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Introduction: Suicide among males is a major public health challenge. In 2019, males accounted for nearly 80% of the suicide deaths in the U.S., and suicide was the eighth leading cause of death for males aged ≥10 years. Males who die by suicide are less likely to have known mental health conditions than females; therefore, it is important to identify prevention points outside of mental health systems. The purpose of this analysis was to compare suicide characteristics among males with and without known mental health conditions by age group to inform prevention.Methods: Suicides among 4 age groups of males were examined using the 3 most recent years of data at the time of the analysis (2016-2018) from the Centers for Disease Control and Prevention's National Violent Death Reporting System. Decedents with and without known mental health conditions were compared within age groups. The analysis was conducted in August 2021.Results: Most male suicide decedents had no known mental health conditions. More frequently, those without known mental health conditions died by firearm, and many tested positive for alcohol. Adolescents, young adults, and middle-aged males without known mental health conditions more often had relationship problems, arguments, and/or a crisis as a precipitating circumstance than those with known mental health conditions.Conclusions: Acute stressors more often precipitated suicides of males without known mental health conditions, and they more often involved firearms. These findings underscore the importance of mitigating acute situational stressors that could contribute to emotionally reactive/impulsive suicides. Suicide prevention initiatives targeting males might focus on age-specific precipitating circumstances in addition to standard psychiatric markers. [ABSTRACT FROM AUTHOR]

Results show that the molecular connection between double-strand break recognition by the protein complexes and cell's ability to activate ATM controlled DNA damage response pathway links hMre11 gene to the complex Ataxia-Telangiectasia disorder.

Background: In the United States (US), 61% of all suicide cases may involve firearms, and some evidence suggests that mental disorders may play a role in suicide by firearm. We performed the first systematic review and meta-analyses to investigate: (i) whether mental disorders are associated with suicide by firearm, and (ii) whether the risk of using a firearm compared with alternative means is associated with higher levels of suicide in individuals with a mental disorder METHODS AND FINDINGS: We searched twelve databases from inception to the 24th of May 2020. We retrieved 22 observational studies conducted in the US. Random-effects meta-analyses showed individuals who had a diagnosis of a mental disorder had lower odds (odds ratios (OR)= 0.50, 95% CI: 0.36 to 0.69; I2=100 (95% CI: 87 to 100%), of dying by suicide with a firearm than those who did not have a diagnosis of a mental disorder. Secondary analysis showed that decedents who had a mental health diagnosis resulted in lower odds of dying by suicide by using firearms than using other means LIMITATIONS: Risk of bias revealed a heterogeneous and poor definition of mental disorders as well as lack of control for potential demographic confounding factors. In the meta-analyses, studies were combined in the same analytic sample as 77% of these studies did not specify the type of mental disorder CONCLUSION: While our results seem to suggest that having a mental disorder may not be consistently associated with the odds of dying by suicide using a firearm, the presence of substantial heterogeneity and high risk of bias precludes any firm conclusions. [ABSTRACT FROM AUTHOR]

Gastrografin challenge is increasingly used as a diagnostic tool to predict patients who may benefit from nonoperative management in adhesive small bowel obstruction. This study explores the optimal timing of Gastrografin in the management of adhesive small bowel obstruction by comparing early versus late Gastrografin challenge. A retrospective chart review from January 2016 to January 2018 identified patients with adhesive small bowel obstruction who underwent Gastrografin challenge. A receiver operating characteristic curve, to predict a duration of stay less than 5 days, calculated a 12-hour limit which separated early and late groups. Nonoperative and operative patients were compared separately. Our primary outcome was duration of stay. Secondary outcomes included operative requirement, time to the operating room, complication rate, and 1-year mortality. In a separate analysis, multivariable logistic regression identified independent risk factors for 1-year mortality. One hundred thirty-four patients were identified (58 early, 76 late). In nonoperative patients, the early group had a shorter duration of stay (3.2 days vs 5.4 days), fewer complications, and a lower complication and 1-year mortality rate (P <.05). In operative patients, the early group had a shorter preoperative duration of stay (1.8 days vs 3.9 days) (P <.05). On multivariable regression, congestive heart failure, any postoperative complication, and operative requirement were the best predictors of 1-year mortality (R2 = 0.321; P <.05). Gastrografin administration within 12 hours of adhesive small bowel obstruction diagnosis had favorable outcomes in terms of duration of stay, complications, and mortality in nonoperative patients. Moreover, in operative patients, preoperative duration of stay was shortened. Our findings suggest protocolizing early Gastrografin challenge may be an important principle in adhesive small bowel obstruction management. [ABSTRACT FROM AUTHOR]

Acute alcohol intoxication is a contributing factor in firearm-involved suicides. However, knowledge of the relationship between alcohol intoxication and firearm-involved suicide by age and sex (defined herein as the biological sex of the decedent) is limited. The purpose of the current study was to evaluate the sex- and age group-specific relationship between alcohol intoxication and firearm-involved suicide. Data from the National Violent Death Reporting System, 2003–2020, on suicide decedents (18+ years of age) were utilized. Age-group- and sex-specific multivariate binary logistic regression analyses were conducted. Statistical analyses were performed in 2023. Alcohol intoxication (i.e., having a blood alcohol concentration of 0.08 g/dL or more) was significantly associated with using a firearm as the method of suicide for young (18–34 years; relative risk (RR)=1.31, 95% CI: 1.22–1.40) and middle-aged (35–64 years; RR=1.34, 95% CI: 1.27–1.39) females but not among older females (65+ years; RR=1.01, 95% CI: 0.87–1.17). Among males, the association was significant for all age-groups (young: RR=1.28, 95% CI: 1.25–1.30; middle-aged: RR=1.17, 95% CI: 1.15–1.19; and older: RR=1.04, 95% CI: 1.01–1.07). Among males of all ages and young and middle-aged females, alcohol intoxication was associated with increased risk of suicide by firearm—an extremely lethal method that accounts for a majority of suicides in the U.S.—compared to their non-intoxicated counterparts. Interventions targeting excessive alcohol consumption may be effective in reducing suicide mortality rates. [ABSTRACT FROM AUTHOR]

Background Premature infants often require oxygen supplementation and, therefore, are exposed to oxidative stress. Following oxygen exposure, preterm infants frequently develop chronic lung disease and have a significantly increased risk of asthma. Objective We sought to identify the underlying mechanisms by which neonatal hyperoxia promotes asthma development. Methods Mice were exposed to neonatal hyperoxia followed by a period of room air recovery. A group of mice was also intranasally exposed to house dust mite antigen. Assessments were performed at various time points for evaluation of airway hyperresponsiveness, eosinophilia, mucus production, inflammatory gene expression, and T H and group 2 innate lymphoid cell (ILC2) responses. Sera from term- and preterm-born infants were also collected and levels of IL-33 and type 2 cytokines were measured. Results Neonatal hyperoxia induced asthma-like features including airway hyperresponsiveness, mucus hyperplasia, airway eosinophilia, and type 2 pulmonary inflammation. In addition, neonatal hyperoxia promoted allergic T H responses to house dust mite exposure. Elevated IL-33 levels and ILC2 responses were observed in the lungs most likely due to oxidative stress caused by neonatal hyperoxia. IL-33 receptor signaling and ILC2s were vital for the induction of asthma-like features following neonatal hyperoxia. Serum IL-33 levels correlated significantly with serum levels of IL-5 and IL-13 but not IL-4 in preterm infants. Conclusions These data demonstrate that an axis involving IL-33 and ILC2s is important for the development of asthma-like features following neonatal hyperoxia and suggest therapeutic potential for targeting IL-33, ILC2s, and oxidative stress to prevent and/or treat asthma development related to prematurity. [ABSTRACT FROM AUTHOR]

Objective: To examine 1) temporal trends between 2005 and 2014 in the three most frequently used suicide means (firearms, hanging/suffocation, alcohol/drug/medicine overdose) by decedents aged 50+ years and 2) associations of suicide means with sociodemographic and precipitating factors.Methods: The National Violent Death Reporting System, 2005-2014, provided data (N = 46,857). Suicide means were identified from ICD-10 codes for underlying cause of death and coroner/medical examiner (CME) reports. Precipitating factors are based on either CME or law enforcement report. Age-group (50-64 and 65+ years) and gender-separate logistic regression analyses were used to examine study questions.Results: In the 50-64 years age group, each advancing year (i.e., from 2005 to 2014) was associated with a 1% decrease in the odds of firearm use and a 6% increase in the odds of hanging/suffocation among men; a 9% increase in the odds of hanging/suffocation among women; and a 4% decrease in the odds of overdose among each gender. In the 65+ years age group, each advancing year was associated with a 4% increase in the odds of overdose among men. Physical health was a significant factor for firearm use among men (adjusted odds ratio: 1.47; 95% CI: 1.39-1.55) only. Regardless of gender and age, mental health and substance abuse problems and prior suicide attempts were associated with hanging/suffocation and overdose.Conclusions: Firearm use decreased among men aged 50-64 years between 2005 and 2014, but its use did not change among the other gender by age groups. With rapidly growing numbers of older adults, routine suicide risk assessments, firearm safety monitoring, and interventions to improve quality of life are needed. [ABSTRACT FROM AUTHOR]

Introduction: Suicide rates and the proportion of alcohol-involved suicides rose during the 2008-2009 recession. Associations between county-level poverty, foreclosures, and unemployment and suicide rates and proportion of alcohol-involved suicides were investigated.Methods: In 2015, National Violent Death Reporting System data from 16 states in 2005-2011 were utilized to calculate suicide rates and a measure of alcohol involvement in suicides at the county level. Panel models with year and state fixed effects included county-level measures of unemployment, foreclosure, and poverty rates.Results: Poverty rates were strongly associated with suicide rates for both genders and all age groups, were positively associated with alcohol involvement in suicides for men aged 45-64 years, and negatively associated for men aged 20-44 years. Foreclosure rates were negatively associated with suicide rates for women and those aged ≥65 years but positively related for those aged 45-64 years. Unemployment rate effects on suicide rates were mediated by poverty rates in all groups.Conclusions: Population risk of suicide was most clearly associated with county-level poverty rates, indicating that programs addressing area poverty should be targeted for reducing suicide risk. Poverty rates were also associated with increased alcohol involvement for men aged 45-64 years, indicating a role for alcohol in suicide for this working-aged group. However, negative associations between economic indicators and alcohol involvement were found for four groups, suggesting that non-economic factors or more general economic effects not captured by these indicators may have played a larger role in alcohol-related suicide increases. [ABSTRACT FROM AUTHOR]

Purpose Few studies have compared acute use of alcohol in suicide decedents with that in a nonsuicide group. This study provides the first national analysis of acute use of alcohol before suicide compared with an estimate of acute use of alcohol in a living sample. Methods Pooled 2003-2011 National Violent Death Reporting System data were used to estimate the prevalence of postmortem blood alcohol content positivity (blood alcohol content >0.0 g/dL) and intoxication (blood alcohol content ≥0.08 g/dL). Population estimates of comparable use of alcohol (within the past 48 hours) were based on the National Epidemiologic Survey on Alcohol and Related Conditions. Results Compared with the living sample, male and female suicide decedents showed, respectively, a 1.83-fold (95% confidence interval [CI], 1.73-1.93) and 2.40-fold (95% CI, 2.24-2.57) increased risk of alcohol ingestion before their death after age, race/ethnicity, and chronic alcohol problems were controlled. Furthermore, male and female decedents exhibited, respectively, a 6.18-fold (95% CI, 5.57-6.86) and a 10.04-fold (95% CI, 8.67-11.64) increased risk of being intoxicated before their death after confounders were considered. Conclusions The findings underscore the crucial need to include among the essential components of suicide prevention policies programs that minimize the use of alcohol, particularly drinking to intoxication. [ABSTRACT FROM AUTHOR]

Background: The differentiation of TH17 cells, which promote pulmonary inflammation, requires the cooperation of a network of transcription factors. Objectives: We sought to define the role of Etv5, an Ets-family transcription factor, in TH17 cell development and function. Methods: TH17 development was examined in primary mouse T cells wherein Etv5 expression was altered by retrovirai transduction, small interfering RNA targeting a specific gene, and mice with a conditional deletion of Etv5 in T cells. The direct function of Etv5 on the Il17 locus was tested with chromatin immunoprecipitation and reporter assays. The house dust mite-induced allergic inflammation model was used to test the requirement for Etv5-dependent TH17 functions in vivo. Results: We identify Etv5 as a signal transducer and activator of transcription 3-induced positive regulator of TH17 development. Etv5 controls TH17 differentiation by directly promoting Il17a and Il17f expression. Etv5 recruits histone-modifying enzymes to the Il17a-Il17f locus, resulting in increased active histone marks and decreased repressive histone marks. In a model of allergic airway inflammation, mice with Etv5-deficient T cells have reduced airway inflammation and IL-17A/F production in the lung and bronchoalveolar lavage fluid compared with wild-type mice, without changes in TH2 cytokine production. Conclusions: These data define signal transducer and activator of transcription 3-dependent feed-forward control of TH17 cytokine production and a novel role for Etv5 in promoting T cell-dependent airway inflammation. [ABSTRACT FROM AUTHOR]

Abstract: Studies have shown that moderate alcohol use confers protection against some of the dominant predictors of long-term care placement, including diminished cognitive functioning, physical disability, and injury. But little is known about the association between alcohol use and the likelihood of placement in long-term care facilities. A nationally representative sample of 5404 community-dwelling Canadians ages 50years and older at baseline (1994/95) was obtained from the longitudinal National Population Health Survey. Alcohol use categories were developed based on the quantity and frequency of use in the 12months before the interview. Cox proportional hazards models were used to estimate the association between alcohol use at baseline and subsequent placement in long-term care facilities after adjusting for covariates measured at baseline. During the 14-year follow-up period, 14% of lifetime abstainers, 10% of former drinkers, 7% of infrequent drinkers, 4% of moderate drinkers, and 3% of heavy drinkers were placed in long-term care facilities. Furthermore, the multivariate analysis revealed that abstainers, former drinkers, and infrequent drinkers were more than twice as likely to be placed in long-term care as moderate drinkers. Moderate drinking was protective against placement in long-term care facilities even after adjusting for an array of well-known confounders. The strong protective effect of moderate alcohol use on long-term care entry is likely due to a complex mix of physical, cognitive and psychosocial health factors. [Copyright &y& Elsevier]

CD4+ T helper cells are obligate regulators of inflammatory disease. An expanding cadre of T helper (Th) subsets, specialized for promoting particular types of inflammation, function through the secretion of a restricted set of cytokines. The latest addition to the list of subsets is the Th9 cell that secretes IL-9 as a signature cytokine and contributes to several classes of inflammatory disease. In this review we focus on recent advances in understanding the development of Th9 cells, and how Th9 cells contribute to the orchestration of disease. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with increased susceptibility to recurrent skin infections. Objective: We sought to determine why a subset of patients with AD have an increased risk of disseminated viral skin infections. Methods: Human subjects with AD with a history of eczema herpeticum (EH) and various control groups were enrolled. Vaccinia virus (VV) expression was measured by means of PCR and immunofluorescent staining in skin biopsy specimens from each study group after incubation with VV. Transgenic mice with a constitutively active signal transducer and activator of transcription 6 gene (STAT6) were characterized for response to VV skin inoculation. Genotyping for 10 STAT6 single nucleotide polymorphisms (SNPs) was performed in a white patient sample (n = 444). Results: VV gene and protein expression were significantly increased in the skin of patients with EH compared with other subject groups after incubation with VV in vitro. Antibody neutralization of IL-4 and IL-13 resulted in lower VV replication in patients with a history of EH. Mice that expressed a constitutively active STAT6 gene compared with wild-type mice had increased mortality and satellite lesion formation after VV skin inoculation. Significant associations were observed between STAT6 SNPs and EH (rs3024975, rs841718, rs167769, and rs703817) and IFN-γ production. The strongest association was observed for a 2-SNP haplotype (patients with AD with a history of EH vs patients with AD without a history of EH, 24.9% vs 9.2%; P = 5.17 × 10−6). Conclusion: The STAT6 gene increases viral replication in the skin of patients with AD with a history of EH. Further genetic association studies and functional investigations are warranted. [ABSTRACT FROM AUTHOR]

T helper (Th) cells are crucial for the development of immunity to infections and inflammatory disease. The acquisition of specific cytokine-secreting profiles, primed by the cytokine microenvironment, is required for effector function of Th cells. The most recent addition to the growing list of effector subsets are Th9 cells that secrete IL-9. In this review, we propose a model for the transcriptional regulation of the Il9 gene in IL-9-expressing T cells and the relatedness of this subset to other Th phenotypes. We suggest that transcription factors restricted to certain Th subsets and common among several subsets might play a role in the plasticity of Th9 cells. [ABSTRACT FROM AUTHOR]

Abstract: Hypertension is one of the most common chronic conditions worldwide. There is strong evidence that low socioeconomic status is associated with elevated rates of blood pressure-related cardiovascular disease. Few studies have examined the association between socioeconomic circumstances and hypertension among people aged 65 years and older. The purpose of this study was to examine the relationship between household income and self-reported hypertension prevalence among persons aged 65 and older in the United States and Canada. Data were obtained from the 2002–2003 Joint Canada/United States Survey of Health for 755 Canadian and 1151 US adults aged 65 and older. Aggregate hypertension prevalence rates in the United States and Canada were generally similar (53.8% versus 48.0%). We found a significant inverse linear relationship between household income and the hypertension prevalence rate in the United States, but no evidence of such a relationship in Canada. In Canada, unlike the United States, the burden of hypertension is approximately equal for socioeconomically advantaged and disadvantaged older adults. It is important to consider these findings in the context of long-term and broader institutional policies. Social disparities and barriers to health care access and primary prevention among non-elderly persons in the United States may play a role in the higher hypertension prevalence rate among low-income older adults. [Copyright &y& Elsevier]

Abstract: Kaplan MS, Cooke J, Collins JG. Intravascular uptake during fluoroscopically guided cervical interlaminar steroid injection at C6-7: a case report. We report 4 cases of intravascular venous uptake of contrast material during fluoroscopically guided cervical interlaminar epidural steroid injection at the C6-7 level. The blood vessel probably involved is the posterior internal vertebral venous plexus, which drains the interlaminar space and returns blood to the right atrium through the paired vertebral veins and right and left brachiocephalic veins. In all 4 cases, intravascular uptake occurred despite negative aspiration of blood before the contrast material was injected. All patients were successfully injected at the C7-T1 level. We recommend the use of fluoroscopic guidance and the injection of contrast to identify potential placement of the injection needle within the vascular space. Potential complications of intravascular venous uptake of contrast material and steroid solution are discussed. [Copyright &y& Elsevier]

Abstract: The objective of this study was to assess the independent effect of income on health-related quality of life (HRQL) among older adults in Canada and the United States. Data were obtained from the 2002–2003 Joint Canada/United States Survey of Health. The sample consisted of 755 Canadians and 1151 Americans aged 65 years or older. HRQL was measured with the multidimensional Health Utilities Index Mark 3 (HUI3). The results indicated that in the elderly population, HRQL was significantly associated with household income in the United States but not in Canada, controlling for sociodemographic and health indicators. Various explanations for the positive linear relationship between HRQL and income in the elderly population are discussed, including the roles of access to health care and socioeconomic inequalities in the United States and Canada. [Copyright &y& Elsevier]

Abstract: Signal transducers and activators of transcription (STAT) are a family of transcription factors that regulate a broad range of cellular processes, such as proliferation, differentiation, and survival, in a large variety of cell types. Because of their regulation of diverse cellular functions, their aberrant activation is frequently associated with disease development, particularly oncogenic diseases. Much evidence exists to suggest that STAT proteins play a significant role in cellular transformation. However, which STAT proteins and to what extent they cause transformation and subsequent disease progression are topics currently being investigated. In this review, we will report on the findings concerning the involvement of Stat6 in the development of lymphoma and leukemia. Mounting evidence, in both patients and mouse models, supports a model where Stat6 is not a mere bystander, but rather, plays an active role in promoting a transformed phenotype. [Copyright &y& Elsevier]

Summary: Mycobacterium avium intracellulare complex (MAC) infection is a common cause of significant morbidity and mortality among human immunodeficiency virus (HIV)-infected patients. It usually presents as a systemic disease process. Endobronchial disease secondary to MAC is distinctly rare and can be a manifestation of the immune reconstitution in response to the highly active antiretroviral therapy. The purpose of this report is to document a case of MAC-related pulmonary mass associated causing endobronchial lesion simulating lung cancer in a patient with immune reconstitution with AIDS along with review of the relevant literature. [Copyright &y& Elsevier]

Newly arrived Hispanic immigrants are generally healthier than the U.S.-born population, but this distinction tends to diminish over time as immigrants adapt to a new and different sociocultural environment.This study sought to determine whether length of residence in the United States was associated with obesity (body mass index [BMI]>30 kg/m2) among Hispanic immigrants.Data for 2420 foreign-born Hispanic adults aged ≥18 years were obtained from the 1998 National Health Interview Survey.The prevalence of obesity among those with 0 to 4, 5 to 9, 10 to 14, and ≥15 years of residence in the United States was 9.4%, 14.5%, 21.0%, and 24.2%, respectively. A logistic regression model adjusted for smoking, physical inactivity, self-assessed health, chronic conditions, functional limitations, nonspecific psychological distress, several sociodemographic characteristics, and access to health services found that longer-term Hispanic immigrants (≥15 years) experienced a nearly four-fold greater risk of obesity than did recent immigrants (<5 years).The higher risk for obesity associated with length of residence may be due to acculturation processes such as the adoption of the unhealthy dietary practices (i.e., a diet high in fat and low in fruits and vegetables) and sedentary lifestyles of the host country. The results of this study may facilitate the planning of public health interventions that are directed at subgroups of the Hispanic population. [Copyright &y& Elsevier]

Background: Acute use of alcohol is a proximal risk factor for suicidal behavior and suicide attempts. Previous studies have established that alcohol consumption prior to suicide increases the risk of suicide completion. Thus, the current study aims to explore the association between alcohol use and suicide mortality in Kazakhstan. This is the first study to address this association in Kazakhstan.Methods: The main outcome measure was the presence of alcohol in blood of suicide decedents. Logistic regression models were used to test unadjusted and adjusted odds ratios of the risk of suicide involving acute use of alcohol. Regression modeling was used to identify significant predictors of alcohol use among suicide decedents.Results: Males (22.5 %) used alcohol more commonly before conducting suicide than females (13.4 %). The odds of alcohol involvement was 2.73 times higher for males compared to females after controlling for age and other covariates. Being a male younger than 45 years old and using suicide methods such as poisoning, immolation, and drowning increased the odds of acute use of alcohol among suicide decedents.Limitations: Data on alcohol use included information only on individuals with a positive alcohol test, and it is unknown how many suicide decedents were not tested for alcohol.Conclusions: Alcohol use is common factor contributing to suicide, particularly among young and middle-aged male adults. Alcohol use is also associated more strongly with certain methods of suicide. Further studies and more detailed data exploring alcohol consumption and suicide risks are needed in countries such as Kazakhstan. [ABSTRACT FROM AUTHOR]

Examines the regional variations in firearm suicide and homicides in the U.S. Patterns on gun ownership; Association of gun availability with firearm suicide and homicide rates; Stratification of gender and race.

Examines the use of firearms in the suicide of older women in the United States. Variations in the risk of using firearms across demographic and geographic subcategories; Characteristic of women more likely associated with the use of firearms as a suicide method; Need for research to assess the effects of limiting firearms on firearm-related suicides.

Bcl6 is required for the development of T follicular helper cells and T follicular regulatory (Tfr) cells that regulate germinal center responses. Bcl6 also affects the function of regulatory T (Treg) cells. The goal of this study was to define the functions of Bcl6 in Treg cells, including Tfr cells, in the context of allergic airway inflammation. We used a model of house dust mite sensitization to challenge wild-type, Bcl6 fl/fl Foxp3-Cre, and Prdm1 (Blimp1)fl/fl Foxp3-Cre mice to study the reciprocal roles of Bcl6 and Blimp1 in allergic airway inflammation. In the house dust mite model, Tfr cells repress the production of IgE and Bcl6+ Treg cells suppress the generation of type 2 cytokine–producing cells in the lungs. In mice with Bcl6-deficient Treg cells, twice as many ST2+ (IL-33R+) Treg cells develop as are observed in wild-type mice. ST2+ Treg cells in the context of allergic airway inflammation are Blimp1 dependent, express type 2 cytokines, and share features of visceral adipose tissue Treg cells. Bcl6-deficient Treg cells are more susceptible, and Blimp1-deficient Treg cells are resistant, to acquiring the ST2+ Treg–cell phenotype in vitro and in vivo in response to IL-33. Bcl6-deficient ST2+ Treg cells, but not Bcl6-deficient ST2+ conventional T cells, strongly promote allergic airway inflammation when transferred into recipient mice. Lastly, ST2 is required for the exacerbated allergic airway inflammation in Bcl6 fl/fl Foxp3-Cre mice. During allergic airway inflammation, Bcl6 and Blimp1 play dual roles in regulating Tfr-cell activity in the germinal center and in the development of ST2+ Treg cells that promote type 2 cytokine responses. [ABSTRACT FROM AUTHOR]

Abstract: Empiric choice of anti-fungal therapy in febrile neutropenia should be based upon a host''s susceptibility to specific fungal pathogens. We present a case of a patient with multiple risk factors for fungemia including HIV infection, Hodgkin''s disease, corticosteroid use and chemotherapy-induced neutropenia who developed disseminated cryptococcal infection while receiving caspofungin. [Copyright &y& Elsevier]

Summary Foxp3+ regulatory T (Treg) cells restrict immune pathology in inflamed tissues; however, an inflammatory environment presents a threat to Treg cell identity and function. Here, we establish a transcriptional signature of central nervous system (CNS) Treg cells that accumulate during experimental autoimmune encephalitis (EAE) and identify a pathway that maintains Treg cell function and identity during severe inflammation. This pathway is dependent on the transcriptional regulator Blimp1, which prevents downregulation of Foxp3 expression and "toxic" gain-of-function of Treg cells in the inflamed CNS. Blimp1 negatively regulates IL-6- and STAT3-dependent Dnmt3a expression and function restraining methylation of Treg cell-specific conserved non-coding sequence 2 (CNS2) in the Foxp3 locus. Consequently, CNS2 is heavily methylated when Blimp1 is ablated, leading to a loss of Foxp3 expression and severe disease. These findings identify a Blimp1-dependent pathway that preserves Treg cell stability in inflamed non-lymphoid tissues. Graphical Abstract Highlights • Most Foxp3+ Treg cells in the inflamed CNS express Blimp1 • Blimp1 inhibits Dnmt3a and prevents methylation of the Foxp3 locus • IL-6 contributes to methylation of the Foxp3 locus in a Dnmt3a-dependent manner • Blimp1 counteracts the IL-6-driven destabilization of Treg cells An inflammatory environment threatens the stability of Foxp3+ Treg cells. Garg et al. show that by expressing the transcriptional regulator Blimp1, Treg cells resist the IL-6-driven loss of Foxp3 in inflamed tissues. Blimp1 prevents the methylation and reduced expression of Foxp3 through inhibition of the methyltransferase Dnmt3a. [ABSTRACT FROM AUTHOR]

Background Mechanisms for the development of food allergy in neonates are unknown but clearly linked in patient populations to a genetic predisposition to skin barrier defects. Whether skin barrier defects contribute functionally to development of food allergy is unknown. Objective The purpose of the study was to determine whether skin barrier mutations, which are primarily heterozygous in patient populations, contribute to the development of food allergy. Methods Mice heterozygous for the filaggrin ( Flg) ft and Tmem79 ma mutations were skin sensitized with environmental and food allergens. After sensitization, mice received oral challenge with food allergen, and then inflammation, inflammatory mediators, and anaphylaxis were measured. Results We define development of inflammation, inflammatory mediators, and food allergen–induced anaphylaxis in neonatal mice with skin barrier mutations after brief concurrent cutaneous exposure to food and environmental allergens. Moreover, neonates of allergic mothers have increased responses to suboptimal sensitization with food allergens. Importantly, responses to food allergens by these neonatal mice were dependent on genetic defects in skin barrier function and on exposure to environmental allergens. ST2 blockade during skin sensitization inhibited the development of anaphylaxis, antigen-specific IgE, and inflammatory mediators. Neonatal anaphylactic responses and antigen-specific IgE were also inhibited by oral pre-exposure to food allergen, but interestingly, this was blunted by concurrent pre-exposure of the skin to environmental allergen. Conclusion These studies uncover mechanisms for food allergy sensitization and anaphylaxis in neonatal mice that are consistent with features of human early-life exposures and genetics in patients with clinical food allergy and demonstrate that changes in barrier function drive development of anaphylaxis to food allergen. [ABSTRACT FROM AUTHOR]

Summary Obesity and type 2 diabetes are associated with metabolic defects and adipose tissue inflammation. Foxp3 + regulatory T cells (Tregs) control tissue homeostasis by counteracting local inflammation. However, if and how T cells interlink environmental influences with adipocyte function remains unknown. Here, we report that enhancing sympathetic tone by cold exposure, beta3-adrenergic receptor (ADRB3) stimulation or a short-term high-calorie diet enhances Treg induction in vitro and in vivo . CD4 + T cell proteomes revealed higher expression of Foxp3 regulatory networks in response to cold or ADRB3 stimulation in vivo reflecting Treg induction. Specifically, Ragulator-interacting protein C17orf59, which limits mTORC1 activity, was upregulated in CD4 + T cells by either ADRB3 stimulation or cold exposure, suggesting contribution to Treg induction. By loss- and gain-of-function studies, including Treg depletion and transfers in vivo , we demonstrated that a T cell-specific Stat6/Pten axis links cold exposure or ADRB3 stimulation with Foxp3 + Treg induction and adipose tissue function. Our findings offer a new mechanistic model in which tissue-specific Tregs maintain adipose tissue function. [ABSTRACT FROM AUTHOR]

Background Atopic dermatitis (AD) is characterized by intense pruritis and is a common childhood inflammatory disease. Many factors are known to affect AD development, including the pleiotropic cytokine IL-4. Yet little is known regarding the direct effects of IL-4 on keratinocyte function. Objective and Methods In this report RNA sequencing and functional assays were used to define the effect of the allergic environment on primary keratinocyte function and wound repair in mice. Results Acute or chronic stimulation by IL-4 modified expression of more than 1000 genes expressed in human keratinocytes that are involved in a broad spectrum of nonoverlapping functions. Among the IL-4–induced changes, repression of fibronectin critically impaired the human keratinocyte wound response. Moreover, in mouse models of spontaneous and induced AD-like lesions, there was delayed re-epithelialization. Importantly, topical treatment with fibronectin restored the epidermal repair response. Conclusion Keratinocyte gene expression is critically shaped by IL-4, altering cell fate decisions, which are likely important for the clinical manifestations and pathology of allergic skin disease. [ABSTRACT FROM AUTHOR]

Background IL-9 is important for the growth and survival of mast cells. IL-9 is produced by T cells, natural killer T cells, mast cells, eosinophils, and innate lymphoid cells, although the cells required for mast cell accumulation during allergic inflammation remain undefined. Objective We sought to elucidate the role of T H 9 cells in promoting mast cell accumulation in models of allergic lung inflammation. Methods Adoptive transfer of ovalbumin-specific T H 2 and T H 9 cells was used to assess the ability of each subset to mediate mast cell accumulation in tissues. Mast cell accumulation was assessed in wild-type mice and mice with PU.1-deficient T cells subjected to acute and chronic models of allergic inflammation. Results Adoptive transfer experiments demonstrated that recipients of T H 9 cells had significantly higher mast cell accumulation and expression of mast cell proteases compared with control or T H 2 recipients. Mast cell accumulation was dependent on IL-9, but not IL-13, a cytokine required for many aspects of allergic inflammation. In models of acute and chronic allergic inflammation, decreased IL-9 levels in mice with PU.1-deficient T cells corresponded to diminished tissue mast cell numbers and expression of mast cell proteases. Mice with PU.1-deficient T cells have defects in IL-9 production from CD4 + T cells, but not natural killer T cells or innate lymphoid cells, suggesting a T H cell–dependent phenotype. Rag1 −/− mice subjected to a chronic model of allergic inflammation displayed reduced mast cell infiltration comparable with accumulation in mice with PU.1-deficient T cells, emphasizing the importance of IL-9 produced by T cells in mast cell recruitment. Conclusion T H 9 cells are a major source of IL-9 in models of allergic inflammation and play an important role in mast cell accumulation and activation. [ABSTRACT FROM AUTHOR]