Impact of Storage Condition on Chemical Composition and Antifungal Activity of Pomelo Extract against Colletotrichum gloeosporioides and Anthracnose in Post-harvest Mango.

Anthracnose caused by Colletotrichum leads to a tremendous post-harvest mango loss. While chemical fungicides are applied to control anthracnose, natural alternatives are preferred due to food safety and environmental concerns. Pomelo extract (PE) exhibits a broad spectrum of antimicrobial activities; however, its effect against anthracnose is unknown. Here we investigated the chemical profile of PE using GC-MS and the anti-anthracnose activity of PE using in vitro and in vivo assays. We also evaluated the impact of storage temperature (0°, 5°, 10°, 20°, -20°, and -80 °C) and light conditions on the composition and antifungal activity of PE. We found that PE inhibited C. gloeosporioides in vitro with an IC50 of 3.2 mL L-1. Applying chitosan-based coating incorporated with 20 mL L-1 PE significantly suppressed anthracnose in post-harvest 'Keitt' mango. A storage temperature below 5 °C substantially preserved major compounds and the antifungal activity of PE after 6 m of storage. Finally, we showed that applying d-limonene, the key constituent of PE, inhibited C. gloeosporioides in vitro (IC50: 10.9 mM) and suppressed anthracnose in vivo. In conclusion, we demonstrated that the application of PE and d-limonene are sustainable methods for anthracnose control in post-harvest crops and established the preservation protocol for PE.

Effects of Ivabradine on Patients with Depressed Left Ventricular Function after Cardiac Resynchronization Therapy.

Background: The potential synergistic effect of ivabradine and cardiac resynchronization therapy (CRT) in heart failure (HF) patients has rarely been studied. We aimed to evaluate the clinical benefits of ivabradine in patients with left ventricular dysfunction following CRT implantation. Methods: Two hundred and thirty-one patients receiving CRT were consecutively enrolled between January 2014 and December 2018 from two HF centers. A total of 123 patients had left ventricular ejection fraction (LVEF) < 40% and resting sinus heart rate (HR) ≥ 75 bpm after six months of CRT implantation. Among these patients, 45 were treated with ivabradine (Group 1), and 78 did not receive ivabradine treatment (Group 2). Results: Baseline characteristics and prescription rates of HF medications other than ivabradine were similar between the two groups. In Group 1, the mean HR decreased from 82.2 ± 11.4 bpm to 76.3 ± 10.5 bpm (p = 0.012), and the mean LVEF increased from 29.9 ± 6.5% to 38.8 ± 12.4% (p < 0.001). Atrial pacing percentage, biventricular pacing percentage, and burden of atrial fibrillation (AF) were not significantly different between the two groups during the study period. The patients' daily physical activity increased significantly in Group 1 compared to Group 2 (Δ daily activity 0.4 ± 0.7 hours/day vs. -0.1 ± 7.2 hours/day, p < 0.001). Conclusions: Ivabradine could effectively reduce HR and improve physical activity. It was safe to use and did not increase AF burden or affect biventricular pacing percentage in CRT recipients.

Sacubitril/valsartan in heart failure with reduced ejection fraction patients: Real world experience on advanced chronic kidney disease, hypotension, and dose escalation.

BACKGROUND: Angiotensin receptor and neprilysin inhibition (ARNI) has been shown to reduce cardiovascular mortality by 20% as compared with enalapril in a randomized controlled trial. However, there is a paucity of real-world data on the effects of ARNI in heart failure patients with reduced ejection fraction (HFrEF), especially those with concurrent renal impairment or hypotension. METHODS: Between 2016 and 2017, we recruited 466 HFrEF patients treated with sacubitril/valsartan (Group A) and 466 patients managed with standard HF treatment without ARNI (Group B) in a HF referral center. Baseline characteristics and clinical outcomes were collected between both groups. RESULTS: Baseline characteristics were comparable between the two groups. During a follow-up period of 15 months, death from cardiovascular causes or first unplanned hospitalization for HF occurred in 100 patients in Group A (21.5%) and 144 in Group B (30.9%, hazard ratio 0.66; 95% CI 0.51-0.85; p=0.001). The incidences of deaths from any causes, cardiovascular death, sudden death, and HF re-hospitalization were all significantly lower in Group A than Group B patients. Among patients with different chronic kidney disease stages and normotensive patients, treatment with sacubitril/valsartan showed more favorable outcomes than treatment with standard HF care without ARNI. However, in patients with baseline systolic blood pressure lower than 100mmHg, there were no significant differences of outcomes in both groups. Among Group A patients, escalation of sacubitril/valsartan was associated with better outcomes. CONCLUSIONS: Our study demonstrated the effectiveness of sacubitril/valsartan on HFrEF patients in real world practice, including those with advanced renal impairment.

Therapeutic drug monitoring in treatment-experienced HIV-infected patients receiving darunavir-based salvage regimens: A case series.

Therapeutic drug monitoring (TDM) constitutes a compelling approach for the optimization of antiretroviral therapy in treatment-experienced HIV-1 patients. While various inhibitory indices have been proposed to predict virologic outcome, there is a lack of consensus on the clinical value of TDM. Here, we report the comparative results of TDM in 14 HIV-1-infected patients who had previously received at least two different PI-based regimens and who initiated darunavir (DRV)-based salvage therapy. Pharmacokinetic/pharmacodynamics (PK/PD) parameters were calculated for each subject. Seventy-nine percent of subjects had a viral load <50 copies/mL at 48 weeks. The only subject with two consecutive viral loads >50 copies/mL at the end of the study period was the patient with the lowest instantaneous inhibitory potential (IIP). The sample size was insufficient to show an association between any of the PK/PD parameters and virologic response. Based on our observations, we suggest that the utility of IIP for antiretroviral combinations for the prediction of virologic outcome in HIV-1 drug-experienced patients should be studied further.

Comparative evaluation of the degree of pegylation of poly(lactic-co-glycolic acid) nanoparticles in enhancing central nervous system delivery of loperamide.

OBJECTIVES: In this study, we examined the relative cellular uptake of nanoparticles (NPs) formulated using poly(lactic-co-glycolic acid) (PLGA) polymers with increasing degree of pegylation (PLGA-PEG) and their potential to deliver loperamide to the brain of a mouse. METHOD: NPs containing coumarin-6 or loperamide HCl were formulated using PLGA and PLGA-PEG, with PEG content of 5-15%, by the solvent evaporation method. NPs were characterised for size, surface charge, morphology, encapsulation efficiency and drug release. Cellular uptake of coumarin-6 NPs was examined in Caco-2 monolayers using confocal microscopy and central nervous system (CNS) delivery of loperamide HCl from the NPs was examined following intranasal administration in a mouse model. KEY FINDINGS: No difference in NP characteristics was observed, irrespective of degree of pegylation, except for the surface charge which increased with increasing PEG content. PLGA-PEG NPs were found to have increased cellular uptake in comparison to PLGA NPs. Interestingly, this pattern was reflected in the CNS delivery of loperamide HCl in the mouse model. CONCLUSION: The results from this study show that PLGA-PEG NPs have the potential to act as carriers for the noninvasive administration of therapeutic agents to the brain and possibly across other physiological barriers.

Whether medically unexplained or not, three or more concurrent somatic symptoms predict psychopathology and service use in community populations.

OBJECTIVES: To examine the frequency of somatic symptoms in a community population of various ethnic backgrounds and to identify correlates of these symptoms such as psychopathology, use of services, and personal distress. METHODS: Using a 14-symptom inventory with interviewer probes for somatic symptoms, we determined the presence of general physical symptoms (GPS) in a sample of 4864 white, Latino, and Asian US community respondents. Medically "edited" verbatim interview responses were used to decide whether or not physical symptoms would qualify as medically unexplained physical symptoms (MUPS). We then assessed the association between GPS and MUPS and psychiatric disorders, psychological distress, and use of services, in both unadjusted and multivariate regression analyses. RESULTS: One-third (33.6%) of the respondents reported at least one GPS and 11.1% reported at least one MUPS within the last year. 10.7% of respondents had three or more GPS and 1.5% had three or more MUPS. Three or more GPS and MUPS were positively associated with depressive, anxiety, and substance use disorders; service use; and psychological distress in unadjusted comparisons. In multivariate regressions, GPS persisted as a significant predictor, but there was no significant independent effect of MUPS, after controlling for GPS and other covariates. CONCLUSIONS: Regardless of the presence or absence of medical explanations, physical symptoms are an important component of common mental disorders such as depression and anxiety and predict service use in community populations. These results suggest that three or more current GPS can be used to designate a "case" and that detailed probes and procedures aimed at determining whether or not physical symptoms are medically unexplained may not be necessary for classification purposes.