Unveiling the immune dynamics of Neisseria persistent oral colonization.

Commensal bacteria are crucial in maintaining host physiological homeostasis, immune system development, and protection against pathogens. Despite their significance, the factors influencing persistent bacterial colonization and their impact on the host still need to be fully understood. Animal models have served as valuable tools to investigate these interactions, but most have limitations. The bacterial genus Neisseria, which includes both commensal and pathogenic species, has been studied from a pathogenicity to humans perspective but lacks models that study immune responses in the context of long-term persistence. Neisseria musculi, a recently described natural commensal of mice, offers a unique opportunity to study long-term host-commensal interactions. In this study, for the first time, we have used this model to study the transcriptional, phenotypic, and functional dynamics of immune cell signatures in the mucosal and systemic tissue of mice in response to N. musculi colonization. We found key genes and pathways vital for immune homeostasis in palate tissue, validated by flow cytometry of immune cells from the lung, blood, and spleen. This study offers a novel avenue for advancing our understanding of host-bacteria dynamics and may provide a platform for developing efficacious interventions against mucosal persistence by pathogenic Neisseria.

Estimation of mean population salt intakes using spot urine samples and associations with body mass index, hypertension, raised blood sugar and hypercholesterolemia: Findings from STEPS Survey 2019, Nepal.

BACKGROUND: High dietary salt intake is recognized as a risk factor for several non-communicable diseases (NCDs), in particular cardiovascular diseases (CVDs), including heart attack and stroke. Accurate measurement of population level salt intake is essential for setting targeted goals and plans for salt reduction strategies. We used a spot urine sample to estimate the mean population salt intake in Nepal and evaluated the association of salt intake with excess weight, hypertension, raised blood sugar and hypercholesterolemia, and a number of socio-demographic characteristics. METHODS: A population-based cross-sectional study was carried out from February to May 2019 using a WHO STEPwise approach to surveillance. Spot urine was collected from 4361 participants aged 15-69 years for the analysis of salt intake. We then used the INTERSALT equation to calculate population salt intake. Student's 't' test, one-way ANOVA and multivariable linear regression were used to assess the association between salt intake and a number of factors. Statistical significance was accepted at P < .05. RESULTS: The average (±SD) age of participants was 40 (14.1) years. Mean salt intake, derived from spot urine samples, was estimated to be 9.1g/d. A total of 70.8% of the population consumed more than the WHO's recommended amount of 5g salt per day, with almost one third of the population (29%) consuming more than 10g of salt per day. Higher salt intake was significantly associated with male gender (ß for male = 0.98g; 95%CI:0.87,1.1) and younger age groups (ß25-39 years = 0.08; 95%CI:-0.08,0.23) and higher BMI (ß = 0.19; 95%CI:0.18,0.21). Participants who were hypertensive and had raised blood cholesterol consumed less salt than people who had normal blood pressure and cholesterol levels (P<0.001). CONCLUSIONS: Salt consumption in Nepal is high, with a total of 70.8% of the population having a mean salt intake >5g/d, well above the World Health Organization recommendation. High salt intake was found to be associated with sex, age group, education, province, BMI, and raised cholesterol level of participants These findings build a strong case for action to reduce salt consumption in Nepal in order to achieve the global target of 30% reduction in population salt intake by 2025.

Prevalence and factors associated with joint pain in Nepal: findings from a countrywide cross-sectional STEPS survey.

OBJECTIVE: This study aims to determine the prevalence of joint pain and its association with demographic, socioeconomic and behavioural factors in Nepal. DESIGN: The study was a national cross-sectional population-based study. SETTING: We used the most recent nationally representative population-based cross-sectional health survey, The WHO STEPwise approach to surveillance (STEPS) survey, 2019 from all seven provinces of Nepal including both urban and rural areas. PARTICIPANTS: The participants were men and women aged 15-69 years, who were usual residents of the households for at least 6 months and have stayed the night before the survey. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome in this study was prevalence of joint pain. The secondary outcome measure was factors associated with joint pain in Nepal. Joint pain in our study was based on any self-reported symptoms of joint pain, stiffness and swelling lasting for more than 1 month in the past 12 months. Data were weighted to generate national estimates. RESULTS: The prevalence of self-reported joint pain in Nepal was 17% (95% CI 14.3% to 20.2%) with higher prevalence for older adults, females, ever married, none/less than primary education, smoker, lowest wealth quintile, homemaker, those with sufficient physical activity and those living in the Karnali province of Nepal. In multivariable analysis self-reported joint pain was found to be associated with advanced age (adjusted OR (AOR)=2.36; 95% CI 1.56 to 3.55), sex (AOR=1.47; 95% CI 1.19 to 1.82) and sufficient physical activity (AOR=0.40; 95% CI 0.25 to 0.65). CONCLUSIONS: The results showed a high prevalence of joint pain in Nepal. Considering the process of ageing and rapid growth in non-communicable disease, this study warrants the need for health policies directed to prevention, treatment and rehabilitation for people affected by chronic musculoskeletal conditions addressing related disabilities and loss of work in Nepal.

Prevalence of non-communicable diseases risk factors and their determinants: Results from STEPS survey 2019, Nepal.

BACKGROUND: The World Health Organization (WHO) recommends ongoing surveillance of non-communicable diseases (NCDs) and their risk factors, using the WHO STEPwise approach to surveillance (STEPS). The aim of this study was to assess the distribution and determinants of NCD risk factors in Nepal, a low-income country, in which two-thirds (66%) of annual deaths are attributable to NCDs. METHODS: A nationally representative NCD risk factors STEPS survey (instrument version 3.2), was conducted between February and May 2019, among 6,475 eligible participants of age 15-69 years sampled from all 7 provinces through multistage sampling process. Data collection involved assessment of behavioral and biochemical risk factors. Complex survey analysis was completed in STATA 15, along with Poisson regression modelling to examine associations between covariates and risk factor prevalence. RESULTS: The most prevalent risk factor was consumption of less than five servings of fruit and vegetables a day (97%; 95% CI: 94.3-98.0). Out of total participants, 17% (95% CI: 15.1-19.1) were current smoker, 6.8% (95% CI: 5.3-8.2) were consuming ≥60g/month alcohol per month and 7.4% (95% CI:5.7-10.1) were having low level of physical activity. Approximately, 24.3% (95% CI: 21.6-27.2) were overweight or obese (BMI≥25kg/m2) while 24.5% (95% CI: 22.4-26.7) and 5.8% (95% CI: 4.3-7.3) had raised blood pressure (BP) and raised blood glucose respectively. Similarly, the prevalence of raised total cholesterol was 11% (95% CI: 9.6-12.6). Sex and education level of participants were statistically associated with smoking, harmful alcohol use and raised BP. Participants of age 30-44 years and 45-69 years were found to have increased risk of overweight, raised BP, raised blood sugar and raised blood cholesterol. Similarly, participants in richest wealth quintile had higher odds of insufficient physical inactivity, overweight and raised blood cholesterol. On average, each participant had 2 NCD related risk factors (2.04, 95% CI: 2.02-2.08). CONCLUSION: A large portion of the Nepalese population are living with a variety of NCD risk factors. These surveillance data should be used to support and monitor province specific NCD prevention and control interventions throughout Nepal, supported by a multi-sectoral national coordination mechanism.

Experience of Treating COVID-19 With Remdesivir and Convalescent Plasma in a Resource-Limited Setting: A Prospective, Observational Study.

BACKGROUND: Convalescent plasma therapy (CPT) and remdesivir (REM) have been approved for investigational use to treat coronavirus disease 2019 (COVID-19) in Nepal. METHODS: In this prospective, multicentered study, we evaluated the safety and outcomes of treatment with CPT and/or REM in 1315 hospitalized COVID-19 patients over 18 years in 31 hospitals across Nepal. REM was administered to patients with moderate, severe, or life-threatening infection. CPT was administered to patients with severe to life-threatening infections who were at high risk for progression or clinical worsening despite REM. Clinical findings and outcomes were recorded until discharge or death. RESULTS: Patients were classified as having moderate (24.2%), severe (64%), or life-threatening (11.7%) COVID-19 infection. The majority of CPT and CPT + REM recipients had severe to life-threatening infections (CPT 98.3%; CPT + REM 92.1%) and were admitted to the intensive care unit (ICU; CPT 91.8%; CPT + REM 94.6%) compared with those who received REM alone (73.3% and 57.5%, respectively). Of 1083 patients with reported outcomes, 78.4% were discharged and 21.6% died. The discharge rate was 84% for REM (n = 910), 39% for CPT (n = 59), and 54.4% for CPT + REM (n = 114) recipients. In a logistic model comparing death vs discharge and adjusted for age, gender, steroid use, and severity, the predicted margin for discharge was higher for recipients of remdesivir alone (0.82; 95% CI, 0.79-0.84) compared with CPT (0.58; 95% CI, 0.47-0.70) and CPT + REM (0.67; 95% CI, 0.60-0.74) recipients. Adverse events of remdesivir and CPT were reported in <5% of patients. CONCLUSIONS: This study demonstrates a safe rollout of CPT and REM in a resource-limited setting. Remdesivir recipients had less severe infection and better outcomes.ClinicalTrials.gov identifier. NCT04570982.

Physical activity and the presence and extent of calcified coronary atherosclerosis.

PURPOSE: Regular physical activity leads to a more favorable cardiovascular risk factor profile and a lower risk of developing incident coronary heart disease (CHD). These correlations suggest that higher levels of physical activity should also attenuate the presence and extent of coronary atherosclerosis. METHODS: Physical activity was measured using the Baecke Physical Activity Index in 630 consecutive asymptomatic men and women ages 39-45 without known heart disease. The degree of physical activity was compared with the cardiovascular risk factor profile and the presence and extent of subclinical atherosclerosis measured using electron beam computed tomography. RESULTS: Sports-related physical activity was associated with lower body mass index (r = -0.11; P = 0.001), higher high-density lipoprotein (HDL) cholesterol (r = 0.13; P = 0.003) and less glucose resistance as assessed by fasting serum insulin levels (r = -0.16; P = 0.001). Leisure-time and work-related physical activity were unrelated to any coronary risk variables. Calcified subclinical atherosclerosis was unrelated to all physical activity dimensions. Comparing the most sedentary (lowest quartile) and most active (highest quartile) patients, the prevalence of coronary calcium (17.0% vs 18.5%; P = 0.92) and mean coronary calcium scores (8 +/- 31 vs 5 +/- 15; P = 0.87) were similar. In a multivariate model controlling for standard cardiovascular risk factors and physical activity level, only low-density lipoprotein (LDL) cholesterol was associated with the presence of coronary calcium. CONCLUSION: Physical activity, particularly high-intensity exercise in sports-related activities, promotes a healthy cardiovascular risk profile, including lower body mass index and insulin resistance, but is unrelated to coronary calcification. This suggests that the risk reduction associated with physical activity is mediated by factors other than retarding the development of calcified atherosclerosis.

Validation of the MEDFICTS dietary questionnaire: a clinical tool to assess adherence to American Heart Association dietary fat intake guidelines.

BACKGROUND: Dietary assessment tools are often too long, difficult to quantify, expensive to process, and largely used for research purposes. A rapid and accurate assessment of dietary fat intake is critically important in clinical decision-making regarding dietary advice for coronary risk reduction. We assessed the validity of the MEDFICTS (MF) questionnaire, a brief instrument developed to assess fat intake according to the American Heart Association (AHA) dietary "steps". METHODS: We surveyed 164 active-duty US Army personnel without known coronary artery disease at their intake interview for a primary prevention cardiac intervention trial using the Block food frequency (FFQ) and MF questionnaires. Both surveys were completed on the same intake visit and independently scored. Correlations between each tools' assessment of fat intake, the agreement in AHA step categorization of dietary quality with each tool, and the test characteristics of the MF using the FFQ as the gold standard were assessed. RESULTS: Subjects consumed a mean of 36.0 +/- 13.0% of their total calories as fat, which included saturated fat consumption of 13.0 +/- 0.4%. The majority of subjects (125/164; 76.2%) had a high fat (worse than AHA Step 1) diet. There were significant correlations between the MF and the FFQ for the intake of total fat (r = 0.52, P < 0.0001) and saturated fat (r = 0.52, P < 0.0001). Despite these modest correlations, the currently recommended MF cutpoints correctly identified only 29 of 125 (23.3%) high fat (worse than AHA Step 1) diets. Overall agreement for the AHA diet step between the FFQ and MF (using the previously proposed MF score cutoffs of 0-39 [AHA Step 2], 40-70 [Step 1], and > 70 [high fat diet]) was negligible (kappa statistic = 0.036). The MF was accurate at the extremes of fat intake, but could not reliably identify the 3 AHA dietary classifications. Alternative MF cutpoints of < 30 (Step 2), 30-50 (Step 1), and > 50 (high fat diet) were highly sensitive (96%), but had low specificity (46%) for a high fat diet. ROC curve analysis identified that a MF score cutoff of 38 provided optimal sensitivity 75% and specificity 72%, and had modest agreement (kappa = 0.39, P < 0.001) with the FFQ for the identification of subjects with a high fat diet. CONCLUSIONS: The MEDFICTS questionnaire is most suitable as a tool to identify high fat diets, rather than discriminate AHA Step 1 and Step 2 diets. Currently recommended MEDFICTS cutpoints are too high, leading to overestimation of dietary quality. A cutpoint of 38 appears to be providing optimal identification of patients who do not meet AHA dietary guidelines for fat intake.

Subclinical calcified atherosclerosis in men and its association with a family history of premature coronary heart disease in first- and second-degree relatives.

The authors examined the associations between coronary artery calcification and a family history of premature coronary heart disease in either first-degree (immediate family) or second-degree (grandparents, aunts, uncles) relatives in 1619 asymptomatic healthy men ages 40-50 years. The prevalence of any coronary artery calcification was 19.3% in participants (n=1102) with no family history, 26.6% in those with a first-degree family history (n=203; 12.5%), 26.5% in those with a second-degree family history (n=215, 13.3%), and 30.3% with both (n=99, 6.1%, p=0.003). After controlling for the Framingham risk score, body mass index, and ethnicity, all categories of family history were significant predictors of coronary artery calcification. The odds ratios for coronary artery calcification associated with a first- (1.49; p=0.026) and second-degree (1.41; p=0.049) family history of coronary heart disease were similar. Clinical coronary risk assessments should broadly include an assessment of premature coronary heart disease in both first- and second-degree relatives.