The E6E7 oncoproteins of cutaneous human papillomavirus type 38 interfere with the interferon pathway

Non-melanoma skin cancer is the most frequent malignancy in Caucasian populations. Evidence suggests the involvement of cutaneous Human Papillomavirus (HPV) of the genus beta (beta) in this disease. The ability of E6 and E7 of mucosal HPV to promote cellular transformation and inhibit immune response-related pathways plays a key role in cervical carcinogenesis. beta HPV-38 E6 and E7 display transforming activities in in vitro and in vivo models, but their impact on immune surveillance is unknown. Here we show that HPV-38 E6 and E7 affect the IFN-induced up-regulation of MHC class I. Expression of the two viral proteins in HaCaT keratinocytes led to a decrease of MHC I levels. This down-regulation is associated with a reduction of expression of MHC I heavy chain, of the peptide chaperone TAP and of the STAT-1 downstream effector IRF-1. The down-regulation of these proteins is ultimately due to the inhibition of STAT-1 expression. Analysis of cells expressing either HPV-38 E6 or E7 suggests that these effects are primarily the result of E6 expression, although a contribution by E7 cannot be excluded. We conclude that HPV-38 encodes oncoproteins that potentially contribute to the evasion of host immune surveillance.     

Human papillomavirus type 45 E7 is a transforming protein inducing retinoblastoma protein degradation and anchorage-independent cell cycle progression

High-risk human papillomaviruses (HPV) cause cervical cancer. The biological properties of HPV-45, the third most prevalent high-risk HPV-genotype, are unknown. We demonstrate here that the HPV-45 E7 protein transforms immortalized NIH3T3 fibroblasts, while mutations in either the conserved LXCXE sequence (C28G) or the carboxyl-terminus (Δ87LQQLF91) significantly abolish this activity. To address the mechanisms underlying cell transformation by HPV-45 E7, we investigated its impact on the cell cycle. We show that HPV-45 E7 associates with the hypophosphorylated form of the retinoblastoma protein (pRb) and induces a significant reduction in the pRb half-life which can be blocked by epoxomicin. Moreover, HPV-45 E7 induces anchorage-independent cell cycle progression of NIH3T3 cells and extends the lifespan of primary human keratinocytes. HPV-45 E7C28G did not bind pRb and could neither induce pRb-proteolysis nor promote cell cycle progression. HPV-45 E7Δ87LQQLF91 had intermediate pRb-binding affinity and retained a residual activity to induce the degradation of pRb but lost the capability to promote cell cycle progression in suspension. Another carboxyl-terminal mutant, HPV-45 E7Δ81AEDL84, showed a trend to reduced transforming activity, had reduced pRb-binding activity and lost the capability to induce pRb-degradation; however, this mutant could induce anchorage-independent cell cycle progression with the same efficiency as HPV-45 E7 wild type. In summary, these data suggest that HPV-45 E7 is a transforming protein and that abrogation of cell cycle control contributes to its oncogenic potential.     

Anatomie et tendinopathie patellaire : un malentendu

The anatomical structure linking the patella and the tibia is called the “patellar ligament” in the international nomenclature. This term is well accepted yet can be a source of confusion for non-specialists. This is because the priority role of this structure is not to maintain joint stability, the primary role of the cruciate ligaments and the collateral ligaments, but rather to prolong the mechanical action of the quadriceps muscle onto the leg skeleton beyond the “patellar sesmoid”. Patellar tendon injuries are a common observation in sports medicine. The proximal third of the tendon below the patella is most generally involved. This highly frequent tendinopathy sometimes termed an “insertion” tendiopathy. Based on 100 consecutive magnetic resonance imaging studies and cadaveric dissection, we confirm that the insertion of the patellar tendon is situated on the anterior aspect of the patella and not the tip. We describe two anatomical variants of the healthy patellar tendon (type 1 and 2) that should not be confused with a site of tendinopathy. The anatomical limits between tendinous tissue and infrapatellar adipose body (the Hoffa adipose ligament), notably on the upper third is still debated and merits further work.     

Le vécu parental à la loupe : résultats d’une enquête en ligne du GREEN

An anonymous online survey was conducted between February 2014 and October 2015 to describe parental perceptions concerning their participation in the care of their neonates hospitalized since birth in a neonatal unit in France. More than 3,300 parents completed the questionnaire. Parents felt very stressed the first time they took part in the caring of their neonates. Most parents reported they felt supported by the caregivers but not enough encouraged by them to do simple caregiving activities for which they felt capable. Skin-to-skin care was described as insufficiently proposed     

Facteurs de risque précoces et trajectoires développementales du trouble déficit de l’attention/hyperactivité (TDAH)

Attention Deficit/Hyperactivity Disorder (ADHD) is associated with a set of early genetic and environmental risk factors. Genetic risk factors, of which existence is supported by genetically informed (i.e. Twin) and molecular studies, are yet partially identified. They do not constitute diagnostic markers or therapeutic targets for preventive interventions. Early environmental risk factors exist and could represent targets for early interventions. However, their causal nature is not determined yet. In addition, early environmental risk factors are distal factors compared with later risk factors, which makes difficult the understanding of their direct links with the ADHD phenotype. Developmental trajectories of ADHD are interesting to study in order to take into account the dimensional and developmental nature of ADHD. Investigating the link between early risk factors and developmental trajectories could allow a better understanding of their interactions along time. The experiment of preventive interventions of ADHD could lead to disentangle mechanisms and provide new tools to treat ADHD.     

Influence of short-chain fatty acids on iron absorption by proximal colon

BACKGROUND: Short-chain fatty acids produced by bacterial fermentation in the colon enhance the local absorption of cations, such as calcium, that could be used to improve the bioavailability of iron if a significant colonic absorption of iron were to occur. METHODS: Iron (iron gluconate, 100 microM) absorption by the caecum of the rat was compared with that in proximal sites of the small bowel using the Ussing chamber model; the influence of probiotic bacteria (Propionibacterium freudenreichii) on iron absorption was assessed and compared with that of two of their fermentation products (acetic and propionic acids) using the Ussing chamber and the ligated colon with gamma emitting iron as experimental models. RESULTS: The caecum absorbed less iron than the duodenum, but significantly more than the jejunum and ileum. This occurred mainly through an enhanced mucosal transfer of iron uptake. Propionibacteria enhanced iron absorption from the proximal colon; the same effect was observed in the presence of viable bacteria, or the culture medium free of viable bacteria, or acetate and propionate or propionate alone. CONCLUSIONS: The proximal colon could be a significant site available for iron absorption; this absorption can be enhanced by local production of short-chain fatty acids such as propionate.     

A randomized controlled trial of cognitive therapy versus intensive behavior therapy in obsessive compulsive disorder

BACKGROUND: The study was designed to compare cognitive therapy (CT) with intensive behavior therapy (BT) in obsessive-compulsive disorder (OCD) and to study their change process. METHODS: Sixty-five outpatients with DSM-4 OCD were randomized into 2 groups for 16 weeks of individual treatment in 3 centers. Group 1 received 20 sessions of CT. Group 2 received a BT program of 20 h in two phases: 4 weeks of intensive treatment (16 h), and 12 weeks of maintenance sessions (4 h). No medication was prescribed. RESULTS: Sixty-two patients were evaluated at week 4, 60 at week 16 (post-test), 53 at week 26 and 48 at week 52 (follow-up). The response rate was similar in the 2 groups. The Beck Depression Inventory (BDI) was significantly more improved by CT (p = 0.001) at week 16. The baseline BDI and Obsessive Thoughts Checklist scores predicted a therapeutic response in CT, while the baseline BDI score predicted a response in BT. At week 16, only the changes in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and a scale measuring the interpretation of intrusive thoughts correlated in CT, while the changes in Y-BOCS, BDI, and interpretation of intrusive thoughts correlated in BT. Improvement was retained at follow-up without a between-group difference. The intent-to-treat analysis (last observation carried forward) found no between-group differences on obsessions, rituals and depression. CONCLUSIONS: CT and BT were equally effective on OCD, but at post-test CT had specific effects on depression which were stronger than those of BT. Pathways to improvement may be different in CT and BT. The outcomes are discussed in the light of an effect size analysis.     

Validation of a scale for responsibility (Salkovskis Responsibility Scale)

Appraisal of inflated responsibility for harm is the cornerstone of Salkovskis's cognitive theory for obsessive compulsive disorder. The aim of our study is to present the validation study of the French translation of the R scale. The present study compared 50 subjects with obsessive compulsive disorder, 37 patients suffering from social phobia and 183 control subjects on a responsibility questionnaire (R scale). The cognitive hypothesis of Obsessive Compulsive Disorder (OCD) specifies two levels of responsibility-related cognitions: responsibility assumptions (attitudes) and responsibility appraisals (interpretations). The R scale evaluates the responsibility assumptions. Such attitudes should reflect the more generalized tendency to assume responsibility in a given situation, particularly situations involving intrusions and doubts. It is possible that such assumptions may be less specific to OCD. The inclusion of social phobia subjects in the present study allows evaluation of the specificity of any findings to OCD. Patients were diagnosed and classified according DSM IV criteria. The control subjects were taken in the general population. No formal interview was conducted. The three groups were compared for sex, age and educational level. Before treatment, all the participants filled in the Responsibility Scale of Salkovskis (27 items), the Beck Depression Inventory (21 items), the Beck Anxiety Inventory and the Bouvard's Obsessive Compulsive Thoughts Checklist. The results indicate that the two anxious groups scored significantly higher than the control group on Beck Depression and Anxiety Inventories but no significant difference was observed between the two anxious groups. OCD patients scored significantly higher than both social phobic patients and control subjects on the Obsessive Compulsive Thoughts Checklist (OCTC). The social phobic group scored this checklist significantly higher than the control group. In sum, the three groups were different on obsessive compulsive thoughts. On the washing subscale of the Obsessive Compulsive Thoughts Checklist, the OCD patients differed significantly from the control group and the social phobia patients. No difference was observed between the social phobia subjects and the control group. On the two other subscales of the OCTC, the checking and the responsibility scales, the three groups were different: OCD patients scored significantly higher than both social phobic patients and control subjects; the social phobic patients scored higher than the control group. Results support the reliability (test retest) and the internal consistency of the questionnaire. Patients with obsessive compulsive disorder (OCD) and social phobia subjects had significantly elevated score on the total scale compared to control subjects. However social phobia patients did not differ from patients with OCD. So, the responsibility for harm, evaluated by the R-scale seems not to be specific of OCD. This finding does not support the results of two studies (28, 30). But these two studies compared OCD patients with an anxious group including panic disorder with agoraphobia, generalized anxiety disorder and social phobia. The correlations with a measure of OCD symptoms were higher than the correlations with anxiety and depression. Finally, the factor structure was only studied on the control group. The exploratory factor analysis indicates that the R scale is a two-dimensional scale, reflecting a need to prevent risks and the belief that one has power to harm. The first dimension is less specific to the pathology than the second. Only patients with OCD had significantly elevated score on the "need to prevent risks" compared to the non-clinical group. The two anxious groups differed on "the belief that one has power to harm" from the non-clinical group but social phobia patients did not differ from patients with OCD. In sum, the two subscales of the R scale did not discriminate OCD patients and social phobic subjects. Further research is needed to replicate the present findings and to confirm the two dimensions of the R scale. Overall, the results are consistent with the hypothesis that responsibility beliefs are important in the experience of obsessional problems. However, responsibility assumptions such as the belief that one has the power to harm are shared with social phobia.