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Norah F Alhur,1 Nourah H Al Qahtani,2 Entissar S AlSuhaibani,1 Eman Alsulmi,2 Noor B Almandil,3 Sayed AbdulAzeez,4 J Francis Borgio4 1College of Science, Zoology Department, King Saud University, Riyadh, Saudi Arabia; 2Obstetrics and Gynecology Department, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 3Department of Clinical Pharmacy Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, 31441, Saudi Arabia; 4Department of Genetic Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi ArabiaCorrespondence: J Francis BorgioDepartment of Genetic Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi ArabiaTel +966 13 3330864Email fbalexander@iau.edu.sa; borgiomicro@gmail.comBackground: Deoxyribonucleic acid from invasive, non-invasive and 9th week embryo can be a resource for the determination of fetal sex using highly sensitive and specific multiplex PCR.Methods: A total of 402 DNA samples were used to test the newly developed novel multiplex PCR including male specific (3 genes: SRY, DAZ2 and TSPY1) Y-biomarkers and internal control, ACTB. The study isolated cffDNA (Cell-free fetal DNA; n = 73) from mother’s plasma, serum and urine, fetal DNA from 9th week embryo and cord blood, and fetal DNA from CD71+ve nucleated red blood cells (fNRBC; n = 73). Paternal and maternal DNA from buccal cells (n = 20) and blood (n = 232) used for male and female confirmation.Results: The study observed that SRY alone cannot be a suitable Y-biomarker. Confirmation from any two Y-biomarkers is mandatory for male fetus identification. Direct sequencing of the gel eluted multiplex and single amplicons confirmed the specific sequences. Presence of two out of 3 Y-biomarkers OR single Y-biomarker with > 1,000,000 intensity is considered positive for male. The multiplex PCR is suitable for determining sex from all source of fetal DNA including highly degraded cffDNA and can detect the sex using 0.5ng DNA. Individual marker-based real-time qPCR followed by combined melt curve analysis showed distinguished melt curve peaks for the markers.Conclusion: The multiplex PCR achieved 100% accuracy on fetal DNA from fNRBC for early determinations (< 13 weeks) of gender. The developed novel and simple multiplex PCR and individual qPCR can be adopted in all types of laboratories for determining human fetal gender using fetal DNA from fNRBC. Early identification of gender can support to prepare for possible X-linked analysis, reduce anxiety in mother, strengthen a bond between mother and fetus, and effective decision making. Non-invasive source of fetal DNA from fNRBC preferred for identifying gender to reduce the risk of invasive procedures in early (8– 13 weeks) pregnancy.Keywords: cffDNA, male PCR, invasive, non-invasive, Y biomarkers, fetal gender, fNRBC

The emergence of multidrug-resistant fungi Candida auris is a worldwide health crisis connected with high rates of mortality. There is a critical need to find novel and unique antifungal compounds for treating infections of multidrug-resistant fungi such as C. auris . This study aimed to illustrate that biosynthetic gene clusters in native bacterial isolates are able to produce antifungal compounds against the multidrug-resistant fungus C. auris. It was successfully achieved using large-scale antifungal activity screening, cytotoxicity analysis, and whole genome sequencing integrated with genome mining-guided analysis and liquid chromatography-mass spectrometry (LC/MS). A list of possible gene candidates was initially identified with genome mining methods to predict secondary metabolite gene clusters of antifungal-compound-producing bacteria. Then, gene clusters present in the antifungal-compound-producing bacteria were identified and aligned with the reference genome using comparative genomic approaches. Bacillus halotolerans AQ11M9 was identified through large-scale antifungal activity screening as a natural compound-producer against multidrug-resistant C. auris , while it was nontoxic to normal human skin fibroblast cells (confirmed using a cell viability assay). The genome (4,197,347 bp) of B. halotolerans AQ11M9 with 2931 predicted genes was first mined for detecting and characterizing biosynthetic gene clusters, which revealed 10 candidate regions with antifungal activity. Clusters of AQ11M9 encoded non-ribosomal peptide synthase (NRPS) (bacilysin, bacillibactin, paenibactin, surfactin, plipastin, and fengycin) and polyketide (macrobrevin). The presence of gene clusters with anti- C. auris activity, and surfactin identified through LC/MS, from AQ11M9 suggests the potential of utilizing it as a source for a novel and powerful anti- C. auris compound.

Background: Enterococcus avium (E. avium) is a Gram-positive nosocomial pathogen that is commonly isolated from the alimentary tract. The objective of this functional genomics study was to identify the resistant genes by analyzing the genome of E. avium IRMC1622a, a type of bacteria found in feces collected from a patient at a Saudi Arabian tertiary hospital., Methods: The bacterial strain IRMC1622a was identified by 16 S rRNA sequencing as Enterococcus sp. The resistance phenomics were performed using VITEK® 2, and morphological analysis was achieved using a scanning electron microscope (SEM). Finally, the whole bacterial genome of the bacterial strain IRMC1622a was subjected to sequencing during October 2023 using Oxford Nanopore long-read sequencing technology, and mining for resistant genes., Results: The results of antimicrobial resistant phenomics indicated that the IRMC1622a strain was sensitive to all tested antimicrobial agents except for erythromycin, and the same result was confirmed by genomic analysis in addition to other classes of antibiotics. SEM showed E. avium IRMC1622a is ovoid shape, in single cells (L 1.2797 ± 0.1490 µm), in pairs (L 1.7333 ± 0.1054 µm), and in chains (L 2.44033 ± 0.1978 µm). The E. avium IRMC1622a genome has 14 (in CARD) antimicrobial resistance genes that were identified with several mechanisms of antimicrobial resistance, such as the efflux pump and conferring antibiotic resistance. The present study revealed that the E. avium IRMC1622a genome contains a high number of genes associated with virulence factors, and 14 matched pathogenic protein families and predicted as human pathogen (probability score 0.855). We report two (ISEnfa4 and ISEfa5) mobile genetic elements for the first time in the E. avium genome., Conclusions: The study concludes that E. avium IRMC1622a is susceptible to all tested antibacterials except erythromycin. The IRMC1622a has 14 genes encoding antimicrobial resistance mechanisms, including the efflux pump and conferring antibiotic resistance. This could indicate a potential rise in E. avium resistance in healthcare facilities. These observations may raise concerns regarding E. avium resistance in healthcare. We need more research to understand the pathophysiology of E. avium, which leads to hospital-acquired infections., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Novel antifungal drugs are urgently needed to treat candidiasis caused by the emerging fungal multidrug-resistant pathogen Candida auris . In this study, the most cost-effective drug repurposing technology was adopted to identify an appropriate option among the 1615 clinically approved drugs with anti- C. auris activity. High-throughput virtual screening of 1,3-beta-glucanosyltransferase inhibitors was conducted, followed by an analysis of the stability of 1,3-beta-glucanosyltransferase drug complexes and 1,3-beta-glucanosyltransferase-dutasteride metabolite interactions and the confirmation of their activity in biofilm formation and planktonic growth. The analysis identified dutasteride, a drug with no prior antifungal indications, as a potential medication for anti- auris activity in seven clinical C. auris isolates from Saudi Arabian patients. Dutasteride was effective at inhibiting biofilm formation by C. auris while also causing a significant reduction in planktonic growth. Dutasteride treatment resulted in disruption of the cell membrane, the lysis of cells, and crushed surfaces on C. auris , and significant ( p -value = 0.0057) shrinkage in the length of C. auris was noted at 100,000×. In conclusion, the use of repurposed dutasteride with anti- C . auris potential can enable rapid recovery in patients with difficult-to-treat candidiasis caused by C. auris and reduce the transmission of nosocomial infection.

We report on a highly virulent, multidrug-resistant strain of Enterococcus faecalis IRMC827A that was found colonizing a long-term male patient at a tertiary hospital in Khobar, Saudi Arabia. The E. faecalis IRMC827A strain carries several antimicrobial drug resistance genes and harbours mobile genetic elements such as Tn6009, which is an integrative conjugative element that can transfer resistance genes between bacteria and ISS1N via an insertion sequence. Whole-genome-sequencing-based antimicrobial susceptibility testing on strains from faecal samples revealed that the isolate E. faecalis IRMC827A is highly resistant to a variety of antibiotics, including tetracycline, doxycycline, minocycline, dalfopristin, virginiamycin, pristinamycin, chloramphenicol, streptomycin, clindamycin, lincomycin, trimethoprim, nalidixic acid and ciprofloxacin. The isolate IRMC827A carries several virulence factors that are significantly associated with adherence, biofilm formation, sortase-assembled pili, manganese uptake, antiphagocytosis, and spreading factor of multidrug resistance. The isolate also encompasses two mutations (G2576T and G2505A) in the 23S rRNA gene associated with linezolid resistance and three more mutations ( gyrA p.S83Y, gyrA p.D759N and parC p.S80I) of the antimicrobial resistance phenotype. The findings through next-generation sequencing on the resistome, mobilome and virulome of the isolate in the study highlight the significance of monitoring multidrug-resistant E. faecalis colonization and infection in hospitalized patients. As multidrug-resistant E. faecalis is a serious pathogen, it is particularly difficult to treat and can cause fatal infections. It is important to have quick and accurate diagnostic tests for multidrug-resistant E. faecalis , to track the spread of multidrug-resistant E. faecalis in healthcare settings, and to improve targeted interventions to stop its spread. Further research is necessary to develop novel antibiotics and treatment strategies for multidrug-resistant E. faecalis infections.

There is a global health concern associated with the emergence of the multidrug-resistant (MDR) fungus Candida auris , which has significant mortality rates. Finding innovative and distinctive anti- Candida compounds is essential for treating infections caused by MDR C. auris . A bacterial strain with anti- Candida activity was isolated and identified using 16 S rRNA gene sequencing. The whole genome was sequenced to identify biosynthesis-related gene clusters. The pathogenicity and cytotoxicity of the isolate were analyzed in Candida and HFF-1 cell lines, respectively. This study set out to show that whole-genome sequencing, cytotoxicity testing, and pathogenicity analysis combined with genome mining and comparative genomics can successfully identify biosynthesis-related gene clusters in native bacterial isolates that encode antifungal natural compounds active against Candida albicans and C. auris . The native isolate MR14M3 has the ability to inhibit C. auris (zone of inhibition 25 mm) and C. albicans (zone of inhibition 25 mm). The 16 S rRNA gene sequence of MR14M3 aligned with Bacillus amyloliquefaciens with similarity (100%). Bacillus amyloliquefaciens MR14M3 establishes bridges of intercellular nanotubes (L 258.56 ± 35.83 nm; W 25.32 ± 6.09 nm) connecting neighboring cells. Candida cell size was reduced significantly, and crushed phenotypes were observed upon treatment with the defused metabolites of B. amyloliquefaciens MR14M3. Furthermore, the pathogenicity of B. amyloliquefaciens MR14M3 on Candida cells was observed through cell membrane disruption and lysed yeast cells. The whole-genome alignment of the MR14M3 genome (3981,643 bp) using 100 genes confirmed its affiliation with Bacillus amyloliquefaciens . Genome mining analysis revealed that MR14M3-coded secondary metabolites are involved in the biosynthesis of polyketides (PKs) and nonribosomal peptide synthases (NRPSs), including 11 biosynthesis-related gene clusters with one hundred percent similarity. Highly conserved biosynthesis-related gene clusters with anti- C. albicans and anti- C. auris potentials and cytotoxic-free activity of B. amyloliquefaciens MR14M3 proposes the utilization of Bacillus amyloliquefaciens MR14M3 as a biofactory for an anti- Candida auris and anti- C. albicans compound synthesizer., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors.)

Clostridium perfringens is a spore-forming, Gram-positive anaerobic pathogen that causes several disorders in humans and animals. A multidrug-resistant Clostridium strain was isolated from the fecal sample of a patient who was clinically suspected of gastrointestinal infection and had a recent history of antibiotic exposure and diarrhea. The strain was identified by 16s rRNA sequencing as Clostridium perfringens . The strain's pathogenesis was analyzed through its complete genome, specifically antimicrobial resistance-related genes. The Clostridium perfringens IRMC2505A genome contains 19 ( Alr , Ddl , dxr , EF-G , EF-Tu , folA , Dfr , folP , gyrA , gyrB , Iso-tRNA , kasA , MurA , rho , rpoB , rpoC , S10p , and S12p ) antibiotic-susceptible genetic species according to the k-mer-based detection of antimicrobial resistance genes. Genome mapping using CARD and VFDB databases revealed significant ( p -value = 1 × 10 -26 ) genes with aligned reads against antibiotic-resistant genes or virulence factors, including phospholipase C, perfringolysin O, collagenase, hyaluronidase, alpha-clostripain, exo-alpha-sialidase, and sialidase activity. In conclusion, this is the first report on C. perfringens from Saudi Arabia that conducted whole genome sequencing of IRMC2505A and confirmed the strain as an MDR bacterium with several virulence factors. Developing control strategies requires a detailed understanding of the epidemiology of C. perfringens , its virulence factors, and regional antimicrobial resistance patterns.

Background: Autism Spectrum Disorder (ASD) is a multifactorial, neurodevelopmental disorder, characterized by deficits in communication, restricted and repetitive behaviors. ASD is highly heritable in Saudi Arabia; indecencies of affected individuals are increasing., Objectives: To identify the most significant genes and SNPs associated with the increased risk of ASD in Saudi females to give an insight for early diagnosis., Methods: Pilot case-control study mostly emphasized on the significant SNPs and haplotypes contributing to Saudi females with ASD patients ( n  = 22) compared to controls ( n  = 51) without ASD. With the use of allelic association analysis tools, 243,345 SNPs were studied systematically and classified according to their significant association. The significant SNPs and their genes were selected for further investigation for mapping of ASD candidate causal variants and functional impact., Results: In females, five risk SNPs at p ≤ 2.32 × 10 -05 was identified in association with autism. The most significant exonic variants at chromosome 6p22.1 with olfactory receptor genes ( OR12D2 and OR5V1 ) clustered with high linkage disequilibrium through haplotyping analysis. Comparison between highly associated genes (56 genes) of male and female autistic patients with female autistic samples revealed that 39 genes are unique biomarkers for Saudi females with ASD., Conclusion: Multiple variations in olfactory receptor genes ( OR5V1 and OR12D2 ) and single variations on SPHK1, PLCL2, AKAP9 and LOC107984893 genes are contributing to ASD in females of Arab origin. Accumulation of these multiple predisposed coding SNPs can increase the possibility of developing ASD in Saudi females., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Almandil, Alismail, Alsuwat, AlSulaiman, AbdulAzeez and Borgio.)

In search of potent urease inhibitor indole analogues ( 1-22 ) were synthesized and evaluated for their urease inhibitory potential. All analogues ( 1-22 ) showed a variable degree of inhibitory interaction potential having IC 50 value ranging between 0.60 ± 0.05 to 30.90 ± 0.90  µ M when compared with standard thiourea having IC 50 value 21.86 ± 0.90  µ M. Among the synthesized analogues, the compounds 1, 2, 3, 5, 6, 8, 12, 14, 18, 20 and 22 having IC 50 value 3.10 ± 0.10, 1.20 ± 0.10, 4.60 ± 0.10, 0.60 ± 0.05, 5.30 ± 0.20, 2.50 ± 0.10, 7.50 ± 0.20, 3.90 ± 0.10, 3.90 ± 0.10, 2.30 ± 0.05 and 0.90 ± 0.05  µ M respectively were found many fold better than the standard thiourea. All other analogues showed better urease interaction inhibition. Structure activity relationship (SAR) has been established for all analogues containing different substituents on the phenyl ring. To understand the binding interaction of most active analogues with enzyme active site docking study were performed.Communicated by Ramaswamy H. Sarma.

Background: Celomic fluid can be considered as an ultra-filtrate of maternal serum, containing a high protein concentration, urea, and many other molecules. It is an important transfer interface and a reservoir of nutrients for the embryo. Celomic fluid contains fetal cells that can be used for prenatal diagnosis of monogenic diseases in an earlier gestational period than villocentesis and amniocentesis., Objective: The purpose of this study was to evaluate the characteristics of celomic fluid and to establish a workflow laboratory procedure for very early prenatal diagnosis of monogenic diseases., Methods: Three hundred and eighty-five celomatic fluids were collected between the seventh and tenth week of gestation. We sampled 1 mL of celomic fluid in all cases. The embryo-fetal erythroid precursor cells were selected by the anti-CD71 microbead method or by a direct micromanipulator pick-up on the basis of their morphology. We amplified the extracted DNA using a nested polymerase chain reaction. Primers for short tandem repeat amplification were used to perform a quantitative fluorescent polymerase chain reaction evaluation to control maternal contamination., Results: We observed maternal contamination in 95% of celomic fluids with a range between 5 and 100%. No fetal cells were observed in 0.78% of celomic fluids. The number of fetal cells ranged from a few units to several hundred. Isolation of embryo-fetal erythroblasts selected by the micromanipulator made diagnosis feasible in all cases., Conclusions: The selection of fetal cells by a micromanipulator and nested polymerase chain reaction analysis made celomatic fluid suitable for early prenatal diagnosis of monogenic disorders even in the presence of high maternal contamination and few fetal cells. The procedure reported in this study provides the opportunity for the use of celomic fluid sampled by celocentesis as an alternative to chorionic villi sampling and amniocentesis, to allow invasive prenatal diagnosis at a very early stage of pregnancy., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Pediatric dental caries is common among Arab children, however we are still searching for possible genes and molecular mechanisms that influence caries development., Aim: To identity genetic predispositions of dental caries among Saudi children with high DMFT (Decayed, Missing, and Filled Teeth)., Design: This case-control study analysed putative functional exonic-variants (n = 243,345) to study the molecular genetics of pediatric caries with high dmft index, 8.75 ± 4.16 on Arab-ancestry subjects with primary dentition (n = 111; 76 cases, dmft>5 and 35 controls, dmft = 0)., Results: Pediatric caries is significantly associated with single nucleotide polymorphisms (SNP) in the GRIN2B-rs4764039C (p-value = 2.03 × 10 -08 ) and CFH-rs1065489G (p-value = 8.26 × 10 -08 ) genes, even after Bonferroni correction. Irregular tooth brushing habits (p = 0.0404) and irregular dental visits (p = 0.0050) are significantly associated with caries. Functional enrichment analysis of significant genes is associated with calcium-activated chloride channel, Staphylococcus aureus infection, and N-linked glycosylation., Conclusion: Genetic predispositions are found to be significantly associated with the high prevalence of pediatric caries, which is a disorder of multigene-environment interaction. The significant functional exonic variants identified can be biomarkers for the early diagnosis of pediatric dental caries in Arabs., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Autism is a complex disease with genetic predisposition factors. Real factors for treatment and early diagnosis are yet to be defined. This study integrated transcriptome and exome genotyping for identifying functional variants associated with autism spectrum disorder and their impact on gene expression to find significant variations. More than 1800 patients were screened, and 70 (47 male/23 female) with an average age of 7.56 ± 3.68 years fulfilled the DSM-5 criteria for autism. Analysis revealed 682 SNPs of 589 genes significantly ( p < 0.001) associated with autism among the putative functional exonic variants ( n = 243,345) studied. Olfactory receptor genes on chromosome 6 were significant after Bonferroni correction (α = 0.05/243345 = 2.05 × 10 -7 ) with a high degree of linkage disequilibrium on 6p22.1 ( p = 6.71 × 10 -9 ). The differentially expressed gene analysis of autistic patients compared to controls in whole RNA sequencing identified significantly upregulated (foldchange ≥0.8 and p -value ≤ 0.05; n = 125) and downregulated (foldchange ≤-0.8 and p -value ≤ 0.05; n = 117) genes. The integration of significantly up- and downregulated genes and genes of significant SNPs identified regulatory variants (rs6657480, rs3130780, and rs1940475) associated with the up- ( ITGB3BP ) and downregulation ( DDR1 and MMP8 ) of genes in autism spectrum disorder in people of Arab ancestries. The significant variants could be a biomarker of interest for identifying early autism among Arabs and helping to characterize the genes involved in the susceptibility mechanisms for autistic subjects.

Inhibition of α-amylase enzyme is of key significance for the therapy of diabetes mellitus (DM). Numerous indole-based compounds have earlier been described for broad range of bioactivities. From our previous study, we knew that indole and thiadiazole are potent inhibitors of diabetics II. We design the hybrid molecules of them and synthesized 18 derivatives of indole-based-thiadiazole ( 1 - 18 ). All synthesized compounds were characterized using different spectroscopic methods and evaluated for their α-amylase inhibitory activities. All synthetic compounds, except 4 , 13 , 15 and 16 , were found to be strongly active (IC 50 values in the range of 0.80 ± 0.05 - 9.30 ± 0.20 µM) than the standard drug, acarbose (IC 50 = 11.70 ± 0.10 µM). Nevertheless, compound 18 was found to be inactive. The modes of binding interactions of five most active compounds 2 , 3 , 5 , 10 and 17 were also studies through molecular docking study. In brief, current study identifies a novel class of α-amylase inhibitors which can be further studied for the treatment of hyperglycemia and obesity.Communicated by Ramaswamy H. Sarma.

Objectives: Medication errors (MEs) are the most common cause of adverse drug events (ADEs) and one of the most encountered patient safety issues in clinical settings. This study aimed to determine the types of MEs in secondary care hospitals in Kuwait and identify their causes. Also, it sought to determine the existing system of error reporting in Kuwait and identify reporting barriers from the perspectives of healthcare professionals (HCPs). Material and Methods: A descriptive cross-sectional study was conducted using a pre-tested self-administered questionnaire. Full-time physicians, pharmacists, and nurses (aged 21 years and older) working in secondary care governmental hospitals in Kuwait were considered eligible to participate in the study. Descriptive statistics and the Statistical Package for Social Science Software (SPSS), version 27 were used to analyze the data. Results: A total of 215 HCPs were approached and asked to take part in the study, of which 208 agreed, giving a response rate of 96.7%. Most HCPs ( n = 129, 62.0%) reported that the most common type of ME is "prescribing error," followed by "compliance error" ( n = 83; 39.9%). Most HCPs thought that a high workload and lack of enough breaks ( n = 128; 61.5%) were the most common causes of MEs, followed by miscommunication, either among medical staff or between staff and patients, which scored ( n = 89; 42.8%) and ( n = 82; 39.4%), respectively. In the past 12 months, 77.4% ( n = 161) of HCPs reported that they did not fill out any ME incident reports. The lack of feedback ( n = 65; 31.3%), as well as the length and complexity of the existing incident reporting forms ( n = 63; 30.3%), were the major barriers against reporting any identified MEs. Conclusions: MEs are common in secondary care hospitals in Kuwait and can be found at many stages of practice. HCPs suggested many strategies to help reduce MEs, including proper communication between HCPs; double-checking every step of the process before administering medications to patients; providing training to keep HCPs up to date on any new treatment guidelines, and computerizing the health system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Alsaleh, Alsaeed, Alsairafi, Almandil, Naser and Bayoud.)

We aimed to identify the prevalence and emerging status of multidrug-resistant bacteria and fungi and their associated mortality in nine countries in the Arabian Peninsula. Original research articles and case studies regarding multidrug-resistant bacteria and fungi in the Arabian Peninsula, published during the last 10 years, were retrieved from PubMed and Scopus. A total of 382 studies were included as per the inclusion and exclusion criteria, as well as the PRISMA guidelines, from a thorough screening of 1705 articles, in order to analyse the emerging status and mortality. The emerging nature of >120 multidrug-resistant (MDR) bacteria and fungi in the Arabian Peninsula is a serious concern that requires continuous monitoring and immediate preventive measures. More than 50% ( n = 453) of multidrug-resistant, microbe-associated mortality ( n = 871) in the Arabian Peninsula was due to MDR Acinetobacter baumannii, Mycobacterium tuberculosis and Staphylococcus aureus infection. Overall, a 16.51% mortality was reported among MDR-infected patients in the Arabian Peninsula from the 382 articles of this registered systematic review. MDR A. baumannii (5600 isolates) prevailed in all the nine countries of the Arabian Peninsula and was one of the fastest emerging MDR bacteria with the highest mortality ( n = 210). A total of 13,087 Mycobacterium tuberculosis isolates were reported in the region. Candida auris (580 strains) is the most prevalent among the MDR fungal pathogen in the Arabian Peninsula, having caused 54 mortalities. Active surveillance, constant monitoring, the development of a candidate vaccine, an early diagnosis of MDR infection, the elimination of multidrug resistance modulators and uninterrupted preventive measures with enhanced data sharing are mandatory to control MDR infection and associated diseases of the Arabian Peninsula. Accurate and rapid detection methods are needed to differentiate MDR strain from other strains of the species. This review summarises the logical relation, prevalence, emerging status and associated mortality of MDR microbes in the Arabian Peninsula.

In this study, we have investigated a series of indole-based compounds for their inhibitory study against pancreatic α-amylase and intestinal α-glucosidase activity. Inhibitors of carbohydrate degrading enzymes appear to have an essential role as antidiabetic drugs. All analogous exhibited good to moderate α-amylase (IC 50  = 3.80 to 47.50 μM), and α-glucosidase inhibitory interactions (IC 50  = 3.10-52.20 μM) in comparison with standard acarbose (IC 50  = 12.28 μM and 11.29 μM). The analogues 4, 11, 12, 15, 14 and 17 had good activity potential both for enzymes inhibitory interactions. Structure activity relationships were deliberated to propose the influence of substituents on the inhibitory potential of analogues. Docking studies revealed the interaction of more potential analogues and enzyme active site. Further, we studied their kinetic study of most active compounds showed that compounds 15, 14, 12, 17 and 11 are competitive for α-amylase and non- competitive for α-glucosidase., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Family trio next-generation sequencing-based variant analysis was done to identify the genomic reason on unexplained recurrent pregnancy loss (RPL). A family (dead fetus and parents) from Saudi Arabia with an earlier history of three unexplained RPLs at the ninth week of pregnancy was included in the study. Whole-genome sequencing (WGS) of a dead fetus and the parents was done to identify the pathogenic variation and confirmed through Sanger sequencing. WGS of dead fetus identifies a novel homozygous exonic variation (NM&#95;017419.3:c.680G>T) in ASIC5 (acid-sensing ion channel subunit family member 5) gene; the parents are heterozygous. Newly designed ARMS PCR followed by direct sequencing confirms the presence of heterozygous in one subject and absence of homozygous novel mutation among randomly selected healthy Saudis. The second family with heterozygous was confirmed with three unexplained RPLs. Pathogenicity analysis of R227I amino acid substitution in ASIC5 protein through molecular docking and interaction analysis revealed that the mutations are highly pathogenic, decrease the stability of the protein, and prevent binding of amiloride, which is an activator to open the acid-sensing ion channel of ASIC5 . The identified rare and novel autosomal recessive mutation, c.680G>T:p.R227I (ASIC5 Saudi ), in two families confirm the ASIC5 gene association with RPL and can be fatal to the fetus., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Al Qahtani, AbdulAzeez, Almandil, Fahad Alhur, Alsuwat, Al Taifi, Al-Ghamdi, Rabindran Jermy, Abouelhoda, Subhani, Al Asoom and Borgio.)

Migraine is a neurological ailment that is characterized by severe throbbing unilateral headache and associated with nausea, photophobia, phonophobia and vomiting. A full and clear mechanism of the pathogenesis of migraine, though studied extensively, has not been established yet. The current available information indicates an intracranial network activation that culminates in the sensitization of the trigemino-vascular system, release of inflammatory markers, and initiation of meningeal-like inflammatory reaction that is sensed as headache. Genetic factors might play a significant role in deciding an individual's susceptibility to migraine. Twin studies have revealed that a single gene polymorphism can lead to migraine in individuals with a monogenic migraine disorder. In this review, we describe recent advancements in the genetics, pathophysiology, diagnosis, treatment, management, and prevention of migraine. We also discuss the potential roles of genetic and abnormal factors, including some of the metabolic triggering factors that result in migraine attacks. This review will help to accumulate current knowledge about migraine and understanding of its pathophysiology, and provides up-to-date prevention strategies., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Endophytic fungi serve as a reservoir for important secondary metabolites. The current study focused on the antibacterial properties of endophytic fungi isolated from Artemisia sieberi . Initially, six endophytic fungi were isolated and purified from the stem of A. sieberi . Endophytic fungi were identified by morphological characteristics, as well as by molecular identification using 18S rRNA gene sequencing method. All the six isolates were subjected to the preliminary screening for their antibacterial activity against nine important pathogenic bacteria using the disk-diffusion method. Crude extracts of the most active isolate were obtained using ethyl acetate. Antibacterial activity of the ethyl acetate extract was evaluated using well diffusion method on the selected isolate. The antibacterial efficiency of the selected isolate was evaluated by determining the Minimum Inhibitory Concentration (MIC). MIC values were in appreciable quantity against both Gram-positive and Gram-negative bacteria ranging from 3.125 to 6.25  µ g/mL and 12.5 to 50  µ g/mL, respectively. This result indicated that Gram-positive bacteria were more susceptible to the endophytic fungi extract. Moreover, the molecular identification results revealed that all the isolates belong to Ascomycota and represented Aspergillus and Penicillium genera and three species: A. oryzae (three isolates), A. niger (one isolate), and P. chrysogenum (two isolates). All six endophytic fungi were able to inhibit the growth of at least two of the tested bacteria. Among the isolated strains, isolate AS2, which identified as P. chrysogenum , exhibited the highest antibacterial activity against all nine tested bacteria and was higher than or equal to the positive control against most of the tested bacteria. Future studies are required to isolate and identify these bioactive substances, which can be considered as a potential source for the synthesis of new antibacterial drugs to treat infectious diseases., Competing Interests: Authors declare that they have no conflicts of interest., (Copyright © 2021 Ibtisam Mohammed Ababutain et al.)

A series of nineteen (1-19) indole-based-thiadiazole derivatives were synthesized, characterized by 1 HNMR, 13 C NMR, MS, and screened for α-glucosidase inhibition. All analogs showed varied α-glucosidase inhibitory potential with IC 50 value ranged between 0.95 ± 0.05 to 13.60 ± 0.30 µM, when compared with the standard acarbose (IC 50  = 1.70 ± 0.10). Analogs 17, 2, 1, 9, 7, 3, 15, 10, 16, and 14 with IC 50 values 0.95 ± 0.05, 1.10 ± 0.10, 1.30 ± 0.10, 1.60 ± 0.10, 2.30 ± 0.10, 2.30 ± 0.10, 2.80 ± 0.10, 4.10 ± 0.20 and 4.80 ± 0.20 µM respectively showed highest α-glucosidase inhibition. All other analogs also exhibit excellent inhibitory potential. Structure activity relationships have been established for all compounds primarily based on substitution pattern on the phenyl ring. Through molecular docking study, binding interactions of the most active compounds were confirmed. We further studied the kinetics study of analogs 1, 2, 9 and 17 and found that they are Non-competitive inhibitors., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Gut microbiota has become an issue of great importance recently due to its major role in autism spectrum disorder (ASD). Over the past three decades, there has been a sustained research activity focused to explain the actual mechanism by which gut microbiota triggers/develops autism. Several genetic and epigenetic factors are involved in this disorder, with epigenetics being the most active area of research. Although the constant investigation and advancements, epigenetic implications in ASD still need a deeper functional/causal analysis. In this review, we describe the major gut microbiota metabolites and how they induce epigenetic changes in ASD along with interactions through the gut-brain axis., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s).)

Autism is heterogeneous multifactorial neurodevelopmental and neuropsychiatric disorder with repetitive and limited behaviors as well as communication deficits. Prevalence of autism in males is predominant than females, but their genetic association is unclear. The study was performed to investigate Y-chromosome haplotypes, significant risk variants and susceptibility genes associated with autistic Saudi young males with autism. Exome genotyping microarray analysis was performed in Saudi young boys with autism (cases, n = 47) and without autism and other genetic or neurodevelopmental disorders (control, n = 43) to identify the functional exonic risk variations among 243,345 exonic variations. The most significant single nucleotide polymorphisms (SNPs) of protein coding associated with autism in Saudi young boys were studied for functional enrichment. Y-chromosome haplotyping analysis of 6 SNPs such as rs1865680, rs2032624, rs2032658, rs2032631, rs9786153 and rs13447352 uncovered the most significant protective (ACGACA p = 2.94 × 10 -9 ) among the controls and the high risk Y-haplotype (GAAGTC p = 6.85 × 10 -6 ) among autistic boys. Exome association study revealed 6 susceptible genes, MCC, AUTS2, VSX1, SETBP1, CNTN3, and PCDH11Y that were known for autistic disorder. The significant predisposed genes with functional variants of Y-chromomere are strongly connected with spermatogenic failure (p = 8.02 × 10 -8 ), azoospermia (p = 6.32 × 10 -7 ), partial chromosome Y deletion (p = 7.66 × 10 -6 ), HDMs demethylate histones pathway (p = 3.55 × 10 -4 ) and immune system diseases (p = 4.11 × 10 -3 ). Y-haplotypes and highly significant pathogenic exonic variants in MCC, AUTS2, VSX1, SETBP1, CNTN3 and PCDH11Y genes are more influential genetic factors for developing autism in boys of Arab origin.

α-Glucosidase and α-amylase are enzymes which are associated with diabetic II. These enzymes break macromolecules of sugar into monosugar molecules which is soluble in body, hence increase the sugar level in blood. There is need to develop economical and save inhibitors to prevent them from breaking sugar macromolecules to soluble molecules which will control the level of sugar in blood. Therefore, we synthesized indole-based derivatives (1-18) and evaluated as dual inhibitor for α-glucosidase and α-amylase. These chemical scaffolds were built with variation in aryl ring which were found active with good to moderate activity for α-glucosidase having IC 50 value ranging from 13.99 ± 0.10 to 59.09 ± 0.30 μM when compared with standard acarbose with IC 50 of 11.29 ± 0.10 μM; for α-amylase IC 50 value ranging from 13.14 ± 0.10 to 58.99 ± 0.30 μM when compared with the standard acarbose with IC 50 of 11.12 ± 0.10 μM. Structure activity relationship (SAR) has been established for all compounds. Enzymatic kinetic study and molecular docking study have been carried out to investigate the binding interactions α-glucosidase and α-amylase enzyme., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A new hybrid composite containing cerium oxide nanoparticle (CeO2NP) and gold nanoparticle (AuNP)-decorated functionalized glassy carbon microspheres (FGCM) was synthesized (Au/CeO2@FGCM). As a result, an Au/CeO2@FGCM-paraffin oil paste electrode (PE) (Au/CeO2@FGCM-PE) was fabricated and employed for the voltammetric sensing of quercetin (QRT). The structure and surface morphology of Au/CeO2@FGCM were studied by X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Cyclic voltammetry (CV), square wave voltammetry (SWV) and electrochemical impedance spectroscopy (EIS) were employed for the investigation of the electrochemical behavior of Au/CeO2@FGCM-PE. Under the optimum conditions, the SWV oxidation peak current showed linear dependence on the QRT concentration in the range from 48 nM to 1.09 μM. The achieved limits of detection and quantitation were 0.37 nM and 1.22 nM, respectively. Au/CeO2@FGCM-PE was reproducible, sensitive and stable and displayed anti-interference ability for various common interferents. The proposed method was also successfully applied for real sample analysis. The QRT content extracted from natural sources was determined, and satisfactory results were achieved. Furthermore, the interaction of QRT with salmon testes and calf thymus dsDNA (st-DNA and ct-DNA) on Au/CeO2@FGCM-PE was studied by CV and SWV. The corresponding binding constant (K), surface concentration (Γ), and Gibbs free energy (ΔG°) were computed for the free QRT and the bound QRT-dsDNA complex. The calculated K values for the QRT-ct-DNA and QRT-st-DNA complexes were found to be 6.24 × 105 M-1 and 3.63 × 105 M-1, respectively, which revealed that QRT strongly interacted with ct-DNA compared to that with st-DNA. The decreased intensity of the QRT oxidation peak resulting from its interaction with dsDNA provides a chance to use QRT as a new indicator to analyze ct-DNA and st-DNA.

A new series of indole-based-sulfonamide derivatives ( A1 - A8 ) was synthesized by treating 5-fluoro-1H-indole-3-carbohydrazide with different aryl-sulfonyl chloride in the presence of pyridine. All synthesized derivatives ( A1 - A8 ) were characterized by different analytical methods. The electrochemical behavior of these compounds ( A1 - A8 ) was investigated in detail using cyclic voltammetry (CV) and square wave voltammetry (SWV) at the pencil graphite electrode (PGE). In the present study, the redox behavior of all derivatives varies due to the nature of substitutions in the indole sulfonamide moiety. Various fundamental electrochemical parameters, including the standard heterogeneous rate constants (k s ), and the electroactive surface coverage ( Г ) were calculated from the obtained CVs. The obtained results shed light on the understanding of structure-activity relationships of this class of compounds., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

In this study, a series of indole based acetohydrazide derivatives (1-22) were synthesized and characterized by 13 C NMR, 1 H NMR and HREI-MS. The resulted derivatives were tested for thymidine phosphorylase inhibitory potential. These derivatives inhibited thymidine phosphorylase at different concentration ranging from 1.10 ± 0.10 to 41.10 ± 1.10 µM when compared with the standard 7-Deazaxanthine (IC 50 value 38.68 ± 1.12 µM). The compound 8 having OH group at 2, 4 and 6 position was found the most potent among the series with IC 50 1.10 ± 0.10 µM. The structure activity relationships (SAR) has been established for all compounds keeping in the view the role of substitution and the effect of functional group which significantly affect thymidine phosphorylase activity. The nature of binding interactions of the most potent compounds and active sites of the enzymes was confirmed through molecular docking study., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: The extreme health and economic problems in the world due to the SARS-CoV-2 infection have led to an urgent need to identify potential drug targets for treating coronavirus disease 2019 (COVID-19). The present state-of-the-art tool-based screening was targeted to identify drug targets among clinically approved drugs by uncovering SARS-CoV-2 helicase inhibitors through molecular docking analysis., Material and Methods: Helicase is a vital viral replication enzyme, which unwinds nucleic acids and separates the double-stranded nucleic acids into single-stranded nucleic acids. Hence, the SARS-CoV-2 helicase protein 3D structure was predicted, validated, and used to screen the druggable targets among clinically approved drugs such as protease inhibitor, nucleoside reverse transcriptase inhibitor, and non-nucleoside reverse transcriptase inhibitors, used to treat HIV infection using molecular docking analysis., Results: Interaction with SARS-CoV-2 helicase, approved drugs, vapreotide (affinity: -12.88; S score: -9.84 kcal/mol), and atazanavir (affinity: -11.28; S score: -9.32 kcal/mol), approved drugs for treating AIDS-related diarrhoea and HIV infection, respectively, are observed with significantly low binding affinity and MOE score or binding free energy. The functional binding pockets of the clinically approved drugs on SARS-CoV-2 helicase protein molecule suggest that vapreotide and atazanavir may interrupt the activities of the SARS-CoV-2 helicase., Conclusions: The study suggests that vapreotide may be a choice of drug for wet lab studies to inhibit the infection of SARS-CoV-2., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2020 Termedia & Banach.)

Introduction: The SARS-CoV-2 (previously 2019-nCoV) outbreak in Wuhan, China and other parts of the world affects people and spreads coronavirus disease 2019 (COVID-19) through human-to-human contact, with a mortality rate of > 2%. There are no approved drugs or vaccines yet available against SARS-CoV-2., Material and Methods: State-of-the-art tools based on in-silico methods are a cost-effective initial approach for identifying appropriate ligands against SARS-CoV-2. The present study developed the 3D structure of the envelope and nucleocapsid phosphoprotein of SARS-CoV-2, and molecular docking analysis was done against various ligands., Results: The highest log octanol/water partition coefficient, high number of hydrogen bond donors and acceptors, lowest non-bonded interaction energy between the receptor and the ligand, and high binding affinity were considered for the best ligand for the envelope (mycophenolic acid: log P = 3.00; D G = -10.2567 kcal/mol; p Ki = 7.713 µM) and nucleocapsid phosphoprotein (1-[(2,4-dichlorophenyl)methyl]pyrazole-3,5-dicarboxylic acid: log P = 2.901; D G = -12.2112 kcal/mol; p Ki = 7.885 µM) of SARS-CoV-2., Conclusions: The study identifies the most potent compounds against the SARS-CoV-2 envelope and nucleocapsid phosphoprotein through state-of-the-art tools based on an in-silico approach. A combination of these two ligands could be the best option to consider for further detailed studies to develop a drug for treating patients infected with SARS-CoV-2, COVID-19., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2020 Termedia & Banach.)

In the Eastern province of Saudi Arabia, thalassemia is highly common. Data on the effect of alpha globin gene variation on the concentration of iron on transfusion dependent Saudis are scanty. A total of 166 transfusions dependent β-thalassemia were included in this study to understand association between the alpha globin gene variation and concentration of iron. Using multiplex PCR, the alpha globin gene deletions were identified. Also, HBA1 and HBA2 genes were sequenced by Sanger sequencing. Saudi transfusion dependent female β-thalassemia patients with wild alpha globin genotype (αα/αα) were observed with iron level beyond the normal range. However, normal range of iron was observed in transfusion dependent Saudi female beta thalassemia patients co-inherited with double (-α 3.7 /-α 3.7 , or -- Fil /αα or -- MED /αα or - (α) 20.5 /αα) or double heterozygosity (- -/-α 3.7 ) alpha globin gene deletions, which is significantly (p < 0.0001) less compared to the Saudi transfused female with wild alpha globin genotype (αα/αα). The co-inheritance alpha globin gene deletions in female beta thalassemia patients were significantly lowering serum iron. Detailed studies can be taken forward to identify the molecular pathways involved in globin gene deletion as modulator.

The prevalence of consanguineous marriage and genetic disorders are high in Saudi Arabia. There were records on the practices of Saudis toward prenatal diagnosis (PND) and termination of pregnancy (TOP), however the sample sizes are small. This study has targeted the Saudi Arabian community and family history of genetic disorders to determine the practices toward PND and TOP. The cross-sectional survey was conducted among Saudis (n = 2761) to determine their practices toward reproductive-decision making. Regression analysis was conducted to identify the association of the limiting factors, relative merits and family history on the outcomes. Total of 2507 participants returned completed questionnaire. The practice towards PND (68%) were more favorable than TOP (33%). PND was found to be a good opportunity for early diagnosis and gives parent's choice. Education, history with affected baby, prior knowledge and religious belief were significant deciding factors of PND and TOP. Down syndrome (n = 161) and sickle cell anemia (n = 152) were commonly available genetic disorder among participant's family. Respondents with autistic cases in their family have higher acceptance rate for TOP. Non-consanguineous are more willing to consider TOP than consanguineous. Participants with abnormal fetus, aged of > 36 years, married and educated Saudis were more likely consider TOP. Though, religion is the most influencing factor for not accepting TOP, comparatively willingness to PND and TOP have increased recently. Awareness campaigns about PND and TOP may increase the chances of accepting prenatal genetic diagnosis.

We have synthesized new series of bisindole analogs ( 1 - 27 ), characterized by 1 HNMR and HR-EI-MS and evaluated for their anti-leishmanial potential. All compounds showed outstanding inhibitory potential with IC 50 values ranging from 0.7 ± 0.01 to 13.30 ± 0.50 µM respectively when compared with standard pentamidine with IC 50 value of 7.20 ± 0.20 µM. All analogs showed greater potential than standard except 10 , 19 and 23 when compared with standard. Structure activity relationship has been also established for all compounds. Molecular docking studies were carried out to understand the binding interaction of active molecules., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

For the determination of paracetamol (PAR) and its primary degradation product ( p -aminophenol, PAP) a highly selective electrochemical sensor was fabricated. A glassy carbon microspheres paste electrode (GCMPE) was modified with a CeO 2 -ZnO-chitosan hybrid nanocomposite (CeO 2 -ZnO-CS) which was characterized by X-ray diffraction and transmission electron microscopy. The CeO 2 -ZnO-CS/GCMPE was characterized by scanning electron microscopy, and cyclic voltammetry. The modified GCMPE exhibits excellent electrocatalytic activity for the determination of PAR and PAP separately or simultaneously, typically at working potentials of 0.38 and 0.09 V vs. Ag/AgCl. The square wave voltammetric response in solutions of near-neutral pH value increases linearly in the 20 nM to 1.8 μM PAR concentration range, and the lower LOD is 0.86 nM. The sensor is shown to enable the determination of PAR even in the presence of a 180-fold excess of PAP. PAR and PAP can also be simultaneously determined, and the LODs for PAR and PAP are 0.98 nM and 9.5 nM, respectively. The results agreed well with data obtained using other electrodes. The sensor is reproducible and stable over eight weeks, and interference by biologically essential compounds is negligible. The method was applied to the determination of PAR in pharmaceutical formulations and in spiked blood serum and urine samples. The relative standard deviations ranged from 97.5 to 102.0%., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Introduction: Abnormality in HBB results in an inherited recessive blood disorder, which can be caused by variants at the transcriptional or translational level affecting the stability and the production of the HBB chain. The severity of the disease relies on the variant's characteristics. This study aimed to identify the common β-globin HBB variants in the population of the Eastern Province, which has the highest prevalence of blood diseases in Saudi Arabia., Material and Methods: Direct sequence of β-globin HBB gene, and alpha-globin HBA1 and HBA2 genes was performed on a total of 545 blood samples (transfusion-dependent: 215, 106 men and 109 women; normal healthy subjects: 330, 197 men and 133 women) collected from Saudi Arabian participants in the Eastern region., Results: A total of 36 variants in HBB gene were revealed with 11 variants that have been reported for the first time in Saudi Arabia, including 7 novel variants that have been identified for the first time in HBB gene. The novel variants consisted of two exonic (HBB:c.252C>T; HBB:c.281G>T) and five intronic variants (c.316-183&#95;316-168del; c.315+241T>A; c.315+376T>C; c.316-114C>G; c.315+208T>G) at HBB gene. The novel exonic variants and three (c.316-183&#95;316-168del; c.315+241T>A; c.315+376T>C) intronic variants were co-inherited with α deletion., Conclusions: This current study updated the HBB gene variations with newly identified variants of HBB gene and co-inheritance with α-globin deletions. The identified β-globin mutations will strengthen the genetic reference that could aid in characterizing mutations that are associated with phenotype of thalassemia in a specific region., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2019 Termedia & Banach.)

Diabetes is one of the pre-dominant metabolic disorders all over the world. It is the prime reason of mortality and morbidity due to hyperglycemia which is link with numerus obstacles. Delaying absorption and digestion of carbohydrate has great therapeutic impact for governing postprandial hyperglycemia. Consequently, alpha glucosidase is one of the potential therapeutic approaches that reduce absorption of glucose and delay carbohydrate digestion hence maintaining blood glucose level. In this regard we have synthesized benzothiazole based oxadiazole in search of potent anti-diabetic agent as α-glucosidase Inhibitors. Benzothiazole based oxadiazole derivatives 1-23 have been synthesized, characterized by 1 HNMR, 13 CNMR, and MS and evaluated for α-glucosidase Inhibition. All analogs exhibited a varying degree of α-glucosidase inhibitory activity with IC 50 values ranging in between 0.5 ± 0.01-30.90 ± 0.70 μM when compared with the standard acarbose (IC 50  = 866.30 ± 3.20 μM). Structure activity relationship has been established for all compounds. Molecular docking studies were performed to predict the binding interaction of the compounds with the active site of enzyme., (Copyright © 2018 Elsevier Inc. All rights reserved.)

New series of quinoline-based thiadiazole analogs (1-20) were synthesized, characterized by EI-MS, 1 H NMR and 13 C NMR. All synthesized compounds were subjected to their antileishmanial potential. Sixteen analogs 1-10, 12, 13, 16, 17, 18 and 19 with IC 50 values in the range of 0.04 ± 0.01 to 5.60 ± 0.21 µM showed tremendously potent inhibition as compared to the standard pentamidine with IC 50 value 7.02 ± 0.09 µM. Analogs 11, 14, 15 and 20 with IC 50 8.20 ± 0.35, 9.20 ± 0.40, 7.20 ± 0.20 and 9.60 ± 0.40 µM respectively showed good inhibition when compared with the standard. Structure-activity relationships have been also established for all compounds. Molecular docking studies were performed to determine the binding interaction of the compounds with the active site target., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This study deals with the synthesis of benzophenone sulfonamides hybrids (1-31) and screening against urease enzyme in vitro. Studies showed that several synthetic compounds were found to have good urease enzyme inhibitory activity. Compounds 1 (N'-((4'-hydroxyphenyl)(phenyl)methylene)-4''-nitrobenzenesulfonohydrazide), 2 (N'-((4'-hydroxyphenyl)(phenyl)methylene)-3''-nitrobenzenesulfonohydrazide), 3 (N'-((4'-hydroxyphenyl)(phenyl)methylene)-4''-methoxybenzenesulfonohydrazide), 4 (3'',5''-dichloro-2''-hydroxy-N'-((4'-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide), 6 (2'',4''-dichloro-N'-((4'-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide), 8 (5-(dimethylamino)-N'-((4-hydroxyphenyl)(phenyl)methylene)naphthalene-1-sulfono hydrazide), 10 (2''-chloro-N'-((4'-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide), 12 (N'-((4'-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide) have found to be potently active having an IC 50 value in the range of 3.90-17.99 µM. These compounds showed superior activity than standard acetohydroxamic acid (IC 50  = 29.20 ± 1.01 µM). Moreover, in silico studies on most active compounds were also performed to understand the binding interaction of most active compounds with active sites of urease enzyme. Structures of all the synthetic compounds were elucidated by 1 H NMR, 13 C NMR, EI-MS and FAB-MS spectroscopic techniques., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

We have synthesized quinoxaline analogs ( 1 ⁻ 25 ), characterized by ¹H-NMR and HREI-MS and evaluated for thymidine phosphorylase inhibition. Among the series, nineteen analogs showed better inhibition when compared with the standard inhibitor 7-Deazaxanthine (IC 50 = 38.68 ± 4.42 µM). The most potent compound among the series is analog 25 with IC 50 value 3.20 ± 0.10 µM. Sixteen analogs 1 , 2 , 3 , 4 , 5 , 6 , 7 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 21 and 24 showed outstanding inhibition which is many folds better than the standard 7-Deazaxanthine. Two analogs 8 and 9 showed moderate inhibition. A structure-activity relationship has been established mainly based upon the substitution pattern on the phenyl ring. The binding interactions of the active compounds were confirmed through molecular docking studies.

β-glucuronidase is a lysosomal glycosidase enzyme which catalyzes the extracellular matrix of cancer and normal cells and the glycosaminoglycans of the cell membrane, which is important for cancer cell proliferation, invasion, and metastasis. Liver cancer, colon carcinoma, and neoplasm bladder are triggered by the increase of the level of β-glucuronidase activity. The most valuable structures are indole and oxadiazole which has gain immense attention because of its pharmacological behavior and display many biological properties. Twenty-two ( 1 ⁻ 2 2 ) analogs of indole based oxadiazole were synthesized and screened for their inhibitory potential against β-glucuronidase. Majority of the compounds showed potent inhibitory potential with IC 50 values ranging between 0.9 ± 0.01 to 46.4 ± 0.9 µM, under positive control of standard drug d-saccharic acid 1,4 lactone (IC 50 = 48.1 ± 1.2 µM). Structural activity relationship (SAR) has been established for all synthesized compounds. To shed light on molecular interactions between the synthesized compounds and β-glucuronidase, 1 , 4 , and 6 compounds were docked into the active binding site of β-glucuronidase. The obtained results showed that this binding is thermodynamically favorable and β-glucuronidase inhibition of the selected compounds increases with the number of hydrogen bonding established in selected compound-β-glucuronidase complexes., Competing Interests: The authors declare no conflict of interest.

One of the most common neurodevelopmental disorders worldwide is autism spectrum disorder (ASD), which is characterized by language delay, impaired communication interactions, and repetitive patterns of behavior caused by environmental and genetic factors. This review aims to provide a comprehensive survey of recently published literature on ASD and especially novel insights into excitatory synaptic transmission. Even though numerous genes have been discovered that play roles in ASD, a good understanding of the pathophysiologic process of ASD is still lacking. The protein⁻protein interactions between the products of NLGN , SHANK , and NRXN synaptic genes indicate that the dysfunction in synaptic plasticity could be one reason for the development of ASD. Designing more accurate diagnostic tests for the early diagnosis of ASD would improve treatment strategies and could enhance the appropriate monitoring of prognosis. This comprehensive review describes the psychotropic and antiepileptic drugs that are currently available as effective pharmacological treatments and provides in-depth knowledge on the concepts related to clinical, diagnostic, therapeutic, and genetic perspectives of ASD. An increase in the prevalence of ASD in Gulf Cooperation Council countries is also addressed in the review. Further, the review emphasizes the need for international networking and multidimensional studies to design novel and effective treatment strategies.

Background: B-cell lymphoma/leukaemia 11A (BCL11A) is a C2H2-type zinc-finger transcription factor protein that is a critical modulator of haemoglobin switching and suppresses the production of foetal haemoglobin. Variation in the BCL11A gene ameliorates the severity of sickle cell disease (SCD) and β-thalassemia (β-thal). The BCL11A gene is located on chromosome 2p16.1 and encodes an 835-amino acid protein., Method: Using state-of-the-art in silico tools, this study examined the most pathogenic non-synonymous single nucleotide polymorphisms (nsSNPs) that disrupt the BCL11A protein and mediate foetal-to-adult globin switching. A total of 11,463 SNPs were retrieved from the Single Nucleotide Polymorphism database (dbSNP). These included 799 in the 5' untranslated region (UTR), 486 in the 3' UTR, and 266 non-synonymous, 189 coding synonymous, six nonsense, and six stop-gained SNPs., Results and Discussion: In silico tools (SIFT, SNAP, PolyPhen-2, PANTHER, I-Mutant, PROVEAN, SNPs&GO, mCSM, and PhD-SNP) predicted the five most-deleterious nsSNPs: rs61742690, rs62142605, rs17028351, rs115666026, and rs74987258. Molecular dynamic simulation and homology modelling of the mutated proteins (S783N, D643N, G451S, K670R, and M313L) of the most deleterious nsSNPs revealed their functional and structural impact. nsSNP rs61742690 was predicted to be the most deleterious, as supported by eight of the nine in silico tools., Conclusions: Complete failure in the protein-protein interactions with functional partners (KLF1 and others) and significant changes (±100% variation) in the interface energy revealed that rs61742690 (S783N) in the zinc-finger domain is a suitable target for disrupting BCL11A-mediated foetal-to-adult globin switching., Competing Interests: The authors have declared that no competing interests exist.

Indole based thiadiazole derivatives ( 1 - 22 ) have synthesized, characterized by NMR and HREI-MS and evaluated for β-Glucuronidase inhibition. All compounds showed outstanding β-glucuronidase activity with IC 50 values ranging between 0.5 ± 0.08 to 38.9 ± 0.8 µM when compared with standard d-saccharic acid 1,4 lactone (IC 50 value of 48.1 ± 1.2 µM). The compound 6 , a 2,3-dihydroxy analog was found the most potent among the series with IC 50 value 0.5 ± 0.08 µM. Structure activity relationship has been established for all compounds. To confirm the binding interactions of these newly synthesized compounds, molecular docking study have been carried out which reveal that these compounds established stronger hydrogen bonding networks with active site residues., Competing Interests: The authors declare that they have no competing interests.

Background: Medication errors have been the largest component of medical errors threatening patient safety worldwide. Several international health bodies advocate measuring safety culture within healthcare organizations as an effective strategy for sustainable safety improvement. To the best of our knowledge, this is the first study conducted in a Middle Eastern country at the level of community pharmacy, to examine safety culture and to evaluate the extent to which patient safety is a strategic priority., Methods: A descriptive cross-sectional study was conducted. The Pharmacy Survey on Patient Safety Culture (PSOPSC), developed by the Agency for Healthcare Research and Quality (AHRQ), was used to collect data. PSOPSC is a self-administered questionnaire which was previously tested for validity and reliability. The questionnaire was distributed among pharmacists who work in community pharmacies from the five governorates of Kuwait (Capital, Hawalli, Farwaniya, Jahra, and Ahmadi). The Statistical Package for Social Science (SPSS) software, version 24 was used for analysing data., Results: A total of 255 community pharmacists from the five governorates were approached to participate in the study, of whom 253 returned a completed questionnaire, with the response rate of 99%. Results from the study showed that patient safety is a strategic priority in many aspects of patient safety standards at the level of community pharmacies. This was reflected by the high positive response rate (PRR) measures demonstrated in the domains of "Teamwork" (96.8%), "Organizational Learning-Continuous Improvement" (93.2%) and "Patient Counselling" (90.9%). On the other hand, the lowest PRR was given to the "Staffing, Work Pressure, and Pace" domain which scored 49.7%., Conclusions: Understanding community pharmacists' perspectives of patient safety culture within their organization is critical. It can help identify areas of strength and those that require improvement, which can help support decision about actions to improve patient safety. The current study showed that urgent attention should be given to the areas of weakness, mainly in the dimension of "Staffing, Work Pressure and Pace." The pharmacists pointed the need for adequate breaks between shifts and less distractible work environment to perform their jobs accurately.

Data on baseline (antipsychotics-naïve) age, weight, and height, and change in these at 3 subsequent follow-up time points up to 313.6 days (95% CI 303.5-323.7) were collected from 181 risperidone-treated children and adolescents (mean age 12.58 years, SD 4.99, range 2.17-17.7) attending a pediatric neurology clinic in Saudi Arabia. Owing to differences in genotypic distributions in the subsamples, results are reported for the white Arab population ( n = 144). Age- and gender-normed body mass index (BMI)-standardized z scores (BMI z ) were calculated (LMSgrowth program). Linear regression was performed for baseline weight and BMI z , while change in BMI z was assessed using random effects ordered logistic regression. The following single nucleotide polymorphisms (SNPs) were analyzed: rs7799039 in the LEP promoter, rs1805094 (previously rs8179183), rs1137100 and rs1137101 in the LEPR , and rs1414334 in HTR2C . We found a nominally significant association between rs7799309 and baseline weight, adjusting for height, age, gender, and diagnosis (A/G, p = 0.035, β = -3.62 vs. G/G). The rs1137101 (G/G, p = 0.018, odds ratio [OR] = 4.13 vs. A/A) and rs1805094 C allele carriers ( p = 0.019, OR = 0.51) showed nominally significant associations with change in BMI z categories. Our data support and replicate previous relevant associations for these variants (including with weight gain when on risperidone), whilst being the first report of such associations in patients of Arab ethnicity.

Introduction: Detection of β-thalassemia trait or carriers (β-TT) depends significantly on an increase in Hemoglobin A 2 (HbA 2 ) levels, which is found at low levels (<3%) in normal healthy individuals and elevated levels (≥3.5%) in β-TT individuals. The study was designed to evaluate the reliability of the diagnostic parameter HbA 2 in the differentiation of β-TT and non-β-TT in Saudis., Methods: The widely used high performance liquid chromatography (Variant II Bio-Rad) was used to measure HbA 2 levels in blood. Sanger sequencing was used to screen the variation in globin genes (HBB, HBD, HBA1, and HBA2). All the study subjects were divided into βTT and non-βTT (wild) categories based on the presence or absence of HBB variations and further sub-divided into false positive, true positive, false negative, and true negative, based on HbA 2 values., Results: Out of 288 samples, 96 had HBB gene mutations. Of the 96 β-TT samples, sickle cell trait (SCT) samples (n = 58) were excluded, while the remaining (38 β-TT) were included in the detailed analysis: seven subjects with the HBB mutation had normal HbA 2 (<3%), and three were borderline (3.1-3.9%). The remainder (n = 28) had an elevated HbA 2 level (>4%). Based on HbA 2 analysis alone, both these groups would be incorrectly diagnosed as normal. Similarly, of the 189 non-β-TT samples, 179 had normal HbA 2 , eight had borderline HbA 2 , and two had a HbA 2 level above 4%. Based on HbA 2 analysis alone, borderline and >4% HbA 2 individuals, negative for β-TT, can be incorrectly diagnosed as carriers., Conclusion: Given the percentage of samples falling in the HbA 2 "borderline" and "normal" categories, it can be concluded that HbA 2 has a measure of unreliability in the diagnosis of β-thalassemia carriers.

Aspergillus flavus is among the most devastating opportunistic pathogens of several food crops including rice, due to its high production of carcinogenic aflatoxins. The presence of these organisms in economically important rice strip farming is a serious food safety concern. Several polymerase chain reaction (PCR) primers have been designed to detect this species; however, a comparative assessment of their accuracy has not been conducted. This study aims to identify the optimal diagnostic PCR primers for the identification of A. flavus, among widely available primers. We isolated 122 A. flavus native isolates from randomly collected rice strips (N = 300). We identified 109 isolates to the genus level using universal fungal PCR primer pairs. Nine pairs of primers were examined for their PCR diagnostic specificity on the 109 isolates. FLA PCR was found to be the optimal PCR primer pair for specific identification of the native isolates, over aflP(1), aflM, aflA, aflD, aflP(3), aflP(2), and aflR. The PEP primer pair was found to be the most unsuitable for A. flavus identification. In conclusion, the present study indicates the powerful specificity of the FLA PCR primer over other commonly available diagnostic primers for accurate, rapid, and large-scale identification of A. flavus native isolates. This study provides the first simple, practical comparative guide to PCR-based screening of A. flavus infection in rice strips., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The regions of Al‑Qatif and Al‑Ahssa in the Eastern Province of Saudi Arabia are known for their high prevalence of hemoglobinopathies, including β‑thalassemia and sickle cell anemia. Previously, the α‑gene deletion has been demonstrated as highly prevalent among populations residing in these two regions. The present study was conducted in order to investigate the implications of the α‑globin gene deletion on fetal hemoglobin (HbF) and hemoglobin α2 (HbA2) concentrations in patients with transfusion‑dependent β‑thalassemia. A total of 166 Saudi patients with transfusion‑dependent β‑thalassemia and 337 healthy Saudi patients were included in the study. The ‑α3.7, ‑α4.2, -‑FIL, -‑SEA, -‑MED and -‑(20.5) gene deletions were identified using multiplex α‑globin deletion polymerase chain reaction. The present study revealed that the ‑α3.7 gene deletion is the most prevalent (43.5%) in the Saudi populations that were analyzed and is characterized by the deletion of 3,804 base pairs. Numerous genotypes, namely ‑3.7α2/α1α2, ‑3.7α2/α1α12, ‑3.7α2/‑3.7α2, ‑3.7α2HphI/α1α2HphI, ‑3.7α2/α1‑4.2, ‑3.7α2/α1polyA‑1α2, ‑3.7α12/α1α12, ‑‑FIL/‑3.7α2 and ‑3.7α2/‑3.7α2Hb Villiers le Bel were also identified in the investigated population. Furthermore, a gradual increase in the concentration of HbF and HbA2 in patients with β‑thalassemia and the number of α‑gene deletions was demonstrated; whereas in healthy patients the level of HbA2 was demonstrated to decrease as the number of α‑gene deletions increased. Therefore, it can be concluded that the high HbF concentration in the present study is predominantly associated with other mutations associated with β‑thalassemia rather than α‑globin deletions. Furthermore, the results of the present study also revealed novel α‑gene deletion genotypes prevalent in the population studied, namely α1α2/α1α2HphI, α1α2HphI/α1α2HphI, α1α2/α1α2Hb Handsworth, ‑3.7α2HphI/α1α2HphI, ‑3.7α2/‑3.7α2Hb Villiers le Bel and ‑-MED/α1α2HphI.

Objectives: To document the knowledge of, attitudes toward, and practices of adverse drug reaction (ADR) reporting and pharmacovigilance systems among healthcare professionals. Methods: This descriptive cross-sectional study was conducted using a questionnaire. This study took place at King Fahd Hospital of the University (KFHU), Khobar, Kingdom of Saudi Arabia,  between  April 2015 and  April 2016. Healthcare professionals, including physicians, pharmacists, pharmacy technicians, and nurses, were considered eligible and invited to take part in the study. A link to the online questionnaire was sent to each participant via E-mail, and a hard copy was circulated at the hospital after the objectives of the study were explained. The questionnaire comprised items regarding knowledge/awareness of pharmacovigilance and ADRs, perception/attitude towards pharmacovigilance and ADR reporting, and practices of ADR reporting. Descriptive statistics were used to analyze the data. Results: A total of 400 questionnaires were distributed to the healthcare professionals and 331 participants responded, providing a response rate of 82.75%. The healthcare professionals comprised 161 physicians, 39 pharmacists, 21 pharmacist technicians, and 110 nurses. Most of the participants were female (n=198) and Saudi (61.9%). Most healthcare professionals (62.5%) were unaware of the term pharmacovigilance; the pharmacists and pharmacist technicians had the highest rate of pharmacovigilance awareness (60.5% of the pharmacists and 40% of pharmacist technicians). Conclusion: There is a lack of awareness and knowledge of pharmacovigilance and ADR reporting among healthcare professionals working at KFHU.

Objectives: The aims of this study were to provide a systematic review and meta-analysis of the effects of atypical antipsychotics in children and adolescents on weight gain (primary objective) and other metabolic parameters (secondary objective)., Methods: A systematic literature review and meta-analysis of double-blind, randomized, controlled trials were conducted. The data sources used were as follows: EMBASE, PubMed, BIOSIS, International Pharmaceutical Abstracts, The Cochrane database (Clinical Trials), Clinical Trials Government Registry, The metaRegister of Controlled Trials, WHO (World Health Organization) Clinical Trials Registry Platform, and PsycINFO(®). Hand searching was also carried out by examining the reference lists of identified studies. Double-blind, randomized, controlled trials investigating the metabolic adverse effects (weight gain, lipid, glucose, and prolactin level abnormalities) associated with atypical antipsychotic use in children and adolescents aged ≤ 18 years were included, irrespective of whether the investigation of adverse effects was a primary or secondary endpoint., Results: We identified 21 studies of drug versus placebo that met the inclusion criteria, with a total of 2,455 patients, 14 studies for risperidone (1,331 patients), three for olanzapine (276 patients), and four for aripiprazole (848 patients). Compared with placebo, the mean weight increases for each drug were olanzapine 3.45 kg (95 % CI 2.93-3.98), risperidone 1.77 kg (95 % CI 1.35-2.20), and aripiprazole 0.94 kg (95 % CI 0.65-1.24). Regarding other metabolic abnormalities, eight studies reported statistically significant increases in prolactin with risperidone; two reported a statistically significant increase in glucose, total cholesterol, and prolactin with olanzapine; and three studies reported a statistically significant decrease in prolactin with aripiprazole. Data on lipid, glucose, and prolactin level changes were too limited to allow us to perform a meta-analysis., Conclusions: Olanzapine, risperidone, and aripiprazole were all associated with statistically significant weight gain. Olanzapine was associated with the most weight gain and aripiprazole the least. For the secondary outcome, although a number of active comparator trials were identified, data were not available for meta-analysis and were too limited to allow firm conclusions to be drawn.

Antipsychotic (neuroleptic) drugs are used in the treatment of various psychiatric disorders in children and adolescents. There is a lack of information about the efficacy and safety of antipsychotics in young people. Much of the information available is extrapolated from adult studies; in particular, little is known about the long-term effects of these drugs on the development of the central nervous system. Over the last two decades, typical antipsychotics have largely been replaced by atypical antipsychotics. With this increase in use of atypical antipsychotic drugs, there has been growing concern about the appropriate use of these drugs and the fact that they appear to be associated with metabolic abnormalities such as weight gain, diabetes and related cardiovascular effects. This paper provides a review of current practice and evidence based use of antipsychotic drugs in children.