Predictors of hip fracture in 15 European countries: a longitudinal study of 48,533 geriatric adults using SHARE dataset.

We investigated the risk factors for hip fracture in 48,533 European older adults for 8 years from 2013 onward. We identified female gender, age above 80, low handgrip strength, and depression as significant risk factors for hip fracture. Our findings may help identify high-risk populations for hip fractures in pre-clinical settings. OBJECTIVES: Hip fracture is a major cause of functional disability, mortality, and health costs. However, the identification and characterization of its causative factors remain poor. METHODS: We investigated demography, handgrip strength (HGS), depression, and multiple age-associated comorbidities for predicting future hip fracture in individuals aged 50 or above from 15 European countries (n = 48,533). All participants were evaluated from 2013 to 2020 using four successive waves of the Survey of Health, Aging, and Retirement in Europe (SHARE). RESULTS: Altogether, 1130 participants developed hip fractures during the study period. We identified female gender, an advancing age from quinquagenarians onward, and a poor socioeconomic status as critical risk factors for future hip fracture. Having mobility difficulty, a low HGS (< 27 kg in men, < 16 kg in women) and higher scores on Euro-D depression scales were also significant risk factors for hip fracture. Summated scales of hypertension, diabetes mellitus, cancer, Alzheimer's disease, and stroke did not appear as risk factors. CONCLUSION: Collectively, we report advancing age, female gender, low HGS, and depression as independent risk factors for hip fracture. Our findings are useful in identifying high-risk populations for hip fractures in pre-clinical settings before rigorous evaluation and treatment in clinics.

Association of VDR gene variant rs2228570-FokI with gestational diabetes mellitus susceptibility in Arab women.

Gestational diabetes mellitus (GDM) has been linked with adverse pregnancy outcomes. Vitamin D receptor (VDR) gene variants have been associated with diabetes mellitus susceptibility and related complications. This study assessed the association between VDR gene polymorphism (rs2228570) and GDM risk among pregnant Arab women. A total of 368 pregnant Saudi women who were screened for GDM at 24-28 weeks of gestation and genotyped for the VDR gene variant (rs2228570) were included in this cross-sectional study. Circulatory insulin levels, fasting blood glucose (FBG), glycated hemoglobin (HbA1c), and vitamin D (25(OH)D) were measured. There were 108 women with GDM and 260 women without GDM. The genotype frequency of women with GDM was CC 60.2 %, CT 33.3 %, TT 6.9 %, and CT + TT 39.8 %; for non-GDM women, were CC 61.1 %, CT 31.5 %, TT 6.9 %, and CT + TT 38.4 %. No association was found between the VDR gene variant (rs2228570-FokI) and GDM susceptibility after adjustment for covariates. Serum 25(OH)D had a significant inverse association with FBG (r = -0.49, p = 0.01) and HbA1c (r = -0.45, p = 0.03) among carriers of the TT-genotype. Furthermore, a significant inverse correlation was observed between serum 25(OH)D and HOMA-ß (r = -0.20, p = 0.035) in individuals with the T-allele. Among pregnant Saudi women, glycemic indices appear to be influenced by vitamin D, suggesting a possible role it may play in mitigating the metabolic changes associated with GDM, particularly among individuals with specific genetic backgrounds. In our study population, rs2228570-FokI did not appear to be a significant contributor to GDM risk.

Biomarkers of Physical and Mental Health for Prediction of Parkinson's Disease: A Population-Based Study from 15 European Countries.

OBJECTIVES: Early diagnosis of Parkinson's disease (PD) is critical for optimal treatment. However, the predictive potential of physical and mental health in PD is poorly characterized. METHODS: We evaluated the potential of multiple demographic, physical, and mental factors in predicting the future onset of PD in older adults aged 50 years or older from 15 European countries. Individual study participants were followed over four waves of the Survey of Health, Ageing, and Retirement in Europe (SHARE) from 2013-2020. RESULTS: Of 57,980 study participants, 442 developed PD during the study period. We identified male sex and advancing age from the sixth decade of life onward as significant predictors of future PD. Among physical factors, a low handgrip strength (HGS; men <27 kg, women <16 kg), being bothered by frailty, and recent falls were significantly associated with future PD. Among mental factors, a higher depression (Euro-D depression score >6) emerged as an independent predictor of future PD. Finally, the presence of hypertension or Alzheimer's disease (AD) increases the risk of future PD. CONCLUSIONS: Altogether, male sex, advancing age, low HGS, frailty, depression, hypertension, and AD were identified as critical risk factors for future PD. Our results may be useful in the early identification and treatment of populations at risk for PD.

Association between handgrip strength and metabolic syndrome in relation to gender and adiposity among middle aged and older Saudi populations.

AIM: This cross-sectional study investigated the association between metabolic syndrome (MetS) and handgrip strength (HGS) with respect to sex and adiposity in Saudi men (n = 287) and women (n = 268). MATERIAL AND METHODS: Anthropometry, body composition, HGS, and blood biochemistry were measured. The average age of the study population was 57.65 ± 9.3 years (men = 55.1 ± 9.3 years, women = 60.4 ± 9.3 years). We report that HGS/body mass index (BMI), HGS/weight, and HGS/fat (%) were significantly higher in controls than in patients with MetS in men but not in women. According to the ROC analysis, relative HGS (RHGS) was higher than HGS alone in the association with MetS, which was significant for men (p < 0.01). At lower quartiles of HGS, the probability of MetS was higher in women, and the same was found in men in the lower quartiles of HGS/%Fat. Multinomial regression revealed significant associations between age and adiposity and MetS in men and HGS in women. Additionally, the linear regression of age, HGS, and weight exhibited significant associations between HGS with WC in both sexes. CONCLUSION: A higher risk of MetS in the lower quartiles of HGS was found in women, and adiposity moderated the relationship between HGS and MetS in men.

Associations of bone mineral density with sex hormone-binding globulin (SHBG) and testosterone in middle-aged Saudi men: a cross-sectional study.

Objective: The present cross-sectional study examined the association between circulating levels of sex hormone-binding globulin (SHBG) and testosterone with bone mineral density (BMD) in middle-aged Arab men. Methods: Clinical data of 103 middle-aged Saudi men (mean age 60.7±7.2) were extracted from the Osteoporosis Registry of the Chair for Biomarkers of Chronic Diseases, King Saud University in Riyadh, Saudi Arabia. Participants were categorized according to the presence of osteopenia (T-score -1.0 to -2.5) (N=47) and controls (N=56). Data collected included demographics and anthropometrics as well as levels of sex hormone-binding globulin (SHBG), testosterone and follicle-stimulating hormone (FSH) which were measured using commercially available assays. Free androgen index (FAI) was calculated. Results: Those with osteopenia had significantly lower levels of FAI (p<0.05), and higher levels of SHBG (p<0.004) and FSH (p<0.005). In the osteopenia group, SHBG was positively correlated with age (r=0.33, p<0.05), while it was inversely correlated with BMD spine (r = -0.39, p<0.05) and T-score femur (r= -0.35, p<0.05) in the same group. Furthermore, testosterone was inversely correlated with BMI in the osteopenia group (r= -0.33, p<0.05) while FAI was positively correlated with T-score femur (r = 0.36, p<0.05) as well as in all participants (r= 0.24, p<0.05). Among controls, FAI had an inverse correlation with FSH (r= -0.28, p<0.05) and over-all (r= -0.22, p<0.05). Conclusion: In summary, the associations elicited suggest that circulating levels of SHBG and FAI may be against age-related bone loss in middle-aged men.

The quality of life in Alzheimer's disease is not associated with handgrip strength but with activities of daily living-a composite study from 28 European countries.

OBJECTIVES: The relationship between handgrip strength (HGS) and quality of life is inconsistent. The purpose of this study was to investigate the potential association between HGS and quality of life in the settings of ageing and Alzheimer's disease (AD). METHODS: We investigated the HGS, CASP-12 (control, autonomy, self-realization, and pleasure) measure of quality of life, and physical capacity in European adults above 50, including controls (n = 38,628) and AD subjects (n = 460) using the survey of health, ageing, and retirement in Europe (SHARE; 2022). RESULTS: AD subjects exhibited lower HGS and CASP-12 scores than controls (both p < 0.05). Participants with higher CASP-12 quartiles had higher HGS in controls but not in AD subjects. A linear positive relation was found between HGS and CASP-12 in controls (0.0842, p < 0.05) but not in AD subjects (0.0636, p = 0.091). There was no effect of gender on this finding. Lastly, we found significant negative associations of difficulties walking, rising from chair, climbing stairs, and fatigue with CASP-12 scores in controls and AD subjects (all p < 0.05). CONCLUSIONS: Altogether, HGS was not associated with quality of life in individuals with AD. Conversely, difficulties in activities of daily living seem to be negatively associated with quality of life; thus, strategies are recommended to improve physical capacity.

Identification of phytoconstituents from Albizia lebbeck as potential therapeutics against HIV-1 reverse transcriptase associated with infective endocarditis: In silico and in vitro approaches.

Acquired immune deficiency syndrome (AIDS) is an unadorned disease affected via the human immunodeficiency virus (HIV), which has become the most infectious diseases worldwide. HIV-1 RT has been shown to be present in the cardiac tissue of patients with HIV-associated infective endocarditis, and to be associated with the development of valvular lesions and other cardiac abnormalities. The use of anti-retroviral therapies has helped to control the virus and reduce the incidence of HIV-1 associated infective endocarditis. Though, these treatments have several adjacent effects, and the improvement of drug-resistant stresses of the virus has become a significant challenge in HIV treatment. This study is to identify A. lebbeck phytoconstituents with HIV-1 RT inhibitory activity for potential therapeutic use against HIV-1 RT associated with infective endocarditis. We performed in silico and in vitro screening of natural cardiovascular phytoconstituents from Albizia lebbeck, a medicinal plant that has been traditionally used for the management of numerous diseases. The in silico results showed that all three compounds (geraldone, luteolin, and isookanin) exhibited affinities of solid binidng to the active amino acids of HIV-1 RT's DNA-polymerase (DNA-p) and Ribonuclease-H (RNA-H) active positions, suggesting their potential as HIV-1 RT inhibitors. In vitro assessment of the three compounds at a concentration of 1 mg/mL revealed that Geraldone exhibited the most effective inhibitory consequence on HIV-1 RT activity (83.45%), followed by Isookanin (75.88%) and Luteolin (66.36%). These findings suggest that these compounds have the potential to inhibit HIV-1 RT associated with infective endocarditis and could assist as main compounds for emerging unique anti-HIV-1 agents. Further studies are needed to confirm the in vitro and in vivo efficacy of these molecules and assess their safety and efficiency as anti-HIV-1 drugs.

ChatGPT Knowledge Evaluation in Basic and Clinical Medical Sciences: Multiple Choice Question Examination-Based Performance.

The Chatbot Generative Pre-Trained Transformer (ChatGPT) has garnered great attention from the public, academicians and science communities. It responds with appropriate and articulate answers and explanations across various disciplines. For the use of ChatGPT in education, research and healthcare, different perspectives exist with some level of ambiguity around its acceptability and ideal uses. However, the literature is acutely lacking in establishing a link to assess the intellectual levels of ChatGPT in the medical sciences. Therefore, the present study aimed to investigate the knowledge level of ChatGPT in medical education both in basic and clinical medical sciences, multiple-choice question (MCQs) examination-based performance and its impact on the medical examination system. In this study, initially, a subject-wise question bank was established with a pool of multiple-choice questions (MCQs) from various medical textbooks and university examination pools. The research team members carefully reviewed the MCQ contents and ensured that the MCQs were relevant to the subject's contents. Each question was scenario-based with four sub-stems and had a single correct answer. In this study, 100 MCQs in various disciplines, including basic medical sciences (50 MCQs) and clinical medical sciences (50 MCQs), were randomly selected from the MCQ bank. The MCQs were manually entered one by one, and a fresh ChatGPT session was started for each entry to avoid memory retention bias. The task was given to ChatGPT to assess the response and knowledge level of ChatGPT. The first response obtained was taken as the final response. Based on a pre-determined answer key, scoring was made on a scale of 0 to 1, with zero representing incorrect and one representing the correct answer. The results revealed that out of 100 MCQs in various disciplines of basic and clinical medical sciences, ChatGPT attempted all the MCQs and obtained 37/50 (74%) marks in basic medical sciences and 35/50 (70%) marks in clinical medical sciences, with an overall score of 72/100 (72%) in both basic and clinical medical sciences. It is concluded that ChatGPT obtained a satisfactory score in both basic and clinical medical sciences subjects and demonstrated a degree of understanding and explanation. This study's findings suggest that ChatGPT may be able to assist medical students and faculty in medical education settings since it has potential as an innovation in the framework of medical sciences and education.

Extraction and determination of aflatoxin B1 in cereal samples using pH-switchable hydrophobic deep eutectic solvents followed by HPLC-FL analysis.

A quick, simple and environmentally friendly liquid phase microextraction (LPME) sample pretreatment procedure was proposed based on pH-switchable hydrophobic deep eutectic solvents (HDESs) and high performance liquid chromatography coupled with a fluorescence detector (HPLC-FL). This method was used for the quantitative study of aflatoxin B1 (AFB1) and applied to eight widely consumed cereal samples. In this method, six different DESs were synthesized and then their pH-switchability was investigated. DESs that could be switched with pH were employed for separation and preconcentration of AFB1 in cereal samples. In this method, dispersing the extractant phase in the aqueous solution and subsequent phase separation are performed only by changing the pH. Important parameters affecting extraction, such as the type of DES and its volume, concentration of KOH, volume of HCL, effect of salt and extraction time were investigated and optimum conditions were obtained. Under the optimum conditions, relative standard deviation (RSD) values for intra-day and inter-day of the method based on seven replicate measurements of 5.0 µg kg-1 of AFB1 in cereal samples were 3.3 and 5.2%, respectively. The calibration graphs were linear in the range of 0.007-20 µg kg-1 and limit of detection (LOD) was 0.002 µg kg-1. The relative recoveries of real cereal samples which have been spiked with different levels of AFB1 were 90.8-107.5%.

Interspecies microbial interactions in bioelectrochemical system and biodegradation: A state of the art review.

Microbial mutualistic interaction or synthetic microbiology evolves closely from the concept of cell-cell relations in a complex microbial community, which plays a crucial role in waste degradation, bioremediation, and bioenergy generation. Recently, the application of synthetic microbial consortia has renewed attention in the field of bioelectrochemistry. In the past few years, the influence of microbial mutualistic interaction has been extensively studied in bioelectrochemical systems (BES), especially in microbial fuel cells (MFCs). Nevertheless, synthetic microbial consortia were found to exhibit superior bioremediation performance compared to single strains of microbes for polycyclic aromatic hydrocarbons, synthetic dyes, polychlorinated biphenyls, and other organic pollutants compared to the respective single microbial species. However, a comprehensive understanding of intermicrobial interactions, specifically the metabolic pathways in a mixed-cultured microbial community system, is still lacking. In this study, we have comprehensively reviewed the possible pathways for executing intermicrobial communication within a complex microbial community consortium with various underlying pathways. The influence of mutualistic interactions on the power generation of MFCs and wastewater biodegradation has been widely reviewed. We argue that this study would motivate the design and construction of potential synthetic microbial consortia to stimulate the extraction of bioelectricity and the biodegradation of contaminants.

Impact of Vitamin D Status Correction on Serum Lipid Profile, Carboxypeptidase N and Nitric Oxide Levels in Saudi Adults.

This study aimed to determine the impact on the lipid profile, carboxypeptidase N (CPN) and nitric oxide (NOx) associated with vitamin D (VD) status correction among Saudi adults with VD deficiency. A total 111 VD deficient (25(OH)D < 50 nmol/L)) adult Saudis aged 18-50 years old (57 females and 54 males) were enrolled in this 6-month interventional study. They were given 50,000 IU VD weekly for the first 2 months and then twice a month for the next 2 months, followed by 1000 IU daily for the last 2 months. The fasting lipid profile and the blood glucose, VD, NOx and CPN concentrations were measured at baseline and after intervention. Post-supplementation, the median VD was significantly higher (p < 0.001) in females [58.3 (50.6-71.2)] and males [57.8 (51.0-71.8)]. HDL cholesterol significantly increased (p = 0.05) and NOx significantly decreased (p = 0.02) in males post-supplementation. Triglycerides were positively associated with NOx in all subjects before (r = 0.44, p = 0.01) and after (r = 0.37, p = 0.01) VD status correction. There was a significant increase in serum levels of CPN2 (p = 0.02) in all subjects. Furthermore, CPN was inversely correlated with NOx (r = -0.35, p = 0.05) in males post-supplementation. In conclusion, VD status correction reduced serum NOx, particularly in males. The inhibition of NOx synthesis may be responsible for the anti-inflammatory effects of VD supplementation. An inverse association was found between NOx and CPN2.

Antidiabetic effect of flavonoid from Rumex vesicarius on alloxan induced diabetes in Male Albino Wistar rats and its validation through in silico molecular docking and dynamic simulation studies.

The leaves of Rumex vescarius L. are used locally to treat diabetes, a chronic illness. A flavonoid called Luteolin from R. vesicarius was chosen to explore for the antidiabetic potential through the in vivo antidiabetic test against male albino Wistar rats that had been induced with diabetes due to alloxan. Additionally, docking screening was carried out with the aid of autodock software to identify probable moiety that might be in charge of its anti-diabetic effect. Given at a dose of 100 mg/kg body weight, luteolin from R. vesicarius leaves had a significant (p < 0.05) hypoglycaemic impact after just one week. The blood glucose level significantly decreased during the third week (p < 0.05). All provided doses of luteolin from R. vesicarius leaves resulted in a reduction, however on all study days, the highest concentration (400 mg/kg body weight) produced the biggest reduction. The results of luteolin's molecular docking and dynamic modelling studies with a variety of targets revealed significant binding interactions at the active site binding pocket, with the target α-glucosidase having the highest binding affinity (-9.35 kcal/mol). In conclusion, the plant and the flavonoid luteolin it contains have potent anti-diabetic properties, possibly through an interaction with the enzyme α-glucosidase.

Genetic Variants of HNF4A, WFS1, DUSP9, FTO, and ZFAND6 Genes Are Associated with Prediabetes Susceptibility and Inflammatory Markers in the Saudi Arabian Population.

Prediabetes is a reversible, intermediate stage of type 2 diabetes mellitus (T2DM). Lifestyle changes that include healthy diet and exercise can substantially reduce progression to T2DM. The present study explored the association of 37 T2DM- and obesity-linked single nucleotide polymorphisms (SNPs) with prediabetes risk in a homogenous Saudi Arabian population. A total of 1129 Saudi adults [332 with prediabetes (29%) and 797 normoglycemic controls] were randomly selected and genotyped using the KASPar SNP genotyping method. Anthropometric and various serological parameters were measured following standard procedures. Heterozygous GA of HNF4A-rs4812829 (0.64; 95% CI 0.47-0.86; p < 0.01), heterozygous TC of WFS1-rs1801214 (0.60; 95% confidence interval (CI) 0.44-0.80; p < 0.01), heterozygous GA of DUSP9-rs5945326 (0.60; 95% CI 0.39-0.92; p = 0.01), heterozygous GA of ZFAND6-rs11634397 (0.75; 95% CI 0.56-1.01; p = 0.05), and homozygous AA of FTO-rs11642841 (1.50; 95% CI 0.8-1.45; p = 0.03) were significantly associated with prediabetes, independent of age and body mass index (BMI). Additionally, C-reactive protein (CRP) levels in rs11634397 (AA) with a median of 5389.0 (2767.4-7412.8) were significantly higher than in the heterozygous GA genotype with a median of 1736.3 (1024.4-4452.0) (p < 0.01). In conclusion, only five of the 37 genetic variants previously linked to T2DM and obesity in the Saudi Arabian population [HNF4A-rs4812829, WFS1-rs1801214, DUSP9-rs5945326, ZFAND6-rs11634397, FTO-rs11642841] were associated with prediabetes susceptibility. Prospective studies are needed to confirm the potential clinical value of the studied genetic variants of interest.

Adverse Effects of Sinopharm COVID-19 Vaccine among Vaccinated Medical Students and Health Care Workers.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease caused a highly problematic situation worldwide. Various vaccines were launched to combat the COVID-19 pandemic. This study aims to investigate the adverse effects of first and second doses of the Sinopharm vaccine among vaccinated medical and dental students and healthcare workers. A well-established questionnaire was distributed online, and 414 medical and dental students and healthcare workers (HCW) comprising 355 females (85.7%) and 59 males (14.3%) participated; all were vaccinated with two doses of Sinopharm. The most common side effect was pain at the injection site after dose one in 253 respondents (61.3%) and after dose two in 161 respondents (38.9%). Other symptoms included general lethargy in 168 (40.6%), myalgia/body pain in 99 (23.9%), low-grade fever in 93 (22.4%), and headache in 87 (21%) respondents. Common side effects reported after the second dose of the vaccine following pain at the injection site included general lethargy in 21.3% (88), headache in 10.4% (43), myalgia/body pain in 9.9% (41), and low-grade fever in 6.1% (25) of the respondents. In conclusion, common adverse effects of the Sinopharm vaccine were pain at the injection site, general lethargy, myalgia, body pain, low-grade fever, and headache. These adverse effects were mild in intensity for both doses but slightly more frequent and severe for the first dose than the second dose.

Heart Rate Variability and Chronotype in Young Adult Men.

Whether morning heart rate variability (HRV) predicts the magnitude of its circadian variation in the absence of disease or is influenced by chronotype is unclear. We aimed to quantify associations between (1) morning HRV and its diurnal change, and (2) morning HRV and a Morningness−Eveningness Questionnaire (MEQ)-derived chronotype. Resting electrocardiograms were obtained in the morning and evening on separate days in a counterbalanced order to determine the mean RR interval, root mean square of successive differences (RMSSD), and standard deviation of normal-to-normal RR intervals (SDNN) in 23 healthy men (24.6 ± 3.4 yrs; body mass index: 25.3 ± 2.8 kg/m2). The MEQ was completed during the first laboratory visit. Morning RMSSD and SDNN were significantly higher (Ps < 0.05) than evening values. Morning RMSSD and SDNN were associated with their absolute (Ps < 0.0001), and relative diurnal changes (Ps < 0.01). No associations were observed between HRV parameters and the MEQ chronotypes (Ps > 0.09). Morning HRV was a stronger determinant of its evening change than chronotype. Greater diurnal variation in HRV was dependent on higher morning values. Strategies to improve basal HRV may therefore support healthier cardio-autonomic circadian profiles in healthy young men.

Comparison of Biological, Pharmacological Characteristics, Indications, Contraindications and Adverse Effects of JYNNEOS and ACAM2000 Monkeypox Vaccines.

Human monkeypox is an emerging viral zoonotic disease, that has caused highly distinctive, challenging and threatening problems worldwide. The US Food and Drug Administration (FDA) has given interim authorization for the JYNNEOS and ACAM2000 vaccines for the outbreak of monkeypox 2022. The present study aims to highlight the globally derived evidence about the biological and pharmacological features, indications, contraindications and adverse effects of JYNNEOS and ACAM2000 vaccines. Initially, 82 documents were selected and, finally, 14 fact sheets, documents and international organizations were included. The data were recorded from the World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), Food and Drug Administration (FDA) USA, ISI-Web of Science, PubMed, EMBASE and Scopus. The data revealed that the JYNNEOS vaccine has been recommended to children, adults, females during pregnancy and people of all age groups with a dose of 0.5 mL, and the complete vaccination cost per person is about USD 115. It provides immunogenicity, and the mean titer of neutralizing antibodies was 153.5. However, the ACAM2000 vaccine is contraindicated in infants and pregnant females, and recommended to people over 18 years of age and older, with a single dose of 0.0025 mL, and a cost of about USD 139. ACAM2000 provides immunogenicity, and the mean titer of neutralizing antibodies was 79.3. The JYNNEOS vaccine has mild adverse effects including pain, redness, swelling or itching at the site of the vaccine shot, fever, fatigue, headache, nausea and muscle pain. However, the ACAM2000 vaccine can cause pain, redness, edema, headache, fever, fatigue, muscle pain, body ache, nausea, vomiting, diarrhea, shortness of breath and increased risk of myopericarditis and cardiomyopathy. The evidence supports the view that both vaccines are beneficial, but the overall impact of JYNNEOS is better than that of ACAM2000.

Effect of Acute Myocardial Infarction on a Disintegrin and Metalloprotease with Thrombospondin Motif 13 and Von Willebrand Factor and Their Relationship with Markers of Inflammation.

OBJECTIVES: Coagulation mechanisms and fibrinolytic assembly are important components role players of acute myocardial infarction (AMI) progression. Our study objective was to see the serial variations in the levels of Von Willebrand factor (VWF) and A Disintegrin and Metalloprotease with ThromboSpondin motif (ADAMTS13) over the course of AMI and to determine their relationship with the cardiovascular risk markers and the patient's clinical characteristics. METHODS: This project was done at the departments of Emergency Medicine, Physiology and Cardiac sciences of King Saud University Medical City. We studied ADAMTS13, VWF, fibrinogen, and CRP levels in 80 patients with AMI when patients were admitted; post AMI by 3-4 days and at follow-up of 3 months. We compared them with a control group consisting of 36 subjects. RESULTS: AMI had significantly lower levels of ADAMTS13 at AMI and after 3-4 days; at follow-up the difference in levels was nonsignificant, when compared with controls. Similarly, VWF levels were significantly higher in AMI and remained high even at follow-up compared to control subjects. VWF/ADAMTS13 ratio was also significantly higher at AMI and 3-4 days while at follow-up difference was nonsignificant compared to control subjects. Regression analysis between hsCRP and ADAMTS13 showed an inverse relationship (r = 0.376, p < 0.01), while correlation with VWF was significantly positive (r = 0.376, p < 0.01), while correlation with VWF was significantly positive (. CONCLUSIONS: Increased levels of VWF and reduced levels of ADAMTS13 activity may contribute to the pathogenesis of acute myocardial infarction and might prove to be important mediators of AMI progression.

Fingolimod Plays Role in Attenuation of Myocardial Injury Related to Experimental Model of Cardiac Arrest and Extracorporeal Life Support Resuscitation.

BACKGROUND: Sudden cardiac arrest is a major global health concern, and survival of patients with ischemia-reperfusion injury is a leading cause of myocardial dysfunction. The mechanism of this phenomenon is not well understood because of the complex pathophysiological nature of the disease. Aim of the study was to investigate the cardioprotective role of fingolimod in an in vivo model of cardiac arrest and resuscitation. METHODS: In this study, an in vivo rat model of cardiac arrest using extracorporeal membrane oxygenation resuscitation monitored by invasive hemodynamic measurement was developed. At the beginning of extracorporeal life support (ECLS), animals were randomly treated with fingolimod (Group A, n = 30) or saline (Group B, n = 30). Half of the animals in each group (Group A1 and B1, n = 15 each) were sacrificed after 1 h, and the remaining animals (Group A2 and B2) after 24 h of reperfusion. Blood and myocardial tissues were collected for analysis of cardiac features, inflammatory biomarkers, and cell signaling pathways. RESULTS: Treatment with fingolimod resulted in activation of survival pathways resulting into reduced inflammation, myocardial oxidative stress and apoptosis of cardiomyocytes. This led to significant improvement in systolic and diastolic functions of the left ventricle and improved contractility index. CONCLUSIONS: Sphingosine1phosphate receptor activation with fingolimod improved cardiac function after cardiac arrest supported with ECLS. Present study findings strongly support a cardioprotective role of fingolimod through sphingosine-1-phosphate receptor activation during reperfusion after circulatory arrest.

Protective effect of fenofibrate against ischemia-/reperfusion-induced cardiac arrhythmias in isolated rat hearts.

Fenofibrate is a peroxisome proliferator-activated receptor (PPAR)-α activator that lowers triglycerides and influences cytochrome P-450 (CYP-450) epoxygenase-dependent arachidonic acid (AA) metabolism. CYP-450 epoxygenase metabolizes AA to epoxyeicosatrienoic acids (EETs). EETs have coronary dilating and cardiac and renal protective properties. Fibrates possess similar properties due to their CYP-450 epoxygenase-inducing properties that lead to increase in endogenous EET production. In the current investigations, fenofibrate (100 mg/kg, orally) for 2 weeks decreased ischemia-/reperfusion (I/R)-induced premature ventricular contractions (PVCs), ventricular tachycardia (VT), and ventricular fibrillation (VF) in the isolated rat hearts. Fenofibrate caused marked inhibition of the reperfusion-induced cardiac arrhythmias. The incidence of reperfusion-induced VF decreased from 80% in the control vehicle-treated animals to 33% in the fenofibrate-treated animals (P < 0.001). PVCs were also significantly (P < 0.01) decreased from 223.2 ± 51 in control vehicle-treated animals to 136.8 ± 22 in fenofibrate-treated animals. Total duration of reperfusion-induced VT decreased from 29.2 ± 6.3 s in control, vehicle-treated animals to 4.8 ± 1.3 s in fenofibrate-treated animals, P < 0.001. Heart rate and perfusion pressure were not significantly affected by fenofibrate pretreatment. Diltiazem, a clinically used anti-arrhythmic agent, produced complete protection against I/R-induced cardiac arrhythmias in this model reducing the incidence of VF from 80% in control, vehicle-treated animals to 10% in diltiazem-treated hearts. These findings indicate that fenofibrate suppresses arrhythmias in isolated rat hearts subjected to I/R-induced injury.

Th-17 regulatory cytokines IL-21, IL-23, and IL-6 enhance neutrophil production of IL-17 cytokines during asthma.

BACKGROUND: In a subset of severe asthma patients, chronic airway inflammation is associated with infiltration of neutrophils, Th-17 cells and elevated expression of Th-17-derived cytokines (e.g., interleukin [IL]-17, IL-21, IL-22). Peripheral neutrophils from allergic asthmatics are known to express higher IL-17 cytokine levels than those from healthy subjects, but the regulatory mechanisms involved are not well understood. We hypothesize that Th-17 regulatory cytokines could modulate IL-17 expression in neutrophils. METHODS: Peripheral blood neutrophils isolated from asthmatics were stimulated with IL-21, IL-23, and IL-6 cytokines and their ability to produce IL-17A and IL-17F was determined relative to healthy controls. Signal transducer and activator of transcription 3 (STAT3) phosphorylation levels were measured in stimulated neutrophil using flow cytometry. The requirement for STAT3 phosphorylation was determined by blocking its activation using a specific chemical inhibitor. RESULTS: Stimulating asthmatic neutrophils with IL-21, 23, and 6 enhanced the production of IL-17A and IL-17F at significantly higher levels comparatively to healthy controls. Stimulating neutrophils with IL-21, IL-23, and IL-6 cytokines enhanced STAT3 phosphorylation, in all cases. Interestingly, inhibiting STAT3 phosphorylation using a specific chemical inhibitor dramatically blocked the ability of neutrophils to produce IL-17, demonstrating that STAT3 activation is the major factor mediating IL-17 gene expression. CONCLUSIONS: These findings suggest that neutrophil infiltration in lungs of severe asthmatics may represent an important source of pro-inflammatory IL-17A and -F cytokines, a production enhanced by Th-17 regulatory cytokines, and thus providing a feedback mechanism that sustains inflammation. Our results suggest that STAT3 pathway could be a potential target for regulating neutrophilic inflammation during severe asthma.