Incidence of Different Characters of Neuropathic Pain in Cancer Patients Coming to Tertiary Care Centre in North India Over A Period of 1 Year - An Observational Study.

Objectives: Pain is classified as nociceptive, neuropathic, or nociplastic. Neuropathic pain presents as variable phenotypes (characters) based on specific aetiology and pathophysiology. This study aimed to find out among cancer patients the incidence of different phenotypes of neuropathic pain and form specific phenotypic clusters based on the underlying neurophysiology and association of sensory profile with various organ systems - A prospective observational study. Materials and methods: The Institutional Ethical Committee clearance (IEC code: 2020-49-MD-EXP-15) https://ctri.nic.in/Clinicaltrials/showallp.php?mid1=44886&EncHid=88651.15716&userName=CTRI/2020/09/027964 approval was obtained. After written and informed consent, patients of age group 18-80 years, registering in the pain and palliative outpatient department or radiotherapy department with complaints of pain and not taking any anti-neuropathic pain medications, were enrolled. They were assessed using Leeds assessment of neuropathic symptoms and signs (LANSS) pain score, and a score of >12 was eligible for assessment of neuropathic pain phenotypes. Results: Out of 210 cancer patients complaining of pain, a neuropathic component with LANSS >12 was found in 73 (34.76%). The most predominant phenotypes, allodynia> tingling> pricking = burning, were found in 72.60%, 56.16%, and 43.84% of patients, respectively. Phenotypes were clustered into Nodes 1 and 2 based on clinically significant separation of phenotypes. Node 1 had neuropathic pain of spontaneous origin found predominantly in gastrointestinal tract (GIT) and genitourinary tract (GUT) cancers. Node 2 had stimulus-evoked negative and positive characters which occurred in head and neck, thoracic, and spinal metastatic cancers. Conclusion: Careful patient assessment reveals the incidence of neuropathic pain in 34.76%; allodynia and tingling astable the most prominent phenotypes. Broadly, sensory characters were clustered into spontaneous and stimulus-evoked sensations with GIT and GUT cancers presenting with Node 1 symptoms.

Microbiome interactions with different risk factors in development of myocardial infarction.

Among all non-communicable diseases, Cardiovascular Diseases (CVDs) stand as the leading global cause of mortality. Within this spectrum, Myocardial Infarction (MI) strikingly accounts for over 15 % of all deaths. The intricate web of risk factors for MI, comprising family history, tobacco use, oral health, hypertension, nutritional pattern, and microbial infections, is firmly influenced by the human gut and oral microbiota, their diversity, richness, and dysbiosis, along with their respective metabolites. Host genetic factors, especially allelic variations in signaling and inflammatory markers, greatly affect the progression or severity of the disease. Despite the established significance of the human microbiome-nutrient-metabolite interplay in associations with CVDs, the unexplored terrain of the gut-heart-oral axis has risen as a critical knowledge gap. Moreover, the pivotal role of the microbiome and the complex interplay with host genetics, compounded by age-related changes, emerges as an area of vital importance in the development of MI. In addition, a distinctive disease susceptibility and severity influenced by gender-based or ancestral differences, adds a crucial insights to the association with increased mortality. Here, we aimed to provide an overview on interactions of microbiome (oral and gut) with major risk factors (tobacco use, alcohol consumption, diet, hypertension host genetics, gender, and aging) in the development of MI and therapeutic regulation.

Androgen deprivation triggers a cytokine signaling switch to induce immune suppression and prostate cancer recurrence.

Androgen deprivation therapy (ADT) is an effective but not curative treatment for advanced and recurrent prostate cancer (PC). We investigated the mechanisms controlling the response to androgen-deprivation by surgical castration in genetically-engineered mouse models (GEMM) of PC, using high frequency ultrasound imaging to rigorously measure tumor volume. Castration initially causes almost all tumors to shrink in volume, but many tumors subsequently recur within 5-10 weeks. Blockade of tumor necrosis factor (TNF) signaling a few days in advance of castration surgery, using a TNFR2 ligand trap, prevents regression in a PTEN-deficient GEMM. Following tumor regression, a basal stem cell-like population within the tumor increases along with TNF protein levels. Tumor cell lines in culture recapitulate these in vivo observations, suggesting that basal stem cells are the source of TNF. When TNF signaling blockade is administered immediately prior to castration, tumors regress but recurrence is prevented, implying that a late wave of TNF secretion within the tumor, which coincides with the expression of NFkB regulated genes, drives recurrence. The inhibition of signaling downstream of one NFkB-regulated protein, chemokine C-C motif ligand 2 (CCL2), prevents post-castration tumor recurrence, phenocopying post-castration (late) TNF signaling blockade. CCL2 was originally identified as a macrophage chemoattractant and indeed at late times after castration gene sets related to chemotaxis and migration are up-regulated. Importantly, enhanced CCL2 signaling during the tumor recurrence phase coincides with an increase in pro-tumorigenic macrophages and a decrease in CD8 T cells, suggesting that recurrence is driven at least in part by tumor immunosuppression. In summary, we demonstrate that a therapy-induced switch in TNF signaling, a consequence of the increased stem cell-like character of the residual tumor cells surviving ADT, induces an immunosuppressive tumor microenvironment and concomitant tumor recurrence.

How Does Tobacco Use Affect the Cognition of Older Adults? A Propensity Score Matching Analysis Based on a Large-Scale Survey.

INTRODUCTION: Tobacco is a well-established risk factor for cancer, but its association with other morbidities needs consideration. The low-income and middle-income countries (LMICs) with unprecedented demographic transformation lack evidence on tobacco use and its impact on cognitive health. AIMS AND METHODS: Using a propensity score matching approach, we utilized data from the Longitudinal Ageing Study of India. Study employed 1:1 nearest neighbor matching with the replacement methodology. We estimated the odds of the poor cognitive score and tobacco use among older adults based on five different models for ever tobacco user, former tobacco user, current tobacco user, current smokers, and current smokeless tobacco users with reference to never tobacco users. RESULTS: The estimated average treatment effect for the treated and the untreated group has shown a higher likelihood of cognitive decline among ever (OR -0.26; 95%CI -0.43 to -0.09), current (OR -0.28; 95%CI -0.45 to -0.10), and former (OR -0.53; 95%CI -0.87 to -0.19) tobacco users compared to never tobacco users. The finding further suggests the odds of lower cognitive scores among older adults who were smokers (OR -0.53; 95%CI -0.87 to -0.19) and smokeless tobacco users (OR -0.22; 95%CI -0.43 to -0.01) as compared to never tobacco users. CONCLUSIONS: Interventions designed to prevent the incidence of cognitive impairment should focus on limiting the use of tobacco. Strategies under the tobacco-free generation initiative should be amplified in order to prevent future generations from productivity loss, premature ageing and to promote healthy aging. IMPLICATIONS: Evidence of a definitive association between tobacco consumption and cognition among older adults is sporadic in LMICs. Though tobacco is a risk factor for various diseases including cancer, the extent of its impact on cognitive health among the older population is limited. This study contributes to the existing literature by highlighting poor cognitive outcomes among older adults who smoke tobacco and/or consume smokeless tobacco as compared to never-tobacco users. Our findings emphasize the need to accelerate programmes related to tobacco-free generation in LMICs to reach a higher quality of life and healthy aging in pursuit of achieving the sustainable development goal of "good health and well-being."

Characterization of physiochemical parameters & their effect on microbial content of smokeless tobacco products marketed in north India.

BACKGROUND OBJECTIVES: Smokeless tobacco (SLT) product consumption has profound public health implications for its users. The p H and moisture of SLTs determine the bioavailability of nicotine, the microbial structure dynamics and the amount of microbial conversion of tobacco alkaloids to carcinogenic tobacco-specific nitrosamines. This study aimed to characterize and compare the p H, moisture and alkaloid content of various SLT products. METHODS: Thirty-seven SLT samples including khaini , snus, moist snuff, gul , pan masala , zarda , Mainpuri kapoori and qiwam were collected from the retail market around the National Capital Region in north India and their p H, moisture, nicotine and alkaloid content were measured. The p H and total nicotine were used to calculate the amount of free nicotine, the readily absorbed form, for each product by applying the Henderson-Hasselbalch equation. RESULTS: The investigation showed that the SLTs varied drastically in their p H (5.36 to 10.27), moisture content (4.7 to 51.7%) and alkaloid content (0.82 to 35.87 mg/g). The p H and free nicotine levels of a product were found to be positively correlated, and the highest free nicotine content was reported in snus samples. Further, the moisture content was seen to impact the bacterial and fungal diversity in these samples. INTERPRETATION CONCLUSIONS: Studies to detect the presence of pathogenic microbiological genera as well as potentially toxic constituents are warranted. The use of SLTs as an alternative to cigarette smoking should be discouraged, and cessation programmes must call attention to their detrimental effects and emphasize on benefits of quitting SLT consumption.

Tobacco exposure among antenatal women in India: Challenges in tobacco screening & cessation counselling.

Links between tobacco use and poor pregnancy outcomes are well established. Despite various tobacco control measures taken by the government, nearly 5-8 per cent of pregnant women consume tobacco in India. Antenatal check-ups are an opportunity to assess and assist women in quitting tobacco during pregnancy. This review highlights the challenges faced in identifying pregnant tobacco users and providing cessation counselling to them in a formal healthcare setup in the Indian context. For this narrative review, open access databases like PubMed and Google Scholar were searched, using the following search terms: challenges, quitting tobacco use, smokeless tobacco, pregnancy and India. Original articles published between 2010 and July 2022 were included in the English language with available free full text. Out of the thirty articles found to be eligible, seven were included in the review. Official websites of the National Health Mission and National Tobacco Control Programme were also searched to retrieve available data on health education and training material for healthcare workers: medical officers, Auxiliary Nurse and Midwives (ANMs), Accredited Social Health Activists (ASHAs) and list of tobacco cessation centres. This review identified the factors such as myths surrounding tobacco use, lack of targeted screening, inadequate training of healthcare workers and inaccessibility of cessation services, which are posing as challenges in controlling tobacco use in this vulnerable section of the population. Specific strategies to address these issues at the micro, meso and macro levels can prove to be vital in controlling tobacco use in pregnant women. This review also identified the vital role of gynaecologists and healthcare workers such as ANMs and ASHA in identifying and providing brief tobacco cessation counselling to pregnant users.

Trends in age of tobacco use initiation over time in Bangladesh, India and Pakistan: analysis of cross-sectional nationally representative surveys.

OBJECTIVE: Tobacco use begins at an early age and typically leads to a long-term addiction. The age of initiation for tobacco use is not well studied in South Asia, where 22% of tobacco smokers and 81% of smokeless tobacco (SLT) users reside. METHODS: Data from the nationally representative Global Adult Tobacco Surveys in India, Bangladesh and Pakistan were analysed to examine patterns of initiation among smokers and smokeless tobacco users. RESULTS: Data on 94 651 individuals were analysed, of which 13 396 reported were ever daily smokers and 17 684 were ever SLT users. The proportion of individuals initiating tobacco use before the age of 15 years has increased over time. The rates of SLT initiation among those aged 15-24 years increased markedly in Bangladesh (by 7.8%) and Pakistan (by 37.7%) between 1983 and 1999-2000. Among males, the increase in SLT initiation was higher in individuals aged below 15 years compared with other age groups in India and Bangladesh. Smoking initiation among females aged below 15 years has also significantly increased in India over time. Compared with the initiation of tobacco smoking before the age of 15 years, a greater increase in the proportion of SLT users was observed in urban areas. CONCLUSION: Our findings indicate that the proportion of youth initiating tobacco (both smoking and smokeless) before the age of 15 years has increased over time in all three countries. Moreover, variations in age at initiation for different types of tobacco products across countries, and by rurality, were noticeable. Younger youths (aged up to 15 years) should therefore be a priority population for tobacco control interventions. Strategies such as raising the legal age of tobacco sale and use to 21 years, and, other measures under WHO Framework Convention on Tobacco Control (FCTC), may prevent underage use and avert lifelong addiction to tobacco products.

Non-Small Cell Lung Cancer: Targetable Variants in Concurrent Tissue and Liquid Biopsy Testing in a North Indian Cohort.

OBJECTIVES: Testing for EGFR, ALK, ROS1 and MET alterations in paired tissue and plasma samples of treatment-naïve patients of NSCLC and correlating their status with overall survival. MATERIALS AND METHODS: One hundred treatment-naïve patients were recruited after obtaining informed consent. Ten ml of blood was collected within a period of two weeks from histological diagnosis, prior to the start of any treatment. DNA & RNA extraction was done from formalin-fixed paraffin embedded (FFPE) tissue and total cell-free nucleic acid extraction was done from plasma samples. EGFR mutation, ALK, ROS1 and MET rearrangements were tested by ARMS (Amplification Refractory Mutation System) PCR. All statistical analyses were conducted in R version 4.1.1. RESULTS: A total of 61 cases showed molecular alterations in tissue samples which included EGFR mutations (47), ALK rearrangements (12), ROS1 fusion (2). MET alteration was not detected. Forty-three cases showed EGFR mutations in plasma, 26 of which were concurrently positive in tissue. Concordance observed was 62%. ALK-EML4 rearrangement, ROS1 fusion and MET were not detected in plasma samples. Sensitivity and specificity for detection of EGFR mutation in plasma were 55.3% and 67.9% respectively. Univariate Cox regression analysis showed a positive association between EGFR mutation in tissue and overall survival (HR = 0.4; 95% CI: 0.2-0.7; p = 0.003) and improved overall survival in those who received targeted therapy (HR = 0.29; 95% CI: 0.1-0.8; p = 0.02). CONCLUSION: Concurrent testing in tissue and liquid biopsy in NSCLC increased the detection of EGFR mutations (47% to 64%). This has substantial implications in deciding treatment and administration targeted therapy and the consequent overall survival.

A Comparative Study of Morphometric Analysis of Nucleolar Organizer Regions in Oral Leukoplakia and Oral Squamous Cell Carcinoma and Significance of AgNOR as a Diagnostic Tool.

Background Silver stainable nucleolar organizer regions (AgNORs) have proven to exhibit utmost importance due to their higher occurrence in the nucleus especially in malignant cells than in normal. Thus, they assist in the examination of nucleolar structures and variations in nucleolar activity. Aim Quantitative and qualitative analysis in relation to the number and area of AgNOR in tissue sections of the normal oral mucosa (NOM), oral leukoplakia (OL), and oral squamous cell carcinoma (OSCC) was the main aim of the study. Materials & method A total of 50 cases comprising 20 OL with dysplasia, 20 OSCC cases, and 10 samples of normal oral mucosa were taken. Silver nitrate (Sol A) & gelatin (Sol B) solutions were freshly prepared for staining the lesional slides. Results The mean value of nuclear profile area (A Nuc) was comparatively higher in oral leukoplakia i.e. 41.97 and in oral squamous cell carcinoma i.e. 62.36 in comparison to the control group where it was 36.19. The mean value of a single AgNOR profile area per nucleus (A NOR) was found to be comparatively lower in both study groups i.e. oral leukoplakia (2.76) and oral squamous cell carcinoma (1.61) in comparison to the control group (3.45) . The mean value of total AgNOR profile area per nucleus (TA NOR) and the number of profiles of AgNORs per nucleus (n NOR) were found higher in both study groups (oral leukoplakia and oral squamous cell carcinoma) as compared to normal oral mucosa of the control group. However, the findings of all four parameters of morphometric analysis were found to be significantly associated with disorder of oral mucosa i.e. cases of oral leukoplakia and oral squamous cell carcinoma (P value <0.01). Conclusion It can thus be suggested that the mean AgNOR count displayed a higher value in OSCC. Hence, the number of AgNORs in nuclei increases as epithelial cells undergo malignant transformation which is designated that mean AgNOR count may contribute to establishing the prognosis of a lesion.

Estimating the weight of consumed tobacco product waste in various Indian states: a novel method to assess the potential burden of tobacco product waste.

INTRODUCTION: The direct morbidity and mortality caused by tobacco are well documented, but such products also contribute to a range of environmental pollutants resulting from tobacco product waste. No previous studies have yet quantified tobacco product waste in a low-income and middle-income country (LMIC). This study estimates the potential annual waste generated due to consumption of smoked and smokeless tobacco products in India and its states. METHODOLOGY: We systematically collected samples of smoked and smokeless tobacco products from 33 districts of 17 Indian states/union territories. Stratified weights of plastic, paper, foil and filter packaging components, and gross empty package weights were recorded. Prevalence of smoking and smokeless tobacco use at national and state-level estimates was derived from the Global Adult Tobacco Survey (2016-2017) to quantify waste potentially generated by tobacco products. RESULTS: We included 222 brands of tobacco products (70 cigarette, 94 bidi and 58 smokeless tobacco brands) in the final analysis. A total of 170 331 (±29 332) tonnes of waste was estimated to be generated annually, out of which 43.2% was plastic, 3.6% was foil and 0.8% was filter. Two-thirds of the overall waste was contributed by smokeless products alone. Maximum waste was generated in Uttar Pradesh (20.9%; 35 723.7±6151.6 tonnes), Maharashtra (8.9%; 15 116.84±2603.12 tonnes) and West Bengal (8.6%; 14 636.32±2520.37 tonnes). CONCLUSION: This study provides first of its kind national-level evidence on the types (plastic, paper, foil and filter) and quantity of waste potentially generated by use of tobacco products in India. Similar studies from other LMICs can serve to raise consciousness about many negative environmental impacts of tobacco products and need for policies to address them.

Determinants of initiation, continuation and cessation of smokeless tobacco use among pregnant and lactating women: a qualitative study from low-income communities in urban India.

Smokeless tobacco (SLT) consumption increases the risk of cardiovascular diseases and cancer and leads to adverse reproductive health outcomes among women and newborns. This study examines the factors associated with initiation, continuation and cessation of SLT use among women in the reproductive age so as to formulate and include prevention and cessation interventions from its inception. The study was conducted in urban low-income communities in India. Using snowball and purposive sampling techniques, in-depth interviews were conducted with 20 pregnant and 22 lactating women who currently used SLT products. Data were analysed using thematic analysis with the help of QSR NVivo software. Findings revealed that factors such as people influencing usage change with different life stages including pre-marital and post-marital periods. Perceived health benefits, altered taste preferences during pregnancy and social influences were also studied. Women were found to be more aware of the harmful effects of tobacco during pregnancy than during breastfeeding. Social stigma around women consuming tobacco acted as a major driving factor for cessation. Most of the participants were willing to quit but were not aware of any technique or programme for cessation. The findings of the study highlight the need to develop behavioural change intervention tools, which are culturally and locally appropriate and have a gender-sensitive approach. Different socio-cultural factors associated with initiation/cessation at different life stages should also be taken into consideration while developing these tools.

Single-cell profiling reveals inflammatory polarization of human carotid versus femoral plaque leukocytes.

Femoral atherosclerotic plaques are less inflammatory than carotid plaques histologically, but limited cell-level data exist regarding comparative immune landscapes and polarization at these sites. We investigated intraplaque leukocyte phenotypes and transcriptional polarization in 49 patients undergoing femoral (n = 23) or carotid (n = 26) endarterectomy using single-cell RNA-Seq (scRNA-Seq; n = 13), flow cytometry (n = 24), and IHC (n = 12). Comparative scRNA-Seq of CD45+-selected leukocytes from femoral (n = 9; 35,265 cells) and carotid (n = 4; 30,655 cells) plaque revealed distinct transcriptional profiles. Inflammatory foam cell-like macrophages and monocytes comprised higher proportions of myeloid cells in carotid plaques, whereas noninflammatory foam cell-like macrophages and LYVE1-overexpressing macrophages comprised higher proportions of myeloid cells in femoral plaque (P < 0.001 for all). A significant comparative excess of CCR2+ macrophages in carotid versus plaque was observed by flow cytometry in a separate validation cohort. B cells were more prevalent and exhibited a comparatively antiinflammatory profile in femoral plaque, whereas cytotoxic CD8+ T cells were more prevalent in carotid plaque. In conclusion, human femoral plaques exhibit distinct macrophage phenotypic and transcriptional profiles as well as diminished CD8+ T cell populations compared with human carotid plaques.

Halomonas gemina sp. nov. and Halomonas llamarensis sp. nov., two siderophore-producing organisms isolated from high-altitude salars of the Atacama Desert.

Introduction: This study aimed to identify and characterize novel siderophore-producing organisms capable of secreting high quantities of the iron-binding compounds. In the course of this, two not yet reported halophilic strains designated ATCHAT and ATCH28T were isolated from hypersaline, alkaline surface waters of Salar de Llamará and Laguna Lejía, respectively. The alkaline environment limits iron bioavailability, suggesting that native organisms produce abundant siderophores to sequester iron. Methods: Both strains were characterized by polyphasic approach. Comparative analysis of the 16S rRNA gene sequences revealed their affiliation with the genus Halomonas. ATCHAT showed close similarity to Halomonas salicampi and Halomonas vilamensis, while ATCH28T was related closest to Halomonas ventosae and Halomonas salina. The ability of both strains to secrete siderophores was initially assessed using the chromeazurol S (CAS) liquid assay and subsequently further investigated through genomic analysis and NMR. Furthermore, the effect of various media components on the siderophore secretion by strain ATCH28T was explored. Results: The CAS assay confirmed the ability of both strains to produce iron-binding compounds. Genomic analysis of strain ATCHAT revealed the presence of a not yet reported NRPS-dependant gene cluster responsible for the secretion of siderophore. However, as only small amounts of siderophore were secreted, further investigations did not lie within the scope of this study. Via NMR and genomic analysis, strain ATCH28T has been determined to produce desferrioxamine E (DFOE). Although this siderophore is common in various terrestrial microorganisms, it has not yet been reported to occur within Halomonas, making strain ATCH28T the first member of the genus to produce a non-amphiphilic siderophore. By means of media optimization, the produced quantity of DFOE could be increased to more than 1000 µM. Discussion: Phenotypic and genotypic characteristics clearly differentiated both strains from other members of the genus Halomonas. Average nucleotide identity (ANI) values and DNA-DNA relatedness indicated that the strains represented two novel species. Therefore, both species should be added as new representatives of the genus Halomonas, for which the designations Halomonas llamarensis sp. nov. (type strain ATCHAT = DSM 114476 = LMG 32709) and Halomonas gemina sp. nov. (type strain ATCH28T = DSM 114418 = LMG 32708) are proposed.

Amyloids and brain cancer: molecular linkages and crossovers.

Amyloids are high-order proteinaceous formations deposited in both intra- and extracellular spaces. These aggregates have tendencies to deregulate cellular physiology in multiple ways; for example, altered metabolism, mitochondrial dysfunctions, immune modulation, etc. When amyloids are formed in brain tissues, the endpoint often is death of neurons. However, interesting but least understood is a close connection of amyloids with another set of conditions in which brain cells proliferate at an extraordinary rate and form tumor inside brain. Glioblastoma is one such condition. Increasing number of evidence indicate a possible link between amyloid formation and depositions in brain tumors. Several proteins associated with cell cycle regulation and apoptotic pathways themselves have shown to possess high tendencies to form amyloids. Tumor suppressor protein p53 is one prominent example that mutate, oligomerize and form amyloids leading to loss- or gain-of-functions and cause increased cell proliferation and malignancies. In this review article, we present available examples, genetic links and common pathways that indicate that possibly the two distantly placed pathways: amyloid formation and developing cancers in the brain have similarities and are mechanistically intertwined together.

Insights from establishing a high throughput viral diagnostic laboratory for SARS-CoV-2 RT-PCR testing facility: challenges and experiences.

Background: The World Health Organization declared the coronavirus disease 2019 (COVID-19) a global pandemic on 11 March 2020. Identifying the infected people and isolating them was the only measure that was available to control the viral spread, as there were no standardized treatment interventions available. Various public health measures, including vaccination, have been implemented to control the spread of the virus worldwide. India, being a densely populated country, required laboratories in different zones of the country with the capacity to test a large number of samples and report test results at the earliest. The Indian Council of Medical Research (ICMR) took the lead role in developing policies, generating advisories, formulating guidelines, and establishing and approving testing centers for COVID-19 testing. With advisories of ICMR, the National Institute of Cancer Prevention and Research (NICPR) established a high-throughput viral diagnostic laboratory (HTVDL) for RT-PCR-based diagnosis of SARS-CoV-2 in April 2020. HTVDL was established during the first lockdown to serve the nation in developing and adopting rapid testing procedures and to expand the testing capacity using "Real-Time PCR." The HTVDL provided its testing support to the national capital territory of Delhi and western Uttar Pradesh, with a testing capacity of 6000 tests per day. The experience of establishing a high-throughput laboratory with all standard operating procedures against varied challenges in a developing country such as India is explained in the current manuscript which will be useful globally to enhance the knowledge on establishing an HTVDL in pandemic or non-pandemic times.

Impact of the COVID-19 pandemic on an online cancer screening training programme for healthcare providers in the public sector in India: learnings from a hub and spoke model perspective.

Introduction: This article elicits our experiences and strategic approaches to ensure the sustainability of the online capacity-building programmes for healthcare providers (HCPs) in comprehensive cancer screening through the 'Hub and Spoke' model during the coronavirus disease (COVID-19) pandemic. Methods: During the first wave of COVID-19, training for three cohorts of medical officers (MO) (Batch-A) was ongoing (May-December 2020). The Indian health system abruptly shifted focus towards containing the COVID-19 spread, leading to new challenges in conducting training courses. A new five-step strategic approach for cohort MO-14 (Batch-B) was adopted to spread awareness about the importance of cancer screening and the roles and responsibilities of HCPs in the implementation and conduct of practical sessions in their states in collaboration with their respective state governments. We also adopted social media - WhatsApp for official communication. Results: Enrolling Batch-B following the new strategic approach reduced refusals by 25% and dropouts by 36% compared to Batch-A. Course compliance and completion was a significant 96% in Batch-B. Conclusion: The COVID-19 pandemic opened a window of opportunity to understand the need for vital changes to improve the quality of our hybrid cancer screening training. Inclusion of the state government in planning and implementing the changes, awareness among HCPs about the importance of training and responsible acceptance of cancer screening, district-wise approach, use of social media in sharing course materials and conducting in-person training in the respective state have demonstrated significant impact on the quality of the training and in scaling-up of cancer screening. Prolonged mentorship, robust Internet connectivity for providers and training on handling gadgets and online video communication would profoundly benefit remote training programmes.A well-devised backup system is essential for training programmes during unforeseen eventualities such as the COVID pandemic.

Rate of castration-induced prostate stroma regression is reduced in a mouse model of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a non-neoplastic proliferative disease producing lower urinary tract symptoms related to the resulting enlarged prostate. BPH is pathologically characterized by hyperplastic growth in both epithelial and stromal compartments. Androgen signaling is essential for prostate function and androgen blockade is the second-line medical therapy to relieve symptoms of BPH. Here we examined the prostates of probasin promoter-driven prolactin (Pb-PRL) transgenic mice, a robust model of BPH that spontaneously develops prostate enlargement, to investigate prostate regression in response to surgical castration. Serial ultrasound imaging demonstrated very uniform self-limited growth of Pb-PRL prostate volume that is consistent with the benign, limited cellular proliferation characteristic of BPH and that contrasts with the highly variable, exponential growth of murine prostate cancer models. Castration elicited only a partial reduction in prostate volume, relative to castration-induced regression of the normal prostate gland. The anti-androgen finasteride induced a diminished reduction of Pb-PRL prostate volume versus castration. The limited extent of Pb-PRL mouse prostate volume regression correlated with the initial volume of the stromal compartment, suggesting a differential sensitivity of the epithelial and stromal compartments to androgen withdrawal. Indeed, two-dimensional morphometric analyses revealed a distinctly reduced rate of regression for the stromal compartment in Pb-PRL mice. The myofibroblast component of the Pb-PRL prostate stroma appeared normal, but the stromal compartment contained more fibroblasts and extracellular collagen deposition. Like normal prostate, the rate of regression of the Pb-PRL prostate was partially dependent on TGFß and TNF signaling, but unlike the normal prostate, the extent of castration-induced regression was not affected by TGFß or TNF blockade. Our studies show that androgen deprivation can effectively reduce the overall volume of hyperplastic prostate, but the stromal compartment is relatively resistant, suggesting additional therapies might be required to offer an effective treatment for the clinical manifestations of BPH.

Smokeless tobacco use and public health nutrition: a global systematic review.

OBJECTIVE: Tobacco consumption among low- and middle-income countries where food insecurity remains a challenge poses several concerns. This review examines the available global evidence linking smokeless tobacco (SLT) use with public health nutrition and its implications. DESIGN: Systematic review of articles extracted from PubMed and Scopus from January 2000 to December 2020. SETTING: Included studies that demonstrated the relationship between SLT and nutrition-related factors, that is, BMI, malnutrition, anaemia, poor birth outcomes and metabolic disorders. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines have been followed to conduct the systematic evidence review. PARTICIPANTS: A total of thirty-four studies were finally used in the systematic review, which included cross-sectional (thirty-one) and cohort (three). RESULTS: SLT use has a huge impact on body weight, alteration in taste, poor oral health, and consumption of fruits and vegetables leading to malnutrition. Maternal use of SLT not only leads to anaemia but also hampers birth outcomes. Increased risk of metabolic syndrome and gallstone disease among SLT users are also well documented in the studies. CONCLUSION: The review highlights the linkages between SLT usage and poor nutritional outcomes. Tobacco control efforts should be convergent with public health nutrition to achieve overall health benefits. Attention is also required to explore suitable mechanisms for SLT cessation combined with enhancing food and nutrition security at the community level in sync with investments in public health nutrition intervention.