Search

ImportanceSARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis.MethodsRECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms.DiscussionRECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options.RegistrationNCT05172024.

As of May 27, 2018, 6 suspected, 13 probable and 35 confirmed cases of Ebola virus disease (EVD) had been reported in Équateur Province, Democratic Republic of Congo. We used reported case counts and time series from prior outbreaks to estimate the total outbreak size and duration with and without vaccine use. We modeled Ebola virus transmission using a stochastic branching process model that included reproduction numbers from past Ebola outbreaks and a particle filtering method to generate a probabilistic projection of the outbreak size and duration conditioned on its reported trajectory to date; modeled using high (62%), low (44%), and zero (0%) estimates of vaccination coverage (after deployment). Additionally, we used the time series for 18 prior Ebola outbreaks from 1976 to 2016 to parameterize the Thiel-Sen regression model predicting the outbreak size from the number of observed cases from April 4 to May 27. We used these techniques on probable and confirmed case counts with and without inclusion of suspected cases. Probabilistic projections were scored against the actual outbreak size of 54 EVD cases, using a log-likelihood score. With the stochastic model, using high, low, and zero estimates of vaccination coverage, the median outbreak sizes for probable and confirmed cases were 82 cases (95% prediction interval [PI]: 55, 156), 104 cases (95% PI: 58, 271), and 213 cases (95% PI: 64, 1450), respectively. With the Thiel-Sen regression model, the median outbreak size was estimated to be 65.0 probable and confirmed cases (95% PI: 48.8, 119.7). Among our three mathematical models, the stochastic model with suspected cases and high vaccine coverage predicted total outbreak sizes closest to the true outcome. Relatively simple mathematical models updated in real time may inform outbreak response teams with projections of total outbreak size and duration.

Anthropogenic activities can lead to changes in animal behavior. Predicting population consequences of these behavioral changes requires integrating short-term individual responses into models that forecast population dynamics across multiple generations. This is especially challenging for long-lived animals, because of the different time scales involved. Beaked whales are a group of deep-diving odontocete whales that respond behaviorally when exposed to military mid-frequency active sonar (MFAS), but the effect of these nonlethal responses on beaked whale populations is unknown. Population consequences of aggregate exposure to MFAS was assessed for two beaked whale populations that are regularly present on U.S. Navy training ranges where MFAS is frequently used. Our approach integrates a wide range of data sources, including telemetry data, information on spatial variation in habitat quality, passive acoustic data on the temporal pattern of sonar use and its relationship to beaked whale foraging activity, into an individual-based model with a dynamic bioenergetic module that governs individual life history. The predicted effect of disturbance from MFAS on population abundance ranged between population extinction to a slight increase in population abundance. These effects were driven by the interaction between the temporal pattern of MFAS use, baseline movement patterns, the spatial distribution of prey, the nature of beaked whale behavioral response to MFAS and the top-down impact of whale foraging on prey abundance. Based on these findings, we provide recommendations for monitoring of marine mammal populations and highlight key uncertainties to help guide future directions for assessing population impacts of nonlethal disturbance for these and other long-lived animals.

Family B G protein-coupled receptors (GPCRs) play vital roles in hormone-regulated homeostasis. They are drug targets for metabolic diseases, including type 2 diabetes and osteoporosis. Despite their importance, the signaling mechanisms for family B GPCRs at the molecular level remain largely unexplored due to the challenges in purification of functional receptors in sufficient amount for biophysical characterization. Here, we purified the family B GPCR human glucagon-like peptide-1 (GLP-1) receptor (GLP1R), whose agonists, e.g. exendin-4, are used for the treatment of type 2 diabetes mellitus. The receptor was expressed in HEK293S GnTl- cells using our recently developed protocol. The protocol incorporates the receptor into the native-like lipid environment of reconstituted high density lipoprotein (rHDL) particles, also known as nanodiscs, immediately after the membrane solubilization step followed by chromatographic purification, minimizing detergent contact with the target receptor to reduce denaturation and prolonging stabilization of receptor in lipid bilayers without extra steps of reconstitution. This method yielded purified GLP1R in nanodiscs that could bind to GLP-1 and exendin-4 and activate Gs protein. This nanodisc purification method can potentially be a general strategy to routinely obtain purified family B GPCRs in the 10s of microgram amounts useful for spectroscopic analysis of receptor functions and activation mechanisms.

Vented tumble dryers release moist warm air from the drying process to the external environment, usually through pipework linking the appliance to a vent in an exterior wall. Although such dryers contain a lint filter to remove fibers from this air stream, recent reports suggest that this process is incomplete, leading to microfibers being released in the ducted warm air and subsequently polluting the external environment. Microfiber release from wash loads comprising 10 100% cotton and 10 100% polyester T-shirts (total load mass ratio 48% cotton, 52% polyester) was measured at different stages of the washing and drying process to compare the quantities of fibers released 'down the drain', collected in the dryer lint filter, and released to air from the tumble dryer. Testing under both European and North American washing conditions found that the quantities of microfibers released to air during tumble drying were significant and comparable to levels released 'down the drain' during washing. Use of conventional rinse-added liquid fabric conditioner increased microfiber accumulation on the dryer lint filter, with reduced release from the dryer exhaust observed at the highest fabric conditioner dose tested (21.6% and 14.2% reduction under North American and European conditions, respectively). Conventional liquid fabric conditioner did not significantly impact microfiber release from the washing machine, in line with previous studies. A fabric conditioner specially designed for anti-wrinkle performance reduced microfiber release from the dryer exhaust at all levels tested (by 17.6-35.6%, depending on dose), apparently by increasing the efficiency of microfiber accumulation in the lint filter. Tumble dryer sheets were also found to cause a reduction in microfiber release from the dryer exhaust (by 14.1-34.9%, depending on the dose/product), likely driven by collection of liberated fibers on the sheet during the drying process. The use of both antiwrinkle liquid fabric conditioner and dryer sheet enabled a 44.9% reduction in microfiber emissions from the dryer exhaust. In all studies, the fiber mass collected on the lint filter or emitted from the dryer exhaust was richer in cotton fibers (range 83.4-96.3% on the lint filter, 93.0-99.8% from the dryer exhaust) than the wash load composition (48% cotton). Moreover, fibers collected by the lint filter contained a higher proportion of polyester than emissions from the dryer exhaust (range 3.7-16.6% on the lint filter, 0.2-7.0% from the dryer exhaust). There is significant variation in the porosity of lint filters among installed vented tumble dryers. Single-variable testing of the impact of lint filter design concluded that reducing screen pore size significantly reduces airborne microfiber release during tumble drying; a reduction in lint filter pore size from 0.2 mm2 to 0.04 mm2 reduced release by 34.8%. As some lint filters have pore sizes of around 1 mm2, there is enormous scope to reduce microfiber release from dryers though improved lint filter design. However, it is suggested that a step-change in appliance design away from vented dryers to only fully-sealed condenser dryers might be necessary to eliminate the contribution of tumble drying to airborne microfiber pollution.

The interaction between infant feeding and maternal lactational physiology influences female inter-birth intervals and mediates maternal reproductive trade-offs. We investigated variation in feeding development in 72 immature wild chimpanzees (Pan troglodytes schweinfurthii) at Ngogo, Kibale National Park, Uganda, and made inferences about maternal lactation over the course of infancy. We compared the percentage (%) of time that mothers nursed infants as a function of infant age and assessed how hourly rates and bout durations of nursing and foraging varied in association with differences in offspring age, sex, and maternal parity. Nursing % times, rates and durations were highest for infants ≤ 6 months old but did not change significantly from 6 months to 5 years old. Nursing continued at a decreasing rate for some 5- to 7-year-olds. Infants ≤ 6 months old foraged little. Foraging rates did not change after 1 year old, but foraging durations and the % time devoted to foraging increased with age. Independent foraging probably became a dietary requirement for infants at 1 year old, when their energy needs may have surpassed the available milk energy. Infants spent as much time foraging by the time they were 4 to 5 years old as adults did. No sex effect on infant nursing or foraging was apparent, but infants of primiparous females had higher foraging rates and spent more time foraging than the infants of multiparous females did. Although no data on milk composition were collected, these findings are consistent with a working hypothesis that like other hominoids, chimpanzee mothers maintained a fixed level of lactation effort over several years as infants increasingly supplemented their growing energy, micronutrient and hydration needs via independent foraging. Plateauing lactation may be a more widespread adaptation that allows hominoid infants time to attain the physiology and skills necessary for independent feeding, while also providing them with a steady dietary base on which they could rely consistently through infancy, and enabling mothers to maintain a fixed, predictable level of lactation effort.

The COVID-19 pandemic has posed unique academic, social, financial, and health-related challenges for young adults. While numerous studies have documented average increases in reported mental health issues in the general population, few have measured the magnitude of changes in mental health symptoms and sleep difficulties within individuals. Here, we measure the impact of the COVID-19 pandemic on mental health and sleep of university students pre- and mid-pandemic. Prior to the pandemic (Fall 2019), individuals (n = 23) were recruited to participate in an eight-day, comprehensive sleep study using Fitbit® actigraphy. Participants also completed detailed mental health and sleep surveys, including depression (BDI-II), anxiety (STAI), and sleep disturbance (PROMIS) surveys. One year later, these individuals repeated the study during the pandemic (Fall 2020); participants completed the original surveys and sleep study, in addition to a targeted survey on mental and sleep health due to the pandemic. Self-reported levels of anxiety, depression, and sleep disturbance, and sleep parameters, measured by actigraphy, were compared within the same individuals pre- and mid-pandemic. Self-report survey data revealed that three-quarters of participants experienced an increase in stress and anxiety due to the pandemic. In addition, intra-individual depression and anxiety symptoms increased to clinically significant levels within individuals from pre- to mid-pandemic. Over two-thirds of participants reported sleeping less, and more than half reported that their sleep health had worsened during the pandemic. Changes in sleep disturbance were positively associated with changes in depression and anxiety, reinforcing the robust relationship between poor sleep quality and mental health. Furthermore, individuals who reported greater sleep disturbance during the pandemic experienced lower relative proportions of both REM and deep sleep. The impact of the COVID-19 pandemic on university students is multi-faceted-mental health, sleep quality, and the amount of restorative sleep are negatively affected by the pandemic environment. These compounded effects exacerbate the health consequences of the pandemic and highlight a need for increased attention to the prevention and treatment of mental health disorders, particularly in vulnerable populations of young adults.

BackgroundMany schools have been cutting physical education (PE) classes due to budget constraints, which raises the question of whether policymakers should require schools to offer PE classes. Evidence suggests that PE classes can help address rising physical inactivity and obesity prevalence. However, it would be helpful to determine if requiring PE is cost-effective.MethodsWe developed an agent-based model of youth in Mexico City and the impact of all schools offering PE classes on changes in weight, weight-associated health conditions and the corresponding direct and indirect costs over their lifetime.ResultsIf schools offer PE without meeting guidelines and instead followed currently observed class length and time active during class, overweight and obesity prevalence decreased by 1.3% (95% CI: 1.0%-1.6%) and was cost-effective from the third-party payer and societal perspectives ($5,058 per disability-adjusted life year [DALY] averted and $5,786/DALY averted, respectively, assuming PE cost $50.3 million). When all schools offered PE classes meeting international guidelines for PE classes, overweight and obesity prevalence decreased by 3.9% (95% CI: 3.7%-4.3%) in the cohort at the end of five years compared to no PE. Long-term, this averted 3,183 and 1,081 obesity-related health conditions and deaths, respectively and averted ≥$31.5 million in direct medical costs and ≥$39.7 million in societal costs, assuming PE classes cost ≤$50.3 million over the five-year period. PE classes could cost up to $185.5 million and $89.9 million over the course of five years and still remain cost-effective and cost saving respectively, from the societal perspective.ConclusionRequiring PE in all schools could be cost-effective when PE class costs, on average, up to $10,340 per school annually. Further, the amount of time students are active during class is a driver of PE classes' value (e.g., it is cost saving when PE classes meet international guidelines) suggesting the need for specific recommendations.

BackgroundDelayed umbilical cord clamping (UCC) after birth is thought to cause placental to infant blood transfusion, but the mechanisms are unknown. It has been suggested that uterine contractions force blood out of the placenta and into the infant during delayed cord clamping. We have investigated the effect of uterine contractions, induced by maternal oxytocin administration, on umbilical artery (UA) and venous (UV) blood flows before and after ventilation onset to determine whether uterine contractions cause placental transfusion in preterm lambs.Methods and findingsAt ~128 days of gestation, UA and UV blood flows, pulmonary arterial blood flow (PBF) and carotid arterial (CA) pressures and blood flows were measured in three groups of fetal sheep during delayed UCC; maternal oxytocin following mifepristone, mifepristone alone, and saline controls. Each successive uterine contraction significantly (pConclusionsWe found no evidence that amplification of uterine contractions with oxytocin increase placental transfusion during DCC. Instead they decreased both UA and UV flow and caused a net loss of blood from the lamb. Uterine contractions did, however, have significant cardiovascular effects and reduced systemic and cerebral oxygenation.

ObjectiveThis study sought to determine the incidence rates of cancer, overall and by site, among active component U.S. Air Force fighter pilots, and to compare the rates with those in other active component Air Force officers.MethodsUsing a matched retrospective cohort design, U.S. Air Force fighter pilots were compared with other commissioned officers who entered active component service between 1 January 1986 and 31 December 2006. The cohort was followed for cancer diagnoses in TRICARE and the Veterans Health Administration from 1 October 1995 through 31 December 2017. Fighter pilots and non-fighter pilot officers were compared after matching on sex, age at first observation (15 age groups), and age at last observation (15 age groups). Sex-stratified overall and site-specific cancer rates were compared with matched Poisson regression to determine incidence rate ratios with 95% confidence intervals.ResultsDuring 1,412,590 person-years of follow-up, among the study population of 88,432 service members (4,949 fighter pilots and 83,483 matched officers), 977 incident cancer cases were diagnosed (86 in fighter pilots and 891 in matched officers). Male fighter pilots and matched officers had similar rates of all malignant cancers (RR = 1.04; 95% CI: 0.83-1.31) and of each cancer site. Female fighter pilots and matched officers also had similar rates of all malignant cancers (RR = 0.99; 95% CI: 0.25-4.04).DiscussionIn the active component U.S. Air Force, fighter pilots and their officer peers had similar overall and site-specific cancer rates.

Radiogenic strontium isotopes (87Sr/86Sr) have long been used in analyses of paleomobility within Mesoamerica. While considerable effort has been expended developing 87Sr/86Sr baseline values across the Maya region, work in central Mexico is primarily focused on the Classic period urban center of Teotihuacan. This study adds to this important dataset by presenting bioavailable 87Sr/86Sr values across central Mexico focusing on the Basin of Mexico. This study therefore serves to expand the utility of strontium isotopes across a wider geographic region. A total of 63 plant and water samples were collected from 13 central Mexican sites and analyzed for 87Sr/86Sr on a Thermo-Finnigan Neptune multi-collector inductively coupled plasma mass spectrometer (MC-ICP-MS). These data were analyzed alongside 16 published 87Sr/86Sr values from two additional sites within the region of interest. A five-cluster k-means model was then generated to determine which regions of the Basin of Mexico and greater central Mexico can and cannot be distinguished isotopically using 87Sr/86Sr values. Although the two clusters falling within the Basin of Mexico overlap in their local 87Sr/86Sr ranges, many locations within the Basin are distinguishable using 87Sr/86Sr values at the site-level. This study contributes to paleomobility studies within central Mexico by expanding knowledge of strontium isotope variability within the region, ultimately allowing researchers to detect intra-regional residential mobility and gain a greater understanding of the sociopolitical interactions between the Basin of Mexico and supporting outlying regions of central Mexico.

Glioblastoma, the most aggressive form of glioma, has a 5-year survival rate of 30% Ki67 and increased tissue vascularization (p

Fiber release during domestic textile washing is a cause of marine microplastic pollution, but better understanding of the magnitude of the issue and role of fabric care products, appliances and washing cycles is needed. Soiled consumer wash loads from U.K. households were found to release a mean of 114 ± 66.8 ppm (mg microfiber per kg fabric) (n = 79) fibers during typical washing conditions and these were mainly composed of natural fibers. Microfiber release decreased with increasing wash load size and hence decreasing water to fabric ratio, with mean microfiber release from wash loads in the mass range 1.0-3.5 kg (n = 57) found to be 132.4 ± 68.6 ppm, significantly (p = 3.3 x 10-8) higher than the 66.3 ± 27.0 ppm of those in the 3.5-6.0 kg range (n = 22). In further tests with similar soiled consumer wash loads, moving to colder and quicker washing cycles (i.e. 15°C for 30 mins, as opposed to 40°C for 85 mins) significantly reduced microfiber generation by 30% (p = 0.036) and reduced whiteness loss by 42% (p = 0.000) through reduced dye transfer and soil re-deposition, compared to conventional 40°C cycles. In multicycle technical testing, detergent pods were selected for investigation and found to have no impact on microfiber release compared to washing in water alone. Fabric softeners were also found to have no direct impact on microfiber release in testing under both European and North American washing conditions. Extended testing of polyester fleece garments up to a 48-wash cycle history under European conditions found that microfiber release significantly reduced to a consistent low level of 28.7 ± 10.9 ppm from eight through 64 washes. Emerging North American High-Efficiency top-loading washing machines generated significantly lower microfiber release than traditional top-loading machines, likely due to their lower water fill volumes and hence lower water to fabric ratio, with a 69.7% reduction observed for polyester fleece (n = 32, p = 7.9 x 10-6) and 37.4% reduction for polyester T-shirt (n = 32, p = 0.0032). These results conclude that consumers can directly reduce the levels of microfibers generated per wash during domestic textile washing by using colder and quicker wash cycles, washing complete (but not overfilled) loads, and (in North America) converting to High-Efficiency washing machines. Moving to colder and quicker cycles will also indirectly reduce microfiber release by extending the lifetime of clothing, leading to fewer new garments being purchased and hence lower incidence of the high microfiber release occurring during the first few washes of a new item.

Human Parainfluenza viruses (HPIV) type 1 and 3 are important causes of respiratory tract infections in young children globally. HPIV infections do not confer complete protective immunity so reinfections occur throughout life. Since no effective vaccine is available for the two virus subtypes, comprehensive understanding of HPIV-1 and HPIV-3 genetic and epidemic features is important for diagnosis, prevention, and treatment of HPIV-1 and HPIV-3 infections. Relatively few whole genome sequences are available for both HPIV-1 and HPIV-3 viruses, so our study sought to provide whole genome sequences from multiple countries to further the understanding of the global diversity of HPIV at a whole-genome level. We collected HPIV-1 and HPIV-3 samples and isolates from Argentina, Australia, France, Mexico, South Africa, Switzerland, and USA from the years 2003-2011 and sequenced the genomes of 40 HPIV-1 and 75 HPIV-3 viruses with Sanger and next-generation sequencing with the Ion Torrent, Illumina, and 454 platforms. Phylogenetic analysis showed that the HPIV-1 genome is evolving at an estimated rate of 4.97 × 10-4 mutations/site/year (95% highest posterior density 4.55 × 10-4 to 5.38 × 10-4) and the HPIV-3 genome is evolving at a similar rate (3.59 × 10-4 mutations/site/year, 95% highest posterior density 3.26 × 10-4 to 3.94 × 10-4). There were multiple genetically distinct lineages of both HPIV-1 and 3 circulating on a global scale. Further surveillance and whole-genome sequencing are greatly needed to better understand the spatial dynamics of these important respiratory viruses in humans.

In systems biology, inference of functional associations among genes is compelling because the construction of functional association networks facilitates biomarker discovery. Specifically, such gene associations in human can help identify putative biomarkers that can be used as diagnostic tools in treating patients. Although biomedical literature is considered a valuable data source for this task, currently only a limited number of webservers are available for mining gene-gene associations from the vast amount of biomedical literature using text mining techniques. Moreover, these webservers often have limited coverage of biomedical literature and also lack efficient and user-friendly tools to interpret and visualize mined relationships among genes. To address these limitations, we developed GAIL (Gene-gene Association Inference based on biomedical Literature), an interactive webserver that infers human gene-gene associations from Gene Ontology (GO) guided biomedical literature mining and provides dynamic visualization of the resulting association networks and various gene set enrichment analysis tools. We evaluate the utility and performance of GAIL with applications to gene signatures associated with systemic lupus erythematosus and breast cancer. Results show that GAIL allows effective interrogation and visualization of gene-gene networks and their subnetworks, which facilitates biological understanding of gene-gene associations. GAIL is available at http://chunglab.io/GAIL/.

OBJECTIVE:To determine whether the expression of IL17A and CD21L genes in inflamed rheumatoid synovia is associated with the neogenesis of ectopic lymphoid follicle-like structures (ELS), and if this aids the stratification of rheumatoid inflammation and thereby distinguishes patients with rheumatoid arthritis that might be responsive to specific targeted biologic therapies. METHODS:Expression of IL17A and CD21L genes was assessed by RT-PCR, qRT-PCR and dPCR in synovia from 54 patients with rheumatoid arthritis. A subset of synovia (n = 30) was assessed by immunohistology for the presence of CD20+ B-lymphocytes and size of CD20+ B-lymphocyte aggregates as indicated by maximum radial cell count. The molecular profiles of six IL17A+/CD21L+ and six IL17A-/CD21L- synovia were determined by complementary DNA microarray analysis. RESULTS:By RT-PCR, 26% of synovia expressed IL17A and 52% expressed CD21L. This provided the basis for distinguishing four subgroups of rheumatoid synovia: IL17A+/CD21L+ (18.5% of synovia), IL17A+/CD21L- (7.5%), IL17A-/CD21L+ (33.3%) and IL17A-/CD21L- (40.7%). While the subgroups did not predict clinical outcome measures, comparisons between the synovial subgroups revealed the IL17A+/CD21L+ subgroup had significantly larger CD20+ B-lymphocyte aggregates (P = 0.007) and a gene expression profile skewed toward B-cell- and antibody-mediated immunity. In contrast, genes associated with bone and cartilage remodelling were prominent in IL17A-/CD21L- synovia. CONCLUSIONS:Rheumatoid synovia can be subdivided on the basis of IL17A and CD21L gene expression. Ensuing molecular subgroups do not predict clinical outcome for patients but highlight high inflammation and the predominance of B-lymphocyte mediated mechanisms operating in IL17A+/CD21L+ synovia. This may provide a rationale for more refined therapeutic selection due to the distinct molecular profiles associated with IL17A+/CD21L+ and IL17A-/CD21L- rheumatoid synovia.

IntroductionA significant population of our wounded veterans suffer long-term functional consequences of visual deficit, disorientation, dizziness, and an impaired ability to read. These symptoms may be related to damage within the otolith pathways that contribute to ocular alignment. The purpose of this study was to compare perception of vertical and torsional ocular alignment between veterans and healthy controls in an upright and supine test position.Materials and methodsVeterans (n = 26) with reports of dizziness were recruited from the East Orange Veterans Administration Hospital. Healthy controls (n = 26) were recruited from both Johns Hopkins University and the East Orange VA. Each subject performed 20 trials each of a novel vertical and torsional binocular alignment perception test. Veterans underwent semicircular canal and otolith pathway function testing.Results88% of the Veterans had an absent otolith response. Only the veterans had an abnormally large variability in perception of both vertical and torsional ocular alignment, and in both upright and supine position. Neither post-traumatic stress disorder, nor depression contributed to the misperception in binocular alignment.ConclusionsOur novel method of measuring vertical and torsional misalignment distinguishes veterans with dizziness from healthy controls. The high prevalence of absent otolith function seems to explain this result. Further studies are needed to better understand the fundamental mechanism responsible for the increased variability of perception of binocular alignment.

In spite of accumulating evidence suggesting that different complex traits share a common risk basis, namely pleiotropy, effective investigation of pleiotropic architecture still remains challenging. In order to address this challenge, we developed ShinyGPA, an interactive and dynamic visualization toolkit to investigate pleiotropic structure. ShinyGPA requires only the summary statistics from genome-wide association studies (GWAS), which reduces the burden on researchers using this tool. ShinyGPA allows users to effectively investigate genetic relationships among phenotypes using a flexible low-dimensional visualization and an intuitive user interface. In addition, ShinyGPA provides joint association mapping functionality that can facilitate biological understanding of the pleiotropic architecture. We analyzed GWAS summary statistics for 12 phenotypes using ShinyGPA and obtained visualization results and joint association mapping results that are well supported by the literature. The visualization produced by ShinyGPA can also be used as a hypothesis generating tool for relationships between phenotypes, which might also be used to improve the design of future genetic studies. ShinyGPA is currently available at https://dongjunchung.github.io/GPA/.

The orexin/hypocretin system is important for appetitive motivation towards multiple drugs of abuse, including nicotine. Both OX1 and OX2 receptors individually have been shown to influence nicotine self-administration and reinstatement. Due to the increasing clinical use of dual orexin receptor antagonists in the treatment of disorders such as insomnia, we examined whether a dual orexin receptor antagonist may also be effective in reducing nicotine seeking. We tested the effect of intracerebroventricular (i.c.v.) administration of the potent and selective dual orexin receptor antagonist TCS1102 on orexin-A-induced food self-administration, nicotine self-administration and reinstatement of nicotine-seeking in rats. Our results show that 30 μg of TCS1102 i.c.v. abolishes orexin-A-induced increases in food self-administration but does not reduce nicotine self-administration. Neither i.c.v. 10 μg nor 30 μg of TCS1102 reduced compound reinstatement after short-term (15 days) self-administration nicotine, but 30 μg transiently reduced cue/nicotine compound reinstatement after chronic self-administration (29 days). These results indicate that TCS1102 has no substantial effect on motivation for nicotine seeking following chronic self-administration and no effect after shorter periods of intake. Orexin receptor antagonists may therefore have little clinical utility against nicotine addiction.

PURPOSE:Inflammatory rheumatic diseases (IRD) are associated with accelerated coronary artery disease (CAD), which may result from both systemic and vascular wall inflammation. There are indications that complement may be involved in the pathogenesis of CAD in Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA). This study aimed to evaluate the associations between circulating complement and complement activation products with mononuclear cell infiltrates (MCI, surrogate marker of vascular inflammation) in the aortic media and adventitia in IRDCAD and non-IRDCAD patients undergoing coronary artery bypass grafting (CABG). Furthermore, we compared complement activation product deposition patterns in rare aorta adventitial and medial biopsies from SLE, RA and non-IRD patients. METHODS:We examined plasma C3 (p-C3) and terminal complement complexes (p-TCC) in 28 IRDCAD (SLE = 3; RA = 25), 52 non-IRDCAD patients, and 32 IRDNo CAD (RA = 32) from the Feiring Heart Biopsy Study. Aortic biopsies taken from the CAD only patients during CABG were previously evaluated for adventitial MCIs. The rare aortic biopsies from 3 SLE, 3 RA and 3 non-IRDCAD were assessed for the presence of C3 and C3d using immunohistochemistry. RESULTS:IRDCAD patients had higher p-TCC than non-IRDCAD or IRDNo CAD patients (p

Family B G protein-coupled receptors (GPCRs) play vital roles in hormone-regulated homeostasis. They are drug targets for metabolic diseases, including type 2 diabetes and osteoporosis. Despite their importance, the signaling mechanisms for family B GPCRs at the molecular level remain largely unexplored due to the challenges in purification of functional receptors in sufficient amount for biophysical characterization. Here, we purified the family B GPCR human glucagon-like peptide-1 (GLP-1) receptor (GLP1R), whose agonists, e.g. exendin-4, are used for the treatment of type 2 diabetes mellitus. The receptor was expressed in HEK293S GnTl- cells using our recently developed protocol. The protocol incorporates the receptor into the native-like lipid environment of reconstituted high density lipoprotein (rHDL) particles, also known as nanodiscs, immediately after the membrane solubilization step followed by chromatographic purification, minimizing detergent contact with the target receptor to reduce denaturation and prolonging stabilization of receptor in lipid bilayers without extra steps of reconstitution. This method yielded purified GLP1R in nanodiscs that could bind to GLP-1 and exendin-4 and activate Gs protein. This nanodisc purification method can potentially be a general strategy to routinely obtain purified family B GPCRs in the 10s of microgram amounts useful for spectroscopic analysis of receptor functions and activation mechanisms.

[This corrects the article DOI: 10.1371/journal.pone.0146574.].

We tested the hypothesis that loss of Nlrp3 would protect mice from Western diet-induced adipose tissue (AT) inflammation and associated glucose intolerance and cardiovascular complications. Five-week old C57BL6J wild-type (WT) and Nlrp3 knockout (Nlrp3-/-) mice were randomized to either a control diet (10% kcal from fat) or Western diet (45% kcal from fat and 1% cholesterol) for 24 weeks (n = 8/group). Contrary to our hypothesis that obesity-mediated white AT inflammation is Nlrp3-dependent, we found that Western diet-induced expression of AT inflammatory markers (i.e., Cd68, Cd11c, Emr1, Itgam, Lgals, Il18, Mcp1, Tnf, Ccr2, Ccl5 mRNAs, and Mac-2 protein) were not accompanied by increased caspase-1 cleavage, a hallmark feature of NLRP3 inflammasome activation. Furthermore, Nlrp3 null mice were not protected from Western diet-induced white or brown AT inflammation. Although Western diet promoted glucose intolerance in both WT and Nlrp3-/- mice, Nlrp3-/- mice were protected from Western diet-induced aortic stiffening. Additionally, Nlrp3-/- mice exhibited smaller cardiomyocytes and reduced cardiac fibrosis, independent of diet. Collectively, these findings suggest that presence of the Nlrp3 gene is not required for Western diet-induced AT inflammation and/or glucose intolerance; yet Nlrp3 appears to play a role in potentiating arterial stiffening, cardiac hypertrophy and fibrosis.

The body image concern (BIC) continuum ranges from a healthy and positive body image, to clinical diagnoses of abnormal body image, like body dysmorphic disorder (BDD). BDD and non-clinical, yet high-BIC participants have demonstrated a local visual processing bias, characterised by reduced inversion effects. To examine whether this bias is a potential marker of BDD, the visual processing of individuals across the entire BIC continuum was examined. Dysmorphic Concern Questionnaire (DCQ; quantified BIC) scores were expected to correlate with higher discrimination accuracy and faster reaction times of inverted stimuli, indicating reduced inversion effects (occurring due to increased local visual processing). Additionally, an induced global or local processing bias via Navon stimulus presentation was expected to alter these associations. Seventy-four participants completed the DCQ and upright-inverted face and body stimulus discrimination task. Moderate positive associations were revealed between DCQ scores and accuracy rates for inverted face and body stimuli, indicating a graded local bias accompanying increases in BIC. This relationship supports a local processing bias as a marker for BDD, which has significant assessment implications. Furthermore, a moderate negative relationship was found between DCQ score and inverted face accuracy after inducing global processing, indicating the processing bias can temporarily be reversed in high BIC individuals. Navon stimuli were successfully able to alter the visual processing of individuals across the BIC continuum, which has important implications for treating BDD.

A sustained inflation (SI) rapidly restores cardiac function in asphyxic, bradycardic newborns but its effects on cerebral haemodynamics and brain injury are unknown. We determined the effect of different SI strategies on carotid blood flow (CaBF) and cerebral vascular integrity in asphyxiated near-term lambs.Lambs were instrumented and delivered at 139 ± 2 d gestation and asphyxia was induced by delaying ventilation onset. Lambs were randomised to receive 5 consecutive 3 s SI (multiple SI; n = 6), a single 30 s SI (single SI; n = 6) or conventional ventilation (no SI; n = 6). Ventilation continued for 30 min in all lambs while CaBF and respiratory function parameters were recorded. Brains were assessed for gross histopathology and vascular leakage.CaBF increased more rapidly and to a greater extent during a single SI (p = 0.01), which then decreased below both other groups by 10 min, due to a higher cerebral oxygen delivery (p = 0.01). Blood brain barrier disruption was increased in single SI lambs as indicated by increased numbers of blood vessel profiles with plasma protein extravasation (p = 0.001) in the cerebral cortex. There were no differences in CaBF or cerebral oxygen delivery between the multiple SI and no SI lambs.Ventilation with an initial single 30 s SI improves circulatory recovery, but is associated with greater disruption of blood brain barrier function, which may exacerbate brain injury suffered by asphyxiated newborns. This injury may occur as a direct result of the initial SI or to the higher tidal volumes delivered during subsequent ventilation.

Many assays have been developed for the detection of influenza virus which is an important respiratory pathogen. Development of these assays commonly involves the use of human clinical samples for validation of their performance. However, clinical samples can be difficult to obtain, deteriorate over time, and be inconsistent in composition. The goal of this study was to develop a simulated respiratory secretion (SRS) that could act as a surrogate for clinical samples. To this end, we determined the effects major respiratory secretion components (Na+, K+, Ca2+, cells, albumin IgG, IgM, and mucin) have on the performance of influenza assays including both nucleic acid amplification and rapid antigen assays. Minimal effects on the molecular assays were observed for all of the components tested, except for serum derived human IgG, which suppressed the signal of the rapid antigen assays. Using dot blots we were able to show anti-influenza nucleoprotein IgG antibodies are common in human respiratory samples. We composed a SRS that contained mid-point levels of human respiratory sample components and studied its effect compared to phosphate buffered saline and virus negative clinical sample matrix on the Veritor, Sofia, CDC RT-PCR, Simplexa, cobas Liat, and Alere i influenza assays. Our results demonstrated that a SRS can interact with a variety of test methods in a similar manner to clinical samples with a similar impact on test performance.

Chromatin remodelling is integral to the formation of long-term memories. Recent evidence suggests that histone modification may play a role in the persistence of memories associated with drug use. The present series of experiments aimed to examine the effect of histone deacetylase (HDAC) inhibition on the extinction and reinstatement of nicotine self-administration. Rats were trained to intravenously self-administer nicotine for 12 days on a fixed-ratio 1 schedule. In Experiment 1, responding was then extinguished through removal of nicotine and response-contingent cues. After each extinction session, the HDAC inhibitor, sodium butyrate (NaB), was administered immediately, or six hours after each session. In Experiment 2, response-contingent cues remained available across extinction to increase rates of responding during this phase, and NaB was administered immediately after the session. Finally, in Experiment 3, the effect of NaB treatment on extinction of responding for sucrose pellets was assessed. Across all experiments reinstatement to the cue and/or the reward itself was then tested. In the first experiment, treatment with NaB significantly attenuated nicotine and nicotine + cue reinstatement when administered immediately, but not six hours after each extinction session. When administered after cue-extinction (Expt. 2), NaB treatment specifically facilitated the rate of extinction across sessions, indicating that HDAC inhibition enhanced consolidation of the extinction memory. In contrast, there was no effect of NaB on the extinction and reinstatement of sucrose-seeking (Expt. 3), indicating that the observed effects are specific to a drug context. These results provide the first demonstration that HDAC inhibition facilitates the extinction of responding for an intravenously self-administered drug of abuse and further highlight the potential of HDAC inhibitors in the treatment of drug addiction.

To examine the association of employment status and characteristics with prevalent and incident memory complaints (MC) in 55-64-year-olds.Subjects were participants of the Longitudinal Aging Study Amsterdam (LASA). Respondents with baseline data were selected to examine the association of employment status (n = 1525) and employment characteristics (n = 1071) with prevalent MC (i.e., MC at baseline). Respondents without MC at baseline were selected to examine the association of employment (n = 526) and employment characteristics (n = 379; working hours, job prestige, job level, psychological job demands, iso-strain) with incident MC (i.e., no MC at baseline and MC at three-year follow-up). Associations were adjusted for relevant covariates (demographics, memory performance, physical health, mental health, personality traits). Logistic regression was applied. Data were weighed according to gender and age of the Dutch population.At baseline 20.5% reported MC. At three-year follow-up, 15.4% had incident MC. No associations were found between employment status and MC. Adjusted analysis revealed that individuals with high occupational cognitive demands were more likely to have prevalent MC.Middle-aged workers are equally as likely to experience MC as non-working age-peers. Among workers, those with cognitively demanding work were more likely to experience MC, independent of memory performance. Memory decline due to ageing may be noticed sooner in 55-64-year-olds performing cognitively demanding work.

Maternal behaviour is a crucial component of reproduction in all mammals; however the quality of care that mothers give to infants can vary greatly. It is vital to document variation in maternal behaviour caused by the physiological processes controlling its expression. This underlying physiology should be conserved throughout reproductive events and should be replicated across all individuals of a species; therefore, any correlates to maternal care quality may be present across many individuals or contexts. Oxytocin modulates the initiation and expression of maternal behaviour in mammals; therefore we tested whether maternal plasma oxytocin concentrations correlated to key maternal behaviours in wild grey seals (Halichoerus grypus). Plasma oxytocin concentrations in non-breeding individuals (4.3 ± 0.5 pg/ml) were significantly lower than those in mothers with dependent pups in both early (8.2 ± 0.8 pg/ml) and late (6.9 ± 0.7 pg/ml) lactation. Maternal plasma oxytocin concentrations were not correlated to the amount of nursing prior to sampling, or a mother's nursing intensity throughout the dependent period. Mothers with high plasma oxytocin concentrations stayed closer to their pups, reducing the likelihood of mother-pup separation during lactation which is credited with causing starvation, the largest cause of pup mortality in grey seals. This is the first study to link endogenous oxytocin concentrations in wild mammalian mothers with any type of maternal behaviour. Oxytocin's structure and function is widely conserved across mammalian mothers, including humans. Defining the impact the oxytocin system has on maternal behaviour highlights relationships that may occur across many individuals or species, and such behaviours heavily influence infant development and an individual's lifetime reproductive success.

Hand-held dynamometry (HHD) has never previously been used to examine isometric muscle power. Rate of force development (RFD) is often used for muscle power assessment, however no consensus currently exists on the most appropriate method of calculation. The aim of this study was to examine the reliability of different algorithms for RFD calculation and to examine the intra-rater, inter-rater, and inter-device reliability of HHD as well as the concurrent validity of HHD for the assessment of isometric lower limb muscle strength and power.30 healthy young adults (age: 23±5 yrs, male: 15) were assessed on two sessions. Isometric muscle strength and power were measured using peak force and RFD respectively using two HHDs (Lafayette Model-01165 and Hoggan microFET2) and a criterion-reference KinCom dynamometer. Statistical analysis of reliability and validity comprised intraclass correlation coefficients (ICC), Pearson correlations, concordance correlations, standard error of measurement, and minimal detectable change.Comparison of RFD methods revealed that a peak 200 ms moving window algorithm provided optimal reliability results. Intra-rater, inter-rater, and inter-device reliability analysis of peak force and RFD revealed mostly good to excellent reliability (coefficients ≥ 0.70) for all muscle groups. Concurrent validity analysis showed moderate to excellent relationships between HHD and fixed dynamometry for the hip and knee (ICCs ≥ 0.70) for both peak force and RFD, with mostly poor to good results shown for the ankle muscles (ICCs = 0.31-0.79).Hand-held dynamometry has good to excellent reliability and validity for most measures of isometric lower limb strength and power in a healthy population, particularly for proximal muscle groups. To aid implementation we have created freely available software to extract these variables from data stored on the Lafayette device. Future research should examine the reliability and validity of these variables in clinical populations.

Human respiratory syncytial virus (RSV) is the leading cause of respiratory tract infections in children globally, with nearly all children experiencing at least one infection by the age of two. Partial sequencing of the attachment glycoprotein gene is conducted routinely for genotyping, but relatively few whole genome sequences are available for RSV. The goal of our study was to sequence the genomes of RSV strains collected from multiple countries to further understand the global diversity of RSV at a whole-genome level.We collected RSV samples and isolates from Mexico, Argentina, Belgium, Italy, Germany, Australia, South Africa, and the USA from the years 1998-2010. Both Sanger and next-generation sequencing with the Illumina and 454 platforms were used to sequence the whole genomes of RSV A and B. Phylogenetic analyses were performed using the Bayesian and maximum likelihood methods of phylogenetic inference.We sequenced the genomes of 34 RSVA and 23 RSVB viruses. Phylogenetic analysis showed that the RSVA genome evolves at an estimated rate of 6.72 × 10(-4) substitutions/site/year (95% HPD 5.61 × 10(-4) to 7.6 × 10(-4)) and for RSVB the evolutionary rate was 7.69 × 10(-4) substitutions/site/year (95% HPD 6.81 × 10(-4) to 8.62 × 10(-4)). We found multiple clades co-circulating globally for both RSV A and B. The predominant clades were GA2 and GA5 for RSVA and BA for RSVB.Our analyses showed that RSV circulates on a global scale with the same predominant clades of viruses being found in countries around the world. However, the distribution of clades can change rapidly as new strains emerge. We did not observe a strong spatial structure in our trees, with the same three main clades of RSV co-circulating globally, suggesting that the evolution of RSV is not strongly regionalized.

Functional sensory and motor areas in the developing mammalian neocortex are formed through a complex interaction of cortically intrinsic mechanisms, such as gene expression, and cortically extrinsic mechanisms such as those mediated by thalamic input from the senses. Both intrinsic and extrinsic mechanisms are believed to be involved in cortical patterning and the establishment of areal boundaries in early development; however, the nature of the interaction between intrinsic and extrinsic processes is not well understood. In a previous study, we used a perinatal bilateral enucleation mouse model to test some aspects of this interaction by reweighting sensory input to the developing cortex. Visual deprivation at birth resulted in a shift of intraneocortical connections (INCs) that aligned with ectopic ephrin A5 expression in the same location ten days later at postnatal day (P) 10. A prevailing question remained: Does visual deprivation first induce a change in gene expression, followed by a shift in INCs, or vice versa? In the present study, we address this question by investigating the neuroanatomy and patterns of gene expression in post-natal day (P) 1 and 4 mice following bilateral enucleation at birth. Our results demonstrate a rapid reduction in dorsal lateral geniculate nucleus (dLGN) size and ephrin A5 gene expression 24-hours post-enucleation, with more profound effects apparent at P4. The reduced nuclear size and diminished gene expression mirrors subtle changes in ephrin A5 expression evident in P1 and P4 enucleated neocortex, 11 and 8 days prior to natural eye opening, respectively. Somatosensory and visual INCs were indistinguishable between P1 and P4 mice bilaterally enucleated at birth, indicating that perinatal bilateral enucleation initiates a rapid change in gene expression (within one day) followed by an alteration of sensory INCs later on (second postnatal week). With these results, we gain a deeper understanding of how gene expression and sensory input together regulate cortical arealization and plasticity during early development.

BACKGROUND:As measurement of arterial oxygen saturation (SpO2) is common in the delivery room, target SpO2 ranges allow clinicians to titrate oxygen therapy for preterm infants in order to achieve saturation levels similar to those seen in normal term infants in the first minutes of life. However, the influence of the onset of ventilation and the timing of cord clamping on systemic and cerebral oxygenation is not known. AIM:We investigated whether the initiation of ventilation, prior to, or after umbilical cord clamping, altered systemic and cerebral oxygenation in preterm lambs. METHODS:Systemic and cerebral blood-flows, pressures and peripheral SpO2 and regional cerebral tissue oxygenation (SctO2) were measured continuously in apnoeic preterm lambs (126±1 day gestation). Positive pressure ventilation was initiated either 1) prior to umbilical cord clamping, or 2) after umbilical cord clamping. Lambs were monitored intensively prior to intervention, and for 10 minutes following umbilical cord clamping. RESULTS:Clamping the umbilical cord prior to ventilation resulted in a rapid decrease in SpO2 and SctO2, and an increase in arterial pressure, cerebral blood flow and cerebral oxygen extraction. Ventilation restored oxygenation and haemodynamics by 5-6 minutes. No such disturbances in peripheral or cerebral oxygenation and haemodynamics were observed when ventilation was initiated prior to cord clamping. CONCLUSION:The establishment of ventilation prior to umbilical cord clamping facilitated a smooth transition to systemic and cerebral oxygenation following birth. SpO2 nomograms may need to be re-evaluated to reflect physiological management of preterm infants in the delivery room.

The contribution of poor finger force control to age-related decline in manual dexterity is above and beyond ubiquitous behavioral slowing. Altered control of the finger forces can impart unwanted torque on the object affecting its orientation, thus impairing manual performance. Anodal transcranial direct current stimulation (tDCS) over primary motor cortex (M1) has been shown to improve the performance speed on manual tasks in older adults. However, the effects of anodal tDCS over M1 on the finger force control during object manipulation in older adults remain to be fully explored. Here we determined the effects of anodal tDCS over M1 on the control of grip force in older adults while they manipulated an object with an uncertain mechanical property. Eight healthy older adults were instructed to grip and lift an object whose contact surfaces were unexpectedly made more or less slippery across trials using acetate and sandpaper surfaces, respectively. Subjects performed this task before and after receiving anodal or sham tDCS over M1 on two separate sessions using a cross-over design. We found that older adults used significantly lower grip force following anodal tDCS compared to sham tDCS. Friction measured at the finger-object interface remained invariant after anodal and sham tDCS. These findings suggest that anodal tDCS over M1 improved the control of grip force during object manipulation in healthy older adults. Although the cortical networks for representing objects and manipulative actions are complex, the reduction in grip force following anodal tDCS over M1 might be due to a cortical excitation yielding improved processing of object-specific sensory information and its integration with the motor commands for production of manipulative forces. Our findings indicate that tDCS has a potential to improve the control of finger force during dexterous manipulation in older adults.

Caffeine is widely consumed throughout the world and appears to indirectly facilitate learning and memory through effects on attention and motivation. Animal work indicates that post-training caffeine administration augments inhibitory avoidance memory, spatial memory, and object memory. In humans, post-training caffeine administration enhances the ability to discern between familiar images and new, similar images. However, the effect of post-training caffeine administration on motor memory has not been examined. Therefore, we tested two groups of low caffeine consumers (average weekly consumption ≤500 mg) in a double-blind, placebo-controlled study involving acquisition of a continuous isometric visuomotor tracking skill. On Day 1, subjects completed 5 blocks (150 repetitions) of training on the continuous isometric visuomotor skill and subsequently ingested either 200 mg of caffeine or placebo. On day 2, subjects completed an additional 5 blocks of training. Day 1 mean performance and performance variability were both similar between groups, suggesting that both groups acquired the motor skill similarly. For mean performance on Day 2, patterns of re-learning, mean performance learning magnitudes, mean performance learning rates, and mean performance retention magnitudes were all similar between groups. For performance variability on Day 2, there was a small trend towards increased variability in the caffeine group during re-learning, but performance variability learning magnitudes and performance variability retention magnitudes did not differ between groups. Because motor skill acquisition can also be conceptualized as a reduction in performance variability, these results suggest that there may be a small negative effect of post-practice caffeine administration on memory of a newly-learned visuomotor skill. Overall, we found no evidence to suggest that post-training caffeine administration enhances 24-hour retention of a newly-learned continuous visuomotor skill, and these results support the notion that memory-enhancing effects of post-training caffeine ingestion may be task-specific.

The Wii Balance Board (WBB) is a globally accessible device that shows promise as a clinically useful balance assessment tool. Although the WBB has been found to be comparable to a laboratory-grade force platform for obtaining centre of pressure data, it has not been comprehensively studied in clinical populations. The aim of this study was to investigate the measurement properties of tests utilising the WBB in people after stroke.Thirty individuals who were more than three months post-stroke and able to stand unsupported were recruited from a single outpatient rehabilitation facility. Participants performed standardised assessments incorporating the WBB and customised software (static stance with eyes open and closed, static weight-bearing asymmetry, dynamic mediolateral weight shifting and dynamic sit-to-stand) in addition to commonly employed clinical tests (10 Metre Walk Test, Timed Up and Go, Step Test and Functional Reach) on two testing occasions one week apart. Test-retest reliability and construct validity of the WBB tests were investigated.All WBB-based outcomes were found to be highly reliable between testing occasions (ICC = 0.82 to 0.98). Correlations were poor to moderate between WBB variables and clinical tests, with the strongest associations observed between task-related activities, such as WBB mediolateral weight shifting and the Step Test.The WBB, used with customised software, is a reliable and potentially useful tool for the assessment of balance and weight-bearing asymmetry following stroke. Future research is recommended to further investigate validity and responsiveness.

BackgroundThe onset of mechanical ventilation is a critical time for the initiation of cerebral white matter (WM) injury in preterm neonates, particularly if they are inadvertently exposed to high tidal volumes (VT) in the delivery room. Protective ventilation strategies at birth reduce ventilation-induced lung and brain inflammation and injury, however its efficacy in a compromised newborn is not known. Chorioamnionitis is a common antecedent of preterm birth, and increases the risk and severity of WM injury. We investigated the effects of high VT ventilation, after chorioamnionitis, on preterm lung and WM inflammation and injury, and whether a protective ventilation strategy could mitigate the response.MethodsPregnant ewes (n = 18) received intra-amniotic lipopolysaccharide (LPS) 2 days before delivery, instrumentation and ventilation at 127±1 days gestation. Lambs were either immediately euthanased and used as unventilated controls (LPSUVC; n = 6), or were ventilated using an injurious high VT strategy (LPSINJ; n = 5) or a protective ventilation strategy (LPSPROT; n = 7) for a total of 90 min. Mean arterial pressure, heart rate and cerebral haemodynamics and oxygenation were measured continuously. Lungs and brains underwent molecular and histological assessment of inflammation and injury.ResultsLPSINJ lambs had poorer oxygenation than LPSPROT lambs. Ventilation requirements and cardiopulmonary and systemic haemodynamics were not different between ventilation strategies. Compared to unventilated lambs, LPSINJ and LPSPROT lambs had increases in pro-inflammatory cytokine expression within the lungs and brain, and increased astrogliosis (pConclusionsVentilation after acute chorioamnionitis, irrespective of strategy used, increases haemodynamic instability and lung and cerebral inflammation and injury. Mechanical ventilation is a potential contributor to WM injury in infants exposed to chorioamnionitis.

To assess the impact of mental health visits (MHV) on the cost of care for Veterans with diabetes and comorbid mental health conditions.A national cohort of 120,852 Veterans with diabetes and at least one mental health diagnosis (i.e., substance abuse, depression or psychoses) in 2002 was followed through 2006. Outcomes were pharmacy, inpatient and outpatient costs in 2012 dollars.Least-square covariate adjusted estimates from the joint model of total VA costs of the number of MHV using December 31, 2012 value dollars indicate that relative to those with fewer MHV, those with 3+ MHV had the lowest mean inpatient cost ($21,406), but the highest mean outpatient and pharmacy cost ($9,727 and $2,015, respectively). If all Veterans who received zero MHV actually received 3+ MHV, we estimate through simulated scenarios that between $32,272,329 and $181,460,247 in inpatient costs would be saved. However, these savings would be offset by additional expenditures of between $1,166,017,547 and $1,166,224,787 in outpatient costs and between $151,604,683 and $161,439,632 in pharmacy costs.Among Veterans with diabetes and comorbid mental disorders having three or more mental health visits is associated with marginally decreased inpatient cost, but these potential savings seem to be offset by increased outpatient and pharmacy costs.

To measure organismal coherence in a pelagic ecosystem, we used moored sensors to describe the vertical dynamics of each step in the food chain in shelf waters off the west shore of Oahu, Hawaii. Horizontally extensive, intense aggregations of phytoplankton, zooplankton, and micronekton exhibited strong diel patterns in abundance and vertical distribution, resulting in a highly variable potential for interaction amongst trophic levels. Only around dusk did zooplankton layers overlap with phytoplankton layers. Shortly after sunset, micronekton ascended from the deep, aggregating on the island's shelf. Short-lived departures in migration patterns were detected in depth, vertical distribution, density, and total abundance of micronekton when zooplankton layers were present with typical patterns resuming within one hour. Layers of zooplankton began to disappear within 20 minutes of the arrival of micronekton with no layers present after 50 minutes. The effects of zooplankton layers cascaded even further up the food chain, affecting many behaviors of dolphins observed at dusk including their depth, group size, and inter-individual spacing. As a result of these changes in behavior, during a 30-minute window just after dusk, the number of feeding events observed for each dolphin and consequently the feeding time for each individual more than doubled when zooplankton layers were present. Dusk is a critical period for interactions amongst species in this system from phytoplankton to top predators. Our observations that short time windows can drive the structure and function of a complex suite of organisms highlight the importance of explicitly adding a temporal dimension at a scale relevant to individual organisms to our descriptions of heterogeneity in ocean ecosystems.