perinatal complications was high. Pregnancy had no adverse effect on renal function and patient survival. Stable renal grafts in women of childbearing age is not necessarily a contraindication for pregnancy.

To know the very early events occurring after heat shock, the changes of membrane lipids were examined. Heat stress induced the production of a certain glycolipid in the myxoamoebae of Physarum polycephalum in a few minutes. The purified glycolipid was determined to be a poriferasterol monoglucoside by structural studies that was previously reported to be expressed during the differentiation of Physarum cells from haploid myxoamoebae to diploid plasmodia (Murakami-Murofushi, K., Nakamura, K., Ohta, J., Suzuki, M., Suzuki, A., Murofushi, H., and Yokota, T. (1987) J. Biol. Chem. 262, 16719-16723). The activity of UDP-glucose:poriferasterol glucosyltransferase (Murakami-Murofushi, K., and Ohta, J. (1989) Biochim. Biophys. Acta 992, 412-415) was also expressed rapidly after heat shock. Thus, the activation of sterol glucosyltransferase and the production of sterol-glucoside were considered to be important events that were involved in the signal transduction system to induce some succeeding heat-shock responses, such as the synthesis of heat-shock proteins.

The role of Plasmodium falciparum and blood monocytes in the erythrocyte damage and pathogenesis of anemia has been investigated using two strains of the parasite; one laboratory-established strain (FSJ-M) and one wild, fresh, clinical isolate (PfPGI). Peripheral blood monocyte-induced growth inhibition of the parasites, erythrocyte membrane lipid peroxidation as seen by the formation of lipid peroxide products, and sensitivity to peroxide hemolysis at atmospheric oxygen were evaluated. The growth inhibition of FSJ-M by activated blood monocytes was greater than that of PfPGI. The extent of lipid peroxidation and sensitivity to hemolysis increased significantly as the parasites matured. These adverse effects were more marked following exposure to activated monocytes, especially in synchronized, parasitized RBCs. In addition, uninfected erythrocytes within the PfPGI parasite culture revealed a significant increase in the lipid peroxide formation (P < 0.01) and susceptibility to lysis (P < 0.05) under similar oxidant stress induced by monocytes from normal healthy donors. Furthermore, there was a direct correlation between membrane lipid peroxidation and peroxide hemolysis, both before and after monocyte exposure, suggesting a primary role of membrane peroxidation in red cell lysis. The contribution of intraerythrocytic parasites and nonspecific activation of blood monocytes in the pathophysiology of erythrocyte damage and anemia of P. falciparum infection is discussed.

This is a report of a postal questionnaire survey of 1250 general dental practitioners regarding occurrence of medical emergencies and their choice of emergency drugs and equipment. The response rate was 65 per cent and the results showed that about one in seven practitioners had had to resuscitate a patient. The most common medical emergencies were adverse reactions to local anaesthetics, grand mal seizures, angina pectoris and hypoglycaemia (insulin shock). Nearly all respondents (96 per cent) believed that dentists need to be competent in cardiopulmonary resuscitation, just over a half (55 per cent) felt they were competent in CPR on graduation and a similar figure (57 per cent) felt they could perform effective single person CPR for five minutes. Almost two-thirds (64 per cent) had undertaken CPR courses since graduation. Additionally, the most commonly kept emergency drugs were oxygen (63 per cent) and adrenaline (22 per cent), while the most commonly kept emergency equipment was a manual resuscitator (recoil bag-valve-mask type) which was kept by 27 per cent of the practitioners.

Background: Capsids of herpes simplex virus 1 (HSV-1) are assembled in the nucleus, translocated either to the perinuclear space by budding at the inner nuclear membrane acquiring tegument and envelope, or released to the cytosol in a "naked" state via impaired nuclear pores that finally results in impairment of the nuclear envelope. The Us3 gene encodes a protein acting as a kinase, which is responsible for phosphorylation of numerous viral and cellular substrates. The Us3 kinase plays a crucial role in nucleus to cytoplasm capsid translocation. We thus investigate the nuclear surface in order to evaluate the significance of Us3 in maintenance of the nuclear envelope during HSV-1 infection. Methods: To address alterations of the nuclear envelope and capsid nucleus to cytoplasm translocation related to the function of the Us3 kinase we investigated cells infected with wild type HSV-1 or the Us3 deletion mutant R7041(?Us3) by transmission electron microscopy, focused ion-beam electron scanning microscopy, cryo-field emission scanning electron microscopy, confocal super resolution light microscopy, and polyacrylamide gel electrophoresis. Results: Confocal super resolution microscopy and cryo-field emission scanning electron microscopy revealed decrement in pore numbers in infected cells. Number and degree of pore impairment was significantly reduced after infection with R7041(?Us3) compared to infection with wild type HSV-1. The nuclear surface was significantly enlarged in cells infected with any of the viruses. Morphometric analysis revealed that additional nuclear membranes were produced forming multiple folds and caveolae, in which virions accumulated as documented by three-dimensional reconstruction after ion-beam scanning electron microscopy. Finally, significantly more R7041(?Us3) capsids were retained in the nucleus than wild-type capsids whereas the number of R7041(?Us3) capsids in the cytosol was significantly lower. Conclusions: The data indicate that Us3 kinase is involved in facilitation of nuclear pore impairment and, concomitantly, in capsid release through impaired nuclear envelope.

OBJECTIVE: This study was performed to investigate bone deteriorations of diabetic mice in response to the treatment of ursolic acid derivative (UAD).METHODS: The biomarkers in serum and urine were measured, tibias were taken for the measurement on gene and protein expression and histomorphology analysis, and femurs were taken for the measurement on bone Ca and three-dimensional architecture of trabecular bone.RESULTS: UAD showed a greater increase in bone Ca, BMD and significantly increased FGF-23 and OCN, reduced PTH and CTX in diabetic mice. UAD reversed STZ-induced trabecular deleterious effects and stimulated bone remodeling. The treatment of STZ group with UAD significantly elevated the ratio of OPG/RANKL. Moreover, insulin and IGF-1 showed a negative correlation with both FBG and Hb1Ac in STZ group. We attributed down-regulating the level of Hb1Ac in diabetic mice to that ursolic acid derivative could primely control blood sugar levels. After analyzing of two adipocyte markers, PPARã and aP2, increased expression in the tibias of diabetic mice, and UAD could improve STZ-induced adipocyte dysfunction.CONCLUSIONS: These results demonstrated that UAD could ameliorate STZ-induced bone deterioration through improving adipocyte dysfunction and enhancing new bone formation and inhibiting absorptive function of osteoclast in the bone of diabetic mice.

The response of the adrenergic system of asthmatic subjects to exercise and the role of plasma catecholamines in exercise-induced asthma were investigated. Plasma levels of norepinephrine and epinephrine were measured at rest, during and after exercise in 7 asthmatic and 9 matched normal subjects. Exercise-induced bronchospasm occurred in all asthmatic subjects following exercise, while no significant change was observed in the normal subjects. The results showed that plasma levels of norepinephrine and epinephrine at rest and changes that occcurred during and after exercise were similar in both normal and asthmatic subjects. These data suggest that the adrenergic response of asthmatics to the same relative exercise stress as reflected in plasma catecholamine levels does not differ from that of normal subjects. It appears that changes in the circulating catecholamines do not play a significant role in the pathogenesis of exercised-induced asthma.

L-lactate uptake of isolated cardiac myocytes was investigated, since due to different lactate concentrations in the interstitial fluid and vascular space, lactate uptake cannot be studied satisfactorily in whole hearts. Lactate uptake exhibits sigmoidal saturation kinetics. Pyruvate (2.3 mM) inhibits L-lactate uptake at lower lactate concentrations (less than 15 mM) and enhances L-lactate uptake at higher (greater than 25 mM) lactate concentration. L-lactate uptake is increased at lowered pH (7.1) to an extent not explainable by non-ionic diffusion. The results are discussed in terms of a complex L-lactate carrier system which might involve cooperative mechanisms and H+-co- or OH- -countertransport.

Sinus histiocytosis with massive lymphadenopathy is an unusual disease characterized by prominent lymph node enlargement, especially in the cervical region. The clinical course is benign although prolonged, and no specific treatment is required. The etiology and pathogenesis are unknown. Four cases of sinus histiocytosis are reported, one in association with mediastinal lymph node enlargement and two in patients with orbital enlargement. One other patient had cervical masses. The radiologic features are reviewed to increase awareness of this entity as a cause of lymph node and orbital enlargement.

Macrophages displayed increased spreading, increased Fc-receptor-mediated phagocytosis, and increased secretion of plasminogen activator when collected from the peritoneal cavities of either Listeria-immune mice challenged intraperitoneally 3 days earlier with Listeria or nonimmune mice injected intraperitoneally 3 days earlier with fluid thioglycolate medium. In contrast, macrophages from the thioglycolate-induced peritoneal exudates were severely impaired in vitro in their ability to destroy Listeria. Injection of thioglycolate markedly interfered with the destruction of sublethal intraperitoneal challenge of Listeria, which resulted in nonimmune animals dying of an overwhelming systemic infection. In animals immune to Listeria, injection of thioglycolate delayed the onset of the expression of immunity to an intraperitoneal challenge of bacteria. The thioglycolate-induced suppression of bactericidal activity was determined to be confined to the site of injection. Results of experiments indicated that the colloidal agar in thioglycolate medium was the cause of the impairment of macrophage bactericidal activity. In addition to the impairment of bactericidal activity induced by agar, additional studies showed that an intraperitoneal injection of colloidal agar (0.075% wt/vol) by itself was a sufficient inflammatory stimulus for the accumulation of a large number of host phagocytic cells.

We performed a prospective study evaluating the incidence of angiographic cystoid macular edema (CME) following extracapsular cataract extraction and posterior chamber intraocular lens implantation. Of the 162 eyes in the study, 141 were randomized into either a primary capsulotomy or a capsule intact group. The remaining eyes were not randomized due to intraoperative surgical complications, but they were included in the follow-up studies. Six weeks after surgery, angiographic CME was documented in 24% of the capsulotomy group and in 16% of the capsule intact group. The differences were not statistically significant. Including nonrandomized cases reduced the overall incidence of angiographic CME and the difference between the two groups. Angiographic CME was usually not extensive, and it was associated with a visual acuity less than 20/40 in 2.5% of eyes six weeks postoperatively. A subgroup of 120 eyes was followed up for approximately six months, when angiographic CME was present in 4% of the capsulotomy and capsule intact groups.

The objective was to characterize the innate immune response in dairy goats after intrauterine infusion of E. coli. A suspension of Escherichia coli (E. coli; 4 ? 10(9) cfu (cfu)/mL; experimental group, n = 6) or 5 mL PBS (control group, n = 6) were infused once into each uterine horn in goats at 25 days postpartum. Blood and endometrial biopsy samples were collected preinoculation (0 h) and at 3, 6, 12, 24, 72, 120, and 168 h post inoculation (pi). Relative gene expression analyses of Toll-like receptor4 (TLR4), tumor necrosis factorá (TNF-á), â-defensin2, and interleukins (IL-1â, IL-6, IL-8) were performed on RNA extracted from endometrial tissue and peripheral white blood cells (WBCs) using quantitative real-time PCR. Endometrial tissue was also used for histopathology and cytology. In experimental goats, the mRNA expression of TLR4 and proinflammatory cytokines were increased within 24 h pi (P < 0.01) in endometrium and WBCs. Similarly, expression of â-defensin2 was higher at 72 h pi in endometrium (P < 0.001), and at 120 h pi in WBCs (P < 0.05). The %PMNs in the experimental group increased up to 92.16 ± 3.95% at 3 h pi (P < 0.001). Endometrial histopathology revealed a severe inflammatory response at 3 to 12 h pi, whereas no changes were detected in the control group. In conclusion, intrauterine infusion of E. coli in goats resulted in a rapid activation of the local innate immune response, characterized by infiltration of PMNs into the endometrium and up-regulation of gene expression for TLR4, cytokines and â-defensin2.

UNLABELLED: The aims of the present study were to describe the preferred and the actual participating roles in treatment decision-making in relation to patients with newly diagnosed, colorectal cancer and to relate this result to the sociodemographic data, the Sense of Coherence Scale (SOC) and the patients' meaning of the disease. Eighty-six patients were studied. The following instruments were used: the Control Preferences Scale (CPS); the eight Lipowski categories of the meaning of the disease (LCMD); and the SOC. The results showed that 62% of the patients preferred a collaborative role and 28% a passive role in treatment decision-making. Agreement between the preferred and the actual participating roles was achieved by 44% of the patients. Seventy-one per cent of the patients showed an optimistic understanding of their disease. The mean SOC score was 150. There was no statistically significant difference between the CPS groups as regarded the sociodemographic data, the SOC and the LCMD.CONCLUSION: Sociodemographic data, the perceived meaning of the disease as well as the patients' sense of coherence were not related to the decision-making preferences in the investigated group of patients. Therefore, further investigations are needed to get an understanding of influencing factors of the decision-making preferences.

Beyond being simply positive or negative, beneficial or inhibitory, microbial interactions can involve a diverse set of mechanisms, dependencies and dynamical properties. These more nuanced features have been described in great detail for some specific types of interactions, (e.g. pairwise metabolic cross-feeding, quorum sensing or antibiotic killing), often with the use of quantitative measurements and insight derived from modeling. With a growing understanding of the composition and dynamics of complex microbial communities for human health and other applications, we face the challenge of integrating information about these different interactions into comprehensive quantitative frameworks. Here, we review the literature on a wide set of microbial interactions, and explore the potential value of a formal categorization based on multidimensional vectors of attributes. We propose that such an encoding can facilitate systematic, direct comparisons of interaction mechanisms and dependencies, and we discuss the relevance of an atlas of interactions for future modeling and rational design efforts.

To examine further the role of charge-pair interactions in the structure and function of lactose permease, Asp237 (helix VII), Asp240 (helix VII), Glu126 (cytoplasmic loop IV/V), Glu269 (helix VIII), and Glu325 (helix X) were replaced individually with Cys in a functional mutant devoid of Cys residues. Each mutant was then oxidized with H2O2 in order to generate a sulfinic and/or sulfonic acid at these positions. Due to the isosteric relationship between aspartate and sulfinate, in particular, and the lower pKa of the sulfinic and sulfonic acid side chains, oxidized derivatives of Cys are useful probes for examining the role of carboxylates. Asp237-->Cys or Asp240-->Cys permease is inactive, as shown previously, but H2O2 oxidation restores activity to an extent similar to that observed when a negative charge is reintroduced by other means. Glu126-->Cys, Glu269-->Cys, or Glu325-->Cys permease is inactive, but oxidation does not restore active lactose transport. The data are consistent with previous observations indicating that Asp237 and Asp240 are not critical for active lactose transport, while Glu126, Glu269, and Glu325 are irreplaceable. Although Glu269-->Cys permease does not transport lactose, the oxidized mutant exhibits significant transport of beta,D-galactosylpyranosyl 1-thio-beta,D-galactopyranoside, a property observed with Glu269-->Asp permease. The observation supports the idea that an acidic residue at position 269 is important for substrate recognition. Finally, oxidized Glu325-->Cys permease catalyzes equilibrium exchange with an apparent pKa of about 6.5, more than a pH unit lower than that observed with Glu325-->Asp permease, thereby providing strong confirmatory evidence that a negative charge at position 325 determines the rate of translocation of the ternary complex between the permease, substrate, and H+.

Individuals with Down syndrome (DS) are at a high risk for developing Alzheimer disease (AD) after the age 40; however, low levels of intellectual functioning, coupled with impaired language ability, confound the detection of AD. Comparative neuropsychological tests developed in animal models of aging and cognition do not require intact language function and can be useful for detecting changes in cognition. Experimental paradigms used to detect age-dependent cognitive deficits in animal models were applied in the present study to measure cognitive function in a group of 20 adults with DS ranging in age from 22 to 58 years. Object discrimination, reversal learning, and spatial and object memory were administered using a modified Wisconsin General Testing Apparatus and reinforcement (penny rewards). When considering age as the only clinical variable to parallel the animal studies, age was significantly correlated with performance on object memory and marginally related to performance on reversal learning and spatial memory. However, when evaluating multiple clinical variables including age, a measure of intellectual ability (FSIQ), scores on the Dementia Questionnaire for Persons with Mental Retardation (DMR), and gender using regression analysis, scores on the DMR were the best predictors of errors of reversal learning, whereas FSIQ was the best predictor of performance on object memory. These results suggest that while age may be related to performance on learning and memory tasks, other clinical variables may be stronger predictors of performance in adults with DS. These changes may reflect prefrontal and medial temporal lobe dysfunction that is associated with the development of AD pathology in DS.

Breast cancer patients are frequent users of complementary and alternative medicine (CAM). They often have complex reasons for, and experiences from, their use of CAM. Bodily experiences are important and almost unexplored elements in CAM use. Our aim was to explore the meaning and importance of bodily experiences among breast cancer patients who were using CAM as a supplement or an alternative to conventional treatment (CT). Our findings based on qualitative interviews with 13 women suggest that bodily experiences were particularly important when positioned outside conventional health care prior to medical diagnosis and as users of CAM as alternative to CT. We introduce three central modes of embodiment related to CAM use: the right to one's body, the body used as a gauge, and the body used as a guide. Patients' positioning between treatment systems should be further explored from a bodily perspective to safeguard and optimize their treatment choices.

Oxidation of the acetate-bridged half-lantern platinum(II) complex cis-[Pt(II)(NH(3))(2)(ì-OAc)(2)Pt(II)(NH(3))(2)](NO(3))(2), [1](NO(3))(2), with iodobenzene dichloride or bromine generates the halide-capped platinum(III) species cis-[XPt(III)(NH(3))(2)(ì-OAc)(2)Pt(III)(NH(3))(2)X](NO(3))(2), where X is Cl in [2](NO(3))(2) or Br in [3](NO(3))(2), respectively. These three complexes, characterized structurally by X-ray crystallography, feature short (?2.6 ?) Pt-Pt separations, consistent with formation of a formal metal-metal bond upon oxidation. Elongated axial Pt-X distances occur, reflecting the strong trans influence of the metal-metal bond. The three structures are compared to those of other known dinuclear platinum complexes. A combination of (1)H, (13)C, (14)N, and (195)Pt NMR spectroscopy was used to characterize [1](2+)-[3](2+) in solution. All resonances shift downfield upon oxidation of [1](2+) to [2](2+) and [3](2+). For the platinum(III) complexes, the (14)N and (195)Pt resonances exhibit decreased line widths by comparison to those of [1](2+). Density functional theory calculations suggest that the decrease in the (14)N line width arises from a diminished electric field gradient at the (14)N nuclei in the higher valent compounds. The oxidation of [1](NO(3))(2) with the alternative oxidizing agent bis(trifluoroacetoxy)iodobenzene affords the novel tetranuclear complex cis-[(O(2)CCF(3))Pt(III)(NH(3))(2)(ì-OAc)(2)Pt(III)(NH(3))(ì-NH(2))](2)(NO(3))(4), [4](NO(3))(4), also characterized structurally by X-ray crystallography. In solution, this complex exists as a mixture of species, the identities of which are proposed.

The effect of the oxidant t-butyl hydroperoxide on intracellular free levels of Ca2+ ([Ca2+]i) in PC12 pheochromocytoma cells was examined by using fura-2 as a fluorescent dye. t-Butyl hydroperoxide induced an increase in [Ca2+]i in a concentration-dependent fashion between 50-250 microM with an EC50 of 100 microM. The [Ca2+]i signal consisted of a slow rise and a sustained phase. The response was decreased by 65% by removal of extracellular Ca2+. In Ca(2+)-free medium, pretreatment with 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) abolished 150 microM t-butyl hydroperoxide-induced [Ca2+]i increase, and conversely, pretreatment with t-butyl hydroperoxide abrogated thapsigargin-induced [Ca2+]i increase. The 150 microM t-butyl hydroperoxide-induced [Ca2+]i increase in Ca2+ medium was reduced by 42 +/- 5% by pretreatment with 0.1 microM nicardipine but not by 10 microM verapamil, nifedipine, nimodipine or diltiazem, or by 50 microM La3+ or Ni2+. Pretreatment with 10 microM t-butyl hydroperoxide for 40 min did not affect 10 microM ATP-induced [Ca2+]i increase. Together, the results show that t-butyl hydroperoxide induced significant [Ca2+]i increase in PC12 cells by causing store Ca2+ release from the thapsigargin-sensitive endoplasmic reticulum pool in an inositol 1,4,5-trisphosphate-independent manner and by inducing Ca2+ influx via a nicardipine-sensitive pathway.

The streptokinase resistance test (SRT) has been studied in a group of patients with recent streptococcal infection and/or titres of antistreptolysin higher than 625 units. These patients generally had a higher SRT.