Association of the HALP Score with Dyslipidemia: A Large, Nationwide Retrospective Study.

Background and Objectives: Dyslipidemia is a major risk factor for cardiovascular disease (CVD). The identification of new biomarkers that may enhance the risk assessment of lipid abnormalities is a promising approach in improving risk prediction of CVD. There is no information on the association of the hemoglobin, albumin, lymphocyte, and platelet (HALP) score with dyslipidemia. The aim of this study was to investigate the clinical utility of the HALP score in light of dyslipidemia. Materials and Methods: A retrospective analysis of 7192 subjects was initiated to assess the association between the HALP score and disturbed lipid markers. Medians were compared by Mann-Whitney U or Kruskal-Wallis tests and the diagnostic performance and risk assessment were calculated. Results: Median HALP score among all subjects was 53.3, with varying values between males and females. Notably, median HALP was significantly elevated in all forms of dyslipidemia and among males and females irrespective of age. The odds of having elevated HALP score values were significantly higher in all lipid abnormalities. Moreover, HALP score was significantly yet weakly correlated with lipid markers, while the highest diagnostic accuracy of the HALP score was observed with an elevated ratio of total cholesterol to high-density lipoprotein (TC/HDL) (area under the curve, AUC = 0.6411, p < 0.0001). The decision curve analysis (DCA) showed that the HALP score can reliably predict the presence of dyslipidemia. Conclusions: This study demonstrates that the HALP score is a novel, cost-effective index that is associated with a disturbed lipid profile. Further investigation of the nature of this association is needed.

Prevalence and association of hyperuricemia with liver function in Saudi Arabia: a large cross-sectional study.

BACKGROUND: Hyperuricemia is linked to an increased risk of various chronic diseases, but data on the prevalence and association of hyperuricemia with liver function in Saudi Arabia are scarce. OBJECTIVES: Evaluate the prevalence, association, and risk measures of hyperuricemia and liver function in the Saudi population. DESIGN: Retrospective, cross-sectional analysis. SETTING: Database on large portion of Saudi population. PATIENTS AND METHODS: Laboratory data, age, and gender of the studied subjects were collected from Al Borg Diagnostics. Subjects were stratified, based on their uric acid (UA) levels, into three groups: hypouricemic, normouricemic, and hyperuricemic. The association of UA with liver enzymes was examined in all three groups. MAIN OUTCOME MEASURES: Association of serum UA levels with alanine transaminase (ALT), aspartate transferase (AST), alkaline phosphatase (ALP), and total bilirubin (TB). SAMPLE SIZE: 13 314 subjects. RESULTS: Our study showed that the prevalence of hyperuricemia in the Saudi population is 17.3% (20.3% in males and 15.1% in females). We also found a positive correlation between ALT, AST, and TB with UA levels. The risk of being hyperuricemic was significantly increased in individuals with elevated ALT, AST, and TB. Individuals with elevated ALT, AST, and total TB had a higher chance of having hyperuricemia than those with normal activity. Notably, ALT, AST, and TB had good discriminating capacity for hyperuricemia. CONCLUSIONS: Hyperuricemia is highly prevalent in the Saudi population and is associated with compromised liver function. However, further studies are needed to elucidate the mechanisms underlying these findings in large prospective cohort studies in different populations. LIMITATIONS: Lack of data on other potential confounding variables.

Lipoprotein(a): Levels and Reference Intervals Among People in Saudi Arabia.

Purpose: Blood Lp(a) concentration is recognized as an independent risk factor for cardiovascular disease (CVD). Population-based lipoprotein(a) (Lp[a]) research in Saudi Arabia is rare. Thus, the primary goal of this pilot study was to identify age- and sex-specific reference ranges for Lp(a) levels, in addition to the associations between Lp(a) levels and other atherosclerotic markers in Saudi individuals. Patients and methods: A five-year retrospective study of Lp(a) and lipid markers in Saudi patients was conducted using the Al-Borg diagnostics database (2015-2020). The population sample consisted of 361 Saudi individuals aged 18-93 years (162 males, 199 females). An immunoturbidimetric technique was used to determine Lp(a) concentration. Results: The mean and median Lp(a) levels in the study population were 35 nmol/L and 50 nmol/L, respectively. Sex and age did not influence Lp(a) values. Lp(a) values showed a minor correlation with other atherosclerotic markers when the Pearson correlation coefficient was used. In Saudi Arabia, the distribution of Lp(a) concentrations is skewed to the left, favoring lower values. Conclusion: Lp(a) levels in individuals residing in Saudi Arabia were comparable to those observed in other ethnic groups. Additionally, standardizing Lp(a) measurements according to sex and age may enhance broader applicability and facilitate comparisons across different populations. However, larger studies are required to provide more comprehensive data for comparison.

Introducing Group Open-Book Exams as a Learning and Assessment Strategy in the Clinical Biochemistry Course for Medical Students.

BACKGROUND: Teachers constantly strive to obtain reliable and appropriate teaching and assessment methods to maximize the learning experience. This study aimed to introduce combined modified team-based learning and open-book exams (TBL/OBEs) as learning and assessment strategies in clinical biochemistry for medical students and assess students' perceptions. METHODS: Second-year medical students enrolled in the clinical biochemistry course were included in this study and subjected to TBL/OBE assessment. The assessment included two parts: the open-book format for half of the questions and the closed-book format for the other as a control. Upon completing the combined TBL/OBE session, the students were required to complete a structured survey to evaluate their perception of the experience. The data were gathered and analyzed. Data were presented as mean±standard error of the mean (SEM), and a p-value ≤0.05 was considered statistically significant. RESULTS: A total of 358 students completed the TBL/OBE and closed-book exam (CBE) and responded to the survey. Of these students, 76% preferred the OBE, and 84% thought it was a suitable learning method. On the one hand, the mean difficulty of the OBE format was 92.7±1.5 SEM, while, for the CBE, the mean difficulty was 88.7±1.9 SEM (p=0.015). On the other hand, the mean discrimination factor for OBE was 0.26±0.04 and, for the CBE, 0.41±0.04 SEM (p=0.0016). Males found the OBE questions easier (p=0.025) and less stressful (p=0.01). CONCLUSION: A combined model of modified TBL and OBE is a successful learning and assessment strategy in clinical biochemistry for medical students.

In vitro studies on the pharmacological potential, anti-tumor, antimicrobial, and acetylcholinesterase inhibitory activity of marine-derived Bacillus velezensis AG6 exopolysaccharide.

In the current study, Bacillus velezensis AG6 was isolated from sediment samples in the Red Sea, identified by traditional microbiological techniques and phylogenetic 16S rRNA sequences. Among eight isolates screened for exopolysaccharide (EPS) production, the R6 isolate was the highest producer with a significant fraction of EPS (EPSF6, 5.79 g L-1). The EPSF6 molecule was found to have a molecular weight (Mw) of 2.7 × 104 g mol-1 and a number average (Mn) of 2.6 × 104 g mol-1 when it was analyzed using GPC. The FTIR spectrum indicated no sulfate but uronic acid (43.8%). According to HPLC, the EPSF6 fraction's monosaccharides were xylose, galactose, and galacturonic acid in a molar ratio of 2.0 : 0.5 : 2.0. DPPH, H2O2, and ABTS tests assessed EPSF6's antioxidant capabilities at 100, 300, 500, 1000, and 1500 µg mL-1 for 15, 60, 45, and 60 minutes. The overall antioxidant activities were dose- and time-dependently increased, and improved by increasing concentrations from 100 to 1500 µg mL-1 after 60 minutes and found to be 91.34 ± 1.1%, 80.20 ± 1.4% and 75.28 ± 1.1% respectively. Next, EPSF6 displayed considerable inhibitory activity toward the proliferation of six cancerous cell lines. Anti-inflammatory tests were performed using lipoxygenase (5-LOX) and cyclooxygenase (COX-2). An MTP turbidity assay method was applied to show the ability of EPSF6 to inhibit Gram-positive bacteria, Gram-negative bacteria, and antibiofilm formation. Together, this study sheds light on the potential pharmacological applications of a secondary metabolite produced by marine Bacillus velezensis AG6. Its expected impact on human health will increase as more research and studies are conducted globally.

Urolithin A's Antioxidative, Anti-Inflammatory, and Antiapoptotic Activities Mitigate Doxorubicin-Induced Liver Injury in Wistar Rats.

Human colon microbiota produce a metabolite called urolithin A (URO A) from ellagic acid and linked compounds, and this metabolite has been demonstrated to have antioxidant, anti-inflammatory, and antiapoptotic activities. The current work examines the various mechanisms through which URO A protects against doxorubicin (DOX)-induced liver injury in Wistar rats. In this experiment, Wistar rats were administered DOX intraperitoneally (20 mg kg-1) on day 7 while given URO A intraperitoneally (2.5 or 5 mg kg-1 d-1) for 14 days. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT) were measured. Hematoxylin and eosin (HE) staining was used to evaluate histopathological characteristics, and then antioxidant and anti-inflammatory properties were evaluated in tissue and serum, respectively. We also looked at how active caspase 3 and cytochrome c oxidase were in the liver. The findings demonstrated that supplementary URO A therapy clearly mitigated DOX-induced liver damage. The antioxidant enzymes SOD and CAT were elevated in the liver, and the levels of inflammatory cytokines, such as TNF-α, NF-kB, and IL-6, in the tissue were significantly attenuated, all of which complemented the beneficial effects of URO A in DOX-induced liver injury. In addition, URO A was able to alter the expression of caspase 3 and cytochrome c oxidase in the livers of rats that were subjected to DOX stress. These results showed that URO A reduced DOX-induced liver injury by reducing oxidative stress, inflammation, and apoptosis.

Differential remodelling of mitochondrial subpopulations and mitochondrial dysfunction are a feature of early stage diabetes.

Mitochondrial dysfunction is a feature of type I and type II diabetes, but there is a lack of consistency between reports and links to disease development. We aimed to investigate if mitochondrial structure-function remodelling occurs in the early stages of diabetes by employing a mouse model (GENA348) of Maturity Onset Diabetes in the Young, exhibiting hyperglycemia, but not hyperinsulinemia, with mild left ventricular dysfunction. Employing 3-D electron microscopy (SBF-SEM) we determined that compared to wild-type, WT, the GENA348 subsarcolemma mitochondria (SSM) are ~ 2-fold larger, consistent with up-regulation of fusion proteins Mfn1, Mfn2 and Opa1. Further, in comparison, GENA348 mitochondria are more irregular in shape, have more tubular projections with SSM projections being longer and wider. Mitochondrial density is also increased in the GENA348 myocardium consistent with up-regulation of PGC1-α and stalled mitophagy (down-regulation of PINK1, Parkin and Miro1). GENA348 mitochondria have more irregular cristae arrangements but cristae dimensions and density are similar to WT. GENA348 Complex activity (I, II, IV, V) activity is decreased but the OCR is increased, potentially linked to a shift towards fatty acid oxidation due to impaired glycolysis. These novel data reveal that dysregulated mitochondrial morphology, dynamics and function develop in the early stages of diabetes.

Mitochondrial Arrest on the Microtubule Highway-A Feature of Heart Failure and Diabetic Cardiomyopathy?

A pathophysiological consequence of both type 1 and 2 diabetes is remodelling of the myocardium leading to the loss of left ventricular pump function and ultimately heart failure (HF). Abnormal cardiac bioenergetics associated with mitochondrial dysfunction occurs in the early stages of HF. Key factors influencing mitochondrial function are the shape, size and organisation of mitochondria within cardiomyocytes, with reports identifying small, fragmented mitochondria in the myocardium of diabetic patients. Cardiac mitochondria are now known to be dynamic organelles (with various functions beyond energy production); however, the mechanisms that underpin their dynamism are complex and links to motility are yet to be fully understood, particularly within the context of HF. This review will consider how the outer mitochondrial membrane protein Miro1 (Rhot1) mediates mitochondrial movement along microtubules via crosstalk with kinesin motors and explore the evidence for molecular level changes in the setting of diabetic cardiomyopathy. As HF and diabetes are recognised inflammatory conditions, with reports of enhanced activation of the NLRP3 inflammasome, we will also consider evidence linking microtubule organisation, inflammation and the association to mitochondrial motility. Diabetes is a global pandemic but with limited treatment options for diabetic cardiomyopathy, therefore we also discuss potential therapeutic approaches to target the mitochondrial-microtubule-inflammatory axis.

Three-dimensional electron microscopy techniques for unravelling mitochondrial dysfunction in heart failure and identification of new pharmacological targets.

A hallmark of heart failure is mitochondrial dysfunction leading to a bioenergetics imbalance in the myocardium. Consequently, there is much interest in targeting mitochondrial abnormalities to attenuate the pathogenesis of heart failure. This review discusses (i) how electron microscopy (EM) techniques have been fundamental for the current understanding of mitochondrial structure-function, (ii) the paradigm shift in resolutions now achievable by 3-D EM techniques due to the introduction of direct detection devices and phase plate technology, and (iii) the application of EM for unravelling mitochondrial pathological remodelling in heart failure. We further consider the tremendous potential of multi-scale EM techniques for the development of therapeutics, structure-based ligand design and for delineating how a drug elicits nanostructural effects at the molecular, organelle and cellular levels. In conclusion, 3-D EM techniques have entered a new era of structural biology and are poised to play a pivotal role in discovering new therapies targeting mitochondria for treating heart failure. LINKED ARTICLES: This article is part of a themed section on Mitochondrial Pharmacology: Featured Mechanisms and Approaches for Therapy Translation. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.22/issuetoc.