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Objective Heart fat deposition has been linked to atherosclerosis, and both accelerate after menopause. Hormone therapy (HT) may differentially slow heart fat deposition and progression of atherosclerosis, depending on the specific HT agent or its route of administration. Our objective was to evaluate the effects of different HT agents, oral and transdermal, on associations between heart fat accumulation and atherosclerosis progression, measured by carotid intima-media thickness (CIMT), in recently menopausal women from the Kronos Early Estrogen Prevention Study (KEEPS) trial. Methods KEEPS was a randomized, placebo-controlled trial of the effects of 0.45 mg/d oral conjugated equine estrogens (o-CEE) or 50 mcg/d transdermal 17β-estradiol (t-E2), compared with placebo, on 48 months progression of CIMT. Epicardial adipose tissue (EAT) and paracardial adipose tissue (PAT) volumes were quantified by computed tomography. Results In all, 467 women (mean age [SD] 52.7 [2.5]; 78.2% White; 30% on o-CEE, 30.8% t-E2, 39.2% placebo) with heart fat volumes and CIMT at baseline and 48 months were included. EAT and PAT changes were not associated with CIMT progression; however, the assigned treatment significantly modified the association between PAT (but not EAT) change and CIMT progression. In the o-CEE group, adjusted CIMT progression was 12.66 μm (95% confidence interval [CI] 1.80, 23.52) lower than in t-E2 group (P = 0.02), and 10.09 μm (95% CI 0.79, 19.39) lower than in placebo group (P = 0.03), as per 1-SD increase in PAT. Conclusion Compared with t-E2, o-CEE appears to slow down the adverse effect of increasing PAT on progression of atherosclerosis. Whether this beneficial association is specific to CEE or to the oral route of CEE administration is unclear and should be assessed further.

Background: Dentistry plays a crucial role in shaping the esthetics of a person and thus boosts the self-esteem of an individual. Whitening of the teeth is the most popular procedure where surface and deep stain removal whitens the teeth. Teeth whitening is achieved by professional application of chemicals and can also be self-administered by numerous products available. The most popular product is teeth whitening paste which is simple in application and easily available. Recently, teeth whitening tooth paste is commercially available where natural ingredients or their derivatives are used instead of chemicals for teeth whitening. Aims: To investigate and compare the effect of commercially available chemical teeth whitening toothpaste and teeth whitening toothpaste containing ingredients of herbal origin on human enamel (at the Department of Oral and Maxillofacial Pathology, Royal Dental College, Kerala, India). Materials and Methods: An in vitro study with a duration of 14 days was conducted. Settings and Design: An in vitro study was conducted twenty samples were taken and assembled in to two groups of 10 each. Group A for teeth treated with conventional chemical toothpaste and group B for teeth treated with toothpaste containing ingredients of herbal origin. Premolars extracted for orthodontic purpose were checked for shade with Vita 3D shade guide and were observed under a stereomicroscope for surface morphology before the procedure. Each section was cleansed twice daily for 1 min with specified toothpaste and soft bristle toothbrush according to their groups and then cleansed with tap water and stored again in the same solution. After 14 days, the teeth were tested for the shade using vita 3D shade guide and surface morphology using stereomicroscope. Statistical Analysis Used: Student's unpaired t-test. Results and Conclusion: In this 14-day in vitro study, the chemical whitening toothpaste showed better whitening of teeth than toothpaste containing ingredient of herbal origin, whereas the surface irregularities was increased on the surface of the enamel with chemical whitening toothpaste when compared with toothpaste containing ingrtedients of herbal origin.

Importance Acutely ill inpatients with COVID-19 typically receive antithrombotic therapy, although the risks and benefits of this intervention among outpatients with COVID-19 have not been established. Objective To assess whether anticoagulant or antiplatelet therapy can safely reduce major adverse cardiopulmonary outcomes among symptomatic but clinically stable outpatients with COVID-19. Design, Setting, and Participants The ACTIV-4B Outpatient Thrombosis Prevention Trial was designed as a minimal-contact, adaptive, randomized, double-blind, placebo-controlled trial to compare anticoagulant and antiplatelet therapy among 7000 symptomatic but clinically stable outpatients with COVID-19. The trial was conducted at 52 US sites between September 2020 and June 2021; final follow-up was August 5, 2021. Prior to initiating treatment, participants were required to have platelet count greater than 100 000/mm3and estimated glomerular filtration rate greater than 30 mL/min/1.73 m2. Interventions Random allocation in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days. Main Outcomes and Measures The primary end point was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause. The primary analyses for efficacy and bleeding events were limited to participants who took at least 1 dose of trial medication. Results On June 18, 2021, the trial data and safety monitoring board recommended early termination because of lower than anticipated event rates; at that time, 657 symptomatic outpatients with COVID-19 had been randomized (median age, 54 years [IQR, 46-59]; 59% women). The median times from diagnosis to randomization and from randomization to initiation of study treatment were 7 days and 3 days, respectively. Twenty-two randomized participants (3.3%) were hospitalized for COVID-19 prior to initiating treatment. Among the 558 patients who initiated treatment, the adjudicated primary composite end point occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5-mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group. The risk differences compared with placebo for the primary end point were 0.0% (95% CI not calculable) in the aspirin group, 0.7% (95% CI, –2.1% to 4.1%) in the 2.5-mg apixaban group, and 1.4% (95% CI, –1.5% to 5.0%) in the 5-mg apixaban group. Risk differences compared with placebo for bleeding events were 2.0% (95% CI, –2.7% to 6.8%), 4.5% (95% CI, –0.7% to 10.2%), and 6.9% (95% CI, 1.4% to 12.9%) among participants who initiated therapy in the aspirin, prophylactic apixaban, and therapeutic apixaban groups, respectively, although none were major. Findings inclusive of all randomized patients were similar. Conclusions and Relevance Among symptomatic clinically stable outpatients with COVID-19, treatment with aspirin or apixaban compared with placebo did not reduce the rate of a composite clinical outcome. However, the study was terminated after enrollment of 9% of participants because of an event rate lower than anticipated. Trial Registration ClinicalTrials.gov Identifier:NCT04498273

Ralstonia solanacearum causes bacterial wilt in ginger. Here the role of signalling pathways such as salicylic acid (SA), ethylene (ET) and jasmonic acid (JA) was studied by comparing the differential expression of the marker genes for these pathways during bacterial wilt in both susceptible (ginger, Zingiber officinale) and resistant (mango ginger, Curcuma amada) ginger species. When expression of marker genes was compared among susceptible and resistant ginger sps., SA pathway marker genes, non-expressor of PR1 genes (NPR1) and TGACG sequence-specific binding protein (TGA6) and the ET pathway marker genes, AP2 domain class transcription factor (AP2) and 4-Coumarate: CoA ligase (4CL1), were expressed with a statistically different (p

Background Heart fats (epicardial and paracardial adipose tissue [PAT]) are greater after menopause. Endogenous estrogen may regulate these fat depots. We evaluated the differential effects of hormone therapy formulations on heart fat accumulations and their associations with coronary artery calcification ( CAC ) progression in recently menopausal women from KEEPS (Kronos Early Estrogen Prevention Study). Methods and Results KEEPS was a multicenter, randomized, placebo‐controlled trial of the effects of 0.45 mg/d oral conjugated equine estrogens and 50 µg/d transdermal 17β‐estradiol, compared with placebo, on 48‐month progression of subclinical atherosclerosis among 727 early menopausal women. CAC progression was defined if baseline CAC score was 0 and 48‐month CAC score was >0 or if baseline CAC score was >0 and CAC score was ≥10. Of 727 KEEPS participants, 474 (mean age: 52.7 [SD: 2.6]; 78.1% white) had computed tomography–based heart fat and CAC measures at both baseline and 48 months. Compared with women on placebo, women on oral conjugated equine estrogens were less likely to have any increase in epicardial adipose tissue (odds ratio for oral conjugated equine estrogens versus placebo: 0.62 [95% CI, 0.40–0.97]; P =0.03). PAT did not change in any group. Changes in epicardial adipose tissue and PAT did not differ by treatment group. CAC increased in 14% of participants. The assigned treatment modified the association between PAT changes and CAC progression ( P =0.02) such that PAT increases were associated with CAC increases only in the transdermal 17β‐estradiol group. Conclusions In recently menopausal women, oral conjugated equine estrogens may slow epicardial adipose tissue accumulation, whereas transdermal 17β‐estradiol may increase progression of CAC associated with PAT accumulation. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00154180.

Objective: Heart fat depots, within [epicardial adipose tissue (EAT)] and outside [paracardial adipose tissue (PAT)] the pericardium, have been linked to carotid atherosclerosis in various populations. Postmenopausal women have greater volumes of heart fat than premenopausal women. Our previous work suggests that lower endogenous estrogen may contribute to heart fat accumulation, although possibly limited to PAT, while postmenopausal oral hormone therapy (HT) may slow its progression. We evaluated the effect modification of HT use over 48 months on associations between heart fat accumulation and carotid artery intima-media thickness (CIMT) progression in recently postmenopausal women. Methods: The Kronos Early Estrogen Prevention Study (KEEPS) was a multi-center, randomized, double-blind placebo-controlled trial to investigate effects over 48 months of oral conjugated equine estrogens (o-CEE) and transdermal 17β-estradiol (t-E2), both given with cyclic progesterone, compared to placebo, on progression of CIMT in recently postmenopausal women. EAT and PAT volumes, and CIMT were measured at baseline and at 48 months. Associations between the absolute changes in heart fat volumes and CIMT as well as effect modification by HT type were tested using linear regression, adjusting for age, race, study site, employment status, diastolic and systolic blood pressure, anti-hypertensive medications, insulin resistance index, lipids, body-mass index, smoking, alcohol consumption, C-reactive protein, and adipokines. Results: Of 727 randomly assigned women, 467 [mean age (SD): 52.7(2.5); 78.2% Caucasian] had heart fat volumes and CIMT measured at both time points. Overall, changes in EAT and PAT were not associated with CIMT progression; however, assigned treatment significantly modified the association between changes in PAT, but not EAT, and CIMT progression in unadjusted model, P=0.04. In o-CEE group, CIMT progression was 0.028mm (SE:0.01mm) lower, per 1 unit increase in log PAT, than in t-E2 group, P=0.01, and trended 0.017mm (SE:0.01mm) lower than in placebo group, P=0.09. Although adjusted analysis attenuated these findings (P-value for interaction 0.09), differences between o-CEE and t-E2 groups remained significant, P=0.03. Conclusion: HT use modified the association between PAT accumulation, but not EAT, and CIMT progression. Our results suggest a potential beneficial impact of o-CEE (but not transdermal E2) on the relationship between adverse changes in PAT and CIMT. The current findings support the notion that EAT and PAT are distinct fat depots and suggest a complex role of HT in the association between heart fat and CIMT progression in recently postmenopausal women.

IntroductionRising burden of cardiovascular disease (CVD) and diabetes is a major challenge to the health system in India. Innovative approaches such as mobile phone technology (mHealth) for electronic decision support in delivering evidence-based and integrated care for hypertension, diabetes and comorbid depression have potential to transform the primary healthcare system.Methods and analysismWellcare trial is a multicentre, cluster randomised controlled trial evaluating the clinical and cost-effectiveness of a mHealth system and nurse managed care for people with hypertension and diabetes in rural India. mWellcare system is an Android-based mobile application designed to generate algorithm-based clinical management prompts for treating hypertension and diabetes and also capable of storing health records, sending alerts and reminders for follow-up and adherence to medication. We recruited a total of 3702 participants from 40 Community Health Centres (CHCs), with ≥90 at each of the CHCs in the intervention and control (enhanced care) arms. The primary outcome is the difference in mean change (from baseline to 1 year) in systolic blood pressure and glycated haemoglobin (HbA1c) between the two treatment arms. The secondary outcomes are difference in mean change from baseline to 1 year in fasting plasma glucose, total cholesterol, predicted 10-year risk of CVD, depression, smoking behaviour, body mass index and alcohol use between the two treatment arms and cost-effectiveness.Ethics and disseminationThe study has been approved by the institutional Ethics Committees at Public Health Foundation of India and the London School of Hygiene and Tropical Medicine. Findings will be disseminated widely through peer-reviewed publications, conference presentations and other mechanisms.Trial registrationmWellcare trial is registered with Clinicaltrial.gov (Registration numberNCT02480062; Pre-results) and Clinical Trial Registry of India (Registration number CTRI/2016/02/006641). The current version of the protocol is Version 2 dated 19 October 2015 and the study sponsor is Public Health Foundation of India, Gurgaon, India (www.phfi.org).

Purpose To evaluate longitudinal vision-related quality of life (VRQoL) in patients with noninfectious uveitis. Design Cohort study using randomized controlled trial data. Participants Patients with active or recently active intermediate uveitis, posterior uveitis, or panuveitis enrolled in the Multicenter Steroid Treatment Trial and Follow-up Study. Methods Data from the 25-item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) for the first 3 years after randomization were evaluated semiannually. Analyses were stratified by assigned treatment (129 implants vs. 126 systemic therapies) because of substantial differences in the trajectories of VRQoL. The impact of baseline measurements of visual function (visual acuity and visual field), demographics, and disease characteristics was assessed using generalized estimating equations. Main Outcome Measures Primary outcome was the NEI-VFQ-25 composite score over 3 years after randomization. Results Individuals in both treatment groups showed similar improvement in NEI-VFQ-25 scores after 3 years of follow-up (implant: 11.9 points; 95% confidence interval [CI], 8.6–15.2; P P P = 0.21 for interaction). Individuals in the implant group showed a substantial improvement during the first 6 months followed by stable scores, whereas individuals in the systemic group showed a steady improvement over the course of follow-up. Worse initial visual acuity and visual fields were associated with lower initial NEI-VFQ-25 scores for both treatment groups. In the systemic group, these differences were maintained throughout follow-up. In the implant group, individuals with initial visual acuity worse than 20/40 showed additional improvement in NEI-VFQ-25 score to come within −7 points (95% CI, −15.0 to 0.9) of those with visual acuity 20/40 or better initially, a clinically meaningful but not statistically significant difference ( P = 0.081). Results based on sensitivity analyses showed similar patterns. Conclusions Both treatment groups demonstrated significant improvements in NEI-VFQ-25 scores; however, the improvement was immediate for the implant group as opposed to gradual for the systemic group. Poorer visual function was associated significantly with initial differences in NEI-VFQ-25 scores. However, only individuals in the implant group with poor visual acuity were able to overcome their initial deficits by the end of 3 years.

Background The high burden of undetected and undertreated hypertension and diabetes mellitus is a major health challenge worldwide. The mP ower Heart Project aimed to develop and test a feasible and scalable intervention for hypertension and diabetes mellitus by task‐sharing with the use of a mobile phone–based clinical decision support system at Community Health Centers in Himachal Pradesh, India. Methods and Results The development of the intervention and mobile phone–based clinical decision support system was carried out using mixed methods in five Community Health Centers. The intervention was subsequently evaluated using pre–post evaluation design. During intervention, a nurse care coordinator screened, examined, and entered patient parameters into mobile phone–based clinical decision support system to generate a prescription, which was vetted by a physician. The change in systolic blood pressure, diastolic blood pressure, and fasting plasma glucose ( FPG ) over 18 months of intervention was quantified using generalized estimating equations models. During intervention, 6797 participants were enrolled. Six thousand sixteen participants had hypertension (mean systolic blood pressure: 146.1 mm Hg, 95% CI : 145.7, 146.5; diastolic blood pressure: 89.52 mm Hg, 95% CI : 89.33, 89.72), of which 3152 (52%) subjects were newly detected. Similarly, 1516 participants had diabetes mellitus (mean FPG : 177.9 mg/dL, 95% CI : 175.8, 180.0), of which 450 (30%) subjects were newly detected. The changes in systolic blood pressure, diastolic blood pressure, and FPG observed at 18 months of follow‐up were −14.6 mm Hg (95% CI : −15.3, −13.8), −7.6 mm Hg ( CI : −8.0, −7.2), and −50.0 mg/dL (95% CI : −54.6, −45.5), respectively, and were statistically significant even after adjusting for age, sex, and Community Health Center. Conclusions A nurse‐facilitated, mobile phone–based clinical decision support system‐enabled intervention in primary care was associated with improvements in blood pressure and blood glucose control and has the potential to scale‐up in resource poor settings. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifiers: NCT 01794052. Clinical Trial Registry—India: CTRI /2013/02/003412.

The Johns Hopkins Children's Medical and Surgery Center developed a Web-based Antimicrobial Stewardship Program (ASP) in 2005. The present study aimed to assess longitudinal antimicrobial request and approval patterns for this ASP.We analyzed a total of 16,229 antimicrobial requests for 3,542 patients between June 1, 2005, and June 30, 2009. Antimicrobial approval was the outcome of interest. We assessed gaming by studying trends in automatically approved requests. Nonparametric tests for trend were performed to detect changes in approval patterns. Multiple logistic regression was used to identify factors associated with approval.The vast majority (91.3%) of antimicrobial requests were approved, with an increase of 6.1% over time (P.01). Renewal requests were more likely than primary requests (adjusted odds ratio [aOR], 1.72; 95% confidence interval [CI], 1.45-2.04) to be approved. Antiviral requests had higher odds of approval than antibiotic requests (aOR, 1.27; 95% CI, 1.04-1.56). Compared with requests by medical services, requests by surgical services had lower odds of approval (aOR, 0.70; 95% CI, 0.59-0.83), whereas pediatric intensive care requests had higher odds of approval (aOR, 1.18; 95% CI, 1.00-1.40). The number of auto-approved requests remained consistent.The Web-based ASP allows management of a large number of antimicrobial requests, without apparent gaming. Observed differences in approval patterns based on patient, requestor, and antimicrobial factors may inform the development of ASPs and evaluation of provider education and training.

To describe the prevalence of postarrest hyperthermia among children during the first 24 hrs after inhospital cardiac arrest and to determine the association of persistent postarrest hyperthermia with neurologic outcome and death before hospital discharge.Multicenter, national registry of inhospital cardiopulmonary resuscitation.A total of 196 hospitals reporting to the American Heart Association's National Registry of Cardiopulmonary Resuscitation from January 1, 2005 to December 31, 2007.A total of 547 pediatric patients who suffered inhospital pulseless cardiac arrests reported to the National Registry of Cardiopulmonary Resuscitation, who survived resuscitative efforts and who had the maximum and the minimum temperature in the first 24 hrs postresuscitation reported to the National Registry of Cardiopulmonary Resuscitation.None.Among 547 children with pulseless cardiac arrests, 238 (43.5%) had at least one temperature of ≥38°C, and 30 (5.5%) had "persistent hyperthermia" (i.e., both the minimum and the maximum temperature of ≥38°C) during the first 24 hrs postarrest. After adjusting for potential confounders by multivariate logistic regression, persistent hyperthermia in the first 24 hrs postarrest was associated with unfavorable neurologic outcome (adjusted odds ratio, 2.7; 95% confidence interval, 1.1-6.7), but not with death before hospital discharge (adjusted odds ratio, 1.2; 95% confidence interval, 0.4-3.4).Despite current guidelines to avoid postarrest hyperthermia, a temperature of ≥38°C occurred commonly among children in the first 24 hrs postarrest. Persistent postarrest hyperthermia was associated with unfavorable neurologic outcomes, even after controlling for potential confounding factors.