Rauvolfia serpentina (L.) Benth. Ex Kurz is a greatly appreciated medicinal plant, well-known for its therapeutic benefits in traditional medicine, particularly in Ayurveda, where the roots and whole plant are used to treat a variety of ailments. However, studies focusing on R. serpentina seeds are relatively scarce. Hence, the present study provides a novel approach by analysing the seed oil of R. serpentina extracted using the supercritical-carbon dioxide-fluid-extraction (SCFE) technique. The research employed advanced analytical methods including gas-chromatography with flame ionization detector (GC-FID), gas-chromatography-tandem mass spectrometry (GC-MS/MS), and high performance thin layer chromatography (HPTLC) to characterise the chemical composition of the extracted oil. Functional moieties were evaluated by Fourier transform infrared spectroscopy (FT-IR), while proton nuclear-magnetic-resonance (¹H NMR) spectroscopy was utilised to identify the phytometabolites as well as to assess the physico-chemical parameters. The anti-microbial potential of the supercritically extracted oil was demonstrated through its activity against Klebsiella pneumoniae. The inhibitory effects on K. pneumoniae were quantified using the broth microdilution method, showing activity at both minimum inhibitory concentrations (MIC₅₀ and MIC₉₀). Furthermore, the oil was found to be non-genotoxic, as demonstrated by the Ames assay, which showed no mutagenic effects against S. typhimurium and E. coli WP2 uvrA. Since previous reports on R. serpentina seeds and their novel contribution in the field of pharmaceutics are rather limited, the present study is of utmost importance. The study may pave the way for future investigations into the therapeutic potentials of R. serpentina seeds.

Hepatocellular carcinoma (HCC), commonly known as primary liver cancer, is a leading cause of cancer-related mortality worldwide, primarily attributed to changing lifestyles and dietary habits. HCC arises from liver cirrhosis, hepatic fibrosis, or hepatitis B virus infection, and is caused by disruptions in protein and lipid metabolism. These metabolic alterations, recognized as a hallmark of cancer, are pivotal in the progression of chronic liver disease to HCC. Due to its asymptomatic nature in early stages, HCC is often diagnosed at advanced stages when treatment options are limited. Despite being a potentially curative option, liver transplantation remains hindered by high costs and donor scarcity, further compounded by suboptimal long-term success rates. This review examines the critical metabolites that play a part in developing HCC, focusing on their roles as possible biomarkers for disease progression and therapeutic targets. Additionally, the influence of the gut microbiome on HCC development is discussed, highlighting its interplay with metabolic pathways. Understanding the roles of metabolites and the gut microbiome in HCC progression underscores the importance of their potential use in early detection and the development of targeted therapies, offering new avenues for improving patient outcomes.

Blunt trauma to the abdomen can result in various injuries which are potentially fatal if not promptly recognized and treated. Mechanism of injury, anatomical location, patient demographics, and clinical profile play crucial roles in diagnosis and management. The article presents 2 cases illustrating the challenges, and successful management of isolated jejunal injuries, and highlight the significance of early recognition and surgical intervention. These injuries are rare and there needs to be a high index of suspicion, especially in cases with atypical presentation. The cases in this article underscore the critical role of early surgical intervention in achieving optimal recovery and reducing the morbidity and mortality associated with isolated jejunal injuries. Clinicians need to consider the possibility of small bowel perforation following apparently trivial injuries, and employ a comprehensive approach to managing abdominal trauma.

Blunt trauma to the abdomen can result in various injuries which are potentially fatal if not promptly recognized and treated. Mechanism of injury, anatomical location, patient demographics, and clinical profile play crucial roles in diagnosis and management. The article presents 2 cases illustrating the challenges, and successful management of isolated jejunal injuries, and highlight the significance of early recognition and surgical intervention. These injuries are rare and there needs to be a high index of suspicion, especially in cases with atypical presentation. The cases in this article underscore the critical role of early surgical intervention in achieving optimal recovery and reducing the morbidity and mortality associated with isolated jejunal injuries. Clinicians need to consider the possibility of small bowel perforation following apparently trivial injuries, and employ a comprehensive approach to managing abdominal trauma.

Purpose: Ankle fracture fixation is the gold standard of treatment but it does have its own complications. There is inadequate data regarding the comparative effectiveness of early vs. delayed fixation for open ankle fracture outcomes. This study compares the clinical and functional outcomes of open ankle fractures treated by early or delayed definitive fixation and identifies the limitations of both methods. Materials and Methods: All 73 patients enrolled in the study underwent surgical intervention within 24 hours of injury. The early fixation group (group A) consisting of 39 patients underwent definitive fixation as an index procedure, while the delayed fixation group (group B) consisted of 34 patients who underwent debridement and external fixator application as an index procedure and definitive fixation when soft tissue condition was conducive. All patients were evaluated at 2, 6, and 12 weeks postoperatively and then three monthly for a year. Results: Enneking and American Orthopaedic Foot and Ankle Society scores were markedly higher in the early fixation group at 6 months postoperatively (p-values <0.001 and 0.011, respectively). However, no discernible intergroup difference was evident at 12 months postoperatively. Between 6 and 12 months, group functional outcome scores were significantly different. At 6 months, there was a substantial difference in dorsiflexion between the two groups (p-values 0.001 and <0.001, respectively), but no difference was observed at 12 months postoperatively. At 6 and 12 months, group average plantar flexions were non-significantly different. Conclusion Early definitive fixation of complex ankle fractures using a targeted approach produced promising results for lower grade open fractures (grades 1 and 2), and delayed definitive fixation, after initial external fixation to allow for soft tissue stabilization, produced promising results for higher grade open fractures (grades 3A and 3B). At 12-month follow-ups, clinical and functional outcomes achieved using these strategies were equivalent.

Blunt trauma to the abdomen can result in various injuries which are potentially fatal if not promptly recognized and treated. Mechanism of injury, anatomical location, patient demographics, and clinical profile play crucial roles in diagnosis and management. The article presents 2 cases illustrating the challenges, and successful management of isolated jejunal injuries, and highlight the significance of early recognition and surgical intervention. These injuries are rare and there needs to be a high index of suspicion, especially in cases with atypical presentation. The cases in this article underscore the critical role of early surgical intervention in achieving optimal recovery and reducing the morbidity and mortality associated with isolated jejunal injuries. Clinicians need to consider the possibility of small bowel perforation following apparently trivial injuries, and employ a comprehensive approach to managing abdominal trauma.

[Objective] To explore the application of Quality by Design (QbD) tools in assessing geographical variations of Phyllanthus emblica (P. emblica) from five distinct Indian states. [Methods] In the current experiment, the Box-Behnken design with a reduced quartic model and 105 runs was employed with the use of the Design Expert software for randomized response surface mapping. Three different extraction methods (Soxhlet, maceration, and sonication) along with three solventst [distilled water, methanol, and water-methanol mixture (50 : 50 v/v)] were considered in the present study. The anti-oxidant activities, total flavonoid content (TFC), and total phenolic content (TPC) in the P. emblica were determined and analysed by gas chromatography-mass spectrometry (GC-MS) to identify the major components. [Results] The QbD overlay plot showed that the extractive value of the P. emblica was no less than 30% w/w, 2,2-diphenyl-1-picrylhydrazyl (DPPH) no less than 60% mcg/mL (micrograms per millilitre), TFC no less than 75 mg QE/g (milligrams of quercetin equivalents per gram), and TPC no less than 80 mg GAE/g (milligrams of gallic acid equivalents per gram). Moreover, the GC-MS data confirmed the presence of variation in the bioactives of P. emblica extracts. [Conclusion] The model was significant in describing the variation in extractive value, DPPH, TFC, and TPC. The QbD approach may tend to prioritize thoroughness in the extraction process, ultimately resulting in improved quality in the extracted products.

Background/Aims: Response to vaccine in patients with inflammatory bowel disease is lower than in the general population. We aimed to evaluate the efficacy of hepatitis B virus (HBV) vaccination in patients with ulcerative colitis (UC) versus controls. Methods: We prospectively compared antibody response to HBV vaccination in 100 patients with UC versus controls. HBV vaccination was given to all the cases and controls at 0, 1 and 6 months. Anti-hepatitis B surface (anti-HBs) titers were then measured 4 weeks after the first and the third dose. Adequate immune response (AIR) was considered if the anti-HBs titer was >10 IU/L and effective immune response (EIR) if the anti-HBs titer was >100 IU/L. Results: Median anti-HBs titer was lower in patients with UC than controls (67 IU/L vs. 105 IU/L, P<0.01). AIR and EIR were significantly lower in patients than in controls (82% vs. 96%, P=0.001; 41% vs. 66%, P<0.001, respectively). Univariate analysis showed that age <30 years, mild to moderate severity of disease, disease duration <5 years, male sex, post first dose anti-HBs titer >2 IU/L and non-exposure to corticosteroids, azathioprine and biologicals were predictors of AIR in patients with UC (P<0.05). Multivariate analysis revealed that only non-exposure to corticosteroids, azathioprine and biologicals, male sex, and disease duration <5 years were independent predictors of AIR. Conclusions Response rate to the HBV vaccination in patients with UC was significantly lower as compared to the controls. Male sex, shorter disease duration, and non-exposure to immunomodulators were independent predictors of AIR.

Background: Founder mutation is a heritable genetic alteration observed with high frequency in a geographically and culturally isolated population where one or more ancestors becomes the forebearer of the altered gene. The current study reports two founder mutations in the BRCA1 gene in the Nepalese people. Methods: Germline BRCA testing in all surface epithelial ovarian cancers and the selected case of breast, prostate, and pancreatic cancers has been the standard practice from 2016 to 2021. One thousand one hundred thirtythree probands were screened for germline BRCA variants by next generation sequencing. The variants were classified as per the American Society of Medical Genetics and Genomics recommendations. Pathogenic (class V) and likely pathogenic (class IV) were considered clinically relevant and utilized for cascade screening. Results: Nepalese population made up a subcohort of 5.12% (58/1,133) of probands tested for germline BRCA1/2 variants. Twenty-seven of these 58 tested harbored pathogenic genetic alterations in BRCA1/2 genes, with 23 being BRCA1 mutant. Sixteen of 23 BRCA1 mutant cases shared one common pathogenic mutation c.2214_2215insT (p.Lys739Ter) (NM_007294.4). Additionally, a second highly recurrent mutation in BRCA1 gene c.5068A>T (p.Lys1690Ter) (NM_007294.4) was noted in six patients from this population. Conclusions The overwhelming abundance of the above two variants in a geographically confined population confers these two genetic alterations a status of founder mutations amongst the people of Nepal. A more extensive population-based study to reaffirm these findings will help establish a dual site-specific germline testing similar to the “Multisite-3-assay” in Ashkenazi Jews as the primary screening tool, especially in a resource-constrained environment.

SMARCA4/BRG1-deficient lung adenocarcinoma (SD-LUAD) is being recognized as a distinct subtype based on subtle differences in its clinical, morphological, and immunophenotypic attributes compared to other non–small cell lung carcinomas. We present here a case of SD-LUAD with curious thyroid transcription factor 1 (TTF1) expression in a morphologically heterogenous lung adenocarcinoma. The better differentiated area showed preservation of TTF1 expression, and a poorly differentiated tumor had loss of TTF1 expression with universal BRG1 loss.