Exploring the Potential of Herbal Compounds as Autophagy Modulators in Alzheimer's Disease: A Comprehensive Review.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that causes atrophy of brain cells, leading to their death, and has become a leading cause of death in aging populations worldwide. AD is characterized by ß-amyloid (Aß) deposition and tau phosphorylation in neural tissues, but the precise pathophysiology of the disease is still obscure. Autophagy is an evolutionarily targeted mechanism that is necessary for the elimination of neuronal and glial misfolded proteins as well as proteins. It also plays an essential role in synaptic plasticity. The aberrant autophagy primarily influences the process of aging and neurodegeneration. Autophagy significantly influences how Aß and tau function physiologically, therefore, atypical autophagy is expected to perform an important role in Aß deposition and tau phosphorylation characteristic in the development of AD. Bioactive phytoconstituents could majorly contribute as a natural yet effective alternative approach to slow down the progression of neurodegeneration and promote the active aging process in elderly patients. Over the recent years, it is well evidenced that different secondary metabolites including polyphenols, alkaloids, terpenes, and phenols exhibited neuroprotective effects, and attenuated brain damage, and cognitive impairment in vitro as well as in vivo. Additionally, the underlying mechanism of action shared by them is the regulation of competent autophagy via the removal of aggregated protein and mitochondrial dysfunction. The present article is structured as a reference for researchers keen to investigate and assess the new natural compound-mediated therapeutic approach for AD treatment through the modulation of autophagy.

Comparative analysis of central aortic blood pressure, pulse wave velocity & arterial stiffness in patients with obstructive airway disease.

BACKGROUND: As the pulmonary system and cardiovascular system are intimately linked, patients with chronic obstructive pulmonary disease (COPD) and asthma have high risk for developing cardiovascular diseases (CVDs) and altered central hemodynamic. OBJECTIVE: We aim to assess the central aortic blood pressure (CABP) indices, pulse wave velocity (PWV) and other indicators of arterial stiffness in Indian patients with COPD and bronchial asthma. METHODS: This is a single-center, cross-sectional study conducted in outpatients diagnosed with either chronic stable phase of COPD or bronchial asthma. CABP indices, vascular age, arterial stiffness and central hemodynamics were measured in patients. RESULTS: Of 193 patients with obstructive airway disease who were enrolled, (n = 81 had COPD and n = 112 had partially-controlled bronchial asthma) the proportion of male patients was higher in both groups. The PWV, augmentation index (AI) and vascular age (VA) were significantly higher in patients with COPD compared to those with bronchial asthma (all, p < 0.05). CONCLUSION: The study showed that PWV, AI and VA were higher in patients with stable COPD without any cardiac comorbidities compared to bronchial asthma.

Understanding innate and adaptive responses during radiation combined burn injuries.

The occurrence of incidents involving radiation-combined burn injuries (RCBI) poses a significant risk to public health. Understanding the immunological and physiological responses associated with such injuries is crucial for developing care triage to counter the mortality that occurs due to the synergistic effects of radiation and burn injuries. The core focus of this narrative review lies in unraveling the immune response against RCBI. Langerhans cells, mast cells, keratinocytes, and fibroblasts, which induce innate immunity, have been explored for their response to radiation, burns, and combined injuries. In the case of adaptive immune response, exploring behavioral changes in T regulatory (Treg) cells, T helper cells (Th1, Th2, and Th17), and immunoglobulin results in delayed healing compared to burn and radiation injury. The review also includes the function of complement system components such as neutrophils, acute phase proteins (CRP, C3, and C5), and cytokines for their role in RCBI. Combined insults resulting in a reduction in the cell population of immune cells display variation in response based on radiation doses, burn injury types, and their intrinsic radiosensitivity. The lack of approved countermeasures against RCBI poses a significant challenge. Drug repurposing might help to balance immune cell alteration, resulting in fast recovery and decreasing mortality, which gives it clinical significance for its implication on the site of such incidence. However, the exact immune response in RCBI remains insufficiently explored in pre-clinical and clinical stages, which might be due to the non-availability of in vitro models, standard animal models, or human subjects, warranting further research.

In the realm of public health, RCBI presents significant risks and obstacles. This hazard is quite serious, and it might get worse in the future as evidenced by incidents like nuclear meltdowns and medical mistakes. Diagnosis and treatment become more challenging when serious injuries, particularly burns, are combined with radiation exposure. Features like early shock, poor wound healing, and hematopoietic instability call for advancements in both diagnosis and therapy. Furthermore, the immune system's response to RCBI is complicated and involves changes in cytokine concentrations, immune cell activity, and adaptive immune responses compared to single injuries. Immune cell radiosensitivity varies depending on the type of cell, radiation dose, and length of exposure, so it's important to understand. Repurposing drugs is one of the potential techniques to reduce mortality and speed up healing which are discussed in the manuscript. Still, more research is needed. To effectively tackle RCBI, more investigation into molecular processes, treatment strategy optimization, and information gap closure are essential.

Torsemide in the Management of Essential Hypertension.

Torsemide, a loop diuretic, is increasingly recognized for its role in managing essential hypertension. Its mechanism of action involves inhibiting the reabsorption of sodium and chloride ions in the ascending loop of Henle in the kidneys. By doing so, torsemide promotes diuresis, which refers to increased urine production, and subsequently lowers blood pressure. Studies have shown that torsemide is comparably effective to other antihypertensive agents in lowering blood pressure, with the added benefit of potentially improving renal function. However, while torsemide shows promise in hypertensive management, further research is necessary to fully understand its long-term effects and to establish optimal dosing strategies. Future research should focus on clarifying its role in long-term blood pressure control and refining its use in clinical practice to maximize efficacy and minimize adverse effects.

Seroprotection achieved with standard four-dose schedule of hepatitis B vaccine in people with chronic kidney disease: A real-life data.

BACKGROUND AND OBJECTIVES: Hepatitis B virus (HBV) infection is common in people with chronic kidney diseases (CKD). The guidelines recommend four doses, 2.0 mL each, of HBV vaccine, given at zero, one, two and six months in these patients. However, real-life data on the effectiveness of this schedule are limited. We retrospectively reviewed the HBV vaccine response in the CKD population. METHODS: The study included adult (≥ 18 years) patients with glomerular filtration rate < 60 mL/min, if they had received four doses (each of 2.0 mL volume) of HBV vaccine and anti-HBs titer was measured at ≥ 1 month of the last dose of vaccine. Participants with hepatitis C or human immunodeficiency virus (HIV) coinfection, organ transplant recipients, active or remote malignancy or use of immunosuppressive medication were excluded. Anti-HBs antibody was measured with two different assays with their limits of detection up to 500 mIU/mL and 1000 mIU/mL. The presence of detectable anti-HBs antibody and anti-HBs titer ≥ 10 mIU/mL defined seroconversion and seroprotection, respectively. RESULTS: The study included 208 patients (71.9% males; age 44 [33-55] years; CKD stage II/III/IV/V in 1.4%/7.2%/26.4%/64.9%; 46% on maintenance hemodialysis [MHD]). Overall, seroconversion and seroprotection were achieved in 174 (83.7%) and 161 (77.4%) participants and anti-HBs titer, measured three (2-8) months after the fourth dose, was 124 (12-500) mIU/mL. The median anti-HBs antibody levels at ≤ 6, 7-12, 13-24 and 24 months after the fourth doses were 116, 478, 43 and 70 mIU/mL, respectively. Age, body mass index, stage of CKD, serum albumin and dialysis status were not associated with seroprotection (p < 0.05). CONCLUSION: A standard vaccination schedule of four 2.0 mL doses of HBV vaccine in CKD patients induces reasonably good and sustained seroprotection.

Obstructive Sleep Apnea in Metabolic Syndrome.

BACKGROUND: The metabolic syndrome (MetS), a cluster of cardiovascular risk factors, is associated with obstructive sleep apnea (OSA). OSA is a major contributor to cardiac, cerebrovascular, and metabolic disorders as well as to premature death. MATERIALS AND METHODS: This cross-sectional study was done for 1 year in 103 patients of MetS diagnosed by the International Diabetes Federation criteria. All patients were subjected to the STOP-Bang questionnaire, and they were classified into low, intermediate, and high risks depending on the score. Patients falling in intermediate-high risk (score 3-8) were taken for overnight polysomnography to confirm the diagnosis of OSA (apnea-hypopnea index [AHI] ≥5) and were considered Group I. Patients with STOP-Bang score ≤2 or score ≥3 with AHI <5 were considered Group II (non-OSA). RESULTS: Out of 103 MetS patients enrolled in the study, only 70 (68.0%) were diagnosed with OSA, so the prevalence of OSA in MetS patients was 68%. The majority of the OSA cases had moderate-to-severe OSA (68.5%), and only 31.4% had mild OSA. The age of patients enrolled in the study ranged between 29 and 78 years, and the mean age of patients was 54.8 ± 9.4 years. Out of 103 MetS enrolled in the study, 59 (57.3%) were male and the rest were female, so the prevalence of severe OSA was higher in males than in females. The prevalence increases with an increase in age groups. Weight, body mass index (BMI), circumference, and waist circumference (WC) of cases of OSA were found to be significantly higher as compared to that of non-OSA. An incremental trend of increase in weight, BMI, neck circumference, and WC was observed with the increase in the severity of OSA. Patients of OSA as compared to non-OSA had significantly increased WC, blood pressure (BP), fasting, postprandial, random blood sugar, and triglyceride (TG) levels. A trend of increase in WC, BP fasting, postprandial, random blood sugar, and TG levels was associated with an increase in the severity of OSA. Snoring and daytime sleepiness were observed in a significantly higher proportion of OSA cases as compared to non-OSA cases. CONCLUSIONS: This study shows that OSA has a high prevalence in subjects with MetS. A high index of clinical suspicion is required for early diagnosis.

Résumé Contexte:Le syndrome métabolique (MetS), un ensemble de facteurs de risque cardiovasculaire, est associé à l'apnée obstructive du sommeil (AOS). L'AOS est un contributeur majeur aux troubles cardiaques, cérébrovasculaires et métaboliques ainsi qu'aux décès prématurés.Matériels et méthodes:ce Une étude transversale a été réalisée pendant 1 an chez 103 patients atteints de MetS diagnostiqués selon les critères de la Fédération internationale du diabète. Tous les patients étaient soumis au questionnaire STOP-Bang, et ils ont été classés en risques faibles, intermédiaires et élevés en fonction du score. Patients présentant un risque intermédiaire-élevé (score 3 à 8) ont été soumis à une polysomnographie nocturne pour confirmer le diagnostic d'AOS (apnée-hypopnée). [AHI] ≥5) et ont été considérés comme le groupe I. Les patients avec un score STOP-Bang ≤2 ou un score ≥3 avec un AHI <5 ont été considérés comme le groupe II (non-AOS).Résultats:Sur 103 patients atteints du MetS inclus dans l'étude, seuls 70 (68,0 %) ont reçu un diagnostic d'AOS, d'où la prévalence de l'AOS dans le MetS. les patients étaient de 68%. La majorité des cas d'AOS présentaient une AOS modérée à sévère (68,5 %), et seulement 31,4 % présentaient une AOS légère. L'âge des patients les patients inscrits à l'étude étaient âgés de 29 à 78 ans et l'âge moyen des patients était de 54,8 ± 9,4 ans. Sur 103 MetS inscrits au Dans l'étude, 59 (57,3 %) étaient des hommes et les autres étaient des femmes, de sorte que la prévalence de l'AOS sévère était plus élevée chez les hommes que chez les femmes. La prévalence augmente avec l'augmentation des tranches d'âge. Le poids, l'indice de masse corporelle (IMC), la circonférence et le tour de taille (WC) des cas d'AOS ont été s'avère significativement plus élevé que celui des personnes non atteintes d'AOS. Une tendance progressive à l'augmentation du poids, de l'IMC, de la circonférence du cou et Le WC a été observé avec l'augmentation de la gravité de l'AOS. Les patients atteints d'AOS par rapport aux patients non atteints d'AOS présentaient une augmentation significative du WC, du sang pression artérielle (TA), niveaux de glycémie à jeun, postprandiaux, aléatoires et de triglycérides (TG). Une tendance à l'augmentation des WC, de la TA à jeun, postprandiale, la glycémie aléatoire et les taux de TG étaient associés à une augmentation de la gravité de l'AOS. Des ronflements et une somnolence diurne ont été observés chez une proportion significativement plus élevée de cas d'AOS par rapport aux cas non AOS.Conclusions:Cette étude montre que l'AOS a une prévalence élevée chez les sujets atteints de MetS. Un indice élevé de suspicion clinique est nécessaire pour un diagnostic précoce.

Sheehan Syndrome Unmasked by Adrenal Crisis Secondary to Severe Dengue Fever.

Background: Sheehan syndrome is the infarction of a pituitary gland that has been physiologically enlarged as a result of postpartum bleeding. Agalactorrhea and amenorrhea are classic symptoms, but a constellation of manifestations occurs in both the acute and chronic forms. These manifestations can remain largely nonemergent unless Sheehan syndrome is complicated by severe adrenal dysfunction secondary to an inciting event such as dengue. We present a case of Sheehan syndrome that was uncovered in a patient with a dengue infection presenting as adrenal crisis. Case Report: A 45-year-old female presented with symptoms of acute gastroenteritis and severe dehydration. Her medical history was significant for secondary amenorrhea for 14 years after her last delivery followed by symptoms of endocrine dysfunction. At presentation, the patient was in adrenal crisis with hypotension, hypoglycemia, and hyperthermia. Dengue nonstructural protein 1 antigen was positive, along with signs of plasma leakage. Bloodwork showed bicytopenia with abnormal liver enzymes. Ultrasonography and computed tomography of the abdomen were suggestive of serositis with acalculous cholecystitis. Magnetic resonance imaging of the brain revealed an empty sella. Anterior pituitary hormone levels were significantly decreased with low serum cortisol, and the patient's thyroid profile analysis suggested secondary hypothyroidism. The final diagnosis was Sheehan syndrome presenting as adrenal crisis precipitated by severe dengue fever. The patient was managed conservatively and discharged on hormone supplement therapy. Conclusion: Sheehan syndrome is an important cause of panhypopituitarism in the developing world. Knowledge of Sheehan syndrome is important to help prevent its occurrence and reduce its resultant multifactorial effects.

Revolutionizing Veterinary Health with Viral Vector-Based Vaccines.

Vaccines signify one of the economical and reasonable means to prevent and eradicate the important infectious diseases. Conventional vaccines like live attenuated and inactivated vaccines comprise of whole pathogen either in attenuated or killed form. While, new generation vaccines have been designed to elicit immune response by genetically modifying only the nucleic acid portion of that pathogen. These new generation therapeutics include mRNA vaccines, DNA plasmid vaccines, chimeric vaccines and recombinant viral vector-based vaccines. Nucleic acid based vaccines use genetic material itself thus, they are highly stable and potent in nature to induce long-lasting immune response. Amongst these novel vaccine platforms, viral vector-based vaccines is one such emerging field which has proven to be extremely effective and potent. Nowadays, veterinary medicine has also accepted this innovative vectored vaccine platform to develop an effective control strategy against certain important viral diseases of animals. Viral vector-based vaccine uses various DNA and RNA viruses of human or animal origin to carry an immunogenic transgene of target pathogen. These vaccines enhance both humoral and cell mediated immune response without use of any accessory immune-stimulants. Till today, several viruses have been modified to be characterized as vaccine vectors. Currently, large number of research programs are going on to develop vectored vaccines and novel viral vector for veterinary use. In the present review, different kinds of viral vectored vaccines having veterinary importance have been discussed.

Epigenome reprogramming through H3K27 and H3K4 trimethylation as a resistance mechanism to DNA methylation inhibition in BRAFV600E-mutated colorectal cancer.

PURPOSE: BRAFV600E-mutated colorectal cancer (CRC) exhibits a strong correlation with DNA hypermethylation suggesting this subgroup of tumors presents unique epigenomic phenotypes. Nonetheless, 5-azacitidine, which inhibits DNA methyltransferase activity, is not efficacious in BRAFV600E CRC in vivo. EXPERIMENTAL DESIGN: We randomized and treated mice implanted with patient-derived tumor xenografts harboring BRAFV600E mutation with control, 5-azacitidine, vemurafenib (BRAF inhibitor), or the combination. Comprehensive epigenomic profiling was conducted on control and 5-azacitidine-treated tumor samples, including DNA methylation, histone modifications, chromatin accessibility, and gene expression. Combinations of epigenetic agents were explored in preclinical BRAFV600E CRC models. RESULTS: A profound reduction of DNA methylation levels upon 5-azacitidine treatment was confirmed, however, transcriptional repression was not relieved. This study unbiasedly explored the adaptive engagement of other epigenomic modifications upon 5-azacitidine treatment. A loss of histone acetylation and a gain of histone methylations, including H3K27 and H3K4 trimethylation, were observed around these hypomethylated regions suggesting the involvement of polycomb repressive complex (PRC) activity around the genome with loss of DNA methylation, therefore maintaining the repression of key tumor suppressor genes. Combined inhibition of PRC activity through EZH2 inhibitor with 5-azacitidine treatment additively improved efficacies in BRAFV600E CRC cells. CONCLUSIONS: In conclusion, DNA hypomethylation by 5-azacitidine exhibits a close association with H3K27me3 and PRC activity in BRAFV600E CRC, and simultaneous blockade of DNMT and EZH2 holds promise as a potential therapeutic strategy for patients with BRAFV600E-mutated CRC.

Exosomes: A new perspective for radiation combined injury as biomarker and therapeutics.

Radiation Combined Injuries (RCI) pose formidable public health risks, particularly in the context of nuclear incidents, necessitating specialized treatments and development of biomarkers. RCI encompasses instances where ionizing radiation exposure coincides with burns, wounds, or trauma. However, the limited understanding of cellular responses hinders progress in developing effective therapies. This article underscores the pivotal role of exosomes, nano-sized particles (30-120 nm) actively secreted by cells, in addressing the intricate challenges posed by RCI. Exosomes serve as vehicles for the transportation of bioactive molecules, including proteins, lipids, and miRNA, thereby facilitating processes critical to radiotherapy, burn injury, and wound healing. Exosomes hold significant promise for the transformation of RCI management by reducing inflammation, promoting wound healing, managing sepsis, altering immunological responses, and modulating signal transduction pathways. Moreover, exosomes are also being explored as biomarker for various diseases and stress conditions including radiation exposure and associated injuries. This comprehensive review highlights the burgeoning potential of exosomes in advancing the management of RCI, thereby enhancing public health preparedness and response.

Role of thoracoscopy in diagnosis of tubercular pleural effusion in low ADA setting- A prospective, observational study.

BACKGROUND: Tubercular Pleural effusion (TBPE) is one of most common extrapulmonary tuberculosis. It can be difficult to diagnose due to low sensitivity of pleural fluid smear, culture and CBNAAT. Diagnosis of TBPE is then dependent on the level of pleural fluid Adenosine Deaminase (ADA). Thoracoscopic pleural biopsy gives definite diagnosis specially in Low Pleural fluid ADA setting. AIMS AND OBJECTIVE: This study was planned to find out the prevalence of tubercular etiology in patients of exudative pleural effusion with low ADA (ADA <40 IU/L). MATERIAL AND METHODS: A Prospective, observational study was carried out in a tertiary teaching institute in north India. Total 142 patients of pleural effusion with low ADA were enrolled. All patients underwent rigid thoracoscopy for confirmation of their diagnosis. RESULTS: Out of 142 patients, male were 78 (55%) and female were 64 (45%). Mean age of patients were 57.4 years. Tuberculosis was diagnosed as a cause of effusion in 22 (15.5%) out of 142 patients. Majority of TBPE patients had pleural thickening as thoracoscopic finding. Mean ADA level in TBPE was 27.36 ± 11.6 as compared to 18.55 ± 9.02 in non tubercular pleural effusion patients and this difference was significant statistically (P- 0.002). CONCLUSION: The diagnosis of patients having exudative, low ADA pleural effusion can be very easily confirmed by thoracoscopy guided pleural biopsy which has a very high diagnostic yield.

Microplastics and heavy metal contamination along a land-use gradient in a Himalayan foothill river: Prevalence and controlling factors.

The co-occurrence of microplastics (MPs) and heavy metals in aquatic systems has raised significant concerns, yet their relationship in freshwater ecosystems remains poorly understood. This study aims to evaluate the prevalence of MPs and factors controlling their distribution in both water and sediment in the Markanda River, Northwest India. MPs were extracted from sediment and water samples using density separation and classified through fluorescence microscopy and Raman spectroscopy. Metal concentrations in river water samples were analyzed using ICP-MS, and their correlation with MP abundance was explored. The results indicated the widespread occurrence of MP pollution across the Markanda River basin, with particle concentrations ranging from 10 to 530 particles L-1 in surface water and 1330-4330 particles kg-1 dry weight (dw) in sediment samples. The variability in MP abundance at sampling sites along the Markanda River courses results from factors such as the proximity of industrial establishments and human habitation, while the influence of grain size on MP distribution appears to be limited. Pellets (88.5 %) and fragments (8.5 %) were the most abundant types of MPs, with polyethylene (45.45 %) and polystyrene (30.9 %) being the dominant forms in water samples. The ICP-MS analysis of heavy metals in water samples indicated elevated levels of As (1.67 to 32.31 ppb) in downstream areas of the river system, influenced by human activities. While metals exhibited correlation with each other, there was a weak association, except for As, with the levels of MPs in the Markanda River. The SEM-EDX analyses to characterize chemical elements absorbed onto the surface of MP showed distinct variations in upstream and downstream sites, with the presence of elements such as Mn, Ni, Cr, Zn, As, Se, and Cu found in downstream areas. We conclude that MPs contaminated with heavy metals potentially threaten the ecological security of freshwater aquatic systems and highlight the importance of management action to reduce plastic pollution worldwide.

Intracellular peroxynitrite perturbs redox balance, bioenergetics, and Fe-S cluster homeostasis in Mycobacterium tuberculosis.

The ability of Mycobacterium tuberculosis (Mtb) to tolerate nitric oxide (•NO) and superoxide (O2•-) produced by phagocytes contributes to its success as a human pathogen. Recombination of •NO and O2•- generates peroxynitrite (ONOO-), a potent oxidant produced inside activated macrophages causing lethality in diverse organisms. While the response of Mtb toward •NO and O2•- is well established, how Mtb responds to ONOO- remains unclear. Filling this knowledge gap is important to understand the persistence mechanisms of Mtb during infection. We synthesized a series of compounds that generate both •NO and O2•-, which should combine to produce ONOO-. From this library, we identified CJ067 that permeates Mtb to reliably enhance intracellular ONOO- levels. CJ067-exposed Mtb strains, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) clinical isolates, exhibited dose-dependent, long-lasting oxidative stress and growth inhibition. In contrast, Mycobacterium smegmatis (Msm), a fast-growing, non-pathogenic mycobacterial species, maintained redox balance and growth in response to intracellular ONOO-. RNA-sequencing with Mtb revealed that CJ067 induces antioxidant machinery, sulphur metabolism, metal homeostasis, and a 4Fe-4S cluster repair pathway (suf operon). CJ067 impaired the activity of the 4Fe-4S cluster-containing TCA cycle enzyme, aconitase, and diminished bioenergetics of Mtb. Work with Mtb strains defective in SUF and IscS involved in Fe-S cluster biogenesis pathways showed that both systems cooperatively protect Mtb from intracellular ONOO- in vitro and inducible nitric oxide synthase (iNOS)-dependent growth inhibition during macrophage infection. Thus, Mtb is uniquely sensitive to intracellular ONOO- and targeting Fe-S cluster homeostasis is expected to promote iNOS-dependent host immunity against tuberculosis (TB).

Effect of preoperative oral carbohydrate loading on postoperative insulin resistance, patient-perceived well-being, and surgical outcomes in elective colorectal surgery: a randomized controlled trial.

BACKGROUND: Insulin resistance (IR) is one of the independent determinants influencing the length of hospital stay (LOHS) and postoperative complications in colorectal procedures. Preoperative oral carbohydrate loading (OCL) has emerged as a prospective countermeasure for IR. This study aimed to investigate the effects of preoperative carbohydrate loading on postoperative IR, inflammatory parameters, and clinical outcomes in patients undergoing elective colorectal surgery. METHODS: This was an open-label, parallel arm, superiority randomized controlled trial conducted over 2 years. Participants were assigned to conventional fasting and oral OCL groups. IR, insulin sensitivity, Glasgow Prognostic Score (GPS), and interleukin 6 levels were analyzed on the day of surgery and on the first postoperative day (POD-1) and third POD (POD-3). Clinical parameters, such as thirst, hunger, dry mouth, anxiety, weakness, pain, nausea, and vomiting, were compared in the perioperative period. In addition, surgical clinical outcomes, such as intestinal recovery, time to independent ambulation, postoperative morbidity, and LOHS, were studied. RESULTS: A total of 72 participants were included, with 36 in each group. In the OCL group, there was a statistically significant decrease in postoperative IR on the day of surgery, POD-1, and POD-3 (P = .0336). Similarly, inflammatory parameters and the GPS were found to be significantly lower in the OCL group (P < .001). Clinical parameters, such as thirst, hunger, and dry mouth, were significantly lower in the intervention group (P =.00), with a shortened LOHS. CONCLUSION: This study demonstrated that preoperative carbohydrate loading is associated with reduced IR and inflammatory markers, shortened hospital stays, and improved overall clinical outcomes in elective colorectal surgery.

Exploring novel Apalutamide analogues as potential therapeutics for prostate cancer: design, molecular docking investigations and molecular dynamics simulation.

Introduction: Prostate cancer (PC) ranks as the second most frequent type of cancer in men and is the fourth largest cause of mortality worldwide. Androgenic hormones such as testosterone and dihydrotestosterone are crucial for the development and progression of the prostate gland. Androgenic hormones bind to androgen receptors (AR) and trigger the synthesis of many genes that stimulate the growth of prostate cells, initiating PC growth. Apalutamide (APL) is a non-steroidal antiandrogen drug used to treat PC; however, it also causes a variety of toxicities and resistance during the treatment. Methods: The purpose of this study was to computationally identify new and safer analogues of APL, focusing on improved pharmacokinetic properties and reduced toxicity. Drug likeness (DL) and drug score (DS) were also calculated. Docking studies on the designed analogues were conducted to predict their binding affinities and compare their orientations with the ligands in the original crystal structure. Molecular dynamics (MD) simulation of docked ligands was done using Schrödinger suite. Results: We generated a total of 1,415 analogues for different groups of APL using the bioisosteric approach. We selected 80 bioisosteres based on pharmacokinetic profiles, DL and DS score predictions, and found that the designed APL bioisosteres were optimal to good compared to APL. Analogues APL19, APL35, APL43, APL76, and APL80, formed hydrogen bonds with protein (PDB ID: 5T8E) which is similar hydrogen bonding to the standard (APL). The MD simulation result confirmed that APL43 and APL80 complexes were stable during the 100 nS run. Discussion: The results suggest that the APL analogues, particularly APL43 and APL80, are predicted to be potential antiandrogen drugs for the treatment of prostate cancer.

Comparison of Potassium-Competitive Acid Blockers and Proton Pump Inhibitors in Patients With Gastroesophageal Reflux Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This meta-analysis evaluated the efficacy and safety of potassium-competitive acid blockers (PCABs) compared to proton pump inhibitors (PPIs) in treating gastroesophageal reflux disease (GERD). A comprehensive literature search was conducted across multiple databases, and 11 randomized controlled trials comparing PCABs with PPIs were included. The primary outcome was the healing of erosive esophagitis (EE), with secondary outcomes, including relief of heartburn symptoms and adverse events. The analysis included 11 studies and a pooled sample of 4,108 GERD patients. Results showed that PCABs were significantly more effective in healing EE compared to PPIs (OR: 1.67, 95% CI: 1.24-2.24, p<0.01). PCABs also demonstrated a higher rate of complete resolution of heartburn symptoms, although this difference did not reach statistical significance (OR: 1.43, 95% CI: 0.98-2.09, p=0.06). In terms of safety, there was no significant difference in adverse events between PCABs and PPIs (OR: 0.91, 95% CI: 0.79-1.04, p=0.18), including serious adverse events. The superior efficacy of PCABs can be attributed to their unique pharmacological properties, which allow for more rapid and potent acid suppression compared to PPIs. However, the long-term safety profile of PCABs, particularly newer agents, requires further investigation. The study was limited by the predominance of vonoprazan among the PCABs studied and the focus on patients with EE rather than non-erosive reflux disease. In conclusion, this meta-analysis suggests that PCABs are more effective than PPIs in treating GERD, particularly in healing EE, while maintaining a comparable safety profile. Future research should focus on evaluating a wider range of PCABs, assessing their efficacy in non-erosive reflux disease, and investigating their long-term safety in GERD management.