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Waleed Hakami,1 Gasim Dobie,1 Khadija A Alneami,1 Misk Shaabi,1 Khaled Essawi,1 Muhammad Saboor,2 Aymen M Madkhali,1 Mohammed H Nahari,3 Hassan H Almasoudi,3 Mohammad S Akhter,1 Fasial H Hakami,4 Fatimah A Zarbatan,5 Ali Hakamy,6 Rama M Chandika,7 Ali A Fageehi,1 Abdullah A Mobarki,1 Hassan A Hamali1 1Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia; 2Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates; 3Department of Medical Laboratory Technology, Najran University, Najran, Saudi Arabia; 4Department of Epidemiology, College of Public Health and Tropical Medicine, Jazan University, Jazan, Saudi Arabia; 5Respiratory Care Department, King Fahad Central Hospital, Jazan, Ministry of Health, Jazan, Saudi Arabia; 6Department of Respiratory Therapy, Faculty of Applied Medical Sciences, Jazan University, Gizan, Saudi Arabia; 7Department of Clinical Nutrition, College of Applied Medical Sciences, Jazan University, Jazan, Saudi ArabiaCorrespondence: Hassan A Hamali, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, P.O. Box 1906, Gizan, 45142, Saudi Arabia, Email hhamali@jazanu.edu.saBackground: Nutritional anemia is a significant public health concern worldwide, particularly affecting young adults and children in Saudi Arabia, where inadequate nutrition is considered a primary contributing factor. This study aims to (i) examine the levels of serum iron, folate, and vitamin B12 in young adult students, with a focus on identifying any deficiencies and their association with anemia; (ii) explore the prevalence of mixed-deficiency anemia resulting from deficiencies in serum iron, folate, and vitamin B12 (iii) explore how sociodemographic characteristics and dietary habits influence serum iron, folate, and vitamin B12 levels.Materials and Methods: This cross-sectional study encompassed 158 young adult students at Jazan University, Saudi Arabia. Blood samples were collected following a comprehensive questionnaire addressing sociodemographic and health characteristics. These samples were analyzed for complete blood count, serum iron, folate, and vitamin B12 levels.Results: The findings of this study revealed a significant decrease in serum iron levels, with 70.6% of males and 88% in females exhibiting reduced level. Additionally, low levels of folate were observed in 4% of the study population, while deficiency in vitamin B12 was found in 2.2% of the study population. However, the simultaneous presence of low serum iron levels along with deficiencies in folate or vitamin B12 was not observed in the study participants.Conclusion: The study indicates that there is a high incidence of low serum iron and ferritin levels among university students in Saudi Arabia, which poses a considerable public health concern. Conversely, the prevalence of folate and vitamin B12 deficiencies among the students was comparatively low, and notably, there were no cases where these deficiencies were observed alongside iron deficiency.Keywords: anemia, folate, vitamin B12, serum iron, iron deficiency

Khaled Essawi,1 Gasim Dobie,1 Misk F Shaabi,1 Waleed Hakami,1 Muhammad Saboor,2 Aymen M Madkhali,1 Abdullah AH Hamami,3 Wael H Allallah,3 Mohammad S Akhter,1 Abdullah A Mobarki,1 Hassan A Hamali1 1Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia; 2Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates; 3Department of Laboratory & Blood Bank, Prince Mohammed bin Nasser Hospital, Ministry of Health, Jazan, Saudi ArabiaCorrespondence: Hassan A Hamali, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, P.O. Box 1906, Gizan, 45142, Saudi Arabia, Email hhamali@jazanu.edu.saBackground: Diabetes mellitus (DM) is a major health burden affecting 537 million adults worldwide, characterized by chronic metabolic disorder and various complications. This case control study aimed to assess the impact of type 2 diabetes mellitus (T2DM), including hyperglycemia levels, on hematological parameters and complete blood count (CBC) derived parameters.Methods: A total of 250 known diabetic patients from the Jazan Diabetic Center, Saudi Arabia, between January 2021 and December 2022, along with 175 healthy adult controls were recruited from Jazan Hospital’s blood donation center. Demographic characteristics, medical histories, and relevant factors such as gender, age, BMI, treatment, disease duration, and comorbidities were collected with informed consent.Results: The results of the red blood cell (RBC) count, RBC indices, and mean platelet volume showed significant differences between patients and controls, while the white cell (WBC) and platelet count were comparable between the two groups. CBC-derived parameters, especially neutrophil/lymphocyte ratio (NLR), and platelet/neutrophil ratio (PNR) exhibited significant differences.Conclusion: CBC and derived parameters serve as inexpensive tools for T2DM patients monitoring, indicating early blood cell alterations and potential development of anemia. Further studies are needed to explore their role in predicting T2DM pathogenesis and progression, aiming to reduce severe complications, mortality and morbidity.Keywords: diabetes mellitus, complete blood count, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, platelet/neutrophil ratio, mean platelet volume/platelet count, disease complication

Mohammed Badedi,1 Hussain Darraj,1 Abdulrahman Hummadi,1 Abdullah Najmi,2 Yahiya Solan,1 Ibrahim Zakry,1 Abdullah Khawaji,1 Sayedah Zaylai,1 Norah Rajeh,1 Hassan Alhafaf,1 Wali Hakami,1 Awaji Bakkari,1 Maryam Kriry,1 Abdulraheem Dagreri,1 Ebrahim Haddad1 1Jazan Diabetes and Endocrine Center, Ministry of Health, Jazan, Saudi Arabia; 2Jazan Health Affairs, Ministry of Health, Jazan, Saudi ArabiaCorrespondence: Mohammed BadediJazan Diabetes Center, Ministry of Health, Saudi Arabia, PO Box 604, Abu Arish, Jazan 45911, Saudi ArabiaTel +966 559154136Email dr.badedi@gmail.comObjective: Knowledge about the effects of khat chewing on type 2 diabetes mellitus (T2DM) development and glycemic control is very sparse. Emerging data suggest that khat chewing may increase the risk of T2DM occurrence. Therefore, this study aimed to measure the prevalence of khat chewing in Saudi people with T2DM in Jazan, Saudi Arabia and to determine the association of khat chewing with T2DM development and glycemic control in T2DM.Methods: This is an analytical, cross-sectional study that included 472 Saudi participants selected randomly from primary healthcare centers in Jazan, Saudi Arabia. A chi-square test and logistic regression were performed in the statistical analysis.Results: The prevalence of khat chewing in Saudi patients with T2DM in Jazan was 29.3%. After adjusting for covariates, khat chewing was significantly associated with T2DM (odds ratio 3.5), indicating that khat chewers had a more than three times higher risk of developing T2DM than those who do not chew khat. However, there was no association between khat chewing and glycemic control in T2DM.Conclusion: Khat chewing was highly prevalent in Saudi people with T2DM in Jazan, Saudi Arabia. There was an association between khat chewing and the development of T2DM. Establishing the causal association of khat chewing with T2DM development and glycemic control and clarifying the biological role of khat in T2DM are important aims for future studies.Keywords: type 2 diabetes mellitus, catha edulis, khat chewing

The construction industry in Yemen is currently facing challenges associated with rapid development of technology; thus, cost estimation is considered a key factor that should align with this technological advancement. The main problem in the area of preliminary estimate in Yemen is how to make estimate accurately. The aim of this study is to analyse a modern method of preliminary cost estimation in Yemen to prove its efficiency over the traditional method. Therefore, a wide range of literature sources regarding the preliminary estimates using Artificial Neural Network (ANN) as a modern technique is considered. Both qualitative and quantitative approaches were adopted in this study depending on the theoretical premises discussed in literature and the ANN technique, respectively. The independent variables were chosen in the course of literature review. The collected data were classified and processed regarding the ANN constraints and encoded for building and analysis of the ANN model. NeuroSolution 6 software was used to build, train, and test the network as well as to perform sensitivity analysis. In addition, the results of training, testing, and sensitivity analysis were obtained and discussed showing high effectiveness of accurate estimates with less than 1 % error. The ANN model is a more powerful technique for estimating costs in the preliminary stage that should be used in the developing countries instead of the traditional methods.

The current study aims to identify research hotspots and trends in Monkeypox (MPX). A total of 2655 MPX-related articles published from 1961 to 2023 were extracted from the Scopus database. Data were analyzed using Scopus Analytics, Microsoft Excel, Bibliometrix, and VOSviewer. The number of MPX papers has been increasing annually, particularly since the most recent outbreak. The United States and India have been productive in this area. The most cited and productive scholar in the field is Inger K. Damon. The MPX research theme map shows clusters with various centralities and densities, focusing on deep learning, molecular docking, and orthopoxviruses. Over the last decade, key terms include "transmission," "pandemic," "deep learning," "docking," "Democratic Republic of Congo," "Ebola," "virulence," "modified vaccinia Ankara," and "orthopoxvirus." Researchers can utilize existing findings to steer future research on this illness, prepare for potential pandemics, and address bioterrorist threats., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Folic acid (FA) plays a crucial role in various biological processes. Insufficient intake of FA during pregnancy can lead to serious clinical complications, including neural tube defect. The current study sought to assess the awareness, knowledge, and usage of FA among young females in Jazan region of Saudi Arabia. This cross-sectional descriptive study involved 472 adult females from October 1 to 9, 2023, in Jazan region, Saudi Arabia. The questionnaire of the study was randomly distributed among females. The data showed that awareness and usage of FA supplementation were poor to fair among females. Furthermore, socio-demographic variables, including age, marital status, monthly income, education levels, number of pregnancies, and current pregnancy status, were found to be associated with awareness and utilization of FA supplementation. The study highlights the need to enhance awareness and knowledge of FA supplementation among females in the Jazan region. Introducing educational programs is essential in Saudi Arabia, particularly in the Jazan region, to enhance the knowledge and awareness of FA within the community., Competing Interests: The Authors declared no conflict of interest, (African Journal of Reproductive Health © 2024.)

Anemia, particularly iron deficiency anemia (IDA), is a prevalent health issue globally and in Saudi Arabia, especially among young adult females. This study investigates the association between anemia and academic achievement among female students at the Female Health Campus of Jazan University, Jazan, Saudi Arabia. This cross-sectional study included 118 randomly selected participants aged 18-22. A validated questionnaire was administered to the study participants. The participants underwent blood tests for complete blood count (CBC) parameters and iron profile analysis. The study reported that 52.5% of the female students had anemia and low serum iron levels. Regarding academic performance, significant positive correlations were found between various CBC parameters including white cell count, hemoglobin, hematocrit, mean cell volume, mean cell hemoglobin, mean cell hemoglobin concentration, and serum iron. However, no significant correlations were observed between red blood cell count and platelet count with academic performance. Demographic variables were also associated with a higher odds ratio of anemia. The study highlights the prevalence of anemia among female students and its potential impact on academic achievement. The current study underscores the importance of addressing anemia in young adult females and implementing appropriate interventions to improve their educational outcomes., Competing Interests: The Authors declared no conflict of interest, (African Journal of Reproductive Health © 2024.)

Background: Human papillomavirus (HPV) infection is a prevalent sexually transmitted infection globally, with significant associations with various cancers. Despite the availability of HPV vaccines, vaccination uptake remains suboptimal in many regions, including Saudi Arabia., Methods: This cross-sectional survey-based study aimed to assess perceptions, attitudes, and barriers related to HPV vaccination among residents in different regions of Saudi Arabia. Participants were recruited using a stratified sampling method, and data were collected through a structured questionnaire administered electronically., Results: A total of 600 participants were included in the study, with diverse demographic profiles observed. The largest age group was 26-35 years old, comprising 42.7% (n = 256) of the sample. The distribution of gender was approximately equal, with 54.7% (n = 328) male participants. Notable perception and knowledge about HPV were observed, with 49.7% (n = 298) reporting being very familiar. Furthermore, 85.8% (n = 515) believed that HPV could cause serious health problems, and 63.7% (n = 382) perceived the vaccine to be very effective. Positive attitudes toward HPV vaccination were prevalent, with a significant proportion expressing a willingness to recommend the vaccine to themselves (70.0%, n = 420) and their children (65.0%, n = 390). Healthcare provider recommendation emerged as a key influencing factor, with 73.8% (n = 443) citing it as influential. Despite favorable attitudes, barriers to HPV vaccination were reported, including vaccine cost (22.5%, n = 135) and lack of awareness (13.7%, n = 82). However, a substantial proportion of unvaccinated participants cited not applicable reasons (57.2%, n = 343), indicating prior vaccination. Factors associated with HPV vaccination uptake included higher education levels, with those holding a master's degree or above exhibiting higher odds of vaccination uptake (OR (odds ratio): 1.80, 95% CI (confidence interval): 1.35-2.40, p < 0.001). Age (26-35 vs. 18-25) also showed a borderline significant association (OR: 1.25, 95% CI: 0.98-1.60, p = 0.074)., Conclusion: The study highlights the importance of understanding perceptions and barriers to HPV vaccination to inform public health policies and programs in Saudi Arabia. Addressing identified barriers, such as educational campaigns and improving access to vaccination services, is essential for enhancing HPV vaccination coverage and reducing the burden of HPV-related diseases in the region., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Faqeeh et al.)

Narcolepsy with cataplexy is a complex disease with both genetic and environmental risk factors. To gain further insight into the homozygous HCRT-related narcolepsy, we present a case series of five patients from two consanguineous families, each harboring a novel homozygous variant of HCRT c.17&#95;18del. All affected individuals exhibited severe cataplexy accompanied by narcolepsy symptoms during infancy. Additionally, cataplexy symptoms improved or disappeared in the majority of patients over time. Pathogenic variants in HCRT cause autosomal recessive narcolepsy with cataplexy. Genetic testing of the HCRT gene should be conducted in specific subgroups of narcolepsy, particularly those with early onset, familial cases, and a predominantly cataplexy phenotype., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hyperuricemia contributes significantly to gout arthritis pathogenesis, which promotes urate crystal deposition in the joints and activates joint-resident macrophages and circulating monocytes to initiate a state of inflammatory arthritis. In the joint, macrophages have an immune defense role where the presence of urate crystals results in the inflammatory mediators secretion, inflammatory cells recruitment to the joint, and shift macrophage population toward M1 pro-inflammatory phenotypes. Current treatment modalities of gout arthritis have side effects that limit their use in the elderly. A novel treatment that targets macrophage polarization to re-establish homeostasis may initiate a drug discovery program of novel disease-modifying agents for gout. Zerumbone (Zer) is a sesquiterpenoid bioactive compound found in the rhizome of Zingiberaceae family and possesses anti-inflammatory, antioxidant, and anti-proliferative activity. Our study hypothesized that soluble uric acid (sUA) and Pam3CSK4 (TLR2 agonist) reduce the anti-inflammatory function of murine M2 bone marrow-derived macrophages and change the expression of M2 genetic markers toward M1 phenotypes. We observed that priming of M2 macrophages with sUA and Pam3CSK4 significantly decreased M2 specific markers expression, e.g., Arg-1, Ym-1, and Fizz-1, enhanced mRNA expression of IL-1β, TNF-α, CXCL2, and iNOS and increased oxidative stress in M2 macrophages, as exhibited by a reduction in Nrf2 expression. We also aimed to study the impact of Zer on reducing the pro-inflammatory effect of sUA in TLR2-stimulated M2 macrophages. We noticed that Zer treatment significantly reduced L-1β and TNF-α production following Pam3CSK4 + sUA treatment on M2 macrophages. Furthermore, Zer reduced the caspase-1 activity without altering cytosolic NLRP3 content in challenged M2 BMDMs. We also observed that Zer significantly enhanced M2-associated marker's expression, e.g., Arg-1, Ym-1, and Fizz-1, and augmented Nrf-2 and other antioxidant proteins, including HMOX1 and srxn1expression following Pam3CSK4 + sUA treatment. We draw the conclusion that Zer is a potentially effective anti-inflammatory treatment for gout arthritis linked to hyperuricemia., Competing Interests: 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., (© 2024 The Author(s).)

Self-medication, the unsupervised use of drugs, is a common global behavior with potential adverse health outcomes. This study explores the prevalence and patterns of self-medication in Saudi Arabia, focusing on factors such as drug availability, economic constraints, and public trust in healthcare systems. Particular emphasis is placed on self-medication with antibiotics and prescription drugs due to their significant public health risks. Our comprehensive, quantitative, cross-sectional study surveyed 1,671 individuals across Saudi Arabia's diverse regions. We found that 75.5% of respondents engaged in self-medication, primarily on an occasional basis. While 59.8% of participants perceived self-medication as safe, 17.5% reported experiencing adverse effects. Respondents strongly advocated for increased regulatory measures (87.7%) and a pressing need for enhanced public education (92.6%) to address the associated risks. The study highlights the widespread practice of self-medication in Saudi Arabia, influenced by various factors, and underscores the need for targeted health policies and educational campaigns to mitigate these risks., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Alhur et al.)

CRISPR-Cas9-based therapeutic genome editing approaches hold promise to cure a variety of human diseases. Recent findings demonstrate pre-existing immunity for the commonly used Cas orthologs from Streptococcus pyogenes (SpCas9) and Staphylococcus aureus (SaCas9) in humans, which threatens the success of this powerful tool in clinical use. Thus, a comprehensive investigation and potential risk assessment are required to exploit the full potential of the system. Here, we investigated existence of immunity to SpCas9 and SaCas9 in control rhesus macaques ( Macaca mulatta) alongside monkeys transplanted with either lentiviral transduced or CRISPR-SpCas9 ribonucleoprotein (RNP)-edited cells. We observed significant levels of Cas9 antibodies in the peripheral blood of all transplanted and non-transplanted control animals. Transplantation of ex vivo transduced or SpCas9-mediated BCL11A enhancer-edited cells did not alter the levels of Cas9 antibodies in rhesus monkeys. Following stimulation of peripheral blood cells with SpCas9 or SaCas9, neither Cas9-specific T cells nor cytokine induction were detected. Robust and durable editing frequencies and expression of high levels of fetal hemoglobin in BCL11A enhancer-edited rhesus monkeys with no evidence of an immune response (>3 years) provide an optimistic outlook for the use of ex vivo CRISPR-SpCas9 (RNP)-edited cells., Competing Interests: S.G. has patent applications in the fields of cell and/or gene therapy for cancer. S.G. is a consultant of TESSA Therapeutics, a DSMB member of Immatics, and has received honoraria from Tidal, Catamaran Bio, Sanofi, and Novartis within the last 2 years.

With the advent of new genome editing technologies and the emphasis placed on their optimization, the genetic and phenotypic correction of a plethora of diseases sit on the horizon. Ideally, genome editing approaches would provide long-term solutions through permanent disease correction instead of simply treating patients symptomatically. Although various editing machinery options exist, the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated protein) editing technique has emerged as the most popular due to its high editing efficiency, simplicity, and affordability. However, while CRISPR technology is gradually being perfected, optimization is futile without accessible, effective, and safe delivery to the desired cell or tissue. Therefore, it is important that scientists simultaneously focus on inventing and improving delivery modalities for editing machinery as well. In this review, we will discuss the critical details of viral and nonviral delivery systems, including payload, immunogenicity, efficacy in delivery, clinical application, and future directions.

Background: Hyperekplexia is a rare disorder characterized by exaggerated startle responses to unexpected sensory stimuli, recurrent apneas, and stiffness. Only few studies have been published on this disorder in populations with high rates of consanguinity., Methods: We retrospectively reviewed Saudi patients with genetically confirmed hereditary hyperekplexia using a standard questionnaire that was sent to nine major referral hospitals in Saudi Arabia., Results: A total of 22 Saudi patients (11 males, 11 females) from 20 unrelated families who had hereditary hyperekplexia were included. Based on molecular studies, they were classified into different subtypes: SLC6A5 variant (12 patients, 54.5%), GLRB variant (seven patients, 31.8%), and GLRA1 variant (three patients, 13.7%). All patients were homozygous for the respective causal variant. The combined carrier frequency of hereditary hyperekplexia for the encountered founder mutations in the Saudi population is 10.9 per 10,000, which translates to a minimum disease burden of 13 patients per 1,000,000., Conclusion: Our study provides comprehensive epidemiologic information, prevalence figures, and clinical characteristics of a large cohort of patients with hereditary hyperekplexia., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most detected pharmaceuticals in wastewater and likely pass to drinking water. Magnetic nanocomposite has been greenly fabricated for removal of different NSAIDs; ibuprofen (IP), ketoprofen (KP), naproxen (NX), and diclofenac sodium salt (DF); from wastewater. Solid-phase fabrication of the magnetically separable nanocomposite has been optimized using iron oxide (Fe 3 O 4 ) and graphene nanoplatelets (GNP) precursors. The characterization showed the homogenous distribution of the magnetite over the GNP with a high specific surface area. Different parameters having a potential influence on the removal of the NSAIDs from wastewater by the Fe 3 O 4 @GNP nanocomposite were studied and optimized for efficient performance that achieves adsorption capacities of 8.76, 10.6, 14.3, and 7.63 mg/g for KP, NX, DF, and IP, respectively (296 K). The adsorption of the four NSAIDs by the Fe 3 O 4 @GNP nanocomposite followed pseudo-second-order kinetics, and it is mainly controlled by the intraparticle diffusion process. The thermodynamic and extra-thermodynamic studies demonstrated that the adsorption is endothermic and is affected by enthalpy-entropy compensation. The molecular interactions of the four drugs with the nanocomposite have been explored. Successful application of the nanocomposite for fast and efficient removal of the NSAIDs from wastewater has been accomplished with an average removal of 71.0%., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: KCNMA1 -linked channelopathy is a rare movement disorder first reported in 2005. Paroxysmal non-kinesigenic dyskinesia (PNKD) in KCNMA1 -linked channelopathy is the most common symptom in patients harboring the KCNMA1 -N999S mutation. PNKD episodes occur up to hundreds of times daily with significant morbidity and limited treatment options, often in the context of epilepsy., Cases: We report 6 cases with the KCNMA1 -N999S variant treated with lisdexamfetamine (0.7-1.25 mg/kg/day), a pro-drug of dextroamphetamine. Data were collected retrospectively from interviews and chart review. Parent-reported daily PNKD episode counts were reduced under treatment, ranging from a 10-fold decrease to complete resolution., Conclusion: Our findings suggest that lisdexamfetamine is an effective therapy for PNKD3 ( KCNMA1 -associated PNKD). Treatment produced dramatic reductions in debilitating dyskinesia episodes, without provocation or exacerbation of other KCNMA1 -associated symptoms such as seizures., (© 2021 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC. on behalf of International Parkinson and Movement Disorder Society.)

Ex vivo gene correction of hematopoietic stem and progenitor cells (HSPCs) has emerged as a promising therapeutic approach for treatment of inherited human blood disorders. Use of engineered nucleases to target therapeutic transgenes to their endogenous genetic loci addresses many of the limitations associated with viral vector-based gene replacement strategies, such as insertional mutagenesis, variable gene dosage, and ectopic expression. Common methods of nuclease-mediated site-specific integration utilize the homology-directed repair (HDR) pathway. However, these approaches are inefficient in HSPCs, where non-homologous end joining (NHEJ) is the primary DNA repair mechanism. Recently, a novel NHEJ-based approach to CRISPR-Cas9-mediated transgene knockin, known as homology-independent targeted integration (HITI), has demonstrated improved site-specific integration frequencies in non-dividing cells. Here we utilize a HITI-based approach to achieve robust site-specific transgene integration in human mobilized peripheral blood CD34+ HSPCs. As proof of concept, a reporter gene was targeted to a clinically relevant genetic locus using a recombinant adeno-associated virus serotype 6 vector and single guide RNA/Cas9 ribonucleoprotein complexes. We demonstrate high levels of stable HITI-mediated genome editing (∼21%) in repopulating HSPCs after transplantation into immunodeficient mice. Our study demonstrates that HITI-mediated genome editing provides an effective alternative to HDR-based transgene integration in CD34+ HSPCs., (Published by Elsevier Inc.)

Diamond Blackfan Anemia (DBA) is a congenital macrocytic anemia associated with ribosomal protein haploinsufficiency. Ribosomal dysfunction delays globin synthesis, resulting in excess toxic free heme in erythroid progenitors, early differentiation arrest, and pure red cell aplasia. In this study, DBA induced pluripotent stem cell (iPSC) lines were generated from blood mononuclear cells of DBA patients with inactivating mutations in RPS19 and subjected to hematopoietic differentiation to model disease phenotypes. In vitro differentiated hematopoietic cells were used to investigate whether eltrombopag, an FDA-approved mimetic of thrombopoietin with robust intracellular iron chelating properties, could rescue erythropoiesis in DBA by restricting the labile iron pool (LIP) derived from excessive free heme. DBA iPSCs exhibited RPS19 haploinsufficiency, reduction in the 40S/60S ribosomal subunit ratio and early erythroid differentiation arrest in the absence of eltrombopag, compared to control isogenic iPSCs established by CRISPR/Cas9-mediated correction of the RPS19 point mutation. Notably, differentiation of DBA iPSCs in the presence of eltrombopag markedly improved erythroid maturation. Consistent with a molecular mechanism based on intracellular iron chelation, we observed that deferasirox, a clinically licensed iron chelator able to permeate into cells, also enhanced erythropoiesis in our DBA iPSC model. In contrast, erythroid maturation did not improve substantially in DBA iPSC differentiation cultures supplemented with deferoxamine, a clinically available iron chelator that poorly accesses LIP within cellular compartments. These findings identify eltrombopag as a promising new therapeutic to improve anemia in DBA.

A stroke should be considered in cases of neurologic decompensation associated with inherited metabolic disorders. A resultant stroke could be a classical ischemic stroke (vascular stroke) or more commonly a "metabolic stroke." A metabolic stroke begins with metabolic dysfunctions, usually caused by a stressor, and leads to the rapid onset of prolonged central neurological deficits in the absence of vessel occlusion or rupture. The cardinal features of a metabolic stroke are stroke-like episodes without the confirmation of ischemia in the typical vascular territories, such as that seen in classic thrombotic or embolic strokes. Identifying the underlying cause of a metabolic stroke is essential for prompt and appropriate treatment. This study reviews the major inherited metabolic disorders that predispose patients to pediatric stroke, with an emphasis on the underlying mechanisms, types, and management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tabarki, Hakami, Alkhuraish, Graies-Tlili, Nashabat and Alfadhel.)

Previous reviews have described the features of brain involvement in pediatric-onset metabolic disorders with Mendelian and mitochondrial inheritance, but only a few have focused on spinal cord abnormalities. An increasing number of metabolic disorders with Mendelian and mitochondrial inheritance in children with predominant spinal cord involvement has been recognized. Spinal cord involvement may be isolated or may occur more frequently with brain involvement. Timely diagnosis and occasional genetic counseling are needed for timely therapy. Therefore, clinicians must be aware of the clinical, laboratory, and radiographic features of these disorders. In this review, we describe pediatric-onset metabolic disorders with Mendelian and mitochondrial inheritance and predominant spinal cord involvement. Furthermore, we provide an overview of these conditions, including background information and examples that require rapid identification, focusing on treatable conditions; that would be catastrophic if they are not recognized., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tabarki, Hakami, Alkhuraish, Tlili-Graies and Alfadhel.)

A 46-year-old man experienced a remote unexpected lung injury with a sharp object. The object migrated over the years, penetrating the mediastinal structure, injuring the pericardium and the right-sided chambers of the heart. The injury was complicated by hemodynamic instability and pericardial tamponade. An emergent pericardiocentesis followed by thoracotomy, foreign body extraction, and puncture site closure. This is a very rare case of remote penetrating lung injury with a dormant course., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)