Improving the treatment and remission of major depression in homeless people with severe mental illness: the multicentric French Housing First (FHF) program. French Housing First Study Group Running title: Major depression in homeless people with severe mental disorders

International audienceObjectiveThe aim of this study was to investigate the factors associated with violent behavior in a large multicenter sample of Homeless Schizophrenia (SZ) and Bipolar Disorder (BD) (HSB) subjects.MethodsThis multicenter study was conducted in 4 French cities: Lille, Marseille, Paris and Toulouse. Violent behavior was defined by at least one episode of verbal or physical violence in the last 6 months.ResultsOverall, 675 HSB patients, mean aged 38 years and 82.5% men were included, 458 SZ (68.4%) and 212 BD (31.6%). During the 6 months before evaluation, 213 (34.3%) committed at least one physical or verbal violence. In multivariate analysis, violence has been associated with younger age (aOR = 0.96[0.94–0.99], p = .001), number of nights in the street (aOR = 1.01[1.01–1.01]), BD diagnosis (aOR = 1.63[1.01–2.65], p = .04), higher current illness severity (CGI score) (aOR = 1.32[1.07–1.64], p = .01), higher rates of current manic episode (aOR = 2.24[1.32–3.81], p = .002), current alcohol use disorder (aOR = 2.05 [1.33–3.15], p = .001), antisocial personality disorder (aOR = 2.51[1.55–4.07], p < .001) and with antidepressant consumption (aOR = 2.01[1.01–4.04], p = .04). No specific antipsychotic or mood stabilizer has been associated with decreased rates of violent behavior, however clozapine, lithium and carbamazepine remained poorly prescribed.ConclusionIn case of violent behavior in HSB subjects, clinicians should focus in priority on the treatment of mania, antidepressant iatrogenic effect and alcohol use disorder by pharmacological and non-pharmacological treatments. Clozapine, lithium and carbamazepine should be chosen as the treatments of reference in this population but may be hard to manage in some cases.The current clinical trial number is NCT01570712

Europeans’ willingness to pay for ending homelessness: A contingent valuation study

The purpose of this study is to assess the utility value European citizens put on an innovative social program aimed at reducing homelessness. The Housing First (HF) model involves access to regular, scattered, independent and integrated housing in the community with the support of a multidisciplinary team. Currently, HF is not implemented by most European countries or funded by healthcare or social plans, but randomised controlled trials have stressed significant results for improved housing stability, recovery and healthcare services use. The broader implementation of HF across Europe would benefit from a better understanding of citizens' preferences and “willingness to pay” (WTP) for medico-social interventions like HF. We conducted a representative telephone survey between March and December 2017 in eight European countries (France, Ireland, Italy, the Netherlands, Poland, Portugal, Spain, and Sweden). Respondent's WTP for HF (N = 5631) was assessed through a contingent valuation method with a bidding algorithm. 42.3% of respondents were willing to pay more taxes to reduce homelessness through the HF model, and significant differences were found between countries (p < 0.001); 30.4% of respondents who did not value the HF model were protest zeros (either contested the payment vehicle-taxes- or the survey instrument). Respondents were willing to pay €28.2 (±11) through annual taxation for the HF model. Respondents with higher educational attainment, who paid national taxes, reported positive attitudes about homelessness, or reported practices to reduce homelessness (donations, volunteering) were more likely to value the HF model, with some countries' differences also related to factors at the environmental level. These findings inform key stakeholders that European citizens are aware of the issue of homelessness in their countries and that scaling up the HF model across Europe is both feasible and likely to have public support

Measuring, in solution, multiple-fluorophore labeling by combining Fluorescence Correlation Spectroscopy and photobleaching

Determining the number of fluorescent entities that are coupled to a given molecule (DNA, protein, etc.) is a key point of numerous biological studies, especially those based on a single molecule approach. Reliable methods are important, in this context, not only to characterize the labeling process, but also to quantify interactions, for instance within molecular complexes. We combined Fluorescence Correlation Spectroscopy (FCS) and photobleaching experiments to measure the effective number of molecules and the molecular brightness as a function of the total fluorescence count rate on solutions of cDNA (containing a few percent of C bases labeled with Alexa Fluor 647). Here, photobleaching is used as a control parameter to vary the experimental outputs (brightness and number of molecules). Assuming a Poissonian distribution of the number of fluorescent labels per cDNA, the FCS-photobleaching data could be easily fit to yield the mean number of fluorescent labels per cDNA strand (@ 2). This number could not be determined solely on the basis of the cDNA brightness, because of both the statistical distribution of the number of fluorescent labels and their unknown brightness when incorporated in cDNA. The statistical distribution of the number of fluorophores labeling cDNA was confirmed by analyzing the photon count distribution (with the cumulant method), which showed clearly that the brightness of cDNA strands varies from one molecule to the other.Comment: 38 pages (avec les figures

Transgenerational Stress Memory Is Not a General Response in Arabidopsis

Adverse conditions can trigger DNA damage as well as DNA repair responses in plants. A variety of stress factors are known to stimulate homologous recombination, the most accurate repair pathway, by increasing the concentration of necessary enzymatic components and the frequency of events. This effect has been reported to last into subsequent generations not exposed to the stress. To establish a basis for a genetic analysis of this transgenerational stress memory, a broad range of treatments was tested for quantitative effects on homologous recombination in the progeny. Several Arabidopsis lines, transgenic for well-established recombination traps, were exposed to 10 different physical and chemical stress treatments, and scored for the number of somatic homologous recombination (SHR) events in the treated generation as well as in the two subsequent generations that were not treated. These numbers were related to the expression level of genes involved in homologous recombination and repair. SHR was enhanced after the majority of treatments, confirming previous data and adding new effective stress types, especially interference with chromatin. Compounds that directly modify DNA stimulated SHR to values exceeding previously described induction rates, concomitant with an induction of genes involved in SHR. In spite of the significant stimulation in the stressed generations, the two subsequent non-treated generations only showed a low and stochastic increase in SHR that did not correlate with the degree of stimulation in the parental plants. Transcripts coding for SHR enzymes generally returned to pre-treatment levels in the progeny. Thus, transgenerational effects on SHR frequency are not a general response to abiotic stress in Arabidopsis and may require special conditions

Intramolecular Folding in Human ILPR Fragment with Three C-Rich Repeats

Enrichment of four tandem repeats of guanine (G) rich and cytosine (C) rich sequences in functionally important regions of human genome forebodes the biological implications of four-stranded DNA structures, such as G-quadruplex and i-motif, that can form in these sequences. However, there have been few reports on the intramolecular formation of non-B DNA structures in less than four tandem repeats of G or C rich sequences. Here, using mechanical unfolding at the single-molecule level, electrophoretic mobility shift assay (EMSA), circular dichroism (CD), and ultraviolet (UV) spectroscopy, we report an intramolecularly folded non-B DNA structure in three tandem cytosine rich repeats, 5'-TGTC4ACAC4TGTC4ACA (ILPR-I3), in the human insulin linked polymorphic region (ILPR). The thermal denaturation analyses of the sequences with systematic C to T mutations have suggested that the structure is linchpinned by a stack of hemiprotonated cytosine pairs between two terminal C4 tracts. Mechanical unfolding and Br2 footprinting experiments on a mixture of the ILPR-I3 and a 5′-C4TGT fragment have further indicated that the structure serves as a building block for intermolecular i-motif formation. The existence of such a conformation under acidic or neutral pH complies with the strand-by-strand folding pathway of ILPR i-motif structures

Organisational and student characteristics, fidelity, funding models, and unit costs of recovery colleges in 28 countries:a cross-sectional survey

Background: Recovery colleges were developed in England to support the recovery of individuals who have mental health symptoms or mental illness. They have been founded in many countries but there has been little international research on recovery colleges and no studies investigating their staffing, fidelity, or costs. We aimed to characterise recovery colleges internationally, to understand organisational and student characteristics, fidelity, and budget. Methods: In this cross-sectional study, we identified all countries in which recovery colleges exist. We repeated a cross-sectional survey done in England for recovery colleges in 28 countries. In both surveys, recovery colleges were defined as services that supported personal recovery, that were coproduced with students and staff, and where students learned collaboratively with trainers. Recovery college managers completed the survey. The survey included questions about organisational and student characteristics, fidelity to the RECOLLECT Fidelity Measure, funding models, and unit costs. Recovery colleges were grouped by country and continent and presented descriptively. We used regression models to explore continental differences in fidelity, using England as the reference group. Findings: We identified 221 recovery colleges operating across 28 countries, in five continents. Overall, 174 (79%) of 221 recovery colleges participated. Most recovery colleges scored highly on fidelity. Overall scores for fidelity (β=–2·88, 95% CI 4·44 to –1·32; p=0·0001), coproduction (odds ratio [OR] 0·10, 95% CI 0·03 to 0·33; p&lt;0·0001), and being tailored to the student (OR 0·10, 0·02 to 0·39; p=0·0010), were lower for recovery colleges in Asia than in England. No other significant differences were identified between recovery colleges in England, and those in other continents where recovery colleges were present. 133 recovery colleges provided data on annual budgets, which ranged from €0 to €2 550 000, varying extensively within and between continents. From included data, all annual budgets reported by the college added up to €30 million, providing 19 864 courses for 55 161 students. Interpretation: Recovery colleges exist in many countries. There is an international consensus on key operating principles, especially equality and a commitment to recovery, and most recovery colleges achieve moderate to high fidelity to the original model, irrespective of the income band of their country. Cultural differences need to be considered in assessing coproduction and approaches to individualising support. Funding: National Institute for Health and Care Research.</p