How many kinases are druggable? A review of our current understanding.

There are over 500 human kinases ranging from very well-studied to almost completely ignored. Kinases are tractable and implicated in many diseases, making them ideal targets for medicinal chemistry campaigns, but is it possible to discover a drug for each individual kinase? For every human kinase, we gathered data on their citation count, availability of chemical probes, approved and investigational drugs, PDB structures, and biochemical and cellular assays. Analysis of these factors highlights which kinase groups have a wealth of information available, and which groups still have room for progress. The data suggest a disproportionate focus on the more well characterized kinases while much of the kinome remains comparatively understudied. It is noteworthy that tool compounds for understudied kinases have already been developed, and there is still untapped potential for further development in this chemical space. Finally, this review discusses many of the different strategies employed to generate selectivity between kinases. Given the large volume of information available and the progress made over the past 20 years when it comes to drugging kinases, we believe it is possible to develop a tool compound for every human kinase. We hope this review will prove to be both a useful resource as well as inspire the discovery of a tool for every kinase.

Structure Activity of ß-Amidomethyl Vinyl Sulfones as Covalent Inhibitors of Chikungunya nsP2 Cysteine Protease with Anti-alphavirus Activity.

Despite their widespread impact on human health there are no approved drugs for combating alphavirus infections. The heterocyclic ß-aminomethyl vinyl sulfone RA-0002034 (1a) is a potent irreversible covalent inhibitor of the alphavirus nsP2 cysteine protease with broad spectrum antiviral activity. Analogs of 1a that varied each of three regions of the molecule were synthesized to establish structure-activity relationships for inhibition of Chikungunya (CHIKV) nsP2 protease and viral replication. The covalent warhead was highly sensitive to modifications of the sulfone or vinyl substituents. However, numerous alterations to the core 5-membered heterocycle and its aryl substituent were well tolerated and several analogs were identified that enhanced CHIKV nsP2 binding. For example, the 4-cyanopyrazole analog 8d exhibited a kinact /Ki ratio >10,000 M-1s-1. 3-Arylisoxazole was identified an isosteric replacement for the 5-membered heterocycle, which circumvented the intramolecular cyclization that complicated the synthesis of pyrazole-based inhibitors like 1a. The accumulated structure-activity data was used to build a ligand-based model of the enzyme active site, which can be used to guide the design of covalent nsP2 protease inhibitors as potential therapeutics against alphaviruses.

Characterization of a Nonselective Opioid Receptor Functional Antagonist: Implications for Development as a Novel Opioid Dependence Medication.

Opioids represent the most extensive category of abused substances in the United States, and the number of fatalities caused by these drugs exceeds those associated with all other drug overdoses combined. The administration of naltrexone, a potent pan-opioid receptor antagonist, to an individual dependent on opioids can trigger opioid withdrawal and induce severe side effects. There is a pressing demand for opioid antagonists free of opioid withdrawal effects. In our laboratory, we have identified a compound with affinity to mu, delta, and kappa opioid receptors in the range of 150-250 nM. This blood-brain barrier (BBB)-permeant compound was metabolically stable in vitro and in vivo. Our in vivo work demonstrated that 1-10 mg/kg intraperitoneal administration of our compound produces moderate efficacy in antagonizing morphine-induced antiallodynia effects in the chemotherapy-induced peripheral neuropathy (CIPN) model. The treatment was well-tolerated and did not cause behavioral changes. We have observed a fast elimination rate of this metabolically stable molecule. Furthermore, no organ toxicity was observed during the chronic administration of the compound over a 14-day period. Overall, we report a novel functional opioid antagonist holds promise for developing an opioid withdrawal therapeutic.

Discovery of a cell-active chikungunya virus nsP2 protease inhibitor using a covalent fragment-based screening approach.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that has been responsible for numerous large-scale outbreaks in the last twenty years. Currently, there are no FDA-approved therapeutics for any alphavirus infection. CHIKV non-structural protein 2 (nsP2), which contains a cysteine protease domain, is essential for viral replication, making it an attractive target for a drug discovery campaign. Here, we optimized a CHIKV nsP2 protease (nsP2pro) biochemical assay for the screening of a 6,120-compound cysteine-directed covalent fragment library. Using a 50% inhibition threshold, we identified 153 hits (2.5% hit rate). In dose-response follow up, RA-0002034, a covalent fragment that contains a vinyl sulfone warhead, inhibited CHIKV nsP2pro with an IC 50 of 58 ± 17 nM, and further analysis with time-dependent inhibition studies yielded a k inact /K I of 6.4 x 10 3 M -1 s -1 . LC-MS/MS analysis determined that RA-0002034 covalently modified the catalytic cysteine in a site-specific manner. Additionally, RA-0002034 showed no significant off-target reactivity against a panel of cysteine proteases. In addition to the potent biochemical inhibition of CHIKV nsP2pro activity and exceptional selectivity, RA-0002034 was tested in cellular models of alphavirus infection and effectively inhibited viral replication of both CHIKV and related alphaviruses. This study highlights the discovery and characterization of the chemical probe RA-0002034 as a promising hit compound from covalent fragment-based screening for development toward a CHIKV or pan-alphavirus therapeutic. Significance Statement: Chikungunya virus is one of the most prominent and widespread alphaviruses and has caused explosive outbreaks of arthritic disease. Currently, there are no FDA-approved drugs to treat disease caused by chikungunya virus or any other alphavirus-caused infection. Here, we report the discovery of a covalent small molecule inhibitor of chikungunya virus nsP2 protease activity and viral replication of four diverse alphaviruses. This finding highlights the utility of covalent fragment screening for inhibitor discovery and represents a starting point towards the development of alphavirus therapeutics targeting nsP2 protease.

Biochar amendment alters root morphology of maize plant: Its implications in enhancing nutrient uptake and shoot growth under reduced irrigation regimes.

Introduction: Biochar amendment provides multiple benefits in enhancing crop productivity and soil nutrient availability. However, whether biochar addition affects root morphology and alters plant nutrient uptake and shoot growth under different irrigation regimes remain largely unknown. Methods: A split-root pot experiment with maize (Zea mays L.) was conducted on clay loam soil mixed with 2% (w/w) of wheat-straw (WSP) and softwood (SWP) biochar. The plants were subjected to full (FI), deficit (DI), and alternate partial root-zone drying (PRD) irrigation from the fourth leaf to the grain-filling stage. Results and discussion: The results showed that, compared to plants grown in unamended soils, plants grown in the biochar-amended soils possessed greater total root length, area, diameter, volume, tips, forks, crossings, and root length density, which were further amplified by PRD. Despite a negative effect on soil available phosphorus (P) pool, WSP addition improved soil available nitrogen (N), potassium (K), and calcium (Ca) pool and cation exchange capacity under reduced irrigation. Even though biochar negatively affected nutrient concentrations in shoots as exemplified by lowered N, P, K (except leaf), and Ca concentration, it dramatically enhanced plant total N, P, K, Ca uptake, and biomass. Principal component analysis (PCA) revealed that the modified root morphology and increased soil available nutrient pools, and consequently, the higher plant total nutrient uptake might have facilitated the enhanced shoot growth and yield of maize plants in biochar-added soils. Biochar amendment further lowered specific leaf area but increased leaf N concentration per area-to-root N concentration per length ratio. All these effects were evident upon WSP amendment. Moreover, PRD outperformed DI in increasing root area-to-leaf area ratio. Overall, these findings suggest that WSP combined with PRD could be a promising strategy to improve the growth and nutrient uptake of maize plants.

Comparison of Structural Diagnosis and Management (SDM) approach and MyoFascial Release (MFR) for improving plantar heel pain, ankle range of motion and disability: A randomized clinical trial.

[Purpose] The purpose of this study was to compare the effectiveness of the Structural Diagnosis and Management (SDM) approach with Myofascial Release (MFR) in improving plantar heel pain, ankle range of motion, and disability. [Subjects] Sixty-four subjects, aged 30-60 years, with a diagnosis of plantar heel pain, plantar fasciitis, or calcaneal spur by a physician according to ICD-10, were equally allocated to the MFR (n = 32) and SDM (n = 32) groups by hospital randomization and concealed allocation. [Methods] In this assessor-blinded randomized clinical trial, the control group performed MFR to the plantar surface of the foot, triceps surae, and deep posterior compartment calf muscles, while the experimental group performed a multimodal approach utilizing the SDM concept for 12 sessions over 4 weeks. Both groups also received strengthening exercises, ice compression, and ultrasound therapy. Pain, activity limitations and disability were assessed as primary outcomes using the Foot Function Index (FFI) and Range of motion (ROM) assessment of the ankle dorsiflexors and plantar flexors using a universal goniometer. Secondary outcomes were measured using the Foot Ankle Disability Index (FADI) and a 10-point manual muscle testing process for the ankle dorsiflexors and plantar flexors. [Results] Both MFR and SDM groups exhibited significant improvements from baseline in all outcome variables, including pain, activity level, disability, range of motion, and function after the 12-week intervention period (p < .05). The SDM group showed more improvements than MFR for FFI pain (p < .01), FFI activity (p < .01), FFI (p < .01) and FADI (p = <.01). [Conclusion] Both MFR and SDM approaches are effective in reducing pain, improving function, ankle range of motion, and reducing disability in plantar heel pain, however, the SDM approach may be a preferred treatment option.

Variable level of genetic dominance controls important agronomic traits in rice populations under water deficit condition.

Plant hybridization is an important breeding technique essential for producing a genotype (hybrid) with favorable traits (e.g., stress tolerance, pest resistance, high yield potential etc.) to increase agronomic, economic and commercial values. Studying of genetic dominance among the population helps to determine gene action, heritability and candidate gene selection for plant breeding program. Therefore, this investigation was aimed to evaluate gene action, heritability, genetic advance and heterosis of rice root, agronomic, and yield component traits under water deficit conditions. In this study, crossing was performed among the four different water-deficit tolerant rice genotypes to produce better hybrid (F1), segregating (F2) and back-cross (BC1 and BC2) populations. The Giza 178, WAB56-204, and Sakha104 × WAB56-104 populations showed the better physiological and agronomical performances, which provided better adaptability of the populations to water deficit condition. Additionally, the estimation of heterosis and heterobeltiosis of some quantitative traits in rice populations were also studied. The inheritance of all studied traits was influenced by additive gene actions. Dominance gene actions played a major role in controlling the genetic variance among studied traits in both crossed populations under well-watered and drought conditions. The additive × additive type of gene interactions was essential for the inheritance of root length, root/shoot ratio, 1,000-grain weight, and sterility % of two crossed populations under both conditions. On the contrary, the additive × dominance type of gene interactions was effective in the inheritance of all studied traits, except duration in Giza178 × Sakha106, and plant height in Sakha104 × WAB56-104 under water deficit condition. In both crosses, the dominance × dominance type of gene interactions was effective in the inheritance of root volume, root/shoot ratio, number of panicles/plant and 1,000-grain weight under both conditions. Moreover, dominance × dominance type of gene interaction played a major role in the inheritance of root length, number of roots/plant, plant height, panicle length, number of filled grain/panicle and grain yield/plant in Giza178 × Sakha106 under both conditions. The studied traits in both crossed populations indicated better genetic advance as they showed advanced qualitative and quantitative characters in rice populations under water deficit condition. Overall, our findings open a new avenue of future phenotypic and genotypic association studies in rice. These insights might be useful to the plant breeders and farmers for developing water deficit tolerant rice cultivars.

A host defense peptide mimetic, brilacidin, potentiates caspofungin antifungal activity against human pathogenic fungi.

Fungal infections cause more than 1.5 million deaths a year. Due to emerging antifungal drug resistance, novel strategies are urgently needed to combat life-threatening fungal diseases. Here, we identify the host defense peptide mimetic, brilacidin (BRI) as a synergizer with caspofungin (CAS) against CAS-sensitive and CAS-resistant isolates of Aspergillus fumigatus, Candida albicans, C. auris, and CAS-intrinsically resistant Cryptococcus neoformans. BRI also potentiates azoles against A. fumigatus and several Mucorales fungi. BRI acts in A. fumigatus by affecting cell wall integrity pathway and cell membrane potential. BRI combined with CAS significantly clears A. fumigatus lung infection in an immunosuppressed murine model of invasive pulmonary aspergillosis. BRI alone also decreases A. fumigatus fungal burden and ablates disease development in a murine model of fungal keratitis. Our results indicate that combinations of BRI and antifungal drugs in clinical use are likely to improve the treatment outcome of aspergillosis and other fungal infections.

Studies on diketopiperazine and dipeptide analogs as opioid receptor ligands.

Using the structure of gliotoxin as a starting point, we have prepared two different chemotypes with selective affinity to the kappa opioid receptor (KOR). Using medicinal chemistry approaches and structure-activity relationship (SAR) studies, structural features required for the observed affinity were identified, and advanced molecules with favorable Multiparameter Optimization (MPO) and Ligand Lipophilicity (LLE) profiles were prepared. Using the Thermal Place Preference Test (TPPT), we have shown that compound2 blocks the antinociceptive effect of U50488, a known KOR agonist. Multiple reports suggest that modulation of KOR signaling is a promising therapeutic strategy in treating neuropathic pain (NP). As a proof-of-concept study, we tested compound 2 in a rat model of NP and recorded its ability to modulate sensory and emotional pain-related behaviors. Observed in vitro and in vivo results suggest that these ligands can be used to develop compounds with potential application as pain therapeutics.

SGC-CLK-1: A chemical probe for the Cdc2-like kinases CLK1, CLK2, and CLK4.

Small molecule modulators are important tools to study both basic biology and the complex signaling of protein kinases. The cdc2-like kinases (CLK) are a family of four kinases that have garnered recent interest for their involvement in a diverse set of diseases such as neurodegeneration, autoimmunity, and many cancers. Targeted medicinal chemistry around a CLK inhibitor hit identified through screening of a kinase inhibitor set against a large panel of kinases allowed us to identify a potent and selective inhibitor of CLK1, 2, and 4. Here, we present the synthesis, selectivity, and preliminary biological characterization of this compound - SGC-CLK-1 (CAF-170). We further show CLK2 has the highest binding affinity, and high CLK2 expression correlates with a lower IC50 in a screen of multiple cancer cell lines. Finally, we show that SGC-CLK-1 not only reduces serine arginine-rich (SR) protein phosphorylation but also alters SR protein and CLK2 subcellular localization in a reversible way. Therefore, we anticipate that this compound will be a valuable tool for increasing our understanding of CLKs and their targets, SR proteins, at the level of phosphorylation and subcellular localization.

Explicating genetic architecture governing nutritional quality in pigmented rice.

Rice is one of the most important staple plant foods that provide a major source of calories and nutrients for tackling the global hunger index especially in developing countries. In terms of nutritional profile, pigmented rice grains are favoured for their nutritional and health benefits. The pigmented rice varieties are rich sources of flavonoids, anthocyanin and proanthocyanidin that can be readily incorporated into diets to help address various lifestyle diseases. However, the cultivation of pigmented rice is limited due to low productivity and unfavourable cooking qualities. With the advances in genome sequencing, molecular breeding, gene expression analysis and multi-omics approaches, various attempts have been made to explore the genetic architecture of rice grain pigmentation. In this review, we have compiled the current state of knowledge of the genetic architecture and nutritional value of pigmentation in rice based upon the available experimental evidence. Future research areas that can help to deepen our understanding and help in harnessing the economic and health benefits of pigmented rice are also explored.

SGC-CAMKK2-1: A Chemical Probe for CAMKK2.

The serine/threonine protein kinase calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) plays critical roles in a range of biological processes. Despite its importance, only a handful of inhibitors of CAMKK2 have been disclosed. Having a selective small molecule tool to interrogate this kinase will help demonstrate that CAMKK2 inhibition can be therapeutically beneficial. Herein, we disclose SGC-CAMKK2-1, a selective chemical probe that targets CAMKK2.

A prospective longitudinal study with treated hypertensive patients in Northern Bangladesh (PREDIcT-HTN) to understand uncontrolled hypertension and adverse clinical events: A protocol for 5-years follow-up.

INTRODUCTION: Uncontrolled hypertension is the most common cause of major adverse clinical events (MACE), such as myocardial infarction, strokes, and death due to CVDs, in both developed and developing countries. Western-led studies found that treated hypertensive adults with uncontrolled hypertension were more at-risk of all-cause and CVD-specific mortality than normotensives. The PRospEctive longituDInal sTudy of Treated HyperTensive patients of Northern-Bangladesh (PREDIcT-HTN) study principally aims to estimate the incidence of MACE in treated hypertensive patients and identify the determinants of MACE. The secondary objective is to find the prevalence of uncontrolled hypertension in treated hypertensive patients and the associated risk factors. METHODS AND ANALYSIS: The treated hypertensive patients were obtained from the Hypertension and Research Center (H&RC), Rangpur, Bangladesh, from January to December 2020. Based on the eligibility criteria, 2643 patients were included to constitute the PREDIcT-HTN cohort. Baseline data was retrieved from the H&RC registry, and five follow-up waves are planned yearly (2021-2025). A questionnaire will be administered at each follow-up visit on hypertension control status, behavioral factors, quality of life, dietary adherence, and high blood pressure compliance-related variables. The participant will be right censored if the patient develops MACE, death due to any cause, loss to follow-up, or at the end of the study. A proportional hazard model will identify the risk factors of MACE. Multinomial logistic regression analyses will be performed to determine the predictors of the hypertension control status by medication and dietary adherence after adjusting confounders. ETHICS AND DISSEMINATION: The ethical approval for this study was obtained from the Institutional Review Board, North South University [Ref: 2019/OR-NSU/IRB-No.0902]. The participants will provide written consent to participate. The findings will be disseminated through manuscripts in clinical/academic journals and presentations at professional conferences and stakeholder communication.

Exogenous putrescine attenuates the negative impact of drought stress by modulating physio-biochemical traits and gene expression in sugar beet (Beta vulgaris L.).

Drought tolerance is a complex trait controlled by many metabolic pathways and genes and identifying a solution to increase the resilience of plants to drought stress is one of the grand challenges in plant biology. This study provided compelling evidence of increased drought stress tolerance in two sugar beet genotypes when treated with exogenous putrescine (Put) at the seedling stage. Morpho-physiological and biochemical traits and gene expression were assessed in thirty-day-old sugar beet seedlings subjected to drought stress with or without Put (0.3, 0.6, and 0.9 mM) application. Sugar beet plants exposed to drought stress exhibited a significant decline in growth and development as evidenced by root and shoot growth characteristics, photosynthetic pigments, antioxidant enzyme activities, and gene expression. Drought stress resulted in a sharp increase in hydrogen peroxide (H2O2) (89.4 and 118% in SBT-010 and BSRI Sugar beet 2, respectively) and malondialdehyde (MDA) (35.6 and 27.1% in SBT-010 and BSRI Sugar beet 2, respectively). These changes were strongly linked to growth retardation as evidenced by principal component analysis (PCA) and heatmap clustering. Importantly, Put-sprayed plants suffered from less oxidative stress as indicated by lower H2O2 and MDA accumulation. They better regulated the physiological processes supporting growth, dry matter accumulation, photosynthetic pigmentation and gas exchange, relative water content; modulated biochemical changes including proline, total soluble carbohydrate, total soluble sugar, and ascorbic acid; and enhanced the activities of antioxidant enzymes and gene expression. PCA results strongly suggested that Put conferred drought tolerance mostly by enhancing antioxidant enzymes activities that regulated homeostasis of reactive oxygen species. These findings collectively provide an important illustration of the use of Put in modulating drought tolerance in sugar beet plants.

Identification and Utilization of a Chemical Probe to Interrogate the Roles of PIKfyve in the Lifecycle of ß-Coronaviruses.

From a designed library of indolyl pyrimidinamines, we identified a highly potent and cell-active chemical probe (17) that inhibits phosphatidylinositol-3-phosphate 5-kinase (PIKfyve). Comprehensive evaluation of inhibitor selectivity confirmed that this PIKfyve probe demonstrates excellent kinome-wide selectivity. A structurally related indolyl pyrimidinamine (30) was characterized as a negative control that lacks PIKfyve inhibitory activity and exhibits exquisite selectivity when profiled broadly. Chemical probe 17 disrupts multiple phases of the lifecycle of ß-coronaviruses: viral replication and viral entry. The diverse antiviral roles of PIKfyve have not been previously probed comprehensively in a single study or using the same compound set. Our scaffold is a distinct chemotype that lacks the canonical morpholine hinge-binder of classical lipid kinase inhibitors and has a non-overlapping kinase off-target profile with known PIKfyve inhibitors. Our chemical probe set can be used by the community to further characterize the role of PIKfyve in virology.

Cannabinoid accumulation in hemp depends on ROS generation and interlinked with morpho-physiological acclimation and plasticity under indoor LED environment.

Manipulation of growth and development of cannabis (Cannabis sativa L.) has received considerable interest by the scientific community due to its high value in medicinal and recreational use worldwide. This study was conducted to investigate the effects of LED spectral changes on reactive oxygen species (ROS) and cannabinoid accumulation by provoking growth, pigmentation, photosynthesis, and secondary metabolites production of cannabis grown in an indoor environment. After three weeks of vegetative growth under greenhouse condition, plants were further grown for 90 days in a plant factory treated with 4 LED light compositions with a canopy-level photosynthetic photon flux density (PPFD) of 300 µmol m-2 s-1 for 16 h. Photosynthetic pigments and photosynthetic rate were linearly increased up to 60 days and then sharply decreased which was found most prominent in L3: MB 240 (Red 85% + Blue 15%) and L4: PF 240 (Red 70% + Blue 30%) LED light compositions. A high concentration of H2O2 was also observed in L3 and L4 treatments which provoked lipid peroxidation in later growth stage. In addition, higher accumulation of cannabinoid was observed under L4 treatment in most cases. It is also evident that higher ROS created a cellular stress in plant as indicated by higher osmolyte synthesis and enzyme activity which initiate quick maturation along with higher cannabinoids accumulation in cannabis plant. Therefore, it can be concluded that ROS metabolism has a crucial role in morpho-physiological acclimation and cannabinoid accumulation in hemp plants. The findings of this study provide further insight on the use of LED light to maximize the production of cannabinoid.

Salt stress proteins in plants: An overview.

Salinity stress is considered the most devastating abiotic stress for crop productivity. Accumulating different types of soluble proteins has evolved as a vital strategy that plays a central regulatory role in the growth and development of plants subjected to salt stress. In the last two decades, efforts have been undertaken to critically examine the genome structure and functions of the transcriptome in plants subjected to salinity stress. Although genomics and transcriptomics studies indicate physiological and biochemical alterations in plants, it do not reflect changes in the amount and type of proteins corresponding to gene expression at the transcriptome level. In addition, proteins are a more reliable determinant of salt tolerance than simple gene expression as they play major roles in shaping physiological traits in salt-tolerant phenotypes. However, little information is available on salt stress-responsive proteins and their possible modes of action in conferring salinity stress tolerance. In addition, a complete proteome profile under normal or stress conditions has not been established yet for any model plant species. Similarly, a complete set of low abundant and key stress regulatory proteins in plants has not been identified. Furthermore, insufficient information on post-translational modifications in salt stress regulatory proteins is available. Therefore, in recent past, studies focused on exploring changes in protein expression under salt stress, which will complement genomic, transcriptomic, and physiological studies in understanding mechanism of salt tolerance in plants. This review focused on recent studies on proteome profiling in plants subjected to salinity stress, and provide synthesis of updated literature about how salinity regulates various salt stress proteins involved in the plant salt tolerance mechanism. This review also highlights the recent reports on regulation of salt stress proteins using transgenic approaches with enhanced salt stress tolerance in crops.

Canopy spectral reflectance indices correlate with yield traits variability in bread wheat genotypes under drought stress.

Drought stress is a major issue impacting wheat growth and yield worldwide, and it is getting worse as the world's climate changes. Thus, selection for drought-adaptive traits and drought-tolerant genotypes are essential components in wheat breeding programs. The goal of this study was to explore how spectral reflectance indices (SRIs) and yield traits in wheat genotypes changed in irrigated and water-limited environments. In two wheat-growing seasons, we evaluated 56 preselected wheat genotypes for SRIs, stay green (SG), canopy temperature depression (CTD), biological yield (BY), grain yield (GY), and yield contributing traits under control and drought stress, and the SRIs and yield traits exhibited higher heritability (H2) across the growing years. Diverse SRIs associated with SG, pigment content, hydration status, and aboveground biomass demonstrated a consistent response to drought and a strong association with GY. Under drought stress, GY had stronger phenotypic correlations with SG, CTD, and yield components than in control conditions. Three primary clusters emerged from the hierarchical cluster analysis, with cluster I (15 genotypes) showing minimal changes in SRIs and yield traits, indicating a relatively higher level of drought tolerance than clusters II (26 genotypes) and III (15 genotypes). The genotypes were appropriately assigned to distinct clusters, and linear discriminant analysis (LDA) demonstrated that the clusters differed significantly. It was found that the top five components explained 73% of the variation in traits in the principal component analysis, and that vegetation and water-based indices, as well as yield traits, were the most important factors in explaining genotypic drought tolerance variation. Based on the current study's findings, it can be concluded that proximal canopy reflectance sensing could be used to screen wheat genotypes for drought tolerance in water-starved environments.

Hypertension and undiagnosed hypertension among Bangladeshi adults: Identifying prevalence and associated factors using a nationwide survey.

Background: Although undiagnosed hypertension (HTN) is a serious concern worldwide, it is less of an importance in Bangladesh, where there is a dearth of research on the subject. So, we aimed to identify the prevalence and associated factors for diagnosed and undiagnosed HTN. Methods: We analyzed the recent 2017-2018 Bangladesh Demographic and Health Survey data. We included 11,981 participants aged 18 years and above for the analysis. The prevalence rates of both diagnosed and undiagnosed hypertension were computed for all individuals and subgroups. The influence of socio-demographic, household, and community-related variables on HTN and undiagnosed HTN was investigated using multinomial regression analysis. Results: The study finds 1,464 (12.2%) of the 11,981 respondents [6,815 females [56.9 %]; mean age 39.4 years] had diagnosed HTN, whereas 1 898 (15.8%) had undiagnosed HTN. The HTN and undiagnosed HTN were significantly prevalent in the elderly, type 2 diabetic (T2DM), and overweight and obese individuals. In terms of residential regions, people from coastal region had a significantly higher prevalence of both HTN (RRR: 1.37; 95% CI: 1.17-1.62) and undiagnosed HTN (RRR: 1.35; 95% CI: 1.17-1.56) compared to those from the central region of Bangladesh. Conclusions: The high prevalence of undetected hypertension in Bangladesh suggests that screening procedures for the current chronic illness may be inadequate in routine clinical practice. All populations should have access to hypertension screening, but it is especially crucial for the elderly, those with diabetes, those who are overweight or obese, and those from coastal and northern regions of Bangladesh.

Health-related quality of life and coping strategies adopted by COVID-19 survivors: A nationwide cross-sectional study in Bangladesh.

INTRODUCTION: This study aims to investigate the health-related quality of life and coping strategies among COVID-19 survivors in Bangladesh. METHODS: This is a cross-sectional study of 2198 adult, COVID-19 survivors living in Bangladesh. Data were collected from previously diagnosed COVID-19 participants (confirmed by an RT-PCR test) via door-to-door interviews in the eight different divisions in Bangladesh. For data collection, Bengali-translated Brief COPE inventory and WHO Brief Quality of Life (WHO-QoLBREF) questionnaires were used. The data collection period was from October 2020 to March 2021. RESULTS: Males 72.38% (1591) were more affected by COVID-19 than females 27.62% (607). Age showed significant correlations (p<0.005) with physical, psychological and social relationships, whereas gender showed only a significant correlation with physical health (p<0.001). Marital status, occupation, living area, and co-morbidities showed significant co-relation with all four domains of QoL (p<0.001). Education and affected family members showed significant correlation with physical and social relationship (p<0.001). However, smoking habit showed a significant correlation with both social relationship and environment (p<0.001). Age and marital status showed a significant correlation with avoidant coping strategies (p<0.001); whereas gender and co-morbidities showed a significant correlation with problem-focused coping strategies (p<0.001). Educational qualification, occupation and living area showed significant correlation with all three coping strategies(p<0.001). CONCLUSION: Survivors of COVID-19 showed mixed types of coping strategies; however, the predominant coping strategy was avoidant coping, followed by problem-focused coping, with emotion-focused coping reported as the least prevalent. Marital status, occupation, living area and co-morbidities showed a greater effect on QoL in all participants. This study represents the real scenario of nationwide health-associated quality of life and coping strategies during and beyond the Delta pandemic.