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.

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.

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.

The Relationship Between Gestational Diabetes and Postpartum Depression: A Systematic Review.

This study aims to examine the relationship between gestational diabetes mellitus (GDM) and the likelihood of postpartum depression (PPD) symptoms. PubMed, Scopus, Web of Science, ScienceDirect, and the Wiley Online Library were systematically searched for relevant literature. Our results included eight studies with a total of 4,209 women diagnosed with GDM and/or PPD. The prevalence of PPD in women diagnosed with GDM ranged from 6.5% to 48.4%. The included studies demonstrated that PPD was more likely to strike women with GDM. One study reported that the most severe type of GDM is more likely to occur in those with a history of depression. Perinatal depression during pregnancy can be strongly predicted by age, BMI, and a personal history of depression. The findings imply that GDM and the likelihood of depression during the postpartum phase are related. It was also found that there was a positive correlation between depression and the chance of having GDM. This emphasizes how the association between GDM and depression appears to be reciprocal. However, the association does not imply causation, and the data at hand do not allow for the establishment of causality. Subsequent studies ought to endeavor to show causative connections between GDM and depression as well as pinpoint shared underlying endocrine variables that may play a role in the genesis of both conditions. The available information that is now available is limited due to the complexity of the etiology of both GD and depression in pregnant women; nonetheless, prevention of both conditions depends on a better understanding of the link between GD and depression. The risk of bias in the included studies was moderate to high.

A rare presentation of inguinal mass in postmenopausal women: leiomyoma of round ligament mimicking an irreducible inguinal hernia.

Tumors of the round ligament rarely happen; leiomyomas are considered the most common. Round ligament leiomyomas are benign tumors mimicking inguinal hernia, lymph nodes, or other inguinal masses. They are usually asymptomatic and take place in premenopausal female patients. This paper will present a case of a postmenopausal female patient who presented to our outpatient surgical clinic complaining of a right groin mass for 3 months. She was clinically diagnosed as a case of an irreducible inguinal hernia. After investigations, it turned out to be a round ligament leiomyoma, confirmed by the histopathological examination. There are broad differential diagnoses of inguinal masses. Although imaging exams could help diagnose leiomyomas, surgical excision followed by histopathological assessment is the best to confirm the diagnoses.

Correction: Rosavin improves insulin resistance and alleviates hepatic and kidney damage via modulating the cGAS-STING pathway and autophagy signaling in HFD/STZ-induced T2DM animals.

[This corrects the article DOI: 10.1039/D4MD00023D.].

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.

Machine-Learning-Based Identification of Key Feature RNA-Signature Linked to Diagnosis of Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is the third prime cause of malignancy-related mortality worldwide. Early and accurate identification of HCC is crucial for good prognosis, efficacy of therapy, and survival rates of the patients. We aimed to develop a machine-learning model incorporating differentially expressed RNA signatures with laboratory parameters to construct an RNA signature-based diagnostic model for HCC. Methods: We have used five classifiers (KNN, RF, SVM, LGBM, and DNNs) to predict the liver disease (HCC). The classifiers were trained on 187 samples and then tested on 80 samples. The model included 22 features (age, sex, smoking, cirrhosis, non-cirrhosis, albumin, ALT, AST bilirubin (total and direct), INR, AFP, HBV Ag, HCV Abs, RQmiR-1298, RQmiR-1262, RQmiR-106b-3p, RQmRNARAB11A, and RQSTAT1, RQmRNAATG12, RQLnc-WRAP53, RQLncRNA- RP11-513I15.6). Results: LGBM achieved the highest accuracy of 98.75% in predicting HCC among all models surpassing Random Forest (96.25%), DNN (91.25%), SVC (88.75%), and KNN (87.50%). Conclusion: Our machine-learning model incorporating the expression data of RAB11A/STAT1/ATG12/miR-1262/miR-1298/miR-106b-3p/lncRNA-RP11-513I15.6/lncRNA-WRAP53 signature and clinical data represents a potential novel diagnostic model for HCC.

Experimental investigation for nonalcoholic fatty pancreas management using probiotics.

BACKGROUND: Nonalcoholic fatty pancreatitis (NAFP) presents a pressing challenge within the domain of metabolic disorders, necessitating further exploration to unveil its molecular intricacies and discover effective treatments. Our focus was to delve into the potential therapeutic impact of ZBiotic, a specially engineered strain of probiotic B. subtilis, in managing NAFP by targeting specific genes linked with necroptosis and the TNF signaling pathway, including TNF, ZBP1, HSPA1B, and MAPK3, along with their upstream epigenetic regulator, miR-5192, identified through bioinformatics. METHODS: Rats were subjected to either a standard or high-fat, high-sucrose diet (HFHS) for eight weeks. Subsequently, they were divided into groups: NAFP model, and two additional groups receiving daily doses of ZBiotic (0.5 ml and 1 ml/kg), and the original B. subtilis strain group (1 ml/kg) for four weeks, alongside the HFHS diet. RESULTS: ZBiotic exhibited remarkable efficacy in modulating gene expression, leading to the downregulation of miR-5192 and its target mRNAs (p < 0.001). Treatment resulted in the reversal of fibrosis, inflammation, and insulin resistance, evidenced by reductions in body weight, serum amylase, and lipase levels (p < 0.001), and decreased percentages of Caspase and Nuclear Factor Kappa-positive cells in pancreatic sections (p < 0.01). Notably, high-dose ZBiotic displayed superior efficacy compared to the original B. subtilis strain, highlighting its potential in mitigating NAFP progression by regulating pivotal pancreatic genes. CONCLUSION: ZBiotic holds promise in curbing NAFP advancement, curbing fibrosis and inflammation while alleviating metabolic and pathological irregularities observed in the NAFP animal model. This impact was intricately linked to the modulation of necroptosis/TNF-mediated pathway-related signatures.

Screening rates for hepatitis B and C among low-income US veterans: Data from the National Veteran Homeless and Other Poverty Experiences Study.

Screening for viral hepatitis is considered a high-priority area in the Veterans Health Administration (VHA). Yet, few studies have examined viral hepatitis screening test use among low-income veterans who are considered high-risk with limited healthcare access. Using cross-sectional data from 933 participants in the 2021-2022 National Veteran Homeless and Other Poverty Experiences (NV-HOPE) study, we examined rates and correlates of lifetime screening for hepatitis B (HBV) and hepatitis C (HCV) infections. Multivariable logistic regression models evaluated characteristics associated with HBV/HCV screening. Nearly 16% and 21% reported lifetime HBV and HCV screening, respectively. These rates are considerably lower than HBV (47.3%) and HCV (92.9%) screening rates documented among contemporaneous veterans in VHA electronic health records. In the NV-HOPE data, veterans 50-79 years were more likely than those ≥80 years of age to ever-screen for HBV/HCV. Whereas, household income was inversely related to lifetime screening behaviours, veterans reporting 'other' employment types (vs. full-time/part-time employment) were more likely to ever-screen for HBV/HCV. Ever-screening for HBV was more likely among veterans reporting non-Hispanic 'other' (vs. non-Hispanic 'white') race, housing instability, Medicaid insurance, as well as drug use and cognitive disorder histories. Living with ≥5 members (vs. alone), histories of alcohol use, cancer, and liver disorders were also correlated with ever-screening for HCV. HIV/AIDS history correlated with ever-screening for HBV/HCV. In conclusion, fewer than one-third of low-income US veterans ever-screened for HBV/HCV, with lower screening rates among those less likely to be exposed to viral hepatitis, thereby informing interventions aimed at promoting available screening, treatment and vaccinations for HBV/HCV.

Small Observational Study of Battlefield Acupuncture for Homeless-Experienced Veterans.

Background: Homeless-experienced veterans (HEVs) are an important but challenging group to care for in the U.S. Department of Veterans Affairs health care system, and there are opportunities to examine the potential of integrative and complementary medicine approaches. Methods: This observational study enrolled 33 HEVs in a one-group observational, prospective study of Battlefield Acupuncture (BFA) with a monthly follow-up for 3 months after initiating BFA. Results: Linear growth curve analyses revealed a significant improvement in overall pain scores and scores on the effects of pain on activity level, mood, and stress. Conclusions: These preliminary findings suggest the potential of BFA to improve pain among HEVs as an area for further research.

Rosavin improves insulin resistance and alleviates hepatic and kidney damage via modulating the cGAS-STING pathway and autophagy signaling in HFD/STZ-induced T2DM animals.

Background: Inflammation-mediated insulin resistance in type 2 diabetes mellitus (T2DM) increases complications, necessitating investigation of its mechanism to find new safe therapies. This study investigated the effect of rosavin on the autophagy and the cGAS-STING pathway-related signatures (ZBP1, STING1, DDX58, LC3B, TNF-α) and on their epigenetic modifiers (miR-1976 and lncRNA AC074117.2) that were identified from in silico analysis in T2DM animals. Methods: A T2DM rat model was established by combining a high-fat diet (HFD) and streptozotocin (STZ). After four weeks from T2DM induction, HFD/STZ-induced T2DM rats were subdivided into an untreated group (T2DM group) and three treated groups which received 10, 20, or 30 mg per kg of R. rosea daily for 4 weeks. Results: The study found that rosavin can affect the cGAS-STING pathway-related RNA signatures by decreasing the expressions of ZBP1, STING1, DDX58, and miR-1976 while increasing the lncRNA AC074117.2 level in the liver, kidney, and adipose tissues. Rosavin prevented further weight loss, reduced serum insulin and glucose, improved insulin resistance and the lipid panel, and mitigated liver and kidney damage compared to the untreated T2DM group. The treatment also resulted in reduced inflammation levels and improved autophagy manifested by decreased immunostaining of TNF-α and increased immunostaining of LC3B in the liver and kidneys of the treated T2DM rats. Conclusion: Rosavin has shown potential in attenuating T2DM, inhibiting inflammation in the liver and kidneys, and improving metabolic disturbances in a T2DM animal model. The observed effect was linked to the activation of autophagy and suppression of the cGAS-STING pathway.

Prevalence of Gastroesophageal Reflux Disease and Its Impact on the Quality of Life Among Obese Individuals in Al-Baha Region, Saudi Arabia.

Background Gastroesophageal reflux disease (GERD) is a global gastrointestinal disorder, and obesity is a particular risk factor. Symptoms of GERD, such as heartburn and acid reflux, are caused by abnormal relaxation in the lower esophagus, causing gastric acid reflux. Persistent symptoms can affect the patient's quality of life (QOL) and can cause complications, such as esophageal adenocarcinoma. Management of GERD includes lifestyle changes, antacids, and anti-reflux surgery. Even though GERD is a common disease, few research has been carried out on it in Saudi Arabia. Aim This study aimed to estimate the prevalence of GERD and its associated risk factors among obese individuals in the Al-Baha region population and the effect of GERD on their QOL. Methods A cross-sectional study included 314 obese participants from the Al-Baha region. A questionnaire was filled out to measure the prevalence of GERD, risk factors, and effects on the QOL of the participants. Data were analyzed by the IBM SPSS Statistics for Windows, version 26.0 (released 2019, IBM Corp., Armonk, NY). Descriptive statistics and the chi-squared test were applied. Logistic regression analysis was used to determine the factors associated with the incidence of GERD. A p-value of <0.05 was considered statistically significant. Results A total of 314 patients who met our inclusion criteria completed the survey; 42% of them were women, the mean age of all patients was 35.3 ± 12.9 years, and 38.2% of the patients were diagnosed with GERD. Epigastric pain and burning sensation were the most common symptoms (44.9%). Five out of six domains in the QOL questionnaire showed more effects among GERD participants than non-GERD participants, and the results were statistically significant (p = 0.001). Logistic regression analysis showed that men are 1.8 times more likely than women to be diagnosed with GERD, and smokers have 2.6 times the risk of being diagnosed with GERD than non-smokers. Conclusion The present study showed a high prevalence of GERD among obese patients in the Al-Baha region, negatively affecting their QOL. Major risk factors included gender, smoking, dyslipidemia, and hypertension. Public health programs to raise awareness of these risk factors and lifestyle habits are necessary to improve QOL and prevent complications.

Synergistic effect of SrTiO3/CuFe2O4/MIL-101(Co) as a MOF composite under Gamma-rays for antimicrobial potential versus bacteria and pathogenic fungi.

The primary emphasis of this study was on the innovative and scientifically valuable hydrothermal synthesis of MIL-101(Co) as a metal-organic framework (MOF) material. Subsequently, the CuFe2O4 was incorporated into the MOF by a reduction-precipitation technique. The SrTiO3/CuFe2O4/MIL-101(Co) composite was synthesized by using hydrothermal in situ growth process. The XRD and FESEM investigations of the SrTiO3/CuFe2O4/MIL-101(Co) composite definitively verified its crystalline structure and proved its production with exact shape and dimensions. The data indicated that Candida albicans displayed the greatest vulnerability to all three produced materials, with reported Minimum Inhibitory Concentration (MIC) values of 500 µg mL-1 for MIL-101(Co). The CuFe2O4/MIL-101(Co) compound, when produced, exhibits MIC values of 200 µg mL-1. Additionally, the combination of CuFe2O4/MIL-101(Co) with SrTiO3, shows MIC values of 50 µg mL-1. The results also indicated that the MIC values for MIL-101(Co), and CuFe2O4/MIL-101(Co) against S. aureus were 100 µg mL-1. Ultimately, SrTiO3/CuFe2O4/MIL-101(Co) exhibited identical MIC values of 50 µg mL-1 against S. aureus. The concentration of the bacterial protein was increased by adding MIL-101(Co), CuFe2O4/MIL-101(Co), and SrTiO3/CuFe2O4/MIL-101(Co). The antibacterial capabilities of the SrTiO3/CuFe2O4/MIL-101(Co) were increased after being subjected to gamma doses of 100.0 kGy. This process paves a ways for manufacturing innovation in near future.

From port to planet: Assessing NO2 pollution and climate change effects with Sentinel-5p satellite imagery in maritime zones.

The growing effects of climate change on Malaysia's coastal ecology heighten worries about air pollution, specifically caused by urbanization and industrial activity in the maritime sector. Trucks and vessels are particularly noteworthy for their substantial contribution to gas emissions, including nitrogen dioxide (NO2), which is the primary gas released in port areas. The application of advanced analysis techniques was spurred by the air pollution resulting from the combustion of fossil fuels such as fuel oil, natural gas and gasoline in vessels. The study utilized satellite photos captured by the Tropospheric Monitoring Instrument (TROPOMI) on the Sentinel-5P satellite to evaluate the levels of NO2 gas pollution in Malaysia's port areas and exclusive economic zone. Before the COVID-19 pandemic, unrestricted gas emissions led to persistently high levels of NO2 in the analyzed areas. The temporary cessation of marine industry operations caused by the pandemic, along with the halting of vessels to prevent the spread of COVID-19, resulted in a noticeable decrease in NO2 gas pollution. In light of these favourable advancements, it is imperative to emphasize the need for continuous investigation and collaborative endeavours to further alleviate air contamination in Malaysian port regions, while simultaneously acknowledging the wider consequences of climate change on the coastal ecology. The study underscores the interdependence of air pollution, maritime activities and climate change. It emphasizes the need for comprehensive strategies that tackle both immediate environmental issues and the long-term sustainability and resilience of coastal ecosystems in the context of global climate challenges.

Is the Risk of Alzheimer's Disease and Related Dementias Among U.S. Veterans Influenced by the Intersectionality of Housing Status, HIV/AIDS, Hepatitis C, and Psychiatric Disorders?

BACKGROUND: Homelessness and housing instability disproportionately affect U.S. veterans with psychiatric disorders, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), hepatitis C, and Alzheimer's disease and related disorders (ADRD). We examined housing status and/or HIV/AIDS in relation to ADRD risk and evaluated hepatitis C, substance use, and mental health disorders as mediators and/or moderators of hypothesized relationships, among U.S. veterans ≥50 years of age seeking Department of Veterans Affairs (VA) healthcare services. METHODS: A retrospective cohort study was conducted using linked VA Homeless Operations Management and Evaluation System and Corporate Data Warehouse databases (2017-2023) on 3 275 098 eligible veterans yielding 133 388 ADRD cases over 5 years of follow-up. Multivariable regression and causal mediation analyses were performed, controlling for demographic and clinical characteristics. RESULTS: Taking stably housed veterans without HIV/AIDS as referent, ADRD risk was higher among veterans with homelessness/housing instability alone (adjusted hazard ratio [aHR] = 1.67, 95% confidence interval [CI]: 1.63,1.72), lower among veterans with HIV/AIDS alone (aHR = 0.65, 95% CI: 0.58,0.73), but similar to veterans with homelessness/housing instability and HIV/AIDS (aHR = 1.01, 95% CI: 0.79,1.29). In adjusted models, hepatitis C and psychiatric disorders were positively related to homelessness/housing instability and ADRD risk, but negatively related to HIV/AIDS. Statistically significant mediation and/or moderation of hepatitis C and psychiatric disorders were observed, although <10% of total effects were explained by these characteristics, controlling for confounders. CONCLUSIONS: Among older veterans, ADRD diagnoses over 5 years were less among those with HIV/AIDS, but more among those with homelessness/housing instability, and these relationships were partly explained by hepatitis C and psychiatric disorders.

Comprehensive machine learning models for predicting therapeutic targets in type 2 diabetes utilizing molecular and biochemical features in rats.

Introduction: With the increasing prevalence of type 2 diabetes mellitus (T2DM), there is an urgent need to discover effective therapeutic targets for this complex condition. Coding and non-coding RNAs, with traditional biochemical parameters, have shown promise as viable targets for therapy. Machine learning (ML) techniques have emerged as powerful tools for predicting drug responses. Method: In this study, we developed an ML-based model to identify the most influential features for drug response in the treatment of type 2 diabetes using three medicinal plant-based drugs (Rosavin, Caffeic acid, and Isorhamnetin), and a probiotics drug (Z-biotic), at different doses. A hundred rats were randomly assigned to ten groups, including a normal group, a streptozotocin-induced diabetic group, and eight treated groups. Serum samples were collected for biochemical analysis, while liver tissues (L) and adipose tissues (A) underwent histopathological examination and molecular biomarker extraction using quantitative PCR. Utilizing five machine learning algorithms, we integrated 32 molecular features and 12 biochemical features to select the most predictive targets for each model and the combined model. Results and discussion: Our results indicated that high doses of the selected drugs effectively mitigated liver inflammation, reduced insulin resistance, and improved lipid profiles and renal function biomarkers. The machine learning model identified 13 molecular features, 10 biochemical features, and 20 combined features with an accuracy of 80% and AUC (0.894, 0.93, and 0.896), respectively. This study presents an ML model that accurately identifies effective therapeutic targets implicated in the molecular pathways associated with T2DM pathogenesis.

Utilizing two different sustainable and green spectrophotometric approaches using derivative ratio spectra for the determination of a ternary severely overlapped mixture: application to veterinary formulation.

Mathematical manipulation technique has proven to be a very powerful tool for efficient processing and handling of highly overlapped spectra. This work introduced two green and sustainable approaches for the successful recovery of the ternary mixture, Tylosin tartarate (TYL), Sulfadimdine (SLD), and Trimethoprim (TRI). The approaches were constructed using three different methods, derivative ratio spectrum zero-crossing method (DRSZ), double divisor ratio spectra derivative method (DDRD), and factorized derivative ratio method coupled with spectrum subtraction (FDRM-SS). The two approaches succeeded in recovering the three drugs (Linearity range achieved were 0.5-5 µg/mL for TYL, 0.3-1.3 µg/mL for SLD, and 0.3-5 µg/mL for TRI), giving convenient standard deviations and satisfactory recovery percentages. The recommended methods have been verified in accordance with (ICH) guidelines. When the results were statistically compared to the official methods, no significant difference was found. Both AGREE-Analytical GREEnness Metric Approach and Software, and White Analytical Chemistry (WAC) RGB model gave scores of 0.93 and 97.2%, respectively, which proved that the approaches were eco-friendly and abiding by the sustainability principles.

Mediating and moderating effects of plasma proteomic biomarkers on the association between poor oral health problems and incident dementia: The UK Biobank study.

The plasma proteome can mediate poor oral health problems (POHP)'s link to incident dementia. We screened 37,269 UK Biobank participants 50-74 years old (2006-2010) for prevalent POHP, further tested against 1463 plasma proteins and incident dementia over up to 15 years of follow-up. Total effect (TE) of POHP-dementia through plasma proteomic markers was decomposed into pure indirect effect (PIE), interaction referent (INTREF), controlled direct effect (CDE), or mediated interaction (INTMED). POHP increased the risk of all-cause dementia by 17% (P < 0.05). Growth differentiation factor 15 (GDF15) exhibited the strongest mediating effects (PIE > 0, P < 0.001), explaining 28% the total effect of POHP on dementia, as a pure indirect effect. A first principal component encompassing top 4 mediators (GDF15, IL19, MMP12, and ACVRL1), explained 11% of the POHP-dementia effect as a pure indirect effect. Pathway analysis including all mediators (k = 173 plasma proteins) revealed the involvement of the immune system, signal transduction, metabolism, disease, and gene expression, while STRING analysis indicated that top mediators within the first principal component were also represented in the two largest proteomic clusters. The dominant biological GO pathway for the GDF15 cluster was GO:0007169 labeled as "transmembrane receptor protein tyrosine kinase signaling pathway." Dementia is linked to POHP mediated by GDF15 among several proteomic markers.

Serum neurofilament light chain as a prognostic marker of all-cause mortality in a national sample of US adults.

Neurofilament light chain (NfL) is a neuron-specific structural protein released into the extracellular space, including body fluids, upon neuroaxonal damage. Despite evidence of a link in neurological disorders, few studies have examined the association of serum NfL with mortality in population-based studies. Data from the National Health and Nutrition Survey were utilized including 2,071 Non-Hispanic White, Non-Hispanic Black and Hispanic adult participants and adult participants of other ethnic groups (20-85 years) with serum NfL measurements who were followed for ≤ 6 years till 2019. We tested the association of serum NfL with mortality in the overall population and stratified by sex with the addition of potential interactive and mediating effects of cardio-metabolic risk factors and nutritional biomarkers. Elevated serum NfL levels (above median group) were associated with mortality risk compared to the below median NfL group in the overall sample (P = 0.010), with trends observed within each sex group (P < 0.10). When examining Loge NfL as a continuum, one standard deviation of Loge NfL was associated with an increased mortality risk (HR = 1.88, 95% CI 1.60-2.20, P < 0.001) in the reduced model adjusted for age, sex, race, and poverty income ratio; a finding only slightly attenuated with the adjustment of lifestyle and health-related factors. Four-way decomposition indicated that there was, among others, mediated interaction between NfL and HbA1c and a pure inconsistent mediation with 25(OH)D3 in predicting all-cause mortality, in models adjusted for all other covariates. Furthermore, urinary albumin-to-creatinine ratio interacted synergistically with NfL in relation to mortality risk both on the additive and multiplicative scales. These data indicate that elevated serum NfL levels were associated with all-cause mortality in a nationally representative sample of US adults.