Significant Increase In Proportion Research Articles

Trends and the Role of Gene-Environment Interactions in Idiopathic Membranous Nephropathy in Northern China.

Idiopathic membranous nephropathy (iMN) has become one of the most prevalent primary glomerular diseases, with a marked increase in prevalence over the past two decades in northern China. Fine particulate matter (PM2.5) is considered to be associated with this rising prevalence. In this study, we aim to evaluate the trends of iMN in relation to improved air quality and conduct a cross-sectional study in Hebei province (northern China, near Beijing) to investigate the role of gene-environment interactions in its development. This study established two cohorts. Cohort 1 included 22,937 pathology reports from Peking University First Hospital (2002-2021) to assess iMN prevalence. Cohort 2 comprised 5,635 iMN patients from 11 cities in Hebei Province (2009-2013). DNA samples from 374 iMN patients and 1,259 controls were genotyped for SNPs rs4664608 (PLA2R1) and rs2187668 (HLA-DQA1). Patients were stratified by air pollution risk levels. The annual percentage change (APC) and average annual percentage change (AAPC) were estimated using a join-point regression model. Gene-environment interactions were analyzed using logistic regression and epinet-calculation. In Cohort 1, 5,586 patients with iMN were identified, representing 24.3% of the 22,937 patients from 2002 to 2021. The general population showed a significant increase in iMN proportion with an APC of +12.7% per year from 2002 to 2014 (95% CI: 10.3 to 17.5, p < 0.001), followed by a decline with an APC of -5.6% per year from 2014 to 2021 (95% CI: -9.6 to -2.6, p < 0.001).In Hebei Province, the iMN frequency rose significantly with an APC of +17.6% per year from 2002 to 2016 (95% CI: 14.5 to 28.6, p < 0.001), peaking at 60%, and then declined with an APC of -5.5% per year from 2016 to 2021 (95% CI: -13.1 to -1.2, p = 0.02). Cohort 2 highlighted significant regional variation in iMN incidence across Hebei Province. Geographic exposure to pollution was identified as an independent risk factor for iMN (RR 1.49, 95% CI 1.38-1.56, p<0.001). Gene-environment interaction analysis revealed that patients with risk alleles in the PLA2R1 gene and exposure to risk environments had a markedly increased risk of developing iMN (OR=38.72, 95% CI 11.95-125.46, p<0.01). The annual growth rate of iMN in northern China appears to be slowing down. Gene-environment interactions may have contributed to the previously observed increase in iMN prevalence.

Changes in practice of exercise advice provision following the publication of ESC 2020 guidelines on sports cardiology and exercise at a central London inherited cardiac conditions outpatient service

Abstract ESC 2005 and AHA guidelines 2015 in sports cardiology restricted individuals with hypertrophic cardiomyopathy (HCM) from moderate and high intensity exercise and limited them to low intensity sport.1,2 Perceived increased risk of sudden cardiac death (SCD) with vigorous exercise in individuals with HCM was based on early registry data from the United States.3 This enforced sedentary lifestyle has led to an increasing trend towards obesity, atrial fibrillation and atherosclerotic coronary artery disease in patients with HCM.4 Recent ESC 2020 guidelines on exercise5 has enabled clinicians to recommend safe levels of exercise for these patients. We audited how well our outpatient practice reflected the guidance set out in 2020 ESC guidelines on exercise for patients with cardiovascular disease. Electronic records of 731 patients with a clinical diagnosis of HCM seen in our outpatient service between 2008-2023 were audited to determine whether written advice on exercise was given and if this was in line with the current ESC guidelines at any encounter. 731 patients with a mean age of 62±14.5 (range 17-91 years) were seen in our specialist outpatient service. 68% were male. 51% of patients received exercise advice either at their initial visit ± a follow-up visit. A significant proportional increase (16%,P&amp;lt;0.001) was seen in the number of patients receiving exercise advice at their initial visit after publication of the ESC 2020 guidelines (Table 1). 43% (270/634) of those who had their initial visit pre-guidelines received updated exercise advice as per 2020 ESC guidelines during follow-up. There was an increase in the proportion of patients receiving exercise advice each year after publication of ESC guidelines (Graph 1). Immediately following the publication, a high proportion received specific advice pertaining to intensity and duration of exercise (68% in 2020) with a slight decline subsequently (43%, 36% and 47% in 2021, 2022 and 2023 respectively). 27 patients had an implantable cardioverter defibrillator (ICD) in situ at the time of initial review with a further 127 undergoing ICD insertion under our care. SCD risk was documented for 66% (468/704) of patients according to the 2014 ESC Risk-SCD Model. 63% (214/338) of low-risk patients received exercise advice, whilst 77% (40/52) and 54% (42/78) of intermediate and high-risk patients received exercise advice respectively. 22 deaths (3%) were recorded during the follow-up period with none occurring during exercise. All cases except 2 were non-cardiac related. An overall improvement was seen in our practice with a significant increase in the number of patients receiving exercise advice after publication of the new guidelines. Despite this, only 51% of our patients received any written guidance on exercise demonstrating a need for further improvement in our outpatient practice to reflect the paradigm shift in the approach to exercise in individual with HCM as set out by the ESC 2020 guidance.

Mechanisms and advancements in microwave-enhanced CO2 mineralization of lightweight porous concrete

Lightweight porous concrete (LPC) typically exhibits low early strength, which can be addressed by enhancing early strength through carbon dioxide (CO2) mineralization curing while achieving permanent CO2 sequestration. The efficacy of this process relies on maintaining optimal moisture levels. This study investigates the influence of moisture content on the performance of solid waste-based lightweight porous concrete blocks (RSFAC) subjected to microwave heating pretreatment. Moisture levels were adjusted to 10%, 20%, 30%, and 40% (initial water-to-cement ratio of 45.4%) before undergoing mineralization curing within an environment set at a temperature of 20 °C, relative humidity 75%, and a CO2 concentration of 40% for a duration of 0.5 h. The impact of moisture content on RSFAC's compressive strength, carbon sequestration rate, mineralization products, and microstructure was evaluated. Results indicate that compared to conventional oven pretreatment methods requiring nearly 10 h, microwave pretreatment technology achieves equivalent water content within just 50 min, significantly reducing the time needed for mineralization pretreatment. RSFAC, when pretreated with microwave heating, outperforms untreated samples (Ref-0 and Ref-1) in terms of compressive strength and carbon sequestration efficiency. Optimal performance was observed at a moisture content level of 30%, with the highest recorded compressive strength achieved at 1, 3, and 7 d respectively. At the curing age of 7 d, the compressive strength reached up to 2.32 MPa while the carbon sequestration rate reached approximately 11.61%. Furthermore, aragonite and calcite (tetrahedral and hexahedral), without poorly crystalline spherulites, were identified as the main crystalline CaCO3 generated by RSFAC under this specific moisture content condition; pores larger than 50 nm served as primary reaction sites for RSFAC mineralization curing, whereas there was a significant increase in pore proportion with sizes less than 20 nm after filling with mineralization products.

Video based educational intervention in waiting area to improve awareness about health screening among patients visiting family medicine clinics

BackgroundMultiple educational modalities have been utilized including leaflet, face-to-face counseling and watching videos in waiting areas for engaging patients. Considering the two challenges of waiting time frustration and lack of health screening awareness, Family Physicians’ waiting area are an ideal place to bridge this gap. The objective of this study is to evaluate the effectiveness of video-based health education intervention in improving knowledge about health screening among patients and their families sitting in waiting area of Family Medicine clinics.MethodsIt was a pre and post quasi-experimental study that was conducted in family medicine clinics located at main campus and Outreach centers of a tertiary care hospital. A total of 300 participants were approached during the six month period. The intervention consisted of an educational video on health screening. The content of the video was taken from the recommended preventive care guidelines from CDC and USPSTF. The pre-and post-intervention knowledge of the participants was assessed through a semi-structured coded questionnaire by an interviewer who was trained in data collection. Data was analyzed using SPSS version 26. Pre and post intervention knowledge adequacy was determined using MacNemar’s Chi-square test.ResultsTotal 300 participants voluntarily participated into the study. Median age of the participants was 28 (IQR = 23.25–36.75) years. Majority of participants were males (56%). Following the intervention, there was significant increase in the proportion of participants (51.3% versus 68%) who had understanding of health screening check-up (p < 0.001). Following the study intervention, there was significant increase in proportion of participants who had adequate knowledge related to diabetes (p = 0.045), hypertension (p < 0.001), cholesterol (p < 0.001), cervical cancer (p < 0.001), colon cancer (p < 0.001) and hepatitis B & C (p < 0.001). No significant improvement in breast cancer related knowledge was observed (p = 0.074). Highest post-intervention increase in knowledge from baseline was observed for hypertension (13.3% versus 63.3%) followed by colon cancer (24.3% versus 59.3%), cholesterol (67 versus 96.7%), hepatitis b & C (56.7% versus 77.3%), diabetes (29.7% versus 48%), cervical cancer (1.7% versus 19%), and breast cancer (7.7% versus 18.3%).ConclusionThis study highlighted a pivotal role of an educational video intervention in clinic waiting area to improve awareness regarding health screening among patients and their families. Further interventional community based or multicenter studies are warranted to assess the long-term impact of these educational videos on knowledge and utilization of health screening among adult population.

Substance Use Disorder Admission Rates Before and After the Lockdown in a Large Addiction Center in Saudi Arabia: A Retrospective Cohort Study

Objective: This study aimed to examine the potential changes in substance use disorder (SUD) admission rates before and after the lockdown in a major addiction center in Saudi Arabia. Method: This retrospective cohort study extracted data from Al-Amal Hospital Electronic Health Record in the city of Dammam, Eastern region of Saudi Arabia. A total of 2,426 cases included in the analysis for patients who received services from the SUD treatment programs from 1/1/2015 to 31/12/2021. Results: Before the pandemic, there was a consistent increase in the admission rates for patients with substance use disorder. The highest proportion of increase were among unemployed, young, newly admitted patients. During lockdown, there was nearly a 70% reduction in SUDs-related admission rate. The age group 18–25 was seven-times more likely to be admitted for SUD after the lockdown. Amphetamine-related admissions were two times more likely to be admitted after the lockdown (Odds ratio (OR) 2.04; confidence interval (CI) 95%[1.64, 2.54]). Conclusions: There was nearly 70% reduction in SUDs admission rates during the lockdown. After the lockdown, a significant proportional increase in amphetamine use disorder admissions was observed mostly among the patients age group 18–24 with a history of a previous admissions. Determining populations at risk for high health care utilization is crucial in building a comprehensive and effective prevention strategy. Therefore, the need to adopt coordinated strategies and innovative, comprehensive approaches to benefit individuals with SUD is imperative to face the increased rate of SUD related admissions.

Single-Cell RNA Sequencing Analysis Reveals Metabolic Changes in Epithelial Glycosphingolipids and Establishes a Prognostic Risk Model for Pancreatic Cancer.

Metabolic reprogramming serves as a distinctive feature of cancer, impacting proliferation and metastasis, with aberrant glycosphingolipid expression playing a crucial role in malignancy. Nevertheless, limited research has investigated the connection between glycosphingolipid metabolism and pancreatic cancer. This study utilized a single-cell sequencing dataset to analyze the cell composition in pancreatic cancer tissues and quantified single-cell metabolism using a newly developed computational pipeline called scMetabolism. A gene signature developed from the differential expressed genes (DEGs), related to epithelial cell glycosphingolipid metabolism, was established to forecast patient survival, immune response, mutation status, and reaction to chemotherapy with pancreatic adenocarcinoma (PAAD). The single-cell sequencing analysis revealed a significant increase in epithelial cell proportions in PAAD, with high glycosphingolipid metabolism occurring in the cancerous tissue. A six-gene signature prognostic model based on abnormal epithelial glycosphingolipid metabolism was created and confirmed using publicly available databases. Patients with PAAD were divided into high- and low-risk categories according to the median risk score, with those in the high-risk group demonstrating a more unfavorable survival outcome in all three cohorts, with higher rates of gene mutations (e.g., KRAS, CDKN2A), increased levels of immunosuppressive cells (macrophages, Th2 cells, regulatory T cells), and heightened sensitivity to Acetalax and Selumetinlb. Abnormal metabolism of glycosphingolipids in epithelial cells may promote the development of PAAD. A model utilizing a gene signature associated with epithelial glycosphingolipids metabolism has been established, serving as a valuable indicator for the prognostic stratification of patients with PAAD.

LSD use in the United States: Examining user demographics and their evolution from 2015–2019

AbstractBackgroundLysergic acid diethylamide (LSD) use has risen in the United States in recent years amid increased interest in therapeutic applications of psychedelics. Despite this, contemporary epidemiological investigations of LSD users are few. To expand the literature on this topic, we sought to characterize past-year LSD users in the United States and investigate recent demographic evolution within this population.MethodsUsing National Survey on Drug Use and Health (NSDUH) data from 2015–2019, we investigated correlates of past-year LSD use and associated changes over the study period.ResultsPast-year LSD use increased by 47% from 2015 to 2019 (0.59%–0.87%). However, among people reporting past-year hallucinogen use disorder there was no significant proportional increase in LSD users. Notable correlates of LSD use on multivariable analysis were: increased LSD access, lower perceived risk of trying LSD, low income, fewer children in the home, being approached by someone selling drugs in the past month, and past-year suicide attempt among people age 18 and older. We found no associations with unemployment, arrest history, or past-year psychological distress. From 2015 to 2019, the proportion of respondents reporting past-year LSD use who were age 26–34 and married increased. Past-year LSD use among lifetime users of methamphetamine also rose.ConclusionsThough still uncommonly used in the United States, LSD's societal acceptance may be increasing. Overall, LSD does not appear to contribute significantly to the country's public health problems.

The impact of complexation or complex coacervation of lactoferrin and osteopontin on simulated infant gastrointestinal digestion, intestinal inflammation, and in vivo bone development.

Lactoferrin (LF) and osteopontin (OPN) are bioactive milk proteins which can form heteroprotein complexes and complex coacervates. This research studied the effect of LF-OPN complexation and complex coacervation on the simulated infant gastrointestinal digestion of LF with subsequent examination of gut and bone health bioactivities in preclinical models. In an infant digestion model, the proteolytic profile of LF was unaltered by the pre-association of LF and OPN. Gastric proteolysis of LF was increased when the model gastric pH was reduced from 5.3 to 4.0, but less so when complexed with OPN. In a model of intestinal inflammation, undigested (79% inhibition) and gastric digestates (26% inhibition) of LF, but not gastrointestinal digestates, inhibited lipopolysaccharide (LPS)-induced NF-κB activation in intestinal epithelial cells. LF-OPN complexation sustained the inhibitory effect (21-43% of the undigested effect, depending on the type of complex) of LF after gastrointestinal digestion, suggesting that the peptides produced were different. In a neonatal rodent model used to study bone development, coacervating LF and OPN improved bone structures with a significant increase of trabecular proportion (BV/TV increase by 21.7%). This resulted in an 11.3% increase in stiffness of bones. Feeding the LF and OPN proteins in coacervate format also increased the levels of OPN, P1NP and M-CSF in blood, signifying a more pronounced impact on bone development. This research demonstrated that LF-OPN complexation and complex coacervation can delay simulated infant gastrointestinal digestion of LF and protect or improve the bioactivity of the proteins.

End of Affirmative Action-Who Is Impacted Most? Analysis of Race and Sex Among US Internal Medicine Faculty.

For over 50 years, the United States (US) used affirmative action as one strategy to increase diversity in higher education including medical programs, citing benefits including training future public and private sector leaders. However, the recent US Supreme Court ending affirmative action in college admissions threatens advancements in the diversity of medical college faculty. Our study evaluated the demographic trends in Internal Medicine (IM) faculty in the US by assessing sex and race/ethnicity diversity to investigate who is likely to be impacted most with the end of affirmative action. Longitudinal retrospective analysis SUBJECTS: IM faculty from the Association of American Medical Colleges faculty roster from 1966 to 2021 who self-reported sex and ethnicity MAIN OUTCOMES: The primary study measurement was the annual proportion of women and racial/ethnic groups among IM faculty based on academic rank and department chairs. Although racial/ethnic diversity increased throughout the era of affirmative action, African American, Hispanic, and American Indian populations remain underrepresented. White physicians occupied > 50% of faculty positions across academic ranks and department chairs. Among the non-White professors, Asian faculty had the most significant increase in proportion from 1966 to 2021 (0.6 to 16.6%). The percentage of women increased in the ranks of professor, associate professor, assistant professor, and instructor by 19.5%, 27.8%, 25.6%, and 26.9%, respectively. However, the proportion of women and racial/ethnic minority faculty decreased as academic rank increased. Despite an increase in the representation of women and racial/ethnic minority IM faculty, there continues to be a predominance of White and men physicians in higher academic ranks. With the end of affirmative action, this trend has the danger of being perpetuated, resulting in decreasing diversity among IM faculty, potentially impacting patient access and health outcomes.

Sex differences in zymosan-induced behavioral visceral hypersensitivity and colorectal afferent sensitization.

Sex differences in visceral nociception have been reported in clinical and preclinical studies, but the potential differences in sensory neural encoding of the colorectum between males and females are not well understood. In this study, we systematically assessed sex differences in colorectal neural encoding by conducting high-throughput optical recordings in intact dorsal root ganglia (DRGs) from control and visceral hypersensitive mice. We found an apparent sex difference in zymosan-induced behavioral visceral hypersensitivity: enhanced visceromotor responses to colorectal distension were observed only in male mice, not in female mice. In addition, a higher number of mechanosensitive colorectal afferents were identified per mouse in the zymosan-treated male group than in the saline-treated male group, whereas the mechanosensitive afferents identified per mouse were comparable between the zymosan- and saline-treated female groups. The increased number of identified afferents in zymosan-treated male mice was predominantly from thoracolumbar (TL) innervation, which agrees with the significant increase in the TL afferent proportion in the zymosan group as compared with the control group in male mice. In contrast, female mice showed no difference in the proportion of colorectal neurons between saline- and zymosan-treated groups. Our results revealed a significant sex difference in colorectal afferent innervation and sensitization in the context of behavioral visceral hypersensitivity, which could drive differential clinical symptoms in male and female patients.NEW & NOTEWORTHY We used high-throughput GCaMP6f recordings to study 2,275 mechanosensitive colorectal afferents in mice. Our results revealed significant sex differences in the zymosan-induced behavioral visceral hypersensitivity, which were present in male but not female mice. Male mice also showed sensitization of colorectal afferents in the thoracolumbar pathway, whereas female mice did not. These findings highlight sex differences in sensory neural anatomy and function of the colorectum, with implications for sex-specific therapies for treating visceral pain.

Abstract 18202: Sex Differences in Transthyretin Amyloid Cardiomyopathy

Introduction: Transthyretin amyloid cardiomyopathy (ATTR-CM) predominantly affects men. It is unknown if women are underdiagnosed or if female sex is protective. We investigated sex differences in clinical presentation and disease outcomes in ATTR-CM. Methods: Patients seen with ATTR-CM at our institution were included for analysis. Chi-squared or Fisher’s exact tests, and Wilcoxon tests were used to assess associations between clinical variables and sex in the overall cohort as well as by genotype (wtATTR and V122I). Hazard ratios with 95% confidence intervals were used to assess outcomes. Results: Of 293 subjects, 235 (80%) were men and 58 (20%) were women. Women vs men were more likely Black in the entire cohort (65% v 39%) and in the wtATTR group (70% v 8.7%, p&lt;0.05). Women were significantly older in wtATTR (84 [6.6] v 79 [7.2] yrs) and V122I (75 [6] v 71 [8.3] yrs), had higher HR (83 v 75 bpm), lower eGFR (54 v 62 mL/min/1.73 m2), and thinner intraventricular septum diameter (1.54 [0.3] v 1.71 [0.3] cm) than men at time of diagnosis (p&lt;0.05). Women with wtATTR had significantly higher mean RAP (14.8 [6.9] v 8.69 [4.8] v mmHg, p&lt;0.05) and a trend toward higher PASP (55.5 [17.0] v 42.9 [12.8] and PCWP (22.5 [6.7] v 17.3 [6.4] mmHg, p=0.06) vs men. There was no difference in HF hospitalization or death at 5 years (HR 0.93 [0.59-1.45], p=0.70) and no significant increase in proportion of women diagnosed over disease eras (pre-2013, 2013-2018, and 2019-2023). Conclusions: In a well characterized cohort with ATTR-CM, women were diagnosed less frequently and at an older age with markers of more advanced disease including higher HR, worse renal function, and higher filling pressures compared to men. Disease recognition in women did not increase over time. While this may be due to the nature of the disease, the characteristics we identified at diagnosis support that women with ATTR-CM are under detected. Future sex-based screening studies are needed to increase detection of ATTR-CM in women.

An intervention to improve self-care among people with diabetes mellitus: A quasi-experimental study

Abstract Background An increased self-efficacy promotes better diabetes self-care behaviours, which help in achieving glycemic targets among patients with diabetes mellitus. Methods A quasi-experimental study was conducted among patients with T2DM living in rural areas of Punjab, North India. A total of 283 in the intervention and 291 in the control arms were participated at baseline, and a total of 242 in the intervention and 237 in the control arms at endline assessments. Summary of diabetes self-care activities and diabetes management self-efficacy questionnaires were used at baseline and endline (after 6 months) surveys. Outcomes were net changes in proportion of population having diabetes self-management self-efficacy, overall diabetes self-care activities (health dietary habits, physical activity, adequate foot care, medication adherence and blood glucose monitoring) and net mean change in HbA1c. Data were analysed using per protocol analysis principle. Difference in difference analysis (DiD) using Generalized Estimating Equation model was done to adjust for confounders. p &amp;lt; 0.05 was considered as significant. Results There was a significant net increase in participants proportion (39%; 95% CI: 25% -52%, p &amp;lt; 0.001) on diabetes management self-efficacy scale. At the baseline assessment for overall self-care behaviours, only 4% of participants in the intervention arm were in the action stage and 12% were in the preparation stage; however, at the post intervention assessment, this proportion increased to 24% for action stage and 67% for preparation stage. There was a significant net increase in participants proportion (49%, 95%CI 37% -60%, p &amp;lt; 0.001) engaged in optimal diabetes self-care. There was a significant net decrease in mean HbA1c (-1.06%; 95%CI: -1.62 - -0.50, p &amp;lt; 0.001) at post intervention phase. Conclusions Diabetes self-care intervention was successful in promoting self-efficacy and self-care practices among patients with T2DM of rural areas. Key messages • Self-efficacy theory-based diabetes self-care intervention successfully improves the diabetes related self-care practices. • There is a need for a structured diabetes self-care management education programme to improve the ability of patients with T2DM who live in rural areas.

Effectiveness of dietary intervention among people with diabetes mellitus: A quasi-experimental study

Abstract Background This study was aimed to evaluate the impact of intervention based on the behaviour change theory on dietary practices among patients with T2DM living in rural areas. Methods A quasi-experimental study was carried out in a rural area of district Fatehgarh Sahib of Punjab, North India. A total of 700 people with T2DM was screened for the eligibility from the randomly selected rural health centeres. The baseline survey included a total of 584 eligible T2DM patients (283 in the intervention and 291 in the control arms), whereas the endline survey included a total of 479 participants (242 in the intervention and 237 in the control arms). A prevalidated and structured food frequency questionnaire at baseline and at the end of 6 months of follow-up. The outcomes of study were mean changes in the total calorie intake from carbohydrate and fat, salt intake, fiber intake and biochemical measurements namely fasting plasma blood glucose, and proportion of population having HbA1c ≤ 7%. Difference in difference analysis (DiD) using Generalized Estimating Equation (GEE) model was applied to adjust for confounders. Statistical significance was considered p &amp;lt; 0.05. Results DiD suggested a significant decrease in mean: total calorie intake (-857 kcal/day; 95% CI -1115 - -599, p &amp;lt; 0.001), calorie intake from carbohydrates (-569 kcal/day; 95% CI -729 - -410, p &amp;lt; 0.001), calories intake from fat (-329 kcal/day; 95% CI -438 - -220, p &amp;lt; 0.001) and dietary salt intake (-5 gm/day; 95% CI -7 - -3, p &amp;lt; 0.001). There was also a significant increase in the mean dietary fiber intake (4 gm/day; 95% CI 0.82 - 7, p = 0.01), a decrease in the mean FPBG (-42 mg/dl; 95%CI: -55 - -29, p &amp;lt; 0.001) and a significant increase in proportion of participants having HbA1c within range (≤7%), (8%; 95%CI:1% - 14%, p = 0.01). Conclusions Study suggested dietary interventions based on the behaviour change theory helped to achieve optimal dietary habits and glycemic stability among patients with T2DM living in rural areas. Key messages • This study emphasised the advantage of behaviour change interventions implementation based on behaviour change theories among patients with T2DM. • T2DM patients can be encouraged to follow healthy dietary habits by using tailored instructions.

The effect of the Covid-19 pandemic on Tuberculosis (TB) case notification in Ogun State, Nigeria.

COVID-19 pandemic has resulted in disruptions in delivery of Tuberculosis services especially, in resource-limited settings. Provisional data by the WHO from 84 countries indicates that about 1.4 million fewer people received care for tuberculosis in 2020 than in 2019. This study assessed the effect of COVID-19 pandemic on tuberculosis case notification rates in Ogun state, Nigeria. A retrospective review of presumptive TB and diagnosed TB cases that were notified in 2019 and 2020. Analysis was done using Epi-info version 7.2.3.1. Level of statistical significance was p < 0.05. A total of 3102 and 3326 confirmed cases were reported in 2019 and 2020 respectively with an increase of 7.2%. There was significant decline in total number of cases notified in Q2, 2020 compared to 2019 (p=0.001) with a significant increase in proportion of TB cases notified by private facilities from 11.65% in 2019 to 20.27% in 2020. Total TB cases notified in Ogun state increased during the covid-19 pandemic. There was significant decline in TB cases during the lockdown but an increase in proportion of TB cases notified by private facilities demonstrating that private facilities can withstand disruptions to TB case notifications due to the Covid-19 pandemic.

Immediate and long-term outcomes after treat-all among people living with HIV in China: an interrupted time series analysis

BackgroundIn 2003, China implemented free antiretroviral therapy (ART) for people living with HIV (PLHIV), establishing an eligibility threshold of CD4 < 200 cells/μl. Subsequently, the entry criteria were revised in 2012 (eligibility threshold: CD4 ≤ 350 cells/μl), 2014 (CD4 ≤ 500 cells/μl), and 2016 (treat-all). However, the impact of treat-all policy on HIV care and treatment indicators in China is unknown. We aimed to elucidate the immediate and long-term impact of the implementation of treat-all policy in China.MethodsAnonymized programmatic data on ART initiation and collection in PLHIV who newly started ART were retrieved between 1 January 2015 and 31 December 2019, from two provincial and municipal Centers for Disease Control and Prevention and ten major infectious disease hospitals specialized in HIV care in China. We used Poisson and quasi-Poisson segmented regression models to estimate the immediate and long-term impact of treat-all on three key indicators: monthly proportion of 30-day ART initiation, mean CD4 counts (cells/μl) at ART initiation, and mean estimated time from infection to diagnosis (year). We built separate models according to gender, age, route of transmission and region.ResultsMonthly data on ART initiation and collection were available for 75,516 individuals [gender: 83.8% males; age: median 39 years, interquartile range (IQR): 28–53; region: 18.5% Northern China, 10.9% Northeastern China, 17.5% Southern China, 49.2% Southwestern China]. In the first month of treat-all, compared with the contemporaneous counterfactual, there was a significant increase in proportion of 30-day ART initiation [+ 12.6%, incidence rate ratio (IRR) = 1.126, 95% CI: 1.033–1.229; P = 0.007] and mean estimated time from infection to diagnosis (+ 7.0%, IRR = 1.070, 95% CI: 1.021–1.120; P = 0.004), while there was no significant change in mean CD4 at ART initiation (IRR = 0.990, 95% CI: 0.956–1.026; P = 0.585). By December 2019, the three outcomes were not significantly different from expected levels. In the stratified analysis, compared with the contemporaneous counterfactual, mean CD4 at ART initiation showed significant increases in Northern China (+ 3.3%, IRR = 1.033, 95% CI: 1.001–1.065; P = 0.041) and Northeastern China (+ 8.0%, IRR = 1.080, 95% CI: 1.003–1.164; P = 0.042) in the first month of treat-all; mean estimated time from infection to diagnosis showed significant increases in male (+ 5.6%, IRR = 1.056, 95% CI: 1.010–1.104; P = 0.016), female (+ 14.8%, IRR = 1.148, 95% CI: 1.062–1.240; P < 0.001), aged 26–35 (+ 5.3%, IRR = 1.053, 95% CI: 1.001–1.109; P = 0.048) and > 50 (+ 7.8%, IRR = 1.078, 95% CI: 1.000–1.161; P = 0.046), heterosexual transmission (+ 12.4%, IRR = 1.124, 95% CI: 1.042–1.213; P = 0.002) and Southwestern China (+ 12.9%, IRR = 1.129, 95% CI: 1.055–1.208; P < 0.001) in the first month of treat-all.ConclusionsThe implementation of treat-all policy in China was associated with a positive effect on HIV care and treatment outcomes. To advance the work of rapid ART, efforts should be made to streamline the testing and ART initiation process, provide comprehensive support services, and address the issue of uneven distribution of medical resources.

Optimal examined lymph node number for accurate staging and long-term survival in rectal cancer: a population-based study.

Although the recommended minimal examined lymph node (ELN) number in rectal cancer (RC) is 12, this standard remains controversial because of insufficient evidence. We aimed to refine this definition by quantifying the relationship between ELN number, stage migration and long-term survival in RC. Data from a Chinese multi-institutional registry (2009-2018) and the Surveillance, Epidemiology, and End Results (SEER) database (2008-2017) on stages I-III resected RC were analysed to determine the relationship between ELN count, stage migration, and overall survival (OS) using multivariable models. The series of odds ratios (ORs) for negative-to-positive node stage migration and hazard ratios (HRs) for survival with more ELNs were fitted using a Locally Weighted Scatterplot Smoothing (LOWESS) smoother, and structural breakpoints were determined using the Chow test. The relationship between ELN and survival was evaluated on a continuous scale using restricted cubic splines (RCS). The distribution of ELN count between the Chinese registry ( n =7694) and SEER database ( n =21332) was similar. With increasing ELN count, both cohorts exhibited significant proportional increases from node-negative to node-positive disease (SEER, OR, 1.012, P <0.001; Chinese registry, OR, 1.016, P =0.014) and serial improvements in OS (SEER: HR, 0.982; Chinese registry: HR, 0.975; both P <0.001) after controlling for confounders. Cut-point analysis showed an optimal threshold ELN count of 15, which was validated in the two cohorts, with the ability to properly discriminate probabilities of survival. A higher ELN count is associated with more precise nodal staging and better survival. Our results robustly conclude that 15 ELNs are the optimal cut-off point for evaluating the quality of lymph node examination and stratification of prognosis.

Concentration-Regulated Fibrillation of Soy Protein: Structure and In Vitro Digestion.

The impact of protein types, heating temperatures, and times on protein fibrillation has been widely studied. However, there is little understanding of the influence of protein concentration (PC) on the protein fibril assembly. In this work, the structure and in vitro digestibility of soy protein amyloid fibrils (SAFs) were investigated at pH 2.0 and different PCs. Significant increases in fibril conversion rate and parallel β-sheets proportion were observed in SAFs upon increasing the PC from 2 to 8% (w/v). The AFM images showed that curly fibrils were prone to form at 2-6% PCs, while rigid, straight fibrils developed at higher PCs (≥8%). As evidenced in XRD results, increasing PC led to a more stable structure of SAFs with enhanced thermal stability and lower digestibility. Moreover, positive correlations among PC, β-sheet content, persistence length, enthalpy, and total hydrolysis were established. These findings would provide valuable insights into concentration-regulated protein fibrillation.

Prevalence and grade of malignancy differences with respect to the area of involvement in multiparametric resonance imaging of the prostate in the diagnosis of prostate cancer using the PI-RADS version 2 classification.

The peripheral zone is histologically different from the transitional zone. The aim of this study is to analyze the differences between the prevalence and grade of malignancy of mpMRI-targeted biopsies that involve the TZ with respect to the PZ. A cross-sectional study of 597 men evaluated for PC screening between February 2016 and October 2022 was conducted. Exclusion criteria were prior BPH surgery, radiotherapy, 5-alpha-reductase inhibitors treatment, UTI, mixed involvement of PZ-TZ or doubts, and central-zone involvement. Hypothesis contrast test was used to study differences proportions of malignancy (ISUP > 0) and significant (ISUP > 1) and high-grade tumor (ISUP > 3) in PI-RADSv2 > 2-targeted biopsies in PZ with respect to TZ, and logistic regression and hypothesis contrast tests were used to study the influence of the area of exposure as an effect-modifying factor in the diagnosis of malignancy with respect to the PI-RADSv2 classification. 473 patients were selected and 573 lesions biopsied (127 PI-RADS3, 346 PI-RADS4 and 100 PI-RADS5). A significant increase was described in the proportion of malignancy and significant and high-grade tumor in PZ compared to TZ (22.6%, 21.3%, and 8.7%, respectively). Significant increase in proportions and malignancy were described in cores targeted to PZ with respect to TZ, highlight the differences between PZ and TZ for ST (37.3%vs23.7% for PI-RADS4, 69.2%vs27.3% for PI-RADS5, respectively). Statistically significant linear trend was described increasing for malignancy, significant and high-grade tumors with respect to the PI-RADSv2 scores (change > 10%). Although the prevalence and grade of malignancy in the TZ is lower than in the PZ, PI-RADS4 and 5-targeted biopsies should not be omitted in this location, but PI-RADS3 could be.

Selection of an anti-pathogen skin microbiome following prophylaxis treatment in an amphibian model system.

With emerging diseases on the rise, there is an urgent need to identify and understand novel mechanisms of prophylactic protection in vertebrate hosts. Inducing resistance against emerging pathogens through prophylaxis is an ideal management strategy that may impact pathogens and their host-associated microbiome. The host microbiome is recognized as a critical component of immunity, but the effects of prophylactic inoculation on the microbiome are unknown. In this study, we investigate the effects of prophylaxis on host microbiome composition, focusing on the selection of anti-pathogenic microbes contributing to host acquired immunity in a model host-fungal disease system, amphibian chytridiomycosis. We inoculated larval Pseudacris regilla against the fungal pathogen Batrachochytrium dendrobatidis (Bd) with a Bd metabolite-based prophylactic. Increased prophylactic concentration and exposure duration were associated with significant increases in proportions of putatively Bd-inhibitory host-associated bacterial taxa, indicating a protective prophylactic-induced shift towards microbiome members that are antagonistic to Bd. Our findings are in accordance with the adaptive microbiome hypothesis, where exposure to a pathogen alters the microbiome to better cope with subsequent pathogen encounters. Our study advances research on the temporal dynamics of microbiome memory and the role of prophylaxis-induced shifts in microbiomes contributing to prophylaxis effectiveness. This article is part of the theme issue 'Amphibian immunity: stress, disease and ecoimmunology'.

Clinical and biological activity of FLX475, an oral CCR4 antagonist, in advanced cancer.

2625 Background: FLX475 is a potent and selective CCR4 antagonist, designed to block the recruitment of immunosuppressive regulatory T cells (Treg) into tumors without affecting healthy tissues. Blocking migration of Treg into the tumor microenvironment (TME) has the potential to restore antitumor immunity and synergize with a variety of conventional and immunotherapy-based approaches to overcome immune resistance and broaden clinical efficacy. In a recent interim clinical update from the ongoing FLX475-02 Phase 1/2 trial, evidence of monotherapy and combination activity were reported. FLX475 monotherapy induced complete responses in two of the six evaluable subjects enrolled with EBV+ NK/T cell lymphoma. In checkpoint inhibitor naïve non-small-cell lung cancer (NSCLC), 4/13 subjects (31%) had confirmed partial responses (PRs) following treatment with the combination of FLX475 and pembrolizumab. In this analysis we present biomarker data from patients with broad range of tumor types treated with FLX475 monotherapy. We provide evidence to substantiate the mechanism of action and support the combination of FLX475 with pembrolizumab. Methods: Flow cytometry was used to measure relative proportions of Treg in the periphery. CD8 and FOXP3 positive cells in tumor biopsies were quantified by immunohistochemistry (IHC).Gene set enrichment analysis and immune deconvolution methods were used to interrogate RNAseq data derived from tumor biopsies. Results: FLX475 monotherapy results in a small but significant increase in proportion of circulating CD25+CD127-/low CD4+ Treg by day 8 of treatment. IHC analysis revealed a trend towards increased CD8:FOXP3 ratio in the TME of patient biopsies. Transcriptomic profiles from tumor biopsies of FLX475 monotherapy treated patients exhibited significant changes in immune pathways likely to benefit the antitumor response. Using global gene expression analyses we identified that FLX475 monotherapy altered the transcriptome of tumors to resemble those from patients with favorable clinical outcome to anti-PD(L)-1 treatment. Consistent with the proposed mechanism of action, immune deconvolution identified that FLX475-treated patients experienced a decrease in Treg cell populations. Conclusions: FLX475 monotherapy results in beneficial changes in the TME consistent with our proposed mechanism of action. FLX475 monotherapy is modifying the tumor microenvironment toward a phenotype associated with response to anti-PD-1/anti-PD-L1. Clinical trial information: NCT03674567 .