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Background: Eczema is a common inflammatory skin disease with a significant global health burden. Eczema has a significant impact on quality of life. Objective: We aimed to estimate the prevalence, severity, and risk factors associated with eczema among schoolchildren in Saudi Arabia. Methods: The standardized Global Asthma Network questionnaires and methodology were used to conduct a nationwide cross-sectional study across 20 regions in Saudi Arabia between March and April 2019. Data were collected from 137 primary schools and 140 intermediate schools by using a multistage stratified cluster sampling method. Results: The study included 3614 young children aged 6 to 7 years and 4068 adolescents aged 13 to 14 years. Current eczema was prevalent among 4.5% of the children and 5.1% of the adolescents. Severe eczema was reported in 0.8% and 0.9% of the young children and adolescents, respectively. Several factors showed significant association with eczema. Among the children, eczema was linked positively to having a history of chest infections and wheezing in early life, as well as to ever attending day care and current exposure to cats. Among the adolescents, the main potential risk factors included paracetamol use in the previous year, adherence to a lifestyle of vigorous physical activity, and current exposure to cats. Conversely, high consumption of nuts was found to be negatively associated with eczema. Conclusion: The prevalence of eczema in schoolchildren in Saudi Arabia is lower than the global average but within the average range for the Eastern Mediterranean region. Further studies in Saudi Arabia should be conducted to identify variation among different regions.

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BACKGROUND: The objective of this study was to describe the prevalence, characteristics, and risk factors of coronavirus disease-2019 (COVID-19) infection among health care workers (HCWs) at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. METHODS: A prospective cross-sectional study of HCWs confirmed to have COVID-19 infection from March 1, 2020 to December 31, 2022. RESULTS: A total of 746 HCWs were diagnosed with COVID-19. Patients' age ranged from 22 to 60 years with a mean ± standard deviation of 37.4 ± 8.7 years. The infection was community-acquired in 584 (78.3%) HCWs. The vast majority (82.6%) of the infected HCWs had no comorbidities. Nurses (400/746 or 53.6%) represented the largest professional group, followed by physicians (128/746 or 17.2%), administrative staff (125/746 or 16.8%), respiratory therapists (54/746 or 7.2%), and physiotherapists (39/746 or 5.2%). Symptoms included fever (64.1%), cough (55.6%), sore throat (44.6%), headache (22.9%), runny nose (19.6%), shortness of breath (19.0%), fatigue (12.7%), body aches (11.4%), diarrhea (10.9%), vomiting (4.4%), and abdominal pain (2.8%). Most (647 or 86.7%) patients were managed as outpatients. Four (0.5%) HCWs died. CONCLUSIONS: HCWs face a dual risk of SARS-CoV-2 infection, both from community exposure and within the hospital setting. Comprehensive infection control strategies are needed to protect HCWs both inside and outside the hospital environment.

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BACKGROUND: The existence of a functional relationship between a certain thyroid hormone analogue and cancer cell radioresistance has been shown by Leith and coworkers. The hormone analogue with relevance to malignant cells' radioresistance is tetraiodothyroacetic acid (tetrac). Tetrac is the deaminated derivative of L-thyroxine (T4), the principal product of the thyroid gland. Preclinical studies demonstrated that tetrac and chemically modified tetrac (CMT), e.g. a fluorobenzyl-conjugated tetrac analogue, restores radiosensitivity in certain radioresistant tumor cells. Due to their molecular, physico-chemical, and biological properties, actions of CMT analogues are believed to be initiated at the thyroid hormone analogue receptor site on plasma membrane integrin αvß3. OBJECTIVE: To explore possible molecular mechanisms of the potentially therapeutically beneficial effect of CMT on cancer cells' sensitivity to radiation, we analyzed actions of CMT analogues on expression of selected sets of genes that have been previously implicated in radioresistance of malignant cells. DISCUSSION AND CONCLUSIONS: In the current study, we report that genome-wide gene expression profiling analysis of human glioblastoma (GBM) and acute myelocytic leukemia (AML) cell lines exposed in vitro to noncytotoxic doses of CMT has identified decreased expression of discrete trios of genes each of which was previously linked to cancer cells' radioresistance. Following the CMT treatment in AML cells, expression of PARP9, PARP15 and STAT3 genes was significantly reduced, while in GBM cells, expression of PRKDC, EGFR and CCNDI was significantly decreased by the drug. Notably, a broader spectrum of genes implicated in cancer cells' radioresistance was observed in primary patient-derived GBM cells after the CMT treatment. Extensive additional experimental and clinical studies are indicated, including analyses of individual patient tumor genomics and of an array of different tumor types to define the sub-sets of tumors manifesting radioresistance in which tetrac-based agents may be expected to enhance therapeutic effects of radiation.

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The prevalence of consanguineous marriages (CMs) varies worldwide from one country to another. However, the Middle East stands out as a region with a notably high rate of CMs. CM is particularly widespread in Saudi Arabia, where the prevalence of autosomal recessive genetic diseases has increased. This study aims to identify the Saudi population's awareness of genetic diseases and premarital screening tests (PMSTs). It also seeks to understand couples' perceptions of genetic diseases before and after marriage and their attitudes towards PMSTs and genetic counselling (GC) in reducing the risk of CM. Through the administration of online questionnaires, this cross-sectional study surveyed 2,057 participants to assess their awareness of genetic diseases and their understanding of testing and preventive measures for inherited diseases. Descriptive analysis, nonparametric chi-square tests and logistic regressions were performed to assess the association of categorical responses. This study included 2,035 Saudi Arabian respondents. A significant correlation was found between positive family history and partner selection (p = 0.001), as well as between partnering within the same tribe (p = 0.000139), with a different tribe (p = 0.000138) and from another family (p = 0.000489). About 91.3% of participants expressed agreement regarding the need to enhance public awareness and knowledge concerning genetic disorders, while 87% agreed that increased government regulations are required to prevent the spread of genetic diseases in affected families. Despite increased awareness of genetic diseases and PMSTs, there appears to be a lack of understanding regarding the limitations of PMSTs. The persistently high rate of CM underscores the challenge of altering marriage customs. Further governmental efforts are required to promote awareness of alternative reproductive options, establish new regulations and expand screening programmes.

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The journal retracts the article, "Anti-Cancer Activities of Thyrointegrin αvß3 Antagonist Mono- and Bis-Triazole Tetraiodothyroacetic Acid Conjugated via Polyethylene Glycols in Glioblastoma" [...].

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Over the last few decades, cancer has been considered a clinical challenge, being among the leading causes of mortality all over the world. Although many treatment approaches have been developed for cancer, chemotherapy is still the most utilized in the clinical setting. However, the available chemotherapeutics-based treatments have several caveats including their lack of specificity, adverse effects as well as cancer relapse and metastasis which mainly explains the low survival rate of patients. Lipid nanoparticles (LNPs) have been utilized as promising nanocarrier systems for chemotherapeutics to overcome the challenges of the currently applied therapeutic strategies for cancer treatment. Loading chemotherapeutic agent(s) into LNPs improves drug delivery at different aspects including specific targeting of tumours, and enhancing the bioavailability of drugs at the tumour site through selective release of their payload, thus reducing their undesired side effects on healthy cells. This review article delineates an overview of the clinical challenges in many cancer treatments as well as depicts the role of LNPs in achieving optimal therapeutic outcomes. Moreover, the review contains a comprehensive description of the many LNPs categories used as nanocarriers in cancer treatment to date, as well as the potential of LNPs for future applications in other areas of medicine and research.

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BACKGROUND: Obesity is a long-standing health issue in Saudi Arabia, known to be associated with various complications. The management of obesity encompasses both non-surgical and surgical interventions, such as sleeve gastrectomy. Although sleeve gastrectomy is one of the effective options for individuals with morbid obesity, it is not without potential complications. This study aims to examine the outcomes of patients who underwent laparoscopic sleeve gastrectomy. METHODS: A descriptive, retrospective study was conducted on adult patients who underwent laparoscopic sleeve gastrectomy at King Fahad General Hospital in Jeddah, Saudi Arabia, between January 2017 and July 2022. RESULTS: Among the 561 adult patients in the study, 53.5% were classified as having class III obesity, and 74.2% had comorbidities. Complications observed following the procedure included leaking (3.2%), symptomatic gallstone disease (2.9%), internal hernia (1.8%), and readmission (2.1%). There were no cases of bleeding, aspiration pneumonia, or mortality reported. Leakage and gallstone disease were more prevalent among patients classified as class I and II obesity, respectively, while internal hernia and readmission were more frequently observed in patients with class III obesity. CONCLUSION: Laparoscopic sleeve gastrectomy is a viable procedure for managing obesity, as it is associated with minimal complications and no recorded mortality.

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Creating ultrathin, mountable fibers from a wide range of polymeric functional materials has made electrospinning an adequate approach to producing highly flexible and elastic materials. In this paper, electrospinning was utilized to produce thermoplastic polyurethane (TPU) nanofibrous membranes for the purpose of studying their thermal and mechanical properties. Towards a study of the effects of fiber orientation and multi-walled carbon nanotubes (MWCNTs) as a filler on both mechanical and thermal characteristics of electrospun TPU mats, an experimental comparison was held between unidirectional and randomly aligned TPU and TPU/MWCNTs nanofibrous structures. The incorporation of MWCNTs into randomly oriented TPU nanofibers resulted in a significant increase in Young's modulus (E), from 3.9 to 7.5 MPa. On the other hand, for unidirectionally spun fibers, Young's modulus increased from 17.1 to 18.4 MPa upon the addition of MWCNTs. However, dynamic mechanical analysis revealed a different behavior. The randomly oriented specimens exhibited a storage modulus with a significant increase from 180 to 614 MPa for TPU and TPU/MWCNTs mats, respectively, and a slight increase from 119 to 143 MPa for unidirectional TPU and TPU/MWCNTs mats, respectively. Meanwhile, the loss modulus increased with the addition of MWCNTs from 15.7 to 58.9 MPa and from 6.4 to 12 MPa for the random and aligned fibers, respectively. The glass transition values for all the mats fell in the temperature range of - 60 to - 20 °C. The thermal degradation of the membranes was not significantly affected by the addition of MWCNTs, indicating that the mixing of the two constituents did not change the TPU's polymer structure and that the TPU/MWCNTs nanocomposite exhibited stable thermal degradation properties.

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Background: Nonalcoholic Fatty Liver Disease (NAFLD) has become a significant public health concern, affecting approximately one-fourth of the population. Despite its prevalence, no FDA-approved drug treatments specifically target NAFLD. Aim: To provide a review of clinical trials investigating the use of herbal remedies and dietary supplements in NAFLD management, utilizing the ClinicalTrials.gov database. Methods: This review evaluates the current evidence by examining completed phase III and IV clinical trials registered on ClinicalTrials.gov. An exhaustive search was performed on April 17, 2023, using the terms "Nonalcoholic Fatty Liver Disease" and "NAFLD." Two independent reviewers appraised eligible trials based on pre-defined inclusion and exclusion criteria. Results: An initial search yielded 1,226 clinical trials, with 12 meeting the inclusion criteria after filtration. The majority of trials focused on Omega-3 fatty acids (20.0%) and vitamin D (26.7%), followed by caffeine, chlorogenic acid, ginger, phosphatidylcholine, Trigonella Foenum-graecum seed extract, vitamin C, and vitamin E (each 6.7%). Most studies were Phase 3 (75.0%) and used a parallel assignment model (91.7%). Quadruple masking was the most prevalent technique (58.3%), and Iran was the leading country in terms of trial locations (25.0%). These interventions constitute two herbal interventions and nine supplement interventions. Conclusion: This reveals a diverse range of nutraceuticals, with Omega-3 fatty acids and vitamin D being predominant in the management of NAFLD. The global distribution of trials highlights the widespread interest in these therapeutics. However, more rigorous, large-scale trials are needed to establish safety, efficacy, and optimal dosages.

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BACKGROUND: Combretastatin A-4 (CA-4) binds ß-tubulin at the colchicine-binding site preventing tubulin from polymerizing into microtubules. CA-4 and cis combretastatin analogs isomerize to the trans form resulting in decreased cytotoxicity and anti-tubulin activity. However, the excellent anti-cancer potential and relatively simple molecular structure of CA-4 provide an encouraging starting point for the development of new, more stable and more potent anti-tubulin compounds. OBJECTIVE: This study aimed to synthesize a new series of compounds derived from 4-(3,4,5- trimethoxyphenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione derivatives (compounds 10-12) with substituted phenyl group at C5 of the triazole ring (B-ring) as analogs of CA-4, with different alkyl and aryl side chain substituents at the triazole moiety, resulting in the permanent cis configuration of the two phenyl rings. Moreover, the anti-cancer activities of the new compounds were assessed. METHODS: Chemical synthesis was carried out by conventional organic methods. The newly synthesized CA-4 analogs were characterized by FT-IR, 1HNMR, 13CNMR, and HR-MS(ESI) techniques. Molecular docking studies, including docking score (ΔG), ADMET, DFT, and molecular similarities, were performed. The anti-proliferative activity of the new compounds against three human cancer cell lines (A549, Hep G2, and HCT-116) and the normal cell line WI-38 was evaluated using the MTT assay, and their ability to inhibit tubulin polymerization, and consequently, their effects on cell cycle progression and induction of apoptosis were assessed. RESULTS: Molecular docking studies showed that compounds 11b and 11d exhibited the highest docking scores (-13.30 and -14.01 Kcal/mol, respectively) into the colchicine-binding site, scores very close to the reference drug colchicine (-13.50 Kcal/mol), and that hydrogen bonding and hydrophobic interaction are essential for binding. The most active cytotoxic compound, 11b, had potent IC50 values against the three human cancer cell lines (3.83, 10.20, and 10.67 µM against Hep G2, HCT- 116, and A549, respectively) while exhibiting low cytotoxicity against non-cancer-human WI-38, suggesting that compound 11b targets rapidly growing cancer cells. Moreover, compound 11b exhibited potent anti-tubulin activity which was comparable to CA-4. Targeting microtubules caused cell cycle arrest at the G2/M phase resulting in the induction of apoptosis. CONCLUSION: These findings indicate that compound 11b is a promising ß-tubulin-binding compound with antimitotic action that has the potential to treat cancer.

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The objective of the current study was to identify potential drug-drug interactions (DDIs) with the drug candidate fb-PMT, a novel anticancer thyrointegrin αvß3 antagonist. This was accomplished by using several in vitro assays to study interactions of fb-PMT with both cytochrome P450 (CYP) enzymes and drug transporters, two common mechanisms leading to adverse drug effects. In vitro experiments showed that fb-PMT exhibited weak reversible inhibition of CYP2C19 and CYP3A4. In addition, fb-PMT did not show time-dependent inhibition with any of the seven CYP isoforms tested, including 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4. Human liver microsomal incubations demonstrated that fb-PMT is stable. Potential transporter-mediated DDIs with fb-PMT were assessed with two ATP binding cassette (ABC) family transporters (P-glycoprotein and breast cancer resistance protein) using Caco2 cells and seven solute carrier family (SLC) transporters (organic cation transporter OCT2, organic anion transporters OAT1 and OAT3, organic anion transporter peptides OATP1B1 and OATP1B3, and the multidrug and toxic extrusion proteins MATE1 and MATE2-K using transfected HEK293 cells). Fb-PMT was not a substrate for any of the nine transporters tested in this study, nor did it inhibit the activity of seven of the transporters tested. However, fb-PMT inhibited the uptake of rosuvastatin by both OATP1B1 and OATP1B3 with half-maximal inhibitory concentrations greater than 3 and less than 10 µM. In summary, data suggest that the systemic administration of fb-PMT is unlikely to lead to DDIs through CYP enzymes or ABC and SLC transporters in humans.

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The advent of Industry 4.0 promises to transform the global business landscape, the nature of markets and industries, and the way multinationals organize their operations as well as how and where they compete. These changes will have important - indeed profound - implications for IB scholarship. In this article, we explain Industry 4.0 and its distinguishing characteristics; discuss its organizational and strategic implications for multinationals; and outline the fundamental questions it raises for future IB research. To spur future analysis, we also present a conceptual foundation that articulates the new features, processes, and capabilities that support MNEs' pursuit of Industry 4.0-related opportunities surrounding digitalization, intelligence, technology, and innovation. We also discuss what Industry 4.0 means for IB research concerning social engagement, environmental sustainability, and international entrepreneurship. We elucidate how this new landscape shapes the extant IB literature and how future research can push it further along.

L'avènement de l'Industrie 4.0 promet de transformer le paysage commercial mondial, la nature des marchés et des industries, la façon d'organiser des opérations des multinationales ainsi que la manière dont et le lieu où ces dernières rivalisent. Ces changements auront des implications importantes, voire profondes, pour la recherche en affaires internationales (International Business ­ IB). Dans cet article, nous expliquons l'Industrie 4.0 et ses caractéristiques distinctives ­ discutons ses implications organisationnelles et stratégiques pour les multinationales ­ et exposons les questions fondamentales qu'elle soulève pour de futures recherches en IB. Afin de stimuler de futures analyses, nous présentons également un fondement conceptuel articulé autour des caractéristiques, capacités et processus nouveaux qui permettent aux multinationales de saisir les opportunités liées à l'Industrie 4.0 en matière de numérisation, d'intelligence, de technologie et d'innovation. Nous examinons également ce que l'Industrie 4.0 signifie pour la recherche en IB en matière d'engagement social, de durabilité environnementale et d'entrepreneuriat international. Nous mettons en lumière comment ce nouveau paysage façonne la littérature existante de l'IB et comment de futures recherches peuvent la faire progresser.

La llegada de la Industria 4.0 promete transformar el panorama empresarial global, la naturaleza de los mercados y las industrias, y el modo en que las multinacionales organizan sus operaciones, así como el modo y el lugar en que compiten. Estos cambios tendrán importantes implicaciones ­ de hecho, profundas ­ para los académicos de negocios internacionales. En este artículo, explicamos la Industria 4.0 y sus características distintivas, analizamos sus implicaciones organizacionales y estratégicas para las multinacionales y esbozamos las cuestiones fundamentales que plantea para la futura investigación sobre negocios internacionales. Para estimular futuros análisis, también presentamos una base conceptual que articula las nuevas características, procesos y capacidades que apoyan la búsqueda de oportunidades relacionadas con la Industria 4.0 por parte de las empresas multinacionales en torno a la digitalización, la inteligencia, la tecnología y la innovación. También analizamos lo que significa la Industria 4.0 para la investigación en negocios internacionales en lo que respecta al compromiso social, la sostenibilidad medioambiental y el emprendimiento internacional. Esclarecemos cómo este nuevo panorama da forma a la literatura existente de negocios internacionales y cómo la investigación futura puede hacerla avanzar.

O advento da Indústria 4.0 promete transformar o cenário global de negócios, a natureza de mercados e indústrias e a forma pela qual multinacionais organizam suas operações, e como e onde competem. Essas mudanças terão implicações importantes ­ realmente profundas ­ para a pesquisa em IB. Neste artigo, explicamos a Indústria 4.0 e suas características distintivas; discutimos suas implicações organizacionais e estratégicas para multinacionais; e delineamos as questões fundamentais que ela levanta para futuras pesquisas em IB. Para estimular futuras análises, também apresentamos uma base conceitual que articula as novas características, processos e capacidades que apoiam a busca de oportunidades relacionadas à Indústria 4.0 por MNEs em torno da digitalização, inteligência, tecnologia e inovação. Também discutimos o que a Indústria 4.0 significa para a pesquisa em IB no que tange ao engajamento social, sustentabilidade ambiental e empreendedorismo internacional. Elucidamos como esse novo cenário molda a literatura existente em IB e como pesquisas futuras podem avançá-la ainda mais.

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The principal hormonal product of the thyroid gland, L-thyroxine (T4), is a prohormone for 3,3',5-triiodo-L-thyronine, T3, the major ligand of nuclear thyroid hormone receptors (TRs). At a cell surface thyroid hormone analogue receptor on cancer cell and endothelial cell plasma membrane integrin αvß3, however, T4 at physiological concentrations is biologically active and is the major ligand. At this site in solid tumor cells, T4 nongenomically initiates cell proliferation, is anti-apoptotic by multiple mechanisms, supports radioresistance and enhances cancer-related angiogenesis. In contrast, hypothyroidism has been reported clinically to slow tumor growth. At physiological levels, T3 is not biologically active at the integrin and maintenance of euthyroidism with T3 in cancer patients may be associated with slowed tumor proliferation. Against this background, we raise the possibility that host serum T4 levels that are spontaneously in the upper tertile or quartile of the normal range in cancer patients may be a factor that contributes to aggressive tumor behavior. Recent observations on tumor metastasis and tumor-associated propensity for thrombosis due to T4 also justify clinical statistical analysis for a relationship to upper tertile hormone levels. That reverse T3 (rT3) may stimulate tumor growth has recently been reported and thus the utility of adding this measurement to thyroid function testing in cancer patients requires assessment. In summary, T4 at physiological concentrations promotes tumor cell division and aggressiveness and euthyroid hypothyroxinemia arrests clinically advanced solid tumors. These findings support the clinical possibility that T4 levels in the upper tertile of the normal range require examination as a tumor supporting factor.

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A new series of 4-(4-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazole-3-thiol derivatives were synthesized as analogs for the anticancer drug combretastatin A-4 (CA-4) and characterized using FT-IR, 1 H-NMR, 13 CNMR, and HR-MS techniques. The new CA-4 analogs were designed to meet the structural requirements of the highest expected anticancer activity of CA-4 analogs by maintaining ring A 3,4,5-trimethoxyphenyl moiety, and at the same time varying the substituents effect of the triazole moiety (ring B). In silico analysis indicated that compound 3 has higher total energy and dipole moment than colchicine and the other analogs, and it has excellent distribution of electron density and is more stable, resulting in an increased binding affinity during tubulin inhibition. Additionally, compound 3 was found to interact with three apoptotic markers, namely p53, Bcl-2, and caspase 3. Compound 3 showed strong similarity to colchicine, and it has excellent pharmacokinetics properties and a good dynamic profile. The in vitro anti-proliferation studies showed that compound 3 is the most cytotoxic CA-4 analog against cancer cells (IC50 of 6.35 µM against Hep G2 hepatocarcinoma cells), and based on its selectivity index (4.7), compound 3 is a cancer cytotoxic-selective agent. As expected and similar to colchicine, compound 3-treated Hep G2 hepatocarcinoma cells were arrested at the G2/M phase resulting in induction of apoptosis. Compound 3 tubulin polymerization IC50 (9.50 µM) and effect on Vmax of tubulin polymerization was comparable to that of colchicine (5.49 µM). Taken together, the findings of the current study suggest that compound 3, through its binding to the colchicine-binding site at ß-tubulin, is a promising microtubule-disrupting agent with excellent potential to be used as cancer therapeutic agent.

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Background: Thyrointegrin αvß3 receptors are unique molecular cancer therapeutic targets because of their overexpression on cancer and rapidly dividing blood vessel cells compared and quiescent on normal cells. A macromolecule, TriAzole Tetraiodothyroacetic acid (TAT) conjugated to polyethylene glycol with a lipophilic 4-fluorobenyl group (fb-PMT and NP751), interacts with high affinity (0.21 nM) and specificity with the thyrointegrin αvß3 receptors on the cell surface without nuclear translocation in contrast to the non-polymer conjugated TAT. Methods: The following in vitro assays were carried out to evaluate NP751 including binding affinity to different integrins, transthyretin (TTR)-binding affinity, glioblastoma multiforme (GBM) cell adhesion, proliferation assays, nuclear translocations, chorioallantoic membrane model of angiogenesis, and microarray for molecular mechanisms. Additionally, in vivo studies were carried out to evaluate the anticancer efficacy of NP751, its biodistribution, and brain GBM tumor versus plasma levels kinetics. Results: NP751 demonstrated a broad spectrum of antiangiogenesis and anticancer efficacy in experimental models of angiogenesis and xenografts of human GBM cells. Tumor growth and cancer cells' viability were markedly decreased (by > 90%; P < .001) in fb-PMT-treated U87-luc or 3 different primary human GBM xenograft-bearing mice based on tumor in vivo imaging system (IVIS) imaging and histopathological examination, without relapse upon treatment discontinuation. Additionally, it effectively transports across the blood-brain barrier via its high-affinity binding to plasma TTR with high retention in brain tumors. NP751-induced effects on gene expression support the model of molecular interference at multiple key pathways essential for GBM tumor progression and vascularization. Conclusions: fb-PMT is a potent thyrointegrin αvß3 antagonist with potential impact on GBM tumor progression.

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In the original publication [...].