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Due to a more physiological reproduction of the in vivo situation, liver‐on‐a‐chip devices in recent studies have shown higher sensitivity and accuracy for hepatotoxicity testing compared to traditional in vitro liver models. In this context, this work presents an original microfluidic device mimicking 3D hepatic cords organized radially, like in the liver lobule. Ten cell‐culture chambers seeded at a high density are disposed with a parallelized flow that emulates blood flow from the portal triad to the central vein in the liver lobule. Using this device, on‐chip differentiation of human HepaRG‐Hepatoblast (HepaRG‐HB) to HepaRG‐Hepatocytes (HepaRG‐HC) has been studied in terms of self‐organization capabilities, bile canaliculi formation and albumin expression. Our results indicate that due to the design of the cell culture chamber, which mechanically constrains tissue proliferation, and the physiologically relevant microfluidic flow condition used during tissue development, the HepaRG‐HBs in the device can proliferate, self‐organize, and spontaneously differentiate in a DMSO free medium forming long, directional bile canaliculi. On the contrary, under the same conditions, differentiated HepaRG‐HC is observed to aggregate without long bile canaliculi and form tissues resembling traditional HepaRG‐HC cultures. © 2024 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC. [ABSTRACT FROM AUTHOR]

Turmeric is well-known for its analgesic, anti-inflammatory and anti-arthritic properties but 69.4% of the turmeric rhizome contains Turmerosaccharides whose clinical benefit is still unexplored. Turmacin®/NR-INF-02 is an aqueous extract of Turmeric containing Turmerosaccharides (>10%w/w) with negligible curcuminoids. Previous study with low dose Turmacin® confirmed its safety and efficacy in alleviating induced knee pain in healthy volunteers. Hence, this study aimed to assess the safety and explore the efficacy of moderately high dose Turmacin®. It was an open-label, single-arm interventional trial conducted from August 2018 - January 2019 in a tertiary care teaching hospital. Turmacin® was administered for seven days to 15 healthy volunteers as four capsules of 500 mg each in the morning with food. The stair mill at a speed of 60 steps per minute was used to induce knee pain and Visual Analogue Scale (VAS) was used to measure the pain intensity. Assessments were performed at baseline, Days 5 and 7. One participant reported dyspepsia of mild grade that resolved on its own. When compared to baseline, time to initial discomfort significantly increased on Day-5 (Mean Difference [MD] = 30s, p = 0.016) and Day-7 (MD = 32s, p = 0.007). Whereas the maximum VAS score decreased with time and on Day-7 and it was significantly low when compared with baseline (MD = -0.93, p = 0.008). In summary, Turmacin® supplements given at a dose of 2 g/day was safe and tolerable. Similar to the previous study with low dose Turmacin®, there was a significant increase in pain threshold and decrease in the maximum pain score post intervention. [ABSTRACT FROM AUTHOR]

Byline: Miteshkumar. Maurya, Sunanda. Gautam, Jeffrey. Raj, Shruti. Saha, Sanchita. Ambre, Aishwarya. Thakurdesai, Aditya. Shah, Urmila. Thatte BACKGROUND: CYP3A5 enzymes belong to the phase I Group of drug-metabolizing enzymes, which [...]

Introduction: Pregnancy results in a lot of changes within the oral cavity, and recent reports have suggested an association between dental issues and poor pregnancy outcomes. Although many studies indicate that dental procedures can be carried out safely on pregnant patients to alleviate pain and promote better oral health, dental health is not given importance in pregnancy mainly due to fear and misconceptions that dental care can adversely affect the foetus. Aim: To summarise the dental presenting complaints and clinical examination findings of pregnant women and to evaluate the proportion of those compliant with the respective dental treatment services recommended by the dentist. Materials and Methods: It was a retrospective observational study analysing data pertaining to all pregnant patients who reported to the Department of Dentistry at Seth G.S. Medical College and King Edward Memorial Hospital in Maharashtra, India between December 2017 and September 2018. There was no formal sample size estimation, and all eligible patients’ data available in the department registry, which was maintained as part of routine clinical care, were analysed. A structured Case Record Form (CRF) was used to collect demographic and clinical data from these registers, and descriptive statistics were used to summarise the data. Results: The mean±Standard Deviation (SD) age of study sample was 27.69±4.584 years. A total of 81 patients’ data were included for the analysis. The most common presenting complaint and examination finding were pain and dental caries, respectively. The most common treatment plan suggested and performed was medication, followed by extraction. The number of patients who followed up was 37 (45.67%). Conclusion: Pain and carious tooth were the most common presenting complaint and examination finding, respectively. The proportion of patients who came for follow-up was not adequate, warranting enhanced awareness activities to reduce stigma over dental care during pregnancy. [ABSTRACT FROM AUTHOR]

Byline: B. Bharathi, Jeffrey. Raj, Kevin. Saldanha, P. Suman Rao, D. Devi INTRODUCTION: Medication errors (MEs) can prolong hospital stay and are a cause of morbidity and mortality. Studies evaluating [...]

Introduction: The institutional ethics committees (IECs) raise queries following protocol reviews. The quality of these queries would be a useful metric to assess how well the IEC executes its fundamental role of protecting participants. Methods: Queries received after the initial review and replies sent by a single research department were evaluated. A content analysis was done to identify the domains and categories of queries. We categorized these queries as administrative, ethics related, and scientific. The impact of each query in improving the science or safeguarding the rights and safety of research participants (ethics) was evaluated by two authors of this manuscript: one affiliated and the other nonaffiliated to the institute. Kappa statistics were used to evaluate for agreement between the two. Results: A total of 13 studies (investigator-initiated studies [IISs]: 7 and pharmaceutical industry-sponsored studies [PSSs]: 6) formed the final sample size for analysis. The total number of queries was 364 (IIS: 106 and PSS: 258; P < 0.001). With regard to the categories, we found n = 42 (11.54%) to be irrelevant at that stage of the review process; n = 51 (14.01%) were about information already available which the IEC had missed; n = 67 (18.41%) queries where the IEC needed paraphrasing; n = 50 (13.74%) were entirely relevant with the need for further clarification; and n = 154 (42.31%) had been missed by the investigator during the initial submission. The overall agreement between the affiliated and unaffiliated investigators was just 12.9% (P < 0.001). Conclusions: We found that approximately 25% of the queries raised by the IEC were redundant. It is our opinion that this redundancy could have been channeled into greater focus on scientific and ethical aspects of the protocol. Ongoing dialog between investigators and ethics committees may help address this. Perspectives between the affiliated and the unaffiliated investigators with regard to the relevance of queries were grossly different. [ABSTRACT FROM AUTHOR]

Byline: Archish. Khivsara, Jeffrey. Raj, Divya. Hegde, Mangala. Rao Idiosyncratic drug-induced liver injury (DILI) is damage to liver occurring at recommended dose of a drug in contrast to toxic or [...]

Introduction: Proton pump inhibitors (PPIs) are liberally used over the counter medication and is largely considered safe. Off late, there are many reports that suggest increased incidence of chronic kidney disease with long-term PPI use. PPIs are often prescribed in patients with diabetes mellitus (DM) and one of the well-known complications of DM is diabetic nephropathy (DN). Thus, the aim of our study was to evaluate association between PPI use and DN. Methods: It was a case-control study conducted over a 2-year period (April 2017--March 2019). Cases were outpatients with type II DM and associated DN. Controls were age and sex-matched type II DM without DN. Results: A total of 200 participants, 100 each in the case and control group, were recruited. The proportion of participants using PPI was 62% in the cases and 42% in the controls (P = 0.005). The most common PPI used was pantoprazole. Increased duration of PPI use was significantly associated with DN [adjusted odds ratio: 1.171; 95% confidence interval: 1.022, 1.341; P = 0.023]. Conclusion: There is a significant association between the use of PPIs and DN in patients with type II DM. Since PPIs have other beneficial effects in patients with DM such as glycaemic control and relief from gastro-oesophageal symptoms, need for risk benefit assessment for long-term use of PPIs in DM is warranted. [ABSTRACT FROM AUTHOR]

Objectives: Posterior urethral valves (PUV) is the commonest obstructive uropathy with varied consequences. Though valve fulguration is the treatment of choice, appropriate bladder management modifies outcome and includes rational use of anticholinergics. Here, we aim to evaluate the effects of oxybutynin on the bladder and urinary tract morphology and function. Concurrently, we document adverse effects encountered, patient compliance, and medication adherence. Methods: A retrospective study of children below 5 years of age (2012–2017) post fulguration and on oxybutynin for at least 6 months. Patient demographics, clinical features, renal ultrasound, micturating cystourethrogram, dimercaptosuccinic acid scan, adverse effects, and pill count for medication adherence were collated. Results: 48 children below the age of 5 years were included, and 12 were excluded either due to the presence of concomitant problems or were not on oxybutynin. Of the 36, four were lost to follow-up and one had died due to an unrelated condition. Thus, a total of 31 children were analyzed. At follow-up, 28/31 patients were asymptomatic, two had daytime incontinence, and one had recurrent urinary tract infection. All patients except one have preserved renal function tests. On ultrasonography, hydroureteronephrosis worsened in only 1/25 children and two showed significant post void residues. The resolution of vesicoureteral reflux was noted in almost 50%. 4/31 renal units had progressive scars. Only two parents defaulted medication. Urodynamic study done in half of these children showed stable bladder pressures except in two. Conclusion: Oxybutynin therapy following adequate valve fulguration aids upper tracts preservation by stabilizing deranged bladder dynamics. The medication is well tolerated with minimal or no side effects. [ABSTRACT FROM AUTHOR]

Introduction: The Investigational New Drug (IND) committee advises the Drug Controller General of India on matters pertaining to clinical trials (CTs) of IND for clinical development. An audit of the minutes of this committee's meetings would shed light on the drug discovery in India. Methods: Minutes of the IND committee meetings available in the public domain (2-year period) were evaluated. The applications which were postponed were excluded from the study. Outcome measures were therapeutic areas of IND, purpose of the applications, status of registration with the CT Registry of India (CTRI), and the innovator country. Results: The minutes of N = 7 meetings were available in the public domain for the period January 2017–December 2018 with N = 45 agenda items. One agenda item was excluded, and n = 44 agenda items were finally analyzed. The total number of therapeutic agents discussed was N = 29, of which n = 7/29 and n = 6/29 belonged to infectious diseases (ID) and oncology, respectively. The total number of purposes of these applications was N = 46, of which n = 35/46 (76%) were to seek permission to conduct a CT, and n = 31/35 (88.6%) were found registered with CTRI as on April 01, 2019. Of the N = 46 purposes, n = 33/46 (71.7%) were approved. Of the n = 29 INDs discussed, n = 19/29 (65.52%) were of the Indian origin. Conclusions: Although a majority (65%) of INDs discussed in the meetings were of the Indian origin, the drug discovery was not in line to tackle the top ten causes of years of life lost prematurely (barring ID). [ABSTRACT FROM AUTHOR]

Background: Abnormal laboratory values are a common reason for the exclusion of participants in clinical studies, increasing the recruitment time and cost during conduct. The use of sample-specific reference intervals (RIs) may help to address this issue. Hence, the present study derived site-specific RIs using the department laboratory database and compare the proportion of "out of range" (OOR) values between the new and the old RIs used by the trial site. Methods: Institutional ethics committee approval was obtained. Data for hematology and biochemistry parameters were analyzed. Normality was assessed and RIs computed using nonparametric method. Data were partitioned for gender and descriptive statistics applied for demographics. The OOR values based on new RIs were compared with old RIs using Chi-squared tests. Between gender OOR proportions compared using Chi-squared test (significance at P < 0.05). Post hoc analysis was performed with Beasley's technique. Results: Data of 601 participants were analyzed. The median (Inter Quartile Range) age was 22 (47) years and 64.72% were male. New RIs for key parameters were: Haemoglobin (9.3–16.5 g/dl), alanine aminotransferase (11.4–47.74 U/I), aspartate aminotransferase (8.8–58 U/I), total bilirubin (0.27–1.4 mg/dl), and creatinine (0.59–1.36 mg/dl). Post partitioning, the RI for hemoglobin (g/dl) was lower (8.72–15.72) in females. The proportion of OOR values were lower with new RIs relative to old laboratory RIs (P < 0.0001). Conclusion: A reduction in the proportion of OORs and a change in the upper and lower bound laboratory intervals with new RIs emphasize the need for sample-specific ranges to prevent unnecessary exclusions of volunteers from trials. [ABSTRACT FROM AUTHOR]

Aim: Emergency intensive care of the elderly is often complicated and multifaceted. Understanding the clinical profile of elderly patients admitted in an emergency department-intensive care unit (ED-ICU) is crucial in planning health policies in geriatric emergency medicine. Thus, the aim of the study was to create a local registry of elderly people utilizing the ED-ICU services and to understand the rate and predictors of mortality. Methods: A retrospective chart analysis was performed including all patients aged ≥60 years who had an ED-ICU admission during a 6-month period (August 2018–January 2019). A structured case record form was used to capture information such as basic demography, clinical profile, and outcomes. Results: Total number of records considered for final analysis were 503. Mortality was seen in 21.07% (n = 106/503). The most common presenting complaint and cause of death was breathing difficulty (n = 48/503; 29.42%) and pneumonia (n = 41/106; 38.67%), repectively. The significant predictors of mortality [adjusted odds ratio; 95% confidence intervals; P value] were hypertension (2.195; 1.255, 3.840; 0.006), chronic liver disease (CLD) (4.324; 1.170, 15.979; 0.028), malignancy (2.854; 1.045, 7.796; 0.041), requiring noninvasive ventilation (NIV) (2.618; 1.449, 4.730; 0.001), requiring intubation (6.638; 3.705, 11.894; <0.001), and requiring vasopressors (3.583; 1.985, 6.465; <0.001). Conlusion: Approximately one in every five elderly patients getting admitted in ED-ICU died, and respiratory illness was the common diagnosis leading to death. Those with comorbidities such as hypertension, CLD, or malignancy and those requiring NIV, intubation, or vasopressors had higher mortality. [ABSTRACT FROM AUTHOR]

Background: Narcotics (e.g., opioids) or non-narcotics (e.g., salicylates and corticosteroids) are used in the management of pain and inflammation, both of which have side effects, thereby emphasizing the search for natural substances. Piperine found naturally in plants of the Piperaceae family has shown inhibitory activity against 5-lipoxygenase and cyclooxygenase-1 in in vitro studies. Objectives: To evaluate the analgesic, anti-inflammatory, and antipyretic activity of piperine in comparison to aspirin. Materials and Methods: Albino Wistar rats of either sex weighing 180–200 g and Swiss mice weighing 25–30 g were used. The tail-flick method and hot plate method in rats and acetic acid-induced writhing method in mice were used for the evaluation of analgesic activity. The carrageenan-induced paw edema method, cotton pellet-induced granuloma method, and formalin-induced arthritis method were used for the evaluation of anti-inflammatory activity. Baker's yeast-induced pyrexia model was used to evaluate antipyretic activity. Results: Piperine showed significant analgesic effect of 40%–55% in tail-flick method, 58% in hot plate method, and 54% in acetic acid-induced writhing model, when compared to negative controls. The percentage inhibition of inflammation, in comparison to controls, was significant at 56% for carrageenan-induced paw edema model and 40% for formalin-induced arthritis model. In the cotton pellet-induced granuloma model, however, it was only 10%. In the yeast model of pyrexia, piperine significantly reduced rectal temperature at 4 h. However, aspirin had better effect than piperine in all these models. Conclusion: Piperine exhibits significant analgesic, anti-inflammatory, and antipyretic activity though not comparable to aspirin. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer is the second most common cancer among adult men in the world, and the diagnosis requires biopsy. Prostate-specific antigen (PSA) test along with digital rectal examination (DRE) increases the detection rate of prostate cancer than DRE alone. The objective of this study was to correlate serum PSA level with histopathological diagnosis, identify the predictors of malignancy, and describe the pharmacotherapy of patients with serum PSA levels >4 ng/ml. Materials and Methods: This was a hospital-based observational study done among patients who presented with lower urinary tract symptoms and PSA levels >4 ng/ml who were planned to undergo prostatic biopsy. DRE followed by transrectal ultrasound (TRUS) assessment and guided sextant (6-core) prostatic biopsy was performed. Results: One hundred and four patients were screened and 87 were included. Nineteen patients were diagnosed with malignancy, and among them, eight had bone metastasis. Spearman's correlation coefficient between PSA and malignancy was 0.449 (P ≤ 0.001). Multivariate analysis suggested that the factors (adjusted odds ratio; 95% confidence interval; P value) such as increasing age (1.127; 1.013, 1.253; 0.027), nodular prostate (22.668; 4.655, 110.377; P < 0.001), and PSA (1.034; 1.004, 1.064; 0.024) were significant predictors of prostate cancer. All patients with benign prostatic hyperplasia were advised a combination therapy with 5-alpha reductase inhibitor and selective alpha-1 receptor antagonist while those with malignancy were prescribed androgen deprivation therapy with antiosteoporosis therapy. Conclusion: In elderly patients with raised PSA levels or suspicious DRE findings, TRUS-guided prostate is recommended to rule out malignancy and plan appropriate management. [ABSTRACT FROM AUTHOR]

Introduction: Physical inactivity is the fourth leading risk factor for mortality and morbidity as per the World Health Organisation (WHO). The current study was conducted in the city of Erode, Tamil Nadu, South India, to estimate the prevalence and predictors of low physical activity (LPA) and assess their knowledge with regards to being overweight/obesity. Methods: It was a cross‑sectional study conducted over 24 months from July 2015 to June 2017. Multi‑stage random sampling was done in 12 randomly chosen corporation wards. All consenting individuals above 18 years of age were included. Data were collected using a semi‑structured questionnaire incorporating the validated International Physical Activity Questionnaire (IPAQ). Results: For the study, 489 individuals were screened and 461 were included. Prevalence of LPA was 49.9% (95% confidence interval [CI]:45.34%, 54.46%). The significant predictors (adjusted odds ratio [OR] [95% CI]) of LPA were patient education 1.129 (1.006, 1.2670); unemployment (2.418 [1.610, 3.631]) and knowledge score (5.172 [1.314, 9.423] 27). In the knowledge assessment, 60.3% of the participants scored less than 50%. The significant predictors of poor knowledge were marital status (unmarried) (3.857 [1.341, 11.091]), lower educational status (1.191 [1.009, 1.362]) and low socioeconomic status (SES) (1.050 [1.005, 1.121]). Conclusion: Prevalence of LPA in our population is fairly high and there is gross knowledge inadequacy. [ABSTRACT FROM AUTHOR]