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Artificial neurons with bio-inspired firing patterns have the potential to significantly improve the performance of neural network computing. The most significant component of an artificial neuron circuit is a large amount of energy consumption. Recent literature has proposed memristors as a promising option for synaptic implementation. In contrast, implementing memristive circuitry through neuron hardware presents significant challenges and is a relevant research topic. This paper describes an efficient circuit-level mixed CMOS memristor artificial neuron network with a memristor synapse model. From this perspective, the paper describes the design of artificial neurons in standard CMOS technology with low power utilization. The neuron circuit response is a modified version of the Morris-Lecar theoretical model. The suggested circuit employs memristor-based artificial neurons with Dual Transistor and Dual Memristor (DTDM) synapse circuit. The proposed neuron network produces a high spiking frequency and low power consumption. According to our research, a memristor-based Morris Lecar (ML) neuron with a DTDM synapse circuit consumes 12.55 pW of power, the spiking frequency is 22.72 kHz, and 2.13 fJ of energy per spike. The simulations were carried out using the Spectre tool with 45 nm CMOS technology.

BackgroundLow back pain stands as a prevalent contributor to pain-related disability on a global scale. In addressing chronic low back pain (CLBP), there is a growing emphasis on incorporating psychological strategies into the management process. Among these, pain education interventions strive to reshape pain beliefs and mitigate the perceived threat of pain. This randomized controlled trial sought to assess the effects of pain education on various aspects, including pain levels, disability, quality of life, self-efficacy, and prognostic characteristics in individuals grappling with CLBP.MethodsThe clinical trial, retrospectively registered with the Clinical Trials Registry of India (CTRI/2021/08/035963), employed a two-arm parallel randomized design. Ninety-two participants with CLBP were randomly assigned to either the standard physiotherapy care with a pain education program or the control group. Both groups underwent a 6-week intervention. Assessment of pain intensity (using NPRS), disability (using RMDQ), self-efficacy (using the general self-efficacy scale), and well-being (using WHO 5I) occurred both before and after the 6-week study intervention.FindingsPost-intervention score comparisons between the groups revealed that the pain education intervention led to a significant reduction in disability compared to the usual standard care at 6 weeks (mean difference 8.2, p < 0.001, effect size Cohen d = 0.75), a decrease in pain intensity (mean difference 3.5, p < 0.001, effect size Cohen d = 0.82), and an improvement in the well-being index (mean difference 13.7, p < 0.001, effect size Cohen d = 0.58).ConclusionThe findings suggest that integrating a pain education program enhances the therapeutic benefits of standard physiotherapy care for individuals dealing with chronic LBP. In conclusion, the clinical benefits of pain education become apparent when delivered in conjunction with standard care physiotherapy during the management of chronic low back pain.

Cultivated beet (Beta vulgaris L. ssp. vulgaris) originated from sea beet (B. vulgaris ssp. maritima (L.) Arcang), a wild beet species widely distributed along the coasts of the Mediterranean Sea and Atlantic Ocean, as well as northern Africa. Understanding the evolution of sea beet will facilitate its efficient use in sugarbeet improvement. We used SNPs (single nucleotide polymorphisms) covering the whole genome to analyze 599 sea beet accessions collected from the north Atlantic Ocean and Mediterranean Sea coasts. All B. maritima accessions can be grouped into eight clusters with each corresponding to a specific geographic region. Clusters 2, 3 and 4 with accessions mainly collected from Mediterranean coasts are genetically close to each other as well as to Cluster 6 that contained mainly cultivated beet. Other clusters were relatively distinct from cultivated beets with Clusters 1 and 5 containing accessions from north Atlantic Ocean coasts, Clusters 7 and Cluster 8 mainly have accessions from northern Egypt and southern Europe, and northwest Morocco, respectively. Distribution of B. maritima subpopulations aligns well with the direction of marine currents that was considered a main dynamic force in spreading B. maritima during evolution. Estimation of genetic diversity indices supported the formation of B. maritima subpopulations due to local genetic drift, historic migration, and limited gene flow. Our results indicated that B. maritima originated from southern Europe and then spread to other regions through marine currents to form subpopulations. This research provides vital information for conserving, collecting, and utilizing wild sea beet to sustain sugarbeet improvement.

Studying the emerging travel trends of City Walk is a beneficial activity for young groups. However, there is a lack of research and understanding regarding the motivation and mechanism behind these trends, both in theory and practice. The aim of this study was to investigate the motivation of persons who follow the travel trend of City Walk and evaluate how behavioral intentions are formed by exploring the link between motivation and behavioral intention using the self-determination theory, and social influence theory. Social influence, variety seeking, and self-identification were extrinsic and intrinsic motivations of behavioral intention. A quantitative purposive survey approach was employed, wherein 315 young individuals aged 18 to 40 were recruited to respond. The findings derived from the partial least squares structural equation modeling demonstrate that extrinsic incentives related to social influence, variety seeking, and health care have a considerable impact on behavioral intention, and to some extent influence self-identification. Self-identification has a mediating role in the relationship between health care and behavioral intention. By examining both theoretical and practical aspects, it seeks to provide useful theoretical insights and practical contributions to advance research and industry in the field of rural tourism. [ABSTRACT FROM AUTHOR]

Artificial neurons with bio-inspired firing patterns have the potential to significantly improve the performance of neural network computing. The most significant component of an artificial neuron circuit is a large amount of energy consumption. Recent literature has proposed memristors as a promising option for synaptic implementation. In contrast, implementing memristive circuitry through neuron hardware presents significant challenges and is a relevant research topic. This paper describes an efficient circuit-level mixed CMOS memristor artificial neuron network with a memristor synapse model. From this perspective, the paper describes the design of artificial neurons in standard CMOS technology with low power utilization. The neuron circuit response is a modified version of the Morris-Lecar theoretical model. The suggested circuit employs memristor-based artificial neurons with Dual Transistor and Dual Memristor (DTDM) synapse circuit. The proposed neuron network produces a high spiking frequency and low power consumption. According to our research, a memristor-based Morris Lecar (ML) neuron with a DTDM synapse circuit consumes 12.55 pW of power, the spiking frequency is 22.72 kHz, and 2.13 fJ of energy per spike. The simulations were carried out using the Spectre tool with 45 nm CMOS technology. [ABSTRACT FROM AUTHOR]

Background Emergency care is vital in low- and middle-income countries (LMICs) but many frontline healthcare workers in low-resource settings have no formal training in emergency care. To address this gap, the World Health Organization (WHO) developed Basic Emergency Care (BEC): Approach to the acutely ill and injured, a multi-day, open-source course for healthcare workers in low-resource settings. Building on the BEC foundation, this study uses an implementation science (IS) lens to develop, implement, and evaluate a comprehensive emergency care curriculum in a single emergency facility in Liberia. Methods A six-month emergency care curriculum consisting of BEC content, standardized WHO clinical documentation forms, African Federation of Emergency Medicine (AFEM) didactics, and clinical mentorship by visiting emergency medicine (EM) faculty was designed and implemented using IS frameworks at Redemption Hospital, a low-resource public referral hospital in Monrovia, the capital of Liberia. Healthcare worker performance on validated knowledge-based exams during pre- and post-intervention testing, post-course surveys, and patient outcomes were used to evaluate the program. Results Nine visiting EM physicians provided 1400 hours of clinical mentorship and 560 hours of didactic training to fifty-six Redemption Hospital staff over six-months. Median test scores improved 20.0% (pDiscussion This study builds on prior research supporting WHO efforts to improve emergency care globally. BEC implementation over a six-month timeframe using IS principles is an effective alternative strategy for facilities in resource-constrained environments wishing to strengthen emergency care delivery.

Peripheral neuropathy is a common cause for neurological consultation, especially among those with diabetes mellitus. However, research on peripheral neuropathy among the general population is lacking in Malaysia. This study aimed to determine the prevalence and factors associated with peripheral neuropathy in a setting of retail pharmacies. This cross-sectional study of 1283 participants was conducted at retail pharmacies in Selangor. Peripheral neuropathy was defined as the final score in the mild to severe category in the severity rating scale using a biothesiometer. SPSS version 26 was used to perform the analysis. Multiple logistic regressions were used to determine the factors associated with peripheral neuropathy. The prevalence of peripheral neuropathy based on the biothesiometer was 26.5%. According to multiple logistic regression, the predictors of peripheral neuropathy were those who have diabetes (AOR = 3.901), aged more than 50 years (AOR = 3.376), have secondary education or below (AOR = 2.330), are male (AOR = 1.816), and have underlying hypertension (AOR = 1.662). Peripheral neuropathy is a reasonably prevalent condition, affecting a quarter of the general population, and often goes undiagnosed. It is crucial for healthcare providers to proactively screen for peripheral neuropathy, particularly in high-risk populations, to prevent potential complications. [ABSTRACT FROM AUTHOR]

Recent evolution in connected devices modelled a massive stipulation for network traffic resources and classification. Software-defined networking (SDN) enables ML techniques with the Internet of Things (IoT) to automate network traffic. This helps to reduce accuracy and improves latency. Problems by conventional techniques to categorize network traffic acquired from IoT and assign resources can be resolved through SDN solutions. This manuscript proposes a proposed network traffic classification technique on IoT with SDN called Gauss Markov and Flow-balanced Vector Radial Learning (GM-FVRL). With the network traffic features acquired from the IoT devices, SDN-enabled Gauss Markov Correlation-based IoT Network Traffic Feature Extraction is applied to extort relevant network aspects. Next, the flow-balanced radial-based ML model for network traffic categorization uses the relevant extracted network traffic features. With the aid of flow, the balanced radial basis function reduces the influence of noise due to distinct network flow. This helps to improve accuracy and minimize latency. Due to this, better precision and recall is ensured. Performance of our method has been evaluated utilizing a scheme using an SDN traffic dataset. The results show that our method classifies the network traffic with high classification accuracy and minimum latency, ensuring better precision and recall. [ABSTRACT FROM AUTHOR]

We measured hair and plasma concentrations of isoniazid among sixteen children with tuberculosis who underwent personal or video-assisted directly observed therapy and thus had 100% adherence. This study therefore defined typical isoniazid exposure parameters after two months of treatment among fully-adherent patients in both hair and plasma (plasma area under the concentration-time curve, AUC, estimated using pharmacokinetic data collected 0, 2, 4, and 6 hours after drug administration). We found that INH levels in hair among highly-adherent individuals did not correlate well with plasma AUC or trough concentrations, suggesting that each measure may provide incremental and complementary information regarding drug exposure in the context of TB treatment.

BackgroundData are limited on genome-wide association studies (GWAS) for incident coronary heart disease (CHD). Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting.MethodsWe performed a two-stage GWAS analysis of incident myocardial infarction (MI) and CHD in a total of 64,297 individuals (including 3898 MI cases, 5465 CHD cases). SNPs that passed an arbitrary threshold of 5×10-6 in Stage I were taken to Stage II for further discovery. Furthermore, in an analysis of prognosis, we studied whether known SNPs from former GWAS were associated with total mortality in individuals who experienced MI during follow-up.ResultsIn Stage I 15 loci passed the threshold of 5×10-6; 8 loci for MI and 8 loci for CHD, for which one locus overlapped and none were reported in previous GWAS meta-analyses. We took 60 SNPs representing these 15 loci to Stage II of discovery. Four SNPs near QKI showed nominally significant association with MI (p-value

Background Protection of islets without systemic immunosuppression has been a long-sought goal in the islet transplant field. We conducted a pilot biocompatibility/safety study in healthy dogs followed by a dose-finding efficacy study in diabetic dogs using polyethylene glycol diacrylate (PEGDA) microencapsulated allogeneic canine islets. Methods Prior to the transplants, characterization of the canine islets included the calculations determining the average cell number/islet equivalent. Following measurements of purity, insulin secretion, and insulin, DNA and ATP content, the islets were encapsulated and transplanted interperitoneally into dogs via a catheter, which predominantly attached to the omentum. In the healthy dogs, half of the microspheres injected contained canine islets, the other half of the omentum received empty PEGDA microspheres. Results In the biocompatibility study, healthy dogs received increasing doses of cells up to 1.7 M cells/kg body weight, yet no hypoglycemic events were recorded and the dogs presented with no adverse events. At necropsy the microspheres were identified and described as clear with attachment to the omentum. Several of the blood chemistry values that were abnormal prior to the transplants normalized after the transplant. The same observation was made for the diabetic dogs that received higher doses of canine islets. In all diabetic dogs, the insulin required to attempt to control blood glucose was cut by 50–100% after the transplant, down to no required insulin for the course of the 60-day study. The dogs had no adverse events and behavioral monitoring suggested normal activity after recovery from the transplant. Conclusions and implications The study provides evidence that PEGDA microencapsulated canine islets reversed the signs of diabetes without immunosuppression and led to states of insulin-independence or significantly lowered insulin requirements in the recipients.

BackgroundHeart failure is a multi-system disease, with non-cardiac systems playing a key role in disease pathogenesis.ObjectiveInvestigate whether longitudinal multi-system trajectories incrementally predict heart failure risk compared to single-occasion traits.MethodsWe evaluated 3,412 participants from the Framingham Heart Study Offspring cohort, free of heart failure, who attended examination cycle 5 and at least one examination between 1995-2008 (mean age 67 years, 54% women). We related trajectories for the following organ systems and metabolic functions to heart failure risk using Cox regression: kidney (estimated glomerular filtration rate), lung (forced vital capacity and the ratio of forced expiratory volume in one second/forced vital capacity), neuromotor (gait time), muscular (grip strength), cardiac (left ventricular mass index and heart rate), vascular function (pulse pressure), cholesterol (ratio of total/high-density lipoprotein), adiposity (body mass index), inflammation (C-reactive protein) and glucose homeostasis (hemoglobin A1c). Using traits selected via forward selection, we derived a trajectory risk score and related it to heart failure risk.ResultsWe observed 276 heart failure events during a median follow up of 10 years. Participants with the 'worst' multi-system trajectory profile had the highest heart failure risk. A one-unit increase in the trajectory risk score was associated with a 2.72-fold increase in heart failure risk (95% CI 2.21-3.34; pConclusionIncorporating multi-system trajectories reflective of the aging process may add incremental information to heart failure risk assessment when compared to using single-occasion traits.

In the present study, white (Baegilmi), brown (hyunmi) and black (chalheugmi) Korean local rice varieties ethanol extracts were analyzed for in-vitro antioxidant assays (ABTS, FRAP and DPPH), cellular antioxidant activities (CAAs) and phenolic phytochemicals content. The highest antioxidant assays, phenolic, flavonoid and anthocyanins content were identified among the free fractions of black rice. Phenolic phytochemicals were detected and quantified using the ultra-high-performance liquid tandem chromatography quadrupole flight mass spectrometry (UHPLC-Q-TOF-MS2). Which indicated the richness of several phytochemicals like ascorbic acid, vanillic acid, p-coumaric acid, catechin, epigallocatechin and quercetin in black rice than in other rice samples. The cellular antioxidant activities (CAA) of black rice were found equivalent to that of ascorbic acid, the standard employed in the assay. The CAAs of free fractions were as follows: white rice < brown rice < black rice. These findings are significant for enhancing human health through increased consumption of black and brown rice in the development of functional food products.

ImportanceCardiovascular Health (CVH) scores are inversely associated with prevalent subclinical (SubDz) and incident cardiovascular disease (CVD). However, the majority of people who develop CVD have intermediate or ideal CVH scores, while many with poor CVH profiles escape CVD development.ObjectiveTo describe the prevalence of paradoxical relations among CVH, SubDz, and CVD.DesignCohort study, Framingham Study data collected prospectively (1995-2016).SettingPopulation-based.Participants7,627 participants (mean age 49 years, 53% women) attending Offspring examinations 6/7 and Third Generation examinations 1/2.ExposuresCVH score (range 0-14) constructed from poor, intermediate, or ideal status for each metric (smoking, diet, physical activity, blood pressure, body mass index, fasting glucose, total cholesterol); and prevalent SubDz (≥1 of: increased carotid intimal media thickness, CIMT; left ventricular hypertrophy, LVH; microalbuminuria, MA; elevated ankle brachial index, ABI; coronary artery calcium score ≥100,CAC).Main outcome(s) and measure(s)Ideal CVH (scores 12-14), intermediate CVH (scores 8-11), and poor CVH (0-7). We described three distinct paradoxical phenomena, involving combinations of CVH, SubDz, and CVD, and generated CVD incidence rates and predicted CVD probabilities for all combinations.ResultsWe observed 842 CVD events (median follow-up 13.7 years); 1,663 participants had SubDz. Most individuals with poor CVH (78%) or SubDz (57% for CIMT to 77% for LVH) did not develop CVD on follow-up. Among participants with incident CVD, the majority had intermediate or ideal CVH (68%) or absent SubDz (46% for CAC to 96% for ABI) at baseline. We observed similar paradoxical results in relations between CVH and prevalent SubDz. Poor CVH and prevalent SubDz were each associated with higher CVD incidence rates compared to intermediate or ideal CVH and absent SubDz, respectively. The predicted CVD probability was nearly three-times greater among participants with poor (22%) versus intermediate or ideal CVH (8%). Mean CVD predicted probabilities were nearly three (26% vs. 10% for MA) to six-times (29% vs. 5% for CAC) greater among participants with SubDz versus without SubDz. Findings were consistent within age and sex strata.Conclusions and relevanceAlthough poor CVH and SubDz presence are associated with CVD incidence, paradoxical phenomena involving CVH, SubDz, and CVD are frequently prevalent in the community. Further studies to elucidate biological mechanisms underlying these phenomena are warranted.

Andaman cattle is a precious indigenous livestock species endemic to Andaman and Nicobar Islands, India. Till date, origin and genetic makeup of the breed which is warranted for breed conservation is not known. Moreover, the spread of zebu cattle from Indus valley to different parts of Island Southeast Asia (ISEA) is not properly understood. Here, we report the genetic diversity, population structure of Andaman cattle and their evolution in the context of epicentre of zebu domestication and ISEA. High genetic diversity in complete mitochondrial D-loop sequences indicated the ability of the breed to withstand impending climate change. Total 81 haplotypes were detected and all of them except three belonged to Bos indicus. The presence of taurine haplotypes in Andaman cattle indicate introgression by European-derived cattle. A poor phylogenetic signal of Andaman cattle with genetic affinities with cattle of Indian subcontinent and ISEA was observed. The poor phylogenetic structure may be due to multidirectional gene flow from Indian subcontinent and ISEA, with which Andaman shares a close cultural and trade relationship from Neolithic age. We hypothesize that Andaman cattle is the outcome of Neolithic diffusion from centre of zebu domestication along with multidirectional commercial exchange between Indian subcontinent and ISEA.

Hepatitis C virus (HCV) infections are public health problem across the globe, particularly in developing countries. Pakistan has the second highest prevalence of HCV infection worldwide. Limited data exist from Pakistan about persons who inject drugs (PWID) and are at significant risk of exposure to HCV infection and transmission. Serum specimens (n = 110) collected from PWID residing in four provinces were tested for molecular markers of HCV infection. Next generation sequencing (NGS) of the hypervariable region (HVR1) of HCV and Global Hepatitis Outbreak and Surveillance Technology (GHOST) were used to determine HCV genotype, genetic heterogeneity, and construct transmission networks. Among tested specimens, 47.3% were found anti-HCV positive and 34.6% were HCV RNA-positive and belonged to four genotypes, with 3a most prevalent followed by 1a, 1b and 4a. Variants sampled from five cases formed phylogenetic cluster and a transmission network. One case harbored infection with two different genotypes. High prevalence of infections and presence of various genotypes indicate frequent introduction and transmission of HCV among PWID in Pakistan. Identification of a transmission cluster across three provinces, involving 20% of all cases, suggests the existence of a countrywide transmission network among PWIDs. Understanding the structure of this network should assist in devising effective public health strategies to eliminate HCV infection in Pakistan.

Listeria monocytogenes is a ubiquitous opportunistic foodborne pathogen capable of survival in various adverse environmental conditions. Pathogenesis of L. monocytogenes is tightly controlled by a complex regulatory network of transcriptional regulators that are necessary for survival and adaptations to harsh environmental conditions both inside and outside host cells. Among these regulatory pathways are members of the DeoR-family transcriptional regulators that are known to play a regulatory role in sugar metabolism. In this study, we deciphered the role of FruR, a DeoR family protein, which is a fructose operon transcriptional repressor protein, in L. monocytogenes pathogenesis and growth. Following intravenous (IV) inoculation in mice, a mutant strain with deletion of fruR exhibited a significant reduction in bacterial burden in liver and spleen tissues compared to the parent strain. Further, the ΔfruR strain had a defect in cell-to-cell spread in L2 fibroblast monolayers. Constitutive activation of PrfA, a pleiotropic activator of L. monocytogenes virulence factors, did not restore virulence to the ΔfruR strain, suggesting that the attenuation was not a result of impaired PrfA activation. Transcriptome analysis revealed that FruR functions as a positive regulator for genes encoding enzymes involved in the pentose phosphate pathway (PPP) and as a repressor for genes encoding enzymes in the glycolysis pathway. These results suggested that FruR may function to facilitate NADPH regeneration, which is necessary for full protection from oxidative stress. Interestingly, deletion of fruR increased sensitivity of L. monocytogenes to H2O2, confirming a role for FruR in survival of L. monocytogenes during oxidative stress. Using anti-mouse neutrophil/monocyte monoclonal antibody RB6-8C5 (RB6) in an in vivo infection model, we found that FruR has a specific function in protecting L. monocytogenes from neutrophil/monocyte-mediated killing. Overall, this work clarifies the role of FruR in controlling L. monocytogenes carbon flow between glycolysis and PPP for NADPH homeostasis, which provides a new mechanism allowing metabolic adaptation of L. monocytogenes to oxidative stress.

Tribolium castaneum is one of the major pests of stored grains which causes extensive damages. To control this insect pest many synthetic chemical pesticides are used. However, continuous usage of synthetic fumigants causes pest resurgence, toxic residues, genetic resistance in pests, environmental contamination and health hazards etc., To avert these problems, essential oils are used as bio-fumigants to control the stored pests. They could act as best alternatives to synthetic fumigant in closed environment. Hence, the present study aimed to evaluate the pesticidal activity of Callistemon citrinus oil against Tribolium castaneum. GC-MS analysis of C. citrinus essential oil (EO) showed 10 compounds; among them, the major constituent was eucalyptol (1, 8-cineole) at 40.44%. The lethal concentration (LC50) values were 37.05 μL/L (adults) and 144.31 μL/L (larvae) at 24 and 48 hrs respectively. Exposure to C. citrinus EO significantly reduced the beetle fecundity, ovicidal activity, egg hatchability, larvae survival and emergence of adult. The effect of EO on enzymatic activity of T. castaneum adults was examined using Acetylcholinesterase, α-Carboxylesterase, β-Carboxylesterase, Glutathione-S-Transferase, Acid and Alkaline phosphatase assays. The results indicated that the activity of detoxification enzymes drastically varied when compared with control. This EO had toxicant effects on all stages of the life of T. castaneum.

ImportanceOrthostatic hypotension (OH) and hypertension (OHT) are aberrant blood pressure (BP) regulation conditions associated with higher cardiovascular disease risk. The relations of OH and OHT with heart failure (HF) risk in the community are unclear and there remains a paucity of data on the relations with HF subtypes [HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF)].ObjectiveRelate OH and OHT with HF risk and its subtypes.DesignProspective observational cohort.SettingCommunity-based individuals in the Framingham Heart Study Original Cohort.Participants1,914 participants (mean age 72 years; 1159 women) attending examination cycle 17 (1981-1984) followed until December 31, 2017 for incident HF or death.ExposuresOH or OHT, defined as a decrease or increase, respectively, of ≥20/10 mmHg in systolic/diastolic BP upon standing from supine position.Outcomes and measuresAt baseline, 1,241 participants had a normal BP response (749 women), 274 had OH (181 women), and 399 had OHT (229 women). Using Cox proportional hazards regression models, we related OH and OHT to risk of HF, HFrEF, and HFpEF compared to the absence of OH and OHT (reference), adjusting for age, sex, body mass index, systolic and diastolic BP, hypertension treatment, smoking, diabetes, and total cholesterol/high-density lipoprotein.ResultsOn follow-up (median 13 years) we observed 492 HF events (292 in women; 134 HFrEF, 116 HFpEF, 242 HF indeterminate EF). Compared to the referent, participants with OH [n = 84/274 (31%) HF events] had a higher HF risk (Hazards Ratio [HR] 1.47, 95% CI 1.13-1.91). Moreover, OH was associated with a higher HFrEF risk (HR 2.21, 95% CI 1.34-3.67). OHT was not associated with HF risk.Conclusions and relevanceOrthostatic BP response may serve as an early marker of HF risk. Findings suggest shared pathophysiology of BP regulation and HF, including HFrEF.

BackgroundHypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals.MethodsUsing a genome-wide association study among 21,267 participants with pharmaceutically treated hypertension, we explored the hypothesis that genetic variants might influence or modify the effectiveness of common antihypertensive therapies on the risk of major cardiovascular outcomes. The classes of drug treatments included angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, each study performed array-based genome-wide genotyping, imputed to HapMap Phase II reference panels, and used additive genetic models in proportional hazards or logistic regression models to evaluate drug-gene interactions for each of four therapeutic drug classes. We used meta-analysis to combine study-specific interaction estimates for approximately 2 million single nucleotide polymorphisms (SNPs) in a discovery analysis among 15,375 European Ancestry participants (3,527 CVD cases) with targeted follow-up in a case-only study of 1,751 European Ancestry GenHAT participants as well as among 4,141 African-Americans (1,267 CVD cases).ResultsAlthough drug-SNP interactions were biologically plausible, exposures and outcomes were well measured, and power was sufficient to detect modest interactions, we did not identify any statistically significant interactions from the four antihypertensive therapy meta-analyses (Pinteraction > 5.0×10-8). Similarly, findings were null for meta-analyses restricted to 66 SNPs with significant main effects on coronary artery disease or blood pressure from large published genome-wide association studies (Pinteraction ≥ 0.01). Our results suggest that there are no major pharmacogenetic influences of common SNPs on the relationship between blood pressure medications and the risk of incident CVD.

Climate projections like UKCP18 predict that the UK will move towards a wetter and warmer climate with a consequent increased risk from surface water flooding (SWF). SWF is typically caused by localized convective rainfall, which is difficult to predict and requires high spatial and temporal resolution observations. The likelihood of SWF is also affected by the microtopographic configuration near buildings and the presence of resilience and resistance measures. To date, most research on SWF has focused on modelling and prediction, but these models have been limited to 2 m resolution for England to avoid excessive computational burdens. The lead time for predicting convective rainfall responsible for SWF can be as little as 30 minutes for a 1 km x 1 km part of the storm. Therefore, it is useful to identify the locations most vulnerable to SWF based on past rainfall data and microtopography to provide better risk management measures for properties. In this study, we present a framework that uses long-term gridded rainfall data to quantify SWF hazard at the 1 km x 1 km pixel level, thereby identifying localized areas vulnerable to SWF. We also use high-resolution photographic (10 cm) and LiDAR (25 cm) DEMs, as well as a property flood resistance and resilience (PFR) database, to quantify SWF exposure at property level. By adopting this methodology, locations and properties vulnerable to SWF can be identified, and appropriate SWF management strategies can be developed, such as installing PFR features for the properties at highest risk from SWF. [ABSTRACT FROM AUTHOR]

Cultivated beet (Beta vulgaris L. ssp. vulgaris) originated from sea beet (B. vulgaris ssp. maritima (L.) Arcang), a wild beet species widely distributed along the coasts of the Mediterranean Sea and Atlantic Ocean, as well as northern Africa. Understanding the evolution of sea beet will facilitate its efficient use in sugarbeet improvement. We used SNPs (single nucleotide polymorphisms) covering the whole genome to analyze 599 sea beet accessions collected from the north Atlantic Ocean and Mediterranean Sea coasts. All B. maritima accessions can be grouped into eight clusters with each corresponding to a specific geographic region. Clusters 2, 3 and 4 with accessions mainly collected from Mediterranean coasts are genetically close to each other as well as to Cluster 6 that contained mainly cultivated beet. Other clusters were relatively distinct from cultivated beets with Clusters 1 and 5 containing accessions from north Atlantic Ocean coasts, Clusters 7 and Cluster 8 mainly have accessions from northern Egypt and southern Europe, and northwest Morocco, respectively. Distribution of B. maritima subpopulations aligns well with the direction of marine currents that was considered a main dynamic force in spreading B. maritima during evolution. Estimation of genetic diversity indices supported the formation of B. maritima subpopulations due to local genetic drift, historic migration, and limited gene flow. Our results indicated that B. maritima originated from southern Europe and then spread to other regions through marine currents to form subpopulations. This research provides vital information for conserving, collecting, and utilizing wild sea beet to sustain sugarbeet improvement. [ABSTRACT FROM AUTHOR]

BackgroundMigraine may lead to a negative impact on the patients' quality of life with a subsequent substantial burden to society. Therapy options for treatment and prevention of migraine have progressed over the years and repetitive transcranial magnetic stimulation (rTMS) is one of the promising non-pharmacological options. It induces and alters electric current in the brain via repetitive non-invasive brain stimulation in high frequency. In migraine patients, two common stimulation sites are the M1 cortex and dorsolateral prefrontal cortex (DLPFC). The mechanism on how rTMS exerts therapeutic effects on migraine is not fully established, but the main postulation is that the neuromodulation via high-frequency rTMS (hf-rTMS) might inhibit pain perception. However, evidence from studies has been conflicting, thus the usefulness of hf-rTMS as migraine preventive treatment is still uncertain at this moment.MethodsThis is a systematic review protocol describing essential reporting items based on the PRISMA for systematic review protocols (PRISMA-P) (Registration number: CRD42020220636). We aim to review the effectiveness, tolerability, and safety of hf-rTMS at DLPFC in randomised controlled trials (RCTs) as migraine prophylactic treatment. We will search Scopus, Cumulative Index to Nursing and Allied Health Literature Plus, PubMed, Cochrane Central Register of Controlled Trials and Biomed Central for relevant articles from randomised controlled clinical trials that used hf-rTMS applied at DLPFC for the treatment of migraine. The risk of bias will be assessed using the version 2 "Risk of bias" tool from Cochrane Handbook for Systematic Reviews of Interventions Version 6.1. We will investigate the evidence on efficacy, tolerability and safety and we will compare the outcomes between the hf-rTMS intervention and sham groups.DiscussionThis systematic review will further determine the efficacy, safety, and tolerability of hf-rTMS applied at DLPFC for migraine prophylaxis. It will provide additional data for health practitioners and policymakers about the usefulness of hf-rTMS for migraine preventive treatment.

BackgroundIncreased oxidative stress, leukocyte telomere length (LTL) shortening, endothelial dysfunction, and lower insulin-like growth factor (IGF)-1 concentrations reflect key molecular mechanisms of aging. We hypothesized that biomarkers representing these pathways are associated with measures of subclinical atherosclerosis and all-cause mortality.Methods and resultsWe evaluated up to 2,314 Framingham Offspring Study participants (mean age 61 years, 55% women) with available biomarkers of aging: LTL, circulating concentrations of IGF-1, asymmetrical dimethylarginine (ADMA), and urinary F2-Isoprostanes indexed to urinary creatinine. We evaluated the association of each biomarker with coronary artery calcium [ln (CAC+1)] and carotid intima-media thickness (IMT). In multivariable-adjusted linear regression models, higher ADMA levels were associated with higher CAC values (βADMA per 1-SD increase 0.25; 95% confidence interval [CI] [0.11, 0.39]). Additionally, shorter LTL and lower IGF-1 values were associated with higher IMT values (βLTL -0.08, 95%CI -0.14, -0.02, and βIGF-1 -0.04, 95%CI -0.08, -0.01, respectively). During a median follow-up of 15.5 years, 593 subjects died. In multivariable-adjusted Cox regression models, LTL and IGF-1 values were inversely associated with all-cause mortality (hazard ratios [HR] per SD increase in biomarker, 0.85, 95% CI 0.74-0.99, and 0.90, 95% CI 0.82-0.98 for LTL and IGF-1, respectively). F2-Isoprostanes and ADMA values were positively associated with all-cause mortality (HR per SD increase in biomarker, 1.15, 95% CI, 1.10-1.22, and 1.10, 95% CI, 1.02-1.20, respectively).ConclusionIn our prospective community-based study, aging-related biomarkers were associated with measures of subclinical atherosclerosis cross-sectionally and with all-cause mortality prospectively, supporting the concept that these biomarkers may reflect the aging process in community-dwelling adults.

BackgroundHospitalization for acute decompensated heart failure (ADHF) remains a major source of morbidity and mortality. The current study aimed to investigate the feasibility, safety, and efficacy of outpatient furosemide intravenous (IV) infusion following hospitalization for ADHF.MethodsIn a single center, prospective, randomized, double-blind study, 100 patients were randomized to receive standard of care (Group 1), IV placebo infusion (Group 2), or IV furosemide infusion (Group 3) over 3h, biweekly for a one-month period following ADHF hospitalization. Patients in Groups 2/3 also received a comprehensive HF-care protocol including bi-weekly clinic visits for dose-adjusted IV-diuretics, medication adjustment and education. Echocardiography, quality of life and depression questionnaires were performed at baseline and 30-day follow-up. The primary outcome was 30-day re-hospitalization for ADHF.ResultsOverall, a total of 94 patients were included in the study (mean age 64 years, 56% males, 69% African American). There were a total of 14 (15%) hospitalizations for ADHF at 30 days, 6 (17.1%) in Group 1, 7 (22.6%) in Group 2, and 1 (3.7%) in Group 3 (overall p = 0.11; p = 0.037 comparing Groups 2 and 3). Patients receiving IV furosemide infusion experienced significantly greater urine output and weight loss compared to those receiving placebo without any significant increase creatinine and no significant between group differences in echocardiography parameters, KCCQ or depression scores.ConclusionThe use of a standardized protocol of outpatient IV furosemide infusion for a one-month period following hospitalization for ADHF was found to be safe and efficacious in reducing 30-day re-hospitalization.

The Arab population encompasses over 420 million people characterized by genetic admixture and a consequent rich genetic diversity. A number of genetic diseases have been reported for the first time from the population. Additionally a high prevalence of some genetic diseases including autosomal recessive disorders such as hemoglobinopathies and familial mediterranean fever have been found in the population and across the region. There is a paucity of databases cataloguing genetic variants of clinical relevance from the population. The availability of such a catalog could have implications in precise diagnosis, genetic epidemiology and prevention of disease. To fill in the gap, we have compiled DALIA, a comprehensive compendium of genetic variants reported in literature and implicated in genetic diseases reported from the Arab population. The database aims to act as an effective resource for population-scale and sub-population specific variant analyses, enabling a ready reference aiding clinical interpretation of genetic variants, genetic epidemiology, as well as facilitating rapid screening and a quick reference for evaluating evidence on genetic diseases.

Pistachios have been implicated in two salmonellosis outbreaks and multiple recalls in the U.S. This study performed an in-depth retrospective data analysis of Salmonella associated with pistachios as well as a storage study to evaluate the survivability of Salmonella on inoculated inshell pistachios to further understand the genetics and microbiological dynamics of this commodity-pathogen pair. The retrospective data analysis on isolates associated with pistachios was performed utilizing short-read and long-read sequencing technologies. The sequence data were analyzed using two methods: the FDA’s Center for Food Safety and Applied Nutrition Single Nucleotide Polymorphism (SNP) analysis and Whole Genome Multilocus Sequence Typing (wgMLST). The year-long storage study evaluated the survival of five strains of Salmonella on pistachios stored at 25 °C at 35% and 54% relative humidity (RH). Our results demonstrate: i) evidence of persistent Salmonella Senftenberg and Salmonella Montevideo strains in pistachio environments, some of which may be due to clonal resident strains and some of which may be due to preharvest contamination; ii) presence of the Copper Homeostasis and Silver Resistance Island (CHASRI) in Salmonella Senftenberg and Montevideo strains in the pistachio supply chain; and iii) the use of metagenomic analysis is a novel tool for determining the composition of serovar survival in a cocktail inoculated storage study.

BackgroundDiarrheal disease is a leading cause of morbidity and mortality globally, especially in low- and middle-income countries. High-throughput and low-cost approaches to identify etiologic agents are needed to guide public health mitigation. Nanoliter-qPCR (nl-qPCR) is an attractive alternative to more expensive methods yet is nascent in application and without a proof-of-concept among hospitalized patients.MethodsA census-based study was conducted among diarrheal patients admitted at two government hospitals in rural Bangladesh during a diarrheal outbreak period. DNA was extracted from stool samples and assayed by nl-qPCR for common bacterial, protozoan, and helminth enteropathogens as the primary outcome.ResultsA total of 961 patients were enrolled; stool samples were collected from 827 patients. Enteropathogens were detected in 69% of patient samples; More than one enteropathogen was detected in 32%. Enteropathogens most commonly detected were enteroaggregative Escherichia coli (26.0%), Shiga toxin-producing E.coli (18.3%), enterotoxigenic E. coli (15.5% heat stable toxin positive, 2.2% heat labile toxin positive), Shigella spp. (14.8%), and Vibrio cholerae (9.0%). Geospatial analysis revealed that the median number of pathogens per patient and the proportion of cases presenting with severe dehydration were greatest amongst patients residing closest to the study hospitals."ConclusionsThis study demonstrates a proof-of-concept for nl-qPCR as a high-throughput low-cost method for enteropathogen detection among hospitalized patients.

BackgroundLung function abnormalities are ubiquitous in heart failure (HF). It is unclear, however, if abnormal lung diffusion capacity is associated with cardiac remodeling and antedates HF. We hypothesized that lower lung diffusion capacity for carbon monoxide (DLCO) is associated with worse left ventricular (LV) systolic and diastolic function cross-sectionally, and with higher risk of HF prospectively.MethodsWe evaluated 2423 Framingham Study participants (mean age 66 years, 55% women) free of HF who underwent routine echocardiography and pulmonary function tests. We used multivariable regression models to relate DLCO, forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV1) to left ventricular ejection fraction (LVEF), left atrial (LA) emptying fraction (LAEF), E/e', E/A, LV mass, and LA diameter (LAD). Multivariable-adjusted Cox proportional hazards regression was used to relate DLCO, FEV1, and FVC to incident HF.ResultsIn multivariable-adjusted cross-sectional analyses, DLCO, FEV1, and FVC (dependent variables) were associated positively with LVEF (βDLCO = 0.208, βFEV1 = 0.021, and βFVC = 0.025 per 5% increment in LVEF; pConclusionsOur large community-based observations are consistent with the concept that lower lung diffusion capacity and expiratory flow rates are associated with cardiac remodeling and may antedate HF. Additional studies are needed to confirm our findings and to evaluate the prognostic utility of pulmonary function testing for predicting HF.

Metagenomic analysis of food is becoming more routine and can provide important information pertaining to the shelf life potential and the safety of these products. However, less information is available on the microbiomes associated with low water activity foods. Pine nuts and sesame seeds, and food products which contain these ingredients, have been associated with recalls due to contamination with bacterial foodborne pathogens. The objective of this study was to identify the microbial community of pine nuts and sesame seeds using targeted 16S rRNA sequencing technology. Ten different brands of each seed type were assessed, and core microbiomes were determined. A total of 21 and 16 unique taxa with proportional abundances >1% in at least one brand were identified in the pine nuts and sesame seeds, respectively. Members of the core pine nut microbiome included the genera Alishewanella, Aminivibrio, Mycoplasma, Streptococcus, and unassigned OTUs in the families of Desulfobacteraceae and Xanthomonadaceae. For sesame seeds, the core microbiome included Aminivibrio, Chryseolina, Okibacterium, and unassigned OTUs in the family Flavobacteriaceae. The microbiomes of these seeds revealed that these products are dominated by environmental bacterial genera commonly isolated from soil, water, and plants; bacterial genera containing species known as commensal organisms were also identified. Understanding these microbiomes can aid in the risk assessment of these products by identifying food spoilage potential and community members which may co-enrich with foodborne bacterial pathogens.

BackgroundCirculating levels of the endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), are positively associated with the prevalence of metabolic syndrome (MetS) in cross-sectional investigations. It is unclear if circulating ADMA and other methylarginines are associated with incident MetS prospectively.MethodsWe related circulating ADMA, symmetric dimethylarginine (SDMA), L-arginine (ARG) concentrations (measured with a validated tandem mass spectrometry assay) and the ARG/ADMA ratio to MetS and its components in 2914 (cross-sectional analysis, logistic regression; mean age 58 years, 55% women) and 1656 (prospective analysis, Cox regression; mean age 56 years, 59% women) individuals from the Framingham Offspring Study who attended a routine examination.ResultsAdjusting for age, sex, smoking, and eGFR, we observed significant associations of ADMA (direct) and ARG/ADMA (inverse) with odds of MetS (N = 1461 prevalent cases; Odds Ratio [OR] per SD increment 1.13, 95%CI 1.04-1.22; and 0.89, 95%CI 0.82-0.97 for ADMA and ARG/ADMA, respectively). Upon further adjustment for waist circumference, systolic and diastolic blood pressure, glucose, high-density lipoprotein cholesterol, and triglycerides, we observed a positive relation between SDMA and MetS (OR per SD increment 1.15, 95% CI 1.01-1.30) but the other associations were rendered statistically non-significant. We did not observe statistically significant associations between any of the methylarginines and the risk of new-onset MetS (752 incident events) over a median follow-up of 11 years.ConclusionIt is unclear whether dimethylarginines play an important role in the incidence of cardiometabolic risk in the community, notwithstanding cross-sectional associations. Further studies of larger samples are needed to replicate our findings.

Handgrip strength is a widely used measure of muscle strength and a predictor of a range of morbidities including cardiovascular diseases and all-cause mortality. Previous genome-wide association studies of handgrip strength have focused on common variants primarily in persons of European descent. We aimed to identify rare and ancestry-specific genetic variants associated with handgrip strength by conducting whole-genome sequence association analyses using 13,552 participants from six studies representing diverse population groups from the Trans-Omics in Precision Medicine (TOPMed) Program. By leveraging multiple handgrip strength measures performed in study participants over time, we increased our effective sample size by 7-12%. Single-variant analyses identified ten handgrip strength loci among African-Americans: four rare variants, five low-frequency variants, and one common variant. One significant and four suggestive genes were identified associated with handgrip strength when aggregating rare and functional variants; all associations were ancestry-specific. We additionally leveraged the different ancestries available in the UK Biobank to further explore the ancestry-specific association signals from the single-variant association analyses. In conclusion, our study identified 11 new loci associated with handgrip strength with rare and/or ancestry-specific genetic variations, highlighting the added value of whole-genome sequencing in diverse samples. Several of the associations identified using single-variant or aggregate analyses lie in genes with a function relevant to the brain or muscle or were reported to be associated with muscle or age-related traits. Further studies in samples with sequence data and diverse ancestries are needed to confirm these findings.

BackgroundCorona virus disease 2019 (COVID-19) which initially started as a cluster of pneumonia cases in the Wuhan city of China has now become a full-blown pandemic. Timely diagnosis of COVID-19 is the key in containing the pandemic and breaking the chain of transmission. In low- and middle-income countries availability of testing kits has become the major bottleneck in testing. Novel methods like pooling of samples are the need of the hour.ObjectiveWe undertook this study to evaluate a novel protocol of pooling of RNA samples/elutes in performance of PCR for SARS CoV-2 virus.Study designExtracted RNA samples were randomly placed in pools of 8 on a 96 well plate. Both individual RNA (ID) and pooled RNA RT-qPCR for the screening E gene were done in the same plate and the positivity for the E gene was seen.ResultsThe present study demonstrated that pool testing with RNA samples can easily detect even up to a single positive sample with Ct value as high as 38. The present study also showed that the results of pool testing is not affected by number of positive samples in a pool.ConclusionPooling of RNA samples can reduce the time and expense, and can help expand diagnostic capabilities, especially during constrained supply of reagents and PCR kits for the diagnosis of SARS-CoV-2 infection.

BACKGROUND:Heart failure (HF) is a clinical syndrome where diagnostic certainty varies. The prognosis of individuals with some clinical features of HF, but without the fully overt syndrome, is unclear. Therefore, we sought to evaluate their natural history. METHODS AND RESULTS:Between 1990 and 2009, all suspected HF cases in the Framingham Heart Study were adjudicated into 3 groups reflecting varying diagnostic certainty: definite (meeting HF diagnostic criteria; n = 479), possible (meeting HF criteria but with an alternative explanation for findings; n = 135), and probable (insufficient criteria for definite HF; n = 121) HF. Age-and-sex-matched individuals (n = 1112) without HF or cardiovascular disease (CVD) were controls. Using multivariable-adjusted Cox regression, we compared the possible/probable HF groups with controls regarding risk of incident definite HF, coronary heart disease (CHD), other CVD or death; and with definite HF regarding risk of latter three outcomes. During follow-up (mean 8.6 years), ~90% of individuals with possible, probable and definite HF experienced CVD events or died. Compared with controls, those with possible or probable HF experienced higher hazards for definite HF, CHD, other CVD and death (hazards ratios [HR] 1.35-9.31; p

BackgroundIt is well established that coronary artery disease progresses along with myocardial disease. However, data on the association between coronary artery calcium (CAC) and echocardiographic variables are lacking.Methods and resultsAmong 2,650 Framingham Study participants (mean age 51 yrs, 48% women; 40% with CAC>0), we related CT-based CAC score to left ventricular (LV) mass index (LVMi), LV ejection fraction (LVEF), E/e', global longitudinal strain (GLS), left atrial emptying fraction (LAEF), and aortic root diameter (AoR), using multivariable-adjusted generalized linear models. CAC score (independent variable) was used as log-transformed continuous [ln(CAC+1)] and as a categorical (0, 1-100, and ≥101) variable. Adjusting for standard risk factors, higher CAC score was associated with higher LVMi and AoR (βLVMI per 1-SD increase 0.012, βAoR 0.008; P58 years; βAoR0.0042;PConclusionsWe observed that subclinical atherosclerosis was associated with ventricular and aortic remodeling. The prognostic significance of these associations warrants evaluation in additional mechanistic studies.

IntroductionObesity, hypertension, and diabetes are independently associated with cardiac remodeling and frequently co-cluster. The conjoint and separate influences of these conditions on cardiac remodeling have not been investigated.Materials and methodsWe evaluated 5,741 Framingham Study participants (mean age 50 years, 55% women) who underwent echocardiographic measurements of left ventricular (LV) mass (LVM), LV ejection fraction (LVEF), global longitudinal strain (GLS), mitral E/e', left atrial end-systolic (peak) dimension (LASD) and emptying fraction (LAEF). We used multivariable generalized linear models to estimate the adjusted-least square means of these measures according to cross-classified categories of body mass index (BMI; normal, overweight and obese), hypertension (yes/no), and diabetes (yes/no).ResultsWe observed statistically significant interactions of BMI category, hypertension, and diabetes with LVM, LVEF, GLS, and LAEF (p for all 3-way interactions ConclusionsObesity, hypertension, and diabetes interact synergistically to influence cardiac remodeling. These findings may explain the markedly heightened risk of heart failure and cardiovascular disease when these factors co-cluster.

BACKGROUND:The fungal toxin acts as effective, low-cost chemical substances for pest control worldwide and also an alternative to synthetic insecticides. This study assessed the larvicidal potential of Metarhizium anisopliae fungi derived metabolites against Aedes aegypti, Anopheles stephensi, Culex quinquefasciatus and non-targeted organisms at 24hr post treatment. METHOD:Isolation of entomopathogenic fungi M. anisopliae from natural traps confirmed by using 18s rDNA biotechnological tools. Crude extracts from M. anisopliae solvent extraction and their secondary metabolites were bio-assayed following WHO standard procedures against Ae. aegypti, An. stephensi and Cx. quinquefasciatus, Artemia nauplii, Eudrilus eugeniae, and Solanum lycopersicum after 24 hr exposure. Histopathological analysis of E. eugeniae treated with fungi metabolites toxicity compared to those treated with Monocrotophos after 24hrpost-treatment. M. anisopliae metabolites were characterized using GC-MS and FT-IR analysis. RESULTS:The larvicidal activity was recorded in highest concentration of 75μg/ml, with 85%, 97% and 89% mortality in Ae. aegypti, An. stephensi and Cx. quinquefasciatus respectively. M. anisopliae metabolites produced LC50 values in Ae. aegypti, 59.83μg/ml, in An. stephensi, 50.16μg/ml and in Cx. quinquefasciatus, 51.15μg/ml respectively. M. anisopliae metabolites produced lower toxic effects on A. nauplii, LC50 values were, 54.96μg/ml respectively. Bio-indicator toxicity results show 18% and 58% mortality was recorded in E. eugeniae and A. nauplii and also there is no phytotoxicity that was observed on S. lycopersicum L. under semi-field condition. E. eugeniae histopathological studies shows fungal metabolites showed lower sub-lethal effects compared to synthetic chemical pesticide at 24hrs of the treatment. The GC-MS and FT-IR analysis identified five major components of active ingredients. CONCLUSION:Findings of this study indicate that, M. anisopliae ethyl acetate derived secondary metabolites are effective against larvae of Ae. aegypti, An. stephensi and Cx. quinquefasciatus mosquito species, lower toxicity effects were observed on non-target organisms such as, Artemia nauplii, Eudrilus eugeniae as well as, no toxicity effect were observed on Solanum lycopersicum. Further research should be conducted in laboratory for separation of single pure molecule and be tested semifield conditions.

BackgroundFew studies examined the individual and conjoint associations of accelerometer-measured physical activity (PA) and sedentary times with the prevalence of chronic kidney disease (CKD) among older adults.MethodsWe evaluated 1,268 Framingham Offspring Study participants (mean age 69.2 years, 53.8% women) between 2011 and 2014. CKD was defined as an estimated glomerular filtration rate (eGFR) ResultsOverall, 258 participants had prevalent CKD (20.4%; 120 women). Higher total PA ([MVPA+LIPA], adjusted-odds ratio [OR] per 30 minutes/day increase, 0.86; 95% CI, 0.78-0.96) and higher LIPA (OR per 30 minutes/day increase, 0.87; 95% CI, 0.76-0.99) were associated with lower odds of CKD. Additionally, higher sedentary time (OR per 30 minutes/day increase, 1.16; 95% CI, 1.04-1.29) was associated with higher odds of CKD. Reallocating 5% of the time from LIPA to sedentary was associated with the largest predicted difference in eGFR (-1.06 ml/min/1.73m2). Reallocating 1% of time spent in MVPA to sedentary status predicted the largest difference in UACR (14.37 μg/mg).ConclusionThe findings suggest that increasing LIPA and maintaining MVPA at the expense of sedentary time may be associated with a lower risk of CKD in community-based older adults.

BackgroundNeurosyphilis (NS) presents with a variety of clinical syndromes that can be attributed to other aetiologies due to difficulties in its diagnosis. We reviewed all cases of NS from the "Top End" of the Australian Northern Territory over a ten-year period to assess incidence, clinical and laboratory manifestations.MethodsPatient data (2007-2016) were extracted from hospital records, centralised laboratory data and Northern Territory Centre for Disease Control records. Clinical records of patients with clinically suspected NS were reviewed. A diagnosis of NS was made based on the 2014 US CDC criteria. Results were also recategorized based on the 2018 US CDC criteria.ResultsThe population of the "Top End" is 185,570, of whom 26.2% are Indigenous. A positive TPPA was recorded in 3126 individuals. A total of 75 (2.4%) of TPPA positive patients had a lumbar puncture (LP), of whom 25 (35%) were diagnosed with NS (9 definite, 16 probable). Dementia was the most common manifestation (58.3%), followed by epilepsy (16.7%), psychosis (12.5%), tabes dorsalis (12.5%) and meningovascular syphilis (8.3%). 63% of probable NS cases were not treated appropriately due to a negative CSF VDRL. Despite increased specificity of the 2018 US CDC criteria, 70% of patient in the probable NS group were not treated appropriately. The overall annual incidence [95%CI] of NS was 2.47[1.28-4.31] per 100 000py in the Indigenous population and 0.95[0.50-1.62] in the non-Indigenous population (rate ratio = 2.60 [1.19-5.70];p = 0.017).ConclusionNeurosyphilis is frequently reported in the NT, particularly in Indigenous populations. Disturbingly, 60% of probable neurosyphilis patients based on the 2014 criteria, and 70% based on the 2018 criteria with were not treated appropriately. It is critical that clinicians should be aware of the diagnosis of NS and treat patients appropriately.

BackgroundCirculating microRNAs may reflect or influence pathological cardiac remodeling and contribute to atrial fibrillation (AF).ObjectiveThe purpose of this study was to identify candidate plasma microRNAs that are associated with echocardiographic phenotypes of atrial remodeling, and incident and prevalent AF in a community-based cohort.MethodsWe analyzed left atrial function index (LAFI) of 1788 Framingham Offspring 8 participants. We quantified expression of 339 plasma microRNAs. We examined associations between microRNA levels with LAFI and prevalent and incident AF. We constructed pathway analysis of microRNAs' predicted gene targets to identify molecular processes involved in adverse atrial remodeling in AF.ResultsThe mean age of the participants was 66 ± 9 years, and 54% were women. Five percent of participants had prevalent AF at the initial examination and 9% (n = 157) developed AF over a median 8.6 years of follow-up (IQR 8.1-9.2 years). Plasma microRNAs were associated with LAFI (N = 73, pConclusionsCirculating microRNAs 106b, 26a-5p, 484, 20a-5p are associated with atrial remodeling and AF.

BackgroundHeart failure (HF) is a heterogeneous clinical syndrome with varying prognosis. Subphenotyping of HF is a research priority to advance our understanding of the syndrome. We formulated a subphenotyping schema and compared long-term mortality risk among the HF subphenotypes in the community-based Framingham Study.Methods and resultsIn hierarchical order, we grouped participants with new-onset HF (stratified by HF with reduced [HFrEF] vs. preserved ejection fraction [HFpEF]) according to the presence of: (1) coronary heart disease (CHD), (2) metabolic syndrome (MetS), (3) hypertension, and (4) 'other' causes. Age at HF onset was lowest in people with the MetS (mean 76 vs. 77 years for HFrEF and HFpEF, respectively) and highest in those with hypertension only (mean 82 and 85 years for HFrEF and HFpEF, respectively). For HFrEF, 10-year cumulative mortality and hazards ratios [HR] were 87% for CHD (n = 219; referent group), 88% for MetS (n = 105; HR 0.95 [95% CI 0.73-1.23]), 82% for hypertension (n = 104; HR 0.71 [0.55-0.91]), and 78% for other (n = 37; HR 0.81 [0.55-1.19]). Corresponding 10-year cumulative mortality and HR data for HFpEF were: 85% for CHD (n = 84; referent), 83% for MetS (n = 118; HR 0.98 [0.72-1.33]), 81% for hypertension (n = 127; HR 0.71 [0.52-0.95]), and 76% for other (n = 43; HR 0.76 [0.50-1.14]). In a sample without overt heart failure (n = 5536), several echocardiographic and vascular indices showed graded worsening of age- and sex adjusted-values among those having CHD, MetS, hypertension, or obesity, compared with individuals not having these risk factors.ConclusionsHF subphenotypes characterized by the presence of CHD or metabolic syndrome present at a younger age and are marked by greater mortality risk. The clinical utility of the proposed subphenotyping schema warrants further research.

The nature of services for psychiatric disorders in public health systems has been understudied, particularly with regard to frequency, duration, and costs. The current study examines patterns of service reception and costs among Medicaid-covered youth newly diagnosed with anxiety, depression, or behavioral disturbance in a large data set of provider billing claims submitted between 2015-2016. Eligibility criteria included: 1) identification of an initial diagnosis of a single anxiety, unipolar mood, or specific behavioral disorder; 2) continuous Medicaid eligibility over the duration of the time period studied; and 3) under 18 years of age on the date of initial psychiatric diagnosis. The final cohort included 7,627 cases with a mean age of 10.65 (±4.36), of which 58.04% were male, 57.09% were Black, 38.97% were White, and 3.95% were of other ethnicities. Data indicated that 65.94% of the cohort received at least some follow-up services within a median 18 days of diagnosis. Of those, 54.27% received a combination of medical and psychosocial services, 32.01% received medical services only, and 13.72% received psychosocial services only. Overall median costs for direct treatment were $576.69, with wide discrepancies between the lowest (anxiety = $308.41) and highest (behavioral disturbance = $653.59) diagnostic categories. Across all categories the frequency and duration of psychosocial services were much lower than would be expected in comparison to data from a well-known effectiveness trial. Overall, follow-up to psychiatric diagnosis could be characterized as highly variable, underutilized, and emphasizing biomedical treatment. Understanding more about these patterns may facilitate systematic improvements and greater cost efficiency in the future.

Autosomal dominant polycystic kidney disease (ADPKD) is caused mostly by mutations in polycystin-1 or polycystin-2. Fluid flow leads to polycystin-dependent calcium influx and nuclear export of histone deacetylase 5 (HDAC5), which facilitates the maintenance of renal epithelial architecture by de-repression of MEF2C target genes. Here, we screened a small-molecule library to find drugs that promotes nuclear export of HDAC5. We found that dopamine receptor antagonists, domperidone and loxapine succinate, stimulate export of HDAC5, even in Pkd1-/-cells. Domperidone targets Drd3 receptor to modulate the phosphorylation of HDAC5. Domperidone treatment increases HDAC5 phosphorylation likely by reducing protein phosphatase 2A (PP2A) activity, thus shifting the equilibrium towards HDAC5-P and export from the nucleus. Treating Pkd1-/-mice with domperidone showed significantly reduced cystic growth and cell proliferation. Further, treated mice displayed a reduction in glomerular cyst and increased body weight and activity. These results suggest that HDAC5 nucleocytoplasmic shuttling may be modulated to impede disease progression in ADPKD and uncovers an unexpected role for a class of dopamine receptors in renal epithelial morphogenesis.

BackgroundApolipoprotein E is a glycoprotein best known as a mediator and regulator of lipid transport and uptake. The APOE-ε4 allele has long been associated with increased risks of Alzheimer's disease and mortality, but the effect of the less prevalent APOE-ε2 allele on diseases in the elderly and survival remains elusive.MethodsWe aggregated data of 38,537 individuals of European ancestry (mean age 65.5 years; 55.6% women) from six population-based cohort studies (Rotterdam Study, AGES-Reykjavik Study, Cardiovascular Health Study, Health-ABC Study, and the family-based Framingham Heart Study and Long Life Family Study) to determine the association of APOE, and in particular APOE-ε2, with survival in the population.ResultsDuring a mean follow-up of 11.7 years, 17,021 individuals died. Compared with homozygous APOE-ε3 carriers, APOE-ε2 carriers were at lower risk of death (hazard ratio,95% confidence interval: 0.94,0.90-0.99; P = 1.1*10-2), whereas APOE-ε4 carriers were at increased risk of death (HR 1.17,1.12-1.21; P = 2.8*10-16). APOE was associated with mortality risk in a dose-dependent manner, with risk estimates lowest for homozygous APOE-ε2 (HR 0.89,0.74-1.08), and highest for homozygous APOE-ε4 (HR 1.52,1.37-1.70). After censoring for dementia, effect estimates remained similar for APOE-ε2 (HR 0.95,0.90-1.01), but attenuated for APOE-ε4 (HR 1.07,1.01-1.12). Results were broadly similar across cohorts, and did not differ by age or sex. APOE genotype was associated with baseline lipid fractions (e.g. mean difference(95%CI) in LDL(mg/dL) for ε2 versus ε33: -17.1(-18.1-16.0), and ε4 versus ε33: +5.7(4.8;6.5)), but the association between APOE and mortality was unaltered after adjustment for baseline LDL or cardiovascular disease. Given the European ancestry of the study population, results may not apply to other ethnicities.ConclusionCompared with APOE-ε3, APOE-ε2 is associated with prolonged survival, whereas mortality risk is increased for APOE-ε4 carriers. Further collaborative efforts are needed to unravel the role of APOE and in particular APOE-ε2 in health and disease.

Flooding is one of the most disastrous global hazards, which has been occurring more frequently in recent times. It is observed that climate change is likely to increase the intensity and the frequency of floods and river basins have become more vulnerable to fluvial flooding. In this study, the impact of climate change on fluvial flooding was analyzed over the Adyar sub-basin. This study applied statistically downscaled Global Climate Model (GCM) data in a CMIP5 dataset of IPCC Assessment Report 5 (AR5). Based on the performance to simulate the observed climate, four GCMs, namely, cesm1-cam5, mpi-esm-mr, ncar-ccsm4, and bnu-esm, for RCP 4.5 were selected for projections of the future scenario. The Intensity-Duration-Frequency (IDF) curves for the past and future scenarios were derived from the IMD-observed and GCM-projected rainfall data. Integrated flood modeling was performed with hydrologic (HEC-HMS) and hydraulic (HEC-RAS) models. Finally, in order to visualize the inundation areas according to the future climate projection, flood inundation maps were prepared geospatially using the ArcGIS software. For the 100-year return period, the results predict that the peak discharge for the future climate scenario would increase by 34.3%-91.9% as compared to the present climate scenario. Similarly, the future projections show an increase in the flooded area ranging from 12.6% to 26.4% based on GCMs. This simulation helps in understanding the flood risk over the Adyar sub-basin under the changing climate and the requirement for the regulation of developmental activities over the flood-prone areas.

BackgroundFibroblast growth factor 23 is an emerging vascular biomarker, recently associated with cerebral small vessel disease and poor cognition in patients on dialysis. It also interacts with klotho, an anti-aging and cognition enhancing protein.ObjectiveTo determine if circulating Fibroblast growth factor 23 (FGF23) is associated with new-onset cognitive outcomes in a community-based cohort of cognitively healthy adults with long-term follow-up.MethodsWe measured serum FGF23 levels in 1537 [53% women, mean age 68.7 (SD 5.7)] dementia-free Framingham Offspring participants at their 7th quadrennial examination (1998-2001), and followed these participants for the development of clinical all-cause dementia and Alzheimer's disease (AD). Secondary outcomes included MRI-based structural brain measures, and neurocognitive test performance at exam 7.ResultsDuring a median (Q1, Q3) 12-year (7.0, 13.3) follow up, 122 (7.9%) participants developed dementia, of whom 91 (5.9%) had AD. Proportional-hazards regression analysis, adjusted for age, sex, education, systolic blood pressure, antihypertensive medication, prevalent cardiovascular disease, diabetes mellitus, smoking status and apoE ε4 carrier status, revealed that higher serum FGF23 levels were associated with an increased risk of incident dementia and AD (Hazard ratio [HR] per 1 standard deviation increment in inverse transformed FGF23 level 1.25, 95% CI 1.02-1.53, and 1.32, 95% CI 1.04-1.69, respectively). There was no significant interaction according to presence/absence of significant renal impairment (eGFR ConclusionsHigher circulating FGF23 is associated with an increased risk of dementia, suggesting that FGF23-related biological pathways may play a role in the development of dementia.