Protocol for a bandit-based response adaptive trial to evaluate the effectiveness of brief self-guided digital interventions for reducing psychological distress in university students: the Vibe Up study.

INTRODUCTION: Meta-analytical evidence confirms a range of interventions, including mindfulness, physical activity and sleep hygiene, can reduce psychological distress in university students. However, it is unclear which intervention is most effective. Artificial intelligence (AI)-driven adaptive trials may be an efficient method to determine what works best and for whom. The primary purpose of the study is to rank the effectiveness of mindfulness, physical activity, sleep hygiene and an active control on reducing distress, using a multiarm contextual bandit-based AI-adaptive trial method. Furthermore, the study will explore which interventions have the largest effect for students with different levels of baseline distress severity. METHODS AND ANALYSIS: The Vibe Up study is a pragmatically oriented, decentralised AI-adaptive group sequential randomised controlled trial comparing the effectiveness of one of three brief, 2-week digital self-guided interventions (mindfulness, physical activity or sleep hygiene) or active control (ecological momentary assessment) in reducing self-reported psychological distress in Australian university students. The adaptive trial methodology involves up to 12 sequential mini-trials that allow for the optimisation of allocation ratios. The primary outcome is change in psychological distress (Depression, Anxiety and Stress Scale, 21-item version, DASS-21 total score) from preintervention to postintervention. Secondary outcomes include change in physical activity, sleep quality and mindfulness from preintervention to postintervention. Planned contrasts will compare the four groups (ie, the three intervention and control) using self-reported psychological distress at prespecified time points for interim analyses. The study aims to determine the best performing intervention, as well as ranking of other interventions. ETHICS AND DISSEMINATION: Ethical approval was sought and obtained from the UNSW Sydney Human Research Ethics Committee (HREC A, HC200466). A trial protocol adhering to the requirements of the Guideline for Good Clinical Practice was prepared for and approved by the Sponsor, UNSW Sydney (Protocol number: HC200466_CTP). TRIAL REGISTRATION NUMBER: ACTRN12621001223820.

A Comparison of Hypertonic Saline and Mannitol on Intraoperative Brain Relaxation in Patients with Raised Intracranial Pressure during Supratentorial Tumors Resection: A Randomized Control Trial.

INTRODUCTION: Hyperosmotic agents are used to decrease intracranial pressure (ICP). We aim to compare the effect of euvolemic solutions of 3% hypertonic saline (HTS) and 20% mannitol on intraoperative brain relaxation in patients with clinical or radiological evidence of raised ICP undergoing surgery for supratentorial tumors. MATERIALS AND METHODS: A.prospective double-blind study was conducted on 30 patients randomized into two equal groups. Each patient was administered 5 ml/kg of either 20% mannitol or 3% HTS over 15 minutes (min) after skin incision. Hemodynamic data, brain relaxation and serum electrolyte levels were recorded. RESULTS: Intraoperative brain relaxation was comparable between the two groups. There was a statistically significant difference in the mean arterial pressures (MAPs) between the two groups after one minutes (min) with a greater degree of decrease in blood pressure recorded in the mannitol group (P = 0.041). MAP with mannitol was significantly lower than the preinduction value after 75 min of administration of drug (P = 0.003). Urine output was significantly higher in the mannitol group (P = 0.00). Administration of HTS was associated with a transient increase in serum sodium concentrations, which was statistically significant but returned to normal within 48 h (P < 0.001). CONCLUSIONS: Both mannitol and HTS provided adequate intraoperative brain relaxation. On the contrary, there was no statistically significant fall in blood pressure with HTS. Thus, we advocate the use of HTS over mannitol as it maintains better hemodynamic stability.

Synthesis and anti-inflammatory activity of some new 4,5-dihydro-1,5-diaryl-1H-pyrazole-3-substituted-heteroazole derivatives.

A series of 4,5-dihydro-1,5-diaryl-1H-pyrazole-3-substituted-heteroazoles were designed and synthesized in order to obtain new compounds with potential anti-inflammatory activity. The title compounds were screened for in vivo anti-inflammatory activity by using Carrageenan induced rat paw edema method. Diclofenac sodium was used as a standard drug for comparison. Out of the 30 compounds tested, compound 19a, 19b, 25a, 25b exhibited significant anti-inflammatory activity. Selected compounds were also screened for in vitro COX-2 inhibition assay and analgesic activity in the acetic acid induced writhing model.

A database for anti-diabetic plants with clinical / experimental trials.

UNLABELLED: A number of plants have been described in Ayurveda and other traditional medicine for the management of diabetes. However, information about them is not easily available. Active constituents of any medicinal plant define the efficacy and safety of treatment to control hyperglycemia. We describe the database to maintain the record of medicinal plants having anti-hyperglycemic or anti-diabetic activity. The database contains information such as plant name, its geographical distribution, useful plant part, known dosage, active constituents, mechanism of action and clinical/experimental data. The database also includes information about plant raw material suppliers or manufacturers in India. The current database includes 238 plants species and 123 Indian industries using them. AVAILABILITY: The database is freely available at http://www.biotechpark.org.in/antidia/index.html.

Oxidative stress in cases of chronic fluoride intoxication.

This study was conducted to find out the level of oxidative stress and effect of supplementation of vitamin C, D and Calcium on levels of SOD, serum and urinary fluoride in children residing in endemic fluorosis area. For this the fluoride belt of Jaipur district was selected. The parameters selected were Super oxide dismutase, serum fluoride and urinary fluoride. The study was conducted on one hundred children, selected from four areas (25 from each area) consuming water containing 1.2, 2.4, 5.6 and 13.6 mg/l of fluoride. Drinking water fluoride, serum and urinary fluoride were measured by Ion selective electrode method. Serum SOD by Xanthine oxidase method using kit of Ransod (kit cat. No. SD125). The post treatment values showed a significant reduction in serum fluoride and SOD. Urinary fluoride levels increased significantly in post treatment stage. The results revealed a normal SOD levels in all groups but an increasing trend was observed with increasing fluoride concentration. Treatment with Calcium, Vitamin D and Vitamin C showed a significant reduction in serum fluoride and SOD and increase in urinary fluoride. A high positive correlation between pretreatment and post treatment group was observed in serum fluoride, SOD and urinary fluoride (P < 0.05). The study indicated an increasing oxidative stress in cases of fluorosis with increasing drinking water fluoride concentration. Treatment with Calcium, Vitamin D and Vitamin C resulted a significant reduction in serum fluoride and SOD and increase in urinary fluoride.

High glucose-altered gene expression in mesangial cells. Actin-regulatory protein gene expression is triggered by oxidative stress and cytoskeletal disassembly.

High extracellular glucose plays a pivotal role in the pathophysiology of diabetic nephropathy. Here we report 200 genes, identified using suppression-subtractive hybridization, that are differentially expressed when human mesangial cells are propagated in high ambient glucose in vitro. The major functional classes of genes identified included modulators and products of extracellular matrix protein metabolism, regulators of cell growth and turnover, and a cohort of actin cytoskeleton regulatory proteins. Actin cytoskeletal disassembly is a prominent feature of diabetic nephropathy. The induction of actin cytoskeleton regulatory gene expression by high glucose was attenuated by the inhibitor of reactive oxygen species generation, carbonyl cyanide m-chlorophenylhydrazone but not by the protein kinase C inhibitor GF 109203X and was not mimicked by the addition of transforming growth factor beta. Enhanced expression of actin cytoskeleton regulatory genes was also observed following disruption of the mesangial cell actin cytoskeleton by cytochalasin D. In aggregate, these results suggest that the induction of genes encoding actin cytoskeleton regulatory proteins (a) is a prominent component of the mesangial cell transcriptomic response in diabetic nephropathy and (b) is dependent on oxidative stress, is independent of protein kinase C and transforming growth factor-beta, and represents an adaptive response to actin cytoskeleton disassembly.