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Abstract We demonstrate a dispersion-free wavefront splitting attosecond resolved interferometric delay line for easy ultrafast metrology of broadband femtosecond pulses. Using a pair of knife-edge prisms, we symmetrically split and later recombine the two wavefronts with a few tens of attosecond resolution and stability and employ a single-pixel analysis of interference fringes with good contrast using a phone camera without any iris or nonlinear detector. Our all-reflective delay line is theoretically analyzed and experimentally validated by measuring 1st and 2nd order autocorrelations and the SHG-FROG trace of a NIR femtosecond pulse. Our setup is compact, offers attosecond stability with flexibility for independent beam-shaping of the two arms. Furthermore, we suggest that our compact and in-line setup can be employed for attosecond resolved pump-probe experiments of matter with few-cycle pulses.

Introduction: Shoulder pain is a common presentation in both hospitals and the community. Shoulder pain can result from a number of different pathologies and to manage the shoulder pain, an accurate diagnosis is needed. Method: An accurate diagnosis can often be made following a detailed history and examination. Investigations, such as imaging and blood tests may also be required. In this study, we provide an algorithmic approach to shoulder pain that can be used in the clinical setting. Summary: This algorithm can be used in hospitals and the community to help identify and manage the different causes of shoulder pain.

Context: Sexually transmitted infections (STIs) are a problem of increasing concern among men and women. They can affect fertility, increase maternal and neonatal morbidity, and can become a burden on both physical and emotional health. Owing to lack of awareness and partly due to the social stigma attached, couples do not come forward for screening. Antenatal testing for STIs is an effective strategy recommended to detect STIs in this subset of the population. Aims: To estimate the seroprevalence of four STIs (hepatitis B, hepatitis C virus, HIV, and syphilis) in pregnant women, to evaluate its correlation with sociodemographic characteristics and sexual behavior, and to check awareness regarding STIs. Settings and Design: It was an observational study on 500 pregnant women attending an antenatal clinic at a tertiary care hospital in rural Haryana, India. Methods and Material: Pregnant women were screened for four STIs – hepatitis B, hepatitis C virus, HIV, and syphilis. Statistical Analysis Used: The sample size was calculated considering the mean reported seroprevalence of infections in pregnant women in previous studies. The power of the study was kept 80% and the alpha error was 0.05. Results: Seroprevalence for STIs in pregnancy was 5.2% – hepatitis C virus (2.6%), hepatitis B (2.4%), and syphilis (0.4%). Conclusions: Viral STIs are more prevalent among pregnant women. Antenatal screening is an effective strategy for the detection of STIs in pregnant women.

Abstract The subgingival microbiome is one of the most stable microbial ecosystems in the human body. Alterations in the subgingival microbiome have been associated with periodontal disease, but their variations over time and between different subgingival sites in periodontally healthy individuals have not been well described. We performed extensive, longitudinal sampling of the subgingival microbiome from five periodontally healthy individuals to define baseline spatial and temporal variations. A total of 251 subgingival samples from 5 subjects were collected over 6–12 months and deep sequenced. The overall microbial diversity and composition differed significantly between individuals. Within each individual, we observed considerable differences in microbiome composition between different subgingival sites. However, for a given site, the microbiome was remarkably stable over time, and this stability was associated with increased microbial diversity but was inversely correlated with the enrichment of putative periodontal pathogens. In contrast to microbiome composition, the predicted functional metagenome was similar across space and time, suggesting that periodontal health is associated with shared gene functions encoded by different microbiome consortia that are individualized. To our knowledge, this is one of the most detailed longitudinal analysis of the healthy subgingival microbiome to date that examined the longitudinal variability of different subgingival sites within individuals. These results suggest that a single measurement of the healthy subgingival microbiome at a given site can provide long term information of the microbial composition and functional potential, but sampling of each site is necessary to define the composition and community structure at individual subgingival sites.

The development of haematopoietic stem cells into mature erythrocytes – erythropoiesis – is a controlled process characterized by cellular reorganization and drastic reshaping of the proteome landscape. Failure of ordered erythropoiesis is associated with anaemias and haematological malignancies. Although the ubiquitin system is a known crucial post-translational regulator in erythropoiesis, how the erythrocyte is reshaped by the ubiquitin system is poorly understood. By measuring the proteomic landscape of in vitro human erythropoiesis models, we found dynamic differential expression of subunits of the CTLH E3 ubiquitin ligase complex that formed maturation stage-dependent assemblies of topologically homologous RANBP9- and RANBP10-CTLH complexes. Moreover, protein abundance of CTLH’s cognate E2 ubiquitin conjugating enzyme UBE2H increased during terminal differentiation, and UBE2H expression depended on catalytically active CTLH E3 complexes. CRISPR-Cas9-mediated inactivation of CTLH E3 assemblies or UBE2H in erythroid progenitors revealed defects, including spontaneous and accelerated erythroid maturation as well as inefficient enucleation. Thus, we propose that dynamic maturation stage-specific changes of UBE2H-CTLH E2-E3 modules control the orderly progression of human erythropoiesis.

Objective To assess the risks and benefits of reverse mentoring of consultants by junior doctors.Design A feasibility study divided into two phases: first a semistructured interview where performance of participating consultants was assessed by junior doctors and then a second phase allowing for feedback to be given on a one-to-one basis. Data collected through questionnaires with free text questions and Likert scores.Setting Tertiary teaching hospital in the UK.Participants Six junior doctors (66.6% male, age range 31–40 years) and five consultants (80% male, age range 35–65 years and consultants for 5–20 years).Intervention Reverse mentoring session.Main outcome measure The concerns and/or benefits of the process of reverse mentoring. Confidence was assessed in 7 domains: clinical practice, approach to juniors, approachability, use of technology, time management, strengths and areas for improvement using Likert scales giving a total out of 35.Results The most common concerns cited were overcoming the hierarchical difference and a selection bias in both mentors and mentees. However, no participant experienced this hierarchical difference through the reverse mentoring process and no relationships were negatively affected. Mentors became more confident in feeding back to seniors (23 vs 29 out of 35, p=0.04) most evident in clinical practice and areas to improve (3 vs 4 out of 5, p=0.041 and 3 vs 5 out of 5, p=0.041, respectively).Conclusion We present the first study of reverse mentoring in an NHS clinical setting. Initial concerns with regard to damaged relationships and hierarchical gradients were not experienced and all participants perceived that they benefited from the process. Reverse mentoring can play a role in engaging and training future leaders at junior stages and provide a means for consultants to receive valuable feedback from junior colleagues.

Abstract In water scarce regions of South Asia, diversification of rice with maize is being advocated towards sustainability of cereal-based cropping systems. Adoption of innovative agronomic management practices, i.e., conservation agriculture (CA) and sub-surface drip irrigation (SSDI) are considered as key strategies for much needed interventions to address the challenges of water scarcity under projected climate change. Benefits from CA and SSDI concerning water economy are well-established, however, information about their complementarity and water budgeting in cereal-based systems are lacking. A field study was conducted with process-based model (HYDRUS-2D) to understand water transport, root water uptake and components of soil water balance in maize grown in rotation with wheat after five years of continuous adoption of conservation agriculture. In this study, altogether eight treatments comprising of 6 CA+ treatments (CA coupled with SSDI); permanent beds using sub-surface drip (PB-SSD) with (WR) and without (WOR) crop residue at different N rates, 0, 120 and 150 kg N ha−1 were compared with CA (PB using furrow irrigation-FI with crop residue-120 kg N ha−1) and conventional tillage practices (CT) (CT using FI without crop residue-120 kg N ha−1). Results showed that the model could simulate the daily changes in profile soil water content with reasonable accuracy in all the treatments. Simulated soil water balance indicated higher cumulative root water uptake (CRWU), lower cumulative evaporation (CE) and higher soil water retention in CA+ (PB-SSD+ crop residue at 150 and 120 kg N ha−1) than CA and CT plots. Hydrus-2D model efficiency > 0, RMSE between 0.009–0.026 and R2 value between 0.80–0.92 at P

Introduction: Anomalies of the developing dentition occur due to absence or interruption of normal tooth development along with genetic and/or environment influences. Craniofacial development and dental malocclusion is an interplay between a number of factors such as tooth size, arch size and shape, the number and arrangement of teeth, size and relationship of the jaws and related soft tissues including lips, cheeks, and tongue. Aim: To evaluate the prevalence and distribution of dental anomalies among different skeletal malocclusions and growth patterns in North Indian population. Materials and Methods: This retrospective cross-sectional study was conducted on pretreatment diagnostic records of 260 patients belonging to the age group of 15-25 years, who had reported to the Out Patient Department (OPD) of Department of Orthodontics, Faculty of Dental Sciences, SGT University, Gurugram, Haryana, India, during the period of April 2012 to December 2020. The analysis was carried out between November 2020 and January 2021. The study sample was grouped into different growth patterns and skeletal malocclusions based on Sella-Nasion-Gonion-Gnathion (SN Go-Gn) and ANB (A point, nasion, B point), Sagittal intermaxillary angle values respectively, which were obtained from the pretreatment lateral cephalometric tracings. The prevalence of dental anomalies was evaluated in each group by examining the pretreatment diagnostic records. Chi-Square/Fisher-Freeman-Halton test were used for statistical analysis. Results: The prevalence of dental anomalies in the study sample was 65 (25%). The most common anomaly found was over retained deciduous teeth, followed by ectopic eruption with prevalence rate of 30 (11.5%) and 24 (9.2%), respectively. A total of 142 (54.6%) patients had hypodivergent growth pattern, 23 (8.8%) had normodivergent growth pattern and 95 (36.5%) had hyperdivergent growth pattern. 36 (13.8%) patients had skeletal class I malocclusion, 205 (78.8%) had skeletal class II malocclusion and 19 (7.3%) patients had skeletal class III malocclusion. Hypodivergent group showed the highest prevalence of dental anomalies with 38 (26.8%), followed by hyperdivergent group with 23 (24.2%) and normodivergent group were 4 (17.4%). Skeletal class I malocclusion group had the highest number of dental anomalies as 13 (36.1%), followed by skeletal class II malocclusion with 50 (24.4%) and skeletal class III malocclusion group with 2 (10.5%). Conclusion: Hypodivergent growth pattern and skeletal class II malocclusion were the most prevalent growth pattern and skeletal malocclusion in North Indian population. Dental anomalies were most prevalent in patients with hypodivergent growth pattern and skeletal class I malocclusion. The results of the present study indicate that dental anomalies are associated with certain malocclusions and growth patterns which may contribute to more accurate treatment predictions.

Introduction: Leptospirosis is an anthropozoonotic disease; it occurs worldwide but is most common in tropical and subtropical countries. It is usually underreported due to a lack of awareness, atypical presentations and lack of diagnostic facilities, especially in a resource-limited setting like India. Knowing the local prevalence of such infections is of utmost importance for appropriate control and management. Aim: To estimate the seroprevalence of leptospirosis among suspected Acute Febrile Illness (AFI) cases and to assess the clinicoepidemiological profile of leptospirosis cases presented at Government Medical College, Amritsar, Punjab, India. Materials and Methods: This hospital-based cross-sectional study was conducted at Government Medical College, Amritsar, Punjab, India from 1st January 2020 to 30th June 2021. A total of 360 clinically suspected AFI cases were enrolled in the study. The demographic and clinical profile of the cases were taken on a semi-structured predesigned proforma. Blood sample was collected from the patients, and an Immunoglobulin M (IgM) Enzyme‑linked Immunosorbent Assay (ELISA) was done for diagnosis. Data analysis was done using International Business Machines (IBM) Statistical Package for the Social Sciences (SPSS) statistical package for windows. Results: Out of 360 AFI cases suspected of leptospirosis, 62 (17.2%) were positive for leptospirosis IgM ELISA. The majority of AFI cases and leptospirosis cases belonged to the 21-40 years age group followed by the 41-60 years age group. Seroprevalence was found to be higher in males (20.8%) as compared to females (12.7%). Maximum seroprevalence (20.1%) was seen during the monsoon season followed by the autumn, summer and winter season. The association between risk exposure to risk factors and leptospirosis seroprevalence was found to be statistically significant (p-value=0.034). Fever, myalgia, headache, nausea/vomiting, icterus and hepatomegaly were common clinical features observed in leptospirosis cases. Conclusion: Leptospirosis has rapidly emerged to become the major cause of AFI in many parts of India. High seroprevalence of leptospirosis was reported among undifferentiated AFI cases in the present study. A programmatic approach towards the prevention, control and management of these emerging diseases in Punjab is highly recommended.

Introduction: Migraine is a disabling headache disorder. Many psychiatric disorders co-exist with migrainous headache which largely remain undiagnosed leading to greater risk of morbidity and significantly impacts quality of life. Migraine patients are particularly at risk for mood and anxiety disorders which negatively impact the prognosis and poor headache outcome. Hence, defining the exact nature of underlying psychiatric conditions in migraine are relevant issues in the clinical practice. Aim: To find the association of psychiatric morbidity and quality of life in migrainous (with and without aura) and non migrainous subjects and to assess the correlation between severity of migraine and quality of life. Materials and Methods: It was a hospital-based cross-sectional study conducted amongst the patients and their healthy attendants visiting the Psychiatry OPD of Rajindra Hospital, Patiala from May 2018 to April 2019, after obtaining ethical clearance. A total of 392 subjects of both gender and in the age group 18-65 years, who gave informed consent were enrolled. Group 1 (n=196) consisted of cases i.e., migrainous patients as per International Classification of Headache Disorders 3rd Edition, β version (ICHD-3) criteria and Group 2 (n=196) consisted non migrainous controls. Psychiatric morbidity was assessed using Mini International Neuropsychiatric Interview (MINI) and confirmed on International Classification of Diseases 10th edition (ICD-10). Severity of migraine was assessed on Migraine Disability Assessment Test (MIDAS) and its impact on quality of life (QOL) by using 36 Item Short Form questionnaire (SF-36 questionnaire). Variables were compared using the independent t-test and Chi-square test. Pearson correlation was used to study the relationship between severity of migraine with QOL in subjects with and without psychiatric morbidity. Results: Psychiatric morbidity was found among 65.3% (n=128) and 19.9% (n=39) subject in Group 1 and Group 2, respectively. Major Depressive Disorder (37.2%, n=73) was the most common psychiatric morbidity, followed by Generalised Anxiety Disorder (8.7%, n=17), Manic episode and Panic disorder each (5.1%, n=10), Hypomanic episode and Obsessive Compulsive Disorder each (3.1%, n=6), Dysthymia (2%, n=4) and Post Traumatic Stress disorder (1%, n=2). Between groups, the association of migraine with Major Depressive Disorder (p≤0.001), General Anxiety Disorder (GAD) (p=0.024), Manic episode (p=0.005), Hypomanic episode (p=0.048) was statistically significant but more in migrainous patients than non migrainous subjects. Migrainous patients had lower QOL in physical and psychological health domains of SF-36 than in non migrainous subjects. Furthermore, migrainous patients with or without psychiatric morbidity had significantly negative correlation in all domains of SF-36. Conclusion: Psychiatric morbidity was significantly higher in migrainous patients than non migrainous subjects with poor quality of life in migrainous patients causing significant disability with an increase in severity of migraine.

Abstract Stagonospora nodorum blotch (SNB) is an economically important wheat disease caused by the necrotrophic fungus Parastagonospora nodorum. SNB resistance in wheat is controlled by several quantitative trait loci (QTLs). Thus, identifying novel resistance/susceptibility QTLs is crucial for continuous improvement of the SNB resistance. Here, the hard winter wheat association mapping panel (HWWAMP) comprising accessions from breeding programs in the Great Plains region of the US, was evaluated for SNB resistance and necrotrophic effectors (NEs) sensitivity at the seedling stage. A genome-wide association study (GWAS) was performed to identify single‐nucleotide polymorphism (SNP) markers associated with SNB resistance and effectors sensitivity. We found seven significant associations for SNB resistance/susceptibility distributed over chromosomes 1B, 2AL, 2DS, 4AL, 5BL, 6BS, and 7AL. Two new QTLs for SNB resistance/susceptibility at the seedling stage were identified on chromosomes 6BS and 7AL, whereas five QTLs previously reported in diverse germplasms were validated. Allele stacking analysis at seven QTLs explained the additive and complex nature of SNB resistance. We identified accessions (‘Pioneer-2180’ and ‘Shocker’) with favorable alleles at five of the seven identified loci, exhibiting a high level of resistance against SNB. Further, GWAS for sensitivity to NEs uncovered significant associations for SnToxA and SnTox3, co-locating with previously identified host sensitivity genes (Tsn1 and Snn3). Candidate region analysis for SNB resistance revealed 35 genes of putative interest with plant defense response-related functions. The QTLs identified and validated in this study could be easily employed in breeding programs using the associated markers to enhance the SNB resistance in hard winter wheat.

Background: The increasing incidence of disconnect between doctors and patients in India makes it imperative to teach principles and practice of ethics to medical graduates before they move into substantive clinical practices. The competency-based medical education (CBME) curriculum was recently introduced in India. The CBME curriculum encompasses teaching ethics at the beginning of the undergraduate medical curriculum. The study was planned to assess the knowledge and awareness of ethics among first-year undergraduate medical students at the beginning of the foundation course and after 40h of ethics training during the course. Materials and Methods: A standard 35-item questionnaire was administered to the first-year medical students at the beginning of the foundation course and after 40h of ethics training/teaching scattered throughout the foundation course. No personal information was recorded on the questionnaire to ensure the confidentiality and anonymity of participants. Results: There was a significant increase in the knowledge regarding some of the items in the questionnaire, such as “patient’s wishes must always be adhered to,” “if the patient refuses to be treated on religious grounds, they should be instructed to find another doctor.” Similarly, there was an improvement in the students’ knowledge of the practice of ethics. The students generally agreed that an awareness of ethics is important and should be an integral part of the MBBS curriculum. Conclusion: To prevent ethical erosion, ethics education should be introduced early during the undergraduate years, and continuous reinforcement is vital. We should strive to promote discussions about real occurrences directly involving students.

Abstract Reduction of excess nutrient application and balanced fertilizer use are the key mitigation options in agriculture. We evaluated Nutrient Expert (NE) tool-based site-specific nutrient management (SSNM) in rice and wheat crops by establishing 1594 side-by-side comparison trials with farmers’ fertilization practices (FFP) across the Indo-Gangetic Plains (IGP) of India. We found that NE-based fertilizer management can lower global warming potential (GWP) by about 2.5% in rice, and between 12 and 20% in wheat over FFP. More than 80% of the participating farmers increased their crop yield and farm income by applying the NE-based fertilizer recommendation. We also observed that increased crop yield and reduced fertilizer consumption and associated greenhouse gas (GHG) emissions by using NE was significantly influenced by the crop type, agro-ecology, soil properties and farmers’ current level of fertilization. Adoption of NE-based fertilizer recommendation practice in all rice and wheat acreage in India would translate into 13.92 million tonnes (Mt) more rice and wheat production with 1.44 Mt less N fertilizer use, and a reduction in GHG of 5.34 Mt CO2e per year over farmers’ current practice. Our study establishes the utility of NE to help implement SSNM in smallholder production systems for increasing crop yields and farmers’ income while reducing GHG emissions.

Background: Autism is reportedly the most severe neuropsychiatric disorder affecting children. Autistic subjects can be characterized by impairments in social interactive behavior along with restricted interests and quite frequently, are seen exhibiting repetitive behavior patterns in stereotyped manner. The inability to perform routine tasks can widely impact the oral health and also, the constant care and sense of helplessness might drastically affect quality of life. Aim: The aim of the study was to assess the oral health status and perceptions regarding an autistic child's oral health among parents. Materials and Methods: Parental perception regarding the quality of life among the afflicted autistic children was done using a self-assessment questionnaire that included eight questions which were replied to in an affirmation or negative answer. 300 parents of autism affected children formed the study participants. Recorded responses were evaluated and percentage of each response was derived. Oral health status was measured by determination of dental caries prevalence and OHI-S index using chair light illumination, mouth mirror, diagnostic probe and a standard WHO periodontal probe. For statistical analysis, the calculations were performed by using the paired t test. Statistical significance, which was fixed at P < 0.05, which is statistically significant.Results: Approximately 18.33% of parents showed were aware that oral health can influence general health; 15% did have exhibit awareness. 15% of parents did not consider that primary teeth were important; 59.1% visited any dentist only when suffering from pain; 5% went for an annual dental examination; 15% and 24.6% parents visited dental practitioners at intervals of 3 and 6 months, respectively. 30%, 25% and 51.66% parents considered obtaining consultation and getting treatment from pediatric dentist; general dentist and general physician. 41.6% parents had taken their children for restorations. 52% reported constant stress whereas 48% reported with constant distressed emotions. No significant difference was determined between the parameters. 75% of autistic children suffered from dental caries whereas oral hygiene scores demonstrated high mean value of 4. Conclusion: Autism is a severely distressing condition wherein oral health along with general physical health is affected. Since parents are directly involved in upbringing of these individuals, they also subsequently show a reduction in quality of life.

Objectives The National Health Service has been moving towards integrated care for the best part of two decades to address the growing financial and service pressures created by an ageing population. Integrated healthcare systems (IHSs) join up health and social care services and have been established to manage the care of individuals with complex chronic conditions but with varied success. It is therefore imperative to conduct a Systematic Literature Review (SLR) to identify and understand the factors that influence their successful functioning, and ascertain the factor with the greatest influence, in order to ensure positive outcomes when establishing future IHSs.Methods Articles published between 1 January 1997 and 8 March 2020 were analysed from the following six databases: Healthcare Management Information Consortium, Nuffield Trust, Cumulative Index to Nursing and Allied Health Literature, PubMed, National Institute for Health and Care Excellence Evidence and Health Systems Evidence. Those deemed relevant after title and abstract screening were procured for subsequent review of the full-text article.Results Thirty-three finalised articles were analysed in this SLR to provide a comprehensive overview of the factors that influence the functioning of IHSs. Factors were stratified into six key categories: organisational culture, workforce management, interorganisational collaboration, leadership ability of staff, economic factors and political factors. Leadership was deemed to be the most influential factor due to its intrinsic and instrumental role in influencing the other key factors.Conclusions The findings of this SLR may serve as a guide to developing tailor-made recommendations and policies that address the identified key factors and thereby improve the functioning of present and future IHSs. Furthermore, due to both its overarching influence and the inadequacy of literature in this field, there is a strong case for further research exploring leadership development specifically for IHSs.

Abstract Background Patients diagnosed with inborn errors of metabolism (IBEM) often present with compromised bone health leading to low bone density, bone pain, fractures, and short stature. Dual-energy X-ray absorptiometry (DXA) is the current gold standard for clinical assessment of bone in the general population and has been adopted for monitoring bone density in IBEM patients. However, IBEM patients are at greater risk for scoliosis, short stature and often have orthopedic hardware at standard DXA scan sites, limiting its use in these patients. Furthermore, DXA is limited to measuring areal bone mineral density (BMD), and does not provide information on microarchitecture. Methods In this study, microarchitecture was investigated in IBEM patients (n = 101) using a new three-dimensional imaging technology high-resolution peripheral quantitative computed tomography (HR-pQCT) which scans at the distal radius and distal tibia. Volumetric BMD and bone microarchitecture were computed and compared amongst the different IBEMs. For IBEM patients over 16 years-old (n = 67), HR-pQCT reference data was available and Z-scores were calculated. Results Cortical bone density was significantly lower in IBEMs associated with decreased bone mass when compared to lysosomal storage disorders (LSD) with no primary skeletal pathology at both the radius and tibia. Cortical thickness was also significantly lower in these disorders when compared to LSD with no primary skeletal pathology at the radius. Cortical porosity was significantly greater in hypophosphatasia when compared to all other IBEM subtypes. Conclusion We demonstrated compromised bone microarchitecture in IBEMs where there is primary involvement of the skeleton, as well as IBEMs where skeletal complications are a secondary outcome. In conclusion, our findings suggest HR-pQCT may serve as a valuable tool to monitor skeletal disease in the IBEM population, and provides insight to the greatly varying bone phenotype for this cohort that can be used for clinical monitoring and the assessment of response to therapeutic interventions.

Context: Tuberculosis (TB) infection is still a major public health burden in India. India accounts for about 25% of the global TB burden. Worldwide India is the country with highest burden of both TB and multidrug-resistant (MDR) TB. Aim: The aim of this study was to evaluate the pattern of resistance of Mycobacterium tuberculosis to first and second line antitubercular drugs among specimens from a multispecialty hospital in Western Maharashtra. Settings and Design: This record-based study was conducted from January 2018. Records of sputum from 2013 to 2017 were obtained from patients with suspected TB. Subjects and Methods: Drug-sensitivity testing was performed by the mycobacterial growth indicator tube method. Sensitivity to first line and second line antitubercular drugs was tested. Statistical Analysis Used: Trend analysis and charts using MS Excel. Results: Among 734 patients, 701 (95.5%) were male and 33 (4.5%) were female. The analysis of our study result showed that 21.7% of patients were monodrug resistant. Out of 734 isolates, 56 (7.62%) showed multi- and 39 (5.6%) out of the 734 samples showed extensive drug-resistant TB. Conclusions: Our study confirms that drug resistance, including MDR, observed against all first-line TB drugs was a real threat in the management of TB infection. The resistance pattern in this study could assist the clinicians in providing appropriate treatment regimen to TB patients and improve their clinical outcome.

The scope of orthodontics has broadened in the current era. It is no longer limited to the treatment of children and adolescents but includes the treatment of adults that are non growing thereby extending the age limit. The number of adults seeking orthodontic treatment has considerably increased over the past few years as people have become aesthetically conscious and aware of treatment modalities available through channels like internet and social media. While treating adult patients, a multidisciplinary approach should be adopted, taking into consideration several factors like systemic diseases and psychological factors so as to formulate a holistic treatment plan. Orthodontists face challenges in treating older adult patients whose growth is already completed. There are various elements that differentiate adult orthodontic treatment from that of children or adolescents. Therefore, this article highlights the constraints or challenges faced by an orthodontist in treating adult patients.

ObjectivesPsychosis is a well established complication of non-prescription drug use. We sought to measure the 1-year mortality of emergency department patients with substance-induced psychosis (SIP).MethodsThis study was a multi-centre, retrospective electronic medical records review of patients presenting to the ED with substance-induced psychosis (SIP). We interrogated the hospital ED database from Jan 1, 2018 and Jan 1, 2019 to identify consecutive patients. All patients were followed for one year from index visit, and classified as alive/dead at that time. Patients were included in the study if they met the following criteria: 1) ED discharge diagnosis of psychosis NOS and a positive urine drugs of abuse screen (UDAS) or the patient verbally endorsed drug use, or 2) Mental disorder due to drug use and "disorganized thought", "bizarre behavior" or "delusional behavior" documented in the chart and one or more of the following criteria: a) arrival with police, b) mental health certification, c) physical restraints, d) chemical restraints. We excluded patients who were not British Columbia residents, since we were unable to ascertain if they were alive or dead at 1 year from their index ED visit. Primary statistical analysis was logistic regression for risk of death in 1 year, based on plausible risk factors, selected a priori.ResultsWe identified 813 presentations for SIP (620 unique patients). The median age of the entire cohort was 35 years (IQR 28-44), and 69.5% (n = 565) were male. Thirty five patients (4.3%; 95% CI 3.2-5.9) had died one year after their initial presentation to the ED for SIP. Separate multivariable logistic regression analyses, controlling for age, demonstrated schizophrenia (OR 4.2, 95% CI 1.8-11.1) significantly associated with increased 1-year mortality.ConclusionsIn our study of patients presenting to the ED with SIP, the 1-year mortality was 4.3%. Controlling for age, schizophrenia was a notable risk factor for increased 1-year mortality.

Abstract A 63‐year‐old man with congenital bicuspid aortic valve disease and complex surgical history (that includes a Ross procedure complicated by cardiac arrest requiring emergency coronary artery bypass graft surgery, multiple subsequent sternotomies to treat a failed pulmonic homograft and pseudoaneurysm repair of the left and right ventricular outflow tracts (LVOT/RVOT), bioprosthetic aortic valve replacement, and aortic valve endocarditis) presented with worsening heart failure symptoms secondary to bioprosthetic aortic valve failure and recurrent pulmonic valve stenosis successfully treated with transcatheter intervention.

Objectives To evaluate the extent to which organisational factors facilitate or inhibit the implementation of the National Health Service (NHS) carbon reduction strategy within acute hospital settings.Setting A single acute NHS Trust with four satellite sites which serve more than 2 million patients annually in Central England.Participants Interviews with a purposive sample of 10 stakeholders, including those who conceptualised the intervention and those who were responsible for its implementation.Intervention The NHS is a major carbon emitter and therefore developed the ‘NHS carbon reduction strategy (NHSCRS)’ in 2009. NHS organisations are contractually obliged to develop a local carbon reduction strategy known as a Sustainable Development Management Plan (SDMP) which details carbon reduction measures (CRM), as described in the NHSCRS. However, the organisational context within which the SDMP is implemented is likely to determine the extent of its success. We undertook an adapted realist evaluation cycle to develop refined initial programme theories. Documents were analysed using thematic content analysis. Interview data were analysed using thematic analysis.Results CRM were most likely to be implemented if the Trust Board were sufficiently pressured by staff and reputational fears, and the potential impacts of CRM were perceived to align with wider organisational aims. Differences in implementation of CRM across hospital sites were related to logistical factors, accessibility to regional partners and contractual relationships. There were expected carbon, energy and long-term financial savings, with variability in the effectiveness of some CRM post implementation.Conclusions Organisational factors, particularly Board leadership and internal implementation pathways, have a significant bearing on whether CRM are implemented or not. However, greater national support and guidance is needed for NHS organisations to effectively reduce their carbon emissions. Further cycles of this evaluation are necessary in multiple case study sites to illuminate the path to a net-zero NHS carbon footprint by 2045.

Objectives People who inject drugs (PWID) experience a high burden of injection drug use-related infectious disease and challenges in accessing adequate care. This study sought to identify programmes and services in Canada addressing the prevention and management of infectious disease in PWID.Design This study employed a systematic integrative review methodology. Electronic databases (PubMed, CINAHL and Web of Science Core Collection) and relevant websites were searched for literature published between 2008 and 2019 (last search date was 6 June 2019). Eligible articles and documents were required to address injection or intravenous drug use and health programmes or services relating to the prevention or management of infectious diseases in Canada.Results This study identified 1607 unique articles and 97 were included in this study. The health programmes and services identified included testing and management of HIV and hepatitis C virus (n=27), supervised injection facilities (n=19), medication treatment for opioid use disorder (n=12), integrated infectious disease and addiction programmes (n=10), needle exchange programmes (n=9), harm reduction strategies broadly (n=6), mobile care initiatives (n=5), peer-delivered services (n=3), management of IDU-related bacterial infections (n=2) and others (n=4). Key implications for policy, practice and future research were identified based on the results of the included studies, which include addressing individual and systemic factors that impede care, furthering evaluation of programmes and the need to provide comprehensive care to PWID, involving medical care, social support and harm reduction.Conclusions These results demonstrate the need for expanded services across a variety of settings and populations. Our study emphasises the importance of addressing social and structural factors that impede infectious disease care for PWID. Further research is needed to improve evaluation of health programmes and services and contextual factors surrounding accessing services or returning to care.PROSPERO registration number CRD42020142947.

Introduction The primary objective of the ReIMAGINE Prostate Cancer Screening Study is to explore the uptake of an invitation to prostate cancer screening using MRI.Methods and analysis The ReIMAGINE Prostate Cancer Screening Study is a prospective single-centre feasibility study. Eligible men aged 50–75 years with no prior prostate cancer diagnosis or treatment will be identified through general practitioner practices and randomly selected for invitation. Those invited will be offered an MRI scan and a prostate-specific antigen (PSA) blood test. The screening MRI scan consists of T2-weighted, diffusion-weighted and research-specific sequences, without the use of intravenous contrast agents. Men who screen positive on either MRI or PSA density will be recommended to have standard of care (National Health Service) tests for prostate cancer assessment, which includes multiparametric MRI. The study will assess the acceptability of an MRI-based prostate screening assessment and the prevalence of cancer detected in MRI-screened men. Summary statistics will be used to explore baseline characteristics in relation to acceptance rates and prevalence of cancer.Ethics and dissemination ReIMAGINE Prostate Cancer Screening is a single-site screening study to assess the feasibility of MRI as a screening tool for prostate cancer. Ethical approval was granted by London–Stanmore Research Ethics Committee Heath Research Authority (reference 19/LO/1129). Study results will be published in peer-reviewed journals after completion of data analysis and used to inform the design of a multicentre screening study in the UK.Trial registration number ClinicalTrials.gov Registry (NCT04063566).

Objective Fatigue in rheumatoid arthritis (RA) is hypothesised to be caused by inflammation. Still ~50% of the variance of fatigue in RA cannot be explained by the Disease Activity Score (DAS), nor by background or psychological factors. Since MRI can detect joint inflammation more sensitively than the clinical joint counts as incorporated in the DAS, we hypothesised that inflammation detected by MRI could aid in explaining fatigue in RA at diagnosis and during the follow-up.Methods 526 consecutive patients with RA were followed longitudinally. Fatigue was assessed yearly on a Numerical Rating Scale. Hand and foot MRIs were performed at inclusion, after 12 and 24 months in 199 patients and were scored for inflammation (synovitis, tenosynovitis and osteitis combined). We studied whether patients with RA with more MRI-inflammation were more fatigued at diagnosis (linear regression), whether the 2-year course of MRI-inflammation associated with the course of fatigue (linear mixed models) and whether decrease in MRI-inflammation in year 1 associated with subsequent improvement in fatigue in year 2 (cross-lagged models). Similar analyses were done with DAS as inflammation measure.Results At diagnosis, higher DAS scores were associated with more severe fatigue (p

Breast cancer type two susceptibility protein (BRCA2) is an essential protein in genome maintenance, homologous recombination (HR), and replication fork protection. Its function includes multiple interaction partners and requires timely localization to relevant sites in the nucleus. We investigated the importance of the highly conserved DNA-binding domain (DBD) and C-terminal domain (CTD) of BRCA2. We generated BRCA2 variants missing one or both domains in mouse embryonic stem (ES) cells and defined their contribution in HR function and dynamic localization in the nucleus, by single-particle tracking of BRCA2 mobility. Changes in molecular architecture of BRCA2 induced by binding partners of purified BRCA2 were determined by scanning force microscopy. BRCA2 mobility and DNA-damage-induced increase in the immobile fraction were largely unaffected by C-terminal deletions. The purified proteins missing CTD and/or DBD were defective in architectural changes correlating with reduced HR function in cells. These results emphasize BRCA2 activity at sites of damage beyond promoting RAD51 delivery.

Introduction: There are many types of coronaviruses that causes respiratory and intestinal infection in humans. Among these coronaviruses, is a group of Severe Acute Respiratory Syndrome (SARS)-like bat coronavirus, including both SARSCoV and SARS-Cov-2 that comprise a unique clade under the subgenus Sarbecovirus. The SARS-CoV-2 strains in India are more closely related to bat-CoVRaTG13 (93% homology) than pangolin CoV (83.5% homology). India reported its first case of Coronavirus Disease 19 (COVID-19) on January 30, 2020. Punjab, a state in northwestern India comprises of 22 districts which are classified into three major distinct regions viz. Majha, Malwa and Doaba. Four districts of Majha region of Indian state of Punjab are Amritsar, Tarn Taran, Gurdaspur and Pathankot. Aim: The present study describes the SARS-CoV-2 epidemiology based on samples tested for this virus; received at Viral Research and Diagnostic Laboratory (VRDL), Government Medical College, Amritsar-Punjab, India. Materials and Methods: This epidemiological study was designed taking into consideration three main factors i.e. the gender, the age groups and the factor whether the individual has any symptoms or not. To study their context of applicability and its interpretation, a total of 3,47,418 samples from period of 01st April 2020 to 31st October 2020 were included in this study. Ribonucleic Acid amplification by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) of SARS-CoV-2 from nasopharyngeal/oropharyngeal swabs of all individuals revealed confirmation of 17,920 positive samples. Total 2,29,310 males and 1,18,108 females were tested for the COVID-19 infection. Social science statistics online tool (https://www.socscistatistics.com/ tests/) was used for χ2 test to analyse different parameters. Results: Maximum number of COVID-19 positive patients was detected in 21 to 30 years age group (p

Introduction: Coronavirus Disease 2019 (COVID-19) pandemic is not the first one which the globe has faced but never came across a health crisis that moved so quickly across continents. COVID-19 outbreak presently posed a very serious threat to the existence of mankind on earth. The massive impact of COVID-19 pandemic was evident in all aspects of life-personal, social as well as professional. The field of dentistry including orthodontics was no exception to this. Aim: To describe the impact of COVID-19 pandemic on orthodontic practice, exploring the basic sterilisation protocols being followed during COVID-19 pandemic and to predict the future of orthodontics in post-COVID era. Materials and Methods: The Department of Orthodontics and Dentofacial Orthopedics, Faculty of Dental Sciences, SGT University, Gurugram, Haryana, India, conducted this questionnaire based cross-sectional survey in May 2020 over a time span of 20 days. A web-based questionnaire of 15 multiple choice questions in English was created as a Google Form in Google Documents. The link to this form was shared online with the orthodontists and postgraduate students (Orthodontics) of dental colleges situated in the National Capital Region (NCR) through WhatsApp groups and e-mails. A total of 254 responses were received. Results: A 97.6% of respondents agreed that COVID-19 affected their orthodontic practice. The odds ratio between those not likely to resume practice and those likely to resume practice taking educational qualification as the significant predictor was calculated to be 8.976 at 95% confidence intervals. There was wide variation in the selection of the safety protocols by the orthodontists in the present study (p

Interleukin-4-induced-1 (IL4i1) is an amino acid oxidase secreted from immune cells. Recent observations have suggested that IL4i1 is pro-tumorigenic via unknown mechanisms. As IL4i1 has homologs in snake venoms (L-amino acid oxidases [LAAO]), we used comparative approaches to gain insight into the mechanistic basis of how conserved amino acid oxidases regulate cell fate and function. Using mammalian expressed recombinant proteins, we found that venom LAAO kills cells via hydrogen peroxide generation. By contrast, mammalian IL4i1 is non-cytotoxic and instead elicits a cell protective gene expression program inhibiting ferroptotic redox death by generating indole-3-pyruvate (I3P) from tryptophan. I3P suppresses ferroptosis by direct free radical scavenging and through the activation of an anti-oxidative gene expression program. Thus, the pro-tumor effects of IL4i1 are likely mediated by local anti-ferroptotic pathways via aromatic amino acid metabolism, arguing that an IL4i1 inhibitor may modulate tumor cell death pathways.

Introduction: Hernia surgery has evolved over a period of 2500 years from the Bassini-Shouldice era to conventional Lichenstein’s meshplasty to the laparoscopic era. Since, inception of the laparoscopic approach 25 years ago, there were several advancements in the techniques of inguinal hernia repairs. The two most commonly practiced laparoscopic approaches are the Total Extra Peritoneal (TEP) and Transabdominal Preperitoneal (TAPP) repair. Aim: To compare the outcomes for TEP and TAPP approaches in laparoscopic inguinal hernia surgery in terms of operative time consumed, postoperative pain, duration of hospital stay, complications and recurrence rate when performed by a single surgeon. Materials and Methods: A prospective interventional cohort study was carried out among 70 patients with uncomplicated inguinal hernia. Patients were divided equally into two groups of 35 patients and underwent TAPP and TEP repairs depending on group randomisation. All surgeries were performed by the same surgeon. Factors including operative time, postoperative pain, duration of hospital stay, complications and recurrence were documented and compared for both the groups. The statistical analysis was done using Statistical Package for the Social Sciences (SPSS) software version 21. Unpaired t-test was used to compare the mean between the two groups. The p-value of

PurposeWe sought to describe the association between serum chloride levels and mortality among unselected cardiac intensive care unit (CICU) patients.Materials and methodsWe retrospectively reviewed adult patients admitted to our CICU from 2007 to 2015. The association of dyschloremia and hospital mortality was assessed in a multiple variable model including additional confounders, and the association of dyschloremia and post-discharge mortality were assessed using Cox proportional-hazards analysis.Results9,426 patients with a mean age of 67±15 years (37% females) were included. Admission hypochloremia was present in 1,384 (15%) patients, and hyperchloremia was present in 1,606 (17%) patients. There was a U-shaped relationship between admission chloride and unadjusted hospital mortality, with increased hospital mortality among patients with hypochloremia (unadjusted OR 3.0, 95% CI 2.5-3.6, pConclusionAbnormal serum chloride on admission to the CICU is associated with increased short- and long-term mortality, with hypochloremia being a strong independent predictor.

Hyperphosphatemia may arise from various conditions including exogenous ingestion, extracellular shifts due to cell death or alterations in acid-base status, increased bone resorption, hormonal dysregulations leading to reduced renal excretion, reduced kidney function, or faulty measurement techniques. We herein present a case of a young pregnant woman who presented with mild acute kidney injury (AKI), invasive mucormycosis receiving liposomal amphotericin, and hyperphosphatemia out of proportion to the degree of kidney injury. While the patient was given routine phosphate-binding agent by her primary care team for presumed AKI-associated hyperphosphatemia, a full investigation by the renal consulting team for contributing factors other than kidney injury revealed that she actually had pseudohyperphosphatemia associated with the use of liposomal amphotericin. Erroneous treatment of pseudohyperphosphatemia may have been detrimental to this pregnant patient. A literature review for conditions associated with pseudohyperphosphatemia other than the use of liposomal amphotericin will be discussed.

Compression at a very low bit rate(≤0.5bpp) causes degradation in video frames with standard decoding algorithms like H.261, H.262, H.264, and MPEG-1 and MPEG-4, which itself produces lots of artifacts. This paper focuses on an efficient pre-and post-processing technique (PP-AFT) to address and rectify the problems of quantization error, ringing, blocking artifact, and flickering effect, which significantly degrade the visual quality of video frames. The PP-AFT method differentiates the blocked images or frames using activity function into different regions and developed adaptive filters as per the classified region. The designed process also introduces an adaptive flicker extraction and removal method and a 2-D filter to remove ringing effects in edge regions. The PP-AFT technique is implemented on various videos, and results are compared with different existing techniques using performance metrics like PSNR-B, MSSIM, and GBIM. Simulation results show significant improvement in the subjective quality of different video frames. The proposed method outperforms state-of-the-art de-blocking methods in terms of PSNR-B with average value lying between (0.7-1.9db) while (35.83-47.7%) reduced average GBIM keeping MSSIM values very close to the original sequence statistically 0.978.

Diabetic muscle infarction (DMI) is a rare complication of poorly controlled type 1 and type 2 diabetes seen mostly in those who have already experienced microvascular complications. Currently, the incidence and prevalence of DMI are difficult to conclude, and there is no clear algorithm or standard of care in managing this condition. Pathogenesis of the microangiopathy of DMI remains unclear. A major finding in this investigation of DMI emphasizes that, within 2–17 weeks, patients who initiate low-dose acetylsalicylic acid, bed rest, and close outpatient follow-up see significant size reduction of lower extremity mass and complete resolution of pain without being subjected to invasive muscle biopsy.

Introduction: Acute Pancreatitis (AP) can present from a mild self-limiting process that requires only supportive care to severe disease that can cause multiple Organ Failure (OF) and high mortality. It is therefore important to identify such patients at increased risk of OF and mortality at the earliest. Aim: To evaluate and compare the efficacy of three prognostic markers namely Haematocrit, Glasgow scoring and Computed Tomography (CT) abdomen in assessing the severity of AP. Materials and Methods: A prospective longitudinal study was done on 120 patients diagnosed with AP, over a period of 18 months. Haematocrit was done at admission and at 48 hours. A fall in haematocrit of more than 10% was considered sensitive. Modified Glasgow score was assessed at admission and after 48 hours. Other variables include blood glucose level, white blood count, blood urea nitrogen, serum calcium, partial oxygen pressure (PaO2), decrease in haematocrit, serum Lactate Dehydrogenase (LDH), serum aspartate aminotransferase (AST) and serum albumin. A score of ≥3 was considered sensitive. CT of abdomen was done at 72 hours and a Computed Tomography Severity Index (CTSI) score of ≥4 was considered sensitive. The results of each prognostic marker were graphed and compared to assess Length of Hospital Stay (LOHS), need for Intensive Care Unit Admission (ICUA), OF and mortality. Results: The mean LOHS was six days. Haematocrit was sensitive in 23 of 79 patients that stayed in hospital for >6 days. Modified Glasgow scores were sensitive in 35 of 79 patients. CT of abdomen was sensitive in 59 out of 79 patients. Total 29 of 120 patients were admitted in the ICU, out of which difference in haematocrit was sensitive in 14 patients, Modified Glasgow coma score of ≥3 was seen in 14 patients and CTSI scores were sensitive in 22 patients. Twelve out of 120 patients developed OF. All 12 patients showed a sensitive Modified Glasgow scores of ≥3 and CTSI ≥4, whereas only five patients were sensitive for fall in haematocrit. Five patients died during the study. All five patients were sensitive for fall in haematocrit Glasgow coma scores and CT abdomen. Among the prognostic markers, haematocrit showed 100% sensitivity, specificity and Positive Predictive Value (PPV) than the other prognostic markers making haematocrit the better prognostic marker. Conclusion: CT of abdomen is a reliable prognostic marker in terms of assessment of LOHS, need for Intensive Care Unit (ICU) care and mortality. Modified Glasgow score is accurate in assessing OF. Haematocrit is specific in assessing the need for ICU care and mortality.

Introduction: Corona Virus Disease-19 (COVID-19) caused by the Severe Acute Respiratory Syndrome-Corona Virus-2 (SARSCoV-2) has led to a global pandemic. Currently, the standard method for the diagnosis of COVID-19 is the detection of SARSCoV-2 by Reverse Transcriptase Quantitative Polymerase Chain Reaction (RT-qPCR). Lower Cycle threshold (Ct) value of PCR is found to be associated with increased probability of progression to severe disease and infectivity. Blood group A individuals have been found to be more susceptible to infection by SARS-CoV-2 while that of O blood group have lower risk of infection. There has been growing scientific interest to obtain data which may characterise the susceptibility to COVID-19 infection and determine the risk factors which may be associated with progression and severity of the disease. Aim: To study the association of RT-qPCR Ct values for SARSCoV-2 with ABO blood group types. Materials and Methods: A prospective observational study was conducted at tertiary care centre in western Maharashtra, India where in a total of 116 symptomatic admitted patients between mid-July to mid-August 2020 and was found to be positive for SARS-CoV-2 by RT-qPCR were enrolled in the study. Ct values for pan-Sarbecovirus E-gene and SARSCoV-2 specific RdRP gene were recorded for each patient. In addition, all the patients were typed for ABO blood grouping. Distribution of different ABO blood group types in SARS-CoV-2 positive patients were analysed and was compared with blood groups in 882 non-COVID-19 blood donors comprising control group. Ct values for E and RdRP gene were also analysed in respect to different age group, gender and blood group types. Blood group records of voluntary healthy blood donors reporting at our centre between September to November 2019 were obtained. Results: Of the 116 patients, 33 (28.45%) comprised of type A, 34 (29.31%) of type B, 41 (35.34%) were of type O and remaining 8 (6.90%) had AB blood group type. Compared to the control group, no significant difference was noted in the distribution of ABO blood types in SARS-CoV-2 positive patients. Also, no statistical significance was found in the Ct values with respect to age, gender and different ABO blood group types. Conclusion: RT-qPCR Ct values for SARS-CoV-2 infection have no association with ABO blood group types.

ObjectivesTo identify studies that have investigated the health outcome and treatment priorities of patients with multimorbidity, clinicians or both, in order to assess whether the priorities of the two groups are in alignment, or whether a disparity exists between the priorities of patients with multimorbidity and clinicians.DesignSystematic review.Data sourcesMEDLINE, EMBASE, CINHAL and Cochrane databases from inception to May 2019 using a predefined search strategy, as well as reference lists containing any relevant articles, as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane guidelines.Eligibility criteriaWe included studies reporting health outcome and treatment priorities of adult patients with multimorbidity, defined as suffering from two or more chronic conditions, or of clinicians in the context of multimorbidity or both. There was no restriction by study design, and studies using quantitative and/or qualitative methodologies were included.Data synthesisWe used a narrative synthesis approach to synthesise the quantitative findings, and a meta-ethnography approach to synthesise the qualitative findings.ResultsOur search identified 24 studies for inclusion, which comprised 12 quantitative studies, 10 qualitative studies and 2 mixed-methods studies. Twelve studies reported the priorities of both patients and clinicians, 10 studies reported the priorities of patients and 2 studies reported the priorities of clinicians alone. Our findings have shown a mostly low level of agreement between the priorities of patients with multimorbidity and clinicians. We found that prioritisation by patients was mainly driven by their illness experiences, while clinicians focused on longer-term risks. Preserving functional ability emerged as a key priority for patients from across our quantitative and qualitative analyses.ConclusionRecognising that there may be a disparity in prioritisation and understanding the reasons for why this might occur, can facilitate clinicians in accurately eliciting the priorities that are most important to their patients and delivering patient-centred care.PROSPERO registration numberCRD42018076076.

Chronic neuropathic pain (NP) is a growing clinical problem for which effective treatments, aside from non-steroidal anti-inflammatory drugs and opioids, are lacking. Cannabinoids are emerging as potentially promising agents to manage neuroimmune effects associated with nociception. In particular, Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and their combination are being considered as therapeutic alternatives for treatment of NP. This study aimed to examine whether sex affects long-term outcomes on persistent mechanical hypersensitivity 7 weeks after ceasing cannabinoid administration. Clinically relevant low doses of THC, CBD, and a 1:1 combination of THC:CBD extracts, in medium chain triglyceride (MCT) oil, were orally gavaged for 14 consecutive days to age-matched groups of male and female sexually mature Sprague Dawley rats. Treatments commenced one day after surgically inducing a pro-nociceptive state using a peripheral sciatic nerve cuff. The analgesic efficacy of each phytocannabinoid was assessed relative to MCT oil using hind paw mechanical behavioural testing once a week for 9 weeks. In vivo intracellular electrophysiology was recorded at endpoint to characterize soma threshold changes in primary afferent sensory neurons within dorsal root ganglia (DRG) innervated by the affected sciatic nerve. The thymus, spleen, and DRG were collected post-sacrifice and analyzed for long-term effects on markers associated with T lymphocytes at the RNA level using qPCR. Administration of cannabinoids, particularly the 1:1 combination of THC, elicited a sustained mechanical anti-hypersensitive effect in males with persistent peripheral NP, which corresponded to beneficial changes in myelinated Aβ mechanoreceptive fibers. Specific immune cell markers associated with T cell differentiation and pro-inflammatory cytokines, previously implicated in repair processes, were differentially up-regulated by cannabinoids in males treated with cannabinoids, but not in females, warranting further investigation into sexual dimorphisms that may underlie treatment outcomes.

Computational models of the heart are increasingly being used in the development of devices, patient diagnosis and therapy guidance. While software techniques have been developed for simulating single hearts, there remain significant challenges in simulating cohorts of virtual hearts from multiple patients. To facilitate the development of new simulation and model analysis techniques by groups without direct access to medical data, image analysis techniques and meshing tools, we have created the first publicly available virtual cohort of twenty-four four-chamber hearts. Our cohort was built from heart failure patients, age 67±14 years. We segmented four-chamber heart geometries from end-diastolic (ED) CT images and generated linear tetrahedral meshes with an average edge length of 1.1±0.2mm. Ventricular fibres were added in the ventricles with a rule-based method with an orientation of -60° and 80° at the epicardium and endocardium, respectively. We additionally refined the meshes to an average edge length of 0.39±0.10mm to show that all given meshes can be resampled to achieve an arbitrary desired resolution. We ran simulations for ventricular electrical activation and free mechanical contraction on all 1.1mm-resolution meshes to ensure that our meshes are suitable for electro-mechanical simulations. Simulations for electrical activation resulted in a total activation time of 149±16ms. Free mechanical contractions gave an average left ventricular (LV) and right ventricular (RV) ejection fraction (EF) of 35±1% and 30±2%, respectively, and a LV and RV stroke volume (SV) of 95±28mL and 65±11mL, respectively. By making the cohort publicly available, we hope to facilitate large cohort computational studies and to promote the development of cardiac computational electro-mechanics for clinical applications.

INTRODUCTION: Dengue and chikungunya (CHIK) infections appear to be increasing in all parts of India. Aedes aegypti mosquitoes are common vectors for dengue virus (DENV) and CHIK virus (CHIKV). In areas where both viruses cocirculate, they can be transmitted together. There are very few studies discussing the dengue-chik coinfection from Punjab region of India. The present study was undertaken to study the clinical features of dengue–CHIK coinfection and compare with monoinfection. MATERIALS AND METHODS: IgM antibody capture (MAC) ELISA for dengue IgM and CHIK IgM and ELISA for nonstructural protein 1 antigen was performed on serum samples obtained from suspected patients. RESULTS: Out of total 3160 samples from suspected patients for dengue infection, 2178 (68.92%) samples were positive for DENV while CHIK IgM antibodies were positive in 127 patients out of the total suspected 373 cases (34.04%). In addition to this, 283 samples were tested for both viruses, out of which 27 sera were positive (9.54%) for coinfection of dengue and CHIK. The comparison of signs and symptoms showed that the coinfected patients had fever in all cases while rash was seen in only 30% cases. Arthralgia (79%) and thrombocytopenia (77%) was seen in significant number of coinfected cases thus revealing overlapping nature of dengue–CHIK coinfection. Conclusions: Increase in the number of Dengue and Chikungunya infections and their cocirculation is an important public health concern which warrants the implementation of strict control measures.

Hemolytic Uremic Syndrome (HUS) associated with Shiga-toxigenic Escherichia coli (STEC) infections is the principal cause of acute renal injury in pediatric age groups. Shiga toxin type 2 (Stx2) has in vitro cytotoxic effects on kidney cells, including human glomerular endothelial (HGEC) and Vero cells. Neither a licensed vaccine nor effective therapy for HUS is available for humans. Recombinant antibodies against Stx2, produced in bacteria, appeared as the utmost tool to prevent HUS. Therefore, in this work, a recombinant FabF8:Stx2 was selected from a human Fab antibody library by phage display, characterized, and analyzed for its ability to neutralize the Stx activity from different STEC-Stx2 and Stx1/Stx2 producing strains in a gold standard Vero cell assay, and the Stx2 cytotoxic effects on primary cultures of HGEC. This recombinant Fab showed a dissociation constant of 13.8 nM and a half maximum effective concentration (EC50) of 160 ng/mL to Stx2. Additionally, FabF8:Stx2 neutralized, in different percentages, the cytotoxic effects of Stx2 and Stx1/2 from different STEC strains on Vero cells. Moreover, it significantly prevented the deleterious effects of Stx2 in a dose-dependent manner (up to 83%) in HGEC and protected this cell up to 90% from apoptosis and necrosis. Therefore, this novel and simple anti-Stx2 biomolecule will allow further investigation as a new therapeutic option that could improve STEC and HUS patient outcomes.

Introduction The intraoperative administration of dexamethasone for prophylaxis against postoperative nausea and vomiting is a common and recommended practice. The safety of the administration of this immunosuppressive agent at a time of significant immunological disruption has not been rigorously evaluated in terms of infective complications.Methods/analysis This is a pragmatic, multicentre, randomised, controlled, non-inferiority trial. A total of 8880 patients undergoing elective major surgery will be enrolled. Participants will be randomly allocated to receive either dexamethasone 8 mg or placebo intravenously following the induction of anaesthesia in a 1:1 ratio, stratified by centre and diabetes status. Patient enrolment into the trial is ongoing. The primary outcome is surgical site infection at 30 days following surgery, defined according to the Centre for Disease Control criteria.Ethics/dissemination The PADDI trial has been approved by the ethics committees of over 45 participating sites in Australia, New Zealand, Hong Kong, South Africa and the Netherlands. The trial has been endorsed by the Australia and New Zealand College of Anaesthetists Clinical Trials Network and the Australian Society for Infectious Diseases Clinical Research Network. Participant recruitment began in March 2016 and is expected to be complete in mid-2019. Publication of the results of the PADDI trial is anticipated to occur in early 2020.Trial registration number ACTRN12614001226695.

Secreted Wnt proteins regulate development and adult tissue homeostasis by binding and activating cell-surface Frizzled receptors and co-receptors including LRP5/6. The hydrophobicity of Wnt proteins has complicated their purification and limited their use in basic research and as therapeutics. We describe modular tetravalent antibodies that can recruit Frizzled and LRP5/6 in a manner that phenocopies the activities of Wnts both in vitro and in vivo. The modular nature of these synthetic Frizzled and LRP5/6 Agonists, called FLAgs, enables tailored engineering of specificity for one, two or multiple members of the Frizzled family. We show that FLAgs underlie differentiation of pluripotent stem cells, sustain organoid growth, and activate stem cells in vivo. Activation of Wnt signaling circuits with tailored FLAgs will enable precise delineation of functional outcomes directed by distinct receptor combinations and could provide a new class of therapeutics to unlock the promise of regenerative medicine.

Bacterial leaf streak (BLS) caused by Xanthomonas campestris pv. translucens is one of the major bacterial diseases threatening wheat production in the United States Northern Great Plains (NGP) region. It is a sporadic but widespread wheat disease that can cause significant loss in grain yield and quality. Identification and characterization of genomic regions in wheat that confer resistance to BLS will help track resistance genes/QTLs in future wheat breeding. In this study, we evaluated a hard winter wheat association mapping panel (HWWAMP) containing 299 hard winter wheat lines from the US hard winter wheat growing region for their reactions to BLS. We observed a range of BLS responses among the lines, importantly, we identified ten genotypes that showed a resistant reaction both in greenhouse and field evaluation. ­Genome-wide association analysis with 15,990 SNPs was conducted using an exponentially compressed mixed linear model. Five genomic regions (p

This document summarizes principles and methodology to guide the creation of Clinical Practice Guidelines, Position Statements und Technological Reviews of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). The purpose of EFSUMB Clinical Practice Guidelines is to provide physicians and sonographers performing or requesting diagnostic and interventional ultrasound examinations with evidence-based recommendations. Position Statements summarize EFSUMB opinions on important current issues in clinical applications, education and training of ultrasound techniques or health care policy related to ultrasound-based imaging and ultrasound-guided interventions. The third type of EFSUMB policy document is the Technological Review, which describes ultrasound techniques and technologies for physicians, medical technicians, engineers and physicists developing ultrasound technology. The whole process of development of EFSUMB policy documents is explained beginning with the decision regarding topics, selection of authors, funding, and planning of the developmental process. Further steps described in this document are the review of the evidence, creation of recommendations, statements and comments, grading of level of evidence and strength of recommendations, and consensus process. Finally, rules for the creation, review, approval, publication and update of EFSUMB policy documents are described.