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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 -
Investigative Ophthalmology & Visual... Jun 2024To assess the association of age-related macular degeneration (AMD) progression and statins, connected with AMD genetic risk, and if there is an interplay between...
PURPOSE
To assess the association of age-related macular degeneration (AMD) progression and statins, connected with AMD genetic risk, and if there is an interplay between statins and genetics.
METHODS
In this analysis, 682 subjects made two visits (6.5-year follow-up) of the Coimbra Eye Study. Subjects who started taking statins at any time point between the two visits were considered. Progressors were defined as not having AMD at baseline and having any AMD at follow-up. Genetic risk scores (GRSs) were calculated individually with 52 independent variants associated with AMD. Time to progression was estimated using unadjusted Kaplan-Meier curves. An extended Cox model was used for the association between statins and GRS with the risk for AMD progression. Multiplicative and additive interactions were assessed.
RESULTS
Median survival time was 7.50 years for subjects not taking statins and 7.62 for subjects taking statins (P < 0.001). Statin intake reduced the risk for progression to AMD in 48%, adjusting for age, sex, body mass index, smoking, and diabetes (model 1) and GRS (model 2). The combined effects of not taking statins and having high GRS increased the progression risk fourfold compared to taking statins and having low GRS (hazard ratio [HR] = 4.25; 95% confidence interval [CI], 1.62-11.16; P = 0.003). For subjects not taking statins, an increased risk of progression was found for those subjects with high GRS compared to subjects with low GRS (HR = 1.80; 95% CI, 1.13-2.85; P = 0.013). No statistically significant multiplicative or additive interactions were found.
CONCLUSIONS
Statins seem to be protective against AMD progression, and genetics may play a role in treatment response.
Topics: Humans; Male; Female; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Aged; Disease Progression; Macular Degeneration; Follow-Up Studies; Risk Factors; Middle Aged; Aged, 80 and over; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease
PubMed: 38935028
DOI: 10.1167/iovs.65.6.38 -
Journal of Family Psychology : JFP :... Jun 2024Protective parenting, when enacted in contexts that do not require it, predicts child anxiety. Both child (e.g., temperament) and maternal (e.g., physiology and...
Protective parenting, when enacted in contexts that do not require it, predicts child anxiety. Both child (e.g., temperament) and maternal (e.g., physiology and cognition) factors relate to parenting behavior, supporting family systems theory. In order to better understand the development of environmental risk for child anxiety, the present study applied the integrated social information and emotion processing theory to protective parenting, assessing concurrent relations among child temperament, maternal physiology, maternal cognitions, and protective parenting in toddlerhood. The present study also investigated whether the theory could be applied to longitudinal relations, testing cognition as a mechanism by which maternal physiology and child temperament predict maternal protective parenting over time. Study participants included 189 mothers (89.9% White, 2.1% Hispanic, 32.3% with annual household income ≤ $40,000) and children (55.6% male, 81.0% White, 3.7% Hispanic). Results indicated that the theory was partially applicable to both concurrent and prospective mother-child relations implicated in child anxiety development. Namely, child inhibited temperament (IT) related concurrently to maternal beliefs about the harm of child anxiety at child age 1 year, and to maternal protective parenting at child ages 2 and 3 years. Maternal baseline respiratory sinus arrythmia related to protective parenting at child age 3 years. Longitudinally, maternal beliefs at child age 1 year predicted maternal perceptions of child IT at child age 2 years. Maternal beliefs at child age 2 years predicted maternal protective parenting at child age 3 years. Although the mechanistic role of cognition was not supported, child emotion processes and maternal cognitions may uniquely contribute to maternal protective parenting. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
PubMed: 38934913
DOI: 10.1037/fam0001252 -
Polish Archives of Internal Medicine Jun 2024The role of iron homeostasis has become increasingly recognized as a key factor in determining the prognosis of patients with heart failure (HF). Disruptions in iron...
INTRODUCTION
The role of iron homeostasis has become increasingly recognized as a key factor in determining the prognosis of patients with heart failure (HF). Disruptions in iron balance, encompassing deficiency and overload, can affect patient prognosis, therefore, these indicators are considered of significant implications for treatment and management strategies.
OBJECTIVES
The current study intends to delve into the association between iron homeostasis-related indicators and long-term mortality as well as first-admission mortality in individuals with HF.
PATIENTS AND METHODS
Data on 3483 HF patients from the MIMIC IV database were retrospectively analyzed. The relationship between iron homeostasis-related indicators (ferritin, serum iron, transferrin, and total iron binding capacity [TIBC]) and the prognosis of HF patients was discerned utilizing the Cox proportional hazards model and Kaplan-Meier survival analysis. Additionally, the predictive capability of these indicators for patient prognosis was assessed using receiver operating characteristic curve (ROC).
RESULTS
Fourth quartile levels of ferritin and serum iron were obviously associated with poor long-term outcomes in HF patients. Conversely, fourth quartile levels of transferrin and TIBC served as protective factors and were associated with a better prognosis. Additionally, iron homeostasis indicators exhibited a certain predictive value for both long-term mortality and first-admission mortality in HF patients.
CONCLUSIONS
This study underscores the significant association between iron homeostasis indicators and the prognosis of HF patients, providing valuable insights for risk stratification and clinical decision-making for this population. Future studies should focus on the dynamic fluctuations in patients' iron homeostasis and explore intervention measures to improve the prognosis of HF patients.
PubMed: 38934851
DOI: 10.20452/pamw.16788 -
Health Promotion International Jun 2024The article examines the experiences of family caregivers engaged in the provision of long-term care for their relatives with complex health needs within the Latvian...
The article examines the experiences of family caregivers engaged in the provision of long-term care for their relatives with complex health needs within the Latvian context. Semi-structured interviews were conducted with seven caregivers who provide care in cases of dementia, depression, schizophrenia, opioid use, Down syndrome and mild cognitive impairment. A thematic analysis of interview transcripts revealed common themes, such as the initial experiences when encountering a family member's disorder and the subsequent reactions, as well as the quest for support and resources. Variations mainly centered around differences in formal aspects and childhood experiences of care. Caregivers reported risk factors such as guilt, lack of support from family and friends, financial difficulties, deficiency of professional care and ignoring the caregiver's own needs. Awareness of personal resources, values and limits, coping with personal stigma and improved overall quality of life were identified as protective factors. The findings underscore several preventive measures that social and mental health services could implement to mitigate the adverse effects of caregiving on caregivers' lives.
Topics: Humans; Caregivers; Latvia; Female; Male; Middle Aged; Aged; Family; Adaptation, Psychological; Social Support; Interviews as Topic; Adult; Quality of Life; Qualitative Research; Social Stigma; Long-Term Care
PubMed: 38934478
DOI: 10.1093/heapro/daae070 -
Immunity, Inflammation and Disease Jun 2024To investigate the prognostic factors of patients with anti-melanoma differentiation-associated gene 5 (MDA5) positive clinically amyopathic dermatomyositis (CADM) and...
OBJECTIVE
To investigate the prognostic factors of patients with anti-melanoma differentiation-associated gene 5 (MDA5) positive clinically amyopathic dermatomyositis (CADM) and interstitial lung disease (ILD).
METHODS
A retrospective analysis was conducted on clinical data of 125 patients with anti-MDA5 + CADM-ILD collected from 10 branches in eastern China between December 2014 and December 2022. Prognostic factors were analyzed using χ test, Log-rank test, COX and logistic regression analysis.
RESULTS
In this cohort, 125 anti-MDA5 + CADM-ILD patients exhibited a rapidly progressive interstitial lung disease (RPILD) incidence of 37.6%, and an overall mortality rate of 24.8%. One patient was lost to follow-up. After diagnosis of RPILD, a mortality rate of 53.2% occurred in patients died within 3 months, and that of 5.6% appeared in those who survived for more than 3 months. Multiple factor analysis revealed that C-reactive protein (CRP) ≥ 10 mg/L (p = 0.01) and recombinant human tripartite motif containing 21 (Ro52) (+) (p = 0.003) were associated with a higher risk of RPILD in anti-MDA5 + CADM-ILD patients; CRP ≥ 10 mg/L (p = 0.018) and the presence of RPILD (p = 0.003) were identified as the factors influencing survival time in these patients, while arthritis was the protective factor (p = 0.016).
CONCLUSION
Patients with anti-MDA5 + CADM-ILD will have a higher mortality rate, and the initial 3 months after diagnosis of RPILD is considered the risk window for the dismal prognosis. Patients with CRP ≥ 10 mg/L, Ro52 (+) and RPILD may be related to a shorter survival time, while patients complicated with arthritis may present with relatively mild conditions.
Topics: Humans; Lung Diseases, Interstitial; Dermatomyositis; Interferon-Induced Helicase, IFIH1; Male; Female; Prognosis; Middle Aged; Retrospective Studies; Adult; Autoantibodies; China; Aged
PubMed: 38934403
DOI: 10.1002/iid3.1332