Vitamin D2 protects acute and repeated noise stress induced behavioral, biochemical, and histopathological alterations: Possible antioxidant effect.

Noise is an environmental stressor which causes distress and hearing loss in individuals residing in urban areas. Psychological deficits such as anxiety, depression, impaired memory and cognitive decline are caused by noise stress. Different vitamins have been used as a potential antioxidant for neuronal protection. In this study we investigate the anxiolytic, antidepressant and memory enhancing effect of vitamin D2 (Vit D2) following noise stress. Thirty-six albino rats were randomly divided into six groups. (i) Unstressed + corn oil (ii) Unstressed + Vit D2 (iii) Acute noise stress + corn oil (iv) Acute noise stress + Vit D2 (v) Repeated noise stress + corn oil (vi) Repeated noise stress + Vit D2. 600 IU/kg body weight of Vit D2 dosage was prepared in corn oil. Corn oil is used as vehicle and all the drugs administered via oral gavage till end of the experiment (day 16). Recorded sound of generator which was amplified by speakers and had 100 dB intensity was used as noise stress. Repeated stressed animals were exposed to noise (4-hrs) daily for 14 days, while acute stressed animals were exposed to noise (4-hrs) once after 14 days. Behavioral tests (elevated plus maze, light dark box, tail suspension test and Morris water maze) of all groups were performed after15 days treatment period. After behavioral tests rats received their last dosage and decapitated after 1-hr. Brain of all animals was removed and used for biochemical (oxidative stress biomarker, antioxidant enzymes and acetylcholinesterase) and histopathological estimations. Results show that Vit D2 decreased time spent in light box and open arm of light dark activity box and elevated plus maze test respectively (used for anxiety evaluation), decreased immobility time in tail suspension test (for depression) and improved cognitive ability evaluated by Morris water maze test in acute and repeated noise stressed rats. Furthermore, increased antioxidant enzymes activity, decreased lipid peroxidation and acetylcholinesterase activity were also observed in Vit D2 treated animals following acute and repeated noise stress. Normalization in histopathological studies was also observed in Vit D2 treated following acute and repeated noise stress. It is concluded that Vit D2 protects from noise stress induced behavioral, biochemical and histopathological impairment through its antioxidant potential.

Implementation of more sensitive cardiac troponin T assay in a state-wide health service.

AIMS: Explore the impact of deploying high-sensitivity (hs) cardiac troponin T (cTnT) assay across a state-wide health service. METHODS AND RESULTS: Presentations to emergency departments of six tertiary hospitals between January 2008 and August 2019 were included; standard cTnT assay was superseded by hs-cTnT in June 2011 without changing the reference range (≥30 ng/L reported as elevated), despite cTnT level of 30 ng/L being equivalent to ∼44 ng/L with hs-cTnT. Clinical outcomes were captured using state-wide linked health records. Interrupted time series analyses were used adjusted for seasonality and multiple co-morbidities using propensity score matching allowing for correlation within hospitals. In total, 614,847 presentations had ≥1 troponin measurement. Clinical ordering of troponin decreased throughout the study with no increase in elevated measurements amongst those tested with hs-cTnT. Small but statistically significant changes in index myocardial infarction (MI) diagnosis (-0.36%/year, 95%CI [confidence interval]:-0.48, -0.24,p < 0.001) and invasive coronary angiography (0.12%/year,95%CI:0, 0.24,p = 0.02) were seen, with no impact on death/MI at 30 days or 3-year survival in episodes of care (EOCs) with elevated cTnT after hs-cTnT implementation. Length of stay (LOS) was shorter among those with an elevated hs-cTnT (-4.44 h/year, 95%CI:-5.27, -3.60, p < 0.001). Non-elevated cTnT EOCs demonstrated shorter total LOS and improved 3-year survival (adjusted hazard ratio:0.90, 95%CI:0.83, 0.97,p = 0.008) although death/MI at 30 days was unchanged using hs-cTnT. CONCLUSION: Widespread implementation of hs-cTnT without altering clinical thresholds reported to clinicians provided significantly shorter LOS without a clinically significant impact on clinical outcomes. A safer cohort with non-elevated cTnT was identified by hs-cTnT compared to the standard cTnT assay.

Reserpine-induced altered neuro-behavioral, biochemical and histopathological assessments prevent by enhanced antioxidant defence system of thymoquinone in mice.

Thymoquinone (Tq), an active compound of Nigella sativa, has been known for its anti-inflammatory, antioxidant, and neuroprotective characteristics. The present study is aimed to evaluate the effect of Tq on reserpine (Rsp)-induced behavioral (anxiety and/or depression) and, memory deficit; hippocampal inflammatory markers, oxidative markers, antioxidant enzymes, acetylcholinesterase (AChE) activity and histopathology in male mice. Animals were injected with Rsp at a dose of 2 mg/ml/kg and doses of Tq (10 and 20 mg/ml/kg) for 28 days. After the treatment period, behavioral tests [Elevated plus maze (Epm); Light dark box test (Lda); Morris water maze (Mwm); Forced swim test (Fst); Tail suspension test (Tst)] were conducted. After analysis of behaviors, mice were decapitated and brain samples were collected, the hippocampus was removed from the whole-brain sample for biochemical analysis and histology. Administration of Tq at both doses prevent adverse effects of Rsp and increased time spent in open arm and lightbox in Lda and Epm respectively, decreased immobility period in Fst and Tst, decreased latency escape in Mwm, reduced lipid peroxidation (lpo) and inflammatory cytokines, increased defensive enzymes, reduced acetylcholinesterase (AChE) activity and corrected histological lines. It is concluded that Rsp-instigated behavioral and memory deficits were prevented by Tq possibly via its strong antioxidant and anti-inflammatory effects.

Vascular effects of serelaxin in patients with stable coronary artery disease: a randomized placebo-controlled trial.

AIMS: The effects of serelaxin, a recombinant form of human relaxin-2 peptide, on vascular function in the coronary microvascular and systemic macrovascular circulation remain largely unknown. This mechanistic, clinical study assessed the effects of serelaxin on myocardial perfusion, aortic stiffness, and safety in patients with stable coronary artery disease (CAD). METHODS AND RESULTS: In this multicentre, double-blind, parallel-group, placebo-controlled study, 58 patients were randomized 1:1 to 48 h intravenous infusion of serelaxin (30 µg/kg/day) or matching placebo. The primary endpoints were change from baseline to 47 h post-initiation of the infusion in global myocardial perfusion reserve (MPR) assessed using adenosine stress perfusion cardiac magnetic resonance imaging, and applanation tonometry-derived augmentation index (AIx). Secondary endpoints were: change from baseline in AIx and pulse wave velocity, assessed at 47 h, Day 30, and Day 180; aortic distensibility at 47 h; pharmacokinetics and safety. Exploratory endpoints were the effect on cardiorenal biomarkers [N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hsTnT), endothelin-1, and cystatin C]. Of 58 patients, 51 were included in the primary analysis (serelaxin, n = 25; placebo, n = 26). After 2 and 6 h of serelaxin infusion, mean placebo-corrected blood pressure reductions of -9.6 mmHg (P = 0.01) and -13.5 mmHg (P = 0.0003) for systolic blood pressure and -5.2 mmHg (P = 0.02) and -8.4 mmHg (P = 0.001) for diastolic blood pressure occurred. There were no between-group differences from baseline to 47 h in global MPR (-0.24 vs. -0.13, P = 0.44) or AIx (3.49% vs. 0.04%, P = 0.21) with serelaxin compared with placebo. Endothelin-1 and cystatin C levels decreased from baseline in the serelaxin group, and there were no clinically relevant changes observed with serelaxin for NT-proBNP or hsTnT. Similar numbers of serious adverse events were observed in both groups (serelaxin, n = 5; placebo, n = 7) to 180-day follow-up. CONCLUSION: In patients with stable CAD, 48 h intravenous serelaxin reduced blood pressure but did not alter myocardial perfusion.

Inter-study repeatability of circumferential strain and diastolic strain rate by CMR tagging, feature tracking and tissue tracking in ST-segment elevation myocardial infarction.

Strain assessment allows accurate evaluation of myocardial function and mechanics in ST-segment elevation myocardial infarction (STEMI). Strain using cardiovascular magnetic resonance (CMR) has traditionally been assessed with tagging but limitations of this technique have led to more widespread use of alternative methods, which may be more robust. We compared the inter-study repeatability of circumferential global peak-systolic strain (Ecc) and peak-early diastolic strain rate (PEDSR) derived by tagging with values obtained using novel cine-based software: Feature Tracking (FT) (TomTec, Germany) and Tissue Tracking (TT) (Circle cvi42, Canada) in patients following STEMI. Twenty male patients (mean age 56 ± 10 years, mean infarct size 13.7 ± 7.1% of left ventricular mass) were randomised to undergo CMR 1-5 days post-STEMI at 1.5 T or 3.0 T, repeated after ten minutes at the same field strength. Ecc and PEDSR were assessed using tagging, FT and TT. Inter-study repeatability was evaluated using Bland-Altman analyses, coefficients of variation (CoV) and intra-class correlation coefficient (ICC). Ecc (%) was significantly lower with tagging than with FT or TT at 1.5 T (- 9.5 ± 3.3 vs. - 17.5 ± 3.8 vs. -15.5 ± 5.2, respectively, p < 0.001) and 3.0 T (- 13.1 ± 1.8 vs. - 19.4 ± 2.9 vs. - 17.3 ± 2.1, respectively, p = 0.001). This was similar for PEDSR (.s-1): 1.5 T (0.6 ± 0.2 vs. 1.5 ± 0.4 vs. 1.0 ± 0.4, for tagging, FT and TT respectively, p < 0.001) and 3.0 T (0.6 ± 0.2 vs. 1.5 ± 0.3 vs. 0.9 ± 0.3, respectively, p < 0.001). Inter-study repeatability for Ecc at 1.5 T was good for tagging and excellent for FT and TT: CoV 16.7%, 6.38%, and 8.65%, respectively. Repeatability for Ecc at 3.0 T was good for all three techniques: CoV 14.4%, 11.2%, and 13.0%, respectively. However, repeatability of PEDSR was generally lower than that for Ecc at 1.5 T (CoV 15.1%, 13.1%, and 34.0% for tagging, FT and TT, respectively) and 3.0 T (CoV 23.0%, 18.6%, and 26.2%, respectively). Following STEMI, Ecc and PEDSR are higher when measured with FT and TT than with tagging. Inter-study repeatability of Ecc is good for tagging, excellent for FT and TT at 1.5 T, and good for all three methods at 3.0 T. The repeatability of PEDSR is good to moderate at 1.5 T and moderate at 3.0 T. Cine-based methods to assess Ecc following STEMI may be preferable to tagging.

Cardiovascular Manifestations of Systemic Sclerosis: A Danish Nationwide Cohort Study.

Background Cardiovascular involvement in systemic sclerosis (SSc) comprises a wide range of manifestations with prevalence and incidence that remain uncertain. Methods and Results In the Danish administrative registries between 1995 and 2015, all patients aged ≥18 years with a first diagnosis of SSc were matched by age and sex with controls (1:5) from the general population. Prevalence of cardiovascular diseases at the time of the SSc diagnosis and incidence during follow-up were assessed by in- and outpatient discharge diagnoses. Conditional logistic and Cox proportional hazards regression models were used respectively to calculate odds ratios for prevalent cardiovascular diseases and hazard ratios (HRs) for incident diseases associated with SSc. Patients with SSc (n=2778; 76% women; mean±SD age: 55±15 years) had more established cardiovascular risk factors than their respective controls at baseline, including greater prevalence of hypertension (31.2% versus 21.0%, P<0.0001) and treated dyslipidemia (9.8% versus 8.5%, P=0.02). SSc was associated with an increased relative risk of developing most cardiovascular diseases, including myocardial infarction (HR: 2.08; 95% CI, 1.65-2.64), peripheral vascular disease (HR: 5.73; 95% CI, 4.63-7.09), pulmonary hypertension (HR: 21.18; 95% CI, 14.73-30.45), mitral regurgitation (HR: 4.60; 95% CI, 3.12-6.79), aortic regurgitation (HR: 3.78; 95% CI, 2.55-5.58), aortic stenosis (HR: 2.99; 95% CI, 2.25-3.97), pericarditis (HR: 8.78; 95% CI, 4.84-15.93), heart failure (HR: 2.86; 95% CI, 2.43-3.37), atrial fibrillation (HR: 1.75; 95% CI, 1.51-2.04), and venous thromboembolism (HR: 2.10; 95% CI, 1.65-2.67). Additional adjustment for medications and comorbidities yielded results similar to the main analyses. Conclusions In this nationwide study, SSc was associated with greater risks of distinct cardiovascular diseases for patients than for matched controls, suggesting a significant disease-related adverse impact across the vascular bed and specific cardiac structures.

Biostial iatrogenic coronary artery stenosis: a rare complication of aortic valve surgery successfully treated with percutaneous coronary stenting.

A 66-year-old woman presented 4 months after conventional surgical aortic valve replacement with an acute coronary syndrome resulting from rare iatrogenic biostial left main and right coronary artery stenoses, which were successfully treated with percutaneous coronary stenting, optimized by intracoronary imaging.

Accelerated patent hemostasis using a procoagulant disk; a protocol designed to minimize the risk of radial artery occlusion following cardiac catheterization.

PURPOSE: Radial artery occlusion flowing cardiac catheterisation has been linked to flow reduction and prolonged compression. We investigate whether these factors can be optimised following transradial cardiac catheterisation by using an accelerated band removal protocol facilitated by a haemostasis promoting pad, in combination with a patent haemostasis technique. METHODS: In this single centre prospective study, 389 consecutive patients undergoing TRA for coronary angiography or angioplasty were randomised to two haemostasis protocols: use of a Helix™ compression device alone (HC) or in combination with a haemostatic pad (StatSeal® disc) and an accelerated haemostasis protocol (AC). A patent haemostasis technique was employed in both study arms. The primary efficacy endpoint was the time to haemostasis and the secondary safety outcome was access site related complications: re-bleeding, haematoma and radial artery patency assessed within 24 h using reverse Barbeau's Test (BT). RESULTS: Between May and Nov 2017, 191 patients were randomised to receive HC and 198 patients to AC. Compression time was significantly higher with HC as compared to AC (165.8 ±â€¯63.1 versus 79.7 ±â€¯41.2 min, p < 0.001). There were no significant differences in re-bleeding and RAO between groups (3.7% versus 5.6%, p = 0.37 and 6.3% versus 4.1%, p = 0.33) respectively. Incidence of haematoma was higher in AC group (4.7% versus 12.1%, p = 0.009). CONCLUSION: A reduction in radial artery compression time can be achieved by using Statseal in association with an accelerated haemostasis protocol without increasing the risk of access site bleeding and RAO. The combination of reduced compression time combined with maintained radial flow via patent haemostasis has the potential to reduce the risk of radial occlusion after transradial catheterisation.

Characterization of the interactions between coumarin-derivatives and acetylcholinesterase: Examination by NMR and docking simulations.

Alzheimer's disease (AD) is one of the most common forms of dementia and a significant threat to the elderly populations, especially in the Western world. The rapid hydrolysis of the principal neurotransmitter into choline and acetate by acetylcholinesterase (AChE) at synapses causes the loss of cognitive response that becomes the real cause of AD. Therefore, inhibition of AChE is the most fundamental therapy among currently available treatments for AD. In this context, we designed and performed molecular recognitions studies of coumarin-based inhibitors towards AChE. STD NMR and Tr-NOESY applications were utilized to evaluate the binding epitope, the dissociation constant (KD) and bound conformations of these inhibitors within this inhibitor-AChE complex. Compound 1, which has a similar inhibition activity to tacrine (a current drug) led in this study as a stronger binder with KD = 30 µM ,even greater than tacrine (KD = 140 µM). Moreover, docking simulations mimic NMR results and provided evidence of synchronizing binding of compound 1 with three sites; the peripheral anionic site, the bottom of the gorge, and the catalytic site. Therefore, we envisioned from our experimental and theoretical results that coumarin-based inhibitors containing a piperidinyl scaffold might be a potential drug candidates for AD in the future.

Trends in incidence, mortality, and causes of death associated with systemic sclerosis in Denmark between 1995 and 2015: a nationwide cohort study.

BACKGROUND: To investigate the incidence and the mortality-rates of systemic sclerosis (SSc), its primary causes of death, and the temporal trends in events in Denmark during the last decades. METHODS: Using the Danish National Patient Registry, we identified all persons aged ≥18 years with a first-time diagnosis of SSc (ICD-10 code M34, excluding M34.2) between 1995 and 2015. RESULTS: A total of 2778 incident SSc cases were identified. The mean age at time of SSc diagnosis was 56 (standard deviation 15) years and 76% were women. The overall incidence rate (per 1,000,000 person-years) of diagnosed SSc was 24.4 (95% confidence interval 23.6-25.4), with a slight increase over the study period, age- and sex-adjusted incidence rate ratio 1.02 (95% confidence interval 1.01-1.02) per 1-year increase. The 1-year all-cause mortality rate per 100 person-years decreased from 6.1 (3.1-12.2) in 1995 to 5.3 (2.5-11.1) in 2015, sex- and age-adjusted hazard ratio 0.96 (95% CI 0.94-0.98) per 1-year increase. Over the period, the average age at SSc diagnosis increased and the proportion of women decreased, whereas the burden of comorbidities increased. One fifth of all deaths were attributable to cardiovascular causes, a fourth to pulmonary diseases, and 15% were due to cancer. CONCLUSIONS: Within the last few decades, the incidence of SSc has increased and the 1-year mortality rate has decreased slightly in Denmark. Almost half of all deaths were attributable to cardiopulmonary causes.