Xylitol is prothrombotic and associated with cardiovascular risk.

BACKGROUND AND AIMS: The pathways and metabolites that contribute to residual cardiovascular disease risks are unclear. Low-calorie sweeteners are widely used sugar substitutes in processed foods with presumed health benefits. Many low-calorie sweeteners are sugar alcohols that also are produced endogenously, albeit at levels over 1000-fold lower than observed following consumption as a sugar substitute. METHODS: Untargeted metabolomics studies were performed on overnight fasting plasma samples in a discovery cohort (n = 1157) of sequential stable subjects undergoing elective diagnostic cardiac evaluations; subsequent stable isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses were performed on an independent, non-overlapping validation cohort (n = 2149). Complementary isolated human platelet, platelet-rich plasma, whole blood, and animal model studies examined the effect of xylitol on platelet responsiveness and thrombus formation in vivo. Finally, an intervention study was performed to assess the effects of xylitol consumption on platelet function in healthy volunteers (n = 10). RESULTS: In initial untargeted metabolomics studies (discovery cohort), circulating levels of a polyol tentatively assigned as xylitol were associated with incident (3-year) major adverse cardiovascular event (MACE) risk. Subsequent stable isotope dilution LC-MS/MS analyses (validation cohort) specific for xylitol (and not its structural isomers) confirmed its association with incident MACE risk [third vs. first tertile adjusted hazard ratio (95% confidence interval), 1.57 (1.12-2.21), P < .01]. Complementary mechanistic studies showed xylitol-enhanced multiple indices of platelet reactivity and in vivo thrombosis formation at levels observed in fasting plasma. In interventional studies, consumption of a xylitol-sweetened drink markedly raised plasma levels and enhanced multiple functional measures of platelet responsiveness in all subjects. CONCLUSIONS: Xylitol is associated with incident MACE risk. Moreover, xylitol both enhanced platelet reactivity and thrombosis potential in vivo. Further studies examining the cardiovascular safety of xylitol are warranted.

Angiotensin II Exaggerates SARS-CoV-2 Specific T-Cell Response in Convalescent Individuals following COVID-19.

Dysregulation of renin-angiotensin systems during coronavirus disease 2019 (COVID-19) infection worsens the symptoms and contributes to COVID-19 severity and mortality. This study sought to investigate the effect of exogenous angiotensin II (Ang-II) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T-cells response in recovered COVID-19 patients. Human peripheral blood mononuclear cells (PBMCs) were treated with Ang II and then stimulated with a SARS-CoV-2 peptide pool. T-cell responses were measured using flow cytometry, while enzyme-linked immunosorbent assay (ELISA) and intracellular cytokine staining (ICS) assays determined functional capability and polarization. Additionally, the relative level of protein phosphorylation was measured using a phosphokinase array. Our results showed that Ang II treatment significantly increased the magnitude of SARS-CoV-2-specific T-cell response in stimulated PBMCs with a SARS-CoV-2 peptide pool. Moreover, the phosphorylation levels of numerous proteins implicated in cardiovascular diseases, inflammation, and viral infection showed significant increases in the presence of Ang II. The mitogenic stimulation of PBMCs after Ang II and SARS-CoV-2 peptide pool stimulation showed functional polarization of T-cells toward Th1/Th17 and Th17 phenotypes, respectively. Meanwhile, ELISA showed increased productions of IL-1ß and IL-6 in Ang II-stimulated PBMCs without affecting the IL-10 level. To our knowledge, this study is the first to demonstrate that Ang II exaggerates SARS-CoV-2-specific T-cells response. Therefore, during COVID-19 infection, Ang II may aggravate the inflammatory response and change the immune response toward a more inflammatory profile against SARS-CoV-2 infection.

Physcion Induces Hemolysis and Premature Phosphatidylserine Externalization in Human Erythrocytes.

The prevalence of cancer-associated anemia (CIA) is high, and the mechanisms governing its development remain poorly understood. Eryptosis, the suicidal cell death of red blood cells (RBCs), may account for CIA as it is triggered by clinically approved chemotherapeutics including cisplatin and paclitaxel. Physcion (PSN), an anthraquinone extracted from rhubarb and other plants, has shown great promise as an anticancer agent. However, the potential toxicity of PSN to RBCs remains elusive. RBCs were isolated from heparinized blood, and incubated with 10-100 µM of PSN for 24 h at 37 °C. Hemolysis was photometrically calculated from hemoglobin concentration in the medium at 405 nm, while flow cytometry was employed to investigate cardinal markers of eryptosis. Phosphatidylserine (PS) exposure was detected by Annexin-V-fluorescein isothiocyanate (FITC), intracellular calcium by Fluo4/AM, cellular volume from forward scatter (FSC), and oxidative stress by 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA). PSN induced overt hemolysis at 50 and 100 µM which was not mediated through calcium influx, protein kinase C, casein kinase 1α, or receptor-interacting protein 1. Moreover, PSN caused significant increase in Annexin-V-FITC and Fluo4 fluorescence with no appreciable influence on FSC or DCF values. Accordingly, PSN stimulates premature eryptosis characterized by PS externalization and intracellular calcium overload without cell shrinkage or oxidative damage. In conclusion, this report shows, for the first time, that PSN is cytotoxic to RBCs by inducing hemolysis and programmed cell death which may limit its success as a chemotherapeutic agent.

In Vitro Evaluation of Translucency and Color Stability of CAD/CAM Polymer-Infiltrated Ceramic Materials after Accelerated Aging.

PURPOSE: To investigate and compare the translucency and color stability of a newly introduced polymer-infiltrated ceramic network (PICN) material (Crystal Ultra) to those of clinically well-established restorative materials. MATERIALS AND METHODS: A total of 80 specimens measuring (12 × 14 × 1 mm ± 0.05 mm) were prepared from five CAD/CAM (IPS e.max (IPS), Lava Ultimate (LU), Cerasmart (CS), Vita Enamic (VE), Crystal Ultra (CU)) high translucency (HT) blocks in A2 or equivalent shades. Specimens were randomly allocated into two groups (A and B) (n = 8), and were subjected to 5,000 thermal-cycles (TC). This was followed by one-week immersion of group A specimens in coffee (staining) solution and group B specimens in distilled water. Following immersion, the specimens from both groups were further subjected to 5,000 TC. A spectrophotometer was used to measure the translucency parameter (TP) and color change (ΔE00 ) of the samples using CIELAB color coordinates at baseline, after 5,000 TC, following immersion, and after further 5,000 TC. Color stability was evaluated using the CIEDE2000 formula. Data were analyzed by non-parametric tests (α = 0.05). RESULTS: The TP values of the CAD/CAM materials ranged from 18.0-22.0. Following the initial TC, the changes in TP values were significant for VE (p = 0.012). Coffee immersion and further TC significantly impacted the TP values of PICN (VE and CU) materials compared to glass- ceramics (IPS), and resin nanoceramic (CS and LU) materials (p = 0.012). The comparison between CAD/CAM materials at different intervals showed a significant difference in the TP values (p < 0.01). The materials showed perceptible color changes following the initial TC except for PICN materials which demonstrated acceptable color changes. The major color difference was noticed for the resin nanoceramic specimens immersed in coffee; LU and CS showed higher color changes (ΔE00 = 2.45 and 2.09, respectively) than VE and CU (ΔE00 < 1.8). CONCLUSIONS: The translucency of the newly introduced Crystal Ultra PICN material was low compared to the resin nanoceramics and lithium disilicate glass-ceramic. The Crystal Ultra material exhibited better color stability compared to resin nanoceramics, but higher color change when compared with Vita Enamic PICN and lithium disilicate glass-ceramic CAD/CAM materials.

Fracture Resistance of Endodontically Treated Teeth Restored with Fiber Posts Luted with Composite Core Materials.

AIM: This study aimed to investigate the influence of using dual-cure composite core materials for fiber post luting on the fracture resistance of endodontically treated maxillary central incisors. MATERIALS AND METHODS: Fifty sound and recently extracted maxillary central incisors were endodontically treated and distributed into five groups. In the control group, access cavities were restored with the composite resin. Experimental groups had the coronal structure trimmed 2 mm above the cementoenamel junction. Teeth were restored with fiber posts and different combinations of luting and core materials: RelyX Unicem for post luting and MultiCore for core buildup; MultiCore for post luting and core buildup; RelyX Unicem for post luting and LuxaCore for core buildup; or LuxaCore for post luting and core buildup. All teeth were restored with zirconium crowns and subjected to thermocycling (6000 cycles 5/55°C). Loading of the teeth was applied at 135° to the palatal surface, using a universal testing machine at a cross-speed of 0.5 mm/minute until failure. The mode of failure was analyzed under a digital microscope. RESULTS: The fracture resistance of the control group was significantly higher than the experimental groups (p < 0.05). There was no significant difference between the experimental groups (p > 0.05). All teeth demonstrated nonrestorable failures. CONCLUSION: With the presence of the ferrule effect and crown restoration, the selected materials for post luting and core buildup have no significant influence on the fracture resistance of the endodontically treated teeth. CLINICAL SIGNIFICANCE: The use of the same dual-cure composite core materials for fiber post luting and core buildup would simplify the clinical procedure without enhancement of the fracture resistance of the endodontically treated tooth.

Gut microbiota-dependent trimethylamine N-oxide in acute coronary syndromes: a prognostic marker for incident cardiovascular events beyond traditional risk factors.

AIMS: Systemic levels of trimethylamine N-oxide (TMAO), a pro-atherogenic and pro-thrombotic metabolite produced from gut microbiota metabolism of dietary trimethylamine (TMA)-containing nutrients such as choline or carnitine, predict incident cardiovascular event risks in stable primary and secondary prevention subjects. However, the prognostic value of TMAO in the setting of acute coronary syndromes (ACS) remains unknown. METHODS AND RESULTS: We investigated the relationship of TMAO levels with incident cardiovascular risks among sequential patients presenting with ACS in two independent cohorts. In the Cleveland Cohort, comprised of sequential subjects (n = 530) presenting to the Emergency Department (ED) with chest pain of suspected cardiac origin, an elevated plasma TMAO level at presentation was independently associated with risk of major adverse cardiac events (MACE, including myocardial infarction, stroke, need for revascularization, or death) over the ensuing 30-day (4th quartile (Q4) adjusted odds ratio (OR) 6.30, 95% confidence interval (CI), 1.89-21.0, P < 0.01) and 6-month (Q4 adjusted OR 5.65, 95%CI, 1.91-16.7; P < 0.01) intervals. TMAO levels were also a significant predictor of the long term (7-year) mortality (Q4 adjusted HR 1.81, 95%CI, 1.04-3.15; P < 0.05). Interestingly, TMAO level at initial presentation predicted risk of incident MACE over the near-term (30 days and 6 months) even among subjects who were initially negative for troponin T (< 0.1 ng/mL) (30 days, Q4 adjusted OR 5.83, 95%CI, 1.79-19.03; P < 0.01). The prognostic value of TMAO was also assessed in an independent multicentre Swiss Cohort of ACS patients (n = 1683) who underwent coronary angiography. Trimethylamine N-oxide again predicted enhanced MACE risk (1-year) (adjusted Q4 hazard ratios: 1.57, 95% CI, 1.03-2.41; P <0.05). CONCLUSION: Plasma TMAO levels among patients presenting with chest pain predict both near- and long-term risks of incident cardiovascular events, and may thus provide clinical utility in risk stratification among subjects presenting with suspected ACS.

Public awareness, knowledge, and attitudes toward epilepsy in the Aseer region, Saudi Arabia - A community-based cross-sectional study.

INTRODUCTION: Epilepsy accounts for 0.5% of the global burden of disease, with more than 50 million people affected worldwide; 80% of them are in developing regions. People with epilepsy and their families can suffer from stigma and discrimination in many parts of the world. Although this disorder is common in Saudi Arabia, with a prevalence of 6.54 per 1000, no study of epilepsy awareness, knowledge, and attitudes has been reported from the Aseer region. METHODS: The study was conducted using a validated self-administered questionnaire to assess awareness, knowledge, and attitudes toward epilepsy and the sociodemographic data of the participants. RESULTS: In the total sample of 1044 (mean age: 28±9years; 53.2% were males; from different educational and social levels), almost all had heard about epilepsy (96.1%), and the majority knew someone with epilepsy (60.7%). In spite of that, knowledge about the etiology and nature of epilepsy was lacking, as 40% of participants thought it was a blood disorder, 21.2% believed it was contagious, and nearly one-third viewed it as due to a mental disorder and emotional stress. Regarding public attitudes toward people with epilepsy, 19.1% would not work with them, 17% would not allow having their child mingle with a child with epilepsy at school, and more than half would not marry a person with epilepsy. Moreover, the study showed inappropriate responses when dealing with someone with a seizure; they would force some medicine down the patient's throat (49.3%), use herbal medicine (68.9%), ask a spiritual healer (31.8%), or even think it is untreatable (35.6%). CONCLUSION: The level of epilepsy awareness in the Aseer region's population is relatively poor and needs improvement.

Microhardness and Gloss of a New CAD/CAM Hybrid Material Following Accelerated Aging and Coffee Immersion.

PURPOSE: To evaluate and compare the effect of accelerated aging and coffee immersion on the microhardness and gloss of a new computer-aided design and computer-aided manufacturing (CAD/CAM) hybrid material (Crystal Ultra) to those of contemporary restorative materials. MATERIALS AND METHODS: A total of 160 specimens (12 × 14 × 1 mm ± 0.05 mm) were obtained from IPS e.max (IPS), VITA Enamic (VE), Crystal Ultra (CU), Lava Ultimate (LU), and CeraSmart (CS) high-translucency CAD/CAM blocks. The Vickers microhardness and gloss of the specimens were determined after thermocycling and coffee immersion. Data analysis was performed using SPSS (α = .05). RESULTS: IPS and CS specimens exhibited the highest (572.66 ± 11.30) and lowest (61.92 ± 3.91) microhardness, respectively. The highest gloss was observed with IPS specimens (3.31 ± 0.32), and LU specimens showed the lowest gloss (2.33 ± 0.06). A significant difference in gloss was observed between the materials at all measurement intervals (P < .01), except at T0 (P = .43). IPS specimens showed no significant changes in either group at any measurement interval. CONCLUSIONS: The microhardness and gloss of the new CU material were comparable to those of the tested contemporary hybrid restorative materials. Glass-ceramic showed superior hardness and gloss compared to hybrid restorative materials. Accelerated aging with thermocycling and staining significantly affected the microhardness and gloss of all tested CAD/CAM materials.

Prevalence of internalized stigma in patients with psychiatric illness in Abha, Southern Region, Saudi Arabia.

BACKGROUND: Mental stigma occurs when patients with various mental disorders are labeled by their disorders. Little is known about the burden of mental stigma on patients with mental disorders. The aim of this study was to evaluate the incidence of mental stigma on patients with psychiatric disorder in Saudi Arabia. MATERIALS AND METHODS: This cross-sectional study was conducted among previously diagnosed patients with any psychiatric disorder attending King Khalid Hospital, Abha, Saudi Arabia. The patients were interviewed with a sociodemographic questionnaire and a validated Arabic version of the Internalized Stigma of Mental Illness (ISMI-29) scale. Chi-square test and t-test were used to assess the association between various demographic characteristics and presence of stigma. RESULTS: The study included 489 patients with different psychiatric disorders. The mean age of the participants was 32.8 years and 54.6% were females. About 39% participants showed no to minimal internalized stigma, 37.4% of total sample had mild stigma, 20% had moderate stigma, and 3.7% had severe stigma. A signficantly higher proportion (71.4%) of widowed patients had stigma (P = 0.032). CONCLUSION: Self-stigma is prevalent among patients with psychiatric disorders in Abha, Saudi Arabia, but lower than the prevalence in developing countries. Marital status has a significant impact on the prevalence and severity of the self-stigma of patients. There is a need for awareness program to reduce self-stigma. Psychiatric institutions should also focus on promotion of patients' social life and increase patient's awareness of certain issues that could prevent stigma.

Angiotensin II modulates THP-1-like macrophage phenotype and inflammatory signatures via angiotensin II type 1 receptor.

Angiotensin II (Ang II) is a major component of the renin-angiotensin or renin-angiotensin-aldosterone system, which is the main element found to be involved in cardiopathology. Recently, long-term metabolomics studies have linked high levels of angiotensin plasma to inflammatory conditions such as coronary heart disease, obesity, and type 2 diabetes. Monocyte/macrophage cellular function and phenotype orchestrate the inflammatory response in various pathological conditions, most notably cardiometabolic disease. An activation of the Ang II system is usually associated with inflammation and cardiovascular disease; however, the direct effect on monocyte/macrophages has still not been well elucidated. Herein, we have evaluated the cellular effects of Ang II on THP-1-derived macrophages. Ang II stimulated the expression of markers involved in monocyte/macrophage cell differentiation (e.g., CD116), as well as adhesion, cell-cell interaction, chemotaxis, and phagocytosis (CD15, CD44, CD33, and CD49F). Yet, Ang II increased the expression of proinflammatory markers (HLA-DR, TNF-α, CD64, CD11c, and CD38) and decreased CD206 (mannose receptor), an M2 marker. Moreover, Ang II induced cytosolic calcium overload, increased reactive oxygen species, and arrested cells in the G1 phase. Most of these effects were induced via the angiotensin II type 1 receptor (AT1R). Collectively, our results provide new evidence in support of the effect of Ang II in inflammation associated with cardiometabolic diseases.

Quantitative proteomics analysis of COVID-19 patients: Fetuin-A and tetranectin as potential modulators of innate immune responses.

Treatment of severe cases of coronavirus disease 2019 (COVID-19) is extremely important to minimize death and end-organ damage. Here we performed a proteomic analysis of plasma samples from mild, moderate and severe COVID-19 patients. Analysis revealed differentially expressed proteins and different therapeutic potential targets related to innate immune responses such as fetuin-A, tetranectin (TN) and paraoxonase-1 (PON1). Furthermore, protein changes in plasma showed dysregulation of complement and coagulation cascades in COVID-19 patients compared to healthy controls. In conclusion, our proteomics data suggested fetuin-A and TN as potential targets that might be used for diagnosis as well as signatures for a better understanding of the pathogenesis of COVID-19 disease.

Effect of Gender on Postoperative Outcome and Duration of Ventilation After Coronary Artery Bypass Grafting (CABG).

INTRODUCTION: The study assessed coronary artery bypass grafting (CABG) postoperative outcomes and associated factors in Saudi male and female patients. This was a retrospective cohort of patients who underwent CABG at the King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia, from January 2015 to December 2022.  Results: We included 392 patients, of whom 63 (16.1%) were female. Female undergoing CABG were significantly older (p=0.0001), had a significantly higher incidence of diabetes (p=0.0001), obesity (p=0.001), hypertension (p=0.001), and congestive heart failure (p=0.005), with a smaller body surface area (BSA) (p=0.0001) than male. Though renal dysfunction, previous cerebrovascular accident/transient ischemic attack (CVA/TIA), and myocardial infarction (MI), incidences were similar in both genders. Females were at significantly higher risk of mortality (p=0.0001), longer hospital stay (p=0.0001), and prolonged ventilation (p=0.0001). Preoperative renal dysfunction was the only statistically significant predictor of postoperative complications (p=0.0001). Female gender and preoperative renal dysfunction, were significant independent predictors of postoperative mortality and prolonged ventilation (p=0.005). CONCLUSION: This study's findings indicated that females have worse CABG outcomes and a higher risk of morbidities and complications. Uniquely our study showed a higher incidence of prolonged ventilation in females postoperatively.

Assessing the relationship between burnout syndrome and irritable bowel syndrome among medical health providers and medical students in Saudi Arabia.

Burnout syndrome, characterized by chronic unmanageable workplace stress, has been linked to lower gastrointestinal disorders, including irritable bowel syndrome. However, the relationship between burnout syndrome and irritable bowel syndrome among medical health providers and medical students in Saudi Arabia has not been fully explored. This cross-sectional correlational study was conducted in Southern Saudi Arabia from 2021 to 2022 and involved 931 medical health providers and medical students who completed an electronic questionnaire. The study assessed the presence and severity of burnout and irritable bowel syndrome and examined their relationship. Burnout syndrome was evaluated using the Maslach Burnout Inventory-Student Survey (MBI-SS), while irritable bowel syndrome criteria and severity were assessed using validated tools. The study found that 85% of medical health providers and medical students experienced high levels of burnout and irritable bowel syndrome severity, with physicians and nurses mainly affected. Occupational exhaustion was high in 44.4% of participants, while depersonalization was high in 53% of participants. Personal accomplishment was low in 73.5% of participants. Mild, moderate, and severe irritable bowel syndrome was reported in 25.6%, 23.8%, and 12% of participants, respectively. The study highlights a significant association between burnout syndrome and irritable bowel syndrome severity among medical health providers and medical students in Saudi Arabia. These findings underscore the importance of developing effective interventions to prevent and manage burnout syndrome and related health issues among healthcare professionals and medical students in the region.

The artificial sweetener erythritol and cardiovascular event risk.

Artificial sweeteners are widely used sugar substitutes, but little is known about their long-term effects on cardiometabolic disease risks. Here we examined the commonly used sugar substitute erythritol and atherothrombotic disease risk. In initial untargeted metabolomics studies in patients undergoing cardiac risk assessment (n = 1,157; discovery cohort, NCT00590200 ), circulating levels of multiple polyol sweeteners, especially erythritol, were associated with incident (3 year) risk for major adverse cardiovascular events (MACE; includes death or nonfatal myocardial infarction or stroke). Subsequent targeted metabolomics analyses in independent US (n = 2,149, NCT00590200 ) and European (n = 833, DRKS00020915 ) validation cohorts of stable patients undergoing elective cardiac evaluation confirmed this association (fourth versus first quartile adjusted hazard ratio (95% confidence interval), 1.80 (1.18-2.77) and 2.21 (1.20-4.07), respectively). At physiological levels, erythritol enhanced platelet reactivity in vitro and thrombosis formation in vivo. Finally, in a prospective pilot intervention study ( NCT04731363 ), erythritol ingestion in healthy volunteers (n = 8) induced marked and sustained (>2 d) increases in plasma erythritol levels well above thresholds associated with heightened platelet reactivity and thrombosis potential in in vitro and in vivo studies. Our findings reveal that erythritol is both associated with incident MACE risk and fosters enhanced thrombosis. Studies assessing the long-term safety of erythritol are warranted.

The Intersection of Health Rehabilitation Services with Quality of Life in Saudi Arabia: Current Status and Future Needs.

Quality of life (QoL) is essential for maintaining a healthy, balanced lifestyle, especially among individuals with chronic diseases. Saudi Arabia (SA) launched a health sector transformation program as part of the nationwide Vision 2030 initiative to ensure the sustainable development of efficient healthcare services, aiming to improve health by increasing well-being and QoL. More investigation into the current status of health rehabilitation services provided to individuals with chronic diseases and future needs to optimize services and improve QoL is needed. This was narratively discussed by experts from different health rehabilitation services in SA. Comprehensive health rehabilitation services including orthopedic, occupational, cardiac, pulmonary, critical care, perioperative, hearing and speech, substance use disorders, and vocational rehabilitation services were addressed. Health rehabilitation services in SA, as in other countries, are suboptimal for individuals in health rehabilitation programs. To optimize the QoL of individuals with chronic diseases, health rehabilitation services should be tailored based on the unique requirements of each service and its serving patients. The shared need to improve health rehabilitation services includes the adoption of home-based and telehealth services, the integration of multi-governmental sectors, the empowerment and allocation of health rehabilitation specialists, public awareness campaigns, policy legislation and guideline development, and the implementation of a long-term follow-up system. This review is one of the first to address the intersection of health rehabilitation services and QoL in SA; urgent and holistic actions are paramount to address the pressing need to optimize SA's health rehabilitation services. The experts' recommendations in this study may be applicable to other countries' health systems, as health rehabilitation services are not well optimized globally.

Induction of hemolysis and eryptosis by occupational pollutant nickel chloride is mediated through calcium influx and p38 MAP kinase signaling.

OBJECTIVES: Nickel (Ni) is an abundant environmental hazard and an occupational pollutant. Exposure to Ni compounds is prevalent in electroplating workers and in the printing industry, among others. The toxicity of Ni manifests as dermatological, gastrointestinal, respiratory, allergic, and cardiovascular symptoms. In particular, hyperbilirubinemia and reticulocytosis have been detected in intoxicated subjects; an observation possibly implicating selective red blood cell (RBC) toxicity. Herein, the interaction of nickel chloride (NiCl2) with human RBCs and associated molecular mechanisms are described. MATERIAL AND METHODS: Cells from healthy donors were incubated for 24 h at 37°C in the presence or absence of 0.5‒10 mM of NiCl2, and cytotoxicity was determined through hemoglobin leakage by colorimetry under different experimental conditions. Eryptotic markers were also identified by flow cytofluorometry using Annexin-V-FITC tagging for phosphatidylserine (PS) exposure, light scatter properties for cellular dimensions, Fluo4/AM labeling for intracellular calcium, and H2DCFDA staining for reactive oxygen species (ROS). Additionally, small molecule inhibitors were used to probe the signaling pathways involved. RESULTS: It was found that NiCl2 at 10 mM caused profound intracellular calcium overload and significant calcium-dependent hemolysis. Also, NiCl2 reduced forward scatter and increased side scatter, Annexin- positive cells, and ROS levels. Importantly, NiCl2-induced hemolysis was significantly attenuated by the exclusion of extracellular calcium, and in the presence of p38 MAP kinase (MAPK) inhibitor SB203580. CONCLUSIONS: It is concluded that NiCl2 induces p38 MAPK-dependent hemolysis, and stimulates the canonical features of premature eryptosis. This report presents the first description of the molecular mechanisms underlying the hemolytic and eryptotic potential of NiCl2 and, thus, may explain changes in hematological parameters observed in poisoning victims. Int J Occup Med Environ Health. 2022;35(1):1-11.

Knowledge and attitude of pregnant women in the Kingdom of Saudi Arabia toward Noninvasive prenatal testing: A single center study.

BACKGROUND: Noninvasive prenatal testing (NIPT) is a screening tool for chromosomal aneuploidies. Prior knowledge of NIPT is an inherent factor in the decision-making process. We assessed the knowledge and attitude of pregnant women related to prenatal testing with a particular focus on NIPT. METHODS: A prospective cross-sectional study, using a culturally validated questionnaire, was conducted with 342 pregnant women of whom 74.9% consented for prenatal screening. Mean age and gestational weeks ± standard deviation was 31 ± 5 and 26 ± 11, respectively. RESULTS: A positive/very positive attitude was observed to ultrasound, followed by FCT, NIPT, and lastly to CVS. More than half of the participants (56.1%) had no previous knowledge of NIPT. A reaching significance association was detected between education and knowledge of NIPT. Significant association was detected between risk for aneuploidy and knowledge of NIPT. The majority (74%) indicated their willingness to perform the test. The effect and value of society on the pregnant women to make a decision regarding NIPT was negligible. CONCLUSION: The pregnant women in the current study displayed a lack of knowledge and awareness regarding prenatal screening, particularly the NIPT. We recommend that pregnant women receive adequate counseling regarding prenatal screening to increase their awareness and knowledge of prenatal testing, including NIPT.

Microhardness and gloss of a new CAD-CAM hybrid material following accelerated aging and coffee immersion.

PURPOSE: To evaluate and compare the effect of accelerated aging and coffee immersion on the microhardness and gloss of a new CAD/CAM hybrid material (Crystal Ultra) to those of contemporary restorative materials. MATERIALS AND METHODS: A total of 160 specimens (12 x 14 x 1 mm ± 0.05 mm) were obtained from (IPS e.max [IPS], VITA Enamic [VE], Crystal Ultra [CU], Lava Ultimate [LU], and CeraSmart [CS]) high-translucency CAD/CAM blocks. The Vickers microhardness and gloss of the specimens were determined following thermocycling and coffee immersion. Data analysis was performed using SPSS (α = .05). RESULTS: IPS and CS specimens exhibited the highest (572.66 ± 11.30) and lowest (61.92 ± 3.91) microhardness, respectively. The highest gloss was observed with IPS specimens (3.31 ± 0.32), and LU specimens showed the lowest gloss (2.33 ± 0.06). A significant difference in gloss was observed between the materials at all measurement intervals (P < .01), except at T0 (P = .43). IPS specimens showed no significant changes in either group at any measurement interval. CONCLUSION: The microhardness and gloss of the new CU material were comparable to those of the tested contemporary hybrid restorative materials. Glass-ceramic showed superior hardness and gloss compared to hybrid restorative materials. Accelerated aging by thermocycling and staining significantly affected the microhardness and gloss of all the tested CAD/CAM materials.

Erythritol modulates the polarization of macrophages: Potential role of tumor necrosis factor-α and Akt pathway.

Low-calorie sweeteners are substitutes for sugar and frequently used by patients with cardiometabolic diseases. Erythritol, a natural low-calorie sugar alcohol, was linked to cardiometabolic diseases in several recent metabolomics studies. However, the characterization of its role in disease development is lacking. Macrophage polarization orchestrates the immune response in various inflammatory conditions, most notably cardiometabolic disease. Therefore, the physiological effects of Erythritol on THP-1 macrophages were investigated. We observed an increased cellular abundance of proinflammatory M1 macrophages, characterized by CD11c, TNF-α, CD64, CD38, and HLA-DR markers and decreased anti-inflammatory M2 macrophages, characterized by mannose receptor CD206. The, Erythritol increased ROS generation, and the activation of the AKT pathway, cytosolic calcium overload, and cell cycle arrest at the G1 phase. Concomitantly, an increased population of necroptotic macrophages was observed. In conclusion, we provide evidence that Erythritol induced the proinflammatory phenotype in THP-1 macrophages and this was associated with an increased population of necroptotic macrophages. PRACTICAL APPLICATIONS: This assessment provides evidence of the effects of Erythritol on macrophages, particularly THP-1-derived macrophages. Our results support the role of Erythritol in driving the inflammation that is associated with cardiometabolic diseases and provide insights in the role of Erythritol as an inducer of necroptosis in THP-1 derived macrophages that could be associated the disease.

Awareness of medical law among health care practitioners in Saudi Arabia.

OBJECTIVES: To determine the level of awareness of medical law among healthcare practitioners and to identify factors that influence that level of awareness in Saudi Arabia. METHODS: This cross-sectional study was carried out in Riyadh, Saudi Arabia in 2020-2021 via a survey including 750 healthcare practitioners, from different specialties including all regions in Saudi Arabia. Participants included consultants, senior registrars, interns, and residents. RESULTS: Majority of enrolled healthcare practitioners had poor awareness of medical law (approximately 97%). Only 1.5% had adequate awareness of medical law, and only 1.5% had moderate awareness. Factors associated with increased medical law awareness were the age group between 25 and 34, being from the central region, and having a clinical practice for less than 10 years p-value of <0.05. CONCLUSION: Awareness of medical law among healthcare practitioners is limited in Saudi Arabia. Professional medico-legal education should be part of required competencies for undergraduate and postgraduate levels of medical education. Health care practitioners must be educated with laws and regulations of practicing health professions in the country.