Study of brainstem auditory evoked response and biochemical markers in patients of alcohol use disorder

Objectives: Data available on brainstem auditory evoked response (BAER) and its correlation with biochemical parameters in patients of alcohol use disorder (AUD) in Indian population is scanty. Therefore, this study was undertaken to focus on the effects of AUD on BAER and liver enzymes. Materials and Methods: This case-control study included 40 males in the study group who had AUD and 40 healthy males in the control group in the age group of 20–60 years. The BAER was performed using octopus NCS/ EMG/EP (Clarity) machine. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase and serum bilirubin were estimated in all the subjects. Results: We observed a highly significant increase in the absolute latencies of waves III and V and interpeak latencies (IPL) I-III and I-V of BAER in the patients of AUD in this study. Significant increase in the liver enzymes and especially AST/ALT ratio of patients of AUD was seen which indicated towards subclinical alcoholic hepatitis. The latencies of waves of EPs (waves III, V, IPL I-III and IPL I-V) were positively correlated with the biochemical parameters and duration of AUD. Conclusion: Our findings indicated that AUD lead to the increase in brainstem transmission time and also lead to subclinical alcoholic hepatitis which is reflected by the increase in the liver enzymes. We concluded that chronic alcohol consumption affected the auditory pathways and delayed the auditory transmission time which was suggestive of possible demyelination of auditory tracts.

Effects of a single session of cathodal transcranial direct current stimulation primed intermittent theta-burst stimulation on heart rate variability and cortical excitability measures

Objectives: Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have been used as neuromodulators in neuropsychiatric conditions. This study is aimed to find the effects of a single session of priming cathodal tDCS with intermittent theta-burst stimulation (iTBS) over left dorsolateral prefrontal cortex on heart rate variability (HRV) and cortical excitability parameters before and after perturbation. Materials and Methods: The neuromodulatory techniques used in the study were Cathodal tDCS for 20 min followed by iTBS for 3 min on the left dorsolateral prefrontal cortex (DLPFC). HRV variables and TMS parameters were recorded before and after this intervention of combined neuromodulation in 31 healthy volunteers (20 males and 11 females; age range of 19–35 years with Mean ± SD = 24.2 ± 4.7 years). Results: The results showed an overall increase in cortical excitability and parasympathetic dominance in healthy volunteers. Other measures of cortical excitability and HRV did not change significantly following single session of combined neuromodulation. Conclusion: This study showed that there is an overall increase in cortical excitability and parasympathetic dominance in the cohort of healthy volunteers following a combination of neuromodulation involving cathodal tDCS followed by iTBS over left DLPFC. Future studies exploring the effects of other possible combinations with sham stimulation could be carried out to explore the utility of dual stimulation as add-on therapy in disorders.

Efficacy of flipped classroom method in teaching-learning physiology

Objectives: The overall goal of the study was to foster self-directed learning, critical thinking and problem-solving skills in 1st-year medical students. Another goal was to create interest in learning by making it more interactive. As per the requirement of a competency-based medical education curriculum, we tried to use a novel teaching method called Flipped classroom method to meet our goals. Hence, the objectives of this study were: (1) To compare the effect of flipped classroom method and didactic lecture on students’ performance in the topics from renal physiology by MCQ test. (2) To obtain students’ perception about flipped classroom method in learning physiology. (3) To obtain teachers’ perception about flipped classroom method in teaching physiology. Materials and Methods: Flipped classroom method was introduced for teaching two topics in renal physiology for first MBBS students. This cross-over experimental study included 112 first M.B.B.S. students, after taking their informed consent and Ethics Committee permission. They were divided into two groups according to odd and even roll numbers. In the first part of the study, Group A (odd roll numbers) attended the didactic lecture on Renal Clearance (RC) and Group B (even roll numbers) attended the didactic lecture on Glomerular Filtration Rate (GFR). These topics were taught by two different teachers in two different classrooms. They were administered pre-test and post-test in the form of case-based MCQs which tests knowledge, critical thinking, and problem-solving skills on the topic. In the second part, two groups were swapped. Group A attended flipped class for G.F.R. and Group B attended flipped class for RC. They were again administered pre-test and post-test in the form of the same MCQ test. The teacher remained the same for the particular topic. For the flipped class, students came prepared with the topic. They were provided with resource materials of the allotted topic 1 week prior, in the form of pre-recorded lectures and videos. Students’ feedback in the form of a questionnaire and teachers’ feedback in the form of the interview was obtained. Marks obtained by students after didactic teaching and flipped classroom method teaching were compared by “Student’s t-test.” Results: The post-test score of students in the flipped class was significantly higher (P < 0.05) than the post-test score of students in didactic class. More than 85% of students agreed and strongly agreed that the flipped classroom method improved their learning in renal physiology and it increased their confidence in answering the topic in the final exam. Near about 50% of students liked the flipped class method because of its interactive nature and discussion which was based on the application of knowledge. The teachers were more satisfied by flipped classroom method of teaching. Conclusion: Flipped classroom method is an effective teaching-learning method in physiology when compared with a didactic lecture.

Levels of glutathione-related antioxidants in some tissues of stressed Wistar rats

Objectives: Oxidative stress (OS)-related pathologic conditions in the tissues of living organism have been linked to exposure to stressful events within the environment. This study examined the impact of different kinds of stress exposure on glutathione (GSH)-related antioxidants. The effect of stress was examined using comparative levels of GSH, glutathione-S-transferase (GST) and glutathione peroxidase (GPx) in female Wistar rats. Materials and Methods: One hundred and sixty-eight adult female Wistar rats with body weights ranging between 150 and 200 g, were used for the study. The animals were distributed into 28 groups of six animals each. The experimental animals were routinely exposed to three different stressors; restraint chamber test, mirror chamber test and intruder chamber test for a duration of 1, 3 or 5 h per day for 1, 2 and 3 weeks, respectively. All animals were allowed free access to food (rat chaws), with water ad libitum. Animals were euthanise through cervical dislocation after the experimental period and the different target tissues were carefully harvested and homogenised for antioxidant estimation following standard procedure. Data obtained were statistically analysed and values expressed as mean ± standard error of mean and P < 0.05 level was considered as statistically significant. Results: Findings from this study elucidated the fact that exposure to stress is capable of causing marked OS and reducing GSH-based antioxidant activities in Wistar rats. A decline in the GSH level and GPx activity as observed in the study is an indication of alterations of kidney and brain tissue cellular integrity by free radicals generated during exposure to the stressors, while the observed significant increase in GST activity level in the affected tissues indicates compromised rapid exhaustion of the cellular system. Conclusion: Hence, we conclude that stress of different nature, intensity and duration can alter the levels of GSH-related antioxidants, especially in the kidney, ovary and brain tissues of stressed Wistar rats. The GSH levels in liver tissues were observed not to have changed significantly despite the oxidative damage caused by the stressors.

Cyclic vomiting syndrome responding to amisulpride – A case report

Cyclic vomiting syndrome (CVS) is an uncommon functional condition defined by recurring episodic stereotyped vomiting with a sudden start and an unknown origin. CVS can be triggered by a variety of conditions, and the course and management are often determined by the triggering factors. We present the case of a 13-year-old female youngster who complained of frequent bouts of vomiting that coincided with the onset of menses. We started her on oral amisulpride 50 mg a few days before each menstrual period. As a result of the treatment, in the following menstrual cycle, she had a dramatic improvement in her symptoms.

Effect of CD34+ cell dose on neutrophil and platelet engraftment kinetics in haematopoietic stem cell transplantation – A single-centre experience

Objectives: Haematopoietic stem cell transplantation (SCT) is curative for a number of benign and malignant hematological disorders. CD34 expression on haematopoietic progenitor cells is used to assess stem cell content in peripheral blood stem cell and bone marrow grafts. This study evaluated the relationship between numbers of CD34+ cells infused per kg and the timing of neutrophil and platelet engraftment. Materials and Methods: The effect of cell dose was studied in consecutive HSCT patients transplanted between November 2008 and December 2017. Neutrophil engraftment was defined as the first of 2 consecutive days with an absolute neutrophil count >0.5 × 109/L and platelet engraftment as unsupported platelet count >20 × 109/L for 7 days. Results: Of a total of 131 patients, 26 (19.8%) underwent an autologous SCT, while 105 (80.2%) underwent an allogeneic SCT. The median CD34 dose infused in the auto-SCT group was 5.29 × 106 CD34+cells/kg (IQR = 2.95–10.98) and 6.42 × 106 CD34+cells/kg (IQR = 4.20–9.20) in the allo-SCT group (P = 0.773). The median time to neutrophil engraftment in the auto-SCT group was 11 days (range 9.5–12) and in the allo-SCT group was 15 days (range 13–17), P ≤ 0.001. The median time to platelet engraftment in both groups was similar (12 days). When patients were divided into three groups based on CD34 dose (<5, 5–8 and >8), no difference was observed in the time to ANC or platelet engraftment. Similarly, no differences in time to engraftment were noted in each quartile of CD34 dosage in auto- and allo-SCT. Conclusion: Thus, it was concluded that a cell dose of approximately 5 × 106/kg provides reasonably rapid engraftment, with no advantage seen for a higher cell dose of >5.

Perivascular histamine receptors mediate vasosensory reflex responses elicited by thermal nociceptive stimuli in anaesthetised rat models

Objectives: Reflex responses elicited by intra-arterial (i.a) instillation of nociceptive agents are known as vasosensory reflex responses. The present study was designed to demonstrate the vasosensory reflex responses evoked by thermal nociceptive stimuli in anaesthetised rat models and to examine the role of perivascular histamine receptors in mediating these responses. Materials and Methods: In this study, saline at different temperatures (0°C/30°C/55°C) was instilled retrogradely into the femoral artery to stimulate the perivascular nociceptive terminals and the respiratory movements, BP and ECG were recorded for 10 min. Experiments were performed in four groups of rats. Two groups were dedicated to study the temperature-induced reflex cardiorespiratory (CVR) responses after i.a instillation of cold (0°C) and warm saline (55°C). The responses in these groups were compared with the responses after instillation of normal saline at room temperature (30°C) in a separate group of rats that served as time matched control group. Another group of rats was pre-treated with pheniramine and the responses elicited by warm saline were studied. Results: Instillation of warm saline produced immediate (2–6 s) hyperventilatory, hypotensive and bradycardiac responses which were short-lived, while equivolume of normal saline at room temperature did not. Cold saline also elicited the CVR changes of similar quality as that of warm saline but of lesser quantity which were not significantly different from the control group. Pre-treatment with pheniramine significantly attenuated the warm saline-induced reflex responses. Conclusion: Activation of perivascular sensory nerve terminals by thermal nociceptive stimuli elicits vasosensory reflex responses altering CVR parameters. Perivascular histamine receptors play a significant role in mediating the temperature-induced vasosensory reflex responses.

Behavioural and molecular effects of alcohol in the stress model of zebrafish

Objectives: Stress and anxiety disorders are common health problems that have been related to an increase in the likelihood of developing addictions, which have individual and social consequences. Although socially acceptable, alcohol is a substance that can generate dependence and abuse. Alcohol misuse, its relationship with stress and its consequences have been studied; however, multiple limitations are placed on clinical research in humans. In this exploratory work, we analysed the behavioural and molecular effects of joint exposure to ethanol and an unpredictable stress protocol (USP) in adult zebrafish. Materials and Methods: Adult zebrafish behaviour was studied employing unpredictable stress and behavioural tests. The tests were performed in stressed and nonstressed animals with and without exposure to known concentrations of alcohol. To evaluate the behaviour, tracking techniques were used on video recordings and parameters such as distance travelled, swimming speed and place preference as well as aggression patterns with mirror proximity tests were measured. In the control and 0.75% alcohol group, the expression of candidate stress-related genes (slc6a4a, slc6a3, comta and bdnf3) was analysed by RT-qPCR. Results: The results showed that concentrations of 0.75% alcohol reduced the locomotor activity of the fish, which can be interpreted as an increase in the anxiolytic effect of alcohol under nonstress conditions. Expression of comta, bdnf3 and slc6a3 was reduced in the stress and stress plus 0.75% ethanol groups and expression of slc6a4a was increased in the stress plus 0.75% alcohol group. Conclusion: Our exploratory work contributes novel insights about the molecular and behavioural effects of the combination of unpredicted stress and alcohol misuse. The USP and ethanol exposure increase anxiety behaviour and reduce the expression of genes involved in brain homeostasis. Future study of other pharmacological compounds and additional genes will be helpful for a deeper understanding of the molecular mechanisms involved in the response to stress and alcohol use.

Characterisation of current pharmacotherapeutic COVID-19 clinical trials in India: A registry-based descriptive analysis

COVID-19 has emerged as a global pandemic. There is currently a spurt of clinical research to generate evidence to treat this novel disease. The aim of the current study is to characterise the pharmacotherapeutic intervention-related clinical trials registered in India. COVID-19 clinical trials registered in India were analysed from data retrieved from Clinical Trial Registry-India, ClinicalTrials.gov and International Clinical Trial Registry Platform. Parameters such as study design, sample size, pharmacotherapeutic interventions and primary outcomes were evaluated. A total of 267 studies were screened among which 103 clinical trials were assessed for descriptive analysis. Majority of registered trials (55.3%) were in Indian System of Medicine followed by antimalarials such as hydroxychloroquine/chloroquine (10.5%) and plasma therapy (7.1%). Most commonly used study design was randomised parallel group in 63%. Open-label study was seen in 47.5%. Primary outcome was improvement of clinical symptoms in 46.6% followed by rate and time of viral load reduction in 18.2%. Maharashtra (n = 35) followed by Delhi (n = 29) had the maximum number of registered trial sites. The study gives broad perspective on the current trend of clinical trials on COVID-19 being conducted in India. The outcomes of these trials will lead to generation of valuable data for evidence-based treatment of COVID-19.

Angiogenesis-modulating properties of ethanolic extract of Ferula assa-foetida oleo-gum-resin

Objectives: Angiogenesis has been known to have a critical role in the tumour growth. Different studies indicated that angiogenesis was stimulated by hypoxia. In the present study, we assessed the anti-angiogenesis activity of ethanolic extract of Ferula assa-foetida (EEFA) on hypoxic-induced human umbilical vein endothelial cells (HUVECs). Materials and Methods: The F. assa-foetida gum extract was characterised by total phenolic contents (TPC) and total flavonoids content (TFC). The active compounds of EEFA were determined by high-performance liquid chromatography (HPLC). Then, cytotoxic effects of EEFA on the growth of HUVECs were assessed using MTT assay, wound healing and cell cycle analysis. The expression of Vascular endothelial growth factor (VEGF), Akt,HIF-1, VEGF receptor 1 (VEGFR-1) and VEGFR-2 genes was also quantified by Real-Time PCR. GeneMANIA and EnrichR databases were used to predict gene network interactions for the studied genes and their mechanism. Results: The TFC and TPC of the extract were 26 mg gallic acid equivalent per gram of extract and 5.45 mg quercetin/g, respectively. HPLC analysis revealed the presence of anti-angiogenic components in EEFA. Our data showed that EEFA had no cytotoxicity effect on HUVECs. The obtained results also indicated that EEFA prevented the proliferation and migration of HUVECs. Expression analysis showed that EEFA significantly decreased the VEGF-A mRNA level in the hypoxia-induced HUVECs. No change was found in the VEGFR-2 gene expression following treatment with EEFA in the HUVECs. However, the significantly upregulation of the VEGFR-1 gene expression was observed in the EEFA-treated HUVECs. The bioinformatics analysis of gene-gene interaction network also showed that the studied genes play an essential role in the regulatory pathways of angiogenesis and cancer. Conclusion: These findings provided evidence about the anti-angiogenesis role of EEFA, suggesting that this could be considered in the cancer therapy.