Rapid Acute Coronary Syndrome Evaluation Over One Hour With High-Sensitivity Cardiac Troponin I: A United States-Based Stepped-Wedge, Randomized Trial.

STUDY OBJECTIVE: The real-world effectiveness and safety of a 0/1-hour accelerated protocol using high-sensitivity cardiac troponin (hs-cTn) to exclude myocardial infarction (MI) compared to routine care in the United States is uncertain. The objective was to compare a 0/1-hour accelerated protocol for evaluation of MI to a 0/3-hour standard care protocol. METHODS: The RACE-IT trial was a stepped-wedge, randomized trial across 9 emergency departments (EDs) that enrolled 32,609 patients evaluated for possible MI from July 2020 through April 2021. Patients undergoing high-sensitivity cardiac troponin I testing with concentrations less than or equal to 99th percentile were included. Patients who had MI excluded by the 0/1-hour protocol could be discharged from the ED. Patients in the standard care protocol had 0- and 3-hour troponin testing and application of a modified HEART score to be eligible for discharge. The primary endpoint was the proportion of patients discharged from the ED without 30-day death or MI. RESULTS: There were 13,505 and 19,104 patients evaluated in the standard care and accelerated protocol groups, respectively, of whom 19,152 (58.7%) were discharged directly from the ED. There was no significant difference in safe discharges between standard care and the accelerated protocol (59.5% vs 57.8%; adjusted odds ratio (aOR)=1.05, 95% confidence interval [CI] 0.95 to 1.16). At 30 days, there were 90 deaths or MIs with 38 (0.4%) in the standard care group and 52 (0.4%) in the accelerated protocol group (aOR=0.84, 95% CI 0.43 to 1.68). CONCLUSION: A 0/1-hour accelerated protocol using high-sensitivity cardiac troponin I did not lead to more safe ED discharges compared with standard care.

Spatio-temporal distribution and source contributions of the ambient pollutants in Lucknow city, India.

Clean air is imperative to the survival of all life forms on the planet. However, recent times have witnessed enormous escalation in urban pollution levels. It is therefore, incumbent upon us to decipher measures to deal with it. In perspective, the present study was carried out to assess PM10 and PM2.5 loading, metallic constituents, gaseous pollutants, source contributions, health impact and noise level of nine-locations, grouped as residential, commercial, and industrial in Lucknow city for 2019-21. Mean concentrations during pre-monsoon for PM10, PM2.5, SO2 and NO2 were: 138.2 ± 35.2, 69.1 ± 13.6, 8.5 ± 3.3 and 32.3 ± 7.4 µg/m3, respectively, whereas post-monsoon concentrations were 143.0 ± 33.3, 74.6 ± 14.5, 12.5 ± 2.1, and 35.5 ± 6.3 µg/m3, respectively. Exceedance percentage of pre-monsoon PM10 over National Ambient Air Quality Standards (NAAQS) was 38.2% while that for post-monsoon was 43.0%; whereas corresponding values for PM2.5 were 15.2% and 24.3%. Post-monsoon season showed higher particulate loading owing to wintertime inversion and high humidity conditions. Order of elements associated with PM2.5 is Co < Cd < Cr < Ni < V < Be < Mo < Mn < Ti < Cu < Pb < Se < Sr < Li < B < As < Ba < Mg < Al < Zn < Ca < Fe < K < Na and that with PM10 is Co < Cd < Ni < Cr < V < Ti < Be < Mo < Cu < Pb < Se < Sr < Li < B < As < Mn < Ba < Mg < Al < Fe < Zn < K < Na < Ca. WHO AIRQ + ascertained 1654, 144 and 1100 attributable cases per 0.1 million of population to PM10 exposure in 2019-21. Source apportionment was carried out using USEPA-PMF and resolved 6 sources with highest percent contributions including road dust re-entrainment, biomass burning and vehicular emission. It is observed that residents of Lucknow city regularly face exposure to particulate pollutants and associated constituents making it imperative to develop pollution abetment strategies.

Whole genome transcriptomic reveals heat stroke molecular signatures in humans.

An evolutionary heat shock response (HSR) protects most living species, including humans, from heat-induced macromolecular damage. However, its role in the pathogenesis of heat stroke is unknown. We examined the whole genome transcriptome in peripheral blood mononuclear cells of a cohort of subjects exposed to the same high environmental heat conditions, who developed heat stroke (n = 19) versus those who did not (n = 19). Patients with heat stroke had a mean rectal temperature at admission of 41.7 ± 0.8°C, and eight were in deep coma (Glasgow Coma Score = 3). The transcriptome showed that genes involved in more than half of the entire chaperome were differentially expressed relative to heat stress control. These include the heat shock protein, cochaperone, and chaperonin genes, indicating a robust HSR. Differentially expressed genes also encoded proteins related to unfolded protein response, DNA repair, energy metabolism, oxidative stress, and immunity. The analysis predicted perturbations of the proteome network and energy production. Cooling therapy attenuated these alterations without complete restoration of homeostasis. We validated the significantly expressed genes by a real-time polymerase chain reaction. The findings reveal the molecular signature of heat stroke. They also suggested that a powerful HSR may not be sufficient to protect against heat injury. The overwhelming proteotoxicity and energy failure could play a pathogenic role. KEY POINTS: Most living species, including humans, have inherent heat stress response (HSR) that shields them against heat-induced macromolecular damage. The role of the HSR in subjects exposed to environmental heat who progressed to heat stroke versus those that did not is unknown. Our findings suggest that heat stroke induces a broad and robust HSR of nearly half of the total heat shock proteins, cochaperones, and chaperonin genes. Heat stroke patients exhibited inhibition of genes involved in energy production, including oxidative phosphorylation and ATP production. Significant enrichment of neurodegenerative pathways, including amyloid processing signalling, the Huntington's and Parkinson's disease signalling suggestive of brain proteotoxicity was noted. The data suggests that more than a powerful HSR may be required to protect against heat stroke. Overwhelming proteotoxicity and energy failure might contribute to its pathogenesis.

Biochemical and Computational Assessment of Acute Phase Proteins in Dairy Cows Affected with Subclinical Mastitis.

Subclinical mastitis (SCM) is a predominant form of mastitis wherein major visible signs of disease are absent. The present study aimed to determine acute phase proteins (APPs) like ferritin, C-reactive protein (CRP), and microalbumin (Malb) in 135 composite milk and serum samples of healthy (n = 25) and SCM (n = 110) cows. As bovine mastitis is an inflammatory disease, the present study also aimed at finding novel anti-inflammatory compounds from natural sources by repurposing approach using computational studies. The findings of the present study revealed substantial elevation (p < 0.001) in milk SCC and an increase in ferritin, CRP, and Malb (p < 0.001) in milk and sera of the SCM group as compared to healthy animals. Receiver operating characteristics of milk SCC, milk, and serum APPs unraveled statistically substantial alteration (p < 0.001). Further, SCC was correlated with milk APPs ferritin (r = 0.26 **, p < 0.002), CRP (r = 0.19 *, p < 0.02), and Malb (r = 0.21 *, p < 0.01). Additionally, milk SCC was correlated with serum ferritin (r = 0.28 **, p < 0.001), CRP (r = 0.16, p > 0.05), and Malb (r = 0.16, p > 0.05). The findings of molecular docking revealed that Chaetoglobosin U was the most effective molecule that showed the highest binding affinity (kcal/mol) of -10.1 and -8.5 against ferritin and albumin. The present study concluded that the estimation of cow-side tests, SCC, and APPs in milk/serum is suitable to detect SCM and screening herd community. Furthermore, Chaetoglobosin U could be developed as a promising anti-inflammatory inhibitor; however, further studies are required to validate these findings.

Differential expression of urease genes and ureolytic activity of uropathogenic Escherichia coli and Pseudomonas aeruginosa isolates in different nutritional conditions.

Uropathogens have adaptation strategies to survive in the host urinary tract by efficiently utilizing and tolerating the urinary metabolites. Many uropathogens harbour the enzyme urease for the breakdown of urea and the enzymatic breakdown of urea increases the pH and facilitate the struvite crystallization. In this study, the differential urease activity of uropathogenic Escherichia coli and Pseudomonas aeruginosa strains was investigated under different nutritional conditions. The experiments included measurement of growth, pH, urease activity, NH4-N generation and urease gene (ureC) expression among the bacterial strains under different conditions. Further, the implications of urea breakdown on the struvite crystallization in vitro and biofilm formation were also assessed. The study included urease positive isolates and for comparison urease negative isolates were included. Compared to the urease negative strains the urease positive strains formed higher biofilms and motility. The urease positive P. aeruginosa showed significantly higher (p < 0.01) pH and urease activity (A557-A630) compared to E. coli under experimental conditions. Further, supplementation of glucose to the growth media significantly increased the urease activity in P. aeruginosa and in contrast, it was significantly lower in E. coli. The expression profile of urease gene (ureC) was significantly higher (p < 0.001) in P. aeruginosa compared to E. coli and was consistent with the biochemical results of the urease activity under the nutritional conditions. The differential urease activity under two nutritional conditions influenced the biogenic struvite crystallization. It correlated with the urease activity showing higher crystallization rate in P. aeruginosa compared to E. coli. The results highlight the differential urease activity in two common uropathogens under different nutritional conditions that may have significant role on the regulation of virulence, pathogenicity and in the kidney stone disease.

Protective effect of chrysin, a flavonoid, on the genotoxic activity of carboplatin in mice.

Carboplatin is amongst the most commonly used anticancer drugs for the management of several human malignancies. However, it has displayed genotoxic properties against normal cells. Evaluation of natural products for their protective effects against chemotherapeutic drug induced toxicity has been growing in recent years. A naturally occurring flavonoid, chrysin, has strong antioxidant abilities and protects against DNA impairment. This study used multiple assays to evaluate the levels of damage to DNA in normal cells and to examine any possible protective role of chrysin against such damage. Male BALB/c mice were administered chrysin orally in two doses of 20 and 40 mg/kg for 10 consecutive days and then a single injection of carboplatin [90 mg/kg body weight (b.w.)] was administered intraperitoneally to induce carboplatin toxicity. 24 h after the carboplatin injection, mice were sacrificed. DNA damage was evaluated using several genotoxicity tests (8-Hydroxydeoxy-guanosine marker, comet assay, micronucleus test, and chromosomal aberration assay) to identify diverse types of damage to the DNA. The results suggest that pretreatment with chrysin significantly decreased the level of DNA damage caused by carboplatin probably due to its potent antioxidant traits. Therefore, chrysin can be considered to be developed as a chemoprotective agent against chemotherapy associated side-effects.

Insight into the Interaction Mechanism of HSA with Aztreonam: A Multispectroscopic and Computational Approach.

Aztreonam is a Gram-negative bacteria-targeting synthetic monobactam antibiotic. Human serum albumin (HSA) plays an important role in the transference of pharmaceuticals, hormones, and fatty acids, along with other compounds, determining their biodistribution and physiological fate. Using several biophysical and in silico approaches, we studied the interaction of aztreonam with HSA under physiological environments in this study. Results confirm the formation of HSA-aztreonam complex where aztreonam showed moderate affinity towards HSA. A static mode of quenching was confirmed from the steady state fluorescence data. FRET findings also showed that there was a significant feasibility of energy transfer between HSA and aztreonam. Site marker displacement experimental conclusion suggested the binding site of aztreonam was the sub-domain IB of HSA. Circular dichroic spectroscopic analysis suggested that aztreonam interaction decreases the α-helical content of HSA. Changes in microenvironment were studied through synchronous fluorescence data. According to molecular docking results, the HSA-aztreonam complex is mostly maintained by non-covalent forces, with a binding energy of 7.7 kcal mol-1. The presence of a hydrogen bond, van der Waal interaction, and pi-anion interaction in the binding process, as well as conformational changes in HSA after binding with aztreonam, are all confirmed by molecular dynamic simulation.

Obesity and COVID-19: what makes obese host so vulnerable?

The disease (COVID-19) novel coronavirus pandemic has so far infected millions resulting in the death of over a million people as of Oct 2020. More than 90% of those infected with COVID-19 show mild or no symptoms but the rest of the infected cases show severe symptoms resulting in significant mortality. Age has emerged as a major factor to predict the severity of the disease and mortality rates are significantly higher in elderly patients. Besides, patients with underlying conditions like Type 2 diabetes, cardiovascular diseases, hypertension, and cancer have an increased risk of severe disease and death due to COVID-19 infection. Obesity has emerged as a novel risk factor for hospitalization and death due to COVID-19. Several independent studies have observed that people with obesity are at a greater risk of severe disease and death due to COVID-19. Here we review the published data related to obesity and overweight to assess the possible risk and outcome in Covid-19 patients based on their body weight. Besides, we explore how the obese host provides a unique microenvironment for disease pathogenesis, resulting in increased severity of the disease and poor outcome.

Quinoline yellow dye stimulates whey protein fibrillation via electrostatic and hydrophobic interaction: A biophysical study.

Amyloid fibril formation of proteins is associated with a number of neurodegenerative diseases. Several small molecules can accelerate the amyloid fibril formation in vitro and in vivo. However, the molecular mechanism of amyloid fibrillation is still unclear. In this study, we investigated how the food dye quinoline yellow (QY) induces amyloid fibrillation in α-lactalbumin (α-LA), a major whey protein, at pH 2.0. We used several spectroscopy techniques and a microscopy technique to explore how QY provokes amyloid fibrillation in α-LA. From turbidity and Rayleigh light scattering experiments, we found that QY promotes α-LA aggregation in a concentration-dependent manner; the optimal concentration for α-LA aggregation was 0.15 to 10.00 mM. Below 0.1 mM, no aggregation occurred. Quinoline yellow-induced aggregation was a rapid process that escaped the lag phase, but it depended on the concentrations of both α-LA and QY. We also demonstrated that aggregation switched the secondary structure of α-LA from α-helices to cross-ß-sheets. We then confirmed the amyloid-like structure of aggregated α-LA by transmission electron microscopy measurements. Molecular docking and simulation confirmed the stability of the α-LA-QY complex due to the formation of 1 hydrogen bond with Lys99 and 2 electrostatic interactions with Arg70 and Lys99, along with hydrophobic interactions with Leu59 and Tyr103. This study will aid in our understanding of how small molecules induce aggregation of proteins inside the stomach (low pH) and affect the digestive process.

Brainstem hemorrhage is uncommon and is associated with high morbidity, mortality, and prolonged hospitalization.

OBJECTIVE: To determine the frequency, risk factors, and outcomes of patients with brainstem hemorrhage in stroke center at King Abdulaziz Medical City, Riyadh. METHODS: A retrospective, observational cohort study including all patients with brainstem hemorrhage from January 2014 to December 2017. The clinical presentation, location of hemorrhage, complications and clinical outcomes were analyzed. RESULTS: Of 1921 stroke patients, 219 had hemorrhagic stroke (11.4%), of whom only 10 (4.6%) had brainstem hemorrhage, comprising 0.5% of all stroke patients. All patients were men; mean age was 58.5 years. Most frequent presenting symptoms were headache (70%), unilateral weakness (60%), and loss of consciousness (50%). All patients had hemorrhage in pons, 5 had concomitant cerebellar hemorrhage (50%), one had medullary hemorrhage, and one midbrain hemorrhage (10% each). Mean ICU stay was 17 days; mean hospital stay was 58 days. At the time of discharge, three (30%) had mRS of 0-2, 5 (50%) had mRS of 3-5, whereas 2 (20%) had died. Glasgow coma scale (GCS) of >8 at presentation was associated with a good outcome at three months (p=0.03). Presentation within six hours of symptom onset (p=0.233), hypertension on presentation (p=0.233), and age less than 60 years (p=0.065) did not affect discharge outcomes. CONCLUSION: Brainstem hemorrhage occurred in 0.5% of all stroke patients. It was associated with high morbidity and mortality. Low Glasgow Coma Scale at presentation was associated with poor outcomes.

Metabolite profile and elemental determination of camel follicular fluid by GC-MS and ICP-MS.

The objective of present study was to determine metabolite profile and inorganic elements of camel follicular fluids (FF) using "gas chromatography-mass spectrometry (GC-MS) and inductively coupled plasma mass spectrometry (ICP-MS)," respectively. Various metabolites were detected in camel FF by the proposed GC-MS technique. The major compounds detected were lactic acid (62.37%), linolenic acid (5.95%), myo-inositol (3.37%), hexadecanoic acid (3.19%), N-ethyl-N-vinylacetamide (3.15%), acetamide (2.89%), tetradecanoic acid (2.64%), and D-xylofuranose (2.25%). The proposed ICP-MS technique was validated in terms of linearity, precision, accuracy, and sensitivity. All quality control validation parameters were found to be satisfactory for the analysis of elements in camel FF. The proposed ICP-MS technique showed the presence of sixteen different elements (out of eighteen standards) in camel FF. Some elements such as Na, K, Ca, and Mg were obtained in higher amounts in camel FF. Overall, the results of this study indicated that the proposed GC-MS and ICP-MS techniques can be successfully applied for metabolite profile and element determination of biological fluids such as FF.

Frequency, risk factors, and outcomes in patients with significant carotid artery disease admitted to King Abdulaziz Medical City, Riyadh with Ischemic Stroke.

OBJECTIVE: To determine the frequency, risk factors, and outcomes of significant carotid artery disease (CAD) in patients with ischemic stroke. METHODS: The frequency of significant CAD in patients admitted to the Stroke Unit between January 2014 and December 2015 was determined from radiological data. Outcomes were determined clinically and radiologically. RESULTS: Among 435 patients, 273 were men (62.8%), with a mean age of 57.4+/-12.2 years. Significant CAD was found in 48 vessels in 40 (9.2%) patients, of which 30 patients were symptomatic. Nine of these patients were treated with carotid artery stenting, one underwent carotid endarterectomy, and 3 underwent an urgent thrombectomy, without stenting. Seventeen symptomatic patients were not treated for the following reasons: patient/family refusal (n=2), contraindications (n=5), and complete occlusion (n=10). One (7.7%) of the 13 treated patients had an ipsilateral stroke on follow up, one (7.7%) had contralateral transient ischemic attack (TIA), 9 (69.2%) had no recurrence, and no clinical data were available for 2 patients. Among the 17 untreated patients, one (5.9%) had an ipsilateral stroke, 7 (41.2%) had no recurrence, and 9 (52.9%) were lost to follow up. CONCLUSION: Significant carotid artery disease is uncommon in our cohort found in less than 10% of patients. Vascular risk factors are more or less similar between patients with or without CAD except obesity which appears to have inverse relation with CAD. A small number of patients received carotid intervention with no recurrence of stroke at limited follow up.

Indoor air pollution and its association with poor lung function, microalbuminuria and variations in blood pressure among kitchen workers in India: a cross-sectional study.

BACKGROUND: The present study is an attempt to explore the association between kitchen indoor air pollutants and physiological profiles in kitchen workers with microalbuminuria (MAU) in north India (Lucknow) and south India (Coimbatore). METHODS: The subjects comprised 145 control subjects, 233 kitchen workers from north India and 186 kitchen workers from south India. Information related to the personal and occupational history and health of the subjects at both locations were collected using a custom-made questionnaire. Worker lung function was measured using a spirometer. Blood pressure was monitored using a sphygmomanometer. Urinary MAU was measured using a urine analyzer. Indoor air monitoring in kitchens for particulate matter (PM), total volatile organic compounds (TVOC), carbon dioxide (CO2) and carbon monoxide (CO) was conducted using indoor air quality monitors. The size and shape of PM in indoor air was assessed using a scanning electron microscope (SEM). Fourier transform infrared (FTIR) spectroscopy was used to detect organic or inorganic compounds in the air samples. RESULTS: Particulate matter concentrations (PM2.5 and PM1) were significantly higher in both north and south Indian kitchens than in non-kitchen areas. The concentrations of TVOC, CO and CO2 were higher in the kitchens of north and south India than in the control locations (non-kitchen areas). Coarse, fine and ultrafine particles and several elements were also detected in kitchens in both locations by SEM and elemental analysis. The FTIR spectra of kitchen indoor air at both locations show the presence of organic chemicals. Significant declines in systolic blood pressure and lung function were observed in the kitchen workers with MAU at both locations compared to those of the control subjects. A higher prevalence of obstruction cases with MAU was observed among the workers in the southern region than in the controls (p < 0.01). CONCLUSIONS: Kitchen workers in south India have lower lung capacities and a greater risk of obstructive and restrictive abnormalities than their north Indian counterparts. The study showed that occupational exposure to multiple kitchen indoor air pollutants (ultrafine particles, PM2.5, PM1, TVOC, CO, CO2) and FTIR-derived compounds can be associated with a decline in lung function (restrictive and obstructive patterns) in kitchen workers with microalbuminuria. Further studies in different geographical locations in India among kitchen workers on a wider scale are required to validate the present findings.

Massive left hemothorax following laparoscopic pyeloplasty.

Laparoscopic pyeloplasty is viable standard minimally invasive alternative to open pyeloplasty for the treatment of ureteropelvic junction obstruction. Intrathoracic bleeding is an extremely rare complication after laparoscopic urological surgery, but it should be suspected and promptly diagnosed in case of worsening hemodynamic status and respiratory parameters during the intra or post-operative course. We report a case of hemothorax complicating an otherwise uneventful LP in an 18-year-old girl.

Modulation of quorum sensing and biofilm of Gram-negative bacterial pathogens by Cinnamomum zeylanicum L.

The development of antibiotic resistant microbial pathogens has become a global health threat and a major concern in modern medicine. The problem of antimicrobial resistance (AMR) has majorly arisen due to sub-judicious use of antibiotics in health care and livestock industry. A slow progress has been made in last two decades in discovery of new antibiotics. A new strategy in combatting AMR is to modulate or disarm the microbes for their virulence and pathogenicity. Plants are considered as promising source for new drugs against AMR pathogens. In this study, fraction-based screening of the Cinnamomum zeylanicum extract was performed followed by detailed investigation of antiquorum sensing and antibiofilm activities of the most active fraction that is, C. zeylanicum hexane fraction (CZHF). More than 75% reduction in violacein pigment of C. violaceum 12472 was overserved. CZHF successfully modulated the virulence of Pseudomonas aeruginosa PAO1 by 60.46%-78.35%. A similar effect was recorded against Serratia marcescens MTCC 97. A broad-spectrum inhibition of biofilm development was found in presence of sub-MICs of CZHF. The colonization of bacteria onto the glass coverslips was remarkably reduced apart from the reduction in exopolymeric substances. Alkaloids and terpenoids were found in CZHF. GC/MS analysis revealed the presence of cinnamaldehyde dimethyl acetal, 2-propenal, coumarin, and α-copaene as major phytocompounds. This study provides enough evidence to support potency of C. zeylanicum extract in targeting the virulence of Gram -ve pathogenic bacteria. The plant extract or active compounds can be developed as successful drugs after careful in vivo examination to target microbial infections. RESEARCH HIGHLIGHTS: Hexane fraction of Cinnamomum zeylanicum is active against QS and biofilms. The broad-spectrum antibiofilm activity was further confirmed by microscopic analysis. Dimethyl acetal, 2-propenal, coumarin, α-copaene, and so forth are major phytocompounds.

Rapid detection of drug-resistant Mycobacterium tuberculosis by Modified MODS assay suitable for resource-poor settings.

BACKGROUND: Cross contamination and biosafety are concerns with the microscopic observation drug susceptibility assay. To address these issues, we modified the MODS technique in the current study. METHODOLOGY/PRINCIPAL FINDINGS: Two hundred and seventy-five samples were processed on LJ media and drug susceptibility was performed by the Indirect agar proportion method. A modified MODS test was done in tissue culture bottles. GenoType MTBDRplus assay was performed to detect the resistance and mutational pattern associated with the resistances. Sensitivity, specificity, positive predictive value, and negative predictive value for the detection of tuberculosis by modified MODS were 97.44%, 80.00%, 97.44%, and 80.00% respectively. The perfect agreement was seen between modified MODS and the Indirect agar proportion method for drug susceptibility testing of isoniazid (kappa = 0.923) and rifampicin (kappa = 1). The contamination rate, cost and TAT for modified MODS were less as compared to the solid media. In the case of MDR-TB isolates S531L (66.66%) was the most prevalent mutation in the rpoB gene followed by S315T2 mutation (58.33%) and T8C (41.66%) in katG and inhA gene respectively. In hetero-resistant strains, C-15T mutation (37.50%) was the most common followed by A-16G (12.50%) in the inhA gene. In INH mono-resistant strains only two mutations were observed i.e., S-315T1(50%) and C-15T (50%) in the katG and inhA genes respectively. CONCLUSIONS/SIGNIFICANCE: Modified MODS proved to be cost-effective and user-friendly, with minimal risk to the handler and no cross-contamination between samples were observed. Hence, it can be used in low-income countries for early detection of tuberculosis and its resistance.

Phenological, nutritional and molecular diversity assessment among 35 introduced lentil (Lens culinaris Medik.) genotypes grown in Saudi Arabia.

Morphological, nutritional and molecular analyses were carried out to assess genetic diversity among 35 introduced lentil genotypes (Lens culinaris Medik.). The genotypes exhibited significant differences for their field parameters and some of them showed noticeable superiority. The nutritional and proximate analysis showed that some genotypes were excellent sources of proteins, essential amino acids, minerals, anti-oxidants, total phenolic contents (TPC) and total flavonoid contents (TFC) and hence, highlights lentil nutritional and medicinal potential. Sequence-related amplified polymorphism (SRAP) and amplified fragments length polymorphism (AFLP) markers were used to estimate the genetic variability at the molecular level. The existence of a considerable amount of genetic diversity among the tested lentil genotypes was also proven at the molecular level. A total of 2894 polymorphic SRAP and 1625 AFLP loci were successfully amplified using six SRAP and four AFLP primer pair combinations. Polymorphism information content (PIC) values for SRAP and AFLP markers were higher than 0.8, indicating the power and higher resolution of those marker systems in detecting molecular diversity. UPGMA (unweighted pair group method with arithmetic average) cluster analysis based on molecular data revealed large number of sub clusters among genotypes, indicating high diversity levels. The data presented here showed that FLIP2009-64L and FLIP2009-69L could be used as a significant source of yield, total protein, essential amino acids, and antioxidant properties. The results suggest potential lentil cultivation in the central region of Saudi Arabia for its nutritional and medicinal properties, as well as sustainable soil fertility crop.

Multi-targeting of virulence factors of P. aeruginosa by ß-lactam antibiotics to combat antimicrobial resistance.

Antimicrobial resistance poses a significant challenge to public health, especially in developing countries, due to a substantial rise in bacterial resistance. This situation has become so concerning that we are now at risk of losing the effectiveness of antibiotics altogether. Recent research has firmly established that bacteria engage in a process called quorum sensing (QS). QS regulates various functions, including nutrient scavenging, immune response suppression, increased virulence, biofilm formation and mobility. Pseudomonas aeruginosa, an opportunistic bacterial pathogen, plays a significant role in various medical conditions such as chronic wounds, corneal infections, burn wounds and cystic fibrosis. While antibiotics are effective in killing bacteria, only a few antibiotics, particularly those from the ß-lactam group, have been studied for their impact on the quorum sensing of P. aeruginosa. Given the lack of concentrated efforts in this area, we have investigated the role of ß-lactam antibiotics on various potential targets of P. aeruginosa. Based on their toxicological profiles and the average binding energy obtained through molecular docking, azlocillin and moxalactam have emerged as lead antibiotics. The binding energy for the docking of azlocillin and moxalactam with LasA was determined to be -8.2 and -8.6 kcal/mol, respectively. Molecular simulation analysis has confirmed the stable interaction of both these ligands with all three target proteins (LasI, LasA and PqsR) under physiological conditions. The results of this research underscore the effectiveness of azlocillin and moxalactam. These two antibiotics may be repurposed to target the quorum sensing of P. aeruginosa.Communicated by Ramaswamy H. Sarma.

Human tolerance to extreme heat: evidence from a desert climate population.

BACKGROUND: Ambient temperatures exceeding 40 °C are projected to become common in many temperate climatic zones due to global warming. Therefore, understanding the health effects of continuous exposure to high ambient temperatures on populations living in hot climatic regions can help identify the limits of human tolerance. OBJECTIVE: We studied the relationship between ambient temperature and non-accidental mortality in the hot desert city of Mecca, Saudi Arabia, between 2006 and 2015. METHODS: We used a distributed lag nonlinear model to estimate the mortality-temperature association over 25 days of lag. We determined the minimum mortality temperature (MMT) and the deaths that are attributable to heat and cold. RESULTS: We analyzed 37,178 non-accidental deaths reported in the ten-year study period among Mecca residents. The median average daily temperature was 32 °C (19-42 °C) during the same study period. We observed a U-shaped relationship between daily temperature and mortality with an MMT of 31.8 °C. The total temperature-attributable mortality of Mecca residents was 6.9% (-3.2; 14.8) without reaching statistical significance. However, extreme heat, higher than 38 °C, was significantly associated with increased risk of mortality. The lag structure effect of the temperature showed an immediate impact, followed by a decline in mortality over many days of heat. No effect of cold on mortality was observed. IMPACT STATEMENT: High ambient temperatures are projected to become future norms in temperate climates. Studying populations familiar with desert climates for generations with access to air-conditioning would inform on the mitigation measures to protect other populations from heat and on the limits of human tolerance to extreme temperatures. We studied the relationship between ambient temperature and all-cause mortality in the hot desert city of Mecca. We found that Mecca population is adapted to high temperatures, although there was a limit to tolerance to extreme heat. This implies that mitigation measures should be directed to accelerate individual adaptation to heat and societal reorganization.

Umbelliferone modulates the quorum sensing and biofilm of Gram - ve bacteria: in vitro and in silico investigations.

In last two decades, the world has seen an exponential increase in the antimicrobial resistance (AMR), making the issue a serious threat to human health. The mortality caused by AMR is one of the leading causes of human death worldwide. Till the end of the twentieth century, a tremendous success in the discovery of new antibiotics was seen, but in last two decades, there is negligible progress in this direction. The increase in AMR combined with slow progress of antibiotic drug discovery has created an urgent demand to search for newer methods of intervention to combat infectious diseases. One of such approach is to look for biofilm and quorum sensing (QS) inhibitors. Plants are excellent source of wide class compounds that can be harnessed to look for the compounds with such properties. This study proves a broad-spectrum biofilm and QS inhibitory potential of umbelliferone. More than 85% reduction in violacein production Chromobacterium violaceum 12472 was found. All tested virulent traits of Pseudomonas aeruginosa PAO1 and Serratia marcescens MTCC 97 were remarkably inhibited that ranged from 56.62% to 86.24%. Umbelliferone also successfully prevented the biofilm of test bacteria at least by 67.68%. Umbelliferone interacted at the active site of many proteins of QS circuit, which led to the mitigation of virulent traits. The stable nature of complexes of umbelliferone with proteins further strengthens in vitro results. After examining the toxicological profile and other drug-like properties, umbelliferone could be potentially developed as new drug to target the infections caused by Gram - ve bacteria.Communicated by Ramaswamy H. Sarma.