Dynamics of change in the practice of female genital cutting in Senegambia: testing predictions of social convention theory.
Recent reviews of intervention efforts aimed at ending female genital cutting (FGC) have concluded that progress to date has been slow, and call for more efficient programs informed by theories on behavior change. Social convention theory, first proposed by Mackie (1996), posits that in the context of extreme resource inequality, FGC emerged as a means of securing a better marriage by signaling fidelity, and subsequently spread to become a prerequisite for marriage for all women. Change is predicted to result from coordinated abandonment in intermarrying groups so as to preserve a marriage market for uncircumcised girls. While this theory fits well with many general observations of FGC, there have been few attempts to systematically test the theory. We use data from a three year mixed-method study of behavior change that began in 2004 in Senegal and The Gambia to explicitly test predictions generated by social convention theory. Analyses of 300 in-depth interviews, 28 focus group discussions, and survey data from 1220 women show that FGC is most often only indirectly related to marriageability via concerns over preserving virginity. Instead we find strong evidence for an alternative convention, namely a peer convention. We propose that being circumcised serves as a signal to other circumcised women that a girl or woman has been trained to respect the authority of her circumcised elders and is worthy of inclusion in their social network. In this manner, FGC facilitates the accumulation of social capital by younger women and of power and prestige by elder women. Based on this new evidence and reinterpretation of social convention theory, we suggest that interventions aimed at eliminating FGC should target women's social networks, which are intergenerational, and include both men and women. Our findings support Mackie's assertion that expectations regarding FGC are interdependent; change must therefore be coordinated among interconnected members of social networks.


COOH-terminal signals mediate the trafficking of a peptide processing enzyme in endocrine cells.
Peptidylglycine alpha-amidating monooxygenase (PAM) catalyzes the COOH-terminal amidation of bioactive peptides through a two step reaction catalyzed by separate enzymes contained within the PAM precursor. To characterize the trafficking of integral membrane PAM proteins in neuroendocrine cells, we have generated stable AtT-20 cell lines expressing full length and COOH-terminally truncated integral membrane PAM proteins. Full length integral membrane PAM was present on the cell surface in low but detectable amounts and PAM proteins which reached the cell surface were rapidly internalized but not immediately degraded in lysosomes. Internalized PAM complexed with PAM antibody was found in a subcellular compartment which overlapped with internalized transferrin and with structures binding WGA. Thus the punctate juxtanuclear staining of full length PAM represents PAM in endosomes. Endoproteolytic processing of full length PAM-1 and PAM-2 resulted in the secretion of soluble PAM proteins; the secretion of these soluble PAM proteins was stimulus dependent. Although some of the truncated PAM protein was also processed and stored in AtT-20 cells, much of the expressed protein was redistributed to the plasma membrane. Soluble proteins not observed in large amounts in cells expressing full length PAM were released from the surface of cells expressing truncated PAM and little internalization of truncated integral membrane PAM was observed. Thus, the COOH-terminal domain of PAM contains information important for its trafficking within the regulated secretory pathway as well as information necessary for its retrieval from the cell surface.


Employee use and perceived benefit of a complementary and alternative medicine wellness clinic at a major military hospital: evaluation of a pilot program.
The objectives of this study were to examine the feasibility of a weekly on-site complementary and alternative medicine (CAM) wellness clinic for staff at a military hospital, and to describe employees' perceptions of program effectiveness. The study setting was the Restore & Renew(®) Wellness Clinic at a United States Department of Defense hospital. The subjects were hospital nurses, physicians, clinicians, support staff, and administrators. The walk-in wellness clinic was open 8:00 am-2:00 pm 1 day a week. Participants selected one or more modalities each visit: ear acupuncture, clinical acupressure, and Zero Balancing.(®) A self-report survey was done after each clinic visit to evaluate clinic features and perceived impact on stress-related symptoms, compassion for patients, sleep, and workplace or personal relationships. Surveys completed after first-time and repeat visits (n=2,756 surveys) indicated that most participants agreed or strongly agreed they felt more relaxed after sessions (97.9%), less stress (94.5%), more energy (84.3%), and less pain (78.8%). Ninety-seven percent (97%) would recommend it to a co-worker. Among surveys completed after five or more visits, more than half (59%-85%) strongly agreed experiencing increased compassion with patients, better sleep, improved mood, and more ease in relations with co-workers. Perceived benefits were sustained and enhanced by number of visits. The most frequently reported health habit changes were related to exercise, stress reduction, diet/nutrition, and weight loss. This evaluation suggests that a hospital-based wellness clinic based on CAM principles and modalities is feasible, well-utilized, and perceived by most participants to have positive health benefits related to stress reduction at work, improved mood and sleep, and lifestyle.


A randomized clinical comparison of the Intersurgical i-gel and LMA Unique in non-obese adults during general surgery.
The i-gel is a cuffless, single-use supralaryngeal airway device designed to provide a more effective seal than the laryngeal mask airway (LMA). Although the superiority of the i-gel compared to the LMA Classic was determined in a previous study, no studies have been performed that compare it to the disposable LMA Unique. The aim of this study was to compare the Intersurgical i-gelTM against the LMA UniqueTM (uLMA) in terms of ease of placement, time of insertion, and adequacy of placement through a randomized, controlled clinical trial. Following Institutional Review Board (IRB) approval and written informed consent, 50 adult patients were recruited for this study. All enrolled patients were ASA 1-2, Mallampati I-II, and scheduled to receive general anesthesia. Patients were randomized to have either the i-gel or the uLMA placed for airway management. After standardized induction techniques, the airway was secured with the assigned device. All patients were interviewed postoperatively for sore throat, hoarseness, and dysphagia. Standard vital signs, end-tidal CO2, tidal volumes, and peak pressures were recorded. Insertion time, leak pressures, and anatomic placement as assessed fiberoptically for the i-gel were recorded. Ease of placement and complications were also recorded. The insertion time was significantly less with the i-gel (21.04±12.6 s vs. 30.04±14.1 s, P=0.02). An inadequate seal was noted in three patients with the i-gel, and it was exchanged for the uLMA in all three cases. There were no significant differences in the ease of insertion, leak pressures, or fiberoptic view. Most of the fiberoptic views, as assessed through the drain tube, demonstrated esophageal mucosa (22/25). Patients receiving the i-gel were significantly more likely to require a second attempt at insertion by the anesthesiologist (OR 8.11, CI 1.1-58.6, P=0.03). Finally, patients receiving the size 5 i-gel were significantly more likely to complain of immediate postoperative symptoms, such as sore throat and dysphagia (OR 29.32, CI 1.4-613.1, P=0.03). Although the i-gel had a faster insertion time in comparison to the uLMA, there was a greater need for repeat insertions. The weight criteria established by the manufacturer may need to be readjusted to recommend a larger size device in some patients less than 90 kg because all of the repeat insertions were in patients weighing more than 80 kg. In all other aspects of its use, the i-gel performed similarly to the uLMA.


Using social network analysis to examine gun violence.
Research has found gun violence is a social contagion that spreads from one individual to another. To understand the social networks of violence, previous research has used social network analysis, a tool that explores the relationships between social actors. Most of the prior research uses coarrest data and incident reports to produce social networks. The current study incorporates the use of an underused data source, ballistic evidence, to better understand gun violence. The aim was to identify drivers of gun violence and to examine network concentration. Specifically, National Integrated Ballistic Information Network (NIBIN) leads and associated criminal incidents in combination with all incident reports were collected from a large urban county in the Pacific Northwest between 2015 and 2017. Social network analysis was conducted to produce a NIBIN network to demonstrate the connections between incidents where the same firearm was used. Social network analysis was also conducted to identify individuals who were the most involved in gun violence. Results reveal gun violence is very interconnected as many of the same firearms were discharged in multiple different incidents with several other individuals involved, indicating a connection between these individuals. This demonstrates the utility of using ballistic evidence beyond using only incident and coarrest data because it provides more information that directly relates to gun violence and the transfer of guns. Additionally, this can be very useful for law enforcement agencies to identify who is integral in the gun violence networks that can be helpful for prevention and intervention strategies.


Associations of filaggrin gene loss-of-function variants with urinary phthalate metabolites and testicular function in young Danish Men.
Filaggrin is an epidermal protein that is crucial for skin barrier function. Up to 10% of Europeans and 5% of Asians carry at least one null allele in the filaggrin gene (FLG). Reduced expression of filaggrin in carriers of the null allele is associated with facilitated transfer of allergens across the epidermis. We hypothesized that these individuals may have increased transdermal uptake of endocrine disruptors, including phthalates. We investigated urinary excretion of phthalate metabolites and testicular function in young men with and without FLG loss-of-function variants in a cross-sectional study of 861 young men from the general Danish population. All men were genotyped for FLG R501X, 2282del4, and R2447X loss-of-function variants. We measured urinary concentrations of 14 phthalate metabolites and serum levels of reproductive hormones. We also evaluated semen quality. Sixty-five men (7.5%) carried at least one FLG-null allele. FLG-null carriers had significantly higher urinary concentrations of several phthalate metabolites, including a 33% higher concentration of MnBP (mono-n-butyl phthalate; 95% CI: 16, 51%). FLG-null variants were not significantly associated with reproductive hormones or semen quality parameters. This study provides evidence that carriers of FLG loss-of-function alleles may have higher internal exposure to phthalates, possibly due to increased transepidermal absorption. FLG loss-of-function variants may indicate susceptible populations for which special attention to transepidermal absorption of chemicals and medication may be warranted.


Tobacco dependence treatment in the emergency department: A randomized trial using the Multiphase Optimization Strategy.
Tobacco dependence remains the leading preventable cause of death in the developed world. Smokers are disproportionately from lower socioeconomic groups, and may use the hospital emergency department (ED) as an important source of care. A recent clinical trial demonstrated the efficacy of a multicomponent intervention to help smokers quit, but the independent contributions of those components is unknown. This is a full-factorial (16-arm) randomized trial in a busy hospital ED of 4 tobacco dependence interventions: brief motivational interviewing, nicotine replacement therapy, referral to a telephone quitline, and a texting program. The trial utilizes the Multiphase Optimization Strategy (MOST) and a novel mixed methods analytic design to assess clinical efficacy, cost effectiveness, and qualitative participant feedback. The primary endpoint is tobacco abstinence at 3months, verified by participants' exhaled carbon monoxide. Study enrollment began in February 2017. As of April 2017, 52 of 1056 planned participants (4.9%) were enrolled. Telephone-based semi-structured participant interviews and in-person biochemical verification of smoking abstinence are completed at the 3-month follow-up. Efficacy and cost effectiveness analyses will be conducted after follow-up is completed. The goal of this study is to identify a clinically efficacious, cost-effective intervention package for the initial treatment of tobacco dependence in ED patients. The efficacy of this combination can then be tested in a subsequent confirmatory trial. Our approach incorporates qualitative feedback from study participants in evaluating which intervention components will be tested in the future trial. Trial (NCT02896400) registered in ClinicalTrials.gov on September 6, 2016.


Mapping of genes in BamHI fragment M of Epstein-Barr virus DNA that may determine the fate of viral infection.
We used nuclease digestion to map RNA transcripts encoded in the BamHI M fragment of the Epstein-Barr virus (EBV) genome (strain B95-8). Of the five RNAs, three are rightwardly transcribed, have different cap sites but common 3' termini, and are unspliced. The two remaining RNAs are leftwardly transcribed and are 5' and 3' coterminal. One of these transcripts is spliced, resulting in the removal of a small intron from the 5' region of this RNA. We have previously published data which indicated that the BamHI M region is the first actively transcribed region of the viral genome during the replicative cycle, suggesting that one or more genes in this region is important in the initiation of EBV replication. We have now mapped two large EcoRI restriction fragments which span approximately 75% of the P3HR-1 defective genome and which contain DNA from the BamHI M region of the standard genome. The data indicate that only the coding and 5' flanking sequences for the leftwardly transcribed RNAs are intact within the defective genome. Fewer than 500 bases coding for the 3'-most regions of the rightwardly transcribed RNAs are intact, and it is unlikely that these encode functional native polypeptides. Therefore, it seems that transcriptional activation of the BamHI M-region genes is not mediated directly by the rearrangement of M genes in defective P3HR-1 EBV.


Mucosal delivery of a respiratory syncytial virus CTL peptide with enterotoxin-based adjuvants elicits protective, immunopathogenic, and immunoregulatory antiviral CD8+ T cell responses.
In an effort to develop a safe and effective vaccine against respiratory syncytial virus (RSV), we used Escherichia coli heat-labile toxin (LT), and LTK63 (an LT mutant devoid of ADP-ribosyltransferase activity) to elicit murine CD8(+) CTL responses to an intranasally codelivered CTL peptide from the second matrix protein (M2) of RSV. M2(82-90)-specific CD8(+) T cells were detected by IFN-gamma enzyme-linked immunospot and (51)Cr release assay in local and systemic lymph nodes, and their induction was dependent on the use of a mucosal adjuvant. CTL elicited by peptide immunization afforded protection against RSV challenge, but also enhanced weight loss. CTL-mediated viral clearance was not dependent on IFN-gamma since depletion using specific mAb during RSV challenge did not affect cellular recruitment or viral clearance. Depletion of IFN-gamma did, however, reduce the concentration of TNF detected in lung homogenates of challenged mice and largely prevented the weight loss associated with CTL-mediated viral clearance. Mice primed with the attachment glycoprotein (G) develop lung eosinophilia after intranasal RSV challenge. Mucosal peptide vaccination reduced pulmonary eosinophilia in mice subsequently immunized with G and challenged with RSV. These studies emphasize that protective and immunoregulatory CD8(+) CTL responses can be mucosally elicited using enterotoxin-based mucosal adjuvants but that resistance against viral infection may be accompanied by enhanced disease.


Analysis of conventional and unconventional trafficking of CFTR and other membrane proteins.
The cystic fibrosis transmembrane conductance regulator (CFTR) is a polytopic transmembrane protein that functions as a cAMP-activated anion channel at the apical membrane of epithelial cells. Mutations in CFTR cause cystic fibrosis and are also associated with monosymptomatic diseases in the lung, pancreas, intestines, and vas deferens. Many disease-causing CFTR mutations, including the deletion of a single phenylalanine residue at position 508 (ΔF508-CFTR), result in protein misfolding and trafficking defects. Therefore, intracellular trafficking of wild-type and mutant CFTR has been studied extensively, and results from these studies significantly contribute to our general understanding of mechanisms involved in the cell-surface trafficking of membrane proteins. CFTR is a glycoprotein that undergoes complex N-glycosylation as it passes through Golgi-mediated conventional exocytosis. Interestingly, results from recent studies revealed that CFTR and other membrane proteins can reach the plasma membrane via an unconventional alternative route that bypasses Golgi in specific cellular conditions. Here, we describe methods that have been used to investigate the conventional and unconventional surface trafficking of CFTR. With appropriate modifications, the protocols described in this chapter can also be applied to studies investigating the intracellular trafficking of other plasma membrane proteins.


Heart failure and palliative care: implications in practice.
The number of people with heart failure is continually rising. Despite continued medical advances that may prolong life, there is no cure. While typical heart failure trajectories include the risk of sudden death, heart failure is typically characterized by periods of stability interrupted by acute exacerbations. The unpredictable nature of this disease and the inability to predict its terminal phase has resulted in few services beyond medical management being offered. Yet, this population has documented unmet needs that extend beyond routine medical care. Palliative care has been proposed as a strategy to meet these needs, however, these services are rarely offered. Although palliative care should be implemented early in the disease process, in practice it is tied to end-of-life care. The purpose of this study was to uncover whether the conceptualization of palliative care for heart failure as end-of-life care may inhibit the provision of these services. The meaning of palliative care in heart failure was explored from three perspectives: scientific literature, health care providers, and spousal caregivers of patients with heart failure. There is confusion in the literature and by the health care community about the meaning of the term palliative care and what the provision of these services entails. Palliative care was equated to end-of-life care, and as a result, health care providers may be reluctant to discuss palliative care with heart failure patients early in the disease trajectory. Most family caregivers have not heard of the term and all would be receptive to an offer of palliative care at some point during the disease trajectory.


Protective Effect of Two Extracts of Cydonia oblonga Miller (Quince) Fruits on Gastric Ulcer Induced by Indomethacin in Rats.
In various studies, Cydonia oblonga Miller (quince) has been reported to have many properties such as antioxidant and anti-ulcerative effects. This study has aimed to investigate the protective effects of quince aqueous extract (QAE) and quince hydroalcoholic extract (QHE) on gastric ulcer caused by indomethacin and the relevant macroscopic, histopathology, and biochemical factors in rats. Ten groups of male Wistar rats, six in each, were used in this study. These groups included: normal (distilled water), control (distilled water + indomethacin), reference (ranitidine or sucralfate + indomethacin), and test groups (QAE or QHE + indomethacin) treated with three increasing doses (200, 500, and 800 mg/kg). Extracts and drugs were given orally to rats 1 h before injecting the indomethacin (25 mg/kg, intraperitoneally). Six hours later, the abdomen of rats was exposed, its pylorus was legated, gastric acid content was extracted, and its pH and the amount of pepsin secreted were measured by Anson method. Then, histopathology indices, ulcer area, ulcer index, and myeloperoxidase (MPO) activity were measured in gastric mucus. Both extracts of quince were effective to reduce the acidity of stomach and pepsin activity. Compared to control group, the average of enzyme activity of MPO was significantly declined in all treated groups. Control group had the highest level of gastric ulcer indices including severity, area, and index while the evaluated parameters had decreased in all extract treated groups although it seems that QAE was somewhat more effective. Protective effect of QAE and QHE on gastric ulcer was done by undermining offensive factors including decreasing the secretion of gastric acid and pepsin activity and by strengthening the protective factors of gastric mucus including antioxidant capacity.


Stem Cell Therapy for Osteonecrosis of the Femoral Head: Current Trends and Comprehensive Review.
Osteonecrosis of the femoral head (ONFH) is a common and frequently occurring disease. It is caused by interruption of blood supply with different etiologies. ONFH leads to degeneration and necrosis of the subchondral bone of the femoral head and eventually collapse of the femoral head. ONFH has a high disability rate, seriously affecting the quality of living of patients, and often involves middle-aged and younger people. In recent years, the technology and understanding of stem cells and regenerative medicine have been developing rapidly. Numerous studies have reported successful results in the treatment of ONFH by stem cell transplantation. Thus, stem cell transplantation is expected to serve as a new method in the treatment of ONFH. In the present report, therefore, we evaluated current techniques and outcomes utilizing stem cells in the treatment of ONFH. A computer-based online search of PubMed and Cochrane Library databases between January 2006 and June 2017 was performed to search related articles using the keywords of "treatment, stem cell, osteonecrosis of the femoral head" in English language. Literature related to the treatment of ONFH was selected. Our search obtained a total of 161 articles, but only 9 articles met our inclusion criteria and were included in our report. The present review reveals that cell technology has demonstrated good evidence in the treatment of ONFH. However, this technology needs additional in-depth study to better explore and appreciate more ideal ways to overcome difficulties associated with source of cells.


Characterizing elemental, equivalent black, and refractory black carbon aerosol particles: a review of techniques, their limitations and uncertainties.
Elemental-, equivalent black- and refractory black-carbon are terms that have been defined in order to dissect the more general term, black carbon, into its component parts related to its specific chemical and optical properties and its impact on climate and health. Recent publications have attempted to clarify the meaning of these terms with respect to their environmental impact, particularly on climate. Here, we focus on the measurement aspects, reviewing the most commonly implemented techniques for the direct and indirect derivation of black carbon properties, their strengths, limitations, and uncertainties, and provide a non-exhaustive bibliography where the reader can find more detailed information. This review paper is designed as a guide for those wishing to learn about the current state of black carbon measurement instrumentation, how calibration is carried out, when one instrument may have the advantage over another, and where new techniques are needed to fill important knowledge gaps.


An optical fiber infrasound sensor: a new lower limit on atmospheric pressure noise between 1 and 10 Hz.
A new distributed sensor for detecting pressure variations caused by distant sources has been developed. The instrument reduces noise due to air turbulence in the infrasound band by averaging pressure along a line by means of monitoring strain in a long tubular diaphragm with an optical fiber interferometer. Above 1 Hz, the optical fiber infrasound sensor (OFIS) is less noisy than sensors relying on mechanical filters. Records collected from an 89-m-long OFS indicate a new low noise limit in the band from 1 to 10 Hz. Because the OFIS integrates pressure variations at light-speed rather than the speed of sound, phase delays of the acoustical signals caused by the sensor are negligible. Very long fiber-optic sensors are feasible and hold the promise of better wind-noise reduction than can be achieved with acoustical-mechanical systems.


Generational status and duration of residence predict diabetes prevalence among Latinos: the California Men's Health Study.
Diabetes disproportionately affects Latinos. However, examining Latinos as one group obscures important intra-group differences. This study examined how generational status, duration of US residence, and language preference are associated with diabetes prevalence and to what extent these explain the higher prevalence among Latinos. We determined nativity, duration of US residence, language preference, and diabetes prevalence among 11 817 Latino, 6109 black, and 52 184 white participants in the California Men's Health Study. We combined generational status and residence duration into a single migration status variable with levels: > or = third generation; second generation; and immigrant living in the US for > 25, 16-25, 11-15, or < or = 10 years. Language preference was defined as language in which the participant took the survey. Logistic regression models were specified to assess the associations of dependent variables with prevalent diabetes. Diabetes prevalence was 22%, 23%, and 11% among Latinos, blacks, and whites, respectively. In age-adjusted models, we observed a gradient of risk of diabetes by migration status among Latinos. Further adjustment for socioeconomic status, obesity and health behaviors only partially attenuated this gradient. Language preference was a weak predictor of prevalent diabetes in some models and not significant in others. In multivariate models, we found that odds of diabetes were higher among US-born Latinos than US-born blacks. Generational status and residence duration were associated with diabetes prevalence among middle-aged Latino men in California. As the Latino population grows, the burden of diabetes-associated disease is likely to increase and demands public health attention.


Cold-adapted and rhizosphere-competent strain of Rahnella sp. with broad-spectrum plant growth-promotion potential.
A phosphate-solubilizing bacterial strain isolated from Hippophae rhamnoides rhizosphere was identified as Rahnella sp. based on its phenotypic features and 16S rRNA gene sequence. The bacterial strain showed the growth characteristics of a cold-adapted psychrotroph, with the multiple plant growth-promoting traits of inorganic and organic phosphate solubilization, 1-aminocyclopropane-1- carboxylate-deaminase activity, ammonia generation, and siderophore production. The strain also produced indole- 3-acetic acid, indole-3-acetaldehyde, indole-3-acetamide, indole-3-acetonitrile, indole-3-lactic acid, and indole-3- pyruvic acid in tryptophan-supplemented nutrient broth. Gluconic, citric and isocitric acids were the major organic acids detected during tricalcium phosphate solubilization. A rifampicin-resistant mutant of the strain exhibited high rhizosphere competence without disturbance to the resident microbial populations in pea rhizosphere. Seed bacterization with a charcoal-based inoculum significantly increased growth in barley, chickpea, pea, and maize under the controlled environment. Microplot testing of the inoculum at two different locations in pea also showed significant increase in growth and yield. The attributes of coldtolerance, high rhizosphere competence, and broad-spectrum plant growth-promoting activity exhibited the potential of Rahnella sp. BIHB 783 for increasing agriculture productivity.


Sensory and physicochemical profiling of traditional and enriched gari in Benin.
Gari is a roasted fermented granular product made from cassava in many African countries. It is consumed raw, or added with water, or cooked into a paste. Up to now, gari enriched with palm oil and/or soybean is not available on Beninese markets. To our knowledge, no sensory profiling using appropriate methodology has been conducted on gari in Benin. The sensory studies on gari in Benin and other African countries only included general descriptors (appearance, taste, odor). The aim of our study was to establish a detailed sensory and physicochemical profile of nine traditional and three enriched gari made using different processes in Benin. Fifteen sensory descriptors of raw gari, and gari added with water, were generated and scored using quantitative descriptive analysis. The enriched gari differed from traditional gari mainly in color and odor, while their swelling capacity, texture during chewing, and light sour taste were similar. Marked variability in particle size, particle heterogeneity, water absorption, and sour taste was found among traditional gari. The physicochemical characteristics, such as degree of starch gelatinization, L-lactic acid, and β-carotene contents, were highly variable among the 12 gari. Multifactor analysis revealed highly significant correlations between some physicochemical and sensory properties. The addition of soybean and/or palm oil did not affect most of the sensory properties of the traditional gari. The acceptability of these enriched gari with higher nutritive value by Beninese consumers should be tested to develop marketing strategies.


Escherichia coli DnaB helicase-DnaC protein complex: allosteric effects of the nucleotides on the nucleic acid binding and the kinetic mechanism of NTP hydrolysis. 3.
Allosteric interactions between the DNA- and NTP-binding sites of the Escherichia coli DnaB helicase engaged in the DnaB-DnaC complex and the mechanism of NTP hydrolysis by the complex have been examined using the fluorescence titration, analytical ultracentrifugation, and rapid quench-flow technique. Surprisingly, the ssDNA affinity of the DnaB-DnaC complex is independent of the structure of the phosphate group of the cofactor bound to the helicase. Thus, the DnaC protein eliminates the antagonistic allosteric effect of NTP and NDP on the ssDNA affinity of the enzyme. The protein changes the engagement of the DNA-binding subsites of the helicase in interactions with the nucleic acid, depending on the structure of the phosphate group of the present nucleotide cofactor and profoundly affects the structure of the bound DNA. Moreover, the ssDNA affinity of the helicase in the DnaB-DnaC complex is under the control of the nucleotide-binding site of the DnaC protein. The protein does not affect the NTP hydrolysis mechanism of the helicase. Nevertheless, the rate of the chemical step is diminished in the DnaB-DnaC complex. In the tertiary DnaB-DnaC-ssDNA complex, the ssDNA changes the internal dynamics between intermediates of the pyrimidine cofactor, in a manner independent of the base composition of the DNA, while the hydrolysis step of the purine cofactor is specifically stimulated by the homoadenosine ssDNA. The significance of these results for functional activities of the DnaB-DnaC complex is discussed.


Increased plasma phenylacetic acid in patients with end-stage renal failure inhibits iNOS expression.
NO prevents atherogenesis and inflammation in vessel walls by inhibition of cell proliferation and cytokine-induced endothelial expression of adhesion molecules and proinflammatory cytokines. Reduced NO production due to inhibition of either eNOS or iNOS may therefore reinforce atherosclerosis. Patients with end-stage renal failure show markedly increased mortality due to atherosclerosis. In the present study we tested the hypothesis that uremic toxins are responsible for reduced iNOS expression. LPS-induced iNOS expression in mononuclear leukocytes was studied using real-time PCR. The iNOS expression was blocked by addition of plasma from patients with end-stage renal failure, whereas plasma from healthy controls had no effect. Hemofiltrate obtained from patients with end-stage renal failure was fractionated by chromatographic methods. The chromatographic procedures revealed a homogenous fraction that inhibits iNOS expression. Using gas chromatography/mass spectrometry, this inhibitor was identified as phenylacetic acid. Authentic phenylacetic acid inhibited iNOS expression in a dose-dependent manner. In healthy control subjects, plasma concentrations were below the detection level, whereas patients with end-stage renal failure had a phenylacetic acid concentration of 3.49 +/- 0.33 mmol/l (n = 41). It is concluded that accumulation of phenylacetic acid in patients with end-stage renal failure inhibits iNOS expression. That mechanism may contribute to increased atherosclerosis and cardiovascular morbidity in patients with end-stage renal failure.


Mythbusters: Credibilising strategies in popular nutrition books by academics.
Healthy eating is a prominent concern amongst public health and diet professionals. Public understanding of healthy eating presents a topic of interest in understanding scientific credibility in the public domain. Three prominent Dutch nutrition scientists, Kok, Seidell and Katan, have produced popular science books on healthy eating, aiming to remove myths about food and nutrition from the public domain. I describe how they do so, and which strategies they have chosen to achieve this goal. In their books, they move beyond traditional academic strategies to build credibility and devise credibilising strategies resembling those of diet authors. While doing so, they move beyond the deficit model, but end up competing for dietary credibility on the diet authors' terms.


Systematic review and meta-analysis of community and facility-based HIV testing to address linkage to care gaps in sub-Saharan Africa.
HIV testing and counselling is the first crucial step for linkage to HIV treatment and prevention. However, despite high HIV burden in sub-Saharan Africa, testing coverage is low, particularly among young adults and men. Community-based HIV testing and counselling (testing outside of health facilities) has the potential to reduce coverage gaps, but the relative impact of different modalities is not well assessed. We conducted a systematic review of HIV testing modalities, characterizing community (home, mobile, index, key populations, campaign, workplace and self-testing) and facility approaches by population reached, HIV positivity, CD4 count at diagnosis and linkage. Of 2,520 abstracts screened, 126 met eligibility criteria. Community HIV testing and counselling had high coverage and uptake and identified HIV-positive people at higher CD4 counts than facility testing. Mobile HIV testing reached the highest proportion of men of all modalities examined (50%, 95% confidence interval (CI) = 47-54%) and home with self-testing reached the highest proportion of young adults (66%, 95% CI = 65-67%). Few studies evaluated HIV testing for key populations (commercial sex workers and men who have sex with men), but these interventions yielded high HIV positivity (38%, 95% CI = 19-62%) combined with the highest proportion of first-time testers (78%, 95% CI = 63-88%), indicating service gaps. Community testing with facilitated linkage (for example, counsellor follow-up to support linkage) achieved high linkage to care (95%, 95% CI = 87-98%) and antiretroviral initiation (75%, 95% CI = 68-82%). Expanding home and mobile testing, self-testing and outreach to key populations with facilitated linkage can increase the proportion of men, young adults and high-risk individuals linked to HIV treatment and prevention, and decrease HIV burden.


Hypericin and 5-aminolevulinic acid-induced protoporphyrin IX induce enhanced phototoxicity in human endometrial cancer cells with non-coherent white light.
The in vitro experiments described in this study were aimed at exploring a synergistic effect between 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) and hypericin. In a previous study, enhanced phototoxicity was observed in a patient during a clinical study on 5-ALA-based photodynamic tumor localization of breast cancer. This patient ingested a hypericin containing plant extract in parallel to orally applied 5-ALA. Human endometrial cancer cells (HEC-1A) were treated with 0.5mM of 5-ALA and 60 nM of hypericin, either separately or combined. Colony formation was assessed after illumination of the cells with both red (635 nm) and white light (400-800 nm) at a dose of 2.5 J/cm(2). Porphyrin metabolites were quantified by HPLC in cells treated with photosensitizers without subsequent illumination. After white light illumination, cells treated with a combination of 5-ALA and hypericin had a significant reduction in colony formation compared with cells treated with 5-ALA only. No significantly enhanced toxicity was found with red light and the 5-ALA plus hypericin combination. In addition, cells treated with both 5-ALA and hypericin tended to produce more PpIX than cells treated with 5-ALA only. This study demonstrated that treatment of endometrial cancer cells with both 5-ALA and hypericin followed by illumination with white light induced a significantly higher phototoxicity as revealed by colony formation. This setting which generated an in vitro effect similar to the patient's situation, might be applied in the future as an affordable and effective photodynamic therapy (PDT) modality.


Functional and morphological differences of the lung upon acute and chronic ozone exposure in mice.
Environmental air pollutants including ozone cause severe lung injury and aggravate respiratory diseases such as asthma and COPD. Here we compared the effect of ozone on respiratory epithelium injury, inflammation, hyperreactivity and airway remodeling in mice upon acute (1ppm, 1 h) and chronic exposure (1.5ppm, 2 h, twice weekly for 6 weeks). Acute ozone exposure caused respiratory epithelial disruption with protein leak and neutrophil recruitment in the broncho-alveolar space, leading to lung inflammation and airway hyperresponsiveness (AHR) to methacholine. All these parameters were increased upon chronic ozone exposure, including collagen deposition. The structure of the airways as assessed by automatic numerical image analysis showed significant differences: While acute ozone exposure increased bronchial and lumen circularity but decreased epithelial thickness and area, chronic ozone exposure revealed epithelial injury with reduced height, distended bronchioles, enlarged alveolar space and increased collagen deposition, indicative of peribronchiolar fibrosis and emphysema as characterized by a significant increase in the density and diameter of airspaces with decreased airspace numbers. In conclusion, morphometric numerical analysis enables an automatic and unbiased assessment of small airway remodeling. The structural changes of the small airways correlated with functional changes allowing to follow the progression from acute to chronic ozone induced respiratory pathology.


Estimation of an overall standardized mean difference in random-effects meta-analysis if the distribution of random effects departs from normal.
The random-effects model, applied in most meta-analyses nowadays, typically assumes normality of the distribution of the effect parameters. The purpose of this study was to examine the performance of various random-effects methods (standard method, Hartung's method, profile likelihood method, and bootstrapping) for computing an average effect size estimate and a confidence interval (CI) around it, when the normality assumption is not met. For comparison purposes, we also included the fixed-effect model. We manipulated a wide range of conditions, including conditions with some degree of departure from the normality assumption, using Monte Carlo simulation. To simulate realistic scenarios, we chose the manipulated conditions from a systematic review of meta-analyses on the effectiveness of psychological treatments. We compared the performance of the different methods in terms of bias and mean squared error of the average effect estimators, empirical coverage probability and width of the CIs, and variability of the standard errors. Our results suggest that random-effects methods are largely robust to departures from normality, with Hartung's profile likelihood methods yielding the best performance under suboptimal conditions.


Perceived Efficacy of Medical Cannabis in the Treatment of Co-Occurring Health-Related Quality of Life Symptoms.
For persons living with chronic conditions, health-related quality of life (HRQoL) symptoms, such as pain, anxiety, depression, and insomnia, often interact and mutually reinforce one another. There is evidence that medical cannabis (MC) may be efficacious in ameliorating such symptoms and improving HRQoL. As many of these HRQoL symptoms may mutually reinforce one another, we conducted an exploratory study to investigate how MC users perceive the efficacy of MC in addressing co-occurring HRQoL symptoms. We conducted a cross-sectional online survey of persons with a state medical marijuana card in Illinois (N = 367) recruited from licensed MC dispensaries across the state. We conducted tests of ANOVA to measure how perceived MC efficacy for each HRQoL symptom varied by total number of treated symptoms reported by participants. Pain was the most frequently reported HRQoL treated by MC, followed by anxiety, insomnia, and depression. A large majority of our sample (75%) reported treating two or more HRQoL symptoms. In general, perceived efficacy of MC in relieving each HRQoL symptom category increased with the number of co-occurring symptoms also treated with MC. Perceived efficacy of MC in relieving pain, anxiety, and depression varied significantly by number of total symptoms experienced. This exploratory study contributes to our understanding of how persons living with chronic conditions perceive the efficacy of MC in treating co-occurring HRQoL symptoms. Our results suggest that co-occurring pain, anxiety, and depression may be particularly amenable to treatment with MC.


Coupling plowing of cartilage explants with gene expression in models for synovial joints.
Articular cartilage undergoes complex loading modalities generally including sliding, rolling and plowing (i.e. the compression by a condyle normally to the tissue surface under simultaneously tangential displacement, thus generating a tractional force due to tissue deformation). Although in in vivo studies it was shown that excessive plowing can lead to osteoarthritis, little quantitative experimental work on this loading modality and its mechanobiological effects is available in the literature. Therefore, a rolling/plowing explant test system has been developed to study the effect on pristine cartilage of plowing at different perpendicular forces. Cartilage strips harvested from bovine nasal septa of 12-months-old calves were subjected for 2h to a plowing-regime with indenter normal force of 50 or 100 N and a sliding speed of 10 mm s(-1). 50 N produced a tractional force of 1.2±0.3N, whereas 100 N generated a tractional force of 8.0±1.4N. Furthermore, quantitative-real-time polymerase chain reaction experiments showed that TIMP-1 was 2.5x up-regulated after 50 N plowing and 2x after 100 N plowing, indicating an ongoing remodeling process. The expression of collagen type-I was not affected after 50 N plowing but it was up-regulated (6.6x) after 100 N plowing, suggesting a possible progression to an injury stage of the cartilage, as previously reported in cartilage of osteoarthritic patients. We conclude that plowing as performed by our mimetic system at the chosen experimental parameters induces changes in gene expression depending on the tractional force, which, in turn, relates to the applied normal force.


Performance of Passive Samplers Analyzed by Computer-Controlled Scanning Electron Microscopy to Measure PM10-2.5.
We report on the precision and accuracy of measuring PM10-2.5 and its components with particles collected by passive aerosol samplers and analyzed by computer-controlled scanning electron microscopy with energy dispersive X-ray spectroscopy. Passive samplers were deployed for week-long intervals in triplicate and colocated with a federal reference method sampler at three sites and for 5 weeks in summer 2009 and 5 weeks in winter 2010 in Cleveland, OH. The limit of detection of the passive method for PM10-2.5 determined from blank analysis was 2.8 μg m(-3). Overall precision expressed as root-mean-square coefficient of variation (CVRMS) improved with increasing concentrations (37% for all samples, n = 30; 19% for PM10-2.5 > 10 μg m(-3), n = 9; and 10% for PM10-2.5 > 15 μg m(-3), n = 4). The linear regression of PM10-2.5 measured passively on that measured with the reference sampler exhibited an intercept not statistically different than zero (p = 0.46) and a slope not statistically different from unity (p = 0.92). Triplicates with high CVs (CV > 40%, n = 5) were attributed to low particle counts (and mass concentrations), spurious counts attributed to salt particles, and Al-rich particles. This work provides important quantitative observations that can help guide future development and use of passive samplers for measuring atmospheric particulate matter.


Major pelvic fractures.
Pelvic fractures associated with blunt trauma contributed significantly to morbidity and mortality in 593 patients with high-velocity deceleration injuries. Those with open, hemorrhagic pelvic fractures required massive blood volume replacement and intensive care for long periods of time and had a 60% mortality. Patients with hemorrhagic pelvic fractures also had a notable blood replacement requirement (mean, 29 units) and a 50% mortality. Patients with open pelvic fractures without significant hemorrhage had a 25% mortality and were at an increased risk of pelvic sepsis. The overall mortality associated with pelvic fractures following high-velocity deceleration accidents was 16.6%. The identifiable causes of death in patients with pelvic fractures were associated injuries, particularly closed head injury, hemorrhage from pelvic vessels, and sepsis. An improved survival rate requires better, more prompt use of available treatment, as well as development of new and better methods of caring for severely injured patients with blunt trauma.


Prospective Assessment of Tumour Burden and Bone Disease in Plasma Cell Dyscrasias Using DW-MRI and Exploratory Bone Biomarkers.
Novel biomarkers for tumour burden and bone disease are required to guide clinical management of plasma cell dyscrasias. Recently, bone turnover markers (BTMs) and Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) have been explored, although their role in the prospective assessment of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) is unclear. Here, we conducted a pilot observational cohort feasibility study combining serum BTMs and DW-MRI in addition to standard clinical assessment. Fifty-five patients were recruited (14 MGUS, 15 smouldering MM, 14 new MM and 12 relapsed MM) and had DW-MRI and serum biomarkers (P1NP, CTX-1, ALP, DKK1, sclerostin, RANKL:OPG and BCMA) measured at baseline and 6-month follow-up. Serum sclerostin positively correlated with bone mineral density (r = 0.40-0.54). At baseline, serum BCMA correlated with serum paraprotein (r = 0.42) and serum DKK1 correlated with serum free light chains (r = 0.67); the longitudinal change in both biomarkers differed between International Myeloma Working Group (IMWG)-defined responders and non-responders. Myeloma Response Assessment and Diagnosis System (MY-RADS) scoring of serial DW-MRI correlated with conventional IMWG response criteria for measuring longitudinal changes in tumour burden. Overall, our pilot study suggests candidate radiological and serum biomarkers of tumour burden and bone loss in MM/MGUS, which warrant further exploration in larger cohorts to validate the findings and to better understand their clinical utility.


Gamma-distorted fringe image modeling and accurate gamma correction for fast phase measuring profilometry.
In fast phase-measuring profilometry, phase error caused by gamma distortion is the dominant error source. Previous phase-error compensation or gamma correction methods require the projector to be focused for best performance. However, in practice, as digital projectors are built with large apertures, they cannot project ideal focused fringe images. In this Letter, a thorough theoretical model of the gamma-distorted fringe image is derived from an optical perspective, and a highly accurate and easy to implement gamma correction method is presented to reduce the obstinate phase error. With the proposed method, high measuring accuracy can be achieved with the conventional three-step phase-shifting algorithm. The validity of the technique is verified by experiments.


Environmental malignant mesothelioma in southern Anatolia: a study of fifty cases.
Malignant mesothelioma is a highly aggressive tumor of the serous membranes, which in humans results from exposure to asbestos and asbestiform fibers. Although occupational malignant mesothelioma is still the most common form of this lesion, naturally contaminated soil can play an important role in the development of environmental malignant mesothelioma in some parts of the world. Fifty cases of malignant mesothelioma (MM) from southern Turkey with no occupational history of asbestos exposure were reviewed regarding pathologic and clinical features. A case of hyaline fibrous plaque of the pleura was also included in this series. Histologically the cases were classified as epithelial (36 cases); sarcomatous (7 cases); and biphasic (7 cases). One of the sarcomatous cases was desmoplastic. Ultrastructural examination of the tumor tissue in three cases revealed long-surface microvilli in epithelial cells. Interstitial cells of the lung in one case showed electron-dense asbestos fibers in the cytoplasm. Mineralogical analyses of the lung tissue in three cases of MM and the case of pleural plaque showed high amounts of asbestos fibers most consistent with tremolite and actinolite. The clinical and pathologic features of our cases support that the environmental inhalation of asbestos is still a major health problem in some parts of Turkey.


CD4+ T cell responses to the Plasmodium falciparum erythrocyte membrane protein 1 in children with mild malaria.
The immune response against the variant surface Ag Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a key component of clinical immunity against malaria. We have investigated the development and maintenance of CD4(+) T cell responses to a small semiconserved area of the Duffy binding-like domain (DBL)α-domain of PfEMP1, the DBLα-tag. Young children were followed up longitudinally, and parasites and PBMCs were isolated from 35 patients presenting with an acute case of uncomplicated malaria. The DBLα-tag from the PfEMP1 dominantly expressed by the homologous parasite isolate was cloned and expressed as recombinant protein. The recombinant DBLα-tag was used to activate PBMCs collected from each acute episode and from an annual cross-sectional survey performed after the acute malaria episode. In this article, we report that CD4(+) T cell responses to the homologous DBLα-tag were induced in 75% of the children at the time of the acute episode and in 62% of the children at the following cross-sectional survey on average 235 d later. Furthermore, children who had induced DBLα-tag-specific CD4(+)IL-4(+) T cells at the acute episode remained episode free for longer than children who induced other types of CD4(+) T cell responses. These results suggest that a wide range of DBLα-tag-specific CD4(+) T cell responses were induced in children with mild malaria and, in the case of CD4(+)IL-4(+) T cell responses, were associated with protection from clinical episodes.


Temporopolar amygdalohippocampectomy: seizure control and postoperative outcomes.
The objective of this study was to evaluate the efficacy and safety of a modified surgical approach for the treatment of temporal lobe epilepsy secondary to hippocampal sclerosis (HS). This modified approach, called temporopolar amygdalohippocampectomy (TP-AH), includes a transsylvian resection of the temporal pole and subsequent amygdalohippocampectomy utilizing the limen insula as an anatomical landmark. A total of 61 patients who were diagnosed with HS and underwent TP-AH between 2013 and 2017 were enrolled. Patients performed pre- and postoperative diffusion tensor imaging and were classified according to Engel's scale for seizure control. To evaluate the functional preservation of the temporal stem white-matter fiber tracts, the authors analyzed postoperative Humphrey perimetries and pre- and postoperative neurocognitive performance (Rey Auditory Verbal Learning Test [RAVLT], Weschler Memory Scale-Revised [WMS-R], intelligence quotient [IQ], Boston Naming Test [BNT], and semantic and phonemic fluency). Demographic data and surgical complications were also recorded and described. After a median follow-up of 36 ± 16 months, 46 patients (75.4%) achieved Engel class I, of whom 37 (60.6%) were Engel class IA. No significant changes in either the inferior frontooccipital fasciculus and optic radiation tractography were observed postoperatively for both left- and right-side surgeries. Reliable perimetry was obtained in 40 patients (65.6%), of whom 27 (67.5%) did not present any visual field defects (VFDs) attributable to surgery, while 12 patients (30%) presented with quadrant VFD, and 1 patient (2.5%) presented with hemifield VFD. Despite a significant decline in verbal memory (p = 0.007 for WMS-R, p = 0.02 for RAVLT recognition), there were significant improvements in both IQ (p < 0.001) and visual memory (p = 0.007). Semantic and phonemic fluency, and scores on the BNT, did not change postoperatively. TP-AH provided seizure control similar to historical temporal lobe approaches, with a tendency to preserve the temporal stem and a satisfactory incidence of VFD. Despite a significant decline in verbal memory, there were significant improvements in both IQ and visual memory, along with preservation of executive function. This approach can be considered a natural evolution of the selective transsylvian approach.


Requirement of poly(rC) binding protein 2 for translation of poliovirus RNA.
Poly(rC) binding protein 2 (PCBP2) is one of several cellular proteins that interact specifically with a major stem-loop domain in the poliovirus internal ribosome entry site. HeLa cell extracts subjected to stem-loop IV RNA affinity chromatography were depleted of all detectable PCBP2. Such extracts were unable to efficiently translate poliovirus RNA, although extracts recovered from control columns of matrix unlinked to RNA retained full translation activity. Both translation and production of infectious progeny virus were restored in the PCBP2-depleted extracts by addition of recombinant PCBP2, but not by PCBP1, which is a closely related member of the protein family. The data show that PCBP2 is an essential factor, which is required for efficient translation of poliovirus RNA in HeLa cells.


Fear of Falling Is Associated with Recurrent Falls in People with Multiple Sclerosis: A Longitudinal Cohort Study.
People with multiple sclerosis (MS) fall frequently, and there are few clinically valid tools to measure the risk factors for falls. We assessed the unidimensionality of the 7-item Falls Efficacy Scale-International (FES-I), a measure of fear of falling, and determined whether the 7-item FES-I is associated with recurrent falls in people with MS. Falls were counted prospectively for 6 months using fall calendars in 58 people with MS (age, 18-50 years; Expanded Disability Status Scale score, 0-6). The FES-I was administered at baseline, and its unidimensionality was assessed by confirmatory factor analysis. The relationship between FES-I score and future falls, after adjusting for recurrent falls in the past year, was assessed by logistic regression. Fifty-four participants who completed all assessments were included in the analysis. Goodness-of-fit indices confirmed a single-factor solution for the 7-item FES-I (discrepancy χ(2), P = .101; Tucker-Lewis index, 0.953; comparative fit index, 0.969; root mean square error of approximation, 0.098). There was a significant association between fear of falling and falls in the following 3 months, independent of recurrent falls in the past year (odds ratio = 1.22, 95% confidence interval, 1.04-1.43, P = .016). The 7-item FES-I demonstrates good construct validity, allowing the total score to be used as a measure of fear of falling in people with MS. Fear of falling, as measured by the 7-item FES-I, is associated with future recurrent falls independent of past recurrent falls in people with MS.


The future of preclinical animal models in pharmaceutical discovery and development: a need to bring in cerebro to the in vivo discussions.
Animal models have provided an important tool to help make the decision to take potential therapies from preclinical studies to humans. In the past several years, the strong reliance of the pharmaceutical discovery and development process on the use of animal models has come under increasing scrutiny for ethical and scientific reasons. Several prominent and widely publicized articles have reported limited concordance of animal experiments with subsequent human clinical trials. Recent assessments of the quality of animal studies have suggested that this translational failure may be due in part to shortcomings in the planning, conduct, and reporting of in vivo studies. This article will emphasize methods to assure best practice rigor in animal study methods and reporting. It will introduce the so-called scientific 3Rs of relevance, robustness, and reproducibility to the in vivo study approach and will review important new trends in the animal research and pharmaceutical discovery and development communities.


Effect of modest caloric restriction on oxidative stress in women, a randomized trial.
It is not established to what extent caloric intake must be reduced to lower oxidative stress in humans. The aim of this study was to determine the effect of short-term, moderate caloric restriction on markers of oxidative stress and inflammation in overweight and obese premenopausal women. Randomized trial comparison of 25% caloric restriction (CR) or control diet in 40 overweight or obese women (body mass index 32±5.8 kg/m(2)) observed for 28 days and followed for the next 90 days. Weight, anthropometry, validated markers of oxidative stress (F(2)-isoprostane) and inflammation (C-reactive protein), adipokines, hormones, lipids, interleukins, and blood pressure were assessed at baseline, during the intervention, and at follow-up. Baseline median F(2)-isoprostane concentration (57.0, IQR = 40.5-79.5) in the CR group was 1.75-fold above average range for normal weight women (32.5 pg/ml). After starting of the caloric restriction diet, F(2)-isoprostane levels fell rapidly in the CR group, reaching statistical difference from the control group by day 5 (median 33.5, IQR = 26.0-48.0, P<0.001) and remained suppressed while continuing on the caloric restriction diet. Three months after resuming a habitual diet, concentrations of F(2)-isoprostane returned to baseline elevated levels in ∼80% of the women. Oxidative stress can be rapidly reduced and sustained through a modest reduction in caloric intake suggesting potential health benefits in overweight and obese women. Clinicaltrials.gov NCT00808275.


Developing Smokeless Tobacco Prevention Messaging for At-Risk Youth: Early Lessons from "The Real Cost" Smokeless Campaign.
Introduction: Smokeless tobacco (SLT) use continues to be a significant public health challenge in the United States, particularly among young males in rural areas, where use remains disproportionately high. In support of the U.S. Food and Drug Administration's first nationwide SLT public education campaign, formative research was conducted to inform campaign strategy development and test creative concepts. Methods: Qualitative research methods were used to inform the strategic direction of the campaign, identify salient message themes, and refine creative concepts. Focus groups were conducted with 252 rural male youth ages 12-17 in seven states. Groups were organized by SLT status (i.e., at-risk for initiating vs. experimenting with SLT) and age group. Results: SLT use is culturally ingrained in rural communities, and rural youth are commonly exposed to SLT through close relationships. Among this group, "dipping" (SLT use) has strong cultural significance and is perceived as safe. Members of the target audience are receptive to straightforward facts delivered by authentic messengers about the potentially harmful consequences of SLT use, specifically those that leverage the progression of short-term consequences (e.g., white patches) to long-term health effects. Conclusions: This study addresses SLT literature gaps related to youth knowledge, attitudes, and beliefs by summarizing audience learnings from formative research that was used to develop the first national SLT public education campaign.


Morphometric Analysis of Thyroid Follicular Cells with Atypia of Undetermined Significance.
Atypia of undetermined significance (AUS) is a category that encompasses a heterogeneous group of thyroid aspiration cytology. It has been reclassified into two subgroups based on the cytomorphologic features: AUS with cytologic atypia and AUS with architectural atypia. The nuclear characteristics of AUS with cytologic atypia need to be clarified by comparing to those observed in Hashimoto thyroiditis and benign follicular lesions. We selected 84 cases of AUS with histologic follow-up, 24 cases of Hashimoto thyroiditis, and 26 cases of benign follicular lesions. We also subcategorized the AUS group according to the follow-up biopsy results into a papillary carcinoma group and a nodular hyperplasia group. The differences in morphometric parameters, including the nuclear areas and perimeters, were compared between these groups. The AUS group had significantly smaller nuclear areas than the Hashimoto thyroiditis group, but the nuclear perimeters were not statistically different. The AUS group also had significantly smaller nuclear areas than the benign follicular lesion group; however, the AUS group had significantly longer nuclear perimeters. The nuclear areas in the papillary carcinoma group were significantly smaller than those in the nodular hyperplasia group; however, the nuclear perimeters were not statistically different. We found the AUS group to be a heterogeneous entity, including histologic follow-up diagnoses of papillary carcinoma and nodular hyperplasia. The AUS group showed significantly greater nuclear irregularities than the other two groups. Utilizing these features, nuclear morphometry could lead to improvements in the accuracy of the subjective diagnoses made with thyroid aspiration cytology.


WITHDRAWN: Occlusal interventions for periodontitis in adults.
Occlusal interventions may be used in adults with periodontitis. At present there is little consensus regarding the indications and effectiveness of occlusal interventions in periodontal patients. To identify and analyse the evidence for the effect of occlusal interventions on adults who have periodontitis in relation to tooth loss, probing depths, clinical attachment level, adverse effects and patient-centred outcomes. The search was last conducted in April 2008. We searched the Cochrane Oral Health Group's Trials Register (to 30th April 2008); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 1); MEDLINE (1966 to 30th April 2008); and EMBASE (1980 to 30th April 2008). There were no language restrictions. We included randomised controlled trials (RCTs) assessing occlusal interventions in patients with periodontitis with a follow up of at least 3 months. Screening of eligible studies, assessment of the methodological quality of the trials and data extraction were conducted in duplicate and independently by two review authors. Any disagreements between the review authors were resolved by discussion. The main investigator of the included trial was contacted to obtain missing information. The Cochrane Collaboration statistical guidelines were to be followed for data synthesis. Abstracts of 54 papers were identified by the search. One paper was eligible for inclusion. This paper studied the effect of occlusal adjustment against no occlusal adjustment in patients who were treated with non-surgical and surgical periodontal therapy. Methodological quality assessment of the included paper revealed that randomisation of the patients into the treatment groups was adequate. Allocation concealment, masking of patients and clinicians were not reported and no response to author contact was received.Mean change in attachment level and mean pocket depth were reported in the included trial. Mean difference in clinical attachment level between occlusal intervention and control in the non-surgical group amounted to 0.38 mm (95% confidence interval (CI) 0.04 to 0.72) favouring the occlusal intervention group and was statistically significant. In the surgical group the mean difference in clinical attachment level between occlusal intervention and control amounted to 0.40 mm (95% CI 0.05 to 0.75) favouring the occlusal intervention group and was also statistically significant. The difference in mean pocket depth reduction between the occlusal intervention and control in both the surgical and non-surgical groups was less than 0.1 mm and was not statistically significant. Tooth loss, patient-centred affects and adverse effects were not reported. Meta-analysis was not possible due to the inclusion of only one study. There is only one randomised trial that has addressed this question. The data from this study are inconclusive. We therefore conclude there is no evidence for or against the use of occlusal interventions in clinical practice. This question can only be addressed by adequately powered bias-protected randomised controlled trials.


Coadministration of entacapone with levodopa attenuates the severity of dyskinesias in hemiparkinsonian rats.
Levodopa-induced dyskinesias (LIDs) have been associated with a sequence of events that includes pulsatile stimulation of dopamine receptors. The degree of nigrostriatal degeneration, the half-life of dopaminomimetic agents, and the dose of levodopa used to treat parkinsonian symptoms are factors directly correlated with the development of motor complications in Parkinson's disease patients. Long-acting agents producing continuous dopaminergic stimulation are less likely to prime for dyskinesia than short-acting drugs that produce pulsatile stimulation of dopamine receptors. Inhibition of the enzyme catechol-O-methyl transferase (COMT) by entacapone extends the half-life of levodopa and minimizes variability in plasma levodopa levels. The aim of the present study was to characterize the effect of the early administration of the COMT inhibitor entacapone in the recently described model of LIDs in rats with a nigrostriatal lesion induced by 6-hydroxydopamine (6-OHDA). Male Sprague-Dawley rats received a unilateral 6-OHDA administration in the nigrostriatal pathway. Animals were treated either with levodopa (6 mg/kg, twice at day, i.p.) plus entacapone (30 mg/kg per day, i.p.) or levodopa (6 mg/kg, twice at day, i.p.) plus vehicle for 22 consecutive days. Early administration of entacapone, in association with levodopa, induces a decrease in the severity of dyskinesia and delays their onset in hemiparkinsonian rats. All dyskinesia subtypes evaluated, such as axial, limb, and orofacial dyskinesias, have shown similar reductions. These results suggest that entacapone, by extending levodopa elimination half-life, might reduce its propensity to induce motor complications.


IMI2-PainCare-BioPain-RCT3: a randomized, double-blind, placebo-controlled, crossover, multi-center trial in healthy subjects to investigate the effects of lacosamide, pregabalin, and tapentadol on biomarkers of pain processing observed by electroencephalography (EEG).
IMI2-PainCare-BioPain-RCT3 is one of four similarly designed clinical studies aiming at profiling a set of functional biomarkers of drug effects on the nociceptive system that could serve to accelerate the future development of analgesics, by providing a quantitative understanding between drug exposure and effects of the drug on nociceptive signal processing in human volunteers. IMI2-PainCare-BioPain-RCT3 will focus on biomarkers derived from non-invasive electroencephalographic (EEG) measures of brain activity. This is a multisite single-dose, double-blind, randomized, placebo-controlled, 4-period, 4-way crossover, pharmacodynamic (PD) and pharmacokinetic (PK) study in healthy subjects. Biomarkers derived from scalp EEG measurements (laser-evoked brain potentials [LEPs], pinprick-evoked brain potentials [PEPs], resting EEG) will be obtained before and three times after administration of three medications known to act on the nociceptive system (lacosamide, pregabalin, tapentadol) and placebo, given as a single oral dose in separate study periods. Medication effects will be assessed concurrently in a non-sensitized normal condition and a clinically relevant hyperalgesic condition (high-frequency electrical stimulation of the skin). Patient-reported outcomes will also be collected. A sequentially rejective multiple testing approach will be used with overall alpha error of the primary analysis split between LEP and PEP under tapentadol. Remaining treatment arm effects on LEP or PEP or effects on EEG are key secondary confirmatory analyses. Complex statistical analyses and PK-PD modeling are exploratory. LEPs and PEPs are brain responses related to the selective activation of thermonociceptors and mechanonociceptors. Their amplitudes are dependent on the responsiveness of these nociceptors and the state of the pathways relaying nociceptive input at the level of the spinal cord and brain. The magnitude of resting EEG oscillations is sensitive to changes in brain network function, and some modulations of oscillation magnitude can relate to perceived pain intensity, variations in vigilance, and attentional states. These oscillations can also be affected by analgesic drugs acting on the central nervous system. For these reasons, IMI2-PainCare-BioPain-RCT3 hypothesizes that EEG-derived measures can serve as biomarkers of target engagement of analgesic drugs for future Phase 1 clinical trials. Phase 2 and 3 clinical trials could also benefit from these tools for patient stratification. This trial was registered 25/06/2019 in EudraCT ( 2019%2D%2D001204-37 ).


Beta-hairpin folding simulations in atomistic detail using an implicit solvent model.
We have used distributed computing techniques and a supercluster of thousands of computer processors to study folding of the C-terminal beta-hairpin from protein G in atomistic detail using the GB/SA implicit solvent model at 300 K. We have simulated a total of nearly 38 micros of folding time and obtained eight complete and independent folding trajectories. Starting from an extended state, we observe relaxation to an unfolded state characterized by non-specific, temporary hydrogen bonding. This is followed by the appearance of interactions between hydrophobic residues that stabilize a bent intermediate. Final formation of the complete hydrophobic core occurs cooperatively at the same time that the final hydrogen bonding pattern appears. The folded hairpin structures we observe all contain a closely packed hydrophobic core and proper beta-sheet backbone dihedral angles, but they differ in backbone hydrogen bonding pattern. We show that this is consistent with the existing experimental data on the hairpin alone in solution. Our analysis also reveals short-lived semi-helical intermediates which define a thermodynamic trap. Our results are consistent with a three-state mechanism with a single rate-limiting step in which a varying final hydrogen bond pattern is apparent, and semi-helical off-pathway intermediates may appear early in the folding process. We include details of the ensemble dynamics methodology and a discussion of our achievements using this new computational device for studying dynamics at the atomic level.


Clinicopathologic Characterization of GREB1-rearranged Uterine Sarcomas With Variable Sex-Cord Differentiation.
Uterine mesenchymal tumors are genetically heterogenous; those with uniform cytomorphology, best exemplified by endometrial stromal tumors, often contain various fusion genes. Novel fusions involving ESR1 and GREB1, key factors in sex hormone pathways, have been implicated in rare uterine mesenchymal tumors. Particularly, the fusions between 5'-ESR1/GREB1 and 3'-NCOA2/NCOA3 were recently identified in 4 uterine tumors resembling ovarian sex-cord tumor (UTROSCT). By RNA sequencing, pathology review, and FISH screening, we identified 4 uterine sarcomas harboring rearranged GREB1, including GREB1-NCOA2 and the novel GREB1-NR4A3, GREB1-SS18, and GREB1-NCOA1, validated by RT-PCR and/or FISH. They occurred in the myometrium of postmenopausal women and were pathologically similar despite minor differences. Tumor cells were generally uniform and epithelioid, with vesicular nuclei and distinct to prominent nucleoli. Growth patterns included solid sheets, trabeculae/cords, nests, and fascicles. Only 1 tumor showed small foci of definitive sex-cord components featuring well-formed tubules, retiform structures, Leydig-like cells, and lipid-laden cells and exhibiting convincing immunoreactivity to sex-cord markers (calretinin, α-inhibin, and Melan-A). In contrast, all the 4 classic UTROSCT we collected occurred in premenopausal patients, consisted predominantly of unequivocal sex-cord elements, prominently expressed multiple sex-cord markers, and harbored ESR1-NCOA3 fusion. Combined with previously reported cases, GREB1-rearranged tumors involved significantly older women (P=0.001), tended to be larger and more mitotically active, showed more variable and often inconspicuous sex-cord differentiation, and appeared to behave more aggressively than ESR1-rearranged UTROSCT. Therefore, these 2 groups of tumors might deserve separate consideration, despite some overlapping features and the possibility of belonging to the same disease spectrum.


Prevalence and persistence of Escherichia coli strains with uropathogenic virulence characteristics in sewage treatment plants.
We investigated the prevalence and persistence of Escherichia coli strains in four sewage treatment plants (STPs) in a subtropical region of Queensland, Australia. In all, 264 E. coli strains were typed using a high-resolution biochemical fingerprinting method and grouped into either a single or a common biochemical phenotype (S-BPT and C-BPT, respectively). These strains were also tested for their phylogenetic groups and 12 virulence genes associated with intestinal and extraintestinal E. coli strains. Comparison of BPTs at various treatment stages indicated that certain BPTs were found in two or all treatment stages. These BPTs constituted the highest proportion of E. coli strains in each STP and belonged mainly to phylogenetic group B2 and, to a lesser extent, group D. No virulence genes associated with intestinal E. coli were found among the strains, but 157 (59.5%) strains belonging to 14 C-BPTs carried one or more virulence genes associated with uropathogenic strains. Of these, 120 (76.4%) strains belonged to seven persistent C-BPTs and were found in all four STPs. Our results indicate that certain clonal groups of E. coli with virulence characteristics of uropathogenic strains can survive the treatment processes of STPs. These strains were common to all STPs and constituted the highest proportion of the strains in different treatment tanks of each STP.


Cortical representation of bimanual movements.
It is well established that the discharge of neurons in primate motor cortex is tuned to the movement direction of the contralateral arm. Interestingly, it has been found that these neurons exhibit a directional tuning to the ipsilateral arm as well and that the preferred directions to both arms tend to be similar. A recent study showed that motor cortex cells are also directionally selective to bimanual movements, but the relationship between the bimanual and unimanual representations remains unclear. To address this issue, we analyzed the responses of motor cortical neurons recorded from two macaque monkeys during unimanual and bimanual reaching movements. We decomposed the bimanual movement representation into contralateral and ipsilateral directionally tuned components. Our major finding is that the movement of the contralateral arm modifies the tuning of the cells to the ipsilateral arm such that: (1) the offset and modulation depth of the tuning are suppressed; and (2) the preferred directions are randomly shifted. Both these effects eliminate the correlation between the contralateral and ipsilateral representations during bimanual movements. We suggest that the modification of the ipsilateral arm representation is caused by the recruitment of local inhibition that conveys callosal inputs during bimanual movements. This hypothesis is supported by the analysis of a model of two motor cortical networks, coupled with sparse random interhemispheric projections that reproduce the main features observed in the data. Finally, we show that the modification of the ipsilateral arm representation reduces the interference between the movements of both arms.


Nitrogenase gene amplicons from global marine surface waters are dominated by genes of non-cyanobacteria.
Cyanobacteria are thought to be the main N(2)-fixing organisms (diazotrophs) in marine pelagic waters, but recent molecular analyses indicate that non-cyanobacterial diazotrophs are also present and active. Existing data are, however, restricted geographically and by limited sequencing depths. Our analysis of 79,090 nitrogenase (nifH) PCR amplicons encoding 7,468 unique proteins from surface samples (ten DNA samples and two RNA samples) collected at ten marine locations world-wide provides the first in-depth survey of a functional bacterial gene and yield insights into the composition and diversity of the nifH gene pool in marine waters. Great divergence in nifH composition was observed between sites. Cyanobacteria-like genes were most frequent among amplicons from the warmest waters, but overall the data set was dominated by nifH sequences most closely related to non-cyanobacteria. Clusters related to Alpha-, Beta-, Gamma-, and Delta-Proteobacteria were most common and showed distinct geographic distributions. Sequences related to anaerobic bacteria (nifH Cluster III) were generally rare, but preponderant in cold waters, especially in the Arctic. Although the two transcript samples were dominated by unicellular cyanobacteria, 42% of the identified non-cyanobacterial nifH clusters from the corresponding DNA samples were also detected in cDNA. The study indicates that non-cyanobacteria account for a substantial part of the nifH gene pool in marine surface waters and that these genes are at least occasionally expressed. The contribution of non-cyanobacterial diazotrophs to the global N(2) fixation budget cannot be inferred from sequence data alone, but the prevalence of non-cyanobacterial nifH genes and transcripts suggest that these bacteria are ecologically significant.


Anti-anxiety activity studies of various extracts of Turnera aphrodisiaca Ward.
Turnera aphrodisiaca Ward (Turneraceae) has been used traditionally for treatment of anxiety neurosis and as an aphrodisiac. Yet, the plant has never been subjected to systematic biological investigation. In the present investigation, petroleum ether (60-80 degrees C), chloroform, methanol, and water extracts of T. aphrodisiaca aerial parts were evaluated for anti-anxiety activity in mice using elevated plus-maze apparatus. Among all the extracts, only methanol exhibited significant anti-anxiety activity at a dose of 25 mg/kg with respect to control as well as standard (diazepam, 2 mg/kg). The bioactive methanol extract was shaken with petroleum ether, chloroform, and n-butyl alcohol, and all the shakings as well as the remaining methanol extract (RME) were further evaluated for anxiolytic activity. Butanol fraction and RME were found to exhibit anxiolytic activity in mice at the dose of 10 mg/kg and 75 mg/kg, respectively.


Perioperative antibiotic prophylaxis in patients undergoing radical surgery for gynecologic cancer: single dose versus multiple dose administration.
A prospective, randomized study comparing single dose intravenous antibiotic prophylaxis with multiple-dose regimen in patients undergoing radical surgery for gynecologic malignancy was carried out. The majority of patients had cervical cancer. Thirty-seven patients in group A received one dose of 4 g piperacillin and 800 mg tinidazole 30 minutes before surgery. Twenty-nine patients in group B additionally received 4g piperacillin 8 hours and 4g piperacillin and 800 mg tinidazole 16 hours after the first dose. There were no significant differences between groups A and B with regard to median patient age, performance status, cardiologic and pulmonary status, or frequency of diabetes. There were also no significant differences between either group with regard to the parameters documented postoperatively, such as median hospital stay, leukocyte values, or febrile episodes. Forty-three per cent of patients in group A and 48% of patients in group B had no complications (p > 0.05). Twenty-three per cent of patients in group A and 31% of patients in group B developed infections (p > 0.05), 85% of which occurred in the urinary tract. The data suggest that a single dose of intravenous antibiotics is as effective as multiple dose administration in the perioperative prophylaxis in radical gynecologic surgery.


Fewer invited talks by women in evolutionary biology symposia.
Lower visibility of female scientists, compared to male scientists, is a potential reason for the under-representation of women among senior academic ranks. Visibility in the scientific community stems partly from presenting research as an invited speaker at organized meetings. We analysed the sex ratio of presenters at the European Society for Evolutionary Biology (ESEB) Congress 2011, where all abstract submissions were accepted for presentation. Women were under-represented among invited speakers at symposia (15% women) compared to all presenters (46%), regular oral presenters (41%) and plenary speakers (25%). At the ESEB congresses in 2001-2011, 9-23% of invited speakers were women. This under-representation of women is partly attributable to a larger proportion of women, than men, declining invitations: in 2011, 50% of women declined an invitation to speak compared to 26% of men. We expect invited speakers to be scientists from top ranked institutions or authors of recent papers in high-impact journals. Considering all invited speakers (including declined invitations), 23% were women. This was lower than the baseline sex ratios of early-mid career stage scientists, but was similar to senior scientists and authors that have published in high-impact journals. High-quality science by women therefore has low exposure at international meetings, which will constrain Evolutionary Biology from reaching its full potential. We wish to highlight the wider implications of turning down invitations to speak, and encourage conference organizers to implement steps to increase acceptance rates of invited talks.


Course and variation of the intercostal artery by CT scan.
It is conventionally taught that the intercostal artery is shielded in the intercostal groove of the superior rib. The continuous course and variability of the intercostal artery, and factors that may influence them, have not been described in a large number of arteries in vivo. Maximal intensity projection reformats in the coronal plane were produced from CT scan pulmonary angiograms to identify the posterolateral course of the intercostal artery (seventh to 11th rib spaces). A novel semiautomated computer segmentation algorithm was used to measure distances between the lower border of the superior rib, the upper border of the inferior rib, and the position of the intercostal artery when exposed in the intercostal space. The position and variability of the artery were analyzed for association with clinical factors. Two hundred ninety-eight arteries from 47 patients were analyzed. The mean lateral distance from the spine over which the artery was exposed within the intercostal space was 39 mm, with wide variability (SD, 10 mm; 10th-90th centile, 28-51 mm). At 3 cm lateral distance from the spine, 17% of arteries were shielded by the superior rib, compared with 97% at 6 cm. Exposed artery length was not associated with age, sex, rib space, or side. The variability of arterial position was significantly associated with age (coefficient, 0.91; P < .001) and rib space number (coefficient, - 2.60; P < .001). The intercostal artery is exposed within the intercostal space in the first 6 cm lateral to the spine. The variability of its vertical position is greater in older patients and in more cephalad rib spaces.


Social networks predict patch discovery in a wild population of songbirds.
Animals use social information in a wide variety of contexts. Its extensive use by individuals to locate food patches has been documented in a number of species, and various mechanisms of discovery have been identified. However, less is known about whether individuals differ in their access to, and use of, social information to find food. We measured the social network of a wild population of three sympatric tit species (family Paridae) and then recorded individual discovery of novel food patches. By using recently developed methods for network-based diffusion analysis, we show that order of arrival at new food patches was predicted by social associations. Models based only on group searching did not explain this relationship. Furthermore, network position was correlated with likelihood of patch discovery, with central individuals more likely to locate and use novel foraging patches than those with limited social connections. These results demonstrate the utility of social network analysis as a method to investigate social information use, and suggest that the greater probability of receiving social information about new foraging patches confers a benefit on more socially connected individuals.


Stress effects on the neural substrates of motivated behavior.
Exposure to stress has profound, but complex, actions on motivated behavior and decision-making. These effects are central to core symptoms of a number of psychiatric disorders that are precipitated or augmented by stress, such as depressive disorders and substance use disorders. Studying the neural substrates of stress's effects on motivation has revealed that stress affects multiple targets on circuits throughout the brain using diverse molecular signaling processes. Moreover, stress does not have unitary effects on motivated behavior, but differences in the intensity, duration, intermittency, controllability and nature of the stressor produce qualitatively and quantitatively different behavioral endpoints. Unsurprisingly, the results of neuroscientific investigations into stress and motivation often open more questions than they resolve. Here we discuss contemporary results pertaining to the neural mechanisms by which stress alters motivation, identify points of contention and highlight integrative areas for continuing research into these multifaceted complexities.


Promoting HIV and sexual safety behaviour in people with severe mental illness: a systematic review of behavioural interventions.
People diagnosed with severe mental illness (SMI) are at greater risk of HIV than the general population. However, little attention has been given to how best to reduce sexual risk taking in this group. The aim of the review was to evaluate the effectiveness of behavioural interventions to promote sexual safety behaviour in people diagnosed with SMI. A comprehensive search of relevant databases was undertaken, and studies were included if they were randomized, controlled trials; behavioural intervention related to sexual behaviour; included adults diagnosed with SMI; and if a behavioural outcome was reported. The Cochrane Assessment of Bias Tool was used. Of the initial 515 papers identified, 11 trials were included for quality assessment and data extraction. The studies were heterogeneous in content and dose of intervention, as well as outcome measure and follow-up periods, and all had some risk of bias. Four of the studies demonstrated significant improvement in safer sexual behaviour at follow up, but this effect diminished over time. The effect sizes were extremely variable. There is emerging evidence to suggest that a behavioural intervention has the potential to reduce sexual risks in people diagnosed with SMI. However, further high-quality research is needed in this area.


Delineation of Campylobacter concisus genomospecies by amplified fragment length polymorphism analysis and correlation of results with clinical data.
Campylobacter concisus has been as frequently isolated from human diarrhea as the important enteropathogen Campylobacter jejuni, but it also occurs in the feces of healthy individuals. The role of C. concisus in human disease has been difficult to determine, since the species comprises at least two phenotypically indistinguishable but genetically distinct taxa (i.e., genomospecies) that may vary in pathogenicity. We examined 62 C. concisus strains by amplified fragment length polymorphism (AFLP) profiling and correlated the results with clinical data. All C. concisus strains gave unique AFLP profiles, and numerical analysis of these data distributed the strains among four clusters. The clustering was of taxonomic significance: two clusters contained, respectively, the type strain (of oral origin) and a reference strain (from diarrhea) of each of the known genomospecies. Genomospecies 2 strains were more frequently isolated from immunocompetent patients and/or patients without concomitant infections that presented with fever, chronic diarrhea, and gut inflammation than was genomospecies 1, clustering with the type strain of oral origin. Bloody diarrhea was recorded only with C. concisus genomospecies 2 infections. We identified two additional C. concisus genomospecies: genomospecies 3 comprised a single strain from an immunocompetent patient, and genomospecies 4 contained five isolates from severely immunodeficient patients, i.e., organ transplantation recipients or those with hematological malignancies. All genomospecies 4 strains were of the same protein profile group and failed to react with a C. concisus species-specific PCR assay based on 23S rRNA gene sequences: the taxonomic position of this group requires closer investigation. Campylobacter concisus is genetically and taxonomically diverse and contains at least four distinct genomospecies that may exhibit differences in their spectra of virulence potential.


The Interaction between Fluid Wall Shear Stress and Solid Circumferential Strain Affects Endothelial Gene Expression.
Endothelial cells lining the walls of blood vessels are exposed simultaneously to wall shear stress (WSS) and circumferential stress (CS) that can be characterized by the temporal phase angle between WSS and CS (stress phase angle - SPA). Regions of the circulation with highly asynchronous hemodynamics (SPA close to -180°) such as coronary arteries are associated with the development of pathological conditions such as atherosclerosis and intimal hyperplasia whereas more synchronous regions (SPA closer to 0°) are spared of disease. The present study evaluates endothelial cell gene expression of 42 atherosclerosis-related genes under asynchronous hemodynamics (SPA=-180 °) and synchronous hemodynamics (SPA=0 °). This study used a novel bioreactor to investigate the cellular response of bovine aortic endothelial cells (BAECS) exposed to a combination of pulsatile WSS and CS at SPA=0 or SPA=-180. Using a PCR array of 42 genes, we determined that BAECS exposed to non-reversing sinusoidal WSS (10±10 dyne/cm2) and CS (4 ± 4%) over a 7 hour testing period displayed 17 genes that were up regulated by SPA = -180 °, most of them pro-atherogenic, including NFκB and other NFκB target genes. The up regulation of NFκB p50/p105 and p65 by SPA =-180° was confirmed by Western blots and immunofluorescence staining demonstrating the nuclear translocation of NFκB p50/p105 and p65. These data suggest that asynchronous hemodynamics (SPA=-180 °) can elicit proatherogenic responses in endothelial cells compared to synchronous hemodynamics without shear stress reversal, indicating that SPA may be an important parameter characterizing arterial susceptibility to disease.


Effects of DNA polymerase inhibitory and antitumor activities of lipase-hydrolyzed glycolipid fractions from spinach.
We succeeded in purifying the major glycolipid fraction in the class of sulfoquinovosyl diacylglycerol, monogalactosyl diacylglycerol and digalactosyl diacylglycerol (DGDG) from a green vegetable, spinach (Spinacia oleracea L.). This glycolipid fraction was an inhibitor of DNA polymerases and a growth inhibitor of NUGC-3 human gastric cancer cells, and, interestingly, the activities were much stronger when the fraction was hydrolyzed by lipase. Glycolipids in the hydrolyzed fraction consisted of sulfoquinovosyl monoacylglycerol (SQMG), monogalactosyl monoacylglycerol (MGMG) and DGDG. In the in vivo antitumor assay using Greene's melanoma, the fraction containing SQMG, MGMG and DGDG showed to be a promising suppressor of solid tumors. Spinach glycolipid fraction might be a potent antitumor compound if directly injected into a tumor-carrying body, and this fraction may be a healthy food material that has antitumor activity.


Bayesian estimation of synaptic physiology from the spectral responses of neural masses.
We describe a Bayesian inference scheme for quantifying the active physiology of neuronal ensembles using local field recordings of synaptic potentials. This entails the inversion of a generative neural mass model of steady-state spectral activity. The inversion uses Expectation Maximization (EM) to furnish the posterior probability of key synaptic parameters and the marginal likelihood of the model itself. The neural mass model embeds prior knowledge pertaining to both the anatomical [synaptic] circuitry and plausible trajectories of neuronal dynamics. This model comprises a population of excitatory pyramidal cells, under local interneuron inhibition and driving excitation from layer IV stellate cells. Under quasi-stationary assumptions, the model can predict the spectral profile of local field potentials (LFP). This means model parameters can be optimised given real electrophysiological observations. The validity of inferences about synaptic parameters is demonstrated using simulated data and experimental recordings from the medial prefrontal cortex of control and isolation-reared Wistar rats. Specifically, we examined the maximum a posteriori estimates of parameters describing synaptic function in the two groups and tested predictions derived from concomitant microdialysis measures. The modelling of the LFP recordings revealed (i) a sensitization of post-synaptic excitatory responses, particularly marked in pyramidal cells, in the medial prefrontal cortex of socially isolated rats and (ii) increased neuronal adaptation. These inferences were consistent with predictions derived from experimental microdialysis measures of extracellular glutamate levels.