Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1 beta production.

Interleukin 1 beta (IL-1 beta) is a potent proinflammatory factor during viral infection. Its production is tightly controlled by transcription of Il1b dependent on the transcription factor NF-kappaB and subsequent processing of pro-IL-1 beta by an inflammasome. However, the sensors and mechanisms that facilitate RNA virus-induced production of IL-1 beta are not well defined. Here we report a dual role for the RNA helicase RIG-I in RNA virus-induced proinflammatory responses. Whereas RIG-I-mediated activation of NF-kappaB required the signaling adaptor MAVS and a complex of the adaptors CARD9 and Bcl-10, RIG-I also bound to the adaptor ASC to trigger caspase-1-dependent inflammasome activation by a mechanism independent of MAVS, CARD9 and the Nod-like receptor protein NLRP3. Our results identify the CARD9-Bcl-10 module as an essential component of the RIG-I-dependent proinflammatory response and establish RIG-I as a sensor able to activate the inflammasome in response to certain RNA viruses.

Potential schistosome-vector snails and associated trematodes in ricefields of Corrients province, Argentina: preliminary results

Considering the possibility of introduction of schistosomiasis mansoni into Argentina as a consequence of dam construction on the Rio De La Plata basin, preliminary studies have been carried out on agrosystems such as ricefields in Corrientes province with the following purposes: 1) to survey and estimate the relative abundance of planorbids and identify potential vector species; 2) to identify environmental factors capable of influencing Biomphalaria population dynamics; and 3) to find out snail-parasite associations and estimate snail infection rates in order to detect possible competitive interactions between larval stages of native trematodes that could be used in biological control of Schistosoma mansoni. Three potential schistosome vectors were detected in ricefields, namely Biomphalaria straminea, B. tenagophila and B. peregrina, although B. orbignyi, a species refractory to infection with S. mansoni, proved the most frequent and abundant. Positive correlations (P<0.05) were found between Biomphalaria abundance and some environmental parameters: conductivity, hardness, calcium, nitrites plus nitrates, ammonium and bicarbonates. Water temperature correlation was negative (P<0.05). No correlation (P>0.05) was found in total iron, phosphates (SRP), pH and soil granulometry. Echinocercariae developed from rediae and belonging to Petasiger sp., Paryphostomum sp., and other undetermined species were found.

Treatment of central retinal vein occlusion-related macular edema with intravitreal bevacizumab (Avastin): preliminary results.

PURPOSE: To assess the safety and efficacy of treatment of macular edema secondary to central retinal vein occlusion (CRVO) with intravitreal bevacizumab. PATIENTS AND METHOD: The ongoing prospective study included 8 consecutive patients (8 eyes) with macular edema secondary to CRVO (6 non ischemic and 2 ischemic), treated with intravitreal injection of 1.25 mg (0.05 mL) of bevacizumab. Main outcome was best corrected visual acuity (BCVA) and central foveal thickness (CFT) measured by optical coherence tomography monthly during one year. Retreatment criteria include decrease of BCVA, persistence of macular edema on angiograms and increase of CFT. RESULTS: Mean age of the eight patients was 68 years (range: 50-82 years). Mean duration of symptoms before injection was 98 days (range: 3-289). Mean follow-up was 3.25 months. At baseline, mean BCVA was 0.84 logMar and mean baseline CFT was 771 microm. Mean BCVA was 0.36 and mean CFT thickness was 275 microm (n = 8) at month 1, 0.41 and 411 microm at month 2 (n = 7), 0.3 and 344 microm at month 3 (n = 6), 0.3 and 397 microm at month 4 (n = 5), respectively. In 75 % of patients, a single injection was not sufficient, and retreatment needed. No serious adverse events were observed. CONCLUSIONS: Treatment of macular edema secondary to CRVO with intravitreal bevacizumab injection of 1.25 mg was well tolerated and associated with marked macular thickness reduction and BCVA improvement in all patients. A trend towards reduction of foveal thickness and improvement of visual acuity was observed in both acute and chronic CRVO.

Reduced quality of life associated adverse events in intermediate hepatocellular carcinoma patients treated with PRECISION TACE with drug eluting beads: Results from the PRECISION V randomized trial : B-241

Purpose: To evaluate the extent of quality of life (QoL) associated adverse events (AEs) following PRECISION TACE with DC Bead compared with conventional transarterial chemoembolisation (cTACE). Methods and Materials: 201 intermediate HCC patients were treated with DC Bead (PRECISION TACE) or conventional TACE (cTACE) with doxorubicin in the PRECISION V clinical study. 93 patients were treated with DC Bead and 108 Patients with cTACE every 2 months and followed up for 6 months. AEs were classified according to the South West Oncology Group criteria. QoL associated AEs were defined as alopecia, constipation, nausea, vomiting, pyrexia, chills, asthenia, fatigue, and headache. Results: The biggest difference in QoL associated AEs was for alopecia: 2 patients (2.2%) for DC-Bead versus 21 patients (19.4%) for cTACE. For other clinical symptoms, constipation (n=10; 10.8% vs. n=13; 12%), vomiting (n=10; 10.8% vs. n=14; 13.0%), pyrexia (n=16; 17.2% vs. n=26; 24.1%), chills (n=1; 1.1% vs. n=5; 4.6%), and headache (n=2; 2.2% vs. n=8; 7.4%) showed lower incidence in the DC Bead group versus cTACE. Nausea, n= 15; 13.9% (n=15; 16.1%) and fatigue, n=6; 5.6% (n=13; 14.0%) were lower for cTACE. Total dose of doxorubicin was on average 35% higher in the DC Bead group. Conclusion: Although patients in the DC Bead group received a higher doxorubicin dose, less QoL associated AEs were reported for this group. Alopecia, the most obvious outward sign of toxicity, was only reported in a tenth of DC Bead patients. Thus, PRECISION TACE with DC Bead improves quality of life associated adverse events.

Known and new results on absolute convergence of Fourier integrals

New sufficient conditions for representation of a function via the absolutely convergent Fourier integral are obtained in the paper. In the main result, Theorem 1.1, this is controlled by the behavior near infinity of both the function and its derivative. This result is extended to any dimension d &= 2.

Psychodynamic interventions in cancer care I: psychometric results of a randomized controlled trial.

OBJECTIVE: This study aimed to assess the effectiveness of psychodynamic interventions in cancer care. METHODS: Between 2006 and 2009, each consecutive outpatient of the Oncology Center of the University Hospital of Lausanne was invited to participate in a trial evaluating the effects of psychological support. Accepting patients were randomly assigned to an immediate intervention or a delayed intervention [4-month waiting list]. Patients who declined support were asked to participate in an observational group [OG]. Socio-demographic and medical data, anxiety, and depression [HADS], psychological distress [SCL-90], alexithymia [TAS] and quality of life [EORTC] were recorded at baseline, and at 1, 4, 8, and 12-months follow-up. RESULTS: Of the 1973 approached patients, 1057 were excluded, 530 refused, and 386 were included with 196 of them participating in the OG. Of the patients in the intervention group [IG] [N = 190], 94 were randomized to the immediate intervention and 96 to the delayed intervention group (dIG). IG patients were younger, predominantly female, and had more psychological symptoms compared with those in the OG. Although patients of the IG and OG showed significant improvement in quality of life from baseline to 12-months follow-up, other outcomes [anxiety, depression, psychological distress, and alexithymia] remained unchanged. CONCLUSIONS: The intervention was not effective with regards to psychometric outcome. The results have to be interpreted in light of the study design [untargeted intervention], the low levels of psychiatric symptoms, dropout of symptomatic patients, and the high prevalence of alexithymia.

Administering brief motivational interventions to young men: Results from a pilot census transmissible study among 19 year-old francophone Swiss men.

AIMS - To pilot the implementation of brief motivational intervention (BMI) among conscripts, and to test the effectiveness of BMI in young men voluntarily showing up for a single face-to-face alcohol BMI session. Participants were conscripts attending the army recruitment process in Lausanne. This process is mandatory for all Swiss males at age 19 and Lausanne serves all francophone Swiss men. METHODS - Of 3'227 young men that were seen during the army recruitment procedures, 445 voluntarily showed up for a BMI and 367 were included in the study (exclusions were random and unsystematic and related to organizational aspects in the recruitment center). After an initial assessment, subjects were randomized into two groups: an immediate BMI and a 6-month delayed BMI (waiting list design). A 6-month follow-up assessment was conducted in both groups. BMI was a face-to-face 20 minutes counseling session with a psychologist trained in motivational interviewing at baseline and a telephone session for the control group at follow-up. Strategies of BMI included the exploration and evocation of a possible behavior change, importance of future change, readiness to change, and commitment to change. A filmed example of such an intervention is available in French at www.alcoologie.ch. RESULTS - All procedures are now fully implemented and working and the provision of preventive efforts found general approval by the army. 3'227 were eligible for BMI and 445 of them (13.8%) showed up for receiving a BMI. 367 were included in the study, 181 in the BMI group and 186 in the control group. More than 86% of those included were reached at follow-up. With one exception all findings on alcohol use went in the expected direction, i.e. a stronger decrease in alcohol use (or a smaller increase as for usual weekly drinking amount) in the BMI group. The risk for risky single occasion drinking (RSOD) decreased from 57% at-risk users at baseline to 50.6%, i.e. a 6.4% point decrease in the BMI group, while there was only a 0.6% point decrease (from 57.5% to 56.9%) in the control group. Moreover, the study showed that there was a likelihood of crossover effects for other substances like tobacco smoking and cannabis use. Despite these encouraging and consistent positive findings, none reached significance at conventional levels (p < 0.05). DISCUSSION - Data suggest a beneficial impact of BMI on alcohol use outcomes and potential effect on other substance use in 19-year old men attending the army recruitment and showing up voluntarily for BMI. As the main aim was to implement and test feasibility of conducting BMI in this setting none of our findings reached statistical significance. The consistency of findings across measures and substances, however, raises hope that non-significance in the present study does not mean no effect, but mainly insufficient power of this pilot study. [Authors]

Health care utilization among immigrants and native-born populations in 11 European countries. Results from the Survey of Health, Ageing and Retirement in Europe

Objective: This study examines health care utilization of immigrants relative to the native-born populations aged 50 years and older in eleven European countries. Methods. We analyzed data from the Survey of Health Aging and Retirement in Europe (SHARE) from 2004 for a sample of 27,444 individuals in 11 European countries. Negative Binomial regression was conducted to examine the difference in number of doctor visits, visits to General Practitioners (GPs), and hospital stays between immigrants and the native-born individuals. Results: We find evidence those immigrants above age 50 use health services on average more than the native-born populations with the same characteristics. Our models show immigrants have between 6% and 27% more expected visits to the doctor, GP or hospital stays when compared to native-born populations in a number of European countries. Discussion: Elderly immigrant populations might be using health services more intensively due to cultural reasons.

Real-time PCR for type-specific identification of herpes simplex in clinical samples: evaluation of type-specific results in the context of CNS diseases.

BACKGROUND: HSV-1 and HSV-2 cause CNS infections of dissimilar clinico-pathological characteristics with prognostic and therapeutic implications. OBJECTIVES: To validate a type-specific real-time PCR that uses MGB/LNA Taqman probes and to review the virologico-clinical data of 25 eligible patients with non-neonatal CNS infections. RESULTS: This real-time PCR was evaluated against conventional PCR (26 CSF and 20 quality controls), and LightCycler assay (51 mucocutaneous, 8 CSF and 32 quality controls) and culture/immunofluorescence (75 mucocutaneous) to assess typing with independent methods. Taqman real-time PCR detected 240 HSV genomes per ml CSF, a level appropriate for the management of patients, and provided unambiguous typing for the 104 positive (62 HSV-1 and 42 HSV-2) out the 160 independent clinical samples tested. HSV type diagnosed by Taqman real-time PCR predicted final diagnosis (meningitis versus encephalitis/meningoencephalitis, p<0.001) in 24/25 patients at time of presentation, in contrast to clinical evaluation. CONCLUSIONS: Our real-time PCR, as a sensitive and specific means for type-specific HSV diagnosis, provided rapid prognostic information for patient management.

A chromosome 9 deletion in Plasmodium falciparum results in loss of cytoadherence

Many lines of Plasmodium falciparum undrgo a deletion of the right end of chromosome 9 during in vitro culture accompanied by loss of cytoadherence and gametocytogenesis. Selection of cytoadherent cells from a mixed population co-selects for those with an undeleted chromosome 9 and selected cells produce gametocytes. The deletion also results in loss of expression of PfEMP1, the putative cytoadherence ligand, suggesting PfEMP1 or a regulatory gene controlling PfEMP1 expression and gametocytogenesis may be encoded in this region. We have isolated several markers for the deleted region and are currently using a YAC-P. falciparum library to investigate this region of the genome in detail.

Canakinumab Reduces The Risk Of Acute Gouty Arthritis Flares During Initiation Of Allopurinol Therapy: Results Of A Double-blind, Randomised Study

RATIONALE: This study assessed the efficacy and safety of canakinumab, a fully human anti-interleukin-1beta monoclonal antibody, for prophylaxis against acute gouty arthritis flares in patients initiating uratelowering therapy.METHODS: In this double-blind, double-dummy, dose-ranging study, 432 patients with gouty arthritis initiating allopurinol therapy were randomised 1:1:1:1:1:1:2 to receive: a single dose of canakinumab, 25, 50, 100, 200, or 300 mg subcutaneously (sc); four 4-weekly doses of canakinumab (50150125125 mg sc); or daily colchicine 0.5 mg orally for 16 weeks. Patients recorded details of flares in diaries. The study aimed to determine the canakinumab dose having equivalent efficacy to colchicine 0.5 mg at 16 weeks.RESULTS: A dose-response for canakinumab was not apparent with any of the four pre-defined dose-responsemodels. The estimated canakinumab dose with equivalent efficacy to colchicinewas belowthe range of doses tested.At 16 weeks, therewas a 62-72% reduction in themean number of flares per patient for canakinumab doses >50 mg vs colchicine based on a negative binomial model (rate ratio: 0.28-0.38, p50.0083), and the percentage of patients experiencing >1 flarewas significantly lower for all canakinumab doses (15- 27%) vs colchicine (44%, p<0.05). Therewas a 64-72%reduction in the risk of experiencing >1 flare for canakinumab doses >50 mg vs colchicine at 16 weeks (hazard ratio: 0.28-0.36, p50.05). The incidence of adverse events was similar across treatment groups.CONCLUSIONS: Single canakinumab doses >50 mg or four 4-weekly doses provided superior prophylaxis against flares compared with daily colchicine 0.5 mg.

PGC1alpha expression is controlled in skeletal muscles by PPARbeta, whose ablation results in fiber-type switching, obesity, and type 2 diabetes.

Mice in which peroxisome proliferator-activated receptor beta (PPARbeta) is selectively ablated in skeletal muscle myocytes were generated to elucidate the role played by PPARbeta signaling in these myocytes. These somatic mutant mice exhibited a muscle fiber-type switching toward lower oxidative capacity that preceded the development of obesity and diabetes, thus demonstrating that PPARbeta is instrumental in myocytes to the maintenance of oxidative fibers and that fiber-type switching is likely to be the cause and not the consequence of these metabolic disorders. We also show that PPARbeta stimulates in myocytes the expression of PGC1alpha, a coactivator of various transcription factors, known to play an important role in slow muscle fiber formation. Moreover, as the PGC1alpha promoter contains a PPAR response element, the effect of PPARbeta on the formation and/or maintenance of slow muscle fibers can be ascribed, at least in part, to a stimulation of PGC1alpha expression at the transcriptional level.