Physio-morphological and molecular characterization of ethyl methanesulfonate-derived mutant population of Gossypium herbaceum L. cv. (Wagad) for drought tolerance.

This study investigates the response of ethyl methanesulfonate-derived twenty mutant lines of Gossypium herbaceum, along with the parent type Wagad cultivar, to drought stress. Physiological parameters, such as relative water content (RWC), net photosynthesis (A), stomatal conductance (g s), transpiration rate (E), and water use efficiency (WUE), were examined. The mutant line mut_3219 exhibited superior drought tolerance, maintaining high RWC and water retention capacity, with minimal reductions in A, g s, and E, leading to higher WUE than parent type and other mutant lines. Chlorophyll pigments declined in all the mutants under drought. However, mut_3219 retained higher levels than mut_4785. Anthocyanin accumulation indicated a protective response. Chlorophyll fluorescence showed mut_3219 is less sensitive to drought-induced PSII damage than mut_4785, with better membrane stability and higher proline accumulation, among all other mutant lines and parent type. The morphological parameters were less affected in mut_3219 compared to mut_4785 and parent type. Molecular analyses under control and drought conditions revealed significant variations in the expression of seven drought-related genes (GhbHLH, GhMYB5, GhWRKY33, GhRAF4, GhRAF19, GhNAC2, and GhCAMTA). The relative expression of GhbHLH, GhNAC2, GhRAF4, GhRAF19, and GhCAMTA increased under drought conditions, with notable changes in mut_3219 compared to parent type and all other mutant lines, indicating its enhanced drought tolerance. These findings provide valuable insights into the molecular and physiological mechanisms underlying drought tolerance in cotton. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04089-1.

Imaging the microstructure of lithium and sodium metal in anode-free solid-state batteries using electron backscatter diffraction.

'Anode-free' or, more fittingly, metal reservoir-free cells could drastically improve current solid-state battery technology by achieving higher energy density, improving safety and simplifying manufacturing. Various strategies have been reported so far to control the morphology of electrodeposited alkali metal films to be homogeneous and dense, but until now, the microstructure of electrodeposited alkali metal is unknown, and a suitable characterization route is yet to be identified. Here we establish a reproducible protocol for characterizing the size and orientation of metal grains in differently processed lithium and sodium samples by a combination of focused ion beam and electron backscatter diffraction. Electrodeposited films at Cu|Li6.5Ta0.5La3Zr1.5O12, steel|Li6PS5Cl and Al|Na3.4Zr2Si2.4P0.6O12 interfaces were characterized. The analyses show large grain sizes (>100 µm) within these films and a preferential orientation of grain boundaries. Furthermore, metal growth and dissolution were investigated using in situ electron backscatter diffraction, showing a dynamic grain coarsening during electrodeposition and pore formation within grains during dissolution. Our methodology and results deepen the research field for the improvement of solid-state battery performance through a characterization of the alkali metal microstructure.

Assessment of fluid responsiveness after tidal volume challenge in renal transplant recipients: a nonrandomized prospective interventional study.

Background: When applying lung-protective ventilation, fluid responsiveness cannot be predicted by pulse pressure variation (PPV) or stroke volume variation (SVV). Functional hemodynamic testing may help address this limitation. This study examined whether changes in dynamic indices such as PPV and SVV, induced by tidal volume challenge (TVC), can reliably predict fluid responsiveness in patients undergoing renal transplantation who receive lung-protective ventilation. Methods: This nonrandomized interventional study included renal transplant recipients with end-stage renal disease. Patients received ventilation with a 6 mL/kg tidal volume (TV), and the FloTrac system was attached for continuous hemodynamic monitoring. Participants were classified as responders or nonresponders based on whether fluid challenge increased the stroke volume index by more than 10%. Results: The analysis included 36 patients, of whom 19 (52.8%) were responders and 17 (47.2%) were nonresponders. Among responders, the mean ΔPPV6-8 (calculated as PPV at a TV of 8 mL/kg predicted body weight [PBW] minus that at 6 mL/kg PBW) was 3.32±0.75 and ΔSVV6-8 was 2.58±0.77, compared to 0.82±0.53 and 0.70±0.92 for nonresponders, respectively. ΔPPV6-8 exhibited an area under the curve (AUC) of 0.97 (95% confidence interval [CI], 0.93-1.00; P≤0.001), with an optimal cutoff value of 1.5, sensitivity of 94.7%, and specificity of 94.1%. ΔSVV6-8 displayed an AUC of 0.93 (95% CI, 0.84-1.00; P≤0.001) at the same cutoff value of 1.5, with a sensitivity of 94.7% and a specificity of 76.5%. Conclusions: TVC-induced changes in PPV and SVV are predictive of fluid responsiveness in renal transplant recipients who receive intraoperative lung-protective ventilation.

Perioperative outcomes of 105 cases of ABO-incompatible live donor kidney transplantation: a retrospective single-center observational study.

Background: ABO-incompatible (ABOi) kidney transplantation poses significant challenges in achieving successful outcomes. This study aimed to investigate the impact of various interventions and techniques on improving the success rates of ABOi kidney transplantation. Methods: We conducted a retrospective observational analysis of patients who underwent ABOi kidney transplantation from November 2012 to March 2023. The study included a total of 105 patients. We collected and analyzed data on patient demographics, preoperative assessments, surgical details, and postoperative outcomes. Results: The mean ages of the donors and recipients were 50.52±10.32 and 36.63±11.61 years, respectively. The majority of recipients were male (81.9%), while most donors were female (89.5%). The most common blood group among recipients was O (69.5%), and among donors, it was B (46.7%). The median durations of chronic kidney disease and dialysis were 12 months (interquartile range [IQR], 7-28 months) and 6 months (IQR, 2-12 months), respectively. Baseline antibody titers (anti-A and anti-B) ranged from 64.0 to 256.0, while on the day of surgery, they were ≤8. Perioperative complications included hypotension (10.5%), acute tubular necrosis (5.7%), delayed graft function (3.8%), and reexploration (3.8%) due to hematoma. Conclusions: ABOi kidney transplantation is a viable option for recipients lacking available donors with an ABO-compatible match. Perioperative concerns, including hypoalbuminemia, heightened risk of infections, coagulopathies, aseptic precautions, and immunological surveillance, must be carefully addressed.

Flavonoids as therapeutics for myocardial ischemia-reperfusion injury: a comprehensive review on preclinical studies.

Ischemic heart disease is the most prevalent cause of death worldwide affecting both the gender of all age groups. The high mortality rate is due to damage of myocardial tissue that emanates at the time of myocardial ischemia and re-oxygenation, thus averting reperfusion injury is recognized as a potential way to reduce acute cardiac injury and subsequent mortality. Flavonoids are polyphenol derivatives of plant origin and empirical shreds of evidence substantiate their numerous activities such as antioxidant, anti-inflammatory, anti-apoptotic, and anti-thrombotic activity, leading to their role in cardio protection. Recent investigations have unveiled the capacity of flavonoids to impede pivotal regulatory enzymes, signaling molecules, and transcription factors that orchestrate the mediators participating in the inflammatory cascade. The present comprehensive review, dwells on the preclinical studies on the effectiveness of flavonoids from the year 2007 to 2023, for the prevention and therapeutics for myocardial ischemia-reperfusion injury.

Microbially derived surfactants: an ecofriendly, innovative, and effective approach for managing environmental contaminants.

The natural environment is often contaminated with hydrophobic pollutants such as long-chain hydrocarbons, petrochemicals, oil spills, pesticides, and heavy metals. Hydrophobic pollutants with a toxic nature, slow degradation rates, and low solubility pose serious threats to the environment and human health. Decontamination based on conventional chemical surfactants has been found to be toxic, thereby limiting its application in pharmaceutical and cosmetic industries. In contrast, biosurfactants synthesized by various microbial species have been considered superior to chemical counterparts due to their non-toxic and economical nature. Some biosurfactants can withstand a wide range of fluctuations in temperature and pH. Recently, biosurfactants have emerged as innovative biomolecules not only for solubilization but also for the biodegradation of environmental pollutants such as heavy metals, pesticides, petroleum hydrocarbons, and oil spills. Biosurfactants have been well documented to function as emulsifiers, dispersion stabilizers, and wetting agents. The amphiphilic nature of biosurfactants has the potential to enhance the solubility of hydrophobic pollutants such as petroleum hydrocarbons and oil spills by reducing interfacial surface tension after distribution in two immiscible surfaces. However, the remediation of contaminants using biosurfactants is affected considerably by temperature, pH, media composition, stirring rate, and microorganisms selected for biosurfactant production. The present review has briefly discussed the current advancements in microbially synthesized biosurfactants, factors affecting production, and their application in the remediation of environmental contaminants of a hydrophobic nature. In addition, the latest aspect of the circular bioeconomy is discussed in terms of generating biosurfactants from waste and the global economic aspects of biosurfactant production.

Therapeutic potential of Ficus benghalensis in thromboembolic disorders.

Ficus benghalensis L. (FB) is a popular plant described in the Indian system of medicine. Traditionally, it is indicated in the treatment of diseases like diabetes mellitus, dysentery, leucorrhoea, menorrhagia, skin disease, rheumatism, inflammatory diseases, blood disorders. This paper accentuates the anti-thrombotic action of FB based on the properties like anti-coagulant, platelet-antiaggregatory, anti-atherogenic hypotensive, hypolipidemic, anti-oxidant, anti-inflammatory and immunomodulatory. All the available data pertaining to FB has been searched in the scientific databases, including PubMed, Google Scholar, ScienceDirect and Scopus. FB is a rich lode of organic compounds such as phenols, flavonoids, alkaloids, tannins, terpenoids and steroids. The various studies show that these phytochemical constituents exhibit wide range of anti-thrombotic actions such as anticoagulant, platelet anti-aggregatory, anti-atherogenic, hypolipidemic, hypotensive, anti-inflammatory, and antioxidant. Various studies (in vitro and in vivo) confirm the potential anti-thrombotic benefit of FB due to the presence of chemical structures that have proven to be effective in thromboembolic conditions. These evidences may benefit in new drug development to treat varied thromboembolic conditions which will not only be cost effective but may allay the fear of side effects.

Precision nutrition-based strategy for management of human diseases and healthy aging: current progress and challenges forward.

Currently, the treatment of various human ailments is based on different therapeutic approaches including traditional and modern medicine systems. Precision nutrition has come into existence as an emerging approach considering the diverse aspects such as age, sex, genetic and epigenetic makeup, apart from the pathophysiological conditions. The continuously and gradually evolving disciplines of genomics about nutrition have elucidated the importance of genetic variations, epigenetic information, and expression of myriads of genes in disease progression apart from the involvement in modulating therapeutic responses. Further, the investigations have presented the considerable role of gut microbiota comprising of commensal and symbionts performing innumerable activities such as release of bioactive molecules, defense against pathogenic microbes, and regulation of immunity. Noteworthy, the characteristics of the microbiome change depending on host attributes, environmental factors, and habitat, in addition to diet, and therefore can be employed as a biomarker to unravel the response to given food. The specific diet and the components thereof can be suggested for supporting the enrichment of the desired microbial community to some extent as an important part of precision nutrition to achieve not only the goal of human health but also of healthy aging.

Rome III and IV criteria are less discordant to diagnose irritable bowel syndrome in clinic patients than in community subjects.

BACKGROUND: Though Rome IV criteria for irritable bowel syndrome (IBS) are less sensitive; they select Rome III patients with greater severity and consultation behavior. Since severity of IBS may determine consultation behavior, we compared Rome III and IV criteria in clinic patients and compared with earlier published data from Indian community hypothesizing that the diagnostic discordance between these criteria would be less in clinic than in community. METHODS: Tertiary clinic patients were screened for IBS using Hindi translated-validated Rome III and IV questionnaires; IBS symptom severity scores (IBS-SSS) was also assessed. Diagnostic discordance between Rome III and IV criteria for IBS was compared with earlier published Indian community data. RESULTS: Of 110 clinic patients with functional gastrointestinal disorders, 72 met IBS criteria (47 [42.7%], 22 [20%] and three [2.7%] both Rome III and IV criteria, Rome III criteria only and Rome IV criteria only, respectively). In contrast, of 40 IBS subjects from Indian community published earlier, nine (22.5%), 28 (70%) and three (7.5%) fulfilled both Rome III and IV, Rome III only, Rome IV only criteria, respectively. Clinic patients with IBS fulfilling both Rome III and IV criteria or Rome IV criteria had higher IBS-SSS than those fulfilling Rome III criteria only (295.3 ± 80.7 vs. 205.6 ± 65.7; p < 0.00001). This difference was primarily related to pain severity and number of days with pain. CONCLUSION: Discordance between Rome IV and Rome III criteria in tertiary care clinic patients is less than in community subjects with IBS in India.

Abatacept: A Promising Repurposed Solution for Myocardial Infarction-Induced Inflammation in Rat Models.

Myocardial infarction (MI) is irreversible damage to the myocardial tissue caused by prolonged ischemia/hypoxia, subsequently leading to loss of contractile function and myocardial damage. However, after a perilous period, ischemia-reperfusion (IR) itself causes the generation of oxygen free radicals, disturbance in cation homeostasis, depletion of cellular energy stores, and activation of innate and adaptive immune responses. The present study employed Abatacept (ABT), which is an anti-inflammatory drug, originally used as an antirheumatic response agent. To investigate the cardioprotective potential of ABT, primarily, the dose was optimized in a chemically induced model of myocardial necrosis. Thereafter, ABT optimized the dose of 5 mg/kg s.c. OD was investigated for its cardioprotective potential in a surgical model of myocardial IR injury, where animals (n = 30) were randomized into five groups: Sham, IR-C, Telmi10 + IR (Telmisartan, 10 mg/kg oral OD), ABT5 + IR, ABT perse. ABT and telmisartan were administered for 21 days. On the 21st day, animals were subjected to LAD coronary artery occlusion for 60 min, followed by reperfusion for 45 min. Further, the cardioprotective potential was assessed through hemodynamic parameters, oxidant-antioxidant biochemical enzymatic parameters, cardiac injury, inflammatory markers, histopathological analysis, TUNEL assay, and immunohistochemical evaluation, followed by immunoblotting to explore signaling pathways. The statistics were performed by one-way analysis of variance, followed by the Tukey comparison post hoc tests. Noteworthy, 21 days of ABT pretreatment amended the hemodynamic and ventricular functions in the rat models of MI. The cardioprotective potential of ABT is accompanied by inhibiting MAP kinase signaling and modulating Nrf-2/HO-1 proteins downstream signaling cascade. Overall, the present work bolsters the previously known anti-inflammatory role of ABT in MI and contributes a mechanistic insight and application of clinically approved drugs in averting the activation of inflammatory response.

Comparison of intrathecal morphine versus erector spinae block for postoperative analgesia in patients with end-stage kidney disease undergoing kidney transplantation: A randomised clinical study.

Background and Aims: Intrathecal morphine (ITM) or erector spinae plane (ESP) block reduces postsurgical pain in patients who underwent kidney transplantation surgeries. We aimed to compare the effectiveness of both modalities in terms of duration and quality of postoperative analgesia along with postoperative fentanyl consumption. Methods: We conducted a randomised study and analysed 60 patients posted for elective live-related kidney transplantation surgery. They were randomised into two groups. Group M patients received ITM, whereas Group E patients received ESP block. We standardised the postoperative analgesia for both groups with intravenous fentanyl-based patient-controlled analgesia. The primary outcome was to compare the quality of analgesia using the numerical rating scale score between the groups. The secondary outcome was to observe the effect of both modalities on the duration of analgesia, postoperative fentanyl consumption, rescue analgesics requirement, catheter-related bladder discomfort and any complications. Results: We found significantly lower pain scores at rest and while coughing in Group M at all time intervals, except at 24 h while coughing. The mean time to first analgesia requirement was significantly longer in Group M than in Group E (P = 0.002). No significant difference was found in postoperative consumption of total fentanyl (P = 0.065) and rescue analgesia in both groups. In Group M, there was significantly more nausea, vomiting and pruritus (P = 0.001). Conclusions: ITM provides long-lasting postoperative analgesia at the cost of higher side effects than ESP block.

Understanding adsorption selectivity in zirconium-pillared clays for biogas upgradation: the role of metal/clay ratio.

Biogas, as a sustainable energy source, encounters challenges in practical applications due to impurities, notably carbon dioxide (CO2), and nitrogen (N2). This study investigates the effect of metal/clay ratio on the adsorption selectivity of porous zirconium-pillared clay adsorbents for biogas upgradation. Comprehensive analyses including nitrogen adsorption/desorption, X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR) were conducted to evaluate the physicochemical properties. Adsorption properties for Zr-pillared clays for biogas components such as CO2, CH4, and N2, at 25 °C under different pressures were investigated. The ideal adsorbed solution theory (IAST) was employed to assess selectivity for three binary gas mixtures (CO2/CH4, CO2/N2, and CH4/N2). Results revealed the substantial impact of Zr/Clay ratio on both adsorption capacity and selectivity of the prepared materials. For instance, the maximum adsorption capacity of gases varies as ZrPILC-4 > ZrPILC-2 > ZrPILC-8 > ZrPILC-1, whereas the adsorption selectivity for CO2/CH4 separation (at 1000 kPa) varies as ZrPILC-1 > ZrPILC-2 > ZrPILC-8 > ZrPILC-4. Interestingly, the ZrPILC-8 with maximum surface area (147 m2∙g-1) did not show maximum adsorption capacity for all the three gases, which was attributed to its lower pore volume, and basal spacing, as compared to ZrPILC-4. Amongst all the pillared samples, the ZrPILC-1 exhibited highest selectivity for all binary mixtures (at 1000 kPa), signifies increased nonspecific interactions due to its lower surface area. Its separation performance, particularly for CO2/CH4 mixture exceeded that of the parent clay by 1.5 times. A significant increase in the working capacity of the prepared samples underscores the efficacy of these pillared materials in separating biogas components. This study provides valuable insights into effects of Zr/clay ratio for developing robust pillared adsorbents, contributing to the advancement of sustainable biomethane production.

Impact of foliar application of iron and zinc fertilizers on grain iron, zinc, and protein contents in bread wheat (Triticum aestivum L.).

Introduction: Micronutrient deficiencies, particularly iron (Fe) and zinc (Zn), are prevalent in a large part of the human population across the world, especially in children below 5 years of age and pregnant women in developing countries. Since wheat constitutes a significant proportion of the human diet, improving grain Fe and Zn content in wheat has become important in improving human health. Objective: This study aimed to quantify the effect of foliar application of iron sulfate heptahydrate (FeSO4.7H2O) and zinc sulfate heptahydrate (ZnSO4.7H2O) and their combination on grain Fe and Zn concentrations, as well as grain protein content (GPC). The study also aimed to assess the utility of these applications in large field conditions. Methods: To address this issue, field experiments were conducted using 10 wheat cultivars and applying a foliar spray of FeSO4.7H2O (0.25%) and ZnSO4.7H2O (0.50%) separately (@400 L of solution in water per hectare during each spray) and in combination at two different crop growth stages (flowering and milking) for three consecutive crop seasons (2017-2020). The study used a split-plot design with two replications to assess the impact of foliar application on GFeC, GZnC, and GPC. In addition, an experiment was also conducted to assess the effect of soil (basal) @ 25 kg/ha ZnSO4, foliar @ 2 kg/ha, ZnSO4.7H2O (0.50%), and the combination of basal + foliar application of ZnSO4 on the grain micronutrient content of wheat cultivar WB 02 under large field conditions. Results: GFeC increased by 5.1, 6.1, and 5.9% with foliar applications of FeSO4, ZnSO4, and their combination, respectively. GZnC increased by 5.2, 39.6, and 43.8% with foliar applications of FeSO4, ZnSO4, and their combination, respectively. DBW 173 recorded the highest increase in GZnC at 56.9% with the combined foliar application of FeSO4 and ZnSO4, followed closely by HPBW 01 at 53.0% with the ZnSO4 foliar application, compared to the control. The GPC increased by 6.8, 4.9, and 3.3% with foliar applications of FeSO4, ZnSO4, and their combination, respectively. Large-plot experiments also exhibited a significant positive effect of ZnSO4 not only on grain Zn (40.3%, p ≤ 0.001) and protein content (p ≤ 0.05) but also on grain yield (p ≤ 0.05) and hectoliter weight (p ≤ 0.01), indicating the suitability of the technology in large field conditions. Conclusion: Cultivars exhibited a slight increase in GFeC with solitary foliar applications of FeSO4, ZnSO4, and their combination. In contrast, a significant increase in GZnC was observed with the foliar application of ZnSO4 and the combined application of FeSO4 and ZnSO4. In terms of GPC, the most significant enhancement occurred with the foliar application of FeSO4, followed by ZnSO4 and their combination. Data demonstrated the significant effect of foliar application of ZnSO4 on enhancing GZnC by 39.6%. Large plot experiments also exhibited an increase of 40.3% in GZnC through the foliar application of ZnSO4, indicating the effectiveness of the technology to be adopted in the farmer's field.

Chitosan nanoemulsion incorporated with Carum carvi essential oil as ecofriendly alternative for mitigation of aflatoxin B1 contamination in stored herbal raw materials.

The present investigation entails the first report on entrapment of Carum carvi essential oil (CCEO) into chitosan polymer matrix for protection of stored herbal raw materials against fungal inhabitation and aflatoxin B1 (AFB1) production. Physico-chemical characterization of nanoencapsulated CCEO was performed through Fourier transform infrared spectroscopy, dynamic light scattering, X-ray diffractometry, and scanning electron microscopy. The nanoencapsulated CCEO displayed improved antifungal and AFB1 suppressing potentiality along with controlled delivery over unencapsulated CCEO. The encapsulated CCEO nanoemulsion obstructed the ergosterol production and escalated the efflux of cellular ions, thereby suggesting plasma membrane as prime target of antifungal action in Aspergillus flavus cells. The impairment in methyglyoxal production and modeling based carvone interaction with Afl-R protein validated the antiaflatoxigenic mechanism of action. In addition, CCEO displayed augmentation in antioxidant potentiality after encapsulation into chitosan nanomatrix. Moreover, the in-situ study demonstrated the effective protection of Withania somnifera root samples (model herbal raw material) against fungal infestation and AFB1 contamination along with prevention of lipid peroxidation. The acceptable organoleptic qualities of W. somnifera root samples and favorable safety profile in mice (animal model) strengthen the application of nanoencapsulated CCEO emulsion as nano-fungitoxicant for preservation of herbal raw materials against fungi and AFB1 mediated biodeterioration.

Health and demographic indicators of selected districts of India: An impact of Swasthya Rakshan Programme (SRP).

Swasthya Rakshan Programme (SRP) provides health care services through Ayurveda, an initiative of the Government of India that aims to survey and create alertness of essential health appliances to ameliorate society from its grassroots level. The present study aimed to survey the prevailing health standards of residents in certain districts of India and to record the prevalence of diseases among them according to their living conditions, food habits, lifestyle, education, occupation and other socio-economic status. Data was collected through a community-based cross-sectional survey conducted from April 2018 to March 2019 in 22 Districts of 19 states in India. A stratified multi-stage sampling design was adopted for the survey. Documentation of demographic profile, food habits, lifestyle, hygiene status, and existing health conditions was assessed. A pre-designed semi-structured questionnaire was used for the collection of the data. Before initiating the programme, written consent was obtained. In this study, from 162 selected villages/colonies/areas, a total of 562,913 population and 81,651 households were surveyed. Sixty-nine thousand three hundred nineteen patients were cared for various ailments through health camps. The study found that the most prevalent disease in the concerned population was 'Sandhivata' (Osteo-arthritis), that is, 43.0%, followed by 'Dourbalya' (Debility), that is, 11.7%. The study includes insightful analyses of comprehensive demographic and health indicators classified by various socio-economic categories. The collected data regarding the prevalence of diseases with their sociodemographic correlations may provide a better understanding of the locality and thus may help in all future health endeavours.

Identification, trace level quantification, and in silico assessment of potential genotoxic impurity in Famotidine.

Potential genotoxic impurities in medications are an increasing concern in the pharmaceutical industry and regulatory bodies because of the risk of human carcinogenesis. To prevent the emergence of these impurities, it is crucial to carefully examine not only the final product but also the intermediates and key starting material (KSM) used in drug synthesis. During the related substances analysis of KSM of Famotidine, an unknown impurity in the range of 0.5-1.0% was found prompting the need for isolation and characterization due to the possibility of its to infiltrate into the final product. In this study, the impurity was isolated and characterized as 5-(2-chloroethyl)-3,3-dimethyl-3,4-dihydro-2H-1,2,4,6-thiatriazine 1,1-dioxide using multiple instrumental analysis, uncovering a structural alert that raises concern. Considering the potential impact of impurity on human health, an in silico genotoxicity assessment was established using Derek and Sarah tool in accordance with ICH M7 guideline. Furthermore, molecular docking and molecular dynamics simulation were performed to evaluate the specific interaction of the impurity with DNA. The findings reveal consistent interaction of the impurity with the dG-rich region of the DNA duplex and binding at the minor groove. Both in silico prediction and molecular dynamic study confirmed the genotoxic character of the impurity. The newly discovered impurity in famotidine has not been reported previously, and there is currently no analytical method available for its identification and control. A highly sensitive HPLC-UV method was developed and validated in accordance with ICH requirements, enabling quantification of the impurity at trace level in famotidine ensuring its safe release.

Arglabin: A mediator of inflammasome modulated and independent myocardial injury (PARA-AMI study).

BACKGROUND: Arglabin is a plant alkaloid (sesquiterpene lactone) that is used as an anticancer drug. It has potential anti-diabetic and anti-atherogenic effects. PURPOSE: Arglabin has drawn particular attention because of its therapeutic effects as an anti-inflammatory agent in multiple diseases. Since arglabin inhibits Epidermal Growth Factor Receptor (EGFR) tyrosine kinase, concerns for cardiotoxic effects are valid. The present study was designed to investigate the protective effects of arglabin on the myocardium. STUDY DESIGN: This study was designed to evaluate the effect of arglabin on the myocardium in an experimental model of myocardial necrosis in rats. Different doses of arglabin (2.5, 5, and 10 µg/kg) were investigated as pre-treatment for 21 days in the isoproterenol (ISO) model of myocardial necrosis groups and per se groups. METHODS: On the 22nd day, hemodynamic, histopathological, electron microscopy, oxidative stress markers, inflammatory mediators, apoptotic markers, inflammasome mediators, and Western blot analysis were performed to evaluate the effects of arglabin. RESULTS: Arglabin pre-treatment showed improvement in hemodynamic parameters and histopathological findings at low doses in isoproterenol-induced myocardial necrosis model of rats. Arglabin administration altered myocardial structure and modulated myocardial function via activation of NFκB/MAPK pathway that led to myocardial injury with an increase in dose. CONCLUSION: Arglabin imparted partial cardio-protection via an inflammasome-dependent pathway and mediated injury through the inflammasome-independent pathway.

Anterior retropharyngeal approach (ARPA) for high cervical spine.

BACKGROUND: One of the major challenges in operating on the spine lies in taking an anterior approach for the high cervical spine. In patients with a short neck, Klippel-Fiel syndrome or when the C3 vertebra is high in relation to the hyoid bone, it will be difficult to access the C3 body. The transoral route is a highly contaminated zone, and therefore, no instrumentation or grafts can be placed through it. METHOD: The anterior retropharyngeal approach (ARPA) for the high cervical spine. CONCLUSION: The anterior retropharyngeal approach is an excellent approach for the high cervical spine where instrumentation is needed. This route provides wide exposure of the C1-C3 region, avoiding the contaminated of the oral cavity.

Design, Synthesis, and Characterization of Organometallic BODIPY-Ru(II) Dyads: Redox and Photophysical Properties with Singlet Oxygen Generation Capability†.

A series of Ru(II)-acetylide complexes (Ru1, Ru2, and Ru1m) with alkynyl-functionalized borondipyrromethene (BODIPY) conjugates were designed by varying the position of the linker that connects the BODIPY unit to the Ru(II) metal center through acetylide linkage at either the 2-(Ru1) and 2,6-(Ru2) or the meso-phenyl (Ru1m) position of the BODIPY scaffold. The Ru(II) organometallic complexes were characterized by various spectroscopic methods, including nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy, CHN, and high-resolution mass spectrometry (HRMS) analyses. The Ru(II)-BODIPY conjugates exhibit fascinating electrochemical and photophysical properties. All BODIPY-Ru(II) complexes exhibit strong absorption (εmax = 29,000-72,000 M-1 cm-1) in the visible region (λmax = 502-709 nm). Fluorescence is almost quenched for Ru1 and Ru2, whereas Ru1m shows the residual fluorescence of the corresponding BODIPY core at 517 nm. The application of the BODIPY-Ru(II) dyads as nonporphyrin-based triplet photosensitizers was explored by a method involving the singlet oxygen (1O2)-mediated photo-oxidation of diphenylisobenzofuran. Effective π-conjugation between the BODIPY chromophore and Ru(II) center in the case of Ru1 and Ru2 was found to be necessary to improve intersystem crossing (ISC) and hence the 1O2-sensitizing ability. In addition, electrochemical studies indicate electronic interplay between the metal center and the redox-active BODIPY in the BODIPY-Ru(II) dyads.

Inter and intra-host diversity of RSV in hematopoietic stem cell transplant adults with normal and delayed viral clearance.

Respiratory syncytial virus (RSV) infection in immunocompromised individuals often leads to prolonged illness, progression to severe lower respiratory tract infection, and even death. How the host immune environment of the hematopoietic stem cell transplant (HCT) adults can affect viral genetic variation during an acute infection is not understood well. In the present study, we performed whole genome sequencing of RSV/A or RSV/B from samples collected longitudinally from HCT adults with normal (<14 days) and delayed (≥14 days) RSV clearance who were enrolled in a ribavirin trial. We determined the inter-host and intra-host genetic variation of RSV and the effect of mutations on putative glycosylation sites. The inter-host variation of RSV is centered in the attachment (G) and fusion (F) glycoprotein genes followed by polymerase (L) and matrix (M) genes. Interestingly, the overall genetic variation was constant between normal and delayed clearance groups for both RSV/A and RSV/B. Intra-host variation primarily occurred in the G gene followed by non-structural protein (NS1) and L genes; however, gain or loss of stop codons and frameshift mutations appeared only in the G gene and only in the delayed viral clearance group. Potential gain or loss of O-linked glycosylation sites in the G gene occurred both in RSV/A and RSV/B isolates. For RSV F gene, loss of N-linked glycosylation site occurred in three RSV/B isolates within an antigenic epitope. Both oral and aerosolized ribavirin did not cause any mutations in the L gene. In summary, prolonged viral shedding and immune deficiency resulted in RSV variation, especially in structural mutations in the G gene, possibly associated with immune evasion. Therefore, sequencing and monitoring of RSV isolates from immunocompromised patients are crucial as they can create escape mutants that can impact the effectiveness of upcoming vaccines and treatments.