ISOLATION OF AnsB GENE FRAGMENT ENCODING L-ASPARAGINASE 2 ENZYME FROM Serratia plymuthica UBCF_13 AND IT’S IN-SILICO DOMAIN CHARACTERISTIC

Objective: To study cross-national inequalities in mortality of adults and of children aged <5 years using a novel approach, with clustering techniques to stratify countries into mortality groups (better-off, worse-off,...

SummaryThe long-term clinical outcomes of severe obesity due to leptin signaling deficiency are unknown. We carry out a retrospective cross-sectional investigation of a large cohort of children with leptin (LEP), LEP receptor (LEPR), or melanocortin 4 receptor (MC4R) deficiency (n = 145) to evaluate the progression of the disease. The affected individuals undergo physical, clinical, and metabolic evaluations. We report a very high mortality in children with LEP (26%) or LEPR deficiency (9%), mainly due to severe pulmonary and gastrointestinal infections. In addition, 40% of surviving children with LEP or LEPR deficiency experience life-threatening episodes of lung or gastrointestinal infections. Although precision drugs are currently available for LEP and LEPR deficiencies, as yet, they are not accessible in Pakistan. An appreciation of the severe impact of LEP or LEPR deficiency on morbidity and early mortality, educational attainment, and the attendant stigmatization should spur efforts to deliver the available life-saving drugs to these children as a matter of urgency.

Identification of a small molecule of nitric oxide donor-aurovertin hybrids as a GPX4 inhibitor inducing ferroptosis and apoptosis in acute T lymphocytic leukemia cells.

BackgroundAs new interventions to reduce childhood mortality are identified, careful consideration must be given to identifying populations that could benefit most from them. Promising reductions in childhood mortality reported in a large cluster randomized trial of mass drug administration (MDA) of azithromycin (AZM) prompted the development of visually compelling, easy-to-use tools that synthesize country-specific data on factors that would influence both potential AZM benefit and MDA implementation success.Methodology/Principal FindingsWe assessed the opportunity to reduce mortality and the feasibility of implementing such a program, creating Opportunity and Feasibility Indices, respectively. Countries with high childhood mortality were included. A Country Ranking Index combined key variables from the previous two Indices and applied a scoring system to identify high-priority countries. We compared four scenarios with varying weights given to each variable.Twenty-five countries met inclusion criteria. We created easily visualized tools to display the results of the Opportunity and Feasibility Indices. The Opportunity Index revealed substantial variation in the opportunity for an MDA of AZM program to reduce mortality, even among countries with high overall childhood mortality. The Feasibility Index demonstrated that implementing such a program would be most challenging in the countries that could see greatest benefit. Based on the Country Ranking Index, Equatorial Guinea would benefit the most from the MZA of AZM in three of the four scenarios we tested.Conclusions/SignificanceThese visually accessible tools can be adapted or refined to include other metrics deemed important by stakeholders, and provide a quantitative approach to prioritization for intervention implementation. The need to explicitly state metrics and their weighting encourages thoughtful and transparent decision making. The objective and data-driven approach promoted by the three Indices may foster more efficient use of resources.

This study explores the relationships between electricity consumption, healthcare spending, carbon dioxide (CO2) emissions, GDP growth, industrialization, urbanization, fertility rates, and child mortality rates in ten countries with the highest and lowest child mortality rates, using Driscoll-Kraay’s standard error approach (DKSE). The DKSE regression results show that in countries with high child mortality, the mortality declines significantly with electricity access, health expenditures, urbanization, and GDP growth, and increases with CO2 emissions and fertility rates. In countries with low child mortality rates, the mortality declines significantly with health expenditures, GDP, and urbanization, and rises with industrialization. Electricity access, CO2 emissions, and fertility rates do not impact child mortality in these countries. The study emphasizes the importance of electricity access, health expenditures, GDP, and tailored urbanization and industrialization strategies in child welfare and the need for comprehensive global policies.

Many HIV-infected children in Southern Africa have been started on antiretroviral therapy (ART), but loss to follow up (LTFU) can be substantial. We analyzed mortality in children retained in care and in all children starting ART, taking LTFU into account. Children who started ART before the age of 16 years in 10 ART programs in South Africa, Malawi, Mozambique, and Zimbabwe were included. Risk factors for death in the first year of ART were identified in Weibull models. A meta-analytic approach was used to estimate cumulative mortality at 1 year. Eight thousand two hundred twenty-five children (median age 49 months, median CD4 cell percent 11.6%) were included; 391 (4.8%) died and 523 (7.0%) were LTFU in the first year. Mortality at 1 year was 4.5% [95% confidence interval (CI): 2.8% to 7.4%] in children remaining in care, but 8.7% (5.4% to 12.1%) at the program level, after taking mortality in children and LTFU into account. Factors associated with mortality in children remaining in care included age [adjusted hazard ratio (HR) 0.37; 95% CI: 0.25 to 0.54 comparing > or =120 months with <18 months], CD4 cell percent (HR: 0.56; 95% CI: 0.39 to 0.78 comparing > or =20% with <10%), and clinical stage (HR: 0.12; 95% CI: 0.03 to 0.45 comparing World Health Organization stage I with III/IV). In children starting ART and remaining in care in Southern Africa mortality at 1 year is <5% but almost twice as high at the program level, when taking LTFU into account. Age, CD4 percentage, and clinical stage are important predictors of mortality at the individual level.

Risk factors for occurrence and death of sepsis-associated acute kidney injury in children with sepsis

BackgroundEarly women's marriage is associated with adverse outcomes for mothers and their offspring, including reduced human capital and increased child undernutrition and mortality. Despite preventive efforts, it remains common in many populations and is often favored by cultural norms. A key question is why it remains common, given such penalties. Using an evolutionary perspective, a simple mathematical model was developed to explore women's optimal marriage age under different circumstances, if the sole aim were to maximize maternal or paternal lifetime reproductive fitness (surviving offspring).MethodsThe model was based on several assumptions, supported by empirical evidence, regarding relationships between women's marital age and parental and offspring outcomes. It assumes that later marriage promotes women's autonomy, enhancing control over fertility and childcare, but increases paternity uncertainty. Given these assumptions, optimal marriage ages for maximizing maternal and paternal fitness were calculated. The basic model was then used to simulate environmental changes or public health interventions, including shifts in child mortality, suppression of women's autonomy, or promoting women's contraception or education.ResultsIn the basic model, paternal fitness is maximized at lower women's marriage age than is maternal fitness, with the paternal optimum worsening child undernutrition and mortality. A family planning intervention delays marriage age and reduces child mortality and undernutrition, at a cost to paternal but not maternal fitness. Reductions in child mortality favor earlier marriage but increase child undernutrition, whereas ecological shocks that increase child mortality favor later marriage but reduce fitness of both parents. An education intervention favors later marriage and reduces child mortality and undernutrition, but at a cost to paternal fitness. Efforts to suppress maternal autonomy substantially increase fitness of both parents, but only if other members of the household provide compensatory childcare.ConclusionEarly women's marriage maximizes paternal fitness despite relatively high child mortality and undernutrition, by increasing fertility and reducing paternity uncertainty. This tension between the sexes over the optimal marriage age is sensitive to ecological stresses or interventions. Education interventions seem most likely to improve maternal and child outcomes, but may be resisted by males and their kin as they may reduce paternal fitness.

BackgroundUganda just like any other Sub-Saharan African country, has a high under-five child mortality rate. To inform policy on intervention strategies, sound statistical methods are required to critically identify factors strongly associated with under-five child mortality rates. The Cox proportional hazards model has been a common choice in analysing data to understand factors strongly associated with high child mortality rates taking age as the time-to-event variable. However, due to its restrictive proportional hazards (PH) assumption, some covariates of interest which do not satisfy the assumption are often excluded in the analysis to avoid mis-specifying the model. Otherwise using covariates that clearly violate the assumption would mean invalid results.MethodsSurvival trees and random survival forests are increasingly becoming popular in analysing survival data particularly in the case of large survey data and could be attractive alternatives to models with the restrictive PH assumption. In this article, we adopt random survival forests which have never been used in understanding factors affecting under-five child mortality rates in Uganda using Demographic and Health Survey data. Thus the first part of the analysis is based on the use of the classical Cox PH model and the second part of the analysis is based on the use of random survival forests in the presence of covariates that do not necessarily satisfy the PH assumption.ResultsRandom survival forests and the Cox proportional hazards model agree that the sex of the household head, sex of the child, number of births in the past 1 year are strongly associated to under-five child mortality in Uganda given all the three covariates satisfy the PH assumption. Random survival forests further demonstrated that covariates that were originally excluded from the earlier analysis due to violation of the PH assumption were important in explaining under-five child mortality rates. These covariates include the number of children under the age of five in a household, number of births in the past 5 years, wealth index, total number of children ever born and the child’s birth order. The results further indicated that the predictive performance for random survival forests built using covariates including those that violate the PH assumption was higher than that for random survival forests built using only covariates that satisfy the PH assumption.ConclusionsRandom survival forests are appealing methods in analysing public health data to understand factors strongly associated with under-five child mortality rates especially in the presence of covariates that violate the proportional hazards assumption.

Acute Lymphoblastic Leukemia

Mortality in diabetic ketoacidosis (DKA) among children has been reported to be 0.3–3 % in developed countries. Based on the limited data from developing countries, the mortality reported is as high as 13.4 %. A prospective study was conducted to identify the factors leading to high mortality in children with DKA in South India. This was a study of 118 episodes of DKA among children, admitted in a pediatric tertiary care center at Chennai. Clinical presentation, laboratory parameters at admission, parameters during treatment, and complications were considered as risk factors. All children were followed up till discharge from hospital or death. Univariate and multivariate analyses for risk factors were undertaken. Altered sensorium and higher osmolality at admission, delayed diagnosis, cerebral edema, shock, renal failure, and sepsis were the major risk factors associated with mortality in multivariate analysis. Cerebral edema was encountered in 23.7 %, shock in 12.7 %, sepsis in 11 %, and renal failure in 9.3 %. The overall mortality rate was 11 %. Delayed diagnosis may be the root cause for high mortality in children with DKA in developing countries. There is an urgent need to create awareness among physicians, teachers, and parents to avoid a delay in diagnosis and decrease the mortality in children with DKA. Higher incidence of cerebral edema, shock, renal failure, and sepsis are unique problems identified in this study. There is a need for further studies on fluid management of shock, strategies for management of renal failure in DKA, and use of antibiotics in DKA in developing countries.

IntroductionThe significance of endothelial injury in children with the acute respiratory distress syndrome (ARDS) has not been well studied. Plasma levels of soluble thrombomodulin (sTM), an endothelial surface protein involved in coagulation, have been associated with endothelial injury. We hypothesized that elevated plasma sTM would correlate with mortality and organ failure in children with ARDS.MethodsWe conducted a multicenter prospective observational study of pediatric patients with ARDS between 2008 and 2014. sTM was measured in plasma collected less than 24 hours from ARDS diagnosis. Outcomes were intensive care unit mortality and organ dysfunction by pediatric logistic organ dysfunction scores. Logistic regression was used to adjust for clinically relevant covariates.ResultsPlasma sTM was higher in patients with indirect lung injury compared to direct lung injury (100 ng/mL vs. 86 ng/mL, p = 0.02). Increased sTM levels were correlated with more organ dysfunction in the entire study population (Spearman’s rho = 0.37, p < 0.01). Overall mortality was 16 %. sTM levels were associated with increased mortality in patients with indirect lung injury (OR 2.7 per log(sTM), p = 0.02). These relationships were independent of age, oxygenation defect, or presence of acute kidney injury.ConclusionElevated plasma sTM levels are associated with organ dysfunction in children with ARDS and with higher mortality in children with indirect lung injury. These findings highlight the importance of endothelial injury in children with ARDS and may guide the development of future therapies targeted toward endothelial stabilization, repair, or functional replacement in this population.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-1145-9) contains supplementary material, which is available to authorized users.

Assessment of the cost effectiveness of interventions designed to achieve the millennium development goals for health is complex. The methods must be capable of showing the efficiency with which current...

Acute leukemia is the most common form of childhood cancer and is the primary cause of cancer-related mortality in children. In the United approximately 3250 cases are diagnosed annually in children and adolescents younger than 20 years, of whom 2400 have acute lymphoblastic leukemia (ALL). Treatment results in childhood ALL continue to improve, and the expected current cure rates approach 75 to 80% of all children with ALL, including T-ALL and mature B-cell ALL, the two variants that, not too long ago, had a considerably poorer prognosis compared with the common form of BpALL. The most significant new development in the past 2 years has been the development of further evidence for fetal origin of childhood leukemias, and additional evidence to support the notion that postnatal events modulating the events of immune-mediated elimination of these leukemic clones play a major role in the eventual development of clinical disease. Other epidemiologic developments include (1) increased appreciation of the role of drug-metabolizing enzymes, both in determining the predisposition to leukemia and response to therapy; and (2) both clinical observations and gene expression studies seeming to identify a new approach to the evaluation and treatment of children with MLL (11q23) rearrangements. A most remarkable new development in the induction therapy of childhood leukemia and lymphoma in the United States is the use of urate oxidase for prevention of tumor lysis syndrome and the associated uric acid nephropathy. Drug resistance, determined either on leukemic blast cells in vitro or by studies of MRD, is being looked at critically in an effort to improve the treatment results further. Consolidation with HDMTX has gained wider popularity with the realization that effective CNS prophylaxis can be achieved with intrathecal therapy plus HDMTX for consolidation. In contrast to ALL, the progress in the therapy of acute myeloid leukemia (AML) lags behind, with cure rates of approximately 40 to 50%. There is no convincing evidence for substitution of daunorubicin with other anthracyclines, nor evidence for using high-dose cytarabine during induction in childhood AML. Rather, a 3 + 10 regimen with total daunorubicin 180 mg/m2 and cytarabine 100 to 200 mg/2 for 10 days appears to yield the best results. The most important component of the postremission chemotherapy continues to be several courses of high-dose cytarabine. The results from the MRC 10, LAME 89/91 studies and the recent BFM 93 trial with high-dose cytarabine and mitoxantrone suggest that there may be some benefit to including this combination in the postremission phase of AML. Despite these improvements in chemotherapy, allogeneic BMT from a matched family donor remains the best option for most patients (excluding Down syndrome, APL, and possibly those with inv16). Newer prognostic markers of interest include FLT3/ITD and minimal residual disease at the end of induction therapy.

Maternal ethnic group, socioeconomic status, and neonatal and child mortality: a nationwide cohort study in England and Wales.