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Purpose: While there is concern about degenerative tissue effects of exposure to space radiation during deep-space missions, there are no pharmacological countermeasures against these adverse effects. γ-Tocotrienol (GT3) is a natural form of vitamin E that has anti-oxidant properties, modifies cholesterol metabolism, and has anti-inflammatory and endothelial cell protective properties. The purpose of this study was to test whether GT3 could mitigate cardiovascular effects of oxygen ion (16O) irradiation in a mouse model. Materials and methods: Male C57BL/6 J mice were exposed to whole-body 16O (600 MeV/n) irradiation (0.26–0.33 Gy/min) at doses of 0 or 0.25 Gy at 6 months of age and were followed up to 9 months after irradiation. Animals were administered GT3 (50 mg/kg/day s.c.) or vehicle, on Monday – Friday starting on day 3 after irradiation for a total of 16 administrations. Ultrasonography was used to measure in vivo cardiac function and blood flow parameters. Cardiac tissue remodeling and inflammatory infiltration were assessed with histology and immunoblot analysis at 2 weeks, 3 and 9 months after radiation. Results: GT3 mitigated the effects of 16O radiation on cardiac function, the expression of a collagen type III peptide, and markers of mast cells, T-cells and monocytes/macrophages in the left ventricle. Conclusions: GT3 may be a potential countermeasure against late degenerative tissue effects of high-linear energy transfer radiation in the heart.

Several male breast cancer (MBC) susceptibility genes have been identified, but the MBC risk for individuals with a pathogenic variant in each of these genes (i.e., penetrance) remains unclear. We conducted a systematic review of studies reporting the penetrance of MBC susceptibility genes to better summarize current estimates of penetrance. A search query was developed to identify MBC-related papers indexed in PubMed/MEDLINE. A validated natural language processing method was applied to identify papers reporting penetrance estimates. These penetrance studies’ bibliographies were reviewed to ensure comprehensiveness. We accessed the potential ascertainment bias for each enrolled study. Fifteen penetrance studies were identified from 12,182 abstracts, covering five purported MBC susceptibility genes: ATM, BRCA1, BRCA2, CHEK2, and PALB2. Cohort (n = 6, 40%) and case–control (n = 5, 33%) studies were the two most common study designs, followed by family-based (n = 3, 20%), and a kin-cohort study (n = 1, 7%). Seven of the 15 studies (47%) adjusted for ascertainment adequately and therefore the MBC risks reported by these seven studies can be considered applicable to the general population. Based on these seven studies, we found pathogenic variants in ATM, BRCA2, CHEK2 c.1100delC, and PALB2 show an increased risk for MBC. The association between BRCA1 and MBC was not statistically significant. This work supports the conclusion that pathogenic variants in ATM, BRCA2, CHEK2 c.1100delC, and PALB2 increase the risk of MBC, whereas pathogenic variants in BRCA1 may not be associated with increased MBC risk.

Aim To compare the demographic, clinical, laboratory and radiological parameters of patients with different clinical outcomes (death or discharge) and analyse them to find out the potential predictors for mortality in children hospitalised with SARS-CoV-2 infection. Methods Retrospective chart review of all patients less than 18 years of age with laboratory-confirmed SARS-CoV-2 infection and requiring hospital admission between 16 April 2020 and 31 October 2020. Results Of 255 children with SARS-CoV-2 infection, 100 patients (median age 62.5 months, 59% males, 70% with moderate to severe disease) were hospitalised, of whom 27 died (median age 72 months, 59% males and 30% severely underweight). The subgroup with comorbidities (n = 14) was older (median age 126 months) and had longer duration of stay (median 10 days). Fever and respiratory symptoms were comparable while gastrointestinal symptoms were more common among non-survivors. Hypoxia at admission (odds ratio (OR) 5.48, P = 0.001), multiorgan dysfunction (OR 75.42, P = 0.001), presence of acute kidney injury (OR 11.66, P = 0.001), thrombocytopenia (OR 4.40, P = 0.003) and raised serum C-reactive protein (CRP) (OR 4.69, P = 0.02) were independently associated with mortality. The median time from hospitalisation to death was 3 days. The deceased group had significantly higher median levels of inflammatory parameters and a higher incidence of complications (myocarditis, encephalitis, acute respiratory distress syndrome and shock). Conclusions Hypoxia at admission, involvement of three or more organ systems, presence of acute kidney injury, thrombocytopenia and raised serum C-reactive protein were found to be independently associated with increased odds of in-hospital mortality in children admitted with SARS-CoV-2 infection.

Background: Malnutrition in children < 5 years is a public health concern due to its associated high morbidity, mortality and serious long-term consequences. The World Health Organization (WHO) recommends 10 steps for the management of severe acute malnutrition (SAM) children which also involves correction of electrolyte disturbances. Treatment with diets having inadequate amounts of minerals like phosphate can result in refeeding syndrome and other abnormalities. We conducted the study among children with medically complicated SAM to evaluate their serum phosphate levels after receiving locally prepared therapeutic feeds and its associations of other factors. Methods: The study was conducted with 120 hospitalized SAM children aged 6 - 59 months with presence of other illnesses. All children were managed according to the WHO protocol and facility-based management of SAM guidelines of the government of India. Basic demographic details of the child were recorded. Weight of the child was recorded daily, while length/height and mid-upper arm circumference (MUAC) were recorded weekly. We evaluated changes in serum phosphate levels at three time points: on admission, during transition and at discharge. Binary logistic regression analysis was conducted to assess the association of hypophosphatemia with several other indicators. Results: Mean serum phosphate was 4.38 ± 1.07, 4.48 ± 1.16 and 5.13 ± 1.10 mg/dL on admission, during transition and at discharge, respectively. Hypophosphatemia was present among 30 (25%) children on admission, 28 (23.3%) children during transition and 10 (8.3%) children at discharge, which showed a decrease in the prevalence of hypophosphatemia from admission to transition and discharge using the current treatment. The finding also showed positive and significant changes in serum phosphate levels among children who were admitted without edema compared to those admitted with edema. Binary logistic regression estimates showed that older children, children with lower WAZ, hypokalemia, hyponatremia and anemia had higher odds of hypophosphatemia. Male children had lower odds of hypophosphatemia. Conclusion: The nutritional therapy with locally prepared starter and catch-up diet was effective in normalizing hypophosphatemia in the majority of children treated. Serum potassium and serum sodium levels were significantly associated with serum phosphate, indicating the need for careful monitoring of serum phosphate in the presence of hypokalemia and hyponatremia among SAM children. Int J Clin Pediatr. 2021;10(2-3):35-42 doi: https://doi.org/10.14740/ijcp458

Objective To detail clinical profile and outcome in children infected with SARS-CoV-2. Methods This retrospective study was undertaken at a tertiary care pediatric teaching hospital in Northern India. The data on clinical characteristics and outcome of children ( 10 y of age with malnutrition and comorbid illness. Supplementary Information The online version contains supplementary material available at 10.1007/s12098-021-03822-5.

OBJECTIVE To assess the point prevalence of peripheral neuropathy (PN) in children with type 1 diabetes mellitus (T1DM) and to determine their predictors. METHODS In this cross-sectional study, children aged 8-18 y with T1DM on insulin therapy for > 2 y and free from acute complications were enrolled. All participants were evaluated for symptoms of PN with diabetic neuropathy symptom (DNS) score and underwent a detailed neurological examination. Assessment of nerve dysfunction was done using nerve conduction studies (NCS). The disease-related factors that increase the risk of PN were determined. RESULTS Fifty children (52% boys) were enrolled with mean age of 12.2 ± 2.8 y and duration of diabetes 5.1 ± 2.1 y. No subject had clinical evidence or DNS score suggestive of PN. Twenty-eight (56%) children demonstrated subclinical neuropathy on NCS. Proportion of children with pure motor, pure sensory, and mixed motor-sensory neuropathy was 40%, 2%, and 14%, respectively. The peroneal nerve was the most common motor nerve affected. Poor glycemic control (HbA1c > 9%) and longer duration of diabetes (> 5 y) were significantly associated with the risk of PN (p value < 0.05). CONCLUSION A large proportion of children with T1DM have subclinical PN. Poor glycemic control and longer duration of diabetes are risk factors for nerve dysfunction. Neurophysiological studies should be performed in these children to facilitate early detection.

Introduction It has always been a concern of ENT surgeon to prevent post operative complications like nasal bleeding, septal hematoma and septal abscess after septoplasty. Traditionally nasal packing has been done to avoid these complications. Although the nasal pack itself has been a concern for several reasons, packing apart from causing breathing distress, has resulted in epiphora, dysphagia, sleep disturbance, post-operative pain, headache, septal infection, septal abscess and even toxic shock syndrome. Materials and Methods This study has compared the efficacy of a newly designed septal splint with clip with nasal packs. This study was done on 60 patients, nasal packing was done in 30 patients and septal splints with clip were applied in 30 patients. Results Post-operative pain, epiphora, dysphagia, dryness of mouth and sleep disturbance was found to be significantly less in patients with septal splints with clip as compared to those with nasal packing. Conclusion Septal splints with clip is more efficacious alternative to nasal packing in patients undergoing septoplasty.

Objective To study the various comorbidities and their impact on outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected children. Methodology Review of medical records of 120 children (58.4% males), aged 1 month to 18 years, admitted between 1 March and 31 December, 2020 with at least one positive RT-PCR test for SARS-CoV-2. Clinical and demographic variables were compared between children with and without co-morbidities. Results 62 (51.7%) children had comorbidities. The most common comorbidity was tuberculosis (32.3%) followed by other infections (27.4%) and hematological (19.4%) conditions. Fever (89.2%) was the most common clinical feature followed by respiratory (52.5%) and gastrointestinal (32.5%) manifestations. There was no significant difference in the severity of COVID illness, length of hospital stay and adverse outcomes (ventilation and mortality) among children with and without comorbidities. Conclusions The presence of a comorbid illness in pediatric inpatients with COVID-19 did not impact the illness severity, length of hospitalization, ventilation requirement and mortality.

Ayurveda is an ancient science of life which deals with physical, mental and spiritual health of human being. Agad tantra is one of the 8 branches of Ayurveda which deals with the study of poisons and its treatment. Madya affect the mind causing inebriation, enhance Tamo guna and affect the intellect the person. Alcohol is a substance which leads to the mal-functioning of the body’s functions which are Dosha, Dhatu and Mala and make them abnormal. The term ‘Madya’ is an indicative word to all of alcoholic beverages mentioned in Ayurveda, the method of preparing alcoholic beverages was a part of culture in this region of world going as far back as the time of Rigveda (3000 B.C.).

Objectives To assess pubertal development and its determinants in adolescents with transfusion-dependent thalassemia (TDT). Methods In this cross-sectional study from a tertiary teaching hospital in Delhi, records of adolescents aged 17-19 years with TDT on regular transfusion at thalassemia day-care centre were reviewed. Pubertal development and its determinants were assessed. Results Records of 58 (33 male) adolescents with TDT were reviewed. Among them, 42 (72.4%) had normal/delayed onset with spontaneous progression of puberty, while 16 (27.6%) had pubertal arrest/failure and received hormonal replacement therapy (HRT). Short stature was observed in all adolescents on HRT. Amongst other endocrinopathies, only hypoparathyroidism was found to be significantly higher in the HRT group. On multivariate analysis, serum ferritin (OR-1.005, 95% CI 1.002, 1.009) was observed to be the only significant determinant of pubertal arrest/failure. Conclusions A significant proportion of adolescents with TDT continue to have pubertal arrest/failure. High systemic iron load is the key determinant for this.

Background: Family history is one of the strongest predisposing factors for male breast cancer (MBC). Several MBC susceptibility genes have been identified, but the risk of MBC for individuals with a pathogenic variant in these genes (i.e., penetrance) remains unclear. We conducted a systematic review of studies reporting the penetrance of MBC susceptibility genes. Methods: A search query was developed to identify MBC-related abstracts indexed in PubMed, with the followings structure: "Breast Neoplasms, Male"[Mesh] OR (((“Men”[MESH]) OR (male*[TIAB]) OR (man[TIAB]) OR (men[TIAB])) AND ((“Breast Neoplasms”[MESH]) OR (Breast Cancer*[TIAB]) OR (Breast neoplasm*[TIAB]))). A validated natural language processing (NLP) method was applied to retrieve and classify abstracts reporting penetrance estimates. Abstracts labeled as relevant were manually reviewed. The full-text papers of identified penetrance studies were then annotated to extract MBC risk data. These penetrance studies’ bibliographies were also reviewed to ensure comprehensiveness. Results: We identified 17 penetrance studies from 11,799 abstracts, covering five MBC susceptibility genes: ATM, BRCA1, BRCA2, CHEK2, and PALB2 (Table 1). 53% of these studies were case-control studies, while the rest were cohort studies. Odds ratio (OR), cumulative risk (CR), and relative risk (RR) were three commonly reported risk measures. For BRCA2, eight out of nine studies reported significantly increased risk of MBC or a lifetime CR of over 6%; only one study reported an increased but not statistically significant risk. For BRCA1, one out of six studies reported an elevated lifetime CR of 5.8%, while a second reported a minor increase (OR=1.49) that was statistically significant. The risks reported in the remaining four studies showed no statistically significant increase in risk. Seven studies reported the penetrance of CHEK2, but the risks diverge between the variants tested (Table 2). All three PALB2 studies reported significantly increased risk, while only one ATM study reported an increased risk of MBC, which did not reach statistical significance. Conclusion: To our knowledge, this review provides the first complete set of reported penetrance data for five MBC susceptibility genes. Contradictory MBC risks (significantly increased risk vs. risks that were not statistically significant) were common, which may be due to the studies’ different ascertainment criteria resulting in risk estimates for differing populations. Risk across these studies cannot be directly compared unless studies adjust for ascertainment, though this cataloging of risk defines our current understanding. Table 1: MBC penetrance studiesGeneNumber of StudiesStudy TypeRisk Estimate ReportedMBC RiskBRCA296 Cohort, 3 Case-controlOR, RR, CRStatistically significant increased risk (or lifetime CR > 6%) in 8/9 studiesCHEK277 Case-controlOR, RRVarying risk by variantBRCA163 Cohort, 3 Case-controlOR, RR, CR, HRStatistically significant increased risk in 1/6 studies, one study report lifetime CR = 5.8%PALB231 Cohort, 2 Case-controlOR, RRStatistically significant increased risk in 3/3 studiesATM11 Case-controlORStatistically significant increased risk in 0/1 studyOR: odds ratio; RR: relative risk; CR: cumulative risk; HR: hazard ratio Table 2: As an example: Reported penetrance of CHEK2 for male breast cancer in studies with varying ascertainment criteriaFirst Author, Year of Publication, Patient Population*Pathogenic VariantNumber of CarriersRisk TypeRisk Estimate (95% CI)Statistical SignificanceMeijers-Heijboer H, 2002, Multiple Countries1100delC57RR10.28 (3.54-29.87)YesSyrjakoski K, 2004, Finland1100delC28OR1.27 (0.04-7.92)NoWasielewski M, 2009, Netherlands1100delC21OR4.1 (1.2-14.3)YesPritzlaff M, 2017, USAAll441OR2.4 (1.4-3.9)Yes1100delC135OR3.8 (1.7-7.8)YesI157T238OR1.3 (0.5-3.0)NoHallamies S, 2017, Finland1100delC30OR4.47 (1.51-13.18)YesI157T104OR1.12 (0.4-3.13)NoLu HM, 2019, USANot specifiedNot specifiedOR1.66 (0.04-10.34)NoKleiblova P, 2019, Czech RepublicTruncations3OR20.21 (3.5-80.0)YesDeleterious missense1OR11.87 (0.25-100.83)NoIntermediate missense2OR1.3 (0.15-5.07)NoNeutral missense2OR9.07 (0.98-40.41)NoOR: odds ratio; RR: relative risk* All studies in Table 2 are case-control studies Citation Format: Reem S Chamseddine, Jin Wang, Kanhua Yin, Preeti Singh, Jingan Zhou, Danielle Braun, Mark E Robson, Kevin S Hughes. Penetrance of male breast cancer susceptibility genes: A systematic review [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-40.

Background: All drugs profoundly modify our biological processes and may manifest as adverse drug reactions (ADRs), which are unpredictable and inevitable consequences. Antibiotics are a common cause of ADR, necessitating stopping or change of antibiotics. The incidence of ADRs increases with the number of drugs prescribed in a prescription, and antibiotics are rarely prescribed as monotherapy.Aim: The study aimed to assess frequency, class of antibiotics, symptoms, causality, the severity of antimicrobial-associated ADRs, and see the demographic distribution.Methods: ADRs were collected and filled in suspected ADR forms and sent via vigiflow to the National Coordination Centre-Pharmacovigilance Programme of India (NCC-PvPI). These ADR reports, termed individual case safety reports (ICSRs), were analyzed from Jan 2016 to Dec 2019.Results: A total of 414 (54.33%) ICSRs of 762 were identified as antimicrobial-associated. Adults in the age group 19–65 years accounted for 345 (83.09%) of ADRs. A total of 192 (46.38%) were males, and 222 (53.14%) were females. Skin and subcutaneous tissue System organ class was involved in 54% of cases. In the causality assessment, 268 (64.49%) were “probable,” 123 (29.71%) were “possible,” and 23 (5.56%) were “certain.” On severity assessment, 256 ADRs (61.83%) were mild, 133 (32.12%) were moderate, and 25 (6.03%) were severe. A total of 54 antimicrobial agents, excluding anti-tubercular drugs, were identified, and antibacterial accounted for 268 (64.73%) ADRs, followed by antiviral 90 (21.73%), antiprotozoal agents 33 (7.97%) antimalarials anti-scabicidal, antifungal accounting for the remaining.Conclusion: Antimicrobials play a crucial role in treating infections, and utmost vigilance during antimicrobials prescription reduces the frequency and severity of the ADRs, thereby reducing the morbidity and mortality and the pharmacoeconomic burden to the health care system. Pharmacovigilance must be boosted to ensure the safe and effective use of antibiotics and reduce the occurrence of ADRs.

OBJECTIVE We sought to assess factors associated with the frequency of self-reported prescription opioid use in persons with migraine, including demographic variables, comorbidities, headache characteristics, and patterns of consultation. BACKGROUND Despite the dose-dependent effect of opioids on migraine progression and the association with negative outcomes, migraine treatment often includes opioids. The Migraine in America Symptoms and Treatment Study focuses on individuals with migraine who receive prescription acute medications, including those receiving and those not receiving opioids. METHODS This web-based panel survey identified people in the United States with migraine using a validated screener. This analysis stratified people with migraine into 4 groups based on days of monthly opioid use: non-opioid users, ≤3 days, 4-9 days, and ≥10 days per month. RESULTS Of 15,133 respondents with migraine, 4701 (31%) reported acute prescription medication use for headache/migraine in the previous 3 months (mean age 45 years, 71.6% [3367/4701] female), of whom 32.5% (1528/4701) reported opioid use. About one-third of respondents with primary care or neurology consults in the prior 6 months reported receiving an opioid, and more than half of respondents (209/391, 53.5%) with a pain clinic consultation did so. Models compared those using opioids ≤3 days/month (879/4701, 18.7%), 4-9 days/month (304/4701, 6.5%), ≥10 days/month (345/4701, 7.3%) to non-opioid users (3173/4701, 67.5%). Compared to non-opioid users, infrequent users (≤3 days/month) were more likely to be male and less likely to have chronic migraine or to screen positive for anxiety and depression; and frequent opioid users (the 4-9 days/month and the ≥10 days/month groups) were more likely to be male, to smoke, to be obese, to report greater pain interference, to have moderate to severe disability, to have symptoms of anxiety and depression, to use fewer triptans and nonsteroidal anti-inflammatory drugs, and to have poor acute treatment optimization. CONCLUSION Among prescription medication users, this cross-sectional analysis shows that increasing use of prescription opioids is associated with male gender, chronic migraine, more severe disability, anxiety and depression, poor acute treatment optimization, and treatment in a pain clinic.

Non-bullous neutrophilic lupus erythematosus is a rare form of cutaneous lupus erythematosus (LE). We hereby present a case of 24-year-old female, known case of discoid LE (DLE) with negative ANA stabilized on hydroxychloroquine for 2 years. She reported new occurrence of erythematous, mildly pruritic, papular lesions and painful mucosal ulceration. The ANA became strongly positive by ELISA and urine showed proteinuria. A provisional diagnosis of Rowell syndrome was made, skin biopsy was taken, and patient started on steroids. Histopathology showed interface vacuolar change and many neutrophils in the dermis with leukocytoclasia without any bulla formation. The skin lesions responded promptly to addition of dapsone following biopsy report. We conclude that the presence of neutrophils associated with interface pathology on biopsy represents a muted form of bullous LE, especially in patients on immunosuppression. This case highlights the importance of histopathologic examination in the evaluation of any new skin lesions in a patient of lupus on therapy.

Many publications have delineated strategies for mental health care to respond to psychological concerns and ramifications related to coronavirus disease 2019 (COVID-19). The current review aims to encapsulate existing guidelines and recommendations of psychological management for mental health care for the general population, health-care professionals, children, and elderly populations, applied to a pandemic in particular reference to COVID-19. The literature on psychological care of such repercussions of COVID-19 was retrieved via a search in PubMed and Google database. Of 91 retrieved initial articles, only 18 were selected for final analysis, which was divided into two categories: (a) guidelines by government/public health bodies (n = 11) and (b) publications in peer-reviewed journals (n = 7). The recommendations can be summed but not limited to psychoeducation from a reliable source, normalization of stress, behavioral activation, scheduling of activities with a bespoke blending of recreational and daily chores, supportive care, staying digitally connected, relaxation techniques, ensuring rest, rotating shifts and short breaks during working hours, curtailing media consumption, fostering community resilience, seeking and sharing support from colleagues/supervisors, avoidance of abusing psychoactive substances, online consultation of mental health professionals on need, and participatory communication in a developmentally appropriate way with children. In the absence of observational and controlled studies on psychological management during pandemic times, we recommend such research soon.

Congenital adrenal hyperplasia (CAH) is an autosomal recessive endocrine disorder which can manifest after birth with ambiguous genitalia and salt-wasting crisis. However, genital ambiguity is not seen in male babies and may be mild in female babies, leading to a missed diagnosis of classical CAH at birth. In this review, we provide a standard operating protocol for routine newborn screening for CAH in Indian settings. A standardization of first tier screening tests with a single consistent set of cut-off values stratified by gestational age is also suggested. The protocol also recommends a two-tier protocol of initial immunoassay/time resolved fluoroimmunoassay followed by liquid chromatography tandem mass spectrometry for confirmation of screen positive babies, wherever feasible. Routine molecular and genetic testing is not essential for establishing the diagnosis in all screen positive babies, but has significant utility in prenatal diagnosis and genetic counseling for future pregnancy.

Background: Folate and vitamin B 12 deficiency can lead to pancytopenia in pregnancy. Some cases of pancytopenia due to COVID-19 infection have also been reported. The two cases that we present are related to the coincidence of pregnancy and deficiency of folic acid and vitamin B12 with COVID-19 infection. Case presentation: A 26-year- woman G3P1L1A1 and 21-year-woman G2P1L1 presented with pancytopenia and mild COVID-19 infection. The antenatal period was uneventful, and both cases also had folate and vitamin B12 deficiency. They received blood products, folic acid, and vitamin B12 supplementation. COVID- 19 infection was managed well with analgesic and vital monitoring. Postpartum hemorrhage occurred in the second case, which was well managed with uterotonics. All laboratory parameters came out to be normal after three months of supplementation of folic acid and vitamin B12. Conclusion: Pancytopenia in pregnancy due to folate and vitamin B12 deficiency and COVID- 19 infection can be easily managed with timely intensive targeted therapy, but we should be extra vigilant while handling such complicated cases, keeping in mind all possible differential diagnoses for pancytopenia.

An 80-year-old lady with uncontrolled type 2 diabetes developed fever and abdominal pain followed by a sudden diminution of vision in her left eye. Right infra-renal abscess accounted for abdominal pain. A metastatic left subretinal abscess was diagnosed subsequently. Medical management for her systemic condition initiated. Vitreous biopsy was performed along-with intravitreal antibiotic administration. Because of no clinical recovery, patient underwent pars plana vitrectomy. Prompt systemic stabilization and a timely surgical intervention in the left eye resulted in a satisfactory visual gain. Metastatic subretinal abscess following a perinephric abscess is rare phenomenon and only a few cases are reported to date.

Objectives The objectives of this study were to determine the rates of nausea, phonophobia, and photophobia reported overall and as the most bothersome symptom (MBS) in individuals with migraine and to identify individual characteristics associated with each of the 3 candidate MBSs. Background The MBS has emerged as an important coprimary efficacy endpoint in clinical trials of acute treatments for migraine, as recommended by the Food and Drug Administration. The current understanding of how persons with migraine designate an associated symptom as the most bothersome has been assessed primarily in the context of randomized trials. Methods Respondents (n = 95,821) in the cross‐sectional, observational Migraine in America Symptoms and Treatment (MAST) study were adults (aged ≥18 years) recruited from a US nationwide online research panel. A validated diagnostic screener identified 15,133 individuals who met modified International Classification of Headache Disorders (ICHD)‐3 beta criteria for migraine and reported at least 1 monthly headache day (MHD) over the previous 3 months. The survey ascertained sociodemographic variables, headache‐related disability, MHDs, cutaneous allodynia, medication overuse, a migraine symptom severity score, pain interference, noncephalic pain, anxiety and depression symptoms, visual aura over the previous year, and acute treatment optimization. The current analysis is based on respondents who also completed a 6‐month follow‐up assessment that included questions about their most bothersome headache symptom. Results A total of 7518 respondents completed the 6‐month follow‐up, and 6045 met inclusion criteria and were included in the analysis. The mean age of respondents was 47 (SD 13.4) years, 76.0% (4596/6045) were women, and 84.8% (5103/6017) were white. Among all respondents, 64.9% reported all 3 migraine symptoms. The MBS was photophobia in 49.1% (2967/6045), nausea in 28.1% (1697/6045), and phonophobia in 22.8% (1381/6045). Respondents reporting photophobia as the MBS were more likely to be men, to be obese, and to report visual aura. Those reporting nausea as the MBS were more likely to be women, to have lower incomes, and to report lower levels of treatment optimization. Respondents reporting phonophobia as the MBS were more likely to have cutaneous allodynia and less likely to have visual aura. Conclusion Most people with migraine in the MAST observational study reported all 3 cardinal symptoms of nausea, photophobia, and phonophobia. As in clinical trials, the most common MBS was photophobia. Patient profiles differed among the groups defined by their MBS.

Cardiovascular disease constitutes an important threat to humans after space missions beyond the Earth's magnetosphere. Epigenetic alterations have an important role in the etiology and pathogenesis of cardiovascular disease. Previous research in animal models has shown that protons and 56Fe ions cause long-term changes in DNA methylation and expression of repetitive elements in the heart. However, astronauts will be exposed to a variety of ions, including the smaller fragmented products of heavy ions after they interact with the walls of the space craft. Here, we investigated the effects of 16O on the cardiac methylome and one-carbon metabolism in male C57BL/6 J mice. Left ventricles were examined 14 and 90 days after exposure to space-relevant doses of 0.1, 0.25, or 1 Gy of 16O (600 MeV/n). At 14 days, the two higher radiation doses elicited global DNA hypomethylation in the 5′-UTR of Long Interspersed Nuclear Elements 1 (LINE-1) compared to unirradiated, sham-treated mice, whereas specific LINE-1 elements exhibited hypermethylation at day 90. The pericentromeric major satellites were affected both at the DNA methylation and expression levels at the lowest radiation dose. DNA methylation was elevated, particularly after 90 days, while expression showed first a decrease followed by an increase in transcript abundance. Metabolomics analysis revealed that metabolites involved in homocysteine remethylation, central to DNA methylation, were unaffected by radiation, but the transsulfuration pathway was impacted after 90 days, with a large increase in cystathione levels at the lowest dose. In summary, we observed dynamic changes in the cardiac epigenome and metabolome three months after exposure to a single low dose of oxygen ions.

One of the major tasks in the society is the enhancement of the cognitive functions, to improve intellectual deficiencies or psychosomatic ailments, hence, improving the quality of life. This new period of therapeutic advances uses various treatments using various sub-disciplines of biomedical engineering and psychology. Neurofeedback (NF) based operant conditioning is one of them. Up till now, many reports have focused on efficacy of NF in context of clinical and non-clinical applications. New advances in cognitive neuroscience and imaging methods have made neuro feedback training (NFT) more efficient. So, there have recently been further developments in traditional NF procedures. A comprehensive review on the recent advancements with major issues and challenges are tabulated. Even though a number of reviews have been proposed in the literature, but not any of the study has executed analysis of the recent advances.

Background: Individually, cognitive behavior therapy (CBT) and paroxetine (PX) are considered as frontline treatments for social anxiety disorder (SAD). However, the possibility of combined interventions of these might be more helpful than either intervention alone has met with mixed reviews. Hence, the goal of the current study was to examine whether combining CBT + PX would be superior to PX alone in the treatment of SAD in various stages of treatment. Methodology: The present study is a single-center, rater-blind, behavioral placebo (Bh. PBO)-controlled study. Sixty-seven participants were prospectively observed in two groups, one receiving CBT + PX and PX + Bh. PBO for 24 weeks. The Social Interaction Anxiety Scale (SIAS) was measured at pre, post (12 weeks), end of booster (24 weeks), and 2-month follow-up (32 weeks) stage. The SIAS was measured at pre, post (12 weeks), end of booster (24 weeks), and 2-month follow-up (32 weeks) stage. Results: Both treatment groups have significant difference in the mean scores of SIAS in posttreatment, booster, and follow-up stages from their respective mean scores at prestage. Mann–Whitney U-test found no significant differences in the mean scores of SIAS between CBT + PX and PX + Bh. PBO at posttreatment and booster phase, whereas a statistically significance difference (P = 0.03) was found in 2-month follow-up stages. Both treatment groups have large effect size in posttreatment and end of booster phase. At 2-month follow-up stage, a large effect size of 1.11 was found in CBT + PX group as compared to medium size of 0.6 in PX + Bh. PBO group. Conclusions: Combined treatment of CBT + PX provided no advantage over PX + Bh. PBO in acute stages of treatment, but the former have significantly better maintenance of treatment gains in 2-month follow-ups than the latter.

Background: Carcinoma of the oral cavity is one of the most common cancers in our country. High mitotic index (MI) rate with growth, proliferation, and carcinoma of tissue linked with a lower survival rate. The combination of MI screening with proliferation and apoptotic assay is more compelling and comprehensive give more conclusion about anti-proliferative targets. Aim: The study aimed to show the impact of the apoptotic index (AI), MI, and turnover index (TI) to access the behavior of the lesion. Materials and Methods: A total of 68 histologically proven cases of premalignant and malignant squamous cell carcinoma were analyzed over a period of 1 year. Biopsy specimen with hematoxylin and eosin-stained sections was evaluated and correlated with different grade of the oral lesion with AI, MI, and TI. Results: Statistical analysis in premalignant between mild, moderate, and severe dysplasia shows no significant difference, whereas premalignant and malignant show a significant difference. Conclusion: Apoptotic, mitotic, and turnover base index can provide useful information and prediction of the nature of the lesion.

Background Acute kidney injury (AKI) has been recognized as a significant risk factor for mortality among adults with severe acute respiratory syndrome coronavirus infection. Aim The aim of this study is to assess the prevalence and risk factors for AKI and mortality in children with coronavirus disease 2019 (COVID19) from a resource-limited setting. Methods Cross-sectional analysis of laboratory confirmed COVID19 children admitted from 1 March to 30 November 2020 in a tertiary care hospital in New Delhi, India was done. Clinical features and associated comorbidities of COVID19 were noted. Baseline serum creatinine (height-independent Hoste’s equation) and peak serum creatinine were used for staging of AKI by the 2012 Kidney Disease Improving Global Outcomes serum creatinine criteria. Univariate analysis and Kaplan–Meier survival analysis were used to compare the overall outcome in the AKI vs. the non-AKI group. Results A total of 64 810 children between 1 month and 18 years visited the hospital; 3412 were tested for suspected COVID19, 295 tested positive and 105 (54% boys) were hospitalized. Twenty-four hospitalized children (22.8%) developed AKI; 8 in Stage 1 (33.3%), 7 in Stage 2 (29.2%) and 9 in Stage 3 (37.5%) respectively. Overall, three patients received KRT. Highest reported mortality was (66.6%) in AKI Stage 3. Risk factors for AKI included associated sepsis (OR 95% CI, 1.22-9.43, p Conclusion AKI is an important modifiable risk factor for mortality in children with COVID19 in a resource-limited setting. Our study supports the strengthening of kidney replacement therapy and its timely initiation to reduce the progression of AKI and thus mortality in children.

A 32-year-old female presented with a sudden loss of vision in the right eye which she had noticed for one week. A week earlier the patient had presented to a physician with a history of sudden ons...

BackgroundPathogenic variants in cancer susceptibility genes can increase the risk of a spectrum of diseases. We aim to evaluate the disease spectrum of breast cancer susceptibility genes (BCSGs) to develop a comprehensive resource of gene-disease associations for clinicians.MethodsThirteen genes (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, RECQL, STK11 and TP53), that have been conclusively established as BCSGs by the Clinical Genome Resource (ClinGen) and the NCCN guidelines, were investigated. For these thirteen genes, potential gene-disease associations were identified and evaluated based on six genetic resources (ClinGen, NCCN, OMIM, Genetics Home Reference, GeneCards and Gene-NCBI) and an additional literature review using a semiautomated natural language processing (NLP) abstract classification procedure.ResultsA total of 40 diseases were confirmed as being associated with one or more of the 13 BCSGs by our evaluation. Malignant diseases including prostate cancer, pancreatic cancer, colorectal cancer, brain tumor, gastric cancer, ovarian cancer, and sarcoma were associated with at least 3 BCSGs. Furthermore, a total of 87 gene-disease associations were confirmed by our evaluation, of which 85% (74/87) were confirmed by ClinGen and/or NCCN. Conversely, 9 gene-disease associations absent from both ClinGen and NCCN were confirmed in the other four genetic resources (≥3) and 4 gene-disease associations were confirmed by the NLP-based procedure.ConclusionThis is the first study to systematically investigate the reported disease spectrum of BCSGs in multiple sources. Our innovative approach provides a general guide for evaluating gene-disease associations, and improves the clinical management for at-risk individuals.

Background: Lurbinectedin was approved on June 15, 2020 by the Food and Drug Administration with the brand name ZEPZELCA as the first systematic approved therapy for patients having Small Cell Lung Cancer (SCLC). Objectives: In this review, an attempt is made to summarize different aspects of Lurbinectedin, including the pathophysiology, chemistry, chemical synthesis, mechanism of action, adverse reactions, and pharmacokinetics. Special attention is given to various reported clinical trials of lurbinectedin. Methods: A comprehensive literature search was conducted in the relevant databases like ScienceDirect, PubMed, ResearchGate and Google Scholar to identify studies. After a thorough study of these reports, significant findings/data were collected and compiled under suitable headings. Important findings related to clinical trials have been tabulated. Conclusion: Lurbinectedin is known to act by inhibiting the active transcription of encoding genes, thereby suppressing tumor-related macrophages with an impact on tumour atmosphere. Lurbinectedin has emerged as a potential drug candidate for the treatment of Small-Cell Lung Cancer (SCLC).

BACKGROUND: Cadmium (Cd) exposure in environmental and occupational settings is a major public health concern. Cd exposure is associated with the production of free radicle and reactive oxygen species. The aim of the present study is to evaluate the effect of occupational exposure to Cd on oxidative stress and pro-inflammatory biomarkers in the workers. METHODS: 100 occupationally exposed individuals working in the metal handicraft industry and welding industry were recruited from the industrial area of Jodhpur, Rajasthan. Blood Cd levels were estimated using atomic absorption spectroscopy. Serum Total Antioxidant Capacity (TAC), Catalase (CAT), Superoxide Dismutase (SOD), and Malondialdehyde (MDA) levels were measured by colorimetric method to assess oxidative status and serum IL-6 and TNF-α were measured by ELISA to assess inflammatory status. RESULTS: The median Cd levels in the study population was 2.40μg/L, with welders having significantly higher Cd levels than metal handicraft workers. Among the oxidative stress markers, TAC and CAT were significantly lower, while MDA was significantly higher in subjects with high Cd levels. The Cd levels showed a significant negative and positive correlation with TAC and MDA, respectively. IL- 6 and TNF-α did not show a significant difference between the study groups, but both had an inverse correlation with antioxidant enzymes. CONCLUSION: Occupational exposure to even low levels of Cd may result in oxidative stress in workers primarily via decrease in antioxidant enzymes and increasing lipid peroxidation. Increased oxidative stress in turn may result in immune cell activation which may result in increased concentration of pro-inflammatory cytokine in the exposed workers.

Background: Central retinal Artery occlusion (CRAO) is an ophthalmic emergency and the ocular analogue of the cerebral stroke. Atrial myxomas are the most common benign primary cardiac tumor. We report a case of undiagnosed left atrium (LA) myxoma who presented with sudden onset blindness in right eye due to CRAO as a sole manifestation and echocardiographic characteristics of myxoma which increases the risk of embolism. Methods: A 52-year old woman presented with history of sudden onset blindness in right eye. Fundus examination was suggestive of CRAO. Transthoracic and transesophageal echocardiogram showed a mass in LA compatible with LA myxoma. Complete surgical resection of myxoma was done although vision could not be restored to normal. Conclusion: Detailed history and complete systemic examination should be done in every patient with embolic phenomena and early neuroimaging with echocardiography using newer modality like 3D imaging should be used even in absence of electrocardiographic or auscultatory abnormalities. Key words: Myxoma, retinal artery occlusion, embolism, 3 dimensional echocardiography

Background We report the feasibility of using telephones for active surveillance of cancer survival and also present absolute survival rate and its predictors for lung cancer (LC) and gallbladder cancer (GBC) in north India. To date, such information from resource intensive settings is limited. Methods Study participants were 530 men and women (259 LC and 271 GBC), registered at ‘Post Graduate Institute of Medical Education and Research’, Chandigarh. Eligible patients were diagnosed with LC or GBC between ages 30 and 69 years during a five-year period from January 1 2010 through December 31 2014, and had a valid telephone number. Information on socio-demographic factors, disease characteristics and treatment status was abstracted from medical records. Participants (or their family/relatives) were followed-up with telephone interviews (March 1 2016 to July 31 2016) to ascertain vital status. Absolute 1-, 3- and 5-year survival rates were calculated using Kaplan-Meier method; weighted Cox Proportional Hazards regression multivariable models were used to evaluate determinants of survival while accounting for losses to follow up. Results Over two-thirds of the participants or their families (66.7%) were successfully followed-up via telephone calls. Survival analysis included 354 participants (N=175 LC; 179 GBC) with 326 deaths observed during follow up (N=158 LC; 168 GBC). Absolute survival rates (expressed as percentages with 95% confidence intervals) for LC were 36.7 (29.5-44.7), 10.2 (6.1-15.6) and 2.1 (0.2-8.1) and for GBC 29.0 (22.6-35.8), 5.4 (2.5-9.8) and nil for 1-year, 3-years and 5-years post-diagnosis, respectively; GBC had lower survival rates than LC (P=0.049). Pre-treatment clinical extent of disease was the only significant predictor of survival rates especially for GBC. Conclusions Active follow-up of cancer patients through telephone calls is feasible and acceptable in India. Poor survival rates of both LC and GBC underscore the importance of active surveillance by reaching out to family members through practically feasible methods.

Background The objective of the current study was to provide insight into the effect of coronavirus disease 2019 (COVID‐19) on breast cancer screening, breast surgery, and genetics consultations. Methods User data from a risk assessment company were collected from February 2 to April 11, 2020. The use of risk assessment was used as a proxy for the use of 3 breast cancer services, namely, breast imaging, breast surgery, and genetics consultation. Changes in the use of these services during the study period were analyzed. Results All 3 services experienced significant declines after the COVID‐19 outbreak. The decline in breast surgery began during the week of March 8, followed by breast imaging and genetics consultation (both of which began during the week of March 15). Breast imaging experienced the most significant reduction, with an average weekly decline of 61.7% and a maximum decline of 94.6%. Breast surgery demonstrated an average weekly decline of 20.5%. When surgical consultation was stratified as breast cancer versus no breast cancer, the decrease among in non–breast cancer patients was more significant than that of patients with breast cancer (a decline of 66.8% vs 11.5% from the pre‐COVID average weekly volume for non–breast cancer patients and patients with breast cancer, respectively). During the week of April 5, use of genetics consultations dropped to 39.9% of the average weekly volumes before COVID‐19. Conclusions COVID‐19 has had a significant impact on the number of patients undergoing breast cancer prevention, screening, diagnosis, and treatment., Coronavirus disease 2019 (COVID‐19) has had a significant impact on the number of patients undergoing breast cancer prevention, screening, diagnosis, and treatment in the United States. In the current study, user data from a risk assessment company were collected from February 2 to April 11, 2020, with the use of risk assessment used as a proxy to analyze changes in the use of 3 breast cancer services: breast imaging, breast surgery, and genetics consultation.

Context: The etiopathogenesis of oral lichen planus (OLP) is still debatable. According to literature, many studies have illustrated OLP as a T-cell-mediated chronic autoimmune disease. Currently, there is increased evidence of chronic inflammation in OLP and its association with vascular adhesion molecules (VAMs). Aim: The aim of this study was to evaluate the expression of VAM (PECAM-1) in OLP. Setting and Design: Tissue samples involved 20 archival cases of histopathologically confirmed OLP (n = 15) and normal mucosa (n = 5) as controls. Materials and Methods: The sections were subjected to immunohistochemical analysis using antibody to PECAM-1. Brown staining of the endothelial cells of blood vessels was considered positive. The expression of PECAM-1 in OLP was statistically analyzed using Wilcoxon sign-rank test. Results: The expression of PECAM-1 in OLP was statistically significant when compared with normal mucosa (P < 0.05). A statistically significant difference was also observed in PECAM-1 expression between the reticular type and erosive type of OLP. Conclusion: PECAM-1 was found to be overexpressed in OLP; difference in PECAM-1 expression was noted between the reticular and erosive types. The VAMs could be exploited as a possible therapeutic target in OLP to modulate the disease process thereby reducing the dependency on corticosteroids.

Purpose Studies are required to determine whether exposures to radiation encountered during manned missions in deep space may have adverse effects on the cardiovascular system. Most of the prior studies on effects of simulated space radiation on the heart and vasculature have been performed in mouse models. To provide data from a second animal species, two studies were performed to assess effects of high-energy charged particle radiation on the heart and abdominal aorta in a rat model. Materials and methods In study A, male Long Evans rats were exposed to whole-body protons (250 MeV, 0.5 Gy) or oxygen ions (16O, 600 MeV/n, 0.5 Gy), and ultrasonography was used to measure in vivo cardiac function and blood flow parameters at 3, 5, 9 and 12 months after radiation, followed by tissue collection at 12 months. In study B, male Long Evans rats were exposed to 16O (1 GeV/n, 0.01-0.25 Gy), and hearts collected at 6 to 7 and 12 months for histology and western-blots. Results Both protons (250 MeV) and 16O (600 MeV/n) caused a decrease in left ventricular posterior wall thickness at 3-5 months, but did not change echocardiographic measures of cardiac function. In Pulsed-wave Doppler assessment of the abdominal aorta, an increase was seen in mean velocity, peak velocity, and velocity time integral at 12 months after 16O (600 MeV/n), suggesting a change in vascular function. There were no significant changes in histopathology or histological quantification of total collagens in heart or aorta. On the other hand, an increase was seen in a 75 kDa peptide of collagen type III in the left ventricle of rats exposed to protons (250 MeV) and 16O (600 MeV/n and 1 GeV/n), suggesting that radiation caused remodeling of existing collagens in the heart. 16O (600 MeV/n and 1 GeV/n) caused increases in left ventricular protein levels of immune cell markers CD2, CD4, CD8, and CD68. Conclusion A single low dose of whole body protons or 16O in male Long Evans rats did not change cardiac function or induce gross pathological changes in the heart or aorta, but induced mild changes in vascular function and remodeling of existing collagens in the heart. Altogether, studies in prior mouse models and the current work in rats indicate minor changes in cardiac function and structure after a low dose of single-ion radiation.

Background Migraine has many presumed comorbidities which have rarely been compared between samples with and without migraine. Examining the association between headache pain intensity and monthly headache day (MHD) frequency with migraine comorbidities is novel and adds to our understanding of migraine comorbidity. Methods The MAST Study is a prospective, web-based survey that identified US population samples of persons with migraine (using modified International Classification of Headache Disorders-3 beta criteria) and without migraine. Eligible migraine participants averaged ≥1 MHDs over the prior 3 months. Comorbidities “confirmed by a healthcare professional diagnosis” were endorsed by respondents from a list of 21 common cardiovascular, neurologic, psychiatric, sleep, respiratory, dermatologic, pain and medical comorbidities. Multivariable binary logistic regression calculated odds ratios (OR) and 95% confidence intervals for each condition between the two groups adjusting for sociodemographics. Modeling within the migraine cohort assessed rates of conditions as a function of headache pain intensity, MHD frequency, and their combination. Results Analyses included 15,133 people with migraine (73.0% women, 77.7% White, mean age 43 years) and 77,453 controls (46.4% women, 76.8% White, mean age 52 years). People with migraine were significantly (P Conclusions In regression models controlled for sociodemographic variables, all conditions studied were reported more often by those with migraine. Whether entered into the models separately or together, headache pain intensity and MHD frequency were associated with increased risk for many conditions. Future work is required to understand the causal sequence of relationships (direct causality, reverse causality, shared underlying predisposition), the potential confounding role of healthcare professional consultation and treatment, and potential detection bias.

Treatment of congenital adrenal hyperplasia (CAH) requires lifelong replacement of glucocorticoids with regular follow up to manage associated morbidities. The current review focuses on follow-up and management of infants diagnosed with classical CAH pertinent to Indian context. Early initiation of oral hydrocortisone in divided doses is recommended after diagnosis in newborn period, infancy and childhood. Fludrocortisone is recommended for all infants with classical CAH. All infants should be monitored as per protocol for disease and treatment related complications. The role of prenatal steroids to pregnant women with previous history of CAH affected infant for prevention of virilization of female fetus is controversial.

Pemphigoid gestationis is a rare subepidermal bullous dermatosis of pregnancy, caused by the interaction of IgG1 auto-antibodies with 180 kD BP Antigen 2. This disease can lead to preterm delivery, but the neonate is affected in only 10% cases. The treatment of choice in pemphigoid gestationis is systemic corticosteroids.

Scheme depicts hypothesized decreases of heart and SKM function during aging via ROS and partial reversal by SFN activation of Nrf2 that results in significant restoration of function of both types of muscle. A decline in heart and skeletal muscle function was observed in aged mice, with altered mitochondrial structure and gene expression, accompnied by decreases in mitochondrial complex activity, Nrf2 binding to antioxidant‐responsive DNA elements and physical endurance. The addition of sulforaphane (SFN) to the diet improved these age‐related changes in older mice to levels observed in younger ones. We demonstrated in this paper that SFN alleviates age‐associated oxidative damage and improves mitochondrial and cardiac function as well as physical endurance in old mice., Age‐associated mitochondrial dysfunction and oxidative damage are primary causes for multiple health problems including sarcopenia and cardiovascular disease (CVD). Though the role of Nrf2, a transcription factor that regulates cytoprotective gene expression, in myopathy remains poorly defined, it has shown beneficial properties in both sarcopenia and CVD. Sulforaphane (SFN), a natural compound Nrf2‐related activator of cytoprotective genes, provides protection in several disease states including CVD and is in various stages of clinical trials, from cancer prevention to reducing insulin resistance. This study aimed to determine whether SFN may prevent age‐related loss of function in the heart and skeletal muscle. Cohorts of 2‐month‐old and 21‐ to 22‐month‐old mice were administered regular rodent diet or diet supplemented with SFN for 12 weeks. At the completion of the study, skeletal muscle and heart function, mitochondrial function, and Nrf2 activity were measured. Our studies revealed a significant drop in Nrf2 activity and mitochondrial functions, together with a loss of skeletal muscle and cardiac function in the old control mice compared to the younger age group. In the old mice, SFN restored Nrf2 activity, mitochondrial function, cardiac function, exercise capacity, glucose tolerance, and activation/differentiation of skeletal muscle satellite cells. Our results suggest that the age‐associated decline in Nrf2 signaling activity and the associated mitochondrial dysfunction might be implicated in the development of age‐related disease processes. Therefore, the restoration of Nrf2 activity and endogenous cytoprotective mechanisms by SFN may be a safe and effective strategy to protect against muscle and heart dysfunction due to aging.

Endocannabinoids level are reported to increase in sepsis, however, the role of vascular cannabinoid receptor-1 (CB1R) in sepsis-induced vascular hyporeactivity is yet to be unravelled. Polymicrobial sepsis was induced by caecal ligation and puncture in mice. Isometric tension in isolated aortic rings during early (6 h) and late (20 h) phases of sepsis was recorded and expression of mRNA of monoacylglycerol lipase (MAGL) and cannabinoid receptor-1 (CB1R) was investigated. Sepsis significantly (p < 0.001) reduced the mean survival time in mice along with increase in bacterial load in blood and peritoneal lavage. Compared to Sham-operated (SO) mice, vascular reactivity to nor-adrenaline (NA) was significantly (p < 0.05) attenuated in both early and late phases of sepsis. NA-induced vasoconstriction was significantly (p < 0.05) potentiated by inhibition of diacylglycerol lipase (DAGL) and attenuated by inhibition of MAGL in SO mice. Pre-incubation with KT 109, a DAGL inhibitor, significantly (p < 0.05) improved the vascular hypo-reactivity to NA during both the phases of sepsis. mRNA expression of MAGL in aorta was significantly (p < 0.05) attenuated during both the phases of sepsis. But in the presence of AM 251, specific antagonist of CB1R, vascular reactivity to NA was significantly (p < 0.05) restored along with significant (p < 0.05) increase in mRNA expression of CB1R in aortic rings from both early and late phases of septic mice. 2-AG regulates vascular response to NA and increased aortic expression of CB1R is responsible for vascular hyporeactivity to NA in sepsis, and in vitro inhibition of this receptor by AM 251 restored the vascular reactivity.

Blindness is a public health problem in developing and developed countries. According to WHO global data for visual impairments 2010, common occurence of blindness was 20.5%.One of the major cause for this is Cataract. Cataract is responsible for about 62.6% of all cases of blindness in India. If cataract left untreated most of the people will in due course become acutely visionless. The motive behind the present study is to find the connection between hypertension and development of cataract. A comparative study was carried for the two months of duration. 200 patients divided in two groups (hypertensive and non-hypertensive) were included in our study. We observed that prevalence of cataract is significantly higher in hypertensive (83.15%) patients as compared to non-hypertensive (70.01%) patients. Hypertension is involved in the pathological pathway of cataract development through an inflammatory mechanism. Nuclear cataract was found to be most common followed by cortical and posterior subcapsular cataract.

Visible impairments in skin appearance, as well as a subtle decline in its functionality at the molecular level, are hallmarks of skin aging. Activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-pathway, which is important in controlling inflammation and oxidative stress that occur during aging, can be triggered by sulforaphane (SFN), an isothiocyanate found in plants from the Brassicaceae family. This study aimed to assess the effects of SFN intake on age-related skin alterations. Male C57BL6 young (2 months) and old (21 months) mice were treated for 3 months with SFN diet (442.5 mg per kg) or control diet. The antioxidant capacities of the skin were increased in old SFN-treated animals as measured by mRNA levels of Nrf2 (P

BackgroundThe ability to reverse exhaustion in CD8+ T cells holds great promise for therapeutic intervention in oncology. Indeed, treatment with therapeutics targeted at checkpoint inhibitors, such as Nivolumab (anti-PD-1), have shown great promise in the treatment of a subset of individuals and tumour types. However, pre-clinical success does not always translate to success in clinical trials and resistance to these approaches is prevalent. As such, there is a pressing need to develop novel approaches that target alternative pathways for use alone or potentially in combination with checkpoint inhibitor modulation. A secondary need is the requirement for advanced assays that accurately recapitulate the pathways and cell phenotypes prevalent in the tumour environment.MethodsHere we describe the characteristics of an in vitro human T cell exhaustion assay whereby in vitro stimulated T cells phenotypically and functionally recapitulate the exhausted T cells found within the tumour microenvironment. We also demonstrate the effect of checkpoint blockade as well as small molecule inhibition of a novel target on the exhausted T cell phenotype.ResultsIn this assay, exhaustion can be partially but not fully reversed by treatment with anti-PD-1 alone. In addition, we demonstrate the effect of a small molecule inhibitor targeting IKZF3, a transcription factor shown to be upregulated in T cell exhaustion, on reversing T cell exhaustion alone and in combination with checkpoint inhibitor blockade.ConclusionsThese assays and approaches enable investigation into the ability of compounds to influence reversal of T cell exhaustion where anti-PD-1 treatment does not fully reverse the exhausted phenotype and offers the ability to test combination therapy approaches.AcknowledgementsThis work was aided by the valuable input and insight of Professor Stephen Anderton.Ethics ApprovalThe study obtained ethics approval from West Midlands – Black Country Research Ethics Committee under IRAS project ID 270936. All donors gave informed consent before taking part.

ObjectivesWe assessed the effectiveness of community health workers (CHWs)-led, technology-enabled programme as a large-scale, real-world solution for screening and long-term management of diabetes and hypertension in low-income and middle-income countries.DesignRetrospective cohort design.SettingForty-seven low-income neighbourhoods of Hyderabad, a large Indian metropolis.ParticipantsParticipants (aged ≥20 years) who subscribed to an ongoing community-based chronic disease management programme employing CHWs and technology to manage diabetes and hypertension.Primary and secondary outcome measuresWe used deidentified programme data between 1 March 2015 and 8 October 2018 to measure participants’ pre-enrolment and post-enrolment retention rate and within time-interval mean difference in participants’ fasting blood glucose and blood pressure using Kaplan-Meier and mixed-effect regression models, respectively.Results51 126 participants were screened (median age 41 years; 65.2% women). Participant acquisition rate (screening to enrolment) was 4%. Median (IQR) retention period was 163.3 days (87.9–288.8), with 12 months postenrolment retention rate as 16.5% (95% CI 14.7 to 18.3). Reduction in blood glucose and blood pressure levels varied by participants’ retention in the programme. Adjusted mean difference from baseline ranged from −14.0 mg/dL (95% CI −18.1 to −10.0) to −27.9 mg/dL (95% CI −47.6 to −8.1) for fasting blood glucose; −2.7 mm Hg (95% CI −7.2 to 2.7) to −7.1 mm Hg (95% CI −9.1 to −4.9) for systolic blood pressure and −1.7 mm Hg (95% CI −4.6 to 1.1) to −4.2 mm Hg (95% CI −4.9 to −3.6) for diastolic blood pressure.ConclusionsCHW-led, technology-enabled private sector interventions can feasibly screen individuals for non-communicable diseases and effectively manage those who continue on the programme in the long run. However, changes in the model (eg, integration with the public health system to reduce out-of-pocket expenditure) may be needed to increase its adoption by individuals and thereby improve its cost-effectiveness.