A2 Milk Enhances Dynamic Muscle Function Following Repeated Sprint Exercise, a Possible Ergogenic Aid for A1-Protein Intolerant Athletes?
Hyperaminoacidemia following ingestion of cows-milk may stimulate muscle anabolism and attenuate exercise-induced muscle damage (EIMD). However, as dairy-intolerant athletes do not obtain the reported benefits from milk-based products, A2 milk may offer a suitable alternative as it lacks the A1-protein. This study aimed to determine the effect of A2 milk on recovery from a sports-specific muscle damage model. Twenty-one male team sport players were allocated to three independent groups: A2 milk (n = 7), regular milk (n = 7), and placebo (PLA) (n = 7). Immediately following muscle-damaging exercise, participants consumed either A2 milk, regular milk or PLA (500 mL each). Visual analogue scale (muscle soreness), maximal voluntary isometric contraction (MVIC), countermovement jump (CMJ) and 20-m sprint were measured prior to and 24, 48, and 72 h post EIMD. At 48 h post-EIMD, CMJ and 20-m sprint recovered quicker in A2 (33.4 ± 6.6 and 3.3 ± 0.1, respectively) and regular milk (33.1 ± 7.1 and 3.3 ± 0.3, respectively) vs. PLA (29.2 ± 3.6 and 3.6 ± 0.3, respectively) (p < 0.05). Relative to baseline, decrements in 48 h CMJ and 20-m sprint were minimised in A2 (by 7.2 and 5.1%, respectively) and regular milk (by 6.3 and 5.2%, respectively) vs. PLA. There was a trend for milk treatments to attenuate decrements in MVIC, however statistical significance was not reached (p = 0.069). Milk treatments had no apparent effect on muscle soreness (p = 0.152). Following muscle-damaging exercise, ingestion of 500 mL of A2 or regular milk can limit decrements in dynamic muscle function in male athletes, thus hastening recovery and improving subsequent performance. The findings propose A2 milk as an ergogenic aid following EIMD, and may offer an alternative to athletes intolerant to the A1 protein.


Mitochondria orchestrate proteostatic and metabolic stress responses.
The eukaryotic cell is morphologically and functionally organized as an interconnected network of organelles that responds to stress and aging. Organelles communicate via dedicated signal transduction pathways and the transfer of information in form of metabolites and energy levels. Recent data suggest that the communication between organellar proteostasis systems is a cornerstone of cellular stress responses in eukaryotic cells. Here, we discuss the integration of proteostasis and energy fluxes in the regulation of cellular stress and aging. We emphasize the molecular architecture of the regulatory transcriptional pathways that both sense and control metabolism and proteostasis. A special focus is placed on mechanistic insights gained from the model organism budding yeast in signaling from mitochondria to the nucleus and how this shapes cellular fitness.


Cardiac Imaging With 123I-meta-iodobenzylguanidine and Analogous PET Tracers: Current Status and Future Perspectives.
Autonomic innervation plays an important role in proper functioning of the cardiovascular system. Altered cardiac sympathetic function is present in a variety of diseases, and can be assessed with radionuclide imaging using sympathetic neurotransmitter analogues. The most studied adrenergic radiotracer is cardiac 123I-meta-iodobenzylguanidine (123I-mIBG). Cardiac 123I-mIBG uptake can be evaluated using both planar and tomographic imaging, thereby providing insight into global and regional sympathetic innervation. Standardly assessed imaging parameters are the heart-to-mediastinum ratio and washout rate, customarily derived from planar images. Focal tracer deficits on tomographic imaging also show prognostic utility, with some data suggesting that the best approach to tomographic image interpretation may differ from conventional methods. Cardiac 123I-mIBG image findings strongly correlate with the severity and prognosis of many cardiovascular diseases, especially heart failure and ventricular arrhythmias. Cardiac 123I-mIBG imaging in heart failure is FDA approved for prognostic purposes. With the robustly demonstrated ability to predict occurrence of potentially fatal arrhythmias, cardiac 123I-mIBG imaging shows promise for better selecting patients who will benefit from an implantable cardioverter defibrillator, but clinical use has been hampered by lack of the randomized trial needed for incorporation into societal guidelines. In patients with ischemic heart disease, cardiac 123I-mIBG imaging aids in assessing the extent of damage and in identifying arrhythmogenic regions. There have also been studies using cardiac 123I-mIBG for other conditions, including patients following heart transplantation, diabetic related cardiac abnormalities and chemotherapy induced cardiotoxicity. Positron emission tomographic adrenergic radiotracers, that improve image quality, have been investigated, especially 11C-meta-hydroxyephedrine, and most recently 18F-fluorbenguan. Cadmium-zinc-telluride cameras also improve image quality. With better spatial resolution and quantification, PET tracers and advanced camera technologies promise to expand the clinical utility of cardiac sympathetic imaging.


Cooperation and the scale of competition in humans.
Explaining cooperation is one of the greatest challenges for evolutionary biology. It is particularly a problem in species such as humans, where there is cooperation between nonrelatives. Numerous possible solutions have been suggested for the problem of cooperation between nonrelatives, including punishment, policing, and various forms of reciprocity. Here, we suggest that local competition for resources can pose a problem for these hypotheses, analogous to how it can select against cooperation between relatives. We extend the prisoner's dilemma (PD) game to show that local competition between interacting individuals can reduce selection for cooperation between nonrelatives. This is because, with local competition, fitness is relative to social partners, and cooperation benefits social partners. We then test whether nonrelated humans adjust their level of cooperation facultatively in response to the scale of competition when playing the PD for cash prizes. As predicted, we found that individuals were less likely to cooperate when competition was relatively local. Cooperation between humans will therefore be most likely when repeated interactions take place on a local scale between small numbers of people, and competition for resources takes place on a more global scale among large numbers of people.


Digital messaging to support control for type 2 diabetes (StAR2D): a multicentre randomised controlled trial.
Failure to take medicines for diabetes as prescribed contributes to poor outcomes from the condition. Mobile phones are ubiquitous and short message service (SMS) texts have shown promise as a low-cost intervention. We tested the effectiveness of SMS-text messaging in improving outcomes in adults with type 2 diabetes. StAR2D was a 12-month two-arm randomised trial of SMS-text messaging and usual care in Cape Town, South Africa and Lilongwe, Malawi. Messages used behaviour change theory and were developed with patients and staff. The intervention group received four messages each week. The primary outcome was change in HbA1c. Secondary outcomes were the proportion of patients who collected > 80% medication and changes in systolic blood pressure, lipids, cardiovascular risk, and the proportion of the participants reaching treatment goals. The trial took place between 1 October, 2016 and 1 October 2018, 1186 participants were randomised to intervention (593) and control (593) groups. 91% of participants completed follow-up. There was a reduction in HbA1c (DCCT) in both groups but not in mean change (95% CI) between groups (- 0.08% (- 0.31 to 0.16) (IFCC - 0.82 mmol/mol (- 3.44 to 1.79). There was a small but not significant increase in the proportions of participants likely to have collected 80% or more of medication (Relative risk 1.11 (0.84 to 1.47; P = 0.47). There was a significant difference between groups in change in systolic blood pressure from baseline of 3.46 mmHg (1.48 to 5.44, P = 0.001) in favour of the intervention group. The between group difference in change in 10-year risk of coronary heart disease was - 0.71% (- 1.46 to 0.04, P = 0.064). The proportion of participants meeting treatment goals in the intervention group was 36.0% and in the control group 26.8% (Relative risk 1.36 (1.13 to 1.63, P = 0.001). Participants reported many challenges to adherence despite finding messages acceptable and useful. Whilst SMS text messages do not lead to improved glycaemia in these low-resource settings there appeared to be an impact on blood pressure and achievement of treatment goals but the mechanisms for this are unclear. Text messages alone, may be unsuccessful unless accompanied by health system strengthening and other forms of self-management support for type 2 diabetes. Trial registration: ISRCTN, ISRCTN70768808. Registered 1 July 2015, http://www.isrctn.com/I ISRCTN70768808.


Photopheresis for the prevention of rejection in cardiac transplantation. Photopheresis Transplantation Study Group.
Photopheresis is an immunoregulatory technique in which lymphocytes are reinfused after exposure to a photoactive compound (methoxsalen) and ultraviolet A light. We performed a preliminary study to assess the safety and efficacy of photopheresis in the prevention of acute rejection of cardiac allografts. A total of 60 consecutive eligible recipients of primary cardiac transplants were randomly assigned to standard triple-drug immunosuppressive therapy (cyclosporine, azathioprine, and prednisone) alone or in conjunction with photopheresis. The photopheresis group received a total of 24 photopheresis treatments, each pair of treatments given on two consecutive days, during the first six months after transplantation. The regimen for maintenance immunosuppression, the definition and treatment of rejection episodes, the use of prophylactic antibiotics, and the schedule for cardiac biopsies were standardized among all 12 study centers. All the cardiac-biopsy samples were graded in a blinded manner at a central pathology laboratory. Plasma from the subgroup of 34 patients (57 percent) who were enrolled at the nine U.S. centers was analyzed by polymerase-chain-reaction amplification for cytomegalovirus DNA. After six months of follow-up, the mean (+/-SD) number of episodes of acute rejection per patient was 1.44+/-1.0 in the standard-therapy group, as compared with 0.91+/-1.0 in the photopheresis group (P=0.04). Significantly more patients in the photopheresis group had one rejection episode or none (27 of 33) than in the standard-therapy group (14 of 27), and significantly fewer patients in the photopheresis group had two or more rejection episodes (6 of 33) than in the standard-therapy group (13 of 27, P=0.02). There was no significant difference in the time to a first episode of rejection, the incidence of rejection associated with hemodynamic compromise, or survival at 6 and 12 months. Although there were no significant differences in the rates or types of infection, cytomegalovirus DNA was detected significantly less frequently in the photopheresis group than in the standard-therapy group (P=0.04). In this pilot study, the addition of photopheresis to triple-drug immunosuppressive therapy significantly decreased the risk of cardiac rejection without increasing the incidence of infection.


The Promise of Mesenchymal Stem Cell Therapy for Diabetic Kidney Disease.
Diabetes mellitus (DM) commonly leads to progressive chronic kidney disease despite current best medical practice. The pathogenesis of diabetic kidney disease (DKD) involves a complex network of primary and secondary mechanisms with both intra-renal and systemic components. Apart from inhibition of the renin angiotensin aldosterone system, targeting individual pathogenic mediators with drug therapy has not, thus far, been proven to have high clinical value. Stem or progenitor cell therapies offer an alternative strategy for modulating complex disease processes through suppressing multiple pathogenic pathways and promoting pro-regenerative mechanisms. Mesenchymal stem cells (MSCs) have shown particular promise based on their accessibility from adult tissues and their diverse mechanisms of action including secretion of paracrine anti-inflammatory and cyto-protective factors. In this review, the progress toward clinical translation of MSC therapy for DKD is critically evaluated. Results from animal models suggest distinct potential for systemic MSC infusion to favourably modulate DKD progression. However, only a few early phase clinical trials have been initiated and efficacy in humans remains to be proven. Key knowledge gaps and research opportunities exist in this field. These include the need to gain greater understanding of in vivo mechanism of action, to identify quantifiable biomarkers of response to therapy and to define the optimal source, dose and timing of MSC administration. Given the rising prevalence of DM and DKD worldwide, continued progress toward harnessing the inherent regenerative functions of MSCs and other progenitor cells for even a subset of those affected has potential for profound societal benefits.


Intestinal helminths in lowland South American Indians: some evolutionary interpretations.
Data on intestinal parasite infections for South American Indians in prehistoric times as revealed by coprolite analysis are being used to support transoceanic migration routes from the Old World to the New World. These same findings on modern semi-isolated aborigines, considered persisting prehistoric patterns, are also of great importance as indicators of pre-Columbian peopling of South America. This is the case for the Lengua Indians from Paraguay, studied in the 1920s, and the Yanomami and the Salumã from Brazil, studied in the 1980s. The intestinal parasitic profile of these groups can be empirically associated with culture change, but no clear correlations with the population biology of their hosts can be made at present because of scarcity of data.


Use of an Electronic Clinical Decision Support System in Primary Care to Assess Inappropriate Polypharmacy in Young Seniors With Multimorbidity: Observational, Descriptive, Cross-sectional Study.
Multimorbidity is a global health problem that is usually associated with polypharmacy, which increases the risk of potentially inappropriate prescribing (PIP). PIP entails higher hospitalization rates and mortality and increased usage of services provided by the health system. Tools exist to improve prescription practices and decrease PIP, including screening tools and explicit criteria that can be applied in an automated manner. This study aimed to describe the prevalence of PIP in primary care consultations among patients aged 65-75 years with multimorbidity and polypharmacy, detected by an electronic clinical decision support system (ECDSS) following the 2015 American Geriatrics Society Beers Criteria, the European Screening Tool of Older Person's Prescription (STOPP), and the Screening Tool to Alert doctors to Right Treatment (START). This was an observational, descriptive, cross-sectional study. The sample included 593 community-dwelling adults aged 65-75 years (henceforth called young seniors), with multimorbidity (≥3 diseases) and polypharmacy (≥5 medications), who had visited their primary care doctor at least once over the last year at 1 of the 38 health care centers participating in the Multimorbidity and Polypharmacy in Primary Care (Multi-PAP) trial. Sociodemographic data, clinical and pharmacological treatment variables, and PIP, as detected by 1 ECDSS, were recorded. A multivariate logistic regression model with robust estimators was built to assess the factors affecting PIP according to the STOPP criteria. PIP was detected in 57.0% (338/593; 95% CI 53-61) and 72.8% (432/593; 95% CI 69.3-76.4) of the patients according to the STOPP criteria and the Beers Criteria, respectively, whereas 42.8% (254/593; 95% CI 38.9-46.8) of the patients partially met the START criteria. The most frequently detected PIPs were benzodiazepines (BZD) intake for more than 4 weeks (217/593, 36.6%) using the STOPP version 2 and the prolonged use of proton pump inhibitors (269/593, 45.4%) using the 2015 Beers Criteria. Being a woman (odds ratio [OR] 1.43, 95% CI 1.01-2.01; P=.04), taking a greater number of medicines (OR 1.25, 95% CI 1.14-1.37; P<.001), working in the primary sector (OR 1.91, 95% CI 1.25-2.93; P=.003), and being prescribed drugs for the central nervous system (OR 3.75, 95% CI 2.45-5.76; P<.001) were related to a higher frequency of PIP. There is a high prevalence of PIP in primary care as detected by an ECDSS in community-dwelling young seniors with comorbidity and polypharmacy. The specific PIP criteria defined by this study are consistent with the current literature. This ECDSS can be useful for supervising prescriptions in primary health care consultations.


Donor information for living donor liver transplantation: where can comprehensive information be found?
Recently published data show that a large number of candidates for living donor liver transplantation (LDLT) actively look for additional information on the Internet because today it represents the main source of information for many of them. However, little is known about the quality of the information on LDLT available on the Internet. Our aim was, therefore, to comprehensively evaluate the online information available for LDLT candidates with the expanded Ensuring Quality Information for Patients (EQIP) tool (0-36 items). One hundred Web sites on LDLT were initially found with the Google, Bing, and Yahoo search engines, and we identified 32 Web sites that provided specific information for such candidates in English. Only 9 Web sites addressed >20 items and the scores tended to be higher for educational (P = 0.13) and scientific sites (P = 0.07) compared to hospital sites. The median number of items from the EQIP tool was only 16 (interquartile range = 13-20), and quantitative postoperative morbidity and mortality risk estimates were available on only 19% and 44% of the Web sites, respectively, despite the idea of major complications being mentioned on most Web sites. This analysis demonstrated several significant shortcomings in the quality of the information provided to potential donors for LDLT according to the EQIP instrument. We conclude that there is an urgent need to produce a Web site compliant with international standards for the quality of donor information.


Fusion of ETV6 to GOT1 in a case with myelodysplastic syndrome and t(10;12)(q24;p13).
The ETV6 gene on 12p13 is involved in different hematologic malignancies through a variety of chromosomal translocations. Here we report the analysis of a t(10;12)(q24;p13) identified in a patient with myelodysplastic syndrome. Our results show that the t(10;12) results in the generation of an in-frame fusion between ETV6 and GOT1, a gene encoding a cytosolic glutamic-oxaloacetic transaminase enzyme. In addition, two other fusion transcripts involving exons from yet unidentified genes were detected, as well as expression of an uncharacterized gene from the 10q24 region. This work identifies GOT1 as a novel fusion partner of ETV6 in myelodysplastic syndrome.


Passive heat stress reduces circulating endothelial and platelet microparticles.
What is the central question of this study? Does passive heat stress of +2°C oesophageal temperature change concentrations of circulating arterial endothelial- and platelet-derived microparticles in healthy adults? What is the main finding and its importance? Concentrations of circulating endothelial- and platelet-derived microparticles were markedly decreased in heat stress. Reductions in circulating microparticles might indicate favourable vascular changes associated with non-pathological hyperthermia. Interest in circulating endothelial- and platelet-derived microparticles (EMPs and PMPs, respectively) has increased because of their potential pathogenic role in vascular disease and as biomarkers for vascular health. Hyperthermia is commonly associated with a pro-inflammatory stress but might also provide vascular protection when the temperature elevation is non-pathological. Circulating microparticles might contribute to the cellular adjustments and resultant vascular impacts of hyperthermia. Here, we determined whether circulating concentrations of arterial EMPs and PMPs are altered by passive heat stress (+2°C oesophageal temperature). Ten healthy young men (age 23 ± 3 years) completed the study. Hyperthermia was achieved by circulating ∼49°C water through a water-perfused suit that covered the entire body except the hands, feet and head. Arterial (radial) blood samples were obtained immediately before heating (normothermia) and in hyperthermia. The mean ± SD oesophageal temperature in normothermia was 37.2 ± 0.1°C and in hyperthermia 39.1 ± 0.1°C. Concentrations of circulating EMPs and PMPs were markedly decreased in hyperthermia. Activation-derived EMPs were reduced by ∼30% (mean ± SD; from 61 ± 8 to 43 ± 7 microparticles μl-1 ; P < 0.05) and apoptosis-derived EMPs by ∼45% (from 46 ± 7 to 23 ± 3 microparticles μl-1 ; P < 0.05). Likewise, circulating PMPs were reduced by ∼75% in response to hyperthermia (from 256 ± 43 to 62 ± 14 microparticles μl-1 ). These beneficial reductions in circulating EMPs and PMPs in response to a 2°C increase in core temperature might partly underlie the reported vascular improvements following therapeutic bouts of physiological hyperthermia.


Factors affecting benthic impacts at Scottish fish farms.
The factors affecting patterns of benthic [seabed] biology and chemistry around 50 Scottish fish farms were investigated using linear mixed-effects models that account for inherent correlations between observations from the same farm. The abundance of benthic macrofauna and sediment concentrations of organic carbon were both influenced by a significant, albeit weak, interaction between farm size, defined as the maximum weight of fish permitted on site at any one time, and current speed. Above a farm size threshold of between 800 and 1000 t, the magnitude of effects at farms located in areas of elevated current speeds were greater than at equivalent farms located in more quiescent waters. Sediment concentrations of total organic matter were influenced by an interaction between distance and depth, indicating that wind-driven resuspension events may help reduce the accumulation of organic waste at farms located in shallow waters. The analyses presented here demonstrate that the production and subsequent fate of organic waste at fish farms is more complex than is often assumed; in isolation, current speed, water depth, and farr size are not necessarily good predictors of benthic impact.


Assessment of vascular involvement.
Our objective was to identify a core set of variables for the assessment of vascular involvement in scleroderma that is simple, reproducible, and reflects the presence of vascular disease in SSc. To do so we carried out an extensive literature review of published studies relating to the assessment of vascular involvement in SSc, i.e. studies dealing with clinical parameters, functional vascular studies, cold presser testing, nailfold capillary microscopy and circulating vascular markers. After extensive review of published studies and critical assessment of proposed vascular parameters, the subcommittee endorsed what it considers to be the minimal requirements for the documentation of vascular involvement in SSc. The core set variables include two parameters: Raynaud's phenomenon and digital ulcers. This set is simple, reproducible and should be included in the assessment of SSc patients in clinical investigational studies. The subcommittee also however recognizes that there exists a promising set of vascular variable that still needs further investigation.


Use of a small DNA virus model to investigate mechanisms of CpG dinucleotide-induced attenuation of virus replication.
Suppression of the CpG dinucleotide is widespread in RNA viruses infecting vertebrates and plants, and in the genomes of retroviruses and small mammalian DNA viruses. The functional basis for CpG suppression in the latter was investigated through the construction of mutants of the parvovirus, minute virus of mice (MVM) with increased CpG or TpA dinucleotides in the VP gene. CpG-high mutants displayed extraordinary attenuation in A9 cells compared to wild-type MVM (>six logs), while TpA elevation showed no replication effect. Attenuation was independent of Toll-like receptor 9 and STING-mediated DNA recognition pathways and unrelated to effects on translation efficiency. While translation from codon-optimized VP RNA was enhanced in a cell-free assay, MVM containing this sequence was highly attenuated. Further mutational analysis indicated that this arose through its increased numbers of CpG dinucleotides (7→70) and separately from its increased G+C content (42.3→57.4 %), which independently attenuated replication. CpG-high viruses showed impaired NS mRNA expression by qPCR and reduced NS and particularly VP protein expression detected by immunofluorescence and replication in A549 cells, effects reversed in zinc antiviral protein (ZAP) knockout cells, even though nuclear relocalization of VP remained defective. The demonstrated functional basis for CpG suppression in MVM and potentially other small DNA viruses and the observed intolerance of CpGs in coding sequences, even after codon optimization, has implications for the use of small DNA virus vectors in gene therapy and immunization.


A shared-care model of obesity treatment for 3-10 year old children: protocol for the HopSCOTCH randomised controlled trial.
Despite record rates of childhood obesity, effective evidence-based treatments remain elusive. While prolonged tertiary specialist clinical input has some individual impact, these services are only available to very few children. Effective treatments that are easily accessible for all overweight and obese children in the community are urgently required. General practitioners are logical care providers for obese children but high-quality trials indicate that, even with substantial training and support, general practitioner care alone will not suffice to improve body mass index (BMI) trajectories. HopSCOTCH (the Shared Care Obesity Trial in Children) will determine whether a shared-care model, in which paediatric obesity specialists co-manage obesity with general practitioners, can improve adiposity in obese children. Randomised controlled trial nested within a cross-sectional BMI survey conducted across 22 general practices in Melbourne, Australia. Children aged 3-10 years identified as obese by Centers for Disease Control criteria at their family practice, and randomised to either a shared-care intervention or usual care. A single multidisciplinary obesity clinic appointment at Melbourne's Royal Children's Hospital, followed by regular appointments with the child's general practitioner over a 12 month period. To support both specialist and general practice consultations, web-based shared-care software was developed to record assessment, set goals and actions, provide information to caregivers, facilitate communication between the two professional groups, and jointly track progress. Primary - change in BMI z-score. Secondary - change in percentage fat and waist circumference; health status, body satisfaction and global self-worth. This will be the first efficacy trial of a general-practitioner based, shared-care model of childhood obesity management. If effective, it could greatly improve access to care for obese children. Australian New Zealand Clinical Trials Registry ACTRN12608000055303.


Strategic management of non-point source pollution from sewage sludge.
In the UK, the recycling of sewage sludge to land is expected to double by 2006 but the security of this route is threatened by environmental concerns and health scares. Strategic investment is needed to ensure sustainable and secure sludge recycling outlets. At present, the security of this landbank for sludge recycling is determined by legislation relating to nutrient rather than potentially toxic elements (PTEs) applications to land--especially the environmental risk linked to soil phosphorus (P) saturation. We believe that not all land has an equal risk of contributing nutrients derived from applications to land to receiving waters. We are currently investigating whether it is possible to minimise nutrient loss by applying sludge to land outside Critical Source Areas (CSAs) regardless of soil P Index status. Research is underway to develop a predictive and spatially-sensitive, semi-distributed model of critical thresholds for sludge application that goes beyond traditional "end-of-pipe" or "edge-of-field" modelling, to include hydrological flow paths and delivery mechanisms to receiving waters from non-point sources at the catchment scale.


Red blood cell omega-3 fatty acid levels and neurocognitive performance in deployed U.S. Servicemembers.
To explore the cross-sectional relationships between blood eicosapentaenoic acid + docosahexaenoic acid (HSOmega-3 Index(®)) and sleep disorders, depression, anxiety, and neurocognitive performance in Servicemembers deployed to Iraq. Servicemembers with mild-to-moderate depression by the Patient Health Questionnarie-9 from two US military camps were invited to participate in this study. A battery of validated psychosocial (Pittsburgh Sleep Quality Index, and Zung Depression, Zung Anxiety, Epworth Sleepiness, and Combat Experiences scales) and computerized neurocognitive tests were completed by each participant. Five neurocognitive domain scores were calculated--Processing Speed, Complex Attention, Reaction Time, Cognitive Flexibility (CF), and Executive Function (EF). A drop of blood was also collected on an anti-oxidant-treated filter paper card and sent for HS-Omega-3 Index(®) analysis. An analysis of variance contrast was used to test for linear trends between quartiles of the HS-Omega-3 Index(®) for both EF and CF. The mean HS-Omega-3 Index(®) was 3.5 ± 0.7% (n = 78). The HS-Omega-3 Index(®) was not significantly associated with scores for anxiety, depression, or sleep, whether assessed as continuous or dichotomous variables, but was directly associated with CF and EF (P < 0.02 and 0.01, respectively), especially in the 81% who reported poor sleep quality. In those with poor sleep quality (n = 63), EF and CF were higher (P = 0.005) in subjects with Omega-3 levels above versus below the mean. Optimal neurocognitive performance is essential during deployment. Our finding that EF and CF were positively related to HS-Omega-3 Index(®) suggests that improving omega-3 status through an increase in omega-3 intake may improve neurocognitive performance and confer an element of resilience to poor sleep.


Maintenance of quantal size and immediately releasable granules in rat chromaffin cells by glucocorticoid.
Glucocorticoid is reported to regulate catecholamine synthesis and storage. However, it is not clear whether the actual amount of catecholamine released from individual granules (quantal size, Q) in mature chromaffin cells is affected by glucocorticoid. Using carbon fiber amperometry, we found that dexamethasone did not affect mean cellular Q or the proportional release from different populations of granules in rat chromaffin cells cultured for 1 day in a serum-free defined medium. After two extra days of culture in the defined medium, there was a rundown in mean cellular Q, and it was associated with a shift in the proportional release from the different granule populations. This phenomenon could not be rescued by serum supplementation but could be prevented by dexamethasone via an action that was independent of changes in voltage-gated Ca(2+) channel (VGCC) density. Using simultaneous measurements of membrane capacitance and cytosolic Ca(2+) concentration, we found that for cells cultured in defined medium dexamethasone enhanced the exocytotic response triggered by a brief depolarization (50 ms) without affecting the VGCC density or the fast exocytotic response triggered via flash photolysis of caged Ca(2+). Thus glucocorticoid may regulate the number of immediately releasable granules that are in close proximity to a subset of VGCC. Because chromaffin cells in vivo are exposed to high concentrations of glucocorticoid, our findings suggest that the paracrine actions of glucocorticoid maintain the mean catecholamine content in chromaffin cell granules as well as the colocalization of releasable granules with VGCCs.


Identification of a functional p53 responsive element within the promoter of XAF1 gene in gastrointestinal cancer cells.
It has been reported that XAF1 expression in gastric cancer is negatively correlated with p53. Our purpose was to clarify the regulatory mechanism of p53 on XAF1 expression. The effects of overexpressed wild-type and mutant p53 on XAF1 expression were evaluated. Binding capacity of core XAF1 promoter sequence to the recombinant p53 protein was examined. Site-directed mutation of putative p53 binding sequence and p53 knockdown by siRNA were performed. The protein expression and promoter activities of XAF1 in cells with null p53 were higher than that with wild-type and mutant p53. Ectopic overexpression of wild-type p53 suppressed XAF1 expression. A half-site (-95 to -86 nt) and a quarter-site (-4 to +1 nt) of p53 responsive element were found within XAF1 promoter. Both sequences bound to recombinant p53 effectively and specifically. Site-mutation of p53 responsive sequences abrogated the binding capacity. However, only the mutation of half-site increased XAF1 promoter activities. Suppression of p53 not only decreased the binding capacity of p53 responsive halfsite but also increased XAF1 transcription. In conclusion, we demonstrated that p53 could suppress the transcription of XAF1 through interaction with a high affinity responsive element (-95 to -86 nt) within XAF1 promoter, indicating a novel exclusive mechanism between these two tumor suppressors.


Systematic pan-cancer analysis of somatic allele frequency.
Imbalanced expression of somatic alleles in cancer can suggest functional and selective features, and can therefore indicate possible driving potential of the underlying genetic variants. To explore the correlation between allele frequency of somatic variants and total gene expression of their harboring gene, we used the unique data set of matched tumor and normal RNA and DNA sequencing data of 5523 distinct single nucleotide variants in 381 individuals across 10 cancer types obtained from The Cancer Genome Atlas (TCGA). We analyzed the allele frequency in the context of the variant and gene functional features and linked it with changes in the total gene expression. We documented higher allele frequency of somatic variants in cancer-implicated genes (Cancer Gene Census, CGC). Furthermore, somatic alleles bearing premature terminating variants (PTVs), when positioned in CGC genes, appeared to be less frequently degraded via nonsense-mediated mRNA decay, indicating possible favoring of truncated proteins by the tumor transcriptome. Among the genes with multiple PTVs with high allele frequency, ARID1, TP53 and NSD1 were known key cancer genes. All together, our analyses suggest that high allele frequency of tumor somatic variants can indicate driving functionality and can serve to identify potential cancer-implicated genes.


Kinetically modulated specificity against single-base mutants in nucleic acid recycling circuitry using the destabilization motif.
Signal amplification in nucleic acid sensing improves detection sensitivity, but difficulties remain in sustaining specificity over time, particularly under excess amounts of single-base mutants. Here, we report simple, self-refining target recycling circuitry, which cumulates differentiation between on and off targets by 2-step cyclic interaction with the sensing probe. In the reaction, the analyte recycles only if the protective strand of the sensing probe is removed. The dissociation kinetics of such interaction was modulated by reacting it with different lengths of assistant strands. When shorter assistant strands are used, the destabilization motif of the sensing probe has to spontaneously dissociate before another assistant strand approaches and fully displaces it. This sets up a high kinetic barrier sensitive to the subtle reaction energy differences imposed by the single-base mutants, and substantially improved specificity. As a proof of concept, a microRNA 21 DNA analogue was chosen as our target analyte together with its 14 point mutants (substitution, insertion, or deletion) for specificity measurements. The experimental results corroborate that our system amplifies signals in a comparable manner to the traditional one-layer recycling approach but with negligible system leakage. With the use of shortened assistant strands, up to 100 fold increase in the discrimination factor against the single-base mutants is observed. Specificity is sustainable or even increased over long period measurements (i.e. 4 days). More importantly, target differentiation is successfully demonstrated even in excess amounts of spurious analogs (100×) and low target frequency mixtures (i.e. 0.1%), which mimic the lean conditions practically encountered. Explicit mechanisms of the system specificity are elucidated through analytical calculations and free energy level diagrams. The modularity of the destabilization motif herein promises detection of different nucleic acid based targets and integration into other signal amplification approaches for specificity enhancement.


Exercise-Based Strategies to Prevent Muscle Injury in Male Elite Footballers: An Expert-Led Delphi Survey of 21 Practitioners Belonging to 18 Teams from the Big-5 European Leagues.
To define based on expert opinion and practical experience using a systematic and scientific approach, (1) the perceived most effective exercise-based strategies to prevent muscle injury in elite footballers; and, (2) when and how these exercise programs are prescribed based on the number of days between games i.e. implementation strategy. A Delphi survey obtained opinions and assessed for agreement. Delphi respondents consisted of 21 experienced sports practitioners (12 ± 5.3 years in elite football and with an academic background) belonging to 18 teams from the Big-5 European football leagues; England, France, Germany, Italy, Spain. Three teams were represented collaboratively by two experts. The Delphi process involves sequential rounds each evolving based on the responses from the previous. The number of rounds is not pre-defined and continues until an agreement is either achieved or it is clear that no agreement will be reached. Frequency of responses was recorded where the agreement was sought (i.e. in closed questions) and an agreement was achieved if ≥ 13/18 (70%) respondents agreed. For open-ended questions, a qualitative content analysis was performed to identify recurring themes and when themes were specified by ≥ 13 (70%), these were also considered as reaching an agreement. Practitioners had the opportunity to raise concerns if they disagreed with the 'agreement from recurrent themes'. There were four Delphi rounds (100% response for each round). Sprinting and High-Speed Running (HSR) focused exercises were agreed as most effective (perceived) to prevent muscle injuries. Eccentric exercise was perceived as the next most effective. It was agreed that sprinting and HSR be integrated into coaches training, and target 100% of players worst-case match scenario (e.g. volume, intensity) based on individual maximum speeds. Eccentric exercise was recommended to be implemented according to the context of the main football session and planned/actual sprinting and HSR content. It was agreed that eccentrics can be performed before or after training, context dependent. The day to perform specific sprinting and HSR or eccentric exercises depended on the proximity of previous and upcoming matches. Other exercises reaching agreement as 'somewhat effective' included concentric and isometric, horizontal and vertical plyometrics, coordination, core and dynamic flexibility in addition to core stability. No agreement was reached for multi-joint, resisted sprinting, kicking or agility exercises nor simultaneous single-leg strength and stability. Finally, no agreement was reached regarding programming variables e.g. sets, repetitions as deemed too contextual. Regarding exercise-based strategies, particular importance agreed by the Delphi expert group was to focus on sprinting, HSR and eccentric exercises, integrated with a variety of other exercise modes which also carry some level of effectiveness in a multidimensional programme. Context was agreed to be key and decision-making about when to undertake/ how to prescribe exercise strategies to be made according to the content of normal football training and the proximity of matches.


Racial disparities in stress test utilization in an emergency department chest pain unit.
Epidemiological studies have demonstrated racial disparities in the workup of emergency department patients with chest pain and the referral of admitted patients for intervention. However, little is known about possible disparities in stress test utilization in low-risk chest pain patients admitted to emergency department chest pain units. A retrospective observational study of consecutive chest pain unit patients was conducted. Eligibility criteria included age >18 years, American Heart Association low-to-intermediate risk, nondynamic electrocardiograms, and normal initial troponin I. Patients aged >75 years with a history of coronary artery heart disease were excluded. On each patient, we calculated a Thrombolysis in Myocardial Infarction (TIMI) risk prediction score and a Diamond and Forrester (D&F) score for likelihood of coronary artery disease. Two separate multivariate analyses were completed, one including the TIMI score and the other including D&F score, using logistic regression to estimate odds ratios (ORs) for receiving testing based on race, controlling for other relevant covariates. Two thousand four hundred fifty-one patients were enrolled over a planned 1.5-year period. In total, 59.7% [95% confidence interval (CI) 57.8-61.7] of patients were white, 11.6% (95% CI 10.4-12.9) African American, and 28.6% (95% CI 26.9-30.4) "other." The overall stress testing rate was 50.3% (95% CI 48.4-52.3). After controlling for insurance and TIMI or D&F scores, African American patients had significantly decreased odds of stress testing (OR(TIMI) 0.68, 95% CI 0.52-0.89; OR(D&F) 0.67, 95% CI 0.51-0.89). Our study confirms racial disparities in the utilization of stress testing in the chest pain unit. Further investigation is needed to identify specific provider or patient-level factors that may contribute to this disparity.


High-Precision Printing of Complex Glass Imaging Optics with Precondensed Liquid Silica Resin.
3D printing of optics has gained significant attention in optical industry, but most of the research has been focused on organic polymers. In spite of recent progress in 3D printing glass, 3D printing of precision glass optics for imaging applications still faces challenges from shrinkage during printing and thermal processing, and from inadequate surface shape and quality to meet the requirements for imaging applications. This paper reports a new liquid silica resin (LSR) with higher curing speed, better mechanical properties, lower sintering temperature, and reduced shrinkage, as well as the printing process for high-precision glass optics for imaging applications. It is demonstrated that the proposed material and printing process can print almost all types of optical surfaces, including flat, spherical, aspherical, freeform, and discontinuous surfaces, with accurate surface shape and high surface quality for imaging applications. It is also demonstrated that the proposed method can print complex optical systems with multiple optical elements, completely removing the time-consuming and error-prone alignment process. Most importantly, the proposed printing method is able to print optical systems with active moving elements, significantly improving system flexibility and functionality. The printing method will enable the much-needed transformational manufacturing of complex freeform glass optics that are currently inaccessible with conventional processes.


Vertebral osteomyelitis after cardiac surgery.
Mediastinitis after open-heart surgery is a serious complication that has a decreasing incidence but still a significantly high mortality rate. Back pain may develop during the course of treatment for mediastinitis, and this should suggest vertebral osteomyelitis in the differential diagnosis. Diagnosis of vertebral osteomyelitis may be difficult because of the insidious onset and delayed diagnosis, and treatment may result in serious neurologic compromise and even death of the patient. This retrospective study involves 5 patients who had open-heart surgery and mediastinitis that was further complicated by vertebral osteomyelitis. Average delay in diagnosis was 18 days after the onset of symptoms. Magnetic resonance imaging was the most helpful tool for diagnosis. Methicilline-resistant Staphylococcus aureus was identified as the responsible microorganism in all patients. Neurologic compromise occured (one paraplegia and one paraparesia) in 2 patients during medical treatment. Along with the medical treatment, all patients were surgically treated due to either one or more of the following reasons: unresolving symptoms, sudden neurologic compromise, or impaired spinal column stability despite appropriate conservative treatment. One patient died 10 days postoperatively. The mean follow-up period for the remaining 4 patients was 47 (12 to 95) months. Complete recovery was achieved, and they were able to return to their routine daily activities. Vertebral osteomyelitis should be borne in mind when a patient develops back pain during the course of mediastinitis. Suspicion, early diagnosis with appropriate imaging, and proper treatment are crucial to prevent catastrophic complications.


Pharmacokinetic and metabolomic analyses of the neuroprotective effects of salvianolic acid A in a rat ischemic stroke model.
Salvianolic acid A (SAA), a water-soluble phenolic acid isolated from the root of Dan Shen, displays distinct antioxidant activity and effectiveness in protection against cerebral ischemia/reperfusion (I/R) damage. However, whether SAA can enter the central nervous system and exert its protective effects by directly targeting brain tissue remains unclear. In this study, we evaluated the cerebral protection of SAA in rats subjected to transient middle cerebral artery occlusion (tMCAO) followed by reperfusion. The rats were treated with SAA (5, 10 mg/kg, iv) when the reperfusion was performed. SAA administration significantly decreased cerebral infarct area and the brain water content, attenuated the neurological deficit and pathology, and enhanced the anti-inflammatory and antioxidant capacity in tMCAO rats. The concentration of SAA in the plasma and brain was detected using LC-MS/MS. A pharmacokinetic study revealed that the circulatory system exposure to SAA was equivalent in the sham controls and I/R rats, but the brain exposure to SAA was significantly higher in the I/R rats than in the sham controls (fold change of 9.17), suggesting that the enhanced exposure to SAA contributed to its cerebral protective effect. Using a GC/MS-based metabolomic platform, metabolites in the serum and brain tissue were extracted and profiled. According to the metabolomic pattern of the tissue data, SAA administration significantly modulated the I/R-caused perturbation of metabolism in the brain to a greater extent than that in the serum, demonstrating that SAA worked at the brain tissue level rather than the whole circulation system. In conclusion, a larger amount of SAA enters the central nervous system in ischemia/reperfusion rats to facilitate its protective and regulatory effects on the perturbed metabolism.


The possible role of vitamin K deficiency in the pathogenesis of Alzheimer's disease and in augmenting brain damage associated with cardiovascular disease.
The incidence of Alzheimer's disease (AD) increases with age and in carriers of the apolipoprotein E4 genotype. A relative deficiency of vitamin K, affecting the extrahepatic functions of the vitamin, is common in ageing men and women. The concentration of vitamin K is lower in the circulating blood of APOE4 carriers than in that of persons with other APOE genotypes. Evidence is accumulating that vitamin K has important functions in the brain, including the regulation of sulfotransferase activity and the activity of a growth factor/tyrosine kinase receptor (Gas 6/Axl). The hypothesis is now proposed that vitamin K deficiency contributes to the pathogenesis of AD and that vitamin K supplementation may have a beneficial effect in preventing or treating the disease. Vitamin K may also reduce neuronal damage associated with cardiovascular disease.


Eccentric cycling does not improve cycling performance in amateur cyclists.
Eccentric cycling training induces muscle hypertrophy and increases joint power output in non-athletes. Moreover, eccentric cycling can be considered a movement-specific type of strength training for cyclists, but it is hitherto unknown if eccentric cycling training can improve cycling performance in trained cyclists. Twenty-three male amateur cyclists were randomized to an eccentric or a concentric cycling training group. The eccentric cycling was performed at a low cadence (~40 revolution per minute) and the intensity was controlled by perceived effort (12-17 on the Borgs scale) during 2 min intervals (repeated 5-8 times). The cadence and perceived effort of the concentric group matched those of the eccentric group. Additionally, after the eccentric or concentric cycling, both groups performed traditionally aerobic intervals with freely chosen cadence in the same session (4-5 x 4-15 min). The participants trained twice a week for 10 weeks. Maximal oxygen uptake (VO2max), maximal aerobic power output (Wmax), lactate threshold, isokinetic strength, muscle thickness, pedaling characteristics and cycling performance (6- and 30-sec sprints and a 20-min time trial test) were assessed before and after the intervention period. Inferences about the true value of the effects were evaluated using probabilistic magnitude-based inferences. Eccentric cycling induced muscle hypertrophy (2.3 ± 2.5% more than concentric) and augmented eccentric strength (8.8 ± 5.9% more than concentric), but these small magnitude effects seemed not to transfer into improvements in the physiological assessments or cycling performance. On the contrary, the eccentric training appeared to have limiting or detrimental effects on cycling performance, measured as Wmax and a 20-min time trial. In conclusion, eccentric cycling training did not improve cycling performance in amateur cyclists. Further research is required to ascertain whether the present findings reflect an actual lack of efficacy, negative effects or a delayed response to eccentric cycling training.


Cooperation in the dark: signalling and collective action in quorum-sensing bacteria.
The study of quorum-sensing bacteria has revealed a widespread mechanism of coordinating bacterial gene expression with cell density. By monitoring a constitutively produced signal molecule, individual bacteria can limit their expression of group-beneficial phenotypes to cell densities that guarantee an effective group outcome. In this paper, we attempt to move away from a commonly expressed view that these impressive feats of coordination are examples of multicellularity in prokaryotic populations. Here, we look more closely at the individual conflict underlying this cooperation, illustrating that, even under significant levels of genetic conflict, signalling and resultant cooperative behaviour can stably exist. A predictive two-trait model of signal strength and of the extent of cooperation is developed as a function of relatedness (reflecting multiplicity of infection) and basic population demographic parameters. The model predicts that the strength of quorum signalling will increase as conflict (multiplicity of infecting strains) increases, as individuals attempt to coax more cooperative contributions from their competitors, leading to a devaluation of the signal as an indicator of density. Conversely, as genetic conflict increases, the model predicts that the threshold density for cooperation will increase and the subsequent strength of group cooperation will be depressed.


Quantum Chemistry on Quantum Computers: A Polynomial-Time Quantum Algorithm for Constructing the Wave Functions of Open-Shell Molecules.
Quantum computers are capable to efficiently perform full configuration interaction (FCI) calculations of atoms and molecules by using the quantum phase estimation (QPE) algorithm. Because the success probability of the QPE depends on the overlap between approximate and exact wave functions, efficient methods to prepare accurate initial guess wave functions enough to have sufficiently large overlap with the exact ones are highly desired. Here, we propose a quantum algorithm to construct the wave function consisting of one configuration state function, which is suitable for the initial guess wave function in QPE-based FCI calculations of open-shell molecules, based on the addition theorem of angular momentum. The proposed quantum algorithm enables us to prepare the wave function consisting of an exponential number of Slater determinants only by a polynomial number of quantum operations.


Molecular cloning of interferon receptors: a short review.
Interferons (IFNs) exert their pleiotropic effects through at least two different receptors. IFNs alpha/beta (type I IFNs) crossreact with presumably common receptors, while IFN gamma (type II IFN) initiates its biological effects through its own specific receptor system. Transmembrane proteins corresponding to the ligand binding chains of these receptors have recently been cloned. But transfection experiments revealed that additional components are probably involved in high affinity binding of some type I IFN subtypes and that a species specific putative signal transducer is required to confer biological responsiveness to IFN gamma. Although some elements involved in transcriptional regulation of interferon inducible genes have been identified, the pathways involved in these regulatory processes are not understood as yet. The current knowledge on the structure of IFN receptors is reviewed in the context of some recent advances on other cytokine receptors.


Accessory middle cerebral artery: is it a variant form of the recurrent artery of Heubner?
Fourteen accessory middle cerebral arteries demonstrated on angiography were reviewed relative to the pertinent literature. The anomalous vessel follows a fairly constant pattern in terms of origin, course, and distribution, and it frequently gives rise to basal perforating arteries. It is suggested that the vessel represents a persistent anastomosis between the anterior and middle cerebral arteries over the tuberculum olfactorium, the anastomosis being a predecessor of the recurrent artery of Heubner in phylogenetic development. Among various descendants of the anastomotic channels could be included both the normal recurrent artery of Heubner and the accessory middle cerebral artery, with or without basal perforating arteries. We believe the simultaneous presence of the recurrent artery of Heubner and the accessory middle cerebral artery on one side may represent the persistence of two anastomoses, one as the recurrent artery of Heubner and the other as the accessory middle cerebral artery; this is similar to the situation of duplication of the recurrent artery of Heubner.


Dynamic replacement of histone H3 variants reprograms epigenetic marks in early mouse embryos.
Upon fertilization, reprogramming of gene expression is required for embryo development. This step is marked by DNA demethylation and changes in histone variant composition. However, little is known about the molecular mechanisms causing these changes and their impact on histone modifications. We examined the global deposition of the DNA replication-dependent histone H3.1 and H3.2 variants and the DNA replication-independent H3.3 variant after fertilization in mice. We showed that H3.3, a euchromatic marker of gene activity, transiently disappears from the maternal genome, suggesting erasure of the oocyte-specific modifications carried by H3.3. After fertilization, H3.2 is incorporated into the transcriptionally silent heterochromatin, whereas H3.1 and H3.3 occupy unusual heterochromatic and euchromatin locations, respectively. After the two-cell stage, H3.1 and H3.3 variants resume their usual respective locations on heterochromatin and euchromatin. Preventing the incorporation of H3.1 and H3.2 by knockdown of the histone chaperone CAF-1 induces a reciprocal increase in H3.3 deposition and impairs heterochromatin formation. We propose that the deposition of different H3 variants influences the functional organization of chromatin. Taken together, these findings suggest that dynamic changes in the deposition of H3 variants are critical for chromatin reorganization during epigenetic reprogramming.


Analysis of meteorology and emission in haze episode prevalence over mountain-bounded region for early warning.
This study investigated the main causes of haze episodes in the northwestern Thailand to provide early warning and prediction. In an absence of emission input data required for chemical transport modeling to predict the haze, the climatological approach in combination with statistical analysis was used. An automatic meteorological classification scheme was developed using regional meteorological station data of 8years (2001-2008) which classified the prevailing synoptic patterns over Northern Thailand into 4 patterns. Pattern 2, occurring with high frequency in March, was found to associate with the highest levels of 24h PM(10) in Chiangmai, the largest city in Northern Thailand. Typical features of this pattern were the dominance of thermal lows over India, Western China and Northern Thailand with hot, dry and stagnant air in Northern Thailand. March 2007, the month with the most severe haze episode in Chiangmai, was found to have a high frequency of occurrence of pattern 2 coupled with the highest emission intensities from biomass open burning. Backward trajectories showed that, on haze episode days, air masses passed over the region of dense biomass fire hotspots before arriving at Chiangmai. A stepwise regression model was developed to predict 24h PM(10) for days of meteorology pattern 2 using February-April data of 2007-2009 and tested with 2004-2010 data. The model performed satisfactorily for the model development dataset (R(2)=87%) and test dataset (R(2)=81%), which appeared to be superior over a simple persistence regression of 24h PM(10) (R(2)=76%). Our developed model had an accuracy over 90% for the categorical forecast of PM(10)>120μg/m(3). The episode warning procedure would identify synoptic pattern 2 and predict 24h PM(10) in Chiangmai 24h in advance. This approach would be applicable for air pollution episode management in other areas with complex terrain where similar conditions exist.


Language control in the bilingual brain.
How does the bilingual brain distinguish and control which language is in use? Previous functional imaging experiments have not been able to answer this question because proficient bilinguals activate the same brain regions irrespective of the language being tested. Here, we reveal that neuronal responses within the left caudate are sensitive to changes in the language or the meaning of words. By demonstrating this effect in populations of German-English and Japanese-English bilinguals, we suggest that the left caudate plays a universal role in monitoring and controlling the language in use.


Occupational exposure to magnetic fields in case-referent studies of neurodegenerative diseases.
Case-referent studies of Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease were conducted to explore the relationship between these neurodegenerative diseases and occupational exposure to magnetic fields. Three methods of exposure assessment were used for the comparison, and the consistency of findings between these approaches was evaluated. Separate case-referent sets were formed from among recorded deaths of males in the state of Colorado for the years 1987 through 1996. The following three methods of exposure assessment were used: a dichotomous grouping of electrical versus nonelectrical occupations, a three-tiered grouping of potential magnetic-field exposure based on a combination of job title and industry, and categories of exposure based on the means of the magnetic fields estimated from a job-exposure matrix. A positive association was observed for Parkinson's disease with all the methods of magnetic-field exposure assessment, the odds ratio (OR) for the highest category in the job-exposure matrix being 1.50 [95% confidence interval (95% CI) 1.02-2.19]. Amyotrophic lateral sclerosis was associated with a history of electrical occupations (OR 2.30, 95% CI 1.29-4.09) but not with magnetic-field exposure as estimated by the job-exposure matrix. No consistent associations with magnetic fields were observed for Alzheimer's disease. This study provides some support for an association between occupational magnetic-field exposure and Parkinson's disease, but the findings are novel and require replication. Associations with the other neurodegenerative diseases were inconsistent and dependent on the method of exposure assessment.


Surface modification of SU-8 for enhanced cell attachment and proliferation within microfluidic chips.
Advances in micro-electro-mechanical systems (MEMS) have led to an increased fabrication of micro-channels. Microfabrication techniques are utilized to develop microfluidic channels for continuous nutrition supply to cells inside a micro-environment. The ability of cells to build tissues and maintain tissue-specific functions depends on the interaction between cells and the extracellular matrix (ECM). SU-8 is a popular photosensitive epoxy-based polymer in MEMS. The patterning of bare SU-8 alone does not provide the appropriate ECM necessary to develop microsystems for biological applications. Manipulating the chemical composition of SU-8 will enhance the biological compatibility, giving the fabricated constructs the appropriate ECM needed to promote a functional tissue array. This article investigates three frequently used surface treatment techniques: (1) plasma treatment, (2) chemical reaction, and (3) deposition treatment to determine which surface treatment is the most beneficial for enhancing the biological properties of SU-8. The investigations presented in this article demonstrated that the plasma, gelatin, and sulfuric acid treatments have a potential to enhance SU-8's surface for biological application. Of course each treatment has their advantages and disadvantages (application dependent). Cell proliferation was studied with the use of the dye Almar Blue, and a micro-plate reader. After 14 days, cell proliferation to plasma treated surfaces was statistically significantly enhanced (p < 0.00001), compared to untreated surfaces. The plasma treated surface is suggested to be the better of the three treatments for biological enhancement followed by gelatin and sulfuric acid treatments, respectively.


Management of decompensated heart failure.
Much has been written about the management of chronic heart failure (HF) and there is strong evidence from many controlled, multicenter trials to support a specific strategy for management of compensated HF. There is little evidence and limited guidance for the management of patients during a period of decompensation. The use of diuretics, inodilators, and vasodilators is based primarily on anecdotal observation. This article reviews selected current literature in three areas (diuretics, vasodilators, and inotropes) to examine objective evidence and expert opinion that are available to guide the advanced practitioner who manages the care of patients with decompensated HF.


Identification of rare DNA sequence variants in high-risk autism families and their prevalence in a large case/control population.
Genetics clearly plays a major role in the etiology of autism spectrum disorders (ASDs), but studies to date are only beginning to characterize the causal genetic variants responsible. Until recently, studies using multiple extended multi-generation families to identify ASD risk genes had not been undertaken. We identified haplotypes shared among individuals with ASDs in large multiplex families, followed by targeted DNA capture and sequencing to identify potential causal variants. We also assayed the prevalence of the identified variants in a large ASD case/control population. We identified 584 non-conservative missense, nonsense, frameshift and splice site variants that might predispose to autism in our high-risk families. Eleven of these variants were observed to have odds ratios greater than 1.5 in a set of 1,541 unrelated children with autism and 5,785 controls. Three variants, in the RAB11FIP5, ABP1, and JMJD7-PLA2G4B genes, each were observed in a single case and not in any controls. These variants also were not seen in public sequence databases, suggesting that they may be rare causal ASD variants. Twenty-eight additional rare variants were observed only in high-risk ASD families. Collectively, these 39 variants identify 36 genes as ASD risk genes. Segregation of sequence variants and of copy number variants previously detected in these families reveals a complex pattern, with only a RAB11FIP5 variant segregating to all affected individuals in one two-generation pedigree. Some affected individuals were found to have multiple potential risk alleles, including sequence variants and copy number variants (CNVs), suggesting that the high incidence of autism in these families could be best explained by variants at multiple loci. Our study is the first to use haplotype sharing to identify familial ASD risk loci. In total, we identified 39 variants in 36 genes that may confer a genetic risk of developing autism. The observation of 11 of these variants in unrelated ASD cases further supports their role as ASD risk variants.


[Primary care and alcohol use disorders: evaluation of a faculty-development program in Venezuela].
Primary care offers an opportunity to identify and treat persons who drink alcohol above permissible levels. In order to prepare primary care practitioners around the world to prevent and treat alcohol-related problems, the National Institute on Alcohol Abuse and Alcoholism of the United States of America has developed and tested a model international program for educating physicians about such problems. The model was designed to increase the clinical, teaching, and research skills of medical school faculty who work with medical students, residents, and primary care physicians. Venezuela was one of the countries selected for the initiative. During September 1999 a five-day faculty-development course consisting of 19 workshops was conducted at the University of Zulia, which is located in the city of Maracaibo, Zulia, Venezuela. Teaching strategies included class presentations, role plays, case presentations, skills-building workshops, and having each participant develop a teaching plan that he or she would use. Thirty-three faculty members from 9 of Venezuela's 10 medical schools participated in the project. The 18 female and 15 male participants had an average age of 44 years. The areas of specialization of the 33 participants were: family medicine (9 participants), psychiatry (7), pediatrics (6), obstetrics (4), internal medicine (3), and unspecified (4). Of the 33 participants, 25 of them (76%) completed a six-month follow-up interview. This group said they had significantly increased their competence in 14 clinical areas and that they had successfully implemented new teaching activities within their respective medical schools and residency programs. This model proved to be an effective strategy for increasing training for physicians in the prevention and treatment of alcohol-related problems in Venezuela. The evaluation confirms similar findings in other countries where the program has been implemented.


Degrees of Freedom in Planning, Running, Analyzing, and Reporting Psychological Studies: A Checklist to Avoid p-Hacking.
The designing, collecting, analyzing, and reporting of psychological studies entail many choices that are often arbitrary. The opportunistic use of these so-called researcher degrees of freedom aimed at obtaining statistically significant results is problematic because it enhances the chances of false positive results and may inflate effect size estimates. In this review article, we present an extensive list of 34 degrees of freedom that researchers have in formulating hypotheses, and in designing, running, analyzing, and reporting of psychological research. The list can be used in research methods education, and as a checklist to assess the quality of preregistrations and to determine the potential for bias due to (arbitrary) choices in unregistered studies.


JF-cut: a parallel graph cut approach for large-scale image and video.
Graph cut has proven to be an effective scheme to solve a wide variety of segmentation problems in vision and graphics community. The main limitation of conventional graph-cut implementations is that they can hardly handle large images or videos because of high computational complexity. Even though there are some parallelization solutions, they commonly suffer from the problems of low parallelism (on CPU) or low convergence speed (on GPU). In this paper, we present a novel graph-cut algorithm that leverages a parallelized jump flooding technique and an heuristic push-relabel scheme to enhance the graph-cut process, namely, back-and-forth relabel, convergence detection, and block-wise push-relabel. The entire process is parallelizable on GPU, and outperforms the existing GPU-based implementations in terms of global convergence, information propagation, and performance. We design an intuitive user interface for specifying interested regions in cases of occlusions when handling video sequences. Experiments on a variety of data sets, including images (up to 15 K × 10 K), videos (up to 2.5 K × 1.5 K × 50), and volumetric data, achieve high-quality results and a maximum 40-fold (139-fold) speedup over conventional GPU (CPU-)-based approaches.


Synaptic phospholipids as a new target for cortical hyperexcitability and E/I balance in psychiatric disorders.
Lysophosphatidic acid (LPA) is a synaptic phospholipid, which regulates cortical excitation/inhibition (E/I) balance and controls sensory information processing in mice and man. Altered synaptic LPA signaling was shown to be associated with psychiatric disorders. Here, we show that the LPA-synthesizing enzyme autotaxin (ATX) is expressed in the astrocytic compartment of excitatory synapses and modulates glutamatergic transmission. In astrocytes, ATX is sorted toward fine astrocytic processes and transported to excitatory but not inhibitory synapses. This ATX sorting, as well as the enzymatic activity of astrocyte-derived ATX are dynamically regulated by neuronal activity via astrocytic glutamate receptors. Pharmacological and genetic ATX inhibition both rescued schizophrenia-related hyperexcitability syndromes caused by altered bioactive lipid signaling in two genetic mouse models for psychiatric disorders. Interestingly, ATX inhibition did not affect naive animals. However, as our data suggested that pharmacological ATX inhibition is a general method to reverse cortical excitability, we applied ATX inhibition in a ketamine model of schizophrenia and rescued thereby the electrophysiological and behavioral schizophrenia-like phenotype. Our data show that astrocytic ATX is a novel modulator of glutamatergic transmission and that targeting ATX might be a versatile strategy for a novel drug therapy to treat cortical hyperexcitability in psychiatric disorders.


Cyclic AMP stimulates sorting of the canalicular organic anion transporter (Mrp2/cMoat) to the apical domain in hepatocyte couplets.
The canalicular membrane of rat hepatocytes contains an ATP-dependent multispecific organic anion transporter, also named multidrug resistance protein 2, that is responsible for the biliary secretion of several amphiphilic organic anions. This transport function is markedly diminished in mutant rats that lack the transport protein. To assess the role of vesicle traffic in the regulation of canalicular organic anion transport, we have examined the redistribution of the transporter to the canalicular membrane and the effect of cAMP on this process in isolated hepatocyte couplets, which retain secretory polarity. The partial disruption of cell-cell contact, due to the isolation procedure, leaves the couplet with both remnant apical membranes, as a source of apical proteins, and an intact apical domain and lumen, to which these proteins are targeted. The changes in distribution of the transporter were correlated to the apical excretion of a fluorescent substrate, glutathione-methylfluorescein. The data obtained in this study show that the transport protein, endocytosed from apical membrane remnants, first is redistributed along the basolateral plasma membrane. Then it is transcytosed to the remaining apical pole in a microtubule-dependent fashion, followed by the fusion of transporter-containing vesicles with the apical membrane. The cAMP analog dibutyrylcAMP stimulates all three steps, resulting in increased apically located transport protein, glutathione-methylfluorescein transport activity and apical membrane circumference. These findings indicate that the organic anion transport capacity of the apical membrane in hepatocyte couplets is regulated by cAMP-stimulated sorting of the multidrug resistance protein 2 to the apical membrane. The relevance of this phenomenon for the intact liver is discussed.


Ethane-freezing/methanol-fixation of cell monolayers: a procedure for improved preservation of structure and antigenicity for light and electron microscopies.
In order to dissect at the ultrastructural level the morphology of highly dynamic processes such as cell motility, membrane trafficking events, and organelle movements, it is necessary to fix/stop time-dependent events in the millisecond range. Ideally, immunoelectron microscopical labeling experiments require the availability of high-affinity antibodies and accessibility to all compartments of the cell. The biggest challenge is to define an optimum between significant preservation of the antigenicity in the fixed material without compromising the intactness of fine structures. Here, we present a procedure which offers an opportunity to unify preparation of cell monolayers for immunocytochemistry in fluorescence and electron microscopy. This novel strategy combines a rapid ethane-freezing technique with a low temperature methanol-fixation treatment (EFMF) and completely avoids chemical fixatives. It preserves the position and delicate shape of cells and organelles and leads to improved accessibility of the intracellular antigens and to high antigenicity preservation. We illustrate the establishment of this procedure using Dictyostelium discoideum, a powerful model organism to study molecular mechanisms of membrane trafficking and cytoskeleton.


A new Burgess Shale-type deposit from the Ediacaran of western Mongolia.
Preservation of soft-bodied organisms is exceedingly rare in the fossil record. One way that such fossils are preserved is as carbonaceous compressions in fined-grained marine sedimentary rocks. These deposits of exceptional preservation are known as Burgess Shale-type (BST) deposits. During the Cambrian Period, BST deposits are more common and provide a crucial view of early animal evolution. The earliest definitive fossil evidence for macroscopic animal-grade organisms is found in the preceding Ediacaran Period. BST deposits from the Ediacaran are rarer and lack conclusive evidence for animals. Here we report the discovery of a new Ediacaran BST deposit with exceptional preservation of non-mineralizing macro-organisms in thinly bedded black shale from Zavkhan Province, western Mongolia. This fossil assemblage, here named the Zuun-Arts biota, currently consists of two new species of probable macroscopic multicellular benthic algae. One species, Chinggiskhaania bifurcata n. gen., n. sp., dominates the biota. The other species, Zuunartsphyton delicatum n. gen., n. sp., is known from three specimens. SEM-EDS analysis shows that the fossils are composed of aluminosilicate clay minerals and some carbon, a composition comparable to fossils from the Cambrian Burgess Shale biota. This discovery opens a new window through which to view late Precambrian life.


Functional implications of the expression of PilC proteins in meningococci.
Multiple forms of PilC were found in Neisseria meningitidis (Nm) strains isolated from the oropharynx, blood or cerebrospinal fluid expressing either Class I or Class II pili. PilC expression was observed less frequently in case as opposed to carrier isolates. Moreover, PilC and pili were not always co-expressed. Several heavily piliated strains had no detectable PilC protein as determined by Western blotting using an antiserum previously used to detect such proteins in adhesive variants (Nassif et al., 1994). Serogroup B strain MC58 produced large numbers of pili, but expressed barely detectable amounts of PilC. A clonal variant of this strain with increased expression of PilC concurrently exhibited increased adherence to Chang conjunctival epithelial cells and human umbilical vein endothelial cells (Huvecs), but with more rapid binding to the former. No alteration in pilin sequence occurred in this variant, suggesting the involvement of PilC in increased adhesion. A Pil- backswitcher isolated from the hyper-adherent variant was PilC+ but was non-adherent, indicating that any PilC adherence function requires pilus expression. Parental variant (low PilC) produced pili in bundles that were easily detached from the bacterial surface and were frequently associated with Huvec surfaces after bacteria had been sheared off, but pili infrequently replaced bacteria during infection with the PilC-expressing variant. The hyper-adherent variant, which appeared to produce morphologically distinct pilus bundles, was able to withstand considerable shearing force and remained firmly attached to Huvecs. This raises the possibility that the observed hyper-adherence may arise from better anchorage of pili to the bacterial surface in addition to increased adhesion to some host cell surfaces.


Vascular endothelial and endocardial progenitors differentiate as cardiomyocytes in the absence of Etsrp/Etv2 function.
Previous studies have suggested that embryonic vascular endothelial, endocardial and myocardial lineages originate from multipotential cardiovascular progenitors. However, their existence in vivo has been debated and molecular mechanisms that regulate specification of different cardiovascular lineages are poorly understood. An ETS domain transcription factor Etv2/Etsrp/ER71 has been recently established as a crucial regulator of vascular endothelial differentiation in zebrafish and mouse embryos. In this study, we show that etsrp-expressing vascular endothelial/endocardial progenitors differentiate as cardiomyocytes in the absence of Etsrp function during zebrafish embryonic development. Expression of multiple endocardial specific markers is absent or greatly reduced in Etsrp knockdown or mutant embryos. We show that Etsrp regulates endocardial differentiation by directly inducing endocardial nfatc1 expression. In addition, Etsrp function is required to inhibit myocardial differentiation. In the absence of Etsrp function, etsrp-expressing endothelial and endocardial progenitors initiate myocardial marker hand2 and cmlc2 expression. Furthermore, Foxc1a function and interaction between Foxc1a and Etsrp is required to initiate endocardial development, but is dispensable for the inhibition of myocardial differentiation. These results argue that Etsrp initiates endothelial and endocardial, and inhibits myocardial, differentiation by two distinct mechanisms. Our findings are important for the understanding of genetic pathways that control cardiovascular differentiation during normal vertebrate development and will also greatly contribute to the stem cell research aimed at regenerating heart tissues.


Chronic pain syndromes in cancer survivors.
Advances in medical knowledge and treatment have resulted in improved five-year survival rates for some forms of cancer. However, pain syndromes resulting from chemotherapy, radiotherapy, surgery or interventional procedures continue to have a significant effect on cancer survivors' quality of life. Nurses are uniquely placed to assess pain in cancer survivors and ensure pain management strategies are initiated. This article focuses on chronic pain syndromes that can occur following cancer treatment, examining the effect of pain on patients' quality of life.


Untargeted Metabolomics to Go beyond the Canonical Effect of Acetylsalicylic Acid.
Given to its ability to irreversibly acetylate the platelet cyclooxygenase-1 enzyme, acetylsalicylic acid (ASA) is successfully employed for the prevention of cardiovascular disease. Recently, an antitumoral effect of ASA in colorectal cancer has been increasingly documented. However, the molecular and metabolic mechanisms by which ASA exerts such effect is largely unknown. Using a new, untargeted liquid chromatography-mass spectrometry approach, we have analyzed urine samples from seven healthy participants that each ingested 100 mg of ASA once daily for 1 week. Of the 2007 features detected, 25 metabolites differing after ASA ingestion (nominal p < 0.05 and variable importance in projection (VIP) score > 1) were identified, and pathway analysis revealed low levels of glutamine and of metabolites involved in histidine and purine metabolisms. Likewise, consistent with an altered fatty acid β-oxidation process, a decrease in several short- and medium-chain acyl-carnitines was observed. An abnormal β-oxidation and a lower than normal glutamine availability suggests reduced synthesis of acetyl-Co-A, as they are events linked to one another and experimentally related to ASA antiproliferative effects. While giving an example of how untargeted metabolomics allows us to explore new clinical applications of drugs, the present data provide a direction to be pursued to test the therapeutic effects of ASA-e.g., the antitumoral effect-beyond cardiovascular protection.


Mixture of spherical distributions for single-view relighting.
We present a method for simultaneously estimating the illumination of a scene and the reflectance property of an object from single view images - a single image or a small number of images taken from the same viewpoint. We assume that the illumination consists of multiple point light sources and the shape of the object is known. First, we represent the illumination on the surface of a unit sphere as a finite mixture of von Mises-Fisher distributions based on a novel spherical specular reflection model that well approximates the Torrance-Sparrow reflection model. Next, we estimate the parameters of this mixture model including the number of its component distributions and the standard deviation of them, which correspond to the number of light sources and the surface roughness, respectively. Finally, using these results as the initial estimates, we iteratively refine the estimates based on the original Torrance-Sparrow reflection model. The final estimates can be used to relight single-view images such as altering the intensities and directions of the individual light sources. The proposed method provides a unified framework based on directional statistics for simultaneously estimating the intensities and directions of an unknown number of light sources as well as the specular reflection parameter of the object in the scene.


Direct real-time PCR-based detection of Neisseria gonorrhoeae 23S rRNA mutations associated with azithromycin resistance.
Surveillance for Neisseria gonorrhoeae azithromycin resistance is of growing importance given increasing use of ceftriaxone and azithromycin dual therapy for gonorrhoea treatment. In this study, we developed two real-time PCR methods for direct detection of two key N. gonorrhoeae 23S rRNA mutations associated with azithromycin resistance. The real-time PCR assays, 2611-PCR and 2059-PCR, targeted the gonococcal 23S rRNA C2611T and A2059G mutations, respectively. A major design challenge was that gonococcal 23S rRNA sequences have high sequence homology with those of commensal Neisseria species. To limit the potential for cross-reaction, 'non-template' bases were utilized in primer sequences. The performance of the methods was initially assessed using a panel of gonococcal (n = 70) and non-gonococcal (n = 28) Neisseria species. Analytical specificity was further assessed by testing N. gonorrhoeae nucleic acid amplification test (NAAT)-negative clinical samples (n = 90), before being applied to N. gonorrhoeae NAAT-positive clinical samples (n = 306). Cross-reactions with commensal Neisseria strains remained evident for both assays; however, cycle threshold (Ct) values were significantly delayed, indicating reduced sensitivity for non-gonococcal species. For the N. gonorrhoeae NAAT-negative clinical samples, 7/21 pharyngeal samples provided evidence of cross-reaction (Ct values >40 cycles); however, the remaining urogenital and rectal swab samples were negative. In total, the gonococcal 2611 and 2059 23S rRNA nucleotides were both successfully characterized in 266/306 (87%) of the N. gonorrhoeae NAAT-positive clinical specimens. Real-time PCR detection of gonococcal 23S rRNA mutations directly from clinical samples is feasible and may enhance culture- and non-culture-based N. gonorrhoeae resistance surveillance.


Exploring the expectations, needs and experiences of general practitioners and nurses towards a proactive and structured care programme for frail older patients: a mixed-methods study.
To report the expectations and experiences of general practitioners and practice nurses regarding the U-CARE programme, to gain a better understanding of the barriers and facilitators in providing proactive, structured care to frail older people and to determine whether implementation is feasible. Care for older patients with complex care needs in primary care is fragmented, reactive and time consuming. A structured, proactive care programme was developed to improve physical functioning and quality of life in frail older patients. An explanatory mixed-methods study nested in a cluster-randomized trial. The barriers to and needs for the provision of structured, proactive care, and expectations regarding the U-CARE programme were assessed with pre-questionnaires sent to all participating general practitioners (n = 32) and practice nurses (n = 21) in October 2010. Postquestionnaires measured experiences with the programme after 5 months. Twelve months later, focus group meetings were conducted. Practice nurses and general practitioners reported that it was difficult to provide proactive and structured care to older patients with multi-morbidity, different cultural backgrounds and low socioeconomic status. Barriers were a lack of time and financial compensation. Most general practitioners and practice nurses indicated that the programme added value for the coordination of care and allowed them to provide structured care. This explanatory mixed-methods study showed that general practitioners and practice nurses perceived the U-CARE programme as feasible in general practice. A transition was made from reactive, ad hoc care towards a proactive and preventive care approach.


Predicting the impact of feed spacer modification on biofouling by hydraulic characterization and biofouling studies in membrane fouling simulators.
Feed spacers are an essential part of spiral-wound reverse osmosis (RO) and nanofiltration (NF) membrane modules. Geometric modification of feed spacers is a potential option to reduce the impact of biofouling on the performance of membrane systems. The objective of this study was to evaluate the biofouling potential of two commercially available reference feed spacers and four modified feed spacers. The spacers were compared on hydraulic characterization and in biofouling studies with membrane fouling simulators (MFSs). The virgin feed spacer was characterized hydraulically by their resistance, measured in terms of feed channel pressure drop, performed by operating MFSs at varying feed water flow rates. Short-term (9 days) biofouling studies were carried out with nutrient dosage to the MFS feed water to accelerate the biofouling rate. Long-term (96 days) biofouling studies were done without nutrient dosage to the MFS feed water. Feed channel pressure drop was monitored and accumulation of active biomass was quantified by adenosine tri phosphate (ATP) determination. The six feed spacers were ranked on pressure drop (hydraulic characterization) and on biofouling impact (biofouling studies). Significantly different trends in hydraulic resistance and biofouling impact for the six feed spacers were observed. The same ranking for biofouling impact on the feed spacers was found for the (i) short-term biofouling study with nutrient dosage and the (ii) long-term biofouling study without nutrient dosage. The ranking for hydraulic resistance for six virgin feed spacers differed significantly from the ranking of the biofouling impact, indicating that hydraulic resistance of clean feed spacers does not predict the hydraulic resistance of biofouled feed spacers. Better geometric design of feed spacers can be a suitable approach to minimize impact of biofouling in spiral wound membrane systems.


Reporting guidelines in health research: A review.
Contemporary health research has come under close scrutiny, exposing alarming flaws in the reporting of research. The reporting guidelines can aid in identification of poorly reported studies and can bring transparency to health research. The guidelines also help journal editors, peer reviewers, funding agencies, and readers to better discern health research. Reporting guidelines encourage accurate and thorough reporting of fundamental aspects of health research so that the results of studies can be replicated by others. Reporting guidelines are potent tools to improve the practice of research and in reducing reporting bias. For the present review, both electronic and manual literature search was carried out. Electronic databases like PubMed, MEDLINE, EBSCO host, and Science Direct were searched for extracting relevant articles. Various key words and their combinations were used for literature search like reporting guidelines, checklist, research, publishing standards, study design, medicine, and dentistry. The search results were scrutinized for relevance to the topic and only full text articles in English were incorporated. Various reporting guidelines were identified and grouped under headings based on study design. This review article attempts to highlight the various reporting guidelines in literature relating to health research, its potential applications, and its limitations.


The relationship of female physical attractiveness to body fatness.
Aspects of the female body may be attractive because they signal evolutionary fitness. Greater body fatness might reflect greater potential to survive famines, but individuals carrying larger fat stores may have poor health and lower fertility in non-famine conditions. A mathematical statistical model using epidemiological data linking fatness to fitness traits, predicted a peaked relationship between fatness and attractiveness (maximum at body mass index (BMI) = 22.8 to 24.8 depending on ethnicity and assumptions). Participants from three Caucasian populations (Austria, Lithuania and the UK), three Asian populations (China, Iran and Mauritius) and four African populations (Kenya, Morocco, Nigeria and Senegal) rated attractiveness of a series of female images varying in fatness (BMI) and waist to hip ratio (WHR). There was an inverse linear relationship between physical attractiveness and body fatness or BMI in all populations. Lower body fat was more attractive, down to at least BMI = 19. There was no peak in the relationship over the range we studied in any population. WHR was a significant independent but less important factor, which was more important (greater r (2)) in African populations. Predictions based on the fitness model were not supported. Raters appeared to use body fat percentage (BF%) and BMI as markers of age. The covariance of BF% and BMI with age indicates that the role of body fatness alone, as a marker of attractiveness, has been overestimated.


[The Medical Carreer and the Key Factors Driving the Exodus of Doctors from the National Health Service in Portugal].
This article addresses the organization and management of medical careers in Portugal within the framework of the National Health Service. It focuses, in particular, on some indicators of motivation and professional satisfaction. This article is part of a broader research project on the organization of medical careers in Portugal. It draws on the results of a survey carried out to active medical doctors, residents and those that have already abandoned the National Health Service. The sample was drawn from the database of physicians enrolled in the Northern Section of the Medical Association. A total of 3253 physicians were surveyed. Physician satisfaction levels vary according to age, type of connection to the National Health Service and are associated with expectations regarding the professional future. Despite the close connection with the National Health Service, younger doctors showed higher levels of professional dissatisfaction and uncertainty regarding their professional future. Although with varying degrees of discontent depending on the groups considered, the dissatisfaction of the professionals interviewed is with the physical conditions of the workplace and with the opportunities for career advancement. At the level of interpersonal relations and training, satisfaction is high. The anticipation of retirement and the transfer to the private sector are options that professionals consider as a strategy to respond to professional dissatisfaction. The study shows that the current functioning of the National Health Service does not diminish the interest in the practice of medicine, but rather motivates the search for more attractive and rewarding working conditions.


Unidirectional P-body transport during the yeast cell cycle.
P-bodies belong to a large family of RNA granules that are associated with post-transcriptional gene regulation, conserved from yeast to mammals, and influence biological processes ranging from germ cell development to neuronal plasticity. RNA granules can also transport RNAs to specific locations. Germ granules transport maternal RNAs to the embryo, and neuronal granules transport RNAs long distances to the synaptic dendrites. Here we combine microfluidic-based fluorescent microscopy of single cells and automated image analysis to follow p-body dynamics during cell division in yeast. Our results demonstrate that these highly dynamic granules undergo a unidirectional transport from the mother to the daughter cell during mitosis as well as a constrained "hovering" near the bud site half an hour before the bud is observable. Both behaviors are dependent on the Myo4p/She2p RNA transport machinery. Furthermore, single cell analysis of cell size suggests that PBs play an important role in daughter cell growth under nutrient limiting conditions.


Adipose tissue fatty acid metabolism during pregnancy in swine.
In vitro adipose tissue fatty acid pool size (POOL), fatty acid release (FAR) and esterification (EST) were measured in peritoneal (PFP) and subcutaneous mammary (MFP) fat pads of swine at d 15, 30, 45, 60, 75, 90, 105 and 112 of pregnancy. Plasma free fatty acids (FFA) and triglycerides (TG) were not altered by stage of pregnancy. Basal EST in PFP was generally constant across pregnancy with a peak at d 75. Basal EST in MFP was elevated at d 30, 75 and 112. Esterification in response to norepinephrine stimulus (NE) was lower than basal rates in both fat depots. Basal FAR was constant throughout pregnancy in PFP, but elevated at d 75 and 90 in MFP. Fatty acid release in response to NE was biphasic with peaks at d 30 and in late pregnancy (in MFP, micromolar FAR in response to NE was 69.3% greater on d 75 to 112 than on d 45 to 60). Basal POOL was constant throughout pregnancy in both depots and lower than NE-stimulated POOL. All responses to NE were greater in MFP than in PFP, indicating that adipose tissue surrounding the developing mammary gland had higher metabolic activity and a greater response to NE than peritoneal adipose. Changes in fatty acid metabolism during pregnancy in swine are temporally related to published values for plasma steroids, fetal growth and mammary development. Metabolic adaptations in adipose and mannary epithelial tissue occur in synchrony with changing plasma estrogen concentrations, redirecting energy flow from maternal adipose tissue toward developing mammary and fetal tissue.