Search

The pervasiveness of microplastics (MPs) in terrestrial and aquatic ecosystems has become a significant environmental concern in recent years. Because of their slow rate of disposal, MPs are ubiquitous in the environment. As a consequence of indiscriminate use, landfill deposits, and inadequate recycling methods, MP production and environmental accumulation are expanding at an alarming rate, resulting in a range of economic, social, and environmental repercussions. Aquatic organisms, including fish and various crustaceans, consume MPs, which are ultimately consumed by humans at the tertiary level of the food chain. Blocking the digestive tracts, disrupting digestive behavior, and ultimately reducing the reproductive growth of entire living organisms are all consequences of this phenomenon. In order to assess the potential environmental impacts and the resources required for the life of a plastic product, the importance of life cycle assessment (LCA) and circularity is underscored. MPs-related ecosystem degradation has not yet been adequately incorporated into LCA, a tool for evaluating the environmental performance of product and technology life cycles. It is a technique that is designed to quantify the environmental effects of a product from its inception to its demise, and it is frequently employed in the context of plastics. The control of MPs is necessary due to the growing concern that MPs pose as a newly emergent potential threat. This is due to the consequences of their use. This paper provides a critical analysis of the formation, distribution, and methods used for detecting MPs. The effects of MPs on ecosystems and human health are also discussed, which posed a great challenge to conduct an LCA related to MPs. The socio-economic impacts of MPs and their management are also discussed. This paper paves the way for understanding the ecotoxicological impacts of the emerging MP threat and their associated issues to LCA and limits the environmental impact of plastic.

Lignocellulosic biomass (LCB) in the form of agricultural, forestry, and agro-industrial wastes is globally generated in large volumes every year. The chemical components of LCB render them a substrate valuable for biofuel production. It is hard to dissolve LCB resources for biofuel production because the lignin, cellulose, and hemicellulose parts stick together rigidly. This makes the structure complex, hierarchical, and resistant. Owing to these restrictions, the junk production of LCB waste has recently become a significant worldwide environmental problem resulting from inefficient disposal techniques and increased persistence. In addition, burning LCB waste, such as paddy straws, is a widespread practice that causes considerable air pollution and endangers the environment and human existence. Besides environmental pollution from LCB waste, increasing industrialization has resulted in the production of billions of tons of dyeing wastewater from several industries, including textiles, pharmaceuticals, tanneries, and food processing units. The massive use of synthetic dyes in various industries can be detrimental to the environment due to the recalcitrant aromatic structure of synthetic dyes, similar to the polymeric phenol lignin in LCB structure, and their persistent color. Synthetic dyes have been described as possessing carcinogenic and toxic properties that could be harmful to public health. Environmental pollution emanating from LCB wastes and dyeing wastewater is of great concern and should be carefully handled to mitigate its catastrophic effects. An effective strategy to curtail these problems is to learn from analogous systems in nature, such as termites, where woody lignocellulose is digested by wood-feeding termites and humus-recalcitrant aromatic compounds are decomposed by soil-feeding termites. The termite gut system acts as a unique bioresource consisting of distinct bacterial species valued for the processing of lignocellulosic materials and the degradation of synthetic dyes, which can be integrated into modern biorefineries for processing LCB waste and bioremediation applications for the treatment of dyeing wastewaters to help resolve environmental issues arising from LCB waste and dyeing wastewaters. This review paper provides a new strategy for efficient management of recalcitrant pollutants by exploring the potential application of termite gut bacteria in biorefinery and bioremediation processing.

This study investigated the impact of wheat processing methods (wheat flour vs wheat pellets) on the growth performance, serum biochemical parameters, and rumen microbiome composition in sheep. Results indicated that feeding of wheat flour resulted in significantly higher terminal weight and average daily gain (P < 0.05) and lower cholesterol and ALP04 levels (P < 0.05) in sheep compared to those fed wheat pellets. Analysis of 16s rDNA high-throughput sequencing data revealed significantly higher microbial richness (Chao1 index) in the rumen of sheep fed wheat flour (P < 0.05), even though the phylum-level composition dominated by Firmicutes, Bacteroidetes, and Proteobacteria was similar in both groups of sheep. Notably, sheep fed wheat flour were found to have a significantly higher relative abundance of Bacteroidetes (P < 0.05). At the genus level, Succinivibrionaceae&#95;UCG-001 and Prevotella&#95;1 were significantly more abundant in the rumen of sheep fed wheat flour (P < 0.05). Correlation analysis identified that both terminal weight and average daily gain were positively correlated with ruminal abundance of Bacteroidetes and Prevotella&#95;1, while ALP04 was negatively correlated with the abundance of these taxa. Functional prediction using PICRUSt2 indicated enrichment of pathways related to the ABC-type glycerol-3-phosphate transport system, and periplasmic components in both wheat flour and pellet fed sheep. Overall, these findings suggest that dietary wheat flour modulates rumen microbiota composition, and improves growth performance in sheep., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Flubendiamide (FBD) is a novel diamide insecticide extensively used with potential human health hazards. This research aimed to examine the effects of FBD on PrEC prostate epithelial cells, including Oxidative stress, pro-inflammatory responses, modifications in the expression of oncogenic and suppressor miRNAs and their target proteins, disruption of the cell cycle, and apoptosis. Additionally, the research investigated the potential alleviative effect of T-SeNPs, which are selenium nanoparticles biosynthesized by Trichoderma aureoviride, against the toxicity induced by FBD. Selenium nanoparticles were herein synthesized by Trichoderma aureoviride. The major capping metabolites in synthesized T-SeNPs were Isochiapin B and Quercetin 7,3',4'-trimethyl ether. T-SeNPs showed a spherical shape and an average size between 57 and 96.6 nm. FBD exposure (12 μM) for 14 days induced oxidative stress and inflammatory responses via overexpression of NF-κB family members. It also distinctly caused upregulation of miR-221, miR-222, and E2F2, escorted by downregulation of miR-17, miR-20a, and P27 kip1 . FBD encouraged PrEC cells to halt at the G 1 /S checkpoint. Apoptotic cells were drastically increased in FBD-treated sets. Treatment of T-SeNPs simultaneously with FBD revealed its antioxidant, anti-inflammatory, and antitumor activities in counteracting FBD-induced toxicity. Our findings shed light on the potential FBD toxicity that may account for the neoplastic transformation of epithelial cells in the prostate and the mitigating activity of eco-friendly synthesized T-SeNPs., 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 © 2024 Elsevier Ltd. All rights reserved.)

Background: The present study aimed to investigate the impact of the light-emitting diode (LED) green light alone or in combination with melatonin on pecking-related hormone regulation during incubation under normal and under hormonal stress conditions in breeder eggs. This study was divided into 2 experiments: In the first experiment effect of LED green light incubation on pecking-related hormones under normal conditions, on Hy-line brown (low pecking phenotype) and Roman pink (high pecking phenotype) eggs were tested. The 296 eggs of each strain were divided into two groups: LED green light incubation and dark incubation (control), each containing four replicates (37 eggs/replicate). The second experiment was conducted to evaluate the effect of LED green light incubation alone or in combination with melatonin under hormonal stress conditions on Roman pink eggs. A total of 704 Roman pink eggs were taken and divided into four groups, each consisting of 176 eggs. Each group was further divided into 2 subgroups, LED green light-regulated incubation and dark incubation with 88 eggs per subgroup, having 4 replicates of 22 eggs each. The groups were as follows: corticosterone solution injection (CI), corticosterone + melatonin mixed solution injection (CMI), Phosphate buffer solution injection (PI), and no injection (UI)., Results: Results of the first experiment revealed a higher level of serotonin hormone and lower corticosterone hormone in Hy-Line brown embryos compared to Roman pink embryos during dark incubation. The LED green light incubation significantly (P < 0.05) increased the level of 5-HT while decreasing the CORT level in Roman pink embryos indicating its regulatory effect on pecking-related hormones. Results of the second experiment showed that LED green light incubation significantly (P < 0.05) alleviated the CORT-induced hyperactivity of plasma 5-HT in Roman pink embryos. Furthermore, Melatonin (MLT) injection and LED green light together significantly (P < 0.05) reduced the hormonal stress caused by corticosterone injection in the eggs., Conclusions: Overall, the LED green light regulatory incubation demonstrated a regulatory effect on hormones that influence pecking habits. Additionally, when coupled with MLT injection, it synergistically mitigated hormonal stress in the embryos. So, LED green light incubation emerged as a novel method to reduce the damaging pecking habits of poultry birds., (© 2024. The Author(s).)

The Middle Eastern prevalence of sickle cell anemia, a genetic disorder that affects red blood cells, necessitates additional research. On a molecular level, we sought to identify and sort the oral microbiota of healthy individuals and those with sickle cell anemia. Furthermore, it is crucial to comprehend how changes in the genetic makeup of the oral microbiota impact the state of sickle cell anemia. Using next-generation sequencing, the 16S rRNA amplicon was examined using saliva samples from 36 individuals with sickle cell anemia and healthy individuals. These samples were obtained from sickle cell anemia patients (18 samples) and healthy control participants (controls, 18 samples). Various analyses are conducted using bioinformatic techniques to identify distinct species and their relative abundance. Streptococcus , followed by Fusobacterium nucleatum , Prevotella , and Veillonella were the most prevalent genera of bacteria in the saliva of the SCA and non-SCA individuals according to our findings. Rothia mucilaginosa , Prevotella scoposa , and Veillonella dispar species were the dominant species in both sickle cell anemia and non-sickle cell anemia subjects. Streptococcus salivarius , Actinomyces graevenitzii , Actinomyces odontolyticus , and Actinomyces georgiae spp. were the most prevalent bacterial spp. in the studied SCA cases. The sequencing of the 16S rRNA gene yielded relative abundance values that were visualized through a heatmap analysis. Alterations in the oral microflora's constitution can significantly affect the susceptibility of sickle cell anemia patients to develop more severe health complications. Salivary diagnosis is a potential tool for predicting and preventing oral microbiome-related diseases in the future.

Diabetic wounds require a multifactorial approach because several factors are involved in its occurrence. Herein we investigated whether transplantation of hyaluronic acid (HA) in combination with menstrual blood derived stem cells (MenSCs) could promote healing in diabetic rats. Thirty days after induction of diabetes, sixty animals were randomly planned into four equal groups: the untreated group, HA group, MenSC group, and HA+MenSC group. Sampling was done for histological, molecular, and tensiometrical assessments. Our results indicated that the wound contraction rate, volumes of new epidermis and dermis, collagen density, as well as tensiometrical parameter were considerably increased in the treatment groups compared to the untreated group and these changes were more obvious in the HA+MenSC ones. In addition, the expression levels of TGF-β and VEGF genes were significantly upregulated in treatment groups in comparison with the untreated group and were greater in the HA+MenSC group. This is while expression levels of TNF-α and IL-1β genes were more considerably downregulated in the HA+MenSC group than the other groups. We concluded that the combined use of HA and MenSCs has more effects on diabetic wound healing., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest associated with this study., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Increasing antimicrobial resistance to the action of existing antibiotics has prompted researchers to identify new natural molecules with antimicrobial potential. In this study, a green system was developed for biosynthesizing gold nanoparticles (BAuNPs) using sage ( Salvia officinalis L.) leaf extract bioconjugated with non-toxic, eco-friendly, and biodegradable chitosan, forming chitosan/gold bioconjugates (Chi/BAuNPs). Characterization of the BAuNPs and Chi/BAuNPs conjugates takes place using transmission electron microscopy (TEM), X-ray spectra, Fourier transform infrared (FT-IR) spectroscopy, and zeta potential (Z-potential). The chemical composition of S. officinalis extract was evaluated via gas chromatography/mass spectrometry (GC/MS). This study evaluated the antioxidant and antimicrobial activities of human pathogenic multidrug-resistant (MDR) and multisensitive (MS) bacterial isolates using the agar diffusion method. Chi/BAuNPs showed inhibition of the MDR strains more effectively than BAuNPs alone as compared with a positive standard antibiotic. The cytotoxicity assay revealed that the human breast adenocarcinoma cancer cells (MCF7) were more sensitive toward the toxicity of 5-Fu + BAuNPs and 5-Fu + Chi/BAuNPs composites compared to non-malignant human fibroblast cells (HFs). The study shows that BAuNPs and Chi/BAuNPs, combined with 5-FU NPs, can effectively treat cancer at concentrations where the free chemical drug (5-Fu) is ineffective, with a noted reduction in the required dosage for noticeable antitumor action.

Brown macroalgae are a rich source of fucoidans with many pharmacological uses. This research aimed to isolate and characterize fucoidan from Dictyota dichotoma var. dichotoma (Hudson) J.V. Lamouroux and evaluate in vitro its antioxidant and antitumor potential. The fucoidan yield was 0.057 g/g algal dry wt with a molecular weight of about 48.6 kDa. In terms of fucoidan composition, the sulfate, uronic acid, and protein contents were 83.3 ± 5.20 mg/g fucoidan, 22.5 ± 0.80 mg/g fucoidan, and 26.1 ± 1.70 mg/g fucoidan, respectively. Fucose was the primary sugar component, as were glucose, galactose, mannose, xylose, and glucuronic acid. Fucoidan exhibited strong antioxidant potential that increased by more than 3 times with the increase in concentration from 0.1 to 5.0 mg/mL. Moreover, different concentrations of fucoidan (0.05-1 mg/mL) showed their ability to decrease the viability of Ehrlich ascites carcinoma cells in a time-dependent manner. These findings provided a fast method to obtain an appreciable amount of natural fucoidan with established structural characteristics as a promising compound with pronounced antioxidant and anticancer activity.

Polyalthia longifolia var. angustifolia Thw. (Annonaceae), is a famous traditional medicinal plant in Asia. Ample data specifies that the medicinal plant P. longifolia has anticancer activity; however, the detailed mechanisms of action still need to be well studied. Recent studies have revealed the cytotoxicity potential of P. longifolia leaf against HeLa cells. Therefore, the current study was conducted to examine the regulation of miRNAs in HeLa cancer cells treated with the standardized P. longifolia methanolic leaf extract (PLME). The regulation of miRNAs in HeLa cancer cells treated with the standardized PLME extract was studied through Illumina, Hi-Seq. 2000 platform of Next-Generation Sequencing (NGS) and various in silico bioinformatics tools. The PLME treatment regulated a subset of miRNAs in HeLa cells. Interestingly, the PLME treatment against HeLa cancer cells identified 10 upregulated and 43 downregulated ( p < 0.05) miRNAs associated with apoptosis induction. Gene ontology (GO) term analysis indicated that PLME induces cell death in HeLa cells by inducing the pro-apoptotic genes. Moreover, the downregulated oncomiRs modulated by PLME treatment in HeLa cells were identified, targeting apoptosis-related genes through gene ontology and pathway analysis. The LC-ESI-MS/MS analysis identified the presence of Vidarabine and Anandamide compounds that were previously reported to exhibit anticancer activity. The findings of this study obviously linked the cell cytotoxicity effect of PLME treatment against the HeLa cells with regulating various miRNAs expression related to apoptosis induction in the HeLa cells. PLME treatment induced apoptotic HeLa cell death mechanism by regulating multiple miRNAs. The identified miRNAs regulated by PLME may provide further insight into the mechanisms that play a critical role in cervical cancer, as well as novel ideas regarding gene therapeutic strategies., 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 Vijayarathna, Oon, Al-Zahrani, Abualreesh, Chen, Kanwar, Sahreen, Ghazanfar, Adnan and Sasidharan.)

Multiple sclerosis (MS) is a chronic, autoimmune condition that primarily affects the myelin sheath covering the neurons of the central nervous system, including those of the brain and spinal cord. Although the etiology is not completely understood, various factors, such as genetic infections and environmental background, play a role in the pathogenesis. Repeated active episodes of MS characterized with marked inflammation results in the scarring of particular nerve segments, and eventually results in functional impairment over a period of time. Based on the clinical course of the disease, four clinical types of MS have been identified, with the relapsing-remitting type being the commonest. MS is known to occur more commonly in females in the age group of 20-40 years. Dysarthria, fatigue, muscle spasm, and numbness are the common presenting symptoms of MS. Diagnosis is generally achieved with MRI brain scans, showing demyelination plaques and lumbar puncture. Treatment of MS's acute phase includes high doses of corticosteroids; whereas preventive treatment of MS includes the prescription of immunosuppressive therapy, including biologics. A large group of MS patients present with oral manifestations, including dysphagia, dysarthria, temporomandibular joint (TMJ) disturbances, facial palsy, and chronic periodontal diseases. Other typical oral manifestations seen in MS patients include trigeminal neuralgia, paresthesia, or orofacial pain. Dental treatment and following drug prescription needs to be tailored to each patient, as there is a possibility of drug interactions. This paper presents a comprehensive, updated review of MS, with emphasis on oral manifestations and dental considerations. Additionally, it presents a case of a 40-year-old female diagnosed with MS that was presented to a dental hospital. The report discusses the oral manifestations and dental management.

This study aims to explore the functional role of Myoz2 in myoblast differentiation, and elucidate the potential factors interact with Myoz2 in promoter transcriptional regulation. The temporal-spatial expression results showed that the bovine Myoz2 gene was highest expressed in longissimus dorsi, and in individual growth stages and myoblast differentiation stages. Knockdown of Myoz2 inhibited the differentiation of myoblast, and negative effect of MyoD, MyoG, MyH and MEF2A expression on mRNA levels. Subsequently, the promoter region of bovine Myoz2 gene with 1.7 Kb sequence was extracted, and then it was set as eight series of deleted fragments, which were ligated into pGL3-basic to detect core promoter regions of Myoz2 gene in myoblasts and myotubes. Transcription factors MyoD and MyoG were identified as important cis-acting elements in the core promoter region (-159/+1). Also, it was highly conserved in different species based on dual-luciferase analysis and multiple sequence alignment analysis, respectively. Furthermore, a chromatin immunoprecipitation (ChIP) analysis combined with site-directed mutation and siRNA interference and overexpression confirmed that the combination of MyoD and MyoG occurred in region -159/+1, and played an important role in the regulation of bovine Myoz2 gene. These findings explored the regulatory network mechanism of Myoz2 gene during the development of bovine skeletal muscle., Competing Interests: Declaration of Competing Interest The authors have declared that no competing interest exists., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Urinary tract infection is among the greatest prevalent infections, and it is also one of the most challenging diseases to treat because there are germs that are resistant to several drugs. Antibiotics are typically provided as the treatment; however, there is a disparity in the type of antibiotic that was being prescribed, the amount of the dosage, and the length of time that patients were required to take antibiotics, which led to the creation of multidrug-resistant infections. The objective of this research is to prescribe Fosfomycin treatment for the infection brought by the Escherichia coli bacterium and to determine whether or not it is effective. Throughout the course of this research, the antimicrobial drugs fosfomycin were factored in the equation at various points. The patients who had exhibited symptoms of urinary tract infection provided their urine for the purpose of giving a sample for the studies, which were carried out on them. The results of these studies showed that there were Fosfomycin antimicrobials that were successful in disrupting the E. coli bacteria, and the least inhibitory concentration (MIC) required for the pathogen to be vulnerable was quite low. In addition, administration of fosfomycin intravenously considerably lowers both the bacterial load and the inflammatory infiltration in the kidney and bladder, which helps to preserve the structural integrity of the kidney., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Estrogen circulating in blood has been proved to be a strong biomarker for breast cancer. A β-glucuronidase enzyme (GUS) from human gastrointestinal tract (GIT) microbiota including probiotics has significant involvement in enhancing the estrogen concentration in blood through deconjugation of glucuronidated estrogens. The present project has been designed to explore GIT microbiome-encoded GUS enzymes (GUSOME) repertoire in normal human and breast cancer patients. For this purpose, a total of nineteen GUS enzymes from human GIT microbes, i.e., seven from healthy and twelve from breast cancer patients have been focused on. Protein sequences of enzymes retrieved from UniProt database were subjected to ProtParam, CELLO2GO, SOPMA (secondary structure prediction method), PDBsum (Protein Database summaries), PHYRE2 (Protein Homology/AnalogY Recognition Engine), SAVES v6.0 (Structure Validation Server), MEME version 5.4.1 (Multiple Em for Motif Elicitation), Caver Web server v 1.1, Interproscan and Predicted Antigenic Peptides tool. Analysis revealed the number of amino acids, isoelectric point, extinction coefficient, instability index and aliphatic index of GUS enzymes in the range of 586−795, 4.91−8.92, 89,980−155,075, 25.88−40.93 and 71.01−88.10, respectively. Sub-cellular localization of enzyme was restricted to cytoplasm and inner-membrane in case of breast cancer patients’ bacteria as compared to periplasmic space, outer membrane and extracellular space in normal GIT bacteria. The 2-D structure analysis showed α helix, extended strand, β turn and random coil in the range of 27.42−22.66%, 22.04−25.91%, 5.39−8.30% and 41.75−47.70%, respectively. The druggability score was found to be 0.05−0.45 and 0.06−0.80 in normal and breast cancer patients GIT, respectively. The radius, length and curvature of catalytic sites were observed to be 1.1−2.8 Å, 1.4−15.9 Å and 0.65−1.4, respectively. Ten conserved protein motifs with p < 0.05 and width 25−50 were found. Antigenic propensity-associated sequences were 20−29. Present study findings hint about the use of the bacterial GUS enzymes against breast cancer tumors after modifications via site-directed mutagenesis of catalytic sites involved in the activation of estrogens and through destabilization of these enzymes.

Introduction: Hematological parameters are critical in disease diagnosis, management, and monitoring; however, complete blood count (CBC) reference intervals vary across populations. The aim of the current study was to provide the reference ranges of hematological parameters/indices in the healthy adult Saudi population., Methods: A multicenter retrospective cross-sectional study was conducted with a sample of employees who were screened pre-employment from January 2015 to December 2019, at tertiary care hospitals in three regions. Demographic and CBC data were extracted from the electronic health system. The 2.5 th and 97.5 th percentiles were used to determine the reference intervals., Results: Of a total of 1,388 participants, 53.82% were male. The majority 96% was less than 40 years old, and 85% were from the Central region. Gender-related differences were observed for the RBC count, Hb, HCT, MCV, MCH, MCHC, and the platelet count. Age-related differences were observed for the RBC, Hb, HCT, and eosinophils. The WBC parameters did not differ by gender or age categories. Region-related differences were observed for the RBC, hemoglobin, HCT, MCV, WBC, and basophils. The platelet count was higher in the female group, the age group 40 years and above, and in the Western region. The prevalence of anemia was high in the female group and the Eastern region. The overall neutropenia rate was 12.8%., Conclusion: The data from this study provide hematological parameter reference ranges for the adult Saudi population by gender, age, and region. Gender and age-related differences were observed for the hematological parameters. Anemia was more frequent in the female group and the Eastern region. Caution must be taken when comparing or interpreting results from different age groups, gender, region of origin, and ethnicity., 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 © 2022 Shaheen, Rehan, Moghairi, Gmati, Damlaj, Salama, Rather, Mendoza, Alanazi, Al Ahmari, Al Zahrani, Al-Hejazi and Alaskar.)

Micro RNAs (miRNAs) are short, non-coding RNAs (Ribonucleic acids) with regulatory functions that could prove useful as biomarkers for asthma diagnosis and asthma severity-risk stratification. The objective of this systematic review is to identify panels of miRNAs that can be used to support asthma diagnosis and severity-risk assessment. Three databases (Medline, Embase, and SCOPUS) were searched up to 15 September 2020 to identify studies reporting differential expression of specific miRNAs in the tissues of adults and children with asthma. Studies reporting miRNAs associations in animal models that were also studied in humans were included in this review. We identified 75 studies that met our search criteria. Of these, 66 studies reported more than 200 miRNAs that are differentially expressed in asthma patients when compared to non-asthmatic controls. In addition, 16 studies reported 17 miRNAs that are differentially expressed with differences in asthma severity. We were able to construct two panels of miRNAs that are expressed in blood and can serve as core panels to further investigate the practicality and efficiency of using miRNAs as non-invasive biomarkers for asthma diagnosis and severity-risk assessment, respectively.

Cytochrome P450s (P450ome) constitute an extended superfamily group of heme-thiolate enzymes identified in all biological domains. P450omes play a critical role in the oxidation of steroids and fatty acids, xenobiotic degradation of hydrophobic compounds, biosynthesis of hormones, and primary and secondary metabolism in organisms. Aspergillus species are among the most economically important fungal organisms in human medicine, industry, and agriculture worldwide. Exploring insight on the genome-wide annotations of cytochrome P450s in Aspergillus species is necessary for their biosynthetic applications. In this present study, we report the identification of 306 cytochrome P450s and their robust profiling in eight notable Aspergillus species ( A. carbonarius , A. clavatus , A. flavus , A. fumigatus , A. nidulans , A. niger , A. oryzae, and A. terreus ). Based on the evolutionary relationship, the Aspergillus P450s families clustered into 15 clades, with clades V, I, and XIII recording higher percentages (17.3%, 15.00%, and 14.71%, respectively) of Cyp families. Cyps were classified into 120 families 64 clans, and their putative functions were also elucidated. P450s were predicted to be located in 13 subcellular components, but the endoplasm reticulum was the dominant location across the eight Aspergillus species. Cyps genes of Aspergillus species were associated with seven secondary metabolism-related gene clusters. Elucidating the genome-wide annotations of P450s enzymes in Aspergillus species will form vital potential biotechnological tools that could be harnessed for industrial, pharmaceutical, and agricultural use.

Essential oils (EOs) are chemical products produced by odoriferous glands from a variety of plants. These essential oils have many health benefits: antiseptic, anti-inflammatory and antimicrobial activities. So due to these medicinal properties, the present study was designed to analyze essential oils of Thymus zygis L. and Thymus willdenowii Boiss. for their chemical composition and biological activities. These two thyme species were collected from the region of Ifrane, Middle Atlas of Morocco. The EO was obtained by hydrodistillation, and the yields were 5.25% for T. zygis and 3.00% for T. willdenowii . The chemical composition of the EOs was analyzed by gas chromatography coupled with mass spectrometry (GC-MS), and the results showed that T. zygis EO is dominated by carvacrol (52.5%), o- cymene (23.14%), and thymol (9.68%), while the EO of T. willdenowii contains germacrene D (16.51%), carvacrol (16.19%), and geranyl acetate (8.35%) as major compounds. The antioxidant activity assessed by Diphenylpicrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays revealed that both EOs have excellent antioxidant activities; by DPPH it resulted in IC 50 = 6.13 ± 0.11 for T. zygis and 6.78 ± 0.3 µg/mL for T. willdenowii , while the one by FRAP yielded EC 50 = 2.46 ± 0.01 ( T. zygis ) and 5.17 ± 0.2 ( T. willdenowii ) µg/mL. The antimicrobial activity of the two essential oils was evaluated against six bacterial strains and five fungal strains by the disk diffusion method to determine the Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and Minimum Fungicidal Concentration (MFC). The EOs revealed variable antimicrobial activities against the different tested microbial strains and showed strong antimicrobial activities, even against strains known as multi-resistant to antibiotics ( Acinetobacter baumannii ) at low concentrations (2 µL/mL). T. zygis EO showed the most powerful activity against all the studied bacteria, while that of T. willdenowii recorded moderate activity when tested against Shigella dysenteriae and Salmonella Typhi. With inhibition diameters that vary between 75 mm and 84 mm for concentrations of 2 µL/mL up to 12 µL/mL, S. aureus was shown to be the most sensitive to T. zygis EO. For the antifungal activity test, T. zygis EO showed the best inhibition diameters compared to T. willdenowii EO. These results showed that T. zygis EO has more powerful antioxidant and antimicrobial activities than T. willdenowii EO, therefore, we deduce that thyme EOs are excellent antioxidants, they have strong antimicrobial properties, and may in the future represent new sources of natural antiseptics that can be used in pharmaceutical and food industry.

The study of bioactive molecules of natural origin is a focus of current research. Thymus algeriensis and Artemisia herba-alba are two medicinal plants widely used by the Moroccan population in the traditional treatment of several pathologies linked to inflammation. This study aimed to evaluate the single and combined antioxidant, anti-inflammatory and analgesic effects of the essential oils extracted from these two medicinal plants, and also their potential toxicity. Essential oils were extracted using hydro-distillation in a Clevenger-type apparatus. The antioxidant activity was evaluated by two methods: the scavenging of the free radical DPPH, and the reduction in iron. Anti-inflammatory activity was evaluated by evaluating the edema development induced by carrageenan injecting, while the analgesic power was evaluated according to the number of abdominal contortions induced by the intraperitoneal injection of acetic acid (0.7%). The acute oral toxicity was performed to assess the potential toxicity of the studied EOs, followed by an analysis of the blood biochemical parameters. The results of the two antioxidant tests indicated that our extract mixture exhibits good iron reduction capacity and very interesting DPPH free radical scavenging power, with an IC 50 of around 4.38 ± 0.98 μg/mL higher than that of the benchmark antioxidant, BHT. The anti-inflammatory test demonstrated that the mixture administered orally at a dose of 150 mg/kg has a better activity, exceeding that of 1% Diclofenac, with a percentage of maximum inhibition of the edema of 89.99 ± 4.08. The number of cramps in the mice treated with the mixture at a dose of 150 mg/kg is significantly lower (29.80 ± 1.92) than those of the group treated with Tramadol (42.00 ± 2.70), respectively. The toxicity results show no signs of toxicity with an LD 50 greater than 150 mg/Kg. These interesting results show that the two plants' EOs had an important anti-inflammatory, analgesic, and antioxidant activity, and also a powerful synergistic effect, which encourages further in-depth investigations on their pharmacological proprieties.

Background: To evaluate the effect of screening for sepsis using an electronic sepsis alert vs. no alert in hospitalized ward patients on 90-day in-hospital mortality., Methods: The SCREEN trial is designed as a stepped-wedge cluster randomized controlled trial. Hospital wards (total of 45 wards, constituting clusters in this design) are randomized to have active alert vs. masked alert, 5 wards at a time, with each 5 wards constituting a sequence. The study consists of ten 2-month periods with a phased introduction of the intervention. In the first period, all wards have a masked alert for 2 months. Afterwards the intervention (alert system) is implemented in a new sequence every 2-month period until the intervention is implemented in all sequences. The intervention includes the implementation of an electronic alert system developed in the hospital electronic medical records based on the quick sequential organ failure assessment (qSOFA). The alert system sends notifications of "possible sepsis alert" to the bedside nurse, charge nurse, and primary medical team and requires an acknowledgment in the health information system from the bedside nurse and physician. The calculated sample size is 65,250. The primary endpoint is in-hospital mortality by 90 days., Discussion: The trial started on October 1, 2019, and is expected to complete patient follow-up by the end of October 2021., Trial Registration: ClinicalTrials.gov NCT04078594 . Registered on September 6, 2019., (© 2021. The Author(s).)

Objective: This study was done to determine UI prevalence among women in Saudi Arabia and identify the associated risk factors., Patients and Methods: This cross-sectional study was conducted from January 2020 to September 2020 in Saudi women who came to the Urology Department at King Khalid Hospital, Majmaah, Saudi Arabia. In the age group of 20 to 50 years, Saudi women who are not seriously ill or pregnant or in the postnatal period or diagnosed with pelvic organ prolapse were included as participants. A semi-structured questionnaire modified from the International Consultation Incontinence Questionnaire-Short Form was used to collect data on frequency, the severity, consequences, and impact of UI on quality of life. Data were analyzed by SPSS 23 (IBM, Armonk, NY, USA) with the calculation of mean and standard deviation for quantitative variables. Logistic regression analyses were applied to determine the predictors of UI., Results: A total of 451 participants were included in the final analysis. The mean age of the study population was 42.52 years (SD 11.75). Among risk factors, 45 (10%) had diabetes, 56 (12.4%) had hypertension, 36 (8%) had asthma, 80 (17.7%) had UTI/STDs. Out of 451 participants, 188 (41.7%) had urinary incontinence (UI). Sociodemographic characteristics and risk factors like family income, urinary and genital infections (UTI/STDs), pelvic/uterine prolapse, any other disease, and cough were found to have a statistically significant association with urinary incontinence (p-value <0.05)., Conclusions: The prevalence of UI was 41.7% among the study population. The various risk factors associated with UI are older age, parity, multiple vaginal deliveries, hypertension, history of asthma, and chronic cough. Poor health-seeking behavior was observed. Creating awareness and the need for early diagnosis with timely intervention is recommended.

Familial thrombocytosis (FT) is a rare hereditary haematological disorder characterised by increased platelet count, usually caused by germ-line mutations in thrombopoietin (THPO), myeloproliferative leukaemia virus oncogene (MPL) or Janus kinase 2 (JAK2) genes, and can be associated with increased risk of thrombosis. We aimed to determine the yield of diagnostic tests, assess treatment received and describe the clinical course of MPL-associated FT. We retrospectively reviewed all paediatric and adult haematology patients diagnosed with MPL-related FT, who were seen in our clinics from March 2013 to February 2021. Of 64 eligible patients, 26 (41%) were aged <14 years, while the remaining 38 (59%) patients were adults. The median (interquartile range) age at diagnosis was 20 (33·5) years. In all, 26 tribes were represented in this cohort of 64 patients, out of which 31 (48%) patients belonged to two tribes. A total of 60 patients (94%) had thrombocytosis on blood count. Additional genetic tests, including myelodysplastic syndrome (MDS) gene panel, Philadelphia gene breakpoint cluster region-Abelson (BCR-ABL) and JAK2, were carried out for 52 patients and only one patient was positive for JAK2 mutation. In all, 21 (33%) patients were prescribed aspirin and seven (11%) were prescribed hydroxyurea. Overall, 63 (98%) patients did not develop any thrombotic or haemorrhagic event. There was no significant association of MPL-mutated FT with thrombosis or haemorrhage., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Background: Little is known about characteristics of seasonal human coronaviruses (HCoVs) (NL63, 229E, OC43, and HKU1) after allogeneic stem cell transplantation (allo-HSCT)., Methods: This was a collaborative Spanish and European bone marrow transplantation retrospective multicenter study, which included allo-HSCT recipients (adults and children) with upper respiratory tract disease (URTD) and/or lower respiratory tract disease (LRTD) caused by seasonal HCoV diagnosed through multiplex polymerase chain reaction assays from January 2012 to January 2019., Results: We included 402 allo-HSCT recipients who developed 449 HCoV URTD/LRTD episodes. Median age of recipients was 46 years (range, 0.3-73.8 years). HCoV episodes were diagnosed at a median of 222 days after transplantation. The most common HCoV subtype was OC43 (n = 170 [38%]). LRTD involvement occurred in 121 episodes (27%). HCoV infection frequently required hospitalization (18%), oxygen administration (13%), and intensive care unit (ICU) admission (3%). Three-month overall mortality after HCoV detection was 7% in the whole cohort and 16% in those with LRTD. We identified 3 conditions associated with higher mortality in recipients with LRTD: absolute lymphocyte count <0.1 × 109/mL, corticosteroid use, and ICU admission (hazard ratios: 10.8, 4.68, and 8.22, respectively; P < .01)., Conclusions: Seasonal HCoV after allo-HSCT may involve LRTD in many instances, leading to a significant morbidity., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Non-T-cell depleted haploidentical hematopoietic stem cell transplantation (HaploSCT) is being increasingly used in acute lymphoblastic leukemia (ALL) with improving patient outcomes. We have recently reported that outcomes of adult patients (pts) with ALL in complete remission (CR) receiving HaploSCT are comparable to unrelated donor transplants. We now compared HaploSCT and matched sibling donor (MSD) transplants in pts with ALL., Aim: To assess transplantation outcomes of HaploSCT and MSD transplants in pts with ALL in CR., Methods: We retrospectively analyzed adult patients (≥ 18 years) with ALL who underwent their first allogeneic stem cell transplantation (alloSCT) in first or second CR between 2012 and 2018, either from a T cell replete Haplo or MSD donor, and whose data were reported to the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT). Multivariate analysis (MVA) adjusting for differences between the groups was performed using the Cox proportional hazards regression model. Propensity score matching was also performed to reduce confounding effects., Results: The analysis comprised 2304 patients: HaploSCT-413; MSD-1891. Median follow-up was 25 months. Median age was 37 (range 18-75) and 38 (18-76) years in HaploSCT and MSD, respectively. HaploSCT patients were transplanted more recently than those transplanted from MSD (2016 vs 2015, p < 0.0001). A higher rate of HaploSCT was in CR2 (33.4% vs 16.7%, p < 0.0001), respectively, and fewer received myeloablative conditioning (68% vs 83.2%, p < 0.0001). Cytomegalovirus (CMV) seropositivity was lower in HaploSCT patients (22% vs 28%, p = 0.01) and donors (27.1% vs 33%, p < 0.02), and a higher proportion of the HaploSCTs were performed using a bone marrow (BM) graft (46.2% vs 18.6%, p < 0.0001). The 2 groups did not differ with regard to gender, Karnofsky performance status score, ALL phenotype, Philadelphia chromosome (Ph) positivity and pre-alloSCT measurable residual disease (MRD). Graft versus host disease (GVHD) prophylaxis was mainly post-transplant cyclophosphamide (PTCy) based (92.7%) in the HaploSCT setting, while it was mostly pharmacologic in the setting of MSD (18.7% received ATG). Cumulative incidence of engraftment at day 60 was higher in MSD transplants compared to HaploSCT (98.7% vs 96.3%, p = 0.001), respectively. Day 180 incidence of acute (a) GVHD II-IV and III-IV was higher in HaploSCT vs. MSD: 36.3% vs 28.9% (p = 0.002 and 15.2% vs 10.5% (p = 0.005), respectively. Conversely, the 2-year chronic (c) GVHD and extensive cGVHD were 32% vs 38.8% (p = 0.009) and 11.9% vs 19.5% (p = 0.001) in HaploSCT vs MSD, respectively. Main causes of death were leukemia (31.8% vs 45%), infection (33.1% vs 19.7%) and GVHD (16.6% vs 19.7%) for HaploSCT and MSD, respectively. Two-year relapse incidence (RI), non-relapse mortality (NRM), leukemia-free survival (LFS), overall survival (OS) and GVHD-free, relapse-free survival (GRFS) were 26% vs 31.6%, 22.9% vs 13%, 51% vs 55.4%, 58.8% vs 67.4% and 40.6% vs 39% for HaploSCT and MSD, respectively. In the MVA, RI was significantly lower in HaploSCT in comparison with MSD, hazard ratio (HR) = 0.66 (95% CI 0.52-0.83, p = 0.004), while NRM was significantly higher, HR = 1.9 (95% CI 1.43-2.53, p < 0.0001). aGVHD grade II-IV and grade III-IV were higher in HaploSCT than in MSD HR = 1.53 (95% CI 1.23-1.9, p = 0.0002) and HR = 1.54 (95% CI 1.1-2.15, p = 0.011), respectively. Extensive cGVHD was lower in HaploSCT compared with MSD, HR = 0.61 (95% CI 0.43-0.88, p = 0.007), while total cGVHD did not differ significantly, HR = 0.94 (95% CI 0.74-1.18, p = 0.58). LFS, OS and GRFS did not differ significantly between the 2 transplant groups, HR = 0.96 (95% CI 0.81-1.14, p = 0.66); HR = 1.18 (95% CI 0.96-1.43, p = 0.11) and HR = 0.93 (95% CI 0.79-1.09, p = 0.37), respectively. These results were confirmed in a matched-pair analysis., Conclusions: Outcomes of adult patients with ALL in CR receiving alloSCT from haploidentical donors are not significantly different from those receiving transplants from MSD in terms of LFS, OS and GRFS.

Cigarette smoking is a major lifestyle factor leading to different human diseases. The DNA repair gene, thymine DNA glycosylase, is important to cell survival because it stops cells from becoming cancerous protecting/preventing DNA. Exposure to CS may induce genetic changes such as single nucleotide polymorphisms in DNA repair genes. Therefore, the purpose of this study was to investigate the genotype and allele distributions of four TDG SNPs with only smoking behavior in normal patients. Four TDG SNPs-rs4135066 (C/T), rs3751209 (A/G), rs1866074 (C/T), and rs1882018 (C/T) were analyzed by genotyping 235 and 239 blood samples collected from cigarette smokers and non-smokers, among the Saudi population. The results showed that TDG rs4135066 has a significant susceptibility effect observed in long-term smokers (>5 years; OR = 4.53; P = 0.0347) but not in short-term smokers (≤5 years) in contrast with non-smokers. Also, in smokers aged less than 29 years, the "CT," "TT," and "CT + TT" alleles of rs1882018 increased the risk of developing all diseases related to smoking by approximately 6, 4, and 5 times, respectively, in contrast with the ancestral "CC" homozygous allele. A comparison of the allele distributions of TDG SNPs in a Saudi population with those in other populations represented in the HapMap project showed that the genetic makeup of the Saudi Arabian population appears to differ from that of other ethnicities. Exceptions include the Yoruba people in Ibadan, Nigeria; those of Mexican ancestry in Los Angeles, California; the Luhya population in Webuye, Kenya; Gujarati Indians in Houston, Texas; and the Tuscan population in Italy, which showed similar allelic frequencies for rs3751209 compared to our Saudi population. In this ethnic, we have found a high variation in the distribution of the alleles and genotype frequencies on TDG gene. This variation on TDG SNP's with smoking could lead to increase the susceptibility to many diseases related to smoking habits in this population., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Preemptive therapy (PET) for cytomegalovirus (CMV) reactivation post allogeneic hematopoietic stem cell transplantation (SCT) was shown to decrease the incidence of CMV disease. However, the optimal PET threshold is elusive., Purpose of the Study: To examine the efficacy of PET initiation at a viral threshold of 1000 copies/mL (1560 IU/mL) in a patient population with high prevalence of CMV seropositive status., Patients and Methods: A single center retrospective review of patients that underwent allogeneic SCT was done., Results: A total of 195 allogeneic SCT recipients were included with median follow up of 18.1 (0.7-95.6) months. A total of 178 (91 %) of patients had a positive CMV PCR with median days to initial reactivation post SCT of 17 (1-1187); 129 patients had peak CMV titer < 1000 copies/mL (low titer) whereas the remaining 49 patients had a peak titer ≥ 1000 copies/mL (high titer). 120 (93 %) of patients with low titers cleared spontaneously with median time to clearance of 40 days (4-188). One patient in the high titer group developed CMV disease. At multivariable analysis; age at SCT HR 1.02 (1.004-1.04; 0.017), malignant vs. benign condition HR 9.4 (2.47-61; 0.0005) and cGVHD HR 0.37 (0.2-0.65; 0.0005) were significant for OS., Conclusions: CMV reactivation post SCT was very common in patients with high prevalence of seropositive status. A PET threshold of 1000 copies/mL (1560 IU/mL) appears desirable as it was associated with spontaneous clearance in over 90 % of patients while minimizing treatment related toxicity. Validation of these observations is warranted., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background and study aims  A reliable outcome measure is needed for bowel preparation quality during capsule endoscopy. Currently, no scales are adequately validated. Our objective was to update an existing small bowel preparation score, create a standardized training module, then determine its inter-rater and intra-rater reliability. Patients and methods  Modification to produce standardized scoring of an existing small bowel preparation score was performed followed by development of a training module and validation to create the new Korea-Canada (KODA) score. Twenty readers from a range of backgrounds, including capsule endoscopists, gastroenterology fellows, residents, medical students, and nurses rated bowel cleanliness in 25 capsule videos consisting of 1,233 images, in duplicate 4 weeks apart, after completing the training module. Sequential images selected in 5-minute intervals during small bowel transit were rated on a scale between 0-3 based on the amount of visualized mucosa and the degree of obstruction. Reliability was assessed using estimates of intraclass correlation coefficients (ICCs). Results  Intraclass correlation coefficients for inter-rater (ICC 0.81, 95 % CI 0.70-0.87) and intra-rater (ICC 0.92, 95 % CI 0.87-0.94) reliability were almost perfect among the 20 readers. Inter-rater reliability ranged between 0.72 (95 % CI 0.57-0.81) and 0.89 (95 % CI 0.79-0.93) for nurses and residents, respectively. Intra-rater reliability was greater than 0.90 for all groups except for nurses, which was still almost perfect (ICC 0.86, 95 % CI 0.79-0.90). Conclusions  Almost perfect inter-rater and intra-rater reliability was observed for the KODA score. This simple score could be used for future clinical trials after completion of the training module., Competing Interests: Competing interests Michael Sai Lai Sey – Received arms-length research grant from Pharmascience Inc. and educational grants from Cook Medical, Medtronic, and Olympus. All other authors declare that they have no conflict of interest.

Background: The occurrence of periodontitis is rather infrequent in children and adolescence and increases with age. We conducted this study because there have been few epidemiological studies on prevalence of periodontitis in children in Saudi Arabia., Objective: Determine the prevalence of periodontitis in high school children in Saudi Arabia., Design: Cross-sectional, using cluster and multistage sampling., Setting: High school children in Saudi Arabia., Participants and Methods: Periodontal examinations were conducted on a randomized sample of high school children between the ages 15 to 19 in Saudi Arabia. The study spanned from September 2012 to January 2016. Clinical examinations included measurements of the probing depth (PD) percentage of PD ≥4 mm per patient., Main Outcome Measures: The prevalence of periodontitis (PD ≥4 mm and CAL ≥1 mm), the mean percentage PD ≥4 mm, the mean percentage CAL ≥1 mm, plaque index (PI) and gingival index (GI)., Sample Size: 2435 high school students., Results: Of 2435 high school children in the sample, 209 students (8.6%) had periodontitis. The mean (standard deviation) for the PD was 0.59 (0.17) mm. Differences in percentage PD ≥4 mm and CAL ≥1 mm were greater in students with periodontitis ( P<.001). The prevalence of periodontitis was higher among non-Saudis, students who did not brush their teeth and did not visit their dentist regularly. In the bivariate analysis, periodontitis was positively associated with GI, PI, number of teeth extracted, mean percentage PD ≥4 mm, and mean PD. However, in the multivariate analysis, tooth brushing was the main factor protective against periodontitis (odds ratio: 0.62, 95% CI 0.42-0.92, P=.017)., Conclusion: Periodontitis prevalence was high compared with Western countries in a nationally representative sample of high school students in Saudi Arabia., Limitations: Partial mouth study design, which may underestimate the disease prevalence., Conflict of Interest: None.

We describe the clinical and genetic characteristics of multi-drug resistant tuberculosis (MDR-TB) in a family cluster in the western region of Kingdom of Saudi Arabia diagnosed between 2012 and 2016. All cases had risk factors for tuberculosis acquisition and they were not household contacts of the index case. Genetic analysis detected both MDR-TB and pre-extensively drug-resistant tuberculosis (pre-XDR TB) strains in the index case and confirmed tuberculosis transmission between two cases. Lack of early diagnosis of MDR-TB by molecular testing and lack of extended contact tracing contributed to the transmission of MDR-TB among this family cluster over four years., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Marginal zone lymphoma of the central nervous system (CNS MZL) is rare. The clinical features, treatment, and prognosis are not well characterized. We performed a multicenter retrospective study of CNS MZL. Twenty-six patients were identified: half with primary and half with secondary CNS involvement. The median age was 59 years (range 26-78), 62% female and 79% with ECOG performance status ≤ 1. The most common disease site was the dura (50%). Treatment was determined by the treating physician and varied substantially. After a median follow up of 1.9 years, the estimated 2-year progression-free (PFS) and overall survival (OS) rates were 59% and 80%, respectively. Secondary CNS MZL was associated with 2-year OS of 58%. CNS MZL is rare, but relative to other forms of CNS lymphoma, outcomes appear favorable, particularly among the subset of patients with dural presentation and primary CNS presentation., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

We analyzed HLA allele and haplotype frequencies from donors from the Eastern region of Saudi Arabia. A cross-sectional study was performed on 2405 bone marrow donors from the Eastern region. HLA typing was carried out by sequencing. The most common HLA allele groups were HLA-A*02:01:01G (11.08%), A*01:01:01G (10.40%), HLA-B*52:01:01G (8.79%), B*18:01:01G (8.07%), HLA-C*04:01:01G (17.88%), C*12:03:01G (10.23%), HLA-DRB1*10:01 (14.89%), DRB1*03:01:01G (14.10%), HLA-DQB1*02:01:01G (24.53%) and DQB1*05:01:01G (20.17%). The most frequent HLA-A ~ C ~ B ~ DRB1 ~ DQB1 haplotypes were HLA-A*01:03 ~ C*15:05:01G ~ B*73:01 ~ DRB1*10:01:01 ~ DQB1*05:01:01G (3.11%) and HLA-A*01:01:01G ~ C*12:02:01G ~ B*52:01:01G ~ DRB1*15:02:01 ~ DQB1*06:01:01G (2.25%). When comparing the allele and haplotype frequencies of the Eastern regions' population to those from the Central region we found significant differences in several allele frequencies including A*01:01:01G (P ≤ 0.0001), B*52:01:01G (P ≤ 0.0001), B*18:01:01G (P = 0.0001), C*12:03:01G (P < 0.0001), DRB1*10:01:01 (P < 0.0001) and DQB1*05:01:01G (P < 0.0001). Our data confirms genetic heterogeneity among the Saudi population., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Since 2004, the Kingdom of Saudi Arabia has pursued a policy of malaria elimination. The distribution of malaria at this time was constrained to regions located in the South Western part of the country. The present study aimed to understand the risk of malaria infection and factors associated with these events between March 2006 and August 2007 in one part of Aseer region., Methods: The study was carried out in Tihama Qahtan area in the far southeastern part of Aseer, historically the most malaria endemic area of this region. The area covers 54 villages served by three primary health care centres (Wadi Alhayah, Alfarsha and Albuqaa). Malaria cases were detected using passive case detection (PCD) at the three health centres for 18 months from March 2006, each positive case was investigated using patient and household level enquiries. In addition, four cross-sectional surveys in 12 villages were undertaken using rapid diagnostic tests within the catchments of each health centre coinciding with malaria transmission seasons., Results: Among 1840 individuals examined in the PCD survey, 49 (2.7%) were positive for malaria, most were Plasmodium falciparum cases and one was a P. vivax case. The majority of these infections were likely to have been acquired outside of the area and represent imported cases, including those from the neighboring region of Jazan. Among the 18 locally acquired cases, the majority were adult males who slept outdoors. 3623 individuals were screened during the cross-sectional surveys, 16 (0.44%) were positive and infections only detected during peak, potential transmission periods., Conclusion: There was evidence of local malaria transmission in the Tihama Qahtan area in 2006-2007, however prevalence and incidence of new infections was very low, making the future ambitions of elimination biologically feasible. The constant source of imported infections must be considered in the area's elimination ambitions, alongside strong behavioural community messages about sleeping outdoors unprotected and travel to malaria endemic areas outside the region.

Background: Response-adapted therapy in advanced classical Hodgkin lymphoma (cHL) using interim functional imaging (IFI) is under active investigation., Patients and Methods: We retrospectively examined patients with advanced cHL receiving 2 front-line regimens stratified by IFI results at our institution. Time to endpoint analysis was estimated using the method of Kaplan-Meier with log ranks. Cox regression modeling was computed for multivariable analysis., Results: A total of 124 patients with advanced cHL with a median follow up of 40.9 months were included. A total of 84 (67.7%) received ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), whereas the remaining 40 (32.3%) received ABVD/eBEACOPP (escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone). A positive IFI was seen in 36 (29%) patients. The corresponding 3-year progression free survival (PFS) stratified by IFI was 81.7% (95% confidence interval [CI], 70.1%-88.8%) versus 48.3% (95% CI, 30.4%-64.1%) (P < .0001) for patients with negative or positive scan, respectively. Escalation to eBEACOPP from ABVD following a positive IFI resulted in a significantly higher 3-year PFS at 58.7% (95% CI, 0.3-0.79) versus 39.7% (95% CI, 0.18-0.61) respectively (P = .00015). Overall survival (OS) was similar across the groups (P = .44) irrespective of therapy received. At multivariable analysis, IFI was the only predictor of PFS with a hazard ratio of 4.6 (95% CI, 1.9-10.8; P = .0008) whereas therapy escalation had a hazard ratio of 0.66 (95% CI, 0.14-3.4; P = .62)., Conclusion: IFI is an independent predictor of PFS in advanced cHL and can guide therapeutic decisions in the real world. Given the inferior outcome seen in patients with a positive IFI, novel approaches of therapy are warranted., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aim: To examine the outcome and prognostic factors for high risk patients with acute lymphoblastic leukemia/lymphoma (ALL/LBL) who underwent allogeneic hematopoietic stem cell transplantation (HCT) at our center during the period of 2010-2017., Methods: After due institutional review board approval, patients with high risk ALL/LBL post HCT were identified and included. All records were retrospectively collected. Time to event analysis was calculated from the date of HCT until event of interest or last follow up with Kaplan-Meir means. Cox regression model was used for multivariable analysis calculation., Results: A total of 69 patients were enrolled and examined with a median age of 21 (14-61). After a median follow up of 15 mo (2-87.3), the 2-year cumulative incidence of relapse, cumulative incidence of non-relapse mortality, progression free survival and overall survival (OS) were 34.1%, 10.9%, 54.9% and 62.8%, respectively. In a multivariable analysis for OS; acute graft vs host disease (GVHD) and chronic GVHD were significant with corresponding hazard ratio 4.9 (1.99-12; P = 0.0007) and 0.29 (0.1-0.67; P = 0.0044), respectively., Conclusion: Allogeneic-HCT for high risk ALL/LBL resulted in promising remissions particularly for patients with cGVHD., Competing Interests: Conflict-of-interest statement: There are no relevant conflicts of interest relevant to the conduct of this study.

Immune thrombocytopenic purpura (ITP) is a common hematological disease treated primarily by corticosteroids. The aim of the present study was to compare response rate between patients, underwent splenectomy vs. rituximab as second-line therapy. Adult patients diagnosed with ITP who did not respond to corticosteroids or relapsed during the period 1990-2014 were included in a quasi-experimental study. Categorical variables were compared using Fisher exact test. Response to treatment was compared using logistic regression. Data were analyzed using SAS V9.2. One-hundred and forty-three patients with ITP were identified through medical records. Of 62 patients treated, 30 (48.38%) required second-line therapy. 19 (63%) patients received rituximab, and 11 (37%) underwent splenectomy. Platelets at diagnosis were not different between study groups (p = 0.062). Splenectomy group patients were younger (p = 0.011). Response to second-line therapy showed no significant difference between two groups (OR 2.03, 95% CI (0.21-22.09), p = 0.549). Results did not show a statistically significant difference in platelet counts over time between treatment groups (p = 0.101). When used exclusively as a second-line therapy for steroid-refractory ITP, the response rate was not statistically different between rituximab and splenectomy. However, further large studies are needed to assess the response rates for these treatment modalities as a second-line therapy.

Griscelli syndrome type 2 (GS2) is a rare and often fatal autosomal recessive, hyperinflammatory disorder. It is associated with hypopigmentation of the skin and the hair, resulting in the characteristic pigment accumulation and clumping in the hair shaft. Loss-of-function mutations in RAB27A, resulting from point mutations, short indel, or large deletions, account for all the cases reported to date. However, several GS2 cases originating from Saudi Arabia lack a genetic diagnosis. Here, we report on a new RAB27A genetic anomaly observed in seven Saudi Arabia families that had remained negative after extensive molecular genomic DNA testing. Linkage analysis and targeted sequencing of the RAB27A genomic region in several of these patients led to the identification of a common homozygous tandem duplication of 38 kb affecting exon 2-5 and resulting in a premature stop codon. The pathogenic effect of this duplication was confirmed by a cDNA analysis and functional assays. The identification of microhomology flanking the breakpoint site suggests a possible underlying mechanism., (© 2017 Wiley Periodicals, Inc.)

Aim: To examine the optimal absolute lymphocyte count (ALC) cut-off utilizing receiver operator characteristics (ROC) in addition to graft characteristics associated with early ALC recovery., Methods: Patients who received T-cell replete peripheral hematopoietic cell transplantation (HCT) for acute leukemia were identified. ALC cut-off was established using ROC analysis and subsequently the cohort was stratified. Time to endpoint analysis and cox regression modelling was computed to analyze outcomes., Results: A total of 72 patients met the inclusion criteria and were analyzed. Optimal ALC cut-off was established to be on day 14 (D14) with ALC > 0.3 × 10 9 /L. At 2 years, cumulative incidence of relapse was 16.9% vs 46.9% ( P = 0.025) for early and delayed lymphocyte recovery cohorts, respectively. Chronic graft vs host disease was more prevalent in the early lymphocyte recovery (ELR) group at 70% vs 27%, respectively ( P = 0.0006). On multivariable analysis for relapse, ELR retained its prognostic significance with HR = 0.27 (0.05-0.94, P = 0.038)., Conclusion: ELR is an independent predictor for relapse in patients receiving allogeneic HCT for acute leukemia. ELR was influenced by graft characteristics particularly CD34 count., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest relevant to the conduct of this study.

Background: Hyper-IgE syndrome (HIES) due to DOCK8 deficiency is an autosomal recessive (AR) primary combined immunodeficiency which results in significant morbidity and mortality at a young age. Different mutations in the DOCK8 gene can lead to variable severity of the disease., Objective: We evaluated the genetic mutations in three related patients with severe clinical manifestations suggestive of AR HIES. We also explored whether treatment with stem cell transplantation could lead to complete disease resolution., Method: We examined the clinical manifestations and immunological workup of these patients. Their DNA was also screened for causative mutation. Post transplantation, clinical and immunological data for the transplanted patient was also collected., Results: All patients had a severe course of the disease with rarely reported severe complications in HIES. One patient died with lymphoma while another died with progressive multifocal leukoencephalopathy (PML) due to a slow virus. All our patients had two novel mutations in the DOCK8 gene. One of these mutations was a novel pathogenic mutation and explains the severity of the disease (homozygous splice site mutation at position 5 after the end of exon 45), while the other mutation was mostly non-pathogenic. Hematopoietic stem cell transplantation (HSCT) was performed in the youngest patient with excellent engraftment and full reversibility of the clinical manifestations., Conclusion: We report 3 patients from a consanguineous family diagnosed with AR-HIES due to a novel pathogenic mutation in DOCK8 gene leading to fatal outcome in 2 patients and complete resolution of the clinical and immunological features in the third patient by HSCT., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), corresponds with a heterogeneous group of mature T-cell lymphomas. Recent gene expression profiling studies have identified at least two molecular subgroups (GATA3 and TBX2). Standard treatment and outcomes remain poor. High-dose chemotherapy with autologous stem cell transplantation is incorporated into primary therapy for young fit patients but remains ineffective for most and has not been tested in a randomized study. Several novel agents have been approved for use in relapsed/refractory PTCLs, and although response rates are modest for most, durable remissions have been reported. Selecting rationale combinations and incorporating predictive biomarkers will be important moving forward to improve outcomes in patients with PTCL., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Molecular genetics techniques are an essential diagnostic tool for primary immunodeficiency diseases (PIDs). The use of next-generation sequencing (NGS) provides a comprehensive way of concurrently screening a large number of PID genes. However, its validity and cost-effectiveness require verification., Objectives: We sought to identify and overcome complications associated with the use of NGS in a comprehensive gene panel incorporating 162 PID genes. We aimed to ascertain the specificity, sensitivity, and clinical sensitivity of the gene panel and its utility as a diagnostic tool for PIDs., Methods: A total of 162 PID genes were screened in 261 patients by using the Ion Torrent Proton NGS sequencing platform. Of the 261 patients, 122 had at least 1 known causal mutation at the onset of the study and were used to assess the specificity and sensitivity of the assay. The remaining samples were from unsolved cases that were biased toward more phenotypically and genotypically complicated cases., Results: The assay was able to detect the mutation in 117 (96%) of 122 positive control subjects with known causal mutations. For the unsolved cases, our assay resulted in a molecular genetic diagnosis for 35 of 139 patients. Interestingly, most of these cases represented atypical clinical presentations of known PIDs., Conclusions: The targeted NGS PID gene panel is a sensitive and cost-effective diagnostic tool that can be used as a first-line molecular assay in patients with PIDs. The assay is an alternative choice to the complex and costly candidate gene approach, particularly for patients with atypical presentation of known PID genes., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

We reviewed our institutional experience from 2011 to 2015 on new cases of Fanconi anemia (FA). Ten unrelated cases were diagnosed during this period. Four patients with severe aplastic anemia (SAA) had c.2392C > T (p.Arg798*) BRIP1/FANCJ mutation. Another child with SAA had novel c.1475T > C (p.Leu492Pro) FANCC mutation. One individual with SAA and acute myeloid leukemia had c.637&#95;643del (p.Tyr213Lysfs*6) FANCG mutation. Three patients presented with early onset of cancer, two had BRCA2 mutation c.7007G > A (p.Arg2336His) and one had a novel c.3425del (p.Leu1142Tyrfs*21) PALB2 mutation. Another infant with c.3425del PALB2 mutation had clonal aberration with partial trisomy of the long arm of chromosome 17. Mutations in FA downstream pathway genes are more frequent in our series than expected. Our preliminary observation will be confirmed in a large multi-institutional study., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Change of water quality in dam reservoir and aquifer complicates safe drinking water supply. Few parameters are monitored to control water quality in these sources. Adequate knowledge on the correlation structure, interaction effect, trends and seasonal variability of these parameters is essential to control water quality. This study applied time series and multivariate analyses on 15 water quality parameters, collected from the King Fahd dam reservoir (L1) and aquifer (L2) in Saudi Arabia during April 2010 to February 2012. Moderate to strong correlations were observed between sulfate, hardness, fluoride, chloride, magnesium, conductivity, turbidity and total dissolved solids (TDS), while separate clusters were visible for TDS-chloride-magnesium-conductivity; fluoride-turbidity; chloride-hardness; ammonia-nitrate; and calcium-magnesium-hardness. Four major principal components explained 81.1% and 83.2% of the overall variances in L1 and L2, respectively. The factor analysis showed that 53% and 67% of the data were necessary to explain 81.3% and 83.2% of total variances for L1 and L2, respectively, indicating the possibility of data reduction. Possible degradation of water quality in these sources was highlighted, while such degradation may require enhanced treatment for producing drinking water in future.

Objective: To determine the use of liver function tests (LFTs) as a selection tool for preoperative endoscopic retrograde cholangiopancreatography (ERCP) in patients with mild gallstone pancreatitis., Methods: All patients admitted with mild gallstone pancreatitis with deranged LFTs in King Saud Medical City, Riyadh, Kingdom of Saudi Arabia between January 2006 and February 2013 were studied retrospectively. Patients' demography, symptoms, laboratory values, imaging studies, ERCP findings, complications and its treatment, surgical intervention, intraoperative and postoperative findings, mortality, and outpatient follow up were collected and analyzed., Results: A total of 245 patients were admitted as mild gallstone pancreatitis with admission day deranged LFTs. Pre-operative ERCP was performed in 74 patients based on admission day LFTs (Group A). Endoscopic retrograde cholangiopancreatography was normal in 65 patients, revealed stones in 5, and sludge in 4 patients. Six patients developed ERCP complications. Endoscopic retrograde cholangiopancreatography was deferred in 171 patients (Group B) until the LFTs were repeated in 3-4 days. Liver function tests remained persistently high in 8 patients. They were submitted to preoperative ERCP, which revealed stones (n=5) and sludge (n=3). Patients with normalized LFTs (n=163) were not submitted to ERCP. Three of them developed gallstone related complications., Conclusion: Patients admitted with predicted mild gallstone pancreatitis, deranged LFTs, and no evidence of cholangitis should not be submitted to ERCP unless a repeat LFT within 3-4 days shows persistently deranged LFTs. This will reduce unnecessary ERCP and its complications.