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Nerve sheath myxoma is a rare benign tumor of peripheral nerve sheath origin arises from the Schwann cell. In 1969 Harkin and Reed first reported a case of Nerve sheath myxoma. The benign tumor clinically present as a nodular soft tissue swelling. Microscopic features are well circumscribed, varying sized nodules comprising of stellate cells in a myxoid background. The cells show diffuse positivity for S100. Nerve sheath myxoma to be differentiated from Neurothekoma, Myxoid Neurofibroma, Myxoid Schwannoma and Perineuroma.

Soybean is a major legume crop cultivated globally due to the high quality and quantity of its seed protein and oil. However, drought stress is the most significant factor that decreases soybean yield, and more than 90% of US soybean acreage is dependent on rainfall. Water use efficiency (WUE) is positively correlated with the carbon isotopic ratio 13C/12C (C13 ratio) and selecting soybean varieties for high C13 ratio may enhance WUE and help improve tolerance to drought. Our study objective was to identify genetic loci associated with C13 ratio using a diverse set of 205 soybean maturity group IV accessions, and to examine the genomic prediction accuracy of C13 ratio across a range of environments. An accession panel was grown and assessed across seven distinct combinations of site, year and treatment, with five site-years under irrigation and two site-years under drought stress. Genome-wide association mapping (GWAM) analysis identified 103 significant single nucleotide polymorphisms (SNPs) representing 93 loci associated with alterations to C13 ratio. Out of these 93 loci, 62 loci coincided with previous studies, and 31 were novel. Regions tagged by 96 significant SNPs overlapped with 550 candidate genes involved in plant stress responses. These confirmed genomic loci could serve as a valuable resource for marker-assisted selection to enhance WUE and drought tolerance in soybean. This study also demonstrated that genomic prediction can accurately predict C13 ratio across different genotypes and environments and by examining only significant SNPs identified by GWAM analysis, higher prediction accuracies (P ≤ 0.05; 0.51 ≤ r ≤ 0.65) were observed. We generated genomic estimated breeding values for each genotype in the entire USDA-GRIN germplasm collection for which there was marker data. This information was used to identify the top ten extreme genotypes for each soybean maturity group, which could serve as valuable genetic and physiological resources for future breeding and physiological studies.

The challenges and drawbacks of manual weeding and herbicide usage, such as inefficiency, high costs, time-consuming tasks, and environmental pollution, have led to a shift in the agricultural industry toward digital agriculture. The utilization of advanced robotic technologies in the process of weeding serves as prominent and symbolic proof of innovations under the umbrella of digital agriculture. Typically, robotic weeding consists of three primary phases: sensing, thinking, and acting. Among these stages, sensing has considerable significance, which has resulted in the development of sophisticated sensing technology. The present study specifically examines a variety of image-based sensing systems, such as RGB, NIR, spectral, and thermal cameras. Furthermore, it discusses non-imaging systems, including lasers, seed mapping, LIDAR, ToF, and ultrasonic systems. Regarding the benefits, we can highlight the reduced expenses and zero water and soil pollution. As for the obstacles, we can point out the significant initial investment, limited precision, unfavorable environmental circumstances, as well as the scarcity of professionals and subject knowledge. This study intends to address the advantages and challenges associated with each of these sensing technologies. Moreover, the technical remarks and solutions explored in this investigation provide a straightforward framework for future studies by both scholars and administrators in the context of robotic weeding.

Abstract Background The incidence and impact of noise in a subcutaneous implantable cardioverter defibrillator (S‐ICD) after left ventricular assist device (LVAD) implantation is not well established. Methods We performed a retrospective study of patients implanted with LVAD and with a pre‐existing S‐ICD between January 2005 and December 2020 at the three Mayo Clinic centers (Minnesota, Arizona, and Florida). Results Of the 908 LVAD patients, a pre‐existing S‐ICD was present in 9 patients (mean age 49.1 ± 13.7 years, 66.7% males), 100% with Boston Scientific third‐generation EMBLEM MRI S‐ICD, 11% with HeartMate II (HM II), 44% with HeartMate 3 (HM 3), and 44% with HeartWare (HW) LVAD. The incidence of noise from LVAD‐related electromagnetic interference (EMI) was 33% and was only seen with HM 3 LVAD. Multiple measures attempted to resolve noise, including using alternative S‐ICD sensing vector, adjusting S‐ICD time zone, and increasing LVAD pump speed, were unsuccessful, necessitating S‐ICD device therapies to be turned off permanently. Conclusions The incidence of LVAD‐related S‐ICD noise is high in patients with concomitant LVAD and S‐ICD with significant impact on device function. As conservative management failed to resolve the EMI, the S‐ICDs had to be programmed off to avoid inappropriate shocks. This study highlights the importance of awareness of LVAD‐SICD device interference and the need to improve S‐ICD detection algorithms to eliminate noise.

Over the decades, agri-food security has become one of the most critical concerns in the world. Sustainable agri-food production technologies have been reliable in mitigating poverty caused by high demands for food. Recently, the applications of agri-food system technologies have been meaningfully changing the worldwide scene due to both external strengths and internal forces. Digital agriculture (DA) is a pioneering technology helping to meet the growing global demand for sustainable food production. Integrating different sub-branches of DA technologies such as artificial intelligence, automation and robotics, sensors, Internet of Things (IoT) and data analytics into agriculture practices to reduce waste, optimize farming inputs and enhance crop production. This can help shift from tedious operations to continuously automated processes, resulting in increasing agricultural production by enabling the traceability of products and processes. The application of DA provides agri-food producers with accurate and real-time observations regarding different features influencing their productivity, such as plant health, soil quality, weather conditions, and pest and disease pressure. Analyzing the results achieved by DA can help agricultural producers and scholars make better decisions to increase yields, improve efficiency, reduce costs, and manage resources. The core focus of the current work is to clarify the benefits of some sub-branches of DA in increasing agricultural production efficiency, discuss the challenges of practical DA in the field, and highlight the future perspectives of DA. This review paper can open new directions to speed up the DA application on the farm and link traditional agriculture with modern farming technologies.

Abstract Background Atrial fibrillation (AF) is relatively less frequent in younger patients (age

It is clear that new approaches are needed to promote broadly protective immunity to viral pathogens, particularly those that are prone to mutation and escape from antibody-mediated immunity. CD4+ T cells, known to target many viral proteins and highly conserved peptide epitopes, can contribute greatly to protective immunity through multiple mechanisms. Despite this potential, CD4+ T cells are often poorly recruited by current vaccine strategies. Here, we have analyzed a promising new adjuvant (R-DOTAP), as well as conventional adjuvant systems AddaVax with or without an added TLR9 agonist CpG, to promote CD4+ T cell responses to the licensed vaccine Flublok containing H1, H3, and HA-B proteins. Our studies, using a preclinical mouse model of vaccination, revealed that the addition of R-DOTAP to Flublok dramatically enhances the magnitude and functionality of CD4+ T cells specific for HA-derived CD4+ T cell epitopes, far outperforming conventional adjuvant systems based on cytokine EliSpot assays and multiparameter flow cytometry. The elicited CD4+ T cells specific for HA-derived epitopes produce IL-2, IFN-γ, IL-4/5, and granzyme B and have multifunctional potential. Hence, R-DOTAP, which has been verified safe by human studies, can offer exciting opportunities as an immune stimulant for next-generation prophylactic recombinant protein-based vaccines.

Abstract Improving water use efficiency (WUE) for soybean [Glycine max (L.) Merr.] through selection for high carbon isotope (C13) ratio may increase drought tolerance, but increased WUE may limit growth in productive environments. An ideal genotype would be plastic for C13 ratio; that is, be able to alter C13 ratio in response to the environment. Our objective was to identify genomic regions associated with C13 ratio plasticity, C13 ratio stability, and overall C13 ratio in two panels of diverse Maturity Group IV soybean accessions. A second objective was to identify accessions that differed in their C13 ratio plasticity. Panel 1 (205 accessions) was evaluated in seven irrigated and four drought environments, and Panel 2 (373 accessions) was evaluated in four environments. Plasticity was quantified as the slope from regressing C13 ratio of individual genotypes against an environmental index calculated based on the mean within and across environments. The regression intercept was considered a measure of C13 ratio over all environments, and the root mean square error was considered a measure of stability. Combined over both panels, genome‐wide association mapping (GWAM) identified 19 single nucleotide polymorphisms (SNPs) for plasticity, 39 SNPs for C13 ratio, and 16 SNPs for stability. Among these SNPs, 71 candidate genes had annotations associated with transpiration or water conservation and transport, root development, root hair elongation, and stomatal complex morphogenesis. The genomic regions associated with plasticity and stability identified in the current study will be a useful resource for implementing genomic selection for improving drought tolerance in soybean.

Hydroponic fodder production in controlled environment (CE) settings have gained more focus in recent years due to the shortage of agricultural land for food production and the adverse effect of climate changes. However, the operation costs and dry matter issues are the major concerns for the sustainability of fodder production in the CE. This study provides a comprehensive literature review on techniques and control strategies for indoor environments and watering that are currently used and could be adopted in the future to achieve the economic and environmental sustainability of controlled environment fodder production (CEFP). The literature indicates fodder production in the modular system is becoming popular in developed countries, and low-tech systems like greenhouse are more prevalent in developing countries. The optimum temperature and RH range between 16-27°C and 70-80% to get efficient biomass yield; however, minimal research has been conducted to optimize the indoor temperature and relative humidity (RH) for efficient and higher efficiency fodder production. Besides, the water-saving techniques and optimal lighting spectrum need to be studied extensively. Automating and monitoring in CEFP system could reduce operating costs and improve quality and yield. Overall, this industry might have great potential for livestock production. Still, more strong research needs to be conducted to answer nutritional concerns and reduce the capital and operating costs for CEFP.

Objective: To develop an artificial intelligence (AI)–enabled electrocardiogram (ECG) algorithm capable of comprehensive, human-like ECG interpretation and compare its diagnostic performance against conventional ECG interpretation methods. Methods: We developed a novel AI-enabled ECG (AI-ECG) algorithm capable of complete 12-lead ECG interpretation. It was trained on nearly 2.5 million standard 12-lead ECGs from over 720,000 adult patients obtained at the Mayo Clinic ECG laboratory between 2007 and 2017. We then compared the need for human over-reading edits of the reports generated by the Marquette 12SL automated computer program, AI-ECG algorithm, and final clinical interpretations on 500 randomly selected ECGs from 500 patients. In a blinded fashion, 3 cardiac electrophysiologists adjudicated each interpretation as (1) ideal (ie, no changes needed), (2) acceptable (ie, minor edits needed), or (3) unacceptable (ie, major edits needed). Results: Cardiologists determined that on average 202 (13.5%), 123 (8.2%), and 90 (6.0%) of the interpretations required major edits from the computer program, AI-ECG algorithm, and final clinical interpretations, respectively. They considered 958 (63.9%), 1058 (70.5%), and 1118 (74.5%) interpretations as ideal from the computer program, AI-ECG algorithm, and final clinical interpretations, respectively. They considered 340 (22.7%), 319 (21.3%), and 292 (19.5%) interpretations as acceptable from the computer program, AI-ECG algorithm, and final clinical interpretations, respectively. Conclusion: An AI-ECG algorithm outperforms an existing standard automated computer program and better approximates expert over-read for comprehensive 12-lead ECG interpretation.

Understanding the mechanisms behind chemical susceptibility differences is key to protecting sensitive populations. However, elucidating gene-environment interactions (GxE) presents a daunting challenge. While mammalian models have proven useful, problems with scalability to an enormous chemical exposome and clinical translation faced by all models remain; therefore, alternatives are needed. Zebrafish (Danio rerio) have emerged as an excellent model for investigating GxE. This study used a combined bioinformatic and experimental approach to probe the mechanisms underlying chemical susceptibility differences in a genetically diverse zebrafish population. Starting from high-throughput screening (HTS) data, a genome-wide association study (GWAS) using embryonic fish exposed to 0.6 μM Abamectin revealed significantly different effects between individuals. A hypervariable region with two distinct alleles–one with G at the SNP locus (GG) and one with a T and the 16 bp deletion (TT)–associated with differential susceptibility was found. Sensitive fish had significantly lower sox7 expression. Due to their location and the observed expression differences, we hypothesized that these sequences differentially regulate sox7. A luciferase reporter gene assay was used to test if these sequences, alone, could lead to expression differences. The TT allele showed significantly lower expression than the GG allele in MCF-7 cells. To better understand the mechanism behind these expression differences, predicted transcription factor binding differences between individuals were compared in silico, and several putative binding differences were identified. EMSA was used to test for binding differences in whole embryo protein lysate to investigate these TF binding predictions. We confirmed that the GG sequence is bound to protein in zebrafish. Through a competition EMSA using an untagged oligo titration, we confirmed that the GG oligo had a higher binding affinity than the TT oligo, explaining the observed expression differences. This study identified differential susceptibility to chemical exposure in a genetically diverse population, then identified a plausible mechanism behind those differences from a genetic to molecular level. Thus, an HTS-compatible zebrafish model is valuable and adaptable in identifying GxE mechanisms behind susceptibility differences to chemical exposure.

Aluminum alloys with ceramic reinforced particulates are made prospective in aerospace, transportation, and industrial applications ampler to their low mass density, stiffness, and high specific strength. In this work, Aluminium Alloy(AA) 7010 - TiB2 (Titanium Diboride) composites with different amounts of reinforcement (5, 7.5 and 10 wt.%) were produced by the exothermic reaction of halide salts K2TiF6 and KBF4 added in 120% excess to the stoichiometric ratio with molten AA7010.The effect and dispersion of TiB2 particulates in AA7010 were analyzed by microstructural, mechanical and corrosion behavior. The dispersion of reinforcement in the matrix alloy was analyzed by optical microscope and field emission scanning electron microscope (FESEM) images. X-ray diffraction patterns of the prepared composites reveal the formation of TiB2 particles in the matrix alloy. Indeed samples are tested according to ASTM G34 standard for ex- foliation corrosion rate by weight loss method. The result shows improved hardness, tensile strength and yield strength of composites to about 35%, 260%, and 240% respectively. The mechanical and corrosion resistance of 10% TiB2 shows better results compared with matrix alloy and other concentrations of reinforcements.

Background: Persistent elevation of serum parathyroid hormone (PTH) despite normocalcemia have been documented in 8- 40% of patients after parathyroidectomy. We hereby report our experience from different centers across India to determine clinical significance of postoperatively elevated PTH levels and review relevant literature. Methods: We conducted a retrospective case series study and reviewed all the patients who underwent surgery for primary hyperparathyroidism (PHPT) from April 2010 to January 2020. Results: Total of 201 patients was diagnosed as PHPT. Out of available follow-up data of 180 patients, a total of 54 patients (30%) had persistently elevated PTH (PePTH) at 1 month. Patients with PePTH were older with higher preoperative serum calcium, iPTH, alkaline phosphatase and lower serum phosphate and 25-hydroxy vitamin D3 levels. Creatinine clearance was found to be significantly lower in patients with PePTH. Multiple linear regression analysis revealed that preoperative 25-OH D3 concentration, creatinine clearance and iPTH are the factors influencing persistent elevation of PTH levels. Significantly lower serum calcium and higher alkaline phosphatase levels were observed in PePTH patients with preoperative 25-OH D3 levels

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor involved in regulating a wide range of biological responses. A diverse array of xenobiotics and endogenous small molecules bind to the receptor and drive unique phenotypic responses. Due in part to its role in mediating toxic responses to environmental pollutants, AhR activation has not been traditionally viewed as a viable therapeutic approach. Nonetheless, the expression and activation of AhR can inhibit the proliferation, migration, and survival of cancer cells, and many clinically approved drugs transcriptionally activate AhR. Identification of novel select modulators of AhR-regulated transcription that promote tumor suppression is an active area of investigation. The development of AhR-targeted anticancer agents requires a thorough understanding of the molecular mechanisms driving tumor suppression. Here, we summarized the tumor-suppressive mechanisms regulated by AhR with an emphasis on the endogenous functions of the receptor in opposing carcinogenesis. In multiple different cancer models, the deletion of AhR promotes increased tumorigenesis, but a precise understanding of the molecular cues and the genetic targets of AhR involved in this process is lacking. The intent of this review was to synthesize the evidence supporting AhR-dependent tumor suppression and distill insights for development of AhR-targeted cancer therapeutics.

Atrial Fibrillation (AF) is the most common cardiac arrhythmia. Signal-processing approaches are widely used for the analysis of intracardiac electrograms (iEGMs), which are collected during catheter ablation from patients with AF. In order to identify possible targets for ablation therapy, dominant frequency (DF) is widely used and incorporated in electroanatomical mapping systems. Recently, a more robust measure, multiscale frequency (MSF), for iEGM data analysis was adopted and validated. However, before completing any iEGM analysis, a suitable bandpass (BP) filter must be applied to remove noise. Currently, no clear guidelines for BP filter characteristics exist. The lower bound of the BP filter is usually set to 3–5 Hz, while the upper bound (BP¯th) of the BP filter varies from 15 Hz to 50 Hz according to many researchers. This large range of BP¯th subsequently affects the efficiency of further analysis. In this paper, we aimed to develop a data-driven preprocessing framework for iEGM analysis, and validate it based on DF and MSF techniques. To achieve this goal, we optimized the BP¯th using a data-driven approach (DBSCAN clustering) and demonstrated the effects of different BP¯th on subsequent DF and MSF analysis of clinically recorded iEGMs from patients with AF. Our results demonstrated that our preprocessing framework with BP¯th = 15 Hz has the best performance in terms of the highest Dunn index. We further demonstrated that the removal of noisy and contact-loss leads is necessary for performing correct data iEGMs data analysis.

Adjuvants are essential components of subunit vaccines added to enhance immune responses to antigens through immunomodulation. Very few adjuvants have been approved for human use by regulatory agencies due to safety concerns. Current subunit vaccine adjuvants approved for human use are very effective in promoting humoral immune responses but are less effective at promoting T-cell immunity. In this study, we evaluated a novel pure enantio-specific cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (R-DOTAP) as an immunomodulator for subunit vaccines capable of inducing both humoral- and cellular-mediated immunity. Using recombinant protein antigens derived from SARS-CoV2 spike or novel computationally optimized broadly reactive influenza antigen (COBRA) proteins, we demonstrated that R-DOTAP nanoparticles promoted strong cellular- and antibody-mediated immune responses in both monovalent and bivalent vaccines. R-DOTAP-based vaccines induced antigen-specific and polyfunctional CD8+ and CD4+ effector T cells and memory T cells, respectively. Antibody responses induced by R-DOTAP showed a balanced Th1/Th2 type immunity, neutralizing activity and protection of mice from challenge with live SARS-CoV2 or influenza viruses. R-DOTAP also facilitated significant dose sparing of the vaccine antigens. These studies demonstrate that R-DOTAP is an excellent immune stimulator for the production of next-generation subunit vaccines containing multiple recombinant proteins.

It is clear that new approaches are needed to promote broadly protective immunity to viral pathogens, particularly those that are prone to mutation and escape from antibody-mediated immunity. Prototypic pathogens of this type are influenza and SARS-CoV-2, where the receptor-binding protein exhibits extremely high variability in its receptor-binding regions. T cells, known to target many viral proteins, and within these, highly conserved peptide epitopes, can contribute greatly to protective immunity through multiple mechanisms but are often poorly recruited by current vaccine strategies. Here, we have studied a promising novel pure enantio-specific cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (R-DOTAP), which was previously recognized for its ability to generate anti-tumor immunity through the induction of potent cytotoxic CD8 T cells. Using a preclinical mouse model, we have assessed an R-DOTAP nanoparticle adjuvant system for its ability to promote CD4 T cell responses to vaccination with recombinant influenza protein. Our studies revealed that R-DOTAP consistently outperformed a squalene-based adjuvant emulsion, even when it was introduced with a potent TLR agonist CpG, in the ability to elicit peptide epitope-specific CD4 T cells when quantified by IFN-γ and IL-2 ELISpot assays. Clinical testing of R-DOTAP containing vaccines in earlier work by others has demonstrated an acceptable safety profile. Hence, R-DOTAP can offer exciting opportunities as an immune stimulant for next-generation prophylactic recombinant protein-based vaccines.

Background: Response rates for cardiac resynchronization therapy (CRT) in patients without intrinsic left bundle-branch block (LBBB) morphology are poor.Objective: We sought to develop a nomogram model to predict response to CRT in patients without intrinsic LBBB.Methods: We searched electronic health records for patients without intrinsic LBBB who underwent CRT at Mayo Clinic. Logistic regression and Cox proportional hazards regression analysis were performed for the odds of response to CRT and risk of death, respectively. Results were used to develop the nomogram model.Results: 761 patients without intrinsic LBBB were identified. Six months after CRT, 47.8% of patients demonstrated improvement of left ventricular ejection fraction by more than 5%. The 1-, 3-, and 5-year survival rates were 95.9, 82.4, and 66.70%, respectively. Patients with CRT upgrade from pacemaker [odds ratio (OR), 1.67 (95% CI, 1.05–2.66)] or atrioventricular node (AVN) ablation [OR, 1.69 (95% CI, 1.09–2.64)] had a greater odds of CRT response than those patients who had new implant, or who did not undergo AVN ablation. Patients with right bundle-branch block had a low response rate (39.2%). Patients undergoing AVN ablation had a lower mortality rate than those without ablation [hazard ratio, 0.65 (95% CI, 0.46–0.91)]. Eight clinical variables were automatically selected to build a nomogram model and predict CRT response. The model had an area under the receiver operating characteristic curve of 0.71 (95% CI, 0.63–0.78).Conclusions: Among patients without intrinsic LBBB undergoing CRT, upgrade from pacemaker and AVN ablation were favorable factors in achieving CRT response and better long-term outcomes.

False smut disease (FSD) of rice incited by Ustilaginoidea virens is an emerging threat to paddy cultivation worldwide. We investigated the spatial distribution of FSD in different paddy ecosystems of South Indian states, viz., Andhra Pradesh, Karnataka, Tamil Nadu, and Telangana, by considering the exploratory data from 111 sampling sites. Point pattern and surface interpolation analyses were carried out to identify the spatial patterns of FSD across the studied areas. The spatial clusters of FSD were confirmed by employing spatial autocorrelation and Ripley’s K function. Further, ordinary kriging (OK), indicator kriging (IK), and inverse distance weighting (IDW) were used to create spatial maps by predicting the values at unvisited locations. The agglomerative hierarchical cluster analysis using the average linkage method identified four main clusters of FSD. From the Local Moran’s I statistic, most of the areas of Andhra Pradesh and Tamil Nadu were clustered together (at I > 0), except the coastal and interior districts of Karnataka (at I < 0). Spatial patterns of FSD severity were determined by semi-variogram experimental models, and the spherical model was the best fit. Results from the interpolation technique, the potential FSD hot spots/risk areas were majorly identified in Tamil Nadu and a few traditional rice-growing ecosystems of Northern Karnataka. This is the first intensive study that attempted to understand the spatial patterns of FSD using geostatistical approaches in India. The findings from this study would help in setting up ecosystem-specific management strategies to reduce the spread of FSD in India.

Drought causes significant soybean [Glycine max (L.) Merr.] yield losses each year in rain-fed production systems of many regions. Genetic improvement of soybean for drought tolerance is a cost-effective approach to stabilize yield under rain-fed management. The objectives of this study were to confirm previously reported soybean loci and to identify novel loci associated with canopy wilting (CW) using a panel of 200 diverse maturity group (MG) IV accessions. These 200 accessions along with six checks were planted at six site-years using an augmented incomplete block design with three replications under irrigated and rain-fed treatments. Association mapping, using 34,680 single nucleotide polymorphisms (SNPs), identified 188 significant SNPs associated with CW that likely tagged 152 loci. This includes 87 SNPs coincident with previous studies that likely tagged 68 loci and 101 novel SNPs that likely tagged 84 loci. We also determined the ability of genomic estimated breeding values (GEBVs) from previous research studies to predict CW in different genotypes and environments. A positive relationship (P ≤ 0.05;0.37 ≤ r ≤ 0.5) was found between observed CW and GEBVs. In the vicinity of 188 significant SNPs, 183 candidate genes were identified for both coincident SNPs and novel SNPs. Among these 183 candidate genes, 57 SNPs were present within genes coding for proteins with biological functions involved in plant stress responses. These genes may be directly or indirectly associated with transpiration or water conservation. The confirmed genomic regions may be an important resource for pyramiding favorable alleles and, as candidates for genomic selection, enhancing soybean drought tolerance.

Abstract Background Atrial fibrillation (AF) among patients with heart failure with reduced ejection fraction (HFrEF) is associated with adverse clinical outcomes. Our primary aim was to evaluate patient‐centered outcomes and surrogate outcomes following catheter ablation (CA) of AF among patients with HFrEF compared to standard medical therapy with or without device therapy (atrioventricular node ablation and cardiac resynchronization therapy). Methods A systematic literature review was performed limiting our searches to randomized control trials reporting outcomes of CA compared to standard medical therapy with or without device therapy were included. Patient‐centered outcomes were relative reduction in all‐cause mortality, heart failure readmissions, and recurrence of AF. Surrogate outcomes of interest were change in ejection fraction, change in peak oxygen consumption, reduction in brain natriuretic peptide levels, change in 6‐minute walk distance, and change in Minnesota living with heart failure score. Results Seven randomized control trials (Patient n = 721) met our inclusion criteria. All trials used radiofrequency energy for CA of AF. CA for AF was associated with significantly lower all‐cause mortality (Risk ratio [RR] = 0.52, 95% confidence interval [CI] = 0.35‐0.76, P = 0.001, I2 = 0%), lower rate of heart failure readmission (RR = 0.58, 95% CI = 0.46‐0.74, P

The diet represents one environmental risk factor controlling the progression of type 1 diabetes (T1D) in genetically susceptible individuals. Consequently, understanding which specific nutritional components promote or prevent the development of disease could be used to make dietary recommendations in prediabetic individuals. In the current study, we hypothesized that the immunoregulatory phytochemcial, indole-3-carbinol (I3C) which is found in cruciferous vegetables, will regulate the progression of T1D in nonobese diabetic (NOD) mice. During digestion, I3C is metabolized into ligands for the aryl hydrocarbon receptor (AhR), a transcription factor that when systemically activated prevents T1D. In NOD mice, an I3C-supplemented diet led to strong AhR activation in the small intestine but minimal systemic AhR activity. In the absence of this systemic response, the dietary intervention led to exacerbated insulitis. Consistent with the compartmentalization of AhR activation, dietary I3C did not alter T helper cell differentiation in the spleen or pancreatic draining lymph nodes. Instead, dietary I3C increased the percentage of CD4+RORγt+Foxp3- (Th17 cells) in the lamina propria, intraepithelial layer, and Peyer’s patches of the small intestine. The immune modulation in the gut was accompanied by alterations to the intestinal microbiome, with changes in bacterial communities observed within one week of I3C supplementation. A transkingdom network was generated to predict host-microbe interactions that were influenced by dietary I3C. Within the phylum Firmicutes, several genera (Intestinimonas, Ruminiclostridium 9, and unclassified Lachnospiraceae) were negatively regulated by I3C. Using AhR knockout mice, we validated that Intestinimonas is negatively regulated by AhR. I3C-mediated microbial dysbiosis was linked to increases in CD25high Th17 cells. Collectively, these data demonstrate that site of AhR activation and subsequent interactions with the host microbiome are important considerations in developing AhR-targeted interventions for T1D.

The present study aimed at investigating scientific irrigation scheduling (SIS) for the sustainable production of olive groves. The SIS allows farmers to schedule water rotation in their fields to abate crop water stress and maximize yields, which could be achieved through the precise monitoring of soil moisture. For this purpose, the study used three kinds of soil moisture sensors, including tensiometer sensors, irrometer sensors, and gypsum blocks for precise measurement of the soil moisture. These soil moisture sensors were calibrated by performing experiments in the field and laboratory at Barani Agricultural Research Institute, Chakwal in 2018 and 2019. The calibration curves were obtained by performing gravimetric analysis at 0.3 and 0.6 m depths, thereby equations were developed using regression analysis. The coefficient of determination (R2) at 0.3 and 0.6 m depth for tensiometer, irrometer, and gypsum blocks was found to be equal to 0.98, 0.98; 0.75, 0.89; and 0.82, and 0.95, respectively. After that, a drip irrigation system was installed with the calibrated soil moisture sensors at 0.3 and 0.6 m depth to schedule irrigation for production of olive groves as compared to conventional farmer practice, thereby soil moisture profiles of these sensors were obtained to investigate the SIS. The results showed that the irrometer sensor performed as expected and contributed to the irrigation water savings between 17% and 25% in 2018 and 2019, respectively, by reducing the number of irrigations as compared toother soil moisture sensors and farmer practices. Additionally, olive yield efficiencies of 8% and 9%were observed by the tensiometer in 2018 and 2019, respectively. The outcome of the study suggests that an effective method in providing sustainable production of olive groves and enhancing yield efficiency.

Vision loss is a major complication in common ocular infections and diseases such as bacterial keratitis, age-related macular degeneration (AMD) and diabetic retinopathy (DR). The prevalence of such ophthalmic diseases represents an urgent need to develop safe, effective, and long-term treatments. Current therapies are riddled with drawbacks and limitations which calls for the exploration of alternative drug delivery mechanisms. Toxicity of the inorganic metals and metal oxides used for drug delivery raise safety concerns that are alleviated with the alternate use of, a natural and organic polymer which is both biocompatible and environmentally friendly. Carbon dots (CDs) represent a great potential in novel biomedical applications due to their tunable fluorescence, biocompatibility, and ability to be conjugated with diverse therapeutic materials. There is a growing interest on the exploitation of these properties for drug delivery with enhanced bio-imaging. However, there are limited reports of CD applications for ophthalmic indications. In this review, we focus on the CD potential and the development of translational therapies for ophthalmic diseases. The current review presents better understanding of fabrication of CDs and how it may be useful in delivering anti-bacterial agents, anti-VEGF molecules as well as imaging for ophthalmic applications.

Phytophthora meadii (McRae) is a hemibiotrophic oomycete fungus that infects tender nuts, growing buds, and crown regions, resulting in fruit, bud, and crown rot diseases in arecanut (Areca catechu L.), respectively. Among them, fruit rot disease (FRD) causes serious economic losses that are borne by the growers, making it the greatest yield-limiting factor in arecanut crops. FRD has been known to occur in traditional growing areas since 1910, particularly in Malnad and coastal tracts of Karnataka. Systemic surveys were conducted on the disease several decades ago. The design of appropriate management approaches to curtail the impacts of the disease requires information on the spatial distribution of the risks posed by the disease. In this study, we used exploratory survey data to determine areas that are most at risk. Point pattern (spatial autocorrelation and Ripley’s K function) analyses confirmed the existence of moderate clustering across sampling points and optimized hotspots of FRD were determined. Geospatial techniques such as inverse distance weighting (IDW), ordinary kriging (OK), and indicator kriging (IK) were performed to predict the percent severity rates at unsampled sites. IDW and OK generated identical maps, whereby the FRD severity rates were higher in areas adjacent to the Western Ghats and the seashore. Additionally, IK was used to identify both disease-prone and disease-free areas in Karnataka. After fitting the semivariograms with different models, the exponential model showed the best fit with the semivariogram. Using this model information, OK and IK maps were generated. The identified FRD risk areas in our study, which showed higher disease probability rates (>20%) exceeding the threshold level, need to be monitored with the utmost care to contain and reduce the further spread of the disease in Karnataka.

Abstract Brain-derived neurotrophic factor (BDNF), a key player in regulating synaptic strength and learning, is dysregulated following traumatic brain injury (TBI), suggesting that stimulation of BDNF signaling pathways may facilitate functional recovery. This study investigates whether CN2097, a peptidomimetic ligand which targets the synaptic scaffold protein, postsynaptic density protein 95, to enhance downstream signaling of tropomyosin-related kinase B, a receptor for BDNF, can improve neurological function after TBI. Moderate to severe TBI elicits neuroinflammation and c-Jun-N-terminal kinase (JNK) activation, which is associated with memory deficits. Here we demonstrate that CN2097 significantly reduces the post-traumatic synthesis of proinflammatory mediators and inhibits the post-traumatic activation of JNK in a rodent model of TBI. The recordings of field excitatory post-synaptic potentials in the hippocampal CA1 subfield demonstrate that TBI inhibits the expression of long-term potentiation (LTP) evoked by high-frequency stimulation of Schaffer collaterals, and that CN2097 attenuates this LTP impairment. Lastly, we demonstrate that CN2097 significantly improves the complex auditory processing deficits, which are impaired after injury. The multifunctionality of CN2097 strongly suggests that CN2097 could be highly efficacious in targeting complex secondary injury processes resulting from neurotrauma.

Ewing's sarcoma is the second most common malignancy of bone among children. It commonly affects the diaphysial region of long bones, while small bones of hands and foot are rarely affected. We report a case of calcaneal Ewing's sarcoma which was misdiagnosed as fungal chronic osteomyelitis and treated inappropriately. High index of suspicion is required in diagnosing tumors at rare sites to avoid undue delay in initiating appropriate therapy.

In order to develop new cancer therapeutics, rapid, reliable, and relevant biological models are required to screen and validate drug candidates for both efficacy and safety. In recent years, the zebrafish (Danio rerio) has emerged as an excellent model organism suited for these goals. Larval fish or immunocompromised adult fish are used to engraft human cancer cells and serve as a platform for screening potential drug candidates. With zebrafish sharing ~80% of disease-related orthologous genes with humans, they provide a low cost, high-throughput alternative to mouse xenografts that is relevant to human biology. In this review, we provide background on the methods and utility of zebrafish xenograft models in cancer research.

Purpose: This article proposes and empirically tests the country of market (COMK) effect, which captures the consumer’s responses of home market to a country where the product is marketed. Design/methodology/approach: Study 1 applies a lab experiment about Chinese consumers’ purchase intention for printers marketed either in the US or China. Study 2 applies country level data to examine the impact of economic development of 22 host countries on the performance of 167 multinational retailers in their home country. Findings: Study 1 shows that the printers marketed in US attract a higher level of purchase intention than printers marketed in China. This COMK effect is more salient for printers manufactured in China than those manufactured in US. In addition, innovation and design factors corresponding to the host country’s image fully mediate the COMK effect. Results in Study 2 show that a retailer that markets its services in a host country with a higher (lower) level of economic development is likely to generate higher (lower) level of retailing performance in its home country. Furthermore, it is found that COMK effect is diminished as the level of economic development of a vendor’s home country increases. Research limitations/implications: In addition to the cognitive components of country image (e.g., design and innovation), consumers’ affective components may also influence the COMK effect. Future research could discuss the impact of consumer ethnocentrism and consumer animosity on consumers’ attitude towards the product marketed in other countries. Practical implications: Strategically, marketing products to a country with a favorable image could benefit vendors from an emerging economy. For manufacturers from developed countries, marketing a product within their own countries may enhance the associated innovation and design images while marketing the same product in an emerging market. Originality/value: This article proposes and tests a demand side country effect on consumers’ purchase intention for products marketed in other countries. It is in sharp contrast to the traditional country effect which focuses on the supply side effect (e.g., country of origin, country of manufacture, country of assembly etc.)

We present a case of incessant wide-complex tachycardia in a patient with left-ventricular assist device, and discuss the differential diagnosis with an in-depth analysis of the intracardiac tracings during the invasive electrophysiologic study, including interpretation of the relative timing of the fascicular signals during tachycardia and in sinus rhythm, and interpretation of pacing and entrainment maneuvers.

Optimum microclimate parameters, including air temperature (T), relative humidity (RH) and vapor pressure deficit (VPD) that are uniformly distributed inside greenhouse crop production systems are essential to prevent yield loss and fruit quality. The objective of this research was to determine the spatial and temporal variations in the microclimate data of a commercial greenhouse with tomato plants located in the mid-west of Iran. For this purpose, wireless sensor data fusion was incorporated with a membership function model called Optimality Degree (OptDeg) for real-time monitoring and dynamic assessment of T, RH and VPD in different light conditions and growth stages of tomato. This approach allows growers to have a simultaneous projection of raw data into a normalized index between 0 and 1. Custom-built hardware and software based on the concept of the Internet-of-Things, including Low-Power Wide-Area Network (LoRaWAN) transmitter nodes, a multi-channel LoRaWAN gateway and a web-based data monitoring dashboard were used for data collection, data processing and monitoring. The experimental approach consisted of the collection of meteorological data from the external environment by means of a weather station and via a grid of 20 wireless sensor nodes distributed in two horizontal planes at two different heights inside the greenhouse. Offline data processing for sensors calibration and model validation was carried in multiple MATLAB Simulink blocks. Preliminary results revealed a significant deviation of the microclimate parameters from optimal growth conditions for tomato cultivation due to the inaccurate timer-based heating and cooling control systems used in the greenhouse. The mean OptDeg of T, RH and VPD were 0.67, 0.94, 0.94 in January, 0.45, 0.36, 0.42 in June and 0.44, 0.0, 0.12 in July, respectively. An in-depth analysis of data revealed that averaged OptDeg values, as well as their spatial variations in the horizontal profile were closer to the plants’ comfort zone in the cold season as compared with those in the warm season. This was attributed to the use of heating systems in the cold season and the lack of automated cooling devices in the warm season. This study confirmed the applicability of using IoT sensors for real-time model-based assessment of greenhouse microclimate on a commercial scale. The presented IoT sensor node and the Simulink model provide growers with a better insight into interpreting crop growth environment. The outcome of this research contributes to the improvement of closed-field cultivation of tomato by providing an integrated decision-making framework that explores microclimate variation at different growth stages in the production season.

Drug delivery to the anterior and posterior segment of eye remains a challenge. Nanoparticle-mediated drug delivery has indicated some promise. The presented review aims to summarize recent advancements in chitosan-based nanotherapies for ocular drug delivery and the challenges encountered during the process. Significant research using chitosan, a cationic linear polymer, is being conducted for ocular drug delivery. A vast number of publications exploit the mucoadhesive properties of the polymer, which arise due to interactions between the amino acids of chitosan and the sialic acid residues in mucous. The high degree of crosslinking in chitosan nanoparticles facilitates a dramatic increase in ocular drug retention of the desired drug, which subsequently helps in ocular penetration and improving the bioavailability of the drugs. A noted decrease in the initial burst of the drug is the basis for developing sustained drug release formulation using biodegradable and biocompatible chitosan polymer. In vitro as well as in vivo studies have indicated enhancement in the uptake, accumulation, and removal of chitosan nanoparticles from the site of delivery. In summary, chitosan- or modified-chitosan-based nanoparticles are being widely tested as drug carriers for treatment of bacterial and viral infections, glaucoma, age-related macular degeneration, and diabetic retinopathy.

Environmental concerns are growing about excessive applying nitrogen (N) fertilizers, especially in oil palm. Some conventional methods which are used to assess the amount of nutrient in oil palm are time-consuming, expensive, and involve frond destruction. Remote sensing as a non-destructive, affordable, and efficient method is widely used to detect the concentration of chlorophyll (Chl) from canopy plants using several vegetation indices (VIs) because there is an influential relation between the concentration of N in the leaves and canopy Chl content. The objectives of this research are to (i) evaluate and compare the performance of various vegetation indices (VIs) for measuring N status in oil palm canopy using SPOT-7 imagery (AIRBUS Defence & Space, Ottobrunn, Germany) to (ii) develop a regression formula that can predict the N content using satellite data to (iii) assess the regression formula performance on testing datasets by testing the coefficient of determination between the predicted and measured N contents. SPOT-7 was acquired in a 6-ha oil palm planted area in Pahang, Malaysia. To predict N content, 28 VIs based on the spectral range of SPOT-7 satellite images were evaluated. Several regression models were applied to determine the highest coefficient of determination between VIs and actual N content from leaf sampling. The modified soil-adjusted vegetation index (MSAVI) generated the highest coefficient of determination (R2 = 0.93). MTVI1 and triangular VI had the highest second and third coefficient of determination with N content (R2 = 0.926 and 0.923, respectively). The classification accuracy assessment of the developed model was evaluated using several statistical parameters such as the independent t-test, and p-value. The accuracy assessment of the developed model was more than 77%.

Resveratrol (3, 4′, 5-trihydroxy-trans-stilbene) is a natural phytoalexin found in grapes and has long been thought to be the answer to the “French Paradox.” There is no shortage of preclinical and clinical studies investigating the broad therapeutic activity of resveratrol. However, in spite of many comprehensive reviews published on the bioactivity of resveratrol, there has yet to be a report focused on the variety and complexity of its structural binding properties, and its multi-targeted role. An improved understanding of disease mechanisms at the systems level has enabled targeted polypharmacology to mature into a rational drug discovery approach. Unlike traditional hit-to-lead campaigns that typically optimize activity and selectivity for a single target, polypharmacological drugs aim to selectively target multiple proteins, while avoiding critical off target interactions. This strategy bears promise of improved efficacy and reduced clinical attrition. This review seeks to investigate whether the bioactivity of resveratrol is due to a polypharmacological effect or promiscuity of the phenolic small molecule by examining the modes of binding with its diverse collection of protein targets. We focused on annotated targets, identified via the ChEMBL database, and matched these targets to a representative structure deposited in the Protein Data Bank (PDB), as crystal structures are most informative in understanding modes of binding at the atomic level. We discuss the structural aspects of resveratrol itself that permits binding to multiple proteins in various signaling pathways. Furthermore, we suggest that resveratrol’s bioactivity is a result of scaffold promiscuity rather than polypharmacology, and the variety of binding modes across targets display little similarity in the pattern of target interaction.

Objectives: With recent advances in nanoparticle manufacturing and applications, potential exposure to nanoparticles in various settings is becoming increasing likely. No investigation has yet been performed to assess whether respiratory tract exposure to cerium oxide (CeO2) nanoparticles is associated with alterations in protein signaling, inflammation, and apoptosis in rat lungs. Methods: Specific-pathogen-free male Sprague-Dawley rats were instilled with either vehicle (saline) or CeO2 nanoparticles at a dosage of 7.0 mg/kg and euthanized 1, 3, 14, 28, 56, or 90 days after exposure. Lung tissues were collected and evaluated for the expression of proteins associated with inflammation and cellular apoptosis. Results: No change in lung weight was detected over the course of the study; however, cerium accumulation in the lungs, gross histological changes, an increased Bax to Bcl-2 ratio, elevated cleaved caspase-3 protein levels, increased phosphorylation of p38 MAPK, and diminished phosphorylation of ERK-1/2-MAPK were detected after CeO2 instillation (p

Background: Depression is most common among psychiatric disorders and with well documented impact on diabetes mellitus outcome. Aims: To assess psychosocial profile and prevalence of depression in subjects with complicated and uncomplicated diabetes mellitus. Methods: This is a cross sectional study of 80 subjects, categorized into two subgroups of diabetes and were administrated ICD 10 criteria for depression after taking informed consent. The sociodemographic profile and psychiatric morbidity of the two groups were analyzed statistically. Results: Statistically significant differences were found between the two groups in sociodemographic factors like age, marital, educational, socioeconomic, employment status and living situations. All the symptom variables of depression with exception of decreased appetite had shown ‘p‘ value of 0.001 which was highly significant suggesting significant presence of depression and meeting criteria for depression in complicated group when compared with uncomplicated group. The prevalence of depression was found to be 72.5% in complicated group and 15% in uncomplicated group. Conclusion: Depression is common co morbidity in diabetes mellitus. The determinants of psychosocial demographic factors influence the outcome of diabetes mellitus.

Glucosinolates (GLS) are a group of plant secondary metabolites mainly found in Cruciferous plants, share a core structure consisting of a β-thioglucose moiety and a sulfonated oxime, but differ by a variable side chain derived from one of the several amino acids. These compounds are hydrolyzed upon cell damage by thioglucosidase (myrosinase), and the resulting degradation products are toxic to many pathogens and herbivores. Human beings use these compounds as flavor compounds, anti-carcinogens, and bio-pesticides. GLS metabolism is complexly linked to auxin homeostasis. Indole GLS contributes to auxin biosynthesis via metabolic intermediates indole-3-acetaldoxime (IAOx) and indole-3-acetonitrile (IAN). IAOx is proposed to be a metabolic branch point for biosynthesis of indole GLS, IAA, and camalexin. Interruption of metabolic channeling of IAOx into indole GLS leads to high-auxin production in GLS mutants. IAN is also produced as a hydrolyzed product of indole GLS and metabolized to IAA by nitrilases. In this review, we will discuss current knowledge on involvement of GLS in auxin homeostasis.

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates the expression of a diverse group of genes. Exogenous AHR ligands include the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which is a potent agonist, and the synthetic AHR antagonist N-2-(1H-indol-3yl)ethyl)-9-isopropyl-2- (5-methylpyridin-3-yl)-9H-purin-6-amine (GNF351). As no experimentally determined structure of the ligand binding domain exists, homology models have been utilized for virtual ligand screening (VLS) to search for novel ligands. Here, we have developed an “agonist-optimized” homology model of the human AHR ligand binding domain, and this model aided in the discovery of two human AHR agonists by VLS. In addition, we performed molecular dynamics simulations of an agonist TCDD-bound and antagonist GNF351-bound version of this model in order to gain insights into the mechanics of the AHR ligand-binding pocket. These simulations identified residues 307–329 as a flexible segment of the AHR ligand pocket that adopts discrete conformations upon agonist or antagonist binding. This flexible segment of the AHR may act as a structural switch that determines the agonist or antagonist activity of a given AHR ligand.

The aging and elderly population are particularly susceptible to cardiovascular disease. Age is an independent risk factor for cardiovascular disease (CVD) in adults, but these risks are compounded by additional factors, including frailty, obesity, and diabetes. These factors are known to complicate and enhance cardiac risk factors that are associated with the onset of advanced age. Sex is another potential risk factor in aging adults, given that older females are reported to be at a greater risk for CVD than age-matched men. However, in both men and women, the risks associated with CVD increase with age, and these correspond to an overall decline in sex hormones, primarily of estrogen and testosterone. Despite this, hormone replacement therapies are largely shown to not improve outcomes in older patients and may also increase the risks of cardiac events in older adults. This review discusses current findings regarding the impacts of age and gender on heart disease.

Background: Insulin resistance (IR) may decrease muscle adaptability. Heat shock proteins (HSPs), mitogen-activated protein kinases (MAPKs), and miRNA are thought to play a role in muscle hypertrophy but it is unclear if IR may affect their regulation. Methods: Soleus muscles of lean Zucker (LZ) and insulin resistant obese Zucker (OZ) rats were overloaded for 7 or 21 days and subjected to immunoblotting and RT-PCR. Results: IR was associated with decreased muscle hypertrophy. Overload increased HSP27 phosphorylation in both the LZ and OZ rats at day 7 but only in the LZ at day 21. IR was associated with diminished overload induced MAPK phosphorylation and decreased expression of miR-1 and miR133. Overload decreased mir-1 levels in both the LZ and OZ but to a greater extent in the LZ animals. Conclusion: These results suggest that alterations in the regulation of HSPs, MAPKs and miRNA may be associated with the diminished hypertrophy of IR muscle.

The myometrium must remain relatively quiescent during pregnancy to accommodate growth and development of the feto-placental unit, and then must transform into a highly coordinated, strongly contracting organ at the time of labour for successful expulsion of the new born. The control of timing of labour is complex involving interactions between mother, fetus and the placenta. The timely onset of labour and delivery is an important determinant of perinatal outcome. Both preterm birth (delivery before 37 week of gestation) and post term pregnancy (pregnancy continuing beyond 42 weeks) are both associated with a significant increase in perinatal morbidity and mortality. There are multiple paracrine/autocrine events, fetal hormonal changes and overlapping maternal/fetal control mechanisms for the triggering of parturition in women. Our current article reviews the mechanisms for uterine distension and reduced contractions during pregnancy and the parturition cascade responsible for the timely and spontaneous onset of labour at term. It also discusses the mechanisms of preterm labour and post term pregnancy and the clinical implications thereof.

Human serum paraoxonase 1 (PON1) is an enzyme with esterase activity, and is physically bound to high-density lipoproteins (HDL). It plays a key role in the action of HDL toward protection of lipoprotein and biological membrane against oxidative damage. It may have a protective role against atherosclerosis by virtue of its action on hydrolyzing lipid peroxides and preventing accumulation of phospholipids in oxidized low-density lipoprotein (LDL). PON1 is hypothesized to be an indicator of the risk of atherosclerosis and coronary artery disease development. Numerous studies have implicated PON1 activity in relation to various endocrine disorders. The current article reviews the clinical perspectives of PON1 activity with regards to obesity, diabetes mellitus with its complications, and dyslipidemia.

Hypertension in children, although an uncommon entity, is associated with end-organ damage. We tried to study the clinical profile of hypertension in children presented to our hospital. The medical records from January 1990 to December 2010 of all children aged 18 years and younger with hypertension were studied. The patients were divided into four age groups (infants, pre-school age, school age and adolescents) Presenting symptoms and other clinical parameters were thoroughly evaluated. The results were compared with previous studies on hypertension in children. A total of 135 patients were selected (male:female 103:32), with mean age of 0.4 ± 2.1 years (range: six months to 17 years). The most common age group affected was the adolescents group (42.9%). The most common clinical feature at presentation was dizziness (30.3%), followed by headache and chest discomfort (22.9%). Transient hypertension was detected in 34 patients (25.2%), and was most common in the adolescent age group, whereas sustained hypertension was noticed in 101 patients (74.8%) and was the most common in the school age group (36/45, 80%). Forty-two patients (31.1%) presented with hypertensive crisis. Nine patients were considered to have essential hypertension. The chief causes included chronic glomerulonephritis in 56 (41.5%), endocrine disorders in 21 (15.5%), obstructive uropathy in 16 (11.8%), reflux nephropathy in 12 (8.8%) and renovascular disease in 5 (3.7%). Takayasu′s disease was the most common cause of renovascular hypertension. Coarctation of aorta was the most common cause of hypertension in infancy, being present in 40% of the cases. Hypertension in children may be easily underestimated but is a potentially life-threatening problem. Most of them are asymptomatic and a large chunk has an underlying etiology. Primary care clinicians should promptly identify patients with hypertension and treat them immediately and appropriately to prevent damage to the cardiovascular organs.

Diabetes Mellitus is a metabolic cum vascular syndrome with resultant abnormalities in both micro- and macrovasculature. The adverse long-term effects of diabetes mellitus have been described to involve many organ systems. Apart from hyperglycemia, abnormalities of angiogenesis may cause or contribute toward many of the clinical manifestations of diabetes. These are implicated in the pathogenesis of vascular abnormalities of the retina, kidneys, and fetus, impaired wound healing, increased risk of rejection of transplanted organs, and impaired formation of coronary collaterals. A perplexing feature of the aberrant angiogenesis is that excessive and insufficient angiogenesis can occur in different organs in the same individual. The current article hereby reviews the molecular mechanisms including abnormalities in growth factors, cytokines, and metabolic derangements, clinical implications, and therapeutic options of dealing with abnormal angiogenesis in diabetes.

The application of an event based physical model, KINEROS2, on a developed tropical watershed in Malaysia was evaluated. Three storm events in different intensities and durations were required for KINEROS2 (K2) calibration. K2 validation was done using two other rainfall events before and after the calibration year. Calibration results showed excellent and very good fittings for runoff and sediment simulations based on the aggregated measure. Validation results demonstrated that the K2 was reliable for runoff modelling while the K2 application for sediment simulation was only valid for the period 1984-1997.