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Background Fungal disease is frequent in India, but its incidence and prevalence are unclear. This review aims at defining the frequency or burden of various fungal infections in India. Methods A systematic review of the literature on the PubMed, Embase, and Web of Science (WOS) databases was conducted using appropriate search strings. Deterministic modeling determined annual incidence and prevalence estimates for multiple life- and sight-threatening infections with significant morbidity. Results Literature searches yielded >2900 papers; 434 papers with incidence/prevalence/proportion data were analyzed. An estimated 57 251 328 of the 1 393 400 000 people in India (4.1%) suffer from a serious fungal disease. The prevalence (in millions) of recurrent vulvovaginal candidiasis is 24.3, allergic bronchopulmonary aspergillosis is 2.0, tinea capitis in school-age children is 25, severe asthma with fungal sensitization is 1.36, chronic pulmonary aspergillosis is 1.74, and chronic fungal rhinosinusitis is 1.52. The annual incidence rates of Pneumocystis pneumonia (58 400), invasive aspergillosis (250 900), mucormycosis (195 000), esophageal candidiasis in HIV (266 600), candidemia (188 000), fungal keratitis (1 017 100), and cryptococcal meningitis (11 500) were also determined. Histoplasmosis, talaromycosis, mycetoma, and chromoblastomycosis were less frequent. Conclusions India's fungal burden is high and underappreciated in clinical practice.

Irregularity in plan shape is very common and sometimes unavoidable for providing proper ventilation in and around a tall building. In this present study, the pros and cons of using irregular type butterfly plan-shaped building over regular square plan-shaped buildings are discussed. Two turbulence models, standard k-epsilon (SKE) and shear stress transport (SST), were used for the validation of the numerical model, and the data were compared with previous experimental results of Commonwealth Advisory Aeronautical Research Council (CAARC) building model from literature. The force coefficients (both X and Y direction) and external pressure coefficients are observed considering four different heights and five different irregularity ratios of the butterfly building for wind incidence angle ranging between 00 and 450 at an interval of 150. The variation of pressure along various faces of the building is analysed with the help of contours and horizontal peripheral lines. With the increase in the irregularity ratio, the overall plan area consumed by the building is increased although the ventilation of the building is improved drastically along with a decrease in the force coefficient acting on the building and the maximum local suction at the corner regions.

Quality education is the 4th goal of Sustainable Development Goals adopted by all United Nations Member States in 2015. ‘Child to Child approach’ is based on the idea of children working together with other children to bring about change. Child to Child Education Programme of Community Health Department of a tertiary care hospital was started in 1999 in a slum community. It provided a conducive-atmosphere to students. This has helped in promoting all-round development of children. The aim of this retrospective study is to show the effectiveness of this programme. Method: This retrospective study was conducted from 15th January 2020 to 31st March 2020, in a slum community of Delhi, for 11362 school going children, who have attended CCEd. programme between the years 1999 to 2019. The Secondary Data was collected. It was cleaned, and tabulated with frequency tables and percentages using MS-Excel. The significance and Odd’s ratio were calculated onMedCalc software. Results: Immediate impact of CCEd. on students was seen as the percentage of merit holders increased and was found to be between 5.23% – 13.26%. They were exposed to several Curricular,Extra-curricular, Social & Health Activities during the years they were part of CCEd. The qualifications of alumni of CCEd. programme showed that 116(76.31%) out of 152 are holding either a graduate degree or post graduates degree. The monthly income of alumni showed that a maximum number of alumni [36(23.68%)] earn Rs. 15000- 20000/ per month and some 6(3.95%) earn Rs. >45000-50000/- per month. They had always desired to be at par with other children/students of their age from privileged communities which they have attained in life. They are happy and satisfied. How to cite this article: Vaghela JF, Wanjari P, Gupta V et al. Child to Child Education Programme: A Model for overall Development of school going Students of Poorer Communities J Adv Res Eng & Edu 2020; 5(1): 1-11. DOI: https://doi.org/10.24321/2456.4370.202001

Fungal diseases have not been taken seriously in public health agendas as well as research priorities, despite of globally causing an estimated two million deaths every year, and the emergence of many troublesome fungal pathogens like Candida auris, azole resistant Aspergillus fumigatus, terbinafine and azole resistant dermatophytes, and zoonotic sporotrichosis in humans. Fungi are also responsible for huge losses of agricultural products and stored crops as well as recent massive and unexpected mortality in animals caused by white-nose syndrome in the bats and Chytridiomycosis in amphibians. This review aims to underscore the need for collaborative, multisectoral, and trans-disciplinary approach to include the One Health approach as an essential component of surveillance, prevention, and control of globally emerging fungal diseases. Rigorous evidence based surveillance of the environment as well as strengthening rapid and quality diagnosis of fungal diseases can save millions of lives and reduce significant morbidity.

Bacterial species are hosts to horizontally acquired mobile genetic elements (MGEs), which encode virulence, toxin, antimicrobial resistance, and other metabolic functions. The bipartite genome of Vibrio cholerae harbors sporadic and conserved MGEs that contribute in the disease development and survival of the pathogens. For a comprehensive understanding of dynamics of MGEs in the bacterial genome, we engineered the genome of V. cholerae and examined in vitro and in vivo stability of genomic islands (GIs), integrative conjugative elements (ICEs), and prophages. Recombinant vectors carrying the integration module of these GIs, ICE and CTXΦ, helped us to understand the efficiency of integrations of MGEs in the V. cholerae chromosome. We have deleted more than 250 acquired genes from 6 different loci in the V. cholerae chromosome and showed contribution of CTX prophage in the essentiality of SOS response master regulator LexA, which is otherwise not essential for viability in other bacteria, including Escherichia coli In addition, we observed that the core genome-encoded RecA helps CTXΦ to bypass V. cholerae immunity and allow it to replicate in the host bacterium in the presence of similar prophage in the chromosome. Finally, our proteomics analysis reveals the importance of MGEs in modulating the levels of cellular proteome. This study engineered the genome of V. cholerae to remove all of the GIs, ICEs, and prophages and revealed important interactions between core and acquired genomes.

Background: Adolescence is the period of growing-up, this phase is characterized by marked and rapid changes: physical, psychological, sexual, socio-economical. There are many workshops and training sessions held for adolescent girls, while the boys in this age group are overlooked. The present study focuses on a series of workshops that were held exclusively for adolescent boys in an urban resettlement colony in Delhi. Method: This retrospective study was conducted from 15th February 2020 to 15th May 2020, in a slum community of Delhi, for 131 adolescent boys, who had attended Adolescent Boys Workshops from February to August 2019. The study was aimed to find out the increase in the awareness and knowledge of adolescent boys who attended these workshops, on various adolescence related topics. Statistical analysis was done in order to obtain mean, median and mode of the test scores. The student T test was applied to find the statistically significant p value. A p-value

IntroductionA major concern amidst the ongoing coronavirus pandemic has been the longer term persistence of morbidities in individuals recovering from COVID-19 disease, called ‘long COVID’. We aimed at documenting the prevalence and key associations of post-COVID symptoms (PCS) in India in telephonic survey among recovered patients in a single hospital in eastern India as well as a parallel web-survey covering a wider population of the country.MethodsSelf-reported PCS, ranging up to one year since the original COVID-19 diagnosis, were documented in a telephonic survey of subjects (analyzed N=986), treated for acute COVID-19 in Infectious Diseases and Beleghata General Hospital, Kolkata, between April 1, 2020 and April 13, 2021. In parallel, we ran a web-based survey (analyzed N=580), to evaluate concordance.ResultsShortness of breath, fatigue and insomnia were identified to be the most commonly reported PCS in both the surveys, with higher prevalence in females. In the telephonic survey, a 3.65% post-discharge mortality was registered within a median of 39 days since COVID diagnosis. Intensive care during acute disease and hypertension were more often associated with PCS, while fatigue was more often reported by the 20-40 years age-group. The web-survey revealed a gradual decline in PCS with time since COVID-19 diagnosis and type 2 diabetes to be associated with higher prevalence of these symptoms.ConclusionsWe assessed the predominant PCS among Indian COVID-19 patients and identified key demographic and clinical associations in our surveys, which warrants deeper epidemiological and mechanistic studies for guiding management of long-COVID in the country.

Background

Significance This study reveals that impaired IKKα expression or activity in lung cancer enhances differentiation of protumorigenic Treg cells through a TNF/TNFR2/NF-κB signaling pathway in both human and mouse lung ADC. Depletion of one of the molecules that are required for Treg cell induction represses lung ADC development. Thus, the components that interfere with this particular Treg differentiation provide targets for the generation of TME-modifying therapies.

Helicobacter pylori is a ubiquitous bacterium and contributes significantly to the burden of chronic gastritis, peptic ulcers, and gastric cancer across the world. Adaptive phenotypes and virulence factors in H. pylori are heterogeneous and dynamic. However, limited information is available about the molecular nature of antimicrobial resistance phenotypes and virulence factors of H. pylori strains circulating in India. In the present study, we analyzed the whole genome sequences of 143 H. pylori strains, of which 32 are isolated from two different regions (eastern and southern) of India. Genomic repertoires of individual strains show distinct region-specific signatures. We observed lower resistance phenotypes and genotypes in the East Indian (Kolkata) H. pylori isolates against amoxicillin and furazolidone antibiotics, whereas higher resistance phenotypes to metronidazole and clarithromycin. Also, at molecular level, a greater number of AMR genes were observed in the east Indian H. pylori isolates as compared to the southern Indian isolates. From our findings, we suggest that metronidazole and clarithromycin antibiotics should be used judicially in the eastern India. However, no horizontally acquired antimicrobial resistance gene was observed in the current H. pylori strains. The comparative genome analysis shows that the number of genes involved in virulence, disease and resistance of H. pylori isolated from two different regions of India is significantly different. Single-nucleotide polymorphisms (SNPs) based phylogenetic analysis distinguished H. pylori strains into different clades according to their geographical locations. Conditionally beneficial functions including antibiotic resistance phenotypes that are linked with faster evolution rates in the Indian isolates.

Increasing occurrence of infections caused by multidrug-resistant Gram-negative bacteria resulted in colistin being the last agent for treatment. Apart from plasmid-mediatedA total of 100 carbapenem-resistantAmong 100 carbapenem-resistantThe performance of cBMD was excellent, whereas the E-test was unacceptable. VITEK-2 and RPNP performed better but remained unreliable due to high error rates. Multiple mutations in the target proteins involving lipopolysaccharide formation, modification, and regulation were seen, resulting in colistin resistance.

Introduction The outbreak of COVID-19 has differentially affected countries in the world, with health infrastructure and other related vulnerability indicators playing a role in determining the extent of the COVID-19 spread. Vulnerability of a geographical region/country to COVID-19 has been a topic of interest, particularly in low- and middle-income countries like India to assess the multi-factorial impact of COVID-19 on the incidence, prevalence or mortality data. Datasets and Methods Based on publicly reported socio-economic, demographic, health-based and epidemiological data from national surveys in India, we compute contextual, COVID-19 Vulnerability Indices (cVIs) across multiple thematic resolutions for different geographical and spatial administrative regions. These multi-resolution cVIs were used in regression models to assess their impact on indicators of the spread of COVID-19 such as the average time-varying instantaneous reproduction number. Results Our observational study was focused on 30 districts of the eastern Indian state of Odisha. It is an agrarian state, prone to natural disasters and one of the largest contributors of an unprotected migrant workforce. Our analyses identified housing and hygiene conditions, availability of health care and COVID preparedness as important spatial indicators. Conclusion Odisha has demonstrated success in containing the COVID-19 infection to a reasonable level with proactive measures to contain the spread of the virus during the first wave. However, with the onset of the second wave of COVID, the virus has been making inroads into the hinterlands and peripheral districts of the state, burdening the already deficient public health system in these areas. The vulnerability index presented in this paper identified vulnerable districts in Odisha. While some of them may not have a large number of COVID-19 cases at a given point of time, they could experience repercussions of the pandemic. Improved understanding of the factors driving COVID-19 vulnerability will help policy makers prioritise resources and regions leading to more effective mitigation strategies for the COVID-19 pandemic and beyond. WHAT IS ALREADY KNOWN Measuring vulnerability to COVID-19 and other pandemics is a complex and layered subject. In Low-to-Middle-Income Country (LMIC) like India, complete reliance on incidence, prevalence or mortality data of the disease may not be the best measure since this data from the health system and DHS in public domain is limited. ADDED VALUE OF THIS STUDY To our knowledge, this is the first study at the district level concerning the COVID-19 situation in Odisha, characterized by a large tribal and migrant population. We defined vulnerability through relevant socio-economic domains that have an influence on mitigation strategies. Although we applied our methods to the districts of Odisha, we believe they can be used in other LMIC regions. IMPLICATIONS OF THE FINDINGS Regions with higher overall or theme-specific vulnerability index might experience potentially severe consequences of the COVID-19 outbreak demanding precise, dynamic and nimble policy decisions to prevent a potentially dire situation.

Colonic and intestinal epithelial cells (EC) attach to a basement membrane of laminins, fibronectin, and collagen IV. Wounding of the epithelial layer can change the types of extracellular matrix (ECM) proteins to which the EC attach. In this study, we determined the effect of culturing Caco-2 cells on different ECM proteins on the capacity of EC to produce TNF-α- or IL-1-stimulated CXCL8. The effect of the ECM proteins was such that CXCL8 secretion by cells cultured on collagen I > collagen IV > fibronectin or laminin-111. However, suppression of ROCK activity resulted in a similar 75 to 85% suppression of CXCL8 secretion regardless of the ECM protein type. This suggests that EC can produce different levels of CXCL8 depending on the type of ECM proteins they attach to, but all cases result in a similar requirement for ROCK activity for optimal CXCL8 secretion. Furthermore, when confluent cells were compared to subconfluent cells, the level of TNF- or IL-1-stimulated CXCL8 secretion was greatly elevated with the subconfluent cells and inhibiting ROCK had no effect on CXCL8 secretion levels by the confluent cells. These experiments suggest that CXCL8 responses by confluent cells, which would model for intact, unwounded epithelial, do not involve ROCK activation. However, CXCL8 responses by subconfluent cells, which would model for cells attaching to and moving on ECM proteins in wounded epithelia, require ROCK activation for greatly elevated CXCL8 responses. These results provide a model to examine the important conditions which regulate chemokine production by EC in wounded epithelia.

Highlights • Potential safety issues have been identified with current PPE ensembles for HCID. • Our novel simulation model tests PPE for both bodily fluid and airborne pathogens. • A new consensus model of PPE for HCID is proposed, with supporting safety data. • The model is explained, together with protocols for donning and doffing PPE safely. • It has been agreed by a working group of expert stakeholders from around the UK., Summary The importance of appropriate personal protective equipment (PPE) as a component of healthcare worker (HCW) protection was highlighted during the Ebola virus disease (EVD) outbreak in West Africa. The large number of HCW deaths in Africa was in part due to lack of resources or prior training in PPE usage. As part of the Ebola legacy, the High Consequence Infectious Disease (HCID) programme was initiated by NHS England and Public Health England (PHE) to improve preparedness for Ebola and other infections that not only endanger the life of the patient, but also pose particular dangers to HCWs. A systematic review identified national standardisation of PPE protocols as a priority, but recognised that a lack of safety data limited the ability to mandate any one protocol. A simulation-based exercise was developed to assess the safety of PPE ensembles in use in the UK during first assessment of a patient with a possible HCID. A mannequin was adapted to expose volunteer HCWs to synthetic bodily fluids (vomit, sweat, diarrhoea and cough), each with a different coloured fluorescent tracer, invisible other than under ultraviolet (UV) light. After exposure, HCWs were examined under UV lights to locate fluorescent contamination, and were screened again after removing PPE (doffing) to detect any personal contamination. The exercise was videoed, allowing retrospective analysis of contamination events and user errors. The simulation testing identified significant HCW contamination events after doffing, related to protocol failure or complications in PPE doffing, providing conclusive evidence that improvements could be made. At a workshop with an expert stakeholder group, the data were examined and a unified PPE ensemble agreed. This ensemble was then tested in the same simulation exercise and no evidence of any HCW contamination was seen after doffing. Following further review by the working group, a consensus agreement has been reached and a unified ‘HCID assessment PPE’ ensemble, with accompanying donning and doffing protocols, is presented here.

Clustering methods for multivariate data exploiting the underlying geometry of the graphical structure between variables are presented. As opposed to standard approaches for graph clustering that assume known graph structures, the edge structure of the unknown graph is first estimated using sparse regression based approaches for sparse graph structure learning. Subsequently, graph clustering on the lower dimensional projections of the graph is performed based on Laplacian embeddings using a penalized k-means approach, motivated by Dirichlet process mixture models in Bayesian nonparametrics. In contrast to standard algorithmic approaches for known graphs, the proposed method allows estimation and inference for both graph structure learning and clustering. More importantly, the arguments for Laplacian embeddings as suitable projections for graph clustering are formalized by providing theoretical support for the consistency of the eigenspace of the estimated graph Laplacians. Fast computational algorithms are proposed to scale the method to large number of nodes. Extensive simulations are presented to compare the clustering performance with standard methods. The methods are applied to a novel pan-cancer proteomic data set, and protein networks and clusters are evaluated across multiple different cancer types.

Nipah virus, an enveloped ribonucleic acid virus, has been a major cause of encephalitis out-breaks with high mortality, primarily in the Indo-Bangladesh regions. Except for the first outbreak in Malaysia-Singapore, which was related to contact with pigs and the outbreak in Philippines associated with horse slaughter, most other outbreaks have affected the Indo- Bangladesh regions. The Indo-Bangladesh outbreaks were associated with consumption of raw date palm sap contaminated by fruit bats and had a very high secondary attack rate. The patient usually presents with fever, encephalitis and/or respiratory involvement with or without thrombocytopenia, leukopenia and transaminitis. Diagnosis can be confirmed by isolation and nucleic acid amplification in the acute phase or antibody detection during the convalescent phase. Treatment is mostly limited to supportive care and syndromic management of acute encephalitis syndrome. Ribavirin, m102.4 monoclonal antibody and favipiravir are the only anti-virals with some activity against Nipah virus. Standard precautions, hand hygiene and personal protective equipments are the cornerstone of comprehensive infection prevention and control strategy. With the recent outbreaks affecting newer geographical areas, there is a need for physicians to be aware of this disease and keep abreast of its current detection and management strategies.

Lung cancer remains one of the leading causes of mortality of cancer patients. Kinase-dead Ikkα knock-in (KA/KA) mice develop CD4 T cell-derived autoimmune disease. Previously, we reported spontaneous lung squamous cell carcinoma (SCC) associated with increase macrophage and CD4 T cell numbers in KA/KA mice. Depleting macrophages dampens lung SCC development in KA/KA mice, but a lot of CD4 T cells remain in the lungs. The activity of CD4 T cells in lung SCC development is unknown. In this study, we attempted to investigate the role of CD4 T cells in lung SCC development. We performed adoptive CD4 T cell transfer experiment and found that KA/KA CD4 T cell transfer, not WT CD4 T cells, recruited marked macrophages to the lungs and induced lung SCC in KA/KA;Rag1-/- mice. The CD4 T cells isolated from the lungs of KA/KA mice and KA/KA;Rag1-/- mice with KA/KA CD4 T cell transfer expressed elevated PD-1, IL-4, IL-5, Il-13, and Il-21 levels compared to WT mice. We found that Il4 ablation, not Il5 deletion, reduced macrophage recruitment and blocked SCC development in KA/KA;Il4-/- mice as well as unlike KA/KA CD4 T cells, KA/KA;Il4-/- CD4 T cells did not induce spontaneous lung SCC in KA/KA;Rag1-/- mice with KA/KA;Il4-/- CD4 T cell injections. Taken together, the finding highlights a pathogenic role of IL-4-producing CD4 T cells in lung carcinogenesis. Citation Format: Gajendra Jogdand, Sayantan Banerjee, Gongping Shi, Jami Willet Brown, Amit Singh, Yongmei Zhao, Jyoti Shetty, Bao Tran, Yinling Hu. Interleukin 4 Producing CD4 T cells initiate a crucial event for lung cancer development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1339.

Previously we reported that bone marrow-derived macrophages are required for lung squamous cell carcinoma development in kinase-dead Ikkα knockin (KA/KA) mice. The KA/KA lungs display strikingly enlarged sizes, sustained inflammation with increased expression of multiple cytokines and chemokines and marked infiltrating macrophages and T cells, and tissue damage, which look like a “burning hill”. To determine a critical event for the pathogenesis of the lung disease and SCC development, in this study, we found that these F4/80+CD11b+CSF1R+ monocyte-derived macrophages isolated from KA/KA lungs showed enlarged sizes carrying many lipid droplets and highly expressed the genes that encode proteins involved in lipid metabolism compared to WT. To determine whether the lung lipid concentrations regulate foamy macrophage development, we incubated Raw macrophages with WT or KA/KA lung extract, respectively, and found that KA/KA lung extracts induced lipid droplets and elevated lipid levels and pathways for lipid metabolism compared to WT lung extracts. Furthermore, we found that cytokines including IL-4, IL-6, IL-33, and IFNb, promoted lipid metabolism in Raw macrophages incubated with WT lung extracts, and also stimulated lipid metabolism in human lung SCC SW900 cells. These results suggest that these cytokines, which were highly expressed in KA/KA lungs, contribute to aberrant lipid metabolism. Because IL-4, which is produced by Th2 T cells, promoted lipid metabolism in macrophages and lung SCC cells, we further showed that KA/KA lung CD4 T cells stimulated lipid gene expression in Raw macrophages compared to WT lung CD4 T cells. Depleting CD4 T cells indeed significantly decreased foamy macrophage formation in the lungs of KA/KA mice. Importantly, treatment with a lipid inhibitor reduced IL-4-mediated lipid metabolism in Raw macrophages and human lung SCC SW900 cells, as well as this treatment attenuated lung foamy macrophage numbers and dampened lung SCC development in irradiated KA/KA mice with KA/KA bone marrow transplants. These findings highlight that the interplay between CD4 T cells, macrophages, cytokines, and epithelial cells contribute to a series of biological events in a landscape scale, which promote lung disease and lung SCC development through aberrant lipid metabolism. Citation Format: Gongping Shi, Sayantan Banerjee, Xin Li, Gajendra Jogdand, Yongmei Zhao, Kunio Nagashima, Thorkell Andresson, Jyoti Shetty, Bao Tran, Yinling Hu. Lipid-rich foamy macrophages along with CD4 T cell-derived signaling drive aberrant lipid metabolism and are a cause of lung cancer development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1355.

// Sweta Ghosh 1 , Junaid Jibran Jawed 1 , Kuntal Halder 1 , Sayantan Banerjee 1 , Bidisha Paul Chowdhury 1 , Akata Saha 2 , Subir Kumar Juin 1 , Suchandra Bhattacharyya Majumdar 1 , Anamika Bose 2 , Rathindranath Baral 2 and Subrata Majumdar 1 1 Division of Molecular Medicine, Bose Institute, Kolkata, West Bengal 700054, India 2 Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), Kolkata, West Bengal 700026, India Correspondence to: Subrata Majumdar, email: subrata@jcbose.ac.in Keywords: melanoma; ceramide; PKCδ; tumor necrosis factor α; cisplatin Received: April 19, 2018 Accepted: December 04, 2018 Published: December 28, 2018 ABSTRACT Ceramide is one of the important cellular components involved in cancer regulation and exerts its pleiotropic role in the protective immune response without exhibiting any adverse effects during malignant neoplasm. Although, the PKCδ-ceramide axis in cancer cells has been an effective target in reduction of cancer, involvement of PKCδ in inducing nephrotoxicity have become a major questionnaire. In the present study, we have elucidated the mechanism by which cisplatin exploits the ceramide to render cancer cell apoptosis leading to the abrogation of malignancy in a PKCδ independent pathway with lesser toxicity. Our study revealed that cisplatin treatment in PKCδ silenced melanoma cells induces ceramide mediated apoptosis. Moreover, cisplatin induced upregulation of the transcription factor IRF1 leading to the induction of the transcriptional activity of the TNFα promoter was evident from the pharmacological inhibition and RNA interference studies. Increased cellular expression of TNFα resulted in an elevated ceramide generation by stimulating acid-sphingomyelinase and cPLA 2 . Furthermore, reciprocity in the regulation of sphingosine kinase 1 (Sphk1) and sphingosine kinase 2 (Sphk2) during PKCδ independent ceramide generation was also observed during cisplatin treatment. PKCδ inhibited murine melanoma model showed reduction in nephrotoxicity along with tumor regression by ceramide generation. Altogether, the current study emphasized the unexplored signaling cascade of ceramide generation by cisplatin during PKCδ silenced condition, which is associated with increased TNFα generation. Our findings enlightened the detailed mechanistic insight of ceramide mediated signaling by chemotherapeutic drugs in cancer therapy exploring a new range of targets for cancer treatment strategies.

Modeling the dynamics of COVID-19 pandemic spread is a challenging and relevant problem. Established models for the epidemic spread such as compartmental epidemiological models e.g. Susceptible-Infected-Recovered (SIR) models and its variants, have been discussed extensively in the literature and utilized to forecast the growth of the pandemic across different hot-spots in the world. The standard formulations of SIR models rely upon summary-level data, which may not be able to fully capture the complete dynamics of the pandemic growth. Since the disease spreads from carriers to susceptible individuals via some form of contact, it inherently relies upon a network of individuals for its growth, with edges established via direct interaction, such as shared physical proximity. Using individual-level COVID-19 data from the early days (January 30 to April 15, 2020) of the pandemic in India, and under a network-based SIR model framework, we performed state-specific forecasting under multiple scenarios characterized by the basic reproduction number of COVID-19 across 34 Indian states and union territories. We validated our short-term projections using observed case counts and the long-term projections using national sero-survey findings. Based on healthcare availability data, we also performed projections to assess the burdens on the infrastructure along the spectrum of the pandemic growth. We have developed an interactive dashboard summarizing our results. Our predictions successfully identified the initial hot-spots of India such as Maharashtra and Delhi, and those that emerged later, such as Madhya Pradesh and Kerala. These models have the potential to inform appropriate policies for isolation and mitigation strategies to contain the pandemic, through a phased approach by appropriate resource prioritization and allocation.

Antimicrobial Stewardship Program (ASP) is one of the most critical interventions required to halt the growing global antimicrobial resistance. The study aimed to evaluate the effect of trainee driven ASP implementation with limited available resources on outcome variables. An ASP team comprising of infectious diseases trainees and consultants was constituted to conduct stewardship activities in the Department of Medicine, All India Institute of Medical Sciences, a tertiary care apex institute in north India. Prospective audit and feedback were conducted by the team, and the following outcome variables were recorded and analyzed: the practice of sending cultures, appropriateness of prescribed empiric antibiotics, gross antimicrobial consumption and mortality. ASP intervention led to an increase in blood culture positivity rates by two folds (p0.001). The trend of empiric prescription choices gradually shifted over time towards the use of more effective antibiotics according to the local antibiogram. Redundant usage of antibiotics substantially reduced over time. There was no impact of the antimicrobial stewardship program on the all-cause mortality rate. ASP had a significant effect on the practice of sending cultures and appropriateness of antibiotic usage. In resource-limited settings, trainee-driven antimicrobial stewardship program can succeed in inculcating rational practices among fellow residents and practicing physicians.

Bacterial species are hosts to horizontally acquired mobile genetic elements (MGEs), which encode virulence, toxin, antimicrobial resistance, and other metabolic functions. The bipartite genome of Vibrio cholerae harbors sporadic and conserved MGEs that contribute in the disease development and survival of the pathogens. For a comprehensive understanding of dynamics of MGEs in the bacterial genome, we engineered the genome of V. cholerae and examined in vitro and in vivo stability of genomic islands (GIs), integrative conjugative elements (ICEs), and prophages. Recombinant vectors carrying the integration module of these GIs, ICE and CTXΦ, helped us to understand the efficiency of integrations of MGEs in the V. cholerae chromosome. We have deleted more than 250 acquired genes from 6 different loci in the V. cholerae chromosome and showed contribution of CTX prophage in the essentiality of SOS response master regulator LexA, which is otherwise not essential for viability in other bacteria, including Escherichia coli. In addition, we observed that the core genome-encoded RecA helps CTXΦ to bypass V. cholerae immunity and allow it to replicate in the host bacterium in the presence of similar prophage in the chromosome. Finally, our proteomics analysis reveals the importance of MGEs in modulating the levels of cellular proteome. This study engineered the genome of V. cholerae to remove all of the GIs, ICEs, and prophages and revealed important interactions between core and acquired genomes.

The management of patients with brain abscess poses a significant challenge to clinicians in patients with chronic kidney disease. Obtaining a biopsy sample from the affected area is the mainstay in the diagnosis, but it is often unavailable. In most cases, therapy is guided by clinical findings and imaging alone. We discuss three cases of brain abscess- each with a different scenario and discuss the issues faced in management. The first case was a 32-year-old post-renal transplant male patient with a brain abscess due to dematiaceous fungi and was treated with amphotericin. The second case was a 42-year-old female patient with stage 5 chronic kidney disease on maintenance hemodialysis who presented with a brain abscess due to suspected fungal infection based on imaging findings and was managed with antibiotics and voriconazole. The third case was a 42-year-old post-renal transplant male patient who presented with a brain abscess due to nocardiosis and was managed with cotrimoxazole, meropenem and linezolid. We also summarize the approach to the management of brain abscess in resource-limited settings.

BackgroundCOVID-19 originated in China and has quickly spread worldwide causing a pandemic. Countries need rapid data on the prevalence of the virus in communities to enable rapid containment. However, the equipment, human and laboratory resources required for conducting individual RT-PCR is prohibitive. One technique to reduce the number of tests required is the pooling of samples for analysis by RT-PCR prior to testing.MethodsWe conducted a mathematical analysis of pooling strategies for infection rate classification using group testing and for the identification of individuals by testing pooled clusters of samples.FindingsOn the basis of the proposed pooled testing strategy we calculate the probability of false alarm, the probability of detection, and the average number of tests required as a function of the pool size. We find that when the sample size is 256, using a maximum pool size of 64, with only 7.3 tests on average, we can distinguish between prevalences of 1% and 5% with a probability of detection of 95% and probability of false alarm of 4%.InterpretationThe pooling of RT-PCR samples is a cost-effective technique for providing much-needed course-grained data on the prevalence of COVID-19. This is a powerful tool in providing countries with information that can facilitate a response to the pandemic that is evidence-based and saves the most lives possible with the resources available.FundingBill & Melinda Gates FoundationAuthors contributionsRL and KRN conceived the study. IF, KT, KRN, SB and RL all contributed to the writing of the manuscript and AH and JJ provided comments. KRN and AH conducted the analysis and designed the figures.Research in contextEvidence before this studyThe pooling of RT-PCR samples has been shown to be effective in screening for HIV, Chlamydia, Malaria, and influenza, among other pathogens in human health. In agriculture, this method has been used to assess the prevalence of many pathogens, including Dichelobacter nodosus, which causes footrot in sheep, postweaning multisystemic wasting syndrome, and antibiotic resistance in swine feces, in addition to the identification of coronaviruses in multiple bat species. In relation to the current pandemic, researchers in multiple countries have begun to employ this technique to investigate samples for COVID-19.Added value of this studyGiven recent interest in this topic, this study provides a mathematical analysis of infection rate classification using group testing and calculates the probability of false alarm, the probability of detection, and the average number of tests required as a function of the pool size. In addition the identification of individuals by pooled cluster testing is evaluated.Implications of all the available evidenceThis research suggests the pooling of RT-PCR samples for testing can provide a cheap and effective way of gathering much needed data on the prevalence of COVID-19 and identifying infected individuals in the community, where it may be infeasible to carry out a high number of tests. This will enable countries to use stretched resources in the most appropriate way possible, providing valuable data that can inform an evidence-based response to the pandemic.

A novel coronavirus (nCoV) spillover event, with its epicenter in Wuhan, People's Republic of China, has emerged as a public health emergency of international concern. This began as an outbreak in December 2019, and till February 28, 2020, there have been 83,704 confirmed cases of novel coronavirus disease 2019 (COVID-19) globally, with 2,859 deaths, resulting in an overall case fatality rate of 3.41 per cent (95% confidence interval 3.29-3.54%). By this time (February 28, 2020) 58 countries or territories and one international conveyance (Diamond Princess Cruise Ship) were affected. As a part of the global response to manage and contain the pandemic, major emphasis was placed on generating research intelligence to guide evidence-based responses to contain the virus, which was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), owing to its genetic similarities with the SARS virus. This review summarizes the emerging evidence which can help guide the public health response, particularly in India. Key areas have been identified in which research needs to be conducted to generate critical intelligence for advising prevention and control efforts. The emergence of SARS-CoV-2 has once again exposed the weaknesses of global health systems preparedness, ability to respond to an infectious threat, the rapidity of transmission of infections across international borders and the ineffectiveness of knee-jerk policy responses to emerging/re-emerging infectious disease threats. The review concludes with the key learning points from the ongoing efforts to prevent and contain COVID-19 and identifies the need to invest in health systems, community-led response mechanisms and the need for preparedness and global health security.

Introduction: Increasing occurrence of infections caused by multidrug-resistant Gram-negative bacteria resulted in colistin being the last agent for treatment. Apart from plasmid-mediated mcr genes, mutations involving several genes like mgrB, phoP/phoQ, pmrA, pmrB, pmrC, and crrABC genes, are leading causes of colistin resistance. Four colistin susceptibility testing methods were compared against broth microdilution (BMD) and determined the presence of the mcr1-5 gene. Methodology: A total of 100 carbapenem-resistant Enterobacterales isolates were tested for colistin susceptibility by commercial broth microdilution (cBMD), E-test, VITEK-2, and rapid polymyxin NP assay (RPNP) and compared with BMD. The presence of the mcr1-5 gene was determined by modified RPNP and PCR. Two non- mcr colistin-resistant XDR isolates were subjected to whole-genome sequencing using Illumina MiSeq sequencing platform. Results: Among 100 carbapenem-resistant Enterobacterales isolates, 15% were resistant to colistin. Essential agreement, categorical agreement, major error, and very major error for cBMD/E-test/VITEK-2/RPNP were 96%/73%/82%/NA; 99%/86%/88%/91%, 1.2%/9.4%/11.8%/8.2% and 0%/40%/13.3%/13.3%, respectively. Only one Klebsiella pneumoniae isolate harbored the mcr-1 gene, observed by both methods. Whole-genome sequencing of two non- mcr XDR Klebsiella pneumoniae showed multiple mutations in 10 genes responsible for lipopolysaccharide biosynthesis. Conclusions: The performance of cBMD was excellent, whereas the E-test was unacceptable. VITEK-2 and RPNP performed better but remained unreliable due to high error rates. Multiple mutations in the target proteins involving lipopolysaccharide formation, modification, and regulation were seen, resulting in colistin resistance.

NOD like receptors (NLR) are essential pathogen associated molecular pattern receptors of cytoplasmic origin. During several intracellular parasitic infections NLR played vital role for host protective immune response against the pathogen. Amongst various classes of NLR, NOD1 and NOD2 had been extensively studied and were found to be the most active member of the NLR family. Therefore, we wanted to study the role of NOD1/NOD2 during Leishmania donovani infection and the mechanism behind the utilization of this pathway as a therapeutic approach. Using the infected model of macrophage and BALB/c mice the expression of NOD1 and NOD2 were analysed. Our study showed that NOD2 but not NOD1 has been exploited during experimental VL, leading to the imbalance between Th-1/Th-2 cytokines profile. Over-expression of NOD2 and stimulation with its ligand muramyl dipeptide leads to successful clearance of parasite. During in vivo experiments we found that arabinosylated lipoarabinomannan helps in the restoration of NOD2 and with MDP in combination leads to effective clearance of parasite which rescued host protective immunity and comparatively more effective than Mw and MDP combination resulting in increase T cell response. Consequently, our study highlighted the significance of NOD2 during infection the immune-modulations of which can be used as a therapeutic target.