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Association between Bullying Victimization and Suicidal Ideation among Adolescents: A Replication Study
No full textThe replicated study is titled “Investigating the Association Between Bullying Victimization and Suicidal Ideation Among Adolescents: Evidence from the 2017 Youth Risk Behavior Survey” by Philip Baiden and Savarra K. Tadeo, published in Child Abuse & Neglect in 2020. The study employed 2017 youth risk behavior survey data publicly available via Center for Disease Control and Prevention (CDC). Descriptive, binary, and multivariate logistic regression was employed to examine the association between bullying victimization and suicidal ideation. The study analysis included 14,603 adolescents aged 14 to 18, of whom 52% were female. Approximately 23% of the sample experienced bullying, and 18% reported suicidal ideation. Bivariate and multivariate logistic regression indicated a significant association between bullying and suicide ideation. The odds of suicidal ideation were 3.26 times greater among adolescents who experienced both school and cyberbullying (AOR = 3.26, p \u3c 0.001, 95 CI = 3.10–3.43), 2.15 times higher among those who experienced only school bullying (AOR = 2.15, p \u3c 0.001, 95 CI = 2.04–2.27), and 2.00 times greater among those who experienced only cyberbullying (AOR = 2.00, p \u3c 0.001, 95 CI = 1.87–2.14). The study analysis also identified other significant risk factors for suicide ideation such as substance use, depression, and forced sexual intercourse.
The primary objective of this replication study was to conduct a pure replication to determine whether original findings can be replicated using original data and methods. While most of the replicated results aligned with the original study showing significant associations between study variables and suicidal ideation, discrepancies were observed in the magnitude of these associations. The pure replication successfully reproduced the original study’s findings in terms of the direction and statistical significance of most associations, with a few exceptions. While the majority of variables showed consistent results, discrepancies emerged for age, sex, alcohol use, and marijuana use, where the replication differed in either significance or magnitude. Measurement and estimated analysis indicated robust results. Linearity assumption for the continuous variable age satisfied through the Box-Tidwell test. Variance inflation factor results showed no multicollinearity among the study variables. A theory of change analysis extended the study by applying Latent Class Analysis (LCA) to identify adolescent subgroups based on bullying victimization, mental health indicators, forced sexual intercourse, and substance use. The analysis revealed that 62.6% were in the low-risk group, 19.9% in the high-risk group, and 17.6% in the moderate-risk group
Targeting Oxidative and Nitrosative Stress: The Role of Omega-3 Derived RvD2 and NRF2 Signaling in Hypertensive-Affected Placenta
Get PDFHypertensive disorders of pregnancy (HDP), include chronic hypertension, gestational hypertension, preeclampsia, and eclampsia, which affect approximately 10% of pregnancies worldwide and significantly increases the risk of adverse maternal and fetal health. HDP is characterized by shallow trophoblast invasion, endothelial dysfunction, oxidative stress, mitochondrial dysfunction, and nitrosative stress, yet the underlying molecular mechanisms remain incompletely understood. A key factor in HDP pathophysiology is the dysregulation of nitric oxide (NO) bioavailability, coupled with increased reactive oxygen/nitrosative species (ROS/RNS), driven by inflammation—particularly the pro-inflammatory cytokine TNFɑ. Nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of antioxidant responses, plays a crucial role in mitigating oxidative and nitrosative damage. However, NRF2 activity is often diminished in the placenta of HDP-affected individuals, exacerbating oxidative stress-induced endothelial dysfunction.
Bulk RNA sequencing was used to investigate differential gene expression in hypertensive versus normotensive human placental tissue, while mitochondrial health was assessed through measurements of oxygen consumption rates (OCR). Analysis revealed dysregulation of immune and metabolic pathways in HDP placentas, with notable upregulation of TNFα, lipopolysaccharide (LPS), arginine vasopressin (AVP), and soluble fms-like tyrosine kinase-1 (sFlt-1) signaling pathways. To model these HDP-related insults, we treated human placental explants with TNFα, LPS, AVP, and sFlt-1, all of which resulted in significant reductions in OCR, indicating compromised mitochondrial function.
We explored the antioxidant potential of the omega-3-derived specialized pro-resolving lipid mediator Resolvin D2 (RvD2). RvD2 was found to attenuate TNFα-induced ROS and mitochondrial dysfunction in trophoblasts. Additionally, RvD2 enhanced NRF2 activity and functioned to increase endogenous antioxidant production.
Using single-walled carbon nanotube sensors, we quantified NO levels in explants treated with TNFα, with or without a pretreatment of RvD2. We found that TNFα disrupted NO homeostasis in hypertensive-affected placental explants, whereas RvD2 effectively restored NO levels in the same explants. We further demonstrated that TNFɑ did not alter NO levels in normotensive placental explants.
Collectively, these findings highlight the therapeutic potential of RvD2 in HDP by mitigating ROS/RNS, improving mitochondrial function, and enhancing placental health. Targeting NRF2 activation and redox homeostasis through omega-3-derived lipid mediators may offer a novel strategy to reduce adverse outcomes associated with HDP
BET Protein Inhibition Relieves Myeloid-Derived Suppressor Cell-mediated Immune Suppression in Chronic Lymphocytic Leukemia
No full textMyeloid-derived suppressor cells (MDSCs) contribute to immune suppression observed in chronic lymphocytic leukemia (CLL). MDSCs are immature myeloid cells hijacked during development and further reprogrammed by the tumor microenvironment to harbor immune-suppressive capacities and inhibit T-cell functions. Bromodomain and extraterminal domain (BET) protein—including BRD4—are epigenetic modulators that regulate important genes implicated in CLL pathogenesis and tumor microenvironment interaction. Previously, our lab has investigated how the novel BET-inhibitor OPN-51107 (OPN5) prevents CLL disease expansion, modulates T-cell immune function, and alters gene expression related to MDSCs. In turn, we hypothesized that BET proteins, especially BRD4, directly contribute to the regulation of MDSC functions; therefore, pharmacological inhibition of BRD4 will alleviate MDSC-mediated immune suppression in CLL. Through the course of this project, we demonstrated that BRD4 is upregulated in MDSCs isolated from Eu-TCL1 mice (a murine model of CLL), and those MDSCs are more immune-suppressive as compared to MDSCs from wild-type counterparts. Furthermore, we demonstrated that ex vivo OPN5 treatment of MDSCs isolated from leukemic mice reverses their immune-suppressive capacity. Finally, utilizing an aggressive adoptive transfer Eu-TCL1 murine model, we demonstrated that OPN5 treatment slows CLL disease progression and modulates immune cell populations. Specifically, OPN5 resulted in phenotypic and functional changes in MDSCs, resulting in decreased immune-inhibitory receptors and attenuated MDSC-mediated T-cell immune suppression as compared to vehicle-treated mice. Altogether, these data support BET proteins as a viable target in MDSCs and BET inhibition as a potential therapeutic approach to reverse MDSC-mediated immune suppression in the context of CLL
Emergency Sheltering for Unhoused Populations during Extreme Winter Weather Events: A Comparison Between Guidance Documents and Local Planning
Get PDFIn a world experiencing drastic climate changes, extreme winter weather is a present and future concern. Regardless of geographic location, extreme winter weather has detrimental effects on communities across the United States. Exposure to extreme winter weather may result in cold-related injuries or death, disproportionately impacting populations that spend more time outside, such as people experiencing homelessness. Gronlund concluded that there is a higher risk of hypothermia, hyperthermia, and mortality among the homeless vs. non-homeless during periods of extreme heat or cold (Gronlund, 2018). Communities across the United States routinely combat the effects of cold weather by implementing various disaster plans. This Capstone compares national and federal guidance for sheltering unhoused populations in extreme winter weather with a sample of existing community emergency sheltering plans. The guidance documents include both government and non-government organizations. The sample of community plans are from cities across the United States, incorporating a variety of geographic locations and climate regions. Guidance documents are compared to the community plans, identifying crucial sheltering strategies, such as shelter plan activation, operations, communication, transportation, capacity, and shelter plan deactivation. After the comparison, common themes are identified, and recommendations are made for each significant sheltering strategy. Each plan or guidance document offers a unique approach to addressing the major strategies in winter sheltering plans. Recommendations for future guidance may be compiled into a single, detailed document, such as a plan component checklist, applicable to any community across the United States
Efficacy and Safety of 4-Month Rifapentine-Based Tuberculosis Treatments in Persons with Diabetes.
Get PDFA previous study demonstrated noninferior efficacy of 4-month rifapentine/moxifloxacin regimen for tuberculosis (TB) treatment compared with the standard regimen. We explored results among study participants with diabetes. Among 2,516 randomized participants, 181 (7.2%) had diabetes. Of 166 participants with diabetes in the microbiologically eligible analysis group, 26.3% (15/57) had unfavorable outcomes in the control regimen, 13.8% (8/58) in the rifapentine/moxifloxacin regimen, and 29.4% (15/51) in the rifapentine regimen. The difference in proportion of unfavorable outcomes between the control and rifapentine/moxifloxacin arms in the microbiologically eligible analysis group was -12.5% (95% CI -27.0% to 1.9%); the difference between the control and rifapentine arms was 3.1% (95% CI -13.8% to 20.0%). Safety outcomes were similar in the rifapentine/moxifloxacin regimen and control arms. Among participants with TB and diabetes, the rifapentine/moxifloxacin arm had fewest unfavorable outcomes and was safe. Our findings indicate that the rifapentine/moxifloxacin regimen can be used in persons with TB and diabetes
Kaposi Sarcoma: A Case of Mistaken Identity in the Immunocompetent
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Comparing Adenoma Detection Rate and Polyp Detection rates as a tool for Colonoscopy Quality Metrics
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Assessing the Association Between Total Cholesterol and Hospitalized Myocardial Infarction in Women Ages 32-70: An Analysis of the Framingham Heart Study
Get PDFObjective
Heart disease is the leading cause of death in women that may go undiagnosed due to unexpected symptoms. The purpose of this analysis was to assess the effect of total cholesterol on the odds of hospitalized myocardial infarction (MI).
Methods
This analysis used a sample of 2,445 women from the Framingham Heart Study, an observational prospective cohort study. The exposure was total cholesterol, and the outcome was hospitalized MI. Logistic regression was used to estimate crude and adjusted odds ratios (OR). The adjusted models controlled for age, blood pressure, and diabetes. Effect modification by diabetes status was evaluated in a secondary stratified analysis.
Results
Higher total cholesterol was associated with 2.71 greater odds of MI (95% CI, 1.29-5.68). Effect modification was also assessed: among individuals with diabetes, the OR was 2.54 (95% CI, 0.11–60.50; p = 0.5644), and among non-diabetics, the OR was 2.56 (95% CI, 1.22–5.38; p = 0.0134).
Conclusion
High total cholesterol was significantly associated with increased odds of hospitalized MI. Diabetes may have a modifying effect on this association
