Single-cell phenotypic profiling and backtracing exposes and predicts clinically relevant subpopulations in isogenic Staphylococcus aureus communities.

Isogenic bacterial cell populations are phenotypically heterogenous and may include subpopulations of antibiotic tolerant or heteroresistant cells. The reversibility of these phenotypes and lack of biomarkers to differentiate functionally different, but morphologically identical cells is a challenge for research and clinical detection. To overcome this, we present ´Cellular Phenotypic Profiling and backTracing (CPPT)´, a fluorescence-activated cell sorting platform that uses fluorescent probes to visualize and quantify cellular traits and connects this phenotypic profile with a cell´s experimentally determined fate in single cell-derived growth and antibiotic susceptibility analysis. By applying CPPT on Staphylococcus aureus we phenotypically characterized dormant cells, exposed bimodal growth patterns in colony-derived cells and revealed different culturability of single cells on solid compared to liquid media. We demonstrate that a fluorescent vancomycin conjugate marks cellular subpopulations of vancomycin-intermediate S. aureus with increased likelihood to survive antibiotic exposure, showcasing the value of CPPT for discovery of clinically relevant biomarkers.

Remote sensing analysis of spatiotemporal impacts of anthropogenic influence on mountain landscape ecology in Pir Chinasi national park.

Mountain landscapes can be fragmented due to various human activities such as tourism, road construction, urbanization, and agriculture. It can also be due to natural factors such as flash floods, glacial lake outbursts, land sliding, and climate change such as rising temperatures, heavy rains, or drought.The study's objective was to analyze the mountain landscape ecology of Pir Chinasi National Park under anthropogenic influence and investigate the impact of anthropogenic activities on the vegetation. This study observed spatiotemporal changes in vegetation due to human activities and associated climate change for the past 25 years (1995-2020) around Pir Chinasi National Park, Muzaffrabad, Pakistan. A structured questionnaire was distributed to 200 residents to evaluate their perceptions of land use and its effects on local vegetation. The findings reveal that 60% of respondents perceived spatiotemporal pressure on the park. On the other hand, the Landsat-oriented Normalized Difference Vegetation Index (NDVI) was utilized for the less than 10% cloud-covered images of Landsat 5, 7, and 8 to investigate the vegetation degradation trends of the study area. During the entire study period, the mean maximum NDVI was approximately 0.28 in 1995, whereas the mean minimum NDVI was - 2.8 in 2010. QGIS 3.8.2 was used for the data presentation. The impact of temperature on vegetation was also investigated for the study period and increasing temperature trends were observed. The study found that 10.81% (1469.08 km2) of the area experienced substantial deterioration, while 23.57% (3202.39 km2) experienced minor degradation. The total area of degraded lands was 34.38% (or 4671.47 km2). A marginal improvement in plant cover was observed in 24.88% of the regions, while 9.69% of the regions experienced a major improvement. According to the NDVI-Rainfall relationships, the area was found to be significantly impacted by human pressures and activities (r ≤ 0.50) driving vegetation changes covering 24.67% of the total area (3352.03 km2). The area under the influence of climatic variability and change (r ≥ 0.50 ≥ 0.90) accounted for 55.84% (7587.26 km2), and the area under both climatic and human stressors (r ≥ 0.50 < 0.70) was 64%. Sustainable land management practices of conservation tillage, integrated pest management, and agroforestry help preserve soil health, water quality, and biodiversity while reducing erosion, pollution, and the degradation of natural resources. landscape restoration projects of reforestation, wetland restoration, soil erosion control, and the removal of invasive species are essential to achieve land degradation neutrality at the watershed scale.

Effects of biochar on growth and yield of Wheat (Triticum aestivum L.) under salt stress.

Globally from abiotic stresses, salt stress is the major stress that limits crop production. One of them is wheat that has been utilized by more than 1/3 of the world population as staple food due to its nutritive value. Biochar is an activated carbon that can ameliorate the negative impacts on plants under saline conditions. The present study was conducted to examine the ameliorative impact of "Biochar application" to Triticum aestivum L. plant grown under salinity stress and evaluated on the basis of various growth, yield, physiological, biochemical attributes. Preliminary experiment was done to select the Triticum aestivum L. varieties with 90% germination rate for further experiment. The selected varieties, FSD08 and PUNJAB-11 of wheat were treated with two levels of sodium chloride (0 mM and 120 mM). Two varieties of wheat included FSD08 and PUNJAB-11 were treated with two levels of sodium chloride (0 mM and 120 mM). To address the impact of salt stress two levels of biochar 0% and 5% was used as exogenous application. A three way completely randomized experimentation was done in 24 pots of two wheat varieties with three replicates. The results demonstrated that salt stress affected growth, physiological attributes, yield and inorganic mineral ions (Ca2+ and K+) in roots and shoots parameters of wheat negatively while biochar overall improved the performance of plant. SOD, CAT, APX and POD activities enhanced during salt stress as the plant self-defense mechanism against salinity to minimize the damaging effect. Salt stress also significantly increased the membrane permeability, and levels of H2O2, MDA, Cl and Na ions. Biochar treatment nullified negative impacts of NaCl and improved the plant growth and yield significantly. Hence, biochar amendment can be suggested as suitable supplement for sustainable crop production under salinization.

Interplay among manures, vegetable types, and tetracycline resistance genes in rhizosphere microbiome.

The rapid global emergence of antibiotic resistance genes (ARGs) is a substantial public health concern. Livestock manure serves as a key reservoir for tetracycline resistance genes (TRGs), serving as a means of their transmission to soil and vegetables upon utilization as a fertilizer, consequently posing a risk to human health. The dynamics and transfer of TRGs among microorganisms in vegetables and fauna are being investigated. However, the impact of different vegetable species on acquisition of TRGs from various manure sources remains unclear. This study investigated the rhizospheres of three vegetables (carrots, tomatoes, and cucumbers) grown with chicken, sheep, and pig manure to assess TRGs and bacterial community compositions via qPCR and high-throughput sequencing techniques. Our findings revealed that tomatoes exhibited the highest accumulation of TRGs, followed by cucumbers and carrots. Pig manure resulted in the highest TRG levels, compared to chicken and sheep manure, in that order. Bacterial community analyses revealed distinct effects of manure sources and the selective behavior of individual vegetable species in shaping bacterial communities, explaining 12.2% of TRG variation. Firmicutes had a positive correlation with most TRGs and the intl1 gene among the dominant phyla. Notably, both the types of vegetables and manures significantly influenced the abundance of the intl1 gene and soil properties, exhibiting strong correlations with TRGs and elucidating 30% and 17.7% of TRG variance, respectively. Our study delineated vegetables accumulating TRGs from manure-amended soils, resulting in significant risk to human health. Moreover, we elucidated the pivotal roles of bacterial communities, soil characteristics, and the intl1 gene in TRG fate and dissemination. These insights emphasize the need for integrated strategies to reduce selection pressure and disrupt TRG transmission routes, ultimately curbing the transmission of tetracycline resistance genes to vegetables.

Understanding the role of magnetic (Fe3O4) nanoparticle to mitigate cadmium stress in radish (Raphanus sativus L.).

Heavy metals stress particularly cadmium contamination is hotspot among researchers and considered highly destructive for both plants and human health. Iron is examined as most crucial element for plant development, but it is available in inadequate amount because they are present in insoluble Fe3+ form in soil. Fe3O4 have been recently found as growth promoting factor in plants. To understand, a sand pot experiment was conducted in completely randomized design (control, cadmium, 20 mg/L Fe3O4 nanoparticles,40 mg/L Fe3O4 nanoparticles, 20 mg/L Fe3O4 nanoparticles + cadmium, 40 mg/L Fe3O4 nanoparticles + cadmium) to study the mitigating role of Fe3O4 nanoparticles on cadmium stress in three Raphanus sativus cultivars namely i.e., MOL SANO, MOL HOL PARI, MOL DAQ WAL. The plant growth, physiological and biochemical parameters i.e.,shoot length, shoot fresh weight, shoot dry weight, root length, root fresh and dry weight, MDA content, soluble protein contents, APX, CAT, POD activities and ion concentrations, membrane permeability, chlorophyll a, chlorophyll b and anthocyanin content, respectively were studied. The results displayed that cadmium stress remarkably reduces all growth, physiological and biochemical parameters for allcultivars under investigation. However, Fe3O4 nanoparticles mitigated the adverse effect of cadmium by improving growth, biochemical and physiological attributes in all radish cultivars. While, 20 mg/L Fe3O4 nanoparticles have been proved to be more useful against cadmium stress. The outcome of present investigation displayed that Fe3O4 nanoparticles can be utilized for mitigating heavy metal stress.

Enhancing drought tolerance in chilli pepper through AdDjSKI-mediated modulation of ABA sensitivity, photosynthetic preservation, and ROS scavenging.

Drought stress threatens the productivity of numerous crops, including chilli pepper (Capsicum annuum). DnaJ proteins are known to play a protective role against a wide range of abiotic stresses. This study investigates the regulatory mechanism of the chloroplast-targeted chaperone protein AdDjSKI, derived from wild peanut (Arachis diogoi), in enhancing drought tolerance in chilli peppers. Overexpressing AdDjSKI in chilli plants increased chlorophyll content, reflected in the maximal photochemical efficiency of photosystem II (PSII) (Fv/Fm) compared with untransformed control (UC) plants. This enhancement coincided with the upregulated expression of PSII-related genes. Our subsequent investigations revealed that transgenic chilli pepper plants expressing AdDjSKI showed reduced accumulation of superoxide and hydrogen peroxide and, consequently, lower malondialdehyde levels and decreased relative electrolyte leakage percentage compared with UC plants. The mitigation of ROS-mediated oxidative damage was facilitated by heightened activities of antioxidant enzymes, including superoxide dismutase, catalase, ascorbate peroxidase, and peroxidase, coinciding with the upregulation of the expression of associated antioxidant genes. Additionally, our observations revealed that the ectopic expression of the AdDjSKI protein in chilli pepper plants resulted in diminished ABA sensitivity, consequently promoting seed germination in comparison with UC plants under different concentrations of ABA. All of these collectively contributed to enhancing drought tolerance in transgenic chilli plants with improved root systems when compared with UC plants. Overall, our study highlights AdDjSKI as a promising biotechnological solution for enhancing drought tolerance in chilli peppers, addressing the growing global demand for this economically valuable crop.

Removal of Cr(VI) from Wastewater Using Acrylonitrile Grafted Cellulose Extracted from Sugarcane Bagasse.

A highly efficient low-cost adsorbent was prepared using raw and chemically modified cellulose isolated from sugarcane bagasse for decontamination of Cr(VI) from wastewater. First, cellulose pulp was isolated from sugarcane bagasse by subjecting it to acid hydrolysis, alkaline hydrolysis and bleaching with sodium chlorate (NaClO3). Then, the bleached cellulose pulp was chemically modified with acrylonitrile monomer in the presence Fenton's reagent (Fe+2/H2O2) to carry out grafting of acrylonitrile onto cellulose by atom transfer radical polymerization. The developed adsorbent (acrylonitrile grafted cellulose) was analyzed by X-ray diffraction analysis (XRD), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR). Both raw cellulose and acrylonitrile grafted cellulose were used for chromium removal from wastewater. The effects of metal ion concentration, pH, adsorbent dose and time were studied, and their values were optimized. The optimum conditions for the adsorption of Cr(VI) onto raw and chemically modified cellulose were: metal ion concentration: 50 ppm, adsorbent dose: 1 g, pH: 6, and time: 60 min. The maximum efficiencies of 73% and 94% and adsorption capacities of 125.95 mg/g and 267.93 mg/g were achieved for raw and acrylonitrile grafted cellulose, respectively. High removal efficiency was achieved, owing to high surface area of 79.92 m2/g and functional active binding cites on grafted cellulose. Isotherm and kinetics studies show that the experimental data were fully fitted by the Freundlich isotherm model and pseudo first-order model. The adsorbent (acrylonitrile grafted cellulose) was regenerated using three different types of regenerating reagents and reused thirty times, and there was negligible decrease (19%) in removal efficiency after using it for 30 times. Hence, it is anticipated that acrylonitrile could be utilized as potential candidate material for commercial scale Cr(VI) removal from wastewater.

An SNP based genotyping assay for genes associated with drought tolerance in bread wheat.

BACKGROUND: SnRK2 plays vital role in responding to adverse abiotic stimuli. The applicability of TaSnRK2.4 and TaSnRK2.9 was investigated to leverage the potential of these genes in indigenous wheat breeding programs. METHODS: Genetic diversity was assessed using pre-existing markers for TaSnRK2.4 and TaSnRK2.9. Furthermore, new markers were also developed to enhance their broader applicability. KASP markers were designed for TaSnRK2.4, while CAPS-based markers were tailored for TaSnRK2.9. RESULTS: Analysis revealed lack of polymorphism in TaSnRK2.4 among Pakistani wheat germplasm under study. To validate this finding, available gel-based markers for TaSnRK2.4 were employed, producing consistent results and offering limited potential for application in marker-assisted wheat breeding with Pakistani wheat material. For TaSnRK2.9-5A, CAPS2.9-5A-1 and CAPS2.9-5A-2 markers were designed to target SNP positions at 308 nt and 1700 nt revealing four distinct haplotypes. Association analysis highlighted the significance of Hap-5A-1 of TaSnRK2.9-5A, which exhibited association with an increased number of productive tillers (NPT), grains per spike (GPS), and reduced plant height (PH) under well-watered (WW) conditions. Moreover, it showed positive influence on NPT under WW conditions, GPS under water-limited (WL) conditions, and PH under both WW and WL conditions. High selection intensity observed for Hap-5A-1 underscores the valuable role it has played in Pakistani wheat breeding programs. Gene expression studies of TaSnRK2.9-5A revealed the involvement of this gene in response to PEG, NaCl, low temperature and ABA treatments. CONCLUSION: These findings propose that TaSnRK2.9 can be effectively employed for improving wheat through marker-assisted selection in wheat breeding efforts.

Physiological and biochemical assortment in different wheat genotypes (Triticum aestivum L.) under rain fed conditions.

Wheat (Triticum aestivum L.) is the most extensively cultivated cereal crop in the world; however, its growth and development are affected by different types of biotic and abiotic stress conditions. The aim of this study was to assess the physico-chemical diversity in different wheat genotypes under rain-fed conditions. Principle component analysis (PCA) showed that significant variation for different components contributed 77.87% of total variability among all genotypes. In the scree plot, the first two PCs (PC1=44.75%, PC2=14.28%) had significant differences for numerous agronomic traits. The scatter biplot depicted eight genotypes (Zardana, NR-462, D-97, BARS-2009 (a check), NR-481, Tarnab-73, NR-489 and Pirsabak-91) with high diversity (variation ~90%) for different morphological traits, identifiable as they were located further away from the origin than other genotypes. Factor analysis of loading factors among wheat genotypes across different morpho-physiological traits also showed significant diversity for positive and negative loads. In cluster analysis, genotypes such as BWP-97, BARS-2009, NR-489, NR-448 and Pak. 13 were outliers, indicating significant diversity among all genotypes for different agronomic traits. Biochemical analysis showed maximum values for antioxidant activity, total phenolic content, and total flavonoid content in lines NR-485 (93.76%), NR-489 (3.55mg gallic acid equivalent (GAE)/g), and the variety Suleman-96 (3.45mg quercetin equivalent (QE)/g), respectively. This study provides new insights for understanding the diversity of different wheat genotypes under rain-fed conditions, and the selected genotypes can be evaluated for further breeding programs.

In-silico analysis and transformation of OsMYB48 transcription factor driven by CaMV35S promoter in model plant - Nicotiana tabacum L. conferring abiotic stress tolerance.

Global crop yield has been affected by a number of abiotic stresses. Heat, salinity, and drought stress are at the top of the list as serious environmental growth-limiting factors. To enhance crop productivity, molecular approaches have been used to determine the key regulators affecting stress-related phenomena. MYB transcription factors (TF) have been reported as one of the promising defensive proteins against the unfavorable conditions that plants must face. Different roles of MYB TFs have been suggested such as regulation of cellular growth and differentiation, hormonal signaling, mediating abiotic stress responses, etc. To gain significant insights, a comprehensive in-silico analysis of OsMYB TF was carried out in comparison with 21 dicot MYB TFs and 10 monocot MYB TFs. Their chromosomal location, gene structure, protein domain, and motifs were analyzed. The phylogenetic relationship was also studied, which resulted in the classification of proteins into four basic groups: groups A, B, C, and D. The protein motif analysis identified several conserved sequences responsible for cellular activities. The gene structure analysis suggested that proteins that were present in the same class, showed similar intron-exon structures. Promoter analysis revealed major cis-acting elements that were found to be responsible for hormonal signaling and initiating a response to abiotic stress and light-induced mechanisms. The transformation of OsMYB TF into tobacco was carried out using the Agrobacterium-mediated transformation method, to further analyze the expression level of a gene in different plant parts, under stress conditions. To summarize, the current studies shed light on the evolution and role of OsMYB TF in plants. Future investigations should focus on elucidating the functional roles of MYB transcription factors in abiotic stress tolerance through targeted genetic modification and CRISPR/Cas9-mediated genome editing. The application of omics approaches and systems biology will be indispensable in delineating the regulatory networks orchestrated by MYB TFs, facilitating the development of crop genotypes with enhanced resilience to environmental stressors. Rigorous field validation of these genetically engineered or edited crops is imperative to ascertain their utility in promoting sustainable agricultural practices.

Molecular docking of bioactive compounds extracted and purified from selected medicinal plant species against covid-19 proteins and in vitro evaluation.

Bioactive compounds are secondary metabolites of plants. They offer diverse pharmacological properties. Peganum harmala is reported to have pharmaceutical effects like insecticidal, antitumor, curing malaria, anti-spasmodic, vasorelaxant, antihistaminic effect. Rosa brunonii has medicinal importance in its flower and fruits effective against different diseases and juice of leaf is reported to be applied externally to cure wounds and cuts. Dryopteris ramosa aqueous leaf extract is used to treat stomach ulcers and stomachaches. Each of these three medicinal plants have been indicated to have anticancer, antiviral, antioxidant, cytotoxic and antifungal effects but efficacy of their bioactive compounds remained unexplored. Study was aimed to explore In-vitro and In-silico anticancer, antiviral, antioxidant, cytotoxic and antifungal effects of bioactive compounds of above three medicinal plants. DPPH and ABTS assay were applied for assessment of antioxidant properties of compounds. Antibacterial properties of compounds were checked by agar well diffusion method. Brine shrimp lethality assay was performed to check cytotoxic effect of compounds. Molecular docking was conducted to investigate the binding efficacy between isolated compounds and targeted proteins. The compound isomangiferrin and tiliroside presented strong antioxidant potential 78.32% (± 0.213) and 77.77% (± 0.211) respectively in DPPH assay while harmaline showed 80.71% (± 0.072) at 200 µg/mL in ABTS assay. The compound harmine, harmaline and PH-HM 17 exhibited highest zone of inhibition 22 mm, 23 mm, 22 mm respectively against Xanthomonas while Irriflophenone-3-C-ß- D-glucopyranoside showed maximum zone of inhibition 34 mm against E. coli. The compound isomangiferrin and vasicine contained strong antibacterial activity 32 mm and 22 mm respectively against S. aureus. The compound mangiferrin, astragalin, tiliroside, quercitin-3-O-rhamnoside showed maximum inhibitory zone 32 mm, 26 mm, 24 mm and 22 mm respectively against Klebsiella pneumoniae. Highest cytotoxic effect was observed by compound tiliroside i.e. 95% with LD50 value 73.59 µg/mL. The compound tiliroside showed the best binding mode of interaction to all targeted proteins presenting maximum hydrophobic interactions and hydrogen bonds. The binding affinity of tiliroside was - 17.9, - 14.9, - 14.6, - 13.8, - 12.8 against different proteins 6VAR, 5C5S, IEA3, 2XV7 and 6LUS respectively. Bioactive compounds are significant natural antioxidants, which could help to prevent the progression of various diseases caused by free radicals. Based on molecular docking we have concluded that phytochemicals can have better anticancer and antiviral potential.

Suicide Rates and Risks Across U.S. Industries: A 29-Year Population-Based Survey.

OBJECTIVE: Suicide rates in the working-age U.S. population have increased by over 40% in the last two decades. Although suicide may be linked with characteristics of workplaces and their industries, few studies have reported industry-level suicide rates. No study has reported suicide rates by industry using nationally representative data. This study estimates suicide risks across industries in the U.S. working population. METHODS: Industry-level estimates of suicide risks require substantial data; we combined 29 years of U.S. suicide data using the National Health Interview Survey (NHIS)-Mortality Linked data from 1986 through 2014, with mortality follow-up through 2015. We conducted survey-weighted Poisson regression analyses to estimate suicide mortality rates and rate ratios across all populations and stratified by gender. All analyses were adjusted first for age, and then for age, employment status, marital status, race/ethnicity, and rurality/urbanicity (demographic-adjusted). Rate ratios compared results for workers in each industry to those for all industries, accounting for the NHIS survey design. RESULTS: A total of 1,943 suicide deaths were recorded. Age-adjusted suicide rates per 100,000 were highest in the furniture, lumber, and wood industry group (29.3), the fabricated metal industry (26.3), and mining (25.8). Demographic-adjusted rates were higher among men than women in most industries. Demographic-adjusted rate ratios were significantly elevated in the furniture, lumber, and wood industries (Rate Ratio, RR = 1.60, 95% confidence interval, CI = 1.18-2.18); chemicals and allied products (RR = 1.49, 95%CI = 1.04-2.13); and construction (RR = 1.21, 95% CI = 1.03-1.41). CONCLUSION: Several industries had significantly high suicide rates. Suicide prevention efforts may be particularly useful for workers in those industries.

[1, 8]-Naphthyridine derivatives as dual inhibitor of alkaline phosphatase and carbonic anhydrase.

[1,8]-Naphthyridine derivatives have been reported to possess important biological activities and may serve as attractive pharmacophores in the drug discovery process. [1,8]-Naphthyridine derivatives (1a-1l) were evaluated for inhibitory potential for isozymes of carbonic anhydrase (CA) and alkaline phosphatase (ALP). CAs have been reported to carry out reversible hydration of CO2 into HCO3-, secretion of electrolytes, acid-base regulation, bone resorption, calcification, and biosynthetic reactions. Whereas ALPs hydrolyze monophosphate esters with the release of inorganic phosphate and play an important role in bone mineralization. Both enzymes have been found to be over-expressed and raised functional activities in patients suffering from rheumatoid arthritis. The discovery of dual inhibitors of these enzymes may provide a synergistic effect to cure bone disorders such as rheumatoid arthritis and ankylosing spondylitis. Among the test compounds, the most potent inhibitors for CA-II, CA-IX, and CA-XII were 1e, 1g, and 1a with IC50 values of 0.44 ± 0.19, 0.11 ± 0.03 and 0.32 ± 0.07 µM, respectively. [1,8]-Naphthyridine derivatives (1a-1l) were approximately 4 folds more potent than standard CA inhibitor acetazolamide. While in the case of ALPs, the most potent compounds for b-TNAP and c-IAP were 1b and 1e with IC50 values of 0.122 ± 0.06 and 0.107 ± 0.02 µM, respectively. Thus, synthesized derivatives proved to be 100 to 800 times more potent as compared to standard inhibitors of b-TNAP and c-IAP (Levamisole and L-phenyl alanine, respectively). In addition, selectivity and dual inhibition of [1,8]-Naphthyridine derivatives confer precedence over known inhibitors. Molecular docking and molecular simulation studies were also conducted in the present studies to define the type of interactions between potential inhibitors and enzyme active sites.

Poverty, Health Care Access Barriers, and Functional Limitations among Individuals with Chronic Obstructive Pulmonary Disease: An 11-Year Cross-sectional Analysis, 2008-2018.

OBJECTIVES: To assess the relationship between poverty, delayed care, unaffordable care, and functional limitations among individuals with chronic obstructive pulmonary disease (COPD). METHODS: Using the National Health Interview Survey data, we selected respondents with COPD, aged 40 years and older. The predictor variables were poverty and measures of delayed and unaffordable care. The outcome variable was functional limitations. We performed a survey-weighted multivariate logistic regression analysis, adjusting for sociodemographic characteristics. RESULTS: Respondents classified as poor had three times the odds of functional limitations compared with those classified as not poor. Respondents who reported having measures of delayed care or unaffordable care had two to nine times and two to four times the adjusted odds of functional limitations compared with those who did not report such measures of delayed and unaffordable care, respectively. CONCLUSIONS: Poverty and delayed and unaffordable care are associated with functional limitations among individuals with COPD.

Synthesis, characterization and biological evaluation of pyrazole-based benzene sulfonamides as inhibitors of human carbonic anhydrase II, IX and XII.

The aberrant level of the carbonic anhydrase isozymes is linked with various disorders which include glaucoma, epilepsy, altitude sickness and obesity. In the present study, a series of the pyrazole-based benzene sulfonamides derivatives (4a-4l) were designed, synthesized and evaluated as the inhibitors of the three isoforms of human carbonic anhydrases (hCAII, hCAIX and hCAXII). A number of the derivatives were found more active inhibitors than acetazolamide used as a standard against the human hCAII, hCAIX and hCAXII. Among the series, the compound 4k inhibited the hCAII to a submicromolar level presenting the IC50 ± SEM concentration of 0.24 ± 0.18 µM, the inhibitor 4j reduced the activity of the hCAIX to the IC50 ± SEM equals 0.15 ± 0.07 µM, whereas, the molecule 4g blocked the catalytic potential of the isozyme hCAXII with as low as IC50 concentration of 0.12 ± 0.07 µM. In addition, compounds 4e and 4k were screened as the preferential inhibitors of the isoform hCAXII as compared to the hCAIX and hCAXII with half of the maximal concentrations of 0.75 ± 0.13 µM, and 0.24 ± 0.18 µM, respectively. Moreover, the compounds 4k, 4j and 4g were docked inside the active pocket of the crystallographic structure of the isoforms hCAXII, hCAIX and hCAXII, respectively. The docked inhibitors showed the binding interactions with the important amino acid residues such as Leu1198, Thr1199, His1094, and Phe1131 in hCAXII isozyme; residues Val121, Thr200, Pro203, and Gln71 in hCAIX; the amino acids Val119, Leu197, Gln89, and Asn64 in the case of hCAXII. In addition, structural geometries, reactivity descriptors, optimization energy and electronic parameters were calculated to predict the activity of the synthesized compounds.

Psychological distress is more common in some occupations and increases with job tenure: a thirty-seven year panel study in the United States.

BACKGROUND: Workers in certain occupations may have elevated risks of psychological distress. However, research is limited. For example, researchers often measure distress that may have existed before occupational exposures. We studied occupations and the development of psychological distress using national data from the United States. METHODS: We reviewed relevant research to identify occupations with low and high risks of mental health problems. We confirmed those individual low and high risk occupations using 1981-2017 data from the Panel Study of Income Dynamics (n = 24,789). We measured new cases of distress using the Screening Scale for Psychological Distress (Kessler K6) and compared distress in the low and high risk groups, adjusted for factors associated with occupational selection and non-occupational distress risks. A subset of participants described their jobs (n = 1,484), including factors such as job demands, social support, and control over work. We examined associations of those factors with psychological distress. RESULTS: Workers in high risk occupations had 20% higher adjusted odds of developing distress than those in low risk occupations (odds ratio, OR 1.20, 95% confidence interval, CI 1.13-1.28). Distress increased with time in a high risk occupation: ≥5 years OR 1.38 (CI 1.18-1.62), ≥ 10 years OR 1.46 (CI 1.07-1.99), and ≥ 15 years OR 1.77 (CI 1.08-2.90; p-trend = 0.0145). The most common positive participant descriptions of their jobs indicated social support (34%), sense of accomplishment (17%), and control over work (15%). Participants reporting such descriptions were significantly less likely to have a high risk occupation (OR 0.66, CI 0.46-0.94, p = 0.0195). The most common negative descriptions were excessive job demands (43%), low social support (27%), and lack of control (14%). Participants reporting such descriptions were significantly more likely to have a high risk occupation (OR 1.49, CI 1.03-2.14, p = 0.0331). CONCLUSION: Certain occupations may have high risks of psychological distress, which may be due to characteristics of the occupations rather than employee characteristics, or in addition to them. Results were consistent with theoretical models of psychosocial work environments. Providers of health care and social services should ask patients or clients about work-related distress.

Road environment characteristics and fatal crash injury during the rush and non-rush hour periods in the U.S: Model testing and cluster analysis.

This study aims to assess the relationship between county-level fatal crash injuries and road environmental characteristics at all times of the day and during the rush and non-rush hour periods. We merged eleven-year (2010 - 2020) data from the Fatality Analysis Reporting System. The outcome variable was the county-level fatal crash injury counts. The predictor variables were measures of road types, junction types and work zone, and weather types. We tested the predictiveness of two nested negative binomial models and adjudged that a nested spatial negative binomial regression model outperformed the non-spatial negative binomial model. The median county crash mortality rates at all times of the day and during the rush and non-rush hour periods were 18.4, 7.7, and 10.4 per 100,000 population, respectively. Fatal crash injury rate ratios were significantly elevated on interstates and highways at all times of the day - rush and non-rush hour periods inclusive. Intersections, driveways, and ramps on highways were associated with elevated fatal crash injury rate ratios. Clusters of high fatal crash injury rates were observed in counties located in Montana, Nevada, Colorado, Kansas, New Mexico, Oklahoma, Texas, Arkansas, Mississippi, Alabama, Georgia, and Nevada. The built and natural road environment factors are associated with county-level fatal crash injuries during the rush and non-rush hour periods. Understanding the association of road environment characteristics and the cluster distribution of fatal crash injuries may inform areas in need of focused intervention.

Prevalence of Human Coronaviruses in Children and Phylogenetic Analysis of HCoV-OC43 during 2016-2022 in Riyadh, Saudi Arabia.

With the emergence of SARS-CoV-2, routine surveillance combined with sequence and phylogenetic analysis of coronaviruses is urgently required. In the current study, the four common human coronaviruses (HCoVs), OC43, NL63, HKU1, and 229E, were screened in 361 clinical samples collected from hospitalized children with respiratory symptoms during four winter seasons. RT-PCR-based detection and typing revealed different prevalence rates of HCoVs across the four seasons. Interestingly, none of the four HCoVs were detected in the samples (n = 100) collected during the winter season of the COVID-19 pandemic. HCoV-OC43 (4.15%) was the most frequently detected, followed by 229E (1.1%). Partial sequences of S and N genes of OC43 from the winter seasons of 2015/2016 and 2021/2022 were used for sequence and phylogenetic analysis. Multiple sequence alignment of the two Saudi OC43s strains with international strains revealed the presence of sequence deletions and several mutations, of which some changed their corresponding amino acids. Glycosylation profiles revealed a number of O-and N-glycosylation sites in both genes. Based on phylogenetic analysis, four genotypes were observed with Riyadh strains grouped into the genotype C. Further long-term surveillance with a large number of clinical samples and sequences is necessary to resolve the circulation patterns and evolutionary kinetics of OC43 in Saudi Arabia.