A study of habits of tobacco use among medical students and influence of various factors including medical education

Background: Tobacco use is a major preventable cause of morbidity and mortality. Tobacco usage among medical professionals should be reduced. It is important that they are aware regarding effects/ill effects of tobacco use, anti tobacco strategies, tobacco cessation technique to reduce tobacco usage among population. Authors undertook this study to understand tobacco use among medical students.Methods: Authors conducted cross sectional, descriptive study by collecting anonymous data of 414 undergraduate medical students of medical college, Jamnagar in predesigned forms. Data were analysed using MS-excel and graphpad prism. Authors used Fagerstrom test for nicotine dependence to assess nicotine dependence.Results: Tobacco users were 19.57%, among them 83.95% were smokers. Prevalence was higher in male (34.35% in male and 1.09% in female subgroup) and students with positive family history (36.81% in positive and 6.03% in negative family history subgroup). Current users were 7.73%. They were 8.20% in hosteller and 2.78% day scholar subgroups. Authors didn’t find statistical significant association of medical education with habit. Leading causes of starting tobacco use were curiosity/recreational purpose (35.8%), peer group pressure (32.10%) and stress (25.93%). Most of current user had low nicotine dependence (73.33%).Conclusions: Tobacco use among medical students is a significant problem. Important factors affecting it are gender, family history, current living status, stress, peer group pressure, media influences. Authors recommend that special awareness programme and specific training regarding tobacco cessation should be given to medical students

A comparative study of the effect of dexmedetomidine and lignocaine on hemodynamic responses and recovery following tracheal extubation in patients undergoing intracranial surgery

Background: Recovery from general anesthesia and extubation is a period of intense physiological stress for patients. The most feared complications after intracranial surgery are development of an intracranial hematoma and major cerebral edema. Both may result in cerebral hypoperfusion and brain injury. Thus, the anesthetic emergence of a neurosurgical patient should include maintenance of stable respiratory and cardiovascular parameters. Minimal reaction to the endotracheal tube removal prevents sympathetic stimulation and increases in venous pressure. In our study, we compared dexmedetomidine HCl, lignocaine HCl and placebo to blunt stress response and providing a smooth transition from extubation phase.Methods: 75 ASA Grade I and II patients aged 18-60 years scheduled for elective intracranial surgery for intracranial space occupying lesions were randomly divided into three groups of 25 each. Balanced general anesthesia was given. Inhalation anesthetic was discontinued and after return of spontaneous respiration patient in Group D received injection dexmedetomidine 0.5 µg/kg intravenous (IV), Group X received injection lignocaine 1.5 mg/kg IV and Group P received 10 ml normal saline IV over 60 sec. Heart rate (HR), mean arterial pressure (MAP), quality of extubation were measured at 1, 3, 5, 10, 15 mins interval after extubation. Emergence time and extubation time were noted and quality of extubation was evaluated on cough grading.Results: There was a significant decrease in MAPs and HR in Group D as compared to Group L and Group P (p<0.05) at all-time interval after extubation. Extubation quality score of the majority of patients was 1 in Group D, 2 in Group X, and 3 in Group P (p<0.001). The duration of emergence and extubation were comparable in all three groups. Sedation score of the most patient was 3 (44%) in Group D and 2 (56%) in Group X. Six patients in Group D and 1 patient in Group X had bradycardia.Conclusion: Single bolus dose of IV dexmedetomidine HCl 0.5 mg/kg given before tracheal extubation effectively attenuates hemodynamic response to extubation as compared to 1.5 mg/kg lignocaine HCl

Genome-Wide TOP2A DNA Cleavage is Biased Toward Translocated and Highly Transcribed Loci

Type II topoisomerases orchestrate proper DNA topology, and they are the targets of anti-cancer drugs that cause treatment-related leukemias with balanced translocations. Here, we develop a high-throughput sequencing technology to define TOP2 cleavage sites at single-base precision, and use the technology to characterize TOP2A cleavage genome-wide in the human K562 leukemia cell line. We find that TOP2A cleavage has functionally conserved local sequence preferences, occurs in cleavage cluster regions (CCRs), and is enriched in introns and lincRNA loci. TOP2A CCRs are biased toward the distal regions of gene bodies, and TOP2 poisons cause a proximal shift in their distribution. We find high TOP2A cleavage levels in genes involved in translocations in TOP2 poison–related leukemia. In addition, we find that a large proportion of genes involved in oncogenic translocations overall contain TOP2A CCRs. The TOP2A cleavage of coding and lincRNA genes is independently associated with both length and transcript abundance. Comparisons to ENCODE data reveal distinct TOP2A CCR clusters that overlap with marks of transcription, open chromatin, and enhancers. Our findings implicate TOP2A cleavage as a broad DNA damage mechanism in oncogenic translocations as well as a functional role of TOP2A cleavage in regulating transcription elongation and gene activation

Changes in the Transcriptome of Human Astrocytes Accompanying Oxidative Stress-Induced Senescence

Aging is a major risk factor for many neurodegenerative disorders. A key feature of aging biology that may underlie these diseases is cellular senescence. Senescent cells accumulate in tissues with age, undergo widespread changes in gene expression, and typically demonstrate altered, pro-inflammatory profiles. Astrocyte senescence has been implicated in neurodegenerative disease, and to better understand senescence-associated changes in astrocytes, we investigated changes in their transcriptome using RNA sequencing. Senescence was induced in human fetal astrocytes by transient oxidative stress. Brain-expressed genes, including those involved in neuronal development and differentiation, were downregulated in senescent astrocytes. Remarkably, several genes indicative of astrocytic responses to injury were also downregulated, including glial fibrillary acidic protein and genes involved in the processing and presentation of antigens by major histocompatiblity complex class II proteins, while pro-inflammatory genes were upregulated. Overall, our findings suggest that senescence-related changes in the function of astrocytes may impact the pathogenesis of age-related brain disorders

Traditional use of medicinal plants by the Jaintia tribes in North Cachar Hills district of Assam, northeast India

The study of ethnobotany relating to any tribe is in itself a very intricate or convoluted process. This paper documents the traditional knowledge of medicinal plants that are in use by the indigenous Jaintia tribes residing in few isolated pockets of northeast India. The present study was done through structured questionnaires in consultations with the tribal practitioners and has resulted in the documentation of 39 medicinal plant species belonging to 27 families and 35 genera. For curing diverse form of ailments, the use of aboveground plant parts was higher (76.59%) than the underground plant parts (23.41%). Of the aboveground plant parts, leaf was used in the majority of cases (23 species), followed by fruit (4). Different underground plant forms such as root, tuber, rhizome, bulb and pseudo-bulb were also found to be in use by the Jaintia tribe as a medicine. Altogether, 30 types of ailments have been reported to be cured by using these 39 medicinal plant species. The study thus underlines the potentials of the ethnobotanical research and the need for the documentation of traditional ecological knowledge pertaining to the medicinal plant utilization for the greater benefit of mankind

Rationale and design of the United Kingdom Heart Failure with Preserved Ejection Fraction Registry

\ua9 Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.Objective: Heart failure with preserved ejection fraction (HFpEF) is a common heterogeneous syndrome that remains imprecisely defined and consequently has limited treatment options and poor outcomes. Methods: The UK Heart Failure with Preserved Ejection Fraction Registry (UK HFpEF) is a prospective data-enabled cohort and platform study. The study will develop a large, highly characterised cohort of patients with HFpEF. A biobank will be established. Deep clinical phenotyping, imaging, multiomics and centrally held national electronic health record data will be integrated at scale, in order to reclassify HFpEF into distinct subgroups, improve understanding of disease mechanisms and identify new biological pathways and molecular targets. Together, these will form the basis for developing diagnostics and targeted therapeutics specific to subgroups. It will be a platform for more effective and efficient trials, focusing on subgroups in whom targeted interventions are expected to be effective, with consent in place to facilitate rapid recruitment, and linkage for follow-up. Patients with a diagnosis of HFpEF made by a heart failure specialist, who have had natriuretic peptide levels measured and a left ventricular ejection fraction &gt;40% are eligible. Patients with an ejection fraction between 40% and 49% will be limited to no more than 25% of the cohort. Conclusions: UK HFpEF will develop a rich, multimodal data resource to enable the identification of disease endotypes and develop more effective diagnostic strategies, precise risk stratification and targeted therapeutics. Trial registration number: NCT05441839

A Pro-Cathepsin L Mutant Is a Luminal Substrate for Endoplasmic-Reticulum-Associated Degradation in C. elegans

Endoplasmic-reticulum associated degradation (ERAD) is a major cellular misfolded protein disposal pathway that is well conserved from yeast to mammals. In yeast, a mutant of carboxypeptidase Y (CPY*) was found to be a luminal ER substrate and has served as a useful marker to help identify modifiers of the ERAD pathway. Due to its ease of genetic manipulation and the ability to conduct a genome wide screen for modifiers of molecular pathways, C. elegans has become one of the preferred metazoans for studying cell biological processes, such as ERAD. However, a marker of ERAD activity comparable to CPY* has not been developed for this model system. We describe a mutant of pro-cathepsin L fused to YFP that no longer targets to the lysosome, but is efficiently eliminated by the ERAD pathway. Using this mutant pro-cathepsin L, we found that components of the mammalian ERAD system that participate in the degradation of ER luminal substrates were conserved in C. elegans. This transgenic line will facilitate high-throughput genetic or pharmacological screens for ERAD modifiers using widefield epifluorescence microscopy

Development and Validation of an Automated High-Throughput System for Zebrafish In Vivo Screenings

The zebrafish is a vertebrate model compatible with the paradigms of drug discovery. The small size and transparency of zebrafish embryos make them amenable for the automation necessary in high-throughput screenings. We have developed an automated high-throughput platform for in vivo chemical screenings on zebrafish embryos that includes automated methods for embryo dispensation, compound delivery, incubation, imaging and analysis of the results. At present, two different assays to detect cardiotoxic compounds and angiogenesis inhibitors can be automatically run in the platform, showing the versatility of the system. A validation of these two assays with known positive and negative compounds, as well as a screening for the detection of unknown anti-angiogenic compounds, have been successfully carried out in the system developed. We present a totally automated platform that allows for high-throughput screenings in a vertebrate organism

Automated High-Content Live Animal Drug Screening Using C. elegans Expressing the Aggregation Prone Serpin α1-antitrypsin Z

The development of preclinical models amenable to live animal bioactive compound screening is an attractive approach to discovering effective pharmacological therapies for disorders caused by misfolded and aggregation-prone proteins. In general, however, live animal drug screening is labor and resource intensive, and has been hampered by the lack of robust assay designs and high throughput work-flows. Based on their small size, tissue transparency and ease of cultivation, the use of C. elegans should obviate many of the technical impediments associated with live animal drug screening. Moreover, their genetic tractability and accomplished record for providing insights into the molecular and cellular basis of human disease, should make C. elegans an ideal model system for in vivo drug discovery campaigns. The goal of this study was to determine whether C. elegans could be adapted to high-throughput and high-content drug screening strategies analogous to those developed for cell-based systems. Using transgenic animals expressing fluorescently-tagged proteins, we first developed a high-quality, high-throughput work-flow utilizing an automated fluorescence microscopy platform with integrated image acquisition and data analysis modules to qualitatively assess different biological processes including, growth, tissue development, cell viability and autophagy. We next adapted this technology to conduct a small molecule screen and identified compounds that altered the intracellular accumulation of the human aggregation prone mutant that causes liver disease in α1-antitrypsin deficiency. This study provides powerful validation for advancement in preclinical drug discovery campaigns by screening live C. elegans modeling α1-antitrypsin deficiency and other complex disease phenotypes on high-content imaging platforms