Risk Y-haplotypes and pathogenic variants of Arab-ancestry boys with autism by an exome-wide association study.

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.

Co-inheritance of alpha globin gene deletion lowering serum iron level in female beta thalassemia patients.

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 ß-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 ß-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 (-α3.7/-α3.7, or --Fil/αα or --MED/αα or - (α) 20.5/αα) or double heterozygosity (- -/-α3.7) 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.

Optimal pcr primers for rapid and accurate detection of Aspergillus flavus isolates.

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.

Phenomics and genomic features of Enterococcus avium IRMC1622a isolated from a clinical sample of hospitalized patient.

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.

The Potential of Dutasteride for Treating Multidrug-Resistant Candida auris Infection.

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.

Genomic Insights into Virulence Factors and Multi-Drug Resistance in Clostridium perfringens IRMC2505A.

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.

Exome-wide analysis identify multiple variations in olfactory receptor genes (OR12D2 and OR5V1) associated with autism spectrum disorder in Saudi females.

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.

Mining the nanotube-forming Bacillus amyloliquefaciens MR14M3 genome for determining anti-Candida auris and anti-Candida albicans potential by pathogenicity and comparative genomics analysis.

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.

Genomic Landscape of Multidrug Resistance and Virulence in Enterococcus faecalis IRMC827A from a Long-Term Patient.

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.

Integration of Transcriptome and Exome Genotyping Identifies Significant Variants with Autism Spectrum Disorder.

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.

Celomic Fluid: Laboratory Workflow for Prenatal Diagnosis of Monogenic Diseases.

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.

Exome array identifies functional exonic biomarkers for pediatric dental caries.

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.

Review on the current use of antipsychotic drugs in children and adolescents.

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.

Emerging Status of Multidrug-Resistant Bacteria and Fungi in the Arabian Peninsula.

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.

Fetal Nucleated Red Blood Cells Preferable Than Cell-Free Fetal DNA for Early Determination of Gender Among Invasive and Non-Invasive Source Using Novel Four Genes Multiplex PCR.

BACKGROUND: 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.

Medication Errors in Secondary Care Hospitals in Kuwait: The Perspectives of Healthcare Professionals.

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.

Genetics, pathophysiology, diagnosis, treatment, management, and prevention of migraine.

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.

Gut microbiota metabolites in autistic children: An epigenetic perspective.

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.

Identification and Antibacterial Characterization of Endophytic Fungi from Artemisia sieberi.

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 µg/mL and 12.5 to 50 µg/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.

Whole-Genome Sequencing Reveals Exonic Variation of ASIC5 Gene Results in Recurrent Pregnancy Loss.

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_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 (ASIC5Saudi), in two families confirm the ASIC5 gene association with RPL and can be fatal to the fetus.