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Abstract Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition that usually affects younger adults but has a second incidence peak in the older population. Although diagnosis of IBD is driven by symptoms, some patients are asymptomatic and incidentally discovered while participating in colon screening program (CSP). We aimed to identify the incidence and outcome of IBD in fecal immunochemical test (FIT) positive patients in the British Columbia CSP. We conducted a retrospective chart review of patients who had colonoscopies for positive FIT and were found to have colitis based on endoscopic and histological assessment. Of 93,994 patients who underwent screening colonoscopy for positive FIT between 2009 and 2017, 608 (0.6%) were found to have colitis. From 11 CSP sites, 191 patients met the inclusion criteria. 58 patients (30.4%) were diagnosed with ulcerative colitis, 109 (57.1%) with Crohn’s disease (CD), and 24 (12.6%) with IBD unclassified. 124 patients (64.9%) received treatment, of which 34 (17.8%) received biologics and 4 (2.1%) required surgery. Our study demonstrated a clinically significant incidence of IBD, with novel finding of CD predominance, within a Canadian provincial CSP. Further research is needed to guide management of older patients with varying rates of IBD progression after incidental diagnosis.

Abstract Time series analysis and prediction have attained significant attention from the research community in the past few decades. However, the prediction accuracy of the models highly depends on the models’ learning process. In order to optimize resource usage, a better learning methodology, in terms of accuracy and learning time, is needed. In this context, the current research work proposes EvoLearn, a novel method to improve and optimize the learning process of neural-based models. The presented technique integrates the genetic algorithm with back-propagation to train model weights during the learning process. The fundamental idea behind the proposed work is to select the best components from multiple models during the training process to obtain an adequate model. To demonstrate the applicability of EvoLearn, the method is tested on the state-of-the-art neural models (namely MLP, DNN, CNN, RNN, and GRU), and performances are compared. Furthermore, the presented study aims to forecast two types of time series, i.e. air pollution and energy consumption time series, using the developed framework. In addition, the considered neural models are tested on two datasets of each time series type. From the performance comparison and evaluation of EvoLearn using a one-tailed paired T-test against the conventional back-propagation-based learning approach, it was found that the proposed method significantly improves the prediction accuracy.

Introduction: Junk food intake has increased many folds in the last two decades. India is still struggling with communicable diseases, though the incidence of non communicable diseases, including metabolic syndrome, has increased several times in the younger age group. There is a scarcity of data and a limited number of international studies on decreasing junk food intake, especially in India. Aim: To assess eating habits, nutritional status, and the effect of behavioural therapy on junk food intake in medical undergraduate students. Materials and Methods: A prospective interventional study was conducted in medical students of a tertiary care hospital in Northern India (Faculty of Medicine and Health Sciences, SGT University, Haryana, India) over a duration of six months, from October 2021 to March 2022. All students were given a pretest in the form of an electronic questionnaire. Students then received four educational sessions based on Cognitive Behavioural Therapy (CBT), one session per week, each lasting 30 minutes. At the end of the four sessions, all students were assessed through a post-test following the same protocol as the pretest. Statistical analysis was conducted using Statistical Packages for Social Sciences (SPSS) version 28.0 The Wilcoxon's signed-rank test was applied for comparison within pre and post-interventions. Results: Most of the students, 302 (68%), included in the study were less than 20 years of age, with a minimum age of 17 years and a maximum age of 25 years. A total of 443 students were included in the study. Of these, 178 out of 443 had a Body Mass Index (BMI)>25 kg/m2, classifying them as overweight (40.18%). The majority of students were not aware of the major side effects of junk food intake, but a significant improvement was noted in the post-test conducted four weeks later. A significant change (p

Introduction: Aspergillus species can affect the respiratory system of genetically predisposed asthma patients. Allergic Broncho-Pulmonary Aspergillosis (ABPA) is one of the manifestations of aspergillosis. Most research on ABPA has been conducted in the adult population, with very few studies including paediatric patients. Aim: To examine the clinical spectrum of aspergillosis in severely asthmatic children aged between 2 and 18 years admitted to the Paediatric Intensive Care Unit (PICU). Materials and Methods: This retrospective observational study was conducted from September 2021 to August 2022. Out of 76 children aged between 2 and 18 years who presented with asthma over one year, 24 children fulfilling the inclusion criteria (severe asthma requiring PICU admission) were included in the study by convenient sampling. Children were diagnosed with ABPA and Severe Asthma with Fungal Sensitisation (SAFS) based on the ISHAM (International Society for Human and Animal Mycology) work group criteria (history of asthma, raised Aspergillus-specific and total Immunoglobulin E (IgE), presence of Aspergillus-specific IgG, eosinophilia, and positive radiological findings). Descriptive statistics elaborated in the form of mean and standard deviation. Results: A total of 24 patients with acute severe asthma were admitted to the PICU over one year. Nearly 60% (15/24) of the patients fulfilled the criteria for subgroup A (comprising poorly controlled asthma, eosinophilia, or positive radiological findings). Among them, six (25%) patients had total serum IgE levels > 1000 IU/mL, three (12.5%) had levels between 500-1000 IU/mL, and six (25%) had levels

Background Insufficient and above WHO-recommended levels of iodine intake during pregnancy can lead to serious health outcomes. This study aimed to assess median urine iodine concentration and its associated risk factors among pregnant women in the Mbeya region, Tanzania. Method A cross sectional survey involving 420 pregnant women (n=420) aged 15-49, registered in Reproductive and Child Health Clinics was conducted. Socio-demographic and dietary factors were assessed by structured questionnaire and the urine samples were analyzed using the ammonium persulfate digestion method. Results Median urinary iodine concentration (mUIC) was 279.4μg/L and it ranged from 26.1 to 1915μg/L. Insufficient mUIC (below 150μg/L) was observed in 17.14% of participants, sufficient mUIC was 24.29% and 58.57% had mUIC above the recommended level (>250μg/L). Sample women who reported consuming fish in the last 24 hours had an increased risk of insufficient mUIC [Adjusted OR= 2.60 (95%CI 1.31-5.15)] while the risk was lower for those who attended at least primary education [AOR= 0.29 (CI 0.08-0.99)]. Further, sample women resident in Mbarali district, in the oldest age group (35-49) and having a higher socio-economic status were associated with an increased risk of having MUIC above recommended level [AOR=4.09 (CI 1.85-9.010], [AOR=2.51 (CI 0.99-6.330] and, [AOR=2.08 (CI 0.91-4.71) respectively. Conclusion This study demonstrated a significant association between geographical, age and socio-economic factors and median urine iodine concentration above the WHO-recommended level. Further, this study found association between inadequate iodine in diet and insufficient median urine iodine concentration. Therefore, educational programs on iodine intake should be strengthened.

Inpatient treatment of hyperkalaemia with insulin and dextrose can be complicated by iatrogenic hypoglycaemia. We sought to assess the incidence of hypoglycaemia in hospitalised patients with renal disease and assess the impact of the introduction of a local guideline incorporating the use of sodium zirconium cyclosilicate (SZC) for patients with moderate hyperkalaemia. After establishing a significant burden of hypoglycaemia in the initial observation period, a requirement for hourly capillary blood glucose monitoring (for up to 6 h) following the administration of insulin for hyperkalaemia was incorporated into the guidelines. The two-fold introduction of SZC alongside changes in patient care after the administration of insulin/dextrose resulted in more appropriate use of insulin/dextrose, as well as a significant (73%) reduction in the iatrogenic burden of hypoglycaemia (P = 0.04).

Human cysticercosis is an infection with the larval form of Taenia solium that commonly involves the central nervous system. Due to the infection, isolated muscular involvement is rare, and very few cases have been reported in the literature. Hereby, the authors present a rare instance of isolated muscular cysticercosis in a 15-year-old girl, resulting in an incomplete claw hand due to the compression of both the ulnar and median nerves. The patient had been experiencing swelling on the anterior aspect of her left forearm for eight months, with recent aggravation. The swelling was gradually followed by an inability to fully extend the middle and ring fingers for the past six months. The patient’s laboratory results were within normal limits, and ultrasound and Magnetic Resonance Imaging (MRI) of the forearm confirmed the presence of cysticercosis. The treatment plan included a course of oral steroids and antihelminthic drugs, along with physiotherapy. In present case, the patient’s condition significantly improved with conservative management. The present case illustrates the diagnostic challenges due to the vague clinical presentation and unfamiliarity of clinicians with present entity, making it difficult to diagnose when seen as an isolated cyst. The unique manifestations of muscular cysticercosis emphasise the importance of early detection and proper management.

Fanconi anaemia is a rare, progressive congenital bone marrow failure syndrome characterised by autosomal recessive inheritance and clinical manifestations, including growth retardation, bone marrow failure leading to pancytopenia, an elevated risk of malignancy, skin pigmentation, and skeletal malformations. Patients who have undergone bone marrow transplantation can be treated comprehensively in the dental clinic like other routine patients, provided their blood indices are within normal limits. Its complications include aplastic anaemia, malignancies like acute myeloid leukaemia, liver tumours, and squamous cell carcinoma, often developing post-bone marrow transplantation. Dental anomalies, altered salivary flow, and increased susceptibility to cancer necessitate early diagnosis and specialised dental care. Hereby, the authors present a case of 15-year-old male with Fanconi Anaemia who had undergone bone marrow transplantation and was treated comprehensively in a hospital setting. The present case report aimed to equip healthcare practitioners, especially dentists, with the knowledge needed for accurate diagnosis and effective management.

Introduction The HEALS Med-Tech program offers a unique blend of lifestyle changes and technology to improve hypertension (HTN) management in African Americans (AAs), a group disproportionately affected by cardiovascular disease (CVD). Methods A randomized controlled trial compared HEALS Med-Tech against usual care for uncontrolled hypertension in AAs, focusing on diet, medication adherence, and telehealth. Results In a study of 61 participants, HEALS Med-Tech significantly reduced systolic blood pressure by 12.95 mm Hg (p = 0.008) and 9.19 mm Hg (p = 0.013) at 3 and 12 months, respectively, demonstrating improved hypertension control. Conclusions HEALS Med-Tech demonstrates potential in HTN management for AAs, advocating for culturally tailored, tech-integrated healthcare expansion.

The complex of methyltransferase-like proteins 3 and 14 (METTL3-14) is the major enzyme that deposits N6-methyladenosine (m6A) modifications on messenger RNA (mRNA) in humans. METTL3-14 plays key roles in various biological processes through its methyltransferase (MTase) activity. However, little is known about its substrate recognition and methyl transfer mechanism from its cofactor and methyl donor S-adenosylmethionine (SAM). Here, we study the MTase mechanism of METTL3-14 by a combined experimental and multiscale simulation approach using bisubstrate analogues (BAs), conjugates of a SAM-like moiety connected to the N6-atom of adenosine. Molecular dynamics simulations based on crystal structures of METTL3-14 with BAs suggest that the Y406 side chain of METTL3 is involved in the recruitment of adenosine and release of m6A. A crystal structure with a BA representing the transition state of methyl transfer shows a direct involvement of the METTL3 side chains E481 and K513 in adenosine binding which is supported by mutational analysis. Quantum mechanics/molecular mechanics (QM/MM) free energy calculations indicate that methyl transfer occurs without prior deprotonation of adenosine-N6. Furthermore, the QM/MM calculations provide further support for the role of electrostatic contributions of E481 and K513 to catalysis. The multidisciplinary approach used here sheds light on the (co)substrate binding mechanism, catalytic step, and (co)product release, and suggests that the latter step is rate-limiting for METTL3. The atomistic information on the substrate binding and methyl transfer reaction of METTL3 can be useful for understanding the mechanisms of other RNA MTases and for the design of transition state analogues as their inhibitors.

India experienced a surge in COVID-19 cases during the second wave in the period of April-June 2021. A rapid rise in cases posed challenges to triaging patients in hospital settings. Chennai, the fourth largest metropolitan city in India with an 8 million population, reported 7564 COVID-19 cases on May 12, 2021, nearly 3 times higher than the number of cases in the peak of COVID-19 in 2020. A sudden surge of cases overwhelmed the health system. We had established standalone triage centers outside the hospitals in the first wave, which catered to up to 2500 patients per day. In addition, we implemented a home-based triage protocol from May 26, 2021, to evaluate patients with COVID-19 who were aged ≤45 years without comorbidities. Among the 27,816 reported cases between May 26 and June 24, 2021, a total of 16,022 (57.6%) were aged ≤45 years without comorbidities. The field teams triaged 15,334 (55.1%), and 10,917 (39.2%) patients were evaluated at triage centers. Among 27,816 cases, 19,219 (69.1%) were advised to self-isolate at home, 3290 (11.8%) were admitted to COVID-19 care centers, and 1714 (6.2%) were admitted to hospitals. Only 3513 (12.7%) patients opted for the facility of their choice. We implemented a scalable triage strategy covering nearly 90% of the patients in a large metropolitan city during the COVID-19 surge. The process enabled early referral of high-risk patients and ensured evidence-informed treatment. We believe that the out-of-hospital triage strategy can be rapidly implemented in low-resource settings.

Chronic kidney disease (CKD) is a complex disease that is asymptomatic in its early stages. Its delayed recognition may predispose patients to adverse outcomes. Early detection and management of kidney disease through screening programs is widely recommended. In the present study, we conducted a screening program at a hospital set up on World Kidney Day for 10 years to detect patients with CKD. The current study constituted 1324 apparently healthy adults, aged >18 years. Information on age, sex, height, weight, history of diabetes mellitus (DM) and hypertension (HTN), and familial history of kidney disease was recorded. Systolic and diastolic blood pressure, random blood sugar; urinalysis, and serum creatinine (Cr) levels were measured. The study outcome was the presence of CKD. Binary logistic regression analysis was applied to find the predictors of CKD. The median age of the study subjects was 40 years. CKD was found in 35.6% of subjects. Age, DM, HTN, and abnormal Cr levels were associated with increasing risk of CKD. The main objective of the present study was to identify the extent of risk relative to the co-factors of CKD and thereby target those who are potentially modifiable, like DM, to intervene at the earliest possible stage to treat the current disease condition and prevent the future health impairment.

Background Human papillomavirus (HPV) E6/E7 mRNA tests determine the oncogenic activity of the virus and represent a good clinical biomarker for predicting the risk of cervical cancer. So, the present study was conducted to know the role of HPV E6/E7 mRNA as a predictive biomarker for cervical carcinoma. Methodology The present study was conducted on 55 clinical samples of cervical scrapings and biopsy from the clinically suspected cases (based on signs and symptoms) of cervical cancer having abnormal PAP smear. The samples were processed in three steps—(1) HPV DNA detection, (2) HPV E6/E7 mRNA detection, and (3) histopathological analysis. Results Out of a total of 55 patients, 16 (29.09%) were positive for both HPV E6/E7 mRNA and HPV DNA and six were positive for only HPV DNA. So, a total of 22 (40%) patients were positive for HPV DNA. Out of these 22 samples, 10 (45.5%) were of HPV-16, six (27.3%) were of HPV-18, four (18.2%) were of HPV-31, and two (9.1%) were of HPV-45. Out of total 16 patients positive for HPV E6/E7 mRNA, 10 (62.5%) were of genotype 16 and six (37.5%) were of genotype 18. The patients who were found positive for HPV 31 and 45 genotypes did not have E6/E7 mRNA expression. On colposcopic-guided biopsy, among these 16 samples, eight (50%) were diagnosed with invasive squamous cell carcinoma, six (37.5%) with cervical intraepithelial neoplasia grade 3 (CIN3), and two (12.5%) with CIN2. Out of those six patients in whom only HPV DNA was positive, five had normal biopsy findings and one had CIN1. Conclusion The present study suggests that HPV E6/E7 mRNA detection could be more reliable than DNA testing for predicting the risk of progression of HPV-induced cervical lesions to cervical carcinoma and it can be used as a non-invasive tool for triage and patient follow-up.

Out of all emerging infectious diseases, approximately 75% are of zoonotic origin, with their source often traced back to animals. The emergence of zoonoses is driven by a complex interplay between anthropogenic, genetic, ecological, socioeconomic, and climatic factors. This intricate web of influences poses significant challenges for the prediction and prevention of zoonotic outbreaks. Effective coordination and collaboration among the animal, human, and environmental health sectors are essential for proactively addressing major zoonotic diseases. Despite advancements in surveillance and diagnostic practices, the emergence of zoonoses continues to be a pressing global concern. Therefore, prioritizing zoonotic disease surveillance is of paramount importance as part of a comprehensive disease prevention and containment strategy. Furthermore, evaluating existing surveillance systems provides insights into the challenges faced, which can be mitigated through implementation of One Health principles involving relevant stakeholders. To initiate multisectoral partnerships, it is crucial to identify the priorities and core themes of surveillance systems with equitable inputs from various sectors. Strengthening surveillance, promoting data sharing, enhancing laboratory testing capabilities, and fostering joint outbreak responses in both the human and animal health sectors will establish the necessary infrastructure to effectively prevent, predict, detect, and respond to emerging health threats, thereby reinforcing global health security. This review assesses existing surveillance approaches by offering an overview of global agencies engaged in monitoring zoonoses and outlines the essential components required at the human–animal–environment interface for designing comprehensive surveillance networks. Additionally, it discusses the key steps necessary for executing effective zoonotic disease surveillance through a One Health approach, while highlighting the key challenges encountered in establishing such a robust surveillance system.

Abstract Surgeons must visually distinguish soft-tissues, such as nerves, from surrounding anatomy to prevent complications and optimize patient outcomes. An accurate nerve segmentation and analysis tool could provide useful insight for surgical decision-making. Here, we present an end-to-end, automatic deep learning computer vision algorithm to segment and measure nerves. Unlike traditional medical imaging, our unconstrained setup with accessible handheld digital cameras, along with the unstructured open surgery scene, makes this task uniquely challenging. We investigate one common procedure, thyroidectomy, during which surgeons must avoid damaging the recurrent laryngeal nerve (RLN), which is responsible for human speech. We evaluate our segmentation algorithm on a diverse dataset across varied and challenging settings of operating room image capture, and show strong segmentation performance in the optimal image capture condition. This work lays the foundation for future research in real-time tissue discrimination and integration of accessible, intelligent tools into open surgery to provide actionable insights.

Aim: We have conducted a study of the clinical profile of esophageal atresia (OA) at our institution over a period of 9 years with an aim toward improving our results. We have attempted to find the significant indicators of mortality to be able to focus on improving the survival of these patients in future. To achieve this end, we applied the Waterston's prognostic classification and the Spitz' prognostic criteria to our patients and studied the effects of each variable independently as a cause of mortality. We have also compared the two prognostic criteria to see, which has more significance for us at our institution. Materials and Methods: Over a period of 9 years, from 2006 to 2014, 73 neonates were treated for OA at our institute. There were 27 mortalities. We analyzed our results using the Waterston and the Spitz criteria and studied each independent variable within the two prognostic classifications for the more highly significant cause of mortality. The variables considered as significant indicators of mortality were low birth weight (LBW), pneumonia, associated congenital heart disease (CHD), other associated anomalies, and very LBW. Results: The Waterston prognostic classification was very highly significant (P < 0.0005) as an indicator of prognosis in this study. The two most significant variables affecting survival were LBW, as described by Waterston (P = 0.005) and the association of major CHD (P = 0.006). We had 63% survival and none below the birth weight of 1.8 kg. Conclusion: The study clearly points out that LBW is a highly significant indicator of prognosis followed by the association of major CHD. Waterston's risk classification continues to be a highly significant indicator of prognosis. Further studies are required to assess the combined effects of more than one variable on babies with OA.

A variety of islet autoantibodies (AAbs) can predict and possibly dictate eventual type 1 diabetes (T1D) diagnosis. Upwards of 75% of those with T1D are positive for AAbs against glutamic acid decarboxylase (GAD65 or GAD), a producer of gamma-aminobutyric acid (GABA) in human pancreatic beta cells. Interestingly, bacterial populations within the human gut also express GAD and produce GABA. Evidence suggests that dysbiosis of the microbiome may correlate with T1D pathogenesis and physiology. Therefore, autoimmune linkages between the gut microbiome and islets susceptible to autoimmune attack need to be further elucidated. Utilizing in silico analyses, we show that 25 GAD sequences from human gut bacterial sources show sequence and motif similarities to human beta cell GAD65. Our motif analyses determined that most gut GAD sequences contain the pyroxical dependent decarboxylase (PDD) domain of human GAD65, which is important for its enzymatic activity. Additionally, we showed overlap with known human GAD65 T cell receptor epitopes, which may implicate the immune destruction of beta cells. Thus, we propose a physiological hypothesis in which changes in the gut microbiome in those with T1D result in a release of bacterial GAD, thus causing miseducation of the host immune system. Due to the notable similarities we found between human and bacterial GAD, these deputized immune cells may then target human beta cells leading to the development of T1D.

Background In low-income countries, vaccination campaigns are lagging, and evidence on vaccine acceptance, a crucial public health planning input, remains scant. This is the first study that reports willingness to take COVID-19 vaccines and its socio-demographic correlates in Ethiopia, Africa’s second most populous country. Methods The analysis is based on a nationally representative survey data of 2,317 households conducted in the informal economy in November 2020. It employs two logistic regression models where the two outcome variables are (i) a household head’s willingness to take a COVID-19 vaccine or not, and (ii) if yes if they would also hypothetically pay (an unspecified amount) for it or not. Predictors include age, gender, education, marital status, income category, health insurance coverage, sickness due to COVID-19, chronic illness, trust in government, prior participation in voluntary activities, urban residence. Results Willingness to take the vaccine was high (88%) and significantly associated with COVID-19 cases in the family, trust in government and pro-social behavior. All other predictors such as gender, education, income, health insurance, chronic illness, urban residence did not significantly predict vaccine willingness at the 5% level. Among those willing to take the vaccine, 33% also answered that they would hypothetically pay (an unspecified amount) for it, an answer that is significantly associated with trust in government, health insurance coverage and income. Conclusion The results highlight both opportunities and challenges. There is little evidence of vaccine hesitancy in Ethiopia among household heads operating in the informal economy. The role played by trust in government and pro-social behavior in motivating this outcome suggests that policy makers need to consider these factors in the planning of COVID-19 vaccine campaigns in order to foster vaccine uptake. At the same time, as the willingness to hypothetically pay for a COVID-19 vaccine seems to be small, fairly-priced vaccines along with financial support are also needed to ensure further uptake of COVID-19 vaccines.

Obesity has already been a global epidemic, and its prevalence has been projected to grow by 40% in the next decade. Its increasing prevalence has implications on the epidemiology of chronic kidney disease (CKD), which, in turn, could impact the health system and thereby the society in an adverse manner. Lack of community-based screening programs can lead to missed or late detection of CKD. The current study aims to estimate the prevalence of CKD in overweight and obese general population attending a screening camp in a tertiary care hospital in a North Indian city. In this cross-sectional study, 103 overweight and obese people from a community attending a health camp were screened for serum creatinine, urine analysis, random blood sugar, and uric acid. Demographic and anthropometric parameters were noted. Binary logistic regression analysis was used to find the predictors of CKD in these patients. The median age of the participants was 43 years with a male predominance (68%). More than half (58.4%) of the participants were obese and the remaining 41.6% were overweight. The overall prevalence of CKD was 17.5%. Individuals with obesity and diabetes were more prone to develop CKD (odds ratio = 4.868 and 7.941, respectively). CKD was prevalent in individuals with obesity. Obesity and diabetes were the significant predictors for the development of CKD. All the overweight and obese individuals should be periodically screened for kidney diseases.

The process of forensic handwriting examination consists of two steps: the first step is the objective phase of the process and requires correct ocular observation to make a note of similarities and dissimilarities in the two samples of writing; the second step is subjective phase and depends on proper evaluation of what is observed based on expert’s belief, assumption and experience. The second phase, because of its subjective nature, can also be exploited by dishonest expert resulting in conflicting evidence. This scenario is obviously disruptive for justice, and generally weakens the credibility of this type of evidence.

Chronic kidney disease (CKD) is no longer considered just a health burden, but a major health priority owing to its high treatment costs and poor outcome. The lack of community-based screening programs has led to the detection of CKD patients at advanced stages. This study aims to estimate the prevalence of CKD and patterns of known risk factors among the general population (middle-aged and elderly) attending a screening camp in a community-based setting. The study participants constituted a part of the general population of Varanasi (aged ≥45 years) who volunteered in a screening camp that was organized as part of the World Kidney Day Initiative at Opal Hospital. Information on age, sex, height, weight, smoking and drug history, history of diabetes, hypertension, and family history of kidney disease was extensively interrogated, while laboratory investigations such as urinalysis and serum creatinine levels were recorded. More than three-fifths of the participants were middle-aged adults (i.e., 45–64 years) and the remaining 34.8% were elderly population, i.e., ≥65 years. The overall prevalence of CKD in the 198 studied participants was 29.3%. Higher number of participants (40.6%) of elderly population had CKD (P = 0.011). The serum creatinine, albuminuria, and estimated glomerular filtration rate levels were strongly associated with CKD (P

We estimated the effectiveness of two doses of the ChAdOx1 nCoV-19 (Covishield) vaccine against any COVID-19 infection among individuals ≥45 years in Chennai, Tamil Nadu, India. A community-based cohort study was conducted from May to September 2021 in a selected geographic area in Chennai. The estimated sample size was 10,232. We enrolled 69,435 individuals, of which 21,793 were above 45 years. Two-dose coverage of Covishield in the 18+ and 45+ age group was 18% and 31%, respectively. Genomic analysis of 74 out of the 90 aliquots collected from the 303 COVID-19-positive individuals in the 45+ age group showed delta variants and their sub-lineages. The vaccine’s effectiveness against COVID-19 disease in the ≥45 age group was 61.3% (95% CI: 43.6–73.4) at least 2 weeks after receiving the second dose of Covishield. We demonstrated the effectiveness of two doses of the ChAdOx1 vaccine against the delta variant in the general population of Chennai. We recommend similar future studies considering emerging variants and newer vaccines. Two-dose vaccine coverage could be ensured to protect against COVID-19 infection.

Objectives Domestic violence and abuse (DVA) is highly prevalent, with severe adverse consequences to the health and well-being of survivors. There is a smaller evidence base on the health of DVA perpetrators and their engagement with healthcare services. This review examines the experiences of perpetrators of DVA of accessing healthcare services and the barriers and facilitators to their disclosure of abusive behaviours in these settings.Design A systematic review and meta-synthesis of qualitative studies.Data sources A systematic search was conducted in Cochrane, MEDLINE, Embase, PsycINFO, HMIC, BNID, CINAHL, ASSIA, IBSS, SSCI (peer-reviewed literature) and NDLTD, OpenGrey and SCIE Online (grey literature). Each database was searched from its start date to 15 March 2020. Eligibility criteria required that studies used qualitative or mixed methods to report on the experiences of healthcare use by perpetrators of DVA. A meta-ethnographic method was used to analyse the extracted data.Results Of 30,663 papers identified, six studies (n=125 participants; 124 men, 1 woman) met the inclusion criteria. Barriers to disclosure of DVA to healthcare staff included perpetrators’ negative emotions and attitudes towards their abusive behaviours; fear of consequences of disclosure; and lack of trust in healthcare services’ ability to address DVA. Facilitators of disclosure of DVA and engagement with healthcare services were experiencing social consequences of abusive behaviours; feeling listened to by healthcare professionals; and offers of emotional and practical support for relationship problems by healthcare staff.Conclusions DVA perpetration is a complex issue with multiple barriers to healthcare engagement and disclosure. However, healthcare services can create positive conditions for the engagement of individuals who perpetrate abuse.PROSPERO registration number CRD42017073818.

At the start of the COVID-19 pandemic, the Centers for Disease Control and Prevention (CDC) designed, manufactured, and distributed the CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel for SARS-CoV-2 detection. The diagnostic panel targeted three viral nucleocapsid gene loci (N1, N2, and N3 primers and probes) to maximize sensitivity and to provide redundancy for virus detection if mutations occurred. After the first distribution of the diagnostic panel, state public health laboratories reported fluorescent signal in the absence of viral template (false-positive reactivity) for the N3 component and to a lesser extent for N1. This report describes the findings of an internal investigation conducted by the CDC to identify the cause(s) of the N1 and N3 false-positive reactivity. For N1, results demonstrate that contamination with a synthetic template, that occurred while the "bulk" manufactured materials were located in a research lab for quality assessment, was the cause of false reactivity in the first lot. Base pairing between the 3' end of the N3 probe and the 3' end of the N3 reverse primer led to amplification of duplex and larger molecules resulting in false reactivity in the N3 assay component. We conclude that flaws in both assay design and handling of the "bulk" material, caused the problems with the first lot of the 2019-nCoV Real-Time RT-PCR Diagnostic Panel. In addition, within this study, we found that the age of the examined diagnostic panel reagents increases the frequency of false positive results for N3. We discuss these findings in the context of improvements to quality control, quality assurance, and assay validation practices that have since been improved at the CDC.

The innate immune response to P. aeruginosa pulmonary infections relies on a network of pattern recognition receptors, including intracellular inflammasome complexes, which can recognize both pathogen- and host-derived signals and subsequently promote downstream inflammatory signaling. Current evidence suggests that the inflammasome does not contribute to bacterial clearance and, in fact, that dysregulated inflammasome activation is harmful in acute and chronic P. aeruginosa lung infection. Given the role of mitochondrial damage signals in recruiting inflammasome signaling, we investigated whether mitochondrial-targeted therapies could attenuate inflammasome signaling in response to P. aeruginosa and decrease pathogenicity of infection. In particular, we investigated the small molecule, ZLN005, which transcriptionally activates peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a master regulator of mitochondrial biogenesis, antioxidant defense, and cellular respiration. We demonstrate that P. aeruginosa infection promotes the expression of inflammasome components and attenuates several components of mitochondrial repair pathways in vitro in lung epithelial cells and in vivo in an acute pneumonia model. ZLN005 activates PGC-1α and its downstream effector, Sirtuin 3 (SIRT3), a mitochondrial-localized deacetylase important for cellular metabolic processes and for reactive oxygen species homeostasis. ZLN005 also attenuates inflammasome signaling induced by P. aeruginosa in bronchial epithelial cells and this action is dependent on ZLN005 activation of SIRT3. ZLN005 treatment reduces epithelial-barrier dysfunction caused by P. aeruginosa and decreases pathogenicity in an in vivo pneumonia model. Therapies that activate the PGC-1α—SIRT3 axis may provide a complementary approach in the treatment of P. aeruginosa infection.

Study Design A multi-centric randomized controlled trial to be conducted at two sites, department of phyhysiotherapypy, Punjabi University, Patiala and rehabilitation department, Indian Spinal Injury Centre, New Delhi, India. Purpose To determine the effectiveness of activity-based therapy in comparison with surface spinal stimulation (SSS) in traumatic incomplete spinal cord injury (SCI) with special reference to locomotion—a central pattern generator controlled function. Overview of Literature A major goal for many patients after SCI is to regain the function of locomotion. It is crucial that rehabilitation strives to maximize locomotor ability and functional recovery after SCI. Experimental evidence of improvement in stepping and motor control after activity-based training in animal models and human SCI has been translated into clinical neuro-rehabilitation. Methods Control group participants will undertake an intensive 24-week duration thrice weekly program of activity-based therapy. In addition to this the participants in experimental group will also receive a session of 45 minutes of SSS on thrice weekly basis. The primary analysis for our study will be at 24 weeks. Linear regression will be used to determine the mean between-group differences and 95% confidence interval for all continuous outcomes using baseline scores and group allocation as covariates. Results The primary outcome measure is improvement in the level of walking index for SCI-II. The secondary outcome measures are modified Ashworth scale, Penn spasm frequency score, spinal cord independence measure-III, SCI functional ambulation inventory, Hoffman’s reflex, somatosensory evoked potential, and American Spinal Injury Association Impairment Scale scores. Conclusions An insight into training-induced mechanisms will be of great importance to fine tune such combined treatments and vindicate their efficacy in restoration of locomotion and functional activities in individuals with SCI.

Introduction: Polycystic ovarian syndrome (PCOS) is a common endocrinopathy typified by oligo-ovulation or anovulation, signs of androgen excess, and multiple small ovarian cysts. Materials and Methods: The study participants included fifty clinically diagnosed PCOS patients (diagnosed using according to the Rotterdam criteria) and twenty group-matched healthy female attendants of these patients. All controls had self-reported spontaneous regular menstrual cycles and no history of sub/infertility. Results: The mean fasting blood sugar levels in the study group of PCOS patients were 79.92 ± 8.55 mg%, the mean body mass index was 26.54 ± 5.14 kg/m2, and mean luteinizing hormone (LH) levels in the study group and control group were 10.46 ± 3.02 mlU/ml and 5.89 ± 2.12 mlU/ml, respectively. The mean difference between two groups was found to be statistically significant (P < 0.001). The mean LH-follicle-stimulating hormone (FSH) ratio in the study group was 1.97 ± 0.83, and in control group, it was 1.17 ± 0.37. The mean LH-FSH ratio was higher in study group than in control group and this difference was found to be statistically significant (P < 0.001). The mean thyroid-stimulating hormone in study group was 2.42 ± 0.99 μIU/ml, and in control group, it was 2.48 ± 0.72 μIU/ml. The difference between them was found to be statistically nonsignificant (P = 0.811). Thirty-six patients, i.e., 72% cases were found to be positive for polycystic ovaries on ultrasonography, while in control group, all women had normal ovaries. Conclusions: The possible pathophysiological mechanism of ovarian cyst formation in patients with PCOS is immune mediated and possibly similar to subclinical hypothyroidism.

Background: Laser etching has several advantages as compared with conventional acid etching. However, results of earlier studies on conditioning surfaces with erbium, chromium:yttrium–scandium–gallium–garnet (Er, Cr:YSGG) before application of the fissure sealant have been inconclusive. Aim: The study aimed to evaluate the microtensile strength of resin-based fissure sealant bonded to primary enamel conditioned by Er, Cr:YSGG laser with varying power outputs. Materials and Methods: Fifty sound primary first molars were randomized into the following five groups based on pretreatment choice: Group 1: 3.5 W laser etching + acid etching; Group 2: 2.5 W laser etching + acid etching; Group 3: 3.5 W laser etching with no acid; Group 4: 2.5 W laser etching with no acid and Group 5: acid etching with no laser. Acid etch was performed with 35% orthophosphoric acid for 30 s. Laser etching was performed with Er, Cr:YSGG (2780 nm) laser using G6 tips and 600 μm diameter, 2.5 W or 3.5 W power outputs, pulse duration of 140 μs and a repetition rate of 20 Hz. Sealant was applied on the buccal surface followed by an incremental buildup with composite resin. Microtensile bond strength was assessed and compared among the five groups using one- and two-way ANOVA. Results: There was no statistical difference in the mean bond strength between groups except in Group 4 (9.66 MPa) (Group 1: 15.57 MPa; Group 2: 14.18 MPa; Group 3: 14.78 MPa; Group 5: 14.63 MPa). Conclusion: Pretreatment with 3.5 W Er, Cr:YSGG laser alone results in microtensile bond strengths similar to that produced by acid etching, indicating that enamel etching using 3.5 W Er, Cr:YSGG laser would result in the long-term success of pit and fissure sealants in primary teeth.

The widespread use of combination antiretroviral therapy (cART) has led to the accelerated aging of the HIV-infected population, and these patients continue to have a range of mild to moderate HIV-associated neurocognitive disorders (HAND). Infection results in altered mitochondrial function. The HIV-1 viral protein Tat significantly alters mtDNA content and enhances oxidative stress in immune cells. Microglia are the immune cells of the central nervous system (CNS) that exhibit a significant mitotic potential and are thus susceptible to telomere shortening. HIV disrupts the normal interplay between microglia and neurons, thereby inducing neurodegeneration. HIV cART contributes to the inhibition of telomerase activity and premature telomere shortening in activated peripheral blood mononuclear cells (PBMC). However, limited information is available on the effect of cART on telomere length (TL) in microglia. Although it is well established that telomere shortening induces cell senescence and contributes to the development of age-related neuro-pathologies, the effect of HIV-Tat on telomere length in human microglial cells and its potential contribution to HAND are not well understood. It is speculated that in HAND intrinsic molecular mechanisms that control energy production underlie microglia-mediated neuronal injury. TL, telomerase and mtDNA expression were quantified in microglial cells using real time PCR. Cellular energetics were measured using the Seahorse assay. The changes in mitochondrial function were examined by Raman Spectroscopy. We have also examined TL in the PBMC obtained from HIV-1 infected rapid progressors (RP) on cART and those who were cART naïve, and observed a significant decrease in telomere length in RP on cART as compared to RP’s who were cART naïve. We observed a significant decrease in telomerase activity, telomere length and mitochondrial function, and an increase in oxidative stress in human microglial cells treated with HIV Tat. Neurocognitive impairment in HIV disease may in part be due to accelerated neuro-pathogenesis in microglial cells, which is attributable to increased oxidative stress and mitochondrial dysfunction.

Non-tuberculous mycobacteria (NTM) have been recognized as a causative agent of various human diseases, including severe infections in immunocompromised patients, such as people living with HIV. The most common species identified is the Mycobacterium avium-intracellulare complex (MAI/MAC), accounting for a majority of infections. Despite abundant information detailing the clinical significance of NTM, little is known about host–pathogen interactions in NTM infection. MicroRNAs (miRs) serve as important post-transcriptional regulators of gene expression. Using a microarray profile, we found that the expression of miR-155 and cyclo-oxygenase 2 (COX-2) is significantly increased in bone-marrow-derived macrophages from mice and human monocyte-derived macrophages from healthy volunteers that are infected with NTM. Antagomir against miR-155 effectively suppressed expression of COX-2 and reduced Prostaglandin E2(PGE2) secretion, suggesting that COX-2/PGE2 expression is dependent on miR-155. Mechanistically, we found that inhibition of NF-κB activity significantly reduced miR-155/COX-2 expression in infected macrophages. Most importantly, blockade of COX-2, E-prostanoid receptors (EP2 and EP4) enhanced killing of MAI in macrophages. These findings provide novel mechanistic insights into the role of miR-155/COX-2/PGE2 signalling and suggest that induction of these pathways enhances survival of mycobacteria in macrophages. Defining host–pathogen interactions can lead to novel immunomodulatory therapies for NTM infections which are difficult to treat.

BACKGROUND AND OBJECTIVES: Conventional tube technique (CTT) has been the mainstay for antibody detection in pretransfusion testing. There have been rapid technological advances in blood banking and methodology of crossmatch has been modified to improve the sensitivity of these tests and to enable automation. This study was done to compare the efficacy of three crossmatch techniques: CTT, tube low-ionic-strength-saline indirect antiglobulin test (tube LISS-IAT), and micro column technology (MCT) used in the blood bank serology laboratory. MATERIALS AND METHODS: In this prospective study, 150 samples from patients who had received two or more transfusions on two different occasions (with at least 72 h between two transfusions) were subjected to cross match by three different techniques – CTT, LISS-IAT, and MCT. RESULTS: A total of 16 cases with antibodies were identified in 150 patients. Out of 16 cases, 14 were clinically significant (anti-c = 5, anti-K = 4, anti-E = 2, anti-S = 2, anti-Jka = 1) and 2 nonclinically significant antibody cases (anti-Lea). MCT detected all the 14 clinically significant antibody cases and no case of nonclinically significant antibody. Tube LISS-IAT detected 14 antibody cases including 2 cases of non-clinically significant antibody but failed to detect 1 case of anti-c and the only case of anti-Jka. CTT detected only 10 antibody cases including 2 cases of non-clinically significant antibody and but failed to detect 3 cases of anti-c, 1 case of anti-K, 1 case of anti-E, and the only case of anti-Jka. CONCLUSION: MCT was found to be most efficacious when compared to CTT and tube LISS-IAT in detecting clinically significant red cell antibodies; although MCT missed 2 cases of Lea antibody which were detected by CTT and LISS-IAT.

Abstract Acute brainstem strokes can present a diagnostic challenge due to its variable clinical presentation. MRI with diffusion‐weighted (axial) imaging is highly sensitive for diagnosing ischemic lesions however even that can fail to identify early lesions in the brainstem. Combining coronal section to standard axial MRI‐DWI can facilitate early diagnosis in these cases.

Background: Human multipotent adult progenitor cells (MAPC®) are an emerging therapy for traumatic brain injury (TBI); however, clinically translating a therapy involves overcoming many factors in vivo which are not present in pre-clinical testing. In this study we examined clinical parameters in vitro that may impact cell therapy efficacy. Methods: MAPC were infused through varying gauged needles and catheters with and without chlorhexidine, and their viability tested with trypan blue exclusion. MAPC were co-cultured with phenytoin and celecoxib at relevant clinical concentrations for 1 h and 24 h. Anti-inflammatory potency was tested using a stimulated rat splenocyte co-culture and ELISA for TNF-α production. MAPC were cultured under different osmolar concentrations and stained with propidium iodide for viability. Anti-inflammatory potency was tested by co-culture of MAPC with naïve lymphocytes activated by CD3/CD28 beads, and Click-iT® Plus EdU was used to quantify proliferation by flow cytometry. Results: The mean viability of the MAPC infused via needles was 95 ± 1%; no difference was seen with varying flow rate, but viability was notably reduced by chlorhexidine. MAPC function was not impaired by co-culture with phenytoin, celecoxib, or combination with both. Co-culture with phenytoin showed a decrease in TNF-α production as compared to the MAPC control. MAPC cultured at varying osmolar concentrations all had viabilities greater than 90% with no statistical difference between them. Co-culture of MAPC with CD3/CD28 activated PBMCs showed a significant reduction in proliferation as measured by EdU uptake. Discussion: Needle diameter, phenytoin, celecoxib, and a relevant range of osmolarities do not impair MAPC viability or anti-inflammatory potency in vitro.

Introduction: Prostate-Specific Antigen (PSA) is an organ specific rather than cancer specific hormone. It is a single chain glycoprotein produced by epithelial cells of the prostate gland. Role of PSA in carcinoma of prostate is well defined but its role in other diseases of prostate is not very clear. Increased PSA levels are not essentially associated with prostate cancer, but can also be elevated in conditions other than cancerous lesions, such as prostate inflammation, bacterial prostatitis, Benign Prostate Hyperplasia (BPH) and Urinary Tract Infection (UTI). BPH is the most common benign tumours in men with prevalence ranging from 50% for men in their 50s to 90% for men in their 90s. Aim: To find the relation of serum PSA levels with age, Prostate Volume (PV) and PSA density in BPH patients. Materials and Methods: The present hospital-based, crosssectional study was conducted on 162 BPH patients who consulted to the Urology Department of Rajindra Hospital, Patiala and were prescribed to undergo serum PSA evaluation. The serum PSA levels of these patients were estimated by the Enzyme-Linked Immunosorbent Assay (ELISA). Routine investigations included Complete Blood Count (CBC), serum urea, serum creatinine, Fasting Blood Glucose (FBG), serum PSA and ultrasonography of the kidneys, ureter, bladder and prostate. Correlations were evaluated using Pearson correlation coefficient. All the statistical graphs were plotted using Microsoft Excel 2009. The results p-value

Introduction: Oral exfoliative cytology is a reasonably effective technique for rapid initial evaluation of suspicious lesions. Exfoliated cells obtained from saliva, lavage or scrapings are ideally stained with Papanicolaou stain. Acridine orange stain imparts nuclear and cytoplasmic fluorescence in malignant cells which have increased nuclear activity. This cytochemical property can be utilized for diagnosis of cancer. Aim: The aim was to determine utility of Acridine Orange (AO) fluorescence microscopy as a rapid and easier method for oral cytodiagnosis as compared to Papanicolaou stain. Materials and Methods: The study group included a total of 50 cases, 25 cases clinically suspicious of malignancy (Group I) and 25 non suspicious cases, e.g., inflammatory lesions etc., (Group II) in both sexes, aged > 40 years. The control group comprised 5 individuals in the age group of 20 years and above, without any clinically observable lesions. Scrapings were obtained from oral mucosa, stained with AO and Pap stains, visualised with fluorescence and light microscopy, respectively, and results were compared & analysed statistically. Results: AO staining: Amongst 25 cases in group I, 18 were confirmed as Squamous Cell Carcinomas (SCC) on histopathology. Sixteen out of 18 confirmed cases (88.89%) showed greenish yellow nuclear fluorescence with brownish red cytoplasmic fluorescence. In group II, 18 cases showed too little fluorescence to be labelled as positive with limited nuclear details which were hence counted as negative for fluorescence. Papanicolaou staining: In group I, 13 out of the 18 confirmed cases (72.22%) were positive for malignancy. In group II, only one case was false positive for malignancy and the rest were negative. The differences between the two groups were compared using Chi-square test. A p value of less than 0.05 was considered statistically significant. Conclusion: AO stain reliably demonstrated malignant cells based on differential fluorescence – a cytochemical criterion. Thus, AO proved to be more sensitive than Papanicolaou staining for diagnosing malignancies. Hence, it can be used for screening and early detection of potentially malignant lesions.

The molecular mechanisms underlying susceptibility to severe respiratory syncytial virus (RSV) infection remain poorly understood. Herein, we report on the role of osteopontin (OPN) in regulation of RSV infection in human epithelial cells and how interleukin-1 beta (IL-1β), a cytokine secreted soon after RSV infection, when persistently expressed can induce OPN expression leading to increased viral infection. We first compared OPN expression in two human epithelial cell lines: HEK-293 and HEp-2. In contrast to HEp-2, HEK-293 expresses low levels of pro-caspase-1 resulting in decreased IL-1β expression in response to RSV infection. We found a correlation between low IL-1β levels and a delay in induction of OPN expression in RSV-infected HEK-293 cells compared to HEp-2. This phenomenon could partially explain the high susceptibility of HEp-2 cells to RSV infection versus the moderate susceptibility of HEK-293 cells. Also, HEK-293 cells expressing low levels of pro-caspase-1 exhibit decreased IL-1β expression and delayed OPN expression in response to RSV infection. HEK-293 cells incubated with human rIL-1β showed a dose-dependent increase in OPN expression upon RSV infection. Also, incubation with rOPN increased RSV viral load. Moreover, HEp-2 cells or mice infected with a mucogenic RSV strain RSV-L19F showed elevated levels of OPN in contrast to mice infected with the laboratory RSV strain rA2. This correlated with elevated levels of OPN following infection with RSV-L19F compared to rA2. Together, these results demonstrate that increased OPN expression is regulated in part by IL-1β, and the interplay between IL-1β and OPN signaling may play a pivotal role in the spread of RSV infection.

To describe longitudinal trends in long-term non-invasive ventilation (NIV) use in children including changes in clinical characteristics, NIV technology, and outcomes.This was a multicenter retrospective cohort of all children started on long-term NIV from 2005 to 2014. All children 0 to 18 years who used NIV continuously for at least 3 months were included. Measures and main outcomes were: 1) Number of children starting NIV; 2) primary medical condition; 3) medical complexity defined by number of comorbidities, surgeries and additional technologies; 4) severity of sleep disordered breathing measured by diagnostic polysomnography; 5) NIV technology and use; 6) reasons for NIV discontinuation including mortality. Data were divided into equal time periods for analysis.A total of 622 children were included in the study. Median age at NIV initiation was 7.8 years (range 0-18 years). NIV incidence and prevalence increased five and three-fold over the 10-year period. More children with neurological and cardio-respiratory conditions started NIV over time, from 13% (95%CI, 8%-20%) and 6% (95%CI, 3%-10%) respectively in 2005-2008 to 23% (95%CI, 18%-28%) and 9% (95%CI, 6%-14%, p = 0.008) in 2011-2014. Medical complexity and severity of the sleep-disordered breathing did not change over time. Overall, survival was 95%; mortality rates, however, rose from 3.4 cases (95% CI, 0.5-24.3) to 142.1 (95% CI 80.7-250.3, p

INTRODUCTION:Typhoid fever (TF) continues to cause considerable morbidity and mortality in Nepal, but only limited epidemiologic data is available about TF outside Kathmandu. METHODS:As part of an interventional trial, we performed a prospective cohort study of bacteremic TF patients in Dhulikhel Hospital between October 2012 and October 2014. Demographic, epidemiological, clinical, and microbiologic data were recorded. RESULTS:116 bacteremic typhoid patients were included in the study. Most were young, healthy, adults (mean age 27.9±12 years), 41.4% of whom were female. More than 70% of patients were employed in non-manual services or were university students. Salmonella Typhi accounted for 64/115 (55.7%) of all isolates, while Salmonella Paratyphi accounted for 51/115 (44.3%), of which 42 were Paratyphi A and 9 Paratyphi B. A significant proportion of TF cases occurred also during the dry season (48/116, 41.6%). The clinical presentation of Salmonella Typhi and Paratyphi infections was similar, except for a greater proportion of arthralgia in patients with Salmonella Typhi. Most Salmonella Typhi and Paratyphi isolates were resistant to nalidixic acid and susceptible to older antibiotics. One Salmonella Paratyphi isolate was resistant to ceftriaxone. CONCLUSIONS:TF remains common in the Dhulikhel area, even among those with a high level of education. Public health measures aimed at reducing the incidence of TF in the Dhulikhel area are warranted. The relative burden of TF caused by Salmonella Paratyphi is rising; a vaccine with activity against Salmonella Paratyphi is needed. Since Salmonella Paratyphi B was more prevalent in this cohort than in large cohorts of patients from Kathmandu, it is likely that there are significant regional variations in the epidemiology of TF outside Kathmandu.

TopicalPdb (http://crdd.osdd.net/raghava/topicalpdb/) is a repository of experimentally verified topically delivered peptides. Data was manually collected from research articles. The current release of TopicalPdb consists of 657 entries, which includes peptides delivered through the skin (462 entries), eye (173 entries), and nose (22 entries). Each entry provides comprehensive information related to these peptides like the source of origin, nature of peptide, length, N- and C-terminal modifications, mechanism of penetration, type of assays, cargo and biological properties of peptides, etc. In addition to natural peptides, TopicalPdb contains information of peptides having non-natural, chemically modified residues and D-amino acids. Besides this primary information, TopicalPdb stores predicted tertiary structures as well as peptide sequences in SMILE format. Tertiary structures of peptides were predicted using state-of-art method PEPstrMod. In order to assist users, a number of web-based tools have been integrated that includes keyword search, data browsing, similarity search and structural similarity. We believe that TopicalPdb is a unique database of its kind and it will be very useful in designing peptides for non-invasive topical delivery.

Introduction: Laparoscopic cholecystectomy is one of the most commonly performed minimally invasive surgery. But in every patient, there are different types of difficulties in performing laparoscopic cholecystectomy and outcome may be different according to the difficulties. Aim: To assess and grade the degree of difficulty in laparoscopic cholecystectomy and their postoperative outcome using intraoperative scoring system devised. Materials and Methods: One hundred three consecutive patients who underwent elective laparoscopic cholecystectomy at Himalayan Institute of Medical Sciences, were included in the study. Inclusion criteria was all the cases of elective laparoscopic cholecystectomy and exclusion criteria was cases in which directly open cholecystectomy was performed. Intraoperative findings were assessed on the basis of five key aspects which includes: 1) Gallbladder appearance and amount of adhesions; 2) Degree of distension/ contraction of the gallbladder; 3) Ease of access; 4) Local/septic complications; and 5) Time taken to identify the cystic artery and duct. Results: Total 103 patients of laparoscopic cholecystectomy were included in this study. The severity score was between 2-4 in 63 (61.16%) patients and between 5-7 in 20 (19.41%) patients. Mild to moderate degree of difficulty was encountered in 80 (77.66%), severe degree in 20 (19.41%) and extreme degree of difficulty in 03 (2.91%) patients in performing cholecystectomy and conversion to open surgery were done in 08 (7.76%) patients with score between 6 to 8. Conclusion: This scoring system is useful and reliable. If the intraoperative severity score is more, the severity of cholecystitis increases and then it is more difficult to perform laparoscopic cholecystectomy.

The molecular mechanisms involved in breast cancer progression and metastasis still remain unclear to date. It is a heterogeneous disease featuring several different phenotypes with consistently different biological characteristics. Neuroligins are neural cell adhesion molecules that have been implicated in heterotopic cell adhesion. In humans, alterations in neuroligin genes are implicated in autism and other cognitive diseases. Until recently, neuroligins have been shown to be abundantly expressed in blood vessels and also play a role implicated in the growth of glioma cells. Here we report increased expression of neuroligin 4X (NLGN4X) in breast cancer. We found NLGN4X was abundantly expressed in breast cancer tissues. NLGN4X expression data for all breast cancer cell lines in the Cancer Cell Line Encyclopedia (CCLE) was analyzed. Correlation between NLGN4X levels and clinicopathologic parameters were analyzed within Oncomine datasets. Evaluation of these bioinfomatic datasets results revealed that NLGN4X expression was higher in triple negative breast cancer cells, particularly the basal subtype and tissues versus non-triple-negative sets. Its level was also observed to be higher in metastatic tissues. RT-PCR, flow cytometry and immunofluorescence study of MDA-MB-231 and MCF-7 breast cancer cells validated that NLGN4X was increased in MDA-MB-231. Knockdown of NLGN4X expression by siRNA decreased cell proliferation and migration significantly in MDA-MB-231 breast cancer cells. NLGN4X knockdown in MDA-MB-231 cells resulted in induction of apoptosis as determined by annexin staining, elevated caspase 3/7 and cleaved PARP by flow cytometry. High NLGN4X expression highly correlated with decrease in relapse free-survival in TNBC. NLGN4X might represent novel biomarkers and therapeutic targets for breast cancer. Inhibition of NLGN4X may be a new target for the prevention and treatment of breast cancer.

THPdb (http://crdd.osdd.net/raghava/thpdb/) is a manually curated repository of Food and Drug Administration (FDA) approved therapeutic peptides and proteins. The information in THPdb has been compiled from 985 research publications, 70 patents and other resources like DrugBank. The current version of the database holds a total of 852 entries, providing comprehensive information on 239 US-FDA approved therapeutic peptides and proteins and their 380 drug variants. The information on each peptide and protein includes their sequences, chemical properties, composition, disease area, mode of activity, physical appearance, category or pharmacological class, pharmacodynamics, route of administration, toxicity, target of activity, etc. In addition, we have annotated the structure of most of the protein and peptides. A number of user-friendly tools have been integrated to facilitate easy browsing and data analysis. To assist scientific community, a web interface and mobile App have also been developed.

Background: Immunotherapy has changed the options for the treatment of various cancer types, but not colon cancer. Current checkpoint blockade approaches are ineffective in a large proportion of colon cancer cases, necessitating studies to elucidate its mechanisms and to identify new targets and strategies against it. Methods: Here, we examined Programmed Death-Ligand 1(PD-L1), cytokine and receptor responses of colon cancer cells exposed to camptothecin (CPT), a clinically used topoisomerase inhibitor. Colon cancer cells were treated with CPT at concentrations of up to 10 µM, and the expressions of PD-L1 and immunoregulatory cytokine genes and receptors were analyzed. Results: PD-L1, a current immunotherapy target for various cancers, was shown to be upregulated in colon cancer cells independent of the cellular p53 status. In metastasis-derived SW620 cells, CPT most extensively upregulated cytokines with T-cell attraction or growth factor functions. Of those modulated genes, SPP1, IL1RN, IL1A, TNFSF13B, OSM, and CSF3 had the most clinical relevance, as their high expression was associated with poor cancer patient overall survival. Conclusions: These findings highlight the need to examine, in preclinical and clinical situations, the potential benefits of combining topoisomerase inhibitors with immune-checkpoint inhibitors.

Brucellosis is endemic among dairy animals in India, contributing to production losses and posing a health risk to people, especially farmers and others in close contact with dairy animals or their products. Growing urban populations demand increased milk supplies, resulting in intensifying dairy production at the peri-urban fringe. Peri-urban dairying is under-studied but has implications for disease transmission, both positive and negative. In this cross-sectional study, five Indian cities were selected to represent different geographies and urbanization extent. Around each, we randomly selected 34 peri-urban villages, and in each village three smallholder dairy farms (defined as having a maximum of 10 dairy animals) were randomly selected. The farmers were interviewed, and milk samples were taken from up to three animals. These were tested using a commercial ELISA for antibodies against Brucella abortus, and factors associated with herd seroprevalence were identified. In all, 164 out of 1163 cows (14.1%, 95% CI 12.2–16.2%) were seropositive for Brucella. In total, 91 out of 510 farms (17.8%, 95% CI 14.6–21.4%) had at least one positive animal, and out of these, just seven farmers stated that they had vaccinated against brucellosis. In four cities, the farm-level seroprevalence ranged between 1.4–5.2%, while the fifth city had a seroprevalence of 72.5%. This city had larger, zero-grazing herds, used artificial insemination to a much higher degree, replaced their animals by purchasing from their neighbors, were less likely to contact a veterinarian in case of sick animals, and were also judged to be less clean. Within the high-prevalence city, farms were at higher risk of being infected if they had a young owner and if they were judged less clean. In the low-prevalence cities, no risk factors could be identified. In conclusion, this study has identified that a city can have a high burden of infected animals in the peri-urban areas, but that seroprevalence is strongly influenced by the husbandry system. Increased intensification can be associated with increased risk, and thus the practices associated with this, such as artificial insemination, are also associated with increased risk. These results may be important to identify high-risk areas for prioritizing interventions and for policy decisions influencing the structure and development of the dairy industry.

Neural stem cells (NSCs) promote recovery from brain trauma, but neuronal replacement is unlikely the sole underlying mechanism. We hypothesize that grafted NSCs enhance neural repair at least partially through modulating the host immune response after traumatic brain injury (TBI). C57BL/6 mice were intracerebrally injected with primed human NSCs (hNSCs) or vehicle 24 h after a severe controlled cortical impact injury. Six days after transplantation, brain tissues were collected for Western blot and immunohistochemical analyses. Observations included indicators of microglia/macrophage activation, M1 and M2 phenotypes, axonal injury detected by amyloid precursor protein (APP), lesion size, and the fate of grafted hNSCs. Animals receiving hNSC transplantation did not show significant decreases of brain lesion volumes compared to transplantation procedures with vehicle alone, but did show significantly reduced injury-dependent accumulation of APP. Furthermore, intracerebral transplantation of hNSCs reduced microglial activation as shown by a diminished intensity of Iba1 immunostaining and a transition of microglia/macrophages toward the M2 anti-inflammatory phenotype. The latter was represented by an increase in the brain M2/M1 ratio and increases of M2 microglial proteins. These phenotypic switches were accompanied by the increased expression of anti-inflammatory interleukin-4 receptor α and decreased proinflammatory interferon-γ receptor β. Finally, grafted hNSCs mainly differentiated into neurons and were phagocytized by either M1 or M2 microglia/macrophages. Thus, intracerebral transplantation of primed hNSCs efficiently leads host microglia/macrophages toward an anti-inflammatory phenotype that presumably contributes to stem cell-mediated neuroprotective effects after severe TBI in mice.

Introduction: Early detection and treatment of vision problems in children is imperative to meet the challenges of childhood blindness. Considering the problems of inequitable distribution of trained manpower and limited access of quality eye care services to majority of our population, innovative community based strategies like ‘Teachers training in vision screening’ need to be developed for effective utilization of the available human resources. Aim: To evaluate the effectiveness of introducing teachers as the first level vision screeners. Materials and Methods: Teacher training programs were conducted for school teachers to educate them about childhood ocular disorders and the importance of their early detection. Teachers from government and semi-government schools located in Ludhiana were given training in vision screening. These teachers then conducted vision screening of children in their schools. Subsequently an ophthalmology team visited these schools for re-evaluation of children identified with low vision. Refraction was performed for all children identified with refractive errors and spectacles were prescribed. Children requiring further evaluation were referred to the base hospital. The project was done in two phases. True positives, false positives, true negatives and false negatives were calculated for evaluation. Results: In phase 1, teachers from 166 schools underwent training in vision screening. The teachers screened 30,205 children and reported eye problems in 4523 (14.97%) children. Subsequently, the ophthalmology team examined 4150 children and confirmed eye problems in 2137 children. Thus, the teachers were able to correctly identify eye problems (true positives) in 47.25% children. Also, only 13.69% children had to be examined by the ophthalmology team, thus reducing their work load. Similarly, in phase 2, 46.22% children were correctly identified to have eye problems (true positives) by the teachers. By random sampling, 95.65% children were correctly identified as normal (true negatives) by the teachers. Conclusion: Considering the high true negative rates and reasonably good true positive rates and the wider coverage provided by the program, vision screening in schools by teachers is an effective method of identifying children with low vision. This strategy is also valuable in reducing the workload of the eye care staff.

Chorangioma is a nontrophoblastic benign vascular tumour of the placenta, arising from the primitive chorionic mesenchyme. The clinical significance is related to the size of the tumours. Small chorangiomas, with a frequency of about 1%, are often asymptomatic. On the contrary, giant chorangiomas, greater than 5 cm in diameter, are rare tumours, with prevalence ranging from 1:9,000 to 1:50,000, and often associated with a variety of pregnancy complications and a poor perinatal outcome. We report a case of 26-year-old female who presented to us at 36 weeks of gestation with pain in the lower abdomen. Ultrasonograpy revealed polyhydramnios and a vascular tumour on the surface of placenta. Proper conservative antenatal management was done and a full term healthy baby was delievered. Histopathological examination of the extracted mass confirmed the diagnosis of chorangioma. The novelty of this report lies in the presence of large nontrophoblastic vascular placental tumour and the absence of any fetal complications. We emphasise the need of regular and timely antenatal management to diagnose and treat the complications of chorangioma at an early stage.

The aim of the present review was to elaborate on the surface modifications of biomaterials which are used in implant dentistry. The ongoing studies on the clinical and laboratory phases and on the biomaterial sciences have largely aimed at invoking a stronger bone response and an earlier and longer functional loading. Surgical grafting procedures to improve the bone bed are used to create an ideal environment for the implant functioning. The implant selection which is based on the available bone, is also an important determiner of the long term clinical success. The interfacial zone between the implant and the bone is composed of a relatively thin layer (

Extra-gonadal Germ cell tumours (EGCTs) are germ cell tumours that are found in locations other than the gonads. These tumours are seen in young males in the midline, mostly in the mediastinum followed by retroperitoneum, pineal gland, and sacrococcygeal area. While most of these are non-seminomatous, few are seminomatous. We present here a case report of a 25-year-old, mentally retarded male patient, with bilaterally normal testes, who presented with a huge mass in abdomen. The ultrasound and CECT (Contrast Enhanced Computerized Tomography) scan done showed two large retroperitoneal masses, which on FNAC (Fine Needle Aspiration Cytology) suggested germ cell tumour. Surgical resection was done and the subsequent histopathological examination provided the diagnosis of seminoma, which was further confirmed by PAS (Periodic Acid Schiff) staining and Immunohistochemistry for PLAP (Placental Alkaline Phosphatase). Retroperitoneum is a common site for sarcomas, which also present as huge, bulky masses. Thus, EGCTs should be considered in the differential diagnosis of a soft-tissue mass in abdomen, especially arising in the retroperitoneum.