Transgenesis: An efficient tool in mulberry breeding

Genetic engineering is the most potent biotechnological approach dealing with transfer of specially constructed gene assemblies through various transformation techniques. Tools of recombinant DNA technology facilitated development of transgenic plants.  The plants obtained through genetic engineering contain a gene or genes usually from an unrelated organisms, and are known as transgenic plants. The combined use of recombinant DNA technology, gene transfer methods and tissue culture techniques has  led to the efficient transformation and production of transgenics in a wide variety of crop plants. In fact transgenesis has emerged as a novel tool for carrying out “single gene breeding” or transgenic breeding of crop plants. Identification, isolation and cloning of resistant genes is the prerequisite for development of transgenic plants for disease resistance. Identification of resistance genes on the basis of amino acid sequence, conservation enables plant breeder to monitor resistance gene segregation using  appropriate DNA probe intend of testing progeny for disease resistance and susceptibility. Significant developments in plant  genetic modification have been achieved in the last 15 years. Some of the success include herbicide tolerant corn, cotton,  soyabeen and papaya; virus resistant corn, potato, cotton among others. In mulberry, little work has been carried out at Delhi University (south campus). They have developed drought and salinity tolerent transgenic mulberry through Agrobacterium mediated transformation. The overexpression of HVA1 gene from barley generates tolerence to salinity and water stress in  transgenic mulberry (Morus indica).Keywords: Transgenic plant, mulberry, resistance, salinity

Investigation of an extensive outbreak of HIV infection among children in Sindh, Pakistan: protocol for a matched case-control study.

INTRODUCTION: In April 2019, 14 children were diagnosed with HIV infection by a private healthcare provider in Larkana district, Sindh province, Pakistan. Over the next 3 months, 930 individuals were diagnosed with HIV, >80% below 16 years, the largest ever outbreak of HIV in children in Pakistan. In this protocol paper, we describe research methods for assessing likely modes of HIV transmission in this outbreak and investigate spatial and molecular epidemiology. METHODS AND ANALYSIS: A matched case-control study will be conducted with 406 cases recruited. Cases will be children aged below 16 years registered for care at the HIV treatment centre at Shaikh Zayed Children Hospital in Larkana City. Controls will be children who are HIV-uninfected (confirmed by a rapid HIV test) matched 1:1 by age (within 1 year), sex and neighbourhood. Following written informed consent from the guardian, a structured questionnaire will be administered to collect data on sociodemographic indices and exposure to risk factors for parenteral, vertical and sexual (only among those aged above 10 years) HIV transmission. A blood sample will be collected for hepatitis B and C serology (cases and controls) and HIV lineage studies (cases only). Mothers of participants will be tested for HIV to investigate the possibility of mother-to-child transmission. Conditional logistic regression will be used to investigate the association of a priori defined risk factors with HIV infection. Phylogenetic analyses will be conducted. Global positioning system coordinates of participants' addresses will be collected to investigate concordance between the genetic and spatial epidemiology. ETHICS AND DISSEMINATION: Ethical approval was granted by the Ethics Review Committee of the Aga Khan University, Karachi. Study results will be shared with Sindh and National AIDS Control Programs, relevant governmental and non-governmental organisations, presented at national and international research conferences and published in international peer-reviewed scientific journals

The status of hepatitis C virus infection among people who inject drugs in the Middle East and North Africa.

BACKGROUND AND AIMS: People who inject drugs (PWID) are a key population at high risk of hepatitis C virus (HCV) infection. The aim of this study was to delineate the epidemiology of HCV in PWID in the Middle East and North Africa (MENA). METHODS: Syntheses of data were conducted on the standardized and systematically assembled databases of the MENA HCV Epidemiology Synthesis Project, 1989-2018. Random-effects meta-analyses and meta-regressions were performed. Meta-regression variables included country, study site, year of data collection and year of publication [to assess trends in HCV antibody prevalence over time], sample size and sampling methodology. Numbers of chronically infected PWID across MENA were estimated. The Shannon Diversity Index was calculated to assess genotype diversity. RESULTS: Based on 118 HCV antibody prevalence measures, the pooled mean prevalence in PWID for all MENA was 49.3% [95% confidence interval (CI) = 44.4-54.1%]. The country-specific pooled mean ranged from 21.7% (95% CI = 4.9-38.6%) in Tunisia to 94.2% (95% CI = 90.8-96.7%) in Libya. An estimated 221 704 PWID were chronically infected, with the largest numbers found in Iran at 68 526 and in Pakistan at 46 554. There was no statistically significant evidence for a decline in HCV antibody prevalence over time. Genotype diversity was moderate (Shannon Diversity Index of 1.01 out of 1.95; 52.1%). The pooled mean percentage for each HCV genotype was highest in genotype 3 (42.7%) and in genotype 1 (35.9%). CONCLUSION: Half of people who inject drugs in the Middle East and North Africa appear to have ever been infected with hepatitis C virus, but there are large variations in antibody prevalence among countries. In addition to > 200 000 chronically infected current people who inject drugs, there is an unknown number of people who no longer inject drugs who may have acquired hepatitis C virus during past injecting drug use. Harm reduction services must be expanded, and innovative strategies need to be employed to ensure accessibility to hepatitis C virus testing and treatment

International longitudinal registry of patients with atrial fibrillation and treated with rivaroxaban: RIVaroxaban Evaluation in Real life setting (RIVER)

Background Real-world data on non-vitamin K oral anticoagulants (NOACs) are essential in determining whether evidence from randomised controlled clinical trials translate into meaningful clinical benefits for patients in everyday practice. RIVER (RIVaroxaban Evaluation in Real life setting) is an ongoing international, prospective registry of patients with newly diagnosed non-valvular atrial fibrillation (NVAF) and at least one investigator-determined risk factor for stroke who received rivaroxaban as an initial treatment for the prevention of thromboembolic stroke. The aim of this paper is to describe the design of the RIVER registry and baseline characteristics of patients with newly diagnosed NVAF who received rivaroxaban as an initial treatment. Methods and results Between January 2014 and June 2017, RIVER investigators recruited 5072 patients at 309 centres in 17 countries. The aim was to enroll consecutive patients at sites where rivaroxaban was already routinely prescribed for stroke prevention. Each patient is being followed up prospectively for a minimum of 2-years. The registry will capture data on the rate and nature of all thromboembolic events (stroke / systemic embolism), bleeding complications, all-cause mortality and other major cardiovascular events as they occur. Data quality is assured through a combination of remote electronic monitoring and onsite monitoring (including source data verification in 10% of cases). Patients were mostly enrolled by cardiologists (n = 3776, 74.6%), by internal medicine specialists 14.2% (n = 718) and by primary care/general practice physicians 8.2% (n = 417). The mean (SD) age of the population was 69.5 (11.0) years, 44.3% were women. Mean (SD) CHADS2 score was 1.9 (1.2) and CHA2DS2-VASc scores was 3.2 (1.6). Almost all patients (98.5%) were prescribed with once daily dose of rivaroxaban, most commonly 20 mg (76.5%) and 15 mg (20.0%) as their initial treatment; 17.9% of patients received concomitant antiplatelet therapy. Most patients enrolled in RIVER met the recommended threshold for AC therapy (86.6% for 2012 ESC Guidelines, and 79.8% of patients according to 2016 ESC Guidelines). Conclusions The RIVER prospective registry will expand our knowledge of how rivaroxaban is prescribed in everyday practice and whether evidence from clinical trials can be translated to the broader cross-section of patients in the real world

Outcomes of obstructed abdominal wall hernia: results from the UK national small bowel obstruction audit

Background: Abdominal wall hernia is a common surgical condition. Patients may present in an emergency with bowel obstruction, incarceration or strangulation. Small bowel obstruction (SBO) is a serious surgical condition associated with significant morbidity. The aim of this study was to describe current management and outcomes of patients with obstructed hernia in the UK as identified in the National Audit of Small Bowel Obstruction (NASBO). Methods: NASBO collated data on adults treated for SBO at 131 UK hospitals between January and March 2017. Those with obstruction due to abdominal wall hernia were included in this study. Demographics, co-morbidity, imaging, operative treatment, and in-hospital outcomes were recorded. Modelling for factors associated with mortality and complications was undertaken using Cox proportional hazards and multivariable regression modelling. Results: NASBO included 2341 patients, of whom 415 (17·7 per cent) had SBO due to hernia. Surgery was performed in 312 (75·2 per cent) of the 415 patients; small bowel resection was required in 198 (63·5 per cent) of these operations. Non-operative management was reported in 35 (54 per cent) of 65 patients with a parastomal hernia and in 34 (32·1 per cent) of 106 patients with an incisional hernia. The in-hospital mortality rate was 9·4 per cent (39 of 415), and was highest in patients with a groin hernia (11·1 per cent, 17 of 153). Complications were common, including lower respiratory tract infection in 16·3 per cent of patients with a groin hernia. Increased age was associated with an increased risk of death (hazard ratio 1·05, 95 per cent c.i. 1·01 to 1·10; P = 0·009) and complications (odds ratio 1·05, 95 per cent c.i. 1·02 to 1·09; P = 0·001). Conclusion: NASBO has highlighted poor outcomes for patients with SBO due to hernia, highlighting the need for quality improvement initiatives in this group

Anemia prevalence in women of reproductive age in low- and middle-income countries between 2000 and 2018

Anemia is a globally widespread condition in women and is associated with reduced economic productivity and increased mortality worldwide. Here we map annual 2000–2018 geospatial estimates of anemia prevalence in women of reproductive age (15–49 years) across 82 low- and middle-income countries (LMICs), stratify anemia by severity and aggregate results to policy-relevant administrative and national levels. Additionally, we provide subnational disparity analyses to provide a comprehensive overview of anemia prevalence inequalities within these countries and predict progress toward the World Health Organization’s Global Nutrition Target (WHO GNT) to reduce anemia by half by 2030. Our results demonstrate widespread moderate improvements in overall anemia prevalence but identify only three LMICs with a high probability of achieving the WHO GNT by 2030 at a national scale, and no LMIC is expected to achieve the target in all their subnational administrative units. Our maps show where large within-country disparities occur, as well as areas likely to fall short of the WHO GNT, offering precision public health tools so that adequate resource allocation and subsequent interventions can be targeted to the most vulnerable populations

Anemia prevalence in women of reproductive age in low- and middle-income countries between 2000 and 2018

Anemia is a globally widespread condition in women and is associated with reduced economic productivity and increased mortality worldwide. Here we map annual 2000–2018 geospatial estimates of anemia prevalence in women of reproductive age (15–49 years) across 82 low- and middle-income countries (LMICs), stratify anemia by severity and aggregate results to policy-relevant administrative and national levels. Additionally, we provide subnational disparity analyses to provide a comprehensive overview of anemia prevalence inequalities within these countries and predict progress toward the World Health Organization’s Global Nutrition Target (WHO GNT) to reduce anemia by half by 2030. Our results demonstrate widespread moderate improvements in overall anemia prevalence but identify only three LMICs with a high probability of achieving the WHO GNT by 2030 at a national scale, and no LMIC is expected to achieve the target in all their subnational administrative units. Our maps show where large within-country disparities occur, as well as areas likely to fall short of the WHO GNT, offering precision public health tools so that adequate resource allocation and subsequent interventions can be targeted to the most vulnerable populations.Peer reviewe

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations

Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017

Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2\ub75th percentile and 100 as the 97\ub75th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59\ub74 (IQR 35\ub74–67\ub73), ranging from a low of 11\ub76 (95% uncertainty interval 9\ub76–14\ub70) to a high of 84\ub79 (83\ub71–86\ub77). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030