Les centres ressource pour les intervenants auprès des auteurs de violences sexuelles (CRIAVS) se sont développés depuis la circulaire DHOS/DGS/O2/6C no 2006-168 du 13 avril 2006. Présent dans ...chaque région en France, les CRIAVS accompagnent les professionnels dans la prise en charge des auteurs de violences sexuelles. La prise en charge de ces problématiques suscite des résistances chez les professionnels confrontés, et ce pour plusieurs raisons : les représentations que nous avons de cette population, les lacunes en matière de formation, mais aussi et surtout la complexité des dispositifs judiciaires qui s’offrent comme cadre à ces prises en charge (soins pénalement ordonnées) dans lesquelles le professionnel peut rencontrer des difficultés à définir ses droits, ses devoirs, mais aussi ses missions vis-à-vis de son patient. En outre, les professionnels soignants (psychiatres, psychologues) peuvent aussi être sollicités sur des missions d’ordre judiciaire : l’expertise ou la coordination médicale des injonctions de soin. Ainsi, la prise en charge, ou plutôt les prises en charges des auteurs de violences sexuelles posent de nombreuses questions cliniques, éthiques, légales et institutionnelles que les CRIAVS ont pour mission d’éclairer afin de soutenir l’ensemble des institutions et professionnels qui en ferait la demande. Or si ces structures sont aujourd’hui bien implantées et actives au plan régional et national (constitution de la Fédération française des CRIAVS), il est néanmoins nécessaire d’en promouvoir l’existence et d’en expliciter les missions afin de rendre l’accès à ses services le plus fluide possible. C’est pourquoi la Fédération française des CRIAVS propose une communication à destination des professionnels de la santé mentale, public privilégié de nos actions, comme invitation à se saisir de l’expertise des professionnels qui y exercent et se mettront volontiers à leur service.
Pneumonia is the leading cause of death of children. Diagnostic tools include chest radiography, but guidelines do not currently recommend the use of lung ultrasound (LUS) as a diagnostic method. We ...conducted a meta-analysis to summarize evidence on the diagnostic accuracy of LUS for childhood pneumonia.
We performed a systematic search in PubMed, Embase, the Cochrane Library, Scopus, Global Health, World Health Organization-Libraries, and Latin American and Caribbean Health Sciences Literature of studies comparing LUS diagnostic accuracy against a reference standard. We used a combination of controlled key words for age <18 years, pneumonia, and ultrasound. We identified 1475 studies and selected 15 (1%) for further review. Eight studies (765 children) were retrieved for analysis, of which 6 (75%) were conducted in the general pediatric population and 2 (25%) in neonates. Eligible studies provided information to calculate sensitivity, specificity, and positive and negative likelihood ratios. Heterogeneity was assessed by using Q and I(2) statistics.
Five studies (63%) reported using highly skilled sonographers. Overall methodologic quality was high, but heterogeneity was observed across studies. LUS had a sensitivity of 96% (95% confidence interval CI: 94%-97%) and specificity of 93% (95% CI: 90%-96%), and positive and negative likelihood ratios were 15.3 (95% CI: 6.6-35.3) and 0.06 (95% CI: 0.03-0.11), respectively. The area under the receiver operating characteristic curve was 0.98. Limitations included the following: most studies included in our analysis had a low number of patients, and the number of eligible studies was also small.
Current evidence supports LUS as an imaging alternative for the diagnosis of childhood pneumonia. Recommendations to train pediatricians on LUS for diagnosis of pneumonia may have important implications in different clinical settings.
Aim
Over the last decades, the shift in age distribution towards older ages and the progressive ageing which has occurred in most populations have been paralleled by a global epidemic of obesity and ...its related metabolic disorders, primarily, type 2 diabetes (T2D). Dysfunction of the adipose tissue (AT) is widely recognized as a significant hallmark of the ageing process that, in turn, results in systemic metabolic alterations. These include insulin resistance, accumulation of ectopic lipids and chronic inflammation, which are responsible for an elevated risk of obesity and T2D onset associated to ageing. On the other hand, obesity and T2D, the paradigms of AT dysfunction, share many physiological characteristics with the ageing process, such as an increased burden of senescent cells and epigenetic alterations. Thus, these chronic metabolic disorders may represent a state of accelerated ageing.
Materials and methods
A more precise explanation of the fundamental ageing mechanisms that occur in AT and a deeper understanding of their role in the interplay between accelerated ageing and AT dysfunction can be a fundamental leap towards novel therapies that address the causes, not just the symptoms, of obesity and T2D, utilizing strategies that target either senescent cells or DNA methylation.
Results
In this review, we summarize the current knowledge of the pathways that lead to AT dysfunction in the chronological ageing process as well as the pathophysiology of obesity and T2D, emphasizing the critical role of cellular senescence and DNA methylation.
Conclusion
Finally, we highlight the need for further research focused on targeting these mechanisms.
Longtemps déniée dans les services prenant en charge les patients souffrant de psychose, la sexualité s’est imposée comme une des dimensions fondamentales de la qualité de vie des patients.
Cet ...article propose une grille de lecture, dimensionnelle et transnosographique, permettant la structuration et la mise en lien des données sur le fonctionnement sexuel et le fonctionnement psychologique, afin d’améliorer l’évaluation et la prise en charge des problématiques sexuelles des patients.
À partir d’une recension narrative des écrits scientifiques, cet article présente les freins conceptuels, cliniques et épistémologiques à la prise en compte de la santé sexuelle des patients vivant avec un handicap psychique ; puis il propose une grille de lecture des dysfonctionnements sexuels. Enfin, il illustre l’intérêt dans son application clinique au travers d’un exemple chez des personnes présentant une schizophrénie.
Nous argumentons la structuration de la grille de lecture selon 2 axes – bio-psychosocial et diachronique-synchronique. Ces deux axes rendent compte de la complexité du fonctionnement sexuel et psychologique, et permettent une démarche compréhensive des dysfonctions sexuelles, en lien avec les altérations des fonctions psychologiques.
La grille de lecture proposée offre un support d’analyse du fonctionnement sexuel de manière transnosographique.
For a long time ignored in mental health services for patients with psychosis, sexuality has now become one of the fundamental dimensions of patients’ quality of life.
In order to improve the assessment and management of patients’ sexual problems, this article proposes a dimensional and transnosographic assessment framework, structuring and linking of data on sexual and psychological functioning.
A narrative review of the scientific literature focusing on the sexual health. This article presents the conceptual, clinical and epistemological obstacles to taking into account the sexual health of patients, living with a psychological disability; then this article proposes an analysis framework of sexual and psychological dysfunctions; Finally, it illustrates the interest in its application through an example in people with schizophrenia.
We argue the relevance of the structuring of the assessment according to 2 axes – bio-psychosocial and diachronic-synchronic. These two axes take into account the complexity of sexual and psychological functioning, and allow a comprehensive approach of sexual dysfunctions, in connection with the alterations of psychological functions.
The proposed assessment offers a support for the analysis of sexual functioning in a transnosographic way.
Aims/hypothesis
Chronic hyperglycaemia aggravates insulin resistance, at least in part, by increasing the formation of advanced glycation end-products (AGEs). Methylglyoxal (MGO) is the most reactive ...AGE precursor and its abnormal accumulation participates in damage in various tissues and organs. Here we investigated the ability of MGO to interfere with insulin signalling and to affect beta cell functions in the INS-1E beta cell line.
Methods
INS-1E cells were incubated with MGO and then exposed to insulin or to glucose. Western blotting was used to study signalling pathways, and real-time PCR to analyse gene expression; insulin levels were determined by radioimmunoassay.
Results
Non-cytotoxic MGO concentrations inhibited insulin-induced IRS tyrosine phosphorylation and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) pathway activation independently from reactive oxygen species (ROS) production. Concomitantly, formation of AGE adducts on immunoprecipitated IRS was observed. Aminoguanidine reversed MGO inhibitory effects and the formation of AGE adducts on IRS. Further, the insulin- and glucose-induced expression of
Ins1
,
Gck
and
Pdx1
mRNA was abolished by MGO. Finally, MGO blocked glucose-induced insulin secretion and PI3K/PKB pathway activation. These MGO effects were abolished by LiCl, which inhibits glycogen synthase kinase-3 (GSK-3).
Conclusions/interpretation
MGO exerted major damaging effects on INS-1E cells impairing both insulin action and secretion. An important actor in these noxious MGO effects appears to be GSK-3. In conclusion, MGO participates not only in the pathogenesis of the debilitating complications of type 2 diabetes, but also in worsening of the diabetic state by favouring beta cell failure.
Aims/hypothesis
Type 2 diabetes and obesity are associated with increased risk of site-specific cancers. We have investigated whether metabolic alterations at the level of adipose-derived ...differentiating cells may affect specific phenotypes of breast cancer cells.
Methods
Growth profiles of breast cancer cell lines were evaluated in co-cultures with differentiated adipocytes or their precursor cells and upon treatment with adipocyte conditioned media. Production and release of cytokines and growth factors were assessed by real-time RT-PCR and multiplex-based ELISA assays.
Results
Co-cultures with either differentiated mouse 3T3-L1 or human mammary adipocytes increased viability of MCF-7 cells to a greater extent, when compared with their undifferentiated precursors. Adipocytes cultured in 25 mmol/l glucose were twofold more effective in promoting cell growth, compared with those grown in 5.5 mmol/l glucose, and activated mitogenic pathways in MCF-7 cells. Growth-promoting action was also enhanced when adipocytes were incubated in the presence of palmitate or oleate. Interestingly, 3T3-L1 and human adipocytes released higher amounts of keratinocyte-derived chemokine/IL-8, the protein ‘regulated upon activation, normally T expressed, and secreted’ (RANTES), and IGF-1, compared with their precursor cells. Their levels were reduced upon incubation with low glucose and enhanced by fatty acids. Moreover, both undifferentiated cells and differentiated adipocytes from obese individuals displayed about twofold higher IGF-1 release and MCF-7 cell growth induction than lean individuals. Finally, inhibition of the IGF-1 pathway almost completely prevented the growth-promoting effect of adipocytes on breast cancer cells.
Conclusions/interpretation
IGF-1 release by adipocytes is regulated by glucose and fatty acids and may contribute to the control of cancer cell growth in obese individuals.
The genomic bases of the adipose tissue abnormalities induced by chronic positive calorie excess have been only partially elucidated. We adopted a genome-wide approach to directly test whether ...long-term high-fat diet (HFD) exposure affects the DNA methylation profile of the mouse adipose tissue and to identify the functional consequences of these changes.
We have used epididymal fat of mice fed either high-fat (HFD) or regular chow (STD) diet for 5 months and performed genome-wide DNA methylation analyses by methylated DNA immunoprecipitation sequencing (MeDIP-seq). Mouse Homeobox (Hox) Gene DNA Methylation PCR, RT-qPCR and bisulphite sequencing analyses were then performed.
Mice fed the HFD progressively expanded their adipose mass accompanied by a significant decrease in glucose tolerance (P<0.001) and insulin sensitivity (P<0.05). MeDIP-seq data analysis revealed a uniform distribution of differentially methylated regions (DMR) through the entire adipocyte genome, with a higher number of hypermethylated regions in HFD mice (P<0.005). This different methylation profile was accompanied by increased expression of the Dnmt3a DNA methyltransferase (Dnmt; P<0.05) and the methyl-CpG-binding domain protein Mbd3 (P<0.05) genes in HFD mice. Gene ontology analysis revealed that, in the HFD-treated mice, the Hox family of development genes was highly enriched in differentially methylated genes (P=0.008). To validate this finding, Hoxa5, which is implicated in fat tissue differentiation and remodeling, has been selected and analyzed by bisulphite sequencing, confirming hypermethylation in the adipose tissue from the HFD mice. Hoxa5 hypermethylation was associated with downregulation of Hoxa5 mRNA and protein expression. Feeding animals previously exposed to the HFD with a standard chow diet for two further months improved the metabolic phenotype of the animals, accompanied by return of Hoxa5 methylation and expression levels (P<0.05) to values similar to those of the control mice maintained under standard chow.
HFD induces adipose tissue abnormalities accompanied by epigenetic changes at the Hoxa5 adipose tissue remodeling gene.
Indoor smoke exposure may affect cardiovascular disease (CVD) risk via lung‐mediated inflammation, oxidative stress, and endothelial inflammation. We sought to explore the association between indoor ...smoke exposure from burning biomass fuels and a selected group of markers for endothelial inflammation. We compared serum concentrations of amyloid A protein, E‐selectin, soluble intercellular adhesion molecule 1 (ICAM‐1) and VCAM‐1, von Willebrand factor (vWF), and high‐sensitivity C‐reactive protein (hs‐CRP) in 228 biomass‐exposed vs. 228 non‐exposed participants living in Puno, Peru. Average age was 56 years (s.d. = 13), average BMI was 26.5 kg/m2 (s.d. = 4.4), 48% were male, 59.4% completed high school, and 2% reported a physician diagnosis of CVD. In unadjusted analysis, serum levels of soluble ICAM‐1 (330 vs. 302 ng/ml; P < 0.001), soluble VCAM‐1 (403 vs. 362 ng/ml; P < 0.001), and E‐selectin (54.2 vs. 52.7 ng/ml; P = 0.05) were increased in biomass‐exposed vs. non‐exposed participants, respectively, whereas serum levels of vWF (1148 vs. 1311 mU/ml; P < 0.001) and hs‐CRP (2.56 vs. 3.12 mg/l; P < 0.001) were decreased, respectively. In adjusted analyses, chronic exposure to biomass fuels remained positively associated with serum levels of soluble ICAM‐1 (P = 0.03) and VCAM‐1 (P = 0.05) and E‐selectin (P = 0.05), and remained negatively associated with serum levels of vWF (P = 0.02) and hs‐CRP (P < 0.001). Daily exposure to biomass fuel smoke was associated with important differences in specific biomarkers of endothelial inflammation and may help explain accelerated atherosclerosis among those who are chronically exposed.
•Clinical characteristics and fosfomycin synergism of KPC-variants were investigated.•KPC-variant detection follows a previous CZA-susceptible KPC-Kp in the same patient.•Treatment with meropenem ...achieved clinical cure in all the patients.•Fosfomycin plus meropenem resulted in full synergism in 40% of cases.•FOS plus MEM may be an option for KPC-variant infections at low risk of mortality.
Little is known regarding outcomes and optimal therapeutic regimens of infections caused by Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) resistant to ceftazidime/avibactam (CZA) and susceptible to meropenem (MEM). Although susceptible to MEM in vitro, the possibility of developing MEM resistance overtime is a concern. We describe the clinical characteristics of patients with colonization/infection due to KPC variants with a focus on the in vitro activity of fosfomycin (FOS)-containing combinations.
Patients with colonization/infection due to a KPC variant were included. Fosfomycin susceptibility was performed by agar dilution method. Synergistic activity of FOS-based combinations was evaluated by gradient strip-agar diffusion method. The emergence of in vitro MEM resistance was also tested.
Eleven patients were included: eight with infection four with ventilator-associated pneumonia and four with bloodstream infections and three with colonization. Previous therapy with CZA was administered to all patients (with a mean cumulative duration of 23 days). All subjects with infection received meropenem, in monotherapy (n = 4) or with amikacin (n = 2) or fosfomycin (n = 2), and achieved clinical cure. A new CZA-susceptible and MEM-resistant KPC-Kp strain was subsequently isolated in three patients (27.3%). Meropenem/vaborbactam (MVB) showed high in vitro activity, while FOS+MEM combination was synergistic in 40% of cases. In vitro resistance to MEM was observed with maintenance of CZA resistance.
Detection of KPC variants may occur within the same patient, especially if CZA has been previously administered. Although clinical success has been obtained with carbapenems, the emergence of MEM resistance is a concern. Fosfomycin plus meropenem is synergistic and may be a valuable combination option for KPC variants, while MVB may be considered in monotherapy. The detection of KPC variants in an endemic setting for KPC-Kp represents a worryingly emerging condition. The optimal therapeutic approach is still unknown and the development of meropenem resistance is of concern, which may lead to therapeutic failure in clinical practice. In these cases, the addition of fosfomycin to meropenem, or a more potent antibiotic, such as meropenem/vaborbactam, may be valuable therapeutic options.
AMP-activated protein kinase (AMPK) serves as a major regulator of energy homeostasis and is activated by different glucose-lowering agents. Indeed, AMPK has been identified as an attractive target ...for the development of innovative molecules to treat type 2 diabetes. In this issue of
Diabetologia
(doi:
10.1007/s00125-011-2366-3
), Huang and co-workers report that arctigenin activates muscle uptake of glucose and inhibits hepatocyte gluconeogenesis and lipogenesis by reducing mitochondrial respiration and inducing AMPK activity. Importantly, it is reported that arctigenin improves glucose and lipid metabolism in
ob/ob
mice. Based on this evidence, Huang and co-workers suggest that arctigenin may represent a valuable lead compound for developing innovative glucose-lowering molecules. While these findings are not entirely novel and mechanistic investigations are needed, the results strongly support the concept that arctigenin deserves to be further considered because of its several potentially beneficial in vivo effects. In particular, the authors conclude that further mechanistic studies on arctigenin might provide novel insight and opportunities for selective modulation of subcutaneous and visceral fat mass.
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