Determining the need for fertility care and the acceptability and feasibility of administering a fertility awareness tool from the user's perspective in a sample of Sudanese infertility patients.

Fertility experts have advocated addressing preventable causes of infertility and early intervention. However, awareness of risk factors is low, especially in low- and middle-income countries where the prevalence of infertility is high. To address this lack of awareness, the Fertility Awareness Tool (FertiSTAT) was adapted for use in Sudan and other low-resource countries. The aims of this study were to ascertain the need for fertility education in Sudan (Aim 1), and to gauge the acceptability and feasibility of implementing the FertiSTAT in Sudan (Aim 2), both from the patients' perspective. Convenience sampling was used to recruit participants for semi-structured-in-depth interviews from a fertility clinic in Sudan. We collected sociodemographic information, medical and reproductive history, asked about fertility knowledge, administered the FertiSTAT and asked about the acceptability of the FertiSTAT. Thematic analysis was conducted for qualitative data. Twenty participants were included; of these, 17 were female, 13 were educated beyond secondary school, the mean age was 32.8 years, and the mean duration of infertility was 4.1 years. Ten themes emerged: of these, three themes addressed Aim 1: 'desire for fertility information', 'state of fertility knowledge' and 'benefits of fertility education'; and seven themes addressed Aim 2: 'specific suggestions for the tool', 'factors influencing the acceptability and feasibility of implementing the tool', 'challenges and barriers to implementation', 'self-disclosure', 'understanding of being at risk', 'compatibility with worldview' and 'cultural tailoring'. Fertility education was viewed as necessary and beneficial; however, participants thought that lack of acceptability of sensitive topics would hinder the implementation of the FertiSTAT. Acceptability and feasibility would be enhanced if challenges were addressed in a culturally sensitive manner using cultural tailoring of materials to increase compatibility with individual worldviews.

An evaluation of comprehensiveness, feasibility and acceptability of a fertility awareness educational tool.

The World Health Organization (WHO) and World Bank have identified infertility as a global public health issue. Since the 1980s, WHO has advocated for a focus on prevention, especially where the burden of prevalence is highest, specifically in women from low- and middle-income countries (LMIC). The aim of the two studies presented here is to demonstrate a process to enhance implementation efforts in fertility awareness programmes that could assist in preventing some forms of infertility, and increase understanding of factors that could result in fertility problems. The fertility status awareness tool (FertiSTAT) for the Middle East was adapted to provide an illustrative example of requirements for region- or country-specific adaptation. The mixed methods approach used included a survey of international medical experts concerning the comprehensiveness of risks included in the original FertiSTAT (Study I), and stakeholder meetings to assess the feasibility and acceptability of using an adapted FertiSTAT in the Middle East (Study II). The results indicate that the content of the original FertiSTAT was acceptable but not comprehensive in its coverage of potential risk factors; for example, it did not include genital tuberculosis, human immunodeficiency virus, consanguineous relationships and female genital mutilation/cutting. Furthermore, stakeholder meetings revealed that implementation in the Middle East would be enhanced by the use of more culturally sensitive wording. The data highlight the importance of implementation research with participants from LMIC, and the need for standardized protocols for adaptation of any fertility awareness programme or tool before practical application.

Association of adiponectin promoter variants with traits and clusters of metabolic syndrome in Arabs: family-based study.

Plasma levels of adiponectin are decreased in type 2 diabetes, obesity and hypertension. Our aim was to use a family-based analysis to identify the genetic variants of the adiponectin (ADIPOQ) gene that are associated with obesity, insulin resistance, dyslipidemia and hypertension, among Arabs. We screened 328 Arabs in one large extended family for single nucleotide polymorphisms (SNPs) in the promoter region of the ADIPOQ gene. Two common SNPs were detected: rs17300539 and rs266729. Evidences of association between traits related to the metabolic syndrome and the SNPs were studied by implementing quantitative genetic association analysis. Results showed that SNP rs266729 was significantly associated with body weight (p-value=0.001), waist circumference (p-value=0.037), BMI (p-value=0.015) and percentage of total body fat (p-value=0.003). Up to 4.1% of heritability of obesity traits was explained by the rs266729 locus. Further cross-sectional analysis showed that carriers of the G allele had significantly higher values of waist circumference, BMI and percentage of total body fat (p-values 0.014, 0.004 and 0.032, respectively). No association was detected between SNP rs266729 and other clusters of metabolic syndrome or their traits except for HOMA-IR and fasting plasma insulin levels, p-values 0.035 and 0.004, respectively. In contrast, both measured genotype and cross-sectional analysis failed to detect an association between the SNP rs17300539 with traits and clusters of metabolic syndrome. In conclusion, we showed family-based evidence of association of SNP rs266729 at ADIPOQ gene with traits defining obesity in Arab population. This is important for future prediction and prevention of obesity in population where obesity is in an increasing trend.

Biodegradation of organophosphate pesticide chloropyrifos by Egyptian bacterial isolates.

Sixteen microbial isolates capable of growing on Dursban as a secondary substrate were isolated from three soil and sewage water samples collected from different localities polluted with pesticides. Six developed isolates only were capable of biodegrading Dursban and utilizing it as only sole source of carbon, energy and phosphorus. The six bacterial isolates were managed to grow on enrichment medium containing Dursban up to 40 ml/liter, for seven days at 25 degrees C. Each isolate exhibited growth and degradation of Dursban concentrations that best bacteria were identified as Pseudomonas stutzeri S7B4 and Flavobacterium balustinum S8B6. These two bacterial isolates were subjected to some environmental and nutritional parameters that affect the biodegradation process of Dursban. The optimum conditions includes :incubation period, 7 days; Dursban concentrations, 10 ml/l; inoculum size, 4 ml/l; incubation temperature, 35 degrees C; optimum pH value, 7; carbon source, fructose and ribose, respectively; nitrogen source, urea and peptone, respectively; amino acid, histidine; and vitamin, yeast extract, under shaking condition (200 rpm). Only the most potent microbial isolate Pseudomonas stutzeri was grown on their own mineral salts medium which contained 40 mlM/l in case of Dursban in the absence and presence of fructose as the best carbon source for two time intervals i.e. 7 and 15 days. Absence of phosphorus and the presence of many oxidized compounds revealed that the ability of P. stutzeri to biodegrade and detoxify Dursban using it as the sole phosphorus, carbon and energy sources. GC-MS analysis of all three treatments of Dursban-bioremediation process showed no detection of any phosphorus compounds especially Dursban in the three treatments, indicated that both bacterial strains i.e. P. stutzeri S7-B4 and F. balustinum S8B6 were able to utilize Dursban pesticide as carbon and phosphorus sources. Thus, it is possible to use both bacterial strains in the bioremediation of pesticides especially Dursban-contaminated sites.

A novel locus for hereditary spastic paraplegia with thin corpus callosum and epilepsy.

BACKGROUND: Hereditary spastic paraplegia (HSP) are classified clinically as pure when progressive spasticity occurs in isolation or complicated when other neurologic abnormalities are present. At least 22 genetic loci have been linked to HSP, 8 of which are autosomal recessive (ARHSP). HSP complicated with the presence of thin corpus callosum (HSP-TCC) is a common subtype of HSP. One genetic locus has been identified on chromosome 15q13-q15 (SPG11) for HSP-TCC, but some HSP-TCC families have not been linked to this locus. METHODS: The authors characterized two families clinically and radiologically and performed a genome-wide scan and linkage analysis. RESULTS: The two families had complicated ARHSP. The affected individuals in Family A had thin corpus callosum and mental retardation, whereas in Family B two of three affected individuals had epilepsy. In both families linkage analysis identified a locus on chromosome 8 between markers D8S1820 and D8S532 with the highest combined lod score of 7.077 at marker D8S505. This 9 cM interval located on 8p12-p11.21 represents a new locus for ARHSP-TCC. Neuregulin and KIF13B genes, located within this interval, are interesting functional candidate genes for this HSP form. CONCLUSION: Two consanguineous families with complicated autosomal recessive hereditary spastic paraplegia were clinically characterized and genetically mapped to a new locus on 8p12-p11.21.

A family study in Oman: large, consanguineous, polygamous Omani Arab pedigrees.

OBJECTIVE: To establish a suitable human model for the study of the genetics of complex diseases. METHODS: We have selected an Omani Arab population to provide the statistical power required to study the genetics of complex diseases with confidence. This model consists of five multigenerational highly inbred pedigrees, descending from a small number of founders just a few generations ago with environmental homogeneity, restricted geographical distribution, detailed records and well-ascertained and -validated pedigrees. Stringent criteria were adopted for defining the phenotypes of hypertension, diabetes mellitus, dyslipidemias and obesity. The SOLAR genetic software package was used to draw the pedigree structure. RESULTS: Outstanding statistical power to detect susceptibility loci was obtained. CONCLUSIONS: This model represents a large homogeneous human family-based population for the study of genetic and environmental factors contributing to complex diseases.

Heterozygous methylene tetrahydrofolate reductase mutation with mild hyperhomocysteinemia associated with deep vein thrombosis.

Hyperhomocysteinemia is known to be associated with arterial occlusive vascular disease and venous thrombosis. Here, we report a young ethnic Omani patient with recurrent venous thrombosis who was found to be heterozygous for 677C-T mutation in the methyltetrahydrofolate reductase (MTHFR) enzyme. Moderate hyperhomocystenemia was also observed, in the presence of normal red cell folate and serum B12 levels. No other documented marker of hereditary thrombophilia could be demonstrated in this patient, in spite of extensive investigation on multiple occasions.

Identification of a locus for a form of spondyloepiphyseal dysplasia on chromosome 15q26.1: exclusion of aggrecan as a candidate gene.

We have investigated a family with an autosomal dominant form of spondyloepiphyseal dysplasia (SED) characterised by short stature and severe premature degenerative arthropathy. Previous studies have excluded linkage between this condition and the locus for the type II collagen gene. Here we report the identification of linkage between this disorder and a locus on the long arm of chromosome 15 between markers D15S979 and D15S1004. According to current linkage maps and sequence data, this locus includes that of the aggrecan gene (AGC1). Our linkage data from the SED family show, however, that AGC1 maps to a locus that is proximal to D15S979. This proximal location for AGC1 is further supported by linkage data from a second family with an autosomal recessive form of multiple epiphyseal dysplasia that also maps to the SED locus. In both families AGC1 is therefore excluded as a candidate gene.

Localisation of a gene for an autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia, and distinctive facies to chromosome 15q26.

BACKGROUND: We have previously described an autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia (MED), and distinctive facies in a large, extended Omani family. The MED observed seems to be part of a larger malformation syndrome, since both craniofacial and central nervous system changes were present in the family. We performed a whole genome scan in this family in order to identify the gene locus for this malformation syndrome. METHODS AND RESULTS: Using homozygosity mapping, we show linkage to the telomeric region of the long arm of chromosome 15. The position of both the disease gene and the principal glycoprotein, chondroitin sulphate proteoglycan (aggrecan, AGC1) on chromosome 15q26, suggested that the aggrecan gene is a candidate for the disease in this family. However, three of the four affected children were heterozygous for a polymorphism at position 831 of the coding sequence of AGC1, providing strong evidence against its involvement. CONCLUSION: We have identified a gene locus for a recessive syndrome of macrocephaly, MED, and distinctive facies in a large Omani family. Aggrecan located on chromosome 15q26, within the critical region determined for this syndrome in this family, was excluded as a candidate gene.

Homozygosity mapping in families with Joubert syndrome identifies a locus on chromosome 9q34.3 and evidence for genetic heterogeneity.

Joubert syndrome is a rare developmental defect of the cerebellar vermis, with autosomal recessive inheritance. The phenotype is highly variable and may include episodic hyperpnea, abnormal eye movements, hypotonia, ataxia, developmental delay, and mental retardation. Even within sibships the phenotype may vary, making it difficult to establish the exact clinical diagnostic boundaries of Joubert syndrome. To genetically localize the gene region, we have performed a whole-genome scan in two consanguineous families of Arabian/Iranian origins, with multiple affected probands. In one family, we detected linkage to the telomeric region of chromosome 9q, close to the marker D9S158, with a multipoint LOD score of Z=+3.7. The second family did not show linkage to this region, giving a first indication of genetic heterogeneity underlying Joubert syndrome. These findings were supported by subsequent analysis of two smaller families-one compatible with linkage to 9q; the other, unlinked. We conclude that Joubert syndrome is clinically and genetically heterogeneous and that one locus maps to chromosome 9q.

Diversity in expression of glucose-6-phosphate dehydrogenase deficiency in females.

The aims of this study were to determine the prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the United Arab Emirates (UAE), to describe the different mutations in the population, to determine its prevalence, and to study inheritance patterns in families of G6PD-deficient individuals. All infants born at Tawam Hospital, Al-Ain, UAE from January 1994 to September 1996 were screened at birth for their G6PD status. In addition, those attending well-baby clinics during the period were also screened for the disorder. Families of 40 known G6PD-deficient individuals, selected randomly from the records of three hospitals in the country, were assessed for G6PD deficiency. Where appropriate, this was followed by definition of G6PD mutations. Of 8198 infants, 746 (9.1%), comprising 15% of males and 5% of females tested, were found to be G6PD deficient. A total of 27 families were further assessed: of these, all but one family had the nt563 Mediterranean mutation. In one family, two individuals had the nt202 African mutation. The high manifestation of G6PD deficiency in women may be due to the preferential expression of the G6PD-deficient gene and X-inactivation of the normal gene, and/or to the presence of an 'enhancer' gene that makes the expression of the G6PD deficiency more likely. The high level of consanguinity which, theoretically, should result in a high proportion of homozygotes and consequently a higher proportion of females with the deficiency, was not found to be a significant factor.

The association of Hb Khartoum [beta124(H2)Pro-->Arg] with gamma+-thalassemia is responsible for hemolytic disease in the newborn of a Sudanese family.

The unstable Hb Khartoum with a Pro-->Arg replacement at position beta124 was identified by isoelectrofocusing, high performance liquid chromatography, and peptide mapping in a mother and two male children of a Sudanese family. All three were heterozygous for the abnormal hemoglobin; the father and a third male child did not carry the mutation. The mother was also homozygous for two putative gamma+-thalassemia point mutations, one affecting both Agamma and Ggamma genes at IVS-II-115 (A-->G), and one affecting the Ggamma gene at the 3' untranslated region (-A) at position -6 from the polyadenylation site. The father had normal gamma genes. All three children were heterozygous for both the gamma+-thalassemia mutations. The two older children, who were compound heterozygotes for Hb Khartoum/gamma+-thalassemia, presented at birth with severe neonatal jaundice which necessitated exchange blood transfusions. Other causes of neonatal jaundice were excluded. The third male child, who did not carry the Hb Khartoum anomaly but was heterozygous for gamma+-thalassemia, did not develop neonatal jaundice. It is concluded that the instability of Hb Khartoum in combination with gamma+-thalassemia is responsible for neonatal hemolytic anemia in this family.

Epidemiology of clinical hyperbilirubinaemia in Al Ain, United Arab Emirates.

All infants born at Al Ain Hospital, United Arab Emirates between 1 January and 30 June 1995 who developed clinically relevant hyperbilirubinaemia defined as jaundice requiring investigation and treatment were prospectively studied. Of the 2300 live births, 85 (3.7%) developed hyperbilirubinaemia. Of these, 22 were premature, 22 had ABO haemolytic disease of the newborn, eight had G6PD deficiency (Mediterranean), seven had breast-milk jaundice, five were born to mothers with diabetes mellitus and one had Rh incompatibility. No specific factor was identified in 20 (24%). Significant differences in the distribution of diagnostic categories were found among the major ethnic groups in the population studied. This first study of the epidemiology of clinically relevant hyperbilirubinaemia in this community identified locally relevant risk factors and highlighted areas of health care which, if modified, might reduce the incidence of hyperbilirubinaemia.

PIP: If untreated, severe unconjugated hyperbilirubinemia is neurotoxic. Management of the condition therefore includes preventing serum bilirubin from reaching toxic levels. Identifying infants at risk of developing severe hyperbilirubinemia and early intervention have reduced levels of morbidity and mortality associated with bilirubin encephalopathy. The incidence of neonatal jaundice and the etiological factors associated with hyperbilirubinemia vary by locale. All infants born at Al Ain Hospital, United Arab Emirates, between January 1 and June 30, 1995, who developed clinically relevant hyperbilirubinemia defined as jaundice requiring investigation and treatment were prospectively studied. 85 (3.7%) of the 2300 live births developed hyperbilirubinemia. Of those, 22 were premature, 22 had ABO hemolytic disease of the newborn, 8 had G6PD deficiency (Mediterranean), 7 had breast milk jaundice, 5 were born to mothers with diabetes mellitus, and 1 had Rh incompatibility. No specific factor was identified in 20 (24%) infants. Significant differences in the distribution of diagnostic categories were found among the major ethnic groups in the population studied.

Antibody responses to Rhoptry-Associated Protein-1 (RAP-1) of Plasmodium falciparum parasites in humans from areas of different malaria endemicity.

Plasma IgM and IgG antibody reactivities against the recombinant Plasmodium falciparum protein, Rhoptry Associated Protein-1 (rRAP-1) were measured by ELISA in individuals from Sudan, Indonesia, Kenya and The Gambia living in areas of different malaria endemicity. IgG and IgM reactivities to rRAP-1 increased with malaria endemicity. IgG reactivities were associated with spleen rates in Indonesia with high malaria endemicity while IgM reactivities were associated with spleen rates in Kenya with low malaria endemicity. IgG and IgM reactivities to rRAP-1 increased during acute episodes of P. falciparum malaria in Sudanese adults and IgG reactivities remained high one month after treatment in all adults tested. Antibody reactivities to rRAP-1 in Gambian children in the dry season were higher in children with parasitaemia than in children without detectable parasitaemia. Antibody reactivities were not associated with protection against clinical episodes in the following rainy season but higher antibody reactivities were detectable at the end of the rainy season. There was no difference in antibody reactivity to rRAP-1 between Gambian children with mild or severe malaria.

Resistance to antifolates in Plasmodium falciparum monitored by sequence analysis of dihydropteroate synthetase and dihydrofolate reductase alleles in a large number of field samples of diverse origins.

Resistance of Plasmodium falciparum to antifolate chemotherapy is a significant problem where combinations such as Fansidar (pyrimethamine-sulfadoxine; PYR-SDX) are used in the treatment of chloroquine-resistant malaria. Antifolate resistance has been associated with variant sequences of dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS), the targets of PYR and SDX respectively. However, while the nature and distribution of mutations in the dhfr gene are well established, this is not yet the case for dhps. We have thus examined by DNA sequence analysis 141 field samples from several geographical regions with differing Fansidar usage (West and East Africa, the Middle East and Viet Nam) to establish a database of the frequency and repertoire of dhps mutations, which were found in 60% of the samples. We have also simultaneously determined from all samples their dhfr sequences, to better understand the relationship of both types of mutation to Fansidar resistance. Whilst the distribution of mutations was quite different across the regions surveyed, it broadly mirrored our understanding of relative Fansidar usage. In samples taken from individual patients before and after drug treatment, we found an association between the more highly mutated forms of dhps and/or dhfr and parasites that were not cleared by antifolate therapy. We also report a novel mutation in a Pakistani sample at position 16 of DHFR (A16S) that is combined with the familiar C59R mutation, but is wild-type at position 108. This is the first observation in a field sample of a mutant dhfr allele where the 108 codon is unchanged.