SAFETY AND EFFICACY OF THYMIC PEPTIDES IN THE TREATMENT OF HOSPITALIZED COVID-19 PATIENTS IN HONDURAS.

Coronavirus disease 2019 (Covid-19) active cases continue to demand the development of safe and effective treatments. This is the first clinical trial to evaluate the safety and efficacy of oral thymic peptides. ; We conducted a nonrandomized phase 2 trial with a historic control group to evaluate the safety and efficacy of a daily 250-mg oral dose of thymic peptides in the treatment of hospitalized Covid-19 patients. Comparisons based on standard care from registry data were performed after propensity score matching. The primary outcomes were survival, time to recovery, and number of participants with treatment-related adverse events or side effects by day 20. ; A total of 44 patients were analyzed in this study: 22 in the thymic peptide group and 22 in the standard care group. There were no deaths in the intervention group compared to 24% mortality in standard care by day 20 (log-rank P=0.02). Kaplan-Meier analysis showed a significantly shorter time to recovery by day 20 in the thymic peptide group than in the standard care group (median, 6 days vs. 12 days; hazard ratio for recovery, 2.75 [95% confidence interval, 1.34 to 5.62]; log-rank P=0.002). No side effects or adverse events were reported. ; In patients hospitalized with Covid-19, the use of thymic peptides resulted in no side effects, adverse events, or deaths by day 20. Compared with the registry data, a significantly shorter time to recovery and mortality reduction were measured.

Child Maltreatment and Substance Use: A Behavior Genetic Analysis.

Child maltreatment is a pervasive social problem often perpetuated by family members and is related to a wide array of negative life outcomes. Although substance use is an outcome commonly associated with experiences of child maltreatment, not all individuals who experience maltreatment struggle with such issues. Many individuals can positively adapt to experiences of maltreatment based on levels of resilience and susceptibility. Research suggests that genetic differences may partly explain why negative outcomes develop for some, but not for others. Few studies have examined the extent to which genetic and environmental factors influence the longitudinal association between child maltreatment and varying forms of substance use, leaving a fundamental gap in our current understanding of this association. The current study aims to address this gap by analyzing a sample of twins from the National Longitudinal Study of Adolescent to Adult Health (Add Health). Findings from a series of univariate and bivariate biometric models reveal that the longitudinal associations between maltreatment, cigarette use, and marijuana use are accounted for by additive genetic and nonshared environmental factors. Moreover, the magnitude of the contribution varies across unique subgroups of cigarette and marijuana use. Directions for future research and theoretical implications are discussed.

Attenuation of atherogenic apo B-48-dependent hyperlipidemia and high density lipoprotein remodeling induced by vitamin C and E combination and their beneficial effect on lethal ischemic heart disease in mice

BACKGROUND AND AIMS: Atherosclerotic cardiovascular disease is highly prevalent and its underlying pathogenesis involves dyslipidemia including pro-atherogenic high density lipoprotein (HDL) remodeling. Vitamins C and E have been proposed as atheroprotective agents for cardiovascular disease management. However, their effects and benefits on high density lipoprotein function and remodeling are unknown. In this study, we evaluated the role of vitamin C and E on non HDL lipoproteins as well as HDL function and remodeling, along with their effects on inflammation/ oxidation biomarkers and atherosclerosis in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. METHODS AND RESULTS: Mice were pre-treated for 5 weeks before and during atherogenic diet feeding with vitamin C and E added to water and diet, respectively. Compared to a control group, combined vitamin C and E administration reduced serum total cholesterol and triglyceride levels by decreasing apo B-48-containing lipoproteins, remodeled HDL particles by reducing phospholipid as well as increasing PON1 and apo D content, and diminished PLTP activity and levels. Vitamin supplementation improved HDL antioxidant function and lowered serum TNF-α levels. Vitamin C and E combination attenuated atherogenesis and increased lifespan in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. CONCLUSIONS: Vitamin C and E administration showed significant lipid metabolism regulating effects, including HDL remodeling and decreased levels of apoB-containing lipoproteins, in mice. In addition, this vitamin supplementation generated a cardioprotective effect in a murine model of severe and lethal atherosclerotic ischemic heart disease.

Effect of Propionibacterium acnes (PA) injection on intervertebral disc degeneration in a rat model: Does it mimic modic changes?

INTRODUCTION: Multiple reports of bacterial isolates in human disc tissue have suggested a role of low-grade infection on intervertebral disc degeneration and modic changes (MC) generation. Animal models have been extensively used to study IDD; however, until recently, no consideration had been given to eventual infectious processes. To reproduce the phenomena by inoculating an infecting agent would support the infectious hypothesis. Therefore, we studied the effect of Propionibacterium acnes (PA) inoculation on rat-tails and determined whether it would produce MCs on the adjacent endplates. HYPOTHESIS: Disc infection with PA would accelerate IDD compared with the standard model and would also lead to MCs on the adjacent endplates. METHODS: Twelve Sprague-Dawley rats were randomized to receive a needle puncture in a caudal tail disc with either saline (control) or an inoculum of 5×107 CFU of strain 1a PA. Twelve weeks later, the rats were euthanized and the tails were analyzed. The main assessment criteria were obtained from the post-mortem MRI: T2 values of punctured discs and adjacent endplates, as well as disc volumes. A histological grading score for IDD was also used, measuring the morphology and cellularity of the nucleus and annulus, as well as endplate disruption. RESULTS: The median T2 value and disc volume were smaller in PA-punctured discs [T2 value: 30ms (23-44) vs. 61ms (38-132), respectively, P=0.01; 0.01mm3 (0.01-0.05) vs. 0.5mm3 (0.01-5.35), respectively; P=0.049]. There was no change in the adjacent endplates. There was no significant difference in histological grading between the test and control [13 (10-14) vs. 10.5 (6-13); P=0.05]. DISCUSSION: Inoculation of caudal discs with PA generated increased degeneration; however, no MCs were observed on the adjacent endplates. A better understanding of low-grade disc infections is still needed. LEVEL OF EVIDENCE: V (animal study).

Expression of stromal-cell-derived factor-1 (SDF-1): a predictor of ischaemic stroke?

BACKGROUND AND PURPOSE: Platelet stromal-cell-derived factor-1 (SDF-1) plays a pivotal role in angiogenesis and the regeneration of ischaemic tissue through the regulation of haematopoietic progenitor cells and is upregulated at the sites of vascular injury and platelet activation. Thus, SDF-1 has recently been discussed as a predictor in ischaemic diseases such as acute myocardial infarction. However, no clinical data pertinent to the investigation of the platelet SDF-1 expression in patients with stroke are available. METHODS: We consecutively evaluated 196 patients who were admitted to the stroke unit with symptoms suspected for stroke. Surface expression of the platelet activation markers (P-selectin and GPIb) and the expression of platelet-bound SDF-1 were determined by two-colour whole blood flow cytometry. RESULTS: Patients with transient ischaemic attack (TIA) as well as with ischaemic stroke showed similar levels of SDF-1 expression on hospital admission compared with patients with non-ischaemic (NI) events and with 30 healthy controls (TIA (mean fluorescence intensity±SD): 31.5±18.2 vs. NI: 26.4±15.7; P=0.361; stroke: 28.7±19.8 vs. NI; P=0.943; control: 26.1±11.3; P>0.05 compared with all). Platelet SDF-1 expression showed a trend with the severity of stroke according to National Institute of Health Stroke Scale score (r=0.125; P=0.085), but significantly correlated with the peak levels of C-reactive protein (r=0.218; P=0.002) and with the levels of platelet activation (P-selectin: r=0.389; P=0.001). Multifactorial analysis of covariance revealed a significant influence on platelet SDF-1 expression by smoking (P=0.019). CONCLUSIONS: Platelet SDF-1 surface expression did not show any significant difference in patients with TIA and ischaemic stroke compared with patients with NI events. Thus, single biomarker evaluation of platelet SDF-1 surface expression is not helpful to predict ischaemic stroke.