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On account of its crucial role in the virus life cycle, SARS-COV-2 NSP13 helicase enzyme was exploited as a promising target to identify a novel potential inhibitor using multi-stage structure-based drug discovery approaches. Firstly, a 3D pharmacophore was generated based on the collected data from a protein-ligand interaction fingerprint (PLIF) study using key interactions between co-crystallised fragments and the NSP13 helicase active site. The ZINC database was screened through the generated 3D-pharmacophore retrieving 13 potential hits. All the retrieved hits exceeded the benchmark score of the co-crystallised fragments at the molecular docking step and the best five-hit compounds were selected for further analysis. Finally, a combination between molecular dynamics simulations and MM-PBSA based binding free energy calculations was conducted on the best hit (compound FWM-1) bound to NSP13 helicase enzyme, which identified FWM-1 as a potential potent NSP13 helicase inhibitor with binding free energy equals −328.6 ± 9.2 kcal/mol., Graphical Abstract

In this study, different assortments of 2-arylquinolines and 2,6-diarylquinolines have been developed. Recently, we have developed a new series of 6,7-dimethoxy-4-alkoxy-2-arylquinolines as Topoisomerase I (TOP1) inhibitors with potent anticancer activity. Utilising the SAR outputs from this study, we tried to enhance anticancer and TOP1 inhibitory activities. Though target quinolines demonstrated potent antiproliferative effect, specifically against colorectal cancer DLD-1 and HCT-116, they showed weak TOP1 inhibition which may be attributable to their non-coplanarity. Thereafter, screening against kinase panel revealed their dual inhibitory activity against EGFR and FAK. Quinolines 6f, 6h, 6i, and 20f were the most potent EGFR inhibitors (IC50s = 25.39, 20.15, 22.36, and 24.81 nM, respectively). Meanwhile, quinolines 6f, 6h, 6i, 16d, and 20f exerted the best FAK inhibition (IC50s = 22.68, 14.25, 18.36, 17.36, and 15.36 nM, respectively). Finally, molecular modelling was employed to justify the promising EGFR/FAK inhibition. The study outcomes afforded the first reported quinolines with potent EGFR/FAK dual inhibition., Graphical Abstract

Topical agents are sometimes applied to surgical wounds after closure; these may include antiseptics or antibiotics. Minimal research has been undertaken to investigate the effect of topical regimens on the tensile strength of suture materials.To investigate the effect of four commonly used wound care regimens on the tensile strength of suture materials.The failure load of 9 different suture materials was tested using the Instron Electroplus E3000 tensile testing machine (Instron Corporation, Norwood, Massachusetts). Tensile strength was represented as the failure load, measured in Newtons (N), and defined as the maximal load that could be applied across the suture prior to failure. Each suture was tested dry and after immersion in one of 4 products for 7 days and tested on day 7. The immersion agents tested were: sodium chloride 0.9%, MicroSafe® (Sonoma Pharmaceuticals, Petaluma, CA), Aqueous Povidone-iodine 10% solution (Betadine-Mundipharma), and Fucidin ointment.Sodium chloride 0.9%, MicroSafe®, Aqueous Povidone-iodine 10%, and Fucidin seem to increase the failure load of most absorbable and non-absorbable sutures. However, the failure load of Polyglactin 910 suture (Surgilactin, coated, violet-Ethicon) is reduced by long-term exposure to either sodium chloride 0.9% or MicroSafe®, while the failure load of the Polydioxanone suture (PDS Plus-Ethicon) is reduced by long-term exposure to MicroSafe® only.In our experiment, the commonly used wound care products have been shown to alter the tensile strength of suture materials. Further human studies are required to ascertain the clinical validity and applicability of our findings.

The Social Vulnerability Index (SVI) is a publicly available dataset to identify communities in greatest need of resources.To examine the utility of using the county-level SVI as predictors of asthma-related outcomes.We used the American Community Survey-derived SVI and the National Environmental Public Health Tracking Network - Query Tool to retrieve data for all counties with available SVI data and at least one matched outcome of interest. Then, we tested SVI as a predictor for emergency department visits (EDV) and hospitalizations, with investigating disparities in primary care physician (PCP) density and emergency department physicians (EDP) density. Linear and logistic regression models were used.Compared to counties of the lowest SVI quartile, counties of mid-low, mid-high, and highest SVI quartiles had 1%, 4%, and 5% higher odds of asthma-related EDV per 10,000 population, respectively, and 4%, 21%, and 24% higher odds of asthma-related hospitalization per 10,000 population, respectively. Moreover, the data showed an apparent resources mismatch between the EDP densities per 10,000 populations and the SVI quartiles, and the effect of the county level SVI on the asthma-related EDV and hospitalization is not strongly affected by PCP or EDP densities.The counties with the highest SVI -and the most vulnerable to asthma hazards- have a lower coverage of PCP and EDP. Interventions directed to address persistent social vulnerability would offer the opportunity of primary prevention with less exhaustion for the medical resources.

Human leukocyte antigen (HLA)-G molecules are proposed to influence susceptibility to coronavirus disease 2019 (COVID-19). A case-control study was conducted on 209 patients with COVID-19 and198 controls to assess soluble HLA-G (sHLA-G) levels and HLA-G 14-bp insertion [Ins]/deletion [Del] polymorphism. Results revealed that median levels of sHLA-G were significantly higher in serum of COVID-19 patients than in controls (17.92 [interquartile range: 14.86-21.15] vs. 13.42 [9.95-17.38] ng/mL; probability0.001). sHLA-G levels showed no significant differences between patients with moderate, severe or critical disease. Del allele was significantly associated with the risk of COVID-19 (odds ratio = 1.89; 95% confidence interval = 1.44-2.48; corrected probability = 0.001), while a higher risk was associated with Del/Del genotype (odds ratio = 2.39; 95% confidence interval = 1.25-4.58; corrected probability = 0.048). Allele and genotype frequencies of HLA-G 14-bp Ins/Del polymorphism stratified by gender or disease severity showed no significant differences in each stratum. Further, there was no significant impact of genotypes on sHLA-G levels. In conclusion, sHLA-G levels were up-regulated in COVID-19 patients regardless of disease severity. Further, it is suggested that HLA-G 14-bp Ins/Del polymorphism is associated with COVID-19 risk.

This paper presents the research results on the contribution of user-centered data mining based on the standard principles, focusing on the analysis of survival and mortality of lung cancer cases. Researchers used anonymized data from previously diagnosed instances in the health database to predict the condition of new patients who have not had their results yet. Medical professionals specializing in this field provided feedback on the usefulness of the new software, which was constructed using WEKA data mining tools and the Naive Bayes method. The results of this article provide elements of interest to discuss the value of identifying or discovering relationships in apparently “hidden” information to propose strategies to counteract health problems or prevent future complications and thus contribute to improving the quality of care. Life of the population, as would be the case of data mining in the health area, has shown applicability in the early detection and prevention of diseases for the analysis of genetic markers to determine the probability of a satisfactory response to medical treatment, and the most accurate model was Naive Bayes (91.1%). The Naive Bayes algorithm’s closest competitor, bagging, came in second with 90.8%. The analysis found that the ZeroR algorithm had the lowest success rate at 80%.

Colon cancer is a disease characterized by the unusual and uncontrolled development of cells that are found in the large intestine. If the tumour extends to the lower part of the colon (rectum), the cancer may be colorectal. Medical imaging is the denomination of methods used to create visual representations of the human body for clinical analysis, such as diagnosing, monitoring, and treating medical conditions. In this research, a computational proposal is presented to aid the diagnosis of colon cancer, which consists of using hyperspectral images obtained from slides with biopsy samples of colon tissue in paraffin, characterizing pixels so that, afterwards, imaging techniques can be applied. Using computer graphics augmenting conventional histological deep learning architecture, it can classify pixels in hyperspectral images as cancerous, inflammatory, or healthy. It is possible to find connections between histochemical characteristics and the absorbance of tissue under various conditions using infrared photons at various frequencies in hyperspectral imaging (HSI). Deep learning techniques were used to construct and implement a predictor to detect anomalies, as well as to develop a computer interface to assist pathologists in the diagnosis of colon cancer. An infrared absorbance spectrum of each of the pixels used in the developed classifier resulted in an accuracy level of 94% for these three classes.

BACKGROUND: Work-related musculoskeletal disorders (WMSDs) among sonographers have raised significant concerns in recent years. OBJECTIVES: This study aimed to estimate the prevalence of WMSDs and identify risk factors for WMSDs among sonographers. To date, there is little research on WMSDs among sonographers in Saudi Arabia. Therefore, this study aimed to contribute to the Saudi literature by filling this gap. METHODS: A cross-sectional study was conducted among sonographers (n = 98) working in four major governmental hospitals in the city of Al-Ahsa, Saudi Arabia. The participants completed a validated, self-administered questionnaire that focused on the analysis of musculoskeletal symptoms among sonographers. RESULTS: The mean age of the respondents was 35.5±9 years. The majority of the participants were female (71.4%), non-Saudi (51%), and working as technicians (49%). The prevalence rates of shoulder and neck disorders among the participants were 65.3% and 57.1%, respectively. Gender (female), job title (sonography technicians), and years of experience (seasoned sonographers) were identified as risk factors for WMSDs. CONCLUSIONS: Among the studied sonographers, WMSDs were a significant, common problem. Being female, being a sonography technician, and being a seasoned sonographer were identified as risk factors for these disorders. Preventive measures should be implemented to reduce the risk of WMSDs in this occupational setting.

Peer reviewed: True, The genus Moricandia (Brassicaceae) comprises about eight species that were used in traditional medicine. Moricandia sinaica is used to alleviate certain disorders such as syphilis and exhibits analgesic, anti-inflammatory, antipyretic, antioxidant, and antigenotoxic properties. Throughout this study, we aimed to figure out the chemical composition of lipophilic extract and essential oil obtained from M. sinaica aerial parts using GC/MS analysis, as well as their cytotoxic and antioxidant activities correlated with the major detected compounds' molecular docking. The results revealed that both the lipophilic extract and the oil were found to be rich in aliphatic hydrocarbons, accounting for 72.00% and 79.85%, respectively. Furthermore, the lipophilic extract's major constituents are octacosanol, γ-sitosterol, α-amyrin, β-amyrin acetate, and α-tocopherol. Contrarily, monoterpenes and sesquiterpenes accounted for the majority of the essential oil. The essential oil and the lipophilic extract of M. sinaica showed cytotoxic properties towards human liver cancer cells (HepG2) with IC50 values of 126.65 and 220.21 µg/mL, respectively. The lipophilic extract revealed antioxidant activity in the DPPH assay with an IC50 value of 2679 ± 128.13 µg/mL and in the FRAP assay, moderate antioxidant potential was expressed as 44.30 ± 3.73 µM Trolox equivalent/mg sample. The molecular docking studies revealed that ꞵ-amyrin acetate, α -tocopherol, γ-sitosterol, and n-pentacosaneachieved the best docking scores for NADPH oxidase, phosphoinositide-3 kinase, and protein kinase B. Consequently, M. sinaica essential oil and lipophilic extract can be employed as a viable management strategy for oxidative stress conditions and the formulation of improved cytotoxic treatment regimens.

This study aimed to utilize cholesterol conjugation of 5-fluorouracil (5-FUC) and liposomal formulas to enhance the partitioning of 5-FU into low density lipoprotein (LDL) to target hepatocellular carcinoma (HCC). Thus, 5-FU and 5-FUCwere loaded into liposomes. Later, the direct loading and transfer of 5-FU, and 5-FUC from liposomes into LDL were attained. The preparations were characterized in terms of particle size, zeta potential, morphology, entrapment efficiency, and cytotoxicity using the HepG2 cell line. Moreover, the drug deposition into the LDL and liver tissues was investigated. The present results revealed that liposomal preparations have a nanosize range (155 − 194 nm), negative zeta potential (- 0.82 to – 16 mV), entrapment efficiency of 69% for 5-FU, and 66% for 5-FUC. Moreover, LDL particles have a nanosize range (28–49 nm), negative zeta potential (- 17 to −27 mV), and the entrapment efficiency is 11% for 5-FU and 85% for 5-FUC. Furthermore, 5-FUC loaded liposomes displayed a sustained release profile (57%) at 24 h compared to fast release (92%) of 5-FU loaded liposomes. 5-FUC and liposomal formulas enhanced the transfer of 5-FUC into LDL compared to 5-FU. 5-FUC loaded liposomes and LDL have greater cytotoxicity against HepG2 cell lines compared to 5-FU and 5-FUC solutions. Moreover, the deposition of 5-FUC in LDL (26.87ng/mg) and liver tissues (534 ng/gm tissue) was significantly increased 5-FUC liposomes compared to 5-FU (11.7 ng/g tissue) liposomal formulation. In conclusion, 5-FUC is a promising strategy for hepatic targeting of 5-FU through LDL-mediated gateway., Graphical abstract

The understanding of coronavirus disease 2019 (COVID-19) immune dysregulation is evolving. Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with alternations in both innate and adaptive immunity, probably caused by a complex interplay of genetics and environmental exposure with various triggers. A rare hematological complication of SLE as well as recently reported in an adult with COVID-19 is thrombotic thrombocytopenic purpura. We report a pediatric case with features suggestive of the multisystem inflammatory syndrome in children with coronary artery ectasia, thrombotic thrombocytopenic purpura, and new-onset SLE.

Durvalumab (IMFINZI®), a fully human monoclonal antibody against programmed cell death-ligand 1 (PD-L1), is approved for use in combination with etoposide and either carboplatin or cisplatin for the first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC). In the pivotal phase III CASPIAN trial in previously untreated adults with ES-SCLC, the addition of durvalumab to chemotherapy for up to 4 cycles followed by maintenance durvalumab was associated with a significantly longer overall survival and a favourable hazard ratio for progression-free survival compared with chemotherapy alone for up to 6 cycles. A higher proportion of patients in the durvalumab plus chemotherapy group had an objective response compared with the chemotherapy alone group. The efficacy of durvalumab was also sustained with longer follow-up. Durvalumab in combination with etoposide and either carboplatin or cisplatin had a manageable tolerability profile in patients with ES-SCLC. Given the available evidence, durvalumab in combination with etoposide and either carboplatin or cisplatin represents a valuable treatment option for the first-line treatment of patients with ES-SCLC, and is an accepted standard of care option in this setting. Supplementary Information The online version contains supplementary material available at 10.1007/s11523-021-00843-0., Plain Language Summary Small cell lung cancer (SCLC) is the most aggressive form of lung cancer; extensive-stage (ES) disease, which accounts for about two-thirds of all SCLC, is associated with high relapse rates and a poor prognosis. Expression of programmed cell death-ligand 1 (PD-L1) on both tumour cells and tumour-associated immune cells is an adaptive immune response that helps tumour cells avoid detection and subsequent elimination by the immune system. Durvalumab (IMFINZI®) is a fully human monoclonal antibody against PD-L1, which blocks the interaction of PD-L1 with its receptors, thus enhancing anti-tumour immune responses. When used in combination with chemotherapy (etoposide and either carboplatin or cisplatin) in adults with untreated ES-SCLC, durvalumab prolonged overall survival compared with chemotherapy alone; the improvements in overall survival were also maintained with additional follow-up. The tolerability profile of durvalumab in combination with chemotherapy was manageable in patients with ES-SCLC. Durvalumab in combination with chemotherapy is an effective and valuable treatment option for previously untreated patients with ES-SCLC. Supplementary Information The online version contains supplementary material available at 10.1007/s11523-021-00843-0.

Although patients with Alzheimer's disease and other cognitive-related neurodegenerative disorders may benefit from early detection, development of a reliable diagnostic test has remained elusive. The penetration of digital voice-recording technologies and multiple cognitive processes deployed when constructing spoken responses might offer an opportunity to predict cognitive status.To determine whether cognitive status might be predicted from voice recordings of neuropsychological testing.Comparison of acoustic and (para)linguistic variables from low-quality automated transcriptions of neuropsychological testing (n = 200) versus variables from high-quality manual transcriptions (n = 127). We trained a logistic regression classifier to predict cognitive status, which was tested against actual diagnoses.Observational cohort study.146 participants in the Framingham Heart Study.Acoustic and either paralinguistic variables (e.g., speaking time) from automated transcriptions or linguistic variables (e.g., phrase complexity) from manual transcriptions.Models based on demographic features alone were not robust (area under the receiver-operator characteristic curve [AUROC] 0.60). Addition of clinical and standard acoustic features boosted the AUROC to 0.81. Additional inclusion of transcription-related features yielded an AUROC of 0.90.The use of voice-based digital biomarkers derived from automated processing methods, combined with standard patient screening, might constitute a scalable way to enable early detection of dementia.

This current study review provides a brief review of a natural bee product known as propolis and its relevance toward combating SARS-CoV viruses. Propolis has been utilized in medicinal products for centuries due to its excellent biological properties. These include anti-oxidant, immunomodulatory, anti-inflammatory, anti-viral, anti-fungal, and bactericidal activities. Furthermore, studies on molecular simulations show that flavonoids in propolis may reduce viral replication. While further research is needed to validate this theory, it has been observed that COVID-19 patients receiving propolis show earlier viral clearance, enhanced symptom recovery, quicker discharge from hospitals, and a reduced mortality rate relative to other patients. As a result, it appears that propolis could probably be useful in the treatment of SARS-CoV-2-infected patients. Therefore, this review sought to explore the natural properties of propolis and further evaluated past studies that investigated propolis as an alternative product for the treatment of COVID-19 symptoms. In addition, the review also highlights the possible mode of propolis action as well as molecular simulations of propolis compounds that may interact with the SARS-CoV-2 virus. The activity of propolis compounds in decreasing the impact of COVID-19-related comorbidities, the possible roles of such compounds as COVID-19 vaccine adjuvants, and the use of nutraceuticals in COVID-19 treatment, instead of pharmaceuticals, has also been discussed.

Objectives To describe the epidemiological characteristics of the first 69,382 patients with COVID-19 infection in Oman. Methods A retrospective case series study of patients diagnosed with SARS-CoV-2 infection in Oman from 24 February to 23 July 2020. The data were obtained from the National surveillance COVID-19 network. Results The overall mean age of patients was 34 (± 14) years, 74% (n = 51,391) were males, 40,859 (59%) were Omani citizens, and 28,523 (41%) were foreign-born individuals. The most common symptoms at presentation were fever 50% (n = 34,600), cough 46% (n = 32,062), sore throat 46% (n = 31,953) and shortness of breath (SOB) 35% (n = 24,567). Overall, 8,960 (12.9%) patients required hospitalization with 1189 (13.3%) individuals requiring admission to the intensive care unit (ICU) and mechanical ventilation (MV). Patients hospitalized with COVID-19 infection were mostly Omani nationals and males between 30 and 39 years old (p n = 359) with rates of 9.4 (n = 278) and 4.8 (n = 81) deaths per 100,000 population in Omani nationals and foreign-born individuals, respectively. Females hospitalized with COVID-19 had a mean age of 64 (± 18) years versus a mean age of 55 (± 17) years in males. Mean age of patients with COVID-19-related mortality was 58 (± 18) years with significant differences in mean age between females and males 64 (± 18) versus 55 (± 17) years, respectively. Conclusions Young Omani males accounted for the highest incidence of COVID-19 infection and hospitalization, while mortality rates were higher among males and the older age (> 50 years). Identifying the epidemiological characteristics and outcomes of COVID-19-infected patients is essential for developing targeted intervention strategies and preparing for the resurgence of anticipated second and third waves of this pandemic.

The complement system represents an innate immune response consisting of a protein network. Over-activation of the complement system plays an important role in inflammation, tissue damage, and infectious disease severity. The prevalence of MERS-CoV in Saudi Arabia remains significant and cases are still being reported. The role of complement in Middle East Respiratory Syndrome coronavirus (MERS-CoV) pathogenesis and complement‐modulating treatment strategies has received limited attention, and studies involving MERS-CoV-infected patients have not been reported. This study offers the first insight into the pulmonary expression profile including Seven complement proteins including complement regulatory factors during MERS-CoV infection. We also measured the expression of lung neutrophil chemoattractant chemokine IL-8 (CXCL8) and RANTES (CCL5). Our results significantly indicate high expression levels of complement anaphylatoxins (C3a and C5a), IL-8, and RANTES in the lungs of MERS-CoV-infected patients. The upregulation of lung complement anaphylatoxins, C5a and C3a, was positively correlated with IL-8, RANTES and the fatality rate. Our results also showed upregulation of the positive regulatory complement factor P (properdin), suggesting positive regulation of the complement during MERS-CoV infection. In addition, we also demonstrated that a high viral load in all patients with MERS-CoV correlated with C5a and C3a levels. Pulmonary complement mediators, disease severity, and an increased fatality rate may be linked to the degree of complement activation against MERS-CoV. High levels of lung C5a, C3a, factor P, IL-8 and RANTES may contribute to the immunopathology, disease severity, ARDS development, and a higher fatality rate in MERS-CoV-infected patients. These findings highlight the potential prognostic utility of C5a, C3a, IL-8 and RANTES as biomarkers for MERS-CoV disease severity and mortality. To further explore the functional partners (protiens) prediction of highly expressed proteins (C5a, C3a, factor P, IL-8 and RANTES), the computational protein–protein interaction (PPI) network was constructed, and six proteins (hub nodes) were identified.

Backgroud Cryptosporidium species are zoonotic protozoan parasites responsible for gastroenteritis in various animals and humans. The diagnosis of Cryptosporidium presents many challenges. This research attempted to match the diagnostic efficiency of the modified Ziehl–Neelsen technique (mZN), immunochromatographic assays (IC), and enzyme-linked immunosorbent assay (ELISA) for the detection of Cryptosporidium in faecal samples of cattle in Kuwait. In addition, polymerase chain reaction (PCR) was utilised to determine the predominant species infecting cattle in Kuwait and correlating the detected species with the results of different diagnostic tests used, the presence or absence of clinical signs, and the age group of the infected cattle. Results Of 400 analysed faecal samples, Cryptosporidium positive samples were 23%, 15.25%, and 14% using IC, ELISA, and mZN. IC had the highest sensitivity (74.07%), and mZN had the highest specificity (98.29%) using a composite reference standard (CRS) as a gold standard. The rapid IC test results in high false-positive results of cryptosporidiosis, whereas using mZN alone is insufficient to declare a negative faecal sample. Only 74.5% (35/47) of Cryptosporidium-positive samples by the three assays could be amplified by PCR. This study was the first to genotype Cryptosporidium in Kuwait. Cryptosporidium parvum (n = 26) was the dominant species detected from cattle samples, followed by C. andersoni (n = 6), C. bovis (n = 2), and C. raynae (n = 1). The findings showed a statistically relevant relationship between diarrhoea and the detection of Cryptosporidium spp. in faecal samples of cattle (p-value = 0.0003). Pre-weaned calves were the most vulnerable age group to Cryptosporidium spp. infection (p-value = 0.0007). Conclusion For screening of Cryptosporidium infection in faecal samples, antigen detection or PCR methods combined with one of the microscopy techniques should be used. Cryptosporidium parvum was the prepoderant Cryptosporidium spp. recovered from cattle samples in Kuwait followed by C. andersoni. Cryptosporidium parvum is a significant risk factor for diarrhoea in pre-weaned calves. However, further study is needed as many other causes of diarrhoea in calves must be ruled out before a diagnosis of Cryptosporidium diarrhoea can be made.

In this article, 34 anticoagulant drugs were screened in silico against the main protease (M

BACKGROUND Dieulafoy's lesion is a rare cause of severe gastrointestinal (GI) bleeding, accounting for approximately 1-2% of all cases of GI hemorrhage. Nevertheless, it can be life-threatening without prompt intervention. Dieulafoy's lesion of jejunal origin can be particularly challenging to identify due to the inability of conventional endoscopic techniques to visualize the jejunum. This case report emphasizes the difficulties in diagnosing and managing jejunal Dieulafoy's lesions and highlights the methods by which to approach refractory bleeding. CASE REPORT This is a case of a 41-year-old man with a history of uncontrolled hypertension who presented with an episode of syncope and melena associated with low hemoglobin levels requiring multiple packed red blood cell transfusions. This warranted searching for a source of bleeding within the gastrointestinal tract via 2 upper-GI endoscopies, a colonoscopy, and an abdominal computed tomography angiogram, all of which failed to localize the site of bleeding. A push enteroscopy was required to identify the lesion in the jejunum, but the bleeding was not controlled despite the application of hemoclips and epinephrine. Consequently, laparotomy and resection of the jejunal segment containing the Dieulafoy's lesion was performed and the diagnosis was established histopathologically. The patient recovered well and was discharged 4 days after the procedure. CONCLUSIONS Suspicion of a jejunal Dieulafoy's lesion should be raised if both upper- and lower-GI endoscopies yield unremarkable findings. Ideally, a push enteroscopy should be utilized diagnostically and to conservatively manage the bleeding. However, laparotomy should be considered in refractory lesions or in the presence of hemodynamic instability.

There is scarce information about the occurrence of extended-spectrum β-lactamases (ESBLs) inTo study the antimicrobial resistance and ESBL encoding genes amongA total of 27This study showed the emergence of ESBL-harboring

The sinoatrial node (SAN) is composed of highly specialized cells that mandate the spontaneous beating of the heart through self-generation of an action potential (AP). Despite this automaticity, the SAN is under the modulation of the autonomic nervous system (ANS). In diabetes mellitus (DM), heart rate variability (HRV) manifests as a hallmark of diabetic cardiomyopathy. This is paralleled by an impaired regulation of the ANS, and by a pathological remodeling of the pacemaker structure and function. The direct effect of diabetes on the molecular signatures underscoring this pathology remains ill-defined. The recent focus on the electrical currents of the SAN in diabetes revealed a repressed firing rate of the AP and an elongation of its tracing, along with conduction abnormalities and contractile failure. These changes are blamed on the decreased expression of ion transporters and cell-cell communication ports at the SAN (i.e., HCN4, calcium and potassium channels, connexins 40, 45, and 46) which further promotes arrhythmias. Molecular analysis crystallized the RGS4 (regulator of potassium currents), mitochondrial thioredoxin-2 (reactive oxygen species; ROS scavenger), and the calcium-dependent calmodulin kinase II (CaMKII) as metabolic culprits of relaying the pathological remodeling of the SAN cells (SANCs) structure and function. A special attention is given to the oxidation of CaMKII and the generation of ROS that induce cell damage and apoptosis of diabetic SANCs. Consequently, the diabetic SAN contains a reduced number of cells with significant infiltration of fibrotic tissues that further delay the conduction of the AP between the SANCs. Failure of a genuine generation of AP and conduction of their derivative waves to the neighboring atrial myocardium may also occur as a result of the anti-diabetic regiment (both acute and/or chronic treatments). All together, these changes pose a challenge in the field of cardiology and call for further investigations to understand the etiology of the structural/functional remodeling of the SANCs in diabetes. Such an understanding may lead to more adequate therapies that can optimize glycemic control and improve health-related outcomes in patients with diabetes.

Objectives: To translate the pregnancy physical activity questionnaire (PPAQ) into Arabic language, cross-culturally adapt and test its reliability and validity among Saudi pregnant women. Methods: Pregnancy physical activity questionnaire, which consisted of 36 items, was translated to Arabic following the World Health Organization’s guidelines for tool translation (forward translation, expert panel and back translation, pretesting and cognitive interviewing, and final version), followed by validation by experts. This is a cross-sectional study and data were collected from 118 healthy pregnant Saudi women from May to June 2019. Validity included content validity indices (CVI) and construct validity by Rasch analysis. Reliability was assessed by test-retest reliability and Cronbach’s alpha coefficient. Results: The mean age of the participants was 30.15 ± 5.59 years; 38.2% of them had normal pre-gestational body mass index (n=45). The median of total energy expenditure in physical activity was 356.1 METs.h/week (IQR=162.3-648.3). Item content validity index was good ranging between 0.8-1. Rasch analysis showed good construct validity and excellent reliability for all types of physical activity (>0.89). Conclusion: This Arabic PPAQ is a reliable and valid tool that can be used in Arab countries.

Biotherapeutics are highly efficacious, but the pain and inconvenience of chronic injections lead to poor patient compliance and compromise effective disease management. Despite innumerable attempts, oral delivery of biotherapeutics remains unsuccessful due to their degradation in the gastrointestinal (GI) environment and poor intestinal absorption. We have developed an orally ingestible robotic pill (RP) for drug delivery, which protects the biotherapeutic drug payload from digestion in the GI tract and auto-injects it into the wall of the small intestine as a safe, pain-free injection since the intestines are insensate to sharp stimuli. The payload is delivered upon inflation of a balloon folded within the RP, which deflates immediately after drug delivery. Here we present results from two clinical studies demonstrating the safety, tolerability and performance of the RP in healthy humans. In the first study, three versions of the RP (A, B and C) were evaluated, which were identical in all respects except for the diameter of the balloon. The RP successfully delivered a biotherapeutic (octreotide) in 3 out of 12 subjects in group A, 10 out of 20 subjects in group B and 16 out of 20 subjects in group C, with a mean bioavailability of 65 ± 9% (based on successful drug deliveries in groups A and B). Thus, reliability of drug delivery with the RP ranged from 25 to 80%, with success rate directly related to balloon size. In a separate study, the deployment of the RP was unaffected by fed or fasting conditions suggesting that the RP may be taken with or without food. These promising clinical data suggest that biotherapeutics currently administered parenterally may be safely and reliably delivered via this versatile, orally ingestible drug delivery platform. Graphical abstract

Background The prevalence of diagnosed chronic hepatitis C virus (HCV) infection among pregnant women in the Netherlands is 0.26%, yet many cases remain undiagnosed. HCV screening and treatment of pregnant HCV carriers could reduce the burden of disease and limit vertical transmission from mother to child. We assessed the impact of HCV screening and subsequent treatment with new direct-acting antivirals (DAAs) among pregnant women in the Netherlands. Methods An HCV natural history Markov transition state model was developed, to evaluate the public-health and economic impact of HCV screening and treatment. Besides all 179,000 pregnant women in the Netherlands (cohort 1), we modelled 3 further cohorts: all 79,000 first-time pregnant women (cohort 2), 33,000 pregnant migrant women (cohort 3) and 16,000 first-time pregnant migrant women (cohort 4). Each cohort was analyzed in various scenarios: i no intervention, i.e., the current practice, ii screen-and-treat, i.e., the most extensive approach involving treatment of all individuals found HCV-positive, and iii screen-and-treat/monitor, i.e., a strategy involving treatment of symptomatic (F1–F4) patients and follow-up of asymptomatic (F0) HCV carriers with subsequent treatment only at progression. Results For all cohorts, comparison between scenarios (ii) and (i) resulted in ICERs between €9,306 and €10,173 per QALY gained and 5 year budget impacts varying between €6,283,830 and €19,220,405. For all cohorts, comparison between scenarios (iii) and (i) resulted in ICERs between €1,739 and €2,749 per QALY gained and budget impacts varying between €1,468,670 and €5,607,556. For all cohorts, the ICERs (scenario iii versus ii) involved in delayed treatment of asymptomatic (F0) HCV carriers varied between €56,607 and €56,892, well above the willingness-to-pay (WTP) threshold of €20,000 per QALY gained and even above a threshold of €50,000 per QALY gained. Conclusion Universal screening for HCV among all pregnant women in the Netherlands is cost-effective. However, it would be reasonable to consider smaller risk groups in view of the budget impact of the intervention.

Heat-related illnesses (HRIs), mainly heat exhaustion (HE) and heat stroke (HS), are characterized by an elevation of core body temperature. In this study, we aimed to explore the HRIs' types and patient characteristics among a sample taken from various representative in-field points in the Hajj season. A cross-sectional study was conducted in 2018 at 80 data collection points distributed in the field. Data related to demographics, features and risk factors were collected and analyzed from all encountered cases with suspected HRIs. Moreover, we developed a diagnostic tree for HRIs by using the XGBoost model. Out of the 1200 persons encountered during the study period, 231 fulfilled the criteria of HRIs spectrum and were included in this study. Around 6% had HS and 20% had HE. All HS cases (100%) were from outside of Saudi Arabia as compared with 72.5% diagnosed with HE (27.5% were from Saudi Arabia). In addition, 16% were considered as heat-induced muscle spasms, and 7% had limb heat edema. Additionally, most of HRIs cases were reported between 11 am and 1 pm. The HRIs diagnostic tree model gave a diagnostic accuracy of 93.6%. This study highlights the magnitude of HRIs among pilgrims in Hajj and provides a diagnostic tree that can aid in the risk stratification and diagnosis of these patients. We advise the implementation of more educational campaigns to pilgrims regarding preventable measures especially for the vulnerable groups (e.g. from outside Saudi Arabia, those with comorbidities and light-skinned people).

Mitochondrial anti-apoptotic Bcl2 and BclxL proteins, are overexpressed in multiple tumour types, and has been involved in the progression and survival of malignant cells. Therefore, inhibition of such proteins has become a validated and attractive target for anticancer drug discovery. In this manner, the present studies developed a series of novel isatin–indole conjugates (7a-j and 9a-e) as potential anticancer Bcl2 and BclxL inhibitors. The progression of the two examined colorectal cancer cell lines was significantly inhibited by all of the prepared compounds with IC50 ranges 132–611 nM compared to IC50 = 4.6 µM for 5FU, against HT-29 and IC50 ranges 37–468 nM compared to IC50 = 1.5 µM for 5FU, against SW-620. Thereafter, compounds 7c and 7g were selected for further investigations. Interestingly, both compounds exhibited selective cytotoxicity against both cell lines with high safety to normal fibroblast (HFF-1). In addition, both compounds 7c and 7g induced apoptosis and inhibited Bcl2 and BclxL expression in a dose-dependent manner. Collectively, the high potency and selective cytotoxicity suggested that conjugates 7c and 7g could be a starting point for further optimisation to develop novel pro-apoptotic and antitumor agents towards colon cancer.

Introduction: There is paucity of data regarding change in arachnoid cyst (AC) volume following surgery. This study aimed at investigating the clinical outcome of ACs and applying 2 volumetric methods for determination of their volume change post microsurgical fenestration. Methods: Twenty-one ACs in 20 patients that underwent microsurgical fenestration were analyzed using 2 volumetric methods; the modified McDonald equation and the picture archiving and communication (PAC) system-based method. Patients were followed up for 23 ± 40.3 months. Results: The majority of the patients (13 or 65%) were children. Preoperative symptoms in children were mainly seizures and less commonly headache. Of the 20 patients, 12 (60%) had complete resolution of their preoperative symptoms with 8 (40.0%) showing partial improvement. Volumetric studies showed a mean reduction in AC size of 73.7% in children and 64.4% in adults using the PAC system versus 67.9% in children and 70.5% in adults using the modified McDonald equation method. There was no correlation between the percentage decrease in AC volume post surgery and degree of symptom improvement (49.2 ± 34.3% in patients with complete vs. 60.9 ± 40.3% in patients with only partial resolution of symptoms, p = 0.57). Discussion/Conclusion: Microsurgical fenestration is an effective approach for ACs with an excellent clinical outcome apparent in the complete or partial improvement of symptoms in all patients. Volumetric estimates of ACs and their change following surgery are feasible using the modified McDonald or PAC system methods. However, there is no correlation between the percentage decrease in AC volume after surgery and degree of clinical improvement.

Sprengel deformity is a congenital anomaly arising mainly in the shoulder girdle, associated with elevation of dysplastic scapula. skeletal anomalies, mainly Klippel-Feil syndrome, hemivertebrae, and omovertebral bone may be present along Sprengel anomaly. The omovertebral bone is an abnormal bone that originates from the superomedial edge of the scapula with different insertion points along the posterior cervical spine, seen in about third of the patients with Sprengel anomaly. While cosmetic to functional impairment is a common presentation to the omovertebral bone, cervical myelopathy is a rare presentation. Here, we described our experience, management and follow up of 13-year-old boy presented with cervical myelopathy secondary to the omovertebral bone.

Objectives: Colorectal cancer (CRC) is the third most prevalent malignant neoplasm. Genetic variations in the xenobiotic metabolising cytochrome enzymes. Family 1 Subfamily A Member 1 (CYP1A1) and Family 1 Subfamily B Member 1 (CYP1B1) might play a role in cancer pathogenesis and prognosis. The aim of this work is to determine the frequency of Single Nucleotide Polymorphisms (SNPs) in CYP1A1 (rs1048943, Ile462VaI and rs4646903/MSP1) and CYP1B1 (rs1056836, Leu432Val) genes in patients with CRC cancer. It was also an attempt to identify the association between SNPs and CRC and its stage and grade at diagnosis. Methods: This case-control study was conducted in Kirkuk/Iraq, 200 patients with CRC and 200 cancer free control subjects were enrolled. Genomic DNA was extracted from venous blood samples and screened for SNPs using Restriction Fragment Length Polymorphism (RFLP) and confirmed by the direct DNA sequencing. Results: The reference genotype of CYP1A1 gene rs1048943 is AA. Both the AG and GG variants were significantly more frequent in the cancer group and associated with increased risks of CRC and its later stages (stages III and IV) and poor differentiation (p0.05) or with tumour stage or its grade (p>0.05). The GG genotype of CYP1B1 rs1056836 was the reference genotype. The CG and CC variants were not associated with increased risks of CRC (P>0.05) or its stage or grade except the CG genotype which was associated with poor differentiation (OR= 3.4, 95 % CI= 1.8 -6.5, P

Coronary artery disease (CAD) is a well-known cause of morbidity and mortality in type 2 diabetes mellitus (T2DM). The role of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in T2DM patients in relation to CAD is not well understood. We examined serum inducible and endothelial nitric oxide synthase activities in patients with T2DM in relation to the presence of coronary artery disease.The present study was conducted in the Department of Physiology, King Saud University, Riyadh, Saudi Arabia. Subjects were grouped into control (Group A, n=87), T2DM without CAD (Group B, n=70), and T2DM patients with CAD (Group C, n=49). The selection of T2DM subjects was according to the American Diabetes Association (ADA). Serum iNOS, eNOS, hsCRP, nitrates and nitrites along with lipid profile were compared between different groups. Spearman's correlation and ROC analysis were also performed.Serum eNOS levels were significantly high in the control group (112.38±47.16 U/ml) than in DM without CAD (81.43±49.91 U/ml) and DM with CAD (84.80±43.32 U/ml, p.001). Serum iNOS levels were significantly higher in DM with CAD (42.87±28.83 U/ml) compared to both control (22.08±11.77 U/ml) and DM without CAD (16.24±12.30 U/ml, p.001). Additionally, the differences in nitrite and NO were not significant between the three groups (34.06±24.75, 33.02±21.50, 38.83±24.34 uM, p = .384), and (56.51±36.78, 49.89±28.83 vs. 55.77±30.34 uM, p=.416) respectively. ROC curve analysis revealed a sensitivity and specificity of 73.5% and 68.6% of iNOS level at a cutoff point of 21.1 U/ml to predict CAD in T2DM patients. The ROC analysis for iNOS, eNOS, and hs-CRP were .782 (p.001), .574 (p=.170), and .726 (p.001), respectively.Patients with T2DM have significantly higher levels of serum iNOS and lower levels of eNOS. However, iNOS levels were significantly higher in T2DM patients with concomitant CAD. Moreover, iNOS activity positively correlated with glycemic control and hsCRP. Therefore, iNOS could be an emerging future marker for CAD in T2DM patients and its antagonists could be useful in the management of these patients.

Exosomes are a type of extracellular vesicles that contain constituents including proteins, DNAs, and RNAs of the cells that secrete them. Cancerous exosomes are potential biomarkers for cancer diagnosis. Biosensors are useful analytical tools for quantification of biomarkers and targeted molecules. An aptasensor uses the aptamer as the biorecognition element to bind to the target and is one main type of biosensors that is promising for exosomes analysis and clinical cancer detection. The assay described in this chapter allows for reliable, sensitive, and specific detection of cancer-derived exosomes using a colorimetric aptasensor that is promising for point-of-care testing.

In this study, the authors hope to demonstrate that when mammography is combined with intelligent segmentation techniques, it can become more effective in diagnosing breast abnormalities and aiding in the early detection of breast cancer. In conjunction with intelligent segmentation techniques, mammography can be made more effective in diagnosing breast abnormalities and aiding in the early diagnosis of breast cancer, hence increasing its overall effectiveness. The methodology, which includes some concepts of digital imaging and machine learning techniques, will be described in the following section after a review of the literature on breast cancer (categories, prevention involving the environment and lifestyle, diagnosis, and tracking of the disease) has been completed (neural networks and random forests). It was possible to achieve these results by working with an image collection that previously had questionable regions (per the given technique). Fiji software extracted problematic candidate regions from mammography images, which were subsequently subjected to further examination. To categorize the results of the picture segmentation, they were sorted into three groups, which were as follows: random forest and neural networks both generated promising results in the segmentation of suspicious parts that were emphasized in the highlight of the image, and this was true for both algorithms. Detection of contours of the regions was carried out, indicating that cuts of these segmented sections may be created. Later on, automatic categorization of the targets can be carried out using a learning algorithm, as illustrated in the experiment.

Background: Social relationships refer to the existing associations between family members, friends, neighbours, co-workers, and other associates. Due to the COVID-19 pandemic, social distancing has been imposed by the curfew program in Jordan. Aim: To evaluate the effects of social distancing on the social relationships of the Jordanian population. Methods: A cross-sectional study using an online survey was conducted in Jordan between the 6th and the 30th of May, 2020. Our questionnaire was constructed to explore the population’s perception of the quarantine period, how it is affecting their relationship with others, and the characteristics of their social relationships and communication with various population categories, including family members and work colleagues. Multiple linear regression was used to identify predictors of better social relationships and communication. Results: A total of 4,301 participants were involved in this study. The average score of the influence of the COVID-19 pandemic on social relationships among the whole study population was 5.68 (SD: 2.33) out of 10 (equal to 56.8%), which indicates the marginal strength of the social relationships. Around 31.6% of the participants reported that their social relationships were affected to a high degree by the COVID-19 pandemic. Participants who were aged 36–45 were positively affected in terms of their social relationships during the COVID-19 pandemic. Conclusion: The COVID-19 pandemic is negatively affecting social relationships, which could ultimately lead to negative health implications. Decision-makers are advised to provide educational campaigns that improve the sociological health of the general population.

Objective: We aimed to assess the cost-effectiveness of hepatitis C virus (HCV) screening strategies among recently arrived migrants in the Netherlands. Methods: A Markov model was used to estimate the health effects and costs of HCV screening from the healthcare perspective. A cohort of 50,000 recently arrived migrants was used. In this cohort, three HCV screening strategies were evaluated: (i) no screening, (ii) screening of migrants from HCV-endemic countries and (iii) screening of all migrants. Results: Strategy (ii) screening of migrants from HCV-endemic countries compared to strategy (i) no screening, yielded an incremental cost-effectiveness ratio (ICER) of &euro, 971 per quality-adjusted life-years (QALYs) gained. Strategy (iii) screening of all migrants compared with strategy (ii) screening of migrants from HCV-endemic countries yielded an ICER of &euro, 1005 per QALY gained. The budget impact of strategy (ii) screening of migrants from HCV-endemic countries and strategy (iii) screening of all migrants was &euro, 13,752,039 and &euro, 20,786,683, respectively. Conclusion: HCV screening is cost-effective. However, the budget impact may have a strong influence on decision making.

Virtual consultations and telemedicine have been an emerging trend in modern medicine, which has seen acceleration in uptake across a wide range of specialties as a result of the COVID-19 pandemic. Following on from previous work by the authors in 2019 examining clinician and patient appetite for virtual consultations in maxillofacial surgery, we sought to evaluate whether there had been a change in attitudes as a result of the pandemic. A clinician survey of the consultants at a large teaching hospital and prospective data collection of virtual consultation outcomes was carried out from the inception of UK government lockdown measures to tackle the pandemic. From 151 consultations, 149 (98.7%) successfully established a working diagnosis and treatment plan and/or concluded an episode of patient care, without the need to convert to a face-to-face encounter between clinician and patient. The total number of consultations (virtual or otherwise) was significantly lower than the same time period the preceding year however (1,223 compared with 465 consultations). All consultants surveyed felt the pandemic had altered their opinion of virtual clinics and their place in maxillofacial surgery but cited a number of issues. Further work is required to understand the driving forces behind staff attitudes and the long-term adoption of telemedicine within the specialty as services return to some sense of normalcy.

Introduction To identify the clinical characteristics and outcomes of hospitalized patients with COVID-19 in Oman. Methods A case series of hospitalized COVID-19 laboratory-confirmed patients between February 24th through April 24th, 2020, from two hospitals in Oman. Analyses were performed using univariate statistics. Results The cohort included 63 patients with an overall mean age of 48 ± 16 years and 84% (n = 53) were males. A total of 38% (n = 24) of the hospitalized patients were admitted to intensive care unit (ICU). Fifty one percent (n = 32) of patients had at least one co-morbidity with diabetes mellitus (DM) (32%; n = 20) and hypertension (32%; n = 20) as the most common co-morbidities followed by chronic heart and renal diseases (12.8%; n = 8). The most common presenting symptoms at onset of illness were fever (84%; n = 53), cough (75%; n = 47) and shortness of breaths (59%; n = 37). All except two patients (97%; n = 61) were treated with either chloroquine or hydroxychloroquine, while the three most prescribed antibiotics were ceftriaxone (79%; n = 50), azithromycin (71%; n = 45), and the piperacillin/tazobactam combination (49%; n = 31). A total of 59% (n = 37), 49% (n = 31) and 24% (n = 15) of the patients were on lopinavir/ritonavir, interferons, or steroids, respectively. Mortality was documented in (8%; n = 5) of the patients while 68% (n = 43) of the study cohort recovered. Mortality was associated with those that were admitted to ICU (19% vs 0; p = 0.009), mechanically ventilated (31% vs 0; p = 0.001), had DM (20% vs 2.3%; p = 0.032), older (62 vs 47 years; p = 0.045), had high total bilirubin (43% vs 2.3%; p = 0.007) and those with high C-reactive protein (186 vs 90 mg/dL; p = 0.009) and low corrected calcium (15% vs 0%; p = 0.047). Conclusions ICU admission, those on mechanical ventilation, the elderly, those with high total bilirubin and low corrected calcium were associated with high mortality in hospitalized COVID-19 patients.

BACKGROUND: Diagnosis of small choroidal melanoma is mainly based on tumour thickness, subretinal fluid, or lipofuscin pigment. Ultra-wide-field imaging (UWF) allows depiction of choroidal lesions through a red (RC) and a green channel (GC). Aim of the study was to determine the utility of this tool in the detection of small choroidal melanoma. METHODS: Retrospective cross-sectional study of patients with small choroidal pigmented lesions up to 3 mm in thickness. All patients underwent clinical and imaging assessment including UWF. Lesions were subcategorized based on thickness and lesion type. A qualitative assessment ensued using the red and green channels feature. RESULTS: A total of 152 patients were included. Melanotic naevi (76/152,50%) and small choroidal melanomas (55/152,36%) were the predominant types. Thickness was

Virtual clinics have been proposed as a method of reducing costs and improving services in the National Health Service (NHS). The aim of this research was to assess the attitudes of clinicians and patients towards virtual consultations in a department of oral and maxillofacial surgery (OMFS). Patients and clinicians at conventional OMFS adult outpatient clinics were prospectively interviewed using a structured questionnaire. Variables recorded included type of consultation, overall attitude, time travelled, and mode of transport. Patients' notes were assessed retrospectively to check if examinations had been done. A total of 146 patients (100%) completed the surveys, and 108 of them (74%) were amenable to having virtual consultations in the future. Such appointments may have been suitable for 19 patients who did not have examinations. Chi squared analysis showed no relation between type of appointment and preference for a virtual consultation (p=0.087). To introduce a virtual consultation system in our department and to assess its efficacy once implemented, further development and research are required.

Poliomyelitis, also known as polio, is a highly infectious viral disease, predominantly affecting children under five years old. The virus is transmitted from person-to-person and mainly spreads through the fecal-oral route. The virus multiplies in the intestine, from where it can invade the nervous system via the bloodstream, potentially causing paralysis. Polio symptoms include fever, fatigue, headache, vomiting, neck stiffness and pain in the limbs. The disease causes permanent paralysis in one out of 200 infections. Currently, there is no cure for polio; it can only be prevented by immunisation.1.

Influenza causes significant morbidity and mortality worldwide. Owing to its ability to rapidly evolve and spread, the influenza virus is of global public health importance. Information on the burden, seasonality and risk factors of influenza in countries of the World Health Organization Eastern Mediterranean Region is emerging because of collaborative efforts between countries, WHO and its partners over the past 10 years. The fourth meeting of the Eastern Mediterranean Acute Respiratory Infection Surveillance network was held in Amman, Jordan on 11–14 December 2017. The meeting reviewed the progress and achievements reported by the countries in the areas of surveillance of and response to seasonal, zoonotic and pandemic influenza. The first scientific conference on acute respiratory infection in the Eastern Mediterranean Region was held at the same time and 38 abstracts from young researchers across the Region were presented on epidemiological and virological surveillance, outbreak detection and response, influenza at the animal-human interface, use and efficacy of new vaccines to control respiratory diseases and pandemic influenza threats. The meeting identified a number of challenges and ways to improve the quality of the surveillance system for influenza, sustain the system so as to address pandemic threats and use the data generated from the surveillance system to inform decision-making, policies and practices to reduce the burden of influenza-associated illnesses in the Region. Keywords: EMARIS, Influenza, Eastern Mediterranean Region, WHO

Aim: To compare the effects of 5- and 50-nm naked and PEG-coated gold nanoparticles (AuNP) on proinflammatory cytokines (IL-1β, IL-6, TNF-α) expression and histopathological changes in liver and kidneys of rats. Materials & methods: Rats were injected with different nanoparticles and sacrificed after 24 h. Results: Both 5- and 50-nm AuNPs, and 50-nm PEG-AuNPs caused granular clumping of cytoplasm, edema and hydropic dystrophy in hepatic cells. Naked AuNPs of both sizes caused mild shrinkage, whereas 50-nm PEG-AuNPs enlarged the Bowman's space and capsule. Larger nanoparticles produced more profound mRNA expression of cytokines in both the organs. Conclusion: These findings suggest the roles of particle size and coating on immunological response and histopathological changes.

Several countries have started to introduce the HPV vaccine into their national immunisation programme, with the majority of these countries being high or upper-middle income countries. Currently, 91 countries have introduced the HPV vaccine globally. One of the regions lagging behind in the introduction of the HPV vaccine is the Eastern Mediterranean Region, with currently only Libya and the United Arab Emirates having introduced the HPV vaccine. In order to support countries in the Eastern Mediterranean Region with their decision-making process for HPV vaccine introduction, a regional workshop was organised to explore the current status of HPV vaccine introduction plans in the Eastern Mediterranean countries, gaps in information about HPV disease burden in the region and the need for quality HPV data to make an informed decision to introduce the HPV vaccine, socio-cultural and religious challenges with HPV vaccine introduction, and the role of NITAGs in formulating recommendations for HPV vaccine introduction. Participating countries reflected on their respective status of decision making process about HPV vaccine introduction; they discussed any needs for operational research to support the decision-making process; and highlighed technical and financial support that might be required from partners to assist with HPV vaccine introduction. Recommendations were made on how to advance the decision-making process for HPV vaccine introduction. The workshop increased the awareness of the need of data on burden of disease and the associated benefits of HPV vaccination in Eastern Mediterranean countries. The importance of collaboration between different programmes including: immunisation, adolescent health, school health, sexual and reproductive health and cancer control programmes was clearly emphasized. (C) 2019 Elsevier Ltd. All rights reserved.

In the current medical era, spirooxindole motif stands out as a privileged heterospirocyclic scaffold that represents the core for a wide range of bioactive naturally isolated products (such as Strychnofoline and spirotryprostatins A and B) and synthetic compounds. Interestingly, no much attention has been paid to develop spirooxindole derivatives with dual antioxidant and anticancer activities. In this context, a series of spirooxindoles 6a-p was examined for their anticancer effect towards HepG2 hepatocellular carcinoma and PC-3 prostate cancer cell lines. Spirooxindole 6a was found to be an efficient anti-proliferative agent towards both HepG2 and PC-3 cells (IC50 = 6.9 and 11.8 µM, respectively). Afterwards, spirooxindole 6a was assessed for its apoptosis induction potential in HepG2 cells, where its pro-apoptotic impact was approved via the significant elevation in the Bax/Bcl-2 ratio and the expression levels of caspase-3

Background Acute otitis media (AOM) is one of the most common infectious diseases that affects children. Breastfeeding has been linked to a lower risk of AOM in the first three years of childhood. The aim of this study was to identify the association between exclusive breastfeeding and the development of acute otitis media (AOM) and investigate the influence of breastfeeding duration on the presence of AOM. Methods In a retrospective case–control study, a sample of 98 children (cases) who were diagnosed with AOM and 98 children (controls) who were not diagnosed with AOM and were younger than two years old were selected from the Jordan University Hospital. Medical records were used to identify children with AOM. For both the case and control groups, the children’s mothers completed a self-administered questionnaire about factors linked to the incidence of AOM.The type of feeding and the duration of breastfeeding were assessed using a validated questionnaire. Results The data indicated that among children who developed AOM, 23.5%were artificiallyfed, while 22.4% and 13.3% were exclusively breastfed for 3 months and 6 months, respectively. Approximately 70.7% of the children without AOM were exclusively breastfed for 6 months, compared with only 29.3% of the children without AOM who were exclusively breastfed for 3 months.Logistic regression revealed that nonexclusive breastfeeding, exclusive breastfeeding for 3 months, and exclusive breastfeeding for 6 months were protective factors against AOM (OR = 0.23, 0.18, and 0.25, respectively; P P Conclusions The escalation of AOM is tightly connected to the early introduction of formula feeding in the first six months of life. Breastfeeding had a protective impact on the occurrence of AOM. Understanding factors that are associated with the occurrence of AOM in children may support the role of public health institutions and primary health care in the prevention and reduction of AOM episodes and the need for national health strategies to promote breastfeeding.

Children with Down syndrome constitute a distinct genetic population who has a greater risk of developing acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) compared to their non-Down syndrome counterparts. The risk for developing solid tumors is also distinct from the non-Down syndrome population. In the case of myeloid leukemias, the process of leukemogenesis in Trisomy 21 begins in early fetal life where genetic drivers including GATA1 mutations lead to the development of the preleukemic condition, transient abnormal myelopoiesis (TAM). Various other mutations in genes encoding cohesin, epigenetic regulators and RAS pathway can result in subsequent progression to Myeloid Leukemia associated with Down Syndrome (ML-DS). The striking paradoxical feature in the Down syndrome population is that even though there is a higher predisposition to developing AML, they are also very sensitive to chemotherapy agents, particularly cytarabine, thus accounting for the very high cure rates for ML-DS compared to AML in children without Down syndrome. Current clinical trials for ML-DS attempt to balance effective curative therapies while trying to reduce treatment-associated toxicities including infections by de-intensifying chemotherapy doses, if possible. The small proportion of patients with relapsed ML-DS have an extremely poor prognosis and require the development of new therapies.

The aim of this study was to determine the physiological and biochemical changes among bakers, induced by heat exposure at the workplace.Information was collected by means of a self-administered questionnaire. Vital signs were measured and recorded by a trained nurse before and after each work shift. A venous blood sample was drawn at the end of each work shift. The mean wet-bulb globe temperature (WBGT) index in the bakeries and offices was measured.This was a cross-sectional study involving 137 bakers working in 20 bakeries, and 107 control subjects comparable in terms of age, race, marital status, years of service, income, and cigarette smoking. There was a significant weight loss and increase in the respiratory rate, the heart rate, and oral body temperature among the bakers compared to the control group. Sodium levels were significantly lower, while blood urea nitrogen levels were significantly higher, among the bakers than in the control group. There were unfavorably hot working conditions in the bakeries: the WBGT index in the bakeries was 37.4°C while the average WBGT for the offices was 25.5°C.The changes in the physiological and biochemical parameters among the bakers were found to be associated with exposure to high environmental heat in the bakeries, as judged by the WBGT index. Preventive measures should be aimed at reducing the adverse effects of heat exposure among bakers and should be directed towards the man-machine-environment triad. Int J Occup Med Environ Health. 2022;35(3):265-72.

Objectives The aim of this study was to determine the hematological changes associated with heat exposure in a population of bakers. Materials and methods Personal information was collected using a questionnaire, and a venous blood sample was drawn at the end of a work shift from the bakers and from a control group. The average wet-bulb globe temperature (WBGT) index was measured in the workplaces of both the bakers and the controls. Results This cross-sectional study involved 137 bakers working in 20 bakeries and 107 controls who were comparable in terms of likely confounding factors. Hemoglobin and platelet values were abnormal among the bakers and statistically significantly different to the control group (P = 0.026, and P = 0.016 respectively). The average WBGT index in the bakeries was 37.4°C, while the average WBGT in the workplaces of the controls was 25.5°C, (P Conclusions The changes in the bakers’ hematological parameters were found to be associated with exposure to high environmental heat at bakeries, as measured by the WBGT index. Preventive measures should be introduced to reduce the adverse effect of heat exposure among bakers and directed toward the worker–equipment–environment triad.

Lipoprotein lipase (LPL) is responsible for the hydrolysis of lipoproteins; hence defective LPL is associated with metabolic disorders. Here, we identify certain intronic insertions and deletions (InDels) and single nucleotide polymorphisms (SNPs) in intron 6 of the

L-377,202 prodrug consists of doxorubicin (Dox) conjugated to a prostate-specific antigen (PSA) peptide substrate that can be cleaved by enzymatically active PSA at the tumor site. Despite the initial promise in phase I trial, further testing of L-377,202 (herein called Dox-PSA) was ceased due to some degree of non-specific activation and toxicity concerns. To improve safety of Dox-PSA, we encapsulated it into low temperature-sensitive liposomes (LTSL) to bypass systemic activation, while maintaining its biological activity upon controlled release in response to mild hyperthermia (HT). A time-dependent accumulation of activated prodrug in the nuclei of PSA-expressing cells exposed to mild HT was observed, showing that Dox-PSA was efficiently released from the LTSL, cleaved by PSA and entering the cell nucleus as free Dox. Furthermore, we have shown that Dox-PSA loading in LTSL can block its biological activity at 37°C, while the combination with mild HT resulted in augmented cytotoxicity in both 2D and 3D PC models compared to the free Dox-PSA. More importantly, Dox-PSA encapsulation in LTSL prolonged its blood circulation and reduced Dox accumulation in the heart of C4-2B tumor-bearing mice over the free Dox-PSA, thus significantly improving Dox-PSA therapeutic window. Finally, Dox-PSA-loaded LTSL combined with HT significantly delayed tumor growth at a similar rate as mice treated with free Dox-PSA in both solid and metastatic PC tumor models. This indicates this strategy could block the systemic cleavage of Dox-PSA without reducing its efficacy in vivo, which could represent a safer option to treat patients with locally advanced PC. Statement of significance: This study investigates a new tactic to tackle non-specific cleavage of doxorubicin PSA-activatable prodrug (L-377,202) to treat advanced prostate cancer. In the present study, we report a nanoparticle-based approach to overcome the non-specific activation of L-377,202 in the systemic circulation. This includes encapsulating Dox-PSA in low temperature-sensitive liposomes to prevent its premature hydrolysis and non-specific cleavage. This class of liposomes offers payload protection against degradation in plasma, improved pharmacokinetics and tumor targeting, and an efficient and controlled drug release triggered by mild hyperthermia (HT) (∼42°C). We believe that this strategy holds great promise in bypassing any systemic toxicity concerns that could arise from the premature activation of the prodrug whilst simultaneously being able to control the spatiotemporal context of Dox-PSA cleavage and metabolism.

Little is known about the efficacy and durability of anti-RBD IgG antibodies induced by certain SARS-CoV-2 vaccines. It has been shown that neutralizing antibodies are associated with the protection against re-infection. This study aims to compare the mean titers, duration, and efficacy of generating protective anti-RBD IgG antibody response among recipients of Pfizer/BioNTech, AstraZeneca, Sputnik V, JohnsonJohnson, Moderna, and Sinopharm COVID-19 vaccines. In addition, we aimed to compare the susceptibility of getting COVID-19 breakthrough infections after various types of vaccines.Samples from 2065 blood bank donors and healthcare workers at King Hussein Cancer Center (KHCC) were collected between February and September 2021. Anti-Spike/RBD IgG levels were measured using Chemiluminescent microparticle-immunoassay (CMIA) (ARCHITECT IgG II Quant test, Abbott, USA).The mean titer of anti-RBD IgG levels was significantly diverse among different types of vaccines. The highest titer level was seen in participants who took a third booster vaccine shot, followed by Pfizer/BioNTech, AstraZeneca, and Sinopharm vaccine. The mean titer levels of anti-RBD IgG antibodies in the Pfizer vaccinated group was the highest after vaccination but started to drop after 60 days from vaccination unlike AstraZeneca and Sinopharm vaccine-induced antibodies where the mean titers continued to be stable until 120 days but their levels were significantly lower. Most of the breakthrough infections were among the Sinopharm vaccinated group and these breakthroughs happened at random times for the three main types of vaccines.Our data demonstrate that the mean-titer of anti-RBD IgG levels drop after four months which is the best time to take the additional booster shot from a more potent vaccine type such as mRNA vaccines that might be needed in Jordan and worldwide.