Effect of fructose on postprandial triglycerides: a systematic review and meta-analysis of controlled feeding trials.
In the absence of consistent clinical evidence, concerns have been raised that fructose raises postprandial triglycerides. A systematic review and meta-analysis was conducted to assess the effect of fructose on postprandial triglycerides. Relevant studies were identified from MEDLINE, EMBASE, and Cochrane databases (through September 3, 2013). Relevant clinical trials of ≥ 7-days were included in the analysis. Two independent reviewers extracted relevant data with disagreements reconciled by consensus. The Heyland Methodological Quality Score (MQS) assessed study quality. Data were pooled by the generic inverse variance method using random effects models and expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). Heterogeneity was assessed (Cochran Q statistic) and quantified (I(2) statistic). Eligibility criteria were met by 14 isocaloric trials (n = 290), in which fructose was exchanged isocalorically for other carbohydrate in the diet, and two hypercaloric trials (n = 33), in which fructose supplemented the background diet with excess energy from high-dose fructose compared with the background diet alone (without the excess energy). There was no significant effect in the isocaloric trials (SMD: 0.14 [95% CI: -0.02, 0.30]) with evidence of considerable heterogeneity explained by a single trial. Hypercaloric trials, however, showed a significant postprandial triglyceride raising-effect of fructose (SMD: 0.65 [95% CI: 0.30, 1.01]). Most of the available trials were small, short, and of poor quality. Interpretation of the isocaloric trials is complicated by the large influence of a single trial. Pooled analyses show that fructose in isocaloric exchange for other carbohydrate does not increase postprandial triglycerides, although an effect cannot be excluded under all conditions. Fructose providing excess energy does increase postprandial triglycerides. Larger, longer, and higher-quality trials are needed. ClinicalTrials.gov identifier, NCT01363791.


Non-Enhancing Intradural Extramedullary Ependymoma: A Case Report.
Spinal ependymomas are generally located in the intramedullary compartment in adults. Intradural extramedullary spinal ependymomas are extremely rare. Spinal ependymomas show various contrast enhancements on MRI. In this study, we report a rare case of a 52-year-old female who had a pathologically confirmed intradural extramedullary ependymoma that showed no enhancement on MRI.


Neuroinflammation, Gut-Brain Axis and Depression.
Psychiatric diseases are the manifestations that result from the individual's genetic structure, physiology, immunology and ways of coping with environmental stressors. The current psychiatric diagnostic systems do not include any systematic characterization in regard to neurobiological processes that reveal the clinical picture in individuals who got psychiatric diagnosis. It is obvious that further research in different areas is needed to understand the psychopathology. The problems in the functions of immune system and the correlation of neuroinflammatory processes with psychiatric disorders have been one of the main research topics of psychiatry in recent years and have contributed to our understanding of psychopathology. Recent advances in the fields of immunology and genetics as well as rapidly increasing knowledge on the effects of immunological processes on brain functions have drawn attention to the correlations between psychiatric disorders and immune system dysfunctions. There are still unfilled gaps in the biology, pathophysiology, and treatment of major depressive disorder, which is quite prevalent among the psychiatric disorders, can lead to significant disability, and frequently has a recurrent course. It appears that low-grade chronic neuroinflammation plays a key role in forming a basis for the interaction between psychological stress, impaired gut microbiota and major depressive disorder. In this review, the role of neuroinflammation in the etiopathogenesis of depression and the mechanism of action of the gut-brain axis that leads to this are discussed in the light of current studies.


Gene expression profiling of human stent-induced neointima by cDNA array analysis of microscopic specimens retrieved by helix cutter atherectomy: Detection of FK506-binding protein 12 upregulation.
Restenosis due to neointima formation is the major limitation of stent-supported balloon angioplasty. Despite abundant animal data, molecular mechanisms of neointima formation have been investigated on only a limited basis in patients. This study sought to establish a method for profiling gene expression in human in-stent neointima and to identify differentially expressed genes that may serve as novel therapeutic targets. We retrieved tissue specimens from patients with symptomatic in-stent restenosis using a novel helix cutter atherectomy device. cDNA samples prepared from neointima (n=10) and, as a control, from the media of normal arteries (n=14) were amplified using a novel polymerase chain reaction protocol and hybridized to cDNA arrays. Immunohistochemistry characterized the atherectomy material as neointima. cDNA arrays readily identified differentially expressed genes. Some of the differentially expressed genes complied with expected gene expression patterns of neointima, including downregulation of desmin and upregulation of thrombospondin-1, cyclooxygenase-1, and the 70-kDa heat shock protein B. Additionally, we discovered previously unknown gene expression patterns, such as downregulation of mammary-derived growth inhibitor and upregulation of FK506-binding protein 12 (FKBP12). Upregulation of FKBP12 was confirmed at the protein level in neointimal smooth muscle cells. Gene expression patterns of human neointima retrieved by helix-cutter atherectomy can be reliably analyzed by cDNA array technology. This technique can identify therapeutic targets in patients, as exemplified by the findings regarding FKBP12. FKBP12 is the receptor for Rapamycin (sirolimus), which in animal models reduced neointima formation. Our study thus yields a rationale for the use of Rapamycin to prevent restenosis in patients.


Completion thyroidectomy for differentiated thyroid cancer (results in a consecutive series of 68 patients).
Completion thyroidectomy plays an important role in the management of patients with thyroid cancer. The aim of this study is to determine the indications for and timing of a second surgery, as well as surgical complications. Operative reports, as well as the hospital and outpatient records of 686 consecutive patients, who had undergone surgery for differentiated thyroid cancer, were reviewed. Among these, 68 (9,9%) patient records of a completion thyroidectomy for cancer were analyzed. The mean time interval between the first and second operation was 3.6 months (range: 1-9). Post-operative complications occurred in 9 patients (12,9%). Among three patients with inferior laryngeal nerve palsy (4,4%) one had definitive palsy (1.4%). Hypoparathyroidism occurred in 6 patients (8,8%) being permanent in one of them (1.4%). No significant difference either for definitive inferior laryngeal nerve lesions (p = 0.9) or for definitive hypocalcemia (p = 1) was found between the groups of patients who had a completion thyroidectomy and those who had a one-step total thyroidectomy for cancer. Correct indications for re-operation, total lobectomy as a primary surgical procedure as well as lateral access to the residual thyroid gland could all reduce the high risks of complications related to this kind of surgery.


Epidemiological research of twig scab on pear as basis for a rational and ecological disease management.
Scab is one of the key parasites in fruit growth. In favourable weather conditions for the pathogen, a complete harvest can be destroyed if no control measurements are undertaken. The scab fungi on pear and apple are two distinct species. They have, however, a similar biological cycle. Despite the similarities, there are also clear differences and these differences are significant for the control of the pathogen. Pear scab does not only infect fruit and leaves as apple scab does, but also infects twigs. Especially in organic fruit growing, twig scab is a big problem. Once twig scab occurs, it seems to be impossible to get rid of scab in these orchards. The only possibility for the fruit grower in this case is a strict spraying schedule to ensure no further spread of the infection. The main goal of the project is a thorough study of the pear scab fungi (biology, sensitivity of different plant parts and cultivars, dispersal of the fungi and infection conditions, the pathogenicity and characterization of different biotypes) to unravel the life of the fungi and to develop a better control strategy. A better control strategy means a reduced fungicide use and a reduction of fungicide residue on the fruits at harvest, without a reduction of the quality of the fruits and cost effectiveness for the fruit grower. Special attention in the project goes to the role and the control of twig scab. The first results of this project will be shown.


Single nocturnal doses of pirenzepine effectively inhibit overnight gastric secretion.
The gastric antisecretory effects of two dose levels of pirenzepine given at night were investigated in a group of healthy male volunteers. Compared with placebo, three days of treatment with pirenzepine 100 mg nocte or 150 mg nocte inhibited mean nocturnal intragastric acidity by 54% and 53%, respectively (p less than 0.01). The volume of gastric juice secreted was reduced by 47% and 52% (p less than 0.005), by 100 mg and 150 mg nocte, respectively. Each dose suppressed mean gastric acid output by 67% (p less than 0.001). Pepsin output was not significantly altered. There were no differences in effect between the two dose levels studied, but side-effects such as dry mouth were only seen with the higher dose. Pirenzepine 100 mg is the optimum dose which can conveniently be given at night. This will limit side-effects, and may be a useful treatment for patients with duodenal ulcer.


Recent patents on new steroid agents targeting the steroidogenesis for endocrine cancer treatments.
Cancer is a leading cause of death in the population and despite the significant technological advances that have been made over the last years, there is a great need for new and better treatments with fewer side effects. Among the various types, hormone-dependent cancers are stimulated by the presence of certain steroidal hormones such as androgens and estrogens, which act through a nuclear receptor. The use of small molecules to block the biosynthesis (steroidogenesis) or the action of hormones (androgens or estrogens) is a therapeutic approach that has yielded interesting results and whose development continues. This review article emphasizes the patents and patent applications published over the last five years. It deals exclusively with steroid compounds developed as inhibitors of key enzymes (17α-hydroxylase/17,20-lyase, steroid sulfatase, 5α-reductases, aromatase and 17β-hydroxysteroid dehydrogenases) involved in the steroidogenesis and identified as therapeutic targets. Such inhibitors could be used as a drug to reduce the concentration of androgens or estrogens and, consequently, for treating hormone-dependent diseases such as prostate cancer, breast cancer and endometriosis.


Does the Broaden-and-Build Theory Explain Reduction in Social Disruption After a Brief Relaxation Intervention for Women With Breast Cancer Undergoing Treatment?
Women with breast cancer experience social disruption during and after treatment. Brief cognitive-behavioral (CBT) and relaxation (RT) interventions may improve social disruption by increasing positive affect. Using the Broaden-and-Build Theory as a framework, this study examined whether short-term CBT- and RT-related increases in positive affect mediate long-term reductions in social disruption in women with breast cancer undergoing treatment (N = 183). This secondary analysis used latent change score and growth models to test 6- and 12-month intervention effects on positive affect and social disruption, respectively; a parallel-process model assessed mediation. RT demonstrated larger reductions in social disruption across 12 months compared to CBT and a health education control. Six-month latent change in positive affect was significant but not driven by condition. There was a significant direct effect linking the latent slopes of positive affect and social disruption but meditation was not observed. These preliminary findings hint at the value of promoting positive affect and inform the development of brief behavioral interventions that aim to augment social functioning among women surviving breast cancer.


Association study of an epidermal growth factor gene functional polymorphism with the risk and prognosis of gliomas in Brazil.
Epidermal growth factor (EGF) plays an important role in cancer. A functional single nucleotide polymorphism (SNP) in the 5'-untranslated region of the EGF gene (+61 A>G) may influence its expression and contribute to cancer predisposition and aggressiveness. Aiming to investigate the role of EGF +61 A>G in the susceptibility to glioma and its prognosis, we performed a case-control study with 165 patients and 200 healthy controls from Brazil. Comparisons of genotype distributions and allele frequencies did not reveal any significant differences between the groups. The mean overall survival was 9.2 months for A/A, 8.2 months for A/G, and 7.7 months for G/G. When survival curves were plotted we found that the +61G allele is associated with poor overall survival (p=0.023) but not with disease-free survival (p=0.527). Our data suggest that, although there is no association between the EGF +61 A>G genotype and glioma susceptibility, this SNP is associated with shorter overall survival of glioma patients in the Brazilian population. Nevertheless, future studies utilizing a larger series are essential for a definitive conclusion.


Changing species distribution and antimicrobial susceptibility pattern of Shigella over a 29-year period (1980-2008).
We studied changes in species distribution and antimicrobial resistance patterns of Shigella during 1980-2008, using the Diarrhoeal Diseases Surveillance system of Dhaka Hospital of ICDDR,B. In hospitalized patients Shigella prevalence decreased steadily from 8-12% in the 1980s to 3% in 2008. Endemic S. flexneri was the most commonly isolated species (54%). Epidemic S. dysenteriae type 1 had two peaks in 1984 and 1993, but was not found after 2000, except for one case in 2004. The therapeutic options are now limited: in 2008 a total of 33% of S. flexneri were resistant to ciprofloxacin and 57% to mecillinam. In the <5 years age group, severely underweight, wasted and stunted children were more at risk of shigellosis compared to well-nourished children (P<0·001). Although hospitalization for Shigella diarrhoea is decreasing, the high levels of antimicrobial resistance and increased susceptibility of malnourished children continue to pose an ongoing risk.


Functional expression of the epithelial Ca(2+) channels (TRPV5 and TRPV6) requires association of the S100A10-annexin 2 complex.
TRPV5 and TRPV6 constitute the Ca(2+) influx pathway in a variety of epithelial cells. Here, we identified S100A10 as the first auxiliary protein of these epithelial Ca(2+) channels using yeast two-hybrid and GST pull-down assays. This S100 protein forms a heterotetrameric complex with annexin 2 and associates specifically with the conserved sequence VATTV located in the C-terminal tail of TRPV5 and TRPV6. Of these five amino acids, the first threonine plays a crucial role since the corresponding mutants (TRPV5 T599A and TRPV6 T600A) exhibited a diminished capacity to bind S100A10, were redistributed to a subplasma membrane area and did not display channel activity. Using GST pull-down and co-immunoprecipitation assays we demonstrated that annexin 2 is part of the TRPV5-S100A10 complex. Furthermore, the S100A10-annexin 2 pair colocalizes with the Ca(2+) channels in TRPV5-expressing renal tubules and TRPV6-expressing duodenal cells. Importantly, downregulation of annexin 2 using annexin 2-specific small interfering RNA inhibited TRPV5 and TRPV6-mediated currents in transfected HEK293 cells. In conclusion, the S100A10-annexin 2 complex plays a crucial role in routing of TRPV5 and TRPV6 to plasma membrane.


Catecholamine-induced transport systems in trout erythrocyte. Na+/H+ countertransport or NaCl cotransport?
It has previously been shown (Baroin, A., F. Garcia-Romeu, T. Lamarre, and R. Motais. 1984a, b. Journal of Physiology. 350:137, 356:21; Mahé, Y., F. Garcia-Romeu, and R. Motais. 1985. European Journal of Pharmacology. 116:199) that the addition of catecholamines to an isotonic suspension of nucleated red blood cells of the rainbow trout first stimulates a cAMP-dependent, amiloride-sensitive Na+/H+ exchange. This stimulation seems to be transient. It is followed by a more permanent activation of a coupled entry of Na+ and Cl-, which is inhibited by amiloride but also by inhibitors of band 3 protein (DIDS, furosemide, niflumic acid). The coupled entry of Na+ and Cl- could therefore result from the parallel and simultaneous exchange of Na+out for H+in (via the cAMP-dependent Na+/H+ antiporter) and Cl- out for HCO3- in (via the anion exchange system located in band 3 protein). However, in view of the following arguments, it had been proposed that NaCl uptake does not proceed by the double-exchanger system but via an NaCl cotransport: (a) Na+ entry requires Cl- as anion (in NO3- medium, the Na uptake is strongly inhibited, whereas NO3- is an extremely effective substitute for Cl- in the anion exchange system); (b) Na uptake is not significantly affected by the presence of HCO3- in the suspension medium despite the fact that in red cells, Cl-/HCO3- exchange occurs more readily than the exchanges of Cl- for basic equivalents in a theoretically CO2-free medium (the so-called Cl-/OH- exchanges). The purpose of the present paper was a reassessment of the two models by using monensin, an ionophore allowing Na+/H+ exchange. From this study, it appears that NaCl entry results from the simultaneous functioning of the Na+/H+ antiporter and the anion exchange system. The apparent Cl dependence is explained by the fact that, in these erythrocytes, NO3- clearly inhibits the turnover rate of the Na+/H+ antiporter. As Na+/H+ exchange is the driving component in the salt uptake process, this inhibition explains the Cl requirement for Na entry. The lack of stimulation of cell swelling by bicarbonate is explained by the fact that the rate of anion exchange in a CO2-free medium (Cl-/OH- exchange) is roughly equivalent to that of Na+/H+ exchange and thus in practice is not limiting to the net influx of NaCl through the two exchangers.(ABSTRACT TRUNCATED AT 400 WORDS)


A study of the antigenicity of T3 and T4 coli-dysentery bacteriophages during the vegetative stage of development.
The development of viral neutralizing antibodies in animals injected with T(3) or T(4) phage is considerably inhibited by the presence of bacterial antigens. A new procedure has been described to liberate phage from infected E. coli B bacteria by inducing lysis with penicillin. By immunological means it has been shown that T(4)-infected cultures of E. coli B, in which phage development has been inhibited with proflavine, contain the viral neutralizing antigen after lysis. In contrast, it has not been possible to demonstrate by immunological means the appearance of viral neutralizing antigen in E. coli B infected with T(3) prior to the appearance of intracellular phage.


A prospective cohort study to investigate cost-minimisation, of Traditional open, open fAst track recovery and laParoscopic fASt track multimodal management, for surgical patients with colon carcinomas (TAPAS study).
The present developments in colon surgery are characterized by two innovations: the introduction of the laparoscopic operation technique and fast recovery programs such as the Enhanced Recovery After Surgery (ERAS) recovery program. The Tapas-study was conceived to determine which of the three treatment programs: open conventional surgery, open 'ERAS' surgery or laparoscopic 'ERAS' surgery for patients with colon carcinomas is most cost minimizing? The Tapas-study is a three-arm multicenter prospective cohort study. All patients with colon carcinoma, eligible for surgical treatment within the study period in four general teaching hospitals and one university hospital will be included. This design produces three cohorts: Conventional open surgery is the control exposure (cohort 1). Open surgery with ERAS recovery (cohort 2) and laparoscopic surgery with ERAS recovery (cohort 3) are the alternative exposures. Three separate time periods are used in order to prevent attrition bias. Primary outcome parameters are the two main cost factors: direct medical costs (real cost price calculation) and the indirect non medical costs (friction method). Secondary outcome parameters are mortality, complications, surgical-oncological resection margins, hospital stay, readmission rates, time back to work/recovery, health status and quality of life. Based on an estimated difference in direct medical costs (highest cost factor) of 38% between open and laparoscopic surgery (alfa = 0.01, beta = 0.05), a group size of 3 x 40 = 120 patients is calculated. The Tapas-study is three-arm multicenter cohort study that will provide a cost evaluation of three treatment programs for patients with colon carcinoma, which may serve as a guideline for choice of treatment and investment strategies in hospitals. ISRCTN44649165.


Avian Schistosomes from the South American Endemic Gastropod Genus Chilina (Pulmonata: Chilinidae), with a Brief Review of South American Schistosome Species.
Our current knowledge of avian schistosomes from South America is scarce in all respects, including species and generic diversity, their life cycles, patterns of host use, potential to cause dermatitis outbreaks, and evolutionary affinities. As a step towards addressing this shortcoming, the goal of this study was to provide discrete reference points relating to snail hosts, locality records, morphological attributes, sequence for nuclear 28S and ITS, and partial mitochondrial cox1 genes, and phylogenetic relationships for schistosome cercariae recovered from different species of Chilina, which are gastropods endemic to South America. In total, 1,308 snails belonging to 6 species of Chilina were collected from 12 localities across Argentina. Thirty-eight snails (2.9%) had schistosome infections. Our data indicate the presence of 3 lineages of Chilina-transmitted schistosomes, all of which group within the major avian schistosome clade. However, none of the lineages grouped within or as sister to other known avian schistosome genera in the tree, indicating they probably represent undescribed genera. The relationships of these schistosomes from Chilina spp. are discussed in relation to their position in the global schistosome phylogenetic tree.


Mental health care in juvenile detention facilities: a review.
Juvenile detention facilities have come under increasing legal pressure to provide mental health services to detainees, and mental health clinicians may be asked to design and implement programs in detention facilities. However, there is little consensus on what types of services should be provided, and virtually no data on the effectiveness of such services in a detention setting. The objective of this article is to provide an overview of the existing literature on mental health services in juvenile detention and to make suggestions about future research needs. Specifically, it highlights the tension surrounding the provision of mental health care in juvenile detention, presents data on the prevalence of psychiatric problems in detention settings and what types of services are currently provided, and draws on the larger child and adolescent mental health literature to suggest what types of services might be most appropriate for juvenile detention settings. We conclude that, although there are some suggestions of promising interventions that may be appropriate, much more research, specifically in detention settings, is needed to determine their effectiveness.


Treatment With Prothrombin Complex Concentrate to Enable Emergency Lumbar Puncture in Patients Receiving Vitamin K Antagonists.
Lumbar punctures are frequently necessary in neurologic emergencies, but effective oral anticoagulation with vitamin K antagonists represents a contraindication. We report the effectiveness of prothrombin complex concentrates to reverse vitamin K antagonist to enable emergency lumbar punctures, as well as evaluate lumbar puncture- and prothrombin complex concentrates-related complications. Consecutive patients treated with prothrombin complex concentrates between December 2004 and June 2014 to enable emergency lumbar puncture were included. International normalized ratio (INR) before and after prothrombin complex concentrates treatment and the time between start of reversal treatment and lumbar puncture were recorded. A target INR of less than or equal to 1.5 was defined as effective prothrombin complex concentrates treatment. Bleeding events, thromboembolic events, and allergic reactions after prothrombin complex concentrates treatment were identified and classified as "related," "probably," "possibly," "unlikely related," or "not related" to the lumbar puncture and prothrombin complex concentrates infusion. Thirty-seven patients were included (64.9% men; median age 76.0 years; interquartile range [IQR] 71.0 to 84.0 years). The intervention with prothrombin complex concentrates was effective in 33 of 37 patients (89.2%; 95% confidence interval [CI], 78.4% to 97.3%). The median INR was 2.2 (IQR 1.8 to 2.9; 95% CI, 1.9 to 2.5) before and 1.3 (IQR 1.2 to 1.4; 95% CI, 1.2 to 1.3) after prothrombin complex concentrates treatment. The median time between start of prothrombin complex concentrates treatment and lumbar puncture was 135 minutes (IQR 76 to 266 minutes; 95% CI, 84 to 198 minutes). One clinically irrelevant intracranial subdural hematoma "related" to the lumbar puncture developed. No allergic reaction was observed, but 2 of 37 patients (5.4%; 95% CI, 0% to 13.5%) experienced a thromboembolic event (1 ischemic stroke, classified "unlikely related," and 1 myocardial infarction, "possibly related" to prothrombin complex concentrates treatment). Reversing the effect of vitamin K antagonist with prothrombin complex concentrates to enable emergency lumbar puncture appears effective and safe, particularly in regard to bleeding events.


Biopsychosocial effects of qigong as a mindful exercise for people with anxiety disorders: a speculative review.
In view of the inadequacies of mainstream treatments for anxiety disorders, we suggest that qigong, an ancient oriental mindful exercise, may be a useful adjunctive treatment. We base this on a biopsychosocial model for health. Evidence suggests that the benefits of exercise on personal well-being can be explained using six theories: cognitive behaviour; distraction; social interaction; cardiovascular fitness; amine; and endorphin theories. To date, not much has been done to employ these theories to analyze the benefits of mindful exercises. We try here to reorganize these theories into psychosocial and physiologic perspectives and integrate them with the "mind regulation," "body regulation," and "breath regulation" components of qigong. We propose, because of its potential therapeutic effects, that qigong can be considered as an alternative therapy to help meet the increasing demand of nonpharmacologic modalities in achieving biopsychosocial health for those suffering from anxiety in the general population.


Immunocytochemistry of canine thyroid tumors.
Immunocytochemical studies using the peroxidase-antiperoxidase method with commercial antibodies against thyroglobulin, calcitonin, calcitonin gene-related peptide (CGRP), neuron specific enolase (NSE), somatostatin, and neurotensin were performed on 38 Bouin-fixed, paraffin-embedded canine thyroid tumors obtained from necropsy and surgical files from 2 Ecoles Nationales Vétérinaires (Alfort and Nantes, France) and from the Laboratoire d'Histo-Cytopathologie Vétérinaire, Maisons-Alfort (France). The tumors consisted of two follicular adenomas, nine follicular carcinomas, nine solid carcinomas, 12 follicular-compact-cellular carcinomas, and six C-cell carcinomas. All 32 follicular-cell tumors were stained positively for thyroglobulin, half of them had weak to moderate positive immunoreactivity for NSE, and all histologic patterns were represented. They had no immunoreactivity for somatostatin or neurotensin. Four C-cell carcinomas had a solid alveolar pattern, while two had a pseudo follicular pattern characterized by uneven, often coalescent, pseudo-follicular formations with a multilayered epithelium surrounding a cavity that often contained red blood cells. Four C-cell carcinomas had uneven immunoreactivity for calcitonin, while all six were positive for CGRP or NSE. Immunoreactivity for CGRP was stronger or more widespread than positivity for calcitonin when both occurred in the same tumor. Some cells of three C-cell carcinomas had positive immunoreactivity for somatostatin. No immunoreactivity for neurotensin was detected. Seven tumors of follicular cell origin contained a few cells positive for calcitonin or CGRP, while three C-cell carcinomas had a few cells positive for thyroglobulin. These tumors were considered to contain entrapped remnants of normal thyroid tissue rather than being dual hormone producing tumors.


Cardiac infarcts increase sodium transporter transcripts (rBSC1) in the thick ascending limb of Henle.
Enhanced expression of the kidney-specific sodium transporter, rBSC1, in the thick ascending limb of Henle (TAL) and of the renal water channel, aquaporin-2 (AQP2), in collecting duct has been identified in rats with congestive heart failure (CHF) as a cause for enhanced sodium and water retention in this condition. However, the mechanism of impaired urinary sodium excretion observed even in rats with mild cardiac dysfunction remains unknown. Male Sprague-Dawley rats with myocardial infarctions measuring 15 to 30% of the left ventricular circumference with no overt CHF were prepared. We measured the amount of rBSC1 or AQP2 mRNA using competitive polymerase chain reaction (PCR) by inducing a point mutation at the middle of the PCR product for rBSC1 or by deleting 180 bp from the 760 bp PCR product for AQP2, respectively. The results were confirmed by in situ hybridization. rBSC1 protein expression was examined by immunohistochemistry and Western blot analysis using a specific antibody against rBSC1. Although plasma renin activity was slightly elevated in rats with myocardial infarction (MI), no significant differences in lung weight or plasma concentrations for aldosterone and atrial natriuretic peptide were observed between control rats and MI rats. Competitive PCR showed a significant increase in rBSC1 mRNA in the renal outer medulla and cortex of MI rats, which was confirmed by in situ hybridization. However, the AQP2 mRNA of these rats remained unchanged throughout the kidney. Renin-angiotensin II blockade by oral captopril administration did not influence the alteration in rBSC1 mRNA induced by myocardial infarction. Immunohistochemistry and Western blots showed the enhanced expression of rBSC1 protein in TAL of rats with small to moderate cardiac infarcts. rBSC1 is up-regulated even in rats with small to moderate myocardial infarctions, which may enhance the sodium transport in the TAL in this pathophysiologic condition.


Couples' treatment preferences for insomnia experienced during pregnancy.
Insomnia during pregnancy is prevalent, yet little is known about preferred treatments for the disorder. The current study investigated both pregnant women's and their partners' preferences for treatment of maternal insomnia, comparing the two most empirically supported therapies: cognitive-behavioral therapy for insomnia (CBT-I) and pharmacotherapy. We recruited pregnant women and their partners (N = 212) from a low-risk maternity clinic in Calgary, AB, Canada. Participants read expert validated treatment descriptions of pharmacotherapy and CBT-I and indicated their preference for treatment of maternal insomnia. Participants also completed the Insomnia Severity Index and Edinburgh Postnatal Depression Scale. The majority of pregnant women (72.6%) and their partners (73.6%) selected CBT-I as their preferred choice for treatment of maternal insomnia, with a high concordance between partners. Correlates of maternal treatment choice included previous use of treatment and partner preference. Findings suggest that pregnant women and their partners prefer CBT-I to pharmacotherapy as a treatment for maternal insomnia. Partners' preference may be an important consideration for women selecting treatment for insomnia. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


The Relationships Among Exposure to Violence, Psychological Distress, and Gun Carrying Among Male Adolescents Found Guilty of Serious Legal Offenses: A Longitudinal Cohort Study.
Gun violence and psychological problems are often conflated in public discourse on gun safety. However, few studies have empirically assessed the effect of exposure to violence when exploring the association between gun carrying and psychological distress. To examine the potential effect of exposure to violence on the associations between gun carrying and psychological distress among vulnerable adolescents. Longitudinal cohort study. The Pathways to Desistance study, a study of youths found guilty of a serious criminal offense in Philadelphia County, Pennsylvania, or Maricopa County, Arizona. 1170 male youths aged 14 to 19 years who had been found guilty of a serious criminal offense. Youths were assessed at baseline and at four 6-month intervals with regard to gun carrying ("Have you carried a gun?"), psychological distress (Global Severity Index), and exposure to violence (modified version of the Exposure to Violence Inventory). At the bivariate level, gun carrying was consistently associated with higher levels of psychological distress. However, the association between psychological distress and gun carrying diminished or disappeared when exposure to violence was considered. Exposure to violence (as either a victim or a witness) was significantly related to gun carrying at all follow-up assessments, with increased odds of gun carrying ranging from 1.43 to 1.87 with each additional report of exposure to violence. The study sample was limited to justice-involved male youths. Precarrying distress and exposure to violence could not be fully captured because many participants had initiated gun carrying before baseline. In male youths involved in the criminal justice system, the relationship between psychological distress and gun carrying seems to be influenced by exposure to violence (either experiencing or witnessing it). Further study is warranted to explore whether interventions after exposure to violence could reduce gun carrying in this population. None.


Does where you shop or who you are predict what you eat?: The role of stores and individual characteristics in dietary intake.
Interventions to address diet, a modifiable risk factor for diabetes, cancer, and cardiovascular disease, have increasingly emphasized the influence of the physical environment on diet, while more traditional approaches have focused on individual characteristics. We examined environmental and individual influences on diet to understand the role of both. Household interviews were conducted in 2011 with 1372 individuals randomly selected from two low-income, predominantly African American neighborhoods in Pittsburgh, PA. Participants reported their sociodemographic characteristics, food shopping behavior, and dietary intake. Both food shopping frequency at different types of food stores and sociodemographic characteristics showed significant associations with diet in adjusted regression models. More frequent shopping at convenience and neighborhood stores and being younger, male, without a college degree, and receiving SNAP benefits were associated with greater intake of sugar-sweetened beverages (SSBs), added sugars, and discretionary fats. Being older, male, and having a college degree were associated with greater intake of fruits and vegetables. However, while food shopping behavior and sociodemographic characteristics accounted for similar amounts of nonoverlapping variance in fruit and vegetable intake, food shopping behavior accounted for much less variance, and little unique variance, in SSBs, added sugars, and discretionary fats in models with sociodemographic characteristics. The current study reinforces the need for policies and interventions at both the environmental and individual levels to improve diet in food desert residents. Individual interventions to address food choices associated with certain sociodemographic characteristics might be particularly important for curbing intake of SSBs, added sugars, and discretionary fats.


Comparison of the inoculum effect of in vitro antibacterial activity of Imipenem/relebactam and Ceftazidime/avibactam against ESBL-, KPC- and AmpC-producing Escherichia coli and Klebsiella pneumoniae.
To evaluate effect of inoculum size of extended-spectrum β-Lactamase (ESBL)-producing-, AmpC-producing-, and KPC-producing Escherichia coli and Klebsiella pneumoniae on the in vitro antibacterial effects of imipenem/relebactam (IMR) and ceftazidime/avibactam (CZA). We compared the impact of inoculum size on IMR and CZA of sixteen clinical isolates and three standard isolates through antimicrobial susceptibility tests, time-kill assays and in vitro PK/PD studies. When inoculum size increased from 105 to 107 CFU/mL, an inoculum effect was observed for 26.3% (5/19) and 52.6% (10/19) of IMR and CZA, respectively; time-kill assays revealed that the concentration of CZA increased from ≥ 4 × MIC to 16 × MIC to reach 99.9% killing rate against K. pneumoniae ATCC-BAA 1705 (KPC-2-, OXA-9- and SHV-182-producing) and 60,700 (SHV-27- and DHA-1-producing). While for IMR, a concentration from 1 × MIC to 4 × MIC killed 99.9% of the four strains. When the inoculum size increased to 109 CFU/mL, neither IMR nor CZA showed a detectable antibacterial effect, even at a high concentration. An in vitro PK/PD study revealed a clear bactericidal effect when IMR administered as 1.25 g q6h when inoculum size increased. An inoculum effect on CZA was observed more frequent than that on IMR. Among the β-lactamase-producing strains, the inoculum effect was most common for SHV-producing and KPC-producing strains.


Single-cell profiling reveals inflammatory polarization of human carotid versus femoral plaque leukocytes.
Femoral atherosclerotic plaques are less inflammatory than carotid plaques histologically, but limited cell-level data exist regarding comparative immune landscapes and polarization at these sites. We investigated intraplaque leukocyte phenotypes and transcriptional polarization in 49 patients undergoing femoral (n = 23) or carotid (n = 26) endarterectomy using single-cell RNA-Seq (scRNA-Seq; n = 13), flow cytometry (n = 24), and IHC (n = 12). Comparative scRNA-Seq of CD45+-selected leukocytes from femoral (n = 9; 35,265 cells) and carotid (n = 4; 30,655 cells) plaque revealed distinct transcriptional profiles. Inflammatory foam cell-like macrophages and monocytes comprised higher proportions of myeloid cells in carotid plaques, whereas noninflammatory foam cell-like macrophages and LYVE1-overexpressing macrophages comprised higher proportions of myeloid cells in femoral plaque (P < 0.001 for all). A significant comparative excess of CCR2+ macrophages in carotid versus plaque was observed by flow cytometry in a separate validation cohort. B cells were more prevalent and exhibited a comparatively antiinflammatory profile in femoral plaque, whereas cytotoxic CD8+ T cells were more prevalent in carotid plaque. In conclusion, human femoral plaques exhibit distinct macrophage phenotypic and transcriptional profiles as well as diminished CD8+ T cell populations compared with human carotid plaques.


Glutamate Decarboxylase from Lactic Acid Bacteria-A Key Enzyme in GABA Synthesis.
Glutamate decarboxylase (l-glutamate-1-carboxylase, GAD; EC 22.214.171.124) is a pyridoxal-5'-phosphate-dependent enzyme that catalyzes the irreversible α-decarboxylation of l-glutamic acid to γ-aminobutyric acid (GABA) and CO2. The enzyme is widely distributed in eukaryotes as well as prokaryotes, where it-together with its reaction product GABA-fulfils very different physiological functions. The occurrence of gad genes encoding GAD has been shown for many microorganisms, and GABA-producing lactic acid bacteria (LAB) have been a focus of research during recent years. A wide range of traditional foods produced by fermentation based on LAB offer the potential of providing new functional food products enriched with GABA that may offer certain health-benefits. Different GAD enzymes and genes from several strains of LAB have been isolated and characterized recently. GABA-producing LAB, the biochemical properties of their GAD enzymes, and possible applications are reviewed here.


Perilymph oxygenation in sudden and progressive sensorineural hearing loss.
The perilymphatic oxygen tension of the vestibular perilymph of 34 patients with different inner ear losses were measured with the polarographic method before and after inhalation with carbogen. Two patterns of disturbed perilymphatic oxygenation were observed: 1) Characterized by low initial values of perilymphatic oxygenation and normal response to carbogen inhalation was present in sudden deafness and sudden cochleovestibular loss of inner ear function. 2) Characterized by normal initial values of perilymphatic oxygenation and a low response to carbogen, was found in presence of a slowly progressive sensorineural hearing loss. The significance of the obtained results in regard to the possible vascular pathology of the inner ear is discussed.


Treatment-related Hypertension as a Pharmacodynamic Biomarker for the Efficacy of Bevacizumab in Advanced Pancreas Cancer: A Pooled Analysis of 4 Prospective Trials of Gemcitabine-based Therapy With Bevacizumab.
Phase III studies of bevacizumab in advanced pancreas cancer (APCA) demonstrated no improvement in outcome. No validated biomarkers for bevacizumab efficacy exist. We evaluated bevacizumab-related hypertension (B-HTN) as a biomarker in APCA patients in a pooled analysis from 4 prospective clinical trials of gemcitabine-based therapy combined with bevacizumab. Data were collected from individual databases from 4 prospective, single-arm phase II trials. Patients were grouped according to B-HTN or no hypertension (HTN), and patients with HTN were further grouped according to highest Common Terminology Criteria for Adverse Events grade of HTN: grade 1-2 or grade 3-4. Clinical outcomes of overall survival, time to progression, overall response rate (ORR), and disease control rate (ORR+SD>16 wk) were compared. A total of 163 patients with stage IV APCA and Eastern Cooperative Oncology Group 0-1 were included. Median age was 59 years (range, 33 to 85 y). Thirty-four patients had B-HTN, and 129 patients had no HTN. Prognostic factors were balanced between groups. Patients with any grade B-HTN had a significantly improved median overall survival (13.1 vs. 8.1 mo, P=0.0006), median time to tumor progression (7.6 vs. 5.5 mo, P=0.0074), ORR (47% vs. 16%, P=0.0001), and disease control rate (85% vs. 59%, P=0.004). There were no differences in outcomes according to HTN grade (1-2 [N=16] vs. 3-4 [N=18]). APCA patients who develop any grade of B-HTN appear to derive benefit from bevacizumab. Additional investigation is needed to identify subgroups of patients who develop B-HTN and are more likely to benefit from bevacizumab.


Quinidine attenuates sympathetically induced poststenotic myocardial ischemia.
Beside its antiarrhythmic properties, which in particular are used for the treatment of atrial fibrillation, quinidine is known to have alpha-adrenoceptor blocking properties. On the other hand, atrial fibrillation is reported to cause activation of the sympathetic nervous system which, in turn, reduces coronary blood flow when the coronary reserve is already compromised. Therefore, we tested the effect of quinidine (3 mg/kg i.v.) on the coronary vasculature during electrical stimulation of cardiac sympathetic nerves in the presence and absence of a stenosis on the left circumflex coronary artery. In 7 anesthetized dogs the end-diastolic distal coronary resistance during cardiac sympathetic nerve stimulation in the presence of a severe stenosis on the left circumflex coronary artery increased by 18% before, and decreased by 17% after administration of quinidine. We conclude that quinidine inhibits the vasoconstriction of poststenotic coronary arteries during cardiac sympathetic nerve stimulation and thus might prevent a poststenotic stress-induced myocardial ischemia.


[The organization of scientific innovative laboratory complex of modern technologies].
The article discusses the actual issues of scientific innovative activity during the realization of principles of private-public partnership. The experience of development of model of scientific innovative complex is presented The possibilities to implement research achievements and their application in the area of cell technologies, technologies of regenerative medicine, biochip technologies are demonstrated. The opportunities to provide high level of diagnostic and treatment in practical health care increase of accessibility and quality of medical care and population health promotion are discussed.


Boiling histotripsy and in-situ CD40 stimulation improve the checkpoint blockade therapy of poorly immunogenic tumors.
Background: Advanced stage cancers with a suppressive tumor microenvironment (TME) are often refractory to immune checkpoint inhibitor (ICI) therapy. Recent studies have shown that focused ultrasound (FUS) TME-modulation can synergize ICI therapy, but enhancing survival outcomes in poorly immunogenic tumors remains challenging. Here, we investigated the role of focused ultrasound based boiling histotripsy (HT) and in-situ anti-CD40 agonist antibody (αCD40) combinatorial therapy in enhancing therapeutic efficacy against ICI refractory murine melanoma. Methods: Unilateral and bilateral large (~330-400 mm3) poorly immunogenic B16F10 melanoma tumors were established in the flank regions of mice. Tumors were exposed to single local HT followed by an in-situ administration of αCD40 (HT+ αCD40: HT40). Inflammatory signatures post treatment were assessed using pan-cancer immune profiling and flow cytometry. The ability of HT40 ± ICI to enhance local and systemic effects was determined by immunological characterization of the harvested tissues, and by tumor growth delay of local and distant untreated tumors 4-6 weeks post treatment. Results: Immune profiling revealed that HT40 upregulated a variety of inflammatory markers in the tumors. Immunologically, HT40 treated tumors showed an increased population of granzyme B+ expressing functional CD8+ T cells (~4-fold) as well as an increased M1 to M2 macrophage ratio (~2-3-fold) and CD8+ T: regulatory T cell ratio (~5-fold) compared to the untreated control. Systemically, the proliferation rates of the melanoma-specific memory T cell population were significantly enhanced by HT40 treatment. Finally, the combination of HT40 and ICI therapy (anti-CTLA-4 and anti-PD-L1) caused superior inhibition of distant untreated tumors, and prolonged survival rates compared to the control. Conclusions: Data suggest that HT40 reprograms immunologically cold tumors and sensitizes them to ICI therapy. This approach may be clinically useful for treating advanced stage melanoma cancers.


Comparative gene expression analyses reveal heterochrony for Sox9 expression in the cranial neural crest during marsupial development.
Compared to placental mammals, marsupials have short gestation period, and their neonates are relatively immature. Despite these features, marsupial neonates must travel from the birth canal to the teat, suckle and digest milk to complete development. Thus, certain organs and tissues of marsupial neonates, such as forelimbs to crawl and jaw elements to suckle, must develop early. Previous reports showed that cranial neural crest (CNC) cells, as the source of ectomesenchyme of jaw elements, are generated significantly early in gray short-tailed opossum (Monodelphis domestica) compared to other amniote models, such as mouse. In this study, we examined the expression of genes known to be important for neural crest formation, such as BMP2/BMP4 (neural crest inducer), Pax7 (neural border specifier), Snail1 and Sox9/Sox10 (neural crest specifier) in Monodelphis domestica, and compared the expression patterns with those in mouse, chicken, and gecko embryos. Among those genes, the expression of Sox9 was turned on early and broadly in the premigratory CNC cells, and persisted in the ectomesenchyme of the cranial anlagen in opossum embryos. In contrast, Sox9 expression diminished in the CNC cells of other animals at the early phase of migration. Comparison of the onset of Pax7 and Sox9 expression revealed that Sox9 expression in the prospective CNC was earlier and broader than Pax7 expression in opossum, suggesting that the sequence of border specification and neural crest specification is altered. This study provides the first clue for understanding the molecular basis for the heterochronic development of the CNC cells and jaw elements in marsupials.


Chronic exposure to interleukin-6 causes hepatic insulin resistance in mice.
Interleukin (IL)-6 is one of several proinflammatory cytokines associated with the insulin resistance of obesity and type 2 diabetes. There is, however, little direct evidence in vivo for a causative role of IL-6 in insulin resistance. Here, a 5-day constant subcutaneous infusion of hIL-6 before portal vein insulin challenge resulted in impairment of early insulin receptor signaling in the liver of mice. Importantly, the sixfold elevation of IL-6 attained with constant infusion was similar to levels reached in obesity. Consistent with an hepatic response to IL-6, STAT3 phosphorylation was increased in livers of IL-6-treated mice at 5 days. Chronic infusion of IL-6 also reduced hepatic insulin receptor autophosphorylation by 60% and tyrosine phosphorylation of insulin receptor substrates-1 and -2 by 60 and 40%, respectively. IL-6 had no effect on the mass of these proteins. IL-6 also decreased refeeding-dependent glucokinase mRNA induction by approximately 40%. Insulin tolerance tests revealed reduced insulin sensitivity. In contrast to hepatic insulin receptor signal transduction, 5-day IL-6 exposure failed to suppress skeletal muscle insulin receptor signal transduction. These data suggest that chronic IL-6 treatment selectively impairs hepatic insulin signaling in vivo, further supporting a role for IL-6 in hepatic insulin resistance of obesity.


Cross-correlation asymmetries and causal relationships between stock and market risk.
We study historical correlations and lead-lag relationships between individual stock risk (volatility of daily stock returns) and market risk (volatility of daily returns of a market-representative portfolio) in the US stock market. We consider the cross-correlation functions averaged over all stocks, using 71 stock prices from the Standard & Poor's 500 index for 1994-2013. We focus on the behavior of the cross-correlations at the times of financial crises with significant jumps of market volatility. The observed historical dynamics showed that the dependence between the risks was almost linear during the US stock market downturn of 2002 and after the US housing bubble in 2007, remaining at that level until 2013. Moreover, the averaged cross-correlation function often had an asymmetric shape with respect to zero lag in the periods of high correlation. We develop the analysis by the application of the linear response formalism to study underlying causal relations. The calculated response functions suggest the presence of characteristic regimes near financial crashes, when the volatility of an individual stock follows the market volatility and vice versa.


Stem cell transplantation for autoimmune disorders. Coincidental autoimmune disease in patients transplanted for conventional indications.
The practice of stem cell transplantation for severe autoimmune diseases refractory to conventional therapy originated from two landmark discoveries: the excellent results of animal experiments, and serendipitous observations in human coincidental diseases. The latter include patients with an often long-standing autoimmune disease who have developed a haematological condition (aplasia, leukaemia, lymphoma) requiring stem cell transplantation (from marrow as well as from blood). Allogeneic and autologous transplants have been performed. The initial information deriving from both procedures is their feasibility, even more convincing since the patients were affected by two simultaneous severe diseases. The information derived from autologous transplants has, however, now been superseded by the considerable and increasing number of those transplants performed for primary autoimmune diseases. On the other hand, allogeneic stem cell transplantation for very severe autoimmune diseases is being cautiously explored in current protocols. Allogeneic transplants in coincidental disease have also suggested a graft-versus-autoimmunity effect, which may become relevant in conjunction with non-myeloablative, less toxic condition regimens.


G protein-coupled receptor kinase 2 inhibition improves erectile function through amelioration of endothelial dysfunction and oxidative stress in a rat model of type 2 diabetes.
Type 2 diabetes mellitus (T2DM) is a common cause of erectile dysfunction (ED). It has been demonstrated that G protein-coupled receptor kinase 2 (GRK2) overexpression contributes to diabetic endothelial dysfunction and oxidative stress, which also underlies ED in T2DM. We hypothesized that GRK2 overexpressed and attenuated endothelial function of the cavernosal tissue in a rat model of T2DM. T2DM rats were established by feeding with a high-fat diet (HFD) for 2 weeks and then administering two intraperitoneal (IP) injections of a low dose of streptozotocin (STZ), followed by continuous feeding with a HFD for 6 weeks. GRK2 was inhibited by IP injection of paroxetine, a selective GRK2 inhibitor, after STZ injection. Insulin challenge tests, intracavernous pressure (ICP), GRK2 expression, the protein kinase B (Akt)/endothelial nitric oxide synthase (eNOS) pathway, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit gp91phox, nitric oxide (NO), reactive oxygen species (ROS) production, and apoptosis in cavernosal tissue were examined. Less response to insulin injection was observed in T2DM rats 2 weeks after HFD. Markedly increased GRK2 expression, along with impaired Akt/eNOS pathway, reduced NO production, increased gp91phox expression and ROS generation, increased apoptosis and impaired erectile function were found in T2DM rats. Inhibition of GRK2 with paroxetine ameliorated Akt/eNOS signaling, restored NO production, downregulated NADPH oxidase, subsequently inhibited ROS generation and apoptosis, and ultimately preserved erectile function. These results indicated that GRK2 upregulation may be an important mechanism underlying T2DM ED, and GRK2 inhibition may be a potential therapeutic strategy for T2DM ED.


Hospital readmissions as a measure of quality of health care: advantages and limitations.
We reviewed the recent literature on hospital readmissions and found that most of them are believed to be caused by patient frailty and progression of chronic disease. However, from 9% to 48% of all readmissions have been judged to be preventable because they were associated with indicators of substandard care during the index hospitalization, such as poor resolution of the main problem, unstable therapy at discharge, and inadequate postdischarge care. Furthermore, randomized prospective trials have shown that 12% to 75% of all readmissions can be prevented by patient education, predischarge assessment, and domiciliary aftercare. We conclude that most readmissions seem to be caused by unmodifiable causes, and that, pending an agreed-on method to adjust for confounders, global readmission rates are not a useful indicator of quality of care. However, high readmission rates of patients with defined conditions, such as diabetes and bronchial asthma, may identify quality-of-care problems. A focus on the specific needs of such patients may lead to the creation of more responsive health care systems for the chronically ill.


The TUBB1 Q43P functional polymorphism reduces the risk of cardiovascular disease in men by modulating platelet function and structure.
The discoid form of platelets is maintained by a marginal band of tightly coiled microtubules. beta1-tubulin is the major isoform within platelet and megakaryocyte microtubules. In 24.2% of 33 unrelated inherited macrothrombocytopenia patients and in 10.6% of 272 subjects of a healthy population a P for Q substitution in beta1-tubulin was found in the highly conserved residue 43. Heterozygous carriers of the Q43P variant showed a reduced platelet protein beta1-tubulin expression. Transfection of green fluorescent protein (GFP)-tagged Q43P beta1-tubulin in megakaryocytic MEG01 cells resulted in a disturbed tubulin organization. Electron microscopy revealed enlarged spherocytic platelets with a disturbed marginal band and organelle-free zones. In addition, platelets with the Q43P beta1-tubulin variant had reduced adenosine triphosphate (ATP) secretion, thrombin receptor activating peptide (TRAP)-induced aggregation and collagen adhesion. The prevalence of the Q43P beta1-tubulin variant was also 2 times higher (odds ratio, [OR] = 2.1;95% confidence interval [CI], 1.22-3.59) among control subjects than among patients with cardiovascular disease (10.4% versus 5.2%, P < .001). By analyzing this protective factor in men and women separately, this association was only found in men. This study thus presents the functional consequences of the platelet Q43P beta1-tubulin substitution that is frequent in the healthy population and may protect men against arterial thrombosis.


Endotoxin Is Inactivated by Ethylene Oxide, Gamma, Electron Beam, and Steam Sterilization.
The effect of sterilization on bacterial endotoxin is receiving greater attention within the medical device industry. Contributing factors to this increased attention include the growing popularity of transferring devices among sterilization modalities and the focus on aspects of microbiological quality other than sterilization. This systematic review examined the effects of sterilization on bacterial endotoxin, with attention drawn to industry standards and regulations to elucidate whether such documents are aligned with published data. In summary, numerous experiments have shown a reduction in pyrogenicity and/or limulus amebocyte lysate reactivity of endotoxin following sterilization, whereas a number of publications and industry standards have claimed (without data or references) that sterilization does not inactivate endotoxin. The results of this review would be useful for device manufacturers when selecting a sterilization modality or deciding whether to test for endotoxin pre- vs poststerilization, as well as for standards developers and regulators in aligning standards and regulations with peer-reviewed data.


[Wegener's granulomatosis: immunologic aspects of diagnosis, etiology and therapy].
Wegener's granulomatosis (WG) is a rare disease, which has, however, been diagnosed more frequently in the past few years. The etiology is unclear; the pathogenesis is only vaguely understood. The association between HLA-DR2 and/or B8 and WG indicates that there is a genetic predisposition. Without treatment WG is said to run a malignant course with a median survival time of approx. 6 months. With immunosuppressive treatment, however, it is said to be possible to induce long-term remission in about 90% of the cases. Our experience only partially confirms these figures from other countries. From the clinical point of view it is particularly important to point out that there are two phases the disease can run through: In one third of the cases WG begins with an initial stage that can last for many years, but generally does not cause any life-threatening complications. This stable phase can lead into the generalized stage. Untreated, the disease, a fulminant WG characterized by a syndrome of rapidly progressive renal failure and/or respiratory insufficiency, now rapidly leads to death. The clinical diagnosis must always be confirmed by biopsy. Whether the newly discovered disease-specific autoantibody will make a histological examination superfluous in the future is not clear, but at the moment it appears rather unlikely. This antibody against intracytoplasmic antigens of cells of the myelomonocytic line (ACPA) is found in only 60% of the cases with WG. ACPA is often demonstrable in the acute generalized phase, but also during instable partial remissions. In contrast, it is only seldom during the initial stage or in full remission. According to this experience it appears clear that we must adapt the treatment of WG to the stage the disease is in. Low-dose cyclophosphamide-cortisone treatment is considered to be a reliable treatment for the acute generalized stage. Whether the fulminant form can be influenced positively by additive (e.g., plasmapheresis) or alternative (e.g., pulse treatment with cyclophosphamide and cortisone) protocols must remain open at present. We must assume that at least the stable phase of the disease (initial stage) can be treated less aggressively. This will only be possible if close-meshed controls can be carried through at a center for vasculitis, where interdisciplinary cooperation (otorhinolaryngology-ophthalmology-general internal medicine) will make it possible to recognize any exacerbation, so often appearing unexpectedly, at an early point, so that the patient is not endangered unnecessarily.


Public knowledge and attitudes towards the use of alcohol and drinking guidelines.
To investigate public knowledge and attitudes towards the use of alcohol with particular focus on drinking guidelines. A telephone survey of 249 people randomly selected from the toll free area of Christchurch. Three key findings were (1) not one respondent was able to quote drinking guidelines that included quantities of alcohol per occasion or quantities of alcohol per week; (2) the majority of the public (74%) thought drinking guidelines were not publicised well enough; and (3) young men (18-24 years) were significantly more likely to state incorrectly that greater than six standard drinks is a safe amount of alcohol to consume on social occasions. More active promotion of drinking guidelines via the electronic and popular print media should be considered. Young men require particular attention related to drinking no more than six standard drinks per occasion of drinking as part of this initiative. Other studies targeting groups such as the more transient, different ethnic groups especially Maori and Pacific Islanders, health professionals and people with alcohol problems would be of interest, as well as a repeat of this study following an interim period in which active promotion of drinking guidelines is undertaken.


Overexpression of Cell Cycle Progression Inhibitor Geminin is Associated with Tumor Stem-Like Phenotype of Triple-Negative Breast Cancer.
Triple-negative breast cancer, has a significant clinical relevance being associated with a shorter median time to relapse and death and does not respond to endocrine therapy or other available targeted agents. For this reason, identifying the molecular pathways associated with increased aggressiveness, for example the presence of stem cell populations within the tumor and alteration of genes associated with cell cycle regulation represents an important objective in the clinical research into this neoplasm. To investigate the role of cell cycle progression inhibitor Geminin in triple-negative breast cancers and its potential correlation with stem-like phenotype of this neoplasm, we used tissue microarray technology to build a specific triple-negative breast cancer tissue micro-array. Geminin and cancer stem cell marker CD133 expression was further investigated at the mRNA level for selected breast tumor samples through realtime polymerase chain reaction quantification. Our results showed that CD133 expression was significantly associated to high Geminin expression (p=0.017), a strong association between Ki-67 and tumor grade (p=0.020) and an inverse association between Geminin expression and lymphonode metastases (p=0.058), and a trend of statistically significance between Geminin marker expression and survival of triple-negative breast cancer patients (p=0.076). The strong association between the expression of CD133 and Geminin could be useful in molecular stratification of breast tumors and in particular of triple-negative breast cancers.


Highly selective and quantitative colorimetric detection of mercury(II) ions by carrageenan-functionalized Ag/AgCl nanoparticles.
The natural algal polysaccharide carrageenan was used for the greener synthesis of silver/silver chloride nanoparticles (Carr-Ag/AgCl NPs) without any toxic chemicals. We report the robust, highly selective, and sensitive colorimetric sensing of Hg2+ ions using Carr-Ag/AgCl NPs without any further surface modification. The dark-brown color of a solution of Carr-Ag/AgCl NPs turned to white in a concentration-dependent manner with the addition of Hg2+ ions, confirming the interaction of Carr-Ag/AgCl NPs with Hg2+ ions. The plot of the extinction ratio of absorbance at 350nm to 450nm (A350/A450) for Carr-Ag/AgCl NPs against the concentration of [Hg2+] ions was linear, and the calibration curve was A350/A450=1.05254+0.00318×CHg with a lower detection limit of 1μM. This portable and cost-effective method for mercury(II) ion sensing is widely applicable in on-field qualitative and quantitative measurements of [Hg2+] ions in environmental or biological samples.


Large Cells With CD30 Expression and Hodgkin-like Features in Primary Cutaneous Marginal Zone B-Cell Lymphoma: A Study of 13 Cases.
The presence of CD30 cells in cutaneous lymphomas has come to prominence in recent years as a potential diagnostic and therapeutic marker. In primary cutaneous marginal zone B-cell lymphomas, the presence of large CD30 cells with Hodgkin-like features and their significance have not yet been studied. Here we describe the main clinical, histologic, immunophenotypic, and molecular characteristics of 13 cases of primary cutaneous marginal zone lymphomas featuring >10% of CD30 large cells, and analyze their relationship with histologic and clinical progression of the disease and with other morphologic and immunophenotypic features. We report 10 male and 3 female patients, 4 with early-local disease and 8 with locoregional advanced disease without extracutaneous involvement but with a high relapse rate of 69%. We describe an association between a high level of CD30 expression and disease progression, with increased clinical recurrence in cases with >15% of CD30 cells. We also discuss the differential diagnosis with other cutaneous and systemic lymphomas, especially Hodgkin lymphoma.


Lifestyle behaviours are not associated with haemolysis: results from Donor InSight.
Lifestyle behaviours such as physical activity, sedentary behaviour and dietary habits have been shown to influence blood lipid levels, and both lifestyle and blood lipids may be associated with haemolysis during storage of blood products. We aimed to investigate whether lifestyle behaviours are associated with degree of haemolysis in red cell concentrates (RCC), and if such associations are mediated by low-density lipoprotein (LDL) cholesterol and triglyceride levels. Cross-sectional analyses were performed in data from 760 Dutch blood donors participating in Donor InSight, an observational cohort study. Linear regression analyses were conducted to assess associations of lifestyle behaviours with haemolysis levels in RCC 28 days after blood sampling. Lifestyle behaviours included moderate-to-vigorous physical activity and sedentary behaviour measured by accelerometry, and self-reported intake of a selection of foods potentially related to blood lipids, i.e. consumption of eggs, meat, nuts and fish. Potential mediating roles of both LDL cholesterol and triglyceride levels were investigated separately. All analyses were adjusted for relevant confounders. No statistically significant nor substantial associations of any of the lifestyle behaviours with haemolysis in RCC were found, nor were there any associations between lifestyle behaviours and blood lipids. We did find consistent positive associations of LDL cholesterol and triglyceride levels with haemolysis in RCC during storage. In this large cohort, blood lipid levels were consistently associated with haemolysis in RCC. Nonetheless, there was no evidence for an association between lifestyle behaviours and haemolysis in RCC, or for mediating effects by blood lipid levels.


The role of primary care in early detection and follow-up of cancer.
Primary care providers have important roles across the cancer continuum, from encouraging screening and accurate diagnosis to providing care during and after treatment for both the cancer and any comorbid conditions. Evidence shows that higher cancer screening participation rates are associated with greater involvement of primary care. Primary care providers are pivotal in reducing diagnostic delay, particularly in health systems that have long waiting times for outpatient diagnostic services. However, so-called fast-track systems designed to speed up hospital referrals are weakened by significant variation in their use by general practitioners (GPs), and affect the associated conversion and detection rates. Several randomized controlled trials have shown primary care-led follow-up care to be equivalent to hospital-led care in terms of patient wellbeing, recurrence rates and survival, and might be less costly. For primary care-led follow-up to be successful, appropriate guidelines must be incorporated, clear communication must be provided and specialist care must be accessible if required. Finally, models of long-term cancer follow-up are needed that provide holistic care and incorporate management of co-morbid conditions. We discuss all these aspects of primary care, focusing on the most common cancers managed at the GP office-breast, colorectal, prostate, lung and cervical cancers.


Targeting Bortezomib to Bone Increases Its Bone Anabolic Activity and Reduces Systemic Adverse Effects in Mice.
Bortezomib (Btz) is a proteasome inhibitor approved by the FDA to treat multiple myeloma. It also increases bone volume by promoting osteoblast differentiation and inhibiting osteoclastogenesis in mice. However, Btz has severe systemic adverse effects, which would limit its use as a bone anabolic agent. Here, we designed and synthesized a bone-targeted form of Btz by conjugating it to a bisphosphonate (BP) with no antiresorptive activity. We report that BP-Btz inhibited osteoclast formation and bone resorption and stimulated osteoblast differentiation in vitro similar to Btz. In vivo, BP-Btz increased bone volume more effectively than Btz in three mouse models: untreated wild-type mice, mice with ovariectomy, and aged mice with tibial factures. Importantly, BP-Btz had significantly less systemic side effects than Btz, including less thymic cell death, sympathetic nerve damage, and thrombocytopenia, and it improved survival rates in aged mice. Thus, BP-Btz represents a novel anabolic agent to treat conditions, such as postmenopausal and age-related bone loss. Bone targeting is an attractive approach to repurpose approved drugs to treat skeletal diseases. © 2019 American Society for Bone and Mineral Research. © 2019 American Society for Bone and Mineral Research.


Pit and fissure sealants.
Through participation in rational, comprehensive preventive programs, completely caries-free dentitions are now a possibility for many adults (Horowitz, 1980). Because of the uniqueness of pit and fissure caries sealants need to be considered for children as one necessary component in such total preventive programs. If the goal of a population free of caries is to be achieved, effective oral hygiene measures, including the use of therapeutic dentifrices, systemic or topically applied fluorides and dietary supervision are other components that should be considered in such a program (Ripa, 1978). Safety and effectiveness of pit and fissure sealants have been clearly established. Cost-effectiveness, however, whether in a private practice or public health setting is a factor of legitimate concern. From the 'Conference on Pit and Fissure Sealants: Why Their Limited Usage?' conducted by the Council on Dental Materials, Instruments and Equipment of the American Dental Association in May 1981, a number of recommendations resulted. Their implementation will help overcome scepticism regarding sealant use. Included in the recommendations are (a) a greater emphasis upon the use of sealants in dental education curricula, (b) development of specific guidelines for sealant use and maintenance, (c) continued long term studies under different program formats and (d) dissemination by the profession, as it did with fluorides, of valid information regarding sealant use (Brown, 1981). Regarding pit and fissure sealants, the apparent consensus from scientific data and clinical practice would suggest that we should be using these materials for our child patients knowledgeably, selectively and with precise application methods.


Antitumorigenic targets of cannabinoids - current status and implications.
Molecular structures of the endocannabinoid system have gained interest as potential pharmacotherapeutical targets for systemic cancer treatment. The present review covers the contribution of the endocannabinoid system to cancer progression. Particular focus will be set on the accumulating preclinical data concerning antimetastatic, anti-invasive and anti-angiogenic mechanisms induced by cannabinoids. The main goal of targeting endocannabinoid structures for systemic anticancer treatment is the comparatively good safety profile of cannabinoid compounds. In addition, antitumorigenic mechanisms of cannabinoids are not restricted to a single molecular cascade but involve multiple effects on various levels of cancer progression such as angiogenesis and metastasis. Particularly the latter effect has gained interest for pharmacological interventions. Thus, drugs aiming at the endocannabinoid system may represent potential 'antimetastatics' for an upgrade of a future armamentarium against cancer diseases.


Mild Endoplasmic Reticulum Stress Protects Against Lipopolysaccharide-Induced Astrocytic Activation and Blood-Brain Barrier Hyperpermeability.
Recent research has revealed that uncontrolled chronic neuroinflammation is closely associated with diverse neurodegenerative diseases, by impairing blood-brain barrier (BBB) function and astrocytic reaction. Endoplasmic reticulum (ER) stress is conventionally linked to the loss of neuronal structure and function and should be widely attenuated. This notion has been questioned by recent experimental studies, which have shown that non-harmful levels of ER stress had numerous beneficial roles against neurodegeneration, including neuroprotection and inhibition of cytokine production. Here, we investigated the mild ER stress-based regulation of LPS-induced inflammatory responses in astrocytes. Primary astrocytes were exposed to tunicamycin (TM), a compound that activates ER stress, with or without the ER-stress inhibitor sodium 4-phenylbutyrate (4-PBA) before LPS treatment. Astrocytic activation, proinflammatory factor production, and the extent of ER stress were assessed. In addition, the effect of mild ER stress on astrocytes and BBB function was determined in vivo. Male Sprague-Dawley rats received intracerebroventricular injections of TM with or without intraperitoneal 4-PBA before LPS administration. The levels of astrocytic activation and BBB permeability were measured after treatment. Our results showed that lower doses of TM resulted in a mild ER-stress response without inducing cytotoxicity and tissue toxicity. Non-toxic ER-stress preconditioning ameliorated LPS-induced overactivation and inflammatory responses in astrocytes. Moreover, pre-exposure to non-lethal doses of TM improved LPS-induced BBB impairment and cognitive ability dysfunction in rats. However, 4-PBA, reversed the protective effect of TM preconditioning in vitro and in vivo. We conclude that mild ER stress ("preconditioning") can alleviate LPS-induced astrocytic activation and BBB disruption. Our findings provide a better understanding for the regulatory role of ER stress in neuroinflammation and indicate that mild ER stress might have therapeutic value for the treatment of neurodegenerative diseases.


Homicide trends in the State of Victoria, Australia.
Limited data about homicide in Australia have been published. Data on homicide occurring in the state of Victoria, Australia, are presented. Since 1945 there has been a doubling of the population and an increase in the rate of homicide. The most common method of killing was shooting, and most homicide victims were known to their assailants. Male assailants far outnumber female assailants. Men are the most frequent victims, but female victims far outnumber female assailants. The data are compared with data on other Australian states and published data from other countries.


Steady-state and pre-steady-state kinetic analysis of dNTP insertion opposite 8-oxo-7,8-dihydroguanine by Escherichia coli polymerases I exo- and II exo-.
Escherichia coli polymerases (pol) I exo-(KF-) and pol II exo- (pol II-) were used as model enzymes with a DNA primer/template complex (12/16-mer) to examine the kinetics of incorporation of dCTP and dATP at the site of an 8-oxo-7,8-dihydroguanine (8-oxoGua) residue; compared to guanine (Gua). In steady-state assays (with DNA in excess) the rate of incorporation (kcat) was dCTP > dATP and the K(m),dATP < K(m),dCTP during incorporation opposite 8-oxoGua with both polymerases. Pre-steady-state kinetic curves (rapid-quench analysis) for the addition of C opposite 8-oxoGua or Gua by KF- and pol II- were all biphasic, with a rapid initial single-turnover burst followed by a slower multiple turnover rate, while addition of A opposite 8-oxoGua did not display burst kinetics with either enzyme. Reduced rates of incorporation of the dCTP alpha S and dATP alpha S phosphorothioate analogs suggest that the rates of incorporation of A and C opposite 8-oxoGua are limited during polymerization by the rate of phosphodiester bond formation. Neither polymerase appears to discriminate between adducted and nonadducted DNA substrate for binding. Kinetic assays performed with varying dCTP concentrations indicate that dCTP has a higher K(d) and lower k(p) (polymerization rate) for incorporation opposite 8-oxoGua compared to Gua. Furthermore, the dATP binding affinities with KF- and pol II- were approximately 10- and approximately 3-fold lower, respectively, than that of dCTP as determined in competition assays with mixtures of dCTP and dATP. Microscopic rate constants were estimated by mathematical analysis of dNTP concentration dependence curves. Both polymerases preferentially extended the A:8-oxoGua pair while extension of the C:8-oxoGua pair was greatly impaired. Based on these findings, the fidelity of KF- and pol II- during replication of 8-oxoGua depends on contributions from nucleotide binding, the rate of phosphodiester bond formation, and the ease of base pair extension.


Maternal and paternal periconceptional nutrition as an indicator of offspring metabolic syndrome risk in later life through epigenetic imprinting: A systematic review.
This review examined whether maternal and paternal periconceptional nutrition effects an offspring's likelihood of developing chronic metabolic related conditions due to epigenetic imprinting. A literature search was conducted in multiple science databases and limited to studies published after 2012, in English language and peer reviewed. The data from selected articles were extracted and a qualitative approach was employed due to heterogeneity of results. Newborns from obese fathers showed altered methylation overall and significant hypomethylation at the Insulin-like Growth Factor 2 (IGF2) gene. High maternal pre-pregnancy body mass index (BMI) was associated with altered offspring DNA methylation levels and gestational diabetes mellitus induced significantly increased methylation levels in offspring. Gestational weight gain was not associated with differentially methylated cord blood. Birth weight was higher in offspring exposed to famine in early gestation. Offspring born post maternal bariatric surgery showed a lower percentage of body fat and improved fasting insulin levels compared to siblings born pre-maternal bariatric surgery. The available evidence suggests that poor maternal and paternal periconceptional nutrition can increase the risk of metabolic syndrome in offspring, through epigenetic imprinting. Potential parents should be advised that maintaining a healthy diet and BMI is likely to reduce the risk of metabolic syndrome in offspring.


Synthesis of magnetic alginate beads based on magnesium ferrite (MgFe2O4) nanoparticles for removal of Sr (II) from aqueous solution: kinetic, equilibrium and thermodynamic studies.
Novel magnetic alginate beads (MagAlgbeads) have been developed by incorporation of magnesium ferrite (MgFe2O4) in alginate beads with the aim of using them in the removal of strontium from aqueous solution. MagAlgbeads were characterized by transmission electron microscopy, scanning electron microscopy, X-ray fluorescence and Fourier transform infrared spectroscopy. The adsorption of strontium onto MagAlgbeads were found to depend on pH and strontium removal increases with increasing pH until pH is 6. Strontium adsorption kinetics run through pseudo-second-order model. Thermodynamically, strontium adsorption was endothermic and spontaneous. Langmuir isotherm gave good fitting for strontium removal with adsorption capacity of 505.5 mg/g. These results proved that the prepared MagAlgbeads are very efficient material for strontium adsorption.


Induction of intercellular adhesion molecule-1 by tumor necrosis factor-alpha through the 55-kDa receptor is dependent on protein kinase C in human retinal pigment epithelial cells.
To determine second messenger signaling pathways associated with tumor necrosis factor-alpha (TNF)-mediated induction of intercellular adhesion molecule (ICAM)-1 expression on human retinal pigment epithelial (HRPE) cells, a cell type known to express only the 55-kDa TNF receptor (TNFR p55). SV 40-immortalized HRPE (SVRPE) cells were exposed to TNF with and without pretreatment with the protein kinase C (PKC) inhibitor calphostin C or the protein kinase A (PKA) inhibitor H8. SV40-immortalized HRPE cells also were treated with the PKC activator phorbol 12-myristate 13-acetate (PMA) or with the PKA activators forskolin plus 3-isobutyl-1-methyl-xanthine or dibutyryl cyclic adenosine monophosphate (cAMP) alone. Membrane fractions from untreated and treated SVRPE cells were assayed for PKC activity, and whole cell lysates were assayed for cAMP accumulation and PKA activity. Flow cytometry was performed on SVRPE cells using a monoclonal antibody specific to ICAM-1. Activation of TNFR p55 on SVRPE cells with TNF resulted in a rapid increase of PKC activity at 1 minute, with a subsequent downregulation to baseline. There was no increase in intracellular cAMP accumulation or PKA activity within the first 10 minutes; however, both increased within 30 minutes and returned to baseline within 1 hour. SV40-immortalized HRPE cells treated with TNF for 1 hour showed maximal induction of ICAM-1 expression at 18 hours. ICAM-1 induction by TNF treatment was inhibited by calphostin C pretreatment and not by H8 pretreatment. Protein kinase C activation with PMA for 3 hours was sufficient to induce ICAM-1 on SVRPE cells at 18 hours, whereas treatment with the PKA activators forskolin or dibutyryl cAMP did not induce ICAM-1 expression. Tumor necrosis factor sequentially activates the PKC and PKA pathways in SVRPE cells by way of the TNFR p55. The PKC pathway in necessary for TNF-mediated ICAM-1 upregulation, and specific activation of the PKC pathway with PMA is sufficient to induce ICAM-1 on these cells. SV40-immortalized HRPE cells may serve as a model in which to study further the functional signaling pathways associated with TNFR p55.


Interactions between Diet and Exposure to Secondhand Smoke on the Prevalence of Childhood Obesity: Results from NHANES, 2007-2010.
Exposure to secondhand smoke (SHS) may increase risk for obesity, but few studies have investigated the joint effects of exposure to SHS and diet. We examined the interaction of exposure to SHS and diet on the prevalence of obesity among 6- to 19-year-olds who participated in the 2007-2010 National Health and Nutrition Examination Survey. We characterized exposure using a novel biomarker [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)], an established biomarker (cotinine), and self-report. Multinomial logistic regression models examined the association of SHS exposure on the prevalence of overweight and obesity as separate outcomes (compared with normal/underweight). Interaction by diet was assessed by introducing interaction terms (with SHS) of the individual nutrients [dietary fiber, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), vitamin C, and vitamin E] into separate models. Approximately half of the children had NNAL and cotinine levels above the limit of detection, indicating exposure to SHS. Interaction results suggest that the prevalence of obesity among children with both high exposure to SHS and low levels of certain nutrients (dietary fiber, DHA, or EPA) is greater than would be expected due to the effects of the individual exposures alone. Little or no evidence suggesting more or less than additive or multiplicative interaction was observed for vitamin C or vitamin E. The association between SHS and obesity did not appear to be modified by dietary vitamin C or vitamin E. Childhood obesity prevention strategies aimed at reducing SHS exposures and improving diets may exceed the expected benefits based on targeting either risk factor alone. Moore BF, Clark ML, Bachand A, Reynolds SJ, Nelson TL, Peel JL. 2016. Interactions between diet and exposure to secondhand smoke on the prevalence of childhood obesity: results from NHANES, 2007-2010. Environ Health Perspect 124:1316-1322; http://dx.doi.org/10.1289/ehp.1510138.


Prevalence of bifid median nerve at wrist assessed through ultrasound.
We performed a prospective study to evaluate the prevalence of bifid median nerve (BMN) and if it has a higher prevalence in carpal tunnel syndrome (CTS) patients than symptom-free subjects. We evaluated by ultrasound (US) 162 median nerves at wrist of 89 consecutive patients with symptoms suggestive of CTS and 104 of 52 consecutive symptom-free subjects. Neurophysiological evaluation confirmed CTS diagnosis. All patients underwent ultrasonographic evaluation of median nerve in the elbow-palm segment through high-frequency probe; BMN was arbitrarily classified as "complete" and "incomplete" on the basis of US results. BMN was observed in 16/104 wrists (15.4%) in control group and in 30/162 (18.5%) wrists in CTS group. Our study showed that BMN is frequent, not always bilateral, more often is "incomplete" and it has similar prevalence in CTS and control group. These findings suggest that BMN is not a risk factor of developing CTS.


[Hypothalamic syndromes after the administration of toxic doses of drugs for terminating pregnancy].
Twenty-five women presented with primary injuries of the hypothalamic area and the hypothalamic syndrome that resulted from the intake of toxic doses of drugs (TDD) for inducing an abortion. The situation was simulated in mature rats. Experiments evidenced a predominant involvement of the hypothalamic area, vs. other portions of the brain. All the patients developed the vegetovascular form of the hypothalamic syndrome, combined with neuroendocrine and thermoregulation disturbances. TDD-induced increase of the vulnerability of the hypothalamus during pregnancy may be explained by structural and functional peculiarities of the female hypothalamus, by suppression of the dominant gestational functional integrating system formed during pregnancy and simultaneous failure of the principal performance system, the hypothalamus.


Xylanase modulates the microbiota of ileal mucosa and digesta of pigs fed corn-based arabinoxylans likely through both a stimbiotic and prebiotic mechanism.
The experimental objective was to characterize the impact of insoluble corn-based fiber, xylanase, and an arabinoxylan-oligosaccharide on ileal digesta and mucosa microbiome of pigs. Three replicates of 20 gilts were blocked by initial body weight, individually-housed, and assigned to 1 of 4 dietary treatments: a low-fiber control (LF), a 30% corn bran high-fiber control (HF), HF+100 mg/kg xylanase (HF+XY), and HF+50 mg/kg arabinoxylan oligosaccharide (HF+AX). Gilts were fed their respective treatments for 46 days. On day 46, pigs were euthanized and ileal digesta and mucosa were collected. The V4 region of the 16S rRNA was amplified and sequenced, generating a total of 2,413,572 and 1,739,013 high-quality sequences from the digesta and mucosa, respectively. Sequences were classified into 1,538 mucosa and 2,495 digesta operational taxonomic units (OTU). Hidden-state predictions of 25 enzymes were made using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2 (PICRUST2). Compared to LF, HF increased Erysipelotrichaceae_UCG-002, and Turicibacter in the digesta, Lachnospiraceae_unclassified in the mucosa, and decreased Actinobacillus in both (Q<0.05). Relative to HF, HF+XY increased 19 and 14 of the 100 most abundant OTUs characterized from digesta and mucosa, respectively (Q<0.05). Notably, HF+XY increased the OTU_23_Faecalibacterium by nearly 6 log2-fold change, compared to HF. Relative to HF, HF+XY increased genera Bifidobacterium, and Lactobacillus, and decreased Streptococcus and Turicibacter in digesta (Q<0.05), and increased Bifidobacterium and decreased Escherichia-Shigella in the mucosa (Q<0.05). Compared to HF, HF+AX increased 5 and 6 of the 100 most abundant OTUs characterized from digesta and mucosa, respectively, (Q<0.05), but HF+AX did not modulate similar taxa as HF+XY. The PICRUST2 predictions revealed HF+XY increased gene-predictions for enzymes associated with arabinoxylan degradation and xylose metabolism in the digesta, and increased enzymes related to short-chain fatty acid production in the mucosa. Collectively, these data suggest xylanase elicits a stimbiotic and prebiotic mechanism.


Parallel packing of alpha-helices in crystals of the zervamicin IIA analog Boc-Trp-Ile-Ala-Aib-Ile-Val-Aib-Leu-Aib-Pro-OMe.2H2O.
An apolar synthetic analog of the first 10 residues at the NH2-terminal end of zervamicin IIA crystallizes in the triclinic space group P1 with cell dimensions a = 10.206 +/- 0.002 A, b = 12.244 +/- 0.002 A, c = 15.049 +/- 0.002 A, alpha = 93.94 +/- 0.01 degrees, beta = 95.10 +/- 0.01 degrees, gamma = 104.56 +/- 0.01 degrees, Z = 1, C60H97N11O13 X 2H2O. Despite the relatively few alpha-aminoisobutyric acid residues, the peptide maintains a helical form. The first intrahelical hydrogen bond is of the 3(10) type between N(3) and O(0), followed by five alpha-helix-type hydrogen bonds. Solution 1H NMR studies in chloroform also favor a helical conformation, with seven solvent-shielded NH groups. Continuous columns are formed by head-to-tail hydrogen bonds between the helical molecules along the helix axis. The absence of polar side chains precludes any lateral hydrogen bonds. Since the peptide crystallizes with one molecule in a triclinic space group, aggregation of the helical columns must necessarily be parallel rather than antiparallel. The packing of the columns is rather inefficient, as indicated by very few good van der Waals' contacts and the occurrence of voids between the molecules.


Mitochondrial localization as a determinant of capacitative Ca2+ entry in HeLa cells.
Whether different subsets of mitochondria play distinct roles in shaping intracellular Ca2+ signals is presently unresolved. Here, we determine the role of mitochondria located beneath the plasma membrane in controlling (a) Ca2+ release from the endoplasmic reticulum (ER) and (b) capacitative Ca2+ entry. By over-expression of the dynactin subunit dynamitin, and consequent inhibition of the fission factor, dynamin-related protein (Drp-1), mitochondria were relocalised from the plasma membrane towards the nuclear periphery in HeLa cells. The impact of these changes on free calcium concentration in the cytosol ([Ca2+]c), mitochondria ([Ca2+]m) and ER ([Ca2+]ER) was then monitored with specifically-targeted aequorins. Whilst dynamitin over-expression increased the number of close contacts between the ER and mitochondria by >2.5-fold, assessed using organelle-targeted GFP variants, histamine-induced changes in organellar [Ca2+] were unaffected. By contrast, Ca2+ influx elicited significantly smaller increases in [Ca2+]c and [Ca2+]m in dynamitin-expressing than in control cells. These data suggest that the strategic localisation of a subset of mitochondria beneath the plasma membrane is required for normal Ca2+ influx, but that the transfer of Ca2+ ions between the ER and mitochondria is relatively insensitive to gross changes in the spatial relationship between these two organelles.


Quality of Life in patients with nonalcoholic fatty liver disease: Structure and related factors focusing on illness uncertainty.
Patients with nonalcoholic fatty liver disease (NAFLD) have a low quality of life (QOL) and illness uncertainty. This study examined the structure of QOL and associated factors, including illness uncertainty, among individuals with NAFLD. A cross-sectional survey was conducted using a self-administered questionnaire for outpatients with NAFLD. QOL was measured using the Short Form-8. Dietary habits, physical activity level, illness uncertainty, health locus of control, and knowledge of NAFLD were assessed. Path analysis was used to study the associated factors of QOL and their structure, including uncertainty of disease. Path analysis of 168 NAFLD patients indicated that a high Physical Component Summary score on the Short Form-8-representing physical QOL-was predicted by a body mass index <25 kg/m2 and high educational level. A high Mental Component Summary score-representing mental QOL-was predicted by being male, good dietary habits, low illness uncertainty, and presence of consultants. The model showed satisfactory goodness-of-fit without being rejected by the chi-square test (goodness-of-fit index = .947, adjusted goodness-of-fit index = .917, comparative fit index = .967, root mean square error of approximation = 0.023). Nurses need to work closely with NAFLD patients as consultants, providing adequate information about the causes, treatments, and dietary habits, and focusing on the individual's perception of health. This could reduce illness uncertainty and contribute to the improvement of QOL.


Regulation of floral organ abscission in Arabidopsis thaliana.
Abscission is a developmental program that results in the active shedding of infected or nonfunctional organs from a plant body. Here, we establish a signaling pathway that controls abscission in Arabidopsis thaliana from ligand, to receptors, to downstream effectors. Loss of function mutations in Inflorescence Deficient in Abscission (IDA), which encodes a predicted secreted small protein, the receptor-like protein kinases HAESA (HAE) and HAESA-like 2 (HSL2), the Mitogen-Activated Protein Kinase Kinase 4 (MKK4) and MKK5, and a dominant-negative form of Mitogen-Activated Protein Kinase 6 (MPK6) in a mpk3 mutant background all have abscission-defective phenotypes. Conversely, expression of constitutively active MKKs rescues the abscission-defective phenotype of hae hsl2 and ida plants. Additionally, in hae hsl2 and ida plants, MAP kinase activity is reduced in the receptacle, the part of the stem that holds the floral organs. Plants overexpressing IDA in a hae hsl2 background have abscission defects, indicating HAE and HSL2 are epistatic to IDA. Taken together, these results suggest that the sequential action of IDA, HAE and HSL2, and a MAP kinase cascade regulates the programmed separation of cells in the abscission zone.