Decreasing rates of disorganised attachment in infants and young children, who are at risk of developing, or who already have disorganised attachment. A systematic review and meta-analysis of early parenting interventions

BACKGROUND: Disorganised attachment patterns in infants have been linked to later psychopathology. Services have variable practices for identifying and providing interventions for families of children with disorganised attachment patterns, which is the attachment pattern leading to most future psychopathology. Several recent government reports have highlighted the need for better parenting interventions in at risk groups. OBJECTIVES: The objective of this review and meta-analysis was to evaluate the clinical effectiveness of available parenting interventions for families of children at high risk of developing, or already showing, a disorganised pattern of attachment. METHODS: Population: Studies were included if they involved parents or caregivers of young children with a mean age under 13 years who had a disorganised classification of attachment or were identified as at high risk of developing such problems. Included interventions were aimed at parents or caregivers (e.g. foster carers) seeking to improve attachment. Comparators included an alternative intervention, an attention control, treatment as usual or no intervention. The primary outcome was a disorganised pattern in childhood measured using a validated attachment instrument. Studies that did not use a true Randomised Controlled Trial (RCT) design were excluded from the review. Both published and unpublished papers were included, there were no restrictions on years since publication and foreign language papers were included where translation services could be accessed within necessary timescales. RESULTS: A comprehensive search of relevant databases yielded 15,298 papers. This paper reports a systematic review as part of an NIHR HTA study identifying studies pre-2012, updated to include all papers to October 2016. Two independent reviewers undertook two stage screening and data extraction of the included studies at all stages. A Cochrane quality assessment was carried out to assess the risk of bias. In total, fourteen studies were included in the review. In a meta-analysis of these fourteen studies the interventions saw less disorganised attachment at outcome compared to the control (OR = 0.50, (0.32, 0.77), p = 0.008). The majority of the interventions targeted maternal sensitivity. We carried out exploratory analyses to examine factors that may influence treatment outcome but these should be treated with caution given that we were limited by small numbers of studies. CONCLUSIONS: Parenting interventions that target parental sensitivity show promise in reducing disorganised attachment. This is limited by few high quality studies and the fact that most studies are with mothers. More high quality randomised controlled trials are required to elucidate this further

SelSA-1, a novel HDAC inhibitor demonstrates enhanced chemotherapeutic potential by redox modulation

Abstract Colorectal cancer (CRC) is a multistep disorder resulting from genetic and epigenetic genome changes. It is the third most common malignancy in developed nations accounting for roughly 600,000 deaths annually. Persistent gut inflammation, as observed in inflammatory bowel disease (IBD), is a key risk factor for CRC development. From an epigenetic viewpoint, the pharmacological inhibition of HDACs using HDAC inhibitors such as SAHA has emerged as a suitable anticancer strategy in the recent past. However, the clinical success of these strategies is limited and has risk factors associated with their uses. Thus, considering the critical involvement of epigenetic regulation of key molecular mechanisms in carcinogenesis as well as HDAC inhibitory and anti-tumorigenic properties of Selenium (Se), we aimed to explore the potentially safer and enhanced chemotherapeutic potential of a Se derivative of SAHA namely SelSA-1, in an experimental model of colitis-associated experimental cancer (CAC) model and mechanism involved therein. The in vitro study indicated improved efficiency, specificity, and better safety margin in terms of lower IC50 value of SelSA-1 than SAHA in both NIH3T3 (9.44 and 10.87 µM) and HCT 115 (5.70 and 7.49 µM) cell lines as well on primary colonocytes (5.61 and 6.30 µM) respectively. In an in vivo experimental model, SelSA-1 efficiently demonstrated amelioration of the multiple plaque lesions (MPLs), tumor burden/incidence, and modulation of various histological and morphological parameters. Further, redox-mediated alterations in apoptotic mediators suggested induction of cancer cell apoptosis by SelSA-1. These findings indicate the enhanced chemotherapeutic and pro-resolution effects of SelSA-1 in part mediated through redox modulation of multiple epigenetic and apoptotic pathways

Resolution of Cox mediated inflammation by Se supplementation in mouse experimental model of colitis

<div><p>UC a form of IBD is a chronic inflammatory disorder of large intestine, with unknown etiology. Reports suggest a critical role of COX-2 dependent prostaglandins (PGs) mediated inflammatory pathway in pathophysiology of UC. However, COX inhibition using NSAIDs exacerbate IBD and thus is not a viable solution. Currently, in DSS induced experimental colitis in mice, we have demonstrated that dietary Se supplementation (0.5ppm as sodium selenite) symptomatically resolves the signs of inflammation in a redox sensitive manner as compared to Se deficient (0.01ppm) conditions, as seen by modulation in oxidative stress markers, morphological changes, histopathological examinations, biochemical studies such as MPO activity, activity of intestinal markers enzymes as well as mRNA and expressions of various pro and anti-inflammatory factors such as, mPGES, hPGDS, TXAS, 15-PGDH, GPX-1 and GPX-2. These findings were validated and correlated with changes in the biophysical parameters such as membrane fluidity, electrical parameters (impedance), transport across the colonic tissue and FTIR. Current study not only concluded that Se at supranutritional concentrations by modulating the redox status relieves the signs of colitis by regulating COX dependent PG biosynthetic pathway, but also sheds light on the biophysical characterization of these inflammatory/resolution pathways involved in UC.</p></div

Biophysical characterization of protective effects of Se.

<p>(a) Demonstrates significant decrease in membrane fluidity in Se-D group in comparison with Se-Ade and Se-Sup groups (b) shows changes in the Histidine transport levels across the epithelial membrane (c, d) shows significant decrease in impedance at 1KHz and 100Hz in Se-Def group in comparison with Se-Ade and Se-Sup groups in series and parallel respectively. Data is represented as mean ± SEM of atleast 4 independent observations and ***, **, * represent p<0.001, p<0.01 & p<0.05.</p

Redox mediated resolution of inflammation by Se.

<p>(a) and (b) shows histopathology images and scoring of colonic tissues in Se-Def, Se-Ade and Se-Sup groups. (c) Increased myeloperoxidase activity in Se-Ade and Se-Sup groups compared to Se Def groups. (d, e) Alteration in MDA levels and catalase activity after DSS treatment in colons of mice fed on diets containing different Se concentration. Data is represented as mean ± SEM of atleast4 independent observations and ***, **, * represent p<0.001, p<0.01& p<0.05 respectively.</p

Protective effects of Se are mediated through modulation of Cox pathway.

<p>(a) and (b) represents the specific activity of intestinal marker disaccharidases in BBM and colon homogenates of Se-Def, Se-Ade and Se-Sup groups. (c) and (d) shows Se concentration dependent significant alterations in the mRNA and protein expressions of pro and anti-inflammatory markers. Data is represented as mean ± SEM of atleast4 independent observations and ***, **, * represent p<0.001, p<0.01& p<0.05 respectively.</p

List of primers used.

<p>List of primers used.</p

Se relives sign of inflammation in DSS colitis model.

<p>(a) Differential GPx activity in Se-Def, Se-Ade and Se-Sup. (b) Shows significant decrease in body weights in Se-Def group when compared with Se-Ade and Se-Sup group. (c, d) shortening of colons of Se-Def mice compared to Se-Ade and Se-Sup groups (e) Percent survival curves of three groups with Se-Def with poor survival when compared to Se-Ade and Se-Sup groups. (f) Disease activity index (DAI). Data is represented as mean ± SEM of atleast4 independent observations and ***, **, * represent p<0.001, p<0.01& p<0.05 respectively).</p

Process and Outcome Evaluations of Smartphone Apps for Bipolar Disorder: Scoping Review

BackgroundMental health apps (MHAs) provide opportunities for accessible, immediate, and innovative approaches to better understand and support the treatment of mental health disorders, especially those with a high burden, such as bipolar disorder (BD). Many MHAs have been developed, but few have had their effectiveness evaluated. ObjectiveThis systematic scoping review explores current process and outcome measures of MHAs for BD with the aim to provide a comprehensive overview of current research. This will identify the best practice for evaluating MHAs for BD and inform future studies. MethodsA systematic literature search of the health science databases PsycINFO, MEDLINE, Embase, EBSCO, Scopus, and Web of Science was undertaken up to January 2021 (with no start date) to narratively assess how studies had evaluated MHAs for BD. ResultsOf 4051 original search results, 12 articles were included. These 12 studies included 435 participants, and of these, 343 had BD type I or II. Moreover, 11 of the 12 studies provided the ages (mean 37 years) of the participants. One study did not report age data. The male to female ratio of the 343 participants was 137:206. The most widely employed validated outcome measure was the Young Mania Rating Scale, being used 8 times. The Hamilton Depression Rating Scale-17/Hamilton Depression Rating Scale was used thrice; the Altman Self-Rating Mania Scale, Quick Inventory of Depressive Symptomatology, and Functional Assessment Staging Test were used twice; and the Coping Inventory for Stressful Situations, EuroQoL 5-Dimension Health Questionnaire, Generalized Anxiety Disorder Scale-7, Inventory of Depressive Symptomatology, Mindfulness Attention Awareness Scale, Major Depression Index, Morisky-Green 8-item, Perceived Stress Scale, and World Health Organization Quality of Life-BREF were used once. Self-report measures were captured in 9 different studies, 6 of which used MONARCA. Mood and energy levels were the most commonly used self-report measures, being used 4 times each. Furthermore, 11 of the 12 studies discussed the various confounding factors and barriers to the use of MHAs for BD. ConclusionsReported low adherence rates, usability challenges, and privacy concerns act as barriers to the use of MHAs for BD. Moreover, as MHA evaluation is itself developing, guidance for clinicians in how to aid patient choices in mobile health needs to develop. These obstacles could be ameliorated by incorporating co-production and co-design using participatory patient approaches during the development and evaluation stages of MHAs for BD. Further, including qualitative aspects in trials that examine patient experience of both mental ill health and the MHA itself could result in a more patient-friendly fit-for-purpose MHA for BD