Family in the spotlight: a systematic review of family factors associated with participation of children with disabilities

QMU Research Centre: FireflyStella Arakelyan - orcid: 0000-0003-0326-707X https://orcid.org/0000-0003-0326-707XUpdate history: 2019-01-09 (Gold OA version deposited, article title updated, deposit exception, publication & AM embargo dates updated); 2018-12-12 (Corrected version of AM deposited)Donald Maciver - orcid: 0000-0002-6173-429X https://orcid.org/0000-0002-6173-429XAIM: The aim of this review was to synthesise empirical evidence of family factors associated with participation of children with disabilities aged 5-12 years to inform the development of family-centred participation-fostering interventions. METHOD: A systematic search was performed for articles published in English between 2001 and 2017 in MEDLINE, PsycINFO, CINAHL, Scopus and ASSIA following the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines (registration no: CRD42017078202). Quality of evidence was appraised using the Research Triangle Institute Item Bank. Family factors associated with participation were identified and assessed using a multistage “semi-quantitative” approach. RESULTS: Thirty studies were included in the review. Four non-modifiable “status” factors consistently associated with participation were parental ethnicity, parental education, family type and family socio-economic status. Six modifiable “process” factors with consistent associations with participation were parental mental and physical health functioning, parental self-efficacy beliefs, parental support, parental time, family preferences and activity orientation. INTERPRETATION: Rehabilitation professionals should direct their focus towards modifiable family factors as primary targets for family-centred interventions. Strategies that can improve families’ access to information, counselling, and community support services are likely to support children’s participation by empowering families and optimizing their health and well-being.Funding: This research was completed as part of a PhD funded by Lothian National Health Service and Queen Margaret University, Edinburgh, Scotland.https://onlinelibrary.wiley.com/journal/1469874961pubpub

No straight lines – young women’s perceptions of their mental health and wellbeing during and after pregnancy: a systematic review and meta-ethnography

Background: Young mothers face mental health challenges during and after pregnancy including increased rates of depression compared to older mothers. While the prevention of teenage pregnancy in countries such as the United States and the United Kingdom has been a focus for policy and research in recent decades, the need to understand young women’s own experiences has been highlighted. The aim of this meta-ethnography was to examine young women’s perceptions of their mental health and wellbeing during and after pregnancy to provide new understandings of those experiences. Methods: A systematic review and meta-ethnographic synthesis of qualitative research was conducted. Seven databases were systematically searched and forward and backward searching conducted. Papers were included if they were from Organisation for Economic Co-operation and Development countries and explored mental health and wellbeing experiences of young mothers (age under 20 in pregnancy; under 25 at time of research) as a primary research question – or where evidence about mental health and wellbeing from participants was foregrounded. Nineteen papers were identified and the Critical Appraisal Skills Programme checklist for qualitative research used to appraise the evidence. Following the seven-step process of meta-ethnography, key constructs were examined within each study and then translated into one another. Results: Seven translated themes were identified forming a new line of argument wherein mental health and wellbeing was analysed as relating to individual bodily experiences; tied into past and present relationships; underpinned by economic insecurity and entangled with feelings of societal surveillance. There were ‘no straight lines’ in young women’s experiences, which were more complex than dominant narratives around overcoming adversity suggest. Conclusions: The synthesis concludes that health and social care professionals need to reflect on the operation of power and stigma in young women’s lives and its impact on wellbeing. It adds to understanding of young women’s mental health and wellbeing during and after pregnancy as located in physical and structural factors rather than individual capacities alone

Detection of Maternal Alcohol Use Problems in the Pediatric Emergency Department

Maternal alcohol use problems may impact the health and well-being of children, but often remain unrecognized. Mothers of young children seldom seek outpatient care for themselves; thus, pediatric settings may present an opportunity for the detection of maternal alcohol use problems. This study examines the feasibility of screening for and prevalence of alcohol use problems in mothers of young children in the context of seeking pediatric emergency care. We also examined the relationship of maternal alcohol use problems with use of pediatric emergency care. Methods : A total of 361 English-speaking mothers of children aged 7 and younger completed screening measures during their child's emergency care visit. TWEAK was used to screen for alcohol use problems. The screening survey also included information on children's health status and health care use, demographics, and the Center for Epidemiological Studies Depression Scale. Results : Of the women approached, 90% agreed to complete the screening measure. On the basis of cutoff score of 2 or more, 7% of women had elevated TWEAK scores. Those women with a TWEAK score >2 reported greater use of the pediatric emergency department (PED) than women scoring below the cutoff. On the basis of multivariate analyses, significant predictors of recent PED use included the presence of child chronic illness, younger maternal age, and TWEAK score. Conclusions : Screening for alcohol use problems among mothers of young children using the TWEAK appears to be feasible in a busy PED setting. The PED setting is promising for identifying risk drinking among women who may be less likely to be otherwise detected and for whom alcohol use may be impacting child outcomes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66222/1/j.1530-0277.2006.00132.x.pd

Kinome rewiring reveals AURKA limits PI3K-pathway inhibitor efficacy in breast cancer.

Dysregulation of the PI3K-AKT-mTOR signaling network is a prominent feature of breast cancers. However, clinical responses to drugs targeting this pathway have been modest, possibly because of dynamic changes in cellular signaling that drive resistance and limit drug efficacy. Using a quantitative chemoproteomics approach, we mapped kinome dynamics in response to inhibitors of this pathway and identified signaling changes that correlate with drug sensitivity. Maintenance of AURKA after drug treatment was associated with resistance in breast cancer models. Incomplete inhibition of AURKA was a common source of therapy failure, and combinations of PI3K, AKT or mTOR inhibitors with the AURKA inhibitor MLN8237 were highly synergistic and durably suppressed mTOR signaling, resulting in apoptosis and tumor regression in vivo. This signaling map identifies survival factors whose presence limits the efficacy of targeted therapies and reveals new drug combinations that may unlock the full potential of PI3K-AKT-mTOR pathway inhibitors in breast cancer

Parents’ marital status and child physical abuse potential: the mediation of depression symptoms

Informed by a social interactional framework of stress and parenting, the aim of this study was to examine the mediating effect of depression symptoms on the asso- ciation between parents’ marital status (married and divorced parents) and child physical abuse potential, in a Portuguese community sample. It was hypothesized that the possible observed differences between divorced and married parents in the child physical abuse potential would be explained by their depression symptoms. Parents (N = 892) were assessed in their marital status, severity of depression symptoms and child physical abuse potential. Results showed that, when compared with married parents, divorced parents had higher child physical abuse potential. However, parents’ depression symptomatology was found as a mediator of the effect of marital status differences on child physical abuse potential. The influence of the status of divorced parents on the increase of child physical abuse potential was explained by the increase of the parents’ depression symptoms. This finding suggested that parents’ divorced status had no longer an effect on child physical abuse potential when parents’ depression symptomatology was tested as a mediator vari- able. The present mediation model explained 47 % of the variability in the child physical abuse potential score. Prac- tical implications of these findings for prevention and psy- chological intervention are also discussed.info:eu-repo/semantics/publishedVersio

Multiple var2csa-Type PfEMP1 Genes Located at Different Chromosomal Loci Occur in Many Plasmodium falciparum Isolates

BACKGROUND:The var2csa gene encodes a Plasmodium falciparum adhesion receptor which binds chondroitin sulfate A (CSA). This var gene is more conserved than other PfEMP1/var genes and is found in all P. falciparum isolates. In isolates 3D7, FCR3/It4 and HB3, var2csa is transcribed from a sub-telomeric position on the left arm of chromosome 12, but it is not known if this location is conserved in all parasites. Genome sequencing indicates that the var2csa gene is duplicated in HB3, but whether this is true in natural populations is uncertain. METHODOLOGY/PRINCIPAL FINDINGS:To assess global variation in the VAR2CSA protein, sequence variation in the DBL2X region of var2csa genes in 54 P.falciparum samples was analyzed. Chromosome mapping of var2csa loci was carried out and a quantitative PCR assay was developed to estimate the number of var2csa genes in P.falciparum isolates from the placenta of pregnant women and from the peripheral circulation of other malaria patients. Sequence analysis, gene mapping and copy number quantitation in P.falciparum isolates indicate that there are at least two loci and that both var2csa-like genes can be transcribed. All VAR2CSA DBL2X domains fall into one of two distinct phylogenetic groups possessing one or the other variant of a large (approximately 26 amino acid) dimorphic motif, but whether either motif variant is linked to a specific locus is not known. CONCLUSIONS/SIGNIFICANCE:Two or more related but distinct var2csa-type PfEMP1/var genes exist in many P. falciparum isolates. One gene is on chromosome 12 but additional var2csa-type genes are on different chromosomes in different isolates. Multiplicity of var2csa genes appears more common in infected placentae than in samples from non-pregnant donors indicating a possible advantage of this genotype in pregnancy associated malaria

Detection of human parvovirus B19 in papillary thyroid carcinoma

To evaluate whether parvovirus B19, a common human pathogen, was also involved in papillary thyroid carcinoma (PTC), 112 paraffin-embedded thyroid specimens of benign nodules, papillary, medullary and follicular carcinomas, and normal controls were examined for B19 DNA and capsid protein by nested PCR, in situ hybridisation (ISH) and immunohistochemistry (IHC). The expression of the nuclear factor-κB (NF-κB) was investigated by IHC. The results showed B19 DNA commonly exists in human thyroid tissues; however, there were significant differences between PTC group and normal controls, and between PTC and nonneoplastic adjacent tissues (P<0.001). The presence of viral DNA in PTC neoplastic epithelium was confirmed by laser-capture microdissection and sequencing of nested PCR products. B19 capsid protein in PTC group was significantly higher than that of all the control groups and nonneoplastic adjacent tissues (P⩽0.001). Compared with control groups, the activation of NF-κB in PTC group was significantly increased (P⩽0.02), except for medullary carcinomas, and the activation of NF-κB was correlated with the viral protein presence (P=0.002). Moreover, NF-κB was colocalised with B19 DNA in the neoplastic epithelium of PTC by double staining of IHC and ISH. These results indicate for the first time a possible role of B19 in pathogenesis of PTC

Enhanced peripheral toll-like receptor responses in psychosis: further evidence of a pro-inflammatory phenotype

Low-grade peripheral inflammation is often present in psychotic patients. Toll-like receptors (TLRs) are pattern-recognition molecules that initiate inflammation. Our objective was to investigate the peripheral TLR activity in psychosis. Forty schizophrenia patients, twenty bipolar patients and forty healthy controls (HC) were recruited. Donated whole blood was cultured with TLR agonists for 24 h. Cell supernatants were analysed using a multiplex enzyme-linked immunosorbent assay approach to measure IL-1β, IL-6, IL-8 and tumour necrosis factor-α (TNFα). Plasma was analysed for cytokines, cortisol and acute phase proteins. Here, we show that selective TLR agonist-induced cytokine (IL-1β, IL-6, IL-8 and TNFα) release is enhanced in stimulated whole blood from schizophrenia and bipolar patients compared with HC. An exaggerated release of IL-1β, IL-6 and TNFα following treatment with the TLR2 agonist HKLM was detected in both disorders compared with controls. Enhanced TLR4-induced increases in IL-1β for both disorders coupled with TNFα increases for bipolar patients were observed. TLR8-induced increases in IL-1β for both disorders as well as IL-6 and TNFα increases for bipolar patients were detected. TLR9-induced increases in IL-8 for schizophrenia patients were also observed. No differences in TLR1, TLR3, TLR5, TLR6 or TLR7 activity were detected. Plasma levels of IL-6 were significantly elevated in bipolar patients while TNFα levels were significantly elevated in schizophrenia patients compared with controls. Plasma acute phase proteins were significantly elevated in bipolar patients. These data demonstrate that specific alterations in TLR agonist-mediated cytokine release contribute to the evidence of immune dysfunction in psychotic disorders

The Viral and Cellular MicroRNA Targetome in Lymphoblastoid Cell Lines

Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus linked to a number of B cell cancers and lymphoproliferative disorders. During latent infection, EBV expresses 25 viral pre-microRNAs (miRNAs) and induces the expression of specific host miRNAs, such as miR-155 and miR-21, which potentially play a role in viral oncogenesis. To date, only a limited number of EBV miRNA targets have been identified; thus, the role of EBV miRNAs in viral pathogenesis and/or lymphomagenesis is not well defined. Here, we used photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) combined with deep sequencing and computational analysis to comprehensively examine the viral and cellular miRNA targetome in EBV strain B95-8-infected lymphoblastoid cell lines (LCLs). We identified 7,827 miRNA-interaction sites in 3,492 cellular 3′UTRs. 531 of these sites contained seed matches to viral miRNAs. 24 PAR-CLIP-identified miRNA:3′UTR interactions were confirmed by reporter assays. Our results reveal that EBV miRNAs predominantly target cellular transcripts during latent infection, thereby manipulating the host environment. Furthermore, targets of EBV miRNAs are involved in multiple cellular processes that are directly relevant to viral infection, including innate immunity, cell survival, and cell proliferation. Finally, we present evidence that myc-regulated host miRNAs from the miR-17/92 cluster can regulate latent viral gene expression. This comprehensive survey of the miRNA targetome in EBV-infected B cells represents a key step towards defining the functions of EBV-encoded miRNAs, and potentially, identifying novel therapeutic targets for EBV-associated malignancies