Association of Lipopolysaccharide-Type Endotoxins with Retinal Neurodegeneration: The Alienor Study.

Purpose: Lipopolysaccharide (LPS)-type endotoxins are naturally found in the gut microbiota and there is emerging evidence linking gut microbiota and neuroinflammation leading to retinal neurodegeneration. Thinning of the retinal nerve fiber layer (RNFL) is a biomarker of retinal neurodegeneration, and a hallmark of glaucoma, the second leading cause of blindness worldwide. We assessed the association of a blood biomarker of LPS with peripapillary RNFL thickness (RNFLT) and its longitudinal evolution up to 11 years. Design: The Alienor study is a single center prospective population-based cohort study. Subjects: The studied sample of this study includes 1062 eyes of 548 participants receiving ≥1 gradable RNFL measurement. Methods: Plasma esterified 3-hydroxy fatty acids (3-OH FAs) were measured as a proxy of LPS burden. Retinal nerve fiber layer thickness was acquired using spectral-domain OCT imaging every 2 years from 2009 to 2020 (up to 5 visits). Main Outcome Measures: Associations of plasma esterified 3-OH FAs with RNFLT were assessed using linear mixed models. Results: Mean age of the included 548 participants was 82.4 ± 4.3 years and 62.6% were women. Higher plasma esterified 3-OH FAs was significantly associated with thinner RNFLT at baseline (coefficient beta = -1.42 microns for 1 standard deviation-increase in 3-OH FAs, 95% confidence interval [-2.56; -0.28], P = 0.02). This association remained stable after multivariate adjustment for potential confounders. No statistically significant association was found between 3-OH FAs and longitudinal RNFLT change. Conclusions: Higher plasma esterified 3-OH FAs were associated with thinner RNFLT at baseline, indicating an involvement of LPS in the early processes of optic nerve neurodegeneration and highlighting the potential importance of the human microbiota in preserving retinal health. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Feasibility of prehabilitation for patients awaiting total knee arthroplasty; a pilot study.

Objective: To examine the feasibility of conducting a preoperative home-based prehabilitation program for total knee arthroplasty patients at risk for delayed in-hospital recovery, and to explore the pre- and postoperative impact of this program. Design: A retrospective cohort study with matched controls, enabling subgroup analyses. Setting: Home-based. Subjects: Patients awaiting primary unilateral total knee arthroplasty between 2019 and 2020, were compared with matched historic cases from 2016 to 2017. Matching criteria were scoring ≤17 points on the De Morton Mobility Index and >12.5 s on the timed-up-and-go test. Intervention: Supervised home-based prehabilitation program versus no prehabilitation. Outcomes: Feasibility, determined by recruitment rate, adherence, and safety of the program. Preoperative impact, assessed for the intervention group by differences in mean values for aerobic capacity, muscle strength and functional mobility between the first and last sessions. Postoperative impact was defined as the time needed to achieve in-hospital independence of physical function and was measured by the differences in mean values between the intervention and control groups. Results: Recruitment rate was 71 %; adherence and drop-out rates were 88 % and 12 % respectively. No adverse events were reported. Preoperatively, the intervention group showed significant improvements in aerobic capacity on the 2-min walking test (84.29 m-98.06 m; p = 0.007) and 2-min step test (40.35 steps to 52.95 steps; p = 0.014), muscle strength on the 30 s chair stand test (7.3 stands to 10.1 stands; p = 0.002), and functional mobility as seen in the timed-up-and-go-test (19.52 s-15.85 s; p = 0.031). Postoperatively, the intervention group achieved in-hospital independence of physical function earlier (mean rank 16.11) than the control group (mean rank 24.89; p=<0.01). Conclusions: It is feasible to conduct a prehabilitation program 4-6 weeks preoperatively, for high-risk patients awaiting total knee arthroplasty. Additionally, the program appears to have a positive impact on physical fitness both pre- and postoperatively.

Using GWAS and Machine Learning to Identify and Predict Genetic Variants Associated with Foodborne Bacteria Phenotypic Traits.

One of the main challenges in food microbiology is to prevent the risk of outbreaks by avoiding the distribution of food contaminated by bacteria. This requires constant monitoring of the circulating strains throughout the food production chain. Bacterial genomes contain signatures of natural evolution and adaptive markers that can be exploited to better understand the behavior of pathogen in the food industry. The monitoring of foodborne strains can therefore be facilitated by the use of these genomic markers capable of rapidly providing essential information on isolated strains, such as the source of contamination, risk of illness, potential for biofilm formation, and tolerance or resistance to biocides. The increasing availability of large genome datasets is enhancing the understanding of the genetic basis of complex traits such as host adaptation, virulence, and persistence. Genome-wide association studies have shown very promising results in the discovery of genomic markers that can be integrated into rapid detection tools. In addition, machine learning has successfully predicted phenotypes and classified important traits. Genome-wide association and machine learning tools have therefore the potential to support decision-making circuits intending at reducing the burden of foodborne diseases. The aim of this chapter review is to provide knowledge on the use of these two methods in food microbiology and to recommend their use in the field.

Potential interventions and interactions of bioactive polyphenols and functional polysaccharides to alleviate inflammatory bowel disease - A review.

Inflammatory bowel disease is a multifaceted condition that is influenced by nutritional, microbial, environmental, genetic, psychological, and immunological factors. Polyphenols and polysaccharides have gained recognition for their therapeutic potential. This review emphasizes the biological effects of polyphenols and polysaccharides, and explores their antioxidant, anti-inflammatory, and microbiome-modulating properties in the management of inflammatory bowel disease (IBD). However, polyphenols encounter challenges, such as low stability and low bioavailability in the colon during IBD treatment. Hence, polysaccharide-based encapsulation is a promising solution to achieve targeted delivery, improved bioavailability, reduced toxicity, and enhanced stability. This review also discusses the significance of covalent and non-covalent interactions, and simple and complex encapsulation between polyphenols and polysaccharides. The administration of these compounds in appropriate quantities has proven beneficial in preventing the development of Crohn's disease and ulcerative colitis, ultimately leading to the management of IBD. The use of polyphenols and polysaccharides has been found to reduce histological scores and colon injury associated with IBD, increase the abundance of beneficial microbes, inhibit the development of colitis-associated cancer, promote the production of microbial end-products, such as short-chain fatty acids (SCFAs), and improve anti-inflammatory properties. Despite the combined effects of polyphenols and polysaccharides observed in both in vitro and in vivo studies, further human clinical trials are needed to comprehend their effectiveness on inflammatory bowel disease.

Warm red light emitting Eu(III) complexes synthesis and analysis including computational methods for photonic applications.

Six luminescent europium organic complexes have been synthesized and studied for their luminescent properties. The synthesized complexes were analyzed through elemental analysis, XRD, SEM, EDAX, FT-IR, NMR and thermogravimetry. The complexes exhibit crystalline behavior and possess decent thermal stability. Photoluminescence study on complexes were conducted in both solid and solution states, the results indicate the characteristic red emission. With the addition of ancillary ligands, water molecules are replaced from inner coordination sphere, leading to enhanced luminescence properties. The colorimetric parameters (CIE, CP%, CCT, u', v') suggest aptness of these complexes in red light illuminating OLEDs. The J-O parameters were calculated experimentally and theoretically with the help of LUMPAC software. Theoretical and experimental results agree well reflecting the efficacy of the outcomes. As a result of red emission, these complexes could have interesting photonics applications. The biological studies indicate the probable use of these complexes in the medical industry.

Prevalência de transtornos psiquiátricos de pessoas em situação de rua em um grande centro urbano no Brasil / Prevalence of psychiatric disorders in homeless people in a large urban center in Brazil / Prevalencia de trastornos psiquiátricos en personas sin hogar en un gran centro urbano de Brasil

Introdução: O presente estudo visa descrever as condições de saúde mental mais prevalentes na população de rua em um grande centro urbano brasileiro. Objetivo: Descrever as condições de saúde mental mais prevalentes na população de moradores de rua em um grande centro urbano brasileiro. Métodos: Este é um estudo transversal realizado nas regiões centrais e periferias da cidade de São Paulo (SP), Brasil. Para a descrição dos transtornos psiquiátricos utilizamos o Patient Health Questionnaire-9 (PHQ-9) para sintomas depressivos, item 9 do Inventário de Depressão de Beck para ideação suicida, pergunta autorreferida para uso de álcool e drogas ilícitas e item 3 do PHQ-9 para qualidade do sono. Resultados: A média de idade dos participantes foi de 44,54 (desvio padrão ­ DP=12,63) anos, e a maioria era do sexo masculino (n=342; 75%). Quanto à frequência de transtornos psiquiátricos identificados, 49,6% (n=226) dos participantes apresentaram sintomas depressivos, 29,8% (n=136) exibiram ideação suicida, 55,7% (n=254) informaram uso de álcool semanalmente, 34,2% (n=156) informaram usar drogas ilícitas semanalmente e 62,3% (n=284) tinham problemas com sono. Conclusões: A prevalência de condições que afetam a saúde mental entre os participantes é alta. Estes resultados poderão auxiliar profissionais de saúde na elaboração de estratégias de prevenção e tratamento nessa população, pouco estudada.

Introduction: The present study aims to describe the most prevalent mental health conditions in the homeless population in a large Brazilian urban center. Objective: To describe the most prevalent mental health conditions in the population of homeless people in a large Brazilian urban center. Methods: This is a cross-sectional study carried out in the central and periphery regions of São Paulo, state of São Paulo, Brazil. For the description of psychiatric disorders, the following instruments were used: Patient Health Questionnaire-9 (PHQ-9) for depressive symptoms, item 9 of the Beck Depression Inventory for suicidal ideation, the self-reported question for the use of alcohol and illicit drugs, and item 3 of the PHQ-9 for sleep quality. Results: The mean age of participants was 44.54 (Standard Deviation=12.63) years, and most were men (n=342; 75%). Regarding the frequency of the identified psychiatric disorders, 49.6% (n=226) of the participants had depressive symptoms, 29.8% (n=136) had suicidal ideation, 55.7% (n=254) reported weekly alcohol use, 34.2% (n=156) reported using illicit drugs weekly, and 62.3% (n=284) had sleep problems. Conclusions: The prevalence of conditions that affect mental health among participants is high. These results may help health professionals to develop prevention and treatment strategies for this understudied population.

Introducción: El presente estudio tiene como objetivo describir las condiciones de salud mental más prevalentes en la población sin hogar en un gran centro urbano brasileño. Objetivo: Describir las condiciones de salud mental más prevalentes en la población de personas sin hogar en un gran centro urbano brasileño. Métodos: Se trata de un estudio transversal realizado en las regiones central y periférica de São Paulo, SP, Brasil. Para la descripción de los trastornos psiquiátricos se utilizó el Cuestionario de Salud del Paciente - 9 (PHQ-9) para síntomas depresivos, el ítem 9 del Inventario de Depresión de Beck para ideación suicida, la pregunta autorreportada para uso de alcohol y drogas ilícitas y ítem 3 del PHQ-9 para la calidad del sueño. Resultados: La edad media de los participantes fue de 44,54 (DE=12,63) años, y la mayoría eran hombres (n=342; 75%). En cuanto a la frecuencia de los trastornos psiquiátricos identificados, el 49,6% (n=226) de los participantes presentaba síntomas depresivos, el 29,8% (n=136) tenía ideación suicida, el 55,7% (n=254) refería consumo semanal de alcohol, el 34,2% (n=156) refirió consumir drogas ilícitas semanalmente y el 62,3% (n=284) presentaba problemas de sueño. Conclusiones: La prevalencia de condiciones que afectan la salud mental entre los participantes es alta. Estos resultados pueden ayudar a los profesionales de la salud a desarrollar estrategias de prevención y tratamiento para esta población poco estudiada.

New-onset atrial fibrillation after coronary surgery and stroke risk: a nationwide cohort study.

BACKGROUND: New-onset postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) increases ischaemic stroke risk, yet factors influencing this risk remain unclear. We sought to identify factors associated with 1-year ischaemic stroke risk, compare the CHA2DS2-VASc (Congestive heart failure, Hypertension, Age ≥75 years, Diabetes, previous Stroke/transient ischaemic attack (TIA), Vascular disease, Age 65-74 years, Sex category) and ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) scores' predictive abilities for ischaemic stroke, and assess oral anticoagulation (OAC) dispensing at discharge in patients with POAF. METHODS: This nationwide cohort study used prospectively collected data from four mandatory Swedish national registries. All first-time isolated CABG patients who developed POAF during 2007-2020 were included. Multivariable logistic models were used to identify ischaemic stroke predictors and C-statistics to assess the predictive abilities of the CHA2DS2-VASc and ATRIA scores in patients without OAC. OAC dispensing patterns were described based on stroke-associated factors. RESULTS: In total, 10 435 patients with POAF were identified. Out of those not receiving OAC (n=6903), 3.1% experienced an ischaemic stroke within 1 year. Advancing age (adjusted OR (aOR) 1.86 per 10-year increase, 95% CI 1.45 to 2.38), prior ischaemic stroke (aOR 18.56, 95% CI 10.05 to 34.28 at 60 years, aOR 5.95, 95% CI 3.78 to 9.37 at 80 years, interaction p<0.001), myocardial infarction (aOR 1.55, 95% CI 1.14 to 2.10) and heart failure (aOR 1.53, 95% CI 1.06 to 2.21) were independently associated with ischaemic stroke. The area under the receiver-operating characteristic curve was 0.72 (0.69-0.76) and 0.74 (0.70-0.78) for CHA2DS2-VASc and ATRIA, respectively (p=0.021). Altogether, 71.0% of patients with a stroke risk >2%/year, according to the CHA2DS2-VASc score, were not discharged on OAC. CONCLUSIONS: Prior ischaemic stroke, advancing age, history of heart failure and myocardial infarction were associated with 1-year ischaemic stroke risk in patients with POAF after CABG. CHA2DS2-VASc and ATRIA scores predicted stroke risk with similar accuracy as in non-surgical atrial fibrillation cohorts. OAC dispense at discharge does not seem to reflect individual stroke risk.

Characterisation of older patients that require, but do not undergo, emergency laparotomy: a multicentre cohort study.

BACKGROUND: Older adults (≥65 yr) account for the majority of emergency laparotomies in the UK and are well characterised with reported outcomes. In contrast, there is limited knowledge on those patients that require emergency laparotomy but do not undergo surgery (NoLaps). METHODS: A multicentre cohort study (n=64 UK surgical centres) recruited 750 consecutive NoLap patients (February 15th - November 15th 2021, inclusive of a 90-day follow up period). Each patient was admitted to hospital with a surgical condition treatable by an emergency laparotomy (defined by The National Emergency Laparotomy Audit (NELA) criteria), but a decision was made not to undergo surgery (NoLap). RESULTS: NoLap patients were predominately female (452 patients, 60%), of advanced age (median age 83.0 yr, interquartile range 77.0-88.8), frail (523 patients, 70%), and had severe comorbidity (750 patients, 100%); 99% underwent CT scanning. The commonest diagnoses were perforation (26%), small bowel obstruction (17%), and ischaemic bowel (13%). The 90-day mortality was 79% and influencing factors were >80 yr, underweight BMI, elevated serum lactate or creatinine concentration. The majority of patients died in hospital (77%), with those with ischaemic bowel dying early. For the 21% of NoLap patients that survived to 90 days, 77% returned home with increased care requirements. CONCLUSIONS: This study reports that the NoLap patient population present significant medical challenges because of their extreme levels of comorbidity, frailty, and physiology. Despite these complexities a fifth remained alive at 90 days. Further work is underway to explore this high-risk decision-making process. CLINICAL TRIAL REGISTRATION: ISRCTN14556210.

Virtual screening, molecular dynamics simulations, and in vitro validation of EGFR inhibitors as breast cancer therapeutics.

A high abundance of Epidermal Growth Factor Receptor (EGFR) in malignant cells makes them a prospective therapeutic target for basal breast tumors. Although EGFR inhibitors are in development as anticancer therapeutics, there exists limitations due to the dose-limiting cytotoxicity that limits their clinical utilization, thereby necessitating the advancement of effective inhibitors. In the present study, we have developed common pharmacophore hypotheses using 30 known EGFR inhibitors. The best pharmacophore hypothesis DHRRR_1 was utilized for virtual screening (VS) of the Phase database containing 4.3 × 106 fully prepared compounds. The top 1000 hits were further subjected to ADME filtration followed by structure-based VS and Molecular Dynamics (MD) simulation investigations. Based on pharmacophore hypothesis matching, XP glide score, interactions between ligands and active site residues, ADME properties, and MD simulations, the five best hits (SN-01 through SN-05) were preferred for in-vitro cytotoxicity studies. All the molecules except SN-02 exhibited cytotoxicity in Triple Negative Breast Cancer (TNBC) cells. These potential EGFR inhibitors effectively downregulated the EGF-induced proliferation, migration, in-vitro tumorigenic capability, and EGFR activation (pEGFR) in the TNBCs. Additionally, in combination with doxorubicin, the identified EGFR inhibitors significantly decreased the EGF-induced proliferation. SN-04, and SN-05 in the presence of a lower concentration of doxorubicin markedly increased the apoptotic markers expression in the TNBCs, an effect which was comparable to a higher concentration of doxorubicin treatment, alone. These observations suggest that both SN-04 and/or SN-05 can improve the efficacy of chemotherapeutic drug, doxorubicin at a lower concentration to avert the higher dose of chemotherapeutic-induced side effects during breast cancer treatment.

Design, synthesis, and biological evaluation of novel imidazole derivatives as analgesic and anti-inflammatory agents: experimental and molecular docking insights.

Imidazole moieties exhibit a broad range of biological activities, including analgesic, anti-depressant, anticancer, anti-fungal, anti-tubercular, anti-inflammatory, antimicrobial, antiviral, and antifungal properties. In this study, we explored the use of Schiff base for the synthesis of new imidazole derivatives as anti-inflammatory and pain-relieving agents. A series of eight novel imidazole analogues (2a-h) were prepared in three steps with excellent yields. All compounds were characterized using IR, NMR, and mass spectral data. Their analgesic and anti-inflammatory activities were evaluated using hot plate and paw oedema methods. Compound 2 g (1-(2,3-dichlorophenyl)-2-(3-nitrophenyl)-4,5-diphenyl-1H-imidazole) showed significant analgesic activity (89% at 100 mg/kg b.w.), while compounds 2a (2-(2,6-dichlorophenyl)-1-(4-ethoxyphenyl)-4,5-diphenyl-1H-imidazole) and 2b (2-(2,3-dichlorophenyl)-1-(2-chlorophenyl)-4,5-diphenyl-1H-imidazole) exhibited good anti-inflammatory activity (100% at 100 mg/kg b.w.), comparable to diclofenac salt (100% at 50 mg/kg b.w.). Molecular docking studies were conducted using Schrödinger software version 2021-2, employing the OPLS4 force field for both receptor and ligand preparation. The results were visualized using molecular visualization software such as PyMOL. These studies revealed that compound 2g exhibited the highest binding affinity with the COX-2 receptor (-5.516 kcal/mol). Compound 2g formed three conventional hydrogen bonds with residues GLN-242 (bond length: 2.3 Å) and ARG-343 (bond lengths: 2.2 Å & 2.4 Å). This binding affinity was comparable to that of Diclofenac salt, which showed the highest binding affinity of -5.627 kcal/mol with the COX-2 receptor. Diclofenac salt formed two conventional hydrogen bonds with the residues ARG-344 (bond length: 2.0 Å) and TRP-140 (bond length: 1.7 Å). Later, molecular dynamic simulations confirmed the stable binding affinity of compound 2g with the protein. Furthermore, other compounds also demonstrated potential binding to the receptor-binding pocket region. The anti-inflammatory potential of the synthesized compounds was evaluated using the carrageenan-induced rat hind paw oedema model, while the analgesic potential was assessed using the hot plate method. These evaluations were conducted in comparison with Diclofenac sodium, serving as the standard compound. However, compound 2g stood out for its superior analgesic activity, as confirmed by in-vivo examination. These findings suggest that these novel imidazole derivatives have potential as anti-inflammatory and analgesic agents.

Shift in Demographic Involvement and Clinical Characteristics of COVID-19 From Wild-Type SARS-CoV-2 to the Delta Variant in the Indian Population: In Silico Analysis.

BACKGROUND: The Delta variant (B.1.617.2) was considered the most dangerous SARS-CoV-2 strain; however, in-depth studies on its impact based on demographic and clinical characteristics of COVID-19 are scarce. OBJECTIVE: We aimed to investigate the shift in demographic and clinical characteristics of the COVID-19 pandemic with the emergence of the SARS-CoV-2 Delta variant compared with the wild-type (WT) strain (B.1). METHODS: A cross-sectional study of COVID-19 cases in the Indian population caused by the WT strain (B.1) and Delta variant of SARS-CoV-2 was performed. The viral genomic sequence metadata containing demographic, vaccination, and patient status details (N=9500, NDelta=6238, NWT=3262) were statistically analyzed. RESULTS: With the Delta variant, in comparison with the WT strain, a higher proportion of young individuals (<20 years) were infected (0-9 years: Delta: 281/6238, 4.5% vs B.1: 75/3262, 2.3%; 10-19 years: Delta: 562/6238, 9% vs B.1: 229/3262, 7%; P<.001). The proportion of women contracting infection increased (Delta: 2557/6238, 41% vs B.1: 1174/3262, 36%; P<.001). However, it decreased for men (Delta: 3681/6238, 59% vs B.1: 2088/3262, 64%; P<.001). An increased proportion of the young population developed symptomatic illness and were hospitalized (Delta: 27/262, 10.3% vs B.1: 5/130, 3.8%; P=.02). Moreover, an increased proportion of the women (albeit not men) from the young (Delta: 37/262, 14.1% vs B.1: 4/130, 3.1%; P<.001) and adult (Delta: 197/262, 75.2% vs B.1: 72/130, 55.4%; P<.001) groups developed symptomatic illness and were hospitalized. The mean age of men and women who contracted infection (Delta: men=37.9, SD 17.2 years; women=36.6, SD 17.6 years; P<.001; B.1: men=39.6, SD 16.9 years; women=40.1, SD 17.4 years; P<.001) as well as developing symptoms or being hospitalized (Delta: men=39.6, SD 17.4 years; women=35.6, SD 16.9 years, P<.001; B.1: men=47, SD 18 years; women=49.5, SD 20.9 years, P<.001) were considerably lower with the Delta variant than the B.1 strain. The total mortality was about 1.8 times higher with the Delta variant than with the WT strain. With the Delta variant, compared with B.1, mortality decreased for men (Delta: 58/85, 68% vs B.1: 15/20, 75%; P<.001); in contrast, it increased for women (Delta: 27/85, 32% vs B.1: 5/20, 25%; P<.001). The odds of death increased with age, irrespective of sex (odds ratio 3.034, 95% CI 1.7-5.2, P<.001). Frequent postvaccination infections (24/6238) occurred with the Delta variant following complete doses. CONCLUSIONS: The increased involvement of young people and women, the lower mean age for illness, higher mortality, and frequent postvaccination infections were significant epidemiological concerns with the Delta variant.

The Correlation Between Genetics and Suicidal Behaviors: a Challenge of Literature.

Suicide and suicidal behaviors seem to have a heritable component, and evidences from adoption, twins and families studies underline observations that greater familial suicidal behavior correlates with earlier onset and higher risk in offspring, supporting the presence of a genetic component. In this paper we report data from the literature, highlighting the scientific relevance of research in important topic as suicidal behaviours.

Association of CACNA1C polymorphisms (rs1006737, rs4765905, rs2007044) with schizophrenia: A meta-analysis and trial sequential analysis.

Schizophrenia is a complex neurological disorder characterized by significant impairment in the perception of reality and changes in behavior. Genetic and environmental factors influence the development of schizophrenia. CACNA1C, which encodes a subunit of a voltage-dependent calcium channel, has been associated with various neurological disorders, including schizophrenia. Several studies have been performed in different populations to explore the association of common genetic variants in the CACNA1C gene with susceptibility to the development of schizophrenia, but results remain contradictory. To draw a definitive conclusion on the association between CACNA1C polymorphisms and schizophrenia, we conducted a meta-analysis focusing on three commonly studied polymorphisms: rs1006737, rs4765905, and rs2007044. For the meta-analysis, a comprehensive literature search was performed using PubMed, Scopus, Science Direct and Google Scholar databases. Data was retrieved, and the meta-analysis was performed using CMA v4 software. The meta-analysis revealed a significant association between rs1006737 and rs2007044 and schizophrenia in the overall population, while no such association was found for rs4765905. Population-wise analysis suggested that all three polymorphisms were significantly associated with schizophrenia in the Asian population and that rs1006737 was significantly associated with schizophrenia in Europeans. We also performed a Trial Sequential Analysis (TSA), which supported our findings. Some report-based assay studies have suggested a role for these polymorphisms in schizophrenia, but further case-control studies are needed to confirm the association of rs4765905 and rs2007044 with the disorder.

Substance use and risk of suicide among adults who sought mental health and addiction specialty services through a centralised intake process in Nova Scotia: a cross-sectional study.

OBJECTIVES: The objectives of this study are as follows: (1) to estimate the prevalence of suicide risk among individuals seeking mental health and addiction (MHA) services in Nova Scotia; (2) to examine the relationship between substance use and suicide risk among this population. SETTING: MHA intake programme, a province-wide centralised intake process established in 2019 by the Department of Health and Wellness of Nova Scotia. PARTICIPANTS: We included 22 500 MHA intake clients aged 19-64 years old who contacted MHA intake from 2020 to 2021. PRIMARY OUTCOME MEASURES: During the intake assessment, clients were assessed for suicide risk (past suicide attempt, suicidal ideation during the interview or 2 weeks before the interview). RESULTS: The lifetime prevalence of suicide attempt was 25.25% in the MHA clients. The prevalence of mild and moderate/high suicide risk was 34.14% and 4.08%, respectively. Clients who used hallucinogens had the highest prevalence of mild and moderate/high suicide risk (61.3% and 12.9%, respectively), followed by amphetamine/methamphetamine (47.6% and 13.3%, respectively) and sedative/hypnotics (47.2% and 8.9%, respectively) users. Stimulant (aOR=1.84, 95% CI 1.23 to 2.75) and hallucinogen (aOR=3.54, 95% CI 1.96 to 6.43) use were associated with increased odds of moderate/high suicide risk compared with denying current use. Additionally, alcohol (aOR=1.17, 95% CI 1.06 to 1.30) and tobacco (aOR=1.20, 95% CI 1.10 to 1.30) use were associated with increased odds of mild suicide risk. CONCLUSION: Suicide behaviours were prevalent among clients seeking MHA services. Substance use is an important factor associated with suicide risk in this population. This result underscored the importance of considering substance use patterns when assessing suicide risk and highlighted the need for targeted interventions and preventive measures for individuals engaging in substance use. Future interventional studies are needed to identify and evaluate effective strategies for reducing substance use and suicide risk among clients of MHA central intake.

Post COVID-19 syndrome among 5248 healthcare workers in England: longitudinal findings from NHS CHECK.

OBJECTIVES: The objectives of this study were to examine post COVID-19 syndrome (PCS) among healthcare workers (HCWs) in England and explore risk factors for the condition. METHODS: Data were collected by National Health Service (NHS) CHECK, a longitudinal study exploring HCWs' mental and physical well-being during and after the COVID-19 pandemic. NHS CHECK collected data at four timepoints: the baseline survey between April 2020 and January 2021, and then three follow-up surveys at approximately 6, 12 and 32 months post baseline. PCS data were collected at 12 and 32 months, while risk factor data were from baseline. HCWs were asked what COVID-19 symptoms they experienced and for how long and were classified as having PCS if they had any symptom for ≥12 weeks. Multilevel regressions were used to examine risk factors for PCS. RESULTS: This study included 5248 HCWs. While 33.6% (n=1730) reported prolonged COVID-19 symptoms consistent with PCS, only 7.4% (n=385) reported a formal diagnosis of PCS. Fatigue, difficult concentrating, insomnia and anxiety or depression were the most common PCS symptoms. Baseline risk factors for reporting PCS included screening for common mental disorders, direct contact with COVID-19 patients, pre-existing respiratory illnesses, female sex and older age. CONCLUSIONS: While a third of HCWs reported prolonged COVID-19 symptoms consistent with PCS, a smaller percentage reported a formal diagnosis of the condition. We replicate findings that direct contact with COVID-19 patients, older age, female sex, pre-existing respiratory illness and symptoms of common mental disorders are associated with increased risk of PCS.

A Cross-Sectional Study of Peri-Implant Diseases in a Random Norwegian Population: Prevalence, Risk Indicators, and Clinical Validation of Patient-Reported Outcomes.

OBJECTIVES: The primary aim of this study was to investigate the prevalence of peri-implant diseases in a randomly selected Norwegian population. The secondary aims were to explore risk indicators for peri-implant diseases and to validate self-reported outcome measures from a survey with clinical parameters. MATERIAL AND METHODS: Patients (n = 3083) rehabilitated with dental implants in 2014 were mailed a questionnaire and invited to a clinical examination. A randomly selected subset of responders underwent a clinical examination (n = 242). Full mouth clinical and radiographic examinations were conducted. Multiple logistic regression was used to assess patient-related risk indicators for peri-implantitis. Self-reported data were compared with data from the clinical examination using Spearman correlation and binary logistic regression. RESULTS: The prevalence of peri-implantitis was 17.0% at patient level and 8.6% at implant level, according to the 2018 classification. Risk indicators for peri-implantitis included smoking and periodontitis in the adjusted model. The correlation was strong (r = 0.91, p < 0.001) between number of self-reported implants and clinical counts, whereas self-reported peri-implant inflammation was associated with peri-implantitis (OR 6.4 [95% CI 3.0, 13.7]). CONCLUSIONS: Smoking and periodontitis were identified as key risk indicators for peri-implantitis. Questionnaire data rendered clinically valid estimates of implant number, and self-reported peri-implant inflammation was associated with clinical peri-implantitis.

Meritocratic beliefs in the United States, Finland, and China: A multidimensional approach using latent class analysis.

This study employs latent class analysis (LCA) as a novel methodology to investigate the multidimensional nature of meritocratic beliefs, addressing the limitations of traditional unidimensional approaches. Using data from the International Social Survey Program 2009 for the United States, Finland, and China, this study demonstrates several advantages of this multidimensional approach. First, LCA effectively identifies dual consciousness, where individuals simultaneously endorse meritocratic and structuralist explanations of social stratification. The analysis reveals three distinct narratives explaining social stratification: purely meritocratic beliefs, predominantly meritocratic beliefs, and dual consciousness. While all three subtypes consider merits highly important, they differ in their perceived importance of structural factors. Second, LCA facilitates cross-national comparisons, unveiling qualitative typological variations in meritocratic beliefs across countries. Unique country-specific subtypes or patterns emerge: Finland exhibits purely meritocratic beliefs, the United States shows predominantly meritocratic beliefs, and China demonstrates a dominance of dual consciousness. Although dual consciousness exists in all three countries, its prevalence varies significantly-dominant in China, moderate in the United States, and least in Finland. Third, this study reveals that the effect of education on meritocratic beliefs varies across the three countries. Education strengthens individual meritocratic beliefs in the United States, weakens them in Finland, and shows no significant effect in China. These findings highlight both within-country and across-country heterogeneity of meritocratic beliefs, underscoring the importance of a multidimensional approach.

Perirenal fat and chronic kidney disease in type 2 diabetes: the mediation role of afferent arteriolar resistance.

AIM: Perirenal fat (PRF) is an independent predictor for chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM) patients. Previous studies speculated that PRF may promote renal dysfunction through affecting renal hemodynamics. To verify this hypothesis, we studied the relationship between PRF and renal hemodynamics in T2DM. METHODS: 91 T2DM patients were included. PRF thickness (PRFT) was measured by magnetic resonance imaging. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined by renal dynamic imaging. Renal vascular resistance (RVR), glomerular hydrostatic pressure (PGLO), afferent (RA) and efferent (RE) arteriolar resistance were calculated by Gomez equations. Multiple linear regression was used to determine the relationship between PRFT and renal hemodynamics. Mediation analysis was conducted to estimate the mediation effects of renal hemodynamics on the relationship between PRF and CKD. RESULTS: All patients were divided into three groups according to the tertiles of PRFT. Compared with patients in tertile 1, GFR and ERPF were significantly decreased in patients in tertile 3, while RVR and RA were significantly increased. PRFT was negatively correlated with GFR, ERPF and PGLO, and positively correlated with RVR and RA after adjustment for sex, age, visceral adipose tissue and treatments with ACE inhibitors/angiotensin receptor blockers and sodium-glucose cotransporter protein-2 inhibitors. Moreover, RVR and RA mediated the effect of PRF on GFR, with a mediated proportion of 29.1% and 41.4% respectively. CONCLUSION: In T2DM patients, PRF was negatively correlated with GFR, and positively correlated with RA. RA mediated the relationship between PRF and CKD.

Flavonoids and Their Derivatives as DNA Topoisomerase Inhibitors with Anti-Cancer Activity in Various Cell Models: Exploring a Novel Mode of Action.

Flavonoids, a diverse group of plant-derived secondary metabolites, have garnered significant attention for their potential anti-cancer properties. This review explores the role of flavonoids as inhibitors of DNA topoisomerases, key enzymes essential for DNA replication, transcription, and cell division. The article offers a comprehensive overview of flavonoid classification, biosynthesis, and their widespread natural occurrence. It further delves into the molecular mechanisms through which flavonoids exert their anti-cancer effects, emphasizing their interactions with topoisomerases. The review provides a thorough analysis of both in vitro and in vivo studies that highlight the topoisomerase inhibitory activities of various flavonoids and their derivatives. Key findings demonstrate that flavonoids can function as catalytic inhibitors, poisons, or DNA intercalators, affecting both type I and type II topoisomerases. The structure-activity relationships of flavonoids concerning their topoisomerase inhibitory potency are also examined. This review underscores the potential of flavonoids as promising lead compounds for the development of novel topoisomerase inhibitors, which could have important implications for cancer therapy. However, it also acknowledges the need for further research to fully understand the intricate interactions between flavonoids and topoisomerases within the cellular environment.

Trend and determinants of unplanned pregnancy among expectant mothers in Ethiopia based on the Ethiopia Demographic and Health Survey (2000-2016) data: a cross-sectional study.

OBJECTIVE: To investigate the trend and determinants of unplanned pregnancy among expectant women using the four Ethiopia Demographic and Health Survey (EDHS) data (2000-2016). DESIGN: Cross-sectional study. SETTING: Secondary data analysis using EDHS data. PARTICIPANTS: The number of weighted participants were 1451 in 2000, 1184 in 2005, 1205 in 2011 and 1135 in 2016. PRIMARY AND SECONDARY OUTCOME MEASURES: Unplanned pregnancy encompasses both mistimed (occurring earlier than desired) and unwanted (occurring when no further children are desired) forms of conception. Trend and multilevel logistic regression analyses were conducted. RESULTS: The rate of unplanned pregnancies in Ethiopia showed a significant decline, decreasing from 45.8% (95% CI 41.8 to 49.8) in 2000 to 29.7% (95% CI 25.3 to 34.4) in 2016, indicating an overall change of 16.1%. Several factors were positively linked to unplanned pregnancy, including being multipara (adjusted OR (AOR)=9.8; 95% CI 1.74 to 15.23) and grand multipara (AOR=12.2; 95% CI 1.62 to 19.3), expressing a lack of desire for additional children (AOR=2.82; 95% CI 1.30 to 6.12), unemployment (AOR=1.91; 95% CI 1.12 to 3.78) and being unmarried (AOR=7.23; 95% CI 4.71 to 15.5), whereas, women residing in the Afar (AOR=0.12; 95% CI 0.02 to 0.79) and Somalia (AOR=0.20; 95% CI 0.07 to 0.67) regions were associated with reduced likelihood of experiencing unplanned pregnancy. CONCLUSION: The study discovered that unplanned pregnancies in Ethiopia decreased significantly from 2000 to 2016. However, around one-third of pregnant women are still affected, indicating a high rate. To address this, policymakers and stakeholders should propose and implement targeted interventions on identified risk factors.