Trends in breeding oat for nutritional grain quality - An overview

Oat is an economically important crop and ranks sixth in world cereal production after maize, wheat, rice, barley and sorghum. It has been primarily utilized as livestock feed. However, the utilization of oats for human consumption has increased progressively, owing to its dietary and health benefits which relies mainly on the total dietary fibre and ?-glucan content, which significantly reduces postprandial blood glucose, insulin and blood lipids, especially serum total and low density lipoprotein cholesterol. Henceforth, enhancing Oat b-glucan content forhuman consumption is desirable. As it is a polygenic trait controlled mainly by genes with additive effects, phenotypic selection for greater b-glucan content would be effective for developing cultivars with elevated b-glucan contents. Oat b-glucan concentration has been found to be positively correlated with protein content and negatively correlated with oil content. ?-glucan yield (i.e., Product of grain yield and ?-glucan content) has been found to correlate positively with both grain yield (r = 0.92) and ?-glucan content (r = 0.66). Hence, this nutritional oat grain quality has been improved through selection for improved grain yield as they both increase simultaneously. Among wild accessions, A. atlantica genotypes have high ?-glucan content (2·2–11·3%) and have been used in breeding programmes for increasing the ?-glucan content of adapted elite local germplasm. Besides conventional breeding approaches, molecular breeding approaches have made possible to identify several molecular markers linked to ?-glucan rich regions across oat genome hence enabling mapping and dissection of ?-glucan rich genomic regions and accelerating the improvement in nutritional grain quality

Prevalence of tobacco use among women: a cross sectional survey from a squatter settlement of Karachi, Pakistan

Background: While the prevalence of tobacco use has been slowly declining in the developed countries, rates have been steadily rising in the developing countries. This has led to a rapid rise in tobacco related lung diseases among women. Objective: Determine the prevalence of tobacco use (both smoking and smokeless) among women in an urban squatter settlement (Orangi Town) in Karachi, Pakistan. Methods: A cross-sectional survey was conducted on 19,325 females aged between 15 and 80 years in Orangi Town, an urban squatter settlement in Karachi, Pakistan. Modified questionnaire, developed by World Health Organization WHO and Global Adult Tobacco survey (GATS), was used in Urdu. A total of 16,987 women agreed to participate. Results: The mean age was 37.3 ± 9.8 years amongst whom 15,255 (89.80%) were married, 9143 (53.82%) admitted that at least one person uses tobacco in some form in their homes. The prevalence of smokeless tobacco was 42.25% (7178). The prevalence of smoking tobacco was low as compared to smokeless tobacco i.e. 18.0% (3058). Among smokers, 85.47% (1789) admitted that they had tried to quit smoking during last 12 months but failed. CONCLUSION: Tobacco use among women in an urban squatter settlement is very high and alarming. Preventive and control measures against tobacco use are required in these communities

Comparative trends in ischemic heart disease admissions, presentation and outcomes due to the COVID-19 pandemic: First insights from a tertiary medical center in Pakistan

Introduction: COVID-19 has manifested a striking disarray in healthcare access and provision, particularly amongst patients presenting with life-threatening ischemic heart disease (IHD). The paucity of data from low-middle income countries has limited our understanding of the consequential burden in the developing world. We aim to compare volumes, presentations, management strategies, and outcomes of IHD amongst patients presenting in the same calendar months before and during the COVID-19 pandemic.Methods: We conducted a retrospective cross-sectional analysis at the Aga Khan University Hospital, one of the premier tertiary care centres in Pakistan. Data were collected on all adult patients (\u3e18 years) who were admitted with IHD (acute coronary syndrome (ACS) and stable angina) from March 1 to June 30, 2019 (pre-COVID) and March 1 to June 30, 2020 (during-COVID), respectively. Group differences for continuous variables were evaluated using student t-test or Mann-Whitney U test. The chi-squared test or Fisher test was used for categorical variables. Values of p less than 0.05 were considered statistically significant. P-value trend calculation and graphical visualization were done using STATA (StataCorp, College Station, TX).Results: Data were assimilated on 1019 patients, with 706 (69.3%) and 313 (30.7%) patients presenting in each respective group (pre-COVID and during-COVID). Current smoking status (p=0.019), admission source (p\u3c0.001), month of admission (p\u3c0.001), proportions ACS (p\u3c0.001), non-ST-elevation-myocardial-infarction (NSTEMI; p\u3c0.001), unstable angina (p=0.025) and medical management (p=0.002) showed significant differences between the two groups, with a sharp decline in the during-COVID group. Monthly trend analysis of ACS patients showed the most significant differences in admissions (p=0.001), geographic region (intra-district vs intracity vs outside city) (p\u3c0.001), time of admission (p=0.038), NSTEMI (p=0.002) and medical management (p=0.001).Conclusion: These data showcase stark declines in ACS admissions, diagnostic procedures (angiography) and revascularization interventions (angioplasty and coronary artery bypass graft surgery, CABG) in a developing country where resources and research are already inadequate. This study paves the way for further investigations downstream on the short- and long-term consequences of untreated IHD and reluctance in health-seeking behaviour

Interindividual Variability in Lymphocyte Stimulation and Transcriptomic Response Predicts Mycophenolic Acid Sensitivity in Healthy Volunteers

Mycophenolic acid (MPA) is an immunosuppressant commonly used to prevent renal transplant rejection and treat glomerulonephritis. MPA inhibits IMPDH2 within stimulated lymphocytes, reducing guanosine synthesis. Despite the widespread use of MPA, interindividual variability in response remains with rates of allograft rejection up to 15% and approximately half of individuals fail to achieve complete remission to lupus nephritis. We sought to identify contributors to interindividual variability in MPA response, hypothesizing that the HPRT1 salvage guanosine synthesis contributes to variability. MPA sensitivity was measured in 40 healthy individuals using an ex vivo lymphocyte viability assay. Measurement of candidate gene expression (n ± 40) and single‐cell RNA‐sequencing (n ± 6) in lymphocytes was performed at baseline, poststimulation, and post‐MPA treatment. After stimulation, HPRT1 expression was 2.1‐fold higher in resistant individuals compared with sensitive individuals (P ± 0.049). Knockdown of HPRT1 increased MPA sensitivity (12%; P ± 0.003), consistent with higher expression levels in resistant individuals. Sensitive individuals had higher IMPDH2 expression and 132% greater stimulation. In lymphocyte subpopulations, differentially expressed genes between sensitive and resistant individuals included KLF2 and LTB. Knockdown of KLF2 and LTB aligned with the predicted direction of effect on proliferation. In sensitive individuals, more frequent receptor‐ligand interactions were observed after stimulation (P ± 0.0004), but fewer interactions remained after MPA treatment (P ± 0.0014). These data identify a polygenic transcriptomic signature in lymphocyte subpopulations predictive of MPA response. The degree of lymphocyte stimulation, HPRT1, KLF2, and LTB expression may serve as markers of MPA efficacy

The Role of Neighborhood Environment in Promoting Risk Factors of Cardiovascular Disease among Young Adults: Data from Middle to High Income Population in an Asian Megacity

Background: Modifiable risk factors of cardiovascular diseases (CVD) have their triggers in the neighborhood environments of communities. Studying the environmental triggers for CVD risk factors is important to understand the situation in a broader perspective. Young adults are influenced the most by the environment profile around them hence it is important to study this subset of the population.Methods: This was a descriptive study conducted using the EPOCH research tool designed by the authors of the PURE study. The study population consisted of young adults aged 18-25 in two areas of Karachi. The study setting was busy shopping malls frequented by young adults in the particular community being studied.Results: Our total sample size was 120 individuals, who consented to be interviewed by our interviewers. Less than 50% of the population recognized some form of restriction regarding smoking in their communities. The largest contributor to tobacco advertising was actors smoking in movies and TV shows with 89% responses from both communities. Only 11.9% of the individuals disapproved of smoking cigarettes among men with wide acceptance of \u27sheesha\u27 across all age groups. Advertising for smoking and junk food was more frequent as compared to smoking cessation, healthy diet and exercise in both the areas. Unhealthy food items were more easily available in contrast to healthier options. The cost of healthy snack food options including vegetables and fruits was higher than sugary drinks and foods.CONCLUSION: This assessment showed that both communities were exposed to environments that promote risk factors for cardiovascular diseases

Pollutant-Induced Modulation in Conformation and β-Lactamase Activity of Human Serum Albumin

Structural changes in human serum albumin (HSA) induced by the pollutants 1-naphthol, 2-naphthol and 8-quinolinol were analyzed by circular dichroism, fluorescence spectroscopy and dynamic light scattering. The alteration in protein conformational stability was determined by helical content induction (from 55 to 75%) upon protein-pollutant interactions. Domain plasticity is responsible for the temperature-mediated unfolding of HSA. These findings were compared to HSA-hydrolase activity. We found that though HSA is a monomeric protein, it shows heterotropic allostericity for β-lactamase activity in the presence of pollutants, which act as K- and V-type non-essential activators. Pollutants cause conformational changes and catalytic modifications of the protein (increase in β-lactamase activity from 100 to 200%). HSA-pollutant interactions mediate other protein-ligand interactions, such as HSA-nitrocefin. Therefore, this protein can exist in different conformations with different catalytic properties depending on activator binding. This is the first report to demonstrate the catalytic allostericity of HSA through a mechanistic approach. We also show a correlation with non-microbial drug resistance as HSA is capable of self-hydrolysis of β-lactam drugs, which is further potentiated by pollutants due to conformational changes in HSA

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely