-
The Journal of School Health Jun 2024Despite historical and contemporary trauma, American Indian and Alaska Native (AIAN; Indigenous) communities responded with resilience to the COVID-19 pandemic. However,...
BACKGROUND
Despite historical and contemporary trauma, American Indian and Alaska Native (AIAN; Indigenous) communities responded with resilience to the COVID-19 pandemic. However, AIANs experienced disproportionate rates of infection, hospitalization, death, and reduced life expectancy. School closures exacerbated disparities, leading to learning loss, economic instability, and mental health challenges among AIAN youth.
METHODS
The Project SafeSchools cohort study employed a comprehensive longitudinal convergent mixed-methods approach, integrating community-based participatory research principles. The study enrolled Navajo Nation caregivers whose children were eligible to attend local reservation-based schools. We conducted an analysis of caregiver self-report baseline data collected between August 2021 and May 2022.
RESULTS
A total of 242 caregivers completed at least part of the baseline assessment and were included in data analysis. Caregivers were primarily female (88.7%), non-Hispanic (97%), and Indigenous (97%). Most caregivers were in their late 30s (mean age 38), with varying educational backgrounds and employment statuses. Children were evenly split between males and females and distributed across different age groups. Most children attended school at baseline in various formats, including in-person, hybrid, and online-only settings. Caregivers reported a range of psychosocial and behavioral risks, including general mental distress, depressive symptoms, and anxiety for themselves and their children. Furthermore, caregivers and children exhibited various protective factors, such as strong cultural identity, resilience, and academic self-efficacy.
CONCLUSIONS
This study highlights the higher rates of mental health distress among participating caregivers and children compared to national averages. Despite these challenges, cultural protective factors remained strong and should guide future crisis response efforts.
PubMed: 38936839
DOI: 10.1111/josh.13487 -
Loss of Gcn2 exacerbates gossypol induced oxidative stress, apoptosis and inflammation in zebrafish.Fish & Shellfish Immunology Jun 2024Gossypol, a naturally occurring compound found in cottonseed meal, shows promising therapeutic potential for human diseases. However, within the aquaculture industry, it...
Gossypol, a naturally occurring compound found in cottonseed meal, shows promising therapeutic potential for human diseases. However, within the aquaculture industry, it is considered an antinutritional factor. The incorporation of cottonseed meal into fish feed introduces gossypol, which induces intracellular stresses and hinders overall health of farmed fish. The aim of this study is to determine the role of General control nonderepressible 2 (gcn2), a sensor for intracellular stresses in gossypol-induced stress responses in fish. In the present study, we established two gcn2 knockout zebrafish lines. A feeding trial was conducted to assess the growth-inhibitory effect of gossypol in both wild type and gcn2 knockout zebrafish. The results showed that in the absence of gcn2, zebrafish exhibited increased oxidative stress and apoptosis when exposed to gossypol, resulting in higher mortality rates. In feeding trial, dietary gossypol intensified liver inflammation in gcn2 zebrafish, diminishing their growth and feed conversion. Remarkably, administering the antioxidant N-acetylcysteine (NAC) was effective in reversing the gossypol induced oxidative stress and apoptosis, thereby increasing the gossypol tolerance of gcn2 zebrafish. Exposure to gossypol induces more severe mitochondrial stress in gcn2 zebrafish, thereby inducing metabolic disorders. These results reveal that gcn2 plays a protective role in reducing gossypol-induced oxidative stress and apoptosis, attenuating inflammation responses, and enhancing the survivability of zebrafish in gossypol-challenged conditions. Therefore, maintaining appropriate activation of Gcn2 may be beneficial for fish fed diets containing gossypol.
PubMed: 38936520
DOI: 10.1016/j.fsi.2024.109727 -
European Journal of Pharmacology Jun 2024Given estrogen's recognized regulatory influence on diverse metabolic and immune functions, this study sought to explore its potential impact on fibrosis and elucidate...
AIM
Given estrogen's recognized regulatory influence on diverse metabolic and immune functions, this study sought to explore its potential impact on fibrosis and elucidate the underlying metabolic regulations.
METHODS
Female mice underwent ovary removal surgery, followed by carbon tetrachloride (CCl) administration to induce liver injury. Biochemical index analysis and histopathological examination were then conducted. The expression levels of alpha-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), and collagen type 1 alpha 1 chain (COL1A1) were assessed using western blotting to further elucidate the extent of liver injury. Finally, metabolite extraction and metabolomic analysis were performed to evaluate metabolic changes.
RESULTS
Ovary removal exacerbated CCl-induced liver damage, while estrogen supplementation provided protection against hepatic changes resulting from OVX. Furthermore, estrogen mitigated liver injury induced by CCl treatment in vivo. Estrogen supplementation significantly restored liver damage induced by OVX and CCl. Comparative analysis revealed significant alterations in pathways including aminoacyl-tRNA biosynthesis, glycine, serine, and threonine metabolism, lysine degradation, and taurine and hypotaurine metabolism in estrogen treatment.
CONCLUSION
Estrogen supplementation alleviates liver injury induced by OVX and CCl, highlighting its protective effects against fibrosis and associated metabolic alterations.
PubMed: 38936452
DOI: 10.1016/j.ejphar.2024.176774 -
General Hospital Psychiatry Jun 2024Caregiving burden is set to increase with the rising incidence of cancer globally. The meta-analysis seeks to investigate the prevalence of suicide, suicidal ideation... (Review)
Review
OBJECTIVE
Caregiving burden is set to increase with the rising incidence of cancer globally. The meta-analysis seeks to investigate the prevalence of suicide, suicidal ideation and self-harm among the caregivers of patients with cancer (CPCs).
METHODS
This PRISMA-adherent systematic review involved a systematic search of PubMed, Embase, Cochrane and PsycINFO for all studies that evaluated the prevalence of suicide, suicidal ideation and self-harm in CPCs. Random effects meta-analyses were used for primary analysis.
RESULTS
Eleven studies were included. Meta-analyses indicated that the prevalence of suicidal ideation in CPCs was 11% (95%CI:6-18), suicide prevalence was 6% (95%CI:3-12), and self-harm prevalence was 15% (95%CI:8-26). Subgroup analyses revealed that CPCs above the age of 50 experienced a greater prevalence of suicidal ideation (17%, 95%CI:10-28) as compared to CPCs below 50 (6%, 95%CI:3-12). Family caregivers particularly spouses were also found to have a higher prevalence of suicidal ideation (17%, 95%CI:13-23), as compared to children (5%, 95%CI:2-10) or mothers (3%, 95%CI:1-8). Systematic review found that having a pre-existing mental health condition and lower socioeconomic status increased likelihood of suicidality.
CONCLUSION
We highlight the need for more support of CPCs at risk of suicidality. Additional research is warranted to identify other risk and protective factors.
PubMed: 38936297
DOI: 10.1016/j.genhosppsych.2024.06.011 -
International Emergency Nursing Jun 2024Workplace wellbeing encompasses all aspects of working life. Peak health organisations recognise that poor workplace wellbeing is costly, both to individuals and to the...
Workplace wellbeing encompasses all aspects of working life. Peak health organisations recognise that poor workplace wellbeing is costly, both to individuals and to the organisation, and the value in promoting healthy workplaces. Workplace wellbeing improves when its barriers are acknowledged and addressed, and protective factors are promoted. The Emergency Department (ED) is a place of intense and challenging activity, exacerbated by high workloads and overcrowding. This impacts negatively on patient care, staff safety and wellbeing. We held focus groups across four EDs to discuss barriers and enablers to wellbeing and found four core themes: Workplace Satisfaction; Barriers to Wellbeing; Organisational Culture that Prioritises Staff Wellbeing; Self-care and Self Compassion. From this, and existing literature, we collaboratively developed a contextualised staff wellbeing framework titled: 'Staff Wellbeing Good Practice Framework: From Surviving to Thriving, How to Protect your Wellbeing in the Emergency Department' that emphasises their values of Competence, Connection and Control.
PubMed: 38936273
DOI: 10.1016/j.ienj.2024.101487 -
Journal of Psychosomatic Research Jun 2024Fibromyalgia (FM) is a chronic pain condition associated with depression. However, self-efficacy (belief in own ability to manage symptoms) and social support may be...
OBJECTIVE
Fibromyalgia (FM) is a chronic pain condition associated with depression. However, self-efficacy (belief in own ability to manage symptoms) and social support may be protective. This study tested three types of social support (emotional, tangible, and instrumental) for moderation of the mediating effect of self-efficacy on the relationship between FM impact and depression over time.
METHODS
Six hundred participants with FM were randomly assigned to no intervention, social support group, or combined self-management and social support. The Fibromyalgia Impact Questionnaire, Norbeck Social Support Questionnaire, FM-modified Arthritis Self-Efficacy Scale, and Center for Epidemiological Studies-Depression surveys were administered at baseline, 6, 12, and 18 months. There were no significant intervention effects on the variables of interest, however, participants' scores were used to assess four longitudinal models.
RESULTS
Self-efficacy showed mediation both between (b = 0.104, p < .001, 95% CI = [0.071, 0.137]) and within (b = 0.89, p < .001, 95% CI = [0.073, 0.106]) individuals. Only tangible support demonstrated moderation of the relationship between FM impact and self-efficacy, and only between individuals (b = 0.154, p = .022, 95% CI = [0.022, 0.287]).
CONCLUSION
The results indicated that self-efficacy attenuated a portion of the effect of FM impact on depression over time. Additionally, higher levels of tangible support (the belief that your social network can provide you with assistance) were related to weaker influence of FM impact on self-efficacy over time. These factors may be important targets for the prevention of depression in people with FM.
PubMed: 38936010
DOI: 10.1016/j.jpsychores.2024.111836 -
PloS One 2024We investigated the interactions of unopsonized and opsonized Mycoplasma mycoides subsp. mycoides (Mmm) with bovine macrophages in vitro. Mmm survived and proliferated...
We investigated the interactions of unopsonized and opsonized Mycoplasma mycoides subsp. mycoides (Mmm) with bovine macrophages in vitro. Mmm survived and proliferated extracellularly on bovine macrophage cell layers in the absence of Mmm-specific antisera. Bovine complement used at non-bactericidal concentrations did neither have opsonizing effect nor promoted intracellular survival, whereas Mmm-specific antisera substantially increased phagocytosis and Mmm killing. A phagocytosis-independent uptake of Mmm by macrophages occurred at a high multiplicity of infection, also found to induce the production of TNF, and both responses were unaffected by non-bactericidal doses of bovine complement. Bovine complement used at higher doses killed Mmm in cell-free cultures and completely abrogated TNF responses by macrophages. These results provide a framework to identify Mmm antigens involved in interactions with macrophages and targeted by potentially protective antibodies and point towards a pivotal role of complement in the control of inflammatory responses in contagious bovine pleuropneumonia.
Topics: Animals; Cattle; Macrophages; Phagocytosis; Complement System Proteins; Mycoplasma; Tumor Necrosis Factor-alpha; Pleuropneumonia, Contagious; Mycoplasma mycoides
PubMed: 38935768
DOI: 10.1371/journal.pone.0305851 -
Science (New York, N.Y.) Jun 2024Innate lymphoid cells (ILCs) and adaptive T lymphocytes promote tissue homeostasis and protective immune responses. Their production depends on the transcription factor...
Innate lymphoid cells (ILCs) and adaptive T lymphocytes promote tissue homeostasis and protective immune responses. Their production depends on the transcription factor GATA3, which is further elevated specifically in ILC2s and T helper 2 cells to drive type-2 immunity during tissue repair, allergic disorders, and anti-helminth immunity. The control of this crucial up-regulation is poorly understood. Using CRISPR screens in ILCs we identified previously unappreciated myocyte-specific enhancer factor 2d (Mef2d)-mediated regulation of GATA3-dependent type-2 lymphocyte differentiation. Mef2d-deletion from ILC2s and/or T cells specifically protected against an allergen lung challenge. Mef2d repressed Regnase-1 endonuclease expression to enhance IL-33 receptor production and IL-33 signaling and acted downstream of calcium-mediated signaling to translocate NFAT1 to the nucleus to promote type-2 cytokine-mediated immunity.
Topics: Animals; Mice; MEF2 Transcription Factors; Th2 Cells; Immunity, Innate; Interleukin-33; NFATC Transcription Factors; Pneumonia; GATA3 Transcription Factor; Mice, Inbred C57BL; Cell Differentiation; Calcium Signaling; Hypersensitivity; Lung; Allergens; Lymphocytes; Interleukin-1 Receptor-Like 1 Protein
PubMed: 38935708
DOI: 10.1126/science.adl0370 -
Neurotoxicity Research Jun 2024Endoplasmic reticulum (ER) stress and oxidative stress (OS) are often related states in pathological conditions including Parkinson's disease (PD). This study...
Endoplasmic reticulum (ER) stress and oxidative stress (OS) are often related states in pathological conditions including Parkinson's disease (PD). This study investigates the role of anti-oxidant protein paraoxonase 2 (PON2) in ER stress and OS in PD, along with its regulatory molecule. PD was induced in C57BL/6 mice using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) treatment and in SH-SY5Y cells using 1-methyl-4-phenylpyridinium. PON2 was found to be poorly expressed in the substantia nigra pars compacta (SNc) of PD mice, and its overexpression improved motor coordination of mice. Through the evaluation of tyrosine hydroxylase, dopamine transporter, reactive oxygen species (ROS), and C/EBP homologous protein (CHOP) levels and neuronal loss in mice, as well as the examination of CHOP, glucose-regulated protein 94 (GRP94), GRP78, caspase-12, sarco/endoplasmic reticulum calcium ATPase 2, malondialdehyde, and superoxide dismutase levels in SH-SY5Y cells, we observed that PON2 overexpression mitigated ER stress, OS, and neuronal apoptosis both in vivo and in vitro. Forkhead box A1 (FOXA1) was identified as a transcription factor binding to the PON2 promoter to activate its transcription. Upregulation of FOXA1 similarly protected against neuronal loss by alleviating ER stress and OS, while the protective roles were abrogated by additional PON2 silencing. In conclusion, this study demonstrates that FOXA1-mediated transcription of PON2 alleviates ER stress and OS, ultimately reducing neuronal apoptosis in PD.
Topics: Animals; Endoplasmic Reticulum Stress; Oxidative Stress; Mice, Inbred C57BL; Endoplasmic Reticulum Chaperone BiP; Apoptosis; Aryldialkylphosphatase; Humans; Cell Line, Tumor; Male; Mice; Hepatocyte Nuclear Factor 3-alpha; Neurons
PubMed: 38935306
DOI: 10.1007/s12640-024-00709-z -
International Journal of Surgery... Jun 2024Breast cancer (BC) is the most common cancer among women worldwide, with 2.3 million new cases and 685,000 deaths annually. It has the highest incidence in North...
BACKGROUND
Breast cancer (BC) is the most common cancer among women worldwide, with 2.3 million new cases and 685,000 deaths annually. It has the highest incidence in North America, Europe, and Australia and lower rates in parts of Asia and Africa. Risk factors include age, family history, hormone replacement therapy, obesity, alcohol consumption, and lack of physical activity. BRCA1 and BRCA2 gene mutations significantly increase the risk. The five-year survival rate is over 90% in developed countries but lower in developing ones. Early screening and diagnosis, using mammography and MRI, are crucial for reducing mortality. In recent years, significant progress has been made in studying BC immunophenotyping, particularly in multicolor flow cytometry, molecular imaging techniques, and tumor microenvironment analysis. These technologies improve diagnosis, classification, and detection of minimal residual disease. Novel immunotherapies targeting the tumor microenvironment, like CAR-T cell therapy, show high efficiency and fewer side effects. High levels of tumor-infiltrating lymphocytes (TILs) correlate with better prognosis, while immune checkpoint molecules (PD-1, PD-L1) help cancer cells evade the immune system. Tumor-associated macrophages (TAMs) promote invasion and metastasis. Blocking molecules like CTLA-4, LAG-3, and TIM-3 enhance anti-tumor responses, and cytokines like IL-10 and TGF-β aid tumor growth and immune evasion. Mendelian randomization (MR) studies use genetic variants to reduce confounding bias and avoid reverse causation, providing robust causal inferences about immune cell phenotypes and BC. This approach supports the development of precision medicine and personalized treatment strategies for BC.
METHODS
This study aims to conduct Mendelian Randomization (MR) analysis on 731 immune cell phenotypes with BC in the BCAC and Finngen R10 datasets, followed by a meta-analysis of the primary results using the inverse-variance weighted (IVW) method and multiple corrections for the significance p values from the meta-analysis. Specifically, the study is divided into three parts: First, data on 731 immune cell phenotypes and BC are obtained and preprocessed from the GWAS Catalog and Open GWAS (BCAC) and the Finngen R10 databases. Second, MR analysis is performed on the 731 immune cell phenotypes with BC data from the BCAC and Finngen R10 databases, followed by a meta-analysis of the primary results using the IVW method, with multiple corrections for the significance p values from the meta-analysis. Finally, the positively identified immune cell phenotypes are used as outcome variables, and BC as the exposure variable for reverse MR validation.
RESULTS
The study found that two immune phenotypes exhibited strong significant associations in MR analysis combined with meta-analysis and multiple corrections. For the immune phenotype CD3 on CD28+ CD4-CD8- T cells, the results were as follows: In the BCAC dataset, the IVW result was Odds Ratio (OR) = 0.942 (95% confidence interval (CI) = 0.915 ~ 0.970, P = 6.76 × 10-5), β = -0.059; MR Egger result was β = -0.095; and the weighted median result was β = -0.060. In the Finngen R10 dataset, the IVW result was OR = 0.956 (95% CI = 0.907 ~ 1.01, P = 0.092), β = -0.045; MR Egger result was β = -0.070; and weighted median result was β = -0.035. The β values were consistent in direction across all three MR methods in both datasets. The meta-analysis of the IVW results from both datasets showed OR = 0.945 (95% CI = 0.922 ~ 0.970, P = 1.70 × 10-5). After Bonferroni correction, the significant P-value was P = 0.01, confirming the immune phenotype as a protective factor against BC. For the immune phenotype HLA DR on CD33- HLA DR+, the results were as follows: In the BCAC dataset, the IVW result was OR = 0.977 (95% CI = 0.964 ~ 0.990, P = 7.64 × 10-4), β = -0.023; MR Egger result was β = -0.016; and the weighted median result was β = -0.019. In the Finngen R10 dataset, the IVW result was OR = 0.960 (95% CI = 0.938 ~ 0.983, P = 6.51 × 10-4), β = -0.041; MR Egger result was β = -0.064; and weighted median result was β = -0.058. The β values were consistent in direction across all three MR methods in both datasets. The meta-analysis of the IVW results from both datasets showed OR = 0.973 (95% CI = 0.961 ~ 0.984, P = 3.80 × 10-6). After Bonferroni correction, the significant P-value was P = 0.003, confirming this immune phenotype as a protective factor against BC. When the immune cell phenotypes CD3 on CD28+ CD4-CD8- T cells and HLA DR on CD33- HLA DR+ were used as outcomes and BC was used as exposure, the data processing and analysis procedures were the same. The MR analysis results are as follows: Data from the FinnGen database regarding the effect of positive immune phenotypes on malignant neoplasm of the breast indicated a β coefficient of -0.011, OR = 0.99 (95% CI = -0.117 ~ 0.096, P = 0.846); data from the BCAC database regarding favorable immune phenotypes for BC demonstrated a β coefficient of -0.052, OR = 0.095 (95% CI = -0.144 ~ 0.040, P = 0.266). The results suggest insufficient evidence in both databases to indicate that BC inversely affects these two immune cell phenotypes.
CONCLUSIONS
Evidence suggests that the immune cell phenotypes CD3 on CD28+ CD4-CD8- T cells and HLA DR on CD33- HLA DR+ protect against BC. This protective effect may be achieved through various mechanisms, including enhancing immune surveillance to recognize and eliminate tumor cells; secreting cytokines to inhibit tumor cell proliferation and growth directly; triggering apoptotic pathways in tumor cells to reduce their number; modulating the tumor microenvironment to make it unfavorable for tumor growth and spread; activating other immune cells to boost the overall immune response; and inhibiting angiogenesis to reduce the tumor's nutrient supply. These mechanisms work together to help protect BC patients and slow disease progression. Both immune cell phenotypes are protective factors for BC patients and can be targeted to enhance their function and related pathways for BC treatment.
PubMed: 38935111
DOI: 10.1097/JS9.0000000000001840