Prenatal aripiprazole induces alterations of rat placenta: a histological, immunohistochemical and ultrastructural study.

Antipsychotic drugs (APDs) are used to treat many psychiatric illnesses as schizophrenia. Typical antipsychotic drugs (TAPDs) are being used; however, they have many side effects. Atypical antipsychotic drugs (AAPDs) are newer medications with known fewer side effects. Aripiprazole (ARI) is an AAPD, recommended by healthcare providers, even during pregnancy. It can cross the placental barrier and enter fetal circulation, so it might be possible that ARI can adversely impair normal placental development and growth, if it is given prenatally. ARI was applied orally to pregnant female rats in two doses (3& 6 mg/kg body weight). On gestation day 20, the mothers were sacrificed, and the placentas were removed and processed for general histological and electron microscopic evaluations. Immunohistochemistry was done using anti-PCNA (proliferating cell nuclear antigen), anti-Bax (for apoptosis) and anti-vascular endothelial growth factor alpha (VEGFA). Morphological evaluation revealed degenerative changes in the placenta as dark nuclei, vacuolization, and cyst formation. Ultra-structurally, there was degeneration of cellular components including organelles and nuclei. These changes were found in different cells of the basal and labyrinth zones and were dose dependent. Immunohistochemistry revealed upregulation of Bax and VEGFA and downregulation of PCNA. Prenatal administration of the AAPD, ARI to pregnant female rats resulted in histological changes in the placenta. Additionally, there was a decrease in cellular proliferation and increase in apoptosis, and vascular impairment. This indicates placental atrophy and dysgenesis and might suggest possible teratogenic effects to ARI, which needs further evaluation.

Plasminogen activator inhibitor-2 and impaired fibrinolysis in pregnancy and sickle cell anemia.

PURPOSE: This is the first study that aimed to determine antigen levels in plasma and genotypes of PAI-2 in pregnant and non-pregnant homozygous sickle cell anemia (SCA) patients. METHODS: The study subjects were all Bahraini females in the reproductive age group. The study population included 31 pregnant homozygous SS (SCA) patients. Three control groups were also studied to evaluate the effect of pregnancy and SCA on PAI-2 levels and fibrinolysis: (1) 31 healthy non-pregnant volunteers; (2) 31 cases of normal pregnancy; and (3) 20 non-pregnant SCA patients. Pregnancies were screened in the second (TM2) and third (TM3) trimesters. Global coagulation, fibrinolysis rate (euglobulin clot lysis time, ECLT), PAI-2 antigen (ELISA), and PAI-2 Ser(413)/Cys polymorphism (restriction fragment length polymorphism analysis) were determined. RESULTS: Feto-maternal complications were documented in both pregnancy groups. PAI-2 antigen levels were undetectable in the non-pregnant groups, but was quantifiable in both pregnant groups. Impaired fibrinolysis rate and rising PAI-2 levels with progression of pregnancy were observed in both healthy and SCA subjects. These changes were more prominent in SCA, although the rise in ECLT was less steep and PAI-2 antigen levels were not significantly different compared to normal pregnancy in the third trimester. No correlation was observed between PAI-2 genotypes and plasma antigen levels. Also, no significant difference in feto-maternal complications was found in normal (n = 25) versus SCA pregnant patients (n = 30). CONCLUSIONS: These observations suggest that with progression of pregnancy, increasing PAI-2 levels contribute to the hypercoagulable state, particularly in SCA patients.

Analysis of the entire mitochondrial genome reveals Leber's hereditary optic neuropathy mitochondrial DNA mutations in an Arab cohort with multiple sclerosis.

Several mitochondrial DNA (mtDNA) mutations of Leber's hereditary optic neuropathy (LHON) have been reported in patients with multiple sclerosis (MS) from different ethnicities. To further study the involvement of LHON mtDNA mutations in MS in the Arab population, we analyzed sequencing data of the entire mitochondrial genome from 47 unrelated Saudi individuals, 23 patients with relapse-remitting MS (RRMS) and 24 healthy controls. Ten LHON mutations/variants were detected in the patients but were absent in the controls. Of them, the common primary pathogenic mutation m.14484T>C and the rare mutation m.10237T>C were found in one patient, whereas the rare mutation m.9101T>C was found in another patient. The remaining were secondary single nucleotide variants (SNVs) found either in synergy with the primary/rare mutations or individually in other patients. Patients carrying LHON variants also exhibited distinct mtDNA variants throughout the mitochondrial genome, eight were previously reported in patients with LHON. Moreover, five other LHON-related SNVs differed significantly in their prevalence among patients and controls (P < 0.05). This study, the first to investigate LHON mtDNA mutations/variants in a Saudi cohort may suggest a role of these mutations/variants in the pathogenesis or genetic predisposition to MS, a possibility which needs to be explored further in a large-scale.

Developing, Validating, and Implementing a Tool for Measuring the Readiness of Medical Teachers for Online Teaching Post-COVID-19: A Multicenter Study.

BACKGROUND: While online education is by no means a new concept, it was recently thrust into the spotlight after school campuses all over the world were forced to close because of the COVID-19 pandemic. The sudden need to shift revealed emerging challenges to online teaching, both logistic and personal. One important challenge is the ability to assess the readiness of educators for online teaching, so that appropriate and specific feedback/training can be offered to those in need. This study aims at developing, validating, and implementing a tool to measure the teachers' readiness for online teaching in three medical schools from three different countries. METHODS: This was a multi-center, cross-sectional study that involved developing a survey through review of literature and previous studies, item development and revision, and pilot testing. The survey was then distributed electronically to a convenient sample of 217 teaching faculty members of different academic ranks from three medical schools in Egypt, Saudi Arabia, and Bahrain. Exploratory factor analysis and reliability study were performed. Descriptive statistics were applied, and the statistical significance level was set at 0.05. RESULTS: Factor analysis produced the following five factors: "Online Teaching and Course Design Skills", "Digital Communication", "Basic Computer Skills", "Advanced Computer Skills" and "Using Learning Management Systems". The tool showed high reliability (alpha = 0.94). Survey results showed highest mean scores for Basic Computer Skills with lower scores for Online Teaching and Course Design Skills and Using Learning Management Systems. ANOVA revealed statistically significant differences between the three studied schools regarding Digital Communication (F=5.13; p=0.007) and Basic Computer Skills (F=4.47; p=0.012) factors. CONCLUSION: The tool proved to be reliable and valid. Results indicated an overall acceptable readiness in the three involved schools, with a need for improvement in "Online Teaching and Course Design" and Using Learning Management Systems.

Expression and clinical significance of miR-1 and miR-133 in pre-diabetes.

Pre-diabetes represents an intermediate state of altered glucose metabolism between normal glucose levels and type 2 diabetes mellitus (T2D), and is considered a significant risk factor for the development of T2D and related complications. Early detection of pre-diabetes may allow for the use of timely and effective treatment strategies to prevent its progression. Circulating microRNAs (miRNAs/miRs) that reflect changes in diabetes-related tissues, including the pancreas, liver, skeletal and heart muscle, and adipose tissue are promising biomarkers of disease progression. In our previous study, it was demonstrated that the cardiac and skeletal muscle specific miR-1 and miR-133 are upregulated in the blood of patients with T2D and cardiovascular disease. Since both miRNAs have been shown to be implicated in insulin resistance, an important feature of pre-diabetes, we hypothesised that their expression may be increased prior to clinical diagnosis of T2D, and may thus serve as biomarkers for pre-diabetes. The expression levels of circulating miRNAs were evaluated by reverse transcription-quantitative PCR in whole blood samples from 55 subjects, including 28 pre-diabetes individuals with impaired fasting glucose (FG) and impaired glucose tolerance, and 27 healthy controls. The individuals with pre-diabetes exhibited significantly higher expression levels of miR-1 and miR-133 compared with the controls (P<0.05). Target prediction search revealed that both miR-1 and miR-133 target several pathways involved in the pathophysiology of diabetes. Pearson's correlation analysis revealed that the two miRNAs were positively correlated with blood glucose parameters, including FG, 2-h oral glucose tolerance test and glycated haemoglobin A1c levels, as well as with insulin resistance (P<0.05). Multivariate logistic regression analysis revealed that the two miRNAs were significantly and directly associated with pre-diabetes, and this association remained significant after adjustment for several confounding variables (P<0.05). Moreover, linear regression analysis showed that the Homeostatic Model Assessment-Insulin Resistance was the only significant predictor to be significantly associated with both miRNAs (P<0.05). In discriminating pre-diabetes individuals from healthy controls, the area under the curves (AUCs) of the receiver operating characteristic curves (ROCs) were 0.813 and 0.810 for miR-1 and miR-133 respectively (P<0.05). Despite the relatively small number of participants, the present study showed for the first time that circulating levels of miR-1 and miR-133 were increased in individuals with pre-diabetes, and they were associated with important features of pre-diabetes. Thus, they may serve as clinical biomarkers for the early-stages of T2D.

Upregulation of Circulating Cardiomyocyte-Enriched miR-1 and miR-133 Associate with the Risk of Coronary Artery Disease in Type 2 Diabetes Patients and Serve as Potential Biomarkers.

Circulating miRNAs are increasingly suggested as clinical biomarker for diseases. We evaluated the expression of circulating cardiomyocyte-enriched miR-1 and miR-133 by real-time PCR in blood from patients with type 2 diabetes (T2D) without and with coronary artery disease (CAD) and healthy controls, investigated their association with the risk of CAD risk and their potential as biomarkers. The two miRNAs were upregulated in patients with T2D and CAD compared with controls, associated with CAD risk and remained significant after adjustment for multiple confounders. LDL-C was a positive predictor for miR-1 and miR-133, and mean blood pressure was also a positive predictor for miR-133. Both miRNAs strongly distinguished CAD from controls. miR-1 significantly distinguished CAD from T2D with higher diagnostic ability than miR-133, whereas the miR-1/miR-133 combination improved the diagnostic value. Upregulation of circulating miR-1 and miR-133 associate with the risk of CAD in T2D patients and may serve as diagnostic biomarkers.

Validating the modified System for Evaluation of Teaching Qualities: a teaching quality assessment instrument.

CONSTRUCT: We assessed the validity of the modified System for Evaluation of Teaching Qualities (mSETQ) in evaluating clinical teachers in Bahrain. BACKGROUND: Clinical teacher assessment tools are essential for improving teaching quality. The mSETQ is a teaching quality measurement tool, and demonstrating the validity of this tool could provide a stronger evidence base for the utilization of this questionnaire for assessing medical teachers in Bahrain. APPROACH: This study assessed the construct validity of this questionnaire in medical schools across Bahrain using 400 medical students and 149 clinical teachers. Data were analyzed using confirmatory factor analysis (CFA). The goodness-of-fit index (GFI), comparative fit index (CFI), root mean square residual, and standardized root mean square error of approximation (RMSEA) indices were used to evaluate the model fit. The internal consistency reliability was assessed using Cronbach's alpha. RESULTS: The results of the CFA revealed an acceptable fit. All criteria for a good model fit were met except for the RMSEA fit index and the standardized root mean square residual (SRMR) value, which was very close to an acceptable value. Good overall reliability was found in the study (α=0.94). CONCLUSION: The overall findings of this study provided some evidence supporting the reliability and validity of the mSETQ instrument.

Distinct HLA class I and II genotypes and haplotypes are associated with multiple sclerosis in Bahrain.

Multiple sclerosis (MS) has become prevalent in the Arabian Gulf area with high incidence in Bahrain due to environmental influences and genetic susceptibilities, but there is a lack of study into human leukocyte antigen (HLA) types in patients with MS in Bahrain. The present study aimed to study the HLA types expressed in MS patients compared with in control subjects. Blood samples from 50 Bahraini patients with MS and 50 Bahraini control subjects' were subjected to HLA tissue typing by polymerase chain reaction using sequence-specific primers. In comparison with those in control subjects, the allele frequencies of HLA class-I antigens A2, A9, A19, B5, B35 and B40 were higher in MS patients. For class II antigens, the allele frequencies of DR3, DR4 and DR16 were higher in MS patients. The allele frequency of DR15 was lower in MS patients than in control subjects but the difference was not statistically significant (P=0.138). The higher prevalence of the HLA-ABDR allele was common among the female patients with MS, in relapse remission stage, in cases with higher expanded disability status scale scores and with disease duration between 4 and 9 years. Haplotype HLA-A2-B40-DR2 exhibited significantly higher frequency in MS patients compared with in control subjects (P=0.03). In conclusion, the results indicated different alleles associated with MS compared with previous reviews. The present study supports the importance of identifying genetic susceptibilities and targets for therapies in specific populations and individuals, to personalize disease management in terms of prediction, protective measures and treatment.

Circulating endothelium-enriched microRNA-126 as a potential biomarker for coronary artery disease in type 2 diabetes mellitus patients.

Circulating microRNAs (miRNAs) have been shown as promising biomarkers for various diseases. We investigated the predictive potential of circulating endothelium-enriched miR-126 in type 2 diabetes patients (T2D) without chronic complications and T2D patients with coronary artery diseases (CAD). The expression levels of circulating miR-126, determined by quantitative real time PCR, were decrease in peripheral blood of T2D patients and T2D with CAD compared with healthy controls. MiR-126 strongly associated with T2D and CAD, negatively correlated with LDL in CAD patients and differentiated between T2D patients, T2D patients with CAD and healthy subjects. Circulating miR-126 may serve as a biomarker for predicting patients with T2D and diabetic CAD.

Morphology of Anterolateral Ligament of the Knee: A Cadaveric Observation with Clinical Insight.

Background. The morphology and function of anterolateral ligament (ALL) of the knee are not clearly understood even today with all the sophisticated techniques available. There have been differing descriptions of the ALL of the knee in literature, and not all of them have been named or described clearly. Aim. The present study was undertaken to provide a clear structure/relationship description on ALL. Materials and Methods. We used 24 formalin-fixed cadaveric limbs. Knee regions of the all the limbs were neatly dissected and the ALL was exposed. Its proximal and distal attachments were traced carefully. Middle portion of ALL was removed and processed for histological analysis. Results. ALL was found in one right knee (4.16%). It extended distally from the lateral femoral condyle to the lateral tibial plateau margin. Its attachment on the tibial plateau was located between head of the fibula and Gerdy's tubercle. A strong connection was identified between the ALL and the periphery of the middle third of the lateral meniscus. Histological analysis of ALL confirmed the presence of true ligamentous structure in it with dense connective tissue and plenty of fibroblasts. Conclusion. The prevalence of ALL in different populations along with its clinical significance has been discussed in detail in this paper.

Lack of association of rs3798220 with small apolipoprotein(a) isoforms and high lipoprotein(a) levels in East and Southeast Asians.

OBJECTIVE: The variant allele of rs3798220 in the apolipoprotein(a) gene (LPA) is used to assess the risk for coronary artery disease (CAD) in Europeans, where it is associated with short alleles of the Kringle IV-2 (KIV-2) copy number variation (CNV) and high lipoprotein(a) (Lp(a)) concentrations. No association of rs3798220 with CAD was detected in a GWAS of East Asians. Our study investigated the association of rs3798220 with Lp(a) concentrations and KIV-2 CNV size in non-European populations to explain the missing association of the variant with CAD in Asians. METHODS: We screened three populations from Africa and seven from Asia by TaqMan Assay for rs3798220 and determined KIV-2 CNV sizes of LPA alleles by pulsed-field gel electrophoresis (PFGE). Additionally, CAD cases from India were analysed. To investigate the phylogenetic origin of rs3798220, 40 LPA alleles from Chinese individuals were separated by PFGE and haplotyped for further SNPs. RESULTS: The variant was not found in Africans. Allele frequencies in East and Southeast Asians ranged from 2.9% to 11.6%, and were very low (0.15%) in CAD cases and controls from India. The variant was neither associated with short KIV-2 CNV alleles nor elevated Lp(a) concentrations in Asians. CONCLUSION: Our study shows that rs3798220 is no marker for short KIV-2 CNV alleles and high Lp(a) in East and Southeast Asians, although the haplotype background is shared with Europeans. It appears unlikely that this SNP confers atherogenic potential on its own. Furthermore, this SNP does not explain Lp(a) attributed risk for CAD in Asian Indians.

Thrombomodulin gene proximal promoter polymorphisms in premature acute coronary syndrome patients in Bahrain.

Thrombomodulin is expressed on endothelial cells and monocytes (mTM) where it has an anticoagulant function. Enzymatic cleavage from the cell surface produces soluble thrombomodulin (sTM) in plasma. Abnormal levels of sTM and mutations in the thrombomodulin gene (THBD) are linked to cardiovascular disease. The aim of this study was to investigate THBD proximal promoter mutations and levels of sTM and mTM in men presenting with premature acute coronary syndrome (ACS). This prospective cross-sectional study included 100 adult men with premature ACS (age <55 years) and 60 healthy age-matched controls. Plasma sTM was assayed by ELISA. mTM expression was assessed by flow cytometry with CD141 antibody. The -33 G/A polymorphism was identified by PCR-restriction fragment length polymorphism analysis and the THBD proximal promoter region was sequenced. Significantly lower sTM (P < 0.001) and higher mTM (P < 0.001) were seen in ACS patients. Heterozygous THBD promoter polymorphisms -33 G/A and -9/-10 GG/AT were found in eight patients and five control individuals. In patients and control individuals, allele frequencies of A were 0.02 and 0.025, and that of AT were 0.025 and 0.017, respectively. There were no significant associations of these polymorphisms with ACS, sTM levels or mTM expression. THBD polymorphisms -33 G/A and -9/-10 GG/AT are present in low frequency in our patient population, and are more frequent in the South Asians as compared to the Arabs. The frequency of -33 G/A is lower, whereas that of -9/-10 GG/AT is higher than that reported in the Orientals. The presence of THBD proximal promoter polymorphisms do not explain variations in levels of sTM and mTM in this patient population.

Relationships between the quality of blended learning experience, self-regulated learning, and academic achievement of medical students: a path analysis.

PURPOSE: This study examined the relationships between the different aspects of students' course experience, self-regulated learning, and academic achievement of medical students in a blended learning curriculum. METHODS: Perceptions of medical students (n=171) from the Royal College of Surgeons in Ireland, Medical University of Bahrain (RCSI Bahrain), on the blended learning experience were measured using the Student Course Experience Questionnaire (SCEQ), with an added e-Learning scale. In addition, self-regulated learning was measured using the Motivated Strategies for Learning Questionnaire (MSLQ). Academic achievement was measured by the scores of the students at the end of the course. A path analysis was created to test the relationships between the different study variables. RESULTS: Path analysis indicated that the perceived quality of the face-to-face component of the blended experience directly affected the motivation of students. The SCEQ scale "quality of teaching" directly affected two aspects of motivation: control of learning and intrinsic goal orientation. Furthermore, appropriate course workload directly affected the self-efficacy of students. Moreover, the e-Learning scale directly affected students' peer learning and critical thinking but indirectly affected metacognitive regulation. The resource management regulation strategies, time and study environment, and effort regulation directly affected students' examination scores (17% of the variance explained). However, there were no significant direct relationships between the SCEQ scales and cognitive learning strategies or examination scores. CONCLUSION: The results of this study will have important implications for designing blended learning courses in medical schools.

Occurrence of the retromolar foramen in dry mandibles of South-eastern part of India: a morphological study with review of the literature.

The retromolar foramen (RMF) is a rare anatomical structure situated in the retromolar fossa behind the third molar tooth. When it is present, the foramen is connected with the mandibular canal and is believed to transmit neurovascular structures that provide accessory source to the mandibular molars and the buccal area. Reports from the literature show that the presence of RMF could pose a challenge in complete blockage of the inferior alveolar nerve during mandibular surgeries. We report the incidence of retromolar foramen from ninety-four dry mandibles of south-eastern part of Karnataka State, India. The foramen was observed in 11 mandibles out of 94 included in the study (11.7%). In three mandibles, the foramen was present bilaterally (3.2%) and in three it was on the left side (3.2%) and in five it was on the right side (5.3%). For the first time, we also measured the dimensions of the retromolar area and distance of the foramen from third molar tooth to understand its risks during the surgical extraction of the lower third molar tooth. A thorough review of the literature has also been done to compare the present findings with the studies reported from the various populations.

Gene frequencies of human platelet alloantigens 1-5 in two Arab populations.

BACKGROUND: Polymorphisms of the human platelet alloantigens (HPA) arise from single base pair substitutions in alleles and lead to changes in amino acids of glycoproteins expressed on platelets. The aim of this study was to determine the gene frequencies of the five common HPA (HPA-1 to -5) in Egyptians and Jordanians and to compare these data with those established for other populations. MATERIALS AND METHODS: HPA genotyping was done by polymerase chain reaction with sequence-specific primers. RESULTS: The gene frequencies obtained in Egyptians were: HPA-1a/b, 0.767/0.233; HPA-2a/b, 0.759/0.241; HPA-3a/b, 0.704/0.296; HPA-4a/b, 1/0; HPA-5a/b, 0.728/0.272, while the frequencies in Jordanians were: HPA-1a/b, 0.821/0.179; HPA-2a/b, 0.877/0.123; HPA-3a/b, 0.660/0.340; HPA-4a/b, 1/0; HPA-5a/b, 0.795/0.205. The observed gene frequencies in both populations were in Hardy-Weinberg equilibrium. The gene frequencies for HPA-2b and HPA-5b among Egyptians were the highest reported among Arabs. Except for HPA-2, there were no significant differences in the distribution of HPA-1 to -5 between the two populations. CONCLUSION: The distributions of HPA alleles among Egyptians and Jordanians are similar to those reported for other Arabs. This study reports the first data on gene frequencies of HPA in Egyptians and Jordanians.

Geographical and social influences on genetic diversity within the Egyptian population: analyses of Alu insertion polymorphisms.

BACKGROUND: The geographical location of Egypt at the crossroads of several major cultural areas between North Africa and the Middle East has contributed to its population history. AIM: To analyse the genetic structure of the population living in two geographical parts of Egypt. SUBJECTS AND METHODS: A sample of 112 Egyptians from the North African part of Egypt (Ismailia sample) and a sample of 52 Egyptians from the Asian part Sinai, have been analysed using 10 Alu insertion polymorphisms. RESULTS: The results of the present study showed a significant genetic difference between the Sinai and Ismailia samples. The latter showed an evident genetic affinity with North African populations; whereas the Sinai sample was found to be genetically closer to the Middle East populations. The Sinai sample showed a low average heterozygosity, unlike that found in the Ismailia sample. CONCLUSION: This study provides new insights into the genetic structure of the Egyptian population living in a land bridge between Africa and Asia. Results suggest a genetic discontinuity between the Sinai population and that of the North African part of Egypt. This discontinuity would have been maintained thanks to geo-climatic and social factors.

Frequency of palmaris longus absence and its association with other anatomical variations in the Egyptian population.

The palmaris longus (PL) is one of the most variable muscles in the human body. Racial differences in its variation have been documented. Several studies have attempted to correlate PL absence with other anatomical variations. This study was conducted to determine the prevalence of absence of PL, correlate it with gender and body side and to determine its association with other anatomical variations in the Egyptian population. The presence of PL was clinically determined in 386 Egyptians using the standard technique. All subjects were examined for the presence of the flexor digitorum superficialis (FDS) to the fifth finger. Allen's test was done to assess the completeness of the superficial palmar arch (SPA). The overall prevalence of absence of the PL in Egyptian subjects was 50.8%. There was no significant difference in PL absence with regard to the body side but a significant difference was seen as regards gender and when bilateral absence of PL was compared to its unilateral absence. Absence of FDS tendon to the fifth finger was seen in 1.3% subjects. There was no association between the absence of the FDS tendon to the fifth finger and either presence or absence of PL and also between the absence of PL and the incompleteness of SPA in both genders. In conclusion, the prevalence of absence of PL in the Egyptian population represents one of the highest rates of absence to be reported for this muscle, which is significantly different from that in other ethnic groups.

Genetic polymorphism of the glutathione S-transferase M1 and T1 genes in three distinct Arab populations.

Deletion polymorphisms for the glutathione S-transferase (GST) gene are associated with increased risk of cancer, and are implicated in detoxifying mutagenic electrophilic compounds. GST Polymorphic variants were reported for different populations. The aim of this study was to investigate the frequencies of GSTM1 and GSTT1 null genotypes among Bahraini, Lebanese and Tunisian Arabs. GST genotyping was done by multiplex PCR-based methods. Study subjects comprised 167 Bahrainis, 141 Lebanese and 186 Tunisians unrelated healthy individuals. GSTM1 deletion homozygosity of 49.7%, 52.5% and 63.4% were recorded for Bahraini, Lebanese and Tunisians, respectively. Among Bahrainis, the prevalence of GSTT1 null homozygotes was 28.7%, while in higher rates were seen in Lebanese (37.6%) and Tunisians (37.1%). Our results indicate that there are no major differences in allelic distribution of GSTM1 and GSTT1 genes between the three Arab populations investigated except between Bahrainis and Tunisians regarding the allelic distribution of GSTM1 gene (P=0.013). Combined analysis of both genes revealed that 14.4% of Bahrainis, 16.3% of Lebanese and 21.0% of Tunisians harbor the deleted genotype of both genes. This is the first study that addresses GST gene polymorphism in Bahraini and Lebanese Arabs, and will help genetic studies on the association of GSTM1 and GSTT1 polymorphisms with disease risks and drug effects in Arab populations.

Growth assessment of diabetic rat fetuses under the influence of insulin and melatonin: a morphologic study.

Hyperglycemia-induced oxidative stress makes an important contribution to the etiology of diabetic teratogenicity namely fetal growth and congenital dysmorphogenesis. The aim of this study is to evaluate the protective roles of melatonin and insulin against diabetic's embryolethality and teratogenicity. Diabetes was induced to virgin Sprague Dawley albino rats by a single peritoneal injection of alloxan. Thirty pregnant rats were divided equally into 5 groups: 1) Control 2) Diabetic 3) Diabetic insulin 4) Diabetic melatonin 5) Diabetic melatonin-insulin. Insulin and melatonin were administered daily throughout the whole gestational period. Fetuses were collected on day 20 of gestation and were examined for malformations and growth disorders. A significant increase in fetal growth parameters (Macrosomia) were noticed in the diabetic group compared to the control. Melatonin prevents the appearance of soft tissue anomalies, but it leads to fetal growth restriction of diabetic rats (Microsomia). No significant changes were noticed in fetal growth parameters in diabetic insulin or in diabetic melatonin-insulin groups compared to the control. Congenital anomalies were not seen in diabetic insulin and in diabetic melatonin-insulin groups while the rate of resorption was reduced in both groups when compared to the diabetic group. In conclusion, co-administration of melatonin with insulin leads to a slight non significant improvement of the protective role of insulin against diabetic embryolethality, teratogenicity and fetal growth changes.

Distribution of four HIV type 1-resistance polymorphisms (CCR5-Delta32, CCR5-m303, CCR2-64I, and SDF1-3'A) in the Bahraini population.

Allelic differences of chemokine (C-C motif ) receptor 5 (CCR5) and CCR2, as well as the ligand for the chemokine receptor CXCR4, stromal-derived factor (SDF-1), are known to suppress HIV-1 transmission and to be involved in delay in HIV-1 disease progression. The aim of our study was to investigate the frequencies of four mutations that confer resistance to HIV-1: CCR5-Delta32, CCR5-m303, CCR2-64I, and SDF1-3'A among Bahrainis. We have studied the DNA polymorphisms in 304 unrelated healthy Bahraini individuals without any known history of HIV-1 infection or AIDS symptoms. The CCR5-Delta32 mutation was detected by PCR analysis, while the CCR5-m303, CCR2-64I, and SDF1-3'A mutations were detected by PCR-restriction fragment length polymorphism (PCR-RFLP) tests. Allele frequencies and the fit to the Hardy-Weinberg equilibrium were evaluated using the Arlequin population genetics application. The frequencies of the CCR5-Delta32, CCR2-64I, and SDF1-3'A alleles were 2.8%, 8.9%, and 26.5%, respectively. No mutant alleles were detected for the CCR5-m303 mutation in 304 individuals. We estimated the risk of AIDS onset (relative hazard), computed from the three-locus genotype data. This is the first report of these four mutations conferring resistance to HIV-1 in the Bahraini population. The presence of the CCR5-Delta32 allele among Bahrainis may be attributed to the admixture with people of European descent. The CCR2-64I allele and especially the SDF1-3'A allele are predominant in the Bahraini population and may be associated with resistance to fast HIV-1 infection in Bahrainis, and thus their genotyping can be used for prognosis in HIV-infected individuals.