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The aim of this study was to investigate inequities in substance use disorder (SUD) diagnosis, opioid misuse, marijuana misuse, SUD treatment utilization, and utilization of university mental health services among sexual and gender minority (SGM) American Indian, Alaska Native, and Native Hawaiian (AI/AN/NH) college students.Data consisting of 8,103 AI/AN/NH students' responses to the American College Health Association's National College Health Assessment survey from fall 2015 through spring 2019 were utilized for this study. Multivariable logistic regression models were used to compare the odds of SUD diagnosis, opioid misuse, and marijuana misuse in SGM AI/AN/NH students to cisgender, heterosexual peers. Unadjusted odds of SUD treatment utilization and utilization of university mental health services were also evaluated.Compared to cisgender females, transgender (aOR = 4.43, 95% CI = 2.67-7.34) and gender diverse (aOR = 2.86, 95% CI = 1.61-5.07) students had significantly higher odds of SUD diagnosis. Similarly, significantly higher odds of SUD diagnosis were observed among sexual minorities, including gay/lesbian (aOR = 2.95, 95% CI = 1.71-5.09) and bisexual (aOR = 1.97, 95% CI = 1.30-2.99) students compared to heterosexual peers. Sexual minority students had significantly higher odds of utilizing university mental health services (uOR = 2.43, 95% CI = 1.22-4.84) than heterosexual peers. Odds of opioid misuse and marijuana misuse were also significantly increased among sexual minority students.AI/AN/NH college students who identify as SGM have higher odds of SUD diagnosis, opioid misuse, and marijuana misuse than their cisgender, heterosexual peers. These findings highlight the need to consider tailored programming for SGM AI/AN/NH students in substance use prevention and intervention efforts in U.S. college settings.

Impaired memory is a hallmark of prodromal Alzheimer’s Disease (AD). Prior knowledge associated with the memoranda has proved to have a powerful effect on memory in healthy subjects. Yet, barely nothing is known about its effect in early AD. We used functional MRI to ask whether prior knowledge enhanced memory encoding in early AD and whether the nature of prior knowledge mattered. Early AD patients and healthy controls underwent a task-based fMRI experiment, being scanned while learning face-scene associations. Famous faces carried Pre-Experimental Knowledge (PEK) while unknown faces repeatedly familiarized prior to learning carried Experimental Knowledge (EK). As expected, PEK increased subsequent memory in healthy elderly. However, patients did not benefit from PEK. Partly non-overlapping brain networks supported PEK vs. EK encoding in healthy controls. Patients displayed impaired activation in a right subhippocampal region where activity predicted successful associative memory formation of PEK stimuli. These findings call for a thorough consideration of how prior knowledge impacts learning and suggest a possible underestimation of the extent of associative memory impairment in early AD.HighlightsLearning is impaired in prodromal AD, but we currently ignore whether prior knowledge available at encoding promotes learning in AD as it does in healthy controls.Patients with AD failed to benefit from pre-experimental prior knowledge (famous faces) by comparison with experimental knowledge (unknown but familiarized faces).fMRI responses at study revealed distinct networks underlying associative encoding for both pre-experimental and experimental knowledge.A subsequent memory effect found in control subjects for associations carrying pre-experimental knowledge in the right subhippocampal structures, including the perirhinal cortex, was absent in patients.Pre-experimental knowledge-based associative encoding relies on brain regions specifically targeted by early tau pathology.Using unfamiliar materials to probe memory in early AD might underestimate learning impairment.

Improved understanding of the overall distribution of workplace coronavirus disease 2019 (COVID-19) outbreaks by industry sector could help direct targeted public health action; however, this has not been described. The Utah Department of Health (UDOH) analyzed COVID-19 surveillance data to describe workplace outbreaks by industry sectors. In this report, workplaces refer to non-health care, noncongregate-living, and noneducational settings. As of June 5, 2020, UDOH reported 277 COVID-19 outbreaks, 210 (76%) of which occurred in workplaces. Approximately 12% (1,389 of 11,448) of confirmed COVID-19 cases in Utah were associated with workplace outbreaks. The 210 workplace outbreaks occurred in 15 of 20 industry sectors;* nearly one half of all workplace outbreaks occurred in three sectors: Manufacturing (43; 20%), Construction (32; 15%) and Wholesale Trade (29; 14%); 58% (806 of 1,389) of workplace outbreak-associated cases occurred in these three sectors. Although 24% of Utah's workforce in all 15 affected sectors identified as Hispanic or Latino (Hispanic) or a race other than non-Hispanic white (nonwhite†) (1), 73% (970 of 1,335) of workplace outbreak-associated COVID-19 cases were in persons who identified as Hispanic or nonwhite. Systemic social inequities have resulted in the overrepresentation of Hispanic and nonwhite workers in frontline occupations where exposure to SARS-CoV-2, the virus that causes COVID-19, might be higher (2); extra vigilance in these sectors is needed to ensure prevention and mitigation strategies are applied equitably and effectively to workers of racial and ethnic groups disproportionately affected by COVID-19. Health departments can adapt workplace guidance to each industry sector affected by COVID-19 to account for different production processes and working conditions.

PROBLEM IDENTIFICATION. Hot flashes (HF) are common and bothersome in breast and prostate cancer and can adversely impact patients’ quality of life. The best approach to manage them is unclear. We sought to perform network meta-analyses (NMA) of the available evidence to compare interventions previously studied in the literature. LITERATURE SEARCH. A librarian searched Medline, Embase, and additional databases for randomized controlled trials (RCTs) evaluating the effects of one or more interventions for hot flashes in patients with a history of breast or prostate cancer. DATA EVALUATION. Outcomes of interest included changes in HF severity, HF frequency, quality of life, and harms. Two reviewers were involved in the phases of study selection, data collection and risk of bias appraisal. Pairwise meta-analyses and NMAs were performed where feasible, with narrative synthesis used where required. SYNTHESIS. 40 RCTs studying drugs, psychological interventions, natural health products and exercise were included. Most interventions were assessed in only one trial, typically versus inactive control. The outcomes of interest were not consistently available from the included studies, and NMAs were feasible for HF frequency and HF score. Findings from NMA for HF frequency suggested several therapies may offer benefits compared to no treatment, though little data suggested differences between active therapies. Findings from NMA for HF score were similar. For remaining outcomes including HF severity, QoL measures and harms, studies were summarized narratively due to limited availability of data. Limited evidence of clear benefits was found for the therapies assessed. IMPLICATIONS FOR RESEARCH. While many interventions may offer improvements for HFs versus no treatment, few data suggest important differences between therapies. Future research is needed to enrich available evidence for decision-making. REVIEW REGISTRATION #: CRD42015024286

BACKGROUND AND PURPOSE Accumulating evidence suggests that there is a sexual dimorphism in brain health, with women exhibiting greater disability following strokes of comparable size and having a higher prevalence of cognitive impairment later in life. Despite the critical implication of the cerebrovascular architecture in brain perfusion and brain health, it remains unclear whether structural differences in vessel density exist across the sexes. METHODS In this study, we used high-density MRI imaging to characterize the intracerebral arterial and venous density of 28 (14 women) sex-matched healthy young volunteers in vivo. Using an in-house vessel segmentation algorithm, we quantified and compared these vascular features across the cortical and subcortical deep gray matter, white matter, and periventricular white matter. RESULTS We found that, on average, women have reduced intracerebral arterial density in comparison to men (F 2.34 ± 0.48%, M 2.67 ± 0.39%; p

Mental health disorders are prevalent among college students in the US. Perceived discrimination is a known risk factor for adverse mental health and is widespread on college campuses.We estimated the association between perceived discrimination and mental health among US college students using the American College Health Association-National College Health Assessment (ACHA-NCHA), a large national cross-sectional survey of college students.7.9% of students reported experiences of discrimination, and that discrimination was more common among minority students. Perceived discrimination was associated with 86 excess cases of students reporting being too depressed to function per 1000 students, and 27 excess cases of students reporting seriously considering suicide per 1000 students. Students who experienced discrimination had a 37% increase in the number of mental health symptoms (IRR 1.37 [95% CI 1.35, 1.39], P .0001) compared to non-discriminated students, and a 94% increase in the number of mental health diagnoses (IRR 1.94 [95% CI 1.89, 1.99], P .0001). Discrimination was positively associated with all mental health symptoms and diagnoses. This pattern was largely held across sub-analyses by race/ethnicity, gender, and sexual orientation, but with varying magnitudes.Inability to distinguish between the forms of discrimination experienced, whether involving gender, sexual orientation, or race/ethnicity.Consequences of perceived discrimination are of clinical relevance for healthcare providers in general and mental health providers in particular. This study confirms the association between perceived discrimination and adverse mental health in college students. Efforts to reduce discrimination and bias in college campuses may improve the mental health of students.

OBJECTIVES To describe the demographics, clinical characteristics, and hospital course among persons METHODS We conducted a retrospective case series of suspected SARS-CoV-2-associated deaths in the United States in persons RESULTS We included 112 SARS-CoV-2-associated deaths from 25 participating jurisdictions. The median age was 17 years (IQR 8.5–19 years). Most decedents were male (71, 63%), 31 (28%) were Black (non-Hispanic) persons, and 52 (46%) were Hispanic persons. Ninety-six decedents (86%) had at least 1 underlying condition; obesity (42%), asthma (29%), and developmental disorders (22%) were most commonly documented. Among 69 hospitalized decedents, common complications included mechanical ventilation (75%) and acute respiratory failure (82%). The sixteen (14%) decedents who met multisystem inflammatory syndrome in children (MIS-C) criteria were similar in age, sex, and race and/or ethnicity to decedents without MIS-C; 11 of 16 (69%) had at least 1 underlying condition. CONCLUSIONS SARS-CoV-2-associated deaths among persons

Reactive oxygen species (ROS) are important signaling molecules mediating the exercise-induced adaptations in skeletal muscle. Acute exercise also drives the expression of genes involved in reesterification and glyceroneogenesis in white adipose tissue (WAT), but whether ROS play any role in this effect has not been explored. We speculated that exercise-induced ROS would regulate acute exercise-induced responses in WAT. To address this question, we utilized various models to alter redox signaling in WAT. We examined basal and exercise-induced gene expression in a genetically modified mouse model of reduced mitochondrial ROS emission [mitochondrial catalase overexpression (MCAT)]. Additionally, H2O2, various antioxidants, and the β3-adrenergic receptor agonist CL316243 were used to assess gene expression in white adipose tissue culture. MCAT mice have reduced ROS emission from WAT, enlarged WAT depots and adipocytes, and greater pyruvate dehydrogenase kinase-4 ( Pdk4) gene expression. In WAT culture, H2O2reduced glyceroneogenic gene expression. In wild-type mice, acute exercise induced dramatic but transient increases in Pdk4 and phosphoenolpyruvate carboxykinase ( Pck1) mRNA in both subcutaneous inguinal WAT and epididymal WAT depots, which was almost completely absent in MCAT mice. Furthermore, the induction of Pdk4 and Pck1 in WAT culture by CL316243 was markedly reduced in the presence of antioxidants N-acetyl-cysteine or vitamin E. Genetic and nutritional approaches that attenuate redox signaling prevent exercise- and β-agonist-induced gene expression within WAT. Combined, these data suggest that ROS represent important mediators of gene expression within WAT.

Objective This open-label, controlled, randomized study assessed the safety, tolerability, and efficacy of StrataGraft tissue compared to autograft in the treatment of deep partial-thickness (DPT) burns. Methods Thirty subjects with DPT thermal burns (3%–43% total body surface area) were treated with StrataGraft tissue as follows: cohort 1, ≤220 cm2 refrigerated tissue; cohort 2, ≤440 cm2 refrigerated tissue; and cohort 3, ≤440 cm2 cryopreserved tissue. On each subject, two comparable areas of DPT burn were randomized to receive StrataGraft tissue or autograft. Coprimary end points were the percent area of the StrataGraft tissue treatment site undergoing salvage autografting by Day 28 and wound closure of treatment sites by 3 months. Results By Day 28, no StrataGraft tissue treatment sites underwent autografting. By 3 months, 93% and 100% of the StrataGraft tissue and autograft treatment sites achieved complete wound closure, respectively. No significant differences in observer total and overall opinion POSAS scores between StrataGraft tissue and autograft treatment sites were observed at any timepoint. The most common adverse event was pruritus (17%). Conclusions StrataGraft tissue treatment of DPT thermal burns reduced the need for autograft, resulted in wound closure and treatment-site cosmesis comparable to that of autograft, and was well tolerated.

Plasmodium sexual differentiation is required for malaria transmission, yet much remains unknown about its regulation. Here, we quantify early gametocyte-committed ring (gc-ring) stage, P. falciparum parasites in 260 uncomplicated malaria patient blood samples 10 days before maturation to transmissible stage V gametocytes using a gametocyte conversion assay (GCA). Seventy six percent of the samples have gc-rings, but the ratio of gametocyte to asexual-committed rings (GCR) varies widely (0–78%). GCR correlates positively with parasitemia and is negatively influenced by fever, not hematocrit, age or leukocyte counts. Higher expression levels of GDV1-dependent genes, ap2-g, msrp1 and gexp5, as well as a gdv1 allele encoding H217 are associated with high GCR, while high plasma lysophosphatidylcholine levels are associated with low GCR in the second study year. The results provide a view of sexual differentiation in the field and suggest key regulatory roles for clinical factors and gdv1 in gametocytogenesis in vivo., Here, the authors quantify early gametocyte-committed ring (gc-ring) stage Plasmodium falciparum parasites in 260 malaria patients 10 days before maturation to transmissible stage V gametocytes, and show that the ratio of circulating gc-rings is positively correlated with parasitemia and negatively correlated with body temperature.

Discrimination has been associated with adverse health behaviors and outcomes, including substance use. Higher rates of substance use are reported among some marginalized groups, such as lesbian, gay, and bisexual populations, and have been partially attributed to discrimination. This study uses 2015–2019 National College Health Assessment data to determine whether college students reporting discrimination due to sexual orientation, race/ethnicity, gender, or age report greater substance use than their peers who do not report such experiences. Additionally, we assess exploratory questions regarding whether substance choices differ among students who reported facing discrimination. Over time, about 8.0% of students reported experiencing discrimination in the past year. After applying inverse probability treatment weights (IPTWs), exposure to discrimination was associated with an excess of 44 cases of marijuana use per 1,000 students, an excess of 39 cases of alcohol use per 1,000 students, and an excess of 11 cases of prescription painkiller use per 1,000 students. Multivariable logistic regression models with IPTW demonstrated that students who experienced discrimination were more than twice as likely to use inhalants and methamphetamine. These students were also significantly more likely to use other drugs, including opiates, non-prescribed painkillers, marijuana, alcohol, hallucinogens, cocaine, and cigarettes; however, the differences with peers were smaller in magnitude. Students who experienced discrimination did not differ from peers who reported non-prescribed antidepressants use and were significantly less likely to use e-cigarettes and smokeless tobacco. Associations between discrimination and substance use vary by race, gender, sexual orientation, and age. These findings indicate that discrimination has significant associations with many kinds of substance use; however, the magnitude varies by substance type. More institutional efforts to address sources of discrimination affecting college students are needed.

Animal models of viral disease are very important for understanding how viruses make people sick and for testing out drugs and vaccines to see if they can prevent disease. In this study, we identify the ferret as a model of encephalitis caused by Rift Valley fever virus (RVFV). This novel model will allow researchers to evaluate ways to prevent RVFV encephalitis., Rift Valley fever virus (RVFV) is a pathogen of both humans and livestock in Africa and the Middle East. Severe human disease is associated with hepatitis and/or encephalitis. Current pathogenesis studies rely on rodents and nonhuman primates, which have advantages and disadvantages. We evaluated disease progression in Mustela putorius furo (the ferret) following intradermal (i.d.) or intranasal (i.n.) infection. Infected ferrets developed hyperpyrexia, weight loss, lymphopenia, and hypoalbuminemia. Three of four ferrets inoculated intranasally with RVFV developed central nervous system (CNS) disease that manifested as seizure, ataxia, and/or hind limb weakness at 8 to 11 days postinfection (dpi). Animals with clinical CNS disease had transient viral RNAemia, high viral RNA loads in the brain, and histopathological evidence of encephalitis. The ferret model will facilitate our understanding of how RVFV accesses the CNS and has utility for the evaluation of vaccines and/or therapeutics in preventing RVFV CNS disease. IMPORTANCE Animal models of viral disease are very important for understanding how viruses make people sick and for testing out drugs and vaccines to see if they can prevent disease. In this study, we identify the ferret as a model of encephalitis caused by Rift Valley fever virus (RVFV). This novel model will allow researchers to evaluate ways to prevent RVFV encephalitis.

We describe coronavirus disease (COVID-19) among US food manufacturing and agriculture workers and provide updated information on meat and poultry processing workers. Among 742 food and agriculture workplaces in 30 states, 8,978 workers had confirmed COVID-19; 55 workers died. Racial and ethnic minority workers could be disproportionately affected by COVID-19.

Since February 12, 2020, approximately 6.5 million cases of SARS-CoV-2 infection, the cause of coronavirus disease 2019 (COVID-19), and 190,000 SARS-CoV-2-associated deaths have been reported in the United States (1,2). Symptoms associated with SARS-CoV-2 infection are milder in children compared with adults (3). Persons aged

IntroductionMusculoskeletal injuries (MSKi) are a common challenge for those in military careers. Compared to their male peers, reports indicate that female military members and recruits are at greater risk of suffering MSKi during training and deployment. The objectives of this study were to identify the types and causes of MSKi among female military personnel and to explore the various risk factors associated with MSKi.Materials and MethodsA scoping review was conducted over a 4-month time frame of English language, peer-reviewed studies published from 1946 to 2019. Search strategies for major biomedical databases (e.g., MEDLINE; Embase Classic + Embase; and the following EBM Reviews—Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Health Technology Assessment, and the NHS Economic Evaluation Database) were developed by a senior medical information specialist and included 2,891 titles/abstracts. Study selection and data collection were designed according to the Population, Concept, and Context framework. Studies were included if the study population provided stratified data for females in a military context.ResultsFrom a total of 2,287 citations captured from the literature searches, 168 peer-reviewed publications (144 unique studies) were eligible for inclusion. Studies were identified from across 10 countries and published between 1977 and 2019. Study designs were primarily prospective and retrospective cohorts. Most studies assessed both prevalence/incidence and risk factors for MSKi (62.50%), with few studies assessing cause (13.69%). For MSKi of female recruits compared to active female members, the prevalence was higher (19.7%-58.3% vs. 5.5%-56.6%), but the incidence (0.02%-57.7% vs. 13.5%-71.9%) was lower. The incidence of stress fractures was found to be much higher in female recruits than in active members (1.6%-23.9% vs. 2.7%). For anthropometric risk factors, increased body fat was a predictor of MSKi, but not stress fractures. For physiological risk factors for both female military groups, being less physically fit, later menarche, and having no/irregular menses were predictors of MSKi and stress fractures. For biomechanical risk factors, among female recruits, longer tibial length and femoral neck diameter increased the risk of stress fractures, and low foot arch increased risk of an ankle sprain. For female active military members, differences in shoulder rotation and bone strength were associated with risk of MSKi. For biological sex, being female compared to male was associated with an increased risk of MSKi, stress fractures, and general injuries. The consequences of experiencing MSKi for active military included limited duties, time off, and discharge. For recruits, these included missed training days, limited duty days, and release.ConclusionsThis scoping review provides insight into the current state of the evidence regarding the types and causes of MSKi, as well as the factors that influence MSKi among females in the military. Future research endeavors should focus on randomized controlled trials examining training paradigms to see if women are more susceptible. The data presented in the scoping review could potentially be used to develop training strategies to mitigate some of the identified barriers that negatively impact women from pursuing careers in the military.

During January 1, 2020-May 18, 2020, approximately 1.3 million cases of coronavirus disease 2019 (COVID-19) and 83,000 COVID-19-associated deaths were reported in the United States (1). Understanding the demographic and clinical characteristics of decedents could inform medical and public health interventions focused on preventing COVID-19-associated mortality. This report describes decedents with laboratory-confirmed infection with SARS-CoV-2, the virus that causes COVID-19, using data from 1) the standardized CDC case-report form (case-based surveillance) (https://www.cdc.gov/coronavirus/2019-ncov/php/reporting-pui.html) and 2) supplementary data (supplemental surveillance), such as underlying medical conditions and location of death, obtained through collaboration between CDC and 16 public health jurisdictions (15 states and New York City).

Meat and poultry processing facilities face distinctive challenges in the control of infectious diseases, including coronavirus disease 2019 (COVID-19) (1). COVID-19 outbreaks among meat and poultry processing facility workers can rapidly affect large numbers of persons. Assessment of COVID-19 cases among workers in 115 meat and poultry processing facilities through April 27, 2020, documented 4,913 cases and 20 deaths reported by 19 states (1). This report provides updated aggregate data from states regarding the number of meat and poultry processing facilities affected by COVID-19, the number and demographic characteristics of affected workers, and the number of COVID-19-associated deaths among workers, as well as descriptions of interventions and prevention efforts at these facilities. Aggregate data on confirmed COVID-19 cases and deaths among workers identified and reported through May 31, 2020, were obtained from 239 affected facilities (those with a laboratory-confirmed COVID-19 case in one or more workers) in 23 states.* COVID-19 was confirmed in 16,233 workers, including 86 COVID-19-related deaths. Among 14 states reporting the total number of workers in affected meat and poultry processing facilities (112,616), COVID-19 was diagnosed in 9.1% of workers. Among 9,919 (61%) cases in 21 states with reported race/ethnicity, 87% occurred among racial and ethnic minority workers. Commonly reported interventions and prevention efforts at facilities included implementing worker temperature or symptom screening and COVID-19 education, mandating face coverings, adding hand hygiene stations, and adding physical barriers between workers. Targeted workplace interventions and prevention efforts that are appropriately tailored to the groups most affected by COVID-19 are critical to reducing both COVID-19-associated occupational risk and health disparities among vulnerable populations. Implementation of these interventions and prevention efforts† across meat and poultry processing facilities nationally could help protect workers in this critical infrastructure industry.

Prior research has shown that sexual minorities are disproportionately affected by substance use disorders and prescription opioid misuse. While most studies explore how single dimensions of sexual orientation (i.e., identity, attraction, and behavior) are associated with substance use disorders, we aimed to explore how multiple dimensions of sexual orientation interact with substance use behaviors. Specifically, we examined sexual identity-attraction discordance, the situation when one's sexual identity does not match their socially-expected sexual attractions, with prescription opioid misuse. This study assessed the association between sexual identity-attraction discordance with prescription opioid misuse utilizing data from the National Survey on Drug Use and Health from 2015 to 2017 among adults while employing propensity score weighting with multivariable logistic regression. The study included 127,430 adult participants, of whom 1.3%, 4.4%, and 10.6% self-reported prescription opioid misuse in the past month, past year, and lifetime, respectively. Those with discordant sexual identity-attractions had higher odds of prescription opioid misuse in their lifetime (aOR= 1.22, 95% CI 1.07–1.40) when compared to those with concordant sexual identity-attractions. When stratified by sex, we found sexual identity-attraction discordant females had higher odds of prescription opioid misuse in their lifetime (aOR= 1.29, 95% CI 1.13–1.49); there was no association among males. These findings further emphasize the need to consider the dynamic nature of sexual orientation in substance use research.

One key item of information retrieved when surveying our visual world is whether or not objects are familiar. However, there is no consensus on the respective roles of medial temporal lobe structures, particularly the perirhinal cortex (PRC) and hippocampus. We considered whether the PRC could support a fast recognition memory system independently from the hippocampus. We recorded the intracerebral electroencephalograph activity of epileptic patients while they were performing a fast visual recognition memory task, constraining them to use their quickest strategy. We performed event-related potential (ERP) and classification analyses. The PRC was, by far, the earliest region involved in recognition memory. This activity occurred before the first behavioral responses and was found to be related to reaction times, unlike the hippocampus. Single-trial analyses showed that decoding power was equivalent in the PRC and hippocampus but occurred much earlier in the PRC. A critical finding was that recognition memory-related activity occurred in different frontal and parietal regions, including the supplementary motor area, before the hippocampus. These results, based on ERP analyses, suggest that the human brain is equipped with a fast recognition memory system, which may bypass the hippocampus and in which the PRC plays a critical role.

Dietary nitrate has been shown to increase cytosolic calcium concentrations within the heart, which would necessitate greater calcium sequestration for relaxation. In the present study we demonstrate that while nitrate supplementation reduced blood pressure, calcium-handling protein content, sarco(endo)plasmic reticulum Ca-ATPase 2a (SERCA) enzymatic properties, and left ventricular function were not altered. In addition, nitrite did not alter in vitro SERCA activity. Combined, these data suggest that in healthy rats, dietary nitrate does not increase left ventricle SERCA-related calcium-handling properties. Novelty Dietary nitrate decreases blood pressure but does not alter left ventricular calcium-handling protein content or SERCA activity in healthy rats.

Background Granulomatous and lymphocytic interstitial lung disease (GLILD) is a life-threatening complication in patients with common variable immunodeficiency (CVID), but the optimal treatment is unknown. Objective Our aim was to determine whether rituximab with azathioprine or mycophenolate mofetil improves the high-resolution computed tomography (HRCT) chest scans and/or pulmonary function test results in patients with CVID and GLILD. Methods A retrospective chart review of clinical and laboratory data on 39 patients with CVID and GLILD who completed immunosuppressive therapy was performed. Chest HRCT scans, performed before therapy and after the conclusion of therapy, were blinded, randomized, and scored independently by 2 radiologists. Differences between pretreatment and posttreatment HRCT scan scores, pulmonary function test results, and lymphocyte subsets were analyzed. Whole exome sequencing was performed on all patients. Results Immunosuppressive therapy improved patients' HRCT scan scores (P Conclusions Immunosuppressive therapy improved the radiographic abnormalities and pulmonary function of patients with GLILD. A majority of patients had sustained remissions.

Macrophage antibody (Ab)-dependent cellular phagocytosis (ADCP) is a major cytotoxic mechanism for both therapeutic unconjugated monoclonal Abs (mAbs) such as rituximab and Ab-induced hemolytic anemia and immune thrombocytopenia. Here, we studied the mechanisms controlling the rate and capacity of macrophages to carry out ADCP in settings of high target/effector cell ratios, such as those seen in patients with circulating tumor burden in leukemic phase disease. Using quantitative live-cell imaging of primary human and mouse macrophages, we found that, upon initial challenge with mAb-opsonized lymphocytes, macrophages underwent a brief burst (

BACKGROUND Whether polymeric bioresorbable vascular scaffolds (BVS) implantation with transradial approach is feasible and safe is unknown. We compared the feasibility and safety of the transradial approach for BVS delivery with metallic drug-eluting stents (DES). METHODS We identified 118 consecutive patients who underwent BVS implantation and we compared 30-days and 1-year results with 118 matched patients with DES. Patients were matched for age, sex, risk factors and clinical indication. RESULTS Rates of transradial approach were 98% in the BVS group vs 95% in the DES group (P = 0.16) with 5Fr used in 38% and 32% (P = 0.34), respectively. The number of stents was similar in both groups, 2.6 ± 1.5 vs 2.4 ± 1.3 (P = 0.23). Although maximal pressure for stent deployment was identical in both groups (16 ± 3 atm), more lesions were pre-dilated (83% vs 52%, P

Background Epileptic patients sometimes report experiential phenomena related to a previous dream they had during seizures or electrical brain stimulation (EBS). This has been alluded to in the literature as “déjà-rêvé” (“already dreamed”). However, there is no neuroscientific evidence to support its existence and this concept is commonly mixed up with déjà-vu. We hypothesized that déjà-rêvé would be a specific entity, i.e., different from other experiential phenomena reported in epileptic patients, induced by EBS of specific brain areas. Methods We collected all experiential phenomena related to dreams induced by electrical brain stimulations (EBS) in our epileptic patients (2003–2015) and in a review of the literature. The content of these déjà-rêvé and the location of EBS were analyzed. Results We collected 7 déjà-rêvé in our database and 35 from the literature, which corresponds to an estimated prevalence of 0.3‰ of all EBS-inducing déjà-rêvé. Déjà-rêvé is a generic term for three distinct entities: it can be the recollection of a specific dream (“episodic-like”), reminiscence of a vague dream (“familiarity-like”) or experiences in which the subject feels like they are dreaming (literally “a dreamy state”). EBS-inducing “episodic-like” and “familiarity-like” déjà-rêvé were mostly located in the medial temporal lobes. “Dreamy states” were induced by less specific EBS areas although still related to the temporal lobes. Conclusions This study demonstrates that déjà-rêvé is a heterogeneous entity that is different from déjà-vu, the historical “dreamy state” definition and other experiential phenomena. This may be relevant for clinical practice as it points to temporal lobe dysfunction and could be valuable for studying the neural substrates of dreams., Highlights • Electrical brain stimulation (EBS) can induce recall of prior dreams (déjà-rêvé). • They can be episodic or familiarity-like. • Déjà-rêvé is a heterogeneous entity, different from déjà-vu and classic dreamy state. • EBS locations are mostly temporal and differ depending on the type of déjà-rêvé. • Déjà-rêvé point to temporal dysfunction in epilepsy and are valuable to study dreams.

In 2006 Mitchell demonstrated that implicit memory was robust to decay. He showed that the ability to identify fragments of pictures seen 17 years before was significantly higher than for new stimuli. Is this true only for implicit memory? In this study, we tested whether explicit memory was still possible for drawings (n = 144) that had been presented once or three times, two seconds each time on average, approximately 12 years earlier. Surprisingly, our data reveal that our participants were able to recognize pictures above chance level. Preserved memory was mainly observed in the youngest subjects, for stimuli seen three times. Despite the fact that confidence judgments were low, reports suggest that recognition could be based on a strong sense of familiarity. These data extend Mitchell's findings and show that familiarity can also be robust to decay.

Autistic Spectrum Disorder (ASD) can be a debilitating, life-long neurocognitive disease. ASD is caused by genetic and epigenetic factors and largely unknown and poorly understood environmental triggers. Signs and symptoms of ASD often appear in the first year of life while the disease strikes other infants who had previously been developing normally at around 2years of age. Ozonoff and her colleagues recently suggested that there are three different pathways or trajectories for the development of ASD in infants 6-24months of age. I hypothesize that pathway 1 is caused by in utero insult/injury, pathway 2 by obstetric complications at birth, and pathway 3 by environmental triggers of ASD affecting infants 0-3years of age. Faster progress can be made in elucidating the underlying causes of neonatal and regressive forms of ASD if the diseases are investigated separately, instead of being part of the same disorder.

Exposure to Polycyclic Aromatic Hydrocarbons (PAHs) occurs by respiratory, digestive and dermal absorption. Biomonitoring takes all pathways into account but sensitive and specific biomarkers are required. Different gaseous PAHs metabolites were used due to their abundance in the atmospheric mixtures but none of them were selected as better biomarker than the others. To identify the best candidates for assessing occupational airborne exposure, relation between atmospheric levels of Naphtalene, Fluorene and Phenanthrene and urinary metabolites concentrations was studied in a carbon electrode workers group. Linear mixed effects models were built to select explanatory variables and estimate variance component. Urinary creatinine was a predictor of metabolites levels confirming the importance of diuresis for interpreting results. High significance of pre-shift sampling time combined with positive coefficients of post-shift indicated that urine should be sampled at the end of the workday in association with pre-shift urine to avoid misinterpretations. Among the 10 metabolites studied, urinary 2-hydroxyfluorene and 2-hydroxyphenanthrene showed the highest increase of variance explained by models after inclusion of individual atmospheric levels as explanatory variable. Priority could be given to 2-hydroxyfluorene due to higher excretion levels than 2-hydroxyphenanthrene.

Introduction We investigated a signal of solid organ transplant (SOT) rejection after immunisation with (AS03) A/H1N1 2009 pandemic influenza vaccines. Methods Potential immunological mechanisms were reviewed and quantitative analyses were conducted. The feasibility of pharmacoepidemiological studies was explored. Results Overall results, including data from a pharmacoepidemiological study, support the safety of adjuvanted (AS03) pandemic influenza vaccination in SOT recipients. The regulatory commitment to evaluate the signal through a stepwise investigation was closed in 2014. Conclusion Lessons learned highlight the importance of investigating plausible biological mechanisms between vaccines and potentially associated adverse outcomes, and the importance of selecting appropriate study settings and designs for safety signal investigations. Electronic supplementary material The online version of this article (doi:10.1007/s40264-017-0532-3) contains supplementary material, which is available to authorized users.

Three major white matter pathways connect the posterior temporal region and the adjacent inferior parietal lobule with the lateral frontal cortex: the arcuate fasciculus (AF), and the second and third branches of the superior longitudinal fasciculus (SLF II and SLF III). These pathways are found also in nonhuman primate brains where they play specific roles in auditory and spatial processing. The precise origin, course, and termination of these pathways has been examined in invasive tract tracing studies in macaque monkeys. Here we use this prior knowledge to improve dissections of these pathways in vivo in the human brain using diffusion Magnetic Resonance Imaging (MRI) tractography. In this study, the AF, originating from the posterior temporal cortex, has been successfully separated from the SLF II and SLF III tracts originating from the angular and supramarginal gyri of the inferior parietal lobule, respectively. The latter two pathways, i.e. SLF II and SLF III, have also been clearly separated from each other. Furthermore, we report for the first time in the human brain the dorsal branch of the AF that targets the posterior dorsolateral frontal region. These improved dissection protocols provide a solid basis for exploring the respective functional roles of these major fasciculi.

During 2017, CDC received 1,521 reports of acute hepatitis A virus (HAV) infections from California, Kentucky, Michigan, and Utah; the majority of infections were among persons reporting injection or noninjection drug use or homelessness. Investigations conducted by local and state health departments indicated that direct person-to-person transmission of HAV infections was occurring, differing from other recent, large HAV outbreaks attributed to consumption of contaminated commercial food products. Outbreaks with direct HAV transmission among persons reporting drug use or homelessness signals a shift in HAV infection epidemiology in the United States, and vaccination of these populations at high risk can prevent future outbreaks.

Key points Although the role of TBC1D1 within the heart remains unknown, expression of TBC1D1 increases in the left ventricle following an acute infarction, suggesting a biological importance within this tissue. We investigated the mechanistic role of TBC1D1 within the heart, aiming to establish the consequences of attenuating TBC1D1 signalling in the development of diabetic cardiomyopathy, as well as to determine potential sex differences. TBC1D1 ablation increased plasma membrane fatty acid binding protein content and myocardial palmitate oxidation. Following high-fat feeding, TBC1D1 ablation dramatically increased fibrosis and induced end-diastolic dysfunction in both male and female rats in the absence of changes in mitochondrial bioenergetics. Altogether, independent of sex, ablating TBC1D1 predisposes the left ventricle to pathological remodelling following high-fat feeding, and suggests TBC1D1 protects against diabetic cardiomyopathy. Abstract TBC1D1, a Rab-GTPase activating protein, is involved in the regulation of glucose handling and substrate metabolism within skeletal muscle, and is essential for maintaining pancreatic β-cell mass and insulin secretion. However, the function of TBC1D1 within the heart is largely unknown. Therefore, we examined the role of TBC1D1 in the left ventricle and the functional consequence of ablating TBC1D1 on the susceptibility to high-fat diet-induced abnormalities. Since mutations within TBC1D1 (R125W) display stronger associations with clinical parameters in women, we further examined possible sex differences in the predisposition to diabetic cardiomyopathy. In control-fed animals, TBC1D1 ablation did not alter insulin-stimulated glucose uptake, or echocardiogram parameters, but increased accumulation of a plasma membrane fatty acid transporter and the capacity for palmitate oxidation. When challenged with an 8 week high-fat diet, TBC1D1 knockout rats displayed a four-fold increase in fibrosis compared to wild-type animals, and this was associated with diastolic dysfunction, suggesting a predisposition to diet-induced cardiomyopathy. Interestingly, high-fat feeding only induced cardiac hypertrophy in male TBC1D1 knockout animals, implicating a possible sex difference. Mitochondrial respiratory capacity and substrate sensitivity to pyruvate and ADP were not altered by diet or TBC1D1 ablation, nor were markers of oxidative stress, or indices of overt heart failure. Altogether, independent of sex, ablation of TBC1D1 not only increased the susceptibility to high-fat diet-induced diastolic dysfunction and left ventricular fibrosis, independent of sex, but also predisposed male animals to the development of cardiac hypertrophy. These data suggest that TBC1D1 may exert cardioprotective effects in the development of diabetic cardiomyopathy.

To examine heart rate variability (HRV) and inflammatory markers as predictors for neurological injury in neonates undergoing therapeutic hypothermia for hypoxic‐ischemic encephalopathy (HIE). We hypothesized that HRV would differentiate between infants with no/mild injury and infants with moderate/severe injury observed on MRI. Because HRV can be associated with the inflammatory cascade, cytokine concentrations were compared with the severity of brain injury indicated by MRI. Further, we studied the effect of temperature, sex, and mechanical ventilation on HRV. HRV was prospectively collected on neonates with HIE using spectral analysis for low and high frequency components (n = 16). A subset (n = 10) of neonates had serum available for inflammatory cytokine analysis obtained during cooling. Neonates were stratified into no/mild or moderate/severe injury based on MRI obtained after rewarming. Differences in HRV were identified; lower low frequency power predicted more injury on MRI. Additionally, in neonates with HIE after cooling procedure, HRV differed by gender. Elevated RANTES (CCL5) and decreased GM‐CSF (Granulocyte‐macrophage colony‐stimulating factor) at 96 hours predicted less severe injury. In this small study, HRV differs between no/mild and moderate/severe injury in neonates with HIE. With further study, this may aid the clinician in real‐time decision making. HRV differs by gender. Finally, inflammatory biomarkers may help elucidate the pathophysiology of HIE.

In daily life, fast visual recognition of surrounding objects is facilitated through context-based expectations. However the ability to rapidly and accurately recognize unexpected stimuli in a given environment is also crucial and this ability is impaired with age. The present fMRI study aimed at comparing in young and older adults the neural correlates of fast object processing. Patterns of cerebral activity were investigated in response to briefly-presented (100 ms) congruent and incongruent natural scenes. Participants were slower and less accurate when categorizing objects in incongruent relative to congruent contexts. This behavioral cost was notably more pronounced in the older group. Height and multivariate patterns of fMRI activity in context-selective regions were equivalent in both age groups, suggesting preserved processing of coarse scene features in older participants. Incongruent scenes elicited additional activity in the parahippocampal gyrus that possibly reflected simultaneous activation of rarely co-occurring neural representations. Contextual effects were observed in object-selective cortex for the young group only, and may be driven by detection of mismatch between actually perceived and previously-experienced associations. In the older group exclusively, increased bilateral prefrontal and left fusiform activity in response to incongruent scenes was observed. However this supplemental activity was not found to efficiently contribute to improve task performance in difficult visual conditions. Altogether these results suggest age-related changes in the interaction between object- and context-processing pathways, that may subserve impairment in fast identification of unexpected objects in natural scenes.

Patients with lower extremity peripheral artery disease (PAD) frequently experience claudication, a clinical symptom indicative of reduced walking capacity. Recommended care consists of exercise rehabilitation combined with optimal medical treatment and surgery. The effects of a single oral dose of sildenafil, a phosphodiesterase type-5 inhibitor, on patients with claudication are discussed. The aim of this study was to test the efficacy of a single 100 mg dose of sildenafil compared to placebo in terms of maximal walking time (MWT) in patients with claudication.The ARTERIOFIL study is a crossover, double-blind, prospective, randomized, single-center study conducted at Angers University Hospital in France. MWT (primary endpoint) was assessed using a treadmill test (10% incline; 3.2 km/h). Secondary endpoints (pain-free walking time (PFWT), transcutaneous oximetry during exercise and redox cycle parameters and safety) were also studied.Fourteen patients were included of whom two were ultimately excluded. In the 12 remaining patients, the MWT was significantly improved during the sildenafil period compared with the placebo period (300 s [95% CI 172 s-428 s] vs 402 s [95% CI 274 s-529 s] p 0.01). Sildenafil had no significant effect on pain-free walking time or skin tissue oxygenation during exercise. According to redox cycle parameters, sildenafil significantly reduced blood glucose and pyruvate levels and the 3-hydroxybutyrate/acetoacetate ratio, while there was no significant effect on lactate, 3-hydroxybutyrate, acetoacetate and free fatty acid levels. Symptomatic transient hypotension was observed in two women.The ARTERIOFIL study has shown that a single 100 mg oral dose of sildenafil had a significant effect on increase in MWT but had no significant effects on PFWT and oxygenation parameters in patients with claudication. A double-blind, prospective, randomized, multicenter study (VIRTUOSE©) is ongoing to evaluate the chronic effect of six month-long sildenafil treatment on MWT in PAD patients with claudication.This clinical trial was registered at clinicaltrials.gov, registration. number: NCT02832570, (https://clinicaltrials.gov/ct2/show/NCT02832570).

International audience; Binding operations carried out in working memory enable the integration of information from different sources during online performance. While available evidence suggests that working memory may involve distinct binding functions, whether or not they all involve the episodic buffer as a cognitive substrate remains unclear. Similarly, knowledge about the neural underpinnings of working memory buffers is limited, more specifically regarding the involvement of medial temporal lobe structures. In the present study, we report on the case of patient KA, with developmental amnesia and selective damage to the whole hippocampal system. We found that KA was unable to hold shape-colours associations (relational binding) in working memory. In contrast, he could hold integrated coloured shapes (conjunctive binding) in two different tasks. Otherwise, and as expected, KA was impaired on three relational memory tasks thought to depend on the hippocampus that are widely used in the early detection of Alzheimer's disease. Our results emphasize a dissociation between two binding processes within working memory, suggesting that the visuo-spatial sketchpad could support conjunctive binding, and may rely upon a large cortical network including sub-hippocampal structures. By contrast, we found evidence for a selective impairment of relational binding in working memory when the hippocampal system is compromised, suggesting that the long-term memory deficit observed in amnesic patients may be related to impaired short-term relational binding at encoding. Finally, these findings may inform research on the early detection of Alzheimer's disease as the preservation of conjunctive binding in KA is in sharp contrast with the impaired performance demonstrated very early in this disease.

Blood flow restricted resistance exercise (BFR-RE) is capable of inducing comparable adaptations to traditional resistance exercise (RE), despite a lower total exercise volume. It has been suggested that an increase in reactive oxygen species (ROS) production may be involved in this response; however, oxygen partial pressure (Low-load blood flow restricted resistance exercise (BFR-RE) training has been proposed to induce comparable adaptations to traditional resistance exercise (RE) training, however, the acute signalling events remain unknown. Although a suggested mechanism of BFR-RE is an increase in reactive oxygen species (ROS) production, oxygen partial pressure (

Worldwide shortages of personal protective equipment during COVID-19 pandemic has forced the implementation of methods for decontaminating face piece respirators such as N95 respirators. The use of UV irradiation to reduce bioburden of used respirators attracts attention, making proper testing protocols of uttermost importance. Currently artificial saliva is used but its comparison to human saliva from the UV disinfection perspective is lacking. Here we characterize UV spectra of human and artificial saliva, both fresh and after settling, to test for possible interference for UV-based disinfection. ASTM 2720 artificial saliva recipe (with either porcine or bovine mucin) showed many discrepancies from average (N = 18) human saliva, with different mucins demonstrating very different UV absorbance spectra, resulting in very different UV transmittance at different wavelength. Reducing porcine mucin concentration from 3 to 1.7 g/L brought UVA254 in the artificial saliva to that of average human saliva (although not for other wavelengths), allowing 254 nm disinfection experiments. Phosphate saline and modified artificial saliva were spiked with 8.6 log CFU/ml B. subtilis spores (ATCC 6633) and irradiated at dose of up to 100 mJ/cm2, resulting in 5.9 log inactivation for a saline suspension, and 2.8 and 1.1 log inactivation for ASTM-no mucin and ASTM-1.7 g/L porcine mucin 2 μL dried droplets, respectively. UVC irradiation of spores dried in human saliva resulted in 2.3 and 1.5 log inactivation, depending on the size of the droplets (2 vs 10 μL, respectively) dried on a glass surface. Our results suggest that in the presence of the current standard dried artificial saliva it is unlikely that UVC can achieve 6 log inactivation of B. subtilis spores using a realistic UV dose (e.g. less than 2 J/cm2) and the ATSM saliva recipe should be revised for UV decontamination studies.

The cellular processes influenced by consuming polyunsaturated fatty acids remains poorly defined. Within skeletal muscle, a rate-limiting step in fatty acid oxidation is the movement of lipids across the sarcolemmal membrane, and therefore, we aimed to determine the effects of consuming flaxseed oil high in α-linolenic acid (ALA), on plasma membrane lipid composition and the capacity to transport palmitate. Rats fed a diet supplemented with ALA (10%) displayed marked increases in omega-3 polyunsaturated fatty acids (PUFAs) within whole muscle and sarcolemmal membranes (approximately five-fold), at the apparent expense of arachidonic acid (−50%). These changes coincided with increased sarcolemmal palmitate transport rates (+20%), plasma membrane fatty acid translocase (FAT/CD36; +20%) abundance, skeletal muscle triacylglycerol content (approximately twofold), and rates of whole body fat oxidation (~50%). The redistribution of FAT/CD36 to the plasma membrane could not be explained by increased phosphorylation of signaling pathways implicated in regulating FAT/CD36 trafficking events (i.e., phosphorylation of ERK1/2, CaMKII, AMPK, and Akt), suggesting the increased n-3 PUFA composition of the plasma membrane influenced FAT/CD36 accumulation. Altogether, the present data provide evidence that a diet supplemented with ALA increases the transport of lipids into resting skeletal muscle in conjunction with increased sarcolemmal n-3 PUFA and FAT/CD36 contents.

To determine predictors of failure of transradial approach (TRA) in patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), and develop a novel score specific for this population.Consecutive patients with STEMI undergoing primary PCI in a tertiary care high-volume radial centre were included. TRA-PCI failure was categorised as primary (primary transfemoral approach (TFA)) or crossover (from TRA to TFA). Multivariate analysis was performed to determine independent predictors of TRA-PCI failure, and an integer risk score was developed. Clinical outcomes up to 1 year were assessed.From January 2006 to January 2011, 2020 patients were studied. Primary TRA-PCI failure occurred in 111 (5%) patients and crossover to TFA in 44 (2.2%) patients. Independent predictors of TRA-PCI failure were: weight ≤65 kg (OR: 3.0; 95% CI 1.9 to 4.8, p0.0001), physician with ≤5% TFA conversion (OR: 0.45; 95% CI 0.2 to 0.9, p=0.033), and physician with ≥10% conversion to TFA (OR: 2.2; 95% CI 1.2 to 3.7, p=0.005), intra-aortic balloon pump (OR: 2.0; 95% CI 0.9 to 4.3, p=0.066), cardiogenic shock (OR: 2.8; 95% CI 1.4 to 5.6, p=0.0035), endotracheal intubation (OR: 107; 95% CI 42 to 339, p0.0001), creatinine133 μmol/L (OR: 3.6; 95% CI 1.9 to 6.8, p0.0001), age ≥75 (OR: 1.7; 95% CI 1.0 to 2.9, p=0.031), prior PCI (OR: 2.6; 95% CI 1.5 to 4.5, p=0.0009), hypertension (OR: 1.8; 95% CI 1.2 to 2.9, p=0.009). An integer risk score ranging from -1 to 12 was developed, and predicted TRA-PCI failure from 0% to 100% (c-statistic of 0.868; 95% CI 0.866 to 0.869). Mortality at 1 year remained significantly higher after TRA-PCI failure (adjusted OR 2.2; 95% CI 1.2 to 3.9, p=0.011).In a high-volume radial centre, the incidence of TRA-PCI failure is low and can be accurately predicted using a 9-variables risk score. Since outcomes after TRA-PCI failure remained inferior, further effort to maximise the use of radial approach for primary PCI should be investigated.

Objective: Ranibizumab, an anti-vascular endothelial growth factor designed for ocular use, has been deemed cost-effective in multiple indications by several Health Technology Assessment bodies. This study assessed the cost-effectiveness of ranibizumab monotherapy or combination therapy (ranibizumab plus laser photocoagulation) compared with laser monotherapy for the treatment of visual impairment due to diabetic macular edema (DME). Methods: A Markov model was developed in which patients moved between health states defined by best-corrected visual acuity (BCVA) intervals and an absorbing ‘death’ state. The population of interest was patients with DME due to type 1 or type 2 diabetes mellitus. Baseline characteristics were based on those of participants in the RESTORE study. Main outputs were costs (in 2013 CA$) and health outcomes (in quality-adjusted life-years [QALYs]) and the incremental cost-effectiveness ratio (ICER) was calculated. This cost-utility analysis was conducted from healthcare system and societal perspectives in Quebec. Results: From a healthcare system perspective, the ICERs for ranibizumab monotherapy and combination therapy versus laser monotherapy were CA$24,494 and CA$36,414 per QALY gained, respectively. The incremental costs per year without legal blindness for ranibizumab monotherapy and combination therapy versus laser monotherapy were CA$15,822 and CA$20,616, respectively. Based on the generally accepted Canadian ICER threshold of CA$50,000 per QALY gained, ranibizumab monotherapy and combination therapy were found to be cost-effective compared with laser monotherapy. From a societal perspective, ranibizumab monotherapy and combination therapy provided greater benefits at lower costs than laser monotherapy (ranibizumab therapy dominated laser therapy). Conclusions: Ranibizumab monotherapy and combination therapy resulted in increased quality-adjusted survival and time without legal blindness, and lower costs from a societal perspective compared with laser monotherapy.

Environmental enrichment is a widely used experimental manipulation that consistently shows measurable effects on rodent behaviour across the lifespan. This scoping review assesses and thematically summarizes the literature of the past decade concerning the effects of environmental enrichment applied during sensitive developmental periods in rodent mothers and offspring. Maternal behaviours as well as maternal and offspring anxiety- and depressive-like behaviours are considered. Relevant terms were searched across five databases (Embase, MEDLINE, PsycINFO, PubMed, Web of Science) and articles were screened with inclusion and exclusion criteria. The remaining articles were thematically analysed. Our results suggest that a greater number of articles reviewed the impacts of environmental enrichment on offspring anxiety-like behaviour (n = 23) rather than on depressive-like behaviour (n = 11) or maternal caregiving behaviour (n = 12). Maternal anxiety- (n = 4) or depressive-like (n = 2) behaviours are not often evaluated for in enrichment studies. The main behavioural tests of anxiety that were reviewed include the elevated plus-maze, the open field test, and the light-dark box whereas those for depression included the forced swim test and the sucrose preference test. Our results yielded mixed findings and significant variation in behavioural responses across all tests. In mothers, trends of increased maternal care behaviours and decreased maternal depressive-like behaviours in enriched mothers were appreciated. Enrichment during the gestational period was identified as pivotal to creating behavioural change in mother subjects. In enriched offspring rodents, a trend towards decreased anxiety-like behaviours was observed most often. Potential confounds inherent in enrichment paradigms and relevant theories of enrichment and their relation to rodent behavioural tests are discussed.

In contrast to most memory systems that decline with age, semantic memory tends to remain relatively stable across the life span. However, what exactly is stable remains unclear. Is it the quantity of information available or the organization of semantic memory, i.e., the connections between semantic items? Even less is known about semantic memory for celebrities, a subsystem of semantic memory. In the present study, we studied the organization of person-specific semantic memory and its stability in aging.We designed a word association task based on a previous study, which consisted in providing the first word that came to the mind of the participants (15 participants for each age group 20-30, 40-50 and 60-70 years old) for 144 celebrities. We developed a new taxonomy of associated responses as the responses associated with celebrities name could in principle be very varied.We found that most responses (90%) could be grouped into five categories (subjective; superordinate general; superordinate specific; imagery and activities). The elderly group did not differ from the other two groups in term of errors or reaction time suggesting they performed the task well. However, they also provided associations that were less precise and less based on imagery. In contrast, the middle-age group provided the most precise associations.These results support the idea of a durable person-specific semantic memory in aging but show changes in the type of associations that elders provide. Future work should aim at studying patients with early semantic impairment, as they could be different from the healthy elders on such semantic association task.

There is considerable variability in an individual's ability to acquire a second language (L2) during adulthood. Using resting-state fMRI data acquired before training in English speakers who underwent a 12 week intensive French immersion training course, we investigated whether individual differences in intrinsic resting-state functional connectivity relate to a person's ability to acquire an L2. We focused on two key aspects of language processing—lexical retrieval in spontaneous speech and reading speed—and computed whole-brain functional connectivity from two regions of interest in the language network, namely the left anterior insula/frontal operculum (AI/FO) and the visual word form area (VWFA). Connectivity between the left AI/FO and left posterior superior temporal gyrus (STG) and between the left AI/FO and dorsal anterior cingulate cortex correlated positively with improvement in L2 lexical retrieval in spontaneous speech. Connectivity between the VWFA and left mid-STG correlated positively with improvement in L2 reading speed. These findings are consistent with the different language functions subserved by subcomponents of the language network and suggest that the human capacity to learn an L2 can be predicted by an individual's intrinsic functional connectivity within the language network.SIGNIFICANCE STATEMENTThere is considerable variability in second-language learning abilities during adulthood. We investigated whether individual differences in intrinsic functional connectivity in the adult brain relate to success in second-language learning, using resting-state functional magnetic resonance imaging in English speakers who underwent a 12 week intensive French immersion training course. We found that pretraining functional connectivity within two different language subnetworks correlated strongly with learning outcome in two different language skills: lexical retrieval in spontaneous speech and reading speed. Our results suggest that the human capacity to learn a second language can be predicted by an individual's intrinsic functional connectivity within the language network.

We investigated longitudinal hospitalization outcomes (total charges, hospital days and admissions) among pediatric and adolescent patients with cancer compared with individuals from the general population without cancer using a novel and efficient three-step regression procedure.The statewide Utah Population Database, with linkages to the Utah Cancer Registry, was used to identify 1,651 patients who were diagnosed with cancer from 1996 to 2009 at ages 0 to 21 years. A comparison group of 4,953 same-sex and -age individuals was generated from birth certificates. Claims-based hospitalization data from 1996 to 2012 were retrieved from the Utah Department of Health. Using the regression method, we estimated survival (differences due to survival) and intensity (differences due to resource accumulation) effects of the cancer diagnosis on hospitalization outcomes within 10 years after diagnosis.At 10 years after diagnosis, on average, patients with cancer incurred $51,723 (95% CI, $48,100 to $58,284) more in charges, spent 30 additional days (95% CI, 27.7 to 36.1 days) in the hospital, and had 5.7 (95% CI, 5.4 to 6.4) more admissions than the comparison group. Our analyses showed that the highest hospitalization burden occurred during the first 4 years of diagnosis. Patients with leukemia incurred the greatest hospitalization burden throughout the 10 years from diagnosis. Intensity effects explained the majority of differences in hospital outcomes.Our results suggest that children and adolescents who were diagnosed with cancer in 2014 in the United States will incur over $800 million more in hospital charges than individuals without cancer by 2024. Interventions to reduce this burden should be explored in conjunction with improving health and survival outcomes.

This article describes the case of a patient who, following herpes simplex encephalitis (HSE), retained the ability to access rich conceptual semantic information for familiar people whom he was no longer able to name. Moreover, this patient presented the very rare combination of name production and name comprehension deficits for different categories of proper names (persons and acronyms). Indeed, besides his difficulty to retrieve proper names, SL presented a severe deficit in understanding and identifying them. However, he was still able to recognize proper names on familiarity decision, demonstrating that name forms themselves were intact. We interpret SL's deficit as a rare form of two-way lexico-semantic disconnection, in which intact lexical knowledge is disconnected from semantic knowledge and face units. We suggest that this disconnection reflects the role of the left anterior temporal lobe in binding together different types of knowledge and supports the classical convergence-zones framework (e.g., Damasio, 1989) rather than the amodal semantic hub theory (e.g., Patterson, Nestor, & Rogers, 2007).

Movement atypicalities in speed, coordination, posture, and gait have been observed across the autism spectrum (AS) and atypicalities in coordination are more commonly observed in AS individuals without delayed speech (DSM‐IV Asperger) than in those with atypical or delayed speech onset. However, few studies have provided quantitative data to support these mostly clinical observations. Here, we compared perceptual and motor performance between 30 typically developing and AS individuals (21 with speech delay and 18 without speech delay) to examine the associations between limb movement control and atypical speech development. Groups were matched for age, intelligence, and sex. The experimental design included: an inspection time task, which measures visual processing speed; the Purdue Pegboard, which measures finger dexterity, bimanual performance, and hand‐eye coordination; the Annett Peg Moving Task, which measures unimanual goal‐directed arm movement; and a simple reaction time task. We used analysis of covariance to investigate group differences in task performance and linear regression models to explore potential associations between intelligence, language skills, simple reaction time, and visually guided movement performance. AS participants without speech delay performed slower than typical participants in the Purdue Pegboard subtests. AS participants without speech delay showed poorer bimanual coordination than those with speech delay. Visual processing speed was slightly faster in both AS groups than in the typical group. Altogether, these results suggest that AS individuals with and without speech delay differ in visually guided and visually triggered behavior and show that early language skills are associated with slower movement in simple and complex motor tasks. Autism Res 2015, 8: 682–693. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research

This study was conducted to determine the impact of dietary acculturation on the health status of newly arrived international students at Virginia Tech in Fall 2010.Thirty-five international students, 18-36 years of age, completed the study.Data were collected at 3 different time periods (V1, V2, and V3) approximately 6 weeks apart. A food frequency- and dietary pattern-related questionnaire was administered and numerically coded responses were analyzed. Twenty-four-hour dietary recall data were also collected at V1, V2, and V3. Body weight, fasting blood glucose level, and blood pressure of study participants were also determined at each time period.Total sample population (TSP) had a significant increase in mean weight of 2.79 lb from visit 1 (V1) to visit 3 (V3) (p = .0082). Ten participants gained an average of 9.0 lb (participants who gained weight; n = 10). There was also an increase in the frequency of consumption of high-calorie American food items from V1 to V3. However, there were no significant changes in mean systolic blood pressure and mean fasting blood glucose was significantly lower at V3 than at V1.There was a gradual shift in the dietary patterns of international students towards the American diet. Dietary acculturation led to weight gain among some of the students, which may potentially have a negative impact on their health status if continued for longer time periods.