Peripheral administration of lactate produces antidepressant-like effects.

This corrects the article DOI: 10.1038/mp.2016.179.

Peripheral administration of lactate produces antidepressant-like effects.

In addition to its role as metabolic substrate that can sustain neuronal function and viability, emerging evidence supports a role for l-lactate as an intercellular signaling molecule involved in synaptic plasticity. Clinical and basic research studies have shown that major depression and chronic stress are associated with alterations in structural and functional plasticity. These findings led us to investigate the role of l-lactate as a potential novel antidepressant. Here we show that peripheral administration of l-lactate produces antidepressant-like effects in different animal models of depression that respond to acute and chronic antidepressant treatment. The antidepressant-like effects of l-lactate are associated with increases in hippocampal lactate levels and with changes in the expression of target genes involved in serotonin receptor trafficking, astrocyte functions, neurogenesis, nitric oxide synthesis and cAMP signaling. Further elucidation of the mechanisms underlying the antidepressant effects of l-lactate may help to identify novel therapeutic targets for the treatment of depression.

European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD) and European Association for the Study of Obesity (EASO) clinical practice recommendations for the management of non-alcoholic fatty liver disease: evaluation of their application in people with Type 2 diabetes.

AIMS: To evaluate the application of the recently proposed recommendations by the European Association for the Study of the Liver, European Association for the Study of Diabetes and European Association for the Study of Obesity for the diagnosis, treatment and follow-up of non-alcoholic fatty liver disease in people with Type 2 diabetes. METHODS: A total of 179 people with Type 2 diabetes were included in this study. Liver fat content (assessed using proton magnetic resonance spectroscopy), fatty liver index score, non-alcoholic fatty liver disease fibrosis score, and SteatoTest and FibroTest scores were determined. RESULTS: According to proton magnetic resonance spectroscopy, 68.7% of participants had steatosis (liver fat content >5.5%). The application of the guidelines using several combinations (fatty liver index + non-alcoholic fatty liver disease fibrosis scores, Steatotest + FibroTest scores, proton magnetic resonance spectroscopy + non-alcoholic fatty liver disease fibrosis score, proton magnetic resonance spectroscopy + FibroTest) resulted in a referral to a liver clinic for 33.5-84.9% people with Type 2 diabetes. CONCLUSIONS: The application of these new algorithms for the diagnosis, and follow-up of non-alcoholic fatty liver disease would lead to an excessive number of people with Type 2 diabetes being referred to a liver clinic. We suggest that new clinical and/or biological biomarkers of steatosis and fibrosis be specifically validated in people with Type 2 diabetes.

Type 1 diabetes is not associated with an increased prevalence of hepatic steatosis.

AIM: Non-alcoholic fatty liver disease (NAFLD) is commonly associated with Type 2 diabetes. Recently, it has been suggested that NAFLD is also frequently associated with Type 1 diabetes and diabetic complications. In this study, we set out to determine whether Type 1 diabetes was associated with liver fat content measured using magnetic resonance imaging. METHODS: One hundred and twenty-eight patients with Type 1 diabetes, 264 patients with Type 2 diabetes and 67 participants without diabetes were included in this study. Hepatic steatosis was defined as a liver fat content > 5.5%. RESULTS: People with Type 1 diabetes and controls were similar for age and BMI. Liver fat content was significantly higher in patients with Type 2 diabetes than in patients with Type 1 diabetes and controls. In the control group, nine people (13.4%) had steatosis compared with six (4.7%) patients with Type 1 diabetes (P = 0.04). Among patients with Type 2 diabetes group, 166 (62.8%) had steatosis. In multivariate analysis that included patients with Type 1 diabetes and participants without diabetes, steatosis was associated only with BMI, whereas age, sex, statin therapy and Type 1 diabetes were not. In patients with Type 1 diabetes, there was no correlation between liver fat content and estimated glomerular filtration rate or carotid intima media thickness. CONCLUSIONS: Our data showed that Type 1 diabetes was not associated with an increased prevalence of steatosis. Moreover, our study provided no specific arguments concerning a link between liver fat content and diabetic complications in patients with Type 1 diabetes.

Body fat distribution and adipokine secretion are not associated with diabetic retinopathy in patients with type 2 diabetes mellitus.

AIMS: The link between diabetic retinopathy (DR) and adipokines is controversial. Some studies suggest that visceral fat and adipokines could be additional risk factors for DR. The aim of this study was to determine the relationship between abdominal fat or adipokine secretion and DR in patients with type 2 diabetes mellitus (DM). METHODS: A total of 179 patients with type 2 DM were included. Each patient underwent measurement of plasma adiponectin and leptin and an evaluation of body fat distribution (visceral and subcutaneous) with MRI. The severity of DR was evaluated according to the classification of the American Academy of Ophthalmology. Patients were classified in 3 groups: absence of DR, mild and moderate DR, and advanced DR (severe, proliferative and laser-treated DR). RESULTS: There were no significant differences between the 3 groups for adiponectin, leptin and visceral or subcutaneous fat accumulation. Patients with DR had a mean duration of diabetes, serum creatinine concentration and percentage of macroalbuminuria significantly higher than patients without DR (p < 0.001, p = 0.003 and p < 0.001, respectively). Serum adiponectin increased with the diabetic nephropathy stage (p = 0.007). CONCLUSIONS: Our study suggests that body fat distribution and adipokine secretion are not associated with DR in patients with type 2 DM.

Small human sperm vacuoles observed under high magnification are pocket-like nuclear concavities linked to chromatin condensation failure.

Since an embryo's ability to grow to the blastocyst stage and implant can be improved by selection of a normal spermatozoon with a vacuole-free head, this study set out to determine the nature of small sperm vacuoles observed under high magnification (>×6300). For 15 infertile men with various sperm profiles, high-magnification microscopy was used to select motile, morphometrically normal spermatozoa with no vacuoles (n=450) or more than two small vacuoles (each of which occupied less than 4% of the head's area; n=450). Spermatozoa acrosome reaction status and degree of chromatin condensation were analysed. Three-dimensional deconvolution microscopy was used to accurately image the nucleus and acrosome at all depths in all spermatozoa. In all 450 spermatozoa with small vacuoles, the latter were seen to be abnormal, DNA-free nuclear concavities. Spermatozoa with small vacuoles were significantly more likely than vacuole-free spermatozoa to have noncondensed chromatin (39.8% versus 9.3%, respectively; P<0.0001). There was no significant difference between the two groups of spermatozoa in terms of acrosome reaction status. No association between chromatin condensation and acrosome reaction status was observed. Small human sperm vacuoles observed under high magnification are pocket-like nuclear concavities related to failure of chromatin condensation.

Self-harm hospitalization following bariatric surgery in adolescents and young adults.

BACKGROUND: While bariatric surgery has demonstrated physical and psychological benefits, a risk of suicide and non-fatal self-harm has also been shown. The aim of this study was to compared the rate of hospitalization for self-harm during a three-year observational follow-up period between adolescents/young adults who underwent bariatric surgery in France in 2013-2014 and two control groups. METHODS: All individuals aged 12-25 years old who underwent bariatric surgery in France between January 1st, 2013, and December 31st, 2014, were identified with a validated algorithm from the French national hospital database, and compared to a healthy sample of the general population matched for age and gender. Information relative to hospitalizations, including for self-harm (ICD-10 codes X60-84), were extracted i) between 2008 and the surgery, and ii) for a three-year follow-up period. A second unmatched control group with obesity but no bariatric surgery was also identified. Survival analyses with adjustments for confounding variables were used. RESULTS: In 2013-2014, 1984 youths had bariatric surgery in France. During follow-up, 1.5% were hospitalized for self-harm vs. 0.3% for controls (p < 0.0001). After adjustment, subsequent hospitalization for self-harm was associated with bariatric surgery (HR 3.64, 95% CI 1.70-7.81), prior psychiatric disorders (HR 7.76, 95% CI 3.76-16.01), and prior self-harm (HR 4.43, 95% CI 1.75-11.24). When compared to non-operated youths with obesity, bariatric surgery was not associated with self-harm while prior mental disorders and self-harm were. Mortality reached 0.3% after surgery. CONCLUSIONS: Bariatric surgery is associated with an increased risk of self-harm, mainly in relation to preexisting psychological conditions. Vigilance and appropriate care are thus warranted in vulnerable individuals.

Large human sperm vacuoles observed in motile spermatozoa under high magnification: nuclear thumbprints linked to failure of chromatin condensation.

BACKGROUND: An embryo's ability to grow and implant can be improved by selection of a normal spermatozoon with a vacuole-free head. However, large vacuoles in spermatozoa have yet to be fully characterized. The present study aimed to determine whether these vacuoles are of nuclear, membrane and/or acrosomal origin. METHODS: We studied 15 infertile patients with differing sperm profiles. For each sperm sample, we used high-magnification (×10 000) contrast microscopy to select and assess 30 normal 'top' spermatozoa and 30 spermatozoa with a large sperm-head vacuole (≥ 25% of the head's cross-sectional area). We subsequently analysed the spermatozoa's degree of chromatin condensation (aniline blue staining), DNA fragmentation (terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labelling assay) and chromosome content (fluorescence in situ hybridization X,Y,18). Atomic force microscopy enabled us to map the plasma sperm membrane in detail. Three-dimensional deconvolution microscopy enabled us to reconstruct images of the nucleus and acrosome in 'top' and 'vacuolated' spermatozoa. RESULTS: We studied a total of 450 'top' spermatozoa and 450 vacuolated spermatozoa. The rate of non-condensed chromatin was higher for 'vacuolated' spermatozoa than for 'top' spermatozoa (36.2 ± 1.9 versus 7.6 ± 1.3%, respectively; P < 0.0001). 'Top' and 'vacuolated' spermatozoa did not differ significantly in terms of DNA fragmentation (0.7 ± 0.4 versus 1.3 ± 0.4% respectively; P = 0.25) or aneuploidy (1.1 ± 0.5 versus 2.2 ± 0.7% respectively; P = 0.21). The majority of aneuploid spermatozoa (9 out of 15) lacked chromatin condensation. In all vacuolated spermatozoa, the acrosome was intact, the plasma membrane was sunken but intact and the large vacuole was identified as an abnormal, 'thumbprint'-like nuclear concavity covered by acrosomal and plasmic membranes. CONCLUSIONS: The large vacuole appears to be a nuclear 'thumbprint' linked to failure of chromatin condensation.

Brain glycogen metabolism: A possible link between sleep disturbances, headache and depression.

The functions of sleep and its links with neuropsychiatric diseases have long been questioned. Among the numerous hypotheses on sleep function, early studies proposed that sleep helps to replenish glycogen stores consumed during waking. Later studies found increased brain glycogen after sleep deprivation, leading to "glycogenetic" hypothesis, which states that there is a parallel increase in synthesis and utilization of glycogen during wakefulness, whereas decrease in the excitatory transmission creates an imbalance causing accumulation of glycogen during sleep. Glycogen is a vital energy reservoir to match the synaptic demand particularly for re-uptake of potassium and glutamate during intense glutamatergic transmission. Therefore, sleep deprivation-induced transcriptional changes may trigger migraine by reducing glycogen availability, which slows clearance of extracellular potassium and glutamate, hence, creates susceptibility to cortical spreading depolarization, the electrophysiological correlate of migraine aura. Interestingly, chronic stress accompanied by increased glucocorticoid levels and locus coeruleus activity and leading to mood disorders in which sleep disturbances are prevalent, also affects brain glycogen turnover via glucocorticoids, noradrenaline, serotonin and adenosine. These observations altogether suggest that inadequate astrocytic glycogen turnover may be one of the mechanisms linking migraine, mood disorders and sleep.

Obesity, type 2 diabetes and risk of digestive cancer.

The frequency of obesity has been increasing worldwide for 20 years. Many epidemiological studies support a correlation between obesity and increased risk of cancer, particularly digestive cancers in both genders, and gynaecological cancer in women. Currently, about 5% of cancers could be directly related to overweight. Carcinogenesis mechanisms induced by obesity involve insulin resistance, adipokine and angiogenic factor secretions, and inflammation. Experimental and clinical evidence suggest that insulin resistance plays a major role in carcinogenesis. Insulin and non-protein banded IGF-1, whose levels are increased in type 2 diabetes, stimulate cellular growth and inhibit apoptosis. Abnormalities in adipokine secretion by the central adipose tissue play a role at different stages of obesity-induced carcinogenesis. Excess of leptin and PAI-1, associated with a decrease in adiponectin secretion in obese people, contributes to carcinogenesis through cellular growth and angiogenesis stimulation. Remodelling of the extracellular matrix due to metalloproteinase stimulation by PAI-1 is also able to promote cell migration. Obesity not only increases cancer frequency, but is also liable to modify the prognosis and the response to antiangiogenic therapy of digestive cancers. This data suggests the need for clinicians to take into account overweight in cancer risk evaluation and to consider obesity and metabolic disorders as confounding factors in designing therapeutic studies.

[Thyroiditis: What's new in 2019?] / Thyroïdites : où en est-on en 2019 ?

Thyroiditis is a frequent and mostly benign disease that can sometimes disrupt the thyroid balance. Their diagnosis, as well as their aetiology, is a necessary step in the management of the patients. Painful thyroiditis includes acute thyroiditis of infectious origin and subacute thyroiditis. The first one can be treated by antibiotics or antifungals depending on the germ found. The second one will be treated with non-steroidal anti-inflammatory drugs or corticosteroids. In cases of Hashimoto's thyroiditis with overt hypothyroidism, replacement therapy with L-thyroxine will be adapted to the TSH level. As amiodarone treatment provides dysthyroidism, the thyroid status should be monitored regularly. Hypothyroidism will be treated using thyroid replacement therapy. Hyperthyroidism imposes a stop of amiodarone when it is possible. Treatment with synthetic antithyroid drugs (propyl-thio-uracil) or corticosteroids could be used whether there is an underlying thyroid disease or not. Immunotherapies with anti-PD-1/PDL1 or anti-CTLA-4 can also provide dysthyroidism. A monitoring of the thyroid assessment needs to be done in these patients, even if there are no clinical signs, which are not very specific in this context. The treatment of hypothyroidism will be based on thyroid replacement therapy according to the TSH level and the presence or absence of anti-TPO antibodies. Treatment of symptomatic hyperthyroidism may involve a prescription of beta-blockers, or synthetic antithyroid drugs in case of positive anti-TSH receptor antibodies. In all cases, it is desirable to contact an endocrinologist to confirm the diagnosis hypothesis and to decide on a suitable treatment.

Whole-exome sequencing identifies the first French MODY 6 family with a new mutation in the NEUROD1 gene.

AIM: The aim of the present study was to identify the affected gene in a French family with maturity-onset diabetes of the young (MODY) using whole-exome sequencing (WES). METHODS: WES was performed in one patient with MODY, and candidate variants were confirmed in members of the immediate family by Sanger sequencing. RESULTS: In the proband, a new heterozygous missense mutation (c.340A>C) was identified in the NEUROD1 gene by WES analysis and confirmed by Sanger sequencing. Additional Sanger sequencing of the proband's sister and mother revealed the same heterozygous mutation. The proband and his sister displayed typical clinical characteristics of MODY, while their mother had the same typical MODY features except for later onset. When clinical and biological profiles were established for all three patients, the severity of diabetes-related complications varied substantially from one family member to another. CONCLUSION: A novel missense mutation found in NEUROD1 was associated with MODY 6 features in a single French family.

Productivity, water-use efficiency and tolerance to moderate water deficit correlate in 33 poplar genotypes from a Populus deltoides x Populus trichocarpa F1 progeny.

Genotypic variability for productivity, water-use efficiency and leaf traits in 33 genotypes selected from an F1 progeny of Populus deltoides Bartr. ex Marsh x Populus trichocarpa L. was explored under optimal and moderate water-deficit conditions. Saplings of the 33 genotypes were grown in a two-plot open field at INRA Orléans (France) and coppiced every year. A moderate water deficit was induced during two successive years on one plot by withholding irrigation, while the second one remained irrigated (control). Stem biomass and leaf structure (e.g., specific leaf area and leaf area) were measured in 2004 and 2005 and functional leaf traits (e.g., carbon isotope discrimination, Delta) were measured only in 2004. Tolerance to water deficit was estimated at genotype level as the ability to limit losses in biomass production in water deficit versus control trees. Stem biomass, leaf structure and Delta displayed a significant genotypic variability whatever the irrigation regime. For all traits, genotype ranks remained stable across years for similar irrigation conditions. Carbon isotope discrimination scaled negatively with productivity and leaf nitrogen content in controls. The most productive genotypes were the least tolerant to moderate water deficit. No relationship was evidenced between Delta and the level of tolerance to water deficit. The relationships between traits evidenced in this collection of P. deltoides x P. trichocarpa F1 genotypes contrast with the ones that were previously detected in a collection of P. deltoides x Populus nigra L. cultivars tested in the same field trial.

[Fast technique to quantify liver steatosis at 3T: principles, parametric imaging and applications]. / Technique rapide de mesure de la stéatose hépatique à 3T: théorie, imagerie paramétrique, applications.

The purpose of this article is to present a fast and clinically usable technique for quantification of liver steatosis. This technique, based on a triple-echo gradient-echo sequence (in-phase, opposed-phase, in-phase), has recently been validated with excellent correlation and accuracy compared to proton MR spectroscopy. The theoretical principles are reviewed, with emphasis on the need to correct for the T2* decay inherent to the use of in-phase and opposed-phase sequences. T1 decay also is negligible due to the use of a low flip angle (20 degrees). The advantage of this technique is that it can generate a parametric representation (map) of liver steatosis, after fast and simple post-processing, based on measurements from standard images (addition, subtraction, division, multiplication) available on the MR scanning console. This parametric method allows quantification of steatosis in focal lesions. The main limitation of the technique relates to its ambiguity with lipid content over 50%, a phenomenon that does not occur with liver steatosis.

CETP activity is not associated with carotid intima-media thickness in patients with poorly controlled type 2 diabetes.

AIM: The impact of cholesteryl ester transfer protein (CETP) on atherosclerotic development in humans remains unclear. Plasma cholesteryl ester transfer was shown to be associated with carotid intima-media thickness in type 2 diabetic (T2D) patients with adequate metabolic control. Since glycation of CETP may influence cholesteryl ester transfer processes, it is important to determine if plasma cholesteryl ester transfer is still a determinant of carotid intima-media thickness (IMT) in patients with poorly controlled diabetes. The aim of the present study was to determine whether CETP activity influences carotid IMT in T2D patients with poor metabolic control. METHODS: In 110 individuals with T2D, we measured CETP mass concentration with ELISA, CETP activity with a radioactivity method and carotid intima-media thickness with high-resolution real-time B-mode ultrasonography. RESULTS: The mean HbA1C was 8.8 ± 1.7%. Carotid IMT did not correlate with CETP activity in the total population. In T2D patients with HbA1C < 8% (n = 33), mean HbA1C was 6.9% and the correlation between carotid IMT and CETP activity was not significant (p = 0.09). In a multivariable analysis that included the total population, carotid intima-media thickness was positively associated with diabetes duration (p = 0.02) but not with CETP activity or HbA1C. CONCLUSIONS: We observed no correlation between carotid intima-media thickness, a marker of early atherosclerosis, and CETP activity in T2D patients with poor metabolic control. Disease duration, which reflects accumulated metabolic abnormalities, may have blunted the potential effect of CETP on atherosclerosis. Metabolic control appears essential to determine the pro- or anti-atherogenic influence of CETP in patients with T2D.

Malnutrition in type 2 diabetic patients does not affect healing of foot ulcers.

AIM: Protein-energy malnutrition is known to be involved in wound healing. While wound healing in patients with diabetic foot ulcers (DFU) is a complex and multifactorial process, the role of malnutrition in this case has rarely been explored. The objective of this study was to determine whether the nutritional status of diabetic patients influences the healing of DFU. METHODS: 48 patients were included in this prospective, single-center study. All patients with comorbidities or factors involving malnutrition or influencing biological measurements were excluded. Patients were followed up for 24 weeks. RESULTS: The malnutrition rate was 29.2% at baseline and 25.6% at the end of the study. The difference was not significant. Of the 35 patients with wound healing, 29% were undernourished at inclusion and 17% at the end of the study. Of the 12 patients without wound healing, 50% were undernourished at inclusion, and 42% at the end of the study. These differences were not significant. Rate and speed of wound healing were not associated with malnutrition at inclusion. 15% of patients without malnutrition at baseline had final malnutrition. CONCLUSION: We demonstrated that wound healing was not affected by the initial presence of malnutrition. In our study, there is no evidence to support nutritional intervention to improve wound healing in diabetic patients. Nevertheless, malnutrition is responsible for an increase in morbidity and mortality and it is essential to identify malnutrition systematically for all patients with DFU, initially and during follow-up to treat it quickly and efficiently.

Type A competitiveness traits correlate with downregulation of c-Fos expression in patients with type 1 diabetes.

AIM: Type A personality has been associated with increased survival in people with type 1 diabetes (T1D). Systemic low-grade inflammation may play a critical role, as suggested in recent reports, although the links between the inflammatory circulating transcriptome and Type A remain unknown. This prompted our exploration of the potential associations between Type A personality and c-Fos gene expression, a candidate gene closely linked to inflammatory processes, in T1D. METHODS: Type A personality was assessed by Bortner questionnaire in patients with T1D, and two subscales - 'speed' and 'competitiveness' - were used to measure these specific dimensions of Type A. Expression of the c-Fos gene was assessed by a quantitative real-time polymerase chain reaction technique. RESULTS: This pilot study included 20 men with T1D. Multivariable analyses showed an independent inverse association between Type A competitiveness score and c-Fos expression, while a regression model adjusted for age, body mass index and HbA1c levels revealed a significant inverse relationship between c-Fos transcripts and Type A competitiveness (P = 0.003). CONCLUSION: This strong association between Type A competitiveness and reduced c-Fos expression is in line with recent data suggesting a psychobiological influence of the Type A profile in T1D via inflammatory pathways.

Specific phenotype associated with diabetes mellitus secondary to chronic hepatitis C infection.

AIM: A link between chronic hepatitis C virus (HCV) infection, Type 2 diabetes mellitus and insulin resistance has been suggested by several studies. However, HCV infection appears to be associated with insulin resistance but not with the metabolic syndrome. The aim of this study was to determine whether chronic HCV infection had an impact on the clinical characteristics of Type 2 diabetes. METHODS: We studied retrospectively a group of patients with diabetes mellitus associated with HCV infection (HCV-DM) and compared them with patients with conventional Type 2 diabetes (DM). RESULTS: The HCV-DM patients had a lower body mass index (P = 0.001) and systolic blood pressure (P = 0.04) compared with patients with DM diabetes. Ten patients (27.0%) in the HCV-DM group and 35 (47.3%) in the DM group had microalbuminuria (P = 0.04). DM patients had significantly higher serum creatinine levels than HCV-DM patients [87 (72-108) vs. 77 (64-86) micromol/l, P = 0.02; median (interquartile range)] but creatinine clearance (Cockroft Gault calculation) was similar. One HCV-DM patient (2.7%) and 44 DM patients (59.4%) were treated with hypolipidaemic therapy (P = 0.0001). Even although nearly two-thirds of the overall DM group were prescribed cholesterol-lowering drugs, DM patients had significantly higher total cholesterol, high-density lipoprotein cholesterol and triglyceride levels than HCV-DM patients. CONCLUSION: Our study provides further evidence that HCV-DM patients have specific clinical characteristics in comparison with classical DM patients. These data suggest an association between HCV virus infection and the development of insulin resistance or diabetes mellitus without the typical features of the metabolic syndrome.

Induction of brain aquaporin 9 (AQP9) in catecholaminergic neurons in diabetic rats.

Aquaporin 9 facilitates the diffusion of water but also glycerol and monocarboxylates, known as brain energy substrates. AQP9 was recently observed in catecholaminergic neurons that are implicated in energy homeostasis and also possibly in neuroendocrine effects of diabetes. Recently it has been observed that the level of AQP9 expression in hepatocytes is sensitive to the blood concentration of insulin. Furthermore, insulin injection in the brain is known to be related to the energy homeostasis. Based on these observations, we investigated if the concentration of insulin affects the level of brain AQP9 expression and if so, in which cell types. This study has been carried out, in a model of the diabetic rat generated by streptozotocin injection and on brainstem slices. In diabetic rats showing a decrease in systemic insulin concentration, AQP9 is only increased in brain areas containing catecholaminergic neurons. In contrast, no significant change is detected in the cerebral cortex and the cerebellum. Using immunocytochemistry, we are able to show that the increase in AQP9 expression is specifically present in catecholaminergic neurons. In brainstem slice cultures, 2 microM insulin induces a significant decrease in AQP9 protein levels 6 h after application, suggesting that brain AQP9 is also regulated by the insulin. These results show that the level of expression of brain AQP9 is affected by variations of the concentration of insulin in a diabetic model and in vitro.

Knowledge, attitudes, and practices about homelessness and willingness-to-pay for housing-first across 8 European countries: a survey protocol.

BACKGROUND: Most European countries report rising numbers of people experiencing homelessness. For those with mental disorders, interventions are centered on achieving mental health and drug rehabilitation alongside housing readiness, often to the detriment of access to housing. Notwithstanding, more European countries are investing in a new model, Housing First (HF), which postulates immediate access to permanent housing with no initial requirements for treatment. While results of the European HF programs are published on individual-level data, little is known about the opinions of the general population about homelessness and the societal value of the HF model, which can represent barriers to the model's dissemination. Therefore, we present the protocol of a study designed for the following objectives: 1) to explore the knowledge, attitudes, and practices (KAP) about homelessness within the general population of 8 European countries, 2) to assess the valuation of the HF model by European citizens, and 3) to estimate the lifetime prevalence of homelessness in the targeted countries. METHODS: A telephone survey was conducted from March to December 2017 among adults selected from opt-in panels from France, Ireland, Italy, the Netherlands, Portugal, Spain, Poland, and Sweden. A total sample of 5600 interviews was expected, with 700 per country. The interviews included three sections: first, the KAP about homelessness; second, the valuation of the HF model by measuring a respondent's willingness-to-pay (WTP) through the contingent valuation method; and third, an assessment of the lifetime prevalence of homelessness among the general population. Descriptive analyses and comparisons between countries will be conducted. KAP indicators will be created and their psychometric properties assessed. Determinants of WTP will be assessed through regression models. DISCUSSION: This survey will highlight Europeans' views of homelessness, especially their level of tolerance towards homelessness, potential misconceptions and the most important barriers for the implementation of the HF model. Additionally, the results on the valuation of the HF model by citizens could be instrumental for key stakeholders in understanding the level of support from the general population. Ethics approval has been obtained from the Aix-Marseille University Ethics Committee (n° 2016-01-02-01) for this study, which is part of HOME_EU: Reversing Homelessness in Europe H2O20-SC6-REVINEQUAL-2016/GA726997.