Dietary proteins in the regulation of food intake and body weight in humans.
This review presents 4 lines of evidence supporting a role for proteins in the regulation of food intake and maintenance of healthy body weights. It is concluded that the protein content of food, and perhaps its source, is a strong determinant of short-term satiety and of how much food is eaten. Although the role of protein in the regulation of long-term food intake and body weight is less clear, the evidence reviewed suggests that further research to define its role is merited. Such research has the potential to lead to new functional foods, food formulations, and dietary recommendations for achieving healthy body weights.


Ocular following response to sampled motion.
We investigate the impact of monitor frame rate on the human ocular following response (OFR) and find that the response latency considerably depends on the frame rate in the range of 80-160 Hz, which is far above the flicker fusion limit. From the lowest to the highest frame rate the latency declines by roughly 10 ms. Moreover, the relationship between response latency and stimulus speed is affected by the frame rate, compensating and even inverting the effect at lower frame rates. In contrast to that, the initial response acceleration is not affected by the frame rate and its expected dependence on stimulus speed remains stable. The nature of these phenomena reveals insights into the neural mechanism of low-level motion detection underlying the ocular following response.


Self-assembling nanofibers inhibit glial scar formation and promote axon elongation after spinal cord injury.
Peptide amphiphile (PA) molecules that self-assemble in vivo into supramolecular nanofibers were used as a therapy in a mouse model of spinal cord injury (SCI). Because self-assembly of these molecules is triggered by the ionic strength of the in vivo environment, nanoscale structures can be created within the extracellular spaces of the spinal cord by simply injecting a liquid. The molecules are designed to form cylindrical nanofibers that display to cells in the spinal cord the laminin epitope IKVAV at nearly van der Waals density. IKVAV PA nanofibers are known to inhibit glial differentiation of cultured neural stem cells and to promote neurite outgrowth from cultured neurons. In this work, in vivo treatment with the PA after SCI reduced astrogliosis, reduced cell death, and increased the number of oligodendroglia at the site of injury. Furthermore, the nanofibers promoted regeneration of both descending motor fibers and ascending sensory fibers through the lesion site. Treatment with the PA also resulted in significant behavioral improvement. These observations demonstrate that it is possible to inhibit glial scar formation and to facilitate regeneration after SCI using bioactive three-dimensional nanostructures displaying high densities of neuroactive epitopes on their surfaces.


Renal Biology Driven Macro- and Microscale Design Strategies for Creating an Artificial Proximal Tubule Using Fiber-Based Technologies.
Chronic kidney disease affects one in six people worldwide. Due to the scarcity of donor kidneys and the complications associated with hemodialysis (HD), a cell-based bioartificial kidney (BAK) device is desired. One of the shortcomings of HD is the lack of active transport of solutes that would normally be performed by membrane transporters in kidney epithelial cells. Specifically, proximal tubule (PT) epithelial cells play a major role in the active transport of metabolic waste products. Therefore, a BAK containing an artificial PT to actively transport solutes between the blood and the filtrate could provide major therapeutic advances. Creating such an artificial PT requires a biocompatible tubular structure which supports the adhesion and function of PT-specific epithelial cells. Ideally, this scaffold should structurally replicate the natural PT basement membrane which consists mainly of collagen fibers. Fiber-based technologies such as electrospinning are therefore especially promising for PT scaffold manufacturing. This review discusses the use of electrospinning technologies to generate an artificial PT scaffold for ex vivo/in vivo cellularization. We offer a comparison of currently available electrospinning technologies and outline the desired scaffold properties required to serve as a PT scaffold. Discussed also are the potential technologies that may converge in the future, enabling the effective and biomimetic incorporation of synthetic PTs in to BAK devices and beyond.


Lack of Ecological and Life History Context Can Create the Illusion of Social Interactions in Dictyostelium discoideum.
Studies of social microbes often focus on one fitness component (reproductive success within the social complex), with little information about or attention to other stages of the life cycle or the ecological context. This can lead to paradoxical results. The life cycle of the social amoeba Dictyostelium discoideum includes a multicellular stage in which not necessarily clonal amoebae aggregate upon starvation to form a possibly chimeric (genetically heterogeneous) fruiting body made of dead stalk cells and spores. The lab-measured reproductive skew in the spores of chimeras indicates strong social antagonism that should result in low genotypic diversity, which is inconsistent with observations from nature. Two studies have suggested that this inconsistency stems from the one-dimensional assessment of fitness (spore production) and that the solution lies in tradeoffs between multiple life-history traits, e.g.: spore size versus viability; and spore-formation (via aggregation) versus staying vegetative (as non-aggregated cells). We develop an ecologically-grounded, socially-neutral model (i.e. no social interactions between genotypes) for the life cycle of social amoebae in which we theoretically explore multiple non-social life-history traits, tradeoffs and tradeoff-implementing mechanisms. We find that spore production comes at the expense of time to complete aggregation, and, depending on the experimental setup, spore size and viability. Furthermore, experimental results regarding apparent social interactions within chimeric mixes can be qualitatively recapitulated under this neutral hypothesis, without needing to invoke social interactions. This allows for simple potential resolutions to the previously paradoxical results. We conclude that the complexities of life histories, including social behavior and multicellularity, can only be understood in the appropriate multidimensional ecological context, when considering all stages of the life cycle.


Rhythmic brain stimulation reduces anxiety-related behavior in a mouse model based on meditation training.
Meditation training induces changes at both the behavioral and neural levels. A month of meditation training can reduce self-reported anxiety and other dimensions of negative affect. It also can change white matter as measured by diffusion tensor imaging and increase resting-state midline frontal theta activity. The current study tests the hypothesis that imposing rhythms in the mouse anterior cingulate cortex (ACC), by using optogenetics to induce oscillations in activity, can produce behavioral changes. Mice were randomly assigned to groups and were given twenty 30-min sessions of light pulses delivered at 1, 8, or 40 Hz over 4 wk or were assigned to a no-laser control condition. Before and after the month all mice were administered a battery of behavioral tests. In the light/dark box, mice receiving cortical stimulation had more light-side entries, spent more time in the light, and made more vertical rears than mice receiving rhythmic cortical suppression or no manipulation. These effects on light/dark box exploratory behaviors are associated with reduced anxiety and were most pronounced following stimulation at 1 and 8 Hz. No effects were seen related to basic motor behavior or exploration during tests of novel object and location recognition. These data support a relationship between lower-frequency oscillations in the mouse ACC and the expression of anxiety-related behaviors, potentially analogous to effects seen with human practitioners of some forms of meditation.


The burden of war-injury in the Palestinian health care sector in Gaza Strip.
War-related injury is a major public health concern, and a leading cause of mortality, morbidity, and disability globally, particularly in low and middle-income countries such as Palestine. Little is known about the burden of war-related injury in the Palestinian context. The objective of this study was to characterize the incidence and pattern of injuries, associated with war in Gaza Strip, from July 8 to August 26, 2014. This was a descriptive study based on an injury registry at hospital facilities in the Gaza Strip. A total of 420 victims records from 2014 Gaza war injuries were randomly selected, proportionate to the size of the study population estimated across five Gaza governorates. Simple descriptive statistics were calculated to explore the frequency and percentage distribution of study variables and injury data. A chi-square test (X2) was used. The significance level was derived at p < 0.05. The data were analyzed by IBM SPSS software, version 23. Males (75.5%) have experienced more war-related injuries than females (24.5%), constituting a male: female ratio of 3.1:1. Almost half (49.5%) of the injured victims were of the age group 20-39, followed by children and adolescents (< 20 years), accounting for 31.4%. More than half of victims were single (53.6%), 44.3% were married and the rest were widowed or divorced. The overall number of injuries was 6.4 per 1000 population, though it varied among regions. North Gaza reported the highest number of injuries (9.0) and Rafah the lowest (4.7) per 1000 population. Blast and explosion were found to be the most common causes of war injuries (72.9%). The highest proportion of injuries were reported in the upper body. Multiple body shrapnel wounds and burns (39.3%) were most frequent. Other types of injuries were multiple organ injury (24.3%), fractures (13.6%), internal organ injury and bleeding (9.8%), amputation (4.5%), abrasions/lacerations and contusions (4.8%), vision or hearing loss or both (1.9%) and respiratory problems (1.9%). The highest percentage of injuries were classified as mild (46.9%), and the rest ranged from moderate-to-severe. Almost 26% of individuals had sustained disability, and most of them had physical/motor impairment. War-related injuries constitute a major problem to public health discipline and clinical medicine as well. A better surveillance system using ICD codes, and development of a comprehensive electronic data network are necessary to make future research easier and more timely.


Suppressing roughness of virtual times in parallel discrete-event simulations.
In a parallel discrete-event simulation (PDES) scheme, tasks are distributed among processing elements (PEs) whose progress is controlled by a synchronization scheme. For lattice systems with short-range interactions, the progress of the conservative PDES scheme is governed by the Kardar-Parisi-Zhang equation from the theory of nonequilibrium surface growth. Although the simulated (virtual) times of the PEs progress at a nonzero rate, their standard deviation (spread) diverges with the number of PEs, hindering efficient data collection. We show that weak random interactions among the PEs can make this spread nondivergent. The PEs then progress at a nonzero, near-uniform rate without requiring global synchronizations.


Adolescent HIV disclosure in Zambia: barriers, facilitators and outcomes.
As adolescents living with HIV gain autonomy over their self-care and begin to engage in sexual relationships, their experiences of being informed about their HIV status and of telling others about their HIV status may affect their ability to cope with having the disease. In 2010, we conducted a qualitative study among adolescents aged 10-19 living with HIV in Zambia, and with their parents and health care providers. Through interviews and focus group discussions, we explored the disclosure of HIV status to adolescents living with HIV; adolescents' disclosure of their status to others; and the impact of both forms of disclosure on adolescents. Our study identified three main barriers to disclosure of HIV status: local norms that deter parents from communicating with their children about sexuality; fear of HIV stigma; and an underlying presumption that adolescents would not understand the consequences of a HIV diagnosis on their lives and relationships. With regard to adolescents' disclosure of their HIV status to their sexual partners, our study identified fear of rejection as a common barrier. In rare cases, open family conversations about HIV helped adolescents come to terms with a HIV diagnosis. Findings indicated that disclosure had various outcomes at the individual and interpersonal levels. At the individual level, some adolescents described being anxious, depressed and blaming themselves after being told they had HIV. At the interpersonal level, disclosure created opportunities for adolescents to access adherence support and other forms of psychosocial support from family members and peers. At the same time, it occasionally strained adolescents' sexual relationships, although it did not always lead to rejection. There is a need for public health interventions that guide adolescents living with HIV, their parents and families through the disclosure process. Such interventions should help parents to assess and understand the evolving cognitive capacity and maturity of their adolescents in order to determine the appropriate time to inform them of their HIV-positive status. Such interventions should also mitigate the risk of HIV stigma, as well as local norms that may prevent discussions of sexuality within families. Adolescents who have been informed of their HIV status should be provided with on-going support to prevent disclosure from negatively affecting their psychological and sexual wellbeing. Further research is needed to explore the potential role of trusted family members in contributing to the disclosure process.


Purification and Properties of White Muscle Lactate Dehydrogenase from the Anoxia-Tolerant Turtle, the Red-Eared Slider, Trachemys scripta elegans.
Lactate dehydrogenase (LDH; E.C. 126.96.36.199) is a crucial enzyme involved in energy metabolism in muscle, facilitating the production of ATP via glycolysis during oxygen deprivation by recycling NAD(+). The present study investigated purified LDH from the muscle of 20 h anoxic and normoxic T. s. elegans, and LDH from anoxic muscle showed a significantly lower (47%) K m for L-lactate and a higher V max value than the normoxic form. Several lines of evidence indicated that LDH was converted to a low phosphate form under anoxia: (a) stimulation of endogenously present protein phosphatases decreased the K m of L-lactate of control LDH to anoxic levels, whereas (b) stimulation of kinases increased the K m of L-lactate of anoxic LDH to normoxic levels, and (c) dot blot analysis shows significantly less serine (78%) and threonine (58%) phosphorylation in anoxic muscle LDH as compared to normoxic LDH. The physiological consequence of anoxia-induced LDH dephosphorylation appears to be an increase in LDH activity to promote the reduction of pyruvate in muscle tissue, converting the glycolytic end product to lactate to maintain a prolonged glycolytic flux under energy-stressed anoxic conditions.


Epidemiology of National Collegiate Athletic Association men's and women's swimming and diving injuries from 2009/2010 to 2013/2014.
Recent injury data for collegiate-level swimming and diving are limited. This study describes the epidemiology of men's and women's swimming and diving injuries reported by the National Collegiate Athletic Association (NCAA) Injury Surveillance Program (ISP) during the 2009/2010 to 2013/2014 academic years. Injuries and athlete-exposure (AE) data reported within 9 men's and 13 women's swimming and diving programmes were analysed. Injury rates, injury rate ratios (IRR), and injury proportions by body site, diagnosis and mechanism were reported with 95% CIs. The ISP captured 149 and 208 injuries for men's and women's swimming and diving, respectively, leading to injury rates of 1.54/1000 and 1.71/1000 AEs. Among females, divers had a higher injury rate (2.49/1000 AEs) than swimmers (1.63/1000 AEs; IRR=1.53; 95% CI 1.07 to 2.19). Injury rates for male divers (1.94/1000 AEs) and swimmers (1.48/1000 AEs) did not differ (IRR=1.33; 95% CI 0.85 to 2.31). Most injuries occurred to the shoulder, resulted in strains and were classified as overuse or non-contact. Female swimmers had a higher overuse injury rate (1.04/1000 AEs) than male swimmers (0.66/1000 AEs; IRR=1.58; 95% CI 1.14 to 2.19). Overuse injury rates for female divers (0.54/1000 AEs) and male divers (0.46/1000 AEs) did not differ (IRR=1.16; 95% CI 0.40 to 3.34). Injury rates in 2012/2013-2013/2014 were lower than those in 2009/2010-2011/2012 for women's swimming (IRR=0.70; 95% CI 0.52 to 0.95) and diving (IRR=0.56; 95% CI 0.30 to 1.08), respectively. No time trends existed for men's swimmers or divers. Shoulder, strain and overuse injuries were common in collegiate men's and women's swimming and diving. Female swimmers were more likely to suffer an overuse injury than male swimmers. In addition, divers may have higher injury rates than swimmers, although small reported numbers warrant additional research.


Pediatric exposure to laundry detergent pods.
Laundry detergent pods are a new product in the US marketplace. This study investigates the epidemiologic characteristics and outcomes of laundry detergent pod exposures among young children in the United States. Using data from the National Poison Data System, exposures to laundry detergent pods among children younger than 6 years of age during 2012-2013 were investigated. There were 17 230 children younger than 6 years exposed to laundry detergent pods in 2012-2013. From March 2012 to April 2013, the monthly number of exposures increased by 645.3%, followed by a 25.1% decrease from April to December 2013. Children younger than 3 years accounted for 73.5% of cases. The major route of exposure was ingestion, accounting for 79.7% of cases. Among exposed children, 4.4% were hospitalized and 7.5% experienced a moderate or major medical outcome. A spectrum of clinical effects from minor to serious was seen with ingestion and ocular exposures. There were 102 patients (0.6%) exposed to a detergent pod via ingestion, aspiration, or a combination of routes, including ingestion, who required tracheal intubation. There was 1 confirmed death. Laundry detergent pods pose a serious poisoning risk to young children. This nationwide study underscores the need for increased efforts to prevent exposure of young children to these products, which may include improvements in product packaging and labeling, development of a voluntary product safety standard, and public education. Product constituent reformulation is another potential strategy to mitigate the severity of clinical effects of laundry detergent pod exposure.


Structure and dynamics of dinuclear zirconium(IV) complexes.
We have determined by X-ray crystallography the structures of three dinuclear zirconium(IV) complexes containing the heptadentate ligand dhpta (where H(5)dhpta = 1,3-diamino-2-propanol-N,N,N',N'-tetraacetic acid, 1) and different countercations: K(2)[Zr(2)(dhpta)(2)].5H(2)O (2.5H(2)O), Na(2)[Zr(2)(dhpta)(2)].7H(2)O.C(2)H(5)OH (3.7H(2)O.C(2)H(5)OH), and Cs(2)[Zr(2)(dhpta)(2)].H(5)O(2).Cl.4H(2)O (4.H(5)O(2).Cl.4H(2)O). In the K(I) complex 2, crystallized from water, the two Zr(IV) ions are 3.5973(4) A apart and bridged via two alkoxo groups (average Zr-O 2.165 A). Each Zr(IV) is eight-coordinate and also bound to two N atoms (average Zr-N 2.448 A), and four carboxylate O atoms (average Zr-O 2.148 A). The two dhpta ligands in the dinuclear unit have different conformations. One face of the complex contains an array of 14 oxygen atoms and interacts strongly with the two K(I) ions, one of which is 6-coordinate, the other 8-coordinate, which are 3.922(4) A apart and bridged by a carboxylate O and by two water molecules. The structures of the dinuclear anion [Zr(2)(dhpta)(2)](2-) in the Na(I) complex 3 and in the Cs(I) complex 4 are essentially identical to that found in complex 2, although the alkali metal ions coordinate differently to the oxygen-rich face. All Zr(IV) ions have a distorted triangulated dodecahedral geometry. Although the crystal structure of complex 2 does not indicate the presence of acidic protons, in 4 an [H(5)O(2)](+) unit is strongly H-bonded to an oxygen atom of a coordinated carboxylate group. 1D and 2D (1)H and (13)C NMR spectroscopic and potentiometric studies reveal two deprotonations with pK(a) values of 9.0 and 10.0. At low pH, two carboxylate groups appear to undergo protonation accompanied by chelate ring-opening, and the complex exhibits dynamic fluxional behavior in which the two magnetically nonequivalent dhpta ligands exchange at a rate of 11 s(-1) at pH 3.30, 298 K, as determined from 2D EXSY NMR studies. Ligand interchange is not observed at high pH (>11). The same crystals of complex 2 were obtained from solutions at pH 3 or 12. The dynamic configurational change is therefore mediated by the aqueous solvent.


The translation research in a dental setting (TRiaDS) programme protocol.
It is well documented that the translation of knowledge into clinical practice is a slow and haphazard process. This is no less true for dental healthcare than other types of healthcare. One common policy strategy to help promote knowledge translation is the production of clinical guidance, but it has been demonstrated that the simple publication of guidance is unlikely to optimise practice. Additional knowledge translation interventions have been shown to be effective, but effectiveness varies and much of this variation is unexplained. The need for researchers to move beyond single studies to develop a generalisable, theory based, knowledge translation framework has been identified.For dentistry in Scotland, the production of clinical guidance is the responsibility of the Scottish Dental Clinical Effectiveness Programme (SDCEP). TRiaDS (Translation Research in a Dental Setting) is a multidisciplinary research collaboration, embedded within the SDCEP guidance development process, which aims to establish a practical evaluative framework for the translation of guidance and to conduct and evaluate a programme of integrated, multi-disciplinary research to enhance the science of knowledge translation. Set in General Dental Practice the TRiaDS programmatic evaluation employs a standardised process using optimal methods and theory. For each SDCEP guidance document a diagnostic analysis is undertaken alongside the guidance development process. Information is gathered about current dental care activities. Key recommendations and their required behaviours are identified and prioritised. Stakeholder questionnaires and interviews are used to identify and elicit salient beliefs regarding potential barriers and enablers towards the key recommendations and behaviours. Where possible routinely collected data are used to measure compliance with the guidance and to inform decisions about whether a knowledge translation intervention is required. Interventions are theory based and informed by evidence gathered during the diagnostic phase and by prior published evidence. They are evaluated using a range of experimental and quasi-experimental study designs, and data collection continues beyond the end of the intervention to investigate the sustainability of an intervention effect. The TRiaDS programmatic approach is a significant step forward towards the development of a practical, generalisable framework for knowledge translation research. The multidisciplinary composition of the TRiaDS team enables consideration of the individual, organisational and system determinants of professional behaviour change. In addition the embedding of TRiaDS within a national programme of guidance development offers a unique opportunity to inform and influence the guidance development process, and enables TRiaDS to inform dental services practitioners, policy makers and patients on how best to translate national recommendations into routine clinical activities.


Repression of p27kip1 synthesis by platelet-derived growth factor in BALB/c 3T3 cells.
We have investigated the regulation of p27kip1, a cyclin-dependent kinase inhibitor, in BALB/c 3T3 cells during growth factor-stimulated transition from quiescence (G0) to a proliferative (G1) state. The level of p27kip1 protein falls dramatically after mitogenic stimulation and is accompanied by a decrease in cyclin E associated p27kip1, as well as a transient increase in cyclin D1-associated p27kip1 that later declines concomitantly with the loss of total p27kip1. Analysis of metabolically labelled cells revealed that cyclin D2, cyclin D3, and cdk4 were also partnered with p27kip1 in quiescent BALB/c 3T3 cells and that this association decreased after platelet-derived growth factor (PDGF) treatment. Furthermore, the decline in p27kip1 and reduced association with cyclin D3, initiated by the addition of PDGF but not plasma-derived factors, suggested that these changes are involved in competence, the first step in the exit from G0. Synthesis of p27kip1 as determined by incorporation of [35S]methionine was repressed upon mitogenic stimulation, and PDGF was sufficient to elicit this repression within 2 to 3 h. Pulse-chase experiments demonstrated the reduced rate of synthesis was not the result of an increased rate of degradation. Full repression of p27kip1 synthesis required the continued presence of PDGF and failed to occur in the presence of the RNA polymerase inhibitor 5,6-dichlorobenzimidazole riboside. These characteristics demonstrate that repression was a late effect of PDGF and was consistent with our finding that conditional expression of activated H-ras did not affect synthesis of p27kip1. Northern (RNA) analysis of p27kip1 mRNA revealed that the repression was not accompanied by a corresponding decrease in p27kip1 mRNA, suggesting that the PDGF-regulated decrease in p27kip1 expression occurred through a translational mechanism.


AN APPROACH FOR JOINTLY MODELING MULTIVARIATE LONGITUDINAL MEASUREMENTS AND DISCRETE TIME-TO-EVENT DATA.
In many medical studies, patients are followed longitudinally and interest is on assessing the relationship between longitudinal measurements and time to an event. Recently, various authors have proposed joint modeling approaches for longitudinal and time-to-event data for a single longitudinal variable. These joint modeling approaches become intractable with even a few longitudinal variables. In this paper we propose a regression calibration approach for jointly modeling multiple longitudinal measurements and discrete time-to-event data. Ideally, a two-stage modeling approach could be applied in which the multiple longitudinal measurements are modeled in the first stage and the longitudinal model is related to the time-to-event data in the second stage. Biased parameter estimation due to informative dropout makes this direct two-stage modeling approach problematic. We propose a regression calibration approach which appropriately accounts for informative dropout. We approximate the conditional distribution of the multiple longitudinal measurements given the event time by modeling all pairwise combinations of the longitudinal measurements using a bivariate linear mixed model which conditions on the event time. Complete data are then simulated based on estimates from these pairwise conditional models, and regression calibration is used to estimate the relationship between longitudinal data and time-to-event data using the complete data. We show that this approach performs well in estimating the relationship between multivariate longitudinal measurements and the time-to-event data and in estimating the parameters of the multiple longitudinal process subject to informative dropout. We illustrate this methodology with simulations and with an analysis of primary biliary cirrhosis (PBC) data.


Determination of Chlorine in Milk via Molecular Absorption of SrCl Using High-Resolution Continuum Source Graphite Furnace Atomic Absorption Spectrometry.
Total chlorine in milk was determined via the molecular absorption of diatomic strontium monochloride at 635.862 nm using high-resolution continuum source graphite furnace atomic absorption spectrometry. The effects of coating the graphite furnace, using different modifiers, amount of molecule-forming element, and different calibrants were investigated and optimized. Chlorine concentrations in milk samples were determined in a Zr-coated graphite furnace using 25 μg of Sr as the molecule-forming reagent and applying a pyrolysis temperature of 600 °C and a molecule-forming temperature of 2300 °C. Linearity was maintained up to 500 μg mL(-1) of Cl. The method was tested by analyzing a certified reference wastewater. The results were in the uncertainty limits of the certified value. The limit of detection of the method was 1.76 μg mL(-1). The chlorine concentrations in various cow milk samples taken from the market were found in the range of 588-1472 mg L(-1).


Characteristics of an autologous leukocyte and platelet-rich fibrin patch intended for the treatment of recalcitrant wounds.
We have investigated the physical, biochemical, and cellular properties of an autologous leukocyte and platelet-rich fibrin patch. This was generated in an automated device from a sample of a patient's blood at the point of care. Using microscopy, cell counting, enzyme-linked immunosorbent assay, antibody arrays, and cell culture assays, we show that the patch is a three-layered membrane comprising a fibrin sheet, a layer of platelets, and a layer of leukocytes. Mean recovery of platelets from the donated blood was 98% (±95%CI 0.8%). Mean levels of platelet-derived growth factor AB, human transforming growth factor beta 1, and vascular endothelial growth factor extracted from the patch were determined as 127 ng (±95% CI 20), 92 ng (±95%CI 17), and 1.35 ng (±95%CI 0.37), respectively. We showed a continued release of PDGF-AB over several days, the rate of which was increased by the addition of chronic wound fluid. By comparison with traditional platelet-rich plasma, differences in immune components were found. The relevance of these findings was assessed by showing a mitogenic and migratory effect on cultured human dermal fibroblasts. Further, we showed that fibrocytes, a cell type important for acute wound healing, could be grown from the patch. The relevance of these findings in relation to the use of the patch for treating recalcitrant wounds is discussed.


Why patterns of assortative mating are key to study sexual selection and how to measure them.
The study of sexual selection is being revolutionised by the realisation that most populations exhibit some degree of polyandry, i.e. females mating with multiple males. Polyandry can drastically change the operation of sexual selection on males as it reduces the reproductive success that males derive by mating with different females, by forcing their ejaculates to compete for fertilisation after copulation (sperm competition). Variation in polyandry within a population means that the impact of polyandry can differ drastically across males, depending on the polyandry of their own mating partners. Because the patterns through which males share mates within a population may have strong repercussions for variation in male reproductive success, measuring such patterns is critical to study the operation of sexual selection. Several methods have been proposed to measure the pattern of mate sharing at the population level. Here, we develop a new method (sperm competition intensity correlation, SCIC) and compare its performance against two established methods (Newman's assortativity and nestedness), using both idealised model populations and random simulated populations, across a range of biologically relevant population parameters: (i) population size, (ii) sex ratio and (iii) the 'mating density' of the population. We conclude that SCIC may be the most promising approach, as it is both internally consistent and robust across the parameter range. We discuss some important caveats and provide advice regarding the choice of method for future studies of sexual selection.


EPA guidance on physical activity as a treatment for severe mental illness: a meta-review of the evidence and Position Statement from the European Psychiatric Association (EPA), supported by the International Organization of Physical Therapists in Mental Health (IOPTMH).
Physical activity (PA) may be therapeutic for people with severe mental illness (SMI) who generally have low PA and experience numerous life style-related medical complications. We conducted a meta-review of PA interventions and their impact on health outcomes for people with SMI, including schizophrenia-spectrum disorders, major depressive disorder (MDD) and bipolar disorder. We searched major electronic databases until January 2018 for systematic reviews with/without meta-analysis that investigated PA for any SMI. We rated the quality of studies with the AMSTAR tool, grading the quality of evidence, and identifying gaps, future research needs and clinical practice recommendations. For MDD, consistent evidence indicated that PA can improve depressive symptoms versus control conditions, with effects comparable to those of antidepressants and psychotherapy. PA can also improve cardiorespiratory fitness and quality of life in people with MDD, although the impact on physical health outcomes was limited. There were no differences in adverse events versus control conditions. For MDD, larger effect sizes were seen when PA was delivered at moderate-vigorous intensity and supervised by an exercise specialist. For schizophrenia-spectrum disorders, evidence indicates that aerobic PA can reduce psychiatric symptoms, improves cognition and various subdomains, cardiorespiratory fitness, whilst evidence for the impact on anthropometric measures was inconsistent. There was a paucity of studies investigating PA in bipolar disorder, precluding any definitive recommendations. No cost effectiveness analyses in any SMI condition were identified. We make multiple recommendations to fill existing research gaps and increase the use of PA in routine clinical care aimed at improving psychiatric and medical outcomes.


Adding chiropractic manipulative therapy to standard medical care for patients with acute low back pain: results of a pragmatic randomized comparative effectiveness study.
Randomized controlled trial. To assess changes in pain levels and physical functioning in response to standard medical care (SMC) versus SMC plus chiropractic manipulative therapy (CMT) for the treatment of low back pain (LBP) among 18 to 35-year-old active-duty military personnel. LBP is common, costly, and a significant cause of long-term sick leave and work loss. Many different interventions are available, but there exists no consensus on the best approach. One intervention often used is manipulative therapy. Current evidence from randomized controlled trials demonstrates that manipulative therapy may be as effective as other conservative treatments of LBP, but its appropriate role in the healthcare delivery system has not been established. Prospective, 2-arm randomized controlled trial pilot study comparing SMC plus CMT with only SMC. The primary outcome measures were changes in back-related pain on the numerical rating scale and physical functioning at 4 weeks on the Roland-Morris Disability Questionnaire and back pain functional scale (BPFS). Mean Roland-Morris Disability Questionnaire scores decreased in both groups during the course of the study, but adjusted mean scores were significantly better in the SMC plus CMT group than in the SMC group at both week 2 (P < 0.001) and week 4 (P = 0.004). Mean numerical rating scale pain scores were also significantly better in the group that received CMT. Adjusted mean back pain functional scale scores were significantly higher (improved) in the SMC plus CMT group than in the SMC group at both week 2 (P < 0.001) and week 4 (P = 0.004). The results of this trial suggest that CMT in conjunction with SMC offers a significant advantage for decreasing pain and improving physical functioning when compared with only standard care, for men and women between 18 and 35 years of age with acute LBP.


Contraceptive use following unintended pregnancy among Ugandan women living with HIV.
Preventing unintended pregnancy is critical for women living with HIV (WLWH) to safely achieve their reproductive goals. Family planning services should support WLWH at risk of repeat unintended pregnancies. We examined the relationship between unintended pregnancy and subsequent contraception use among WLWH in Uganda. This was a retrospective analysis of data from a longitudinal cohort of individuals initiating antiretroviral therapy (ART), restricted to women with pregnancy (confirmed via urine β-hcg testing) between 2011-2013. The exposure of interest was intended vs unintended pregnancy, and the outcome was self-report of modern contraceptive use (hormonal methods, intrauterine device, sterilization, and/or consistent condom use) at 12 (range 6-18) months post-partum. A log-binomial model was used to estimate relative risks of modern contraceptive use post-partum based on intent of the index pregnancy, adjusted for age, socioeconomic status, education, relationship and HIV status of pregnancy partner, contraceptive use prior to pregnancy, years since HIV diagnosis, ART regimen, and CD4 cell count. Among 455 women, 110 women reported 110 incident pregnancies with report on intent. Women had a baseline median age of 29 years, baseline CD4 count 403 cells/mm3, and were living with HIV for 3.8 years. Fifty pregnancies (45%) were reported as unintended and 60 (55%) as intended. Postpartum, 64% of women with unintended and 51% with intended pregnancy reported modern contraception (p = 0.24). In adjusted models, there was no association between pregnancy intent and post-partum contraception. However, contraceptive use prior to the referent pregnancy was positively associated with post-partum contraceptive use (aRR 1.97 (95% CI 1.12-3.48, p = 0.02), while higher baseline CD4 cell count was associated with lower post-partum contraceptive use (aRR 0.95, 95% CI 0.90-0.99, p = 0.02). Almost half of incident pregnancies among WLWH in this cohort were unintended. Experiencing an unintended pregnancy was not associated with post-partum contraceptive use. Creative strategies to support contraceptive uptake for birth spacing and prevention of unintended pregnancies in the post-partum period are needed.


Evidence-based intervention in physical activity: lessons from around the world.
Promotion of physical activity is a priority for health agencies. We searched for reviews of physical activity interventions, published between 2000 and 2011, and identified effective, promising, or emerging interventions from around the world. The informational approaches of community-wide and mass media campaigns, and short physical activity messages targeting key community sites are recommended. Behavioural and social approaches are effective, introducing social support for physical activity within communities and worksites, and school-based strategies that encompass physical education, classroom activities, after-school sports, and active transport. Recommended environmental and policy approaches include creation and improvement of access to places for physical activity with informational outreach activities, community-scale and street-scale urban design and land use, active transport policy and practices, and community-wide policies and planning. Thus, many approaches lead to acceptable increases in physical activity among people of various ages, and from different social groups, countries, and communities.


Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons.
Many pregnant persons in the United States are receiving messenger RNA (mRNA) coronavirus disease 2019 (Covid-19) vaccines, but data are limited on their safety in pregnancy. From December 14, 2020, to February 28, 2021, we used data from the "v-safe after vaccination health checker" surveillance system, the v-safe pregnancy registry, and the Vaccine Adverse Event Reporting System (VAERS) to characterize the initial safety of mRNA Covid-19 vaccines in pregnant persons. A total of 35,691 v-safe participants 16 to 54 years of age identified as pregnant. Injection-site pain was reported more frequently among pregnant persons than among nonpregnant women, whereas headache, myalgia, chills, and fever were reported less frequently. Among 3958 participants enrolled in the v-safe pregnancy registry, 827 had a completed pregnancy, of which 115 (13.9%) resulted in a pregnancy loss and 712 (86.1%) resulted in a live birth (mostly among participants with vaccination in the third trimester). Adverse neonatal outcomes included preterm birth (in 9.4%) and small size for gestational age (in 3.2%); no neonatal deaths were reported. Although not directly comparable, calculated proportions of adverse pregnancy and neonatal outcomes in persons vaccinated against Covid-19 who had a completed pregnancy were similar to incidences reported in studies involving pregnant women that were conducted before the Covid-19 pandemic. Among 221 pregnancy-related adverse events reported to the VAERS, the most frequently reported event was spontaneous abortion (46 cases). Preliminary findings did not show obvious safety signals among pregnant persons who received mRNA Covid-19 vaccines. However, more longitudinal follow-up, including follow-up of large numbers of women vaccinated earlier in pregnancy, is necessary to inform maternal, pregnancy, and infant outcomes.


Lipid remodelling is a widespread strategy in marine heterotrophic bacteria upon phosphorus deficiency.
Upon phosphorus (P) deficiency, marine phytoplankton reduce their requirements for P by replacing membrane phospholipids with alternative non-phosphorus lipids. It was very recently demonstrated that a SAR11 isolate also shares this capability when phosphate starved in culture. Yet, the extent to which this process occurs in other marine heterotrophic bacteria and in the natural environment is unknown. Here, we demonstrate that the substitution of membrane phospholipids for a variety of non-phosphorus lipids is a conserved response to P deficiency among phylogenetically diverse marine heterotrophic bacteria, including members of the Alphaproteobacteria and Flavobacteria. By deletion mutagenesis and complementation in the model marine bacterium Phaeobacter sp. MED193 and heterologous expression in recombinant Escherichia coli, we confirm the roles of a phospholipase C (PlcP) and a glycosyltransferase in lipid remodelling. Analyses of the Global Ocean Sampling and Tara Oceans metagenome data sets demonstrate that PlcP is particularly abundant in areas characterized by low phosphate concentrations. Furthermore, we show that lipid remodelling occurs seasonally and responds to changing nutrient conditions in natural microbial communities from the Mediterranean Sea. Together, our results point to the key role of lipid substitution as an adaptive strategy enabling heterotrophic bacteria to thrive in the vast P-depleted areas of the ocean.


An efficient palladium catalyst system for the oxidative carbonylation of glycerol to glycerol carbonate.
Glycerol carbonate can be readily synthesized from the oxidative carbonylation of glycerol catalyzed by PdCl(2)(phen) (phen=1,10-phenanthroline) with the aid of CuI. High conversion (95 %) and selectivity (98 %) are achieved and the turnover frequency (TOF) reaches 455 h(-1). Furthermore, a new zeolite-Y-confined Pd catalyst, PdCl(2)(phen)@Y, has been successfully prepared by a ''flexible ligand'' method. The structure and composition of the heterogeneous catalyst have been characterized by atomic absorption spectroscopy, elemental analysis, N(2) sorption, XRD, FTIR, solid-state NMR, and X-ray photoelectron spectroscopy. This catalyst exhibits a comparable activity to its homogeneous counterpart and could be reused five times without significant decrease in activity. This is the most efficient heterogeneous system for synthesizing glycerol carbonate by the oxidative carbonylation of glycerol to date.


Increased expression of the LAZ3 (BCL6) proto-oncogene accompanies murine skeletal myogenesis.
The structural alterations of the LAZ3 (BCL6) gene are one of the most frequent events found in non-Hodgkin lymphoma. LAZ3 encodes a transcriptional repressor with a POZ/zinc finger structure similar to several Drosophila development regulators and to the human promyelocytic leukemia-associated PLZF gene. Consistent with the origin of LAZ3-associated malignancies, LAZ3 is expressed in mature B-cells and required for germinal center formation. However, its ubiquitous expression, with predominant levels in skeletal muscle, suggests that it may act outside the lymphoid system. To study how LAZ3 could be involved in skeletal muscle differentiation, we examined its expression in the C2 muscle cells. We report here that LAZ3 is upregulated at both mRNA and protein levels during the differentiation of proliferating C2 myoblasts into post-mitotic myotubes. This rise in LAZ3 expression is both precocious and sustained, and is not reversed when myotubes are re-exposed to mitogen-rich medium, suggesting that irreversible evens occurring upon myogenic terminal differentiation contribute to lock LAZ3 upregulation. In addition, using two different models, we found that a "simple" growth-arrest upon serum starvation is not sufficient to induce LAZ3 upregulation which rather appears as a feature of myogenic commitment and/or differentiation. Finally, BrdU incorporation assays in C2 cells entering the differentiation pathway indicate that "high" LAZ3 expression strongly correlates with their exit from the cell cycle. Taken as a whole, these findings suggest that LAZ3 could play a role in muscle differentiation. Together with some results reported in other cell types, we propose that LAZ3 may contribute to events common to various differentiation processes, possibly the induction and stabilization of the withdrawal from the cell cycle.


Visual feedback from a virtual body modulates motor illusion induced by tendon vibration.
Frequency-specific tendon vibration (TV) elicits illusory kinesthetic sensations around the vibrated body parts. Studies indicate that vision plays a fundamental role in modulating such illusions. In our current study, we used immersive virtual reality (IVR) to investigate the role of body-related visual feedback in modulating illusory sensation of movement in the left arm. Thirty healthy participants were asked to evaluate the onset of motor illusion and four illusion-related features (vividness, duration, extension and aftereffect), in the presence and absence of real and virtual visual feedback. Additionally, subjective reports of the embodiment illusion (the sense of embodying a virtual surrogate) were collected in virtual conditions. Results showed a progressive decrease in the perception of the motor illusion along a continuum ranging from the absence of visual feedback (maximal illusory perception) to the observation of one's own real arm (minimal illusory perception). Interestingly, the appearance of the virtual limbs affected the movement illusion differently. Specifically, TV evoked a stronger kinesthetic illusion when observing the virtual hand detached from the limb than during the observation of the virtual full limb and virtual object. This suggests that a closer visual resemblance between the virtual and real limb results in a greater effect on proprioceptive processing. However, no significant correlation was found between the illusion of arm movement and the illusion of embodiment, indicating that the two phenomena may not be directly related. These findings provide new insight into the role of body-related visual feedback in modulating motor illusions.


Visible Light Induced Cationic Polymerization of Epoxides by Using Multiwalled Carbon Nanotubes.
The visible light induced cationic polymerization of epoxides can be achieved by means of multiwalled carbon nanotubes (MWCNTs), which act as visible light photoinitiators via a radical-induced cationic photopolymerization process. When MWCNTs are irradiated with longer wavelengths (above 400 nm), they generate carbon radicals, by means of hydrogen abstraction from the epoxy monomer; these radicals are oxidized in the presence of iodonium salt to a carbocation that is sufficiently reactive to start the cationic ring-opening polymerization of an epoxy monomer. These mechanisms have been supported by electron paramagnetic resonance analysis.


Structural and antigenic analysis of Chlamydia pneumoniae.
Several isolates of Chlamydia pneumoniae were compared with each other and to Chlamydia trachomatis and Chlamydia psittaci by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblots. Protein profiles of the C. pneumoniae isolates appeared to be the same and were distinct from the other Chlamydia species. A 39.5-kilodalton (kDa) protein, similar in molecular weight to the major outer membrane proteins (MOMP) of C. trachomatis and C. psittaci, was found in the Sarkosyl-insoluble fraction, demonstrating its association with the outer membrane complex. In the outer membrane complex, the MOMP was shown to exist in disulfide-linked protein complexes. Electron microscopy of the Sarkosyl-extracted elementary bodies showed that the structural rigidity and pear-shaped morphology remained intact. Rabbit immune sera prepared against C. pneumoniae demonstrated immunoreactive proteins of 98-, 77-, 75-, 66-, 60-, 39.5-, 28-, and 17.5-kDa proteins. Cross-reactivity experiments revealed that most of the antigenic reactivities shared between C. psittaci and C. trachomatis extend to C. pneumoniae and that the 98-kDa protein recognition appeared to be C. pneumoniae specific. In contrast to the other Chlamydia spp., the recognition of the C. pneumoniae MOMP by homologous immune sera was weak and was cross-reactive with the MOMPs of the other Chlamydia species. These results suggest that the C. pneumoniae MOMP is less immunogenic and antigenically complex than are the MOMPs of C. trachomatis and C. psittaci.


Computer Simulations Imply Forelimb-Dominated Underwater Flight in Plesiosaurs.
Plesiosaurians are an extinct group of highly derived Mesozoic marine reptiles with a global distribution that spans 135 million years from the Early Jurassic to the Late Cretaceous. During their long evolutionary history they maintained a unique body plan with two pairs of large wing-like flippers, but their locomotion has been a topic of debate for almost 200 years. Key areas of controversy have concerned the most efficient biologically possible limb stroke, e.g. whether it consisted of rowing, underwater flight, or modified underwater flight, and how the four limbs moved in relation to each other: did they move in or out of phase? Previous studies have investigated plesiosaur swimming using a variety of methods, including skeletal analysis, human swimmers, and robotics. We adopt a novel approach using a digital, three-dimensional, articulated, free-swimming plesiosaur in a simulated fluid. We generated a large number of simulations under various joint degrees of freedom to investigate how the locomotory repertoire changes under different parameters. Within the biologically possible range of limb motion, the simulated plesiosaur swims primarily with its forelimbs using an unmodified underwater flight stroke, essentially the same as turtles and penguins. In contrast, the hindlimbs provide relatively weak thrust in all simulations. We conclude that plesiosaurs were forelimb-dominated swimmers that used their hind limbs mainly for maneuverability and stability.


Interstitial Mycosis Fungoides With Lichen Sclerosus-Like Clinical and Histopathological Features.
Mycosis fungoides (MF) simulates a variety of dermatologic disorders histopathologically and clinically, well deserving the designation of a great mimicker. Interstitial MF is a rare, but well-recognized histopathological variant resembling the interstitial form of granuloma annulare or the inflammatory phase of morphea. From a clinical standpoint, MF can have a wide array of manifestations, including an anecdotal presentation with lesions clinically suggestive of lichen sclerosus (LS). We herein report a 25-year-old man with a history of patch-stage MF who later developed widespread LS-like lesions histopathologically consistent with interstitial MF. In some biopsies, additional features resembling LS were discerned. We think that our case might represent a unique variant of interstitial MF presenting with LS-like lesions. The diagnostic challenge arising from this uncommon presentation is discussed together with review of the literature.


Immunohistochemistry in Ureteropelvic Junction Obstruction and Its Correlation to Postoperative Outcome.
To investigate the correlation between the status of interstitial cells of Cajal (ICC) in ureteropelvic junction (UPJ) and the resected ureteric margin and the postoperative outcome of Anderson-Hynes pyeloplasty in UPJ obstruction (UPJO) and to compare the ICC in the UPJ and the resected margin of the normal ureter. An observational study was conducted over a period of 2 years at the Department of Pediatric Surgery at Niloufer Institute of Women and Child Health. Children with intrinsic UPJO who underwent Anderson-Hynes dismembered pyeloplasty were included in the study. Six months postoperatively, the patients were divided into two groups based on diuretic isotopic renogram using technetium-99m-labeled diethylene triaminepentaacetic acid. Group 1 comprised patients with good surgical outcome. Group 2 comprised patients with a poor outcome. The histologic specimens were evaluated for ICC, and the immunohistochemical findings were correlated with the outcome. Twenty-five patients were included in this study (19 male and 6 female). Seventy-six percent of patients were under the age of 1 year. Group 1 had 23 cases and Group 2 had 2 cases. Out of the two patients with a poor outcome, one had negative grading at the UPJ and one had positive grading. Both these patients had a negative grading at the lower resected margins. More number of patients (24%) had +++ grading at the lower resected margin when compared to the UPJ (8%). This is the first study which correlates the status of ICC in UPJ with the outcome of pyeloplasty in pediatric patients. Both the cases with bad outcome had no ICC at the lower margin of the resected specimen and one case had no ICC at the UPJ. There is a statistically significant difference (P = 0.001) in the number of ICC at the UPJ and the resected margin.


Graphene supported graphone/graphane bilayer nanostructure material for spintronics.
We report an investigation into the magnetic and electronic properties of partially hydrogenated vertically aligned few layers graphene (FLG) synthesized by microwave plasma enhanced chemical vapor deposition. The FLG samples are hydrogenated at different substrate temperatures to alter the degree of hydrogenation and their depth profile. The unique morphology of the structure gives rise to a unique geometry in which graphane/graphone is supported by graphene layers in the bulk, which is very different from other widely studied structures such as one-dimensional nanoribbons. Synchrotron based x-ray absorption fine structure spectroscopy measurements have been used to investigate the electronic structure and the underlying hydrogenation mechanism responsible for the magnetic properties. While ferromagnetic interactions seem to be predominant, the presence of antiferromagnetic interaction was also observed. Free spins available via the conversion of sp(2) to sp(3) hybridized structures, and the possibility of unpaired electrons from defects induced upon hydrogenation are thought to be likely mechanisms for the observed ferromagnetic orders.


Linking intra- and interspecific assortative mating: Consequences for asymmetric sexual isolation.
Assortative mating is of interest because of its role in speciation and the maintenance of species boundaries. However, we know little about how within-species assortment is related to interspecific sexual isolation. Most previous studies of assortative mating have focused on a single trait in males and females, rather than utilizing multivariate trait information. Here, we investigate how intraspecific assortative mating relates to sexual isolation in two sympatric and congeneric damselfly species (genus Calopteryx). We connect intraspecific assortment to interspecific sexual isolation by combining field observations, mate preference experiments, and enforced copulation experiments. Using canonical correlation analysis, we demonstrate multivariate intraspecific assortment for body size and body shape. Males of the smaller species mate more frequently with heterospecific females than males of the larger species, which showed less attraction to small heterospecific females. Field experiments suggest that sexual isolation asymmetry is caused by male preferences for large heterospecific females, rather than by mechanical isolation due to interspecific size differences or female preferences for large males. Male preferences for large females and male-male competition for high quality females can therefore counteract sexual isolation. This sexual isolation asymmetry indicates that sexual selection currently opposes a species boundary.


Maternal high-fat diet leads to hippocampal and amygdala dendritic remodeling in adult male offspring.
Early-life exposure to calorie-dense food, rich in fat and sugar, contributes to the increasing prevalence of obesity and its associated adverse cognitive and emotional outcomes at adulthood. It is thus critical to determine the impact of such nutritional environment on neurobehavioral development. In animals, maternal high-fat diet (HFD) consumption impairs hippocampal function in adult offspring, but its impact on hippocampal neuronal morphology is unknown. Moreover, the consequences of perinatal HFD exposure on the amygdala, another important structure for emotional and cognitive processes, remain to be established. In rats, we show that adult offspring from dams fed with HFD (45% from fat, throughout gestation and lactation) exhibit atrophy of pyramidal neuron dendrites in both the CA1 of the hippocampus and the basolateral amygdala (BLA). Perinatal HFD exposure also impairs conditioned odor aversion, a task highly dependent on BLA function, without affecting olfactory or malaise processing. Neuronal morphology and behavioral alterations elicited by perinatal HFD are not associated with body weight changes but with higher plasma leptin levels at postnatal day 15 and at adulthood. Taken together, our results suggest that perinatal HFD exposure alters hippocampal and amygdala neuronal morphology which could participate to memory alterations at adulthood.


A new method for detecting anaerobic threshold by gas exchange.
Excess CO2 is generated when lactate is increased during exercise because its [H+] is buffered primarily by HCO-3 (22 ml for each meq of lactic acid). We developed a method to detect the anaerobic threshold (AT), using computerized regression analysis of the slopes of the CO2 uptake (VCO2) vs. O2 uptake (VO2) plot, which detects the beginning of the excess CO2 output generated from the buffering of [H+], termed the V-slope method. From incremental exercise tests on 10 subjects, the point of excess CO2 output (AT) predicted closely the lactate and HCO-3 thresholds. The mean gas exchange AT was found to correspond to a small increment of lactate above the mathematically defined lactate threshold [0.50 +/- 0.34 (SD) meq/l] and not to differ significantly from the estimated HCO-3 threshold. The mean VO2 at AT computed by the V-slope analysis did not differ significantly from the mean value determined by a panel of six experienced reviewers using traditional visual methods, but the AT could be more reliably determined by the V-slope method. The respiratory compensation point, detected separately by examining the minute ventilation vs. VCO2 plot, was consistently higher than the AT (2.51 +/- 0.42 vs. 1.83 +/- 0.30 l/min of VO2). This method for determining the AT has significant advantages over others that depend on regular breathing pattern and respiratory chemosensitivity.


10-Gingerol Inhibits Ovarian Cancer Cell Growth by Inducing G2 Arrest.
Purpose: Gingerol homologs found in the rhizomes of ginger plants have the potential to benefit human health, including the prevention and treatment of cancer. This study evaluated the effect of 10-gingerol on ovarian cancer cell (HEY, OVCAR3, and SKOV-3) growth. Methods: Cell growth was measured by MTT assays, flow cytometry was used to assess cell proliferation, cytotoxicity and cell cycle progression, and western blotting was used to measure cyclin protein expression. Results: Ovarian cancer cells that were treated with 10-gingerol experienced a time- and dose-dependent decrease in cell number, which was due to a reduction in cell proliferation rather than a cytotoxic effect. Reduced proliferation of 10-gingerol-treated ovarian cancer cells was associated with an increased percentage of cells in G2 phase of the cell cycle and a corresponding reduction in the percentage of cells in G1. Ovarian cancer cells also showed decreased cyclin A, B1, and D3 expression following exposure to 10-gingerol. Conclusion: These findings revealed that 10-gingerol caused a G2 arrest-associated suppression of ovarian cancer cell growth, which may be exploited in the management of ovarian cancer.


Women's evaluation of abuse and violence care in general practice: a cluster randomised controlled trial (weave).
Intimate partner abuse (IPA) is a major public health problem with serious implications for the physical and psychosocial wellbeing of women, particularly women of child-bearing age. It is a common, hidden problem in general practice and has been under-researched in this setting. Opportunities for early intervention and support in primary care need to be investigated given the frequency of contact women have with general practice. Despite the high prevalence and health consequences of abuse, there is insufficient evidence for screening in primary care settings. Furthermore, there is little rigorous evidence to guide general practitioners (GPs) in responding to women identified as experiencing partner abuse. This paper describes the design of a trial of a general practice-based intervention consisting of screening for fear of partner with feedback to GPs, training for GPs, brief counselling for women and minimal practice organisational change. It examines the effect on women's quality of life, mental health and safety behaviours. weave is a cluster randomised controlled trial involving 40 general practices in Victoria, Australia. Approximately 500 women (16-50 years) seen by the GP in the previous year are mailed a short lifestyle survey containing an item to screen for IPA. Women who indicate that they were afraid of a partner/ex-partner in the last year and provide contact details are invited to participate. Once baseline data are collected, GPs are randomly assigned to either a group involving healthy relationship and responding to IPA training plus inviting women for up to 6 sessions of counselling or to a group involving basic education and usual care for women. Outcomes will be evaluated by postal survey at 6 and 12 months following delivery of the intervention. There will be an economic evaluation, and process evaluation involving interviews with women and GPs, to inform understanding about implementation and outcomes. The weave trial responds to an urgent need for more evidence on what can be achieved in primary care with regard to responding to women who experience IPA. It will provide important knowledge about the effectiveness of a brief method of screening, professional IPA training program and brief counselling for women. [ACTRN12608000032358].


Under-utilization of evidence-based drug treatment in patients with heart failure is only partially explained by dissimilarity to patients enrolled in landmark trials: a report from the Euro Heart Survey on Heart Failure.
Surveys on heart failure management suggest under-utilization of life-saving evidence-based treatment. Evidence-based medicine and clinical guidelines are based on the results of randomized controlled trials. Therefore, we investigated how patients who fulfilled the enrolment criteria of randomized trials were treated in real life. We selected three large placebo-controlled trials of patients with chronic heart failure, in which ACE-inhibitors (ACE-Is), beta-blockers, and spironolactone proved to be safe and effective. The major enrolment criteria of trials were identified and applied to patients enrolled in the Euro Heart Survey on Heart Failure to identify the proportion of patients eligible for treatment and also treated appropriately. Of the 10 701 patients who were enrolled in the Euro Heart Survey on Heart Failure, only a small percentage (13%) would have qualified for participation in at least one of the selected trials. Patients who fulfilled enrolment criteria of the identified trials were more likely to be treated with ACE-Is (83% of SOLVD-eligible patients), beta-blockers (54% of MERIT-HF-eligible patients), and aldosterone antagonists (43% of RALES-eligible patients) than trial-ineligible patients. Almost half of SOLVD-eligible patients who were treated with ACE-Is received the target dose as recommended in the guidelines, but only <10% of MERIT-HF eligible patients who were treated with beta-blockers received the target dose. ACE-Is are widely utilized but given in lower doses than proven effective in clinical trials. beta-Blockers are underused and given in lower doses to patients who fulfil the enrolment criteria of relevant landmark trials.


Can Decision Making Research Provide a Better Understanding of Chemical and Behavioral Addictions?
We reviewed the cognitive and neurobiological commonalities between chemical and behavioral addictions. Poor impulse control, limited executive function and abnormalities in reward processing are seen in both group of entities. Brain imaging shows consistent abnormalities in frontoparietal regions and the limbic system. In drug addiction, exaggerated risk taking behavior and temporal discounting may reflect an imbalance between a hyperactive mesolimbic and hypoactive executive systems. Several cognitive distortions are found in pathological gambling that seems to harness the brain reward system that has evolved to face situations related to skill, not random chance. Abnormalities in risk assessment and impulsivity are found in variety of eating disorders, in particularly related to eating behavior. Corresponding findings in eating disorder patients include abnormalities in the limbic system, i.e. orbitofrontal cortex (OFC), striatum and insula. Similarly, internet addiction disorder is associated with risky decision making and increased choice impulsivity with corresponding discrepant activation in the dorsolateral prefrontal cortex, OFC, anterior cingulate cortex, caudate and insula. Sexual addictions are in turn associated with exaggerated impulsive choice and suggestive evidence of abnormalities in reward processing. In sum, exploration of executive function and decision making abnormalities in chemical and behavioral addictions may increase understanding in their psychopathology and yield valuable targets for therapeutic interventions.


Transcriptional profiling of Rickettsia prowazekii coding and non-coding transcripts during in vitro host-pathogen and vector-pathogen interactions.
Natural pathogen transmission of Rickettsia prowazekii, the etiologic agent of epidemic typhus, to humans is associated with arthropods, including human body lice, ticks, and ectoparasites of eastern flying squirrel. Recently, we have documented the presence of small RNAs in Rickettsia species and expression of R. prowazekii sRNAs during infection of cultured human microvascular endothelial cells (HMECs), which represent the primary target cells during human infections. Bacterial noncoding transcripts are now well established as critical post-transcriptional regulators of virulence and adaptation mechanisms in varying host environments. Despite their importance, little is known about the expression profile and regulatory activities of R. prowazekii sRNAs (Rp_sRs) in different host cells encountered as part of the natural life-cycle. To investigate the sRNA expression profile of R. prowazekii during infection of arthropod host cells, we employed an approach combining in vitro infection, bioinformatics, RNA sequencing, and PCR-based quantitation. Global analysis of R. prowazekii transcriptome by strand-specific RNA sequencing enabled us to identify 67 cis-acting (antisense) and 26 trans-acting (intergenic) Rp_sRs expressed during the infection of Amblyomma americanum (AAE2) cells. Comparative evaluation of expression during R. prowazekii infection of HMECs and AAE2 cells by quantitative RT-PCR demonstrated significantly higher expression of four selected Rp_sRs in tick AAE2 cells. Examination of the coding transcriptome revealed differential up-regulation of >150 rickettsial genes in either HMECs or AAE2 cells and yielded evidence for host cell-dependent utilization of alternative transcription start sites by 18 rickettsial genes. Our results thus suggest noticeable differences in the expression of both Rp_sRs as well as the coding transcriptome and the exploitation of multiple transcription initiation sites for select genes during the infection of human endothelium and tick vector cells as the host and yield new insights into rickettsial virulence and transmission mechanisms.


Beta-cell lines derived from transgenic mice expressing a hybrid insulin gene-oncogene.
Three pancreatic beta-cell lines have been established from insulinomas derived from transgenic mice carrying a hybrid insulin-promoted simian virus 40 tumor antigen gene. The beta tumor cell (beta TC) lines maintain the features of differentiated beta cells for about 50 passages in culture. The cells produce both proinsulin I and II and efficiently process each into mature insulin, in a manner comparable to normal beta cells in isolated islets. Electron microscopy reveals typical beta-cell type secretory granules, in which insulin is stored. Insulin secretion is inducible up to 30-fold by glucose, although with a lower threshold for maximal stimulation than that for normal beta cells. beta TC lines can be repeatedly derived from primary beta-cell tumors that heritably arise in the transgenic mice. Thus, targeted expression of an oncogene with a cell-specific regulatory element can be used both to immortalize a rare cell type and to provide a selection for the maintenance of its differentiated phenotype.


Stimulation of glucose uptake by the natural coenzyme alpha-lipoic acid/thioctic acid: participation of elements of the insulin signaling pathway.
Thioctic acid (alpha-lipoic acid), a natural cofactor in dehydrogenase complexes, is used in Germany in the treatment of symptoms of diabetic neuropathy. Thioctic acid improves insulin-responsive glucose utilization in rat muscle preparations and during insulin clamp studies performed in diabetic individuals. The aim of this study was to determine the direct effect of thioctic acid on glucose uptake and glucose transporters. In L6 muscle cells and 3T3-L1 adipocytes in culture, glucose uptake was rapidly increased by (R)-thioctic acid. The increment was higher than that elicited by the (S)-isomer or the racemic mixture and was comparable with that caused by insulin. In parallel to insulin action, the stimulation of glucose uptake by thioctic acid was abolished by wortmannin, an inhibitor of phosphatidylinositol 3-kinase, in both cell lines. Thioctic acid provoked an upward shift of the glucose-uptake insulin dose-response curve. The molar content of GLUT1 and GLUT4 transporters was measured in both cell lines. 3T3-L1 adipocytes were shown to have >10 times more glucose transporters but similar ratios of GLUT4:GLUT1 than L6 myotubes. The effect of (R)-thioctic acid on glucose transporters was studied in the L6 myotubes. Its stimulatory effect on glucose uptake was associated with an intracellular redistribution of GLUT1 and GLUT4 glucose transporters, similar to that caused by insulin, with minimal effects on GLUT3 transporters. In conclusion, thioctic acid stimulates basal glucose transport and has a positive effect on insulin-stimulated glucose uptake. The stimulatory effect is dependent on phosphatidylinositol 3-kinase activity and may be explained by a redistribution of glucose transporters. This is evidence that a physiologically relevant compound can stimulate glucose transport via the insulin signaling pathway.


Accelerated and exacerbated effects of high dietary fat on neuronal damage induced by transient cerebral ischemia in the gerbil septum.
Obesity induced by high-fat diet (HFD) is one of the most widespread metabolic disorders in current society. However, there has been little research regarding the effects of HFD-induced obesity in the septa of animal models of cerebral ischemia. Therefore, in the present study, we investigated septal effects of HFD on neuronal damage and gliosis induced by transient cerebral ischemia. Body weight, blood glucose levels and serum lipid profiles levels were measured both in the normal diet (ND) and HFD-group. We also investigated the effects of ND and HFD on neuronal damage and gliosis in the septum after transient cerebral ischemia using immunohistochemistry. The levels of blood glucose, serum triglyceride, and total cholesterol were significantly increased in the HFD-fed gerbils compared with the ND-fed gerbils, although body weight was not significantly changed after HFD feeding. In the ND-fed gerbils, ischemia-induced neuronal damage was found in the septohippocampal nucleus (SHN) of the septum 7 days after ischemia. In the HFD-fed gerbils, ischemia-induced neuronal damage in the SHN was much more severe compared with that of the ND-fed gerbils 4 and 7 days after ischemia. In addition, we found that ischemia-induced glial activation including astrocytes and microglia was accelerated and exacerbated in the HFD-fed gerbils compared with that in the ND-fed gerbils. These results indicate that HFD can lead to much more severe effects in ischemia-induced neuronal damage/death in the septum after ischemia-reperfusion, and that it may be associated with accelerated change in glial activation.


Hypothalamic FTO is associated with the regulation of energy intake not feeding reward.
Polymorphism in the FTO gene is strongly associated with obesity, but little is known about the molecular bases of this relationship. We investigated whether hypothalamic FTO is involved in energy-dependent overconsumption of food. We determined FTO mRNA levels in rodent models of short- and long-term intake of palatable fat or sugar, deprivation, diet-induced increase in body weight, baseline preference for fat versus sugar as well as in same-weight animals differing in the inherent propensity to eat calories especially upon availability of diverse diets, using quantitative PCR. FTO gene expression was also studied in organotypic hypothalamic cultures treated with anorexigenic amino acid, leucine. In situ hybridization (ISH) was utilized to study FTO signal in reward- and hunger-related sites, colocalization with anorexigenic oxytocin, and c-Fos immunoreactivity in FTO cells at initiation and termination of a meal. Deprivation upregulated FTO mRNA, while leucine downregulated it. Consumption of palatable diets or macronutrient preference did not affect FTO expression. However, the propensity to ingest more energy without an effect on body weight was associated with lower FTO mRNA levels. We found that 4-fold higher number of FTO cells displayed c-Fos at meal termination as compared to initiation in the paraventricular and arcuate nuclei of re-fed mice. Moreover, ISH showed that FTO is present mainly in hunger-related sites and it shows a high degree of colocalization with anorexigenic oxytocin. We conclude that FTO mRNA is present mainly in sites related to hunger/satiation control; changes in hypothalamic FTO expression are associated with cues related to energy intake rather than feeding reward. In line with that, neurons involved in feeding termination express FTO. Interestingly, baseline FTO expression appears linked not only with energy intake but also energy metabolism.


Interleukin 6 knockout prevents angiotensin II hypertension: role of renal vasoconstriction and janus kinase 2/signal transducer and activator of transcription 3 activation.
Chronic angiotensin II (Ang II) infusion stimulates interleukin (IL) 6 release, and we and others have shown that preventing the increase in IL-6 significantly attenuates Ang II hypertension. This study measured renal blood flow (RBF) chronically, using Transonic flow probes in wild-type (WT) and IL-6 knockout (KO) mice, to determine the role of RBF regulation in that response. Ang II infusion at 200, 800, and 3600 ng/kg per minute caused a dose-dependent decrease in RBF in WT mice, and the response at 800 ng/kg per minute was compared between WT and IL-6 KO mice. Ang II infusion increased plasma IL-6 concentration in WT mice and increased mean arterial pressure (19 h/d with telemetry) from 113±4 to 149±4 mm Hg (Δ36 mm Hg) over the 7-day infusion period, and that effect was blocked in IL-6 KO mice (119±7 to 126±7 mm Hg). RBF decreased to an average of 61±8% of control over the 7-day period (control: 0.86±0.02 mL/min) in the WT mice; however, the average decrease to 72±6% of control (control: 0.88±0.02 mL/min) in the KO mice was not significantly different. There also was no difference in afferent arteriolar constriction by Ang II in blood-perfused juxtamedullary nephrons in WT versus KO mice. Phosphorylation of janus kinase 2 and signal transducer and activator of transcription 3 in renal cortex homogenates increased significantly in Ang II-infused WT mice, and that effect was prevented completely in Ang II-infused IL-6 KO mice. These data suggest that IL-6-dependent activation of the renal janus kinase 2/signal transducer and activator of transcription 3 pathway plays a role in Ang II hypertension but not by mediating the effect of Ang II to decrease total RBF.


Clonal anergy blocks in vivo growth of mature T cells and can be reversed in the absence of antigen.
Experiments in various models have indicated that immunological tolerance can result from the physical elimination (deletion) of reactive lymphocytes as well as from anergy. We have previously reported that mature CD4-CD8+ T cells when confronted with their antigen can proliferate extensively but are finally eliminated or become intrinsically anergic such that remaining cells are refractory to stimulation by any T cell receptor ligands, even in the presence of exogenous interleukin 2. Here we show that in vivo the anergy can be reversed in the absence of antigen, such that the cells are then able to proliferate extensively in vivo to a new challenge with the antigen in question.


The World Health Organization. Histological typing of breast tumors.
The WHO Histological Classification of Breast Tumors, published in 1968 has been completely revised. This second edition provides a recommended nomenclature, definitions and code numbers for both tumors and tumor-like lesions. It aims at promoting uniformity in recording and reporting diagnoses in order to facilitate international and other comparisons.


Pain self-efficacy, race, and motivation to quit smoking among persons living with HIV (PLWH).
Pain and cigarette smoking are commonly co-occurring and costly public health issues, and rates of both conditions are elevated among persons living with HIV (PLWH). Recent work has focused on elucidating the role of cognitive factors in pain-smoking interrelations, and PLWH have endorsed various beliefs regarding pain and smoking. There is reason to suspect that pain self-efficacy (i.e., belief in one's ability to cope with pain) may be associated with the maintenance of smoking. However, no previous research has examined relations between pain self-efficacy and motivation to quit. The goal of this study was to conduct the first test of cross-sectional associations between pain self-efficacy and motivation to quit smoking among PLWH. Race was tested as a moderator of the hypothesized associations. Participants (N = 76 daily smokers; 37% female; Mage = 50.6; MCPD = 13.7) were recruited from an outpatient infectious disease clinic for a primary study examining the effects of a personalized feedback intervention for PLWH. Results indicated that pain self-efficacy was positively associated with perceived importance of quitting and intention to quit within the next six months across the entire sample (ps < 0.05), and positively associated with readiness to consider smoking cessation and confidence in quitting among Black/African American participants (but not among other participants; ps < 0.05). These data provide initial evidence that pain self-efficacy may be related to motivation and intention to quit smoking, particularly among Black/African American PLWH. Future research should test prospective associations between pain self-efficacy and the initiation/maintenance of smoking cessation.


Polymorphisms in type II SH2 domain-containing inositol 5-phosphatase (INPPL1, SHIP2) are associated with physiological abnormalities of the metabolic syndrome.
Type II SH2 domain-containing inositol 5-phosphatase (INPPL1, or SHIP2) plays an important role in the control of insulin sensitivity. INPPL1 mutations affecting gene function have been found in rat models of type 2 diabetes and hypertension and in type 2 diabetic patients. We investigated the influence of nucleotide variation in INPPL1 on components of the metabolic syndrome. Following comprehensive resequencing of the gene, we genotyped 12 informative polymorphisms in 1,304 individuals from 424 British type 2 diabetes families that were characterized for several metabolic phenotypes. We have found highly significant associations of single nucleotide polymorphisms (SNPs) and haplotypes of INPPL1 with hypertension as well as with other components of the metabolic syndrome. In a cohort of 905 French type 2 diabetic patients, we found evidence of association of INPPL1 SNPs with the presence of hypertension. We conclude that INPPL1 variants may impact susceptibility to disease and/or to subphenotypes involved in the metabolic syndrome in some diabetic patients.


A framework for selecting analytical techniques in profiling authentic and counterfeit Viagra and Cialis.
Several analytical techniques aimed at profiling drugs are deemed costly and time consuming, and may not be promptly available for analysis when required. This paper proposes a method for identifying the analytical techniques providing the most relevant data for classification of drug samples into authentic and unauthentic categories. For that matter, we integrate principal components analysis (PCA) to k-Nearest Neighbor (KNN) and Support Vector Machine (SVM) classification tools. PCA is first applied to data from five techniques, i.e., physical profile, X-ray fluorescence (XRF), direct infusion electrospray ionization mass spectrometry (ESI-MS), active pharmacological ingredients profile (ultra performance liquid chromatography, UPLC-MS), and infrared spectroscopic profile (ATR-FTIR). Subsets of PCA scores are then combined with a "leave one subset out at a time" approach, and the classification accuracy using KNN and SVM evaluated after each subset is omitted. Subsets yielding the maximum accuracy indicate the techniques to be prioritized in profiling applications. When applied to data from Viagra and Cialis, the proposed method recommended using the data from UPLC-MS, physical profile and ATR-FTIR techniques, which increased the categorization accuracy. In addition, the SVM classification tool is suggested as more accurate when compared to the KNN.


Green process to regenerate keratin from feathers with an aqueous deep eutectic solvent.
Poultry feathers, a source of keratin, are a significant side stream from the food industry, for which valorization is essential considering the circular economy aspects. For this, ecofriendly processes are the tools that allow the easy and feasible transformation of the feathers. Deep eutectic solvents (DESs) are generally considered as inexpensive, relatively simple, mild and environmentally friendly solvents which can dissolve proteins from protein-rich biomasses. In this work, feathers were processed with an aqueous DES to produce a uniform keratin feedstock. The proposed DES is composed of non-toxic sodium acetate and urea, with a small amount of water. After the DES treatment, water was used to dilute the DES components and regenerate the dissolved keratin. The processing conditions were optimized in terms of keratin yield and properties by varying the dissolution time from 2 h to 24 h and temperature from 80 °C to 100 °C. The yield of regenerated keratin was followed at different sodium acetate-urea molar ratios, and compared to the treatment performed with choline chloride-urea or 8 M urea as reference solvents. Sodium acetate-urea in the molar ratio of 1 : 2 at 100 °C and with 6 h dissolution time dissolved 86% of the feathers with a regenerated keratin yield of 45%. In the characterization of regenerated keratin, it was found that when the dissolution temperature was higher and the dissolution time longer, the disulfide and total sulfur content of feather keratin decreased, the range of molecular weights became wider, and some of the ordered secondary structure and crystallinity were lost.


Measuring and modeling short-term variability of PCBs in air and characterization of urban source strength in Zurich, Switzerland.
Diel (24-h) variations of concentrations of polychlorinated biphenyls (PCBs) in air are reported at two sites in Zurich, Switzerland, a city surrounded by hills. One site was located in the valley near the city center and the other site was on a hill called Uetliberg, 411 m higher and about 5 km distant from the city center site. Air samples were collected simultaneously at both sites over 4-h time periods for 3 consecutive days under stable meteorological conditions during a high pressure system in August 2007. PCB concentrations at the city site were markedly higher than those at Uetliberg, indicating that the city site is influenced by urban sources of PCBs. Concentrations measured at both sites show a clear diel cycle but have opposite phases: in the city concentrations were lower during the day and higher at night, while at Uetliberg concentrations were higher during the day and lower at night. These observations are explained and interpreted using a multimedia mass balance model that includes a stable night-time inversion layer that formed over the city but below the hilltop site. At Uetliberg the concentration of PCBs is consistent with background levels and the diel concentration pattern can be explained bytemperature-mediated air-surface exchange and the influence of nearby woodland canopies. The diel pattern and concentrations in the city are attributable to volatilization from urban sources. We have developed a new method to estimate the strength of the urban PCB source using the model scenarios for the two sampling sites. Emission estimates derived from this method are in good agreement with earlier estimates derived from PCB production, consumption, and usage estimates. This study demonstrates the potential for estimating the strength of diffuse, regional sources of persistent organic pollutants (POPs) using a combined measurement and modeling approach. Such studies can provide important information to derive regional and national POPs emission inventories as required under the Stockholm Convention, and to quantify the effectiveness of actions to reduce POP emissions.


Self-efficacy to quit in HIV-infected smokers.
Tobacco use is epidemic among persons living with HIV (PLWH), and several studies have shown self-efficacy (SE) to be a predictor of successful cessation. This study examined sociobehavioral correlates of SE and its predictive value for successful cessation in a group of PLWH smokers. The study was conducted on combined patient data from 2 separate randomized controlled trials of tobacco treatment for PLWH smokers. Both trials utilized the same SE scale at the same timepoints, and both had the same smoking cessation endpoint (biochemically confirmed, 7-day, point prevalence abstinence at 3 months). Univariate and multivariate techniques were used to analyze the merged dataset. Baseline SE data were available for 272 subjects. The Self-Efficacy/Temptations Scale-Long Form demonstrated good internal reliability with overall and subscale Cronbach's alpha of .77-.92. Younger age, HIV risk other than injection drug use, recent alcohol use, and higher scores for anxiety, depression, loneliness, and nicotine dependence were all significantly correlated with lower baseline SE. Posttreatment SE was significantly predictive of successful cessation, whereas baseline SE was not. Subjects randomized to the treatment interventions were significantly more likely to quit (AOR = 2.99 [1.26-7.01], p = .01), and logistic regression suggested a possible mediating effect of posttreatment SE. SE is tightly correlated with a number of modifiable affective and behavioral factors in PLWH smokers, and measures aimed at increasing the SE to abstain in such individuals may enhance the effect of targeted tobacco treatment strategies.


Superior outcomes in pediatric renal transplantation.
Nationally, results of renal transplantation in children, particularly in small children, are inferior to those obtained in adults. To determine factors important for success in renal transplantation in children. Results of 108 consecutive renal transplantations performed in patients aged 7 months to 18 years were reviewed and compared with those reported by the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS), the national registry. One-, 2-, and 3-year graft survival rates (+/-SE) were 99% +/- 1%, 95% +/- 3%, and 93% +/- 4%, respectively, for living donor grafts and 97% +/- 3%, 92% +/- 6%, and 92% +/- 6%, respectively, for cadaver grafts. Incidence of acute rejection was half that reported by NAPRTCS. There were no graft losses for technical reasons (19% in NAPRTCS). Twelve percent of patients were younger than 2 years (6% in NAPRTCS); 17% were 2 to 5 years old (16% in NAPRTCS). Most small children received an adult-sized kidney. Ninety-three percent of recipients weighing 15 kg or less received postoperative mechanical ventilation assistance to optimize fluid resuscitation and perfusion of adult-sized kidneys. Structural abnormalities of the urinary tract were present in 53.7% of the patients (48.5% in NAPRTCS; adults, 5.3%). Nephroureterectomy was required in 38 children; in 27 (71%) of them, it was performed at the time of transplant surgery. Excellent results can be obtained in pediatric renal transplantation by strict adherence to surgical detail, tight immunosuppressive management, aggressive fluid management in the small child, and careful integration of urologic and transplant surgery.


An animal model mimicking pedunculopontine nucleus cholinergic degeneration in Parkinson's disease.
A rostral brainstem structure, the pedunculopontine nucleus (PPN), is severely affected by Parkinson's disease (PD) pathology and is regarded a promising target for therapeutic deep-brain stimulation (DBS). However, understanding the PPN's role in PD and assessing the potential of DBS are hampered by the lack of a suitable model of PPN degeneration. Rats were rendered Parkinsonian through a unilateral substantia nigra pars compacta (SNpc) stereotaxic injection of the proteasome inhibitor Lactacystin, to investigate whether the lesion's pathological effects spread to impact the integrity of PPN cholinergic neurons which are affected in PD. At 5 weeks post-surgery, stereological analysis revealed that the lesion caused a 48 % loss of dopaminergic SNpc neurons and a 61 % loss of PPN cholinergic neurons, accompanied by substantial somatic hypotrophy in the remaining cholinergic neurons. Magnetic resonance imaging revealed T2 signal hyper-/hypointensity in the PPN of the injected hemisphere, respectively at weeks 3 and 5 post-lesion. Moreover, isolated PPN cholinergic neurons revealed no significant alterations in key autophagy mRNA levels, suggesting that autophagy-related mechanisms fail to protect the PPN against Lactacystin-induced cellular changes. Hence, the current results suggest that the Lactacystin PD model offers a suitable model for investigating the role of the PPN in PD.


Wilson's disease presenting with rapidly progressive visual loss: another neurologic manifestation of Wilson's disease?
Wilson's disease (WD) is a rare autosomal recessive disorder of copper metabolism resulting in copper-induced tissue damage that primarily involves the liver and central nervous system. The neurologic manifestations of WD almost universally involve a derangement of basal ganglia function or psychiatric disturbance. We report the case of a 46-year-old man presenting with end-stage liver disease caused by WD who had associated rapidly progressive optic neuropathy. We also discuss the possible association between the two conditions.


Geographic Variability of Nodular Lymphocyte-Predominant Hodgkin Lymphoma.
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) differs from classic Hodgkin lymphoma (CHL) in terms of clinicopathologic features, including Epstein-Barr virus (EBV) association. CHL geographic variability is well known, with higher frequencies of mixed-cellularity subtype and EBV positivity in low/middle-income countries (LMICs), but there are few well-characterized series of NLPHL from LMICs. We detail clinicopathologic findings of 21 NLPHL cases received in consultation from Kenya and summarize reports of NLPHL with EBV testing published since 2000. Median age of consultation cases was 36 years, and male/female ratio was 3.2. All cases involved peripheral lymph nodes and showed at least some B-cell-rich nodular immunoarchitecture, with prominent extranodular lymphocyte-predominant (LP) cells and T-cell-rich variant patterns most commonly seen. LP cells expressed pan-B-cell markers, including strong OCT2; lacked CD30 and CD15 expression in most cases; and were in a background of expanded/disrupted follicular dendritic cell meshworks and increased T-follicular helper cells. LP cells were EBV negative in 18 cases. Historical cases showed a low rate of EBV positivity with no significant difference between LMICs and high-income countries. Unlike CHL, NLPHL shows few geographic differences in terms of clinicopathologic features and EBV association. These findings have implications for diagnosis, prognostication, and treatment of patients with NLPHL in LMICs.


Threshold regression to accommodate a censored covariate.
In several common study designs, regression modeling is complicated by the presence of censored covariates. Examples of such covariates include maternal age of onset of dementia that may be right censored in an Alzheimer's amyloid imaging study of healthy subjects, metabolite measurements that are subject to limit of detection censoring in a case-control study of cardiovascular disease, and progressive biomarkers whose baseline values are of interest, but are measured post-baseline in longitudinal neuropsychological studies of Alzheimer's disease. We propose threshold regression approaches for linear regression models with a covariate that is subject to random censoring. Threshold regression methods allow for immediate testing of the significance of the effect of a censored covariate. In addition, they provide for unbiased estimation of the regression coefficient of the censored covariate. We derive the asymptotic properties of the resulting estimators under mild regularity conditions. Simulations demonstrate that the proposed estimators have good finite-sample performance, and often offer improved efficiency over existing methods. We also derive a principled method for selection of the threshold. We illustrate the approach in application to an Alzheimer's disease study that investigated brain amyloid levels in older individuals, as measured through positron emission tomography scans, as a function of maternal age of dementia onset, with adjustment for other covariates. We have developed an R package, censCov, for implementation of our method, available at CRAN.


No sympathy for the devil: attributing psychopathic traits to capital murderers also predicts support for executing them.
Mental health evidence concerning antisocial and psychopathic traits appears to be introduced frequently in capital murder trials in the United States to argue that defendants are a "continuing threat" to society and thus worthy of execution. Using a simulation design, the present research examined how layperson perceptions of the psychopathic traits exhibited by a capital defendant would impact their attitudes about whether he should receive a death sentence. Across three studies (total N = 362), ratings of a defendant's perceived level of psychopathy strongly predicted support for executing him. The vast majority of the predictive utility was attributable to interpersonal and affective traits historically associated with psychopathy rather than traits associated with a criminal and socially deviant lifestyle. A defendant's perceived lack of remorse in particular was influential, although perceptions of grandiose self-worth and a manipulative interpersonal style also contributed incrementally to support for a death sentence. These results highlight how attributions regarding socially undesirable personality traits can have a pronounced negative impact on layperson attitudes toward persons who are perceived to exhibit these characteristics.