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Introduction: The National Viral Hepatitis Control Program launched by the Government of India aims to end viral hepatitis by the year 2030. The main key objective of the programme is to enhance community awareness about the virus, the disease and the preventive measures for tackling the burden of hepatitis. Lack of knowledge and awareness regarding the disease, its modes of spread and the available preventive strategies would seriously limit in achieving the goal of reduction in burden and elimination of HBV. Objective: To assess the knowledge, attitude and practice on epidemiology of Hepatitis B among residents in a coastal village of Puducherry, Southern India. Method: A community-based, cross-sectional survey was conducted for three months among 796 adults aged ≥18 years residing in a coastal village which was one of the rural field practice areas of a private medical college in Puducherry. Multi-stage sampling technique was followed. A pre-validated, semi-structured questionnaire incorporated in Epicollect 5 software was utilized to capture the data through face-to-face interviews. The data analysis was performed using SPSS, v24.0. Results: About 66.3% of participants had heard of Hepatitis with 55.9% specifically aware of Hepatitis B as a viral disease. More than half (59.3%) believed they could contract Hepatitis B. About three-fourth (73.1%) had not undergone screening for Hepatitis B, and 67.1% had not received the Hepatitis B vaccination. Age, gender and socio-economic status of the respondents were associated with knowledge attitude and practice on Hepatitis B among participants which was found to be statistically significant (p-value < 0.0001). Conclusion: The findings from the study showed that more than two third of participants had heard of Hepatitis. More than half of the respondents believed they could contract Hepatitis B. Nearly two-third respondents had not received Hepatitis B vaccination.

Additive manufacturing (AM) is projected to require 60,000 jobs in the UK by 2025, but there are a series of barriers to the industrial application. One of the most problematic is non-comprehensive knowledge in design for AM (DfAM). This study aims to test the effect of two undergraduate DfAM teaching approaches. A visual and audial approach (design lecture) and a kinaesthetic, problem-based learning (PBL) approach (manufacturing laboratory) were compared against technical and participant perspective criteria to assess the learning, engagement, and self-efficacy of the students. The participants were set a DfAM challenge; to redesign a bracket. The technical merits of the designs were evaluated after teaching through a design lecture alone or after a design lecture and manufacturing-laboratory. The participant's perspective was evaluated at the end of the study. The groups who undertook both the design lecture and manufacturing laboratory showed a mean technical mark of 100% for criteria (C) 13 ("Parts have been consolidated into one part"), 91.7% for C14 ("The bracket is hollowed where possible") and 100% for C16 ("Manufacture was successful"). These technical marks demonstrate a statistically significant increase over those of the groups who undertook the design lecture alone. The participant evaluation reinforced this result; the manufacturing laboratory was chosen more frequently in answer to questions on applicability (Q13 = 83%), preparedness (Q15 = 83%), and gaining confidence in DfAM (Q31 = 74%). This study demonstrates the importance of PBL in DfAM, both to increase technical aptitude of the student (creativity and manufacturing) and their perspective on their own learning and self-efficacy.

Abstract A generalized data scheme for transferable classical force fields used in molecular simulations, i.e. molecular dynamics and Monte Carlo simulation, is presented. The data scheme is implemented in an SQL-based data format. The data scheme and data format is machine readable, re-usable, and interoperable. A transferable force field is a chemical construction plan specifying intermolecular and intramolecular interactions between different types of atoms or different chemical groups and can be used for building a model for a given component. The data scheme proposed in this work (named TUK-FFDat) formalizes digitally these chemical construction plans, i.e. transferable force fields. It can be applied to all-atom as well as united-atom transferable force fields. The general applicability of the data scheme is demonstrated for different types of force fields (TraPPE, OPLS-AA, and Potoff). Furthermore, conversion tools for translating the data scheme between .xls spread sheet format and the SQL-based data format are provided. The data format can readily be integrated in existing workflows, simulation engines, and force field databases as well as for linking such.

Abstract Primary dural Hodgkin lymphoma (PDHL) is an extremely rare subset of Hodgkin lymphoma (HL). Its existence is controversial, as Hodgkin lymphoma is not traditionally thought to arise from the central nervous system (CNS) or its meninges and only 0.02% of patients with Hodgkin lymphoma have any CNS involvement. We report a case of a 71‐year‐old Caucasian man who presented with progressive fatigue and sudden onset slurred speech, disorientation, and memory loss. Brain imaging identified a large extra‐axial right frontal mass, and he underwent urgent subtotal resection. Pathology and subsequent workup revealed Stage IAE classical Hodgkin lymphoma of the right frontal dura, with no extra‐cranial disease or leptomeningeal spread detected. The patient was subsequently treated with ABVD chemotherapy (completed 2.5 of 4 planned cycles) and 36 Gy in 20 fractions of consolidative involved‐site radiotherapy (ISRT). He has been followed for 5 years with no clinical or radiological signs of recurrence. This is the second confirmed case of intracranial PDHL reported in the literature, with the longest follow‐up for any case of PDHL.

Introduction: Heart failure due to myocardial infarction is a progressive and debilitating condition, affecting millions worldwide. Novel treatment strategies are desperately needed to minimise cardiomyocyte damage after myocardial infarction and to promote repair and regeneration of the injured heart muscle. Plasma polymerized nanoparticles (PPN) are a new class of nanocarriers which allow for a facile, one-step functionalization with molecular cargo.Methods: Here, we conjugated platelet-derived growth factor AB (PDGF-AB) to PPN, engineering a stable nano-formulation, as demonstrated by optimal hydrodynamic parameters, including hydrodynamic size distribution, polydisperse index (PDI) and zeta potential, and further demonstrated safety and bioactivity in vitro and in vivo. We delivered PPN-PDGF-AB to human cardiac cells and directly to the injured rodent heart.Results: We found no evidence of cytotoxicity after delivery of PPN or PPN-PDGFAB to cardiomyocytes in vitro, as determined through viability and mitochondrial membrane potential assays. We then measured contractile amplitude of human stem cell derived cardiomyocytes and found no detrimental effect of PPN on cardiomyocyte contractility. We also confirmed that PDGF-AB remains functional when bound to PPN, with PDGF receptor alpha positive human coronary artery vascular smooth muscle cells and cardiac fibroblasts demonstrating migratory and phenotypic responses to PPN-PDGF-AB in the same manner as to unbound PDGF-AB. In our rodent model of PPN-PDGF-AB treatment after myocardial infarction, we found a modest improvement in cardiac function in PPN-PDGF-AB treated hearts compared to those treated with PPN, although this was not accompanied by changes in infarct scar size, scar composition, or border zone vessel density.Discussion: These results demonstrate safety and feasibility of the PPN platform for delivery of therapeutics directly to the myocardium. Future work will optimize PPN-PDGF-AB formulations for systemic delivery, including effective dosage and timing to enhance efficacy and bioavailability, and ultimately improve the therapeutic benefits of PDGF-AB in the treatment of heart failure cause by myocardial infarction.

Objectives To describe mortality due to opioid toxicity among people who experienced incarceration in Ontario between 2015 and 2020, during the fentanyl-dominant era.Design In this retrospective cohort study, we linked Ontario coronial data on opioid toxicity deaths between 2015 and 2020 with correctional data for adults incarcerated in Ontario provincial correctional facilities.Setting Ontario, Canada.Participants Whole population data.Main outcomes and measures The primary outcome was opioid toxicity death and the exposure was any incarceration in a provincial correctional facility between 2015 and 2020. We calculated crude death rates and age-standardised mortality ratios (SMR).Results Between 2015 and 2020, 8460 people died from opioid toxicity in Ontario. Of those, 2207 (26.1%) were exposed to incarceration during the study period. Among those exposed to incarceration during the study period (n=1 29 152), 1.7% died from opioid toxicity during this period. Crude opioid toxicity death rates per 10 000 persons years were 43.6 (95% CI=41.8 to 45.5) for those exposed to incarceration and 0.95 (95% CI=0.93 to 0.97) for those not exposed. Compared with those not exposed, the SMR for people exposed to incarceration was 31.2 (95% CI=29.8 to 32.6), and differed by sex, at 28.1 (95% CI=26.7 to 29.5) for males and 77.7 (95% CI=69.6 to 85.9) for females. For those exposed to incarceration who died from opioid toxicity, 10.6% died within 14 days of release and the risk was highest between days 4 and 7 postrelease, at 288.1 per 10 000 person years (95% CI=227.8 to 348.1).Conclusions The risk of opioid toxicity death is many times higher for people who experience incarceration compared with others in Ontario. Risk is markedly elevated in the week after release, and women who experience incarceration have a substantially higher SMR than men who experience incarceration. Initiatives to prevent deaths should consider programmes and policies in correctional facilities to address high risk on release.

A flexible operation of multiple robotic manipulators operating in a dynamic environment requires online trajectory planning to ensure collision-free trajectories. In this work, we propose a real-time capable motion control algorithm, based on nonlinear model predictive control, which accounts for static and dynamic obstacles. The proposed algorithm is realized in a distributed scheme, where each robot optimizes its own trajectory with respect to the related objective and constraints. We propose a novel approach for collision avoidance between multiple robotic manipulators, where each robot accounts for the predicted movement of the neighboring robots. Additionally, we propose a method to reliably detect and resolve deadlocks occurring in a setup of multiple robotic manipulators. We validate our approach on pick and place scenarios involving multiple robotic manipulators operating in a common workspace in a realistic simulation environment set up in Gazebo. The robots are controlled using the Robot Operating System. Our approach scales up to 4 manipulators and computes a path for each robot in a simultaneous pick and place operation in 94% of all investigated cases without deadlock detection and 100 % of cases with the proposed deadlock resolution algorithm. In contrast, the investigated conventional path planners, such as PRM, PRM*, CHOMP and RRT-Connect, successfully plan a trajectory in at most 54% of all investigated cases for a simultaneous operation of 4 robotic manipulators hindering their application in setups of multiple manipulators.

Rationale: Anxiety is a common comorbidity of chronic obstructive pulmonary disease (COPD) that is associated with higher morbidity and mortality. We evaluated three anxiety screening questionnaires: the Generalized Anxiety Disorder 7-Item Scale (GAD-7), the Hospital Anxiety and Depression Scale Anxiety subscale (HADS-A), and the Anxiety Inventory for Respiratory Disease (AIR).Objectives: To evaluate and compare the test performance characteristics of three anxiety screening questionnaires, using the Mini-International Neuropsychiatric Interview (MINI), version 7.0, as the "gold standard."Methods: Individuals with COPD were recruited at 16 centers. The MINI and questionnaires were administered by trained research coordinators at an in-person visit and readministered by telephone 2-4 weeks later. A composite score for the presence of any Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V) anxiety disorder was computed, based on the MINI as the gold standard, compared with a participant screening positive on self-report measures for these analyses.Results: Two hundred and twenty eligible individuals with COPD were enrolled; 219 completed the study. Eleven percent were identified as having a DSM-V anxiety disorder, based on the MINI. Elevated anxiety symptoms based on questionnaires were 38% for the AIR, 30% for the GAD-7, and 20% for the HADS-A. Area under the receiver operating characteristic curve (AUC) was highest for the GAD-7 (0.78; 95% confidence interval [CI], 0.69-0.87), followed by the HADS-A (0.74; 95% CI, 0.64-0.84) and the AIR (0.66; 95% CI, 0.56-0.76). The AUC for the GAD-7 was significantly greater than for the AIR (P = 0.014). Sensitivity was not statistically different among the questionnaires: 77% for the GAD-7, 63% for the HADS-A, and 66% for the AIR. The HADS-A had the highest specificity, 85%, which was significantly higher than that of the GAD-7 (77%; P

Bone regeneration involves activation of tissue resident stem cells. Here the authors show that mesenchymal progenitors from skeletal muscle mediate the fibrotic response to bone injury and also contribute to bone repair; processes that are impaired when both muscle and bone are injured.

Abstract Background Corticosteroids (CS)s suppress cytokine production and induce apoptosis of inflammatory cells. Prednisone and dexamethasone are oral CSs prescribed for treating asthma exacerbations. While prednisone is more commonly prescribed, dexamethasone is long acting and a more potent glucocorticoid receptor (GR) agonist. It can be administered as a one or two dose regime, unlike the five to seven days required for prednisone, a feature that increases compliance. We compared the relative ability of these two oral CSs to suppress type 2 inflammation. Since progesterone has affinity for the GR and women are more likely to relapse following an asthma exacerbation, we assessed its influence on CS action. Results Dexamethasone suppressed the level of IL-5 and IL-13 mRNA within Th2 cells with ~ 10-fold higher potency than prednisolone (the active form of prednisone). Dexamethasone induced a higher proportion of apoptotic and dying cells than prednisolone, at all concentrations examined. Addition of progesterone reduced the capacity of both CS to drive cell death, though dexamethasone maintained significantly more killing activity. Progesterone blunted dexamethasone-induction of FKBP5 mRNA, indicating that the mechanism of action was by interference of the CS:GR complex. Conclusions Dexamethasone is both more potent and effective than prednisolone in suppressing type 2 cytokine levels and mediating apoptosis. Progesterone attenuated these anti-inflammatory effects, indicating its potential influence on CS responses in vivo. Collectively, our data suggest that when oral CS is required, dexamethasone may be better able to control type 2 inflammation, eliminate Th2 cells and ultimately lead to improved long-term outcomes. Further research in asthmatics is needed.

Patients with primary biliary cholangitis (PBC) with incomplete response to ursodeoxycholic acid are at risk of disease progression and need additional therapy. Obeticholic acid (OCA) was approved in Canada in May 2017, but its effectiveness in a real‐world setting has not been described. We sought to describe our experience with OCA in a Canadian cohort. OCA‐naive patients treated at two Canadian centers were included. Clinical and biochemical data were collected at OCA initiation and during follow‐up. Primary outcomes were changes in serum alkaline phosphatase (ALP), gamma‐glutamyl transferase (GGT), and total bilirubin (TB) over the duration of therapy. Secondary outcomes were changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), immunoglobulin M (IgM), platelets, and albumin; and achievement of the primary endpoint of the original phase 3 study that led to OCA approval (A Placebo‐Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis [POISE]), dose reductions, discontinuations, and tolerability. Repeated‐measures models were used to assess changes in biochemistry over time. Sixty‐four patients were included; 4 carried a diagnosis of overlap with autoimmune hepatitis. Mean age was 54.6 years, median ALP was 250 U/L, TB was 13 µmol/L, platelet count was 225 × 109/L, and 24% had liver stiffness measurements ≥16.9 kPa. There was a significant reduction in mean ALP of 55 U/L (P

Inflammatory pseudotumors of the liver are rare, non-neoplastic liver tumors. Due to the nonspecific clinical presentation, imaging features, and histopathological findings, they can mimic malignant tumors requiring invasive diagnostics. We present a case of a 61-year-old female patient with a history of type 2 diabetes mellitus, hypothyroidism, hyperlipidemia, and polymyalgia rheumatica who had initially presented with abdominal pain for 3 weeks. Further workup showed normal liver chemistries and tumor markers: AFP and CA 19-9. Magnetic resonance imaging (MRI) of the abdomen showed a segment 6 lesion measuring 4.1 × 4.0 × 3.7 cm. A liver biopsy then confirmed the diagnosis of an inflammatory pseudotumor of the liver with negative IgG4. On follow-up imaging, a rapid growth of this liver lesion was noted. Laparoscopy was done but did not show any distinct liver lesion. Follow-up imaging confirmed a decrease in the size of the mass. Interestingly, the patient had been on a higher dose of steroids for her polymyalgia rheumatic leading up to the follow-up imaging. This is the first case of an inflammatory pseudotumor of the liver in a patient with polymyalgia rheumatica. With this case, we would like to increase the awareness for inflammatory pseudotumors of the liver as a differential diagnosis of liver lesions in patients with underlying autoimmune disorders.

BackgroundThe prison setting and health status of people who experience imprisonment increase the risks of COVID-19 infection and sequelae, and other health impacts of the COVID-19 pandemic.ObjectivesTo conduct a mixed methods systematic review on the impacts of the COVID-19 pandemic on the health of people who experience imprisonment.Data sourcesWe searched Medline, PsycINFO, Embase, the Cochrane Library, Social Sciences Abstracts, CINAHL, Applied Social Sciences Index and Abstracts, Sociological Abstracts, Sociology Database, Coronavirus Research Database, ERIC, Proquest Dissertations and Theses, Web of Science, and Scopus in October 2021. We reviewed reference lists for included studies.Study eligibility criteriaOriginal research conducted in or after December 2019 on health impacts of the COVID-19 pandemic on adults in prisons or within three months of release.Study appraisal and synthesis methodsWe used the Joanna Briggs Institute's Critical Appraisal Checklist for Qualitative Research for qualitative studies and the Joanna Briggs Institute's Critical Appraisal Checklist for Studies Reporting Prevalence Data for quantitative studies. We qualitized quantitative data and extracted qualitative data, coded data, and collated similar data into categories.ResultsWe identified 62 studies. People in prisons had disproportionately high rates of COVID-19 infection and COVID-19 mortality. During the pandemic, all-cause mortality worsened, access to health care and other services worsened, and there were major impacts on mental wellbeing and on relationships with family and staff. There was limited evidence regarding key primary and secondary prevention strategies.LimitationsOur search was limited to databases. As the COVID-19 pandemic is ongoing, more evidence will emerge.ConclusionsPrisons and people who experience imprisonment should be prioritized for COVID-19 response and recovery efforts, and an explicit focus on prisons is needed for ongoing public health work including emergency preparedness.Prospero registration number239324.

Statin intolerance, primarily myalgia, is not uncommon in patients treated for elevated low-density lipoprotein cholesterol. Nonstatin drugs, such as ezetimibe, can spare patients from statin exposure, while still reducing low-density lipoprotein cholesterol. Ezetimibe is generally very well tolerated, although gastrointestinal and musculoskeletal symptoms have been occasionally reported. We describe an extremely rare case of an ezetimibe-associated liver injury who required protracted treatment with prednisone and azathioprine. Ezetimibe-associated liver injury should be suspected with development of hepatic abnormalities concurrent with the timing of ezetimibe treatment and in the absence of other possible precipitating factors. Résumé: L’intolérance aux statines, se manifestant principalement par une myalgie, n’est pas rare chez les patients traités pour des taux élevés de cholestérol à lipoprotéines à basse densité (LDL). Des médicaments n’appartenant pas à la classe des statines, comme l’ézétimibe, permettent d’éviter l’exposition aux statines chez les patients, tout en réduisant le taux le cholestérol LDL. L’ézétimibe est généralement bien toléré, bien que des symptômes gastro-intestinaux et musculosquelettiques aient été signalés à l’occasion. Nous décrivons un cas extrêmement rare de lésion hépatique associée à l’ézétimibe ayant nécessité un traitement prolongé par la prednisone et l’azathioprine. Il faut soupçonner une lésion hépatique liée à l’ézétimibe lors de la survenue d’anomalies hépatiques pendant le traitement par l’ézétimibe en l’absence d’autres facteurs déclencheurs.

Abstract Background Glucocorticosteroids (GCs) are the main treatment for asthma as they reduce type 2 cytokine expression and induce apoptosis. Asthma severity is associated with type 2 inflammation, circulating Th2 cells and higher GC requirements. Objective The aim of this study was to assess whether ex vivo production of interleukin 2 (IL‐2), a T‐cell survival factor, associated with clinical features of asthma severity, the proportion of blood Th2 cells and Th2 cell responses to GC. Methods Peripheral blood from asthma patients (n = 18) was obtained and the proportion of Th2 cells determined by flow cytometry. Peripheral blood cells were activated with mitogen (24 hours) and supernatant levels of IL‐2 and IL‐13 measured by enzyme‐linked immunosorbent assay. In vitro differentiated Th2 cells were treated with dexamethasone (DEX) and IL‐2 and assessed for apoptosis by flow cytometry (annexin V). Level of messenger RNA (mRNA) for antiapoptotic (BCL‐2) and proapoptotic (BIM) genes, IL‐13, GC receptor (GR) and FKBP5 were determined by quantitative real‐time polymerase chain reaction. GR binding was assessed by chromatin immunoprecipitation. Results IL‐2 produced by activated peripheral blood cells correlated negatively with lung function and positively with a daily dose of inhaled GC. When patients were stratified based on IL‐2 level, high IL‐2 producers made more IL‐13 and had a higher proportion of circulating Th2 cells. In vitro, increasing the level of IL‐2 in the culture media was associated with resistance to DEX‐induced apoptosis, with more BCL‐2/less BIM mRNA. Th2 cells cultured in high IL‐2 had more IL‐13, less GR mRNA, showed reduced binding of the GR to FKBP5, a known GC‐induced gene, and required higher concentrations of DEX for cytokine suppression. Conclusions and Clinical Relevance IL‐2 downregulates Th2 cell responses to GC, supporting both their survival and pro‐inflammatory capacity. These results suggest that a patient's potential to produce IL‐2 may be a determinant in asthma severity.

Embedding digital technologies in healthcare has the potential to streamline and personalize medical care. However, healthcare systems are often fragmented, and therefore achieving a truly integrated digital health program can be challenging. To promote a streamlined, evidence-based approach to implementing digital health solutions in a healthcare system, the Murdoch Children's Research Institute (MCRI) established the Digital Health Translation and Implementation Program (DHTI) bringing together clinicians, researchers and digital health experts. From the program commencement, frontline clinical innovators have collaborated with DHTI team members to develop and implement digital solutions to address pain-points in the healthcare system. Throughout this program, important lessons have been learnt relating to the development, evaluation and implementation of digital solutions in the healthcare system. This paper explores these lessons and makes recommendations for the successful implementation of digital health solutions in healthcare systems under five main categories: (1) design and usability, (2) stakeholder engagement and uptake, (3) project management and resourcing, (4) process and implementation, and (5) evaluation. Recommendations suggested here are designed to support future healthcare-based digital health programs to maximize the impact digital solutions can have on the healthcare system and patients.