CONDUCTOMETRIC DETERMINATION OF THE ANTIHISTAMINIC DIPHENHYDRAMINE HYDROCHLORIDE USING SILVER NITRATE AS A TITRANT

Objectives: The present study developed and validated a conductometric method for determination of Diphenhydramine HCl (DPH) in its pure form and in a syrup formulation using silver nitrate (AgNO3 ).Methods: Conductometric titration method was achieved by using AgNO3. The method is built on the reaction of chloride ions coming from the DPH with AgNO3 yielding silver chloride precipitate. Conductance of the solution is measured as a function of the volume of titrant. The proposed method is linear over the range of 1-10mg.Results: Statistical analysis of the experimental results indicates that the method is precise and accurate. The accuracy of the method is indicated by the excellent recovery and the precision is supported by the low relative standard deviation (< 0.935). The method was also applied successively to a pharmaceutical syrup formulation. The proposed method provides a high degree of accuracy and precision. Results showed that there is no significant difference between the proposed method and the reported one.Conclusions: This proposed method is described as an alternative approach to the more complex and expensive previously reported methods for assay of DPH and is highly reproducible as compared to similar reported methods.Â

Characterizing the morbid genome of ciliopathies

Background Ciliopathies are clinically diverse disorders of the primary cilium. Remarkable progress has been made in understanding the molecular basis of these genetically heterogeneous conditions; however, our knowledge of their morbid genome, pleiotropy, and variable expressivity remains incomplete. Results We applied genomic approaches on a large patient cohort of 371 affected individuals from 265 families, with phenotypes that span the entire ciliopathy spectrum. Likely causal mutations in previously described ciliopathy genes were identified in 85% (225/265) of the families, adding 32 novel alleles. Consistent with a fully penetrant model for these genes, we found no significant difference in their “mutation load” beyond the causal variants between our ciliopathy cohort and a control non-ciliopathy cohort. Genomic analysis of our cohort further identified mutations in a novel morbid gene TXNDC15, encoding a thiol isomerase, based on independent loss of function mutations in individuals with a consistent ciliopathy phenotype (Meckel-Gruber syndrome) and a functional effect of its deficiency on ciliary signaling. Our study also highlighted seven novel candidate genes (TRAPPC3, EXOC3L2, FAM98C, C17orf61, LRRCC1, NEK4, and CELSR2) some of which have established links to ciliogenesis. Finally, we show that the morbid genome of ciliopathies encompasses many founder mutations, the combined carrier frequency of which accounts for a high disease burden in the study population. Conclusions Our study increases our understanding of the morbid genome of ciliopathies. We also provide the strongest evidence, to date, in support of the classical Mendelian inheritance of Bardet-Biedl syndrome and other ciliopathies

Characterization of greater middle eastern genetic variation for enhanced disease gene discovery

The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia1-3, has resulted in an elevated burden of recessive disease4. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized ‘genetic purging’. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics

Patterns of folic acid use in pregnant Saudi women and prevalence of neural tube defects — Results from a nested case–control study

Background: Although the role of folic acid (FA) in preventing neural tube defects (NTDs) is well documented, its optimal intake in pregnant women is still low in many countries. Here, we prospectively studied the prevalence of NTDs in the newborns and the patterns of FA intake in pregnant Saudi mothers. Methods: This case–control study was nested within a 3-year project (July 2010 to June 2013) to study the patterns of birth defects in the offspring of Saudi women who received their antenatal care and delivered at Prince Sultan Military Medical City, Riyadh—Saudi Arabia. Enrolled mothers were divided into 4 groups: group 1 (FA taken before pregnancy and continued regularly after conception), group 2 (FA taken post-conception), group 3 (no FA intake), and group 4 (did not remember or were unsure of taking FA). Control mothers were randomly selected from those with normal first obstetrical ultrasound scan at 18–22 weeks of gestation. Results: The cohort included 30,531 mothers giving birth to 28,646 infants. We studied 1179 mothers of babies with birth defects (BDs) and 1262 control mothers. There were 237 (9.7%) mothers in-group 1; 2001 (82%) in-group 2; 154 (6.3%) in-group 3; and 49 (2%) in-group 4. There were 49 babies with NTDs, a prevalence of 1.7/1000 total births. Among the studied mothers 2274 (93%) took FA either full or partial course. Conclusion: The high prevalence of NTDs and the low optimal FA intake highlight the need for a strict implementation of staple food fortification and health education program for Saudi women

PRUNE Syndrome Is a New Neurodevelopmental Disorder

PRUNE syndrome, or neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies (OMIM#617481), is a new rare autosomal recessive neurodevelopmental disease that is caused by homozygous or compound heterozygous mutation in PRUNE1 on chromosome 1q21. Here, We report on 12-month-old and 30-month-old girls from 2 unrelated Saudi families with typical presentations of PRUNE syndrome. Both patients had severe developmental delay, progressive microcephaly, and dysmorphic features. Brain magnetic resonance imaging showed slight thinning in the corpus callosum, mild frontal brain atrophy, and delayed myelination in one of the patients. Both patients had the same missense mutation in PRUNE1 (c.383G>A, p.Arg128Gln), which was not reported before in a homozygous state. We compared our patients to previously reported cases. In conclusion, We suggest that clinicians consider PRUNE syndrome in any child presenting with dysmorphic features, developmental delay, progressive microcephaly, central hypotonia, peripheral spasticity, delayed myelination, brain atrophy, and a thin corpus callosum

Kinetic characterisation of the FAD dependent monooxygenase TropB and investigation of its biotransformation potential

Achieving regio-specific hydroxylation of aromatic compounds remains a major challenge in synthetic chemistry. By contrast, this transformation is readily accomplished in nature through the action of FAD-dependant monooxygenase enzymes. Here, we report the kinetic characterisation of one such enzyme, TropB, from the stipitatic acid biosynthetic pathway. Analogues of the TropB natural substrate, 3-methyl-orcinaldehyde, were synthesised and used to examine the substrate selectivity of this enzyme. TropB displays broad substrate tolerance, for instance accepting single-ring aromatic substrates containing a range of C-1 substituents with varying electronic and steric properties. These include nitro, nitrosyl, alkyl, and aryl keto groups. Bicyclic substrates, however, were rejected by TropB. Additionally, C-5 substituents on single-ring aromatic substrates were not tolerated whereas the presence of a 6-methyl group was found to be important for substrate binding. Docking studies were employed to investigate and understand the broad substrate selectivity of TropB and identifies the key structural elements of its substrates. Our work has shown that TropB is an attractive target for biocatalyst engineering and industrial aromatic hydroxylation.Al Baha University, Saudi ArabiaEP/F066104/1BB/I003355/

Supportive Care Needs Assessment for Cancer Survivors at a Comprehensive Cancer Center in the Middle East: Mending the Gap

Background: Cancer survivors are often underprepared for what to expect post-treatment, and there are knowledge gaps regarding cancer survivors’ supportive care needs in Jordan and neighboring Arab countries. This study aimed to identify gaps in supportive care needs among adult cancer survivors seen at King Hussein Cancer Center in Amman, Jordan, and explore predictors of unmet needs. Methods: This was an observational cross-sectional study using a modified version of the Supportive Care Needs Survey 34 item short form (SCNS-SF34). Results: Two hundred and forty adult cancer survivors completed the study questionnaire. The assessed needs were highest in the financial domain, including covering living expenses, managing cancer treatment adverse effects and co-morbidities. The least prevalent reported needs were in sexuality and reproductive consultations. Late-stage diagnosis was independently associated with higher physical, psychological, health system/information, financial and overall need scores, with p-values of 0.032, 0.027, 0.052, 0.002 and 0.024, respectively. The overall quality of life score was independently and inversely associated with physical, psychological, health system/information, financial and overall need domains, with p-values of 0.015, \u3c0.0001, 0.015, 0.004 and 0.0003, respectively. Conclusions: This needs assessment identified problem areas for targeting interventions across the Jordanian cancer survivor population, and understanding these findings highlights opportunities for intervention to address gaps in care

Mycoplasmosis in Poultry: An Evaluation of Diagnostic Schemes and Molecular Analysis of Egyptian <i>Mycoplasma gallisepticum</i> Strains

Infections with Mycoplasma gallisepticum (MG) in poultry are associated with a wide range of disease conditions, including those affecting the respiratory and reproductive systems. The purpose of this study was to endorse the more sensitive diagnostic scheme for MG infection and identify the best molecular marker for MG phylogenetic analysis using six housekeeping genes: mgc2, mraW, atpG, ugpA, DUF31196, and lgT. For these purposes, 55 poultry flocks of different species were screened using either qRT-PCR or PCR techniques analogous to conventional culturing from non-cultured and cultured swabs on PPLO broth. The rate of MG positivity was the highest when using qRT-PCR from cultured broth (89.0%) and the lowest when using conventional culturing (34.5%). Compared to qRT-PCR from broth, statistical analysis using the Roc curve in MedCalc statistical software showed that the PCR schemes (qRT-PCR from swabs and PCR from swabs and broth) performed better than conventional culturing in terms of sensitivity, accuracy, and area under the curve (AUC), suggesting that they may be more reliable schemes. Further support was added by Cohen’s kappa test, showing moderate agreement between the molecular approaches. Among the six screened genes, mgc2 and mraW had the highest detection rates (69% and 65.4%, respectively). The comparative phylogenetic analysis revealed that mgc2 or atpG gene sequences distinguished MG isolates into different clades with high discriminatory power