Association between proton pump inhibitor therapy and clostridium difficile infection: a contemporary systematic review and meta-analysis.

Abstract Introduction Emerging epidemiological evidence suggests that proton pump inhibitor (PPI) acid-suppression therapy is associated with an increased risk of Clostridium difficile infection (CDI). Methods Ovid MEDLINE, EMBASE, ISI Web of Science, and Scopus were searched from 1990 to January 2012 for analytical studies that reported an adjusted effect estimate of the association between PPI use and CDI. We performed random-effect meta-analyses. We used the GRADE framework to interpret the findings. Results We identified 47 eligible citations (37 case-control and 14 cohort studies) with corresponding 51 effect estimates. The pooled OR was 1.65, 95% CI (1.47, 1.85), I2 = 89.9%, with evidence of publication bias suggested by a contour funnel plot. A novel regression based method was used to adjust for publication bias and resulted in an adjusted pooled OR of 1.51 (95% CI, 1.26–1.83). In a speculative analysis that assumes that this association is based on causality, and based on published baseline CDI incidence, the risk of CDI would be very low in the general population taking PPIs with an estimated NNH of 3925 at 1 year. Conclusions In this rigorously conducted systemic review and meta-analysis, we found very low quality evidence (GRADE class) for an association between PPI use and CDI that does not support a cause-effect relationship

Prognostic and therapeutic significance of carbohydrate antigen 19-9 as tumor marker in patients with pancreatic cancer

In pancreatic cancer ( PC) accurate determination of treatment response by imaging often remains difficult. Various efforts have been undertaken to investigate new factors which may serve as more appropriate surrogate parameters of treatment efficacy. This review focuses on the role of carbohydrate antigen 19- 9 ( CA 19- 9) as a prognostic tumor marker in PC and summarizes its contribution to monitoring treatment efficacy. We undertook a Medline/ PubMed literature search to identify relevant trials that had analyzed the prognostic impact of CA 19- 9 in patients treated with surgery, chemoradiotherapy and chemotherapy for PC. Additionally, relevant abstract publications from scientific meetings were included. In advanced PC, pretreatment CA 19- 9 levels have a prognostic impact regarding overall survival. Also a CA 19- 9 decline under chemotherapy can provide prognostic information for median survival. A 20% reduction of CA 19- 9 baseline levels within the first 8 weeks of chemotherapy appears to be sufficient to define a prognostic relevant subgroup of patients ('CA 19- 9 responder'). It still remains to be defined whether the CA 19- 9 response is a more reliable method for evaluating treatment efficacy compared to conventional imaging. Copyright (c) 2006 S. Karger AG, Basel

Seasonal and spatial variations of saltmarsh benthic foraminiferal communities from North Norfolk, England

Time series foraminiferal data were obtained from samples collected from three sites at Brancaster Overy Staithe, Burnham Overy Staithe and Thornham on the North Norfolk coast over a 1-year period. At each collection point, six environmental variables—temperature, chlorophyll, sand, mud, pH and salinity—were also measured. The principle aim of this study was to examine the benthic foraminiferal fauna in regard to the temporal variability of foraminiferal abundance, seasonal trend, dominant species, species diversity and the impact of environmental variables on the foraminiferal communities in the top 1 cm of sediment over a 1-year time series. The foraminiferal assemblages at the three sites were dominated by three species: Haynesina germanica, Ammonia sp. and Elphidium williamsoni. Foraminiferal species showed considerable seasonal and temporal fluctuation throughout the year at the three investigated sites. The foraminiferal assemblage at the three low marsh zones showed a maximum abundance in autumn between September and November and a minimum abundance observed between July and August. There were two separate peaks in the abundance of Ammonia sp. and E. williamsoni, one in spring and another in autumn. In contrast, H. germanica showed a single peak in its abundance in autumn. A generalized additive modelling approach was used to explain the variation in the observed foraminiferal abundance and to estimate the significant impact of each of the environmental variables on living foraminiferal assemblages, with taxa abundance as the dependent variable. When included in the model as predictors, most of the environmental variables contributed little in explaining the observed variation in foraminiferal species abundance. However, the hypotheses for differences amongst sites, salinity and pH were significant and explained most of the variability in species relative abundance

An overview of the recent developments on fructooligosaccharide production and applications

Over the past years, many researchers have suggested that deficiencies in the diet can lead to disease states and that some diseases can be avoided through an adequate intake of relevant dietary components. Recently, a great interest in dietary modulation of the human gut has been registered. Prebiotics, such as fructooligosaccharides (FOS), play a key role in the improvement of gut microbiota balance and in individual health. FOS are generally used as components of functional foods, are generally regarded as safe (generally recognized as safe status—from the Food and Drug Administration, USA), and worth about 150€ per kilogram. Due to their nutrition- and health-relevant properties, such as moderate sweetness, low carcinogenicity, low calorimetric value, and low glycemic index, FOS have been increasingly used by the food industry. Conventionally, FOS are produced through a two-stage process that requires an enzyme production and purification step in order to proceed with the chemical reaction itself. Several studies have been conducted on the production of FOS, aiming its optimization toward the development of more efficient production processes and their potential as food ingredients. The improvement of FOS yield and productivity can be achieved by the use of different fermentative methods and different microbial sources of FOS producing enzymes and the optimization of nutritional and culture parameter; therefore, this review focuses on the latest progresses in FOS research such as its production, functional properties, and market data.Agencia de Inovacao (AdI)-Project BIOLIFE reference PRIME 03/347. Ana Dominguez acknowledges Fundacao para a Ciencia e a Tecnologia, Portugal, for her PhD grant reference SFRH/BD/23083/2005

Current strategies for treatment of intervertebral disc degeneration: substitution and regeneration possibilities

Background: Intervertebral disc degeneration has an annual worldwide socioeconomic impact masked as low back pain of over 70 billion euros. This disease has a high prevalence over the working age class, which raises the socioeconomic impact over the years. Acute physical trauma or prolonged intervertebral disc mistreatment triggers a biochemical negative tendency of catabolic-anabolic balance that progress to a chronic degeneration disease. Current biomedical treatments are not only ineffective in the long-run, but can also cause degeneration to spread to adjacent intervertebral discs. Regenerative strategies are desperately needed in the clinics, such as: minimal invasive nucleus pulposus or annulus fibrosus treatments, total disc replacement, and cartilaginous endplates decalcification. Main Body: Herein, it is reviewed the state-of-the-art of intervertebral disc regeneration strategies from the perspective of cells, scaffolds, or constructs, including both popular and unique tissue engineering approaches. The premises for cell type and origin selection or even absence of cells is being explored. Choice of several raw materials and scaffold fabrication methods are evaluated. Extensive studies have been developed for fully regeneration of the annulus fibrosus and nucleus pulposus, together or separately, with a long set of different rationales already reported. Recent works show promising biomaterials and processing methods applied to intervertebral disc substitutive or regenerative strategies. Facing the abundance of studies presented in the literature aiming intervertebral disc regeneration it is interesting to observe how cartilaginous endplates have been extensively neglected, being this a major source of nutrients and water supply for the whole disc. Conclusion: Severalinnovative avenues for tackling intervertebral disc degeneration are being reported â from acellular to cellular approaches, but the cartilaginous endplates regeneration strategies remain unaddressed. Interestingly, patient-specific approaches show great promise in respecting patient anatomy and thus allow quicker translation to the clinics in the near future.The authors would like to acknowledge the support provided by the Portuguese Foundation for Science and Technology (FCT) through the project EPIDisc (UTAP-EXPL/BBBECT/0050/2014), funded in the Framework of the “International Collaboratory for Emerging Technologies, CoLab”, UT Austin|Portugal Program. The FCT distinctions attributed to J. Miguel Oliveira (IF/00423/2012 and IF/01285/ 2015) and J. Silva-Correia (IF/00115/2015) under the Investigator FCT program are also greatly acknowledged.info:eu-repo/semantics/publishedVersio

Targeting of MuLV Gag to the plasma membrane is mediated by PI(4,5)P2 and PhosphatidylSerine

Oral presentationInternational audienceMembrane targeting by the modern human immunodeficiency viruses is dependent on the plasma membrane-located phospholipid PI(4,5)P2. In order to determine if evolutionarily distant retroviruses are targeted by a similar mechanism, we generated mutant Gag constructs in the matrix (MA) domain of the Murine Leukemia Virus (MuLV) and examined their binding to membrane models and phenotypes in cell culture. Mutations in the MA polybasic region altered Gag localization, membrane binding and virion production. In addition, we show that MA binds with good affinity to all the phosphatidylinositol phosphates but displays a strong specificity for PI(4,5)P2 only if enhanced by phophatidylserine. Virus production was strongly impaired by PI(4,5)P2 depletion under 5ptaseIV overexpression. Our results suggest that the N-terminal polybasic region of MA is essential for Gag targeting to the plasma membrane and Gag cellular trafficking. The binding of the MA domain to PI(4,5)P2 appears to be a conserved feature among retroviruses, despite the fact that the MuLV-MA domain is structurally different from that of HIV-1 and -2 and lacks a readily identifiable PI(4,5)P2 binding cleft

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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Parathyroid hormone receptor 1 (PTHR1) is a prognostic indicator in canine osteosarcoma

Osteosarcoma (OS) is the most common malignant primary bone tumour in humans and dogs. Several studies have established the vital role of parathyroid hormone-related protein (PTHrP) and its receptor (PTHR1) in bone formation and remodeling. In addition, these molecules play a role in the progression and metastasis of many human tumour types. This study investigated the expression of PTHR1 and PTHrP in canine OS tissues and assessed their prognostic value. Formalin-fixed, paraffin-embedded tissue samples from 50 dogs diagnosed with primary OS were immunolabeled with antibodies specific for PTHR1 and PTHrP. The immunostaining intensity of tumours from patients with OS was correlated with survival time. Both PTHR1 and PTHrP were detected in all OS samples (n = 50). Dogs with OS tumours showing high immunostaining intensity for PTHR1 (n = 36) had significantly shorter survival times (p = 0.028, Log Rank; p = 0.04, Cox regression) when compared with OS that had low immunostaining intensity for PTHR1 (n = 14).PTHrP immunostaining intensity did not correlate with survival time (p > 0.05). The results of this study indicate that increased expression of PTHR1 antigen in canine OS is associated with poor prognosis. This suggests that PTHR1 may be useful as a prognostic indicator in canine OS

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112