Comparative Evaluation of Oral Aprepitant vs. Injection Palonosetron for Preventing Post-operative Nausea and Vomiting in Laparoscopic Cholecystectomy Patients under General Anaesthesia: A Randomized Trial

Background: Post-operative nausea and vomiting (PONV) are common and distressing complications in individuals undergoing surgical procedures, particularly laparoscopic cholecystectomy. Effective management of PONV is crucial for patient comfort, quicker recovery, and reduced healthcare costs. This study focused to compare the efficacy of oral aprepitant and injection palonosetron in preventing PONV in such surgical settings. Methods: A randomized controlled trial was conducted, involving 120 participants undergoing laparoscopic cholecystectomy. Individuals were divided into three groups: Group A (oral aprepitant), Group P (injection palonosetron), and Group C (placebo). The occurrence of nausea and vomiting was monitored at various intervals post-surgery, and statistical analysis was performed to estimate the efficacy of the treatments. Results: While all groups demonstrated some effectiveness in preventing nausea, with no significant statistical differences, Group A (Aprepitant) showed a significantly higher efficacy in preventing vomiting compared to Groups P and C. Aprepitant was notably more effective, suggesting its superiority as an antiemetic in this surgical context. Conclusion: Aprepitant emerges as a potentially more effective antiemetic agent for preventing vomiting in patients undergoing laparoscopic cholecystectomy, compared to palonosetron and placebo. Recommendations: Future research should focus on optimizing antiemetic regimens tailored to individual patient needs and specific surgical procedures. Further studies are also recommended to explore the long-term effects and cost-effectiveness of using aprepitant in perioperative care

ASSESSING THE EFFECT OF DEXMEDETOMIDINE DOSAGES ON SHORT-TERM COGNITIVE FUNCTION IN GERIATRIC PATIENTS UNDERGOING HEAD AND NECK CANCER SURGERY: A CROSS-SECTIONAL STUDY.

Background. Geriatric patients undergoing head and neck cancer surgery often face cognitive challenges postoperatively. The study aims to evaluate the impact of varying dosages of Dexmedetomidine (DEX) on short-term cognitive function in this vulnerable population. Methods. A prospective study was carried out, and patients were divided into two groups based on DEX infusion rates. Inclusion criteria encompassed specified surgical regions, while exclusion criteria ensured study population homogeneity. Data on demographics, medical history, surgical details, and DEX infusion were collected. Short-term cognitive function was assessed using the Mini-Mental State Examination (MMSE) on postoperative Day 2.  Results. Ninety participants were enrolled, with Group A (lower DEX rates, n=40) and Group B (higher DEX rates, n=50). Baseline characteristics were similar between groups. Mean MMSE scores were considerably higher in Group A (27.5, 95% CI: 26.8-28.2) compared to Group B (26.0, 95% CI: 25.3-26.7) (p < 0.05). The incidence of postoperative delirium was lower in Group A (10%) than in Group B (20%) (p = 0.12). Hemodynamic stability and pain scores were similar between groups.  Conclusion. Lower DEX infusion rates were associated with better short-term cognitive function in geriatric patients undertaking head and neck cancer surgery. However, further research is needed to validate these findings and explore potential mechanisms underlying cognitive effects.  Recommendations. Based on these findings, clinicians may consider adjusting DEX infusion rates to optimize cognitive outcomes in geriatric patients undergoing similar surgical procedures

Assessing the effect of Dexmedetomidine Dosages on Short-Term Cognitive Function in Geriatric Patients undergoing Head and Neck Cancer Surgery

Background: Geriatric patients undergoing head and neck cancer surgery often face cognitive challenges postoperatively. The study aims to assess the impact of varying dosages of Dexmedetomidine (DEX) on short-term cognitive function in this vulnerable population. Methods: A prospective study was conducted, and patients were divided into two groups based on DEX infusion rates. Inclusion criteria encompassed specified surgical regions, while exclusion criteria ensured study population homogeneity. Data on demographics, medical history, surgical details, and DEX infusion were collected. Short-term cognitive function was assessed using the Mini-Mental State Examination (MMSE) on postoperative Day 2. Results: Ninety participants were enrolled, with Group A (lower DEX rates, n=40) and Group B (higher DEX rates, n=50). Baseline characteristics were similar between groups. Mean MMSE scores were significantly higher in Group A (27.5, 95% CI: 26.8-28.2) compared to Group B (26.0, 95% CI: 25.3-26.7) (p < 0.05). Incidence of postoperative delirium was lower in Group A (10%) than Group B (20%) (p = 0.12). Hemodynamic stability and pain scores were similar between groups. Conclusion: Lower DEX infusion rates were associated with better short-term cognitive function in geriatric patients undergoing head and neck cancer surgery. However, further research is needed to validate these findings and explore potential mechanisms underlying cognitive effects. Recommendations: Based on these findings, clinicians may consider adjusting DEX infusion rates to optimize cognitive outcomes in geriatric patients undergoing similar surgical procedures

Myeloid-derived suppressor cells mediate T cell dysfunction in nonhuman primate TB granulomas

Myeloid-derived suppressor cells (MDSCs) represent an innate immune cell population comprised of immature myeloid cells and myeloid progenitors with very potent immunosuppressive potential. MDSCs are reported to be abundant in the lungs of active tuberculosis (TB) patients. We sought to perform an in-depth study of MDSCs during latent TB infection (LTBI) and active TB (ATB) using the nonhuman primate (NHP) model of pulmonary TB. We found a higher proportion of granulocytic, polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in the lungs of ATB animals compared to those with LTBI or naive control animals. Active disease in the lung, but not LTBI, was furthermore associated with higher proliferation, expansion, and immunosuppressive capabilities of PMN-MDSCs, as shown by enhanced expression of Ki67, indoleamine 2,3-dioxygenase (IDO1), interleukin-10 (IL-10), matrix metallopeptidase 9 (MMP-9), inducible nitric oxide synthase (iNOS), and programmed death-ligand 1 (PD-L1). These immunosuppressive PMN-MDSCs specifically localized to the lymphocytic cuff at the periphery of the granulomas in animals with ATB. Conversely, these cells were scarcely distributed in interstitial lung tissue and the inner core of granulomas. This spatial regulation suggests an important immunomodulatory role of PMN-MDSCs by restricting T cell access to the TB granuloma core and can potentially explain dysfunctional anti-TB responses in active granuloma. Our results raise the possibility that the presence of MDSCs can serve as a biomarker for ATB, while their disappearance can indicate successful therapy. Furthermore, MDSCs may serve as a potential target cell for adjunctive TB therapy

Identification of Host-Dependent Survival Factors for Intracellular Mycobacterium tuberculosis through an siRNA Screen

The stable infection of host macrophages by Mycobacterium tuberculosis (Mtb) involves, and depends on, the attenuation of the diverse microbicidal responses mounted by the host cell. This is primarily achieved through targeted perturbations of the host cellular signaling machinery. Therefore, in view of the dependency of the pathogen on host molecules for its intracellular survival, we wanted to test whether targeting such factors could provide an alternate route for the therapeutic management of tuberculosis. To first identify components of the host signaling machinery that regulate intracellular survival of Mtb, we performed an siRNA screen against all known kinases and phosphatases in murine macrophages infected with the virulent strain, H37Rv. Several validated targets could be identified by this method where silencing led either to a significant decrease, or enhancement in the intracellular mycobacterial load. To further resolve the functional relevance of these targets, we also screened against these identified targets in cells infected with different strains of multiple drug-resistant mycobacteria which differed in terms of their intracellular growth properties. The results obtained subsequently allowed us to filter the core set of host regulatory molecules that functioned independently of the phenotypic variations exhibited by the pathogen. Then, using a combination of both in vitro and in vivo experimentation, we could demonstrate that at least some of these host factors provide attractive targets for anti-TB drug development. These results provide a “proof-of-concept” demonstration that targeting host factors subverted by intracellular Mtb provides an attractive and feasible strategy for the development of anti-tuberculosis drugs. Importantly, our findings also emphasize the advantage of such an approach by establishing its equal applicability to infections with Mtb strains exhibiting a range of phenotypic diversifications, including multiple drug-resistance. Thus the host factors identified here may potentially be exploited for the development of anti-tuberculosis drugs

Western Indian Rural Gut Microbial Diversity in Extreme Prakriti Endo-Phenotypes Reveals Signature Microbes

Heterogeneity amidst healthy individuals at genomic level is being widely acknowledged. This, in turn, is modulated by differential response to environmental cues and treatment regimens, necessitating the need for stratified/personalized therapy. We intend to understand the molecular determinants of Ayurvedic way (ancient Indian system of medicine) of endo-phenotyping individuals into distinct constitution types termed “Prakriti,” which forms the basis of personalized treatment. In this study, we explored and analyzed the healthy human gut microbiome structure within three predominant Prakriti groups from a genetically homogenous cohort to discover differentially abundant taxa, using 16S rRNA gene based microbial community profiling. We found Bacteroidetes and Firmicutes as major gut microbial components in varying composition, albeit with similar trend across Prakriti. Multiple species of the core microbiome showed differential abundance within Prakriti types, with gender specific signature taxons. Our study reveals that despite overall uniform composition of gut microbial community, healthy individuals belonging to different Prakriti groups have enrichment of specific bacteria. It highlights the importance of Prakriti based endo-phenotypes to explain the variability amongst healthy individuals in gut microbial flora that have important consequences for an individual's health, disease and treatment

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field