Expressive writing for high-risk drug dependent patients in a primary care clinic: A pilot study

BACKGROUND: Previous research has shown that expressive writing is beneficial in terms of both physical and emotional health outcomes. This study aimed to investigate the effectiveness and acceptability of a brief expressive writing intervention for high-risk drug dependent patients in a primary care clinic, and to determine the relationship between linguistic features of writing and health outcomes. METHODS: Participants completed four 15-minute expressive writing tasks over a week, in which they described their thoughts and feelings about a recent stressful event. Self-report measures of physical (SF-12) and psychological health (DASS-21) were administered at baseline and at a two-week follow-up. Fifty-three participants were recruited and 14 (26%) completed all measures. RESULTS: No statistically significant benefits in physical or psychological health were found, although all outcomes changed in the direction of improvement. The intervention was well-received and was rated as beneficial by participants. The use of more positive emotion words in writing was associated with improvements in depression and stress, and flexibility in first person pronoun use was associated with improvements in anxiety. Increasing use of cognitive process words was associated with worsening depressive mood. CONCLUSION: Although no significant benefits in physical and psychological health were found, improvements in psychological wellbeing were associated with certain writing styles and expressive writing was deemed acceptable by high-risk drug dependent patients. Given the difficulties in implementing psychosocial interventions in this population, further research using a larger sample is warranted

Mental health service use among mothers involved in public family law proceedings: linked data cohort study in South London 2007-2019

PURPOSE: Mental health problems and substance misuse are common among the mothers of children who experience court-mandated placement into care in England, yet there is limited research characterising these health needs to inform evidence-based policy. In this descriptive study, we aimed to generate evidence about the type, severity, and timing of mental health and substance misuse needs among women involved in public family law proceedings concerning child placement into care ('care proceedings'). METHODS: This is a retrospective, matched cohort study using linked family court and mental health service records for 2137 (66%) of the 3226 women involved in care proceedings between 2007 and 2019 in the South London and Maudsley NHS Mental Health Trust (SLaM) catchment area. We compared mental health service use and risk of dying with 17,096 female-matched controls who accessed SLaM between 2007 and 2019, aged 16-55 years, and were not involved in care proceedings. RESULTS: Most women (79%) were known to SLaM before care proceedings began. Women had higher rates of schizophrenia spectrum disorders (19% vs 11% matched controls), personality disorders (21% vs 11%), and substance misuse (33% vs 12%). They were more likely to have a SLaM inpatient admission (27% vs 14%) or to be sectioned (19% vs 8%). Women had a 2.15 (95% CI 1.68-2.74) times greater hazard of dying, compared to matched controls, adjusted for age. CONCLUSION: Women involved in care proceedings experience a particularly high burden of severe and complex mental health and substance misuse need. Women's increased risk of mortality following proceedings highlights that interventions responding to maternal mental health and substance misuse within family courts should offer continued, long-term support

Rationale, Design, and Baseline Characteristics of a Community-based Comparative Effectiveness Trial to Prevent Type 2 Diabetes in Economically Disadvantaged Adults: The RAPID Study

Reaching Out and Preventing Increases in Diabetes (RAPID) is a community-based randomized trial evaluating the comparative costs and effectiveness of a group-based adaption of the DPP lifestyle intervention developed and implemented in partnership with the YMCA. RAPID enrolled adult primary care patients, with BMI 24 kg/m2 or higher and abnormal glucose metabolism (HbA1c 5.7–6.9% or fasting plasma glucose 100–125 mg/dL). 509 participants were enrolled and randomized to one of two groups: standard clinical advice plus free-of-charge access to a group-based adaption of the DPP offered by the Y, versus standard clinical advice alone. Key outcomes for future analysis will include differences in body weight and other cardiovascular risk factors over a 24-month intervention period. At baseline, RAPID participants had a mean (SD) age of 51 ± 12.1 years, weight of 225.1 ± 56.2 lbs, and BMI of 36.9 ± 8.6 kg/m2. 70.7% were women, 57.2% were African American, 35.4% were non-Hispanic White, and 3.2% were Hispanic. Mean HbA1c was 6.05 ± 0.34%. Additionally, 55.4% of participants had a baseline systolic blood pressure of ≥ 130 mm Hg, 33.1% had a total blood cholesterol exceeding 200 mg/dL, and 74% reported a household income of < $25,000. The RAPID Study successfully randomized a large cohort of participants with a wide distribution of age, body weight, and race who are at high risk for developing type 2 diabetes

Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis.

The TAR DNA-binding protein 43 (TDP-43) has been identified as the major disease protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U), defining a novel class of neurodegenerative conditions: the TDP-43 proteinopathies. The first pathogenic mutations in the gene encoding TDP-43 (TARDBP) were recently reported in familial and sporadic ALS patients, supporting a direct role for TDP-43 in neurodegeneration. In this study, we report the identification and functional analyses of two novel and one known mutation in TARDBP that we identified as a result of extensive mutation analyses in a cohort of 296 patients with variable neurodegenerative diseases associated with TDP-43 histopathology. Three different heterozygous missense mutations in exon 6 of TARDBP (p.M337V, p.N345K, and p.I383V) were identified in the analysis of 92 familial ALS patients (3.3%), while no mutations were detected in 24 patients with sporadic ALS or 180 patients with other TDP-43-positive neurodegenerative diseases. The presence of p.M337V, p.N345K, and p.I383V was excluded in 825 controls and 652 additional sporadic ALS patients. All three mutations affect highly conserved amino acid residues in the C-terminal part of TDP-43 known to be involved in protein-protein interactions. Biochemical analysis of TDP-43 in ALS patient cell lines revealed a substantial increase in caspase cleaved fragments, including the approximately 25 kDa fragment, compared to control cell lines. Our findings support TARDBP mutations as a cause of ALS. Based on the specific C-terminal location of the mutations and the accumulation of a smaller C-terminal fragment, we speculate that TARDBP mutations may cause a toxic gain of function through novel protein interactions or intracellular accumulation of TDP-43 fragments leading to apoptosis

Diversity patterns of ground beetles and understorey vegetation in mature, secondary and plantation forest regions of temperate Northern China

Plantation and secondary forests form increasingly important components of the global forest cover, but our current knowledge about their potential contribution to biodiversity conservation is limited. We surveyed understory plant and carabid species assemblages at three distinct regions in temperate northeastern China, dominated by mature forest (Changbaishan Nature Reserve, sampled in 2011 and 2012), secondary forest (Dongling Mountain, sampled in 2011 and 2012), and forest plantation habitats (Bashang Plateau, sampled in 2006 and 2007), respectively. The α-diversity of both taxonomic groups was highest in plantation forests of the Bashang Plateau. Beetle α-diversity was lowest, but plant and beetle species turnover peaked in the secondary forests of Dongling Mountain, while habitats in the Changbaishan Nature Reserve showed the lowest turnover rates for both taxa. Changbaishan Nature Reserve harbored the highest proportion of forest specialists. Our results suggest that in temperate regions of northern China, the protected larch plantation forest established over extensive areas might play a considerable role in maintaining a high biodiversity in relation to understory herbaceous plant species and carabid assemblages, which can be seen as indicators of forest disturbance. The high proportion of phytophagous carabids and the rarity of forest specialists reflect the relatively homogenous, immature status of the forest ecosystems on the Bashang Plateau. China's last remaining large old-growth forests like the ones on Changbaishan represent stable, mature ecosystems which require particular conservation attention

Application of pharmacogenomics and bioinformatics to exemplify the utility of human <i>ex vivo</i> organoculture models in the field of precision medicine

Here we describe a collaboration between industry, the National Health Service (NHS) and academia that sought to demonstrate how early understanding of both pharmacology and genomics can improve strategies for the development of precision medicines. Diseased tissue ethically acquired from patients suffering from chronic obstructive pulmonary disease (COPD), was used to investigate inter-patient variability in drug efficacy using ex vivo organocultures of fresh lung tissue as the test system. The reduction in inflammatory cytokines in the presence of various test drugs was used as the measure of drug efficacy and the individual patient responses were then matched against genotype and microRNA profiles in an attempt to identify unique predictors of drug responsiveness. Our findings suggest that genetic variation in CYP2E1 and SMAD3 genes may partly explain the observed variation in drug response

Manual / Issue 4 / Blue

Manual, a journal about art and its making. Blue.The fourth issue. Indigo blue, ultramarine blue, cobalt blue, cerulean blue, zaffre blue, indanthrone blue, phthalo blue, cyan blue, Han blue, French blue, Berlin blue, Prussian blue, Venetian blue, Dresden blue, Tiffany blue, Lanvin blue, Majorelle blue, International Klein Blue, Facebook blue. The names given to different shades of blue speak of plants, minerals, and modern chemistry; exoticism, global trade, and national pride; capitalist branding and pure invention. The fourth issue of Manual is a meditation on blue. From precious substance to controllable algorithm to the wide blue yonder, join us as we leap into the blue. Softcover, 64 pages. Published 2015 by the RISD Museum. Proceeds from RISD Museum publications support the work of the museum. Manual 4 (Blue) contributors include Lawrence Berman, A. Will Brown, Linda Catano, Spencer Fitch, Jessica Helfand, Kate Irvin, Oda van Maanen, Dominic Molon, Maggie Nelson, Ingrid A. Neuman, Margot Nishimura, Karen B. Schloss, Anna Strickland, Louis van Tilborgh, and Elizabeth A. Williams.https://digitalcommons.risd.edu/risdmuseum_journals/1003/thumbnail.jp

Structural analysis of MDM2 RING separates degradation from regulation of p53 transcription activity

MDM2–MDMX complexes bind the p53 tumor-suppressor protein, inhibiting p53's transcriptional activity and targeting p53 for proteasomal degradation. Inhibitors that disrupt binding between p53 and MDM2 efficiently activate a p53 response, but their use in the treatment of cancers that retain wild-type p53 may be limited by on-target toxicities due to p53 activation in normal tissue. Guided by a novel crystal structure of the MDM2–MDMX–E2(UbcH5B)–ubiquitin complex, we designed MDM2 mutants that prevent E2–ubiquitin binding without altering the RING-domain structure. These mutants lack MDM2's E3 activity but retain the ability to limit p53′s transcriptional activity and allow cell proliferation. Cells expressing these mutants respond more quickly to cellular stress than cells expressing wild-type MDM2, but basal p53 control is maintained. Targeting the MDM2 E3-ligase activity could therefore widen the therapeutic window of p53 activation in tumors

Identifying clusters of falls-related hospital admissions to inform population targets for prioritising falls prevention programmes

Background There has been limited research investigating the relationship between injurious falls and hospital resource use. The aims of this study were to identify clusters of community-dwelling older people in the general population who are at increased risk of being admitted to hospital following a fall and how those clusters differed in their use of hospital resources. Methods Analysis of routinely collected hospital admissions data relating to 45 374 fall-related admissions in Victorian community-dwelling older adults aged =65 years that occurred during 2008/2009 to 2010/2011. Fall-related admission episodes were identified based on being admitted from a private residence to hospital with a principal diagnosis of injury (International Classification of Diseases (ICD)-10-AM codes S00 to T75) and having a first external cause of a fall (ICD-10-AM codes W00 to W19). A cluster analysis was performed to identify homogeneous groups using demographic details of patients and information on the presence of comorbidities. Hospital length of stay (LOS) was compared across clusters using competing risks regression. Results Clusters based on area of residence, demographic factors (age, gender, marital status, country of birth) and the presence of comorbidities were identified. Clusters representing hospitalised fallers with comorbidities were associated with longer LOS compared with other cluster groups. Clusters delineated by demographic factors were also associated with increased LOS. Conclusions All patients with comorbidity, and older women without comorbidities, stay in hospital longer following a fall and hence consume a disproportionate share of hospital resources. These findings have important implications for the targeting of falls prevention interventions for community-dwelling older people

Abnormal Expression Of Homeobox Genes And Transthyretin In C9Orf72 Expansion Carriers

Objective: We performed a genome-wide brain expression study to reveal the underpinnings of diseases linked to a repeat expansion in chromosome 9 open reading frame 72 (C9ORF72). Methods: The genome-wide expression profile was investigated in brain tissue obtained from C9ORF72 expansion carriers (n = 32), patients without this expansion (n = 30), and controls (n = 20). Using quantitative real-time PCR, findings were confirmed in our entire pathologic cohort of expansion carriers (n = 56) as well as nonexpansion carriers (n = 31) and controls (n = 20). Results: Our findings were most profound in the cerebellum, where we identified 40 differentially expressed genes, when comparing expansion carriers to patients without this expansion, including 22 genes that have a homeobox (e.g., HOX genes) and/or are located within the HOX gene cluster (top hit: homeobox A5 [HOXA5]). In addition to the upregulation of multiple homeobox genes that play a vital role in neuronal development, we noticed an upregulation of transthyretin (TTR), an extracellular protein that is thought to be involved in neuroprotection. Pathway analysis aligned with these findings and revealed enrichment for gene ontology processes involved in (anatomic) development (e.g., organ morphogenesis). Additional analyses uncovered that HOXA5 and TTR levels are associated with C9ORF72 variant 2 levels as well as with intron-containing transcript levels, and thus, disease-related changes in those transcripts may have triggered the upregulation of HOXA5 and TTR. Conclusions: In conclusion, our identification of genes involved in developmental processes and neuroprotection sheds light on potential compensatory mechanisms influencing the occurrence, presentation, and/or progression of C9ORF72-related diseases