Basma Basha

Endothelial dysfunction in diabetes mellitus: possible involvement of endoplasmic reticulum stress?

The vascular complications of diabetes mellitus impose a huge burden on the management of this disease. The higher incidence of cardiovascular complications and the unfavorable prognosis among diabetic individuals who develop such complications have been correlated to the hyperglycemia-induced oxidative stress and associated endothelial dysfunction. Although antioxidants may be considered as effective therapeutic agents to relieve oxidative stress and protect the endothelium, recent clinical trials involving these agents have shown limited therapeutic efficacy in this regard. In the recent past experimental evidence suggest that endoplasmic reticulum (ER) stress in the endothelial cells might be an important contributor to diabetes-related vascular complications. The current paper contemplates the possibility of the involvement of ER stress in endothelial dysfunction and diabetes-associated vascular complications.

Novel MIR143-NOTCH Fusions in Benign and Malignant Glomus Tumors

Glomus tumors (GT) have been classified among tumors of perivascular smooth muscle differentiation, together with myopericytoma, myofibroma/tosis, and angioleiomyoma, based on their morphologic overlap. However, no molecular studies have been carried out to date to investigate their genetic phenotype and to confirm their shared pathogenesis. RNA sequencing was performed in three index cases (GT1, malignant GT; GT2, benign GT and M1, multifocal myopericytoma), followed by FusionSeq data analysis, a modular computational tool developed to discover gene fusions from paired‐end RNA‐seq data. A gene fusion involving MIR143 in band 5q32 was identified in both GTs with either NOTCH2 in 1p13 in GT1 or NOTCH1 in 9q34 in GT2, but none in M1. After being validated by FISH and RT‐PCR, these abnormalities were screened on 33 GTs, 6 myopericytomas, 9 myofibroma/toses, 18 angioleiomyomas and in a control group of 5 sino‐nasal hemangiopericytomas. Overall NOTCH2 gene rearrangements were identified in 52% of GT, including all malignant cases and one NF1‐related GT. No additional cases showed NOTCH1 rearrangement. As NOTCH3 shares similar functions with NOTCH2 in regulating vascular smooth muscle development, the study group was also investigated for abnormalities in this gene by FISH. Indeed, NOTCH3 rearrangements were identified in 9% of GTs, all present in benign soft tissue GT, one case being fused to MIR143. Only 1/18 angioleiomyomas showed NOTCH2 gene rearrangement, while all the myopericytomas and myofibroma/toses were negative. In summary, we describe novel NOTCH1–3 rearrangements in benign and malignant, visceral, and soft tissue GTs.

Impact of lifestyle and dietary habits on hypovitaminosis D in type 1 diabetes mellitus and healthy children from Qatar, a sun-rich country.

BACKGROUND There are no population-based studies that have examined the association between vitamin D and type 1 diabetes mellitus (T1DM) and the role of lifestyle habits and dietary factors in young children in the Arabian Gulf and Middle East region. Little data on the intake of these nutrients in Mediterranean countries exist, and predictors of their suboptimal intake are not well defined. OBJECTIVE The objective of this study was to determine the association between vitamin D status and T1DM and assess the impact of lifestyle and dietary habits on hypovitaminosis D in the young population of the State of Qatar. A matched case-control study was carried out among T1DM children and healthy subjects <16 years of age at the pediatric endocrinology outpatient clinics of the Hamad General Hospital and the primary health care clinics center. The survey was conducted over a period from 6 August to 25 December 2007. The sample included 170 cases and 170 controls matched by age, gender and ethnicity. METHODS Face to face interviews were based on a questionnaire that included variables such as sociodemographic information, assessment of non-dietary covariates, assessment of dietary intake including vitamin D, type of feeding, clinical manifestations and laboratory investigations. Their health status was assessed by medical conditions, family history, body mass index, past or present clinical manifestations, serum 25(OH) vitamin D, calcium, alkaline phosphates, phosphorus, hemoglobin A1C, parathyroid hormone, magnesium and creatinine analysis. RESULTS The study revealed that the incidence of severe vitamin D deficiency was considerably higher in T1DM (28.8%) compared with healthy children (17.1%). Although the mean serum level of vitamin D was significantly lower in T1DM children (15.80+/-9.23 ng/ml), compared with nondiabetic children (18.45+/-9.56 ng/ml), both groups belonged to the mild-moderate vitamin D deficiency category. A family history of vitamin D deficiency (35.3%; p=0.012) and diabetes mellitus (56.5%; p<0.001) was significantly higher in diabetic children. More than half of the diabetic (67.1%) and healthy children (51.2%) had no physical activity in their daily life. Both groups (65.9 vs. 62.9%) had very limited exposure to sunlight. Vitamin D supplement intake was very poor in diabetic children compared with healthy children; 60% of diabetic and 40.6% of healthy children never had any vitamin D supplement. The study revealed that vitamin D serum concentration, phosphorus, hemoglobin A1C, magnesium and creatinine show statistically significant differences between T1DM and healthy control subjects. A significant difference was noted between diabetic and healthy children for fractures (p=0.005), weakness (p=0.001) and gastroenteritis (p=0.025). CONCLUSIONS The present study revealed that vitamin D deficiency is a common problem in Qatari children, but the incidence of vitamin D deficiency becomes very severe in T1DM children, compared with healthy children. This suggests that there is an association between vitamin D deficiency and T1DM. The data show that vitamin D status is dependent on sunshine exposure and dietary vitamin D intake. The results suggest the necessity of nutrition education to promote healthy eating habits among adolescents and their parents.

Measuring burden of diseases in a rapidly developing economy: state of Qatar

Background: The Global Burden of Disease (GBD) study has provided a conceptual and methodological framework to quantify and compare the health of populations. Aim: The objective of the study was to assess the national burden of disease in the population of Qatar using the disability-adjusted life year (DALYs) as a measure of disability. Methods: We adapted the methodology described by the World Health Organization for conducting burden of disease to calculate years of life lost due to premature mortality (YLL), years lived with disability (YLD) and disability adjusted life years (DALYs). The study was conducted during the period from November 2011 to October 2012. Results:: The study findings revealed that ischemic heart disease (11.8%) and road traffic accidents (10.3%) were the two leading causes of burden of diseases in Qatar in 2010. The burden of diseases among men (222.04) was found three times more than of womens (71.85). Of the total DALYs, 72.7% was due to non fatal health outcomes and 27.3% was due to premature death. For men, chronic diseases like ischemic heart disease (15.7%) and road traffic accidents (13.7%) accounted great burden and an important source of lost years of healthy life. For women, birth asphyxia and birth trauma (12.6%) and abortion (4.6%) were the two leading causes of disease burden. Conclusion:: The results of the study have shown that the national health priority areas should cover cardiovascular diseases, road traffic accidents and mental health. The burden of diseases among men was three times of womens.

Breast Cancer Screening Barriers: Knowledge, Attitudes and Practices of Women Toward Breast Cancer

To the Editor: Breast cancer appears to be a major global health problem of both the developing and developed countries. Global statistics show that the annual incidence of breast cancer is increasing and it has been reported that each year over 1.5 million women worldwide are diagnosed with breast cancer (1). Sadler et al. (2) reported that early detection offers the greatest chance of long-term survival. Early detection of breast cancer can be achieved by performing breast self examination (BSE), clinical breast examination (CBE), and mammography. A recent study (3) conducted in the State of Qatar reported that the incidence rate of breast cancer was high (30.1 ⁄ 100,000). The increasing trend of incidence rate of breast cancer (4) shows the lack of knowledge about breast cancer and the screening methods among women in Qatar. The aim of this study was to evaluate knowledge, attitude, and practice about breast cancer, and its screening procedures among Qatari women. The cross-sectional study was based on the Primary Health Care Centers and the outpatient clinics of the Women’s hospital among Qatari women from December 2008 to April 2009. Of the sample size of 1200, 1002 Qatari women of age group 30–55 years agreed to participate in the study (83.5%). A questionnaire was designed and qualified nurses were instructed to structurally interview and complete a questionnaire for randomly selected Qatari women. Student t-test, nonparametric Mann–Whitney test, Chi-square and Fisher’s exact test (two-tailed) were performed for statistical analysis. Majority of the Qatari women agreed that breast cancer is the most common cancer in women (70.3%). It was worthy to observe that most of the women with higher education correctly identified that BSE is good in finding lumps (64.9%), and unattended lumps will turn into cancer (72.1%), mammography can show a lump before doing BSE or CBE (68.1%), and women should go for mammogram at certain intervals (57.1%). Despite having a sufficient level of knowledge about breast cancer, our results confirm low breast cancer screening in Qatari women; BSE (24.9%), CBE (23.3%), and mammography (22.5%). Seventy-two percent of Qatari women thought that BSE is easy to learn and 63.1% agreed to have CBE by a doctor, but most of them were afraid (63.5%) of having mammography tests. In our study sample, fear and worries were the general potential barriers toward breast cancer screening (46.5%). Embarrassment of CBE (53.3%) and fear of mammography results (54.9%) were the frequently reported barriers. Positive family history, level of education, living in an urban area, and medical check up when healthy, were significant common predictors for CBE and mammography. In conclusion, our study revealed that although Qatari women had adequate general knowledge about breast cancer, the screening rates of BSE, CBE, and mammography were low in women for early detection of cancer. Education appeared to be the major determinant of level of knowledge and for practicing screening procedures (5,6,7).

The impact of the interpregnancy interval on birth weight and other pregnancy outcomes

Objectives: to investigate the relationship between the interpregnancy interval and low birth weight and other pregnancy outcomes. Methods: this case-control study was carried out in hospitals from January 2010 to April 2011. For cases, mothers of 1216 newborns with birth weight <2500 g were approached and 854 mothers participated (70.2%). For controls, mothers of 1158 newborns with E2500 g were approached and 854 mothers participated in this study (73.7%). Face-toface interviews were conducted to complete the questionnaires. Results: of the newborn babies with low birth weight, the risk was higher among mothers with a short interpregnancy interval (40.3%), whereas for infants with normal birth weight, the majority of the mothers had a longer interpregnancy interval of 24 months (44.7%). A short interpregnancy interval of 612 months was more common among women of <25 years (49.4%; p<0.001) and those who were illiterate (13.1%; p=0.043) with a higher risk of low birth weight compared to the controls. Prenatal care during the 1st trimester was lower in women with low birth weight children (p<0.001). Normal delivery was observed less in women with a short birth interval among cases (58.7%) compared to controls (79%) (p=0.001). A J-shaped association was observed between low birth weight and the interpregnancy interval.

CD4-3 Vitamin D deficiency in the young population with Type 1 diabetes: a case-control study

of T1D were examined over time, between areas of differing socioeconomic status, and in urban and rural Canterbury. Second, cluster analysis using the spatial scan statistic was employed to test for spatial-temporal clustering of T1D within the Canterbury region. Finally, Poisson and zero-inflated Poisson regression analyses were utilised to investigate the association between T1D and various measures of population mixing at the area level. Standardised incidence ratios revealed that childhood T1D was higher in the more affluent CAUs in Canterbury, and in areas classed as satellite urban communities. Geographical patterns in incidence were evident and a number of significant spatialtemporal clusters of the disease were noted. Regression analyses revealed significantly higher T1D incidence rate ratios in CAUs which had increased the most in population mixing for three out of four of the analysis periods (1987-1992, 1993-1998 and 19992004). Supporting evidence for this relationship was especially strong in the most recent period (1999-2004) where T1D incidence was positively associated with three different population mixing measures: change in the percentage of total migrants, change in the percentage of child migrants and change in the one year mobility percentage. It is postulated that where population mixing is low in early life, children miss out on important immune system stimulation from common infectious exposure. Subsequent increases in population mixing which introduce new infections to the area could trigger the onset of T1D in genetically susceptible individuals. This study is the first to consider the role of population mixing in the aetiology of type 1 diabetes in New Zealand. Study limitations mean that no causal relationships can be proved, but the associations found highlight the need to investigate the role of population mixing and infections in the pathogenesis of T1D further.