Hisham Darwish

The calcidiol (25-hydroxyvitamin D3) 24-hydroxylase is one of the key enzymes in the metabolism of vitamin D. This enzyme acts on both calcidiol and calcitriol (1,25-dihydroxyvitamin D3) to initiate degradation of these potent vitamin D metabolites and is tightly regulated. Calcitriol itself induces this enzyme and acts at the transcriptional level. Transcriptional regulation of genes by calcitriol has been shown to occur via the vitamin D-receptor binding to a vitamin D-response element located upstream of the transcription start site. We now report a vitamin D-response element located between nt -262 and nt -238 of the rat calcidiol 24-hydroxylase gene. This sequence binds the calcitriol receptor and confers vitamin D-dependent transactivation of transcription to its own, as well as heterologous, promoter.

The ependyma in six infants dying with cerebro-hepato-renal (CHR) disease showed similar but less extensive morphological and immunohistochemical abnormalities to those previously demonstrated in lissencephaly/pachygyria. More than two-thirds of the ependyma lining all ventricles was a pseudostratified columnar epithelium resembling midfetal life. Discontinuities did not correlate with minimal ventriculomegaly. Subventricular rosettes were common and not confined to regions of gaps in the overlying ependyma. Subependymal gliosis and glial nodules were absent. Immunoreactivity of ependymal cells for vimentin and GFAP was normal for age, but abnormally positive for S-100 protein and cytokeratin, as in lissencephaly; unlike lissencephaly, the rosettes in CHR disease also are reactive. Ependymal abnormalities may contribute to the pathogenesis of cerebral dysgenesis in CHR disease as in other genetic disorders of neuroblast migration.

This study evaluated the association of vitamin D and bone markers with the development osteoporosis in Palestinian postmenopausal women. Even though vitamin D deficiency was very high for the recruited subjects, it was not associated with osteoporosis except for bones of the hip. Age and obesity were the strongest determining factors of the disease. The purpose of this study was to investigate the association of bone mineral density (BMD) with serum vitamin D levels, parathyroid hormone (PTH), calcium, obesity, and bone turnover markers in Palestinian postmenopausal women. Three hundred eighty-two postmenopausal women (≥45 years) were recruited from various women clinics for BMD assessment (131 women had osteoporosis and 251 were normal and served as controls). Blood samples were obtained for serum calcium, PTH, 25(OH)D, bone formation (N-terminal propeptide (PINP)), and bone resorption (serum C-terminal telopeptide of type I collagen (CTX1)) markers. Women with osteoporosis had st...

The purpose of the study is to compare the potential of HbA1c to diagnose diabetes among Palestinian Arabs compared to fasting plasma glucose (FPG). A cross-sectional sample of 1370 Palestinian men (468) and women (902) without known diabetes and above the age of 30 years were recruited. Whole blood was used to estimate HbA(1c) and plasma for FPG and total lipid profile. Fasting plasma glucose was used as a reference to diagnose diabetes (≥ 126 mg/dL) and prediabetes (100-125 mg/dL). The area under the receiver operating characteristic curve (AUC) for HbA(1c) was 81.9% to diagnose diabetes and 63.9% for prediabetes. The agreement between HbA(1c) and diabetes as diagnosed by FPG was moderate (ĸ  =  0.498) and low with prediabetes (ĸ = 0.142). The optimal cut-off value for HbA1c to diagnose diabetes was ≥ 6.3% (45 mmol/mol). The sensitivity, specificity and the discriminant ability were 65.6% (53.1-76.3%), 94.5% (93.1-95.6%), 80.0% (72.8-87.3%), respectively. However, using cut-off value of ≥ 6.5% (48 mmol/mol) improved specificity. At this cut-off value, the sensitivity, specificity and the discriminant ability were 57.4% (44.9-69.0%), 97.1% (96.0-97.9%) and 77.3% (71.0-83.5%). For diagnosing prediabetes with HbA1c between 5.7-6.4% (39-46 mmol/mol), the sensitivity, specificity and the discriminant ability were 62.7% (57.1-67.9%), 56.3% (53.1-59.4%) and 59.5% (56.3-62.5%), respectively. HbA(1c) at cut-off value of ≥ 6.5% (48 mmol/mol) by itself diagnosed 5.3% and 48.3% as having diabetes and prediabetes compared to 4.5% and 24.2% using FPG, respectively. Mean HbA(1c) and FPG increase significantly with increasing body mass index. In conclusion, the ROC curves showed HbA1c could be used for diagnosing diabetes when compared to FPG but not for prediabetes in Palestinians Arabs even though only about 50% of the diabetic subjects were identified by the both HbA1c and FPG.

The need for simple self-assessment tools is necessary to predict women at high risk for developing osteoporo-sis. In this study, tools like the IOF One Minute Test, Fracture Risk Assessment Tool (FRAX), and Simple Calculated Osteoporosis Risk Estimation (SCORE) were found to be valid for Palestinian women. The threshold for predicting women at risk for each tool was estimated. Purpose The purpose of this study is to evaluate the validity of the updated IOF (International Osteoporosis Foundation) One Minute Osteoporosis Risk Assessment Test, FRAX, SCORE as well as age alone to detect the risk of developing osteoporosis in postmenopausal Palestinian women. Methods Three hundred eighty-two women 45 years and older were recruited including 131 women with osteoporosis and 251 controls following bone mineral density (BMD) measurement , 287 completed questionnaires of the different risk assessment tools. Receiver operating characteristic (ROC) curves were evaluated for each tool using bone BMD as the gold standard for osteoporosis. Results The area under the ROC curve (AUC) was the highest for FRAX calculated with BMD for predicting hip fractures (0.897) followed by FRAX for major fractures (0.826) with cutoff values 1.5 and 7.8%, respectively. The IOF One Minute Test AUC (0.629) was the lowest compared to other tested tools but with sufficient accuracy for predicting the risk of developing osteoporosis with a cutoff value 4 total yes questions out of 18. SCORE test and age alone were also as good predictors of risk for developing osteoporosis. According to the ROC curve for age, women ≥64 years had a higher risk of developing osteoporosis. Higher percentage of women with low BMD (T-score ≤−1.5) or osteoporosis (T-score ≤−2.5) was found among women who were not exposed to the sun, who had menopause before the age of 45 years, or had lower body mass index (BMI) compared to controls. Women who often fall had lower BMI and approximately 27% of the recruited postmenopausal Palestinian women had accidents that caused fractures. Conclusions Simple self-assessment tools like FRAX without BMD, SCORE, and the IOF One Minute Tests were valid for predicting Palestinian postmenopausal women at high risk of developing osteoporosis.