Redox activity of melanin from the ink sac of Sepia officinalis by means of colorimetric oxidative assay

The redox properties of natural extract from cuttlefish ink sac (Sepia officinalis) and synthetic melanin used as a biomimetic in melanin structural investigation were determined by comparison of this phenol-based heterogeneous pigment with gallic acid used as a standard in Folinâ Ciocalteu colorimetric assay widely employed for characterisation of oxidative properties of biomaterials. Reactivity of sepia melanin reported here is much higher than previously indicated and this protocol should allow the redox characterisation of all melanins irrespective of their origin and composition.European Union’s Seventh Framework Programme (FP7/2007-2013) [grant agreement number REGPOT-CT2012-316331-POLARIS

The Water Absorption and Thermal Properties of Green Pterocarpus Angolensis (Mukwa)-Polylactide Composites

The water absorption, chemical resistance, and biological properties are contributing factors to the overall performance of bio-composites, especially for outdoor applications. The functional properties of bio-composites are dependent on the interfacial bonding mechanism, which is controlled by the surface modification and processing parameters of natural fibers. Therefore, this study aims to investigate the potential of enhancing the mukwa/polylactide (mukwa/PLA) interface through an economic and ecological surface modification of recycled mukwa wood fibers via alkali-laccase modification. The fabricated bio-composites intended for making durable farm poles for semi-arid conditions of Southern Africa were characterized via water absorption, chemical resistance, thickness swelling, hardness, and thermal properties. Less thickness swelling and water absorption were found on the alkali-laccase/PLA composites. The less-dense (1.09 g/cm3) alkali-laccase treated composites showed better chemical resistance. Much swelling of the composites was observed on the 40% nitric acid (HNO3), while 60%NaOH shrunk the composites and PLA by <3.5%. The laccase/PLA bio-composite showed a maximum thermal stability of 733 °C. The activation energy (Ea) optimized on the laccase/PLA composite with the highest of 104 kJ mol−1. Maximum crystallinity of 45.8% was achieved on the untreated/PLA composites. The alkali-laccase modification maximized the hardness of composites with 35.45 HV on alkali-laccase/PLA

Effect of melanomal proteins on sepia melanin assembly

Accepted manuscriptMelanins are phenol-based pigments with the potential for widespread applications including bioelectronics and tissue engineering. The concentration-dependent structural transition of sepia melanin in water is analyzed. This biopolymer at high concentration gives the well-known nanospheres, whereas sample dilution gives unforeseen nanofibres exhibiting the structural features of mature amyloid fibrils. We propose a mechanism of pigment self-assembly dependent on the interaction of residual melanosomal protein(s) with eumelanin heteropolymer. Our results contribute to understanding the peculiar physico-chemical properties of this ubiquitous pigmentEuropean Union's Seventh Framework Programme (FP7/2007–2013) under grant agreement No. REGPOT-CT2012–316331-POLARI

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir

Heart failure family-based education: a systematic review

Objective: To systematically review evidence for the efficacy of family-based education for heart failure (HF) patients and carers.Method: A systematic review was conducted. Databases CINAHL, MEDLINE Complete, Cochrane, PubMed, Web of Science, EMBASE, PsycINFO, and Scopus were searched between 1 January 2005 and 1 May 2015. Randomised controlled trials included HF patient and carer dyads or carers alone. The primary outcome was HF knowledge. Secondary outcomes included self-care behaviour, dietary and treatment adherence, quality of life, depression, perceived control, hospital readmissions, and carer burden.Result: Six trials reported in nine papers were included. Wide variation in the quality of the studies was found. Two studies only examined HF knowledge; a significant improvement among patients and carers was reported. Other significant findings were enhanced patient self-care, boosted dietary and treatment adherence, enriched patient quality of life, improved perceived control among patients but not carers, and reduced carer burdenConclusion: Modest evidence was found for family-based education among HF patients and carers. Methodological shortcomings of trials signify the need for empirically sound future research.Practice implication: Family-based HF education needs to include strategies that are tailored to the HF patient and carer, and sustainable in nature. (C) 2015 Elsevier Ireland Ltd. All rights reserved

Randomized controlled trial of family-based education for patients with heart failure and their carers

AIM: The aim of this study was to evaluate a heart failure education programme developed for patients and carers in Thailand. BACKGROUND: Heart failure is major health problem. This is the first trial of a family-based education programme for heart failure patients and carers residing in rural Thailand. DESIGN: Randomized controlled trial. METHODS: One hundred patient-carer dyads attending cardiac clinics in southern Thailand from April 2014 - March 2015 were randomized to usual care (n = 50) or a family-based education programme (n = 50) comprising face-to-face counselling, a heart failure manual and DVD and telephone support. Assessments of heart failure knowledge, health-related quality of life, self-care behaviours and perceived control were conducted at baseline, three and six months. RESULTS: Linear mixed-effects model revealed that patients and carers who received the education programme had higher knowledge scores at three and six months than those who received usual care. Among those who received the education programme, when compared with those who received usual care, patients had better self-care maintenance and confidence, and health-related quality of life scores at three and six months, and better self-care management scores at six months, whereas carers had higher perceived control scores at three months. CONCLUSION: Addressing a significant service gap in rural Thailand, this family-based heart failure programme improved patient knowledge, self-care behaviours and health-related quality of life and carer knowledge and perceived control