Nitric oxide activity through guanylate cyclase and phosphodiesterase modulation is impaired in fetal lambs with congenital diaphragmatic hernia.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypertension and death. Administration of nitric oxide (NO) alone remains ineffective in CDH cases. We investigated in near full-term lambs with and without CDH the role of guanylate cyclase (GC), the enzyme activated by NO in increasing cyclic 3'-5'-guanylosine monophosphate, and the role of phosphodiesterase (PDE) 5, the enzyme-degrading cyclic 3'-5'-guanylosine monophosphate. METHODS: Congenital diaphragmatic hernia was surgically created in fetal lambs at 85 days of gestation. Pulmonary hemodynamics were assessed by means of pressure and blood flow catheters (135 days). In vitro, we tested drugs on rings of isolated pulmonary vessels. RESULTS: In vivo, sodium nitroprusside, a direct NO donor, and methyl-2(4-aminophenyl)-1,2-dihydro-1-oxo-7-(2-pyridinylmethoxy)-4-(3,4,5 trimethoxyphenyl)-3-isoquinoline carboxylate sulfate (T-1032) and Zaprinast, both PDE 5 blockers, reduced pulmonary vascular resistance in CDH and non-CDH animals. The activation of GC by sodium nitroprusside and the inhibition of PDE 5 by T-1032 were less effective in CDH animals. In vitro, the stimulation of GC by 3(5'hydroxymethyl-2'furyl)-1-benzyl indazole (YC-1) (a benzyl indazole derivative) and the inhibition of PDE 5 by T-1032 were less effective in pulmonary vascular rings from CDH animals. The YC-1-induced vasodilation in rings from CDH animals was higher when associated with the PDE 5 inhibitor T-1032. CONCLUSIONS: Guanylate cyclase and PDE 5 play a role in controlling pulmonary vascular tone in fetal lambs with or without CDH. Both enzymes seem to be impaired in fetal lambs with CDH.

Successful Transapical Aortic Valve Implantation in a Congenital Bicuspid Aortic Valve.

Transcatheter stent-valve implantation in stenosed congenital bicuspid aortic valves is under debate. Heavily calcified elliptic bicuspid valves represent a contraindication to catheter-based valve therapies because of a risk of stent-valve displacement, distortion, or malfunctioning after the implantation. In this case report we illustrate our experience with a patient suffering from stenosed congenital bicuspid aortic valve who successfully underwent a transapical 26-mm Edwards Sapien stent-valve (Edwards Lifesciences Inc, Irvine, CA) implantation. Postoperative distortion, malfunctioning, and paravalvular leaks were not detected.

Transmission of HIV-1 drug resistance in Switzerland: a 10-year molecular epidemiology survey.

OBJECTIVES: Representative prevalence data of transmitted drug-resistant HIV-1 are essential to establish accurate guidelines addressing resistance testing and first-line treatments. METHODS: Systematic resistance testing was carried out in individuals in Switzerland with documented HIV-1 seroconversion during 1996-2005 and available samples with RNA > 1000 copies/ml obtained within 1 year of estimated seroconversion. Resistance interpretation used the Stanford list of mutations for surveillance of transmitted drug resistance and the French National Agency for AIDS Research algorithm. RESULTS: Viral sequences from 822 individuals were available. Risk groups were men having sex with men (42%), heterosexual contacts (32%) and intravenous drug users (20%); 30% were infected with non-B subtype viruses. Overall, prevalence of transmitted resistance was 7.7% [95% confidence interval (CI), 5.9-9.5] for any drug, 5.5% (95% CI, 3.9-7.1) for nucleoside reverse transcriptase inhibitors, 1.9% (95% CI, 1.0-2.8) for non-nucleoside reverse transcriptase inhibitors and 2.7% (95% CI, 1.6-3.8) for protease inhibitors. Dual- or triple-class resistance was observed in 2% (95% CI, 0.8-2.5). No significant trend in prevalence of transmitted resistance was observed over years. There were no differences according to ethnicity, risk groups or gender, but prevalence of transmitted resistance was highest among individuals infected with subtype B virus. CONCLUSIONS: The transmission rate of drug-resistant HIV-1 has been stable since 1996, with very rare transmission of dual- or triple-class resistance. These data suggest that transmission of drug resistance in the setting of easy access to antiretroviral treatment can remain stable and be kept at a low level.

Discovery of the faithfulness gene: a model of transmission and transformation of scientific information.

The purpose of this paper is to study the diffusion and transformation of scientific information in everyday discussions. Based on rumour models and social representations theory, the impact of interpersonal communication and pre-existing beliefs on transmission of the content of a scientific discovery was analysed. In three experiments, a communication chain was simulated to investigate how laypeople make sense of a genetic discovery first published in a scientific outlet, then reported in a mainstream newspaper and finally discussed in groups. Study 1 (N=40) demonstrated a transformation of information when the scientific discovery moved along the communication chain. During successive narratives, scientific expert terminology disappeared while scientific information associated with lay terminology persisted. Moreover, the idea of a discovery of a faithfulness gene emerged. Study 2 (N=70) revealed that transmission of the scientific message varied as a function of attitudes towards genetic explanations of behaviour (pro-genetics vs. anti-genetics). Pro-genetics employed more scientific terminology than anti-genetics. Study 3 (N=75) showed that endorsement of genetic explanations was related to descriptive accounts of the scientific information, whereas rejection of genetic explanations was related to evaluative accounts of the information.

Registration of congenital anomalies in Switzerland by EUROCAT.

Since 1988 the epidemiological surveillance of congenital anomalies (malformations, chromosomal aberrations, metabolic diseases, hereditary diseases, neurosensorial defects, etc.) is carried out by the Swiss registry of EUROCAT (European Registry of Congenital Anomalies and Twins). Several Swiss cantons collaborate through their own local registry, transmitting data to the central registry in Lausanne. We present the main objectives and methods of registration and give the global prevalence rates for the main malformations for 1996 and the period 1993-1996.

Multiples hyperplasies nodulaires focales hépatiques associées à une agénésie congénitale de la veine porte [Multiple focal nodular hyperplasia of the liver associated with congenital absence of the portal vein]

We report the 32nd case of congenital absence of portal vein in an 18-year-old female adult associated with multiple focal nodular hyperplasia of the liver. The association of various hepatic tumors has been observed in half of the publications about congenital absence of portal vein. Hepatic tumors seem to result from systemic diversion of portal vein flow with a resultant increase of arterial flow causing important vascular and nutritif changes the liver and consequent parenchymal transformation.

Infrequent transmission of HIV-1 drug-resistant variants.

Transmission of drug-resistant variants is influenced by several factors, including the prevalence of drug resistance in the population of HIV-1-infected patients, HIV-1 RNA levels and transmission by recently infected patients. In order to evaluate the impact of these factors on the transmission of drug-resistant variants, we have defined the population of potential transmitters and compared their resistance profiles to those of newly infected patients. Sequencing of pol gene was performed in 220 recently infected patients and in 373 chronically infected patients with HIV-1 RNA >1000 copies/ml. Minimal and maximal drug-resistance profiles of potential transmitters were estimated by weighting resistance profiles of chronically infected patients with estimates of the Swiss HIV-1-infected population, the prevalence of exposure to antiviral drugs and the proportion of infections attributed to primary HIV infections. The drug-resistance prevalence in recently infected patients was 10.5% (one class drug resistance: 9.1%; two classes: 1.4%; three classes: 0%). Phylogenetic analysis revealed significant clustering for 30% of recent infections. The drug-resistance prevalence in chronically infected patients was 72.4% (one class: 29%; two classes: 27.6%; three classes: 15.8%). After adjustment, the risk of transmission relative to wild-type was reduced both for one class drug resistance (minimal and maximal estimates: odds ratio: 0.39, P<0.001; and odds ratio: 0.55, P=0.011, respectively), and for two to three class drug resistance (odds ratios: 0.05 and 0.07, respectively, P<0.001). Neither sexual behaviour nor HIV-1 RNA levels explained the low transmission of drug-resistant variants. These data suggest that drug-resistant variants and in particular multidrug-resistant variants have a substantially reduced transmission capacity.

The impact of transmission clusters on primary drug resistance in newly diagnosed HIV-1 infection.

OBJECTIVES: To monitor HIV-1 transmitted drug resistance (TDR) in a well defined urban area with large access to antiretroviral therapy and to assess the potential source of infection of newly diagnosed HIV individuals. METHODS: All individuals resident in Geneva, Switzerland, with a newly diagnosed HIV infection between 2000 and 2008 were screened for HIV resistance. An infection was considered as recent when the positive test followed a negative screening test within less than 1 year. Phylogenetic analyses were performed by using the maximum likelihood method on pol sequences including 1058 individuals with chronic infection living in Geneva. RESULTS: Of 637 individuals with newly diagnosed HIV infection, 20% had a recent infection. Mutations associated with resistance to at least one drug class were detected in 8.5% [nucleoside reverse transcriptase inhibitors (NRTIs), 6.3%; non-nucleoside reverse transcriptase inhibitors (NNRTIs), 3.5%; protease inhibitors, 1.9%]. TDR (P-trend = 0.015) and, in particular, NNRTI resistance (P = 0.002) increased from 2000 to 2008. Phylogenetic analyses revealed that 34.9% of newly diagnosed individuals, and 52.7% of those with recent infection were linked to transmission clusters. Clusters were more frequent in individuals with TDR than in those with sensitive strains (59.3 vs. 32.6%, respectively; P < 0.0001). Moreover, 84% of newly diagnosed individuals with TDR were part of clusters composed of only newly diagnosed individuals. CONCLUSION: Reconstruction of the HIV transmission networks using phylogenetic analysis shows that newly diagnosed HIV infections are a significant source of onward transmission, particularly of resistant strains, thus suggesting an important self-fueling mechanism for TDR.

Superantigen-induced immune stimulation amplifies mouse mammary tumor virus infection and allows virus transmission.

Endogenous and infectious mouse mammary tumor viruses (MMTVs) encode in their 3' long terminal repeat a protein that exerts superantigen activity; that is, it is able to interact with T cells via the variable domain of the T cell receptor (TCR) beta chain. We show here that transmission of an infectious MMTV is prevented when superantigen-reactive cells are absent through either clonal deletion due to the expression of an endogenous MTV with identical superantigen specificity or exclusion due to expression of a transgenic TCR beta chain that does not interact with the viral superantigen. A strict requirement for superantigen-reactive T cells is also seen for a local immune response following MMTV infection. This immune response locally amplifies the number of MMTV-infected B cells, most likely owing to their clonal expansion. Collectively, our data indicate that a superantigen-induced immune response is critical for the MMTV life cycle.

Analysis by optical absorption and transmission electron microscopy of the strain inhomogeneities in InGaAs/InP strained layers

Optical absorption spectra and transmission electron microscopy (TEM) observations on InGaAs/InP layers under compressive strain are reported. From the band¿gap energy dispersion, the magnitude of the strain inhomogeneities. Is quantified and its microscopic origin is analyzed in view of the layer microstructure. TEM observations reveal a dislocation network at the layer interface the density of which correlates with ¿¿. It is concluded that local variations of dislocation density are responsible for the inhomogeneous strain field together with another mechanism that dominates when the dislocation density is very low.

Congenital diaphragmatic hernia: evaluation of prenatal diagnosis in 20 European regions.

OBJECTIVE: To evaluate prenatal diagnosis of congenital diaphragmatic hernia by ultrasound in well-defined European populations. DESIGN: Data from 20 registries of congenital malformations in 12 European countries were included. The prenatal ultrasound screening programs in the countries ranged from no routine screening to three ultrasound investigations per patient being routinely performed. RESULTS: There were 187 cases with congenital diaphragmatic hernia, with an overall prenatal detection rate of 59% (110/187). There was considerable variation in prenatal detection rate between regions. There was a significant difference in the detection rate of isolated congenital diaphragmatic hernia (59/116, 51%) compared with congenital diaphragmatic hernia associated with multiple malformations, karyotype anomalies or syndromes (51/71, 72%) (P = 0.01). Termination of pregnancy was performed in 39 cases (21%) of which 14 cases were isolated congenital diaphragmatic hernia. Mean gestational age at discovery was 24.2 weeks (range, 11-38 weeks). CONCLUSIONS: The overall prenatal detection rate of congenital diaphragmatic hernia is high (59%) but varies significantly between European regions. The gestational age at discovery was greater than 24 weeks in half of the prenatally diagnosed cases.

Micro-Raman study of stress distribution in local isolation structures and correlation with transmission electron microscopy

Stress in local isolation structures is studied by micro‐Raman spectroscopy. The results are correlated with predictions of an analytical model for the stress distribution and with cross‐sectional transmission electron microscopy observations. The measurements are performed on structures on which the Si3N4 oxidation mask is still present. The influence of the pitch of the periodic local isolation pattern, consisting of parallel lines, the thickness of the mask, and the length of the bird"s beak on the stress distribution are studied. It is found that compressive stress is present in the Si substrate under the center of the oxidation mask lines, with a magnitude dependent on the width of the lines. Large tensile stress is concentrated under the bird"s beak and is found to increase with decreasing length of the bird"s beak and with increasing thickness of the Si3N4 film.

Transgenerational transmission of trauma in families of Holocaust survivors: The consequences of extreme family functioning on resilience, Sense of Coherence, anxiety and depression.

BACKGROUND: The psychological transmission of the noxious effects of a major trauma from one generation to the next remains unclear. The present study aims to identify possible mechanisms explaining this transmission among families of Holocaust Survivors (HS). We hypothesized that the high level of depressive and anxiety disorders (DAD) among HS impairs family systems, which results in damaging coping strategies of their children (CHS) yielding a higher level of DAD. METHODS: 49 CHS completed the Resilience Scale for Adults, the Hopkins Symptom Check List-25, the 13-Item Sense of Coherence (SOC) scale, and the Family Adaptability and Cohesion Scale. We test a mediation model with Family types as the predictor; coping strategies (i.e. Resilience or SOC) as the mediator; and DAD as the outcome variable. RESULTS: Results confirm that the CHS׳ family types are more often damaged than in general population. Moreover, growing in a damaged family seems to impede development of coping strategies and, therefore, enhances the occurrence of DAD. LIMITATIONS: The present investigation is correlational and should be confirmed by other prospective investigations. CONCLUSIONS: At a theoretical level we propose a mechanism of transmission of the noxious effects of a major trauma from one generation to the next through family structure and coping strategies. At a clinical level, our results suggest to investigate the occurrence of trauma among parents of patients consulting for DAD and to reinforce their coping strategies.

Financial Integration, Trade Openness and International Transmission

[cat] Com afecten l’obertura comercial i financera a la volatilitat macroeconòmica? La literatura existent, tant empírica com teòrica, no ha assolit encara un consens. Aquest article usa un model microfonamentat de dos països simètrics amb entrada endògena d’empreses per estudiar-ho. L’anàlisis es du a terme per tres règims econòmics diferents amb diferents nivells d’integració internacional: una economia tancada, una autarquia financera i una integració plena. Es consideren diversos nivells d’obertura comercial, en forma de biaix domèstic de la demanda i l’economia pot patir pertorbacions en la productivitat del treball i en innovació. El model conclou que la incertesa macroeconòmica, representada principalment per la volatilitat del consum, la producció i la relació real d’intercanvi internacional, depèn del grau d’obertura i del tipus de pertorbació.

Price transmission and market power analysis in the Spanish seafood market chain

[cat] Espanya és un dels principals mercats de productes pesquers d’Europa i del món. El consum de productes pesquers ha estat tradicionalment molt important a Espanya, el 2005 es varen consumir 36,7 kg per persona (MAPA, diversos anys). Malgrat això, el mercat i cóm interactuen els diversos nivells de la cadena de comercialització han gaudit de poca atenció. En aquest estudi, utilitzant dades setmanals, s’analitza per als dotze principals productes pesquers, l’elasticitat en la transmissió de preus al llarg de la cadena de comercialització a Espanya (llotja, mercat central i detallista). Finalment s’investiga la presència d’assimetria en la transmissió de preus entre aquests nivells de mercat. Els resultats obtinguts tenen importants implicacions a l’hora d’analitzar la demanda, poder de mercat i marges al llarg del mercat per als productes pesquers.