Beneath the surface: assessing pollution levels near major solid waste dumpsites in Lagos, Nigeria.

Effective solid waste management is a critical environmental challenge, particularly in rapidly growing Global South countries like Nigeria. This issue is exacerbated by burgeoning populations, lax waste regulations, and the widespread practice of open dumping. The deterioration of soil quality and alteration of water quality are major consequences of open waste dumping, posing significant environmental and public health risks. This study aims to assess the environmental risk and pollution status of soil and water resources near major dumpsites in Lagos. It aims to offer insights that can inform targeted interventions and policy measures not only in Lagos but also in comparable urban settings worldwide. Results indicated that important soil parameters, including TN (11.89-13.83 mg/kg), pH (6.45-7.35), sulfate (36.71-39.49 mg/kg), phosphate (9.31-14.39 mg/kg), and electrical conductivity (342-566 µS/cm), were significantly affected by the dumpsites. Additionally, concentrations of heavy metals varied, with some exceeding permissible limits set by international standards, highlighting the environmental challenges posed by improper waste disposal in urban settings like Lagos. The analyzed parameters for water were mostly within acceptable limits, indicating a lesser impact of the waste dump on water resources. Water samples from boreholes and hand-dug wells near three dumpsites showed that pH, TDS, and heavy metal concentrations were mostly within WHO limits, with borehole water deemed safe for drinking and hand-dug wells suitable for cleaning. To alleviate the environmental impacts of open dumpsites, it is recommended to implement effective waste segregation, recycling programs, controlled landfilling, and investment in waste treatment technologies, along with regular water quality monitoring to prevent further pollution and protect public health. While these measures offer opportunities, they also face significant challenges due to financial and land constraints. Therefore, strong public awareness, infrastructure investment, and government commitment are essential, along with coordinated efforts among the government, private sector, and communities.

Associations between AHA's Life's Essential 8 and cognition in midlife and older adults.

INTRODUCTION: This study evaluated the associations between Life's Essential 8 (LE8) and cognitive performance, and compared the strength of the relationships of Life's Simple 7 (LS7) and LE8 to cognition in midlife and older adults. METHODS: Participants (N = 1539) were from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. Cross-sectional multivariable regression examined the associations between LE8 and cognition. Secondary analyses compared model performance between LE8 and LS7 measures on cognition from the same available sample. RESULTS: Higher LE8 scores were associated with better global cognitive performance, working memory, and attention. The LS7 model outperformed the LE8 model on global cognitive performance, but the LE8 model outperformed the LS7 model for the working memory domain. DISCUSSION: Better cardiovascular health (CVH) was associated with better cognitive performance among US middle-aged and older adults. However, the association between CVH and specific cognitive domains varies when using LE8 versus LS7. HIGHLIGHTS: Cardiovascular health (CVH) is associated with cognitive performance. Life's Essential 8 (LE8) is a new construct to quantify CVH. Associations between LE8 and cognition were assessed. Higher LE8 was associated with better global cognitive performance. Higher LE8 was also associated with better working memory and attention.

Efficacy of pCONUS Devices in the Management of Intracranial Aneurysms: Outcomes of 190 Patients.

Intracranial aneurysms (IAs) pose a significant health concern, necessitating effective treatment modalities. The pCONUS device has emerged as a promising option for managing complex IAs, particularly wide-necked bifurcation aneurysms. Evaluating its efficacy across multiple studies is essential for establishing therapeutic guidelines. A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify studies assessing the efficacy of pCONUS devices in treating cerebral aneurysms. PubMed, Google Scholar, and Scopus were searched for relevant articles published from January 1, 2000, to December 31, 2021. Inclusion criteria encompassed clinical trials examining pCONUS device benefits for ruptured or unruptured cerebral aneurysms. Data extraction and quality assessment were performed independently by two reviewers. Out of 390 initially identified articles, eight studies met the inclusion criteria. These studies collectively involved 190 participants with intracranial aneurysms. The sample sizes ranged from seven to 40 patients, predominantly in retrospective designs. Complete occlusion rates varied from 46.8% to 100%, with a mean diameter of treated aneurysms ranging from 2.5 mm to 8.83 mm. This systematic review suggests that pCONUS devices are feasible and effective for treating complex bifurcation cerebral aneurysms, with acceptable complication rates. Despite limitations such as retrospective study designs and limited follow-up durations, the findings support the beneficial role of pCONUS devices in managing challenging intracranial aneurysms. Larger collaborative efforts with longer follow-up durations are warranted to validate these findings and establish wider therapeutic guidelines.

Father-separation and well-being in forcibly displaced Syrian children.

Forcibly displaced children often face separation from their parents, particularly fathers. These children endure the hardships of war, displacement, and the loss of a key attachment figure. Despite the critical role of attachment in children's well-being during periods of heightened stress, the impact of separation due to war and displacement has received little attention in empirical work. Findings from 1544 Syrian refugee children (Mage = 10.97, SD = 2.27) living in informal settlements in Lebanon with their mothers (Mage = 38.07, SD = 8.49), including 367 father-separated children, show that father-separated children experienced more war-related events and worse refugee environments. Structural equation modelling showed that beyond the direct relation of war exposure and quality of the refugee environment on well-being, father separation was uniquely related to more depressive symptoms and worse self-development, but not to anxiety, PTSD, or externalising problems in children. Maternal parenting did not explain these outcomes, though it had a protective function for children's well-being.

Longitudinal association of homocysteine with depressive and anxiety symptoms among urban adults: healthy aging in neighborhoods of diversity across the life span study.

Longitudinal associations of homocysteine (HCY) with depressive symptoms scores among urban adults remain under-studied, especially across sex, race and levels of anxiety. We examined longitudinal associations of homocysteine (HCY) with depressive symptoms scores among urban adults, before and after stratifying by sex, race and anxiety level, using data from 1460 Healthy Aging in Neighborhoods of Diversity across the Lifespan Study (HANDLS) participants aged 30-64 y at v1 (2004-2009), followed across 3 visits up to 2017. In addition to LnHcyv1, we used group-based trajectory models predicting z-transformed likelihood of greater LnHcy with age (Hcytraj). Total and domain-specific depression symptoms were scored using Center for Epidemiologic Studies Depression (CES-D) scale. Mixed-effects linear regression models and Cox proportional hazards models were utilized. A positive association was found between baseline LnHcyv1 and CES-D total scores in reduced socio-demographic- adjusted Model 1 (ß (standard error [SE]) = + 2.337 (0.902), P = 0.010), a relationship slightly attenuated in fully adjusted Model 2 (Model 1 adjusting for lifestyle and health factors) with a ß (SE) = + 1.825 (0.883), P = 0.039. Individuals with lower anxiety levels experienced faster CES-D domain 2 score annualized increase over time (interpersonal problems) with higher LnHcyv1 (ß (SE) = 0.041 (0.018), P = 0.024). Hcytraj was linked to incident elevated depressive symptoms (CES-D total score ≥16) overall (fully adjusted model: HR = 1.09, 95% CI: 1.03-1.14, P = 0.001), particularly among women and those living in poverty. Baseline and "high trajectory" of LnHcy were positively associated with depressive symptoms and elevated depressive symptom incidence, in a sex-, race-, poverty status- and anxiety-level specific manner.

Adult-Onset Still's Disease and Pulmonary Embolism: A Case Report.

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder characterized by fever, rash, arthralgia, and systemic inflammation. Pulmonary embolism (PE), a potentially life-threatening complication, is infrequently associated with AOSD. This report presents a unique case that highlights the importance of considering atypical presentations of PE in this patient population despite the absence of classical risk factors. An 84-year-old male with hypertension, benign prostatic hypertrophy, and AOSD diagnosed six years prior, presented with confusion, fever, and malaise for two days. He denied any recent travel or immobilization. Examination revealed tachycardia and reduced oxygen saturation on room air. D-dimer was elevated, and CT chest angiography (CTCA) confirmed left upper and lower segmental PE without cardiac strain. Investigations for infection were negative. Initial treatment with intravenous heparin was switched to apixaban. The patient was eventually discharged home with stable vital signs. The inflammatory state in AOSD might contribute to hypercoagulability, increasing the risk of PE. This case emphasizes the importance of considering PE in AOSD patients, even in the absence of classical risk factors, to prevent potentially fatal complications. A literature review revealed few cases of AOSD presenting with PE, highlighting the atypical presentation and need for increased awareness. This case underscores the rare, but potentially serious, association between AOSD and unprovoked PE. Clinicians managing AOSD should maintain a high index of suspicion for PE, particularly in patients presenting with unexplained respiratory symptoms.

Tailored guidance to apply the Estimand framework to Trials within Cohorts (TwiCs) studies.

Objective: The estimand framework offers a structured approach to define the treatment effect to be estimated in a clinical study. Defining the estimand upfront helps formulating the research question and informs study design, data collection and statistical analysis methods. Since the Trials within Cohorts (TwiCs) design has unique characteristics, the objective of this study is to describe considerations and provide guidance for formulating estimands for TwiCs studies. Methods: The key attributes of an estimand are the target population, treatments that are compared, the endpoint, intercurrent events and their handling, and the population-level summary measure. The estimand framework was applied retrospectively to two TwiCs studies: the SPONGE and UMBRELLA Fit trial. The aim is to demonstrate how the estimand framework can be implemented in TwiCs studies, thereby focusing on considerations relevant for defining the estimand. Three estimands were defined for both studies. For the SPONGE trial, estimators were derived. Results: Intercurrent events considered to occur exclusively or more frequently in TwiCs studies compared to conventional randomized trials included intervention refusal after randomization, misalignment of timing of routine cohort measurements and the intervention period, and participants in the control arm initiating treatments similar to the studied intervention. Considerations for handling refusal after randomization related to decisions on whether the target population should include all eligible participants or the subpopulation that would accept (or undergo) the intervention when offered. Considerations for handling treatment initiation in the control arm and misalignments of timing related to decisions on whether such events should be considered part of treatment policy or whether interest is in a hypothetical scenario where such events do not occur. Conclusion: The TwiCs study design has unique features that pose specific considerations when formulating an estimand. The examples in this study can provide guidance in the definition of estimands in future TwiCs studies.

Uncovering mediational pathways behind racial and socioeconomic disparities in brain volumes: insights from the UK Biobank study.

Mediation pathways explaining racial/ethnic and socioeconomic (SES) disparities in structural MRI markers of brain health remain underexplored. We examined racial/ethnic and SES disparities in sMRI markers and tested total, direct, and indirect effects through lifestyle, health-related, and cognition factors using a structural equations modeling approach among 36,184 UK Biobank participants aged 40-70 years at baseline assessment (47% men). Race (non-White vs. White) and lower SES-predicted poorer brain sMRI volumetric outcomes at follow-up, with racial/ethnic disparities in sMRI outcomes involving multiple pathways and SES playing a central role in those pathways. Mediational patterns differed across outcomes, with the SES-sMRI total effect being partially mediated for all outcomes. Over 20% of the total effect (TE) of race/ethnicity on WMH was explained by the indirect effect (IE), by a combination of different pathways going through SES, lifestyle, health-related, and cognition factors. This is in contrast to < 10% for total brain, gray matter (GM), white matter (WM), and frontal GM left/right. Another significant finding is that around 57% of the total effect for SES and the normalized white matter hyperintensity (WMH) was attributed to an indirect effect. This effect encompasses many pathways that involve lifestyle, health-related, and cognitive aspects. Aside from WMH, the percent of TE of SES mediated through various pathways ranged from ~ 5% for WM to > 15% up to 36% for most of the remaining sMRI outcomes, which are composed mainly of GM phenotypes. Race and SES were important determinants of brain volumetric outcomes, with partial mediation of racial/ethnic disparities through SES, lifestyle, health-related, and cognition factors.

Physical activity at diagnosis is associated with tumor downstaging after neoadjuvant chemoradiotherapy in patients with rectal cancer.

BACKGROUND: Patients with rectal cancer are often treated with neoadjuvant chemoradiotherapy, followed by a waiting period and surgical resection. Good or complete response to neoadjuvant chemoradiotherapy might enable organ preservation, which highlights the need to increase response rates. Pre-clinical studies suggest that physical activity during neoadjuvant chemoradiotherapy may improve tumor downstaging. PURPOSE: To investigate whether physical activity and physical functioning of patients with rectal cancer at diagnosis are associated with tumor downstaging after neoadjuvant chemoradiotherapy. MATERIALS AND METHODS: Patients were included if they participated in the Dutch Prospective ColoRectal Cancer Cohort, a nationwide cohort providing an infrastructure for scientific research, and received neoadjuvant chemoradiotherapy for rectal cancer. Tumor downstaging was dichotomized into good/complete or moderate/poor downstaging. Physical activity (total physical activity, moderate-to-vigorous physical activity (MVPA), and Dutch physical activity guideline adherence) and physical functioning were assessed using questionnaires. Logistic regression analyses were performed to examine associations of physical activity and physical functioning with tumor downstaging, adjusted for relevant confounders. RESULTS: 268 patients (aged 62 ± 11 years, 33 % female) with rectal cancer were included. Patients with moderate (OR = 2.07; 95%CI = 1.07 - 4.07; p = 0.03) or high (OR = 2.05; 95%CI = 1.05 - 4.07; p = 0.04) levels of MVPA were more likely to have good/complete tumor downstaging than patients with low levels. No significant associations with tumor downstaging were found for total physical activity, Dutch physical activity guideline adherence, and physical functioning. CONCLUSIONS: We found augmented tumor downstaging in patients with rectal cancer with moderate or high levels of self-reported MVPA before the start of neoadjuvant chemoradiotherapy compared to patients with low levels.

Poor sleep quality, dementia status and their association with all-cause mortality among older US adults.

BACKGROUND: Evidence points to associations between sleep quality, dementia, and mortality. We examined whether poor sleep quality mediated or moderated the association between dementia and mortality risk among older US adults and vice versa, and whether these associations differed by sex and by race. METHODS: The study investigated bi-directional associations between sleep quality, dementia and mortality in older US adults using data from the Health and Retirement Study (N = 6,991, mean age = 78.1y, follow-up: 2006-2020, number of deaths = 4,938). It tested interactions and mediating effects, using Cox proportional hazards models and four-way decomposition models. RESULTS: Poor sleep quality was associated with increased mortality risk, particularly among male and White older adults. However, the association was reversed in the fully adjusted model, with a 7% decrease in risk per tertile. Probable dementia was associated with a two-fold increase in mortality risk, with a stronger association found among White adults. The association was markedly attenuated in the fully adjusted models. Sleep quality-stratified models showed a stronger positive association between dementia and mortality among individuals with better sleep quality. Both mediation and interaction were involved in explaining the total effects under study, though statistically significant total effects were mainly composed of controlled direct effects. CONCLUSIONS: Poor sleep quality is directly related to mortality risk before lifestyle and health-related factors are adjusted. Dementia is linked to mortality risk, especially in individuals with better sleep quality, males, and White older adults. Future research should explore the underlying mechanisms.

Plasma homocysteine and longitudinal change in cognitive function among urban adults.

BACKGROUND: Cross-sectional and longitudinal studies have inconsistently linked cognitive performance and change over time to an elevated level of homocysteine (Hcy), with few conducted among urban adults. METHODS: Longitudinal data [Visit 1 (2004-2009) and Visit 2 (2009-2013)] were analyzed from up to 1430 selected Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) participants. Baseline and follow-up blood Hcy was measured, while 11 cognitive function test scores were assessed at either of these two visits. Overall, sex- and race-stratified associations were evaluated using mixed-effects linear regression models, adjusting for key potential confounders. Interaction effects between Hcy and serum levels of folate and vitamin B-12 were also tested. RESULTS: We found that greater LnHcyv1 was significantly associated with poorer baseline attention based on higher Loge (TRAILS A, in seconds) [ß (SE): 0.101 (0.031), P = 0.001]. Heterogeneity was also found by sex and by race. Most notably, among men only, LnHcyv1 was associated with faster decline on the BVRT (# of errors), a measure of visuo-spatial memory (ß (SE): 0.297(0.115), P = 0.010, reduced model); while among African American adults only, an elevated and increasing LnHcy over time was associated with faster rate of decline on Loge (TRAILS B, in seconds) [ß (SE): +0.012 (0.005), p = 0.008], a measure of executive function. Interactions between Hcy, folate and vitamin B-12 blood exposures were also detected. CONCLUSIONS: In summary, sex- and race-specific adverse association between elevated Hcy and cognitive performance over time were detected among middle-aged urban adults, in domains of attention, visuo-spatial memory and executive functioning.

Cocktail Approach with Polyserotonin Nanoparticles and Peptides for Treatment of Streptococcus mutans.

Dental plaque, formed by a Streptococcus mutans biofilm, is a major contributor to cavity formation. While antimicrobial strategies exist, the growing risk of antibiotic resistance necessitates alternative therapeutic solutions. Polyserotonin nanoparticles (PSeNPs), recently recognized for their photothermal property and promising biomedical applications, open up a new avenue for antimicrobial use. Here, we introduced a UV-initiated synthetic route for PSeNPs with improved yield. Using these PSeNPs, a cocktail treatment to reduce the viability of this cavity-causing bacteria was developed. This cocktail comprises an S. mutans-targeting antimicrobial peptide (GH12), an intraspecies competence-stimulating peptide that triggers altruistic cell death in S. mutans, and laser-activated heating of PSeNPs. The "peptide + PSeNP + laser" combination effectively inhibits S. mutans growth in both planktonic and biofilm states. Moreover, the cocktail approach remains effective in reducing the viability of S. mutans in a more virulent dual-species biofilm with Candida albicans. Overall, our results reinforce the utility of a multipronged therapeutic strategy to reduce cariogenic bacteria in the complex model oral biofilm.

Infection burden, periodontal pathogens, and their interactive association with incident all-cause and Alzheimer's disease dementia in a large national survey.

INTRODUCTION: Relationships and interplay of an infection burden (IB) and periodontal pathogens or periodontal disease (Pd) markers with Alzheimer's disease (AD) and all-cause dementia among US adults were examined. METHODS: Less than or equal to 2997 participants from the National Health and Nutrition Survey III were linked to CMS-Medicare [≥45 years (1988-1994); ≤30 years follow-up]. RESULTS: Hepatitis C (hazard ratio = 3.33, p = 0.004) and herpes simplex virus 2 were strongly associated with greater all-cause dementia risk. Porphyromonas gingivalis and Streptococcus oralis were associated with greater AD risk at higher IB. The red-green periodontal pathogen cluster coupled with higher IB count increased the risk of all-cause dementia among minority racial groups. Pocket probing depth associated with dementia risk at lower IB in the overall sample. DISCUSSION: Select viruses and bacteria were associated with all-cause and AD dementia, while the IB interacted with Pd markers in relation to these outcomes. HIGHLIGHTS: Interplay of infection burden (IB) and periodontal disease with dementia was tested. ≤2997 participants from NHANES III were linked to Medicare. Hepatitis C and herpes simplex virus 2 strongly associated with dementia risk. Tetanus sero-positivity increased Alzheimer's disease (AD) risk. Porphyromonas gingivalis and Streptococcus oralis associated with AD at higher IB. Red-green periodontal cluster at high IB, increased dementia in racial minorities. Pocket probing depth associated with dementia risk at lower IB.

Stress-induced eosinophil activation contributes to postoperative morbidity and mortality after lung resection.

Respiratory failure occurs more frequently after thoracic surgery than abdominal surgery. Although the etiology for this complication is frequently attributed to underlying lung disease present in patients undergoing thoracic surgery, this notion is often unfounded because many patients with normal preoperative pulmonary function often require prolonged oxygen supplementation even after minimal resection of lung tissue. Using a murine model of pulmonary resection and peripheral blood samples from patients undergoing resection of the lung or abdominal organs, we demonstrated that lung surgery initiates a proinflammatory loop that results in damage to the remaining lung tissue, noncardiogenic pulmonary edema, hypoxia, and even death. Specifically, we demonstrated that resection of murine lung tissue increased concentrations of the homeostatic cytokine interleukin-7, which led to local and systemic activation of type 2 innate lymphoid cells. This process activated lung-resident eosinophils and facilitated stress-induced eosinophil maturation in the bone marrow in a granulocyte-macrophage colony-stimulating factor-dependent manner, resulting in systemic eosinophilia in both mice and humans. Up-regulation of inducible nitric oxide synthase in lung-resident eosinophils led to tissue nitrosylation, pulmonary edema, hypoxia, and, at times, death. Disrupting this activation cascade at any stage ameliorated deleterious outcomes and improved survival after lung resection in the mouse model. Our data suggest that repurposing US Food and Drug Administration-approved eosinophil-targeting strategies may potentially offer a therapeutic intervention to improve outcomes for patients who require lung resection for benign or malignant etiology.

Investigation of plasmid-mediated quinolone resistance among extended-spectrum ß-lactamase isolates of E. coli and K. pneumoniae.

Escherichia coli and Klebsiella pneumoniae are important members of the Enterobacteriaceae family, involved in many infections. The increased resistance rate towards ß-lactams and fluoroquinolones -which are the main therapeutic options- limits their treatment options. This study aimed to assess the local resistance patterns against different antimicrobials and to determine the extended-spectrum ß-lactamase (ESBLs) producers. The study revealed that 36% of clinical isolates were ESBL producers, showing high resistance rates towards ß-lactams and non-ß-lactams, especially sulphamethoxazole-trimethoprim and fluoroquinolones. However, they were susceptible to chloramphenicol and doxycycline (33% and 20%; respectively). Also, the investigation aimed to screen the plasmid profile of quinolone-resistant ESBLs-producers and to detect the plasmid-mediated quinolone resistance genes including qnrA, qnrS, qnrB, qnrC, qnrD, and qnrVC. Moreover, the conjugative plasmid among the quinolone-resistant isolates was elucidated. The results showed that extracted plasmids of sizes ranging from ≈0.9 to 21.23 Kb, divided into 7 plasmid patterns were detected. A plasmid of approximately 21.23 Kb was found in all isolates and the QnrS gene was the most predominant gene. Moreover, the frequency of transconjugation within the same genus was higher than that recorded between different genera; where 68% of E. coli isolates transferred the resistance genes compared to Klebsiella isolates (36.6%). Plasmid profiles of transconjugants demonstrated great similarity, where 21.23 Kb plasmid was detected in all transconjugants. Since these transconjugants were quinolone-resistant ESBL producers, it has been suggested that quinolone resistance determinants might be carried on that plasmid.

Nifedipine Improves the Ketogenic Diet Effect on Insulin-Resistance-Induced Cognitive Dysfunction in Rats.

Insulin resistance, induced by high fructose consumption, affects cognitive function negatively. Nifedipine may be suggested for neurological disorders. This study aimed to assess the effect of nifedipine with either a normal diet (ND) or a ketogenic diet (KD) in cognitive dysfunction. Male Wistar rats received 10% fructose in drinking water for 8 weeks to induce insulin resistance. Rats received nifedipine (5.2 mg/kg/day; p.o.) later with ND or KD for an additional five weeks. One and two-way ANOVAs were used in analyzing the data. Reversion to the ND improved insulin resistance and lipid profile, besides brain-derived neurotrophic factor (BDNF), glycogen synthase kinase-3 beta (GSK3ß), and insulin-degrading enzyme (IDE) levels. Rats fed KD alone and those that received nifedipine with KD did not show similar improvement in the previously mentioned parameters as the ND group. However, nifedipine-ND rats showed improvement in cognitive behavior and insulin resistance. Treatment with nifedipine-KD ameliorated GSK3ß, amyloid ß (Aß), and tau protein levels. As the nifedipine-KD combination succeeded in diminishing the accumulated Aß and tau protein, KD may be used for a while due to its side effects, then nifedipine treatment could be continued with an ND. This conclusion is based on the finding that this combination mitigated insulin resistance with the associated improved behavior.

Role of homelessness and psychiatric disorders in suicide deaths among veterans: A four-way decomposition analysis.

Homelessness and suicide are top priorities in the U.S. Department of Veterans Affairs (VA). This study examined the various pathways involving homelessness, substance use, and mental health disorders in relation to suicide deaths among veterans in the VA healthcare system. A retrospective cohort study was conducted among 6,128,921 veterans-399,125 homeless and 5,729,796 non-homeless-followed-up between 2017 and 2021 using VA/Department of Defense linked databases. Multivariable Cox regression was applied for homelessness and psychiatric disorders as predictor of suicide deaths, sequentially controlling for demographic, clinical, substance use, and mental health characteristics. Four-way decomposition analysis was used to calculate proportions of suicide deaths mediated and/or moderated by homelessness, substance use, and mental health disorders. The relationship between homelessness and suicide-specific mortality risk was reduced from 40 % greater risk in unadjusted to 9 % greater risk in fully-adjusted models. Nearly 26 % of the total effect of homelessness on suicide-specific mortality risk was mediated by substance use disorders, whereas 49 % was mediated and 36 % was moderated by mental health disorders. In conclusion, excess suicide-specific mortality risk in homeless veterans is partly explained by substance use and mental health disorders, highlighting the importance of wrap-around health and social services for homeless veterans in mitigating suicide risk.

Functional analysis of a panel of molecular markers for diagnosis of systemic lupus erythematosus in rats.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a diverse autoimmune disease that arises from a combination of complex genetic factors and environmental influences. While circRNAs and miRNAs have recently been identified as promising biomarkers for disease diagnosis, their specific expression patterns, and clinical implications in SLE are not yet fully understood. AIM OF THE WORK: The aim of the present study was to determine the role of a panel of noncoding-RNAs specifically circRNAs (circ-TubD1, circ-CDC27, and circ-Med14), along with miRNA (rno-miR-146a-5p) and mRNA (TRAF6), as novel minimally invasive diagnostic biomarkers for experimentally induced SLE. Additionally, the study involved an insilico bioinformatics analysis to explore potential pathways involved in the pathogenesis of SLE, aiming to enhance our understanding of the disease, enable early diagnosis, and facilitate improved treatment strategies. MATERIALS AND METHODS: SLE was induced in rats using single IP injection of incomplete Freund's adjuvant (IFA). The Induction was confirmed by assessing the ANA and anti-ds DNA levels using ELSA technique. qPCR analysis was conducted to assess the expression of selected RNAs in sera collected from a group of 10 rats with induced SLE and a control group of 10 rats. In addition, bioinformatics and functional analysis were used to construct a circRNA-miRNA-mRNA network and to determine the potential function of these differentially expressed circRNAs. RESULTS: SLE rats demonstrated significantly higher expression levels of circ-CDC27, circ-Med14, and rno-miR-146a-5p as well as TRAF6, with lower expression level of circ-TubD1 in sera of SLE rats relative to controls. ROC curve analysis indicated that all the selected non-coding RNAs could serve as potential early diagnostic markers for SLE. In addition, the expression level of circ-TubD1 was negatively correlated with rno-miR-146a-5p, however, rno-miR-146a-5p was positively correlated with TRAF6. Bioinformatic analysis revealed the incorporation of the circRNAs targeted genes in various immune system and neurodegeneration pathways. CONCLUSIONS: Therefore, circRNAs; circ-TubD1, circ-CDC27, and circ-Med14, in addition to the miRNA (rno-miR-146a-5p) and mRNA (TRAF6) may be involved in the development of SLE and may have promising roles for future diagnosis and targeted therapy.

Mediating and moderating effects of plasma proteomic biomarkers on the association between poor oral health problems and brain white matter microstructural integrity: the UK Biobank study.

The plasma proteome can mediate associations between periodontal disease (Pd) and brain white matter integrity (WMI). We screened 5089 UK Biobank participants aged 40-70 years for poor oral health problems (POHP). We examined the association between POHP and WMI (fractional anisotropy (FA), mean diffusivity (MD), Intracellular Volume Fraction (ICVF), Isotropic Volume Fraction (ISOVF) and Orientation Diffusion (OD)), decomposing the total effect through the plasma proteome of 1463 proteins into pure mediation, pure interaction, neither, while adjusting for socio-demographic and cardiovascular health factors. Similarly, structural equations modeling (SEM) was conducted. POHP was more prevalent among men (12.3% vs. 9.6%), and was associated with lower WMI on most metrics, in a sex-specific manner. Of 15 proteins strongly associated with POHP, growth differentiation factor 15 (GDF15) and WAP four-disulfide core domain 2 (WFDC2; also known as human epididymis protein 4; HE4) were consistent mediators. Both proteins mediated 7-8% of total POHP effect on FAmean. SEM yielded significant total effects for FAmean, MDmean and ISOVFmean in full models, with %mediated by common latent factor (GDF15 and WFDC2) ranging between 13% (FAmean) and 19% (ISOVFmean). For FA, mediation by this common factor was found for 16 of 49 tract-specific and global mean metrics. Protein metabolism, immune system, and signal transduction were the most common pathways for mediational effects. POHP was associated with poorer WMI, which was partially mediated by GDF15 and WFDC2.