Prenatal genotyping of Gaucher disease in Egypt

Objective: To use chorionic villi sampling (CVS) and amniocentesis to determine the genotyping of Gaucher Disease (GD) of fetuses of pregnant mothers who had a previous child affected by GD.Methods: The study was conducted between January 2009 and December 2012. It included 42 pregnant women that gave informed written consent. Thirty mothers presented early so they underwent CVS at 10–12 weeks of pregnancy while 12 mothers presented later and underwent amniocentesis at 14–16 weeks. Strip assay for the identification of Glucocerebrosidase (GBA) gene mutations in the samples of chrorionic villi and amniotic fluid was based on polymerase chain reaction (PCR) and reverse hybridization.Results: The age of the studied pregnant women ranged from 19 to 26 years. Consanguinity was present in 38 cases. Eighteen women were pregnant in affected fetuses. The results of genotyping revealed 15 cases were homozygous L444P/L444P and one case homozygous (N370s/N370s) while two cases were heterogeneous (L444P/D409H). Twenty-four pregnant women had carrier fetuses which were all heterozygous L444P.Conclusion: This study highlights the findings of an extended gene mutation examination for prenatal diagnosis of Guacher Disease. The study found out that the most common mutation was L444P/L444P.Keywords: Gaucher diseases; Prenatal diagnosis; Egypt; Gene; Mutatio

The relation between oxidative stress and adhesion molecules in Egyptian children and adolescents with type 1 diabetes mellitus

Background: Antioxidant potential decreases while plasma lipid peroxidation products increase in type1 diabetes mellitus. The vascular endothelium is a major target of oxidative stress (OS). Reactive oxygen species signal events leading to impairment of endothelial function and promotion of leukocyte adhesion to the vascular endothelium.. Objective: To explore the relation between OS and adhesion molecules in type1 diabetes and correlate it with the state of metabolic control, disease duration and microvascular complications (MVCs). Design: Thirty-eight type 1 diabetics were included: 22 patients with disease duration less than 5 years and 16 patients with duration of 5 years or more. Thirty healthy age and sex matched subjects served as controls. They were assessed clinically. Laboratory investigations included, random blood sugar (RBS), glycated hemoglobin (HbA1c), fasting lipid profile and measurement of serum malondialdehyde (MDA) as a marker of lipid peroxidation and serum soluble P-selectin as a marker of endothelial/platelet activation. Results: Serum MDA and P-selectin were significantly elevated in type 1 diabetics compared to controls with the highest level in diabetics with disease duration of 5 years or more (p <0.0001). Both MDA and P-selectin levels were significantly elevated in complicated compared to non complicated diabetics (P < 0.0001) with strong relation to complication severity. Serum MDA level was positively correlated with serum P-selectin level in diabetics (p 0.0001). Serum MDA and P-selectin were positively and significantly correlated with disease duration (p < 0.0001 ), RBS (p < 0.0001,p=0.001 respectively), HbA1c (p < 0.0001), diastolic blood pressure (p=0.03,p=0.005 respectively), total cholesterol (p=0.04,p=0.02, respectively), triglycerides (p=0.006, p < 0.0001 respectively) and low density lipoproteins (p=0.03,p=0.05 respectively) but negatively correlated with high density lipoproteins(p=0.03). On multiple regression analysis, HbA1c had the strongest effect on both MDA and P-selectin levels (P <0.0001). Cut off values for serum MDA and Pselectin equal to 8.035 nmoles/ml and 45.15ng/dl respectively for early detection of diabetic MVCs were defined. Conclusion: Levels of MAD and P-selectin are elevated in type1 diabetics with evident relation to disease duration, metabolic control and severity of MVCs. Hence both of them might act as good markers to identify diabetics who are more susceptible to develop vascular disease.Keywords: Type1 diabetes, oxidative stress, P-selectin, adhesion molecules, microvascular complicationsEgypt J Pediatr Allergy Immunol 2009; 7(2): 65-7

Schools of Public Health in Low and Middle-Income Countries: An Imperative Investment for Improving the Health of Populations?

BACKGROUND: Public health has multicultural origins. By the close of the nineteenth century, Schools of Public Health (SPHs) began to emerge in western countries in response to major contemporary public health challenges. The Flexner Report (1910) emphasized the centrality of preventive medicine, sanitation, and public health measures in health professional education. The Alma Ata Declaration on Primary Health Care (PHC) in 1978 was a critical milestone, especially for low and middle-income countries (LMICs), conceptualizing a close working relationship between PHC and public health measures. The Commission on Social Determinants of Health (2005-2008) strengthened the case for SPHs in LMICs as key stakeholders in efforts to reduce global health inequities. This scoping review groups text into public health challenges faced by LMICs and the role of SPHs in addressing these challenges. MAIN TEXT: The challenges faced by LMICs include rapid urbanization, environmental degradation, unfair terms of global trade, limited capacity for equitable growth, mass displacements associated with conflicts and natural disasters, and universal health coverage. Poor governance and externally imposed donor policies and agendas, further strain the fragile health systems of LMICs faced with epidemiological transition. Moreover barriers to education and research imposed by limited resources, political and economic instability, and unbalanced partnerships additionally aggravate the crisis. To address these contextual challenges effectively, SPHs are offering broad based health professional education, conducting multidisciplinary population based research and fostering collaborative partnerships. SPHs are also looked upon as the key drivers to achieve sustainable development goals (SDGs). CONCLUSION: SPHs in LMICs can contribute to overcoming several public health challenges being faced by LMICs, including achieving SDGs. Most importantly they can develop cadres of competent and well-motivated public health professionals: educators, practitioners and researchers who ask questions that address fundamental health determinants, seek solutions as agents of change within their mandates, provide specific services and serve as advocates for multilevel partnerships. Funding support, human resources, and agency are unfortunately often limited or curtailed in LMICs, and this requires constructive collaboration between LMICs and counterpart institutions from high income countries

An Experimental Study of Effects of Step Roughness in Skimming Flows on Stepped Chutes

On a spillway chute, a stepped design increases the rate of energy dissipation on the chute itself and reduces the size of a downstream energy dissipator. Up to date, the effects of step roughness on the flow properties remain unknown despite the practical relevance to damaged concrete steps, rock chutes and gabions weirs. New measurements were conducted in a large-size laboratory facility with two step conditions (smooth and rough) and three types of step roughness. Detailed air-water flow properties were measured systematically for several flow rates. The results showed faster flow motion on rough step chutes. Although the finding is counter-intuitive, it is linked with the location of the inception point of free-surface aeration being located further downstream than for a smooth stepped chute for an identical flow rate. In the aerated flow region, the velocities on rough-step chutes were larger than those of smooth chute flows for a given flow rate and dimensionless location from the inception point of free-surface aeration both at step edges and between step edges. The results suggest that design guidelines for smooth (concrete) stepped spillway may not be suitable to rough stepped chutes including gabion stepped weirs, and older stepped chutes with damaged steps

Schools of public health in low and middle-income countries: an imperative investment for improving the health of populations?

BACKGROUND: Public health has multicultural origins. By the close of the nineteenth century, Schools of Public Health (SPHs) began to emerge in western countries in response to major contemporary public health challenges. The Flexner Report (1910) emphasized the centrality of preventive medicine, sanitation, and public health measures in health professional education. The Alma Ata Declaration on Primary Health Care (PHC) in 1978 was a critical milestone, especially for low and middle-income countries (LMICs), conceptualizing a close working relationship between PHC and public health measures. The Commission on Social Determinants of Health (2005-2008) strengthened the case for SPHs in LMICs as key stakeholders in efforts to reduce global health inequities. This scoping review groups text into public health challenges faced by LMICs and the role of SPHs in addressing these challenges. MAIN TEXT: The challenges faced by LMICs include rapid urbanization, environmental degradation, unfair terms of global trade, limited capacity for equitable growth, mass displacements associated with conflicts and natural disasters, and universal health coverage. Poor governance and externally imposed donor policies and agendas, further strain the fragile health systems of LMICs faced with epidemiological transition. Moreover barriers to education and research imposed by limited resources, political and economic instability, and unbalanced partnerships additionally aggravate the crisis. To address these contextual challenges effectively, SPHs are offering broad based health professional education, conducting multidisciplinary population based research and fostering collaborative partnerships. SPHs are also looked upon as the key drivers to achieve sustainable development goals (SDGs). CONCLUSION: SPHs in LMICs can contribute to overcoming several public health challenges being faced by LMICs, including achieving SDGs. Most importantly they can develop cadres of competent and well-motivated public health professionals: educators, practitioners and researchers who ask questions that address fundamental health determinants, seek solutions as agents of change within their mandates, provide specific services and serve as advocates for multilevel partnerships. Funding support, human resources, and agency are unfortunately often limited or curtailed in LMICs, and this requires constructive collaboration between LMICs and counterpart institutions from high income countries

Resource allocation within the National AIDS Control Program of Pakistan: a qualitative assessment of decision maker's opinions

BACKGROUND: Limited resources, whether public or private, demand prioritisation among competing needs to maximise productivity. With a substantial increase in the number of reported HIV cases, little work has been done to understand how resources have been distributed and what factors may have influenced allocation within the newly introduced Enhanced National AIDS Control Program of Pakistan. The objective of this study was to identify perceptions of decision makers about the process of resource allocation within Pakistan's Enhanced National AIDS Control Program. METHODS: A qualitative study was undertaken and in-depth interviews of decision makers at provincial and federal levels responsible to allocate resources within the program were conducted. RESULTS: HIV was not considered a priority issue by all study participants and external funding for the program was thought to have been accepted because of poor foreign currency reserves and donor agency influence rather than local need. Political influences from the federal government and donor agencies were thought to manipulate distribution of funds within the program. These influences were thought to occur despite the existence of a well-laid out procedure to determine allocation of public resources. Lack of collaboration among departments involved in decision making, a pervasive lack of technical expertise, paucity of information and an atmosphere of ad hoc decision making were thought to reduce resistance to external pressures. CONCLUSION: Development of a unified program vision through a consultative process and advocacy is necessary to understand goals to be achieved, to enhance program ownership and develop consensus about how money and effort should be directed. Enhancing public sector expertise in planning and budgeting is essential not just for the program, but also to reduce reliance on external agencies for technical support. Strengthening available databases for effective decision making is required to make financial allocations based on real, rather than perceived needs. With a large part of HIV program funding dedicated to public-private partnerships, it becomes imperative to develop public sector capacity to administer contracts, coordinate and monitor activities of the non-governmental sector

Anti-Cripto Mab inhibit tumour growth and overcome MDR in a human leukaemia MDR cell line by inhibition of Akt and activation of JNK/SAPK and bad death pathways

Doxorubicin (DOX) selection of CCRF-CEM leukaemia cell line resulted in multidrug resistance (MDR) CEM/A7R cell line, which overexpresses MDR, 1 coded P-glycoprotein (Pgp). Here, we report for the first time that oncoprotein Cripto, a founding member of epidermal growth factor-Cripto-FRL, 1-Criptic family is overexpressed in the CEM/A7R cells, and anti-Cripto monoclonal antibodies (Mab) inhibited CEM/A7R cell growth both in vitro and in an established xenograft tumour in severe combined immunodeficiency mice. Cripto Mab synergistically enhanced sensitivity of the MDR cells to Pgp substrates epirubicin (EPI), daunorubicin (DAU) and non-Pgp substrates nucleoside analogue cytosine arabinoside (AraC). In particular, the combination of anti-Cripto Mab at less than 50% of inhibition concentrations with noncytotoxic concentrations of EPI or DAU inhibited more than 90% of CEM/A7R cell growth. Cripto Mab slightly inhibited Pgp expression, and had little effect on Pgp function, indicating that a mechanism independent of Pgp was involved in overcoming MDR. We demonstrated that anti-Cripto Mab-induced CEM/A7R cell apoptosis, which was associated with an enhanced activity of the c-Jun N-terminal kinase/stress-activated protein kinase and inhibition of Akt phosphorylation, resulting in an activation of mitochondrial apoptosis pathway as evidenced by dephosphorylation of Bad at Ser136, Bcl-2 at Ser70 and a cleaved caspase-9

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks