Bolstering Buck Fertility: The Impact of Asparagus racemosus Aqueous Extract on Semen Cryopreservation and Antioxidant Defense System.

Importance of Study: Semen cryopreservation results in sperm damage due to lipid peroxidation or oxidative stress, leading to a decrease in conception rate. The sperm damage during cryopreservation can be minimized with the use of suitable antioxidant supplements in semen diluent. Some herbs have potent antioxidant potential and can be used in semen diluent to protect the spermatozoa. Objective: Hence, the investigation was planned to evaluate the effect of Asparagus racemosus (A. racemosus) aqueous extract on buck semen quality during cryopreservation. Methodology: In the current study, semen was collected from eight Sirohi bucks, and from each buck, 8 ejaculates were collected. Good-quality semen samples were pooled during each collection. Pooled semen samples were then divided into four equal parts and diluted in TRIS buffer containing different concentrations of A. racemosus aqueous extract (different groups, i.e., G I -5 mg, G II -2.5 mg, G III -1.25 mg, and G IV -0 mg of A. racemosus aqueous extract in 1 mL TRIS buffer). All the diluted semen samples were kept at equilibration temperature (5°C) for 2 hours and then cryopreserved by the manual method. Semen samples were evaluated for various sperm characteristics and antioxidant status before and after cryopreservation. Results: Asparagus racemosus aqueous extract showed significant (p < 0.05) enhancement of sperm viability, sperm motility, acrosomal integrity, and plasma membrane integrity, whereas it reduced sperm abnormality. Furthermore, in the experimental groups, the antioxidant gene expression was found to be increased compared to that of the treatment group. G III (p < 0.05) showed significantly better results in terms of sperm viability, sperm motility, acrosomal integrity, and plasma membrane integrity. Conclusion: Asparagus racemosus aqueous extract has the antioxidant potential to protect buck spermatozoa during semen cryopreservation.

High performance Pt-anchored MoS2 based chemiresistive ascorbic acid sensor.

Ascorbic acid (AA), known as Vitamin C, is a vital bioactive compound that plays a crucial role in several metabolic processes, include the synthesis of collagen and neurotransmitters, the removal of harmful free radicals, and the uptake of iron by cells in the human intestines. As a result, there is an absolute need for a highly selective, sensitive, and economically viable sensing platform for ascorbic acid (AA) detection. Herein, we demonstrate a Pt-decorated MoS2 for efficient detection of an AA biosensor. MoS2 hollow rectangular structure were synthesised using an easy and inexpensive chemical vapor deposition (CVD) approach to meet the increasing need for a reliable detection platform. The synthesized MoS2 hollow rectangular structure are characterized through field effect scanning electron microscopy (FESEM), energy-dispersive spectroscopy (EDX) elemental mapping, Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). We fabricate the chemiresistive biosensor based on Pt-decorated MoS2 that measures AA with great precision and high sensitivity. The experiments were designed to evaluate the response of the Pt-decorated MoS2 biosensor in the presence and absence of AA, and selectivity was evaluated for a variety of biomolecules, and it was observed to be very selective towards AA. The Pt-MoS2 device had a higher response of 125% against 1mM concentration of AA biomolecules, when compared to that of all other devices and 2.2 times higher than that of the pristineMoS2 device. The outcomes of this study demonstrate the efficacy of Pt-decorated MoS2 as a promising material for AA detection. This research contributes to the ongoing efforts to enhance our capabilities in monitoring and detecting AA, fostering advancements in environmental, biomedical, and industrial applications. .

Emerging molecules, tools, technology, and future of surgical knife in gastroenterology.

The 21st century has started with several innovations in the medical sciences, with wide applications in health care management. This development has taken in the field of medicines (newer drugs/molecules), various tools and technology which has completely changed the patient management including abdominal surgery. Surgery for abdominal diseases has moved from maximally invasive to minimally invasive (laparoscopic and robotic) surgery. Some of the newer medicines have its impact on need for surgical intervention. This article focuses on the development of these emerging molecules, tools, and technology and their impact on present surgical form and its future effects on the surgical intervention in gastroenterological diseases.

Failure of senolytic treatment to prevent cognitive decline in a female rodent model of aging.

There are sex differences in vulnerability and resilience to the stressors of aging and subsequent age-related cognitive decline. Cellular senescence occurs as a response to damaging or stress-inducing stimuli. The response includes a state of irreversible growth arrest, the development of a senescence-associated secretory phenotype, and the release of pro-inflammatory cytokines associated with aging and age-related diseases. Senolytics are compounds designed to eliminate senescent cells. Our recent work indicates that senolytic treatment preserves cognitive function in aging male F344 rats. The current study examined the effect of senolytic treatment on cognitive function in aging female rats. Female F344 rats (12 months) were treated with dasatinib (1.2 mg/kg) + quercetin (12 mg/kg) or ABT-263 (12 mg/kg) or vehicle for 7 months. Examination of the estrus cycle indicated that females had undergone estropause during treatment. Senolytic treatment may have increased sex differences in behavioral stress responsivity, particularly for the initial training on the cued version of the watermaze. However, pre-training on the cue task reduced stress responsivity for subsequent spatial training and all groups learned the spatial discrimination. In contrast to preserved memory observed in senolytic-treated males, all older females exhibited impaired episodic memory relative to young (6-month) females. We suggest that the senolytic treatment may not have been able to compensate for the loss of estradiol, which can act on aging mechanisms for anxiety and memory independent of cellular senescence.

Mechanisms of Gelofusine Protection against Polymyxin B-associated Renal Injury.

INTRODUCTION: Polymyxins are a last-resort treatment option for multidrug-resistant Gram-negative bacterial infections, but they are associated with nephrotoxicity. Gelofusine was previously shown to reduce polymyxin-associated kidney injury in an animal model. However, the mechanism(s) of renal protection has not been fully elucidated. Here, we report the use of a cell culture model to provide insights into the mechanisms of renal protection. METHODS: Murine epithelial proximal tubular cells were exposed to polymyxin B. Cell viability, polymyxin B uptake, mitochondrial superoxide production, nuclear morphology, and apoptosis activation were evaluated with or without concomitant gelofusine. A megalin-knockout cell line was used as an uptake inhibition control. Methionine was included in selected experiments as an antioxidant control. RESULTS: A polymyxin B concentration-dependent reduction in cell viability was observed. Increased viability was observed in megalin-knockout cells following comparable polymyxin B exposures. Compared to polymyxin B exposure alone, concomitant gelofusine and methionine significantly increased cell viability, reduced mitochondrial superoxide production, and improved nuclear morphology. Gelofusine, but not methionine, significantly reduced polymyxin B uptake and ratio of Bax/Bcl-2 protein (a biomarker of intrinsic apoptosis). Gelofusine and methionine were more effective at reducing renal cell injury in combination than either agent alone. CONCLUSION: The mechanisms of renal protection by gelofusine involve decreasing cellular drug uptake, reducing subsequent oxidative stress and apoptosis activation. These findings would be valuable for translational research into clinical strategies to attenuate drug-associated acute kidney injury.

Synthesis and in silico inhibitory action studies of azo-anchored imidazo[4,5-b]indole scaffolds against the COVID-19 main protease (Mpro).

The present work elicits a novel approach to combating COVID-19 by synthesizing a series of azo-anchored 3,4-dihydroimidazo[4,5-b]indole derivatives. The envisaged methodology involves the L-proline-catalyzed condensation of para-amino-functionalized azo benzene, indoline-2,3-dione, and ammonium acetate precursors with pertinent aryl aldehyde derivatives under ultrasonic conditions. The structures of synthesized compounds were corroborated through FT-IR, 1H NMR, 13C NMR, and mass analysis data. Molecular docking studies assessed the inhibitory potential of these compounds against the main protease (Mpro) of SARS-CoV-2. Remarkably, in silico investigations revealed significant inhibitory action surpassing standard drugs such as Remdesivir, Paxlovid, Molnupiravir, Chloroquine, Hydroxychloroquine (HCQ), and (N3), an irreversible Michael acceptor inhibitor. Furthermore, the highly active compound was also screened for cytotoxicity activity against HEK-293 cells and exhibited minimal toxicity across a range of concentrations, affirming its favorable safety profile and potential suitability. The pharmacokinetic properties (ADME) of the synthesized compounds have also been deliberated. This study paves the way for in vitro and in vivo testing of these scaffolds in the ongoing battle against SARS-CoV-2.

A mobile application-based post-stroke care strategy for survivors and their caregivers for prevention and management of post-stroke complications - "Stroke Home Care:" Development and feasibility.

Objectives: In developing nations such as India, a disparity exists between the available resources for stroke rehabilitation and the substantial burden of stroke cases. Consequently, the provision of cost-effective and multidisciplinary post-stroke rehabilitation care to stroke survivors becomes of paramount importance. The utilization of mobile applications (apps) for stroke care has been on the rise, offering a personalized and pragmatic solution with the potential for wider reach in settings constrained by limited resources. To address the unmet needs in the prevention and management of post-stroke complications, we conceptualized a strategy known as a mobile application-based post-stroke care strategy for both survivors and their caregivers. Materials and Methods: The scope of the app's focus was determined based on the incidence of post-stroke complications within a prospective cohort of stroke patients, in conjunction with existing literature. An initial "web-based mobile app" prototype was crafted to align with the identified focus area. Before the development of the final app version, a feasibility study was conducted involving 30 participant dyads (comprising a patient and a caregiver). Content validity was evaluated by a panel of 20 stroke experts encompassing neurologists, nurses, physiotherapists, and psychologists. Results: The "Stroke Home Care" (SHC) mobile app was conceived as a web-based educational tool aimed at preventing and managing post-stroke complications. It seeks to train caregivers of immobile stroke patients in the administration of preventive and therapeutic care procedures, thereby potentially enhancing survivors' quality of life and alleviating caregivers' burden. The feasibility and validity studies indicated "high satisfaction" levels among most caregivers and experts (>75%), with the remainder expressing "satisfaction" and no "dissatisfaction" regarding app utilities. Stroke experts unanimously deemed the app "appropriate", with consensus on contents, video quality, video length, and voice clarity. Caregivers reported "satisfactory" user experiences, encountering no issues during app installation or operation. Suggestions from both caregivers and experts were integrated into the final app version. Conclusion: The "SHC" app represents a feasible and well-received innovation tailored for the use by caregivers of stroke survivors. Consequently, the initial feasibility of the developed app serves as a precursor to a randomized controlled clinical trial aimed at substantiating its effectiveness within the post-stroke survivor and caregiver population. Notably, within resource-constrained contexts, this app has the potential to be a pivotal tool for post-stroke care.

ß1 integrins regulate cellular behavior and cardiomyocyte organization during ventricular wall formation.

AIMS: The mechanisms regulating the cellular behavior and cardiomyocyte organization during ventricular wall morphogenesis are poorly understood. Cardiomyocytes are surrounded by extracellular matrix (ECM) and interact with ECM via integrins. This study aims to determine whether and how ß1 integrins regulate cardiomyocyte behavior and organization during ventricular wall morphogenesis in the mouse. METHODS AND RESULTS: We applied mRNA deep sequencing and immunostaining to determine the expression repertoires of α/ß integrins and their ligands in the embryonic heart. Integrin ß1 subunit (ß1) and some of its ECM ligands are asymmetrically distributed and enriched in the luminal side of cardiomyocytes, and fibronectin surrounds cardiomyocytes, creating a network for them. Itgb1, which encodes the ß1, was deleted via Nkx2.5Cre/+ to generate myocardial-specific Itgb1 knockout (B1KO) mice. B1KO hearts display an absence of a trabecular zone but a thicker compact zone. The levels of hyaluronic acid and versican, essential for trabecular initiation, were not significantly different between control and B1KO. Instead, fibronectin, a ligand of ß1, was absent in the myocardium of B1KO hearts. Furthermore, B1KO cardiomyocytes display a random cellular orientation and fail to undergo perpendicular cell division, be organized properly, and establish the proper tissue architecture to form trabeculae. Mosaic clonal lineage tracing showed that Itgb1 regulates cardiomyocyte transmural migration and proliferation autonomously. CONCLUSIONS: ß1 is asymmetrically localized in the cardiomyocytes, and some of its ECM ligands are enriched along the luminal side of the myocardium, and fibronectin surrounds cardiomyocytes. ß1 integrins are required for cardiomyocytes to attach to the ECM network. This engagement provides structural support for cardiomyocytes to maintain shape, undergo perpendicular division, and establish cellular organization. Deletion of Itgb1 leads to loss of ß1 and fibronectin and prevents cardiomyocytes from engaging the ECM network, resulting in failure to establish tissue architecture to form trabeculae.

Soleus Muscle H-reflex: Reference Data of Adult Population From a Tertiary Care Center in India.

Introduction The Hoffmann reflex (H reflex) is one of the most studied reflexes in human neurophysiological literature. Detection of the H reflex is useful in the diagnosis of early polyneuropathy, S1 radiculopathy, early GBS, tibial neuropathy and sciatica, and sacral plexopathy. The H reflex is also used as a tool to measure the excitability of the nervous components of the arc, regardless of the sensitivity of the sensory organs. The monosynaptic nature of reflex circuits makes H-reflex an attractive tool for clinical neurophysiology and research. Objective The objective is to create reference data of soleus H-reflex latency in an adult population from a tertiary care center in India. Materials and methods Seven hundred eighty-four healthy volunteers underwent a physical examination and brief electrophysiological examination before elicitation of the soleus H reflex of both lower extremities using standard techniques. Reference values ​​are expressed as mean ± standard deviation as well as the third and 97th percentiles for latency as the dependent variable. Results The study population included 346 (44.1%) women and 438 (55.9%) men. The men were aged 40.46 ± 14.76 years, and the women were aged 41.63 ± 13.49 years. The average weight of the men was 73.32 ± 10.28 kilograms, and the women were 62.91 ± 7.46 kilograms. The average height of the men was 172.06 ± 4.22 cm, and the women were 159.12 ± 2.42 cm. The third and 97th percentiles for H-reflex latency on the right side were 22.86 ms to 34.22 ms and on the left side were 22.86 ms to 35.39 ms. The average right tibial H latency and left tibial H latency were 28.18 ± 2.59 ms and 28.14 ± 2.70 ms, respectively. Conclusion A sizable subject population was used to provide reference data for this study. Because of the huge sample size and nearly appropriate coverage of different age groups, reference ranges have been established for various age, height, and BMI groups.

Chronic fistula in ano associated with adenocarcinoma: a case report with a review of the literature.

The malignant transformation of chronic fistula in ano is rare, accounting for 3% to 11% of all anal canal malignancies. It results from long-standing inflammation and chronic irritation. No guidelines are available for the management of these cases. We herein present a case report of a 55-year-old man who presented with a history of constipation, perianal pain, and discharging fistula in ano of 4-year duration and underwent fistula surgery with recurrence. Biopsy of the fistulous tract revealed adenocarcinoma. He received neoadjuvant chemoradiotherapy, followed by abdominoperineal excision including excision of the fistulous tract. After 18 months of follow-up, he is free of recurrence. We present this case with a review of the literature, highlighting the management strategies.

Protocol for process evaluation of ARTEMIS cluster randomised controlled trial: an intervention for management of depression and suicide among adolescents living in slums in India.

INTRODUCTION: There are around 250 million adolescents (10-19 years) in India. The prevalence of mental health-related morbidity among adolescents in India is approximately 7.3%. Vulnerable subpopulations among adolescents such as those living in slum communities are particularly at risk due to poor living conditions, financial difficulty and limited access to support services. Adolescents' Resilience and Treatment nEeds for Mental Health in Indian Slums (ARTEMIS) is a cluster randomised controlled trial of an intervention that intends to improve the mental health of adolescents living in slum communities in India. The aim of this paper is to describe the process evaluation protocol for ARTEMIS trial. The process evaluation will help to explain the intervention outcomes and understand how and why the intervention worked or did not work. It will identify contextual factors, intervention barriers and facilitators and the adaptations required for optimising implementation. METHODS: Case study method will be used and the data will include a mix of quantitative metrics and qualitative data. The UK Medical Research Council's guidance on evaluating complex interventions, the Reach, Efficacy, Adoption, Implementation and Maintenance Framework and the Affordability, Practicability, Effectiveness and cost-effectiveness, Acceptability, Safety/Side Effects and, Equity criteria will be used to develop a conceptual framework and a priori codes for qualitative data analysis. Quantitative data will be analysed using descriptive statistics. Implementation fidelity will also be measured. DISCUSSION: The process evaluation will provide an understanding of outcomes and causal mechanisms that influenced any change in trial outcomes. ETHICS AND DISSEMINATION: Ethics Committee of the George Institute for Global Health India (project number 17/2020) and the Research Governance and Integrity Team, Imperial College, London (ICREC reference number: 22IC7718) have provided ethics approval. The Health Ministry's Screening Committee has approved to the study (ID 2020-9770). TRIAL REGISTRATION NUMBER: CTRI/2022/02/040307.

A multifunctional silk-hyaluronic acid self-healing hydrogel laden with alternatively activated macrophage-derived exosomes reshape microenvironment of diabetic wound and accelerate healing.

The impairment of phenotype switching of pro-inflammatory M1 to pro-healing M2 macrophage induced by hyperglycemic microenvironment often elevates oxidative stress, impairs angiogenesis, and leads to chronic non-healing wounds in diabetic patients. Administration of M2 macrophage-derived exosomes (M2Exo) at wound site is known to polarize M1 to M2 macrophage and can accelerate wound healing by enhancing collagen deposition, angiogenesis, and re-epithelialization. In the present study, M2Exo were conjugated with oxidized hyaluronic acid and mixed with PEGylated silk fibroin to develop self-healing Exo-gel to achieve an efficient therapy for diabetic wounds. Exo-gel depicted porous networked morphology with self-healing and excellent water retention behaviour. Fibroblast cells treated with Exo-gel showed significant uptake of M2Exo that increased their proliferation and migration in vitro. Interestingly, in a diabetic wound model of wistar rats, Exo-gel treatment induced 75 % wound closure within 7 days with complete epithelial layer regeneration by modulating cytokine levels, stimulating fibroblast-keratinocyte interaction and migration, angiogenesis, and organized collagen deposition. Taken together, this study suggests that Exo-gel depict properties of an excellent wound healing matrix and can be used as a therapeutic alternative to treat chronic non-healing diabetic wounds.

Serine racemase expression profile in the prefrontal cortex and hippocampal subregions during aging in male and female rats.

Aging is associated with a decrease in N-methyl-D-aspartate (NMDA) receptor function, which is critical for maintaining synaptic plasticity, learning, and memory. Activation of the NMDA receptor requires binding of the neurotransmitter glutamate and also the presence of co-agonist D-serine at the glycine site. The enzymatic conversion of L-serine to D-serine is facilitated by the enzyme serine racemase (SR). Subsequently, SR plays a pivotal role in regulating NMDA receptor activity, thereby impacting synaptic plasticity and memory processes in the central nervous system. As such, age-related changes in the expression of SR could contribute to decreased NMDA receptor function. However, age-associated changes in SR expression levels in the medial and lateral prefrontal cortex (mPFC, lPFC), and in the dorsal hippocampal subfields, CA1, CA3, and dentate gyrus (DG), have not been thoroughly elucidated. Therefore, the current studies were designed to determine the SR expression profile, including protein levels and mRNA, for these regions in aged and young male and female Fischer-344 rats. Our results demonstrate a significant reduction in SR expression levels in the mPFC and all hippocampal subfields of aged rats compared to young rats. No sex differences were observed in the expression of SR. These findings suggest that the decrease in SR levels may play a role in the age-associated reduction of NMDA receptor function in brain regions crucial for cognitive function and synaptic plasticity.

Post Cholecystectomy Bile Duct Injury in an Acute Setting: Categorization, Triaging, and Management Algorithm.

Background Postcholecystectomy bile duct injury (BDI) is a management challenge with significant morbidity, mortality, and effects on long-term quality of life. Early referral to a specialized hepatobiliary center and appropriate early management are crucial to improving outcomes and overall quality of life. In this retrospective analysis, we examined patients who were managed at our center over the past 10 years and proposed a triage and management algorithm for BDI in acute settings. Methods Patients referred to our center with BDI from January 2011 to December 2020 were reviewed retrospectively. The primary objective of initial management is to control sepsis and minimize BDI-related morbidity and mortality. All the patients were resuscitated with intravenous fluid, antibiotics (preferably culture-based), correction of electrolyte deficiencies, and organ support if required. A triage module and management algorithm were framed based on our experience. All the patients were triaged based on the presence or absence of bile leaks. Each group was further subdivided into red, yellow, and green zones (depending on the presence of sepsis, organ failure, and associated injuries), and the results were analyzed as per the proposed algorithm. Results One hundred twenty-eight patients with acute BDI were referred to us during the study period, and 116 patients had BDI with a bile leak and 12 patients were without a bile leak. Out of bile leak patients, 106 patients (91.38%) had sepsis with or without organ failure (red and yellow zone) and required invasive intervention in the form of PCD insertion (n=99, 85.34%) and/or laparotomy, lavage, and drainage (n=7, 6.03%). Another 10 patients (8.62%) had controlled external biliary fistula (green zone), of which four were managed with antibiotics, four underwent endoscopic retrograde cholangiopancreatography stenting, and only two (1.7%) patients could undergo Roux-en-Y hepaticojejunostomy upfront due to late referral. Among patients with BDI without bile leaks, nine (75%) had cholangitis (red and yellow zones). Out of these, five required PTBD along with antibiotics and four were managed with antibiotics alone. Only three (25%) patients in this group could undergo definitive repair without any restriction on the timing of referral and were sepsis-free at presentation (green zone). A total of nine patients had a vascular injury, and four of them required digital subtraction angiography and coil embolization. There were three (2.34%) mortalities; all were in the red zone of rest and had successful initial management. In total, five patients were managed with early repair in the acute setting, and the rest underwent definitive intervention at subsequent admissions after being converted to green zone patients with initial management. Conclusion The presented categorization, triaging, and management algorithm provides optimum insight to understand the severity, simplify these complex scenarios, expedite the decision-making process, and thus enhance patient outcomes in early acute settings following BDI.

Caudal duplication syndrome: A rare entity.

The rare caudal duplication syn drome is a spectrum of anomalie s primarily involving par tial or compl ete dupl ication of organ s comp risin g the gastro intest ina l, genitourinary and distal neu ral tube system s. These findings are considered to be a result of aberrant embryogenesis. We hereby report a case of an adult female with comple te duplicat ion o f the genital and ur inary systems (ureth ra and bladder), hindgut a nd lower end of vertebral col umn with no functional impairment. She presented in her first pregnancy at 36 weeks gestation, in labo ur. To the author's knowle dge this is the first case of caudal duplication syn drom e with pregnanc y fro m Pakistan.

Psychometric evaluation of the Chinese version of the burnout syndrome assessment scale in nurses.

Objective: This study aimed to translate the Burnout Syndrome Assessment Scale (BOSAS) into Chinese and validate its reliability and validity among Chinese emergency department and ICU nurses. Methods: The scale was translated into Chinese using Brislin's translation principle. A total of 626 nurses from Jiangxi, Zhejiang, and Fujian provinces in China participated in an online questionnaire survey. The survey included the general information questionnaire for nurses developed by the research team and the Chinese version of the Burnout Syndrome Assessment Scale. Reliability and validity of the Chinese version of the scale were analyzed using SPSS.25 and AMOS.24 software. Results: The Chinese version of the Burnout Syndrome Assessment Scale consists of a total of 20 items, encompassing two dimensions: personal burnout and job burnout. This structure is consistent with the original English version of the scale. The Chinese version of BOSAS demonstrated high internal consistency, with a Cronbach's α coefficient of 0.941. Additionally, the scale exhibited good split-half reliability (0.765) and test-retest reliability (0.871). The content validity index (S-CVI) was 0.971, indicating strong content validity. Exploratory factor analysis confirmed the same 2-factor structure as the original scale, and confirmatory factor analysis further validated this structure, with all fit indices indicating appropriateness. Conclusion: The Burnout Syndrome Assessment Scale has been successfully introduced and its reliability and validity have been verified in Chinese emergency department and ICU nurses.

Comparison of propofol and desflurane for postoperative neurocognitive function in patients with aneurysmal subarachnoid hemorrhage: A prospective randomized trial.

Background: Following aneurysmal subarachnoid hemorrhage, 40-50% of survivors experience cognitive dysfunction, which affects their quality of life. Anesthetic agents play a pivotal role in aneurysm surgeries. However, substantial evidence regarding their effects on neurocognitive function is lacking. This study evaluated the effects of propofol and desflurane on postoperative neurocognitive function and serum S-100B levels. Methods: One hundred patients were equally randomized to receive either propofol (Group P) or desflurane (Group D). Cognitive function was assessed using the Montreal Cognitive Assessment scale at three different time points: Preoperatively, at the time of discharge, and one month after surgery. Perioperative serum levels of S-100B were also measured. Results: The preoperative mean cognitive score in Group P was 21.64 + 4.46 and in Group D was 21.66 + 4.07 (P = 0.79). At discharge, a significant decrease in cognitive scores was observed compared to preoperative scores (Group P- 20.91 + 3.94, P = 0.03 and Group D-19.28 + 4.22, P = 0.00); however, scores were comparable between the two groups (P = 0.09). One month following surgery, mean cognitive scores were 22.63 + 3.57 in Group P and 20.74 + 3.89 in Group D, and the difference was significant (P = 0.04). Higher memory and orientation scores were observed in Group P than in Group D at one month (P < 0.05) in the subgroup analysis. Both groups had similar serum S-100B levels. Conclusion: The mean cognitive scores one month after surgery improved significantly with propofol compared with desflurane, but without clinical significance. Individual domain analysis demonstrated that orientation and memory scores were better preserved with propofol.

Unconventional Activation of IRE1 Enhances TH17 Responses and Promotes Airway Neutrophilia.

Heightened unfolded protein responses (UPRs) are associated with the risk for asthma, including severe asthma. Treatment-refractory severe asthma manifests a neutrophilic phenotype with TH17 responses. However, how UPRs participate in the deregulation of TH17 cells leading to neutrophilic asthma remains elusive. This study found that the UPR sensor IRE1 is induced in the murine lung with fungal asthma and is highly expressed in TH17 cells relative to naïve CD4+ T cells. Cytokine (e.g. IL-23) signals induce the IRE1-XBP1s axis in a JAK2-dependent manner. This noncanonical activation of the IRE1-XBP1s pathway promotes UPRs and cytokine secretion by both human and mouse TH17 cells. Ern1 (encoding IRE1)-deficiency decreases the expression of ER stress factors and impairs the differentiation and cytokine secretion of TH17 cells. Genetic ablation of Ern1 leads to alleviated TH17 responses and airway neutrophilia in a fungal airway inflammation model. Consistently, IL-23 activates the JAK2-IRE1-XBP1s pathway in vivo and enhances TH17 responses and neutrophilic infiltration into the airway. Taken together, our data indicate that IRE1, noncanonically activated by cytokine signals, promotes neutrophilic airway inflammation through the UPR-mediated secretory function of TH17 cells. The findings provide a novel insight into the fundamental understanding of IRE1 in TH17-biased TH2-low asthma.

Lipophilic bioactive compounds from thermophilic cyanobacterium Leptolyngbya sp. HNBGU-004: Implications for countering VRSA resistance.

Extremophiles thrive in extreme conditions, showcasing rich and unexplored diversity. This resilience hints at the existence of novel biochemical pathways and unique bioactive compounds. In contrast, the issue of drug resistance and excessive misuse of antibiotics in various settings, such as healthcare, agriculture, and veterinary medicine, has contributed to the emergence and spread of drug-resistant microorganisms. In the present research, Leptolyngbya sp. HNBGU-004, was obtained from an extreme location, a hot water spring in the Garhwal Himalayan region of India. The lipophilic fraction derived from Leptolyngbya sp. HNBGU-004 exhibited significant inhibitory effects against vancomycin-resistant Staphylococcus aureus (VRSA), displaying a bactericidal concentration of 0.5 mg mL-1. Furthermore, gas chromatography-mass spectrometry (GC-MS) analysis of the lipophilic extract unveiled the major constituents. Leptolyngbya sp. HNBGU-004 holds significant promise as a primary source of potent anti-vancomycin-resistant S. aureus components. These findings emphasize the importance of Leptolyngbya sp. HNBGU-004 as a foundational source for use as both a synergistic and alternative agent against VRSA.