Epidemiology of undiagnosed trichomoniasis in a probability sample of urban young adults.
T. vaginalis infection (trichomoniasis) is the most common curable sexually transmitted infection (STI) in the U.S. It is associated with increased HIV risk and adverse pregnancy outcomes. Trichomoniasis surveillance data do not exist for either national or local populations. The Monitoring STIs Survey Program (MSSP) collected survey data and specimens which were tested using nucleic acid amplification tests to monitor trichomoniasis and other STIs in 2006-09 among a probability sample of young adults (N = 2,936) in Baltimore, Maryland--an urban area with high rates of reported STIs. The estimated prevalence of trichomoniasis was 7.5% (95% CI 6.3, 9.1) in the overall population and 16.1% (95% CI 13.0, 19.8) among Black women. The overwhelming majority of infected men (98.5%) and women (73.3%) were asymptomatic. Infections were more common in both women (OR = 3.6, 95% CI 1.6, 8.2) and men (OR = 9.0, 95% CI 1.8, 44.3) with concurrent chlamydial infection. Trichomoniasis did not vary significantly by age for either men or women. Women with two or more partners in the past year and women with a history of personal or partner incarceration were more likely to have an infection. Overall, these results suggest that routine T vaginalis screening in populations at elevated risk of infection should be considered.


Frailty in HIV: Epidemiology, Biology, Measurement, Interventions, and Research Needs.
Frailty is a critical aging-related syndrome marked by diminished physiologic reserve and heightened vulnerability to stressors, predisposing to major adverse clinical outcomes, including hospitalization, institutionalization, disability, and death in the general population of older adults. As the proportion of older adults living with HIV increases in the era of antiretroviral therapy, frailty is increasingly recognized to be of significant clinical and public health relevance to the HIV-infected population. This article reviews current knowledge on the epidemiology and biology of frailty and its potential role as a target for reducing disparities in outcomes in HIV; conceptual frameworks and current approaches to frailty measurement; existing data on frailty interventions; and important areas for future research focus necessary to develop and advance effective strategies to prevent or ameliorate frailty and its marked adverse consequences among people living with HIV.


Histogram of Gabor phase patterns (HGPP): a novel object representation approach for face recognition.
A novel object descriptor, histogram of Gabor phase pattern (HGPP), is proposed for robust face recognition. In HGPP, the quadrant-bit codes are first extracted from faces based on the Gabor transformation. Global Gabor phase pattern (GGPP) and local Gabor phase pattern (LGPP) are then proposed to encode the phase variations. GGPP captures the variations derived from the orientation changing of Gabor wavelet at a given scale (frequency), while LGPP encodes the local neighborhood variations by using a novel local XOR pattern (LXP) operator. They are both divided into the nonoverlapping rectangular regions, from which spatial histograms are extracted and concatenated into an extended histogram feature to represent the original image. Finally, the recognition is performed by using the nearest-neighbor classifier with histogram intersection as the similarity measurement. The features of HGPP lie in two aspects: 1) HGPP can describe the general face images robustly without the training procedure; 2) HGPP encodes the Gabor phase information, while most previous face recognition methods exploit the Gabor magnitude information. In addition, Fisher separation criterion is further used to improve the performance of HGPP by weighing the subregions of the image according to their discriminative powers. The proposed methods are successfully applied to face recognition, and the experiment results on the large-scale FERET and CAS-PEAL databases show that the proposed algorithms significantly outperform other well-known systems in terms of recognition rate.


Novel morphological features of developing white matter pericytes and rapid scavenging of reactive oxygen species in the neighbouring endothelia.
Capillary endothelia and pericytes form a close morphological arrangement allowing pericytes to regulate capillary blood flow, in addition to contributing to vascular development and support. Vascular changes associated with oxidative stress are implicated in important pathologies in developing whiter matter, but little is known about the vascular unit in white matter of the appropriate age or how it responds to oxidative stress. We show that the ultrastructural arrangement of post-natal day 10 (P10) capillaries involves the apposition of pericyte somata to the capillary inner basement membrane and penetration of pericyte processes onto the abluminal surface where they form close connections with endothelial cells. Some pericytes have an unusual stellate morphology, extending processes radially from the vessel. Reactive oxygen species (ROS) were monitored with the ROS-sensitive dye 2',7'-dichlorofluorescin (DCF) in the endothelial cells. Exposure to exogenous ROS (100 μm H(2) O(2) or xanthine/xanthine oxidase), evoked an elevation in intracellular ROS that declined to baseline during the ongoing challenge. A second challenge failed to evoke an intracellular ROS rise unless the nerve was rested for > 4 h or exposed to very high levels of exogenous ROS. Exposure to a first ROS challenge prior to loading with DCF also prevented the intracellular ROS rise from a second challenge, proving that dye washout during exposure to ROS is not responsible for the loss of a second response. Perfusion with 30 μm extracellular Ca(2+) or the voltage-gated Ca(2+) antagonist diltiazem partially prevented this rapid scavenging of intracellular ROS, but blocking either catalase or glutathione peroxidase did not. The phenomenon was present over a range of post-natal ages and may contribute to the high ROS-tolerance of endothelial cells and act to limit the release of harmful ROS onto neighbouring pericytes.


Thiopurine S-methyltransferase genotypic analysis in autoimmune bullous diseases.
Thiopurine S-methyltransferase (TPMT) activity is inversely related to the risk of developing severe hematopoietic toxicity in patients treated with azathioprine. The aim of this study was to evaluate the usefulness of TPMT genotyping in severe cases of autoimmune bullous diseases treated with azathioprine. A retrospective study of TPMT genotyping was performed in patients with autoimmune bullous diseases hospitalized in a single centre between 1999 and 2006 and susceptible of being treated by azathioprine. Among 75 patients tested, 70 (93%) had a high TPMT activity and 5 (7%) an intermediate activity. TPMT genotyping was performed in 33/34 patients currently treated with azathioprine. Haematopoietic side-effects (usually moderate) were observed in 12/34 patients treated with a mean dosage of 2.7 mg/kg/day and occurred, despite a high predicted TPMT activity. No myelotoxicity was observed in the two patients with intermediate predicted TPMT activity (mean dosage: 1.7 mg/kg/day), who obtained a clinically complete remission. Although strongly recommended before azathioprine treatment, predicting TPMT activity appears only marginally helpful in patients with autoimmune bullous diseases, mainly for adjusting the azathioprine dosage. In addition, a normal TPMT genotyping is not a guarantee against the occurrence of haematological side-effects.


The chemical, mechanical, and physical properties of 3D printed materials composed of TiO2-ABS nanocomposites.
To expand the chemical capabilities of 3D printed structures generated from commercial thermoplastic printers, we have produced and printed polymer filaments that contain inorganic nanoparticles. TiO2 was dispersed into acrylonitrile butadiene styrene (ABS) and extruded into filaments with 1.75 mm diameters. We produced filaments with TiO2 compositions of 1%, 5%, and 10% (kg/kg) and printed structures using a commercial 3D printer. Our experiments suggest that ABS undergoes minor degradation in the presence of TiO2 during the different processing steps. The measured mechanical properties (strain and Young's modulus) for all of the composites are similar to those of structures printed from the pure polymer. TiO2 incorporation at 1% negatively affects the stress at breaking point and the flexural stress. Structures produced from the 5 and 10% nanocomposites display a higher breaking point stress than those printed from the pure polymer. TiO2 within the printed matrix was able to quench the intrinsic fluorescence of the polymer. TiO2 was also able to photocatalyze the degradation of a rhodamine 6G in solution. These experiments display chemical reactivity in nanocomposites that are printed using commercial 3D printers, and we expect that our methodology will help to inform others who seek to incorporate catalytic nanoparticles in 3D printed structures.


Zinc and the immune system.
Zn is an essential trace element for all organisms. In human subjects body growth and development is strictly dependent on Zn. The nervous, reproductive and immune systems are particularly influenced by Zn deficiency, as well as by increased levels of Zn. The relationship between Zn and the immune system is complex, since there are four different types of influence associated with Zn. (1) The dietary intake and the resorption of Zn depends on the composition of the diet and also on age and disease status. (2) Zn is a cofactor in more than 300 enzymes influencing various organ functions having a secondary effect on the immune system. (3) Direct effects of Zn on the production, maturation and function of leucocytes. (4) Zn influences the function of immunostimulants used in the experimental systems. Here we summarize all four types of influence on the immune function. Nutritional aspects of Zn, the physiology of Zn, the influence of Zn on enzymes and cellular functions, direct effects of Zn on leucocytes at the cellular and molecular level, Zn-altered function of immunostimulants and the therapeutic use of Zn will be discussed in detail.


Multicenter clinical validation of PITX2 methylation as a prostate specific antigen recurrence predictor in patients with post-radical prostatectomy prostate cancer.
Radical prostatectomy is potentially curative in patients with clinically localized prostate cancer. However, biochemical recurrence affects 15% to 30% of men who undergo radical prostatectomy. We previously reported the prognostic potential of PITX2 gene promoter methylation using conventional assays. In the current study we validated PITX2 methylation status as a biochemical recurrence predictor after radical prostatectomy using a novel microarray based platform in a multi-institutional setting. PITX2 methylation status was assessed in formalin fixed, paraffin embedded prostatectomy tumor tissue samples from 476 patients from a total of 4 institutions on customized EpiChip PITX2 microarrays. Associations between PITX2 methylation and biochemical recurrence were assessed using the log rank test and Cox regression controlling for prostate cancer features. On multivariate analysis men with high methylation status were at significantly higher risk for biochemical recurrence than those with low methylation status (HR 3.0, 95% CI 2.0-4.5, p <10(-5)). The biochemical recurrence-free survival rate 5 years after surgery was 85% and 61% in the low and high methylation groups, respectively. In men with pathological Gleason 7 tumors the relative risk of biochemical recurrence was twice as high for high than for low PITX2 methylation (HR 2.0, 95% CI 1.2-3.3, p = 0.005). PITX2 methylation status assessed by EpiChip PITX2 identifies patients with prostate cancer who are most likely to have biochemical recurrence. This test independently adds to the prognostic information provided by standard clinicopathological analysis, improving prostatectomy case stratification into those at high and low risk for biochemical recurrence. This new clinical tool would be of particular benefit to assess intermediate risk cases (Gleason 7) in which risk stratification remains a challenge.


A clinically applicable non-invasive method to quantitatively assess the visco-hyperelastic properties of human heel pad, implications for assessing the risk of mechanical trauma.
Pathological conditions such as diabetic foot and plantar heel pain are associated with changes in the mechanical properties of plantar soft tissue. However, the causes and implications of these changes are not yet fully understood. This is mainly because accurate assessment of the mechanical properties of plantar soft tissue in the clinic remains extremely challenging. To develop a clinically viable non-invasive method of assessing the mechanical properties of the heel pad. Furthermore the effect of non-linear mechanical behaviour of the heel pad on its ability to uniformly distribute foot-ground contact loads in light of the effect of overloading is also investigated. An automated custom device for ultrasound indentation was developed along with custom algorithms for the automated subject-specific modeling of heel pad. Non-time-dependent and time-dependent material properties were inverse engineered from results from quasi-static indentation and stress relaxation test respectively. The validity of the calculated coefficients was assessed for five healthy participants. The implications of altered mechanical properties on the heel pad's ability to uniformly distribute plantar loading were also investigated in a parametric analysis. The subject-specific heel pad models with coefficients calculated based on quasi-static indentation and stress relaxation were able to accurately simulate dynamic indentation. Average error in the predicted forces for maximum deformation was only 6.6±4.0%. When the inverse engineered coefficients were used to simulate the first instance of heel strike the error in terms of peak plantar pressure was 27%. The parametric analysis indicated that the heel pad's ability to uniformly distribute plantar loads is influenced both by its overall deformability and by its stress-strain behaviour. When overall deformability stays constant, changes in stress/strain behaviour leading to a more "linear" mechanical behaviour appear to improve the heel pad's ability to uniformly distribute plantar loading. The developed technique can accurately assess the visco-hyperelastic behaviour of heel pad. It was observed that specific change in stress-strain behaviour can enhance/weaken the heel pad's ability to uniformly distribute plantar loading that will increase/decrease the risk for overloading and trauma.


Antipsychotic drug exposure and risk of pulmonary embolism: a population-based, nested case-control study.
Only three observational studies investigated whether exposure to antipsychotics is associated with an increased risk of pulmonary embolism, with conflicting results. This study was therefore carried out to establish the risk of pulmonary embolism associated with antipsychotic drugs, and to ascertain the risk associated with first- and second-generation antipsychotic drugs, and with exposure to individual drugs. We identified 84,253 adult individuals who began antipsychotic treatment in a large Italian health care system. Cases were all cohort members who were hospitalized for non-fatal or fatal pulmonary embolism during follow-up. Up to 20 controls for each case were extracted from the study cohort using incidence density sampling and matched by age at cohort entry and gender. Each individual was classified as current, recent or past antipsychotic user. The occurrence non-fatal or fatal pulmonary embolism was the outcome of interest. Compared to past use, current antipsychotic use more than double the risk of pulmonary embolism (odds ratio 2.31, 95% confidence interval 1.16 to 4.59), while recent use did not increase the risk. Both conventional and atypical antipsychotic exposure was associated with an increase in risk, and the concomitant use of both classes increased the risk of four times (odds ratio 4.21, 95% confidence interval 1.53 to 11.59). Adding the results of this case-control study to a recent meta-analysis of three observational studies substantially changed the overall estimate, which now indicates that antipsychotic exposure significantly increases the risk of pulmonary embolism.


MicroRNA-146a inhibits glioma development by targeting Notch1.
Dysregulated epidermal growth factor receptor (EGFR) signaling through either genomic amplification or dominant-active mutation (EGFR(vIII)), in combination with the dual inactivation of INK4A/ARF and PTEN, is a leading cause of gliomagenesis. Our global expression analysis for microRNAs revealed that EGFR activation induces miR-146a expression, which is further potentiated by inactivation of PTEN. Unexpectedly, overexpression of miR-146a attenuates the proliferation, migration, and tumorigenic potential of Ink4a/Arf(-/-) Pten(-/-) Egfr(vIII) murine astrocytes. Its ectopic expression also inhibits the glioma development of a human glioblastoma cell line in an orthotopic xenograft model. Such an inhibitory function of miR-146a on gliomas is largely through downregulation of Notch1, which plays a key role in neural stem cell maintenance and is a direct target of miR-146a. Accordingly, miR-146a modulates neural stem cell proliferation and differentiation and reduces the formation and migration of glioma stem-like cells. Conversely, knockdown of miR-146a by microRNA sponge upregulates Notch1 and promotes tumorigenesis of malignant astrocytes. These findings indicate that, in response to oncogenic cues, miR-146a is induced as a negative-feedback mechanism to restrict tumor growth by repressing Notch1. Our results provide novel insights into the signaling pathways that link neural stem cells to gliomagenesis and may lead to new strategies for treating brain tumors.


The asymmetrical relationship between the health care professional and the patient in public hospitals.
The relationship between the health care professional and the patient is universally seen, in medicine, as the core of medical practice. Through it, the doctor acquires professional abilities and pursues the objectives of medicine, among them, that of curing. This relation is contextualized here by using articles 47 and 48, from the chapter on Human Rights, found in the Code of Ethical Medicine of the Federal Council of Medicine of the Federative Republic of Brazil--both in the sense of the transformational link between two people, and as a relationship of interpersonal tolerance. The objectives of this article are: 1) to evaluate the asymmetry present in the clinical doctor-patient encounter, with respect to the doctor's social and political commitment regarding the patient. Recorded testimonies were used, of individuals who utilize medical assistance in Public Hospitals, carried out in the hallways of the 'das Clínicas Hospital' in Recife, Pernambuco; and 2) to weave an analogy with the book "Masters and Slaves" ('Casa Grande & Senzala'): 'Formation of the Brazilian Family under the Regime of a Patriarchal Economy', written by the Pernambucan sociologist Gilberto Freyre. Among the recorded talks, the resentment regarding discrimination and the authority of the doctor's position can be clearly observed. As a result, this power relation was considered the focus of our discussion--the same power relation as that which reigned over the Brazilian colonization period, in the times of "Masters and Slaves" (Casa Grande & Senzala).


Does physical inactivity cause nonalcoholic fatty liver disease?
While physical activity represents a key element in the prevention and management of many chronic diseases, we and others believe that physical inactivity is a primary cause of obesity and associated metabolic disorders. Unfortunately, accumulating evidence suggests that we have engineered physical activity out of our normal daily living activity. One such consequence of our sedentary and excessive lifestyle is nonalcoholic fatty liver disease (NAFLD), which is now considered the most common cause of chronic liver disease in Westernized societies. In this review, we will present evidence that physical inactivity, low aerobic fitness, and overnutrition, either separately or in combination, are an underlying cause of NAFLD.


A novel family of mobile genetic elements is limited to the germline genome in Tetrahymena thermophila.
In the ciliated protozoan Tetrahymena thermophila, extensive DNA elimination is associated with differentiation of the somatic macronucleus from the germline micronucleus. This study describes the isolation and complete characterization of Tlr elements, a family of approximately 30 micronuclear DNA sequences that are efficiently eliminated from the developing macronucleus. The data indicate that Tlr elements are comprised of an approximately 22 kb internal region flanked by complex and variable termini. The Tlr internal region is highly conserved among family members and contains 15 open reading frames, some of which resemble genes encoded by transposons and viruses. The Tlr termini appear to be long inverted repeats consisting of (i) a variable region containing multiple direct repeats which differ in number and sequence from element to element and (ii) a conserved terminal 47 bp sequence. Taken together, these results suggest that Tlr elements comprise a novel family of mobile genetic elements that are confined to the Tetrahymena germline genome. Possible mechanisms of developmentally programmed Tlr elimination are discussed.


Study of cell antigens and intracellular DNA by identification of element-containing labels and metallointercalators using inductively coupled plasma mass spectrometry.
The enumeration of absolute cell numbers and cell proliferation in clinical samples is important for diagnostic and research purposes. Detection of cellular DNA with fluorescent dyes is the most commonly used approach for cell enumeration in cytometry. Inductively coupled plasma mass spectrometry (ICPMS) has been recently introduced to the field of protein and cell surface antigen identification via ICPMS-linked immunoassays using element-labeled affinity reagents such as gold and lanthanide-conjugated antibodies. In the present work, we describe novel methods for using metallointercalators that irreversibly bind DNA and low concentrations of rare earth metals added to cell growth media for rapid and sensitive measurement of cell numbers by mass spectrometry. We show that Ir- and Rh-containing metallointercalators are useful reagents for labeling cells and normalizing signals when studying antigen expression on different types and numbers of cells. Results are presented for solution analysis performed by conventional ICPMS and compared to measurements obtained on the novel flow cytometer mass spectrometer (FC-MS) instrument, designed to analyze multiple antigens and DNA simultaneously in single cells.


Climate modifies response of non-native and native species richness to nutrient enrichment.
Ecosystem eutrophication often increases domination by non-natives and causes displacement of native taxa. However, variation in environmental conditions may affect the outcome of interactions between native and non-native taxa in environments where nutrient supply is elevated. We examined the interactive effects of eutrophication, climate variability and climate average conditions on the success of native and non-native plant species using experimental nutrient manipulations replicated at 32 grassland sites on four continents. We hypothesized that effects of nutrient addition would be greatest where climate was stable and benign, owing to reduced niche partitioning. We found that the abundance of non-native species increased with nutrient addition independent of climate; however, nutrient addition increased non-native species richness and decreased native species richness, with these effects dampened in warmer or wetter sites. Eutrophication also altered the time scale in which grassland invasion responded to climate, decreasing the importance of long-term climate and increasing that of annual climate. Thus, climatic conditions mediate the responses of native and non-native flora to nutrient enrichment. Our results suggest that the negative effect of nutrient addition on native abundance is decoupled from its effect on richness, and reduces the time scale of the links between climate and compositional change.


Student perceptions of a healthy university.
As complex environments within which individuals and populations operate, universities present important contexts for understanding and addressing health issues. The healthy university is an example of the settings approach, which adopts a whole system perspective, aiming to make places within which people, learn, live, work and play supportive to health and well-being. The UK Healthy Universities Network has formulated an online toolkit, which includes a Self-Review Tool, intended to enable universities to assess what actions they need to take to develop as a healthy university. This paper presents findings from consultative research undertaken with students from universities in England, Scotland and Wales, which explored what they believe, represents a healthy university. Student surveys and focus groups were used to collect data across eleven universities in England, Scotland and Wales. A priori themes were used to develop our own model for a healthy university, and for the thematic coding phase of analysis. A healthy university would promote student health and well-being in every aspect of its business from its facilities and environment through to its curriculum. Access to reasonably priced healthy food and exercise facilities were key features of a healthy university for students in this study. The Self-Review Tool has provided a crucial start for universities undertaking the journey towards becoming a healthy university. In looking to the future both universities and the UK Healthy Universities Network will now need to look at what students want from their whole university experience, and consider how the Self-Review Tool can help universities embrace a more explicit conceptual framework. The concept of a healthy university that can tailor its facilities and supportive environments to the needs of its students will go some way to developing students who are active global citizens and who are more likely to value and prioritise health and well-being, in the short and long term through to their adult lives.


Comparison of the capture efficiency, prey processing, and nutrient extraction in a generalist and a specialist spider predator.
Predators are traditionally classified as generalists and specialists based on the presence of adaptations that increase efficiency of prey capture and consumption and selection of particular prey types. Nevertheless, empirical evidence comparing foraging efficiency between generalist and specialist carnivores is scarce. We compared the prey-capture and feeding efficiency in a generalist and a specialist (araneophagous) spider predator. By using two related species, the generalist Harpactea rubicunda (Dysderidae) and the specialist Nops cf. variabilis (Caponiidae), we evaluated their fundamental trophic niche by studying the acceptance of different prey. Then, we compared their predatory behavior, efficiency in capturing prey of varying sizes, feeding efficiency, and nutrient extraction. Nops accepted only spiders as prey, while Harpactea accepted all offered prey, confirming that Nops is stenophagous, while Harpactea is euryphagous. Further, Nops displayed more specialized (stereotyped) capture behavior than Harpactea, suggesting that Nops is a specialist, while Harpactea is a generalist. The specialist immobilized prey faster, overcame much larger prey, and gained more mass (due to feeding on larger prey) than the generalist. Both the specialist and the generalist spider extracted more proteins than lipids, but the extraction of macronutrients in the specialist was achieved mainly by consuming the prosoma of the focal prey. We show that the specialist has more efficient foraging strategy than the generalist.


The Epidemic Diseases Act of 1897: public health relevance in the current scenario.
Recently, many states in India have invoked various provisions of the Epidemic Diseases Act of 1897 to control communicable diseases. In this context, the Act was reviewed with reference to its relevance in the current context of surveillance and other relevant Acts and legislations at the national and international levels. It is felt that the Act has major limitations in the current scenario as it is outdated, merely regulatory and not rights-based, and lacks a focus on the people. There is a need for an integrated, comprehensive, actionable and relevant legal provision for the control of outbreaks in India.


Substance use disorders, psychiatric disorders, and mortality after release from prison: a nationwide longitudinal cohort study.
High mortality rates have been reported in people released from prison compared with the general population. However, few studies have investigated potential risk factors associated with these high rates, especially psychiatric determinants. We aimed to investigate the association between psychiatric disorders and mortality in people released from prison in Sweden. We studied all people who were imprisoned since Jan 1, 2000, and released before Dec 31, 2009, in Sweden for risks of all-cause and external-cause (accidents, suicide, homicide) mortality after prison release. We obtained data for substance use disorders and other psychiatric disorders, and criminological and sociodemographic factors from population-based registers. We calculated hazard ratios (HRs) by Cox regression, and then used them to calculate population attributable fractions for post-release mortality. To control for potential familial confounding, we compared individuals in the study with siblings who were also released from prison, but without psychiatric disorders. We tested whether any independent risk factors improved the prediction of mortality beyond age, sex, and criminal history. We identified 47,326 individuals who were imprisoned. During a median follow-up time of 5·1 years (IQR 2·6-7·5), we recorded 2874 (6%) deaths after release from prison. The overall all-cause mortality rate was 1205 deaths per 100,000 person-years. Substance use disorders significantly increased the rate of all-cause mortality (alcohol use: adjusted HR 1·62, 95% CI 1·48-1·77; drug use: 1·67, 1·53-1·83), and the association was independent of sociodemographic, criminological, and familial factors. We identified no strong evidence that other psychiatric disorders increased mortality after we controlled for potential confounders. In people released from prison, 925 (34%) of all-cause deaths in men and 85 (50%) in women were potentially attributable to substance use disorders. Substance use disorders were also an independent determinant of external-cause mortality, with population attributable fraction estimates at 42% in men and 70% in women. Substance use disorders significantly improved the prediction of external-cause mortality, in addition to sociodemographic and criminological factors. Interventions to address substance use disorders could substantially decrease the burden of excess mortality in people released from prison, but might need to be provided beyond the immediate period after release. Wellcome Trust, Swedish Research Council, and the Swedish Research Council for Health, Working Life and Welfare.


Coded multiple exposure holograms.
Experiments have been performed in which 1000 holograms have been superimposed one upon the other in the same area of photographic emulsion. Each hologram was formed with a uniquely coded reference beam allowing reconstruction of only one of the superimposed holograms while the unaddressed holograms contribute incoherent noise. Signal-to-noise ratios are calculated and measured as a function of the number of superimposed exposures. For the 1000-exposure hologram, the observed signal-to-noise ratio for any one of the individual holograms was 10 dB.


Multiple independent evolutionary solutions to core histone gene regulation.
Core histone genes are periodically expressed along the cell cycle and peak during S phase. Core histone gene expression is deeply evolutionarily conserved from the yeast Saccharomyces cerevisiae to human. We evaluated the evolutionary dynamics of the specific regulatory mechanisms that give rise to the conserved histone regulatory phenotype. In contrast to the conservation of core histone gene expression patterns, the core histone regulatory machinery is highly divergent between species. There has been substantial evolutionary turnover of cis-regulatory sequence motifs along with the transcription factors that bind them. The regulatory mechanisms employed by members of the four core histone families are more similar within species than within gene families. The presence of species-specific histone regulatory mechanisms is opposite to what is seen at the protein sequence level. Core histone proteins are more similar within families, irrespective of their species of origin, than between families, which is consistent with the shared common ancestry of the members of individual histone families. Structure and sequence comparisons between histone families reveal that H2A and H2B form one related group whereas H3 and H4 form a distinct group, which is consistent with the nucleosome assembly dynamics. The dissonance between the evolutionary conservation of the core histone gene regulatory phenotypes and the divergence of their regulatory mechanisms indicates a highly dynamic mode of regulatory evolution. This distinct mode of regulatory evolution is probably facilitated by a solution space for promoter sequences, in terms of functionally viable cis-regulatory sites, that is substantially greater than that of protein sequences.


Dendritic cells induce T lymphocytes to release B cell-stimulating factors by an interleukin 2-dependent mechanism.
Dendritic cells (DC) are essential accessory cells for T-dependent antibody responses in culture (1). We have outlined a three-stage mechanism to explain the capacity of DC to stimulate primary antibody responses to heterologous erythrocytes. First, DC induced T cells to produce and to become responsive to interleukin 2 (IL-2). This stage corresponded to the syngeneic mixed leukocyte reaction (2) and involved the clustering of DC and T cells into discrete aggregates. Isolated clusters, representing 5-10% of the culture, were critical for IL-2 release and the production of IL-2-responsive T blasts. In the second stage, IL-2 directly triggered the responsive T cells to release B cell helper factors. This role for IL-2 was documented with a rabbit anti-IL-2 reagent, purified IL-2, and T cells that had been rendered IL-2 responsive by an initial co-culture with DC. T cell growth was not required for IL-2-mediated helper factor release, since irradiated and untreated responders produced similar levels of factor and did so within 3 h of the addition of IL-2. In the final stage, helper factors stimulated the development of antibody-secreting cells from purified B lymphocytes. The helper factors were not H-2 restricted, but for both sheep and horse erythrocytes, the response to factors was antigen dependent and specific. The IL-2 that was present in the DC/T cell-conditioned medium did not act on B cells, since helper activity was neither neutralized nor absorbed by our anti-IL-2 reagent. We conclude that the ability of the DC to induce IL-2 release and responsiveness underlies its capacity to trigger both T and B lymphocyte reactions.


Chaperone-like properties of tobacco plastid thioredoxins f and m.
Thioredoxins (Trxs) are ubiquitous disulphide reductases that play important roles in the redox regulation of many cellular processes. However, some redox-independent functions, such as chaperone activity, have also been attributed to Trxs in recent years. The focus of our study is on the putative chaperone function of the well-described plastid Trxs f and m. To that end, the cDNA of both Trxs, designated as NtTrxf and NtTrxm, was isolated from Nicotiana tabacum plants. It was found that bacterially expressed tobacco Trx f and Trx m, in addition to their disulphide reductase activity, possessed chaperone-like properties. In vitro, Trx f and Trx m could both facilitate the reactivation of the cysteine-free form of chemically denatured glucose-6 phosphate dehydrogenase (foldase chaperone activity) and prevent heat-induced malate dehydrogenase aggregation (holdase chaperone activity). Our results led us to infer that the disulphide reductase and foldase chaperone functions prevail when the proteins occur as monomers and the well-conserved non-active cysteine present in Trx f is critical for both functions. By contrast, the holdase chaperone activity of both Trxs depended on their oligomeric status: the proteins were functional only when they were associated with high molecular mass protein complexes. Because the oligomeric status of both Trxs was induced by salt and temperature, our data suggest that plastid Trxs could operate as molecular holdase chaperones upon oxidative stress, acting as a type of small stress protein.


WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): update 2013.
Functional enrichment analysis is an essential task for the interpretation of gene lists derived from large-scale genetic, transcriptomic and proteomic studies. WebGestalt (WEB-based GEne SeT AnaLysis Toolkit) has become one of the popular software tools in this field since its publication in 2005. For the last 7 years, WebGestalt data holdings have grown substantially to satisfy the requirements of users from different research areas. The current version of WebGestalt supports 8 organisms and 201 gene identifiers from various databases and different technology platforms, making it directly available to the fast growing omics community. Meanwhile, by integrating functional categories derived from centrally and publicly curated databases as well as computational analyses, WebGestalt has significantly increased the coverage of functional categories in various biological contexts including Gene Ontology, pathway, network module, gene-phenotype association, gene-disease association, gene-drug association and chromosomal location, leading to a total of 78 612 functional categories. Finally, new interactive features, such as pathway map, hierarchical network visualization and phenotype ontology visualization have been added to WebGestalt to help users better understand the enrichment results. WebGestalt can be freely accessed through http://www.webgestalt.org or http://bioinfo.vanderbilt.edu/webgestalt/.


Attitudes towards antipsychotics among patients with schizophrenia on first- or second-generation medications.
Given the paucity of research in this area, this study attempted to assess attitudes toward antipsychotic medications and its correlates among patients with schizophrenia, either on first-generation antipsychotics (FGAs) or second-generation antipsychotics (SGAs) medications. Structured assessments of attitudes to antipsychotics, psychopathology, insight and side-effects were carried out in 120 patients with DSM-IV schizophrenia; 89 of these were on SGAs and 31 on FGAs. Patients had predominantly positive attitudes toward antipsychotics. Severity of side-effects was the principal correlate of attitudes, explaining 19.5% of the variance, followed by greater insight (4.2% of the variance). Other factors such as younger age, male gender, employment, higher family income, urban residence and lower symptom-severity explained only a negligible proportion of the variance (0.2%) in attitudes. Patients on SGAs had more positive views of their medications than those on FGAs. They felt more normal on their medications, believed that their thoughts were clearer on medications, felt that good things about their medications outweighed the bad and believed that their medications helped them from falling ill again. In addition, they did not feel as tired and sluggish on their medications and did not believe that medications were unnatural or controlled their bodies. Positive attitudes toward antipsychotics were common among patients with schizophrenia. Attitudes were principally determined by severity of side-effects and insight levels. Patients on SGAs had better attitudes, possibly because of less severe side-effects and greater insight among them. The importance of exploring patients' attitudes toward their antipsychotics is highlighted by this study.


Estradiol inhibits plasma somatostatin 14 (SRIF-14) levels and inhibits the response of somatotrophic cells to SRIF-14 challenge in vitro in rainbow trout, Oncorhynchus mykiss.
In the present study, the effects of 17 beta-estradiol (E2) treatment on plasma growth hormone (GH) and somatostatin 14 (SRIF-14) concentrations were investigated, as well as the effect of in vivo E2 treatment on the in vitro GH response to SRIF-14 challenge in sexually immature rainbow trout (Oncorhynchus mykiss). Two weeks after receiving a steroid hormone implant, plasma E2 and GH levels were significantly (P < 0.05) elevated, and plasma SRIF levels were significantly (P < 0.05) lowered relative to the control. Pituitary glands were taken from E2-primed and control fish and challenged with a single pulse of SRIF-14 (10(-8) M) in a perifusion unit to evaluate the effect of E2 on the response of somatotrophs to the effect of SRIF-14. Whereas SRIF-14 challenge significantly (P < 0.01) inhibited GH release from pituitary fragments taken from control fish, there was no such response in E2-primed fish. Furthermore, GH release following SRIF-14 administration (at the point of maximal inhibition) was significantly depressed in control fish with respect to the E2 treatment group. These data suggest that E2 treatment may increase plasma GH concentrations by altered somatotroph responsiveness to SRIF-14 inhibition. Furthermore, E2 may increase plasma GH by suppressing plasma SRIF-14 levels, although the role of circulating SRIF-14 on the regulation of GH release has not been fully determined in teleosts.


The Central Nervous System of Jawless Vertebrates: Encephalization in Lampreys and Hagfishes.
Lampreys and hagfishes are the sole surviving representatives of the early agnathan (jawless) stage in vertebrate evolution, which has previously been regarded as the least encephalized group of all vertebrates. Very little is known, however, about the extent of interspecific variation in relative brain size in these fishes, as previous studies have focused on only a few species, even though lampreys exhibit a variety of life history traits. While some species are parasitic as adults, with varying feeding behaviors, others (nonparasitic species) do not feed after completing their macrophagous freshwater larval phase. In addition, some parasitic species remain in freshwater, while others undergo an anadromous migration. On the basis of data for postmetamorphic individuals representing approximately 40% of all lamprey species, with representatives from each of the three families, the aforementioned differences in life history traits are reflected in variations in relative brain size. Across all lampreys, brain mass increases with body mass with a scaling factor or slope (α) of 0.35, which is less than those calculated for different groups of gnathostomatous (jawed) vertebrates (α = 0.43-0.62). When parasitic and nonparasitic species are analyzed separately, with phylogeny taken into account, the scaling factors of both groups (parasitic α = 0.43, nonparasitic α = 0.45) approach those of gnathostomes. The relative brain size in fully grown adults of parasitic species is, however, less than that of the adults of nonparasitic species, paralleling differences between fully grown adults and recently metamorphosed individuals of anadromous species. The average degree of encephalization is found in anadromous parasitic lampreys and might thus represent the ancestral condition for extant lampreys. These results suggest that the degree of encephalization in lampreys varies according to both life history traits and phylogenetic relationships.


Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin.
Our ultimate goal in treating patients is to improve their quality of life and to increase survival. The optimal treatment for primary pulmonary hypertension will continue to change as our understanding of its causes improves and as progress is made in lung transplantation. There is no one best treatment for all patients. Optimal medical and surgical treatment must be tailored to the individual with changes in therapeutic regimens based on serial evaluations. Quality of life and survival have improved with current treatments and the future should offer additional therapies-inhaled nitric oxide, endothelin receptor blockers, and other modulators of the pulmonary vascular bed-to improve further the treatment of this disease. In conclusion, although primary pulmonary hypertension, if untreated, is most often a rapidly progressive and fatal disease, recent advances in the treatment have significantly improved the outcome for patients. Although transplantation is often considered the only definitive treatment for patients with primary pulmonary hypertension, medical treatment seems to be an effective long term palliation to successful transplantation as well as a possible alternative treatment to transplantation in selected children and adults. Quality of life and cost analyses, as well as longer follow up studies are needed to determine the best treatment for patients with primary pulmonary hypertension.


VisioTracker, an innovative automated approach to oculomotor analysis.
Investigations into the visual system development and function necessitate quantifiable behavioral models of visual performance that are easy to elicit, robust, and simple to manipulate. A suitable model has been found in the optokinetic response (OKR), a reflexive behavior present in all vertebrates due to its high selection value. The OKR involves slow stimulus-following movements of eyes alternated with rapid resetting saccades. The measurement of this behavior is easily carried out in zebrafish larvae, due to its early and stable onset (fully developed after 96 hours post fertilization (hpf)), and benefitting from the thorough knowledge about zebrafish genetics, for decades one of the favored model organisms in this field. Meanwhile the analysis of similar mechanisms in adult fish has gained importance, particularly for pharmacological and toxicological applications. Here we describe VisioTracker, a fully automated, high-throughput system for quantitative analysis of visual performance. The system is based on research carried out in the group of Prof. Stephan Neuhauss and was re-designed by TSE Systems. It consists of an immobilizing device for small fish monitored by a high-quality video camera equipped with a high-resolution zoom lens. The fish container is surrounded by a drum screen, upon which computer-generated stimulus patterns can be projected. Eye movements are recorded and automatically analyzed by the VisioTracker software package in real time. Data analysis enables immediate recognition of parameters such as slow and fast phase duration, movement cycle frequency, slow-phase gain, visual acuity, and contrast sensitivity. Typical results allow for example the rapid identification of visual system mutants that show no apparent alteration in wild type morphology, or the determination of quantitative effects of pharmacological or toxic and mutagenic agents on visual system performance.


Overexpression of AtABCG36 improves drought and salt stress resistance in Arabidopsis.
Drought and salt are major abiotic stresses that adversely affect crop productivity. Thus, identification of factors that confer resistance to these stresses would pave way to increasing agricultural productivity. When grown on soil in green house longer than 5 weeks, transgenic Arabidopsis plants that overexpress an ATP-binding cassette (ABC) transporter, AtABCG36/AtPDR8, produced higher shoot biomass and less chlorotic leaves than the wild-type. We investigated whether the improved growth of AtABCG36-overexpressing plants was due to their improved resistance to abiotic stresses, and found that AtABCG36-overexpressing plants were more resistant to drought and salt stress and grew to higher shoot fresh weight (FW) than the wild-type. On the contrary, T-DNA insertional knockout lines were more sensitive to drought stress than wild-type and were reduced in shoot FW. To understand the mechanism of enhanced salt and drought resistance of the AtABCG36 overexpressing plants, we measured sodium contents and found that AtABCG36 overexpressing plants were lower in sodium content than the wild-type. Our data suggest that AtABCG36 contributes to drought and salt resistance in Arabidopsis by a mechanism that includes reduction of sodium content in plants.


Job satisfaction among anesthesiologists at a tertiary hospital in Nigeria.
We assessed job satisfaction among anesthesiologists at a tertiary hospital in Nigeria and identified elements of job stress and dissatisfaction. A cross-sectional study design was employed; a structured self-administered questionnaire was distributed, which focused on sociodemographic data, rating of job satisfaction, identification of stressors, and work relationships. Out of 55 questionnaires distributed, 46 (83.6%) completed questionnaires were returned. Overall, 27 (58.7%) of the anesthesiologists were satisfied with their job. While 8.7% were very satisfied (grade 5), 6.5% were very dissatisfied (grade 1) with their job. The stressors identified by the respondents were time pressures, long working hours with complaints of insufficient sleep, and employment status. Among the respondents, the medical officers were the most discontented (9 out of 12, 75%), followed by senior registrars (5 out of 9, 56%). A high percentage of participants (54.1%) declared that the one change if implemented that would enhance their job satisfaction was having a definite closing time. Our results showed that despite the demanding nature of anesthesiology as a specialty, many anesthesiologists were contented with their job.


Dynamics of Gene Expression in Single Root Cells of Arabidopsis thaliana.
Single cell RNA sequencing can yield high-resolution cell-type-specific expression signatures that reveal new cell types and the developmental trajectories of cell lineages. Here, we apply this approach to Arabidopsis (Arabidopsis thaliana) root cells to capture gene expression in 3,121 root cells. We analyze these data with Monocle 3, which orders single cell transcriptomes in an unsupervised manner and uses machine learning to reconstruct single cell developmental trajectories along pseudotime. We identify hundreds of genes with cell-type-specific expression, with pseudotime analysis of several cell lineages revealing both known and novel genes that are expressed along a developmental trajectory. We identify transcription factor motifs that are enriched in early and late cells, together with the corresponding candidate transcription factors that likely drive the observed expression patterns. We assess and interpret changes in total RNA expression along developmental trajectories and show that trajectory branch points mark developmental decisions. Finally, by applying heat stress to whole seedlings, we address the longstanding question of possible heterogeneity among cell types in the response to an abiotic stress. Although the response of canonical heat-shock genes dominates expression across cell types, subtle but significant differences in other genes can be detected among cell types. Taken together, our results demonstrate that single cell transcriptomics holds promise for studying plant development and plant physiology with unprecedented resolution.


Operating room practices for the control of infection in U. S. hospitals, October 1976 to July 1977.
We estimated the frequency of selected infection control practices in the operating room from a nationwide survey of hospitals. Our survey confirmed that, in many hospitals, practices which have not received scientific or budgetary scrutiny have become part of the perioperative routine. Almost half of the hospitals reported using nonrecommended tacky, or disinfectant, mats at the entrance to operating rooms, and more than three-fourths were performing nonrecommended environmental cultures in the operating room at a cost ranging from $2,000 to $20,000 per year. When routine nose and throat cultures were taken of operating room personnel, we found an obvious pecking order, rather than a scientific rationale for culturing. In almost all instances, we found wide variations in practice among hospitals. This nonuniformity may be due to such factors as lack of a convincing scientific basis for evaluating the relative efficacy of alternative practices, the strong influence of industry marketing, the individual preferences of surgeons and operating room supervisors and the lack of completeness and agreement of statements from various scientific and professional organizations.


Significance of T2 Hyperintensity on Magnetic Resonance Imaging After Cervical Cord Injury and Return to Play in Professional Athletes.
Cervical cord magnetic resonance imaging (MRI) T2 hyperintensity is used as evidence of cord trauma in the evaluation and management of athletes in contact sports. The long-term pathophysiologic and prognostic value of this finding is poorly understood, especially in return to play (RTP). To examine the significance of T2 hyperintensity in the cervical spinal cord of professional athletes. Retrospective review of MRI T2 hyperintensity findings between 2007 and 2014 in 5 professional athletes. Pertinent examination and demographics, including mechanism of injury, surgical intervention, radiographs, MRI studies, long-term outcomes, and RTP recommendations were collected. Four National Football League players and 1 professional wrestler had prior traumatic neurapraxia that at the time of initial consultation had resolved. MRIs showed congenitally small cervical canal (1) and multilevel spondylosis/stenosis/disc herniation (4) along with focal cord T2 hyperintensity (5). The signal abnormalities were at C3/C4 (3), C4 mid-vertebral body (1), and C5/C6 (1). Four athletes had single-level anterior cervical discectomy and fusion, and 1 was nonoperative. Serial MRI imaging at 3 months after surgery showed hyperintensity partially resolved (4) and unchanged (1), and at 9-months 3 of the 5 completely resolved. Based on the author's RTP criteria, 4 of 5 were released to return to their sport. Clearance for RTP preceded complete resolution of MRI T2 hyperintensity in 3 of 4 athletes. The 2 athletes that have returned to profession sport have not had any additional episodes of neurapraxia or any cervical spine-related complications. MRI T2 hyperintensity in contact sport athletes who are symptom-free with normal examination and no evidence of spinal instability may not be a contraindication to RTP. Additional observations are needed to confirm this observation.


[Metachronous lung cancer: indication and outcome].
Although lobectomy is the standard surgical treatment for primary lung cancer, it is unclear whether lobectomy will be benefit for patients with metachronous lung cancer. The purpose of this study is to evaluate the difference of benefit between lobectomy and limited resection at second lung resection. Forty-eight patients, who had already undergone lobectomy due to primary lung cancer, undergoing second lobectomy (n = 30) or limited resection (n = 18) for metachronous lung cancer were investigated. The over-all 5-year survival rate of second operation was 51.9%. Although there was no significant difference of 5-year survival rates between lobectomy and limited resection, 50.4% and 49.4%, respectively, lobectomy for T1N0 subset prolonged the survival compared to limited resection, 5-year survival rates, 69.6% and 31.7%, respectively. However, lobectomy resulted in more postoperative complications and less preservation of lung function. Lobectomy should be considered the surgical procedure of choice for patients with metachronous T1N0 lung cancer when lung function is preserved.


Changes in service availability in california hospitals, 1995 to 2002.
Hospitals face serious financial challenges in the current healthcare marketplace. In response to these challenges, they may alter their service offerings, eliminating services that are perceived as money-losing or adding new services in areas where profitability is expected to be greater. Although research has examined hospital closures, the more subtle phenomenon of hospital service changes has not been systematically studied. This issue is important because different types of hospital service changes could have different effects on hospital financial viability: extensive service closures could contribute to a downward spiral leading to hospital closure, whereas adding new services might help improve a hospital's finances. This article' examines changes in hospital service availability in California general acute care hospitals between 1995 and 2002. Our major findings indicate that many California hospitals made changes in their service offerings during the study period, although few made extensive changes. Altogether, about half of the hospitals in our study population either closed or opened at least one service. Nearly one-fourth of the hospitals in our study population closed one or more services, whereas just under one-third opened one or more new services. However, the vast majority of the hospitals that closed or added a service made only one or two such changes. In addition, few hospitals both closed and opened services. The service closed most frequently was normal newborn labor and delivery (obstetrics), whereas inpatient rehabilitation was the most frequently opened service. Hospitals that made the most service changes tended to be small, rural, and financially troubled at the start of the study period. Among this group of hospitals, service closures were associated with continued financial deterioration, whereas new service openings were associated with improvements in key financial ratios.


Intragenic deletion in the gene encoding L-gulonolactone oxidase causes vitamin C deficiency in pigs.
The absence of L-ascorbic acid (L-AA, or AA) synthesis in scurvy-prone organisms, including humans, other primates, guinea pigs, and flying mammals, was traced to the lack of L-gulonolactone oxidase (GULO) activity. GULO is a microsomal enzyme that catalyzes the terminal step in the biosynthesis of L-AA. Clinical cases of scurvy were described in a family of Danish pigs. This trait is controlled by a single autosomal recessive allele designated od (osteogenic disorder). Here we demonstrate that the absence of GULO activity and the associated vitamin C deficiency in od/od pigs is due to the occurrence of a 4.2-kbp deletion in the GULO gene. This deletion includes 77 bp of exon VIII, 398 bp of intron 7 and 3.7 kbp of intron 8, which leads to a frame shift. The mutant protein is truncated to 356 amino acids, but only the first 236 amino acids are identical to the wild-type GULO protein. In addition, the od allele seems to be less expressed in deficient and heterozygous pigs compared with the normal allele in heterozygous and wild-type animals as determined by ribonuclease protection assay. We also developed a DNA-based test for the diagnosis of the deficient allele. However, we failed to identify the mutated allele in other pig populations.


Spiral calcium wave propagation and annihilation in Xenopus laevis oocytes.
Intracellular calcium (Ca2+) is a ubiquitous second messenger. Information is encoded in the magnitude, frequency, and spatial organization of changes in the concentration of cytosolic free Ca2+. Regenerative spiral waves of release of free Ca2+ were observed by confocal microscopy in Xenopus laevis oocytes expressing muscarinic acetylcholine receptor subtypes. This pattern of Ca2+ activity is characteristic of an intracellular milieu that behaves as a regenerative excitable medium. The minimal critical radius for propagation of focal Ca2+ waves (10.4 micrometers) and the effective diffusion constant for the excitation signal (2.3 x 10(-6) square centimeters per second) were estimated from measurements of velocity and curvature of circular wavefronts expanding from foci. By modeling Ca2+ release with cellular automata, the absolute refractory period for Ca2+ stores (4.7 seconds) was determined. Other phenomena expected of an excitable medium, such as wave propagation of undiminished amplitude and annihilation of colliding wavefronts, were observed.


Validity of weak-scattering models in forward two-dimensional optical scattering.
The exact solution for scattering from cylindrical objects is compared with the following weak-scattering models: the first Born approximation, the Rytov approximation, the straight-ray model of geometric optics, and ray tracing. Computer calculations of the various approximate and the exact virtual fields at the center of a transparent cylinder are compared in order to find the practical limitations of the various approximations with respect to cylinder radii and indices of refraction. It is found that the Rytov approximation introduces a phase error that increases linearly with the cylinder radius. The straightray model yields better results than the first Rytov approximation for all cylinder radii and real indices of refraction, even at the edges. The first Born approximation is best for cylinders with radii less than a wavelength.


Effect of opponent type on moral emotions and responses to video game play.
This study suggests that fighting against different types of opponents in video games (e.g., human opponents vs. monster opponents) may lead to different emotional responses and moral judgments toward game characters. Based on Bandura's moral disengagement theory, this study proposes that shooting at monster opponents makes game players feel less guilty and judge the player-controlled character as more morally justified. An experiment was conducted in which participants played shooting games with either human opponents or monster opponents. The results show that when playing against monster opponents, participants felt both less ashamed and less guilty, reported enjoying the game more, and judged their character as more justified than participants who played against human opponents.


IL-1 mediates TNF-induced osteoclastogenesis.
TNF-induced receptor activator NF-kappaB ligand (RANKL) synthesis by bone marrow stromal cells is a fundamental component of inflammatory osteolysis. We found that this process was abolished by IL-1 receptor antagonist (IL-1Ra) or in stromal cells derived from type I IL-1 receptor-deficient (IL-1RI-deficient) mice. Reflecting sequential signaling of the cytokines TNF and IL-1, TNF induces stromal cell expression of IL-1 and IL-1RI. These data suggest that TNF regulates RANKL expression via IL-1, and, therefore, IL-1 plays a role in TNF-induced periarticular osteolysis. Consistent with this posture, TNF-stimulated osteoclastogenesis in cultures consisting of WT marrow macrophages and stromal cells exposed to IL-1Ra or in cocultures established with IL-1RI-deficient stromal cells was reduced approximately 50%. The same magnitude of osteoclast inhibition occurred in IL-1RI-deficient mice following TNF administration in vivo. Like TNF, IL-1 directly targeted osteoclast precursors and promoted the osteoclast phenotype in a TNF-independent manner in the presence of permissive levels of RANKL. IL-1 is able to induce RANKL expression by stromal cells and directly stimulate osteoclast precursor differentiation under the aegis of p38 MAPK. Thus, IL-1 mediates the osteoclastogenic effect of TNF by enhancing stromal cell expression of RANKL and directly stimulating differentiation of osteoclast precursors.


Eggshell Types and Their Evolutionary Correlation with Life-History Strategies in Squamates.
The eggshell is an important physiological structure for the embryo. It enables gas exchange, physical protection and is a calcium reserve. Most squamates (lizards, snakes, worm lizards) lay parchment-shelled eggs, whereas only some gekkotan species, a subgroup of lizards, have strongly calcified eggshells. In viviparous (live-bearing) squamates the eggshell is reduced or completely missing (hereafter "shell-less"). Recent studies showed that life-history strategies of gekkotan species differ between species with parchment- and rigid-shelled eggshells. Here we test if the three different eggshell types found in the squamates are also associated with different life-history strategies. We first investigated the influence of the phylogeny on the trait "eggshell type" and on six life-history traits of 32 squamate species. Phylogenetic principal component analysis (pPCA) was then conducted to identify an association between life-history strategies and eggshell types. Finally, we also considered adult weight in the pPCA to examine its potential effect on this association. Eggshell types in squamates show a strong phylogenetic signal at a low taxonomical level. Four out of the six life-history traits showed also a phylogenetic signal (birth size, clutch size, clutches per year and age at female maturity), while two had none (incubation time, maximum longevity). The pPCA suggested an association of life-history strategies and eggshell types, which disappeared when adult weight was included in the analysis. We conclude that the variability seen in eggshell types of squamates is weakly influenced by phylogeny. Eggshell types correlate with different life-history strategies, and mainly reflect differences in adult weights of species.


Bent Ferroelectric Domain Walls as Reconfigurable Metallic-Like Channels.
Use of ferroelectric domain-walls in future electronics requires that they are stable, rewritable conducting channels. Here we demonstrate nonthermally activated metallic-like conduction in nominally uncharged, bent, rewritable ferroelectric-ferroelastic domain-walls of the ubiquitous ferroelectric Pb(Zr,Ti)O3 using scanning force microscopy down to a temperature of 4 K. New walls created at 4 K by pressure exhibit similar robust and intrinsic conductivity. Atomic resolution electron energy-loss spectroscopy confirms the conductivity confinement at the wall. This work provides a new concept in "domain-wall nanoelectronics".


Evaluation of Short-term Mortality of Status Epilepticus and Its Risk Factors.
Status epilepticus (SE) is defined as epileptic seizures of greater than five minutes or more than one seizure within a five minute period without returning to normal consciousness between them. It is a life-threatening condition particularly if treatment is delayed. Previous studies reported age, duration and etiology of SE as primary determinants of mortality. This prospective cross-sectional study performed on the patients with status epilepticus admitted in Rasoul-e-Akram hospital in Tehran. Patients followed at 30th day after SE to assess their living status. Sixty-five patients, (56.9% was male) with 15 to 88 years of age entered the study. Mean duration of SE was 40 minutes and for hospital stay was 7 days. 84.6% of patients responded to treatment and 11 patients (16.9%) died within 30 days after SE. Mortality rate in patients with refractory SE was 70%. Mean interval between SE and death was 11.9 ± 11.7 days. Age, duration of SE and hospital stay, history of head trauma and neurosurgery were not predictors of mortality. Negative history for epilepsy had significantly higher mortality rate. Anoxic encephalopathy increased the mortality rate and response to treatment decreased it. Short-term mortality rate of SE was comparable with most of the previous reports Since our hospital has equipped emergency department, resuscitation and primary treatment of SE is usually start soon, percentage of anoxic encephalopathy is decreased and lower mortality rate is expected. We conclude that early treatment by decrease chance of anoxic encephalopathy, has significant role in outcome of SE.


Exploring structural and electronic effects in three isomers of tris{bis(trifluoromethyl)phenyl}borane: towards the combined electrochemical-frustrated Lewis pair activation of H2.
Three structural isomers of tris{bis(trifluoromethyl)phenyl}borane have been studied as the acidic component of frustrated Lewis pairs. While the 3,5-substituted isomer is already known to heterolytically cleave H2 to generate a bridging-hydride; ortho-substituents in the 2,4- and 2,5-isomers quench such reactivity through electron donation into the vacant boron pz orbital and steric blocking of the boron centre; as shown by electrochemical, structural and computational studies. Electrochemical studies of the corresponding borohydrides identify that the two-electron oxidation of terminal-hydrides occurs at more positive potentials than observed for [HB(C6F5)3](-), while the bridging-hydride oxidizes at a higher potential still, comparable to that of free H2.


Effectiveness of primate seed dispersers for an "oversized" fruit, Garcinia benthamii.
The largest fruits found in tropical forests may depend on complementary seed dispersal strategies. These fruits are dispersed most effectively by megafauna, but populations can persist where megafauna are absent or erratic visitors. Smaller animals often consume these large fruits, but their capacity to disperse these seeds effectively has rarely been assessed. We evaluated the contributions of gibbons (Hylobates lar) and other frugivores in the seed dispersal of the megafaunal fruit Garcinia benthamii, using the SDE (seed dispersal effectiveness) landscape. Gibbons preferentially consumed G. benthamii fruits and were the main seed disperser that we observed. However, gibbons became satiated when availability was high, with 57% of fruits falling to the ground unhandled. Recruitment of seedlings from gibbon-dispersed seeds was also very low. Elephants consumed G. benthamii fruit, but occurred at low density and were rare visitors to the trees. We suggest that gibbons might complement the seed dispersal role of elephants for G. benthamii, allowing limited recruitment in areas (such as the study site) where elephants occur at low density. Fruit availability varied between years; when availability was low, gibbons reliably consumed most of the crop and dispersed some seeds that established seedlings, albeit at low numbers (2.5 seedlings per crop). When fruit availability was high, the fruit supply overwhelmed the gibbons and other arboreal frugivores, ensuring a large abundance of fruit available to terrestrial seed dispersers. Although gibbons effectively dispersed more seeds at these times (20.7 seedlings per crop), there was the potential for elephants to move many more seeds. Complementary seed dispersal strategies may be important for megafaunal fruit, because they ensure that very large fruits are able to benefit from megafaunal dispersal but also persist where this dispersal becomes erratic. However, our data suggest that smaller seed dispersers might not be capable of replacing large dispersers, leading to potential changes in landscape-scale dispersal patterns where megafauna are absent.


Venous thrombosis in patients with short- and long-term central venous catheter-associated Staphylococcus aureus bacteremia.
Infection and thrombosis are important complications of intravascular catheters. The purpose of this study was to determine the incidence of thrombosis in patients with central venous catheter-associated Staphylococcus aureus bacteremia and the utility of physical examination for diagnosing upper extremity or neck venous thrombosis. Prospective observational cohort. Tertiary care facility. In all, 65 consecutive patients with catheter-associated S. aureus bacteremia with central venous catheters of the internal jugular, brachial, or subclavian veins were eligible for participation. From July 1999 through August 2004, enrolled patients underwent physical examination and ultrasonography independently to identify the presence of catheter-associated thrombosis. Study ultrasonograms were interpreted blindly using defined criteria. Outcomes were defined at 12-wk follow-up. A total of 48 patients were enrolled. By ultrasonography, definite or possible thrombosis was present in 34 of 48 patients (71%) in this cohort. Death or recurrent bacteremia occurred in 11/34 (32%) infected patients with thrombosis and two of 14 (14%) infected patients without thrombosis (p = .29). Sensitivity of all physical examination findings, either alone or in combination, was low (< or = 24%). Only engorged veins upon hand elevation and the presence of multiple physical examination abnormalities were specific (100% each). Thrombosis is a common complication of central venous catheter-associated S. aureus bacteremia. Patients with central venous catheter-associated S. aureus bacteremia should undergo ultrasonography to detect thromboses even if the physical examination is normal.


Perspectives on Cognitive Phenotypes and Models of Vascular Disease.
Clinical investigations have established that vascular-associated medical conditions are significant risk factors for various kinds of dementia. And yet, we are unable to associate certain types of vascular deficiencies with specific cognitive impairments. The reasons for this are many, not the least of which are that most vascular disorders are multi-factorial and the development of vascular dementia in humans is often a multi-year or multi-decade progression. To better study vascular disease and its underlying causes, the National Heart, Lung, and Blood Institute of the National Institutes of Health has invested considerable resources in the development of animal models that recapitulate various aspects of human vascular disease. Many of these models, mainly in the mouse, are based on genetic mutations, frequently using single-gene mutations to examine the role of specific proteins in vascular function. These models could serve as useful tools for understanding the association of specific vascular signaling pathways with specific neurological and cognitive impairments related to dementia. To advance the state of the vascular dementia field and improve the information sharing between the vascular biology and neurobehavioral research communities, National Heart, Lung, and Blood Institute convened a workshop to bring in scientists from these knowledge domains to discuss the potential utility of establishing a comprehensive phenotypic cognitive assessment of a selected set of existing mouse models, representative of the spectrum of vascular disorders, with particular attention focused on age, sex, and rigor and reproducibility. The workshop highlighted the potential of associating well-characterized vascular disease models, with validated cognitive outcomes, that can be used to link specific vascular signaling pathways with specific cognitive and neurobehavioral deficits.


Modular skeletal evolution in sticklebacks is controlled by additive and clustered quantitative trait Loci.
Understanding the genetic architecture of evolutionary change remains a long-standing goal in biology. In vertebrates, skeletal evolution has contributed greatly to adaptation in body form and function in response to changing ecological variables like diet and predation. Here we use genome-wide linkage mapping in threespine stickleback fish to investigate the genetic architecture of evolved changes in many armor and trophic traits. We identify >100 quantitative trait loci (QTL) controlling the pattern of serially repeating skeletal elements, including gill rakers, teeth, branchial bones, jaws, median fin spines, and vertebrae. We use this large collection of QTL to address long-standing questions about the anatomical specificity, genetic dominance, and genomic clustering of loci controlling skeletal differences in evolving populations. We find that most QTL (76%) that influence serially repeating skeletal elements have anatomically regional effects. In addition, most QTL (71%) have at least partially additive effects, regardless of whether the QTL controls evolved loss or gain of skeletal elements. Finally, many QTL with high LOD scores cluster on chromosomes 4, 20, and 21. These results identify a modular system that can control highly specific aspects of skeletal form. Because of the general additivity and genomic clustering of major QTL, concerted changes in both protective armor and trophic traits may occur when sticklebacks inherit either marine or freshwater alleles at linked or possible "supergene" regions of the stickleback genome. Further study of these regions will help identify the molecular basis of both modular and coordinated changes in the vertebrate skeleton.


Role of Iodine in Metabolism.
The natural resources of iodine are seawater, seaweeds and saltpeter-nitrate deposits in Chile. Over 1/3 of the global population is exposed to iodine deficiency, especially in the mountains. Iodine is a component of the thyroid hormones and a strong antioxidant with electric potential of -0.54 V. Iodine as iodide is taken up by the thyroid gland, gastric mucosa, salivary glands and mammary glands in pregnant and breast-feeding women. The transport of iodine to the thyroid gland is regulated by specific enzymes: Natrium Iodine Symporter, Na+/K+ATPase, Pendrin and Apical Iodine Transporter. In the thyrocytes, the thyroid hormones biosynthesis is carried out by iodization of tyrosine to T3 and T4. Secretion of T3 and T4 is regulated by TSH. On the tissue level, the active hormones are T3 and its derivative thyroamine. The most important target is the cardiac muscle, where T3 action results in an increase in the inotropic action and thyroamines exert a negative inotropic and chronotropic effects. The consequences of iodine deficiency are endemic goiter, irreversible brain damage, cretinism, impaired thyroid function and thyroid, gastric and mammary glands cancers. In 1994, the World Health Organization proposed the main strategy for iodine prophylaxis, i.e. Universal Salt Iodization. In Poland, a new model of iodine prophylaxis was introduced in 1996; the model includes obligatory iodization of household salt and neonate formulas and recommendation to take an additional daily dose of iodine for pregnant and breast-feeding women. This model allowed for eliminating endemic goiter in schoolchildren, eradicating cretinism in mountainous areas, and markedly diminished thyroid and gastric cancer incidence. In 2002, WHO classified Poland as a country with a proper daily iodine intake on the population level. No relevant patents were reported for this WHO report.


Prioritising patients for bariatric surgery: building public preferences from a discrete choice experiment into public policy.
To derive priority weights for access to bariatric surgery for obese adults, from the perspective of the public. Australian public hospital system. Adults (N=1994), reflecting the age and gender distribution of Queensland and South Australia. A discrete choice experiment in which respondents indicated which of two individuals with different characteristics should be prioritised for surgery in repeated hypothetical choices. Potential surgery recipients were described by seven key characteristics or attributes: body mass index (BMI), presence of comorbid conditions, age, family history, commitment to lifestyle change, time on the surgical wait list and chance of maintaining weight loss following surgery. A multinomial logit model was used to evaluate preferences and derive priority weights (primary analysis), with a latent class model used to explore respondent characteristics that were associated with variation in preference across the sample (see online supplementary analysis). A preference was observed to prioritise individuals who demonstrated a strong commitment to maintaining a healthy lifestyle as well as individuals categorised with very severe (BMI≥50 kg/m2) or (to a lesser extent) severe (BMI≥40 kg/m2) obesity, those who already have obesity-related comorbidity, with a family history of obesity, with a greater chance of maintaining weight loss or who had spent a longer time on the wait list. Lifestyle commitment was considered to be more than twice as important as any other criterion. There was little tendency to prioritise according to the age of the recipient. Respondent preferences were dependent on their BMI, previous experience with weight management surgery, current health state and education level. This study extends our understanding of the publics' preferences for priority setting to the context of bariatric surgery, and derives priority weights that could be used to assist bodies responsible for commissioning bariatric services.


A Novel, Optimized Method to Accelerate the Preparation of Injectable Poly-L-Lactic Acid by Sonication.
Current consensus for preparing injectable poly-L-lactic acid (PLLA) suggests adequate hydration (less than equal to 2-24 hours of reconstitution) of the lyophilized particles before injection, but the volume of reconstitution and the duration of hydration time varies. This study established a method to evaluate the distribution of PLLA particles after hydration and found that longer hydration time increased the effective portion (particles less than 60 μm) of PLLA products. Further investigation of the feasibility of reconstitution with sonication revealed that 2-hour hydration of PLLA powders with additional 5-minute-sonication could yield a comparable particle distribution with 48-hour-hydration of PLLA. Moreover, adding lidocaine into the diluent did not alter the distribution of PLLA particles. We proposed a new, feasible and efficient method of preparing PLLA injectable products: 2-hour hydration of the powders, sonication of the bottle or vial containing PLLA products for at least 5 minutes, and finalization with 1-2 mL of lidocaine immediately before injection. J Drugs Dermatol. 2018;17(8):894-898.


Significance of axillary lymph node metastasis in primary breast cancer.
Axillary lymph node status is the single most important prognostic variable in the management of patients with primary breast cancer. Yet, it is not known whether metastasis to the axillary nodes is simply a time-dependent variable or also a marker for a more aggressive tumor phenotype. The purpose of this study was to determine whether nodal status at initial diagnosis predicts outcome after relapse and therefore also serves as a marker of breast cancer phenotype. Survival experience after first relapse in 1,696 primary breast cancer cases was analyzed using Cox proportional hazards regression. The following explanatory variables and their first-order interactions were considered: number of axillary lymph nodes involved (zero v one to three v four or more), hormone receptor status (any estrogen receptor [ER] negativity v ER negativity/progesterone receptor positivity v other ER positivity), primary tumor size (< 2 cm v 2 to 5 cm v > 5 cm), site of relapse (locoregional v distant), disease-free interval (< 1.5 years v 1.5 to 3 years v > 3 years), adjuvant endocrine therapy (none v any), adjuvant chemotherapy (none v any), and menopausal status (pre-, peri-, or postmenopausal). Axillary lymph node status, site of relapse, and hormone receptor status were all highly significant as main effects in the model. After adjustment for other variables, disease-free interval alone was only modestly significant but interacted with nodal status. After disease-free interval, hormone receptor status, and site of relapse were accounted for, survival after relapse was poorer in node-positive cases, when compared with node-negative cases. The hazard ratios for patients with one to three and four or more involved nodes were 1.2 (95% confidence interval [CI], 0.8 to 1.9) and 2.5 (95% CI, 1.8 to 3.4), respectively. Patients with four or more involved nodes at initial diagnosis have a significantly worse outcome after relapse than node-negative cases, regardless of the duration of the disease-free interval. We conclude that nodal metastasis is not only a marker of diagnosis at a later point in the natural history of breast cancer but also a marker of an aggressive phenotype.


Membrane destruction and phospholipid extraction by using two-dimensional MoS2 nanosheets.
The interaction of two-dimensional (2D) nanomaterials and bacterial membranes has attracted tremendous attention in antibacterial applications. Various peculiarities of 2D nanomaterials may lead to multiple mechanisms of their interactions with membranes. Here, we investigated the interaction between molybdenum disulfide (MoS2) nanosheets and the bacterial membrane by using both theoretical and experimental approaches. Molecular dynamics simulation presented that MoS2 nanosheets can disrupt the structure of the lipid membrane by making dents on its surface and extracting phospholipid molecules to reduce the integrity of the membrane. This is attributed to the combination of the dispersion interaction of lipid tails with S atoms and the electrostatic interactions of lipid head groups with the Mo and S atoms in the lateral edges of the MoS2 nanosheet. Scanning electron microscopy and transmission electron microscopy confirmed the dents and the destruction of the cell membrane, which would lead to the loss of cytoplasm and the death of bacteria. It should be noted that the phenomenon where MoS2 induces a dent is different from the direct insertion of graphene-based nanomaterials, which might be due to the thicker and stiffer structure of MoS2. Therefore, we believe that the molecular interactions of 2D nanomaterials with bacterial membranes should be highly correlated with their structural characteristics. This newly discovered mechanism of MoS2 nanomaterials to disrupt the cell membrane may promote the application of transition metal dichalcogenide (TMD) nanomaterials in designing remarkable antibacterial materials in the near future.


Resolution for spatial segregation and spatial localization by motion signals.
We investigated two types of spatial resolution for perceiving motion-defined contours: grating acuity, the capacity to discriminate alternating stripes of opposed motion from transparent bi-directional motion; and alignment acuity, the capacity to localize the position of motion-defined edges with respect to stationary markers. For both tasks the stimuli were random noise patterns, low-pass filtered in the spatial dimension parallel to the motion. Both grating and alignment resolution varied systematically with spatial frequency cutoff and speed. Best performance for grating resolution was about 10 c/deg (for unfiltered patterns moving at 1-4 deg/s), corresponding to a stripe resolution of about 3'. Grating resolution corresponds well to estimates of smallest receptive field size of motion units under these conditions, suggesting that opposing signals from units with small receptive fields (probably located in V1) are contrasted efficiently to define edges. Alignment resolution was about 2' at best, under similar conditions. Whereas alignment judgment based on luminance-defined edges is typically 3-10 times better than resolution, alignment based on motion-defined edges is only 1.1-1.5 times better, suggesting motion contours are less effectively encoded than luminance contours.


Molecular interactions with mercury in the kidney.
Mercury is unique among the heavy metals in that it can exist in several physical and chemical forms, including elemental mercury, which is a liquid at room temperature. All forms of mercury have toxic effects in a number of organs, especially in the kidneys. Within the kidney, the pars recta of the proximal tubule is the most vulnerable segment of the nephron to the toxic effects of mercury. The biological and toxicological activity of mercurous and mercuric ions in the kidney can be defined largely by the molecular interactions that occur at critical nucleophilic sites in and around target cells. Because of the high bonding affinity between mercury and sulfur, there is particular interest in the interactions that occur between mercuric ions and the thiol group(s) of proteins, peptides and amino acids. Molecular interactions with sulfhydryl groups in molecules of albumin, metallothionein, glutathione, and cysteine have been implicated in mechanisms involved in the proximal tubular uptake, accumulation, transport, and toxicity of mercuric ions. In addition, the susceptibility of target cells in the kidneys to the injurious effects of mercury is modified by a number of intracellular and extracellular factors relating to several thiol-containing molecules. These very factors are the theoretical basis for most of the currently employed therapeutic strategies. This review provides an update on the current body of knowledge regarding the molecular interactions that occur between mercury and various thiol-containing molecules with respect to the mechanisms involved in the renal cellular uptake, accumulation, elimination, and toxicity of mercury.


Phylogeographic structure across one of the largest intact tropical savannahs: Molecular and morphological analysis of Australia's iconic frilled lizard Chlamydosaurus kingii.
The spectacular threat display of the savannah specialist Australo-Papuan frilled lizards has made them one of the world's most iconic reptiles. They are increasingly used as a model system for research in evolutionary biology and ecology but little is known of their population structure. Their distribution across northern Australia and southern New Guinea also provides an opportunity to examine biogeographic patterns as they relate to the large-scale movement of savannah habitat during the Plio/Pleistocene and the associated increase in aridity. We generated sequence data for one mitochondrial and four nuclear DNA loci (5052 base pairs) for 83 frilled lizards sampled throughout their range. We also quantified body proportion variation for 279 individuals. Phylogenetic analyses based on maximum likelihood and Bayesian species-tree methods revealed three shallow clades that replace each other across the monsoon tropics. We found the expected pattern of male biased sexual size dimorphism in both maximum body size and head size but there was no sexual dimorphism in overall body shape or in frill size, relative to head size, supporting the hypothesis that the frill is used primarily as a threat display rather than a sexual display. The genetic clades are broadly consistent with known clinal variation in frill color that gradually shifts from west to east (red, orange, yellow/white) but otherwise show little morphological differentiation in body proportion measures. The biogeographic breaks between clades occur at the Carpentaria Gap and the lowlands surrounding the Ord River, and our ecological niche modeling predicts lower habitat suitability for C. kingii in these regions. While this biogeographic pattern is consistent with numerous other taxonomic groups in northern Australia, the overall low genetic diversity in frilled lizards across the entire monsoon tropics and southern New Guinea contrasts starkly to patterns seen in other terrestrial vertebrates. Extremely low intra-clade genetic diversity over vast geographic areas is indicative of recent gene flow that would likely have been facilitated by widespread savannah during interglacials, or alternatively may reflect population bottlenecks induced by extreme aridity during Pleistocene glacials. The shallow divergence between Australian and New Guinean samples is consistent with recent connectivity between Australia and New Guinea that would have been possible via a savannah corridor across the Torres Strait. Based on our molecular and morphological data, we do not support taxonomic recognition of any of the frilled lizard clades and instead consider C. kingii a single species with shallow phylogeographic structure and clinal variation in frill color.


Natural course of pain and disability following primary lumbar discectomy: protocol for a systematic review and meta-analysis.
Knowledge about the natural clinical course is needed to improve understanding of recovery postsurgery as outcome is poor for some patients. Knowledge of the natural clinical course of symptoms and disability will inform optimal timing and the nature of rehabilitation intervention. The objective of this study is to provide first evidence synthesis investigating the natural clinical course of disability and pain in patients aged >16 years post primary lumbar discectomy. A systematic review and data synthesis will be conducted. Prospective cohorts that include a well-defined inception cohort (point of surgery) of adult participants who have undergone primary lumbar discectomy/microdiscectomy will be included. Outcomes will include measurements reported on 1 or more outcomes of disability and pain, with a baseline presurgery measurement. Following development of the search strategy, 2 reviewers will independently search information sources, assess identified studies for inclusion, extract data and assess risk of bias. A third reviewer will mediate on any disagreement at each stage. The search will employ sensitive topic-based strategies designed for each database from inception to 31 January 2016. There will be no language or geographical restrictions. Risk of bias will be assessed using a modified QUality In Prognostic Studies (QUIPS) tool . Data will be extracted for time points where follow-up was at least 80%. Means and 95% CIs will be plotted over time for pain and disability. All results will be reported in the context of study quality. This review will provide the first rigorous summary of the course of pain and disability across all published prospective cohorts. The findings will inform our understanding of when to offer and how to optimise rehabilitation following surgery. Results will be published in an open access journal. The study raises no ethical issues. CRD42015020806.


STAT3-mediated signaling in the determination of rod photoreceptor cell fate in mouse retina.
The purpose of this study was to determine the intracellular pathways by which ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) negatively regulate the development of rod photoreceptors in the mouse retina. Retina explant cultures derived from timed-pregnant CD-1 mice were used to monitor rod photoreceptor differentiation. CNTF was used to activate the signal transducer and activator of transcription (STAT)-3 and mitogen-activated protein kinase (MAPK) signal transduction pathways. Activation of STAT3 and MAPK were manipulated by using dominant-negative STAT3 recombinant adenoviruses and a specific inhibitor of MAPK, respectively. Explanted retinas were harvested at distinct time points and processed for immunohistochemistry. Blocking of the MAPK pathway by the MAPK inhibitor PD98059 did not affect normal development of rods in retina explants or the suppression of their appearance by treatment with CNTF. In contrast, activated STAT3 was necessary for suppression of the rod cell fate decision. A deficiency of the STAT3 pathway induced by a dominant negative STAT3 abolished inhibition of rod development by CNTF. These results indicate that STAT3, but not MAPK, can critically regulate photoreceptor development during mouse retina development.


Effects of homocysteine on adipocyte differentiation and CD36 gene expression in 3T3-L1 adipocytes.
The aim of this study was to investigate the effects of homocysteine (Hcy), a risk factor for cardiovascular diseases, hypertension, stroke and obesity, on expression of CD36 that regulates uptake of oxidized low-density lipoprotein (Ox-LDL) by adipocytes and differentiation of 3T3-L1 cells to adipocytes. Cell viability was determined using MTT assay, and density of triglycerides were measured with Oil Red O staining. The expression levels of CD36 were analyzed using SYBR green assay by quantitative RT-PCR. Our results showed that the addition of Hcy inhibited differentiation of 3T3-L1 preadipocytes in a dose-dependent manner without a significant cell toxicity (p < 0.05). Percentage CD36 gene expression increased in the Hcy treatment groups, but not statistically significantly (p > 0.05) compared to differentiated adipocytes. Hcy reduced adipocyte differentiation, but had no effect on the expression level of CD36 in vitro conditions. The effect of Hcy on uptake and clearance of Ox-LDL by adipose tissue now needs to be investigated in vivo.


Mechanical pressure versus intrinsic effects of hypertension on large arteries in humans.
Brachial artery diameter and compliance were measured in 23 normotensive control subjects and 49 hypertensive patients. The results were compared in isobaric conditions by a modeling analysis extrapolating from the measured data a short segment of the pressure-diameter and pressure-compliance curves in the artery. A logarithmic diameter-pressure function was used as well as measurements of brachial artery blood pressure and lumen diameter (by pulsed Doppler), and of brachial-to-radial pulse wave velocity (by mechanography). The measured values of diameter and compliance in the hypertensive patients were 109% and 63%, respectively, of the control group values. By extrapolating the data via the model at the same pressure level in all subjects (the average level of mean blood pressure of the two groups), the isobaric values of diameter and compliance in the hypertensive patients were 107% and 81%, respectively, of the control group values. Overall, measured isobaric diameters and measured compliance correlated with systolic, diastolic, and mean blood pressure values (p less than 0.001), whereas isobaric compliance correlated only with systolic (p less than 0.05) and pulse (p less than 0.01) pressure values. Thus, the increased diameter and reduced compliance of the brachial artery observed in hypertensive humans cannot be attributed solely to the stretching effect of elevated blood pressure, but also to intrinsic alteration of the arterial walls. These could represent either adaptative structural or functional changes secondary to the chronic increase in arterial pressure, or primary abnormalities of the vessel wall.