Global geoepidemiology of gastrointestinal surgery rates in Crohn's disease.

BACKGROUND: Data regarding the worldwide gastrointestinal surgery rates in patients with Crohn's disease (CD) remains limited. AIM: To systematically review the global variation in the rates of surgery in CD. METHODS: A comprehensive search analysis was performed using multiple electronic databases from inception through July 1, 2020, to identify all full text, randomized controlled trials and cohort studies pertaining to gastrointestinal surgery rates in adult patients with CD. Outcomes included continent based demographic data, CD surgery rates over time, as well as the geoepidemiologic variation in CD surgery rates. Statistical analyses were conducted using R. RESULTS: Twenty-three studies spanning four continents were included. The median proportion of persons with CD who underwent gastrointestinal surgery in studies from North America, Europe, Asia, and Oceania were 30% (range: 1.7%-62.0%), 40% (range: 0.6%-74.0%), 17% (range: 16.0%-43.0%), and 38% respectively. No clear association was found regarding the proportion of patients undergoing gastrointestinal surgery over time in North America (R 2 = 0.035) and Europe (R 2 = 0.100). A moderate, negative association was seen regarding the proportion of patients undergoing gastrointestinal surgery over time (R 2 = 0.520) in Asia. CONCLUSION: There appears to be significant inter-continental variation regarding surgery rates in CD. Homogenous evidence-based guidelines accounting for the geographic differences in managing patients with CD is prudent. Moreover, as a paucity of data on surgery rates in CD exists outside the North American and European continents, future studies, particularly in less studied locales, are warranted.

Predictive ability of complete blood count, mean platelet ratio, mean platelet volume, and neutrophil/lymphocyte ratio for severe pneumonia among RT-PCR or radiologically proven COVID-19 patients.

Background: Immuno-inflammatory markers related to white blood cells, and platelets are shown to be associated with COVID-19 infection, and considered to be independent markers for clinical outcomes and mortality. The present study aimed to study the predictive value of these hematologic parameters in progression of COVID-19 to severe pneumonia. Methods: This was an analytical cross-sectional study conducted among RT-PCR or radiologically proven COVID-19 patients in a tertiary care hospital in Rajasthan. Semi-structured questionnaire was used to collect the epidemiological information of the patients with COVID-19. Complete blood count and other laboratory parameters were also studied among the patients. Results: Mean age of participants in the study was 52 years, with about 70% being males. Cough and breathlessness were the most common symptoms among the patients. It was found that the parameters related to white blood cells were significantly different between patients with COVID-19 infection and severe pneumonia (except absolute monocyte count). NLR was significantly higher among those with severe pneumonia. In the univariate analysis, age (OR - 1.02), NLR (OR - 1.16), and albumin (OR - 0.45) were found to be significant predictors of progression to severe pneumonia. In the final model, adjusted for confounders, only NLR and albumin levels significantly predicted progression to severe pneumonia among COVID-19 patients. Conclusion: The study consolidates the predictive ability of NLR for severe pneumonia. It is an important finding, as health facilities with limited access to laboratory investigations can rely on simple markers in routine practice to predict the progression of COVID-19 infection to severe pneumonia.

Malaria Vector Bionomics: Countrywide Surveillance Study on Implications for Malaria Elimination in India.

BACKGROUND: The biological characteristics of mosquito vectors vary, impacting their response to control measures. Thus, having up-to-date information on vector bionomics is essential to maintain the effectiveness of existing control strategies and tools, particularly as India aims for malaria elimination by 2030. OBJECTIVE: This study aims to assess the proportions of vector species resting indoors and outdoors, determine their preference for host biting/feeding, identify transmission sites, and evaluate the susceptibility of vectors to insecticides used in public health programs. METHODS: Mosquito collections were conducted in 13 districts across 8 Indian states from 2017 to 2020 using various methods to estimate their densities. Following morphological identification in the field, sibling species of Anopheles mosquitoes were identified molecularly using polymerase chain reaction (PCR)-specific alleles. Plasmodium falciparum and Plasmodium vivax infections in the vectors were detected using enzyme-linked immunosorbent assay (ELISA) and PCR assays. In addition, we assessed the insecticide susceptibility status of primary malaria vectors following the World Health Organization (WHO) protocol. RESULTS: Anopheles culicifacies, a primary malaria vector, was collected (with a man-hour density ranging from 3.1 to 15.9) from all states of India except those in the northeastern region. Anopheles fluviatilis, another primary vector, was collected from the states of Madhya Pradesh, Maharashtra, Karnataka, and Odisha. In Haryana and Karnataka, An. culicifacies sibling species A predominated, whereas species C and E were predominant in Madhya Pradesh and Maharashtra. An. culicifacies displayed mainly endophilic behavior across all states, except in Madhya Pradesh, where the proportion of semigravid and gravid mosquitoes was nearly half of that of unfed mosquitoes. The human blood index of An. culicifacies ranged from 0.001 to 0.220 across all study sites. The sporozoite rate of An. culicifacies ranged from 0.06 to 4.24, except in Madhya Pradesh, where none of the vector mosquitoes were found to be infected with the Plasmodium parasite. In the study area, An. culicifacies exhibited resistance to DDT (dichlorodiphenyltrichloroethane; with <39% mortality). Moreover, it showed resistance to malathion (with mortality rates ranging from 49% to 78%) in all districts except Angul in Odisha and Palwal in Haryana. In addition, resistance to deltamethrin was observed in districts of Maharashtra, Gujarat, Haryana, and Karnataka. CONCLUSIONS: Our study offers vital insights into the prevalence, resting behavior, and sibling species composition of malaria vectors in India. It is evident from our findings that resistance development in An. culicifacies, the primary vector, to synthetic pyrethroids is on the rise in the country. Furthermore, the results of our study suggest a potential change in the resting behavior of An. culicifacies in Madhya Pradesh, although further studies are required to confirm this shift definitively. These findings are essential for the development of effective vector control strategies in India, aligning with the goal of malaria elimination by 2030.

Recent Advances in Metal-Catalyzed Approaches for the Synthesis of Quinazoline Derivatives.

Quinazolines are an important class of heterocyclic compounds that have proven their significance, especially in the field of organic synthesis and medicinal chemistry because of their wide range of biological and pharmacological properties. Thus, numerous synthetic methods have been developed for the synthesis of quinazolines and their derivatives. This review article briefly outlines the new synthetic methods for compounds containing the quinazoline scaffold employing transition metal-catalyzed reactions.

RFX6 haploinsufficiency predisposes to diabetes through impaired beta cell function.

AIMS/HYPOTHESIS: Regulatory factor X 6 (RFX6) is crucial for pancreatic endocrine development and differentiation. The RFX6 variant p.His293LeufsTer7 is significantly enriched in the Finnish population, with almost 1:250 individuals as a carrier. Importantly, the FinnGen study indicates a high predisposition for heterozygous carriers to develop type 2 and gestational diabetes. However, the precise mechanism of this predisposition remains unknown. METHODS: To understand the role of this variant in beta cell development and function, we used CRISPR technology to generate allelic series of pluripotent stem cells. We created two isogenic stem cell models: a human embryonic stem cell model; and a patient-derived stem cell model. Both were differentiated into pancreatic islet lineages (stem-cell-derived islets, SC-islets), followed by implantation in immunocompromised NOD-SCID-Gamma mice. RESULTS: Stem cell models of the homozygous variant RFX6-/- predictably failed to generate insulin-secreting pancreatic beta cells, mirroring the phenotype observed in Mitchell-Riley syndrome. Notably, at the pancreatic endocrine stage, there was an upregulation of precursor markers NEUROG3 and SOX9, accompanied by increased apoptosis. Intriguingly, heterozygous RFX6+/- SC-islets exhibited RFX6 haploinsufficiency (54.2% reduction in protein expression), associated with reduced beta cell maturation markers, altered calcium signalling and impaired insulin secretion (62% and 54% reduction in basal and high glucose conditions, respectively). However, RFX6 haploinsufficiency did not have an impact on beta cell number or insulin content. The reduced insulin secretion persisted after in vivo implantation in mice, aligning with the increased risk of variant carriers to develop diabetes. CONCLUSIONS/INTERPRETATION: Our allelic series isogenic SC-islet models represent a powerful tool to elucidate specific aetiologies of diabetes in humans, enabling the sensitive detection of aberrations in both beta cell development and function. We highlight the critical role of RFX6 in augmenting and maintaining the pancreatic progenitor pool, with an endocrine roadblock and increased cell death upon its loss. We demonstrate that RFX6 haploinsufficiency does not affect beta cell number or insulin content but does impair function, predisposing heterozygous carriers of loss-of-function variants to diabetes. DATA AVAILABILITY: Ultra-deep bulk RNA-seq data for pancreatic differentiation stages 3, 5 and 7 of H1 RFX6 genotypes are deposited in the Gene Expression Omnibus database with accession code GSE234289. Original western blot images are deposited at Mendeley ( https://data.mendeley.com/datasets/g75drr3mgw/2 ).

Dysregulation of Autophagy Occurs During Congenital Cataract Development in ßA3ΔG91 Mice.

Purpose: To examine lens phenotypic characteristics in ßA3ΔG91 mice and determine if ßA3ΔG91 affects autophagy in the lens. Methods: We generated a ßA3ΔG91 mouse model using CRISPR/Cas9 methodology. Comparative phenotypic and biochemical characterizations of lenses from postnatal day 0 (P0), P15, and 1-month-old ßA3ΔG91 and wild-type (WT) mice were performed. The methodologies used included non-invasive slit-lamp examination, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot, and immunohistochemical (IHC) analyses to determine the levels of autophagy-related genes and proteins. Transmission electron microscopy (TEM) analysis of lenses was performed to assess organelle degradation and the presence of autophagic vesicles. TUNEL staining was used to determine apoptosis in the lens. Results: Relative to WT lenses, 1-month-old ßA3ΔG91 mice developed congenital nuclear cataract and microphthalmia and showed an early loss of endoplasmic reticulum (ER) in the cortex and attenuation of nuclei degradation. This observation was confirmed by TEM analysis, as was the presence of autophagic vesicles in ßA3ΔG91 lenses. Comparative IHC and RT-qPCR analyses showed relatively higher levels of autophagy markers (ubiquitinated proteins and p62, LC3, and LAMP2 proteins) in ßA3ΔG91 lenses compared to WT lenses. Additionally, ßA3ΔG91 lenses showed relatively greater numbers of apoptotic cells and higher levels of cleaved caspase-3 and caspase-9. Conclusions: The deletion of G91 in ßA3ΔG91 mice leads to higher levels of expression of autophagy-related proteins and their transcripts relative to WT lenses. Taken together, G91 deletion in ßA3/A1-crystallin is associated with autophagy disruption, attenuation of nuclei degradation, and cellular apoptosis in the lens, which might be congenital cataract causative factors.

A phase III, single-arm, 6-month trial of a wide-dose range oral testosterone undecanoate product.

Background: Oral testosterone undecanoate (TU) formulations may provide effective, safe, and easily titratable testosterone replacement therapy. Objective: Demonstrate efficacy and safety of a novel oral TU formulation. Design: An open-label, single-arm, multi-center trial treated 155 hypogonadal men for 180 days. Treatment began at 200 mg TU twice daily with meals; doses were titrated over two 28-day cycles to between 100 and 800 mg TU daily, measuring average testosterone (T Cavg) after 90 days. Ambulatory blood pressure monitoring (ABPM) occurred at baseline, 120, and 180 days. Methods: Titrations used a randomized blood sample taken 3-, 4-, or 5-h post-morning dose. Outcomes used sodium fluoride/ethylenediaminetetraacetate plasma testosterone (T) values; serum results were also reported. Blood pressure (ABPM and in-clinic) was evaluated for change from baseline. Results: After titration, 87.8% of KYZATREX™ treated participants (worse-case scenario) and 96.1% of 90-day completers achieved eugonadal mean plasma T values. Serum T Cavg was 452 ng/dL and maximum T concentrations (T Cmax) met all FDA criteria. Participant eugonadal percentages were comparable across subgroups for age, weight, and body mass index. Diet had no effect on participant eugonadal percentages. KYZATREX was well tolerated, with no drug-related serious adverse events (SAE) and one adverse drug reaction (hypertension) observed in 2% or more of participants. Systolic ambulatory blood pressure increased 1.7 mmHg (95% confidence interval: 0.3-3.1). At baseline, 36% of 155 participants were receiving anti-hypertensive medication and 22% were diabetic. No dose increases occurred in existing anti-hypertensive medication; five participants (3.2%) started anti-hypertensive medication. Conclusion: KYZATREX provided safe and effective testosterone levels within the normal range in hypogonadal male study participants. Clinical trial registration: URL: https://clinicaltrials.gov/ unique identifier NCT04467697, conducted under NCT03198728. Post-completion, clinicaltrials.gov requested creation of the separate NCT04467697 identifier. All subjects were recruited under NCT03198728.

Consensus statement-graft treatment in cardiovascular bypass graft surgery.

Coronary artery bypass grafting (CABG) is and continues to be the preferred revascularization strategy in patients with multivessel disease. Graft selection has been shown to influence the outcomes following CABG. During the last almost 60 years saphenous vein grafts (SVG) together with the internal mammary artery have become the standard of care for patients undergoing CABG surgery. While there is little doubt about the benefits, the patency rates are constantly under debate. Despite its acknowledged limitations in terms of long-term patency due to intimal hyperplasia, the saphenous vein is still the most often used graft. Although reendothelialization occurs early postoperatively, the process of intimal hyperplasia remains irreversible. This is due in part to the persistence of high shear forces, the chronic localized inflammatory response, and the partial dysfunctionality of the regenerated endothelium. "No-Touch" harvesting techniques, specific storage solutions, pressure controlled graft flushing and external stenting are important and established methods aiming to overcome the process of intimal hyperplasia at different time levels. Still despite the known evidence these methods are not standard everywhere. The use of arterial grafts is another strategy to address the inferior SVG patency rates and to perform CABG with total arterial revascularization. Composite grafting, pharmacological agents as well as latest minimal invasive techniques aim in the same direction. To give guide and set standards all graft related topics for CABG are presented in this expert opinion document on graft treatment.

Health trends in Canada 1990-2019: An analysis for the Global Burden of Disease Study.

OBJECTIVE: Monitoring trends in key population health indicators is important for informing health policies. The aim of this study was to examine population health trends in Canada over the past 30 years in relation to other countries. METHODS: We used data on disability-adjusted life years (DALYs), years of life lost (YLL), years lived with disability, life expectancy (LE), and child mortality for Canada and other countries between 1990 and 2019 provided by the Global Burden of Disease Study. RESULTS: Life expectancy, age-standardized YLL, and age-standardized DALYs all improved in Canada between 1990 and 2019, although the rate of improvement has leveled off since 2011. The top five causes of all-age DALYs in Canada in 2019 were neoplasms, cardiovascular diseases, musculoskeletal disorders, neurological disorders, and mental disorders. The greatest increases in all-age DALYs since 1990 were observed for substance use, diabetes and chronic kidney disease, and sense organ disorders. Age-standardized DALYs declined for most conditions, except for substance use, diabetes and chronic kidney disease, and musculoskeletal disorders, which increased by 94.6%, 14.6%, and 7.3% respectively since 1990. Canada's world ranking for age-standardized DALYs declined from 9th place in 1990 to 24th in 2019. CONCLUSION: Canadians are healthier today than in 1990, but progress has slowed in Canada in recent years in comparison with other high-income countries. The growing burden of substance abuse, diabetes/chronic kidney disease, and musculoskeletal diseases will require continued action to improve population health.

RéSUMé: OBJECTIF: La surveillance des tendances des indicateurs clés de la santé de la population est importante pour éclairer les politiques de santé. Dans cette étude, nous avons examiné les tendances de la santé de la population au Canada au cours des 30 dernières années par rapport à d'autres pays. MéTHODES: Nous avons utilisé des données sur les années de vie ajustées en fonction de l'incapacité (DALY), les années de vie perdues (YLL), les années vécues avec un handicap, l'espérance de vie (LE) et la mortalité infantile pour le Canada et d'autres pays entre 1990 et 2019, fournies par l'Étude mondiale sur le fardeau de la maladie. RéSULTATS: L'espérance de vie, les YLL ajustées selon l'âge et les DALY ajustées selon l'âge ont tous connu une amélioration au Canada entre 1990 et 2019, bien que le taux d'amélioration se soit stabilisé depuis 2011. Les cinq principales causes des DALY pour tous les âges au Canada en 2019 étaient les néoplasmes, les maladies cardiovasculaires, les affections musculosquelettiques, les affections neurologiques et les troubles mentaux. Les plus fortes augmentations des DALY pour tous les âges depuis 1990 ont été observées pour l'usage de substances, le diabète et les maladies rénales chroniques, ainsi que les troubles des organes sensoriels. Les DALY ajustées selon l'âge ont diminué pour la plupart des conditions, à l'exception de l'usage de substances, du diabète et des maladies rénales chroniques, ainsi que des troubles musculosquelettiques, qui ont augmenté de 94,6 %, 14,6 % et 7,3 % respectivement depuis 1990. Le classement mondial du Canada pour les DALY ajustées selon l'âge est diminué de la 9ième place en 1990 à la 24ième place en 2019. CONCLUSION: Les Canadiens sont en meilleure santé aujourd'hui qu'en 1990, mais les progrès se sont ralentis ces dernières années par rapport à d'autres pays à revenu élevé. La croissance du fardeau lié à l'abus de substances, au diabète/maladies rénales chroniques et aux affections musculosquelettiques exigera des actions continues pour améliorer la santé de la population.

Stronger genetic differentiation among within-population genetic groups than among populations in Scots pine provides new insights into within-population genetic structuring.

We investigated the presence of spatial genetic groups within forest tree populations and determined if the genetic divergence among these groups is greater than that between populations using Scots pine (Pinus sylvestris) as a model species. We genotyped 890 adult trees of Scots pine in six natural populations in Lithuania at 11 nuclear microsatellite loci. We used a Bayesian clustering approach to identify the within-population genetic groups within each of the six populations. We calculated the differentiation indexes among the genetic groups within each population and among the six populations by ignoring the genetic groups. The Bayesian clustering revealed 2 to 6 distinct genetic groups of varying size as the most likely genetic structures within populations. The genetic differentiation indexes among the genetic groups within populations were nearly tenfold greater (FST = 0.012-0.070) than those between the populations (FST = 0.003). We conclude on the existence of markedly stronger structuring of genetic variation within populations than between populations of Scots pine in large forest tracts of northern Europe. Such genetic structures serve as a contributing factor to large within population genetic diversity in northern conifers. We assume that within population mating in Scots pine is not completely random but rather is stratified into genetic clusters. Our study provides pioneering novel key insights into structuring of genetic variation within populations. Our findings have implications for examining within-population genetic diversity and genetic structure, conservation, and management of genetic resources.

Fruit waste-derived cellulose-polyaniline composite for adsorption-coupled reduction of chromium oxyanions.

Hexavalent chromium oxyanions, known as potentially toxic micropollutants, exist in the effluents and discharges of metallurgical, electroplating, refractory, chemical, and tanning industries. The exposure of chromium-contaminated water causes severe health hazards. The present work outlines a facile approach to grow polyaniline (PANI) on fruit-waste-derived cellulose (CEL) via oxidative polymerization of aniline; followed by chemical processing with NH4OH to obtain CEL-PANI-EB composites for adsorptive separation-coupled reduction of highly toxic hexavalent chromium oxyanions. The spectroscopic analyses of the CEL-PANI-EB composite before and after adsorption of Cr(VI) oxyanions revealed hydrogen bonding, electrostatic, and complexation as major interactive pathways. The adsorbed hexavalent chromium oxyanions are reduced into Cr(III) species by oxidation of PANI-based benzenoid amine into quinoid imine in the CEL-PANI-EB composite. The adsorption of Cr(VI) oxyanions by the CEL-PANI-EB composite showed negligible effects of other anionic co-pollutants, like NO3- and SO42-. The CEL-PANI-EB composite adsorbed Cr(VI) oxyanions with a removal capacity of 469 mg g-1, based on the Langmuir adsorption isotherm model. The hydroxyl functionalities in cellulose and amine/imine functionalities in PANI facilitate the electrostatic attraction between the CEL-PANI-EB and Cr(VI) oxyanions in an acidic environment beside the hydrogen linkages. The adsorbed Cr(VI) oxyanions are reduced to Cr(III)-based species by the benzenoid amines of PANI, as revealed from the XPS analyses. The CEL-PANI-EB composite showed excellent recyclability and maintained 83.4% adsorption efficiency after seven runs of chromium adsorption-desorption. The current findings reveal the potential of CEL-PANI-EB composites for the adsorptive removal of Cr(VI) oxyanions and their conversion into a lesser toxic form, making them promising materials for wastewater treatment applications.

Coronavirus infection and ABO blood grouping: Correlation or coincidence?

Background: Association between the ABO blood group and patient outcomes in COVID-19 patients is still unexplored. A known association may help to understand possible risks in advance to the management of such COVID-19 patients. The present study was designed to test such association if there is any, between the ABO blood group and the severity of COVID-19 patients. Methods: The present hospital-based observational study was conducted at a COVID-19 dedicated tertiary care hospital in North India over a period of six months during the first wave of the pandemic in the country. Five hundred consecutive patients, who tested positive for COVID-19 using RT-PCR on oropharyngeal/nasopharyngeal swabs, admitted to the hospital were included in the study. ABO and Rhesus (Rh) blood grouping was done on leftover hematology blood samples using gel column agglutination technology. Required clinical details of patients including age, gender, clinical symptoms, comorbidities, outcomes, etc., were obtained from the patient's case sheets. Results: The most common blood group was 'B' (42.8%) followed by 'O' (23.4%), and 'A' (22.4%) while the least common was 'AB' (11.4%). Rh positive was seen in 96.2% while 3.8% were negative. Baseline characteristics were comparable including length of hospital stay, duration of symptoms, and associated comorbid illnesses. The need for intensive care unit (ICU) admissions (P = 0.05) and intubations (P = 0.20) was similar across all four blood groups. Differences in the severity of COVID-19 disease and mortalities among the groups were non-significant. Conclusion: There was no observed association found between the ABO blood group and COVID-19 infection requiring hospitalization, ICU admission, intubation, and outcomes. However, there was a higher proportion of breathlessness and the presence of at least one comorbidity in blood group O as compared to others.

Unraveling Compositional Study, Chemometric Analysis, and Cell-Based Antioxidant Potential of Selective High Nutraceutical Value Amaranth Cultivars Using a GC-MS and NMR-Based Metabolomics Approach.

Amaranthus (family Amaranthaceae) is a potentially nutritious pseudocereal also known as a functional food owing to its high nutritional quality grains especially rich in essential amino acids. Emerging study, however, unambiguously indicates that apart from essential nutrients like protein, other phytochemicals present in amaranth seeds provide excellent health benefits. Squalene is one such phytonutrient found in Amaranthus seeds, which is also its largest vegetal source. In this research work, GC-MS and NMR spectroscopy-based metabolomics have been utilized for the compositional analysis of Amaranthus seeds coupled with a multivariate data set. Investigation of nonpolar and polar seed extracts of six different cultivars of amaranth identified 47 primary and secondary metabolites. One-way ANOVA showed significant quantitative metabolic variations in different cultivars of amaranth. Multivariate principal component analysis of both the GC-MS and NMR analyzed data broadly classified in two groups showed significant variations in the polar (lysine, arginine, GABA, and myoinositol) and nonpolar (squalene, tryptophan, and alkylated phenols, which are potential nutraceutical agents) metabolites. The squalene content estimated using HPLC varied significantly (1.61 to 4.72 mg g-1 seed dry weight) among six different cultivars. Positive correlations were found among the cellular antioxidant activity and squalene content. Cultivar AM-3 having the maximum squalene content showed the highest antioxidant activity evaluated on the cellular level over human embryonic kidney cells, clearly revealing potent intercellular reactive oxygen species scavenging capacity and strong membrane lipid peroxidation inhibition potential. Oxidative stress markers such as MDA, SOD, GSH, and CAT levels in cells further corroborated the research work. The study also indicated high concentrations of lysine (80.49 mg g-1 dry seeds) in AM-2, squalene (0.47% by weight) in AM-3, and 2,4-di-tert-butyl phenol (18.64% peak area) and myoinositol (79.07 mg g-1 dry seeds) in AM-5. This novel comparative metabolomic study successfully profiles the nutrient composition of amaranth cultivars and provides the opportunity for the development of nutraceuticals and natural antioxidants from this functional food.

Postglacial phylogeography, admixture, and evolution of red spruce (Picea rubens Sarg.) in Eastern North America.

Climate change is a major evolutionary force that can affect the structure of forest ecosystems worldwide. Red spruce (Picea rubens Sarg.) has recently faced a considerable decline in the Southern Appalachians due to rapid environmental change, which includes historical land use, and atmospheric pollution. In the northern part of its range, red spruce is sympatric with closely related black spruce (Picea mariana (Mill.) B.S.P.), where introgressive hybridization commonly occurs. We investigated range-wide population genetic diversity and structure and inferred postglacial migration patterns and evolution of red spruce using nuclear microsatellites. Moderate genetic diversity and differentiation were observed in red spruce. Genetic distance, maximum likelihood and Bayesian analyses identified two distinct population clusters: southern glacial populations, and the evolutionarily younger northern populations. Approximate Bayesian computation suggests that patterns of admixture are the result of divergence of red spruce and black spruce from a common ancestor and then introgressive hybridization during post-glacial migration. Genetic diversity, effective population size (Ne) and genetic differentiation were higher in the northern than in the southern populations. Our results along with previously available fossil data suggest that Picea rubens and Picea mariana occupied separate southern refugia during the last glaciation. After initial expansion in the early Holocene, these two species faced a period of recession and formed a secondary coastal refugium, where introgressive hybridization occurred, and then both species migrated northward. As a result, various levels of black spruce alleles are present in the sympatric red spruce populations. Allopatric populations of P. rubens and P. mariana have many species-specific alleles and much fewer alleles from common ancestry. The pure southern red spruce populations may become critically endangered under projected climate change conditions as their ecological niche may disappear.

Role of Fibroblast Growth Factor Receptor 2 (FGFR2) in Corneal Stromal Thinning.

Purpose: To determine the role of fibroblast growth factor receptor 2 (FGFR2)-mediated signaling in keratocytes during corneal development, a keratocyte-specific FGFR2-knockout (named FGFR2cKO) mouse model was generated, and its phenotypic characteristics were determined. Methods: A FGFR2cKO mouse model was generated by the following method: FGFR2 flox mice were crossed with the inducible keratocyte specific-Cre mice (Kera-rtTA/tet-O-Cre). Both male and female FGFR2cKO- and control mice (1 to 3-months-old) were analyzed for changes in corneal topography and pachymetry maps using the optical coherence tomography (OCT) method. The comparative TUNEL assay and immunohistochemical analyses were performed using corneas of FGFR2cKO and control mice to determine apoptotic cells, and expression of collagen-1 and fibronectin. Transmission electron microscopic analysis was conducted to determine collagen structures and their diameters in corneas of FGFR2cKO and control mice. Results: OCT-analyses of corneas of FGFR2cKO mice (n = 24) showed localized central thinning and an increased corneal steepness compared to control mice (n = 23). FGFR2cKO mice further showed a decreased expression in collagen-1, decreased collagen diameters, acute corneal hydrops, an increased fibronectin expression, and an increased number of TUNEL-positive cells suggesting altered collagen structures and keratocytes' apoptosis in the corneas of FGFR2cKO mice compared to control mice. Conclusions: The FGFR2cKO mice showed several corneal phenotypes (as described above in the results) that are also exhibited by the human keratoconus corneas. The results suggested that the FGFR2cKO mouse model serves to elucidate not only the yet unknown role of FGFR2-mediated signaling in corneal physiology but also serves as a model to determine molecular mechanism of human keratoconus development.

Genetic differentiation among Aedes aegypti populations from different eco-geographical zones of India.

The present study explicitly evaluated the genetic structure of Aedes aegypti Linn, the vector of dengue, chikungunya, and Zika viruses, across different geo-climatic zones of India and also elucidated the impact of ecological and topographic factors. After data quality checks and removal of samples with excess null alleles, the final analysis was performed on 589 individual samples using 10 microsatellite markers. Overall findings of this study suggested that, Ae. aegypti populations are highly diverse with moderate genetic differentiation between them. Around half of the populations (13 out of 22) formed two genetic clusters roughly associated with geographical regions. The remaining nine populations shared genetic ancestries with either one or both of the clusters. A significant relationship between genetic and geographic distance was observed, indicating isolation by distance. However, spatial autocorrelation analysis predicted the signs of long-distance admixture. Post-hoc environmental association analysis showed that 52.7% of genetic variations were explained by a combination of climatic and topographic factors, with latitude and temperature being the best predictors. This study indicated that though overall genetic differentiation among Ae. aegypti populations across India is moderate (Fst = 0.099), the differences between the populations are developing due to the factors associated with geographic locations. This study improves the understanding of the Ae. aegypti population structure in India that may assist in predicting mosquito movements across the geo-climatic zones, enabling effective control strategies and assessing the risk of disease transmission.

A sustainable management of polycyclic aromatic hydrocarbons to synthesize microporous organic polymers for adsorptive desulphurization of fuels.

A sustainable management of carcinogenic polycyclic aromatic hydrocarbons (PAHs) to synthesize a series of high surface area (SABET of 563-1553 m2 g-1) microporous polymeric adsorbents is reported. The products with high yield (>90%) were obtained within only 30 min at a low temperature of 50 °C using a microwave-assisted approach with 400 W microwave power followed by 30 min of ageing by raising the temperature to 80 °C. The synthesized adsorbents are used for removing another category of carcinogenic pollutants i.e., polycyclic aromatic sulphur heterocycles (PASHs) from model and real fuels. Adsorptive desulphurization experiment in batch mode could reduce the sulphur from high concentrated model (100 ppm) and real (102 ppm) fuels to 8 ppm and 45 ppm respectively. Similarly, desulphurization of model and real fuels with ultralow sulphur concentrations of 10 and 9 ppm, respectively, reduced the final concentration of sulphur to 0.2 and 3 ppm, respectively. Adsorption isotherms, kinetics, and thermodynamic studies have been conducted using batch mode experiments. Adsorptive desulphurization using fixed bed column studies show the breakthrough capacities of 18.6 and 8.2 mgS g-1, for the same high concentrated model and real fuels, respectively. The breakthrough capacities of 1.1 and 0.6 mgS g-1 are estimated for the ultralow sulphur model and real fuels, respectively. The adsorption mechanism, based on the spectroscopic analysis (FTIR and XPS) demonstrates the role of π-π interactions between the adsorbate and adsorbent. The adsorptive desulphurization studies of model and real fuels from batch to fixed bed column mode would offer an in-depth understanding to demonstrate the lab-scale findings for industrial applications. Thus, the present sustainable strategy could manage two classes of carcinogenic petrochemical pollutants, PAHs and PASHs, simultaneously.

Air quality and respiratory health in children.

Air pollution is a leading modifiable risk factor for various cardio-respiratory outcomes globally, both for children and for adults. Children are particularly susceptible to the adverse effects of air pollution due to various physiological and behavioural factors. Children are at a higher risk of outcomes such as acute respiratory infections, asthma and decreased lung function due to air pollution exposure; the risk varies in different geographical regions, depending on the source of air pollution, duration of exposures and concentration. Prenatal exposure to air pollution may also contribute to adverse respiratory outcomes later in life.