Familial Clustering and Genetic Analysis of Severe Thumb Carpometacarpal Joint Osteoarthritis in a Large Statewide Cohort.

PURPOSE: Our goals were to identify individuals who required surgery for thumb carpometacarpal (CMC) joint osteoarthritis (OA), determine if CMC joint OA clusters in families, define the magnitude of familial risk of CMC joint OA, identify risk factors associated with CMC joint OA, and identify rare genetic variants that segregate with familial CMC joint OA. METHODS: We searched the Utah Population Database to identify a cohort of CMC joint OA patients who required surgery. Affected individuals were mapped to pedigrees to identify high-risk families with excess clustering of CMC joint OA. Cox regression models were used to calculate familial risk of CMC joint OA in related individuals. Risk factors were evaluated using logistic regression models. Whole exome sequencing was used to identify rare coding variants associated with familial CMC joint OA. RESULTS: We identified 550 pedigrees with excess clustering of severe CMC joint OA. The relative risk of CMC joint OA requiring surgical treatment was elevated significantly in first- and third-degree relatives of affected individuals, and significant associations with advanced age, female sex, obesity, and tobacco use were observed. We discovered candidate genes that dominantly segregate with severe CMC joint OA in 4 independent families, including a rare variant in Chondroitin Sulfate Synthase 3 (CHSY3). CONCLUSIONS: Familial clustering of severe CMC joint OA was observed in a statewide population. Our data indicate that genetic and environmental factors contribute to the disease process, further highlighting the multifactorial nature of the disease. Genomic analyses suggest distinct biological processes are involved in CMC joint OA pathogenesis. CLINICAL RELEVANCE: Awareness of associated comorbidities may guide the diagnosis of CMC joint OA in at-risk populations and help identify individuals who may not do well with nonoperative treatment. Further pursuit of the genes associated with severe CMC joint OA may lead to assays for detection of early stages of disease and have therapeutic potential.

Screening for Hypertension in Asymptomatic Individuals in India: An Expert Consensus Statement.

INTRODUCTION: Hypertension (HTN) is a rapidly growing epidemic in India. It is no larger restricted to older adults as more young Indians are being diagnosed with HTN. Despite its significant prevalence, the awareness, treatment, and control of HTN remain low in India. Thus, early diagnosis is essential to control HTN and prevent future complications. Screening for HTN can help identify undiagnosed and asymptomatic HTN, and thereby the early use of interventions to control the blood pressure (BP). However, no comprehensive guidelines have been established for effective HTN screening in asymptomatic individuals in an Indian setting. OBJECTIVE: To provide consensus recommendations for hypertension screening in India. CONSENSUS RECOMMENDATIONS: Screening for HTN can provide more effective control of HTN and reduce the complications. Experts recommended that the initial age at screening should be 18 years. In individuals at a high risk of HTN, targeted screening can be undertaken. BP measurement using an electronic BP recorder (with at least two readings) are required for identifying HTN during screening. In asymptomatic adults with BP <130/85 mmHg and BP of 130-139/85- 89 mmHg, rescreening should be conducted every 3-5 years and at least every year, respectively. Screening for HTN can be cost effective even when universal screening of the entire population is undertaken. CONCLUSION: The consensus recommendations would increase the awareness of HTN screening. Screening for HTN can provide more effective control of HTN and reduce the complications.

Genomic attributes of airway commensal bacteria and mucosa.

Microbial communities at the airway mucosal barrier are conserved and highly ordered, in likelihood reflecting co-evolution with human host factors. Freed of selection to digest nutrients, the airway microbiome underpins cognate management of mucosal immunity and pathogen resistance. We show here the initial results of systematic culture and whole-genome sequencing of the thoracic airway bacteria, identifying 52 novel species amongst 126 organisms that constitute 75% of commensals typically present in heathy individuals. Clinically relevant genes encode antimicrobial synthesis, adhesion and biofilm formation, immune modulation, iron utilisation, nitrous oxide (NO) metabolism and sphingolipid signalling. Using whole-genome content we identify dysbiotic features that may influence asthma and chronic obstructive pulmonary disease. We match isolate gene content to transcripts and metabolites expressed late in airway epithelial differentiation, identifying pathways to sustain host interactions with microbiota. Our results provide a systematic basis for decrypting interactions between commensals, pathogens, and mucosa in lung diseases of global significance.

Developing culturally congruent weight maintenance programs for African American church members.

OBJECTIVES: Developing community-based and culturally congruent weight loss maintenance programs is an important component of weight reduction interventions in high-risk populations. This qualitative investigation was conducted to guide development of faith-based weight maintenance programs for African American church members. DESIGN: Twenty African American church members who previously participated in a church-based group weight loss program were recruited to participate in focus groups. This qualitative inquiry focused on the role of faith in maintaining healthy lifestyle behaviors, such as healthy eating and regular physical activity. Within these groups, a nominal group process was used to identify activities and language to be included within a faith-based maintenance program. RESULTS: Content analysis identified seven conceptual domains that participants thought were important aspects of a faith-based weight maintenance program: (1) accountability for change targets, (2) programmatic tools, (3) group benefits and support, (4) keys to successful behavior change, (5) keys to church and programmatic level success, (6) addressing barriers, and (7) faith. The faith sub-domains included faith in the Lord, using the body for God, and a spiritual focus. The nominal group process resulted in 11 recommended components for a faith-based weight maintenance program. The top four included scriptures and prayers are 'walk of faith,' healthy diet, exercise, and focusing on God. CONCLUSIONS: The results suggest that integrating faith themes into a weight loss maintenance program may increase its long-term impact on participants' health behavior change.

Obesity in sub-Saharan Africa: development of an ecological theoretical framework.

The prevalence of overweight and obesity is increasing in sub-Saharan Africa (SSA). There is a need for theoretical frameworks to catalyze further research and to inform the development of multi-level, context-appropriate interventions. In this commentary, we propose a preliminary ecological theoretical framework to conceptualize factors that contribute to increases in overweight and obesity in SSA. The framework is based on a Causality Continuum model [Coreil et al. Social and Behavioral Foundations of Public Health. Sage Publications, Thousand Oaks] that considers distant, intermediate and proximate influences. The influences incorporated in the model include globalization and urbanization as distant factors; occupation, social relationships, built environment and cultural perceptions of weight as intermediate factors and caloric intake, physical inactivity and genetics as proximate factors. The model illustrates the interaction of factors along a continuum, from the individual to the global marketplace, in shaping trends in overweight and obesity in SSA. The framework will be presented, each influence elucidated and implications for research and intervention development discussed. There is a tremendous need for further research on obesity in SSA. An improved evidence base will serve to validate and develop the proposed framework further.

Differences in Health Care Access and Use by Gender, Race, Income, Age and Employment among Residents of the Rural South.

Understanding how disparities are experienced by subpopulations within rural areas may inform efforts to mitigate persistent inequities in access to health care. Among 2,545 randomly sampled adults who completed a mailed survey in ten rural counties in Georgia as part of a health equity initiative, 50.8% of respondents were aged 35-64, 65.9% were women, 16.6% identified as Black, 36.0% worked full-time, and 39% had a high school degree or less. Significant disparities were observed in health care access, use and financial burden by age, employment status, race, and annual household income. In an examination of intersectionality of race and income, all sub-groups except for higher income Black respondents were more likely to report no health insurance and not seeing a doctor in the past 12 months due to cost relative to higher income White respondents. The findings shed insight into inequities in health care access within rural communities.

Nano Modification of Antrodia Cinnamomea Exhibits Anti-Inflammatory Action and Improves the Migratory Potential of Myogenic Progenitors.

The skeletal muscle progenitors' proliferation and migration are crucial stages of myogenesis. Identifying drug candidates that contribute to myogenesis can have a positive impact on atrophying muscle. The purpose of the study is to synthesize the Antrodia cinnamomea (AC)-ß-cyclodextrin (BCD) inclusion complex (IC) and understand its in vitro pro-regenerative influence in murine skeletal C2C12 myoblasts. The IC was subjected to various nano-characterization studies. Fluorescent IC was synthesized to understand the cellular uptake of IC. Furthermore, 25 µg/mL, 12.5 µg/mL, and 6.25 µg/mL of IC were tested on murine C2C12 skeletal muscle cells for their anti-inflammatory, pro-migratory, and pro-proliferative action. The cellular internalization of IC occurred rapidly via pinocytosis. IC (252.6 ± 3.2 nm size and -37.24 ± 1.55 surface charge) exhibited anti-inflammatory action by suppressing the secretion of interleukin-6 and enhanced cell proliferation with promising cytocompatibility. A 12.5 µg/mL dose of IC promoted cell migration in 24 h, but the same dose of AC significantly reduced cell migration, suggesting modification by BCD. Molecular studies revealed that IC promoted C2C12 myoblasts migration by upregulating long non-coding RNA (lncRNA) NEAT-1, SYISL, and activating the pPKC/ß-catenin pathway. Our study is the first report on the pro-proliferative and pro-migratory effects of BCD-modified extracts of AC.

Association of masking policies with mask adherence and distancing during the SARS-COV-2 pandemic.

BACKGROUND: Quantification of the impact of local masking policies may help guide future policy interventions to reduce SARS-COV-2 disease transmission. This study's objective was to identify factors associated with adherence to masking and social distancing guidelines. METHODS: Faculty from 16 U.S. colleges and universities trained 231 students in systematic direct observation. They assessed correct mask use and distancing in public settings in 126 US cities from September 2020 through August 2021. RESULTS: Of 109,999 individuals observed in 126 US cities, 48% wore masks correctly with highest adherence among females, teens and seniors and lowest among non-Hispanic whites, those in vigorous physical activity, and in larger groups (P < .0001). Having a local mask mandate increased the odds of wearing a mask by nearly 3-fold (OR = 2.99, P = .0003) compared to no recommendation. People observed in non-commercial areas were least likely to wear masks. Correct mask use was greatest in December 2020 and remained high until June 2021 (P < .0001). Masking policy requirements were not associated with distancing. DISCUSSION: The strong association between mask mandates and correct mask use suggests that public policy has a powerful influence on individual behavior. CONCLUSIONS: Mask mandates should be considered in future pandemics to increase adherence.

Off-pump trans-apical trans-catheteraortic valve implantation: first successful case report in India.

Trans-catheter aortic valve implantation has emerged as an alternative to conventional aortic valve replacement for patients with symptomatic severe aortic stenosis considered to be at very high or prohibitive operative risk. We report the first successful Off-pump trans-apical trans-catheter aortic valve implantation in India for a case of severe calcific aortic stenosis with a Logistic Euroscore of 20%.

Influence of Alkalinization Over Metal Organic Frameworks MIL-100(Fe) for Enhanced Volatile Organic Compounds (VOCs) Adsorbents.

Substantial attempts have been undertaken for the improvement of the air quality over decades; and Volatile Organic Compounds (VOCs) from the chemical and textile industries are truly listed as severe issue to be controlled. To come up with modus operandi for this issue, a novel composite of metal organic frameworks (MOFs) MIL-100(Fe) with salient tuned features of natrite was designed by a green and facile method. Mineralized composite MOFs exhibited enhanced crystallinity than pure MIL-100(Fe) as well showcased a higher surface area of 1300 m² g-1. Through dynamic acetone pressure swing adsorption setup, MIL-0.05Na (MIL-100(Fe) synthesized with 0.05 mM Na2CO3 solution) revealed an enhanced acetone adsorption of 210 mg g 1 at room temperature. Gas phase adsorption isotherms confirmed the mono layer adsorption behavior. The kinetics models evaluated that the external mass transfer was the rate limiting step for surface adsorption. The thermodynamic study manifested that the adsorption reaction was spontaneous and exothermic. The proposed mechanism of adsorption was the act of physisorption which enriched the adsorbents reusability. This research work provides a futuristic vista to design mineralized Fe-MOFs composites for an energy saving adsorbents for VOCs removal.

Enhanced Photocatalytic Degradation of Antibiotic and Hydrogen Production by Iron Doped Cerium(IV) Oxide.

Norfloxacin (NF) is an emerging antibiotic contaminant due to its significant accumulation in the environment. Photocatalytic degradation is an effective method for removing emerging contaminant compounds in aqueous solution; however, it is not commonly applied because of the poor solubility of contaminant compounds in water. In this study, a photocatalytic degradation experiment was carried out on NF using a self-made ceria catalyst. At an initial concentration of NF of 2.5 mg L-1, the dosage of CeO2 was 0.1 g L-1 photocatalyst in water, and the initial pH of the NF solution was 8.0. With a reaction time of 180 min, the total removal rate of NF could reach 95%. Additionally, the studies on hydrogen production show that the maximum hydrogen production with 2% Fe-CeO2 can reach 25,670 µmol h-1 g-1 under close to 8 W of 365 nm, a methanol concentration of 20%, and a catalyst dose of 0.1 g L-1 photocatalyst in water. Furthermore, the intensities of photoluminescence (PL) emission peaks decreased with increased Fe-doped amounts on CeO2, suggesting that the irradiative recombination seemed to be weakened.

Familial Clustering of Erosive Hand Osteoarthritis in a Large Statewide Cohort.

OBJECTIVE: Erosive hand osteoarthritis (OA) is a severe and rapidly progressing subset of hand OA. Its etiology remains largely unknown, which has hindered development of successful treatments. This study was undertaken to test the hypothesis that erosive hand OA demonstrates familial clustering in a large statewide population linked to genealogical records, and to determine the association of potential risk factors with erosive hand OA. METHODS: Patients diagnosed as having erosive hand OA were identified by searching 4,741,840 unique medical records from a comprehensive statewide database, the Utah Population Database (UPDB). Affected individuals were mapped to pedigrees to identify high-risk families with excess clustering of erosive hand OA as defined by a familial standardized incidence ratio (FSIR) of ≥2.0. The magnitude of familial risk of erosive hand OA in related individuals was calculated using Cox regression models. Association of potential erosive hand OA risk factors was analyzed using multivariate conditional logistic regression and logistic regression models. RESULTS: We identified 703 affected individuals linked to 240 unrelated high-risk pedigrees with excess clustering of erosive hand OA (FSIR ≥2.0, P < 0.05). The relative risk of developing erosive hand OA was significantly elevated in first-degree relatives (P < 0.001). There were significant associations between a diagnosis of erosive hand OA and age, sex, diabetes, and obesity (all P < 0.05). CONCLUSION: Familial clustering of erosive hand OA observed in a statewide database indicates a potential genetic contribution to the etiology of the disease. Age, sex, diabetes, and obesity are risk factors for erosive hand OA. Identification of causal gene variants in these high-risk families may provide insight into the genes and pathways that contribute to erosive hand OA onset and progression.

Therapeutic adherence in hypertension: Current evidence and expert opinion from India.

Hypertension (HTN) is a globally prevalent non-communicable disease contributing significantly to cardiovascular (CV) morbidity and mortality. In achieving control of HTN, therapeutic adherence plays a crucial role. Studies from India identify varying rates of adherence to antihypertensive medications. Multiple factors determine treatment adherence in HTN. In India, factors such as lower socioeconomic status, health literacy, asymptomatic nature of disease, forgetfulness, cost of medications, and duration of HTN determine the adherence. An excellent physician-patient relationship incorporating adequate counseling along with the use of other methods can identify poor adherence. Improving adherence necessitates incorporating a multipronged approach with strategies directed at physicians, patients, and health systems. With innovation in therapeutics, the pharmaceutical sector can contribute significantly to improve adherence. Furthermore, increasing adherence to lifestyle interventions can help achieve better HTN control and improve CV outcomes. In the Indian context, more emphasis is necessary on patient education, enhanced physician-patient relationship and communication, increased access to health care, and affordability in improving therapeutic adherence in HTN.

Augmentation of Photocatalytic Degradation of Oxytetracycline by Cu-CdS and Deciphering the Contribution of Reactive Oxygen Species.

Production of Copper (Cu) modified Cadmium sulfide (CdS) nanomaterial, named as Cu-CdS, was successfully synthesized through hydrothermal and photo deposition method to degrade oxytetracycline (OTC) antibiotics in aqueous solution. Uniform surface loading of copper was observed on CdS using Scanning Electron Microscopy-mapping (SEM-mapping). The Cu induced improvement in the visible light absorption was observed using UV-vis absorption spectrum. Thus, this material can exhibit excellent oxytetracycline (OTC) degradation by photocatalysis. The best OTC degradation efficiency of 90% was be achieved under the optimal concentration of 4% Cu-CdS, with 0.1 g L-1 dosage (pH 5) under UV irradiation. 0.167 mg L-1 min-1 was observed as the reaction kL-H on the peripheral of the catalyst. In addition, OTC can also be degraded under visible light with removal efficiency approximately 90%. Moreover, the contribution of main reactive oxygen species (ROS), including hydroxyl radicals, superoxide radical and holes, is evaluated as 18%, 43% and 29%.

Heart Rate in Hypertension: Review and Expert Opinion.

Heart rate (HR) is strongly associated with both peripheral and central blood pressures. This association has implications in hypertension (HTN) prognosis and management. Elevated HR in HTN further elevates the risk of adverse outcomes. Evidence suggests that HR is an independent risk factor for cardiovascular (CV) and total mortality in patients with HTN. With objective to engage physicians and researchers in India to identify and discuss the implications related to HR management in HTN, experts in the HTN management provided consensus recommendations. The key expert recommendations included the following. (i) Heart rate (HR) has inverse relationship with the central aortic pressure, whereby reduction in HR is associated with an increase in central aortic pressure. This counter-balances the benefit of HR reduction with the harmful effects of rising central aortic pressure. (ii) Increase in the resting HR is associated with increased risk of incident HTN. A linear association between the two is observed especially in individuals with HR >80 bpm. (iii) A reduced HR variability further adds to the propensity for the development of HTN, especially in men. (iv) Each 10 beats per minute increase in the resting HR can substantially increase the risk of adverse CV and mortality outcomes. On treatment HR provides a better prognostic guide. (v) Ambulatory HR with day-time and night-time HR evaluation may also suggest different impact on outcomes. (vi) Target HR in patients with HTN remains unclear. Generally, HR<70 bpm on beta blocker (BB) treatment is advised which may be further lowered in patients with comorbidities like heart failure and coronary artery disease. (vii) Adopting healthy lifestyle approaches to keep check on BP and HR is essential. (viii) Use selective beta-1 blocker in symptomatic cases with elevated HR beyond 80-85 mmHg. BBs are expected to benefit by lowering HR by nearly 10 bpm. Preference should be given to newer beta-blockers which reduce HR and both peripheral and central blood pressure to derive comprehensive advantage of this dual action. (ix) It still remains unclear whether reducing HR in HTN without comorbidities alters the CV and mortality outcomes.

Time to shift from contemporary to high-sensitivity cardiac troponin in diagnosis of acute coronary syndromes.

Early rule-in and rule-out of non-ST-segment elevation myocardial infarction (NSTEMI) is a challenge. In patients with inconclusive findings on ECG, cardiac biomarkers play a crucial role in the diagnosis. The introduction of the new high-sensitive cardiac troponin test (hs-TnI assay) has changed the landscape of NSTEMI diagnosis. The new hs-TnI assay can detect troponin values at a lower level compared with a contemporary cardiac troponin (cTn) assay. The hs-cTnI assay has a coefficient of variation of ≤10%, well below the 99th percentile value. It reduces the time to diagnose acute myocardial infarction from 6h to 3h. A recent study has demonstrated that hs-cTnI can further reduce the time to 1h in 70% of all patients with chest pain. The European Society of Cardiology 2015 guidelines recommend including a second sample of hs-cTnI within 3h of presentation This increases the sensitivity of the hs-TnI assay from 82.3% (at admission) to 98.2% and negative predictive value from 94.7% (at admission) to 99.4%. Combining the 99th percentile at admission with serial changes in troponin increases the positive predictive value to rule in acute coronary syndrome from 75.1% at admission to 95.8% after 3h. The 2015 ESC Guidelines recommend the use of a rapid rule out protocol (0h and 1h) when hs-cTnI with a validated 0 to1h algorithm is available. Training and displaying the clinical algorithm depicting the role of hs-TnI assay in acute cardiac care units and in EDs are an efficient way to deliver the new standard of care to patients. Compared with contemporary troponin assays, the hs-cTn assay accelerates the diagnostic pathway to 0-1h, thus reducing the time for diagnosis of NSTEMI and hence, its management.

Cardiovascular risk profile and management of atrial fibrillation in India: Real world data from RealiseAF survey.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia with high risk for many cardiovascular (CV) complications. Adherence to recommended management guidelines is important to avoid complications. In India, there is little knowledge on how AF is managed in real world. METHODS: This is a cross-sectional study of patients in India enrolled in RealiseAF survey between February 2010 and March 2010 with a diagnosis of AF within the last 12 months. RESULTS: From 15 centers, 301 patients {mean age 59.9 years (14.4); 52.5% males} were recruited. AF was controlled in 50% of patients with 77 (26.7%) in sinus rhythm and 67 (23.3%) with heart rate <80beats/min. Hypertension (50.8%), valvular heart disease (40.7%), heart failure (25.9%), and diabetes (20.4%) were the most common underlying CV diseases. Increased risk for stroke (CHADS2 score≥2) was present in 36.6%. Most of the patients (85%) were symptomatic. AF was paroxysmal, persistent, and permanent in 28.7%, 22.7%, and 34.3% respectively. In 14%, AF was diagnosed as first episode. Forty-six percent of patients had rate control, 35.2% rhythm control, 0.3% both strategies, and 18.4% received no therapy for AF before the visit. At the end of the visit, adoption to rate control strategy increased to 52.3% and patients with no therapy decreased to 7%. CONCLUSION: AF in India is not adequately controlled. Concomitant CV risk factors and risk of stroke are high. The study underscores the need for improved adoption of guideline-directed management for optimal control of AF and reducing the risk of stroke.

Congenital Long QT Syndrome presenting as epilepsy.

Epilepsy can sometimes be mimicked in children by other organic conditions. We present a 11 year old boy with the congenital long QT syndrome who had recurrent "seizures" for five years which had been treated as epilepsy.