Acceptability of a technology-supported and solution-focused intervention (DIALOG+) for chronic depression: views of service users and clinicians.

BACKGROUND: Treating chronic depression represents a significant burden for the NHS, yet there is a lack of evidence-based interventions and research specifically focused on this condition. DIALOG+, a technology-assisted and resource-oriented intervention found effective for people with psychosis, may improve care for this service user group. The aim of this study was to explore the acceptability and relevance of DIALOG+ for the treatment of chronic depression in community-based settings. METHODS: A convenience sample of 16 mental health professionals and 29 service users with chronic depression tested the DIALOG+ intervention in routine community care appointments for 3 months across 3 different mental health NHS Trusts in England. Of these, 15 clinicians and 19 service users were individually interviewed about their experiences. Interview transcripts were analysed using thematic analysis by an analytic team which included a service user researcher. RESULTS: Analysis of the combined dataset identified five overarching themes: DIALOG+ Structure; Therapeutic Communication; Reflecting and Monitoring; Empowerment and Powerlessness; and The Impact of Technology. Overall, service users and clinicians were interested in the continued use of DIALOG+ as part of routine care. CONCLUSIONS: DIALOG+ was viewed as acceptable by both service users with chronic depression and their clinicians who work in community care settings, albeit with some caveats. Clinician training required significant improvements to address the issues that were referenced, most notably around support with using technology

Defect-free outer-selective hollow fiber thin-film composite membranes for forward osmosis applications

© 2019 Elsevier B.V. This study presents the successful fabrication of a novel defect-free outer-selective hollow fiber (OSHF) thin-film composite (TFC) membrane for forward osmosis (FO) applications. Thin and porous FO membrane substrates made of polyether sulfone (PES) with a dense and smooth outer surface were initially fabricated at different air-gap distances. A modified vacuum-assisted interfacial polymerization (VAIP) technique was then successfully utilised for coating polyamide (PA) layer on the hollow fiber (HF) membrane substrate to prepare OSHF TFC membranes. Experimental results showed that the molecular weight cut-off (MWCO) of the surface of the membrane substrate should be less than 88 kDa with smooth surface roughness to obtain a defect-free PA layer via VAIP. The FO test results showed that the newly developed OSHF TFC membranes achieved water flux of 30.2 L m−2 h−1 and a specific reverse solute flux of 0.13 g L−1 using 1 M NaCl and DI water as draw and feed solution, respectively. This is a significant improvement on commercial FO membranes. Moreover, this OSHF TFC FO membrane demonstrated higher fouling resistance and better cleaning efficiency against alginate-silica fouling. This membrane also has a strong potential for scale-up for use in larger applications. It also has strong promise for various FO applications such as osmotic membrane bioreactor (OMBR) and fertilizer-drawn OMBR processes

Surface modification of thin-film composite forward osmosis membranes with polyvinyl alcohol–graphene oxide composite hydrogels for antifouling properties

© 2020 Elsevier B.V. In this study, the polyamide (PA) layers of commercial thin-film composite (TFC) forward osmosis (FO) membranes were coated with glutaraldehyde cross-linked polyvinyl alcohol (PVA) hydrogel comprising of graphene oxide (GO) at various loadings to enhance their fouling resistance. The optimal GO concentration of 0.02 wt% in hydrogel solution was confirmed from the FO membrane performance, and its influence on membrane antifouling properties was studied. The properties of the modified membranes, such as surface morphology, surface charge and wettability, were also investigated. PVA/GO coating was observed to increase the smoothness and hydrophilicity of the membrane surface. The foulant resistances of the pristine, PVA-coated and PVA/GO-coated membranes were also reported. PVA hydrogel-coated TFC membrane with a GO loading of 0.02 wt% showed a 55% reduction in specific reverse solute flux, only a marginal reduction in the water flux, and the best antifouling property with a 58% higher flux recovery than the pristine TFC membrane. The significant improvement in the selectivity of the modified membranes meant that the hydrogel coating could be used to seal PA defects. The biocidal GO flakes in PVA hydrogel coating also improved the biofouling resistance of the modified membranes, which could be attributed to their morphologies and superior surface properties

Potentiation of Acetylcholine-Induced Relaxation of Aorta in Male UC Davis Type 2 Diabetes Mellitus (UCD-T2DM) Rats: Sex-Specific Responses

Previous reports suggest that diabetes may differentially affect the vascular beds of females and males. The objectives of this study were to examine whether there were (1) sex differences in aortic function and (2) alterations in the relative contribution of endothelium-derived relaxing factors in modulating aortic reactivity in UC Davis Type 2 Diabetes Mellitus (UCD-T2DM) rats. Endothelium-dependent vasorelaxation (EDV) in response to acetylcholine (ACh) was measured in aortic rings before and after exposure to pharmacological inhibitors. Relaxation responses to sodium nitroprusside were assessed in endothelium-denuded rings. Moreover, contractile responses to phenylephrine (PE) were measured before and after incubation of aortic rings with a nitric oxide synthase (NOS) inhibitor in the presence of indomethacin. Metabolic parameters and expression of molecules associated with vascular and insulin signaling as well as reactive oxygen species generation were determined. Diabetes slightly but significantly impaired EDV in response to ACh in aortas from females but potentiated the relaxation response in males. The potentiation of EDV in diabetic male aortas was accompanied by a traces of nitric oxide (NO)- and prostanoid-independent relaxation and elevated aortic expression of small- and intermediate conductance Ca2+-activated K+ channels in this group. The smooth muscle sensitivity to NO was not altered, whereas the responsiveness to PE was significantly enhanced in aortas of diabetic groups in both sexes. Endothelium-derived NO during smooth muscle contraction, as assessed by the potentiation of the response to PE after NOS inhibition, was reduced in aortas of diabetic rats regardless of sex. Accordingly, decreases in pAkt and peNOS were observed in aortas from diabetic rats in both sexes compared with controls. Our data suggest that a decrease in insulin sensitivity via pAkt-peNOS-dependent signaling and an increase in oxidative stress may contribute to the elevated contractile responses observed in diabetic aortas in both sexes. This study demonstrates that aortic function in UCD-T2DM rats is altered in both sexes. Here, we provide the first evidence of sexual dimorphism in aortic relaxation in UCD-T2DM rats

Experiences of reduction and discontinuation of antipsychotics: a qualitative investigation within the RADAR trial

Background Antipsychotics are a core treatment for psychosis, but the evidence for gradual dose reductions guided by clinicians is under-developed. The RADAR randomised controlled trial (RCT) compared antipsychotic reduction and possible discontinuation with maintenance treatment for people with recurrent psychotic disorders. The current study explored participants’ experiences of antipsychotic reduction or discontinuation within this trial. Methods This qualitative study was embedded within the RADAR RCT (April 2017–March 2022) that recruited 253 participants from specialist community mental health services in 19 public healthcare localities in England. Participants were adults with recurrent non affective psychosis who were taking antipsychotic medication. Semi-structured interviews, lasting 30–90 min, were conducted after the trial final 24-month follow-up with 26 people who reduced and/or discontinued antipsychotics within the trial, sampled purposively for diversity in sociodemographic characteristics, trial variables, and pre-trial medication and clinical factors. Data were analysed using thematic analysis and findings are reported qualitatively. Findings Most participants reported reduced adverse effects of antipsychotics with dose reductions, primarily in mental clouding, emotional blunting and sedation, and some positive impacts on social functioning and sense of self. Over half experienced deteriorations in mental health, including psychotic symptoms and intolerable levels of emotional intensity. Nine had a psychotic relapse. The trial context in which medication reduction was explicitly part of clinical care provided various learning opportunities. Some participants were highly engaged with reduction processes, and despite difficulties including relapses, developed novel perspectives on medication, dose optimisation, and how to manage their mental health. Others were more ambivalent about reduction or experienced less overall impact. Interpretation Experiences of antipsychotic reductions over two years were dynamic and diverse, shaped by variations in dose reduction profiles, reduction effects, personal motivation and engagement levels, and relationships with prescribers. There are relapse risks and challenges, but some people experience medication reduction done with clinical guidance as empowering. Clinicians can use findings to inform and work flexibly with service users to establish optimal antipsychotic doses

Analyses of Genetic Variations of Glutathione S-Transferase Mu1 and Theta1 Genes in Bangladeshi Tannery Workers and Healthy Controls

Glutathione S-transferases (GSTs) belong to a group of multigene detoxification enzymes, which defend cells against oxidative stress. Tannery workers are at risk of oxidative damage that is usually detoxified by GSTs. This study investigated the genotypic frequencies of GST Mu1 (GSTM1) and GST Theta1 (GSTT1) in Bangladeshi tannery workers and healthy controls followed by their status of oxidative stress and total GST activity. Of the 188 individuals, 50.0% had both GSTM1 and GSTT1 (+/+), 12.2% had GSTM1 (+/−), 31.4% had GSTT1 (−/+) alleles, and 6.4% had null genotypes (−/−) with respect to both GSTM1 and GSTT1 alleles. Among 109 healthy controls, 54.1% were double positive, 9.2% had GSTM1 allele, 32.1% had GSTT1 allele, and 4.6% had null genotypes. Out of 79 tannery workers, 44.3% were +/+, 16.8% were +/−, 30.5% were −/+, and 8.4% were −/−. Though the polymorphic genotypes or allelic variants of GSTM1 and GSTT1 were distributed among the study subjects with different frequencies, the differences between the study groups were not statistically significant. GST activity did not vary significantly between the two groups and also among different genotypes while level of lipid peroxidation was significantly higher in tannery workers compared to controls irrespective of their GST genotypes

Telomere length is associated with growth in children in rural Bangladesh

Background: Previously, we demonstrated that a water, sanitation, handwashing, and nutritional intervention improved linear growth and was unexpectedly associated with shortened childhood telomere length (TL) (Lin et al., 2017). Here, we assessed the association between TL and growth. Methods: We measured relative TL in whole blood from 713 children. We reported differences between the 10th percentile and 90th percentile of TL or change in TL distribution using generalized additive models, adjusted for potential confounders. Results: In cross-sectional analyses, long TL was associated with a higher length-for-age Z score at age 1 year (0.23 SD adjusted difference in length-for-age Z score (95% CI 0.05, 0.42; FDR-corrected p-value = 0.01)). TL was not associated with other outcomes. Conclusions: Consistent with the metabolic telomere attrition hypothesis, our previous trial findings support an adaptive role for telomere attrition, whereby active TL regulation is employed as a strategy to address ‘emergency states’ with increased energy requirements such as rapid growth during the first year of life. Although short periods of active telomere attrition may be essential to promote growth, this study suggests that a longer overall initial TL setting in the first two years of life could signal increased resilience against future telomere erosion events and healthy growth trajectories