Cell cycle arrest induces lipid droplet formation and confers ferroptosis resistance.

How cells coordinate cell cycling with cell survival and death remains incompletely understood. Here, we show that cell cycle arrest has a potent suppressive effect on ferroptosis, a form of regulated cell death induced by overwhelming lipid peroxidation at cellular membranes. Mechanistically, cell cycle arrest induces diacylglycerol acyltransferase (DGAT)-dependent lipid droplet formation to sequester excessive polyunsaturated fatty acids (PUFAs) that accumulate in arrested cells in triacylglycerols (TAGs), resulting in ferroptosis suppression. Consequently, DGAT inhibition orchestrates a reshuffling of PUFAs from TAGs to phospholipids and re-sensitizes arrested cells to ferroptosis. We show that some slow-cycling antimitotic drug-resistant cancer cells, such as 5-fluorouracil-resistant cells, have accumulation of lipid droplets and that combined treatment with ferroptosis inducers and DGAT inhibitors effectively suppresses the growth of 5-fluorouracil-resistant tumors by inducing ferroptosis. Together, these results reveal a role for cell cycle arrest in driving ferroptosis resistance and suggest a ferroptosis-inducing therapeutic strategy to target slow-cycling therapy-resistant cancers.

Blueprint designing and validation for competency-based curriculum for theory assessment in community medicine.

Background: Blueprint provides a base for assessment by assigning proportionate weightage to various content areas and helps the paper setter to construct a uniform and valid assessment. This study aimed to design and validate a blueprint for theory in Community Medicine as per the new curriculum for Medical Undergraduates in India. Methods: Blueprint in community medicine was designed by assigning impact score (I) and frequency score (F) for the competencies. Blueprint was validated using the Content Validity Index (CVI), and inter-rater agreement for subject experts using Fleiss' kappa statistics was calculated. Feedback from faculty and students was obtained afterward to assess the postimplementation response. Results: Blueprint was designed by an expert group where impact score and frequency score were assigned to 146 competencies in the theory of Community Medicine. In Delphi survey I, 63.2% of subject experts responded, while in Delphi survey II, a response rate of 58.3% was achieved. Value of the Fleiss' Kappa test for an inter-rater agreement was 0.68, i.e. "substantial agreement," while CVI among the raters came out to be 0.86, i.e. overall valid assessment. Feedback of faculty (n = 11) suggested that the blueprint was helpful and standardized the paper setting, whereas feedback from students (n = 138) depicted that it helped in preparing for exams, and they would recommend it to other students. Conclusion: Validated blueprint by consensus of subject experts has impact score and frequency score along with topic-wise distribution of marks for the convenience of faculty and its utility is well proven among learners too.

Use of exemplars-based feedforward to improve the performance of medical students in constructed response assessment.

Background: Exemplars are the graded responses to theory questions from previous examinations and are considered as means to guide students about what is valued by assessors; hence giving feed forward to students before the exam and developing self-regulated learning among students. The present study was undertaken to compare the effect on performance of students between intervention (didactic lecture and exemplar) and control group (didactic lecture). Methods: This study was an interventional study conducted among 256 students of a medical college in Rajasthan, India. Participants were randomized to either the control group A or to the interventional group B. Outcomes included a post intervention test evaluating the knowledge gained after the session and students 'attitudes about the same. A focus group discussion was conducted investigating the perceptions. The feedback from faculty was also taken. Results: The mean post test score of intervention group was found to be 6.1 ± 1.74 and of the control group was 5.5 ± 1.6; significantly higher with p-value of 0.03. Out of 128 participants in group B, majority (n = 94,73%) believed that exemplars improve learning and created their interest in topic (n = 78, 60.9%). Most of students (66%) were of the opinion that exemplars should be regularly used with didactic lectures. Key themes identified from focus group were: advantages of the exemplars-based feedforward, challenges in implementation and ways to improve the method. Conclusion: Exemplars improved the performance of students. The faculty members and students agreed that they are an effective tool to enhance learning.

Spectrum and Trends of Intestinal Parasitic Infections at a Tertiary Care Hospital during Pandemic Times: A Laboratory-Based Retrospective Study.

Introduction Intestinal parasitic infections continue to loom in developing countries with low sanitation and socioeconomic conditions. Pandemic times are especially important to study the prevalence of these pathogens since the focus of all healthcare services was coronavirus disease 2019 (COVID-19). This study aimed to evaluate the prevalence and time-trend of intestinal parasitic infections in the capital region of India during the pandemic times. Methods In this cross-sectional study, a retrospective review based on data from the past 2 years in the post-COVID-19 pandemic was used. Descriptive and time-trend analyses were applied to the data. Time series analysis was analyzed using the best fit autoregressive integrated moving average (ARIMA) model to look for seasonality in trends and forecasting. Results A total of 7267 patients' stool samples over a 2-year pandemic period were included in the study. Intestinal parasites were detected in 11.18% (813/7276) patients. Giardia lamblia (2.28%) and Blastocystis hominis (3.78%) were the predominant ones. Time-trend analysis from 2020 to 2021 using ARIMA model predicted an increasing trend with waning of pandemic. The most prevalent infection was found in the monsoon and autumn months. Conclusion Rates of infection with Giardia lamblia and Blastocystis hominis have increased in comparison to other protozoan infections like Entamoeba histolytica when compared with prepandemic hospital-based studies. With fading of the pandemic, further increasing trends are predicted.

Airway management, procedural data, and in-hospital mortality records of patients undergoing surgery for mucormycosis associated with coronavirus disease (COVID-19).

PURPOSE: Although unexpected airway difficulties are reported in patients with mucormycosis, the literature on airway management in patients with mucormycosis associated with Coronavirus disease is sparse. METHODS: In this retrospective case record review of 57 patients who underwent surgery for mucormycosis associated with coronavirus disease, we aimed to evaluate the demographics, airway management, procedural data, and in-hospital mortality records. RESULTS: Forty-one (71.9%) patients had a diagnosis of sino-nasal mucormycosis, fourteen (24.6%) patients had a diagnosis of rhino-orbital mucormycosis, and 2 (3.5%) patients had a diagnosis of palatal mucormycosis. A total of 44 (77.2%) patients had co-morbidities. The most common co-morbidities were diabetes mellitus in 42 (73.6%) patients, followed by hypertension in 21 (36.8%) patients, and acute kidney injury in 14 (28.1%) patients. We used the intubation difficulty scale score to assess intubating conditions. Intubation was easy to slightly difficult in 53 (92.9%) patients. In our study, mortality occurred in 7 (12.3%) patients. The median (range) mortality time was 60 (27-74) days. The median (range) time to hospital discharge was 53.5 (10-85) days. The median [interquartile range] age of discharged versus expired patients was 47.5 [41,57.5] versus 64 [47,70] years (P = 0.04), and median (interquartile range) D-dimer levels in discharged versus expired patients was 364 [213, 638] versus 2448 [408,3301] ng/mL (P = 0.03). CONCLUSION: In patients undergoing surgery for mucormycosis associated with the coronavirus disease, airway management was easy to slightly difficult in most patients. Perioperative complications can be minimized by taking timely and precautionary measures.

Combining ability and heterosis studies for grain iron and zinc concentrations in pearl millet [Cenchrus americanus (L). Morrone].

Iron (Fe) and zinc (Zn) deficiency has been identified as a major food-related health issue, affecting two billion people globally. Efforts to enhance the Fe and Zn content in food grains through plant breeding are an economic and sustainable solution to combat micronutrient deficiency in resource-poor populace of Asia and Africa. Pearl millet, Cenchrus americanus (L). Morrone, considered as a hardy nutri-cereal, is the major food crop for millions of people of these nations. As an effort to enhance its grain mineral content, an investigation was conducted using line × tester analysis to generate information on the extent of heterosis, gene action, combining ability for grain yield potential, and grain mineral nutrients (Fe and Zn). The partitioning of variance attributable to parents indicated that the lines and testers differed significantly for the traits studied. For most of the attributes, hybrids that were superior to the parents in the desired direction in terms of per se performance were identified. The analysis of combining ability variance indicated the preponderance of both additive and non-additive genetic effects. Thus, reciprocal recurrent selection can be used to develop a population with high-grain Fe and Zn contents. The Fe and Zn content in grain exhibited a highly significant and positive association between them, whereas the Fe and Zn contents individually showed a negative, albeit weak, correlation with grain yield and a moderate positive relation with grain weight. This indicates that mineral nutrient contents in grains can be improved without significant compromise on yield. The consistency of these trends across the environment suggests that these findings could be directly used as guiding principles for the genetic enhancement of Fe and Zn grain content in pearl millet.

Detection of three pandemic causing coronaviruses from non-respiratory samples: systematic review and meta-analysis.

SARS-CoV-2 has posed an unprecedented challenge to the world. Pandemics have been caused previously by viruses of this family like Middle East Respiratory Corona Virus (MERS CoV), Severe Acute Respiratory Syndrome Corona Virus (SARS CoV). Although these viruses are primarily respiratory viruses, but they have been isolated from non-respiratory samples as well. Presently, the detection rate of SARS-CoV-2 RNA from different clinical specimens using Real Time Reverse Transcriptase Polymerized Chain Reaction (qRT-PCR) after onset of symptoms is not yet well established. Therefore, the aim of this systematic review was to establish the profile of detecting SARS-CoV-2, MERS CoV, SARS CoV from different types of clinical specimens other than the respiratory using a standard diagnostic test (qRT-PCR). A total of 3429 non-respiratory specimens were recorded: SARS CoV (total sample-802), MERS CoV (total sample-155), SARS CoV-2 (total sample-2347). Out of all the samples studied high positive rate was seen for saliva with 96.7% (14/14; 95% CI 87.6-100.0%) for SARS CoV and 57.5% (58/250; 95% CI - 1.2 to 116.2%) for SARS CoV-2, while low detection rate in urine samples for SARS CoV-2 with 2.2% (8/318; 95% CI 0.6-3.7%) and 9.6% (12/61; 95% CI - 0.9 to 20.1%) for SARS CoV but there was relatively higher positivity in urine samples for MERS CoV with detection rate of 32.4% (2/38; 95% CI - 37.3 to 102.1%). In Stool sample positivity was 54.9% (396/779; 95% CI 41.0-68.8%), 45.2% (180/430; 95% CI 28.1-62.3%) and 34.7% (4/38; 95% CI - 29.5 to 98.9%) for SARS CoV-2, MERS CoV, and SARS CoV, respectively. In blood sample the positivity was 33.3% (7/21; 95% CI 13.2-53.5%), 23.7% (42/277; 95% CI 10.5-36.9%) and 2.5% (2/81; 95% CI 0.00-5.8%) for MERS CoV, SARS CoV-2 and SARS CoV respectively. SARS-CoV-2 along with previous two pandemic causing viruses from this family, were highly detected stool and saliva. A low positive rate was recorded in blood samples. Viruses were also detected in fluids along with unusual samples like semen and vaginal secretions thus highlighting unique pathogenic potential of SARS-CoV-2.

Salinity Stress in Potato: Understanding Physiological, Biochemical and Molecular Responses.

Among abiotic stresses, salinity is a major global threat to agriculture, causing severe damage to crop production and productivity. Potato (Solanum tuberosum) is regarded as a future food crop by FAO to ensure food security, which is severely affected by salinity. The growth of the potato plant is inhibited under salt stress due to osmotic stress-induced ion toxicity. Salinity-mediated osmotic stress leads to physiological changes in the plant, including nutrient imbalance, impairment in detoxifying reactive oxygen species (ROS), membrane damage, and reduced photosynthetic activities. Several physiological and biochemical phenomena, such as the maintenance of plant water status, transpiration, respiration, water use efficiency, hormonal balance, leaf area, germination, and antioxidants production are adversely affected. The ROS under salinity stress leads to the increased plasma membrane permeability and extravasations of substances, which causes water imbalance and plasmolysis. However, potato plants cope with salinity mediated oxidative stress conditions by enhancing both enzymatic and non-enzymatic antioxidant activities. The osmoprotectants, such as proline, polyols (sorbitol, mannitol, xylitol, lactitol, and maltitol), and quaternary ammonium compound (glycine betaine) are synthesized to overcome the adverse effect of salinity. The salinity response and tolerance include complex and multifaceted mechanisms that are controlled by multiple proteins and their interactions. This review aims to redraw the attention of researchers to explore the current physiological, biochemical and molecular responses and subsequently develop potential mitigation strategies against salt stress in potatoes.

Comparison of Mc Grath-MAC and C-MAC video laryngoscopes for intubation in a COVID simulated mannequin by novice users wearing face protective gear: A randomized crossover trial.

INTRODUCTION: Intubation in COVID patients is challenging. Various guidelines suggest the use of video-laryngoscope (VL) as the first device to aid intubation in a COVID patient. The best VL to facilitate intubation in such a setting especially by novices is not ascertained. We compared intubation characteristics by two VL's (McGrath-MAC and C-MAC) for intubation in a COVID simulated mannequin by novices. METHODOLOGY: This prospective randomized manikin-based crossover study was done in thirty medical professionals with no previous experience of intubation with VL. All participants were trained on Laerdel airway management trainer and were allowed 5 practice sessions with each scope with an intubation box while wearing face protective personal protective equipment (PPE). Participants were randomized into two groups of 15 each, one group performed the intubation first with McGrath and the other with C-MAC before crossing over. RESULTS: The mean (S. D.) time to intubation was similar with both McGrath-VL and CMAC VL [31.33 (14.72) s vs 26.47 (8.5) s, P = (p-0.063)]. POGO score [mean (S. D.)] was better with CMAC [81.33 (16.24) vs 60.33 (14.73), p-0.00. The majority of the users preferred C-MAC VL for intubation (93.33%). The incidence of failed intubation and multiple attempts at intubating were similar with the two scopes. CONCLUSION: The time to intubation was similar with both VL's but the majority of novices preferred CMAC probably due to a bigger screen that helped them to have a better view of glottis in the COVID simulated mannequin.

Energy-stress-mediated AMPK activation inhibits ferroptosis.

Energy stress depletes ATP and induces cell death. Here we identify an unexpected inhibitory role of energy stress on ferroptosis, a form of regulated cell death induced by iron-dependent lipid peroxidation. We found that ferroptotic cell death and lipid peroxidation can be inhibited by treatments that induce or mimic energy stress. Inactivation of AMP-activated protein kinase (AMPK), a sensor of cellular energy status, largely abolishes the protective effects of energy stress on ferroptosis in vitro and on ferroptosis-associated renal ischaemia-reperfusion injury in vivo. Cancer cells with high basal AMPK activation are resistant to ferroptosis and AMPK inactivation sensitizes these cells to ferroptosis. Functional and lipidomic analyses further link AMPK regulation of ferroptosis to AMPK-mediated phosphorylation of acetyl-CoA carboxylase and polyunsaturated fatty acid biosynthesis. Our study demonstrates that energy stress inhibits ferroptosis partly through AMPK and reveals an unexpected coupling between ferroptosis and AMPK-mediated energy-stress signalling.

Neglected health literacy undermining fluorosis control efforts: A pilot study among schoolchildren in an endemic village of rural Rajasthan, India.

BACKGROUND: Ingestion of excess fluoride can cause fluorosis which adversely affects teeth and bones. Fluorosis is a major public health problem in the state of Rajasthan with all its 32 districts having variable fluoride contamination, and many initiatives are currently implemented in this region to mitigate the fluorosis burden. OBJECTIVE: The objective of this study was to assess fluorosis, its risk factors, and the awareness among school students and teachers in endemic villages of Jodhpur district, Rajasthan. MATERIALS AND METHODS: A representative sample of 300 students of age 12-15 years were enrolled for cross-sectional study in selected villages. Data were collected regarding awareness, behavioral and preventive practices about fluorosis and clinical assessment and fluoride estimation in water and urine samples was done. RESULTS: Dental fluorosis through Dean's index was observed in 24.5% of students. The awareness and practices for fluorosis prevention and its risk factors were poor among both students and teachers. Intake of piped water supply was reported by majority of students (95.8%). High fluoride concentration was found in 35 (81.3%) out of 43 urine samples. CONCLUSION: Improvement in drinking water supply in the endemic village of Rajasthan has decreased the burden of fluorosis, but low level of awareness and prevailing dietary and behavioral practices still pose them at risk of high fluoride intake. This signifies the need to address nonconventional sources of fluoride intake (diet and toothpaste) and early screening of disease by involving teachers and family physicians in fluoride mitigation efforts.

Mobile phone use and possible cancer risk: Current perspectives in India.

Mobile communication is now essentially ruling our daily lives through better connectivity and intelligent smartphone services. There has been a tremendous growth in Indian communication industry along with growing concerns regarding health effects of mobile radiation exposure. Concerns posed are especially regarding carcinogenesis and other health-related effects of mobile radiation exposure. In the effort to establish or refute any such concerns, many studies have been undertaken in the past three decades, mostly case-control designs or cross-sectional surveys. However, most of them considerably failed to establish causal association primarily owing to potential biases and errors in their conduct and analysis. Past cohort studies have provided contradictory results leading to continued uncertainty regarding tumorigenic potential of mobile radiation exposure. In India, there remains a huge knowledge gap pertaining to this particular topic and only few studies are presently underway such as the Indian Council of Medical Research (ICMR) cell phone study in the National capital region (NCR). International Agency for Research on Cancer (IARC) has classified radiofrequency electromagnetic fields associated with wireless phone use as possibly carcinogenic to humans (Group 2B), causing major concerns worldwide among mobile companies and subscribers equivocally. The World Health Organization (WHO) is presently carrying formal risk assessment of all studied health outcomes from radio frequency field's exposures and is likely to publish it by the year 2016.

Recombinant outer membrane protein C of Aeromonas hydrophila elicits mixed immune response and generates agglutinating antibodies.

Aeromonas hydrophila is a gram-negative fish pathogenic bacterium, also responsible for causing opportunistic pathological conditions in humans. It causes a number of diseases in fish due to which the fish industry incurs huge economic losses annually. Due to problems of antibiotic resistance, and the rapidity with which the infection spreads among fishes, vaccination remains the most effective strategy to combat this infection in fish populations. Among various virulence factors associated with bacterial virulence, outer membrane proteins have been widely evaluated for their vaccine potential owing to their surface exposure and related role in pathogenicity. In the present study, we have investigated the immunogenic potential of a non-specific porin, outer membrane protein C (OmpC) whose expression is regulated by the two-component regulatory system and plays a major role in the survival of A. hydrophila under different osmolaric conditions. The full-length gene (~1 kb) encoding OmpC of A. hydrophila was cloned, characterized and expressed in E. coli. High yield (~112 mg/L at shake flask level) of the recombinant OmpC (rOmpC) (~40 kDa) of A. hydrophila was obtained upon purification from inclusion bodies using Ni(2+)-NTA affinity chromatography. Immunization with purified rOmpC in murine model generated high endpoint (>1:40,000) titers. IgG isotyping, ELISA and ELISPOT assay indicated mixed immune response with a TH2 bias. Also, the anti-rOmpC antibodies were able to agglutinate A. hydrophila in vitro and exhibited specific cross-reactivity with different Aeromonas strains, which will facilitate easy detection of different Aeromonas isolates in infected samples. Taken together, these data clearly indicate that rOmpC could serve as an effective vaccine against different strains of Aeromonas, a highly heterogenous group of bacteria.

Sexual and Reproductive Health: Knowledge, Attitude, and Perceptions among Young Unmarried Male Residents of Delhi.

Context. Men play a significant role in all spheres of domestic life including reproduction. Youth is a period of critical development and ignoring sexual and reproductive health (SRH) needs of young men ought to have wider social and health consequences. Aims and Objectives. To assess the knowledge, attitude, and perceptions regarding SRH among young unmarried men (18-25 years). Settings and Design. A semiqualitative study conducted across four health centers (2 rural, 2 urban) across Delhi. Materials and Methods. Focus group discussions (FGDs) were held among sixty-four participants regarding various aspects of SRH. Data Analysis. The data generated were analyzed using free listing and thematic content analysis along with simple quantitative proportions for different variable groups. Results. Good knowledge regarding HIV/AIDS was observed though found poor regarding other STIs/RTIs. Inadequate knowledge and negative attitude towards SRH and condom use were observed among rural participants. Peer group and mass media were the commonest SRH information sources among rural and urban participants, respectively. Conclusions. Poor SRH knowledge, perceptions, and available nonformal, unreliable information sources expose young men to poor SRH outcomes. Early, comprehensive SRH information provision can have life-long protective benefits to them and their partners.