Examining the mental health outcomes of peer-led school-based interventions on young people aged between 4 and 18 years old: a systematic review protocol.
Recent estimates suggest that one in ten young people worldwide experiences a diagnosable mental health disorder, with many more suffering subsyndromal levels of psychological distress. As young people spend much of their time in schools, the role of educational settings in the delivery of mental health provision is increasingly recognised. Advances in neurodevelopmental research have highlighted the important and complex role of peer influence on adolescent behaviours, suggesting peer-led support schemes have high potential utility. Schools worldwide have implemented peer-led interventions with mixed results, but the global evidence base on their effectiveness remains limited. This systematic review aims to examine the evidence base of the outcomes of school-based peer-led interventions on the mental health of young people aged 4-18. Eligible studies will be randomised controlled trials and observational studies that report on the mental health outcomes of a peer-led school-based intervention. Eligible participants will be aged 4-18 and will be current students of the intervention school. Individual- and group-based interventions will be included. The following 11 databases will be screened based upon their reach in healthcare and education: PsycINFO, MEDLINE, EMBASE, CINAHL, CENTRAL, BEI, Scopus, Web of Science, ERIC, SSCI and Social Care Online. There will be no restriction placed on publication period, original language or country of publication. Papers will be systematically screened for eligibility by two review authors. Data will be presented as a descriptive report. A meta-analysis will be carried out if a subset of studies allows, given the anticipated high levels of heterogeneity. This systematic review will be the first to synthesise the global evidence on the mental health outcomes of peer-led interventions for children and adolescents in a school setting. It will analyse the available data in order to understand the role of these interventions in schools, inform future developers of peer support programmes and identify gaps in current research. This review will be of value to policy makers, health and education services, researchers and those involved in delivering peer support initiatives. PROSPERO CRD42018116243.


Different T helper cell types and antibody isotypes generated by saline and gene gun DNA immunization.
Several routes and methods of DNA immunization have been shown to generate Ab, Th cells, and CTL responses. However, few studies have directly compared the immune responses generated by different routes and methods of DNA immunization. Utilizing an influenza hemagglutinin (H1)-expressing plasmid, we compared the immune response produced by saline injection of DNA into skin or muscle, and gene gun immunization of skin or muscle. We found that saline-DNA immunization raised a predominantly Th1 response with mostly IgG2a anti-H1 Ab, while gene gun DNA immunization produced a predominantly Th2 response with mostly IgG1 anti-H1 Abs. These distinct types of immune responses were generated by the method, not the route, of DNA immunization. The initial immunization established the Th cell-type of the immune response. The Th cell-type did not change with further DNA immunizations by the same or the alternate method, or after a viral challenge. The ability to generate different Th types was not due to differences in the doses of DNA used in saline and gene gun DNA immunization. These findings have important implications for vaccine design and studies of the mechanism of Th cell differentiation.


Observation of laser-induced stress waves and mechanism of structural changes inside rock-salt crystals.
The structural changes inside rock-salt crystals after femtosecond (fs) laser irradiation are investigated using a microscopic pump-probe technique and an elastic simulation. The pump-probe imaging shows that a squircle-shaped stress wave is generated after the fs laser irradiation as a result of the relaxation of thermal stress in the photoexcited region. Pump-probe crossed-Nicols imaging and elastic simulation elucidate that shear stresses and tensile stresses are concentrated in specific regions during the propagation of the stress wave. The shear stresses and tensile stresses observed in this study can explain the characteristic laser-induced structural changes inside rock-salt crystals.


How protein coronas determine the fate of engineered nanoparticles in biological environment.
Nanomedicine is a booming medical field that utilises nanoparticles (NPs) for the development of medicines, medical devices, and diagnostic tools. The behaviour of NPs in vivo may be quite complex due to their interactions with biological molecules. These interactions in biological fluids result in NPs being enveloped by dynamic protein coronas, which serve as an interface between NPs and their environment (blood, cell, tissue). How will the corona interact with this environment will depend on the biological, chemical, and physical properties of NPs, the properties of the proteins that make the corona, as well as the biological environment. This review summarises the main characteristics of protein corona and describes its dynamic nature. It also presents the most common analytical methods to study the corona, including examples of protein corona composition for the most common NPs used in biomedicine. This knowledge is necessary to design NPs that will create a corona with a desired efficiency and safety in clinical use.


Mechanobehavior and Ontogenesis of the Temporomandibular Joint.
Craniofacial secondary cartilages of the mandibular condyle and temporomandibular joint (TMJ) eminence grow in response to the local mechanical environment. The intervening TMJ disc distributes normal loads over the cartilage surfaces and provides lubrication. A better understanding of the mechanical environment and its effects on growth, development, and degeneration of the TMJ may improve treatments aimed at modifying jaw growth and preventing or reversing degenerative joint disease (DJD). This review highlights data recorded in human subjects and from computer modeling that elucidate the role of mechanics in TMJ ontogeny. Presented data provide an approximation of the age-related changes in jaw-loading behaviors and TMJ contact mechanics. The cells of the mandibular condyle, eminence, and disc respond to the mechanical environment associated with behaviors and ultimately determine the TMJ components' mature morphologies and susceptibility to precocious development of DJD compared to postcranial joints. The TMJ disc may be especially prone to degenerative change due to its avascularity and steep oxygen and glucose gradients consequent to high cell density and rate of nutrient consumption, as well as low solute diffusivities. The combined effects of strain-related hypoxia and limited glucose concentrations dramatically affect synthesis of the extracellular matrix (ECM), which limit repair capabilities. Magnitude and frequency of jaw loading influence this localized in situ environment, including stem and fibrocartilage cell chemistry, as well as the rate of ECM mechanical fatigue. Key in vivo measurements to characterize the mechanical environment include the concentration of work input to articulating tissues, known as energy density, and the percentage of time that muscles are used to load the jaws out of a total recording time, known as duty factor. Combining these measurements into a mechanobehavioral score and linking these to results of computer models of strain-regulated biochemical events may elucidate the mechanisms responsible for growth, maintenance, and deterioration of TMJ tissues.


2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative.
To develop criteria for the classification of macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (JIA). A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of 28 experts was first asked to classify 428 patient profiles as having or not having MAS, based on clinical and laboratory features at the time of disease onset. The 428 profiles comprised 161 patients with systemic JIA-associated MAS and 267 patients with a condition that could potentially be confused with MAS (active systemic JIA without evidence of MAS, or systemic infection). Next, the ability of candidate criteria to classify individual patients as having MAS or not having MAS was assessed by evaluating the agreement between the classification yielded using the criteria and the consensus classification of the experts. The final criteria were selected in a consensus conference. Experts achieved consensus on the classification of 391 of the 428 patient profiles (91.4%). A total of 982 candidate criteria were tested statistically. The 37 best-performing criteria and 8 criteria obtained from the literature were evaluated at the consensus conference. During the conference, 82% consensus among experts was reached on the final MAS classification criteria. In validation analyses, these criteria had a sensitivity of 0.73 and a specificity of 0.99. Agreement between the classification (MAS or not MAS) obtained using the criteria and the original diagnosis made by the treating physician was high (κ = 0.76). We have developed a set of classification criteria for MAS complicating systemic JIA and provided preliminary evidence of its validity. Use of these criteria will potentially improve understanding of MAS in systemic JIA and enhance efforts to discover effective therapies, by ensuring appropriate patient enrollment in studies.


Posterior cerebral artery infarcts and semantic category dissociations: a study of 28 patients.
In this study we analysed the relationship between damage in the territory of the posterior cerebral artery and semantic knowledge, with special reference to category dissociations. Twenty-eight posterior cerebral artery stroke patients (18 left, 8 right and 2 bilateral posterior cerebral artery infarctions) completed a neuropsychological battery aimed at assessing semantic knowledge. The battery included picture naming, word-picture matching, a verbal semantic questionnaire and a picture reality decision task. For each participant, the lesion was reconstructed on the basis of MRI images, and was classified according to the involvement of the areas supplied by posterior cerebral artery. Defective naming scores were observed in 12 of 18 left posterior cerebral artery cases (67%), four of eight right posterior cerebral artery cases (50%), and one of two bilateral posterior cerebral artery cases (50%). Only in the bilateral posterior cerebral artery lesion case did we observe the pattern expected in pure visual agnosia, i.e. poor picture naming, poor picture reality decision, and normal verbal semantic questionnaire. Nine left posterior cerebral artery cases and two right posterior cerebral artery cases presented with poor performance on both the picture naming task and the verbal semantic questionnaire, thus suggesting semantic impairment. For 5 of the 12 left posterior cerebral artery patients who fared poorly on the naming task, biological stimuli (overall) were significantly more impaired than artifacts. In three of these five subjects, performance on plant-life stimuli was significantly less accurate than that on animals. A further left posterior cerebral artery patient presented a disproportionate impairment on plant-life stimuli only on the word-picture matching and on the questionnaire. The patterns of performance in these subjects suggest that the observed dissociations originated at the semantic level. Among left posterior cerebral artery patients, a naming deficit only occurred when damage to the fusiform gyrus extended anterior to Talairach's y-coordinate -50, and a disproportionate impairment of biological categories only when the lesion extended anterior to y = -32.5. Results show that the semantic deficit for the category of plant life is a genuine cognitive pattern, and does not depend on loss of colour knowledge. The contrast of left posterior cerebral artery strokes and herpes simplex encephalitis cases shows that the neural substrates for the semantic representation of plant life and animals are, at least in part, distinct. Middle and posterior portions of the left fusiform are crucial for the representation of plant-life knowledge, whereas left anterior temporal areas are more crucial than left posterior and basal temporal areas for the representation of knowledge about animals.


Co-occurrence of potentially preventable factors in 256 dog bite-related fatalities in the United States (2000-2009).
To examine potentially preventable factors in human dog bite-related fatalities (DBRFs) on the basis of data from sources that were more complete, verifiable, and accurate than media reports used in previous studies. Prospective case series. 56 DBRFs occurring in the United States from 2000 to 2009. DBRFs were identified from media reports and detailed histories were compiled on the basis of reports from homicide detectives, animal control reports, and interviews with investigators for coding and descriptive analysis. Major co-occurrent factors for the 256 DBRFs included absence of an able-bodied person to intervene (n = 223 [87.1%]), incidental or no familiar relationship of victims with dogs (218 [85.2%]), owner failure to neuter dogs (216 [84.4%]), compromised ability of victims to interact appropriately with dogs (198 [77.4%]), dogs kept isolated from regular positive human interactions versus family dogs (195 [76.2%]), owners' prior mismanagement of dogs (96 [37.5%]), and owners' history of abuse or neglect of dogs (54 [21.1%]). Four or more of these factors co-occurred in 206 (80.5%) deaths. For 401 dogs described in various media accounts, reported breed differed for 124 (30.9%); for 346 dogs with both media and animal control breed reports, breed differed for 139 (40.2%). Valid breed determination was possible for only 45 (17.6%) DBRFs; 20 breeds, including 2 known mixes, were identified. Most DBRFs were characterized by coincident, preventable factors; breed was not one of these. Study results supported previous recommendations for multifactorial approaches, instead of single-factor solutions such as breed-specific legislation, for dog bite prevention.


Image registration of pre-procedural MRI and intra-procedural CT images to aid CT-guided percutaneous cryoablation of renal tumors.
To determine whether a non-rigid registration (NRR) technique was more accurate than a rigid registration (RR) technique when fusing pre-procedural contrast-enhanced MR images to unenhanced CT images during CT-guided percutaneous cryoablation of renal tumors. Both RR and NRR were applied retrospectively to 11 CT-guided percutaneous cryoablation procedures performed to treat renal tumors (mean diameter; 23 mm). Pre-procedural contrast-enhanced MR images of the upper abdomen were registered to unenhanced intra-procedural CT images obtained just prior to the ablation. RRs were performed manually, and NRRs were performed using an intensity-based approach with affine and Basis-Spline techniques used for modeling displacement. Registration accuracy for each technique was assessed using the 95% Hausdorff distance (HD), Fiducial Registration Error (FRE) and the Dice Similarity Coefficient (DSC). Statistical differences were analyzed using a two-sided Student's t-test. Time for each registration technique was recorded. Mean 95% HD (1.7 mm), FRE (1.7 mm) and DSC (0.96) using the NRR technique were significantly better than mean 95% HD (6.4 mm), FRE (5.0 mm) and DSC (0.88) using the RR technique (P < 0.05 for each analysis). Mean registration times of NRR and RR techniques were 15.2 and 5.7 min, respectively. The non-rigid registration technique was more accurate than the rigid registration technique when fusing pre-procedural MR images to intra-procedural unenhanced CT images. The non-rigid registration technique can be used to improve visualization of renal tumors during CT-guided cryoablation procedures.


Nicotinic acetylcholine receptors contribute to learning-induced metaplasticity in the hippocampus.
Hippocampal learning is thought to induce metaplasticity, which can facilitate subsequent learning. Administered at single low doses, the N-methyl-d-aspartate-type glutamate receptor antagonist memantine predominantly blocks α7 nicotinic acetylcholine receptors (α7 nAChRs). Placebo-controlled administration of a single low dose of memantine in a pharmaco-fMRI experiment may thus help characterize the role of α7 nAChRs in hippocampal metaplasticity. We hypothesized that if α7 nAChRs contribute to learning-induced metaplasticity in the hippocampus, blockade of these receptors with low-dose memantine would selectively interfere with a facilitation of subsequent learning without impairing hippocampal learning per se. To specifically test this hypothesis, we devised a randomized controlled trial in which healthy volunteers were administered a 20-mg single oral dose of memantine or placebo and scanned on three subsequent runs of a hippocampal learning task. Our results indicate no discrepancies in behavioral learning between low-dose memantine- and placebo-treated participants in the first and second run of this task. In the third run, however, only the placebo-treated group showed facilitated behavioral learning, an effect paralleled by decreased neural responses in the hippocampal cornu ammonis region. Our findings suggest that blockade of α7 nAChRs selectively interfered with a learning-induced facilitation of subsequent learning while leaving unimpaired hippocampal learning per se. Taken together, our results provide support for a relevant contribution of α7 nAChRs to learning-associated metaplasticity in the hippocampus.


The population genomics of repeated evolution in the blind cavefish Astyanax mexicanus.
Distinct populations of Astyanax mexicanus cavefish offer striking examples of repeatable convergence or parallelism in their independent evolutions from surface to cave phenotypes. However, the extent to which the repeatability of evolution occurred at the genetic level remains poorly understood. To address this, we first characterized the genetic diversity of 518 single-nucleotide polymorphisms (SNPs), obtained through RAD tag sequencing and distributed throughout the genome, in seven cave and three groups of surface populations. The cave populations represented two distinct lineages (old and new). Thirty-one SNPs were significantly differentiated between surface and old cave populations, two SNPs were differentiated between surface and new cave populations, and 44 SNPs were significantly differentiated in both old and new cave populations. In addition, we determined whether these SNPs map to the same locations of previously described quantitative trait loci (QTL) between surface and cave populations. A total of 25 differentiated SNPs co-map with several QTL, such as one containing a fibroblast growth factor gene (Fgf8) involved in eye development and lens size. Further, the identity of many SNPs that co-mapped with QTL was the same in independently derived cave populations. These conclusions were further confirmed by haplotype analyses of SNPs within QTL regions. Our findings indicate that the repeatability of evolution at the genetic level is substantial, suggesting that ancestral standing genetic variation significantly contributed to the population genetic variability used in adaptation to the cave environment.


Burden and depressive symptoms associated with adult-child caregiving for individuals with heart failure.
The primary purpose of this study was to investigate adult-child caregiver burden in heart failure (HF) patients. Secondary purpose of the study was to identify the possible influencing factors for caregiver burden and depressive symptoms in a young adult-child caregiver group. A total of 138 adult-child caregivers and 138 patients with HF participated in this study. Caregivers' burden, depressive symptoms, and anxiety levels were assessed by using Zarit Caregiver Burden Scale (ZCBS), Beck Depression Inventory, and State-Trait Anxiety Inventory, respectively. The mean ZCBS scores of the female caregivers were significantly higher than male caregivers. Approximately one-third of the adult-child caregivers had at least mild depressive symptoms. Caregivers with higher depressive symptoms had higher levels of caregiver burden. There were positive correlations between caregiving time, severity of depressive symptoms, and perceived caregiver burden. There was a negative correlation between education level of caregivers and perceived caregiver burden. Age, socioeconomic level, and marital status of patients were affecting factors for depressive symptoms in caregivers. Among caregiver characteristics, gender, marital status, and ZCBS scores seem to influence the depression in caregivers. The study findings suggest significant levels of burden and depressive symptoms even in adult-child caregivers of HF patients.


An "epithelial" preparation from the canine gastric mucosa: responses to secretagogues.
Isolated mucosal preparations from the stomach are generally obtained by removing the external muscle layers, leaving intact the muscularis mucosae. By carefully dissecting off the muscularis mucosa, we have obtained "epithelial" preparations from the canine stomach. Such preparations responded to secretagogues, histamine, pentagastrin, and a cholinergic agonist (cis-2-methyl 4-dimethylaminomethyl 1,3-dioxolane methiodide). Epithelial preparations were, in general, more sensitive than mucosal preparations. Of the three secretagogues tested, histamine was the most consistent stimulant, with well-sustained responses being noted. Responses to the other agonists were more variable. Pentagastrin produced brief but explosive increases in acid output.


Regenerative Agriculture: An agronomic perspective.
Agriculture is in crisis. Soil health is collapsing. Biodiversity faces the sixth mass extinction. Crop yields are plateauing. Against this crisis narrative swells a clarion call for Regenerative Agriculture. But what is Regenerative Agriculture, and why is it gaining such prominence? Which problems does it solve, and how? Here we address these questions from an agronomic perspective. The term Regenerative Agriculture has actually been in use for some time, but there has been a resurgence of interest over the past 5 years. It is supported from what are often considered opposite poles of the debate on agriculture and food. Regenerative Agriculture has been promoted strongly by civil society and NGOs as well as by many of the major multi-national food companies. Many practices promoted as regenerative, including crop residue retention, cover cropping and reduced tillage are central to the canon of 'good agricultural practices', while others are contested and at best niche (e.g. permaculture, holistic grazing). Worryingly, these practices are generally promoted with little regard to context. Practices most often encouraged (such as no tillage, no pesticides or no external nutrient inputs) are unlikely to lead to the benefits claimed in all places. We argue that the resurgence of interest in Regenerative Agriculture represents a re-framing of what have been considered to be two contrasting approaches to agricultural futures, namely agroecology and sustainable intensification, under the same banner. This is more likely to confuse than to clarify the public debate. More importantly, it draws attention away from more fundamental challenges. We conclude by providing guidance for research agronomists who want to engage with Regenerative Agriculture.


Indoor Scene Reconstruction Using Near-Light Photometric Stereo.
We propose a novel framework for photometric stereo (PS) under low-light conditions using uncalibrated near-light illumination. It operates on free-form video sequences captured with a minimalistic and affordable setup. We address issues such as albedo variations, shadowing, perspective projections, and camera noise. Our method uses specular spheres detected with a perspective-correcting Hough transform to robustly triangulate light positions in the presence of outliers via a least-squares approach. Furthermore, we propose an iterative reweighting scheme in combination with an ℓp-norm minimizer to robustly solve the calibrated near-light PS problem. In contrast to other approaches, our framework reconstructs depth, albedo (relative to light source intensity), and normals simultaneously and is demonstrated on synthetic and real-world scenes.


Chemoprevention of lung cancer: prospects and disappointments in human clinical trials.
Decreasing the risk of lung cancer, or preventing its development in high-risk individuals, would have a huge impact on public health. The most effective means to decrease lung cancer incidence is to eliminate exposure to carcinogens. However, with recent advances in the understanding of pulmonary carcinogenesis and the identification of intermediate biomarkers, the prospects for the field of chemoprevention research have improved dramatically. Here we review the most recent research in lung cancer chemoprevention-focusing on those agents that have been investigated in human clinical trials. These agents fall into three major categories. First, oxidative stress plays an important role in pulmonary carcinogenesis; and therefore, antioxidants (including vitamins, selenium, green tea extracts, and isothiocyanates) may be particularly effective in preventing the development of lung cancer. Second, inflammation is increasingly accepted as a crucial factor in carcinogenesis, and many investigators have focused on anti-inflammatory agents, such as glucocorticoids, NSAIDs, statins, and PPARγ agonists. Finally, the PI3K/AKT/mTOR pathway is recognized to play a central role in tobacco-induced carcinogenesis, and inhibitors of this pathway, including myoinositol and metformin, are promising agents for lung cancer prevention. Successful chemoprevention will likely require targeting of multiple pathways to carcinogenesis-both to minimize toxicity and maximize efficacy.


Mental fatigue, work and sleep.
The study examined the multivariate relationship between mental fatigue and different work-related (work load, work hours) and background/life style factors, as well as disturbed sleep. A total of 5720 healthy employed men and women living in the greater Stockholm area participated in a questionnaire study on cardiovascular risk factors. The data were analysed using a multiple logistic regression analysis with self-rated fatigue as the dependent variable. Fatigue was predicted by disturbed sleep (4.31; 3.50-5.45, high immersion in work (4.17; 2.93-5.94), high work demands (2.39; 1.54-3.69), social support, being a female, being a supervisor and high age. Shift work, work hours (including overtime) and influence at work did not become significant predictors. With control for work demands a high number of work hours was associated with lower fatigue. Disturbed sleep is an important predictor of fatigue, apparently stronger than previously well-established predictors such as work load, female gender, lack of exercise, etc.


Subtrochanteric fractures after long-term treatment with bisphosphonates: a European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, and International Osteoporosis Foundation Working Group Report.
This paper reviews the evidence for an association between atypical subtrochanteric fractures and long-term bisphosphonate use. Clinical case reports/reviews and case-control studies report this association, but retrospective phase III trial analyses show no increased risk. Bisphosphonate use may be associated with atypical subtrochanteric fractures, but the case is yet unproven. A Working Group of the European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis and the International Osteoporosis Foundation has reviewed the evidence for a causal association between subtrochanteric fractures and long-term treatment with bisphosphonates, with the aim of identifying areas for further research and providing recommendations for physicians. A PubMed search of literature from 1994 to May 2010 was performed using key search terms, and articles pertinent to subtrochanteric fractures following bisphosphonate use were analysed. Several clinical case reports and case reviews report a possible association between atypical fractures at the subtrochanteric region of the femur in bisphosphonate-treated patients. Common features of these 'atypical' fractures include prodromal pain, occurrence with minimal/no trauma, a thickened diaphyseal cortex and transverse fracture pattern. Some small case-control studies report the same association, but a large register-based study and retrospective analyses of phase III trials of bisphosphonates do not show an increased risk of subtrochanteric fractures with bisphosphonate use. The number of atypical subtrochanteric fractures in association with bisphosphonates is an estimated one per 1,000 per year. It is recommended that physicians remain vigilant in assessing their patients treated with bisphosphonates for the treatment or prevention of osteoporosis and advise patients of the potential risks. Bisphosphonate use may be associated with atypical subtrochanteric fractures, but the case is unproven and requires further research. Were the case to be proven, the risk-benefit ratio still remains favourable for use of bisphosphonates to prevent fractures.


Coralline algae in a naturally acidified ecosystem persist by maintaining control of skeletal mineralogy and size.
To understand the effects of ocean acidification (OA) on marine calcifiers, the trade-offs among different sublethal responses within individual species and the emergent effects of these trade-offs must be determined in an ecosystem setting. Crustose coralline algae (CCA) provide a model to test the ecological consequences of such sublethal effects as they are important in ecosystem functioning, service provision, carbon cycling and use dissolved inorganic carbon to calcify and photosynthesize. Settlement tiles were placed in ambient pH, low pH and extremely low pH conditions for 14 months at a natural CO2 vent. The size, magnesium (Mg) content and molecular-scale skeletal disorder of CCA patches were assessed at 3.5, 6.5 and 14 months from tile deployment. Despite reductions in their abundance in low pH, the largest CCA from ambient and low pH zones were of similar sizes and had similar Mg content and skeletal disorder. This suggests that the most resilient CCA in low pH did not trade-off skeletal structure to maintain growth. CCA that settled in the extremely low pH, however, were significantly smaller and exhibited altered skeletal mineralogy (high Mg calcite to gypsum (hydrated calcium sulfate)), although at present it is unclear if these mineralogical changes offered any fitness benefits in extreme low pH. This field assessment of biological effects of OA provides endpoint information needed to generate an ecosystem relevant understanding of calcifying system persistence.


Translocation of 40 nm diameter nanowires through the intestinal epithelium of Daphnia magna.
Nanowires (NWs) have unique electrical and optical properties of value for many applications including lighting, sensing, and energy harnessing. Consumer products containing NWs increase the risk of NWs being released in the environment, especially into aquatic ecosystems through sewage systems. Daphnia magna is a common, cosmopolitan freshwater organism sensitive to toxicity tests and represents a likely entry point for nanoparticles into food webs of aquatic ecosystems. Here we have evaluated the effect of NW diameter on the gut penetrance of NWs in Daphnia magna. The animals were exposed to NWs of two diameters (40 and 80 nm) and similar length (3.6 and 3.8 μm, respectively) suspended in water. In order to locate the NWs in Daphnia, the NWs were designed to comprise one inherently fluorescent segment of gallium indium phosphide (GaInP) flanked by a gallium phosphide (GaP) segment. Daphnia mortality was assessed directly after 24 h of exposure and 7 days after exposure. Translocation of NWs across the intestinal epithelium was investigated using confocal fluorescence microscopy directly after 24 h of exposure and was observed in 89% of Daphnia exposed to 40 nm NWs and in 11% of Daphnia exposed to 80 nm NWs. A high degree of fragmentation was observed for NWs of both diameters after ingestion by the Daphnia, although 40 nm NWs were fragmented to a greater extent, which could possibly facilitate translocation across the intestinal epithelium. Our results show that the feeding behavior of animals may enhance the ability of NWs to penetrate biological barriers and that penetrance is governed by the NW diameter.


Preoperative briefing in the operating room: shared cognition, teamwork, and patient safety.
Contemporary preoperative team briefings conducted to improve patient safety focus mainly on supplying identification details regarding the patient and the surgical procedure. Drawing on cognitive theory principles, in this study a briefing protocol was developed that presents a broader perspective model of the patient and the planned procedure. In addition to customary identification details and drug sensitivities, the new briefing also includes review of significant background information, needed equipment, planned surgery stages, and so forth. The briefing content was developed following 130 continuous, nonstructured observations conducted in gynecologic and orthopedic operating rooms. The briefing form was designed as a large poster hung in a visible position on the operating room wall. The poster guides the team members (ie, nurses, surgeons, and anesthesiologists) in their conduct. Briefing is conducted orally, and no written records are required. The number of nonroutine events (ie, situations that, if not corrected, might lead to patient harm) observed in the 130 surgeries conducted without briefing was compared with the number of events in 102 surgeries in which briefing was conducted. There was a 25% reduction in the number of nonroutine events when briefing was conducted and a significant increase in the number of surgeries in which no nonroutine event was observed. Team members evaluated the briefing as most valuable for their own work, the teamwork, and patient safety. Following the study, the new briefing format was accepted and adopted for routine use. Team briefings designed to supply a broader-perspective surgery model may be an easy-to-apply tool to reduce the number of nonroutine events during surgery and increase patient safety.


Total pancreatectomy with islet autotransplantation: summary of a National Institute of Diabetes and Digestive and Kidney diseases workshop.
A workshop sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases focused on research gaps and opportunities in total pancreatectomy with islet autotransplantation (TPIAT) for the management of chronic pancreatitis (CP). The session was held on July 23, 2014, and structured into 5 sessions: (1) patient selection, indications, and timing; (2) technical aspects of TPIAT; (3) improving success of islet autotransplantation; (4) improving outcomes after total pancreatectomy; and (5) registry considerations for TPIAT. The current state of knowledge was reviewed; knowledge gaps and research needs were specifically highlighted. Common themes included the need to identify which patients best benefit from and when to intervene with TPIAT, current limitations of the surgical procedure, diabetes remission and the potential for improvement, opportunities to better address pain remission, gastrointestinal complications in this population, and unique features of children with CP considered for TPIAT. The need for a multicenter patient registry that specifically addresses the complexities of CP and total pancreatectomy outcomes as well as postsurgical diabetes outcomes was repeatedly emphasized.


Clinical implications of non-contrast-enhanced computed tomography for follow-up after endovascular abdominal aortic aneurysm repair.
There is growing concern over the long-term radiation exposure from serial computed tomographic (CT) scan follow-up after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAAs). Screening for endoleaks with non-contrast-enhanced volumetric CT has been shown to significantly reduce radiation doses. We evaluated the use of NCT as the primary method of follow-up after EVAR of AAAs. Our institutional post-EVAR CT protocol consisted of contrast-enhanced CT angiography (CTA) 1 month after repair, followed by NCT at 3 or 6 and 12 months, and annually thereafter. At each follow-up scan, immediate 3-dimensional volume analysis was performed. If the volume change was <2%, NCT follow-up was continued. If the volume increased by ≥2% on nonenhanced images, contrast-enhanced CT was performed immediately to identify potential endoleaks. All images were reviewed by an experienced cardiovascular radiologist. End points included identification of endoleak, reintervention, and rupture. Over a 7-year period, 126 patients were followed. Serial CTA was performed in 59 patients, while 67 patients were followed with the NCT protocol. The mean follow-up was 2.07 years. There were no differences in age, sex, or initial aneurysm volume or size. There were 35 total endoleaks identified. Twenty of these were early endoleaks (<30 days post-EVAR). The remaining 15 leaks were late in nature (10 in the contrast group and 5 in the noncontrast group; P=0.17). NCT aneurysm sac volume changes prompted contrasted studies in all 5 late leaks. The mean volume change was 11.2 cm3, an average change of 5.88%. These findings were not significantly different than the late leaks found by routine contrast studies (8.9 cm3; 4.98% [P=0.58]). There were no delayed ruptures or emergent reinterventions in the NCT group. Serial NCT appears to be safe and effective as the sole means of follow-up after EVAR for AAAs. AAA volume increases of ≥2% should prompt further contrast-enhanced CT imaging. Changes of <2% can be safely followed with serial NCT. This protocol requires dedicated cardiovascular radiologist involvement, and patients should be retained in the radiology suite until real-time image evaluation can be completed.


SPADEVizR: an R package for visualization, analysis and integration of SPADE results.
Flow, hyperspectral and mass cytometry are experimental techniques measuring cell marker expressions at the single cell level. The recent increase of the number of markers simultaneously measurable has led to the development of new automatic gating algorithms. Especially, the SPADE algorithm has been proposed as a novel way to identify clusters of cells having similar phenotypes in high-dimensional cytometry data. While SPADE or other cell clustering algorithms are powerful approaches, complementary analysis features are needed to better characterize the identified cell clusters. We have developed SPADEVizR, an R package designed for the visualization, analysis and integration of cell clustering results. The available statistical methods allow highlighting cell clusters with relevant biological behaviors or integrating them with additional biological variables. Moreover, several visualization methods are available to better characterize the cell clusters, such as volcano plots, streamgraphs, parallel coordinates, heatmaps, or distograms. SPADEVizR can also generate linear, Cox or random forest models to predict biological outcomes, based on the cell cluster abundances. Additionally, SPADEVizR has several features allowing to quantify and to visualize the quality of the cell clustering results. These analysis features are essential to better interpret the behaviors and phenotypes of the identified cell clusters. Importantly, SPADEVizR can handle clustering results from other algorithms than SPADE. SPADEVizR is distributed under the GPL-3 license and is available at https://github.com/tchitchek-lab/SPADEVizR . email@example.com. Supplementary data are available at Bioinformatics online.


Type 2 diabetes mellitus prevalence between 2005 and 2018 in population under 30 using data from the Ministry of Health of Peru.
Type 2 diabetes mellitus is a health problem in low and middle-income countries like Peru. There are few published reports on trends and surveillance of this disease in the young Peruvian population. To describe the prevalence of type 2 diabetes mellitus in the population under 30 registered between 2005 and 2018 by the Ministry of Health of Peru. A descriptive study was conducted from a secondary analysis of the national registries of type 2 diabetes (ICD 10: E11) in the population under 30 treated in the health facilities of the Ministry of Health of Peru between 2015 and 2018. Described by department and geographic region, the prevalence of diabetes was adjusted for age and sex. In the period between 2005 and 2018, the national prevalence of type 2 diabetes mellitus increased from 2.1 to 22.1 cases/100 000 population. Women had a higher prevalence. Geographic regions with the highest prevalence increase were the Coast from 3.8 to 35.3/100 000 population and the Rainforest from 1.1 to 22.1/100 000 population. In the same period, the departments with the highest prevalence increase were Cajamarca (1733.3%) and Puno (1704.2%). Furthermore, Tumbes, Ica, Lambayeque, Callao, Lima, Loreto, and Madre de Dios reported prevalence rates over the national average. The prevalence of type 2 diabetes mellitus in the population under 30 and covered by the Peruvian Ministry of Health has increased more than ten times in the period between 2005 and 2018. The Coast and the cities with the highest population density had the highest prevalence. A greater focus to improve the strategies of risk factor control in the population under 30 is needed, including preventive actions on obesity and inadequate lifestyles, as well as a screening at a younger age for diabetes in the population at risk.


Mitochondria Permeability Transition versus Necroptosis in Oxalate-Induced AKI.
Serum oxalate levels suddenly increase with certain dietary exposures or ethylene glycol poisoning and are a well known cause of AKI. Established contributors to oxalate crystal-induced renal necroinflammation include the NACHT, LRR and PYD domains-containing protein-3 (NLRP3) inflammasome and mixed lineage kinase domain-like (MLKL) protein-dependent tubule necroptosis. These studies examined the role of a novel form of necrosis triggered by altered mitochondrial function. To better understand the molecular pathophysiology of oxalate-induced AIK, we conducted in vitro studies in mouse and human kidney cells and in vivo studies in mice, including wild-type mice and knockout mice deficient in peptidylprolyl isomerase F (Ppif) or deficient in both Ppif and Mlkl. Crystals of calcium oxalate, monosodium urate, or calcium pyrophosphate dihydrate, as well as silica microparticles, triggered cell necrosis involving PPIF-dependent mitochondrial permeability transition. This process involves crystal phagocytosis, lysosomal cathepsin leakage, and increased release of reactive oxygen species. Mice with acute oxalosis displayed calcium oxalate crystals inside distal tubular epithelial cells associated with mitochondrial changes characteristic of mitochondrial permeability transition. Mice lacking Ppif or Mlkl or given an inhibitor of mitochondrial permeability transition displayed attenuated oxalate-induced AKI. Dual genetic deletion of Ppif and Mlkl or pharmaceutical inhibition of necroptosis was partially redundant, implying interlinked roles of these two pathways of regulated necrosis in acute oxalosis. Similarly, inhibition of mitochondrial permeability transition suppressed crystal-induced cell death in primary human tubular epithelial cells. PPIF and phosphorylated MLKL localized to injured tubules in diagnostic human kidney biopsies of oxalosis-related AKI. Mitochondrial permeability transition-related regulated necrosis and necroptosis both contribute to oxalate-induced AKI, identifying PPIF as a potential molecular target for renoprotective intervention.


Accuracy of blood pressure monitors available in high street pharmacies.
The aim of this study was to assess the accuracy of automated blood pressure monitors on sale to the UK general public. We conducted static pressure accuracy testing on all compatible (19 out of 22 available) blood pressure monitors available for sale in pharmacies within the city of Oxford, UK, and tested two devices for accuracy in measurement of systolic and diastolic blood pressures in 21 adults. The devices showed good accuracy when measuring static pressure in laboratory bench testing, with the median error per device ranging from -2.2 to +1.2 mmHg; however, the two devices tested performed worse in vivo than in laboratory tests, with median errors as high as 6 mmHg. The monitors showed good accuracy in static pressure testing, with a lack of correlation between monitor price and accuracy. However, higher error rates seen during in-vivo testing of a subset of monitors may indicate that static testing may not be appropriate for routine accuracy assessment of these monitors.


Conditions for the abrupt bifurcation to chaotic scattering.
One of the generic ways in which chaotic scattering can come about as a system parameter is varied is the so-called "abrupt bifurcation" in which the scattering is nonchaotic on one side of the bifurcation and is chaotic and hyperbolic on the other side. Previous work demonstrating the abrupt bifurcation [S. Bleher et al., Phys. Rev. Lett. 63, 919 (1989); Physica D 46, 87 (1990)] was primarily for the case where the scattering potential had maxima ("hilltops") which had locally circular isopotential contours. Here we extend these considerations to the more general case of locally elliptically shaped isopotential contours at the hilltops. It turns out that the conditions for the abrupt bifurcation change drastically as soon as even a small amount of noncircularity is included (i.e., the circular case is singular). The illustrative case of scattering from three isolated potential hills is dealt with in detail. One interesting result is a simple geometrical sufficient condition for an abrupt bifurcation in the case of large enough ellipticity of the hill with lowest potential at its hilltop.


Dental opinion leaders' perspectives on barriers and facilitators to HPV-related prevention.
Evidence suggests a causal connection between the Human Papillomavirus (HPV) and oropharyngeal cancers. HPV-related oropharyngeal cancers are increasing and are the most common HPV-associated cancer. Previous research suggests that dental professionals recognize a role in the prevention of HPV and oropharyngeal cancers. As an initial step to investigating effective mechanisms of incorporating HPV prevention into dental practices, including the HPV vaccine, this qualitative study explored dental opinion leaders' perspectives on barriers and facilitators to HPV-related prevention in the dental profession. Dental opinion leaders were identified through: (1) national professional organizations and advocacy groups, (2) by indication of an expert panel, and (3) focus groups conducted with oral health providers. Thirteen participants representing 11 organizations were interviewed via telephone. Interview recordings were transcribed verbatim and thematically coded using a priori and emergent codes. Opinion leaders described multi-level factors influencing dental providers' HPV-related prevention practice behaviors. Barriers included HPV as a sensitive topic and the need for HPV-related education and skills. Facilitators included perceptions of HPV prevention as part of the dental providers' role and the potential development of passive educational methods to provide HPV-related information to patients. Opinion leaders reported dental providers have a role in the prevention of HPV and oropharyngeal cancer; yet, to fully incorporate this topic into their practice, dental providers need further education and skill-based training. Opinion leaders have significant role in shaping this topic as a priority and identifying potential interventions to assist dental providers' HPV-related prevention. Future research should maximize the role of opinion leaders as key change agents.


Tick-borne encephalitis virus sequenced directly from questing and blood-feeding ticks reveals quasispecies variance.
The increased distribution of the tick-borne encephalitis virus (TBEV) in Scandinavia highlights the importance of characterizing novel sequences within the natural foci. In this study, two TBEV strains: the Norwegian Mandal 2009 (questing nymphs pool) and the Swedish Saringe 2009 (blood-fed nymph) were sequenced and phylogenetically characterized. Interestingly, the sequence of Mandal 2009 revealed the shorter form of the TBEV genome, similar to the highly virulent Hypr strain, within the 3' non-coding region (3'NCR). A different genomic structure was found in the 3'NCR of Saringe 2009, as in-depth analysis demonstrated TBEV variants with different lengths within the poly(A) tract. This shows that TBEV quasispecies exists in nature and indicates a putative shift in the quasispecies pool when the virus switches between invertebrate and vertebrate environments. This prompted us to further sequence and analyze the 3'NCRs of additional Scandinavian TBEV strains and control strains, Hypr and Neudoerfl. Toro 2003 and Habo 2011 contained mainly a short (A)3C(A)6 poly(A) tract. A similar pattern was observed for the human TBEV isolates 1993/783 and 1991/4944; however, one clone of 1991/4944 contained an (A)3C(A)11 poly(A) sequence, demonstrating that quasispecies with longer poly(A) could be present in human isolates. Neudoerfl has previously been reported to contain a poly(A) region, but to our surprise the re-sequenced genome contained two major quasispecies variants, both lacking the poly(A) tract. We speculate that the observed differences are important factors for the understanding of virulence, spread, and control of the TBEV.


Reduction of 18F-FDG Dose in Clinical PET/MR Imaging by Using Silicon Photomultiplier Detectors.
Purpose To determine the level of clinically acceptable reduction in injected fluorine 18 (18F) fluorodeoxyglucose (FDG) dose in time-of-flight (TOF)-positron emission tomography(PET)/magnetic resonance (MR) imaging by using silicon photomultiplier (SiPM) detectors compared with TOF-PET/computed tomography (CT) using Lu1.8Y0.2SiO5(Ce), or LYSO, detectors in patients with different body mass indexes (BMIs). Materials and Methods Patients were enrolled in this study as part of a larger prospective study with a different purpose than evaluated in this study (NCT02316431). All patients gave written informed consent prior to inclusion into the study. In this study, 74 patients with different malignant diseases underwent sequential whole-body TOF-PET/CT and TOF-PET/MR imaging. PET images with simulated reduction of injected 18F-FDG doses were generated by unlisting the list-mode data from PET/MR imaging. Two readers rated the image quality of whole-body data sets, as well as the image quality in each body compartment, and evaluated the conspicuity of malignant lesions. Results The image quality with 70% or 60% of the injected dose of 18F-FDG at PET/MR imaging was comparable to that at PET/CT. With 50% of the injected dose, comparable image quality was maintained among patients with a BMI of less than 25 kg/m2. PET images without TOF reconstruction showed higher artifact scores and deteriorated sharpness than those with TOF reconstruction. Conclusion Sixty percent of the usually injected 18F-FDG dose (reduction of up to 40%) in patients with a BMI of more than 25 kg/m2 results in clinically adequate PET image quality in TOF-PET/MR imaging performed by using SiPM detectors. Additionally, in patients with a BMI of less than 25 kg/m2, 50% of the injected dose may safely be used. © RSNA, 2017 Online supplemental material is available for this article.


The transmembrane protein p23 contributes to the organization of the Golgi apparatus.
In previous studies we have shown that p23, a member of the p24-family of small transmembrane proteins, is highly abundant in membranes of the cis-Golgi network (CGN), and is involved in sorting/trafficking in the early secretory pathway. In the present study, we have further investigated the role of p23 after ectopic expression. We found that ectopically expressed p23 folded and oligomerized properly, even after overexpression. However, in contrast to endogenous p23, exogenous p23 molecules did not localize to the CGN, but induced a significant expansion of characteristic smooth ER membranes, where they accumulated in high amounts. This ER-derived, p23-rich subdomain displayed a highly regular morphology, consisting of tubules and/or cisternae of constant diameter, which were reminiscent of the CGN membranes containing p23 in control cells. The expression of exogenous p23 also led to the specific relocalization of endogenous p23, but not of other proteins, to these specialized ER-derived membranes. Relocalization of p23 modified the ultrastructure of the CGN and Golgi membranes, but did not affect anterograde and retrograde transport reactions to any significant extent. We conclude (i) that p23 has a morphogenic activity that contributes to the morphology of CGN-membranes; and (ii) that the presence of p23 in the CGN is necessary for the proper organization of the Golgi apparatus.


The hypothalamus predates the origin of vertebrates.
The hypothalamus coordinates neuroendocrine functions in vertebrates. To explore its evolutionary origin, we describe integrated transcriptome/connectome brain maps for swimming tadpoles of Ciona, which serves as an approximation of the ancestral proto-vertebrate. This map features several cell types related to different regions of the vertebrate hypothalamus, including the mammillary nucleus, the arcuate nucleus, and magnocellular neurons. Coronet cells express melanopsin and share additional properties with the saccus vasculosus, a specialized region of the hypothalamus that mediates photoperiodism in nontropical fishes. Comparative transcriptome analyses identified orthologous cell types for mechanosensory switch neurons, and VP+ and VPR+ relay neurons in different regions of the mouse hypothalamus. These observations provide evidence that the hypothalamus predates the evolution of the vertebrate brain. We discuss the possibility that switch neurons, coronet cells, and FoxP+ /VPR+ relay neurons comprise a behavioral circuit that helps trigger metamorphosis of Ciona larvae in response to twilight.


Dynamic Lunatic fringe expression is correlated with boundaries formation in developing mouse teeth.
The formation of boundaries is a fundamental organizing principle during development. The Notch signalling pathway regulates this developmental patterning mechanism in many tissues. Recent data suggest that Notch receptors are involved in boundary determination during odontogenesis. It remains, however, uncertain if other components of the Notch pathway are also important for compartmental lineage restrictions in teeth. Here we report on the expression of the Lunatic fringe gene, which encodes a secreted signalling molecule regulating the Notch pathway, during the development of mouse teeth. Lunatic fringe is expressed in both epithelial and mesenchymal components of the developing molar. The expression pattern of Lunatic fringe in the epithelium is complementary to that of the Notch receptors. Lunatic fringe is asymmetrically expressed in the incisor epithelium during its antero-posterior rotation. This expression pattern defines the lingual comportment of the incisor epithelium whereas the labial comportment is defined by Notch2 expression.


Comparative life tables of the potato tuberworm, Phthorimaea operculella, on leaves and tubers of different potato cultivars.
The potato tuberworm, Phthorimaea operculella Zeller (Lepidoptera: Gelechiidae), is a serious pest of the potato, Solanum tuberosum L. (Solanales: Solanaceae), in both fields and stores in tropical and subtropical regions. In the present study, the susceptibility of different potato cultivars to P. operculella was evaluated by measuring life table parameters. Tests were undertaken with leaves and tubers of 10 potato cultivars in the laboratory: Agria, Agata, Almera, Arinda, Baneba, Fiana, Marfona, Ramus, Satina, and Volvox. All parameters showed significant differences among tested cultivars. The longest mean generation times were observed on Marfona and Satina cultivars in the experiments on potato leaves and tubers, respectively. The lowest reproductive rate was observed on leaves and tubers of Marfona cultivar. Correspondingly, the lowest values of intrinsic rate of increase and the lowest finite rate of increase were also obtained on Marfona cultivar in tests on potato leaves and tubers. The highest intrinsic rate of incrase values were observed on Arinda and Baneba in the tests on leaves and tubers, respectively. The intrinsic rates of increase were significantly higher on potato leaves than on potato tubers. The lower performance of P. operculella on Marfona cultivar indicated that this cultivar is relatively less susceptible this pest and could be used in integrated pest management programs of P. operculella.


Posttransplant bone disease: evidence for a high bone resorption state.
Loss of bone is a significant problem after renal transplant. Although bone loss in the first post transplant year has been well documented, conflicting data exist concerning bone loss after this time. It is equally unclear whether bone loss in long-term renal transplant recipients correlates with bone turnover as it does in postmenapausal osteoporosis. To examine these issues, we conducted a cross-sectional study to define the prevalence of osteoporosis in long-term (> 1 year) renal transplant recipients with preserved renal function (mean creatinine clearance 73 +/- 23 ml/min). Bone mineral density (BMD) was measured at the hip, spine and wrist by DEXA in 69 patients. Markers for bone formation (serum osteocalcin) and bone resorption [urinary levels of pyridinoline (PYD) and deoxypyridinoline (DPD)] were also measured as well as parameters of calcium metabolism. Correlations were made between these parameters and BMD at the various sites. The mean age of the patients was 45 +/- 11 years. Eighty eight percent of patients were on cyclosporine (12% on tacrolimus) and all but 2 were on prednisone [mean dose 9 +/- 2 mg/day)]. Osteoporosis (BMD more than 2.5 SD below peak adult BMD) at the spine or hip was diagnosed in 44% of patients and osteopenia was present in an additional 44%. Elevated levels of intact parathyroid hormone (i PTH) were observed in 81% of patients. Elevated urinary levels of PYD or DPD were present in 73% of patients and 38% had elevated serum levels of osteocalcin. Levels of calcium, and of 25(OH) and 1,25(OH)2 vitamin D were normal. In a stepwise multiple regression model that included osteocalcin, PYD, DPD, intact PTH, age, years posttransplant, duration of dialysis, cumulative prednisone dose, smoking, and diabetes: urinary PYD was the strongest predictor of bone mass. These results demonstrate that osteoporosis is common in long-term renal transplant recipients. The data also suggest that elevated rates of bone resorption contribute importantly to this process.


Vascular oxidative stress and inflammation increase with age: ameliorating effects of alpha-lipoic acid supplementation.
Increased oxidative stress and inflammation causally contribute to cardiovascular diseases, for which advanced age is a major risk factor. We found that indicators of oxidative stress, including NADPH oxidase activity and superoxide levels, were significantly increased in aortas of old (22-24 months) versus young (3-4 months) male F344 rats, whereas superoxide dismutase (SOD) activity was decreased. Aortic mRNA and protein levels of NOX4, the principal catalytic subunit of NADPH oxidase in vascular cells, also were increased with age, but not NOX2 and p22(phox). Indicators of inflammation, including activation of NFkappaB and upregulation of vascular cell adhesion molecule-1 (VCAM-1) in aorta, and monocyte chemotactic protein-1 (MCP-1) in plasma, also were significantly increased in old rats. Supplementation with 0.2% (wt/wt) (R)-alpha-lipoic acid (LA) for 2 weeks caused a nonsignificant decrease in NADPH oxidase activity in aged aorta and a significant decrease in mRNA--but not protein--levels of NOX4 and VCAM-1. Furthermore, LA reversed the age-dependent changes in aortic SOD activity and plasma MCP-1 levels. Hence, vascular oxidative stress and inflammation increase with age and are ameliorated by LA supplementation.


Loss of enteroendocrine cells in mice alters lipid absorption and glucose homeostasis and impairs postnatal survival.
At least 10 enteroendocrine cell types have been identified, and the peptide hormones they secrete have diverse functions that include regulation of glucose homeostasis, food intake, and gastric emptying. Mice lacking individual enteroendocrine hormones, their receptors, or combinations of these have shed light on the role of these hormones in the regulation of energy homeostasis. However, because enteroendocrine hormones have partially overlapping functions, these loss-of-function studies produced only minor phenotypes, and none of the enteroendocrine hormones was shown to be essential for life. To examine the effect of loss of all enteroendocrine cells and hormones on energy homeostasis, we generated mice with intestinal-specific ablation of the proendocrine transcription factor neurogenin 3 (referred to herein as Ngn3Deltaint mice). Ngn3Deltaint mice were deficient for all enteroendocrine cells and hormones, and died with a high frequency during the first week of life. Mutant mice were growth retarded and had yellowish stool suggestive of steatorrhea. Subsequent analyses revealed that Ngn3Deltaint mice had impaired lipid absorption, reduced weight gain, and improved glucose homeostasis. Furthermore, intestinal epithelium of the mutant mice showed an enlarged proliferative crypt compartment and accelerated cell turnover but no changes to goblet and Paneth cell numbers. Enterocytes had shorter microvilli, but the expression of the main brush border enzymes was unaffected. Our data help unravel the role of enteroendocrine cells and hormones in lipid absorption and maintenance of the intestinal epithelium.


Familial and cultural perceptions and beliefs of oral hygiene and dietary practices among ethnically and socio-economicall diverse groups.
OBJECTIVE; The aim of this international study was to develop a valid and reliable psychometric measure to examine the extent to which parents' attitudes about engaging in twice-daily tooth brushing and controlling sugar snacking predict these respective behaviours in their children. A supplementary objective was to assess whether ethnic group, culture, level of deprivation or children's caries experience impact upon the relationships between oral health related behaviours, attitudes to these respective behaviours and to dental caries. Nurseries, health centres and dental clinics in 17 countries. 2822 children aged 3 to 4 years and their parents. Dental examination of children and questionnaire to parents. Factor analysis identified 8 coherent attitudes towards toothbrushing, sugar snacking and childhood caries. Attitudes were significantly different in families from deprived and non-deprived backgrounds and in families of children with and without caries. Parents perception of their ability to control their children's toothbrushing and sugar snacking habits were the most significant predictor of whether or not favourable habits were reported. Some differences were found by site and ethnic group. This study supports the hypothesis that parental attitudes significantly impact on the establishment of habits favourable to oral health. An appreciation of the impact of cultural and ethnic diversity is important in understanding how parental attitudes to oral health vary. Further research should examine in a prospective intervention whether enhancing parenting skills is an effective route to preventing childhood caries.


Investigation of two-photon-induced polarization spectroscopy of the a-X (1,0) transition in molecular nitrogen at elevated pressures.
Two-photon-induced polarization spectroscopy of molecular nitrogen in the alpha 1IIg(nu' =) <-- X 1Sigma(g)+ (nu" =) system near 283 nm was performed, and its signal dependence investigated over the pressure range from 1.2 to 5 bars at 300 K. A significant increase of the signal intensity with pressure beyond the expected square law for a two-photon process was observed for pure nitrogen. Similar behavior was also found for a constant nitrogen partial pressure with increasing partial pressures of argon buffer gas. In both cases the spectral linewidth of the excited transitions increased dramatically with overall pressure. A possible explanation is given for the observed behavior in terms of contributions to the nonlinear susceptibility of the medium from the population of one-photon resonantly absorbing excited-state nitrogen and ground state N(2)(+) ions created in the multiphoton absorption process at the high laser intensities required.


Plasma Proteomic Biomarkers Relating to Alzheimer's Disease: A Meta-Analysis Based on Our Own Studies.
Background and Objective: Plasma biomarkers for the diagnosis and stratification of Alzheimer's disease (AD) are intensively sought. However, no plasma markers are well established so far for AD diagnosis. Our group has identified and validated various blood-based proteomic biomarkers relating to AD pathology in multiple cohorts. The study aims to conduct a meta-analysis based on our own studies to systematically assess the diagnostic performance of our previously identified blood biomarkers. Methods: To do this, we included seven studies that our group has conducted during the last decade. These studies used either Luminex xMAP or ELISA to measure proteomic biomarkers. As proteins measured in these studies differed, we selected protein based on the criteria that it must be measured in at least four studies. We then examined biomarker performance using random-effect meta-analyses based on the mean difference between biomarker concentrations in AD and controls (CTL), AD and mild cognitive impairment (MCI), MCI, and CTL as well as MCI converted to dementia (MCIc) and non-converted (MCInc) individuals. Results: An overall of 2,879 subjects were retrieved for meta-analysis including 1,053 CTL, 895 MCI, 882 AD, and 49 frontotemporal dementia (FTD) patients. Six proteins were measured in at least four studies and were chosen for meta-analyses for AD diagnosis. Of them, three proteins had significant difference between AD and controls, among which alpha-2-macroglobulin (A2M) and ficolin-2 (FCN2) increased in AD while fibrinogen gamma chain (FGG) decreased in AD compared to CTL. Furthermore, FGG significantly increased in FTD compared to AD. None of the proteins passed the significance between AD and MCI, or MCI and CTL, or MCIc and MCInc, although complement component 4 (CC4) tended to increase in MCIc individuals compared to MCInc. Conclusions: The results suggest that A2M, FCN2, and FGG are promising biomarkers to discriminate AD patients from controls, which are worthy of further validation.


Influence of dietary calcium and phosphorus content in a fixed ratio on growth and development in Great Danes.
To study the musculoskeletal development of Great Dane puppies fed various dietary concentrations of calcium (Ca) and phosphorus (P) in fixed ratio by use of dual energy x-ray absorptiometry (DEXA), determination of serum insulin-like growth factor 1 and parathyroid hormone concentrations, radiography, and blood chemistry analysis results. 32 purebred Great Dane puppies from 4 litters. At weaning, puppies were assigned randomly to 1 of 3 diets. Blood was collected for biochemical analyses and hormone assays, and radiography and DEXA were performed through 18 months of age. Changes in body weight, bone mineral content, fat tissue weight, lean mass, result of serum biochemical analyses, hormonal concentrations, and radius lengths were analyzed through 18 months of age. Bone mineral content of puppies correlated positively with Ca and P content of the diets fed. Significant differences between groups in bone mineral content, lean mass, and body fat were apparent early. The disparity among groups increased until 6 months of age and then declined until body composition was no longer different at 12 months of age. Accretion rates for skeletal mineral content, fat, and lean tissue differed from each other and by diet group. Ca and P concentrations in the diet of young Great Dane puppies are rapidly reflected in the bone mineral content of the puppies until 5 to 6 months of age, after which hormonal regulation adjusts absorption and excretion of these minerals. Appropriate Ca and P concentrations in diets are important in young puppies < 6 months of age.


Synbiotic-driven improvement of metabolic disturbances is associated with changes in the gut microbiome in diet-induced obese mice.
The gut microbiota is an important influencing factor of metabolic health. Although dietary interventions with probiotics, prebiotics, and synbiotics can be effective means to regulate obesity and associated comorbidities, the underlying shifts in gut microbial communities, especially at the functional level, have not been characterized in great details. In this study, we sought to investigate the effects of synbiotics on the regulation of gut microbiota and the alleviation of high-fat diet (HFD)-induced metabolic disorders in mice. Specific pathogen-free (SPF) male C57BL/6J mice were fed diets with either 10% (normal diet, ND) or 60% (high-fat diet, HFD) of total calories from fat (lard). Dietary interventions in the HFD-fed mice included (i) probiotic (Bifidobacterium animalis subsp. lactis and Lactobacillus paracasei subsp. paracasei DSM 46331), (ii) prebiotic (oat β-glucan), and (iii) synbiotic (a mixture of i and ii) treatments for 12 weeks. Besides detailed characterization of host metabolic parameters, a multi-omics approach was used to systematically profile the microbial signatures at both the phylogenetic and functional levels using 16S rRNA gene sequencing, metaproteomics and targeted metabolomics analysis. The synbiotic intervention significantly reduced body weight gain and alleviated features of metabolic complications. At the phylogenetic level, the synbiotic treatment significantly reversed HFD-induced changes in microbial populations, both in terms of richness and the relative abundance of specific taxa. Potentially important species such as Faecalibaculum rodentium and Alistipes putredinis that might mediate the beneficial effects of the synbiotic were identified. At the functional level, short-chain fatty acid and bile acid profiles revealed that all dietary interventions significantly restored cecal levels of acetate, propionate, and butyrate, while the synbiotic treatment reduced the bile acid pools most efficiently. Metaproteomics revealed that the effects of the synbiotic intervention might be mediated through metabolic pathways involved in carbohydrate, amino acid, and energy metabolisms. Our results suggested that dietary intervention using the novel synbiotic can alleviate HFD-induced weight gain and restore gut microbial ecosystem homeostasis phylogenetically and functionally.


Air pollution, aeroallergens and cardiorespiratory emergency department visits in Saint John, Canada.
Existing studies of the association between air pollution, aeroallergens and emergency department (ED) visits have generally examined the effects of a few pollutants or aeroallergens on individual conditions such as asthma or chronic obstructive pulmonary disease. In this study, we considered a wide variety of respiratory and cardiac conditions and an extensive set of pollutants and aeroallergens, and utilized prospectively collected information on possible effect modifiers which would not normally be available from purely administrative data. The association between air pollution, aeroallergens and cardiorespiratory ED visits (n = 19,821) was examined for the period 1992 to 1996 using generalized additive models. ED visit, air pollution and aeroallergen time series were prefiltered using LOESS smoothers to minimize temporal confounding, and a parsimonious model was constructed to control for confounding by weather and day of week. Multipollutant and multi-aeroallergen models were constructed using stepwise procedures and sensitivity analyses were conducted by season, diagnosis, and selected individual characteristics or effect modifiers. In single-pollutant models, positive effects of all pollutants but NO2 and COH were observed on asthma visits, and positive effects on all respiratory diagnosis groups were observed for O3, SO2, PM10, PM2.5, and SO4(2-). Among cardiac conditions, only dysrhythmia visits were positively associated with all measures of particulate matter. In the final year-round multipollutant models, a 20.9% increase in cardiac ED visits was attributed to the combination of O3 (16.0%, 95% CI 2.8-30.9) and SO2 (4.9%, 95%CI 1.7-8.2) at the mean concentration of each pollutant. In the final multipollutant model for respiratory visits, O3 accounted for 3.9% of visits (95% CI 0.8-7.2), and SO2 for 3.7% (95% CI 1.5-6.0), whereas a weak, negative association was observed with NO2. In multi-aeroallergen models of warm season asthma ED visits, Ascomycetes, Alternaria and small round fungal spores accounted for 4.5% (95% CI 1.8-7.4), 4.7% (95% CI 1.0-8.6) and 3.0% (95% CI 0.8-5.1), respectively, of visits at their mean concentrations, and these effects were not sensitive to adjustment for air pollution effects. In conclusion, we observed a significant influence of the air pollution mix on cardiac and respiratory ED visits. Although in single-pollutant models, positive associations were noted between ED visits and some measures of particulate matter, in multipollutant models, pollutant gases, particularly ozone, exhibited more consistent effects. Aeroallergens were also significantly associated with warm season asthma ED visits.


Endometrial decidualization and deciduosis in aged rhesus macaques (Macaca mulatta).
Superficial decidualization of the endometrial stroma is an essential feature of the implantation stage of pregnancy in rhesus macaques and other primates. Decidualization involves proliferation of the endometrial stromal cells, with differentiation into morphologically distinct decidual cells. Previous reports involving nonpregnant rhesus monkeys have described local- ized and widespread endometrial decidualization in response to administration of progesterone and synthetic progestogens. Ectopic decidua or 'deciduosis' describes the condition in which groups of decidual cells are located outside of the endometrium, most often in the ovaries, uterus and cervix but also in various other organs. In humans, most cases of deciduosis are associated with normal pregnancy, and ectopic decidua can be found in the ovary in nearly all term pregnancies. Here we describe pronounced endometrial decidualization in 2 rhesus macaques. Both macaques had been treated long-term with medroxyprogesterone acetate for presumed endometriosis, which was confirmed in one of the macaques at postmortem examination. In one animal, florid extrauterine and peritoneal serosal decidualization was admixed multifocally with carcinomatosis from a primary colonic adenocarcinoma. Cells constituting endometrial and serosal decidualization reactions were immunopositive for the stromal markers CD10, collagen IV, smooth muscle actin, and vimentin and immunonegative for cytokeratin. In contrast, carcinomatous foci were cytokeratin-positive. To our knowledge, this report describes the first cases of serosal peritoneal decidualization in rhesus macaques. The concurrent presentation of serosal peritoneal decidualization with carcinomatosis is unique.


Optogenetic control of the lac operon for bacterial chemical and protein production.
Control of the lac operon with isopropyl β-D-1-thiogalactopyranoside (IPTG) has been used to regulate gene expression in Escherichia coli for countless applications, including metabolic engineering and recombinant protein production. However, optogenetics offers unique capabilities, such as easy tunability, reversibility, dynamic induction strength and spatial control, that are difficult to obtain with chemical inducers. We have developed a series of circuits for optogenetic regulation of the lac operon, which we call OptoLAC, to control gene expression from various IPTG-inducible promoters using only blue light. Applying them to metabolic engineering improves mevalonate and isobutanol production by 24% and 27% respectively, compared to IPTG induction, in light-controlled fermentations scalable to at least two-litre bioreactors. Furthermore, OptoLAC circuits enable control of recombinant protein production, reaching yields comparable to IPTG induction but with easier tunability of expression. OptoLAC circuits are potentially useful to confer light control over other cell functions originally designed to be IPTG-inducible.


Mindfulness-based stress reduction and health benefits. A meta-analysis.
Mindfulness-based stress reduction (MBSR) is a structured group program that employs mindfulness meditation to alleviate suffering associated with physical, psychosomatic and psychiatric disorders. The program, nonreligious and nonesoteric, is based upon a systematic procedure to develop enhanced awareness of moment-to-moment experience of perceptible mental processes. The approach assumes that greater awareness will provide more veridical perception, reduce negative affect and improve vitality and coping. In the last two decades, a number of research reports appeared that seem to support many of these claims. We performed a comprehensive review and meta-analysis of published and unpublished studies of health-related studies related to MBSR. Sixty-four empirical studies were found, but only 20 reports met criteria of acceptable quality or relevance to be included in the meta-analysis. Reports were excluded due to (1) insufficient information about interventions, (2) poor quantitative health evaluation, (3) inadequate statistical analysis, (4) mindfulness not being the central component of intervention, or (5) the setting of intervention or sample composition deviating too widely from the health-related MBSR program. Acceptable studies covered a wide spectrum of clinical populations (e.g., pain, cancer, heart disease, depression, and anxiety), as well as stressed nonclinical groups. Both controlled and observational investigations were included. Standardized measures of physical and mental well-being constituted the dependent variables of the analysis. Overall, both controlled and uncontrolled studies showed similar effect sizes of approximately 0.5 (P<.0001) with homogeneity of distribution. Although derived from a relatively small number of studies, these results suggest that MBSR may help a broad range of individuals to cope with their clinical and nonclinical problems.


Optimal Frequency and Amplitude of Vertical Viewpoint Oscillation for Improving Vection Strength and Reducing Neural Constrains on Gait.
Inducing self-motion illusions referred as vection are critical for improving the sensation of walking in virtual environments (VE). Adding viewpoint oscillations to a constant forward velocity in VE is effective for improving vection strength under static conditions. However, the effects of oscillation frequency and amplitude on vection strength under treadmill walking conditions are still unclear. Besides, due to the visuomotor entrainment mechanism, these visual oscillations would affect gait patterns and be detrimental for achieving natural walking if not properly designed. This study was aimed at determining the optimal frequency and amplitude of vertical viewpoint oscillations for improving vection strength and reducing gait constraints. Seven subjects walked on a treadmill while watching a visual scene. The visual scene presented a constant forward velocity equal to the treadmill velocity with different vertical viewpoint oscillations added. Five oscillation patterns with different combinations of frequency and amplitude were tested. Subjects gave verbal ratings of vection strength. The mediolateral (M-L) center of pressure (CoP) complexity was calculated to indicate gait constraints. After the experiment, subjects were asked to give the best and the worst oscillation pattern based on their walking experience. The oscillation frequency and amplitude had strong positive correlations with vection strength. The M-L CoP complexity was reduced under oscillations with low frequency. The medium oscillation amplitude had greater M-L CoP complexity than the small and large amplitude. Besides, subjects preferred those oscillation patterns with large gait complexity. We suggested that the oscillation amplitude with largest M-L CoP complexity should first be chosen to reduce gait constraints. Then, increasing the oscillation frequency to improve vection strength until individual preference or the boundary of motion sickness. These findings provide important guidelines to promote the sensation of natural walking in VE.


Assessing young unmarried men's access to reproductive health information and services in rural India.
We investigated the accessibility of reproductive health information and contraceptives in a relatively less developed area of rural central India and assessed the risks facing young unmarried men. This cross-sectional study used both qualitative and quantitative methods. Participants included 38 unmarried rural men in four focus-group discussions and a representative sample of 316 similarly profiled men, aged 17-22 years, in a survey. Information was collected on the men's socioeconomic characteristics; awareness, knowledge, and perceptions of family planning; attitudes toward future contraceptive use; intra-family communication; knowledge about STIs/HIV/AIDS; and access and use of condoms. Content analysis for qualitative information and descriptive analysis for survey data were used to draw conclusions. Young unmarried rural Indian men's sexual and reproductive health (SRH) knowledge is limited, although the majority is familiar with condoms (99%). The young men identified electronic mass media (67%) as the prime source of reproductive health information, yet they lacked detailed knowledge of various contraceptives and felt ignored by health providers, who, they felt, would be capable of providing SRH information through interpersonal communication. Young men are more concerned about avoiding infections and securing sexual pleasure and less concerned about avoiding potential pregnancies. For example, 68% of the young men were aware of condoms and their HIV/AIDS preventive role, but only about two-fifths mentioned condom use to prevent unwanted pregnancies. Although most young men (96%) knew where to access a condom, they felt uncomfortable or embarrassed doing so in their own villages or close by because of socio-cultural norms that prevented them from using contraceptives. Very few respondents (4%) disclosed using condoms themselves, but 59% said they knew someone from their peer group who had used them. Young unmarried men in rural India are underserved with regard to SRH information and services, because they are not recognized as key targets under the public health system, and they receive their limited knowledge and information mainly from the mass media; this situation could be greatly improved by public health service providers. It is important that programmers involve young men with effective communication strategies to enable them to act responsibly with regard to their own sexual health needs.


Pilot assessment of supply chains for pharmaceuticals and medical commodities for malaria, tuberculosis and HIV infection in Ethiopia.
To obtain preliminary data on the drug supply management system in Ethiopia, selected facilities were assessed for the availability of essential drugs and commodities for malaria, TB and HIV. Of the 48 surveyed hospitals and health centers, 9 (19%), 9 (19%) and 10 (21%) did not have malaria, TB or HIV drugs, respectively. Similarly, of 27 health posts, 9 (33%) and 6 (22%) did not have rapid diagnostic tests and antimalarial drugs, respectively. The findings indicated an inadequate availability of essential drugs and commodities in the surveyed facilities as well as weaknesses in human resources and training. Assessments of commodity supply chains to ensure operational program success and impact are important.


Assistive products and the Sustainable Development Goals (SDGs).
The Sustainable Development Goals (SDGs) have placed great emphasis on the need for much greater social inclusion, and on making deliberate efforts to reach marginalized groups. People with disabilities are often marginalized through their lack of access to a range of services and opportunities. Assistive products can help people overcome impairments and barriers enabling them to be active, participating and productive members of society. Assistive products are vital for people with disabilities, frailty and chronic illnesses; and for those with mental health problems, and gradual cognitive and physical decline characteristic of aging populations. This paper illustrates how the achievement of each of the 17 SDGs can be facilitated by the use of assistive products. Without promoting the availability of assistive products the SDGs cannot be achieved equitably. We highlight how assistive products can be considered as both a mediator and a moderator of SDG achievement. We also briefly describe how the Global Cooperation on Assistive Technology (GATE) is working to promote greater access to assistive products on a global scale.


Evaluation of the Aries Bordetella Assay for Detection and Identification of Bordetella pertussis in Nasopharyngeal Swab Specimens.
The Aries Bordetella assay (Aries BA) (Luminex Corporation) recently received FDA clearance for the detection and differentiation of Bordetella pertussis and Bordetella parapertussis nucleic acids in nasopharyngeal swab (NPS) samples. The objective of this study was to evaluate the performance of the Aries BA in comparison to that of the BioFire FilmArray respiratory panel (RP). The Aries BA was evaluated using retrospective, remnant nasopharyngeal swabs (NPS), previously tested by FilmArray RP. Performance characteristics evaluated included positive percent agreement (PPA) and negative percent agreement (NPA) with the FilmArray RP. Discordant analysis was performed using bidirectional sequencing. A time and motion study was performed to compare the laboratory workflow of the two tests. Three hundred samples were included in the study. There were no samples positive for B. parapertussis The PPA and NPA of the Aries BA were 61.1% (95% confidence interval [CI], 35.8 to 82.7%) and 100% (95% CI, 98.7 to 100%). Discordant results included five Bordetella bronchiseptica results that were incorrectly identified as B. pertussis by the FilmArray RP and one false-negative result for both the Aries BA and the FilmArray RP. The overall agreement between the Aries BA and FilmArray RP for the detection of B. pertussis was considered good at 97.7% with a kappa value of 0.71 (95% CI, 0.51 to 0.9). The Aries BA offers a new diagnostic option for the rapid and targeted approach to the diagnosis of pertussis. Unlike the FilmArray RP, the Aries BA did not cross-react with B. bronchiseptica in our study, although a larger sample set should be tested to confirm this finding.


Pharmacokinetic analysis and comparison of caffeine administered rapidly or slowly in coffee chilled or hot versus chilled energy drink in healthy young adults.
There is a paucity of data describing the impact of type of beverage (coffee versus energy drink), different rates of consumption and different temperature of beverages on the pharmacokinetic disposition of caffeine. Additionally, there is concern that inordinately high levels of caffeine may result from the rapid consumption of cold energy drinks. The objective of this study was to compare the pharmacokinetics of caffeine under various drink temperature, rate of consumption and vehicle (coffee versus energy drink) conditions. Five caffeine (dose = 160 mg) conditions were evaluated in an open-label, group-randomized, crossover fashion. After the administration of each caffeine dose, 10 serial plasma samples were harvested. Caffeine concentration was measured via liquid chromatography-mass spectrometry (LC-MS), and those concentrations were assessed by non-compartmental pharmacokinetic analysis. The calculated mean pharmacokinetic parameters were analyzed statistically by one-way repeated measures analysis of variance (RM ANOVA). If differences were found, each group was compared to the other by all pair-wise multiple comparison. Twenty-four healthy subjects ranging in age from 18 to 30 completed the study. The mean caffeine concentration time profiles were similar with overlapping SDs at all measured time points. The ANOVA revealed significant differences in mean Cmax and Vd ss/F, but no pair-wise comparisons reached statistical significance. No other differences in pharmacokinetic parameters were found. The results of this study are consistent with previous caffeine pharmacokinetic studies and suggest that while rate of consumption, temperature of beverage and vehicle (coffee versus energy drink) may be associated with slightly different pharmacokinetic parameters, the overall impact of these variables is small. This study suggests that caffeine absorption and exposure from coffee and energy drink is similar irrespective of beverage temperature or rate of consumption.


Educational attainment and risk of HIV infection, response to antiretroviral treatment, and mortality in HIV-infected patients.
To estimate association between educational attainment and risk of HIV diagnosis, response to HAART, all-cause, and cause-specific mortality in Denmark in 1998-2009. Prospective, population-based cohort study including 1277 incident HIV-infected patients without hepatitis C virus or intravenous drug abuse identified in the Danish HIV Cohort Study and 5108 individually matched population controls. Data on educational attainment, categorized as low, medium, or high, were identified in The Danish Attainment Register. Logistic and Poisson regression were used to estimate odds ratios (ORs) and mortality rate ratios (MRRs). OR of HIV diagnosis was 1.7 (95% confidence interval, CI 1.3-2.3) among heterosexual individuals with low educational attainments, but no associations between educational attainment and time to HAART initiation, CD4 cell count, or viral suppression were identified. All-cause MRRs were 1.8 (95% CI 1.0-3.2) and 1.8 (1.1-2.8) for HIV-infected patients and population controls with low educational attainment compared with medium and high educational attainment. MRRs for smoking and alcohol-related deaths were 3.6 (95% CI 1.5-8.9) for HIV-infected patients and 2.0 (95% CI 1.2-3.4) for population controls with low educational attainment compared with medium and high educational attainment. With free and equal access to healthcare, low educational attainment might increase risk of HIV infection among heterosexual individuals, but was not associated with late/very late presentation of HIV, time to HAART initiation, or HAART response. However, low educational attainment substantially increased lifestyle-related mortality, which indicates that increased mortality in HIV-infected patients with low educational attainments stems from risk factors unrelated to HIV.


Do I really want to be going on a bloody diet? Gendered narratives in older men with painful knee osteoarthritis.
Small reductions in body weight can decrease osteoarthritic knee pain. Intuitively this should provide a strong incentive for weight-loss. However many people undergoing knee joint replacement (KJR) are categorised as obese. Gender theories can help us to understand differential responses to illness and therefore make an important contribution to rehabilitation. We aimed to explore barriers to weight loss in a group of older men with osteoarthritis. We conducted 12 in-depth interviews, before and 1 year after surgery, with six obese men listed for KJR. Analysis was influenced by constructivist grounded theory. We abstracted conceptual themes from the data through constant comparison. We identified the following themes: (1) I am big and healthy and don't need to lose weight; (2) being this size isn't good for me; (3) men don't have to worry about that sort of thing; (4) I am not as active as I used to be; (5) I have worked hard all my life; (6) what is the point in trying anyway? Gendered narratives can make it challenging for men to lose weight. Healthcare professionals cannot ignore the influence of gender on rehabilitation and should consider gender specific strategies. Implications for rehabilitation Men may not associate being overweight with being unhealthy. Men may take pride in being in good shape and may respond better to weight loss strategies that focus on fitness not body size. Men may link weight gain with decrease in activity levels rather than overeating. Health care professionals should challenge the assumption that weight loss will follow surgery. Health care professionals cannot ignore the influence of gender on the success of rehabilitation.


A new photopolymerizable blood vessel glue that seals human vessel anastomoses without augmenting thrombogenicity.
A new nonbiologic photopolymerizable glue, polyethyleneglycol 400 diacrylate, was studied with respect to its mechanical and biochemical interaction with human blood vessels. Using the human placental artery model, we tested the ability of polyethyleneglycol 400 diacrylate to prevent leakage of blood at the site of vascular anastomoses, which are made porous by the presence of tissue gaps and suture puncture sites. Fibrin glue is known to augment local vessel thrombogenicity through the presence of the coagulation enzyme thrombin. We tested the effect of externally applied polyethyleneglycol 400 diacrylate (which does not contain thrombin) on luminal thrombin activity and platelet deposition from flowing human blood. At a shear rate of 312 per second and a transmural pressure of 80 cm H2O, the leakage rate of saline from human placental artery anastomoses was 1.0 +/- 1.2 ml/min (n = 8). When the same anastomoses were then glued, 7 of 8 of the anastomoses leaked less than 0.05 ml/min (p < 0.05). Platelet deposition to human vessels was not influenced by the external application of polyethyleneglycol 400 diacrylate either on intact vessels (no polyethyleneglycol 400 diacrylate, 0.51 +/- 0.28 x 10(6) platelets/cm2; with polyethyleneglycol 400 diacrylate, 0.47 +/- 0.26 x 10(6) platelets/cm2; n = 7) or at anastomoses (no polyethyleneglycol 400 diacrylate, 0.69 +/- 0.36 x 10(6) platelets/cm2; with polyethyleneglycol 400 diacrylate, 0.53 +/- 0.33 x 10(6) platelets/cm2; n = 8), p > 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)


Mast cell degranulation by a hemolytic lipid toxin decreases GBS colonization and infection.
Ascending infection of microbes from the lower genital tract into the amniotic cavity increases the risk of preterm birth, stillbirth, and newborn infections. Host defenses that are critical for preventing ascending microbial infection are not completely understood. Group B Streptococcus (GBS) are Gram-positive bacteria that frequently colonize the lower genital tract of healthy women but cause severe infections during pregnancy, leading to preterm birth, stillbirth, or early-onset newborn infections. We recently described that the GBS pigment is hemolytic, and increased pigment expression promotes GBS penetration of human placenta. Here, we show that the GBS hemolytic pigment/lipid toxin and hyperpigmented GBS strains induce mast cell degranulation, leading to the release of preformed and proinflammatory mediators. Mast cell-deficient mice exhibit enhanced bacterial burden, decreased neutrophil mobilization, and decreased immune responses during systemic GBS infection. In a vaginal colonization model, hyperpigmented GBS strains showed increased persistence in mast cell-deficient mice compared to mast cell-proficient mice. Consistent with these observations, fewer rectovaginal GBS isolates from women in their third trimester of pregnancy were hyperpigmented/hyperhemolytic. Our work represents the first example of a bacterial hemolytic lipid that induces mast cell degranulation and emphasizes the role of mast cells in limiting genital colonization by hyperpigmented GBS.


Transition to retirement and risk of cardiovascular disease: prospective analysis of the US health and retirement study.
Transitioning from work to retirement could be either beneficial or harmful for health. We investigated the association between transition to retirement and risk of stroke and myocardial infarction (MI). We followed US Health and Retirement Study participants age 50+ working full-time for pay and free of major cardiovascular disease (n = 5422) in 1998 up to 10 years for transition to full retirement and self- or proxy-report of either stroke or MI (CVD; 665 events). We used discrete-time survival analysis to compare the CVD incidence for the fully retired versus the full-time working population. To distinguish short-term from long-term risks, we compared the association in the first year after retirement to estimates 2+ years after retirement. In the full model adjusting for age, sex, childhood and adult SES, behavior, and co-morbidities, being retired was associated with elevated odds of CVD onset (OR = 1.40, 95% CI: 1.04, 1.90) compared to those remaining in the full-time labor force. The odds ratio for CVD incidence within the first year of retirement was 1.55 (95% CI: 1.03, 2.33). From the second year post-retirement and thereafter, the retired had marginally elevated risk of CVD compared to those still working (OR = 1.35; 95% CI: 0.96, 1.91). Although confidence intervals were wide for some sub-groups, there were no significant interactions by sex or socioeconomic status. Results suggest that CVD risk is increased after retirement.