Baicalein antagonizes rotenone-induced apoptosis in dopaminergic SH-SY5Y cells related to Parkinsonism

<p>Abstract</p> <p>Background</p> <p>Two active compounds, baicalein and its glycoside baicalin were found in the dried root of <it>Scutellaria baicalensis </it>Georgi, and reported to be neuroprotective <it>in vitro </it>and <it>in vivo</it>. This study aims to evaluate the protective effects of baicalein on the rotenone-induced apoptosis in dopaminergic SH-SY5Y cells related to parkinsonism.</p> <p>Methods</p> <p>Cell viability and cytotoxicity were determined by MTT assay. The degree of nuclear apoptosis was evaluated with a fluorescent DNA-binding probe Hoechst 33258. The production of reactive oxidative species (ROS) and loss of mitochondrial membrane potential (ΔΨm) were determined by fluorescent staining with DCFH-DA and Rhodanmine 123, respectively. The expression of Bax, Bcl-2, cleaved caspase-3 and phosphorylated ERK1/2 was determined by the Western blots.</p> <p>Results</p> <p>Baicalein significantly increased viability and decreased rotenone-induced death of SH-SY5Y cells in a dose-dependent manner. Pre- and subsequent co-treatment with baicalein preserved the cell morphology and attenuated the nuclear apoptotic characteristics triggered by rotenone. Baicalein antagonized rotenone-induced overproduction of ROS, loss of ΔΨm, the increased expression of Bax, cleaved caspase-3 and phosphorylated ERK1/2 and the decreased expression of Bcl-2.</p> <p>Conclusion</p> <p>The antioxidative effect, mitochondrial protection and modulation of anti-and pro-apoptotic proteins are related to the neuroprotective effects of baicalein against rotenone induced cell death in SH-SY5Y cells.</p

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Mini-storage in Hong Kong : capacities and achievements of regulatory coordination

published_or_final_versionPolitics and Public AdministrationMasterMaster of Public Administratio

Compliance with the Dietary Approaches to Stop Hypertension (DASH) Diet: A Systematic Review

<div><p>Background</p><p>The Dietary Approaches to Stop Hypertension (DASH) diet has been recognized as effective to lower blood pressure in feeding trials, but compliance with the diet must be persistent to maximize health benefits in clinical practice. This paper reports a systematic review of the latest evidence on the method to assess DASH compliance and the corresponding patients' compliance in interventional settings.</p><p>Methods</p><p>The databases including MEDLINE, EBM Reviews, EMBASE, and CINAHL Plus were searched for original research studies published in the period of January 1992- December 2012 that evaluated compliance with DASH diet. Studies written in English language, with DASH intervention, with complete documentation of the degree of DASH compliance and the assessment method used were included in this review. The search terms included: dietary approaches to stop hypertension, DASH, compliance, adherence, consistency, and concordance.</p><p>Results</p><p>Nine studies were included. Different types of interventions were identified, ranging from feeding trial to dietary counseling. These studies differed in the assessment methods used to evaluate DASH compliance, which included objective approaches like measurement of urinary excretion, and subjective approaches like dietary intake assessment for DASH target comparison and construction of DASH scoring systems. Compliance levels were lower in educational interventions than that of the original DASH feeding trial.</p><p>Conclusions</p><p>To conclude, although no consensus existed regarding the best approach to assess DASH compliance, its suboptimal compliance warrants attention. This study implied a need to investigate effective approaches to sustain the DASH dietary pattern beyond counselling alone.</p></div

Dietary counselling has no effect on cardiovascular risk factors among Chinese grade 1 hypertensive patients: a randomized controlled trial

Aims To evaluate the effectiveness of Dietary Approaches to Stop Hypertension (DASH) by one-off dietary counselling on reducing cardiovascular risk factors among Chinese Grade 1 hypertensive patients in primary care. Methods and results A parallel-group, randomized controlled trial (ChiCTR-TRC-13003014) was conducted among patients (40–70 years old) newly diagnosed with Grade 1 hypertension in primary care settings in Hong Kong. Subjects were randomized to usual care (standard education, control) (n = 275), or usual care plus DASH-based dietary counselling (intervention) (n = 281). The study endpoints included blood pressure (BP), lipid profile, and body mass index (BMI) at 6- and 12-months. Outcome data were available for 504 (90.6%) and 485 (87.2%) patients at 6 and 12 months, respectively. Blood pressure levels reduced in both groups at follow-ups. However, the intervention group did not show a significantly greater reduction in either systolic BP (−0.7 mmHg, 95%CI −3.0–1.5 at 6-month; −0.1 mmHg, 95%CI −2.4–2.2 at 12-month) or diastolic BP (−1.0 mmHg, 95%CI −2.7–0.7 at 6-month; −1.1 mmHg, 95%CI −2.9–0.6 at 12-month), when compared with the control group. The improvements in lipid profile and BMI were observed among all subjects, yet no significant differences were detected between intervention and control groups. Conclusion The DASH diet by one-off dietitian counselling which resembled the common primary care practice might confer no added long-term benefits on top of physician's usual care in optimizing cardiovascular risk factors. Physicians may still practice standard usual care, yet further explorations on different DASH delivery models are warranted to inform best clinical practice

Flow diagram of study selection.

<p>Flow diagram of study selection.</p

Characteristics of included DASH randomized controlled trials.

<p>Characteristics of included DASH randomized controlled trials.</p

Actionable pharmacogenetic variants in Hong Kong Chinese exome sequencing data and projected prescription impact in the Hong Kong population.

Preemptive pharmacogenetic testing has the potential to improve drug dosing by providing point-of-care patient genotype information. Nonetheless, its implementation in the Chinese population is limited by the lack of population-wide data. In this study, secondary analysis of exome sequencing data was conducted to study pharmacogenomics in 1116 Hong Kong Chinese. We aimed to identify the spectrum of actionable pharmacogenetic variants and rare, predicted deleterious variants that are potentially actionable in Hong Kong Chinese, and to estimate the proportion of dispensed drugs that may potentially benefit from genotype-guided prescription. The projected preemptive pharmacogenetic testing prescription impact was evaluated based on the patient prescription data of the public healthcare system in 2019, serving 7.5 million people. Twenty-nine actionable pharmacogenetic variants/ alleles were identified in our cohort. Nearly all (99.6%) subjects carried at least one actionable pharmacogenetic variant, whereas 93.5% of subjects harbored at least one rare deleterious pharmacogenetic variant. Based on the prescription data in 2019, 13.4% of the Hong Kong population was prescribed with drugs with pharmacogenetic clinical practice guideline recommendations. The total expenditure on actionable drugs was 33,520,000 USD, and it was estimated that 8,219,000 USD (24.5%) worth of drugs were prescribed to patients with an implicated actionable phenotype. Secondary use of exome sequencing data for pharmacogenetic analysis is feasible, and preemptive pharmacogenetic testing has the potential to support prescription decisions in the Hong Kong Chinese population