Molecular Characterization of Glucose-6-Phosphate Dehydrogenase Deficiency in a University Community in Malaysia

Purpose: To determine the prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency among staff and students of a university community in Malaysia as well as to identify molecular genetics by determination of G6PD mutations.Methods: Cross-sectional and experimental studies were carried out on the staff and students of Advanced Medical and Dental Institute (AMDI) of Universiti Sains Malaysia (USM) from July 2009 to April 2010. Venous blood samples were collected from 87 individuals (45 males and 42 females), all of whom gave informed consent. Full blood count, reticulocyte count, screening test and quantitative determination of G6PD were performed. The deficient subjects were confirmed by standard PCR restriction enzyme. DNA samples from these subjects were analyzed for certain known G6PDmutations by digesting them with appropriate restriction enzymes.Results: Out of the 87 subjects (80 were Malay, 2 were Chinese, 1 was Indian and 4 were others). The total prevalence of G6PD deficiency among the subjects was 4.59 % (4/87), all of whom were Malay males. One of the deficient subjects had G6PD Viangchan, while the other three were G6PDMahidol (487 G>A).Conclusion: The finding of this study demonstrate that the most common mutation among AMDI staff and students is Mahidol (487G>A), followed by mutation Viangchan (871G>A).Keywords: Glucose-6-Phosphate Dehydrogenase, Mahidol, Viangchan, Haemolytic anaemi

Molecular Characterization of Glucose-6-Phosphate Dehydrogenase Deficiency in Abu Dhabi District, United Arab Emirates

Purpose: To investigate the frequency of glucose-6-phosphate dehydrogenase (G6PD) variants and their associated enzyme deficiencies among different age groups of individuals in Abu Dhabi, United Arab Emirates (UAE).Methods: A total of 15,995 patients (6302 UAE nationals and 9693 non-UAE nationals) who presented at Mafraq Hospital, Abu Dhabi, UAE between January 2006 and January 2009 were screened for G6PD deficiency using fluorescent spot test. Molecular analysis including polymerase chain reaction– restriction fragment length polymorphism (PCR-RFLP), denaturing high performance liquid chromatography (DHPLC) and DNA sequencing were utilized to identify common mutations in individuals with G6PD deficiency.Results: The prevalence of G6PD deficiency among UAE nationals was 7.4% and non-UAE nationals 3.8%. UAE males showed prevalence of 11.6% while for UAE females it was 3.6%. The prevalence of G6PD deficiency among non-UAE nationals was 5 and 1.7% for males and females, respectively. The Mediterranean mutation, 563C→T, was predominant in non-UAE nationals.Conclusion: G6PD Mediterranean mutation is the most prevalent mutation underlying G6PD deficiency followed by Aures mutations in both UAE nationals and non-UAE nationals. On the other hand, Africa Awas found to be more in non-UAE compared with UAE nationals.Keywords: Glucose-6-Phosphate Dehydrogenase deficiency, Mutation, Abu Dhabi, Polymerase chain reaction–restriction, Fragment length polymorphis

In vitro Anti-proliferative and Apoptotic Activities of Eurycoma longifolia Jack (Simaroubaceae) on HL-60 Cell Line

Purpose: To investigate the anti-proliferative, apoptotic and differentiating activities of Eurycoma longifolia root extracts on HL-60 leukemic cells.Methods: HL-60 cells were treated with different partially purified sub-fractions (F1 – F3) derived from the resin chromatography of the crude methanol root extract of E. longifolia roots, at different doses andtime points. The anti-proliferative activity of E. longifolia was assessed via cell counting and trypan blue exclusion. Apoptosis was evaluated via Annexin-V FITC/IP and Hoechst staining. Flow cytometry and Wright staining were used to assess its differentiation activities.Results: F1 showed unremarkable growth inhibition rate while F2 and F3 showed growth inhibitory effects with median inhibitory concentration (IC50) values of 15.2 and 28.6 ìg/ml, respectively. Treatment with F2 and F3 (100 ìg/ml) for 96 h increased cell death from 3.3 to 95.5 and 76.3 %,respectively. Treatment with F2 (50 ìg/ml) induced apoptosis by 14, 19.5 and 25 % after 24, 48 and 72 h, respectively. No differentiation activity was observed, as indicated by absence of myeloid maturation and a non-significant CD14 positivity (p > 0.05).Conclusion: E. longifolia extract (F2) showed promising anti-leukemic activity and can be a candidate for the development of a drug for the treatment of acute promyelocytic leukemia (APL).Keywords: Acute promyelocytic leukemia (APL), HL-60 cells, Eurycoma longifolia, Apoptosis, Antiproliferation, Differentiatio

LCA applied to perennial cropping systems: a review focused on the farm stage

International audienc

Negative feedback regulation of the ERK1/2 MAPK pathway

The extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) signalling pathway regulates many cellular functions, including proliferation, differentiation, and transformation. To reliably convert external stimuli into specific cellular responses and to adapt to environmental circumstances, the pathway must be integrated into the overall signalling activity of the cell. Multiple mechanisms have evolved to perform this role. In this review, we will focus on negative feedback mechanisms and examine how they shape ERK1/2 MAPK signalling. We will first discuss the extensive number of negative feedback loops targeting the different components of the ERK1/2 MAPK cascade, specifically the direct posttranslational modification of pathway components by downstream protein kinases and the induction of de novo gene synthesis of specific pathway inhibitors. We will then evaluate how negative feedback modulates the spatiotemporal signalling dynamics of the ERK1/2 pathway regarding signalling amplitude and duration as well as subcellular localisation. Aberrant ERK1/2 activation results in deregulated proliferation and malignant transformation in model systems and is commonly observed in human tumours. Inhibition of the ERK1/2 pathway thus represents an attractive target for the treatment of malignant tumours with increased ERK1/2 activity. We will, therefore, discuss the effect of ERK1/2 MAPK feedback regulation on cancer treatment and how it contributes to reduced clinical efficacy of therapeutic agents and the development of drug resistance

Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants

BACKGROUND: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age-standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are affecting the number of adults with diabetes. METHODS: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence—defined as fasting plasma glucose of 7·0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs—in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue. FINDINGS: We used data from 751 studies including 4 372 000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4·3% (95% credible interval 2·4–7·0) in 1980 to 9·0% (7·2–11·1) in 2014 in men, and from 5·0% (2·9–7·9) to 7·9% (6·4–9·7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28·5% due to the rise in prevalence, 39·7% due to population growth and ageing, and 31·8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target. INTERPRETATION: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults affected, has increased faster in low-income and middle-income countries than in high-income countries. FUNDING: Wellcome Trust

Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults.

BACKGROUND: Underweight, overweight, and obesity in childhood and adolescence are associated with adverse health consequences throughout the life-course. Our aim was to estimate worldwide trends in mean body-mass index (BMI) and a comprehensive set of BMI categories that cover underweight to obesity in children and adolescents, and to compare trends with those of adults. METHODS: We pooled 2416 population-based studies with measurements of height and weight on 128·9 million participants aged 5 years and older, including 31·5 million aged 5-19 years. We used a Bayesian hierarchical model to estimate trends from 1975 to 2016 in 200 countries for mean BMI and for prevalence of BMI in the following categories for children and adolescents aged 5-19 years: more than 2 SD below the median of the WHO growth reference for children and adolescents (referred to as moderate and severe underweight hereafter), 2 SD to more than 1 SD below the median (mild underweight), 1 SD below the median to 1 SD above the median (healthy weight), more than 1 SD to 2 SD above the median (overweight but not obese), and more than 2 SD above the median (obesity). FINDINGS: Regional change in age-standardised mean BMI in girls from 1975 to 2016 ranged from virtually no change (-0·01 kg/m2 per decade; 95% credible interval -0·42 to 0·39, posterior probability [PP] of the observed decrease being a true decrease=0·5098) in eastern Europe to an increase of 1·00 kg/m2 per decade (0·69-1·35, PP>0·9999) in central Latin America and an increase of 0·95 kg/m2 per decade (0·64-1·25, PP>0·9999) in Polynesia and Micronesia. The range for boys was from a non-significant increase of 0·09 kg/m2 per decade (-0·33 to 0·49, PP=0·6926) in eastern Europe to an increase of 0·77 kg/m2 per decade (0·50-1·06, PP>0·9999) in Polynesia and Micronesia. Trends in mean BMI have recently flattened in northwestern Europe and the high-income English-speaking and Asia-Pacific regions for both sexes, southwestern Europe for boys, and central and Andean Latin America for girls. By contrast, the rise in BMI has accelerated in east and south Asia for both sexes, and southeast Asia for boys. Global age-standardised prevalence of obesity increased from 0·7% (0·4-1·2) in 1975 to 5·6% (4·8-6·5) in 2016 in girls, and from 0·9% (0·5-1·3) in 1975 to 7·8% (6·7-9·1) in 2016 in boys; the prevalence of moderate and severe underweight decreased from 9·2% (6·0-12·9) in 1975 to 8·4% (6·8-10·1) in 2016 in girls and from 14·8% (10·4-19·5) in 1975 to 12·4% (10·3-14·5) in 2016 in boys. Prevalence of moderate and severe underweight was highest in India, at 22·7% (16·7-29·6) among girls and 30·7% (23·5-38·0) among boys. Prevalence of obesity was more than 30% in girls in Nauru, the Cook Islands, and Palau; and boys in the Cook Islands, Nauru, Palau, Niue, and American Samoa in 2016. Prevalence of obesity was about 20% or more in several countries in Polynesia and Micronesia, the Middle East and north Africa, the Caribbean, and the USA. In 2016, 75 (44-117) million girls and 117 (70-178) million boys worldwide were moderately or severely underweight. In the same year, 50 (24-89) million girls and 74 (39-125) million boys worldwide were obese. INTERPRETATION: The rising trends in children's and adolescents' BMI have plateaued in many high-income countries, albeit at high levels, but have accelerated in parts of Asia, with trends no longer correlated with those of adults. FUNDING: Wellcome Trust, AstraZeneca Young Health Programme

The mediating effects of first call resolution on call centers’ performance

This article aims to examine and validate the prepositions of the mediating impacts of first call resolution (FCR) on caller satisfaction within the contact center industry.A survey of 168 call center managers was analyzed through structural equation modeling, constituting an overall 43.3 per cent response rate for this study.The results show that FCR positively mediates the relationship between knowledge management, technology-based CRM and caller satisfaction within the inbound customer contact centers.We have empirically assessed call centers/contact centers’ success through caller satisfaction (an observed variable through their 2009 customer survey in Malaysia).Consequently, this study cannot generalize its findings in all other countries.Our strong argument is that within the operational variables, FCR is statistically significant and positively mediates knowledge management applications. But very important to note is that the customer contact centers are first touch points to a company's goods or services, and that many other factors such as product quality, company policy, target markets, decision-making processes and so on are also determinants of caller satisfaction, but fall outside the operational control of contact center activities.This research has empirically established that a company's capability in effectively acquiring a valid understanding of its current and potential customers’ information through CRM technologies will positively impact its acquisitions, customization, management and retention of customers.It also avails both the academic and contact center management the benefits that are inherent in measuring the impact of knowledge management and technology-based CRM on inbound FCR and caller satisfaction.This study finally recommends alternative areas for future research