OBJECTIVES: Clinical biochemistry reference intervals (RIs) play a crucial role in interpreting patient test results and making informed clinical decisions. Using data from an ongoing Indian Council of Medical Research-National task force study on healthy women, normative ranges for commonly analyzed biochemical analytes were established. MATERIALS AND METHODS: A total of 13,181 women of reproductive age (18–40 years) were recruited from different urban and rural regions of the country, of which 9898 women signed an informed consent were included. Among these, women having features of hyperandrogenism, menstrual cycle irregularities, and comorbidities were excluded. RIs of 22 analytes were computed in the remaining 938 women controls. To estimate the 95% range of the reference distribution, the limits of the 2.5^th percentile and the 97.5^th percentile were used in the study. RESULTS: Mean ± standard deviation of age and body mass index of participants was 30.12 ± 6.32 years and 22.8 ± 3.36 kg/m² respectively. Centiles (2.5^th–97.5^th) of liver function parameters, lipid parameters, glycaemic parameters, and renal parameters are presented. No significant difference in analytes was observed in relation to the area of residence, and age groups except in albumin (P = 0.03). The distribution of most of the parameters was consistent with the various RI studies conducted in India as well as other countries. CONCLUSION: This is the first study generating biochemical RIs data among a large representative sample of healthy reproductive-age women recruited using a robust design across the country. The resource may serve as a reference range for common biochemical analytes for future in this age group.

CONTEXT: Ventilator-associated pneumonia (VAP) develops nearly in about one-third of the patients, 48 h after receiving mechanical ventilation. Common pathogens are Pseudomonas aeruginosa, Staphylococcus aureus, Acinetobacter spp., Klebsiella spp., Escherichia coli, Proteus spp., Enterobacter spp. and Enterococcus spp. including multidrug-resistant pathogens. AIM: The study aims to assess the pattern of antimicrobial drug use in VAP and to assess the etiological organisms and their drug sensitivity and resistance pattern. SETTINGS AND DESIGN: Study participants admitted to Kempegowda Institute of Medical Sciences Hospital and Research Centre, Bengaluru, and who developed VAP were included in this prospective observational study. SUBJECTS AND METHODS: Bronchial secretions were subjected to microbiological analysis. The etiological organisms, their drug sensitivity and resistance pattern, and the outcome of drug therapy were recorded. The clinical course of the study participants was monitored till either the resolution of pneumonia or the demise of the participant. STATISTICAL ANALYSIS USED: Qualitative data were analyzed using the Chi-square test or Fischer's exact test and quantitative data using the independent t-test. RESULTS: Early VAP was seen in 91.7% and late VAP in 8.3% of the participants. The organisms isolated were S. aureus, Enterococcus spp., Acinetobacter spp., Klebsiella pneumoniae and P. aeruginosa. Majority of the study participants with early VAP (75%, n = 41) completely recovered from pneumonia and 80%, n = 4 participants with late VAP recovered completely. CONCLUSION: The organisms had a varied sensitivity and resistance pattern. The clinical outcome was multifactorial and its association with specific antimicrobial agents cannot be drawn.

OBJECTIVES: Colon carcinoma stands as the most familiar malignancy throughout across the globe. Raptinal induce apoptosis through the alteration of cellular events. Thus, in the present investigation, the anticancer activity of raptinal counter to 1,2-dimethylhydrazine (DMH) persuaded colon carcinoma has been evaluated through both in vivo and in vitro systems. MATERIALS AND METHODS: The pharmacophore analysis demonstrated the binding efficacy of raptinal with the apoptotic proteins. The chemotherapeutic activity of raptinal was examined through HT-29 human colorectal cancer (CRC) cell line as well as DMH persuaded CRC in the rat model. The cytotoxicity analysis, flow cytometry, and DAPI analysis have been carried out on HT-29 cell line through in vitro assessment. The colon carcinoma has been induced through DMH administration and subsequently Dextran sulfate sodium treatment in male Wistar rats. After 18 weeks of raptinal treatment, the colon tissues have been investigated for aberrant crypt foci (ACF) count, antioxidant status, histology, immunohistochemical assessment, and apoptotic analysis. RESULTS: The raptinal therapy on HT-29 cells demonstrated a substantial % of early apoptosis followed by G0 and G1 phase arrest, which subsequently led to apoptosis. Furthermore, it inhibits ACF development with improved colonic abrasions and structural integrity of colonic mucosa with increased levels of antioxidants, proapoptotic biomarkers including p53, caspase-3, Bax and downstream effects of Bcl-2, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 mutation. CONCLUSIONS: These findings indicate the raptinal effectively reduces colon cancer by inducing apoptosis through p53/Bcl2/Bax/caspase-3 pathway and suppressing IL-6, TNF-mediated chronic inflammation in the colon cancer microenvironment.

BACKGROUND AND OBJECTIVES: Induced pluripotent stem cells (iPSCs) derived three-dimensional (3D) model for rare neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) is emerging as a novel alternative to human diseased tissue to explore the disease etiology and potential drug discovery. In the interest of the same, we have generated a TDP-43-mutated human iPSCs (hiPSCs) derived 3D organoid model of ALS disease. The high-resolution mass spectrometry (MS)-based proteomic approach is used to explore the differential mechanism under disease conditions and the suitability of a 3D model to study the disease. MATERIALS AND METHODS: The hiPSCs cell line was procured from a commercial source, grown, and characterized following standard protocols. The mutation in hiPSCs was accomplished using CRISPR/Cas-9 technology and predesigned gRNA. The two groups of organoids were produced by normal and mutated hiPSCs and subjected to the whole proteomic profiling by high-resolution MS in two biological replicates with three technical replicas of each. RESULTS: The proteomic analysis of normal and mutated organoids revealed the proteins associated with pathways of neurodegenerative disorders, proteasomes, autophagy, and hypoxia-inducible factor-1 signaling. Differential proteomic analysis revealed that the mutation in TDP-43 gene caused proteomic deregulation, which impaired protein quality mechanisms. Furthermore, this impairment may contribute to the generation of stress conditions that may ultimately lead to the development of ALS pathology. CONCLUSION: The developed 3D model represents the majority of candidate proteins and associated biological mechanisms altered in ALS disease. The study also offers novel protein targets that may uncloud the precise disease pathological mechanism and be considered for future diagnostic and therapeutic purposes for various neurodegenerative disorders.

Sodium-glucose co-transporter 2 inhibitors (SGLT2is) are recommended as the next step therapy for the management of diabetes mellitus. The large clinical trials of SGLT2is demonstrated benefits on various renal endpoints. We conducted this meta-analysis of large trials on cardiovascular and renal safety trials to explore the renoprotective effect of this group of drugs. PubMed, Cochrane CENTRAL, and EMBASE databases were searched with specific keywords till January 19, 2021. Randomized trials of SGLT2is that evaluated the cardiovascular or renal composite outcome as a primary outcome measure were eligible. Random-effects model was used to calculate the overall risk ratios. The search yielded 716 studies and 10 studies were included. The SGLT2is reduced the risk of composite renal outcome (risk ratio [RR] = 0.64, 95% confidence interval [CI] = 0.58–0.72), decline in estimated glomerular filtration rate (eGFR) (RR = 0.62, 95% CI = 0.50–0.77), doubling of serum creatinine (RR = 0.67, 95% CI = 0.56–0.81), dialysis or renal replacement therapy (RR = 0.71, 95% CI = 0.59–0.86), sustained eGFR of <15 ml per min per 1.73 m² for at least 30 days or more (RR = 0.66, 95% CI = 0.55–0.81), end-stage renal disease (RR = 0.70, 95% CI = 0.56–0.87), and acute kidney injury (RR = 0.79, 95% CI = 0.71–0.89). This analysis establishes the renoprotective effect of SGLT2is. This benefit is noted in patients who had eGFR of more or <60 ml per min per 1.73 m². This benefit was uniform across all the SGLT2 inhibitors except ertugliflozin and sotagliflozin.

As frontline health workers, nursing professionals have a crucial role in reporting medical device-associated adverse events (MDAEs). A questionnaire-based study was carried out to evaluate the knowledge, attitude, and practice of senior nursing officers (SNOs), nursing officers (NOs), and nursing students (NSs) toward MDAE. The response rate of the survey was 84% (n = 134). The mean score of knowledge of SNOs, NOs, and NSs was 2.03 ± 0.92, 1.71 ± 0.96, and 1.52 ± 0.82, respectively (P = 0.9). A large proportion of study participants (97%) considered that the use of medical device could sometimes cause untoward occurrences and detecting and reporting those events will enhance the safety of patients. However, many of them (67%) have not reported it during clinical posting. The participants of this survey possessed limited knowledge of MDAE. However, their attitude toward MDAE was encouraging and a continuous training program may improve their knowledge regarding MDAE and enhance the reporting practice.

BACKGROUND: Aspirin is indicated in the emergency management of acute coronary syndrome. However, oral aspirin has erratic bioavailability compared to i.v. formulation. OBJECTIVE: The objective of this study was to evaluate the comparative efficacy and safety of intravenous (IV) and oral aspirin in acute coronary syndrome. STUDY DESIGN: This was a systematic review and meta-analysis. RESULTS: Two randomized controlled trials were included. Compared to oral aspirin, lower platelet aggregability was seen with IV aspirin at 5 min and 20 min. Lower thromboxane B2 and lower platelet CD-62p levels were noted in the IV group; however, no significant difference was observed in terms of “composite cardiovascular death, stroke, and myocardial infarction (MI) at 4–6 weeks,” “any cause mortality,” “cardiovascular mortality,” “occurrence of stroke,” and “occurrence of MI/reinfarction.” However, no difference was noted in terms of the occurrence of serious adverse events. CONCLUSION: IV aspirin showed some advantages in terms of platelet aggregability biomarkers at 20 min and 1 week with comparable safety to oral aspirin. No difference was seen in terms of clinical outcomes (at 24 h, 7, and 30 days) and the occurrence of serious adverse events.

All-trans-retinoic acid (ATRA) has transformed the treatment of acute promyelocytic leukemia. Most of the adverse effects associated with this drug are minor barring differentiation syndromes. Genital ulcers feature among the underreported adverse effects of ATRA which needs to be kept in mind to avoid life-threatening complications. We describe two cases who developed genital ulcers while treated with ATRA.