Self-harm with suicidal and non-suicidal intent in young people in sub-Saharan Africa: a systematic review

Background: Self-harm, whether attributed to suicidal or non-suicidal motives, is associated with several poor outcomes in young people, including eventual suicide. Much of our understanding of self-harm in young people is based on literature from Europe (particularly, the UK), North America, and Australia. We aimed to synthesise the available evidence on prevalence, the commonly reported self-harm methods, correlates, risk and protective factors, and reasons for self-harm, in adolescents (aged 10–25 years) in sub-Saharan Africa. Method: We searched MEDLINE, PsycINFO, PubMed, African Journals OnLine, and African Index Medicus for records from 1950 through August 2019, without language restrictions. We supplemented the database searches by searching relevant portals for postgraduate theses, reference harvesting, contacting authors for unpublished studies, and hand searching relevant print sources. We applied narrative synthesis to the evidence. Results: Seventy-four studies from 18 sub-Saharan African countries met the inclusion criteria. The median lifetime prevalence estimate was 10·3% (interquartile range [IQR] 4·6% – 16·1%); median 12-month prevalence estimate was 16·9% (IQR: 11·5% – 25·5%); median 6-month prevalence estimate was 18·2% (IQR: 12·7% – 21·8%); and the median 1-month prevalence estimate was 3·2% (IQR: 2·5–14·8%). Studies from Western sub-Saharan Africa reported the highest 12-month prevalence estimates (median = 24·3%; IQR = 16·9% – 27·9%). Clinical samples commonly reported overdose, whereas self-cutting was most commonly reported in non-clinical samples. Academic failure, sexual, emotional, and physical abuse, romantic relationship problems, family conflict, depression, and previous self-harm were identified as key correlates of self-harm. No study reported protective factors against self-harm. Conclusion: Variation in estimates was explained by small sample sizes and variation in definitions and measures used. Exploration of associations, risks and protective factors was based upon concepts and measures derived from high income countries. More detailed and culturally sensitive research is needed to understand the context-specific risks and protective factors for self-harm in adolescents in sub-Saharan Africa

Implementation of a problem-solving training initiative to reduce self-harm in prisons: a qualitative perspective of prison staff, field researchers and prisoners at risk of self-harm.

BACKGROUND:Social problem-solving is one technique used to help reduce incidence of self-harm. Our study evaluated the feasibility and acceptability of the adaptation and implementation of a brief Problem-Solving Training (PST) intervention to reduce self-harm in prisons. METHODS:The process involved i) adaptation of the training materials using focus groups with prison staff and prisoners, ii) training frontline prison staff to use the skills, and iii) implementation of the skills with prisoners at risk of self-harm. Qualitative interviews were conducted with prison staff, prisoners and field researchers and were analysed using a thematic framework to produce a model of the barriers and facilitators to the process. RESULTS:We conducted 43 interviews across three prison sites. The interviews included 19 prison staff, 18 prisoners and six field researcher meetings. The adaptation to the training and intervention materials were well received. The findings identified the need to support training using a collaborative and flexible approach. Prisoner engagement was affected by their own personal circumstances and by a range of contextual issues relating to the prison environment. Implementation of the skills by prison staff were hindered by resource constraints, the prison environment and staff attitudes. CONCLUSIONS:We found that it was feasible to adapt an existing intervention and contextualise it within the prison environment. Although we could train large numbers of staff it was deemed unfeasible for staff to implement the problem-solving skills to prisoners at risk of self-harm. Prisoners who engaged with the intervention reported a range of benefits. Alternative implementation mechanisms to tackle the contextual barriers proposed by staff and prisoners included delivery of the intervention using an educational setting and/or use of a prisoner peer-led scheme

Problem-solving training: assessing the feasibility and acceptability of delivering and evaluating a problem-solving training model for front-line prison staff and prisoners who self-harm

Objectives: Problem-solving skills training is adaptable, inexpensive and simple to deliver. However, its application with prisoners who self-harm is unknown. The study assessed the feasibility and acceptability of a problem-solving training (PST) intervention for prison staff and prisoners who self-harm, to inform the design of a large-scale study. Design and setting: A mixed-methods design used routinely collected data, individual outcome measures, an economic protocol and qualitative interviews at four prisons in Yorkshire and Humber, UK. Participants: (i) Front-line prison staff, (ii) male and female prisoners with an episode of self-harm in the previous 2 weeks. Intervention: The intervention comprised a 1 hour staff training session and a 30 min prisoner session using adapted workbooks and case studies. Outcomes: We assessed the study processes—coverage of training; recruitment and retention rates and adequacy of intervention delivery—and available data (completeness of outcome data, integrity of routinely collected data and access to the National Health Service (NHS) resource information). Prisoner outcomes assessed incidence of self-harm, quality of life and depression at baseline and at follow-up. Qualitative findings are presented elsewhere. Results: Recruitment was higher than anticipated for staff n=280, but lower for prisoners, n=48. Retention was good with 43/48 (89%) prisoners completing the intervention, at follow-up we collected individual outcome data for 34/48 (71%) of prisoners. Access to routinely collected data was inconsistent. Prisoners were frequent users of NHS healthcare. The additional cost of training and intervention delivery was deemed minimal in comparison to ‘treatment as usual’. Outcome measures of self-harm, quality of life and depression were found to be acceptable. Conclusions: The intervention proved feasible to adapt. Staff training was delivered but on the whole it was not deemed feasible for staff to deliver the intervention. A large-scale study is warranted, but modifications to the implementation of the intervention are required

Paracrine effects of TLR4-polarised mesenchymal stromal cells are mediated by extracellular vesicles

Mesenchymal stromal cells (MSCs) are adult stem cells able to give rise to bone, cartilage and fat cells. In addition, they possess immunomodulatory and immunosuppressive properties that are mainly mediated through secretion of extracellular vesicles (EVs). In a previous issue of Journal of Translational Medicine, Ti and colleagues demonstrated that preconditioning of MSCs with bacterial lipopolysaccharides results in secretion of EVs that can polarise mac‑ rophages towards anti-inflammatory M2 phenotype. Moreover, the authors suggest that EVs of lipopolysaccharide (LPS)-treated MSCs are superior to EVs of untreated MSCs concerning their ability to support wound healing. Our commentary critically discusses parallel efforts of other laboratories to generate conditioned media from stem cells for therapeutic applications, and highlights impact and significance of the study of Ti et al. Finally, we summarise its limitations and spotlight areas that need to be addressed to better define the underlying molecular mechanisms

Cognitive and affective perspective-taking in conduct-disordered children high and low on callous-unemotional traits

<p>Abstract</p> <p>Background</p> <p>Deficits in cognitive and/or affective perspective-taking have been implicated in Conduct-Disorder (CD), but empirical investigations produced equivocal results. Two factors may be implicated: (a) distinct deficits underlying the antisocial conduct of CD subgroups, (b) plausible disjunction between cognitive and affective perspective-taking with subgroups presenting either cognitive or affective-specific deficits.</p> <p>Method</p> <p>This study employed a second-order false-belief paradigm in which the cognitive perspective-taking questions tapped the character's thoughts and the affective perspective-taking questions tapped the emotions generated by these thoughts. Affective and cognitive perspective-taking was compared across three groups of children: (a) CD elevated on Callous-Unemotional traits (<it>CD-high-CU</it>, <it>n </it>= 30), (b) CD low on CU traits (<it>CD-low-CU</it>, <it>n </it>= 42), and (c) a 'typically-developing' comparison group (<it>n </it>= 50), matched in age (7.5 – 10.8), gender and socioeconomic background.</p> <p>Results</p> <p>The results revealed deficits in <it>CD-low-CU </it>children for both affective and cognitive perspective-taking. In contrast <it>CD-high-CU </it>children showed relative competency in cognitive, but deficits in affective-perspective taking, a finding that suggests an affective-specific defect and a plausible dissociation of affective and cognitive perspective-taking in <it>CD-high-CU </it>children.</p> <p>Conclusion</p> <p>Present findings indicate that deficits in cognitive perspective-taking that have long been implicated in CD appear to be characteristic of a subset of CD children. In contrast affective perspective-taking deficits characterise both CD subgroups, but these defects seem to be following diverse developmental paths that warrant further investigation.</p

The role of the ubiquitination–proteasome pathway in breast cancer: Ubiquitin mediated degradation of growth factor receptors in the pathogenesis and treatment of cancer

Aberrant activity of growth factor receptors has been implicated in the pathogenesis of a wide variety of malignancies. The negative regulation of signaling by growth factor receptors is mediated in large part by the ubiquitination, internalization, and degradation of the activated receptor. Over the past few years, considerable insight into the mechanisms that control receptor downregulation has been gained. There are also data suggesting that mutations that lead to inhibition of downregulation of growth factor receptors could play a role in the pathogenesis of cancer. Therapies directed at enhancing the degradation of growth factor receptors offer a promising approach to the treatment of malignancies

A Probabilistic Model of Local Sequence Alignment That Simplifies Statistical Significance Estimation

Sequence database searches require accurate estimation of the statistical significance of scores. Optimal local sequence alignment scores follow Gumbel distributions, but determining an important parameter of the distribution (λ) requires time-consuming computational simulation. Moreover, optimal alignment scores are less powerful than probabilistic scores that integrate over alignment uncertainty (“Forward” scores), but the expected distribution of Forward scores remains unknown. Here, I conjecture that both expected score distributions have simple, predictable forms when full probabilistic modeling methods are used. For a probabilistic model of local sequence alignment, optimal alignment bit scores (“Viterbi” scores) are Gumbel-distributed with constant λ = log 2, and the high scoring tail of Forward scores is exponential with the same constant λ. Simulation studies support these conjectures over a wide range of profile/sequence comparisons, using 9,318 profile-hidden Markov models from the Pfam database. This enables efficient and accurate determination of expectation values (E-values) for both Viterbi and Forward scores for probabilistic local alignments

Uncovering Dangerous Cheats: How Do Avian Hosts Recognize Adult Brood Parasites?

BACKGROUND: Co-evolutionary struggles between dangerous enemies (e.g., brood parasites) and their victims (hosts) lead to the emergence of sophisticated adaptations and counter-adaptations. Salient host tricks to reduce parasitism costs include, as front line defence, adult enemy discrimination. In contrast to the well studied egg stage, investigations addressing the specific cues for adult enemy recognition are rare. Previous studies have suggested barred underparts and yellow eyes may provide cues for the recognition of cuckoos Cuculus canorus by their hosts; however, no study to date has examined the role of the two cues simultaneously under a consistent experimental paradigm. METHODOLOGY/PRINCIPAL FINDINGS: We modify and extend previous work using a novel experimental approach--custom-made dummies with various combinations of hypothesized recognition cues. The salient recognition cue turned out to be the yellow eye. Barred underparts, the only trait examined previously, had a statistically significant but small effect on host aggression highlighting the importance of effect size vs. statistical significance. CONCLUSION: Relative importance of eye vs. underpart phenotypes may reflect ecological context of host-parasite interaction: yellow eyes are conspicuous from the typical direction of host arrival (from above), whereas barred underparts are poorly visible (being visually blocked by the upper part of the cuckoo's body). This visual constraint may reduce usefulness of barred underparts as a reliable recognition cue under a typical situation near host nests. We propose a novel hypothesis that recognition cues for enemy detection can vary in a context-dependent manner (e.g., depending on whether the enemy is approached from below or from above). Further we suggest a particular cue can trigger fear reactions (escape) in some hosts/populations whereas the same cue can trigger aggression (attack) in other hosts/populations depending on presence/absence of dangerous enemies that are phenotypically similar to brood parasites and costs and benefits associated with particular host responses

Drosophila cbl Is Essential for Control of Cell Death and Cell Differentiation during Eye Development

Activation of cell surface receptors transduces extracellular signals into cellular responses such as proliferation, differentiation and survival. However, as important as the activation of these receptors is their appropriate spatial and temporal down-regulation for normal development and tissue homeostasis. The Cbl family of E3-ubiquitin ligases plays a major role for the ligand-dependent inactivation of receptor tyrosine kinases (RTKs), most notably the Epidermal Growth Factor Receptor (EGFR) through ubiquitin-mediated endocytosis and lysosomal degradation.Here, we report the mutant phenotypes of Drosophila cbl (D-cbl) during eye development. D-cbl mutants display overgrowth, inhibition of apoptosis, differentiation defects and increased ommatidial spacing. Using genetic interaction and molecular markers, we show that most of these phenotypes are caused by increased activity of the Drosophila EGFR. Our genetic data also indicate a critical role of ubiquitination for D-cbl function, consistent with biochemical models.These data may provide a mechanistic model for the understanding of the oncogenic activity of mammalian cbl genes

Accurate classification of RNA structures using topological fingerprints

While RNAs are well known to possess complex structures, functionally similar RNAs often have little sequence similarity. While the exact size and spacing of base-paired regions vary, functionally similar RNAs have pronounced similarity in the arrangement, or topology, of base-paired stems. Furthermore, predicted RNA structures often lack pseudoknots (a crucial aspect of biological activity), and are only partially correct, or incomplete. A topological approach addresses all of these difficulties. In this work we describe each RNA structure as a graph that can be converted to a topological spectrum (RNA fingerprint). The set of subgraphs in an RNA structure, its RNA fingerprint, can be compared with the fingerprints of other RNA structures to identify and correctly classify functionally related RNAs. Topologically similar RNAs can be identified even when a large fraction, up to 30%, of the stems are omitted, indicating that highly accurate structures are not necessary. We investigate the performance of the RNA fingerprint approach on a set of eight highly curated RNA families, with diverse sizes and functions, containing pseudoknots, and with little sequence similarity–an especially difficult test set. In spite of the difficult test set, the RNA fingerprint approach is very successful (ROC AUC \u3e 0.95). Due to the inclusion of pseudoknots, the RNA fingerprint approach both covers a wider range of possible structures than methods based only on secondary structure, and its tolerance for incomplete structures suggests that it can be applied even to predicted structures. Source code is freely available at https://github.rcac.purdue.edu/mgribsko/XIOS_RNA_fingerprint