Generation of antigen-specific memory CD4 T cells by heterologous immunization enhances the magnitude of the germinal center response upon influenza infection.

Current influenza vaccine strategies have yet to overcome significant obstacles, including rapid antigenic drift of seasonal influenza viruses, in generating efficacious long-term humoral immunity. Due to the necessity of germinal center formation in generating long-lived high affinity antibodies, the germinal center has increasingly become a target for the development of novel or improvement of less-efficacious vaccines. However, there remains a major gap in current influenza research to effectively target T follicular helper cells during vaccination to alter the germinal center reaction. In this study, we used a heterologous infection or immunization priming strategy to seed an antigen-specific memory CD4+ T cell pool prior to influenza infection in mice to evaluate the effect of recalled memory T follicular helper cells in increased help to influenza-specific primary B cells and enhanced generation of neutralizing antibodies. We found that heterologous priming with intranasal infection with acute lymphocytic choriomeningitis virus (LCMV) or intramuscular immunization with adjuvanted recombinant LCMV glycoprotein induced increased antigen-specific effector CD4+ T and B cellular responses following infection with a recombinant influenza strain that expresses LCMV glycoprotein. Heterologously primed mice had increased expansion of secondary Th1 and Tfh cell subsets, including increased CD4+ TRM cells in the lung. However, the early enhancement of the germinal center cellular response following influenza infection did not impact influenza-specific antibody generation or B cell repertoires compared to primary influenza infection. Overall, our study suggests that while heterologous infection or immunization priming of CD4+ T cells is able to enhance the early germinal center reaction, further studies to understand how to target the germinal center and CD4+ T cells specifically to increase long-lived antiviral humoral immunity are needed.

Maternal Helminth Infection Causes Dysfunctional B Cell Development in Male Offspring.

Infections during pregnancy are known to trigger alterations in offspring immunity, often leading to increased disease susceptibility. Maternal helminth infections correlate with lower Ab titers to certain childhood immunizations and putative decreased vaccine efficacy. The mechanisms that underlie how maternal infection blunts offspring humoral responses are unclear. Using our murine model of maternal schistosomiasis, we found that maternal helminth infection decreases the germinal center response of all offspring to tetanus immunization. However, only male offspring have defects in memory B cell and long-lived plasma cell generation. We found this sex-specific aberration begins during B cell development within the bone marrow via alteration of the IL-7 niche and persists throughout antigenic activation in the germinal center in the periphery. Critically, these defects in males are cell intrinsic, persisting following adoptive transfer to control male pups. Together, these data show that maternal infections can alter both the bone marrow microenvironment and the development of B lymphocytes in a sex-specific manner. This study correlates maternal infection induced defects in early life B cell development with ineffective Ab responses after vaccination.

Conducting Comparative Effectiveness, Multisite Palliative Care and Advance Care Planning Trials: Lessons Learned and Future Directions From PCORI-Funded Studies.

The Patient-Centered Outcomes Research Institute (PCORI) funded multiple large-scale comparative effectiveness clinical trials evaluating palliative care (PC) and advance care planning (ACP) healthcare delivery models. This article provides an overview of the most common barriers our investigative teams encountered while implementing these trials and the strategies we utilized to overcome these challenges, with particular attention to identifying research partners for multisite trials; addressing contracting and regulatory issues; creating a team governance structure; training and engaging study staff across sites; recruiting, consenting, and enrolling study participants; collecting PC and ACP data and study outcomes; and managing multisite collaborations. The goal of this article is to provide guidance on how to best plan for and conduct rigorous trials evaluating PC and ACP healthcare delivery interventions moving forward.

Altered Offspring Immunity in Maternal Parasitic Infections.

Maternal infection during pregnancy is known to alter the development and function of offspring's immune system, leading to inappropriate immune responses to common childhood infections and immunizations. Although this is an expanding field, maternal parasitic infections remain understudied. Millions of women of reproductive age are currently at risk for parasitic infection, whereas many pregnant, chronically infected women are excluded from mass drug administration due partially to a lack of resources, as well as fear of unknown adverse fetal developmental outcomes. In areas endemic for multiple parasitic infections, such as sub-Saharan Africa, there are increased rates of morbidity and mortality for various infections during early childhood in comparison with nonendemic areas. Despite evidence supporting similar immunomodulatory effects between various parasite species, there is no clear mechanistic understanding of how maternal infection reprograms offspring immunity. This brief review will compare the effects of selected maternal parasitic infections on offspring immunity.

A qualitative exploration of children's lives with rare diseases.

BACKGROUND: Rare diseases encompass a diverse group of debilitating and sometimes life-threatening conditions that affect a small percentage of the population, posing a significant public health challenge. Despite their rarity, around 70% of these diseases afflict children, yet limited research has focused on their experiences. This study aimed to gain insights into the day-to-day challenges children living with rare diseases face. METHODS: We conducted semistructured one-to-one interviews with 11 children and young people (7-16 years) diagnosed with a range of rare diseases, purposively sampled from a tertiary pediatric healthcare setting in Ireland. We analyzed the interview transcripts, and themes were devised inductively. RESULTS: Two themes were identified: "Knowledge and Understanding of Rare Diseases" and "Fitting in Versus Feeling Different." These themes emerged across various settings-the home, hospital, school, and social environments-to illustrate the impact of rare diseases on the participants' daily lives. A conceptual framework was developed to illustrate how the children's knowledge, experiences, and emotions shape their identity in a rare disease context. CONCLUSIONS: Our analysis revealed a complex interplay between the participants' sense of belonging and their awareness of being different, influenced by the manifestations and demands of their rare conditions or illnesses. This duality in their identity was most pronounced in social settings, where the participants felt the most significant impact of their rare diseases. Understanding this interplay sheds light on the unique social challenges children with rare medical conditions face. Raising awareness about these conditions could mitigate these children's social challenges, fostering a more inclusive society for those with rare diseases.

Sleep disturbances and interrelationship between persons with dementia and family caregivers: The lived experiences of Korean American Dyads.

BACKGROUND: Little research has investigated sleep quality in dyadic interrelationships between persons with dementia (PWD) and family caregivers, particularly among immigrant ethnic minorities, such as Korean Americans. PURPOSE: The study aimed to describe lived experiences of sleep disturbances and sleep interrelationships between Korean American PWD and their family caregivers. METHODS: A descriptive qualitative design used semi-structured interviews with cohabitating PWD-caregiver dyads. RESULTS: Eleven Korean American dyads participated (PWD mean age: 82.7, SD=2.3; caregivers mean age: 69.1, SD=10.2). Major themes included (1) linked sleep disturbances between PWD and caregivers, (2) interrelationship in dyads, (3) language challenges within and outside the dyads, and (4) strategies that improve sleep quality for dyads. CONCLUSION: Findings demonstrated bidirectional influences in dyadic sleep disturbances, where caregiving reciprocally impacted PWD sleep as part of an interactional unit. Communication barriers and limited community resources posed challenges for these dyads. Future sleep interventions should consider culturally competent, dyadic approaches.

COVID-19 disaster recovery capitals: A conceptual framework to guide holistic and strengths-based support strategies.

ISSUE ADDRESSED: The COVID-19 pandemic bears many similarities to other disasters such as bushfires, earthquakes and floods. It also has distinctive features including its prolonged and recurrent nature and the social isolation induced by pandemic responses. Existing conceptual frameworks previously applied to the study of disaster, such as the Recovery Capitals Framework (RCF), may be useful in understanding experiences of the COVID-19 pandemic and in guiding agencies and governments tasked with supporting communities. METHODS: This paper presents an analysis of interviews conducted with residents of the Australian state of Victoria in 2020-2021. The RCF was used to analyse how participant experiences and well-being were influenced by seven forms of capital-social, human, natural, financial, built, cultural and political-with particular focus on the interactions between these capitals. RESULTS: Social capital featured most prominently in participants' accounts, yet the analysis revealed important interactions between social and other capitals that shaped their pandemic experiences. The RCF supported a strengths-based and holistic analysis while also revealing how inequities and challenges were compounded in some cases. CONCLUSIONS: Findings can be leveraged to develop effective and innovative strategies to support well-being and disrupt patterns of compounding inequity. Applying the RCF in the context of COVID-19 can help to link pandemic research with research from a wide range of disasters. SO WHAT?: In an increasingly complex global landscape of cascading and intersecting disasters including pandemics, flexible and nuanced conceptual approaches such as the RCF can generate valuable insights with practical implications for health promotion efforts.

Maternal schistosomiasis impairs offspring Interleukin-4 production and B cell expansion.

Epidemiological studies have identified a correlation between maternal helminth infections and reduced immunity to some early childhood vaccinations, but the cellular basis for this is poorly understood. Here, we investigated the effects of maternal Schistosoma mansoni infection on steady-state offspring immunity, as well as immunity induced by a commercial tetanus/diphtheria vaccine using a dual IL-4 reporter mouse model of maternal schistosomiasis. We demonstrate that offspring born to S. mansoni infected mothers have reduced circulating plasma cells and peripheral lymph node follicular dendritic cells at steady state. These reductions correlate with reduced production of IL-4 by iNKT cells, the cellular source of IL-4 in the peripheral lymph node during early life. These defects in follicular dendritic cells and IL-4 production were maintained long-term with reduced secretion of IL-4 in the germinal center and reduced generation of TFH, memory B, and memory T cells in response to immunization with tetanus/diphtheria. Using single-cell RNASeq following tetanus/diphtheria immunization of offspring, we identified a defect in cell-cycle and cell-proliferation pathways in addition to a reduction in Ebf-1, a key B-cell transcription factor, in the majority of follicular B cells. These reductions are dependent on the presence of egg antigens in the mother, as offspring born to single-sex infected mothers do not have these transcriptional defects. These data indicate that maternal schistosomiasis leads to long-term defects in antigen-induced cellular immunity, and for the first time provide key mechanistic insight into the factors regulating reduced immunity in offspring born to S. mansoni infected mothers.

Metabolic reprogramming of the myeloid lineage by Schistosoma mansoni infection persists independently of antigen exposure.

Macrophages have a defined role in the pathogenesis of metabolic disease and cholesterol metabolism where alternative activation of macrophages is thought to be beneficial to both glucose and cholesterol metabolism during high fat diet induced disease. It is well established that helminth infection protects from metabolic disease, but the mechanisms underlying protection are not well understood. Here, we investigated the effects of Schistosoma mansoni infection and cytokine activation in the metabolic signatures of bone marrow derived macrophages using an approach that integrated transcriptomics, metabolomics, and lipidomics in a metabolic disease prone mouse model. We demonstrate that bone marrow derived macrophages (BMDM) from S. mansoni infected male ApoE-/- mice have dramatically increased mitochondrial respiration compared to those from uninfected mice. This change is associated with increased glucose and palmitate shuttling into TCA cycle intermediates, increased accumulation of free fatty acids, and decreased accumulation of cellular cholesterol esters, tri and diglycerides, and is dependent on mgll activity. Systemic injection of IL-4 complexes is unable to recapitulate either reductions in systemic glucose AUC or the re-programing of BMDM mitochondrial respiration seen in infected males. Importantly, the metabolic reprogramming of male myeloid cells is transferrable via bone marrow transplantation to an uninfected host, indicating maintenance of reprogramming in the absence of sustained antigen exposure. Finally, schistosome induced metabolic and bone marrow modulation is sex-dependent, with infection protecting male, but not female mice from glucose intolerance and obesity. Our findings identify a transferable, long-lasting sex-dependent reprograming of the metabolic signature of macrophages by helminth infection, providing key mechanistic insight into the factors regulating the beneficial roles of helminth infection in metabolic disease.

Telephone Outreach Enhances Recruitment of Underrepresented Seriously Ill Patients for an Advance Care Planning Pragmatic Trial.

BACKGROUND: Patients experiencing systemic patterns of disadvantage, such as racial/ethnic minorities and those with limited English proficiency, are underrepresented in research. This is particularly true for large pragmatic trials of potentially sensitive research topics, such as advance care planning (ACP). It is unclear how phone outreach may affect research participation by underrepresented individuals. OBJECTIVE: To assess the effect of phone outreach, in addition to standard mail survey recruitment, in a population-based ACP pragmatic trial at three academic health systems in California. DESIGN: Retrospective cohort study PATIENTS: Primary care patients with serious illness were mailed a survey in their preferred language. Patients who did not initially respond by mail received up to three reminder phone calls with the option of survey completion by phone. MAIN MEASURES: Effect of phone outreach on survey response rate associated with respondent demographic characteristics (e.g., Social Vulnerability Index [SVI], range 0 (low) to 1 (high)). RESULTS: Across the health systems, 5998 seriously ill patients were mailed surveys. We obtained completed surveys from 1215 patients (20% response rate); 787 (65%) responded after mail alone and 428 (35%) participated only after phone outreach. Patients recruited after phone outreach compared to mail alone were more socially vulnerable (SVI 0.41 v 0.35, P < 0.001), were more likely to report being a racial/ethnic minority (35% v 28%, P = 0.006), and non-English speaking (16% v 10%, P = 0.005). Age and gender did not differ significantly. The inclusion of phone outreach resulted in a sample that better represented the baseline population than mail alone in racial/ethnic minority (28% mail alone, 30% including phone outreach, 36% baseline population), non-English language preference (10%, 12%, 15%, respectively), and SVI (0.35, 0.37, 0.38, respectively). CONCLUSIONS: Phone outreach for a population-based survey in a pragmatic trial concerning a potentially sensitive topic significantly enhanced recruitment of underrepresented seriously ill patients.

Children and young people's experiences of living with rare diseases: An integrative review.

PROBLEM: Rare diseases are any disease affecting fewer than five people in 10,000. More than 8000 rare diseases and 50-75% of all rare diseases affect children. The purpose of this review was to critically appraise and synthesize existing literature relating to the impact of rare diseases on children's day-to-day lives. ELIGIBILITY CRITERIA: An integrative literature review was conducted using the CINAHL Plus, PsycINFO, and PubMed databases. Studies were included if they were a primary source was published between the years 2005 and 2019 and written in the English language. SAMPLE: Eight primary sources met the inclusion criteria. RESULTS: Seven main themes emerged from the review as follows: (i) the experience of stigmatisations, (ii) self-consciousness, (iii) restrictions in independent living, (iv) developing resilience/coping strategies, (v) psychological and emotional impact, (vi) social impact vs social connectedness and (vii) transition challenges. CONCLUSIONS: The experience of having a rare illness differed across different age groups. Children (typically aged 3-10) with rare diseases generally view themselves and their lives the same way like their healthy peers. They were more likely to report being adaptive and resilient than those aged 12 or older. Young people reported being different compared to young children, and they faced numerous challenges related to their illness. IMPLICATIONS FOR PRACTICE: To provide the best possible level of care for children and families with rare disorders, health services must be informed and equipped to provide the necessary supports specific to the unique needs of children and young people living with rare diseases.

A repeated cross-sectional and longitudinal study of mental health and wellbeing during COVID-19 lockdowns in Victoria, Australia.

BACKGROUND: Population surveys across the world have examined the impact of the COVID-19 pandemic on mental health. However, few have simultaneously examined independent cross-sectional data with longitudinal data, each of which have different strengths and weaknesses and facilitate the investigation of distinct research questions. This study aimed to investigate psychological distress and life satisfaction during the first and second lockdowns in the state of Victoria, Australia, and the social factors that may be affected by lockdowns and could affect mental health. METHODS: The VicHealth Victorian Coronavirus Wellbeing Impact Study included two 20-min opt-in online panel surveys conducted in May and September 2020 in Victoria, each with a sample of 2000 adults aged 18 + . A two-part study design was used: a repeated cross-sectional study of respondents who participated in Survey One and Survey Two, followed by a longitudinal nested cohort study. The primary exposures were social solidarity, social connectedness and staying connected with family and friends. Using logistic regression modelling, we explored the associations between our exposures and primary outcomes of psychological distress and life satisfaction with and without adjustment for covariates, both cross-sectionally and longitudinally. The results from the multivariable models were summarised using adjusted Odds Ratios (aOR), 95% Confidence Intervals (CI). RESULTS: Cross-sectional results indicated that the percentage of participants with low life satisfaction was significantly higher in the second survey sample (53%) compared to the first (47%). The percentage of participants with high psychological distress was higher but not significantly different between the two survey samples (14% first survey vs 16% second survey). Longitudinal study results indicated that lower social connectedness was significantly associated with higher psychological distress (aOR:3.3; 95% CI: 1.3-8.4) and lower life satisfaction (aOR:0.2; 95% CI: 0.1-0.4). Younger adults had higher psychological distress compared to older adults (aOR:6.8; 95% CI:1.5-31.1). Unemployment at the time of the first survey was significantly associated with lower life satisfaction at the second survey (aOR:0.5; 95% CI: 0.3-0.9). CONCLUSION: This study supports the findings of other international studies. It also highlights the need to promote increased social connection and maintain it at times of isolation and separation, particularly amongst younger adults.

Quarantine preparedness - the missing factor in COVID-19 behaviour change? Qualitative insights from Australia.

BACKGROUND: A key feature of the global public health response to contain and slow the spread of COVID-19 has been community-based quarantine and self-isolation. As part of The Optimise Study, this research sought to understand the factors that influence people's ability to undertake home-based quarantine and isolation to contain the spread of COVID-19. METHODS: Semi-structured qualitative phone interviews (n = 25) were conducted by telephone with people who participated in community-based quarantine in Australia before 31 March 2020. The Capability Opportunity Motivation Behaviour model was used to conduct a thematic analysis. RESULTS: Participants required clear, accessible and trusted information to guide them in home-based quarantine and isolation. A sense of social responsibility and belief in the efficacy of the restrictions to reduce viral transmission aided their motivation. Access to essential needs, supportive living environments, and emotional support were required to adhere to restrictions, but few were prepared. CONCLUSIONS: Findings demonstrate that in addition to having the capability and motivation to adhere to restrictions, it is vital that people are also encouraged to prepare for the challenge to ensure access to physical, social and emotional support. Findings also illustrate the importance of engaging communities in planning and preparedness for quarantine and self-isolation public health responses.

Think Big: A multinational collaboration to promote children's role as coresearchers in participatory research.

The field of participatory research with children developed largely thanks to shared learning between different cultures, places, and disciplines. However, grand narratives and power relationships in academia inherited from colonialism and imperialism can threaten to obstruct the transformative value of this approach. In this article, we present the case of Think Big, a multinational collaboration for participatory research with children that involved adult and child coresearchers from Australia, Chile, Colombia, and the United Kingdom. Our aim was to explore how this project helped build solidarities between adult researchers from different countries and disciplines. We applied a methodology of diffraction to explore the processes and outcomes of this collaboration and presented our insights using the metaphor of a tree to explain the roots (knowledges and frameworks), trunk (ongoing collaboration and communication between the teams from different countries), branches (local projects), and fruits (research outcomes) of our work. Based on our experience, we proposed that multinational collaborations for participatory research offer important opportunities for adult researchers to collaborate with children to generate more democratic knowledge about their lives and to generate more egalitarian relationships between adult researchers from different places and backgrounds. However, it is important to anticipate that multinational collaborations are more likely to be affected by social and political upheavals, and language barriers must be overcome to decentralize academia. Also, the organizations involved in these collaborations need to develop strategies that facilitate funding, ethics clearance, and international research agreements.

A Culturally and Linguistically Appropriate Telephone Support Intervention for Diverse Family Caregivers of Persons With Dementia During the COVID-19 Pandemic.

Caregivers of persons with dementia (PWDs) were socially isolated with little support during the COVID-19 pandemic "Stay-At-Home" order in the United States. To enhance social and emotional connection for diverse caregivers, a culturally/linguistically appropriate telephone intervention provided compassionate listening, mindful breathing, and COVID-19 safety education. The study purpose was to understand caregiving challenges and to evaluate the intervention for caregivers during the early pandemic using a qualitative approach. Twenty-three caregivers participated in the intervention provided by bilingual research assistants for 3 months. Call logs were used to describe the caregivers' dialogue. Thematic analysis identified (a) the challenges, including fear of coronavirus disease, providing around-the-clock care, and forced isolation and negative emotions; and (b) caregivers' experience with the intervention, including connecting with the outside, relief from emotional stress, reliable COVID-19 information, and reinformed caregiving skills. Results suggest that the telephone support was of benefit to diverse caregivers of PWDs during the pandemic by promoting social connection and reducing emotional distress.

Nutrition and oral health in early childhood: associations with formal and informal childcare.

OBJECTIVE: To examine associations between childcare type and nutrition and oral health indicators. DESIGN: Cross-sectional data extracted from a longitudinal birth cohort. Parent-completed FFQ and questions regarding oral health and childcare use. The associations between childcare type, classified into four groups: parent care only (PCO), formal childcare only (FCO), informal childcare only (ICO) or combination of care (F&I), and nutrition and oral health indicators were examined. SETTING: Home and childcare. PARTICIPANTS: Families with children aged 3 years (n 273) and 4 years (n 249) in Victoria, Australia. RESULTS: No associations were observed between childcare type and core food/beverage consumption or oral health indicators. For discretionary beverages, compared with children receiving PCO at age 3 years, children in FCO or F&I were less likely to frequently consume fruit juice/drinks (FCO: adjusted OR (AOR) 0·41, 95 % CI 0·17, 0·96, P = 0·04; F&I: AOR 0·32, 95 % CI 0·14, 0·74, P = 0·008). At age 4 years, children receiving FCO or ICO were less likely to consume sweet beverages frequently compared with children receiving PCO: fruit juice/drink (ICO: AOR 0·42, 95 % CI 0·19, 0·94, P = 0·03; FCO: AOR 0·35, 95 % CI 0·14, 0·88, P = 0·03) and soft drink (ICO: AOR 0·23, 95 % CI 0·07, 0·74, P = 0·01; FCO: AOR 0·14, 95 % CI 0·03, 0·76, P = 0·02). CONCLUSIONS: Associations between childcare type and discretionary beverage intake were observed. Investigation into knowledge, attitudes and activities in formal and informal childcare settings is required to explore different health promotion practices that may influence nutrition and oral health.

The dynamic course of psychological outcomes following the Victorian Black Saturday bushfires.

OBJECTIVES: To profile the long-term mental health outcomes of those affected by the 2009 Black Saturday bushfires and to document the course of mental health since the disaster. METHOD: The longitudinal Beyond Bushfires study included 1017 respondents (Wave 1; 3-4 years after the fires), 736 (76.1%) at Wave 2 (5 years after the fires) and 525 (51.6%) at Wave 3 (10 years after the fires). The survey indexed fire-related and subsequent stressful events, probable posttraumatic stress disorder, major depressive disorder, alcohol use, severe distress and receipt of health services for mental health problems. RESULTS: Relative to their status 3-4 years after the fires, there were reduced rates of fire-related posttraumatic stress disorder (6.2% vs 12.2%), general posttraumatic stress disorder (14.9% vs 18.7%) and severe distress (4.4% vs 7.5%) at 10 years. There were comparable rates between Wave 1 and Wave 3 for depression (10.9% vs 8.3%) and alcohol abuse (21.8% vs 18.5%). Of people in high-affected regions, 22.1% had posttraumatic stress disorder, depression or severe distress at Wave 3. One-third to one-half of participants who reported probable posttraumatic stress disorder or depression at any assessment did not display the disorder at the next assessment. Worsening of mental health at Wave 3 was associated with the extent of property loss, exposure to recent traumatic events or recent stressful life events. Only 24.6% of those with a probable disorder had sought professional help for this in the previous 6 months. CONCLUSION: Approximately one-fifth of people from high-affected areas have a probable psychological disorder a decade after the fires. Mental health appears to fluctuate for those who are not consistently resilient, apparently as a result of ongoing stressors. The observation that most people with probable disorder are not receiving care highlights the need for further planning about managing long-term mental health needs of disaster-affected communities.

Anger Dimensions and Mental Health Following a Disaster: Distribution and Implications After a Major Bushfire.

Anger is an important dimension of affect and a prominent feature of posttraumatic mental health, but it is commonly overlooked in postdisaster settings. We aimed to examine the distribution and implications of significant anger problems in the aftermath of a natural disaster, via analyses of Beyond Bushfires survey data from 736 residents of rural communities 5 years after the 2009 Black Saturday bushfires in Victoria, Australia. Assessments included the five-item Dimensions of Anger Reaction (DAR-5) scale along with measures of PTSD, depression, and significant mental illness, and indicators of life satisfaction, suicidality, hostile aggressive behavior, and violence exposure. The results indicated that approximately 10% of respondents from areas highly affected by the bushfires scored above the provisional cutoff criteria for significant anger problems on the DAR-5, which was a more than 3-fold increase, OR = 3.26, relative to respondents from areas of low-to-moderate bushfire impact. The rates were higher among women, younger participants, and those who were unemployed, and co-occurred commonly, although not exclusively, with other postdisaster mental health problems. Anger problems were also associated with lower life satisfaction, ß = -.31, an 8-fold increase in suicidal ideation, OR = 8.68, and a nearly 13-fold increase in hostile aggressive behavior, OR = 12.98. There were associations with anger problems and violence exposure, which were reduced when controlling for covariates, including probable PTSD. The findings provide evidence indicating that anger is a significant issue for postdisaster mental health and should be considered routinely alongside other posttraumatic mental health issues.

IL-4 promotes stromal cell expansion and is critical for development of a type-2, but not a type 1 immune response.

IL-4 is critical for differentiation of Th2 cells and antibody isotype switching, but our work demonstrated that it is produced in the peripheral LN under both Type 2, and Type 1 conditions, raising the possibility of other functions. We found that IL-4 is vital for proper positioning of hematopoietic and stromal cells in steady state, and the lack of IL-4 or IL-4Rα correlates with disarrangement of both follicular dendritic cells and CD31+ endothelial cells. We observed a marked disorganization of B cells in these mice, suggesting that the lymphocyte-stromal cell axis is maintained by the IL-4 signaling pathway. This study showed that absence of IL-4 correlates with significant downregulation of Lymphotoxin alpha (LTα) and Lymphotoxin beta (LTß), critical lymphokines for the development and maintenance of lymphoid organs. Moreover, immunization of IL-4 deficient mice with Type 2 antigens failed to induce lymphotoxin production, LN reorganization, or germinal center formation, while this process is IL-4 independent following Type 1 immunization. Additionally, we found that Type 1 antigen mediated LN reorganization is dependent on IFN-γ in the absence of IL-4. Our findings reveal a role of IL-4 in the maintenance of peripheral lymphoid organ microenvironments during homeostasis and antigenic challenge.

Natural history of dental caries: Baseline characteristics of the VicGen birth cohort study.

BACKGROUND: Early-life dental caries is a major global health problem. Children's first dental visit is recommended at 2 years age. The VicGeneration (VicGen) oral health birth cohort study aims to understand the multifactorial nature of early childhood caries. This report describes the baseline characteristics of children in the VicGen study. METHODS: We merged data between the first (at birth) and fourth waves (18 month age) to assess dental caries among children (primary outcome) and other oral diseases (secondary outcomes) employing t tests, chi-square tests, Fisher's exact tests, and Cochran-Mantel-Haenszel tests using IBM-SPSS(v25). RESULTS: Most children lived in metros with two-parent families. Most guardians were women graduated from high school. Twenty-seven of 389 (6.94%) 18-month-old children experienced dental caries. More children living in rural areas (vs. urban) experienced caries. Females were more likely to experience caries (OR: 2.16). Several children had other oral health problems. In early life, children's oral examination was conducted by midwives, breastfeeding/lactation consultants, hospital nurses, speech pathologists, and breastfeeding clinic staff. CONCLUSION: VicGen baseline characteristics show that almost 7% of the 18-month-old children experienced caries. There is a need to advance children's recommended first dental visit date and to train early-life healthcare professionals about oral diseases.