Increased Functional Brain Network Efficiency During Audiovisual Temporal Asynchrony Integration Task in Aging.
Audiovisual integration significantly changes over the lifespan, but age-related functional connectivity in audiovisual temporal asynchrony integration tasks remains underexplored. In the present study, electroencephalograms (EEGs) of 27 young adults (22-25 years) and 25 old adults (61-76 years) were recorded during an audiovisual temporal asynchrony integration task with seven conditions [auditory (A), visual (V), AV, A50V, A100V, V50A and V100A]. We calculated the phase lag index (PLI)-weighted connectivity networks modulated by the audiovisual tasks and found that the PLI connections showed obvious dynamic changes after stimulus onset. In the theta (4-7 Hz) and alpha (8-13 Hz) bands, the AV and V50A conditions induced stronger functional connections and higher global and local efficiencies, reflecting a stronger audiovisual integration effect, which was attributed to the auditory information arriving at the primary auditory cortex earlier than the visual information reaching the primary visual cortex. Importantly, the functional connectivity and network efficiencies of old adults revealed higher global and local efficiencies and higher degree in both the theta and alpha bands. These larger network efficiencies indicated that old adults might experience more difficulties in attention and cognitive control during the audiovisual integration task with temporal asynchrony than young adults. There were significant associations between network efficiencies and peak time of integration only in young adults. We propose that an audiovisual task with multiple conditions might arouse the appropriate attention in young adults but would lead to a ceiling effect in old adults. Our findings provide new insights into the network topography of old adults during audiovisual integration and highlight higher functional connectivity and network efficiencies due to greater cognitive demand.


Early pregnancy maternal progesterone administration alters pituitary and testis function and steroid profile in male fetuses.
Maternal exposure to increased steroid hormones, including estrogens, androgens or glucocorticoids during pregnancy results in chronic conditions in offspring that manifest in adulthood. Little is known about effects of progesterone administration in early pregnancy on fetal development. We hypothesised that maternal early pregnancy progesterone supplementation would increase fetal progesterone, affect progesterone target tissues in the developing fetal reproductive system and be metabolised to other bioactive steroids in the fetus. We investigated the effects of progesterone treatment during early pregnancy on maternal and fetal plasma progesterone concentrations, transcript abundance in the fetal pituitary and testes and circulating steroids, at day 75 gestation, using a clinically realistic ovine model. Endogenous progesterone concentrations were lower in male than female fetuses. Maternal progesterone administration increased male, but not female, fetal progesterone concentrations, also increasing circulating 11-dehydrocorticosterone in male fetuses. Maternal progesterone administration altered fetal pituitary and testicular function in ovine male fetuses. This suggests that there may be fetal sex specific effects of the use of progesterone in early pregnancy, and highlights that progesterone supplementation should be used only when there is clear evidence of efficacy and for as limited time as necessary.


Projections of temperature-related excess mortality under climate change scenarios.
Climate change can directly affect human health by varying exposure to non-optimal outdoor temperature. However, evidence on this direct impact at a global scale is limited, mainly due to issues in modelling and projecting complex and highly heterogeneous epidemiological relationships across different populations and climates. We collected observed daily time series of mean temperature and mortality counts for all causes or non-external causes only, in periods ranging from Jan 1, 1984, to Dec 31, 2015, from various locations across the globe through the Multi-Country Multi-City Collaborative Research Network. We estimated temperature-mortality relationships through a two-stage time series design. We generated current and future daily mean temperature series under four scenarios of climate change, determined by varying trajectories of greenhouse gas emissions, using five general circulation models. We projected excess mortality for cold and heat and their net change in 1990-2099 under each scenario of climate change, assuming no adaptation or population changes. Our dataset comprised 451 locations in 23 countries across nine regions of the world, including 85 879 895 deaths. Results indicate, on average, a net increase in temperature-related excess mortality under high-emission scenarios, although with important geographical differences. In temperate areas such as northern Europe, east Asia, and Australia, the less intense warming and large decrease in cold-related excess would induce a null or marginally negative net effect, with the net change in 2090-99 compared with 2010-19 ranging from -1·2% (empirical 95% CI -3·6 to 1·4) in Australia to -0·1% (-2·1 to 1·6) in east Asia under the highest emission scenario, although the decreasing trends would reverse during the course of the century. Conversely, warmer regions, such as the central and southern parts of America or Europe, and especially southeast Asia, would experience a sharp surge in heat-related impacts and extremely large net increases, with the net change at the end of the century ranging from 3·0% (-3·0 to 9·3) in Central America to 12·7% (-4·7 to 28·1) in southeast Asia under the highest emission scenario. Most of the health effects directly due to temperature increase could be avoided under scenarios involving mitigation strategies to limit emissions and further warming of the planet. This study shows the negative health impacts of climate change that, under high-emission scenarios, would disproportionately affect warmer and poorer regions of the world. Comparison with lower emission scenarios emphasises the importance of mitigation policies for limiting global warming and reducing the associated health risks. UK Medical Research Council.


Topologies for optical interconnection networks based on the optical transpose interconnection system.
Many results exist in the literature describing technological and theoretical advances in optical network topologies and design. However, an essential effort has yet to be made in linking those results together. We propose a step in this direction by giving optical layouts for several graph-theoretical topologies studied in the literature, using the optical transpose interconnection system (OTIS) architecture. These topologies include the family of partitioned optical passive star (POPS) and stack-Kautz networks as well as a generalization of the Kautz and the de Bruijn digraphs.


Role of Flagella in Adhesion of Escherichia coli to Abiotic Surfaces.
Understanding the interfacial activity of bacteria is of critical importance due to the huge economic and public health implications associated with surface fouling and biofilm formation. The complexity of the process and difficulties of predicting microbial adhesion to novel materials demand study of the properties of specific bacterial surface features and their potential contribution to surface attachment. Here, we examine flagella, cell appendages primarily studied for their cell motility function, to elucidate their potential role in the surface adhesion of Escherichia coli-a model organism and potential pathogen. We use self-assembled monolayers (SAMs) of thiol-bearing molecules on gold films to generate surfaces of varying hydrophobicity, and measure adhesion of purified flagella using quartz crystal microbalance. We show that flagella adhere more extensively and bind more tightly to hydrophobic SAMs than to hydrophilic ones, and we propose a two-step vs a single-step adhesion mechanism that accounts for the observed dissipation and frequency changes for the two types of surfaces, respectively. Subsequently, study of the adhesion of wild-type and flagella knockout cells confirms that flagella improve adhesion to hydrophobic substrates, whereas cells lacking flagella do not show preferred affinity to hydrophobic substrates. Together, these properties bring about an interesting ability of cells with flagella to stabilize emulsions of aqueous culture and dodecane, not observed for cells lacking flagella. This work contributes to our overall understanding of nonspecific bacterial adhesion and confirms that flagella, beyond motility, may play an important role in surface adhesion.


Improvement of Fermentation and Nutritive Quality of Straw-grass Silage by Inclusion of Wet Hulless-barley Distillers' Grains in Tibet.
In order to develop methods that would enlarge the feed resources in Tibet, mixtures of hulless-barley straw and tall fescue were ensiled with four levels (0, 10%, 20%, and 30% of fresh weight) of wet hulless-barley distillers' grains (WHDG). The silos were opened after 7, 14 or 30 d of ensiling, and the fermentation characteristics and nutritive quality of the silages were analyzed. WHDG addition significantly improved fermentation quality, as indicated by the faster decline of pH, rapid accumulation of lactic acid (LA) (p<0.05), and lower butyric acid content and ammonia-N/total N (p<0.05) as compared with the control. These results indicated that WHDG additions not only effectively inhibited the activity of aerobic bacteria, but also resulted in faster and greatly enhanced LA production and pH value decline, which restricted activity of undesirable bacteria, resulting in more residual water soluble carbohydrates (WSC) in the silages. The protein content of WHDG-containing silages were significantly higher (p<0.05) higher than that of the control. In conclusion, the addition of WHDG increased the fermentation and nutritive quality of straw-grass silage, and this effect was more marked when the inclusion rate of WHDG was greater than 20%.


Clinical features associated with linezolid resistance among multidrug resistant tuberculosis patients at a tertiary care hospital in Mumbai, India.
Multidrug-resistant tuberculosis (MDR-TB) is an increasing problem worldwide, and 24% occurs in India. Linezolid is associated with improved MDR-TB treatment outcomes but causes significant side-effects and drug susceptibility testing (DST) is rarely available. This study assessed whether clinical factors could predict linezolid resistance. An observational cohort of adults and adolescents with MDR-TB at a tertiary care hospital in Mumbai, India was analyzed for clinical, laboratory, and radiographic findings associated with linezolid resistance. In total, 343 MDR-TB patients had linezolid DST performed, and 23 (6.7%) had linezolid-resistant MDR-TB. Univariable analysis associated linezolid resistance with underweight (odds ratio (OR)-1.07, 95% confidence interval (CI):1.01-1.12); number of previous providers (OR:1.03, 95% CI:1.00-1.05); previous treatment with linezolid (OR:1.12, 95% CI:1.06-1.05), bedaquiline (OR:1.55, 95% CI:1.22-1.98), or clofazimine (OR:1.08 95% CI:1.03-1.16); cavitary disease (OR:1.10, 95% CI:1.04-1.16) and percent lung involvement (OR:1.02, 95% CI:1.01-1.03) on radiograph. DST associated linezolid resistance with resistance to fluoroquinolones (OR:1.08, 95% CI:1.01-1.14), injectables (OR:1.09, 95% CI:1.03-1.15), ethionamide (OR:1.09, 95% CI:1.03-1.15), and PAS (OR:1.13, 95% CI:1.06-1.21). In multivariate analysis, only prior linezolid and percent lung involvement were associated with linezolid resistance. To maximize treatment benefits while minimizing toxicity, DST remains an important tool to identify linezolid resistance.


Brefeldin A inhibits the formation of constitutive secretory vesicles and immature secretory granules from the trans-Golgi network.
The effects of brefeldin A (BFA) on membrane traffic between the trans-Golgi network (TGN) and the plasma membrane were investigated in intact PC12 cells and in a cell-free system derived from PC12 cells. In intact cells, BFA caused a virtually complete block of constitutive secretion, as indicated by the lack of release from, and accumulation in, the cells of a [35S]sulfate-labeled heparan sulfate proteoglycan (hsPG). Pulse-chase experiments with [35S]sulfate followed by subcellular fractionation showed that this block was due to the inhibition of formation of constitutive secretory vesicles (CSVs) from the TGN. BFA did not block the depolarization-induced release of [35S]sulfate-labeled chromogranin B (CgB) and secretogranin II (SgII) from secretory granules formed prior to the addition of the drug, showing that BFA does not block secretory granule fusion with the plasma membrane. The presence of BFA did, however, prevent the appearance of [35S]sulfate-labeled CgB and SgII in secretory granules, indicating that the drug inhibits the formation of secretory granules from the TGN. Evidence for a direct block of vesicle formation by BFA was obtained using a cell-free system derived from [35S]sulfate-labeled PC12 cells. In this system, low concentrations of BFA (5 micrograms/ml) inhibited the formation of the hsPG-containing CSVs and that of the SgII-containing secretory granules from the TGN to the same extent (50-60%) as, and in a non-additive manner with, the nonhydrolyzable GTP analogue GTP gamma S. Consistent with the inhibitory effects of BFA on vesicle formation from the TGN, BFA treatment of intact PC12 cells led to the hypersialylation of CgB, which presumably was due to the increased residence time of the protein in the TGN. In conclusion, our data are consistent with, and allow the generalization of, the concept that the BFA-induced block of anterograde membrane traffic results from the inhibition of vesicle formation from a donor compartment.


DARK Classics in Chemical Neuroscience: Ibogaine.
The West African iboga plant has been used for centuries by the Bwiti and Mbiri tribes to induce hallucinations during religious ceremonies. Ibogaine, the principal alkaloid responsible for iboga's psychedelic properties, was isolated and sold as an antidepressant in France for decades before its adverse effects precipitated its removal from the market. An ibogaine resurgence in the 1960s was driven by U.S. heroin addicts who claimed that ibogaine cured their opiate addictions. Behavioral pharmacologic studies in animal models provided evidence that ibogaine could blunt self-administration of not only opiates but cocaine, amphetamines, and nicotine. Ibogaine displays moderate-to-weak affinities for a wide spectrum of receptor and transporter proteins; recent work suggests that its actions at nicotinic acetylcholine receptor subtypes may underlie its reputed antiopiate effects. At micromolar levels, ibogaine is neurotoxic and cardiotoxic and has been linked to several deaths by cardiac arrest. Structure-activity studies led to the isolation of the ibogaine analog 18-methoxycoronaridine (18-MC), an α3β4 nicotinic receptor modulator that retains ibogaine's anticraving properties with few or no adverse effects. Clinical trials of 18-MC treatment of nicotine addiction are pending. Ibogaine analogs may also hold promise for treating anxiety and depression via the "psychedelic-assisted therapy" approach that employs hallucinogens including psilocybin and methylenedioxymethamphetamine ("ecstasy").


BRAFO tiered approach for Benefit-Risk Assessment of Foods.
BRAFO stands for Benefit-Risk Analysis for Foods. This European Commission funded project aims at developing a framework that allows quantitative comparison of human health risks and benefits of foods and food compounds based on a common scale of measurement. A methodology group brought together methodologies from several disciplines relevant to the evaluation of risks and benefits in food. This group reviewed and assembled the methodologies available. They produced this guidance document that describes a tiered ('stepwise') approach for performing a risk and benefit assessment of foods. This process starts with pre-assessment and problem formulation to set the scope of the assessment. This includes defining two scenarios, the reference and an alternative that are compared in the assessment. The approach consists of four tiers. In many cases, a lower tier assessment in which risks and benefits are qualitatively evaluated may be sufficient to show a clear difference between the health impacts of the two scenarios. In other cases, increasingly sophisticated methods to integrate risks and benefits quantitatively are used at higher tiers to assess the net health impact.


A comparison of the Charlson comorbidity index derived from medical records and claims data from patients undergoing lung cancer surgery in Korea: a population-based investigation.
Calculating the Charlson comorbidity index (CCI) from medical records is a time-consuming and expensive process. The objectives of this study are to 1) measure agreement between medical record and claims data for CCI in lung cancer patients and 2) predict health outcomes of lung cancer patients based on CCIs from both data sources. We studied 392 patients who underwent surgery for pathologic stages I-III of lung cancer. The kappa value was used to measure the agreement between the 17 comorbidities of the CCI prevalence obtained from medical records and claims data. Multiple linear regression analyses were used to evaluate the relationships between CCI and length of stay and reimbursement cost. Out of 17 comorbidities identified in the Charlson comorbidity index, ten had a higher prevalence, four had a lower prevalence and three had a similar prevalence in claims data to those of medical records. The kappa values calculated from the two databases ranged from 0.093 to 0.473 for nine comorbidities. In predicting length of stay and reimbursement cost after surgical resection for lung cancer patients, the CCI scores derived from both the medical records and claims data were not statistically significant. Poor agreement between medical record data and claims data may result from different motivations for collecting data. Further studies are needed to determine an appropriate method for predicting health outcomes based on these data sources.


"Part of our world": Influences on caregiver decisions about communication choices for children with hearing loss.
Caregivers of young children with hearing loss make decisions about which communication mode/s and spoken language/s their children and family will use. Influences on decision-making about communication were examined for 177 caregivers of Australian children with hearing loss through a questionnaire. The majority of the 157 children used speech as part or all of their communication system (n = 138, 87.9%), and approximately one-third of the children (n = 52, 33.1%) currently or had previously used sign as part or all of their communication system. Twenty-two (14.0%) children and 35 (19.8%) caregivers used a spoken language other than English. Four themes emerged from the qualitative analysis of caregiver responses about the most important influences on their decision-making. Theme one identified caregivers' sources of information, including advice from professionals, family, and friends, as well as caregivers' own research and preferences. Theme two related to practicalities of communication within the family and the community, as well as the need for one language or communication mode to be acquired before another was introduced. Theme three described the influence of children's individual characteristics on caregivers' decision-making, including children's ability to access speech through audition, communication skills, additional disabilities, and children's own preferences about communication. Finally, in theme four caregivers expressed their hopes for their children's future lives, specifically fostering a sense of belonging, creating future opportunities and successes, and giving children the opportunity to choose their own method of communication. The findings can assist families and professionals to make informed decisions about children's communication.


Effects of Two Weekly Servings of Cod for 16 Weeks in Pregnancy on Maternal Iodine Status and Infant Neurodevelopment: Mommy's Food, a Randomized-Controlled Trial.
Background: Mild-to-moderate iodine deficiency is still present in many countries, particularly in pregnant women. Observational studies suggest that mild-to-moderate iodine deficiency during pregnancy may be associated with impaired thyroid function and child neurodevelopment. Randomized-controlled food trials to increase iodine status are scarce. We assessed the impact of an increased intake of cod during pregnancy on maternal iodine status and infant neurodevelopment. Methods: In this randomized-controlled trial, pregnant women in Bergen, Norway, recruited through Haukeland University Hospital, were randomly assigned (1:1) to an intervention of 200 g of cod twice a week for 16 weeks (gestational week 20-36) or to continue with their standard diet (control group). Randomization was done by lottery. Primary outcome was urinary iodine concentration (UIC) (spot samples from six consecutive days) measured postintervention. Secondary outcome was infant neurodevelopment assessed by the cognitive, language, and motor scales of the Bayley Scales of Infant and Toddler Developmental third edition (Bayley-III) at 11 months of age. In addition, maternal thyroid function was measured (thyrotropin [TSH], free triiodothyronine [fT3], free thyroxine [fT4]) at baseline and postintervention. Results: Between January 2016 until February 2017, 137 women were recruited. Postintervention UIC was higher in the intervention group (n = 61) [median (interquartile range, IQR) 98 (64-145) μg/L], compared with control (n = 61) [median (IQR) 73 (52-120) μg/L] (p = 0.028), also after adjusting for baseline UIC (p = 0.048). Infants of mothers in the intervention group had a lower cognitive composite score on the Bayley-III compared with the control group (p = 0.045). There were no group differences in the Bayley III language- or motor composite scores. Maternal thyroid hormones (TSH, fT3, fT4) did not differ between the groups postintervention. Conclusions: Increased cod intake during pregnancy improved the iodine status in women with mild-to-moderate iodine deficiency, however, did not affect thyroid function. The negative effect on cognition should be followed up to assess whether this is a stable effect over time. More studies are warranted to enable good health advice on iodine nutrition in pregnancy. ClinicalTrials.gov NCT02610959. Registered November 20, 2015.


Molecular diversity of visual pigments in Stomatopoda (Crustacea).
Stomatopod crustaceans possess apposition compound eyes that contain more photoreceptor types than any other animal described. While the anatomy and physiology of this complexity have been studied for more than two decades, few studies have investigated the molecular aspects underlying the stomatopod visual complexity. Based on previous studies of the structure and function of the different types of photoreceptors, stomatopod retinas are hypothesized to contain up to 16 different visual pigments, with 6 of these having sensitivity to middle or long wavelengths of light. We investigated stomatopod middle- and long-wavelength-sensitive opsin genes from five species with the hypothesis that each species investigated would express up to six different opsin genes. In order to understand the evolution of this class of stomatopod opsins, we examined the complement of expressed transcripts in the retinas of species representing a broad taxonomic range (four families and three superfamilies). A total of 54 unique retinal opsins were isolated, resulting in 6-15 different expressed transcripts in each species. Phylogenetically, these transcripts form six distinct clades, grouping with other crustacean opsins and sister to insect long-wavelength visual pigments. Within these stomatopod opsin groups, intra- and interspecific clusters of highly similar transcripts suggest that there has been rampant recent gene duplication. Some of the observed molecular diversity is also due to ancient gene duplication events within the stem crustacean lineage. Using evolutionary trace analysis, 10 amino acid sites were identified as functionally divergent among the six stomatopod opsin clades. These sites form tight clusters in two regions of the opsin protein known to be functionally important: six in the chromophore-binding pocket and four at the cytoplasmic surface in loops II and III. These two clusters of sites indicate that stomatopod opsins have diverged with respect to both spectral tuning and signal transduction.


Myocardial salvage by reperfusion 12 hours after coronary ligation in dogs.
It is not clear why late reperfusion therapy in patients with acute myocardial infarction is effective. An investigation was carried out as to whether or not reperfusion conducted 12 h after coronary occlusion causes myocardial salvage in dogs. Coronary arteries were occluded in 11 mongrel dogs and a portion of the occlusion (late reperfusion area; LR area) reperfused 12 h later; the other part was left occluded (permanent occlusion area; PO area). The dogs were maintained for 4 weeks after reperfusion. Regional myocardial blood flow (Qm) was measured by the non-radioactive colored microsphere method. In both areas, the transmurality of necrosis was measured by triphenyl tetrazolium chloride staining, and the amount of viable myocardium and the extent of fibrosis was determined by Azan-Mallory staining. Qm decreased markedly after coronary occlusion to similar levels in both areas until 12 h. Qm transiently increased in the LR area only following reperfusion after 12 h. The transmurality of necrosis in the PO area was 83.8+/-10.5%, but that in the LR area was 58.7+/-21.3%, a significant decrease (p<0.01). In the outer layer, the amount of viable myocardium was significantly greater, and the extent of myocardial fibrosis was significantly less in the LR area. Evaluation in the same heart of dogs confirmed the myocardial salvage effects of late reperfusion (12 h after coronary occlusion).


Comparing CATCH, CHALICE and PECARN clinical decision rules for paediatric head injuries.
Many children present to emergency departments following head injury (HI), with a small number at risk of avoidable poor outcome. Difficulty identifying such children, coupled with increased availability of cranial CT, has led to variation in practice and increased CT rates. Clinical decision rules (CDRs) have been derived for paediatric HI but there is no published comparison to assist in deciding which to implement. The content of the three of highest quality and accuracy are described and compared. Systematic reviews of paediatric HI CDRs were published in 2009 and 2011. To identify CDRs published since the most recent review, key databases were searched, selecting studies which included CDRs involving children aged 0-18 years with a history of HI. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies Tool, and performance evaluated by reported accuracy. Three high quality CDRs were identified: CATCH (Canadian Assessment of Tomography for Childhood Head Injury) CHALICE (Children's Head Injury Algorithm for the Prediction of Important Clinical Events) and PECARN (Paediatric Emergency Care Applied Research Network). All were derived with high methodological standards but differed in key areas, including study population, outcomes and severity of HI. Each stated different predictor variables and only PECARN provided a separate algorithm for young children. CATCH and CHALICE identify children requiring CT and PECARN those who do not. All perform with high sensitivity and low specificity. PECARN is the only validated CDR, and none has undergone impact analysis. These three CDRs should undergo validation and comparison in a single population, with analysis of their impact on practice and financial implications, to aid relevant bodies in deciding which to implement.


A critical evaluation of the application of biomarkers in epidemiological studies on diet and health.
One of the problems which may beset epidemiological studies is the difficulty of accurately measuring the dietary intakes of participants. Biomarkers of diet promise to provide a more accurate measure of dietary intake and a more objective one in that they are not reliant on the subject's memory. This review considers some issues of importance in epidemiology when information is obtained from biomarkers. The approach taken is to use examples both of normal dietary constituents and of contaminants in relation to a range of diet and health questions to illustrate these points. A brief overview of the role of sample collection, processing and storage is given including some generic recommendations for maximising the reliability of subsequent analytical data. Using the examples of phytoestrogens and iodine the question of whether biomarkers can accurately reflect the intake of the dietary constituents of interest at the population level or at the individual level is considered. The relationship of the biomarker to the natural history of the disease is exemplified using the role of folate in neural tube defects. Finally, intakes of vitamin D and heterocyclic amines are used to illustrate the integration of biomarkers into epidemiological studies of prostate and colorectal cancer, respectively. It is concluded that biomarkers may provide a more accurate and objective measure of diet than estimates of current or usual intake but that this approach also has limitations. A combination of methods will probably prove to be most valuable and this approach is being taken in current large prospective studies.


Surfactant protein-A as an anti-inflammatory component in the amnion: implications for human pregnancy.
The mechanism of mouse parturition is thought to involve myometrial infiltration by amniotic fluid (AF) macrophages, activated by surfactant protein-A (SP-A). In humans, the concentration of AF SP-A decreases during labor, and no fetal macrophages are found in the myometrium after labor. Therefore, it appears that the mechanisms of labor in mice and humans are different. We investigated a potential role for SP-A in human pregnancy and parturition by examining SP-A expression patterns in AF and amnion. High molecular mass (>250 kDa) oligomeric SP-A was increased in AF with advancing gestation. Interestingly, these oligomers were more abundant in placental amnion before labor at term, while they increased primarily in reflected amnion during labor (p < 0.05). Immunoblotting showed a binding of high molecular mass SP-A in AF to amnion. In C57BL/6 mice, oligomeric SP-A was also readily detected in AF from E15 onwards, but not in amnion. Macrophage density in mice myometrium did not change with advancing gestational age. Microarray analysis of human amnion explants incubated with SP-A revealed a molecular signature of inhibited cytokine-cytokine receptor interaction with downregulation of IL-1beta, CXCL2, and CXCL5 mRNA expression. The findings in this study strongly suggest that SP-A signals amniotic anti-inflammatory response via AF during pregnancy. We propose that an SP-A interaction among AF, placental amnion, and reflected amnion is a unique mechanism for immunoregulation in human pregnancy akin to that established in lung biology. However, AF SP-A and fetal macrophages by themselves do not seem to be exclusive effectors of parturition in humans.


The death of bioethics (as we once knew it).
Fast forward 50 years into the future. A look back at what occurred in the field of bioethics since 2010 reveals that a conference in 2050 commemorated the death of bioethics. In a steady progression over the years, the field became increasingly fragmented and bureaucratized. Disagreement and dissension were rife, and this once flourishing, multidisciplinary field began to splinter in multiple ways. Prominent journals folded, one by one, and were replaced with specialized publications dealing with genethics, reproethics, nanoethics, and necroethics. Mainstream bioethics organizations also collapsed, giving way to new associations along disciplinary and sub-disciplinary lines. Physicians established their own journals, and specialty groups broke away from more general associations of medical ethics. Lawyers also split into three separate factions, and philosophers rejected all but the most rigorous, analytic articles into their newly established journal. Matters finally came to a head with global warming, the world-wide spread of malaria and dengue, and the cost of medical treatments out of reach for almost everyone. The result was the need to develop plans for strict rationing of medical care. At the same time, recognition emerged of the importance of the right to health and the need for global justice in health. By 2060, a spark of hope was ignited, opening the door to the resuscitation of bioethics and involvement of the global community.


The Effect of the Alternative Prey, Paramecium caudatum (Peniculida: Parameciidae), on the Predation of Culex pipiens (Diptera: Culicidae) by the Copepods Macrocyclops albidus and Megacyclops viridis (Cyclopoida: Cyclopidae).
Biological control can be an effective tool to combat public health risks associated with mosquito-borne disease. However, target impacts of biological control agents may be reduced by biotic contexts such as the presence of alternative prey. In turn, this can impede our ability to realistically assess biocontrol agent efficacy. Here, we examine the effects of alternative ciliate prey on the predation potential of two cyclopoid copepods, Macrocyclops albidus Jurine (Cyclopoida: Cyclopidae) and Megacyclops viridis Jurine (Cyclopoida: Cyclopidae), toward larvae of the West Nile virus vector mosquito Culex pipiens Linnaeus (Diptera: Culicidae). Using functional responses (FRs; resource use under different resource densities), we demonstrate that both copepods exhibit potentially destabilizing type II FRs toward mosquito prey. However, where the alternative prey was present, we observed species-specific modulations to FR form and magnitude. For M. albidus, FRs remained type II where ciliate prey were present, however, maximum feeding rates on mosquito larvae were reduced. Conversely, for M. viridis, FRs moved toward more stabilizing type III, while maximum feeding rates on mosquito larvae were not significantly reduced. While both species of cyclopoid copepod were able to effectively target and consume larval mosquitoes in the presence of alternative prey, we demonstrate that overall efficacies may be reduced in aquatic habitats which contain multiple prey types. We thus advocate that biotic contexts such as prey selectivity should be integrated into predatory biocontrol agent examinations for mosquitoes which vector pathogens and parasites, to more holistically assess their efficacy.


Skeletal adaptations to alterations in weight-bearing activity: a comparison of models of disuse osteoporosis.
The removal of regular weight-bearing activity generates a skeletal adaptive response in both humans and animals, resulting in a loss of bone mineral. Human models of disuse osteoporosis, namely bed rest, spinal cord injury and exposure to micro-gravity demonstrate the negative calcium balance, alterations in biochemical markers of bone turnover and resultant loss of bone mineral in the lower limbs that occurs with reduced weight-bearing loading. The site-specific nature of the bone response is consistent in all models of disuse; however, the magnitude of the skeletal adaptive response may differ across models. It is important to understand the various manifestations of disuse osteoporosis, particularly when extrapolating knowledge gained from research using one model and applying it to another. In rats, hindlimb unloading and exposure to micro-gravity also result in a significant bone response. Bone mineral is lost, and changes in calcium metabolism and biochemical markers of bone turnover similar to humans are noted. Restoration of bone mineral that has been lost because of a period of reduced weight bearing may be restored upon return to normal activity; however, the recovery may not be complete and/or may take longer than the time course of the original bone loss. Fluid shear stress and altered cytokine activity may be mechanistic features of disuse osteoporosis. Current literature for the most common human and animal models of disuse osteoporosis has been reviewed, and the bone responses across models compared.


Influence of coffee drinking on subsequent risk of hepatocellular carcinoma: a prospective study in Japan.
An association between coffee drinking and reduced risk of liver cancer has been suggested by animal studies, but epidemiologic evidence of such an association in a high-risk population is lacking. We conducted a large-scale population-based cohort study of the association between coffee drinking and hepatocellular carcinoma (HCC) in a Japanese population. Newly diagnosed case patients (250 men and 84 women) with HCC were identified from a 10-year follow-up of the Japan Public Health Center-based Prospective Study, which consists of 90,452 middle-aged and elderly Japanese subjects (43,109 men and 47,343 women). Case patients were grouped according to coffee intake and were stratified by hepatitis virus infection, sex, age, diet, lifestyle factors, and previous history of liver disease. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CIs) for HCC were calculated with Cox proportional-hazards modeling. All statistical tests were two-sided. Subjects (men and women combined) who consumed coffee on a daily or almost daily basis had a lower HCC risk than those who almost never drank coffee (HR = 0.49 [95% CI = 0.36 to 0.66]); risk decreased with the amount of coffee consumed (compared with nondrinkers, the HR for 1-2 cups per day = 0.52 [95% CI = 0.38 to 0.73]; for 3-4 cups per day = 0.48 [95% CI = 0.28 to 0.83]; for > or =5 cups per day = 0.24 [95% CI = 0.08 to 0.77], P(trend) < .001). The risk of liver cancer in almost never drinkers in this population was 547.2 cases per 100,000 people over 10 years, but it was 214.6 cases per 100 000 people with drinking coffee on a daily basis. The inverse association persisted when the participants were stratified by lifestyle factors. Similar associations were observed when the analysis was restricted to hepatitis C virus-positive patients (all daily drinkers compared with nondrinkers: HR =0.57 [95% CI = 0.37 to 0.86]), to hepatitis B virus-positive patients (HR = 0.60 [95% CI = 0.31 to 1.18]) and to subjects with no past history of chronic liver disease (HR = 0.45 [95% CI = 0.30 to 0.67]). In the Japanese population, habitual coffee drinking may be associated with reduced risk of HCC.


Imaging subcellular scattering contrast by using combined optical coherence and multiphoton microscopy.
The structural origin of scattering contrast from single cells is examined by using a combined optical coherence and multiphoton microscope based on a 12 fs Ti:sapphire source and a 0.95 NA objective. High-resolution coherence-gated scattering images from single cells are coregistered and compared with two-photon-excited fluorescence images. Scattering contrast is observed from mitochondria, plasma membrane, actin filaments, and the boundary between cytoplasm and nucleus. There is little contribution to scattering from regions inside the nuclear core. These results confirm that light scattering signals from specific subcellular structures can be visualized by using coherent reflectance geometry.


Cyclic ADP-ribose-induced Ca2+ release from rat brain microsomes.
Cyclic ADP-ribose (cADPR), an endogenous NAD+ metabolite in many mammalian and invertebrate tissues, is a potent mediator of calcium mobilization in sea urchin eggs. Our results show that cADPR also stimulates calcium release from rat brain microsomes, marked release occurring over the concentration range 10-250 nM. This is not inhibited by concentrations of heparin which completely abolish inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release. Ryanodine (100 microM) inhibits the cADPR response. Our results are consistent with cADPR being an endogenous messenger mediating Ca2+ release from ryanodine-sensitive pools in brain.


Prediction of protein functions with gene ontology and interspecies protein homology data.
Accurate computational prediction of protein functions increasingly relies on network-inspired models for the protein function transfer. This task can become challenging for proteins isolated in their own network or those with poor or uncharacterized neighborhoods. Here, we present a novel probabilistic chain-graph-based approach for predicting protein functions that builds on connecting networks of two (or more) different species by links of high interspecies sequence homology. In this way, proteins are able to "exchange" functional information with their neighbors-homologs from a different species. The knowledge of interspecies relationships, such as the sequence homology, can become crucial in cases of limited information from other sources of data, including the protein-protein interactions or cellular locations of proteins. We further enhance our model to account for the Gene Ontology dependencies by linking multiple but related functional ontology categories within and across multiple species. The resulting networks are of significantly higher complexity than most traditional protein network models. We comprehensively benchmark our method by applying it to two largest protein networks, the Yeast and the Fly. The joint Fly-Yeast network provides substantial improvements in precision, accuracy, and false positive rate over networks that consider either of the sources in isolation. At the same time, the new model retains the computational efficiency similar to that of the simpler networks.


Strong diversifying selection on domains of the Plasmodium falciparum apical membrane antigen 1 gene.
The surface-accessible ectodomain region of the Plasmodium falciparum apical membrane antigen 1 (AMA1) is a malaria vaccine candidate. The amino acid sequence may be under selection from naturally acquired immune responses, and previous analyses with a small number of allele sequences indicate a non-neutral pattern of nucleotide variation. To investigate whether there is selection to maintain polymorphism within a population, and to identify the parts of the ectodomain under strongest selection, a sample of 51 alleles from a single endemic population was studied. Analyses using Fu and Li's D and F tests, Tajima's D test, and the McDonald-Kreitman test (with the chimpanzee parasite P. reichenowi as outgroup) show significant departure from neutrality and indicate the selective maintenance of alleles within the population. There is also evidence of a very high recombination rate throughout the sequence, as estimated by the recombination parameter, C, and by the rapid decline in linkage disequilibrium with increasing nucleotide distance. Of the three domains (I-III) encoding structures determined by disulfide bonds, the evidence of selection is strongest for Domains I and III. We predict that these domains in particular are targets of naturally acquired protective immune responses in humans.


Type of clinical outcomes used by healthcare professionals to evaluate health-related quality of life domains to inform clinical decision making for chronic pain management.
To evaluate the health-related quality of life (HRQoL) domains currently assessed by healthcare professionals (HCPs) in secondary and tertiary hospital-based chronic pain clinics and the type of clinical outcomes (CO) used. Electronic cross-sectional survey (May to September 2016) based on domains of HRQoL included in the Patient-Reported Outcomes Measurement Information System (PROMIS) framework. HCPs response rate was 53% (36/68). Their mean clinical experience was 14.8 years (± 11.1), and their mean experience treating chronic pain (CP) population was 10.2 years (± 7.8). All PROMIS-HRQoL domains were assessed by HCPs (range 28-97%, mean = 64%) with a preponderance of domains related to physical health (mean = 82%). Standardized outcome measures (OMs) including performance outcomes and patient-reported outcomes (PROs) were not frequently used (mean 0.5% and 3%, respectively) for assessing HRQoL domains compared to clinician reported outcomes (patient interviews, patient observation) (mean = 87%). Forty different OMs for assessing HRQoL domains were reported, and 30% of OMs were used by more than one HCP. HCPs expressed a need (range from 2.3 to 26.3%) for using more than one type of CO for assessing most domains of HRQoL (range from 2.3 to 26.3%) with a preference of using more PROs combined with CROs. All domains of HRQoL are assessed by at least some HCPs for chronic pain management. Standardized OMs including performance-based measures and PROs were not frequently used, and there was no consistent use of the same OM across HCPs. A consensus among different stakeholders in chronic pain management on core domains of HRQoL and their associated OMs to promote a more evidence-based assessment is needed.


Interactions between a pollinating seed predator and its host plant: the role of environmental context within a population.
Plant-insect interactions often are important for plant reproduction, but the outcome of these interactions may vary with environmental context. Pollinating seed predators have positive and negative effects on host plant reproduction, and the interaction outcome is predicted to vary with density or abundance of the partners. We studied the interaction between Silene stellata, an herbaceous perennial, and Hadena ectypa, its specialized pollinating seed predator. Silene stellata is only facultatively dependent upon H. ectypa for pollination because other nocturnal moth co-pollinators are equally effective at pollen transfer. We hypothesized that for plants without conspecific neighbors, H. ectypa would have higher visitation rates compared to co-pollinators, and the plants would experience lower levels of H. ectypa pollen deposition. We predicted similar oviposition throughout the study site but greater H. ectypa predation in the area without conspecific neighbors compared to plants embedded in a naturally high density area. We found that H. ectypa had consistently higher visitation than moth co-pollinators in all host plant contexts. However, H. ectypa pollinator importance declined in areas with low conspecific density because of reduced pollen deposition, resulting in lower seed set. Conversely, oviposition was similar across the study site independent of host plant density. Greater likelihood of very high fruit predation combined with lower pollination by H. ectypa resulted in reduced S. stellata female reproductive success in areas with low conspecific density. Our results demonstrate local context dependency of the outcomes of pollinating seed predator interactions with conspecific host plant density within a population.


Molecular forceps from combinatorial libraries prevent the farnesylation of Ras by binding to its carboxyl terminus.
Ras is one of the major oncogenes. In order to function properly it has to undergo post-translational processing at its carboxyl terminus. It has been shown that inhibitors of farnesyl transferase, the first enzyme in the processing chain, can suppress the transforming activity of oncogenic Ras. We have identified molecular forceps, branched peptidic molecules, from combinatorial libraries that bind to the carboxyl terminus of Ras and interfere with its farnesylation without inhibiting the farnesyl transferase. The active molecules were selected by a screening against the carboxy-terminal octapeptide of Ras. The implications of our findings are twofold. First, we demonstrate that it is possible to prevent enzymatic transformations by blocking the enzyme's access to its substrate using a synthetic small molecule to mask the substrate. Second, we show that it is feasible to derive molecules from combinatorial libraries that bind a specific epitope on a protein by selecting these molecules with the isolated peptide epitope.


Modelling impact of early vigour on wheat yield in dryland regions.
Early vigour, or faster early leaf area development, has been considered an important trait for rainfed wheat in dryland regions such as Australia. However, early vigour is a genetically complex trait, and results from field experiments have been highly variable. Whether early vigour can lead to improved water use efficiency and crop yields is strongly dependent on climate and management conditions across the entire growing season. Here, we present a modelling framework for simulating the impact of early vigour on wheat growth and yield at eight sites representing the major climate types in Australia. On a typical soil with plant available water capacity (PAWC) of 147 mm, simulated yield increase with early vigour associated with larger seed size was on average 4% higher compared with normal vigour wheat. Early vigour through selection of doubled early leaf sizes could increase yield by 16%. Increase in yield was mainly from increase in biomass and grain number, and was reduced at sites with seasonal rainfall plus initial soil water <300 mm. Opportunities exists for development of early vigour wheat varieties for wetter sites. Soil PAWC could play a significant role in delivering the benefit of early vigour and would require particular attention.


[Bronchopulmonary diseases in workers engaged in carbonyl production of nickel in the Kola Arctic].
The paper gives data on the prevalence and pattern of chronic bronchopulmonary diseases (CBPD) in 188 workers engaged in carbonyl production of nickel versus 162 auxiliary process workers. Chronic bronchitis was the most common disease in both groups (11.2 and 5.6%, respectively). 9.6% of the carbonyl production workers were found to have toxic pneumofibrosis developing mainly in those having a service length of more than 20 years. As compared with auxiliary process workers, the nickel production process workers had a higher risk of CBPD (odds ratio 1.80; 95% confidence interval 1.00-3.22; p = 0.04496) who also came to the front in the pattern of occupational diseases (73.2% of all cases).


Association of the homeobox transcription factor, ENGRAILED 2, 3, with autism spectrum disorder.
Mouse mutants of the homeobox transcription factor Engrailed2 (En2) and autistic individuals display similar cerebellar morphological abnormalities, which include hypoplasia and a decrease in the number of Purkinje cells. Human EN2 maps to 7q36, a chromosomal region that has demonstrated suggestive linkage to autism spectrum disorder (ASD). To investigate EN2 for evidence of association with ASD, four single-nucleotide polymorphisms (SNPs) (rs3735653, rs1861972, rs1861973, rs2361689) that span the majority of the 8.0 kb gene were assessed by the transmission/disequilibrium test. Initially, 138 triads of autistic individuals and their parents were tested. Two intronic SNPs (rs1861972 and rs1861973) demonstrated significant association with autism (rs1861972, P=0.0018; rs1861973, P=0.0003; haplotype, P=0.000005). Flanking exonic SNPs (rs3735653 and rs2361689) did not display association. This analysis was then extended to include 167 small nuclear ASD pedigrees and significant association was again only observed for rs1861972 and rs1861973 under both the narrow and broad diagnostic criteria (narrow: rs1861972 P=0.0290, rs1861973 P=0.0073, haplotype P=0.0009; broad: rs1861972 P=0.0175, rs1861973 P=0.0107, haplotype P=0.0024). These data demonstrate association between a cerebellar patterning gene and ASD, suggesting a role for EN2 as a susceptibility locus and supporting a neurodevelopmental defect hypothesis in the etiology of autism.


EHD2 is a mechanotransducer connecting caveolae dynamics with gene transcription.
Caveolae are small invaginated pits that function as dynamic mechanosensors to buffer tension variations at the plasma membrane. Here we show that under mechanical stress, the EHD2 ATPase is rapidly released from caveolae, SUMOylated, and translocated to the nucleus, where it regulates the transcription of several genes including those coding for caveolae constituents. We also found that EHD2 is required to maintain the caveolae reservoir at the plasma membrane during the variations of membrane tension induced by mechanical stress. Metal-replica electron microscopy of breast cancer cells lacking EHD2 revealed a complete absence of caveolae and a lack of gene regulation under mechanical stress. Expressing EHD2 was sufficient to restore both functions in these cells. Our findings therefore define EHD2 as a central player in mechanotransduction connecting the disassembly of the caveolae reservoir with the regulation of gene transcription under mechanical stress.


Anthropometric study of alar cartilage in Asians.
Measurements of 52 alar cartilages in 26 Koreans were obtained for an anthropometric study during primary open-approach rhinoplasties. The lateral crura were found most commonly to be concave, exhibited in 40% of the male patients and in 50% of the female patients. The medial crura were most often straight, found in 56% of the male patients and in 46% of the female patients. The average length, width, and thickness of the lateral crura were 19.7 mm, 10.5 mm, and 0.55 mm, respectively, in men; and 16.8 mm, 9.8 mm, and 0.54 mm, respectively, in women. The lengths of the columellar and footplate segments of the medial crura were 10.0 mm and 7.8 mm in men, and were 8.0 mm and 6.3 mm in women. These data suggest that the alar cartilage in Asians, contrary to popular myth, is not markedly smaller than that of whites. However, differences were found in the configuration of the cartilage and the length of the footplate of the medial crus.


Impact of Type 1 Diabetes Technology on Family Members/Significant Others of People With Diabetes.
The aim was to explore the impact of diabetes-related technology to ensure that such devices are used in a way that returns maximum benefit from a medical and psychological perspective. Spouses and caregivers of people with type 1 diabetes were invited to complete an online questionnaire about their experiences with diabetes technologies used by their family members. Participants were recruited via the Glu online community website. Questions explored impact on daily living, frequency and severity of hypoglycemia, and diabetes-related distress. In all, 100 parents/caregivers and 74 partners participated in this survey. Average (mean) duration of living with a person with type 1 diabetes was 16 years (SD = 13) for partners, with duration of diabetes for children being 4.2 ± 3.2 years. Average duration of current therapy was 8.3 ± 7.3 years for adults and 3.4 ± 2.9 years for children. Of the participants, 86% partners and 82% parents/caregivers reported diabetes technology had made it easier for their family members to achieve blood glucose targets. Compared to partners, parents/caregivers reported more negative emotions (P < .001) and decreased well-being (P < .001) related to their family members type 1 diabetes. Diabetes-related distress was common, as was sleep disturbance associated with device alarms and fear of hypoglycemia. Reduced frequency and severity of hypoglycemia related to device use was reported by approximately half of participants. There is little doubt about the medical benefit of diabetes technologies and their uptake is increasing but some downsides were reported. Barriers to uptake of technologies lie beyond the mechanics of diabetes management. Supporting users in using diabetes technology to achieve the best possible glycemic control, in the context of their own life, is crucial. Furthermore, understanding these issues with input from the type 1 diabetes community including family members and caregivers will help innovation and design of new technology.


Interactions of arene ruthenium metallaprisms with human proteins.
Interactions between three hexacationic arene ruthenium metallaprisms, [(p-cymene)6Ru6(tpt)2(dhnq)3](6+), [(p-cymene)6Ru6(tpt)2(dhbq)3](6+) and [(p-cymene)6Ru6(tpt)2(oxa)3](6+), and a series of human proteins including human serum albumin, transferrin, cytochrome c, myoglobin and ubiquitin have been studied using NMR spectroscopy, mass spectrometry and circular dichroism spectroscopy. All data suggest that no covalent adducts are formed between the proteins and the metallaprisms. Indeed, in most cases electrostatic interactions, leading to precipitation of protein-metallaprism aggregates, have been observed. In addition, with the smallest proteins, ubiquitin, myoglobin and cytochrome c, the presence of the hexacationic arene ruthenium metallaprisms induces structural changes of the proteins, as emphasized by circular dichroism. The results suggest that proteins are certainly a biological target for these metalla-assemblies.


Physical activity in the United States measured by accelerometer.
To describe physical activity levels of children (6-11 yr), adolescents (12-19 yr), and adults (20+ yr), using objective data obtained with accelerometers from a representative sample of the U.S. population. These results were obtained from the 2003-2004 National Health and Nutritional Examination Survey (NHANES), a cross-sectional study of a complex, multistage probability sample of the civilian, noninstitutionalized U.S. population in the United States. Data are described from 6329 participants who provided at least 1 d of accelerometer data and from 4867 participants who provided four or more days of accelerometer data. Males are more physically active than females. Physical activity declines dramatically across age groups between childhood and adolescence and continues to decline with age. For example, 42% of children ages 6-11 yr obtain the recommended 60 min x d(-1) of physical activity, whereas only 8% of adolescents achieve this goal. Among adults, adherence to the recommendation to obtain 30 min x d(-1) of physical activity is less than 5%. Objective and subjective measures of physical activity give qualitatively similar results regarding gender and age patterns of activity. However, adherence to physical activity recommendations according to accelerometer-measured activity is substantially lower than according to self-report. Great care must be taken when interpreting self-reported physical activity in clinical practice, public health program design and evaluation, and epidemiological research.


Quantum fluctuations and isotope effects in ab initio descriptions of water.
Isotope substitution is extensively used to investigate the microscopic behavior of hydrogen bonded systems such as liquid water. The changes in structure and stability of these systems upon isotope substitution arise entirely from the quantum mechanical nature of the nuclei. Here, we provide a fully ab initio determination of the isotope exchange free energy and fractionation ratio of hydrogen and deuterium in water treating exactly nuclear quantum effects and explicitly modeling the quantum nature of the electrons. This allows us to assess how quantum effects in water manifest as isotope effects, and unravel how the interplay between electronic exchange and correlation and nuclear quantum fluctuations determine the structure of the hydrogen bond in water.


Persistent and recurrent neovascularization after krypton laser photocoagulation for neovascular lesions of age-related macular degeneration. Macular Photocoagulation Study Group.
The persistence and recurrence of choroidal neovascularization after initial treatment with laser photocoagulation have been shown to be major contributors to loss of visual acuity. The 247 eyes assigned to krypton red laser photocoagulation in the Age-Related Macular Degeneration Study-Krypton Laser were examined to describe the incidence, timing, visual impact, and potential risk factors for persistence and recurrence. Persistent neovascularization detected within 6 weeks of initial treatment was observed in 32% of treated eyes, and recurrent neovascularization was estimated by life-table methods to develop in an additional 47% over a 5-year period. Both persistence and recurrence were accompanied by an increased frequency of severe visual loss. The persistence rate among eyes having 10% or more of the foveal side of the neovascular membrane not covered by treatment was twice as high as in eyes having more extensive coverage. Patients having a fellow eye with a neovascular membrane or scar, a fellow eye with 20 or more drusen in the central macula, or a fellow eye with nongeographic atrophy at initial visit had more recurrences than patients without these characteristics. Ophthalmologists treating similar lesions may be able to reduce persistent neovascularization and the associated visual loss by covering the entire lesion with treatment.


Lipid residues in pottery from the Indus Civilisation in northwest India.
This paper presents novel insights into the archaeology of food in ancient South Asia by using lipid residue analysis to investigate what kinds of foodstuffs were used in ceramic vessels by populations of the Indus Civilisation in northwest India. It examines how vessels were used in urban and rural Indus settlements during the Mature Harappan period (c.2600/2500-1900 BC), the relationship between vessels and the products within them, and identifies whether changes in vessel use occurred from the Mature Harappan to Late Harappan periods, particularly during climatic instability after 4.2 ka BP (c.2100 BC). Despite low lipid concentrations, which highlight challenges with conducting residue analysis in arid, seasonally-wet and alkaline environments, 71% of the vessels yielded appreciable quantities of lipid. Lipid profiles revealed the use of animal fats in vessels, and contradictory to faunal evidence, a dominance of non-ruminant fats, with limited evidence of dairy processing. The absence of local modern reference fats makes this dataset challenging to interpret, and it is possible that plant products or mixtures of plant and animal products have led to ambiguous fatty acid-specific isotopic values. At the same time, it appears that urban and rural populations processed similar types of products in vessels, with limited evidence for change in vessel use from the urban to the post-urban period. This study is a systematic investigation into pot lipid residues from multiple sites, demonstrating the potential of the method for examining ancient Indus foodways and the need for the development of further research in ancient organic residues in South Asia.


Pineal gland abnormality in major depressive disorder.
Patients with major depressive disorder (MDD) often have circadian rhythm alteration and sleep disturbance. The pineal gland regulates the circadian rhythm and sleep by the secretion of melatonin neurohormone. However, the relationship between pineal abnormality and MDD remains elusive. 50 patients with MDD and 35 gender- and age-matched healthy controls underwent high-resolution structural MRI. Pineal parenchymal volume (PPV) was measured manually. Inter-group differences in prevalence of pineal cyst and PPV were examined. In addition, we investigated the correlations between PPV and symptom severity as well as sleep variables in the patient group. Compared to healthy controls, patients with MDD had a higher prevalence of pineal cyst. Moreover, patients had significantly decreased PPV relative to controls. However, no significant correlations were observed between PPV and symptom severity as well as sleep variables. Our findings suggest that pineal abnormality may play a critical role in depression.


Assessment of Streptococcus pneumoniae pilus islet-1 prevalence in carried and transmitted isolates from mother-infant pairs on the Thailand-Burma border.
Streptococcus pneumoniae pilus islet-1 (PI-1)-encoded pilus enhances in vitro adhesion to the respiratory epithelium and may contribute to pneumococcal nasopharyngeal colonization and transmission. The pilus subunits are regarded as potential protein vaccine candidates. In this study, we sought to determine PI-1 prevalence in carried pneumococcal isolates and explore its relationship with transmissibility or carriage duration. We studied 896 pneumococcal isolates collected during a longitudinal carriage study that included monthly nasopharyngeal swabbing of 234 infants and their mothers between the ages of 1 and 24 months. These were cultured according to the WHO pneumococcal carriage detection protocol. PI-1 PCR and genotyping by multilocus sequence typing were performed on isolates chosen according to specific carriage and transmission definitions. Overall, 35.2% of the isolates were PI-1-positive, but PI-1 presence was restricted to ten of the 34 serotypes studied and was most frequently associated with serotypes 19F and 23F; 47.5% of transmitted and 43.3% of non-transmitted isolates were PI-1-positive (OR 1.2; 95% CI 0.8-1.7; p 0.4). The duration of first-ever infant pneumococcal carriage was significantly longer with PI-1-positive organisms, but this difference was not significant at the individual serotype level. In conclusion, PI-1 is commonly found in pneumococcal carriage isolates, but does not appear to be associated with pneumococcal transmissibility or carriage duration.


GPER/ERK&AKT/NF-κB pathway is involved in cadmium-induced proliferation, invasion and migration of GPER-positive thyroid cancer cells.
The higher incidence of thyroid cancer in women during reproductive years compared with men and the increased risk associated with the therapeutic use of estrogen have strongly suggested that estrogen may be involved in the occurrence and development of thyroid cancer. Cadmium (Cd) is a potent metalloestrogen that disrupts the endocrine system by mimicking the effects of 17β-estradiol (E2). In the present study, we demonstrate that similar to E2 and G1, a specific agonist for G protein-coupled estrogen receptor (GPER), Cd induces the proliferation, invasion and migration of human WRO and FRO thyroid cancer cells that have endogenous GPER. Moreover, like E2 and G1, Cd leads to a rapid activation of ERK/AKT, and then nuclear translocation of NF-κB, increased expression of cyclin A and D1, and secretion of IL-8, all of which are significantly attenuated by GPER blockage or knock-down in both WRO and FRO cells. Furthermore, the Cd-induced proliferation, invasion and migration are suppressed either by specific inhibitors for GPER, ERK, AKT and NF-κB, or by knock-down of GPER. These results suggest that GPER/ERK&AKT/NF-κB signaling pathway is involved in the Cd-induced proliferation, invasion and migration of GPER-positive thyroid cancer cells.


The Development and Validation of the LIMPRINT Methodology.
The acronym Limprint stands for Lymphedema IMpact and PRevalence INTernational and was run under the auspices of the International Lymphedema Framework (ILF), a charity dedicated to improving provision of care globally. The primary aim was to identify the number of people with chronic edema (chronic edema present for >3 months and due to a range of underlying etiologies and associated risk factors) within diverse health services in nine participating countries and to determine its impact using validated methods. An international protocol and sampling framework, online data capture system, and standard operating procedures were adopted. An international consensus was used to create a core data tool that covered 13 domains. Specialist data on demographics and disability, details of swelling, wounds, cancer, and health-related quality of life were also available for sites. The study protocol was designed to allow flexibility in the types of studies undertaken within complex health care systems. All cases were confirmed using the modified pitting test. Sensitivity and specificity for this method were determined in Japanese and European populations. Following confirmation of a chronic edema case, Lymphologists defined whether it was a primary of a secondary form. The study was designed to provide robust evidence that chronic edema is an important and unrecognized public health problem in health services with significant morbidity. Without evidence of the size and complexity, it will remain considered a rare phenomenon and people affected will be denied access to appropriate treatment that would allow them to have fulfilled and productive lives.


Monitoring and external control of pH in microfluidic droplets during microbial culturing.
Cell-based experimentation in microfluidic droplets is becoming increasingly popular among biotechnologists and microbiologists, since inherent characteristics of droplets allow high throughput at low cost and space investment. The range of applications for droplet assays is expanding from single cell analysis toward complex cell-cell incubation and interaction studies. As a result of cellular metabolism in these setups, relevant physicochemical alterations frequently occur before functional assays are conducted. However, to use droplets as truly miniaturized bioreactors, parameters like pH and oxygen availability should be controlled similar to large-scale fermentation to ensure reliable research. Here, we introduce a comprehensive strategy to monitor and control pH for large droplet populations during long-term incubation. We show the correlation of fluorescence intensity of 6-carboxyfluorescein and pH in single droplets and entire droplet populations. By taking advantage of inter-droplet transport of pH-mediating molecules, the average pH value of several million droplets is simultaneously adjusted in an a priori defined direction. To demonstrate the need of pH control in practice, we compared the fermentation profiles of two E. coli strains, a K12-strain and a B-strain, in unbuffered medium with 5 g/L glucose for standard 1 L bioreactors and 180 pL droplets. In both fermentation formats, the commonly used B-strain E. coli BL21 is able to consume glucose until depletion and prevent a pH drop, while the growth of the K12-strain E. coli MG1655 is soon inhibited by a low pH caused by its own high acetate production. By regulating the pH during fermentation in droplets with our suggested strategy, we were able to prevent the growth arrest of E. coli MG1655 and obtained an equally high biomass yield as with E. coli BL21. We demonstrated a comparable success of pH monitoring and regulation for fermentations in 1 L scale and 180 pL scale for two E. coli strains. This strategy has the potential to improve cell-based experiments for various microbial systems in microfluidic droplets and opens the possibility for new functional assay designs.


Impact of point-of-care ultrasound on disposition time of patients presenting with lower extremity deep vein thrombosis, done by emergency physicians.
Point-of-care venous compression ultrasound (VCU) is highly accurate in deep vein thrombosis (DVT) diagnosis; however, waiting to perform this exam by radiologists, may cause delay in patients' disposition. To compare the effect of point-of-care VCU on patients' disposition time, done by emergency physician versus radiologists. A total of 50 patients suspected of having lower extremity DVT, were randomized into 2 equal groups and they underwent a point-of-care VCU performed either by an emergency physician (emergency medicine (EM) group) or a radiologist (radiology group). The mean time of patients' disposition and management were compared between the two groups. The EM group consisted of 16 males and 9 females while the radiology group consisted of 13 males and 12 females. The median time elapsed from triage to performing ultrasonography and the median time elapsed from triage to final disposition were significantly lower in the EM group than those in the radiology group (50 min vs. 142 min, and 69 min vs. 260 min, respectively; p < .001). The final diagnosis was confirmed to be DVT in 14 patients (56%) in the EM group and in 17 patients (68%) in the radiology group (p = .38). There was no false positive or negative diagnosis. Performing VCU in patients suspected of having DVT by a trained emergency physician could significantly reduce the time of patients' disposition in the emergency setting.


Multimodal Advertisement of Pregnancy in Free-Ranging Female Japanese Macaques (Macaca fuscata).
The role of multiple sexual signals in indicating the timing of female ovulation, and discrimination of this timing by males, has been particularly well studied among primates. However the exhibition of pregnancy signals, and how such signals might modulate male post-conception mating decisions, is still poorly understood. Here we aimed to determine if Japanese macaque males use changes in female sexual signals (behavioral, visual and auditory) to discriminate pregnancy and adjust their socio-sexual behaviors. We combined behavioral observations, digital photography and endocrinological (progestogen and estrogen) data, collected systematically during three one-month periods: the pre-conceptive period, the 1st month of pregnancy and the 2nd month of pregnancy. We analyzed variation in the probability of detecting male and female socio-sexual behaviors and estrus calls, as well as changes in female face color parameters, in relation to female reproductive state. Based on our focal observations, we found that males did not copulate during the pregnancy period, and that female socio-sexual behaviors generally decreased from the pre-conceptive to post-conceptive periods. Female face luminance decreased from the pre-conceptive month to the pregnancy period whereas face color only varied between the 1st and 2nd month of gestation. Our results suggest that Japanese macaque females display sexual cues of pregnancy that males might use to reduce energy wasted on non-reproductive copulations with pregnant females. We hypothesize that females advertize their pregnancy through changes in behavioral, visual and potential auditory signals that males can use to adjust their mating behaviors. We finish by discussing implications for male and female post-conception strategies.


The co-existence of elevated high sensitivity C-reactive protein and homocysteine levels is associated with increased risk of metabolic syndrome: A 6-year follow-up study.
Accumulating evidence has revealed that both high sensitivity C-reactive protein (hsCRP) and homocysteine (HCY) are associated with increased risk of metabolic syndrome (MetS) and cardiovascular disease. However, it is unclear whether the coexistence of these conditions accelerates the risk of metabolic syndrome (MetS). We hypothesized that the combination of high sensitivity C-reactive protein (hsCRP) and homocysteine (HCY) levels could exacerbate the development of MetS in a large prospective cohort study. We selected data from 3,170 individuals (1,614 men and 1,556 women) who participated in the Korean Genome and Epidemiology Study. Participants with high hsCRP and HCY levels were categorized into quartiles. MetS was defined based on the criteria of the modified National Cholesterol Education Program, Adult Treatment Panel III. The prevalence of MetS was higher in participants with concurrent high hsCRP and HCY compared to those with low hsCRP and HCY levels. The incidence of MetS at the 6-year follow-up was the highest in participants with concomitant high hsCRP and HCY levels, regardless of obesity. Even after adjusting for potential confounding factors including body mass index in a multivariate logistic regression model, subjects with elevated hsCRP and HCY levels had a 2.50-fold increased risk of developing MetS at the six-year follow-up compared to those who did not have high hsCRP and HCY level. MetS is more prevalent in the concurrent presence of elevated hsCRP and HCY levels. The combination of the two conditions may contribute to an increased risk of MetS, but these factors may not be synergistic.


Stereopsis after congenital cataract.
The authors determined whether stereopsis can be demonstrated in children treated for congenital cataract after compensating for their amblyopia and strabismus. A custom-made set of large stereograms was used to compensate for amblyopia and presented in a synoptophore to facilitate motor fusion. Each pair of stereograms contained five wide vertical bars of high contrast, of which two or three were in crossed disparity. The authors aligned the stimuli in the synoptophore, then decreased the disparity until the child could no longer identify which bars appeared to be "in front." In normal children (n = 25), stereo acuity on this test (Tytla-Lewis-Maurer-Brent [TLMB] test) correlated well with the Titmus and Randot results within the ranges measured by those tests. Seven children in whom a traumatic cataract had developed after 6 yr of age (four with no clinical stereopsis) had TLMB test stereo acuities ranging from 225 to 28 arc-sec. Of 30 children treated for congenital cataract with no clinical stereopsis, 5 regularly achieved a TLMB stereo acuity of up to 225 arc-sec, and 2 with Titmus stereo acuities up to 200 arc-sec, each had a TLMB stereo acuity of 112 arc-sec. These seven congenital cases (two unilateral and five bilateral) with measurable TLMB acuities are among those with the shortest deprivation, the highest minimum resolvable acuity, and the highest contrast sensitivity. By compensating for amblyopia and strabismus, stereopsis can be demonstrated in some form-deprived amblyopic patients.


Glucuronidase Expression in Transgenic Tobacco Roots with a Parasponia Promoter on Infection with Meloidogyne javanica.
The expression of a g-us reporter gene linked to a Parasponia andersonii hemoglobin promoter has been studied in transgenic tobacco plants after infection by Meloidogyne javanica. Transgenic roots were harvested at different times after nematode inoculation, and stained histochemically for expression of the gus gene. During the early stages of infection (0-2 weeks) there was little expression in giant cells, in contrast to other cells of the root. In later stages of infection (3-6 weeks) there was strong gus expression in giant cells, with virtually no expression in other cells of the root. The Parasponia hemoglobin promoter therefore appears to direct down-regulation of linked genes on induction of giant cells, but up-regulation in mature giant cells. This reflects different metabolic activities in the giant cells depending on their stage of development. The Parasponia hemoglobin promoter may respond to oxygen tension in giant cells. This suggests that oxygen tension may be limited in the metabolically active giant cells that are associated with egg-laying females.


Altered expression of androgen receptor in the malignant epithelium and adjacent stroma is associated with early relapse in prostate cancer.
The molecular basis of androgen-independent prostate cancer is unknown; however, functional androgen receptor (AR) signaling is maintained after the acquisition of hormone-refractory disease. Because normal and malignant prostate epithelial cell proliferation is regulated by androgen stimulation via both the AR-positive stroma and epithelium, we sought to evaluate patterns of AR expression in these cells and to determine any relationships with prostate cancer progression. AR expression in the malignant epithelium and associated periepithelial and nonperiepithelial stroma was measured in a cohort of 96 patients with clinically localized prostate cancer treated with radical prostatectomy. Data were evaluated for disease relapse using the Kaplan-Meier method and in a Cox proportional hazards model with other variables of known clinical relevance, including Gleason score, pathological stage, clinical stage, and pretreatment prostate-specific antigen concentration. Concurrent overexpression of AR (> or = 70% positive nuclei) in the malignant epithelium and loss of AR immunoreactivity in the adjacent periepithelial stroma (< or = 30%) was associated with higher clinical stage (P = 0.01), higher pretreatment prostate-specific antigen level (P = 0.03), and earlier relapse after radical prostatectomy (log-rank P = 0.009). These data identify a pattern of AR expression in malignant epithelium and adjacent stroma that is associated with a poor clinical outcome in prostate cancer. Equally important, they identify the need to further investigate the mechanistic basis of loss of AR expression in the malignant stroma and its potential role in deregulation of prostate epithelial cell proliferation.


Leptospirosis in sheep and goats under tropical conditions.
Inadequate management practices and poor reproductive performance have been reported as fundamental factors on reducing the levels of productivity in livestock. Different pathogens have been reported in small ruminants' herds/flocks with reproductive failures. The aim of the present study was to review aspects of leptospirosis in small ruminants, mainly its impact on reproduction and consequently on productivity of the herds/flocks under tropical conditions. Leptospiral infection in goats and sheep is common in several countries, and those species can also act as carriers of leptospires. Severe disease is often associated to young animals and is frequently associated to incidental serovars. In contrast, subclinical infection is mainly characterized by reproductive problems, such as infertility, abortion, occurrence of stillbirths, and weak lambs/goat kids. Moreover, laboratorial tests are essential to achieve an accurate diagnosis of the infection. Microscopic agglutination test is the most common indirect test of leptospirosis, being used worldwide. In small ruminants, PCR consists on a recommendable method for diagnosing animals that carry leptospires. Control of leptospirosis in small ruminants involves measures such as the identification and treatment of the carriers and other sources of infection, quarantine in acquired animals, and systematic immunization with commercial vaccines containing the circulating serovars in the herd/flock. Productivity of small ruminant breeding can dramatically increase with adequate sanitary conditions and control of leptospirosis. Immunization of all the animals combined to the treatment of carriers may successfully control the infection and importantly reduce the economic reproductive hazards that are observed under tropical conditions.


Structural brain differences and cognitive functioning related to body mass index in older females.
Little is known about the effect of obesity on brain structures and cognition in healthy older adults. This study examined the association between body mass index (BMI), regional volume differences in gray and white matter measured by magnetic resonance imaging (MRI), and cognitive functioning in older females. Participants included 95 community-dwelling older females (ages 52-92 years) who underwent extensive neuropsychological testing and high-resolution MRI scanning. Optimized voxel-based morphometry techniques were employed to determine the correlation between BMI and regional gray and white matter volumes. Volumes of significant regions were then correlated with cognitive functioning. Higher BMI was associated with decreased gray matter volumes in the left orbitofrontal, right inferior frontal, and right precentral gyri, a right posterior region including the parahippocampal, fusiform, and lingual gyri, and right cerebellar regions, as well as increased volumes of white matter in the frontal, temporal, and parietal lobes, even when hypertension was considered. Compared to normal weight women, obese women performed poorer on tests of executive functioning. Smaller gray matter volume in the left orbitofrontal region was associated with lower executive functioning. Additionally, despite the lack of significant group differences in memory and visuomotor speed, gray and white matter volumes predicted performance on these measures. The results provide additional evidence for a negative link between increased body fat and brain functioning in older females.


Chaos and band structure in a three-dimensional optical lattice.
Classical chaos is known to affect wave propagation because it signifies the presence of broken symmetries. The effect of chaos has been observed experimentally for matter waves, electromagnetic waves, and acoustic waves. When these three types of waves propagate through a spatially periodic medium, the allowed propagation energies form bands. For energies in the band gaps, no wave propagation is possible. We show that optical lattices provide a well-defined system that allows a study of the effect of chaos on band structure. We have determined the band structure of a body-centered-cubic optical lattice for all theoretically possible couplings, and we find that the band structure for those lattices realizable in the laboratory differs significantly from that expected for the bands in an "empty" body-centered-cubic crystal. However, as coupling is increased, the lattice becomes increasingly chaotic and it becomes possible to produce band structure that has behavior qualitatively similar to the "empty" body-centered-cubic band structure, although with fewer degeneracies.


Tropomyosin-like properties of clathrin light chains allow a rapid, high-yield purification.
The light chains (LCa and LCb) of bovine brain clathrin are resistant to heat denaturation by boiling, a property shared by tropomyosin (Bailey, K., 1948, Biochem. J., 43:271-281). Light chains were partially purified by boiling and centrifugation of a Tris-extract of crude membranes prepared from bovine brains (Keen, J. H., M. C. Willingham, and I. H. Pastan, 1979, Cell., 16:303-312). Contaminant polypeptides were then removed by size-exclusion high-pressure liquid chromatography. The purified light chains were separated from each other by using an immunoaffinity column prepared from a monoclonal antibody CVC.7 specific for LCa and not LCb.


Pregnant rat uterus expresses high levels of the type 3 iodothyronine deiodinase.
Although thyroid hormones are critically important for the coordination of morphogenic processes in the fetus and neonate, premature exposure of the embryo to levels of the hormones present in the adult is detrimental and can result in growth retardation, malformations, and even death. We report here that the pregnant rat uterus expresses extremely high levels of the type 3 iodothyronine deiodinase (D3), which inactivates thyroxine and 3,3', 5-triiodothyronine by 5-deiodination. Both D3 mRNA and activity were present at the implantation site as early as gestational day 9 (E9), when expression was localized using in situ hybridization to uterine mesometrial and antimesometrial decidual tissue. At later stages of gestation, uterine D3 activity remained very high, and the levels exceeded those observed in the placenta and in fetal tissues. After days E12 and E13, as decidual tissues regressed, D3 expression became localized to the epithelial cells lining the recanalized uterine lumen that surrounds the fetal cavity. These findings strongly suggest that the pregnant uterus, in addition to the placenta, plays a critical role in determining the level of exposure of the fetus to maternal thyroid hormones.


Diagnosis, Treatment, and Management of Orthotopic Liver Transplant Candidates With Portopulmonary Hypertension.
Portopulmonary hypertension (POPH) is seen in 5-8% of orthotopic liver transplantation (OLT) candidates and has significant implications for clinical outcomes. POPH is characterized by vasoconstriction and remodeling of the pulmonary vasculature. It is exacerbated by the hyperdynamic circulation that is common in advanced liver disease. Screening all OLT candidates with transthoracic echocardiography to assess pulmonary pressures and right ventricular function is crucial, as clinical symptoms alone are not reliable. Any significant right ventricular dysfunction or dilatation along with an elevation in estimated pulmonary pressures usually triggers further investigation with right heart catheterization. The mainstays of therapy of POPH are vasodilators that are used in pulmonary arterial hypertension. They include monotherapy or combination therapy with prostanoids, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors/guanylate cyclase stimulator. Limited evidence from smaller studies and case series suggests that a timely diagnosis of POPH and the early initiation of treatment improve patient outcomes, whether or not OLT is ultimately undertaken. Given the historically high perioperative mortality rate of more than 35%, POPH remains a contraindication to OLT unless it is treated and responsive to vasodilator therapy. We review the current literature and International Liver Transplant Society practice guidelines (2016) for the latest in understanding POPH, its pathogenesis, diagnosis, modern pharmacological treatment, indications, and contraindications for OLT, as well as perioperative management.


[Sexual behavior, knowledge and attitudes to AIDS and sexually transmitted diseases of students at the University of Benin (Togo)].
Many studies have shown that in Africa, particularly in Togo, the 20- to 29-year-old age group is the age group most frequently affected by AIDS. This age group accounts for 84% of the students of the University of Benin. We studied students, most of the age group thought to be most at risk, investigating sexual behavior, knowledge and attitudes to AIDS and sexually transmitted diseases (STDs). The level of knowledge about the problems of AIDS and STDs was similar for both sexes and for all ages and levels of education of the students. Students had a reasonable knowledge of AIDS, particularly concerning the transmission of HIV (88.6% of students aware), risk behavior (80.8%), AIDS treatment (57.0%) and more general information about HIV (49.4%). They were poorly informed about the transmission (42.9%) and complications (0.69%) of other STDs. Most students had positive attitudes towards HIV issues, particularly the use of preventive measures (3.41 in 5) and the acceptance of infected individuals (3.98 in 5). However, few had seriously considered that AIDS and STDs might impact on their own sex lives (1. 84 in 5) and some were even fatalistic concerning HIV infection. The students were highly sexually active, having intercourse a mean of 31 times per year. Their sexual behavior depended on age and sex. The 15- to 19-year-olds preferred occasional partners. They had sexual intercourse 1 to 3 times per month and used condoms 10 to 20% of the time. The 20- to 29-year-olds had multiple partners. They had sexual intercourse 3 to 5 times per month and used condoms more than 30% of the time. Students over the age of 30 had many partners in addition to their regular partner. They had sexual intercourse 5 to 10 times per month and used condoms 0 to 20% of the time. Significantly more women than men had high-risk sexual behavior (40. 5% of men claimed to regularly use condoms, versus only 22.7% of the women and 11.9% of the women accepted anal penetration versus only 8. 4% of men). The general assumption is that students, who have a high level of education, should be well informed concerning AIDS and STDs and should therefore have positive attitudes and responsible sexual behavior. This study demonstrates that the assumption bears no resemblance to reality. The students were aware of the way in which HIV is transmitted and of what construes risky behavior, but there was nonetheless a high frequency of high-risk behavior (e.g. multiple sexual partners, anal and oral sex, homosexuality, intravenous drug use). The behavior of the students was not significantly different from that of young people living on the streets of Lomé. There were significant relationships between knowledge and attitudes and between some types of sexual behavior and knowledge. However, there was no correlation between attitudes and behavior. The education of young people should focus on both the prevention of AIDS and STDs and on facing up to these diseases.


The neural correlates of regulating another person's emotions: an exploratory fMRI study.
Studies investigating the neurophysiological basis of intrapersonal emotion regulation (control of one's own emotional experience) report that the frontal cortex exerts a modulatory effect on limbic structures such as the amygdala and insula. However, no imaging study to date has examined the neurophysiological processes involved in interpersonal emotion regulation, where the goal is explicitly to regulate another person's emotion. Twenty healthy participants (10 males) underwent fMRI while regulating their own or another person's emotions. Intrapersonal and interpersonal emotion regulation tasks recruited an overlapping network of brain regions including bilateral lateral frontal cortex, pre-supplementary motor area, and left temporo-parietal junction. Activations unique to the interpersonal condition suggest that both affective (emotional simulation) and cognitive (mentalizing) aspects of empathy may be involved in the process of interpersonal emotion regulation. These findings provide an initial insight into the neural correlates of regulating another person's emotions and may be relevant to understanding mental health issues that involve problems with social interaction.


Electrophysiological monitoring of injury progression in the rat cerebellar cortex.
The changes of excitability in affected neural networks can be used as a marker to study the temporal course of traumatic brain injury (TBI). The cerebellum is an ideal platform to study brain injury mechanisms at the network level using the electrophysiological methods. Within its crystalline morphology, the cerebellar cortex contains highly organized topographical subunits that are defined by two main inputs, the climbing (CFs) and mossy fibers (MFs). Here we demonstrate the use of cerebellar evoked potentials (EPs) mediated through these afferent systems for monitoring the injury progression in a rat model of fluid percussion injury (FPI). A mechanical tap on the dorsal hand was used as a stimulus, and EPs were recorded from the paramedian lobule (PML) of the posterior cerebellum via multi-electrode arrays (MEAs). Post-injury evoked response amplitudes (EPAs) were analyzed on a daily basis for 1 week and compared with pre-injury values. We found a trend of consistently decreasing EPAs in all nine animals, losing as much as 72 ± 4% of baseline amplitudes measured before the injury. Notably, our results highlighted two particular time windows; the first 24 h of injury in the acute period and day-3 to day-7 in the delayed period where the largest drops (~50% and 24%) were observed in the EPAs. In addition, cross-correlations of spontaneous signals between electrode pairs declined (from 0.47 ± 0.1 to 0.35 ± 0.04, p < 0.001) along with the EPAs throughout the week of injury. In support of the electrophysiological findings, immunohistochemical analysis at day-7 post-injury showed detectable Purkinje cell loss at low FPI pressures and more with the largest pressures used. Our results suggest that sensory evoked potentials (SEPs) recorded from the cerebellar surface can be a useful technique to monitor the course of cerebellar injury and identify the phases of injury progression even at mild levels.


Manifestations of Alzheimer's disease genetic risk in the blood are evident in a multiomic analysis in healthy adults aged 18 to 90.
Genetics play an important role in late-onset Alzheimer's Disease (AD) etiology and dozens of genetic variants have been implicated in AD risk through large-scale GWAS meta-analyses. However, the precise mechanistic effects of most of these variants have yet to be determined. Deeply phenotyped cohort data can reveal physiological changes associated with genetic risk for AD across an age spectrum that may provide clues to the biology of the disease. We utilized over 2000 high-quality quantitative measurements obtained from blood of 2831 cognitively normal adult clients of a consumer-based scientific wellness company, each with CLIA-certified whole-genome sequencing data. Measurements included: clinical laboratory blood tests, targeted chip-based proteomics, and metabolomics. We performed a phenome-wide association study utilizing this diverse blood marker data and 25 known AD genetic variants and an AD-specific polygenic risk score (PGRS), adjusting for sex, age, vendor (for clinical labs), and the first four genetic principal components; sex-SNP interactions were also assessed. We observed statistically significant SNP-analyte associations for five genetic variants after correction for multiple testing (for SNPs in or near NYAP1, ABCA7, INPP5D, and APOE), with effects detectable from early adulthood. The ABCA7 SNP and the APOE2 and APOE4 encoding alleles were associated with lipid variability, as seen in previous studies; in addition, six novel proteins were associated with the e2 allele. The most statistically significant finding was between the NYAP1 variant and PILRA and PILRB protein levels, supporting previous functional genomic studies in the identification of a putative causal variant within the PILRA gene. We did not observe associations between the PGRS and any analyte. Sex modified the effects of four genetic variants, with multiple interrelated immune-modulating effects associated with the PICALM variant. In post-hoc analysis, sex-stratified GWAS results from an independent AD case-control meta-analysis supported sex-specific disease effects of the PICALM variant, highlighting the importance of sex as a biological variable. Known AD genetic variation influenced lipid metabolism and immune response systems in a population of non-AD individuals, with associations observed from early adulthood onward. Further research is needed to determine whether and how these effects are implicated in early-stage biological pathways to AD. These analyses aim to complement ongoing work on the functional interpretation of AD-associated genetic variants.