749 research outputs found

    Genetic steps to organ laterality in zebrafish.

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    All internal organs are asymmetric along the left-right axis. Here we report a genetic screen to discover mutations which perturb organ laterality. Our particular focus is upon whether, and how, organs are linked to each other as they achieve their laterally asymmetric positions. We generated mutations by ENU mutagenesis and examined F3 progeny using a cocktail of probes that reveal early primordia of heart, gut, liver and pancreas. From the 750 genomes examined, we isolated seven recessive mutations which affect the earliest left-right positioning of one or all of the organs. None of these mutations caused discernable defects elsewhere in the embryo at the stages examined. This is in contrast to those mutations we reported previously (Chen et al., 1997) which, along with left-right abnormalities, cause marked perturbation in gastrulation, body form or midline structures. We find that the mutations can be classified on the basis of whether they perturb relationships among organ laterality. In Class 1 mutations, none of the organs manifest any left-right asymmetry. The heart does not jog to the left and normally leftpredominant BMP4 in the early heart tube remains symmetric. The gut tends to remain midline. There frequently is a remarkable bilateral duplication of liver and pancreas. Embryos with Class 2 mutations have organotypic asymmetry but, in any given embryo, organ positions can be normal, reversed or randomized. Class 3 reveals a hitherto unsuspected gene that selectively affects laterality of heart. We find that visceral organ positions are predicted by the direction of the preceding cardiac jog. We interpret this as suggesting that normally there is linkage between cardiac and visceral organ laterality. Class 1 mutations, we suggest, effectively remove the global laterality signals, with the consequence that organ positions are effectively symmetrical. Embryos with Class 2 mutations do manifest linkage among organs, but it may be reversed, suggesting that the global signals may be present but incorrectly orientated in some of the embryos. That laterality decisions of organs may be independently perturbed, as in the Class 3 mutation, indicates that there are distinctive pathways for reception and organotypic interpretation of the global signals

    Open tension free repair of inguinal hernias; the Lichtenstein technique

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    BACKGROUND: Recurrences have been a significant problem following hernia repair. Prosthetic materials have been increasingly used in hernia repair to prevent recurrences. Their use has been associated with several advantages, such as less postoperative pain, rapid recovery, low recurrence rates. METHODS: In this retrospective study, 540 tension-free inguinal hernia repairs were performed between August 1994 and December 1999 in 510 patients, using a polypropylene mesh (Lichtenstein technique). The main outcome measure was early and late morbidity and especially recurrence. RESULTS: Inguinal hernia was indirect in 55 % of cases (297 patients), direct in 30 % (162 patients) and of the pantaloon (mixed) type in 15 % (81 patients). Mean patient age was 53.7 years (range, 18 – 85). Follow-up was completed in 407 patients (80 %) by clinical examination or phone call. The median follow-up period was 3.8 years (range, 1 – 6 years). Seroma and hematoma formation requiring drainage was observed in 6 and 2 patients, respectively, while transient testicular swelling occurred in 5 patients. We have not observed acute infection or abscess formation related to the presence of the foreign body (mesh). In two patients, however, a delayed rejection of the mesh occurred 10 months and 4 years following surgery. There was one recurrence of the hernia (in one of these patients with late mesh rejection) (recurrence rate = 0.2 %). Postoperative neuralgia was observed in 5 patients (1 %). CONCLUSION: Lichtenstein tension-free mesh inguinal hernia repair is a simple, safe, comfortable, effective method, with extremely low early and late morbidity and remarkably low recurrence rate and therefore it is our preferred method for hernia repair since 1994

    Randomized clinical trial to evaluate the effect of fecal microbiota transplant for initial Clostridium difficile infection in intestinal microbiome

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    Objective The aim of this study was to evaluate the impact of fecal donor-unrelated donor mix (FMT-FURM) transplantation as first-line therapy for C. difficile infection (CDI) in intestinal microbiome. Methods We designed an open, two-arm pilot study with oral vancomycin (250mg every 6 h for 10–14 days) or FMT-FURM as treatments for the first CDI episode in hospitalized adult patients in Hospital Universitario “Dr. Jose Eleuterio Gonzalez”. Patients were randomized by a closed envelope method in a 1: 1 ratio to either oral vancomycin or FMT-FURM. CDI resolution was considered when there was a reduction on the Bristol scale of at least 2 points, a reduction of at least 50% in the number of bowel movements, absence of fever, and resolution of abdominal pain (at least two criteria). From each patient, a fecal sample was obtained at days 0, 3, and 7 after treatment. Specimens were cultured to isolate C. difficile, and isolates were characterized by PCR. Susceptibility testing of isolates was performed using the agar dilution method. Fecal samples and FMT-FURM were analyzed by 16S rRNA sequencing. Results We included 19 patients; 10 in the vancomycin arm and 9 in the FMT-FURM arm. However, one of the patients in the vancomycin arm and two patients in the FMT-FURM arm were eliminated. Symptoms resolved in 8/9 patients (88.9%) in the vancomycin group, while symptoms resolved in 4/7 patients (57.1%) after the first FMT-FURM dose (P = 0.26) and in 5/7 patients (71.4%) after the second dose (P = 0.55). During the study, no adverse effects attributable to FMT-FURM were observed in patients. Twelve isolates were recovered, most isolates carried tcdB, tcdA, cdtA, and cdtB, with an 18-bp deletion in tcdC. All isolates were resistant to ciprofloxacin and moxifloxacin but susceptible to metronidazole, linezolid, fidaxomicin, and tetracycline. In the FMT-FURM group, the bacterial composition was dominated by Firmicutes, Bacteroidetes, and Proteobacteria at all-time points and the microbiota were remarkably stable over time. The vancomycin group showed a very different pattern of the microbial composition when comparing to the FMT-FURM group over time. Conclusion The results of this preliminary study showed that FMT-FURM for initial CDI is associated with specific bacterial communities that do not resemble the donors’ sample.Peer reviewedFinal Published versio

    Two-channel Kondo effect and renormalization flow with macroscopic quantum charge states

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    Many-body correlations and macroscopic quantum behaviors are fascinating condensed matter problems. A powerful test-bed for the many-body concepts and methods is the Kondo model which entails the coupling of a quantum impurity to a continuum of states. It is central in highly correlated systems and can be explored with tunable nanostructures. Although Kondo physics is usually associated with the hybridization of itinerant electrons with microscopic magnetic moments, theory predicts that it can arise whenever degenerate quantum states are coupled to a continuum. Here we demonstrate the previously elusive `charge' Kondo effect in a hybrid metal-semiconductor implementation of a single-electron transistor, with a quantum pseudospin-1/2 constituted by two degenerate macroscopic charge states of a metallic island. In contrast to other Kondo nanostructures, each conduction channel connecting the island to an electrode constitutes a distinct and fully tunable Kondo channel, thereby providing an unprecedented access to the two-channel Kondo effect and a clear path to multi-channel Kondo physics. Using a weakly coupled probe, we reveal the renormalization flow, as temperature is reduced, of two Kondo channels competing to screen the charge pseudospin. This provides a direct view of how the predicted quantum phase transition develops across the symmetric quantum critical point. Detuning the pseudospin away from degeneracy, we demonstrate, on a fully characterized device, quantitative agreement with the predictions for the finite-temperature crossover from quantum criticality.Comment: Letter (5 pages, 4 figures) and Methods (10 pages, 6 figures

    Childbearing intentions in a low fertility context: the case of Romania

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    This paper applies the Theory of Planned Behaviour (TPB) to find out the predictors of fertility intentions in Romania, a low-fertility country. We analyse how attitudes, subjective norms and perceived behavioural control relate to the intention to have a child among childless individuals and one-child parents. Principal axis factor analysis confirms which items proposed by the Generation and Gender Survey (GGS 2005) act as valid and reliable measures of the suggested theoretical socio-psychological factors. Four parity-specific logistic regression models are applied to evaluate the relationship between the socio-psychological factors and childbearing intentions. Social pressure emerges as the most important aspect in fertility decision-making among childless individuals and one-child parents, and positive attitudes towards childbearing are a strong component in planning for a child. This paper also underlines the importance of the region-specific factors when studying childbearing intentions: planning for the second child significantly differs among the development regions, representing the cultural and socio-economic divisions of the Romanian territory

    Variability in testing policies and impact on reported Clostridium difficile infection rates: results from the pilot Longitudinal European Clostridium difficile Infection Diagnosis surveillance study (LuCID)

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    Lack of standardised Clostridium difficile testing is a potential confounder when comparing infection rates. We used an observational, systematic, prospective large-scale sampling approach to investigate variability in C. difficile sampling to understand C. difficile infection (CDI) incidence rates. In-patient and institutional data were gathered from 60 European hospitals (across three countries). Testing methodology, testing/CDI rates and case profiles were compared between countries and institution types. The mean annual CDI rate per hospital was lowest in the UK and highest in Italy (1.5 vs. 4.7 cases/10,000 patient bed days [pbds], p < 0.001). The testing rate was highest in the UK compared with Italy and France (50.7/10,000 pbds vs. 31.5 and 30.3, respectively, p < 0.001). Only 58.4 % of diarrhoeal samples were tested for CDI across all countries. Overall, only 64 % of hospitals used recommended testing algorithms for laboratory testing. Small hospitals were significantly more likely to use standalone toxin tests (SATTs). There was an inverse correlation between hospital size and CDI testing rate. Hospitals using SATT or assays not detecting toxin reported significantly higher CDI rates than those using recommended methods, despite testing similar testing frequencies. These data are consistent with higher false-positive rates in such (non-recommended) testing scenarios. Cases in Italy and those diagnosed by SATT or methods NOT detecting toxin were significantly older. Testing occurred significantly earlier in the UK. Assessment of testing practice is paramount to the accurate interpretation and comparison of CDI rates

    Lung fibroblasts from patients with emphysema show markers of senescence in vitro

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    BACKGROUND: The loss of alveolar walls is a hallmark of emphysema. As fibroblasts play an important role in the maintenance of alveolar structure, a change in fibroblast phenotype could be involved in the pathogenesis of this disease. In a previous study we found a reduced in vitro proliferation rate and number of population doublings of parenchymal lung fibroblasts from patients with emphysema and we hypothesized that these findings could be related to a premature cellular aging of these cells. In this study, we therefore compared cellular senescence markers and expression of respective genes between lung fibroblasts from patients with emphysema and control patients without COPD. METHODS: Primary lung fibroblasts were obtained from 13 patients with moderate to severe lung emphysema (E) and 15 controls (C) undergoing surgery for lung tumor resection or volume reduction (n = 2). Fibroblasts (8E/9C) were stained for senescence-associated β-galactosidase (SA-β-Gal). In independent cultures, DNA from lung fibroblasts (7E/8C) was assessed for mean telomere length. Two exploratory 12 k cDNA microarrays were used to assess gene expression in pooled fibroblasts (3E/3C). Subsequently, expression of selected genes was evaluated by quantitative PCR (qPCR) in fibroblasts of individual patients (10E/9C) and protein concentration was analyzed in the cell culture supernatant. RESULTS: The median (quartiles) percentage of fibroblasts positive for SA-β-Gal was 4.4 (3.2;4.7) % in controls and 16.0 (10.0;24.8) % in emphysema (p = 0.001), while telomere length was not different. Among the candidates for differentially expressed genes in the array (factor ≥ 3), 15 were upregulated and 121 downregulated in emphysema. qPCR confirmed the upregulation of insulin-like growth factor-binding protein (IGFBP)-3 and IGFBP-rP1 (p = 0.029, p = 0.0002), while expression of IGFBP-5, -rP2 (CTGF), -rP4 (Cyr61), FOSL1, LOXL2, OAZ1 and CDK4 was not different between groups. In line with the gene expression we found increased cell culture supernatant concentrations of IGFBP-3 (p = 0.006) in emphysema. CONCLUSION: These data support the hypothesis that premature aging of lung fibroblasts occurs in emphysema, via a telomere-independent mechanism. The upregulation of the senescence-associated IGFBP-3 and -rP1 in emphysema suggests that inhibition of the action of insulin and insulin-like growth factors could be involved in the reduced in vitro-proliferation rate

    Gravito-electromagnetic analogies

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    We reexamine and further develop different gravito-electromagnetic (GEM) analogies found in the literature, and clarify the connection between them. Special emphasis is placed in two exact physical analogies: the analogy based on inertial fields from the so-called "1+3 formalism", and the analogy based on tidal tensors. Both are reformulated, extended and generalized. We write in both formalisms the Maxwell and the full exact Einstein field equations with sources, plus the algebraic Bianchi identities, which are cast as the source-free equations for the gravitational field. New results within each approach are unveiled. The well known analogy between linearized gravity and electromagnetism in Lorentz frames is obtained as a limiting case of the exact ones. The formal analogies between the Maxwell and Weyl tensors are also discussed, and, together with insight from the other approaches, used to physically interpret gravitational radiation. The precise conditions under which a similarity between gravity and electromagnetism occurs are discussed, and we conclude by summarizing the main outcome of each approach.Comment: 60 pages, 2 figures. Improved version (compared to v2) with some re-write, notation improvements and a new figure that match the published version; expanded compared to the published version to include Secs. 2.3 and

    Large Differences in Publicly Visible Health Behaviours across Two Neighbourhoods of the Same City

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    Background: There are socioeconomic disparities in the likelihood of adopting unhealthy behaviours, and success at giving them up. This may be in part because people living in deprived areas are exposed to greater rates of unhealthy behaviour amongst those living around them. Conventional self-report surveys do not capture these differences in exposure, and more ethological methods are required in order to do so. Methodology/Principal Findings: We performed 12 hours of direct behavioural observation in the streets of two neighbourhoods of the same city which were similar in most regards, except that one was much more socioeconomically deprived than the other. There were large differences in the publicly visible health behaviours observed. In the deprived neighbourhood, we observed 266 more adults smoking (rate ratio 3.44), 53 more adults drinking alcohol (rate ratio not calculable), and 38 fewer adults running (rate ratio 0.23), than in the affluent neighbourhood. We used data from the Health Survey for England to calculate the differences we ought to expect to have seen given the individual-level socioeconomic characteristics of the residents. The observed disparities between the two neighbourhoods were considerably greater than this null model predicted. There were also different patterns of smoking in proximity to children in the two neighbourhoods. Conclusions/Significance: The differences in observed smoking, drinking alcohol, and physical activity between these tw
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