COMPARISON OF 1% CHLOROPROCAINE IN SUB-ARACHNOID BLOCK WITH OR WITHOUT FENTANYL FOR ENHANCED RECOVERY AFTER PERIANAL SURGERIES

Objective: Spinal anesthesia is a reliable and safe technique for procedures of lower abdomen, perianal surgeries, and lower limbs. The current availability of short acting local anesthetic agents like preservative free 1% chloroprocaine has renewed the interest for this technique in short- and ultra-short procedures. Opioids continue to be the most commonly added adjuvants in local anesthetics for potentiation of analgesic action. In this study, we investigated the effect of intrathecal fentanyl as an adjuvant to 1% chloroprocaine in patients undergoing perianal surgeries. Methods: This prospective, randomized, and comparative study was conducted in 80 ASA Physical status I and II adult patients (age 20–80 years) undergoing perianal surgeries under spinal anesthesia. Group A patients received 1% chloroprocaine 3 ml (30 mg) and 0.4ml saline and Group B patients received 1% chloroprocaine 3 ml (30 mg) with fentanyl 0.4 ml (20 μg). Primary objectives were duration of analgesia and time to unassisted ambulation. Onset and duration of sensory and motor blockade, maximum height of sensory block, 2 segment regression, hemodynamic parameters, time to voiding, home discharge eligibility, and any side effects were also recorded. Results: There were no significant differences in demographic characteristics and hemodynamic parameters. The duration of sensory block and duration of analgesia were statistically prolonged in Group B than Group A (p<0.001) without affecting recovery from motor block and time to unassisted ambulation. The adverse effects were comparable in both the groups. Conclusion: The addition of fentanyl to 1% chloroprocaine intrathecally prolonged the duration of analgesia and sensory block in patients undergoing perianal surgeries

To study the efficacy and tolerability of fenugreek seed powder as add-on therapy with metformin in patients of type-2 diabetes mellitus

Background: Fenugreek, an ancient herb has been known for its culinary and medicinal value in Indian Subcontinent. Its seeds, rich in fibers and phytochemical compounds, have been investigated for their hypoglycemic and multiple benefits. This study was thus undertaken to assess the anti-hyperglycemic effect of fenugreek seeds in patients of Type 2 Diabetes Mellitus (DM) as add-on therapy with metformin.Methods: An open-labelled comparative study of 12 weeks duration was conducted on patients (randomly divided in 2 groups of 30 each) of Type 2 DM. Group 1 was given metformin 500 mg twice a day while group 2 was given 500 mg of metformin along with fenugreek seed powder capsule,1 gm thrice a day. Weekly evaluation for fasting and post-prandial blood sugar was done. HbA1c estimation was done at the beginning and at the end of the study. Student’s t-test (paired and unpaired) was applied for statistical analysis.Results: After 12 weeks of treatment, there was significant fall in fasting, as well as postprandial blood sugar and HbA1c levels in group 1 and group 2. However this improvement was statistically more significant in group 2 when compared to group 1.Conclusions: This study shows the beneficial effects of fenugreek seeds on glycemic profile in patients of Type 2 DM and can be used as an add-on therapy with metformin in management of Type 2 DM

Comparison of intraperitoneal instillation of ropivacaine with normal saline in laparoscopic cholecystectomy

Background: Local anesthetics are now widely used, as they have a good safety profile and are available in long acting preparation. They provide the benefit of analgesia without systemic side effects that may result from use of enterally and parenterally administered drugs.Methods: This prospective randomized double-blind study was conducted on 100 patients with symptomatic gall stones disease undergoing laparoscopic cholecystectomy. Patients were randomized to receive either 0.5% of 3mg/kg of Ropivacaine diluted in 100 ml NS, instillation at intraperitoneal space before creation of pneumoperitoneum (group I) or 100 ml NS instillation at intra peritoneal space before creation of pneumoperitoneum (group II). VAS score for pain abdomen as well as shoulder were recorded postoperatively at various time intervals and compared in both the groups. Total analgesic consumption in 24hrs was also noted and compared.Results: The mean postoperative VAS score for abdomen and shoulder pain was significantly (p values<0.05) lower in group I than in group II till 24 hrs postoperatively. The latency time from end of operation to first analgesic requirement was significantly longer in group I than in group II.Conclusions: Intraperitoneal instillation of Ropivacaine before the creation of pneumoperitoneum significantly decreased the total abdominal pain, shoulder tip pain with lower analgesic consumption. As it is safe and without apparent side effects, we believe that intraperitoneal instillation of local anaesthetic in patients undergoing elective laparoscopic cholecystectomy is an effective modality for postoperative pain management

Fast dissolving oral films technology: A recent trend for an innovative oral drug delivery system

Over the past few decades, there has been increased interest for innovative drug delivery system to improve the safety, efficacy and patient compliance, thereby increasing the product patent life cycle. In  the  recent  years,  many of  the  pharmaceutical  groups  are  focusing  their  research  on  rapid dissolving  technology. Fast dissolving oral films are the most advanced form of oral solid dosage form due to more flexibility and comfort. It improve the efficacy of APIs by dissolving within minute in oral cavity after the contact with less saliva as compared to fast dissolving tablets, without chewing and no need of water for administration. These films have a potential to deliver the drug systemically through intra-gastric, sublingual or buccal route of administration and also has been used for local action. This type of technology offer a convenient way of dosing medication, not to special population groups like pediatric, geriatric, bedridden patients, mentally ill patients, but also to the general population. Fast dissolving oral films are found to be satisfactory in many situations like allergic conditions, cold and cough, sore throat, nausea, pain, mouth ulcers, CNS disorders and CVS disorders. Oral film includes various ingredients for its formulation which includes polymers, active pharmaceutical ingredient, film stabilizing agents, plasticizers, sweeteners, flavours, colors, saliva stimulating agents, surfactants etc. The present review reflects  information regarding  formulation  ingredients,  technologies  and  evaluation  tests  employed  in  the  preparation  of  fast dissolving oral films. However, for future growth point of view the fast dissolving oral films sector is well-positioned. It seems that the value of the overall oral thin films market will grow significantly

Trustworthy Explainability Acceptance: A New Metric to Measure the Trustworthiness of Interpretable AI Medical Diagnostic Systems

We propose, Trustworthy Explainability Acceptance metric to evaluate explainable AI systems using expert-in-the-loop. Our metric calculates acceptance by quantifying the distance between the explanations generated by the AI system and the reasoning provided by the experts based on their expertise and experience. Our metric also evaluates the trust of the experts to include different groups of experts using our trust mechanism. Our metric can be easily adapted to any Interpretable AI system and be used in the standardization process of trustworthy AI systems. We illustrate the proposed metric using the high-stake medical AI application of Predicting Ductal Carcinoma in Situ (DCIS) Recurrence. Our metric successfully captures the explainability of AI systems in DCIS recurrence by experts

Rational design of reduced alphabet proteins

Conventional protein design approaches generally utilize a design space limited to the standard 20 amino acid alphabet (AAA), restricting the incorporation of unnatural amino acids, and associated novel functions. Reducing the standard AAA can free up codon space for the abovementioned purpose along with accelerating in silico protein design. However, previously designed reduced AAA protein variants have shown little to no activity relative to their wild-type counterparts. The overarching goal of this thesis was to identify and employ the protein design rules observed in nature for the development of a generalizable RAP design pipeline. Since dynamics are integral to maintaining protein function, data presented in this thesis investigates the structural dynamics of proteins using Molecular Dynamics simulations. This insight into the structural dynamics of proteins assisted in designing RAPs and in the characterization of a receptor targeted by a virus pathogenic to humans, offering potential pharmaceutical and astrobiology applications

Lenalidomide Augments Differentiation of Cultured Hair Follicle Derived Melanocyte Stem Cells Into Functional Melanocytes

Introducion: Melanocyte progenitors are embryonically derived from the neural crest and subsequently get localized in hair follicles and epidermis to provide hair and skin pigmentation. These progenitor cells in hair follicles repeatedly proliferate and differentiate to maintain pigmentation. Vitiligo, a pigmentary disorder, is associated with loss of melanocytes. Repigmentation of vitiligo lesions mainly depends upon the proliferation, migration and differentiation of melanocyte stem cells (MelSCs) into functional melanocytes. Current study is designed to check the efficacy of lenalidomide, an imide drug in the differentiation of MelSCs into functional melanocytes. Objectives: Aim of the study is to check the effect of lenalidomide in the proliferation, migration of cultured hair follicle derived melanocyte stem cells and their differentiation into functional melanocytes. Methods: Primary culture of MelSCs was established from whisker hair of C57BL/6 mice. Proliferation and migration of cultured cells were done by MTT assay and boyden’s chamber migration assay, respectively. Effect of lenalidomide on the MelSCs differentiation was checked at gene level by qPCR & protein expression was checked by immunocytochemistry. Results: A significant increase in the migration of MelSCs in comparison to control was also observed. Lenalidomide treatment significantly increased the expression of melanocyte specific genes in cultured MelSCs as compared to control. Conclusion: From the results we concluded that lenalidomide induce the proliferation and migration of MelSCs and accelerate the differentiation of MelSCs into functional melanocytes.

Trustworthy Acceptance: A New Metric for Trustworthy Artificial Intelligence Used in Decision Making in Food–Energy–Water Sectors

We propose, for the first time, a trustworthy acceptance metric and its measurement methodology to evaluate the trustworthiness of AI-based systems used in decision making in Food Energy Water (FEW) management. The proposed metric is a significant step forward in the standardization process of AI systems. It is essential to standardize the AI systems’ trustworthiness, but until now, the standardization efforts remain at the level of high-level principles. The measurement methodology of the proposed includes human experts in the loop, and it is based on our trust management system. Our metric captures and quantifies the system’s transparent evaluation by field experts on as many control points as desirable by the users. We illustrate the trustworthy acceptance metric and its measurement methodology using AI in decision-making scenarios of Food-Energy-Water sectors. However, the proposed metric and its methodology can be easily adapted to other fields of AI applications. We show that our metric successfully captures the aggregated acceptance of any number of experts, can be used to do multiple measurements on various points of the system, and provides confidence values for the measured acceptance

OX40/OX40 Ligand Interactions in T-Cell Regulation and Asthma

The OX40 receptor is preferentially expressed by T cells, and its cognate ligand OX40L is primarily expressed by antigen-presenting cells such as dendritic cells following activation by thymic stromal lymphopoietin (TSLP). TSLP is released by the bronchial epithelium, airway smooth muscle, and some inflammatory cells in response to numerous insults such as allergens, viruses, and physical damage. OX40L is a costimulatory molecule that plays a sentinel role in the adaptive immune response by promoting T helper (Th) 2 polarization of naive T cells within the lymph node. These polarized T cells produce Th2 cytokines such as IL-4, IL-5, and IL-13, which have been implicated particularly in allergic eosinophilic asthma. Animal models have positioned both TSLP and OX40/OX40L as critical in the development of airway inflammation and hyperreactivity. In human disease, there is good evidence that TSLP is upregulated in asthma, but there are limited data to demonstrate overexpression of OX40 or OX40L in disease. Targeting the OX40/OX40L axis or TSLP presents a novel therapeutic strategy that has the potential of modifying the disease process and, therefore, impacting on its natural history. Whether this approach can demonstrate efficacy in established disease rather than at disease onset is unknown. Biologic therapies directed toward OX40/OX40L are in early phases of development, and results from these studies are eagerly awaited

Spin distribution as a probe to investigate the dynamical effects in fusion reactions

The spin distributions are measured for the compound nucleus 80Sr populated in the reactions 16O+64Zn and 32S+48Ti. The comparison of the experimental results for both the systems shows that the mean γ-ray multiplicity values for the system 32S+48Ti are lower than those for 16O+64Zn. The spin distribution of the compound nucleus populated through the symmetric channel is also found to be lower than the asymmetric channel. Present investigation directly shows the effect of entrance channel mass asymmetry on the reaction dynamics