Perceptions of Medical Students on Research Curriculum: A Cross-sectional Study

Introduction: Medical colleges promote research by incorporating it into the curriculum, which enables students to acknowledge it as a career prospect. The aim of the study was to assess the perceptions of medical students on research curriculum. Methods: This cross-sectional study was conducted among 544 medical students (interns and post-graduates) at AIIMS Rishikesh in 2020. Data was collected thorough online self-administered questionnaire. A comparison between groups was made using the Mann-Whitney test or chi-square test p < 0.05 was considered statistically significant. Results: Out of 544 participants, 218 (40.1%) responded with complete data. The total median score for the self-perceived ability of study participants regarding performing the research tasks differed significantly between interns and post-graduates [29.5 (24.0–34.2) vs 33 (25.2–39.7), p = 0.03]. They suggested that mandatory research projects, workshops, and training should be included in the curriculum. Conclusion: Feedback from medical students regarding the need for guided research projects, hands-on training, and inclusion of research methodology as a course in UG curriculum and provision of support in the form of incentives, academic credits, and motivation are well noted and guide the resource faculties to modify their teaching and student support programs

Targeting Apoptotic Pathway of Cancer Cells with Phytochemicals and Plant-Based Nanomaterials

Apoptosis is the elimination of functionally non-essential, neoplastic, and infected cells via the mitochondrial pathway or death receptor pathway. The process of apoptosis is highly regulated through membrane channels and apoptogenic proteins. Apoptosis maintains cellular balance within the human body through cell cycle progression. Loss of apoptosis control prolongs cancer cell survival and allows the accumulation of mutations that can promote angiogenesis, promote cell proliferation, disrupt differentiation, and increase invasiveness during tumor progression. The apoptotic pathway has been extensively studied as a potential drug target in cancer treatment. However, the off-target activities of drugs and negative implications have been a matter of concern over the years. Phytochemicals (PCs) have been studied for their efficacy in various cancer cell lines individually and synergistically. The development of nanoparticles (NPs) through green synthesis has added a new dimension to the advancement of plant-based nanomaterials for effective cancer treatment. This review provides a detailed insight into the fundamental molecular pathways of programmed cell death and highlights the role of PCs along with the existing drugs and plant-based NPs in treating cancer by targeting its programmed cell death (PCD) network

Protective Immunity to Mycobacterium tuberculosis Infection by Chemokine and Cytokine Conditioned CFP-10 Differentiated Dendritic Cells

BACKGROUND: Dendritic cells (DCs) play major roles in mediating immune responses to mycobacteria. A crucial aspect of this is the priming of T cells via chemokines and cytokines. In this study we investigated the roles of chemokines RANTES and IP-10 in regulating protective responses from Mycobacterium tuberculosis (M. tb) 10 kDa Culture Filtrate Protein-10 (CFP-10) differentiated DCs (CFP10-DCs). METHODS AND FINDINGS: Infection of CFP10-DCs with mycobacteria down-modulated RANTES and IP-10 levels. Pathway specific microarray analyses showed that in addition to RANTES and IP-10, mycobacteria infected CFP10-DCs showed reduced expression of many Th1 promoting chemokines and chemokine receptors. Importantly, T cells co-cultured with RANTES and IP-10 conditioned CFP10-DCs mediated killing of mycobacteria from infected macrophages. Similarly, T cells recruited by RANTES and IP-10 conditioned CFP10-DCs mediated significant killing of mycobacteria from infected macrophages. IFN-gamma treatment of CFP10-DCs restored RANTES and IP-10 levels and T cells activated by these DCs mediated significant killing of virulent M. tb inside macrophages. Adoptive transfer of either RANTES and IP-10 or IL-12 and IFN-gamma conditioned CFP10-DCs cleared an established M. tb infection in mice. The extent of clearance was similar to that obtained with drug treatment. CONCLUSIONS: These results indicate that chemokine and cytokine secretion by DCs differentiated by M. tb antigens such as CFP-10 play major roles in regulating protective immune responses at sites of infection

Prevalence of asymptomatic bacteriuria (ASB) in pregnant women in India: A systematic review and meta-analysis

Background: Asymptomatic bacteriuria is prevalent during pregnancy. If it goes undetected, it can lead to urinary tract infection with severe maternal and neonatal complications. Until date, India does not have any guidelines to test for ASB during pregnancy. Objective: To estimate the pooled prevalence of asymptomatic bacteriuria in pregnant women at national level in India. Material and Methods: We searched Medline, Embase, Web of Science, and Google Scholar using search strategy with keyword. Two authors independently assessed the eligibility of study. The checklist of the JBI was used for evaluating the quality of reporting. The extracted data were analyzed, and the results were reported using a random-effects model with 95% confidence interval (CI). Subgroup analysis was conducted for zones of India, parity and trimester. Publication bias is reported as funnel plot. Result: Pooled prevalence of asymptomatic bacteriuria among pregnant women in India is 13.5% [CI 11.1; 15.8]. Subgroup analysis based on the various geographic zones of the country the pooled prevalence ranged from 9.2% in central zone to 14.8% in south zone. Distribution of prevalence of ASB as per parity was approximately identical. The prevalence of ASB was found to be high in third (21.8%). Conclusion: The prevalence of ASB is found to be high among Indian pregnant women, especially in third trimester. It is therefore recommended for guideline to screen and treat every pregnant woman for ASB to prevent further complications

Mycobacterium tuberculosis and Dendritic Cells: Recognition, Activation and Functional Implications

279-288The highly complex nature of interactions of Mycobacterium tuberculosis with cells of the immune system has puzzled researchers the world-over in understanding the pathogenesis and immunology associated with tuberculosis (TB). This has contributed to the delay in development of effective vaccine(s) for TB. Several excellent studies have provided only a glimpse of the kind and degree of immune responses elicited following infection by mycobacteria. Preferred entry via respiratory route results in the capture of mycobacteria by alveolar macrophages that eventually become their long-term hosts. Since the pathogen is rarely cleared this has resulted in the human population serving as a large reservoir for mycobacteria. Owing to their unique ability to prime naïve and memory T cells, dendritic cells (DCs) play important and indispensable roles in the initiation and maintenance of protective immune responses following infection. The kind of immune response initiated by DCs with respect to mycobacteria determines the character of immune responses mounted by the host against the pathogen. The profile of cytokines and chemokines secreted as a result of infection of DCs by mycobacteria further plays an important role in defining the course of infection. This minireview attempts to highlight key interactions of mycobacteria with dendritic cells. We discus the uptake of mycobacteria by DCs followed by DC activation and the spectrum of immune responses initiated by infected/activated DCs, followed by numerous ways the pathogen has devised to subvert protective responses

Impaired Generation of Reactive Oxygen Species during Differentiation of Dendritic Cells (DCs) by Mycobacterium tuberculosis Secretory Antigen (MTSA) and Subsequent Activation of MTSA-DCs by Mycobacteria Results in Increased Intracellular Survival

We investigated the role of reactive oxygen species (ROS) in dendritic cell (DC) differentiation by 10-kDa Mycobacterium tuberculosis secretory Ag (MTSA) and survival of mycobacteria therein. Compared with GM-CSF, MTSA induced lower ROS production during DC differentiation from precursors. This result correlated with higher superoxide dismutase 1 expression in MTSA stimulated precursors as compared with GM-CSF stimulation. Furthermore, a negative regulation of protein kinase C (PKC) activation by ROS was observed during DC differentiation. ROS inhibited the rapid and increased phosphorylation of PKC alpha observed during DC differentiation by MTSA. In contrast, ROS inhibition increased the weak and delayed PKCa phosphorylation by GM-CSF. Similar to DC differentiation, upon activation with either M. tuberculosis cell extract (CE) or live Mycobacterium bovis bacillus Calmette-Guerin (BCG), DCs differentiated with MTSA (MTSA-DCs) generated lower ROS levels when compared with DCs differentiated with GM-CSF (GM-CSF-DCs). Likewise, a negative regulation of PKCa phosphorylation by ROS was once again observed in DCs activated with either M. tuberculosis CE or live M. bovis BCG. However, a reciprocal positive regulation between ROS and calcium was observed. Compared with MTSA-DCs, stimulation of GM-CSF-DCs with M. tuberculosis CE induced a 2-fold higher ROS-dependent calcium influx. However, pretreatment of MTSA-DCs with H2O2 increased calcium mobilization. Finally, lower ROS levels in MTSA-DCs correlated with increased intracellular survival of A bovis BCG when compared with survival in GM-CSF-DCs. Although inhibiting ROS in GM-CSF-DCs increased M. bovis BCG survival, H2O2 treatment of MTSA-DCs decreased survival of M. bovis BCG. Overall our results suggest that DCs differentiated with Ags such as MTSA may provide a niche for survival and/or growth of mycobacteria following sequestration of ROS

Organoids and Commercialization

Organoids are 3D miniature tissue mimics and have been effectively used for various purposes, including disease modeling, various drug screening, mechanism of pathogenesis, stem cell research, and tumor immunology. Organoids are as varied as the body’s tissues and organs and have enormous economic potential. They can open new ways to tailored therapy and precision medicine. In clinical investigations, patient-derived organoids have been used to predict patient responses to therapeutic regimens and perhaps improve cancer treatment outcomes. Recent developments in stem cell research and genomic technologies have led to breakthrough innovations in organoid bioengineering, large-scale manufacturing, biobanking, and commercialization. This chapter reviews the notion of organoid biobanking, companies involved and the commercialization aspect, and ethical considerations