Proton Conduction via Water and Ammonia Coordinated Metal Cationic Species in MOF and MHOF Platforms.

Although metal-organic frameworks (MOFs) and metalo hydrogen-bonded organic frameworks (MHOFs) are designed as promising solid-state proton conductors by incorporating various protonic species intrinsically or extrinsically, design and development of such materials by employing the concept of proton conduction through coordinated polar protic solvent is largely unexplored. Herein, we have constructed two proton-conducting materials having different solvent coordinated metal cationic species: In-H2O-MOF, ({[In(H2O)6][In3(Pzdc)6]·15H2O}n; H2Pzdc: pyrazine-2,3-dicarboxylic acid) with coordinated water molecules from hexaaquaindium cationic species, and MHOF-4, ([{Co(NH3)6}2(2,6-NDS)2(H2O)2]n; 2,6-H2NDS: 2,6-naphthalenedisulfonic acid) with coordinated ammonia from hexaammoniacobalt cationic species. Interestingly, higher proton conductivity was achieved for In-H2O-MOF (1.5 × 10-5 S cm-1) than MHOF-4 (6.3 × 10-6 S cm-1) under the extreme conditions (80 ºC and 95% RH), which could be attributed to enhanced acidity of coordinated water molecules having much lower pKa value than that of coordinated ammonia. Greater charge polarization on hydrogen atoms of In3+-coordinated water molecules than that of Co2+-coordinated ammonia led to the high conductivity of In-H2O-MOF, as evident by quantum chemical studies. Such a comparative study on metal-coordinated protic polar solvents in achieving proton conduction in crystalline solids is yet to be made.

Microleakage of Class II Posterior Composite Restorations with and Without use of Liners - A Comparative Study.

AIM: This study aims to compare the effect of liner on microleakage in Class II restorations at the occlusal and gingival levels when restored with a nanocomposite. METHODOLOGY: A total of 60 mandibular molars were selected and divided into three groups. Cavities in Group A were restored with posterior nanocomposite without liner, samples of Group B were restored with posterior nanocomposite with flowable composite liner and in Group C samples were restored with posterior nanocomposite with resin-modified glass ionomer cement (RMGIC) liner. Samples were stored at 37°C in 100% humidity for 14 days. Samples were subsequently immersed in 0.5% methylene blue dye and then placed under water for 15 mins. Teeth were sectioned mesiodistally with a diamond disc and examined under a stereomicroscope. RESULTS: All the cavities exhibited dye penetration along the occlusal and gingival margins of the restored cavities. Group A showed maximum leakage compared to Groups B and C, which was statistically significant (P = 0.001 and P < 0.0001). No significant difference in microleakage was observed between Groups B and C. Microleakage was more in gingival margins as compared to occlusal margins in all the groups. CONCLUSION: Based on the results of the present study, it may be concluded that the placement of liner beneath nanocomposite restoration results in a significant reduction in microleakage.

Bacteremia Due to Lactococcus lactis cremoris Following Food Poisoning: A Case Report.

Lactococcus lactis (L. lactis) cremoris is a catalase-negative, gram-positive cocci, rarely reported as a cause of human infections. We report a case of probable food poisoning caused by L. lactis cremoris in an adult female. A 58-year-old female was brought to the Emergency Department with a history of sudden onset of high-grade fever, vomiting, and febrile seizures. On investigation, all parameters were within normal range. However, L. lactis cremoris was isolated from her blood culture. The patient gave a history of travel to a local pilgrimage and consumption of unpasteurized dairy products for a week leading up to the incident. The patient was treated with intravenous doxycycline and recovered after seven days of treatment with sterile blood cultures on follow-up.

Diabetes Mellitus as a Risk Factor for Tuberculosis: A Community Based Case Control Study.

Background: Prevention of diabetes in the general population can help reduce the incidence of tuberculosis. Hence it is necessary to document that diabetes is strongly associated with tuberculosis as a risk factor. Objective: To study if diabetes is associated with tuberculosis compared to controls. Materials and Methods: A community based case-control study was carried out. 215 newly diagnosed cases of tuberculosis on treatment for not more than three months were selected randomly from the randomly selected tuberculosis unit. 215 neighbourhood controls were selected. They were matched for the age group of ± 10 years and sex. Fasting blood sugar (FBS) was estimated using a glucometer. Results: Tobacco chewing, residence and family history of TB were significantly more in cases (P < 0.05). Mean BMI was significantly lower in cases compared to controls. The proportion of TB cases among the known cases of diabetes was 67% compared to 33% in controls, which was statistically significant. Mean FBS was significantly higher in cases compared to controls (P < 0.05). The odds of cases being diabetic was 2.456 times more than those of controls. On binary logistic regression, diabetes was an independent risk factor for tuberculosis. Other independent risk factors were tobacco chewing, and family history of TB. Conclusion: Family history of tuberculosis, and tobacco chewing were positively associated with tuberculosis whereas body mass index was negatively associated with tuberculosis. Diabetes was significantly associated with tuberculosis.

Advancing CAR T-cell therapies: Preclinical insights and clinical translation for hematological malignancies.

Chimeric antigen receptor (CAR) T-cell therapy has achieved significant success in achieving durable and potentially curative responses in patients with hematological malignancies. CARs are tailored fusion proteins that direct T cells to a specific antigen on tumor cells thereby eliciting a targeted immune response. The approval of several CD19-targeted CAR T-cell therapies has resulted in a notable surge in clinical trials involving CAR T cell therapies for hematological malignancies. Despite advancements in understanding response mechanisms, resistance patterns, and adverse events associated with CAR T-cell therapy, the translation of these insights into robust clinical efficacy has shown modest outcomes in both clinical trials and real-world scenarios. Therefore, the assessment of CAR T-cell functionality through rigorous preclinical studies plays a pivotal role in refining therapeutic strategies for clinical applications. This review provides an overview of the various in vitro and animal models used to assess the functionality of CAR T-cells. We discuss the findings from preclinical research involving approved CAR T-cell products, along with the implications derived from recent preclinical studies aiming to optimize the functionality of CAR T-cells. The review underscores the importance of robust preclinical evaluations and the need for models that accurately replicate human disease to bridge the gap between preclinical success and clinical efficacy.

A biodegradable microgrooved and tissue mechanocompatible citrate-based scaffold improves bladder tissue regeneration.

Chronic bladder dysfunction due to bladder disease or trauma is detrimental to affected patients as it can lead to increased risk of upper urinary tract dysfunction. Current treatment options include surgical interventions that enlarge the bladder with autologous bowel tissue to alleviate pressure on the upper urinary tract. This highly invasive procedure, termed bladder augmentation enterocystoplasty (BAE), significantly increases the risk of patient morbidity and mortality due to the incompatibility between bowel and bladder tissue. Therefore, patients would significantly benefit from an alternative treatment strategy that can regenerate healthy tissue and restore overall bladder function. Previous research has demonstrated the potential of citrate-based scaffolds co-seeded with bone marrow-derived stem/progenitor cells as an alternative graft for bladder augmentation. Recognizing that contact guidance can potentially influence tissue regeneration, we hypothesized that microtopographically patterned scaffolds would modulate cell responses and improve overall quality of the regenerated bladder tissue. We fabricated microgrooved (MG) scaffolds using the citrate-based biomaterial poly (1,8-octamethylene-citrate-co-octanol) (POCO) and co-seeded them with human bone marrow-derived mesenchymal stromal cells (MSCs) and CD34+ hematopoietic stem/progenitor cells (HSPCs). MG POCO scaffolds supported MSC and HSPC attachment, and MSC alignment within the microgrooves. All scaffolds were characterized and assessed for bladder tissue regeneration in an established nude rat bladder augmentation model. In all cases, normal physiological function was maintained post-augmentation, even without the presence of stem/progenitor cells. Urodynamic testing at 4-weeks post-augmentation for all experimental groups demonstrated that bladder capacity increased and bladder compliance was normal. Histological evaluation of the regenerated tissue revealed that cell-seeded scaffolds restored normal bladder smooth muscle content and resulted in increased revascularization and peripheral nerve regeneration. The presence of microgrooves on the cell-seeded scaffolds increased microvasculature formation by 20 % and urothelial layer thickness by 25 % in the regenerating tissue. Thus, this work demonstrates that microtopography engineering can influence bladder tissue regeneration to improve overall anatomical structure and re-establish bladder physiology.

Clinical and Immunological Profile of Pediatric-Onset Systemic Lupus Erythematosus in Eastern India: A Prospective Observational Study.

BACKGROUND: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with a strong female predisposition. pSLE often results in a worse prognosis compared to adult SLE. Studies on pSLE from the Indian subcontinent are scarce. OBJECTIVE: This study aims to describe the clinical manifestations, laboratory and serological parameters, management, and outcomes of pSLE patients from a premier tertiary care institute in Eastern India. METHODS: This prospective observational study was conducted at Kalinga Institute of Medical Sciences, Bhubaneswar, from September 2020 to October 2023. Children aged 1-14 years fulfilling the Systemic Lupus International Collaborating Clinics criteria for SLE were included. A detailed history, clinical examination, and laboratory investigations were performed. Data on complications, treatment, and outcomes were collected. Statistical analysis was done using SPSS Statistics version 21 (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.). RESULTS: Out of 114,009 patients (outdoor and indoor), 40 were diagnosed with pSLE, resulting in an incidence of 0.35 per 1000 children. The female-to-male ratio was 7:1. The mean age of presentation was 11.67 ± 2.37 years. Among the predominant symptoms observed, mucocutaneous manifestations were seen in 39 (97.5%), followed by pallor in 36 (90%), and fever in 33 (82.5%). The most common organ system involved was mucocutaneous, observed in 39 (97.5%) patients, followed by hematological in 36 (90%) and renal in 19 (47.5%). Lupus nephritis was observed in 19 (47.5%) patients, with class IV being the most common. Anti-nuclear antibody and anti-double-stranded DNA were positive in 39 (97.5%) and 27 (68%) of children, respectively. Complete remission was achieved in 14 (35%), improvement in 16 (40%), and flare-ups in 3 (7.5%) patients. CONCLUSION: pSLE is an uncommon but severe autoimmune disease with significant multi-system involvement. Early identification and prompt treatment are crucial to minimizing adverse outcomes. This study provides detailed insights into the clinical and immunological profile of pSLE in Eastern India, underscoring the need for larger multicentric studies with long-term follow-ups.

Immunofluorescence detection of Ecytonucleospora hepatopenaei (EHP) in Penaeus vannamei.

Hepatopancreatic microsporidiosis (HPM), caused by the microsporidium Ecytonucleospora hepatopenaei (EHP) leads to retarded growth and enhanced susceptibility to other diseases in shrimp resulting in a major loss for the shrimp industry worldwide. It is little understood how EHP infects its host and hijacks its cellular machinery to replicate and exert clinical manifestations in infected shrimp. Since the initial record of HPM, histopathology and polymerase chain reaction (PCR)-based assays were developed for the detection of EHP to prevent spread of the disease. Availability of an antibody-based detection method would complement these existing diagnostic tools and be useful in studying EHP pathogenesis. We describe here an immunofluorescence assay (IFA) for detecting EHP using monoclonal antibodies (mAbs) that were originally developed against Cryptosporidium parvum, a coccidian parasite that infects calves (Bos taurus), other agriculturally important animals, and humans. Forty-one mAbs were screened and two mAbs, 3E2 and 3A12, were found to detect EHP successfully. The utility of these mAbs in detecting EHP was further assessed by testing 36 experimentally challenged EHP-infected shrimp (Penaeus vannamei). EHP-detection data from infected shrimp were compared by Hematoxylin and Eosin (H&E) histology, real-time PCR, and immunofluorescence. The data show IFA using mAbs 3E2 and 3A12 could successfully detect EHP and that the sensitivity of detection is comparable to H&E histology and quantitative PCR. Availability of mAbs that can detect EHP is expected to be immensely beneficial in HPM diagnosis. Since the pathobiology of C. parvum has been so widely studied, these cross-reactive mAbs may also aid in gaining some insight into EHP pathogenesis and disease.

Development of a simple and reproducible HPTLC method on protective effect induced by bark of Acacia nilotica on poisoning caused by use of nicotine containing tobacco products.

Tobacco (Nicotiana tobacum) and tobacco products are the most critical public health challenges today across the globe. Nicotine is the main chemical composition of tobacco and is associated with withdrawal syndrome. A laboratory animal is commonly employed as a model to investigate nicotine toxicity, drug dependence, reinforcing effects, and the protective effects of samples against nicotine-induced toxicity. The first in-vitro model was developed to prove the protective effect of Babbul (Acacianilotica Linn.) against nicotine poisoning caused by consumption of tobacco products. The HPTLC method for estimating the protective effect against nicotine poisoning was performed by taking the solvent systems dichloromethane, methanol, and liquid ammonia (25 %)(9:1:0.04v/v/v). This in-vitro approach was done by treating the bark of the Acacia nilotica extract with a standard solution of nicotine, which reduced the concentration of nicotine by 39.12 %. The prescribed HPTLC method can be used successfully to assess Acacia nilotica's protective impact against nicotine toxicity caused by intake of nicotine containing tobacco products.

Timing of Pediatric Breast Reduction and Insurance Coverage: Single-institution Retrospective Study.

Background: Although long-term benefits of reduction mammaplasty have been proven, the appropriate age for adolescent reduction mammaplasty has been highly debated due to possible need for revision surgery. Practitioners often delay offering breast reduction to adolescents below age 18 based on presumed insurance denial. We reviewed trends in insurance denial at a single children's hospital to analyze whether age and/or insurance carriers have a significant impact on coverage of breast reduction. Methods: A retrospective chart review from 2012 to 2022 of cisgender female patients with macromastia aged 12-20 years at the time of diagnosis was analyzed for differences in breast reduction insurance coverage based on age and body mass index at the time of diagnosis, referral to plastic surgery, and surgery. Results: A total of 121 cisgender women were included. There were no significant differences in the mean ages of patients who underwent breast reduction versus those who did not (16.46 years versus 16.96 years, respectively; P = 0.089), or in the mean body mass index for patients who did versus those who did not receive breast reduction (28.58 kg/m² versus 29.05kg/m², P = 0.382). Furthermore, there were no significant differences in the proportion of patients undergoing breast reduction by age (P = 0.200) or by insurance class (P = 0.403). Conclusion: Although insurance varies with carrier, the present findings suggest that surgeons need not delay in facilitating preauthorization for breast reduction in symptomatic patients presenting anytime during their teenage years.

Enhanced Optoelectronic Properties of Polythiophene-g-Poly(dimethyl amino ethyl methacrylate)-b-Poly(diethylene glycol methyl ether methacrylate) Copolymers using "Grafting onto" Synthetic Strategy.

The optoelectronic properties of polythiophene (PT) graft block copolymers are most important for fabricating optoelectronic devices, and recently, we reported a single-pot atom-transfer radical polymerization (ATRP) technique for preparation of PT graft block copolymers between thermoresponsive poly(diethylene glycol methyl ether methacrylate) (PDEGMEM) and pH-responsive poly(dimethyl amino ethyl methacrylate) (PDMAEMA) from the PT backbone via the "grafting from" strategy with an 11 mol % contamination. A "grafting onto" strategy has been opted to eliminate the contamination from the block copolymer where we synthesized poly(thiophene acetic acid) (P3TAA) followed by the coupling with PDEGMEM-b-PDMAEMA-Cl, PDMAEMA-b-PDEGMEM-Cl, and PDMAEMA-ran-PDEGMEM-Cl copolymers, produced separately by the ATRP technique. The polymers were characterized using 1H NMR, SEC, etc. TEM study exhibits mostly vesicular morphology and optical properties measured using UV-vis and photoluminescence spectroscopy showing pH dependent behavior. dc conductivity values indicate semiconducting nature in the order P2 > P3 > P1. The abrupt hike of P2 (∼80 times) in conductivity at pH 3 from that of previously prepared P2 copolymers formed by the grafting from process is attributed to the absence of ∼11 mol % contamination. Conductivity decreases with increasing pH, due to coiling of the PT backbone in accordance with the blue shifts of λabs peaks. The current (I)-voltage (V) plots exhibit bimodal memory and organic mixed ionic and electronic conductivity. Higher current (3.3 mA for P2, pH 3) and electronic memory occur upon light irradiation than that of dark. Photoswitching property decreases with increase of pH, showing highest photocurrent gain of 8.05 for P2 at pH 3. Photocurrent gain follows the order P2 > P3 > P1 indicating P2 is the best to develop photoswitches in the P-series polymers. Fitting of growth and decay curves suggests that they are a two-stage process: photocurrent raises fast at the on state initially and then at a slower rate and similar at an off state. Impedance spectra suggest charge-transfer resistance and Warburg impedance values follow the order of P1 > P3 > P2, whereas capacitance value follows the opposite order.

Genetic dissection of value-added quality traits and agronomic parameters through genome-wide association mapping in bread wheat (T. aestivum L.).

Bread wheat (T. aestivum) is one of the world's most widely consumed cereals. Since micronutrient deficiencies are becoming more common among people who primarily depend upon cereal-based diets, a need for better-quality wheat varieties has been felt. An association panel of 154 T. aestivum lines was evaluated for the following quality traits: grain appearance (GA) score, grain hardness (GH), phenol reaction (PR) score, protein percent, sodium dodecyl sulfate (SDS) sedimentation value, and test weight (TWt). In addition, the panel was also phenotyped for grain yield and related traits such as days to heading, days to maturity, plant height, and thousand kernel weight for the year 2017-18 at the Borlaug Institute for South Asia (BISA) Ludhiana and Jabalpur sites. We performed a genome-wide association analysis on this panel using 18,351 genotyping-by-sequencing (GBS) markers to find marker-trait associations for quality and grain yield-related traits. We detected 55 single nucleotide polymorphism (SNP) marker trait associations (MTAs) for quality-related traits on chromosomes 7B (10), 1A (9), 2A (8), 3B (6), 2B (5), 7A (4), and 1B (3), with 3A, 4A, and 6D, having two and the rest, 4B, 5A, 5B, and 1D, having one each. Additionally, 20 SNP MTAs were detected for yield-related traits based on a field experiment conducted in Ludhiana on 7D (4) and 4D (3) chromosomes, while 44 SNP MTAs were reported for Jabalpur on chromosomes 2D (6), 7A (5), 2A (4), and 4A (4). Utilizing these loci in marker-assisted selection will benefit from further validation studies for these loci to improve hexaploid wheat for better yield and grain quality.

Classification of Internal and External Distractions in an Educational VR Environment Using Multimodal Features.

Virtual reality (VR) can potentially enhance student engagement and memory retention in the classroom. However, distraction among participants in a VR-based classroom is a significant concern. Several factors, including mind wandering, external noise, stress, etc., can cause students to become internally and/or externally distracted while learning. To detect distractions, single or multi-modal features can be used. A single modality is found to be insufficient to detect both internal and external distractions, mainly because of individual variability. In this work, we investigated multi-modal features: eye tracking and EEG data, to classify the internal and external distractions in an educational VR environment. We set up our educational VR environment and equipped it for multi-modal data collection. We implemented different machine learning (ML) methods, including k-nearest-neighbors (kNN), Random Forest (RF), one-dimensional convolutional neural network - long short-term memory (1D-CNN-LSTM), and two-dimensional convolutional neural networks (2D-CNN) to classify participants' internal and external distraction states using the multi-modal features. We performed cross-subject, cross-session, and gender-based grouping tests to evaluate our models. We found that the RF classifier achieves the highest accuracy over 83% in the cross-subject test, around 68% to 78% in the cross-session test, and around 90% in the gender-based grouping test compared to other models. SHAP analysis of the extracted features illustrated greater contributions from the occipital and prefrontal regions of the brain, as well as gaze angle, gaze origin, and head rotation features from the eye tracking data.

Corneal densitometry changes post-CXL for keratoconus: Comparative evaluation of epithelium-off, contact lens-assisted, and transepithelial techniques.

PURPOSE: To evaluate changes in corneal backscattering after collagen cross-linking (CXL) for progressive keratoconus and compare its course with different techniques - standard epithelium-off CXL (SCXL), contact lens-assisted CXL (CACXL), and transepithelial CXL (TECXL). SETTING: Advanced Eye Center, Post Graduate Institute of Medical Education and Research, Chandigarh, India. DESIGN: Retrospective comparative study. METHODS: Ninety-four eyes (SCXL: 47, CACXL: 30, and TECXL: 17) were compared. Corneal haze was quantified using Scheimpflug tomography, pre- and post-CXL at 1, 3, 6, and 12 months. RESULTS: The baseline mean density score of the central anterior stromal layer was 16.14 ± 7.07, 15.85 ± 7.89 and 15.89 ± 7.21 in SCXL, CACXL, and TECXL groups, respectively (P 0.93). After SCXL, the score increased to 28.83 and 31.34 at 1 and 3 months, respectively (both P < 0.001) and dropped at 6 months (28.66, P < 0.001) and 12 months (23.72, P 0.003). Post-CACXL, the mean densitometry peaked at 3 months (20.35, P 0.14) and returned toward baseline at 6 months (18.82, P 0.15). After TECXL, it increased slightly at 1 month (18.47, P 0.17), decreased at 3 months (14.88, P 0.7), and plateaued over 1 year. No correlation with visual acuity was seen. CONCLUSION: Corneal haze increased significantly after SCXL, peaking at 3 months, declining over 6-12 months, and returning to baseline at 12 months. In contrast, post-TECXL and -CACXL, there was an insignificant increase in anterior corneal haze, which returned to baseline within 3-6 months.

A Sustainable Solution for Reducing Draping Waste in Cleft Surgeries.

OBJECTIVE: This study aims to reduce the waste generated from primary cleft lip and/or palate (CL/P) repair. DESIGN: A retrospective chart review examined a single surgeon's experience with CL/P repair using standard draping technique and reduced draping technique. Fisher's exact tests were performed comparing complication rates between techniques. SETTING: All procedures were conducted at a single academic medical center under the care of a board-certified pediatric plastic surgeon and fellowship-trained pediatric anesthesiologists. PATIENTS: The study included all patients ≤ 24 months of age who underwent primary CL/P repair using a reduced draping technique at the senior author's institution. An equivalent number of patients who underwent CL/P repair by the senior author immediately prior to implementation of the reduced draping technique were included for comparison. INTERVENTION: Patients undergoing CL/P repair before the change in technique were draped using the standard CL/P draping. The senior author then switched to using a reduced draping on all CL/P repairs afterwards. MAIN OUTCOME MEASURES: Weights and costs of both draping sets were obtained and differences calculated. A manual chart review was performed to assess rates of accidental intraoperative extubation, postoperative infection, fistula formation, and wound dehiscence. RESULTS: The implementation of a reduced draping technique resulted in a 530 gram weight savings and $7.49 cost savings per procedure. Fisher's exact tests revealed no statistically significant differences in complication rates except for oral mucosal dehiscence, which was lower in the reduced draping group. CONCLUSIONS: Reduced draping in CL/P repairs significantly reduces operative waste without compromising surgical outcomes.

Assessing the prevalence and impact of preserved ratio impaired spirometry in low-income and middle-income countries: a post-hoc cross-sectional analysis.

BACKGROUND: More than 90% of the morbidity and mortality from chronic respiratory disease occurs in low-income and middle-income countries (LMICs), with substantial economic impact. Preserved ratio impaired spirometry (PRISm) is a prevalent lung function abnormality associated with increased mortality in high-income countries. We aimed to conduct a post-hoc analysis of a cross-sectional study to assess the prevalence of, the risk factors for, and the impact of PRISm in three diverse LMIC settings. METHODS: We recruited a random, age-stratified and sex-stratified sample of the population in semi-urban Bhaktapur, Nepal; urban Lima, Peru; and rural Nakaseke, Uganda. Quality-assured post-bronchodilator spirometry was performed to American Thoracic Society standards and PRISm was defined as a forced expiratory volume in one second (FEV1) of less than 80% predicted with a FEV1/forced vital capacity ratio of 0·70 or more. We used t tests and χ2 analyses to assess the relationships between demographic, biometric, and comorbidity variables with PRISm. Multivariable logistic models with random intercept by site were used to estimate odds ratios (ORs) with 95% CIs. FINDINGS: 10 664 participants were included in the analysis, with a mean (SD) age of 56·3 (11·7) years and an equal distribution by sex. The prevalence of PRISm was 2·5% in Peru, 9·1% in Nepal, and 16·0% in Uganda. In multivariable analysis, younger age (OR for each decile of age 0·87, 95% CI 0·82-0·92) and being female (1·37, 1·18-1·58) were associated with increased odds of having PRISm. Biomass exposure was not consistently associated with PRISm across sites. Individuals with PRISm had impairment in respiratory-related quality of life as measured by the St George's Respiratory Questionnaire (OR by decile 1·18, 95% CI 1·10-1·25). INTERPRETATION: The prevalence of PRISm is heterogeneous across LMIC settings and associated with age, female sex, and biomass exposure, a common exposure in LMICs. A diagnosis of PRISm was associated with worse health status when compared with those with normal lung function. Health systems in LMICs should focus on all spirometric abnormalities as opposed to obstruction alone, given the disease burden, reduced quality of life, and size of the undiagnosed population at risk. FUNDING: Medical Research Council.

Analysis of sociodemographic profile of glaucoma patients with risk factors, subtypes, and disease severity in a tertiary eye care facility in Northern India.

PURPOSE: To study the different subtypes of glaucoma and to analyze the demographic and clinical profile of glaucoma patients along with associated risk factors in a multi-locational North Indian study. METHODS: Newly diagnosed and known glaucoma patients on treatment were enrolled in the study. Complete history was taken, and clinical evaluation was done by senior glaucoma experts. RESULTS: Five hundred and eighty-six patients (1121 eyes) were included with 383 males (65.4%) and 203 females (34.6%). Of these, 508 (86.7%) had primary glaucoma and 78 (13.3%) had secondary glaucoma. Also, 263 (44.9%) patients had primary open angle glaucoma (POAG) and 172 (29.4%) had primary angle closure glaucoma. Four hundred and fifty-one (77%) were graduates or postgraduates and 293 (50%) were dependents on family income. One hundred and forty-one (24%) had a positive family history. Secondary glaucoma patients had a lower average age (52.6 ± 16.8 years) and higher average intraocular pressure (IOP; 34.23 ± 13 mm) compared to primary glaucoma patients (26.6 ± 9.7 mm) (P < 0.0001). Thirty-three (47.8%) out of 78 secondary glaucoma patients had advanced disease. Seventy-four (12.6%) were first-time diagnosed and 18 had advanced disease. In addition, 161 eyes had one or more glaucoma surgeries done (128 trabeculectomy and 28 phacotrabeculectomy). Ninety-five (16.2%) patients were advised surgery at our centers (46 trab, 26 phacotrab, 15 phaco, five Ahmed glaucoma valve implantation, and three pars plana vitrectomy). Disease progression was noted in 62 patients reporting good compliance to medicines. CONCLUSION: POAG was the most common variant in this study. Secondary glaucoma patients were youngest in age and had the highest IOP. Trabeculectomy was the most performed surgery. A good literacy rate did not prevent late presentations.

A-Kinase-Anchoring-Protein Subtypes Differentially Regulate GPCR Signaling and Function in Human Airway Smooth Muscle.

A-kinase-anchoring proteins (AKAPs) act as scaffold proteins that anchor the regulatory subunits of the cAMP-dependent protein kinase A (PKA) to coordinate and compartmentalize signaling elements and signals downstream of Gs-coupled G protein-coupled receptors (GPCRs). The beta-2-adrenoceptor (ß2AR), as well as the Gs-coupled EP2 and EP4 receptor subtypes of the E-prostanoid (EP) receptor subfamily, are effective regulators of multiple airway smooth muscle (ASM) cell functions whose dysregulation contributes of asthma pathobiology. Here, we identify specific roles of the AKAPs Ezrin and Gravin, in differentially regulating PKA substrates downstream of the ß2AR, EP2 receptor (EP2R) and EP4 receptor (EP4R). Knockdown of Ezrin, Gravin, or both in primary human ASM cells caused differential phosphorylation of the PKA substrates vasodilator-stimulated phosphoprotein (VASP) and heat shock protein 20 (HSP20). Ezrin knockdown, as well as combined Ezrin + Gravin knockdown significantly reduced the induction of phospho-VASP and phospho-HSP20 by ß2AR, EP2R, and EP4R agonists. Gravin knockdown inhibited the induction of phospho-HSP20 by ß2AR, EP2R, and EP4R agonists. Knockdown of Ezrin, Gravin, or both also attenuated histamine-induced phosphorylation of MLC20. Moreover, knockdown of Ezrin, Gravin or both suppressed the inhibitory effects of Gs-coupled receptor agonists on cell migration in ASM cells. These findings demonstrate the role of AKAPs in regulating Gs-coupled GPCR signaling and function in ASM, and suggest the therapeutic utility of targeting specific AKAP family members in the management of asthma.

In-silico based Designing of benzo[d]thiazol-2-amine Derivatives as Anal-gesic and Anti-inflammatory Agents.

BACKGROUND: Benzo[d]thiazoles represent a significant class of heterocyclic com-pounds renowned for their diverse pharmacological activities, including analgesic and anti-inflammatory properties. This molecular scaffold holds substantial interest among medicinal chemists owing to its structural versatility and therapeutic potential. Incorporating the benzo[d]thiazole moiety into drug molecules has been extensively investigated as a strategy to craft novel therapeutics with heightened efficacy and minimized adverse effects. AIMS: The aim of the present research work was to design, synthesize and characterize the new benzo[d]thiazol-2-amine derivatives as potent analgesic and anti-inflammatory agents. MATERIALS AND METHODS: The synthesis of the presented benzo[d]thiazol-2-amine derivatives was performed by condensing-(4-chlorobenzylidene) benzo[d]thiazol-2-amine with a number of substituted phenols in the presence of potassium iodide and anhydrous potassium carbonate in dry acetone. IR spectroscopy, 1HNMR spectroscopy, 13CNMR spectroscopy and Mass spectroscopy methods were used to characterize the structural properties of all 13 newly syn-thesized derivatives. The molecular properties of these newly synthesized derivatives were estimated to study the attributes of drug-like candidates. Benzo[d]thiazol-2-amine derivatives were molecularly docked with selective enzymes COX-1 and COX-2. Analgesic and anti-inflammatory activities of synthesized compounds were evaluated by us-ing albino rats. RESULTS: Findings of the research suggested that compounds G3, G4, G6, G8 and G11 possess higher binding affinity than diclofenac sodium, when docking was performed with enzyme COX-1. Compounds G1, G3, G6, G8andG10 showed lower binding affinity than Indometha-cin when docking was performed with enzyme COX-2.In vitro evaluation of the COX-1 and COX-2 enzyme inhibitory activities was performed for synthesized compounds. DISCUSSION: Compounds G10 and G11 exhibited significant COX-1 and COX-2 enzyme in-hibitory action with an IC50 value of 5.0 and 10 µM, respectively. Using the hot plate method and the carrageenan-induced rat paw edema model, the synthesized compounds were screened for their biological activities, including analgesic and anti-inflammatory activities. Highest analgesic action was exhibited by derivative G11 and the compound G10 showed the highest anti-inflammatory response. Inhibition of COX may be considered as a mechanism of action of these compounds. CONCLUSION: It was concluded that synthesized derivatives G10 and G11 exhibited significant analgesic and anti-inflammatory effect; therefore, the said compounds may be subjected to further clinical investigation for establishing these as future compounds for the treatment of pain and inflammation.

An overview of the development of pharmacotherapeutics targeting SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) was declared a global pandemic in March 2020, which precipitated urgent public health responses. The causative agent, SARS-CoV-2, spreads primarily via respiratory droplets, necessitating precautions to mitigate transmission risks. Biopharmaceutical industries and academic institutions worldwide swiftly redirected their research endeavors towards developing therapeutic interventions, focusing on monoclonal antibodies, antiviral agents, and immunomodulatory therapies. The evolving body of evidence surrounding these treatments has prompted successive updates and revisions from the FDA, delineating the evolving landscape of COVID-19 therapeutics. This review comprehensively examines each treatment modality within the context of their developmental trajectories and regulatory approvals throughout the pandemic. Furthermore, it elucidates their mechanisms of action and presents clinical data underpinning their utility in combating the COVID-19 crisis.