Efficacy of endoscopic gastrojejunal bypass in obese Yucatan pigs: a comparative animal study.

BACKGROUND: Natural orifice transluminal endoscopy surgery (NOTES) gastrojejunal anastomosis (GJA) with duodenal exclusion (DE) could be used as a less invasive alternative to surgical gastric bypass. The aim of this study was to compare the efficacy and safety of both methods for bariatric purpose. METHODS: This was a prospective, experimental and comparative study on 27 obese living pigs, comparing 4 groups: GJA alone (group 1, G1), GJA + DE (group 2, G2), surgical gastric bypass (group 3, G3), control group (group 4, G4). GJA was endoscopically performed, using NOTES technic and LAMS, while DE was performed surgically for limb length selection. Animals were followed for 3 months. Primary outcome included technical success and weight change, while secondary endpoints included the rate of perioperative mortality and morbidity, histological anastomosis analysis and biological analysis. RESULTS: Technical success was 100% in each intervention group. No death related to endoscopic procedures occurred in the endoscopic groups, while early mortality (< 1 month) was 57,1% in the surgical group, all due to anastomotic dehiscence. At 3 months, compared to baseline, mean weight change was + 3,1% in G1 (p = 0,46); -14,9% in G2 (p = 0,17); +5,6% in G3 (p = 0,38) and + 25% in G4 (p = 0,029). Histopathological analysis of endoscopic GJA showed complete fusion of different layers without leak or abscess. CONCLUSIONS: Endoscopic GJA with DE provides the efficacy of bypass on weight control in an animal model. Next steps consist of the development of devices to perform exclusively endoscopically limb length selection and DE.

Switching from tenofovir/emtricitabine and nevirapine to a tenofovir/emtricitabine/rilpivirine single-tablet regimen in virologically suppressed, HIV-1-infected subjects.

OBJECTIVES: Nevirapine is an inducer of hepatic metabolism. After discontinuation, nevirapine has an inductive effect on cytochrome P450 3A4, which persists for a few weeks and which, after switching to rilpivirine, may reduce rilpivirine exposures and have a negative clinical impact. This study evaluates the virological outcome, pharmacokinetics and safety of switching virologically suppressed, HIV-1-infected patients from nevirapine to rilpivirine. PATIENTS AND METHODS: This 24 week open-label single-centre study included HIV-1-infected adults with HIV-1 RNA <50 copies/mL for >6 months on tenofovir/emtricitabine and nevirapine, who were willing to simplify their regimen to tenofovir/emtricitabine/rilpivirine. Virological suppression, safety and nevirapine and rilpivirine pharmacokinetics were assessed. RESULTS: At weeks 12 and 24, all 32 subjects remained virologically suppressed. One subject discontinued at week 1 for rilpivirine-associated insomnia and two patients chose to resume tenofovir/emtricitabine and nevirapine after week 12 because of rilpivirine-associated food constraint. There was no grade 3/4 laboratory abnormality. Rilpivirine trough concentrations were above the mean trough concentrations observed in Phase 3 studies by 1 week post-switch. Twenty-seven out of 32 patients had no measurable levels of nevirapine by 2 weeks post-switch. The meal accompanying tenofovir/emtricitabine/rilpivirine intake satisfied food requirements in 81% of cases. Overall general satisfaction was improved in 90% of the subjects despite food constraints. CONCLUSION: Nevirapine has a short and limited inductive effect on rilpivirine metabolism, which is not clinically significant. Tenofovir/emtricitabine/rilpivirine is an efficacious and safe option for virologically suppressed HIV-infected patients on nevirapine wishing to simplify their regimen.

Bioabsorbable staple-line reinforcement for pancreatectomy in a porcine model: a preliminary study.

BACKGROUND: We conducted an exploratory study to assess the use of FOREseal® bioabsorbable reinforcement sleeves in stapling of the pancreatic parenchyma. METHODS: A left pancreatectomy was carried out with linear stapler on 12 pigs: in the FOREseal group (n = 6), the stapling was reinforced with FOREseal, while in the control group (n = 6), simple stapling was applied. RESULTS: The mean operating time was not different between the two groups. No additional haemostasis of the stapling transection was necessary with FOREseal, while in the control group, four pigs required additional haemostasis (p = 0.03). The mean postoperative drainage volume and the mean duration of drainage were, respectively, in the FOREseal group versus the control group: 82 versus 204 ml (p = 0.2) and 3.2 versus 4.7 days (p = 0.3). No adverse event occurred in the FOREseal group. There was no anatomopathological difference between the two groups. CONCLUSION: A good tolerance of FOREseal was observed when used on the pancreatic stump. In this study, it was demonstrated a better haemostatic control of the pancreatic stump with FOREseal which also tends to reduce the volume of postoperative drainage liquid.

Factors associated with red blood cells transfusion during first bloodless priming cardiac surgery in children.

INTRODUCTION: Red blood cell (RBC) transfusion is often required during cardiac surgery in children. However, RBC is a rare product, and its transfusion is associated with adverse events and a worse surgical outcome. Characterization of factors related to RBC transfusion during cardiac surgery in children would provide prevention strategies. METHODS: We conducted a retrospective single-center study, including all children who underwent their first cardiac surgery using bloodless priming cardiopulmonary bypass (CPB). RESULTS: The study included 173 children between 2011 and 2019,; 57 had intraoperative transfusion and 17 postoperative transfusion. Age (OR: 0.76, p<0.001), weight (OR: 0.93, p<0.001), body mass index ([BMI] OR: 0.83, p<0.001), hemoglobin level (OR: 0.68, p<0.05), hematocrit level (OR: 0.88, p<0.05), mean corpuscular volume ([MCV] (OR: 0.86, p<0.001), hemodilution (OR: 100, p<0.01), and CPB duration (OR: 1.01, p<0.05) were associated with an increased risk of intraoperative transfusion in univariate analysis. In multivariate analysis, only CPB duration (OR: 1.02, p<0.001) and MCV (OR: 0.89, p<0.05) were associated with transfusion. Concerning postoperative transfusions, the RACHS surgical difficulty score (OR: 6.83, p<0.01), duration of CPB (OR: 1.01, p<0,001), length of stay in the PICU (OR: 2.37, p<0.001), length of hospitalization (OR: 1.2, p<0.001), and reoperation (OR: 20.59, p<0.001) were significant using univariate analysis, and only the need for a reoperation (OR: 19.16, p<0.01) remained significant in multivariate analysis. CONCLUSION: Low MCV appears to be one of the main risk factors for intraoperative transfusion in RBC. It may reflect iron deficiency that should be checked and supplemented preoperatively in order to reduce the risk of transfusion.

Systematic skin and nasal decolonization lowers Staphylococcus infection in pediatric cardiac surgery.

BACKGROUND: Postoperative infections occur in approximately 10% of pediatric cardiac surgeries, involving Staphylococcus species in most cases. Nasal decontamination of Staphylococcus with mupirocin has been reported to reduce postoperative Staphylococcus infections after cardiac surgery in adults, but the effect of preoperative decontamination in children undergoing cardiac surgery has not been sufficiently studied to reach consensus. METHODS: We conducted a single-center retrospective study to evaluate the impact of systematic preoperative decolonization with intranasal mupirocin application and skin-washing with chlorhexidine soap on postoperative Staphylococcus infection in children undergoing cardiac surgery. Our population was divided into three groups according to decolonization protocol (group N: no decolonization; group T: targeted decolonization in Staphylococcus aureus [SA] carriers only; and group S: systematic decolonization). RESULTS: A total of 393 children were included between October 2011 and August 2015 (122 in group N, 148 in group T, and 123 in group S). The Staphylococcus infection rate significantly decreased in group S compared to group N (0.8% vs. 7.7%; p < 0.05) and tended to decrease in group S compared to group T (0.8% vs. 4.7%; p = 0.06). Systematic decontamination also significantly reduced the rate of infections starting from the skin (including surgical site infections and bloodstream infections) compared to targeted decolonization or lack of decolonization, but had no effect on the rate of pulmonary infections. CONCLUSION: The results of our study suggest that systematic preoperative skin and nasal decontamination, regardless of SA carriage status, could reduce the rate of postoperative Staphylococcus infections after cardiac surgery in children.

Switching from abacavir/lamivudine plus nevirapine to abacavir/lamivudine/dolutegravir in virologically controlled HIV-infected adults (SWAD study).

INTRODUCTION: The metabolic pathways of dolutegravir suggest a potential predator effect of nevirapine on dolutegravir pharmacokinetics and switching from a nevirapine- to a dolutegravir-containing regimen could lead to a lower and suboptimal exposure to dolutegravir several weeks after the switch in case of persistent inducer effect. PATIENTS AND METHOD: Prospective, pilot, single-arm, open-label, non-comparative, bicentric study to evaluate the pharmacokinetics, virologic outcomes, safety, and patient satisfaction of switching from abacavir/lamivudine and nevirapine to a single tablet of abacavir/lamivudine/dolutegravir. The primary endpoint was the maintenance of virologic suppression (HIV-1 RNA<50 copies/mL) at week 12. Secondary endpoints were virologic suppression at week 48, safety and tolerability, patient satisfaction, and pharmacokinetic interaction between nevirapine and dolutegravir. Fifty-three adults on stable abacavir/lamivudine and nevirapine regimen for a median duration of 6years and virologically suppressed for 9.6years were included. RESULTS: Dolutegravir reached steady state by week 4/week 12 when expected by day 5/day 10. All subjects maintained plasma HIV-RNA˂50 copies/mL at week 12 and week 48. Abacavir/lamivudine/dolutegravir was well-tolerated, with two cases of serious adverse events deemed unrelated to study drugs (coronary syndrome in both cases), and one discontinuation for renal impairment at week 24 with a slight improvement after dolutegravir discontinuation. Level of treatment satisfaction remained high after the switch. CONCLUSION: The transient predator effect of nevirapine on dolutegravir had no clinical consequences after switching from nevirapine to dolutegravir, neither on safety nor maintenance of virologic suppression. It also had no consequences on patient satisfaction.

Mortality induced by PM2.5 exposure following the 1783 Laki eruption using reconstructed meteorological fields.

The 1783-1784 Laki eruption provides a natural experiment to evaluate the performance of chemistry-transport models in predicting the health impact of air particulate pollution. There are few existing daily meteorological observations during the second part of the 18th century. Hence, creating reasonable climatological conditions for such events constitutes a major challenge. We reconstructed meteorological fields for the period 1783-1784 based on a technique of analogues described in the Methods. Using these fields and including detailed chemistry we describe the concentrations of sulphur (SO2/SO4) that prevail over the North Atlantic, the adjoining seas and Western Europe during these 2 years. To evaluate the model, we analyse these results through the prism of two datasets contemporary to the Laki period: • The date of the first appearance of 'dry fogs' over Europe, • The excess mortality recorded in French parishes over the period June-September 1783. The sequence of appearances of the dry fogs is reproduced with a very-high degree of agreement to the first dataset. High concentrations of SO2/SO4 are simulated in June 1783 that coincide with a rapid rise of the number of deceased in French parishes records. We show that only a small part of the deceased of the summer of 1783 can be explained by the present-day relationships between PM2.5 and relative risk. The implication of this result is that other external factors such as the particularly warm summer of 1783, and the lack of health care at the time, must have contributed to the sharp increase in mortality over France recorded from June to September 1783.

Interest of proviral HIV-1 DNA genotypic resistance testing in virologically suppressed patients candidate for maintenance therapy.

Switch of antiretroviral therapy in virologically suppressed HIV-infected patients is frequent, to prevent toxicities, for simplification or convenience reasons. Pretherapeutic genotypic resistance testing on RNA can be lacking in some patients, which could enhance the risk of virologic failure, if resistance-associated mutations of the new regimen are not taken into account. Proviral DNA resistance testing in 69 virologically suppressed patients on antiretroviral treatment with no history of virological failure were pair-wised compared with pre-ART plasma RNA resistance testing. The median time between plasma (RNA testing) and whole blood (proviral DNA testing) was 47 months (IQR 29-63). A stop codon was evidenced in 23% (16/69) of proviral DNA sequences; these strains were considered as defective, non-replicative, and not taken into consideration. Within the non defective strains, concordance rate between plasma RNA and non-defective proviral DNA was high both on protease (194/220 concordant resistance-associated mutations=88%) and reverse transcriptase (28/37 concordant resistance-associated mutations=76%) genes. This study supports that proviral DNA testing might be an informative tool before switching antiretrovirals in virologically suppressed patients with no history of virological failure, but the interpretation should be restricted to non-defective viruses.

A multiparametric flow cytometry method for detection of modifications of antigen expression in polymorphonuclear cells infected by human cytomegalovirus.

Human cytomegalovirus (CMV) has been shown to alter adhesion molecule expression on permissive cells such as endothelial cells. The aim of the present study was to investigate expression of receptors for these molecules on CMV infected polymorphonuclear leukocytes (PMNLs). CMV-induced variations on cellular integrin expression were examined using an in vitro system to obtain infected PMNLs. A triparametric flow cytometry approach was developed, which allows combined detection, in a single experiment, of both viral intranuclear antigen in the selected PMNLs and cellular CD11/CD18 expression. Comparison of infected PMNLs with uninfected cells showed a decrease of up to 50% in the expression of CD11b, CD11c, and CD18. This study thus demonstrates that the presence of CMV in PMNLs, which characterizes active infection, modifies the expression of integrins and may thus affect cell-to-cell interactions and immune functions.

Transdisciplinary synthesis for ecosystem science, policy and management: The Australian experience.

Mitigating the environmental effects of global population growth, climatic change and increasing socio-ecological complexity is a daunting challenge. To tackle this requires synthesis: the integration of disparate information to generate novel insights from heterogeneous, complex situations where there are diverse perspectives. Since 1995, a structured approach to inter-, multi- and trans-disciplinary(1) collaboration around big science questions has been supported through synthesis centres around the world. These centres are finding an expanding role due to ever-accumulating data and the need for more and better opportunities to develop transdisciplinary and holistic approaches to solve real-world problems. The Australian Centre for Ecological Analysis and Synthesis (ACEAS ) has been the pioneering ecosystem science synthesis centre in the Southern Hemisphere. Such centres provide analysis and synthesis opportunities for time-pressed scientists, policy-makers and managers. They provide the scientific and organisational environs for virtual and face-to-face engagement, impetus for integration, data and methodological support, and innovative ways to deliver synthesis products. We detail the contribution, role and value of synthesis using ACEAS to exemplify the capacity for synthesis centres to facilitate trans-organisational, transdisciplinary synthesis. We compare ACEAS to other international synthesis centres, and describe how it facilitated project teams and its objective of linking natural resource science to policy to management. Scientists and managers were brought together to actively collaborate in multi-institutional, cross-sectoral and transdisciplinary research on contemporary ecological problems. The teams analysed, integrated and synthesised existing data to co-develop solution-oriented publications and management recommendations that might otherwise not have been produced. We identify key outcomes of some ACEAS working groups which used synthesis to tackle important ecosystem challenges. We also examine the barriers and enablers to synthesis, so that risks can be minimised and successful outcomes maximised. We argue that synthesis centres have a crucial role in developing, communicating and using synthetic transdisciplinary research.

Identification of a duplicated V3 domain in NS5A associated with cirrhosis and hepatocellular carcinoma in HCV-1b patients.

BACKGROUND: The NS5A protein of the hepatitis C virus has been shown to be involved in the development of hepatocellular carcinoma. OBJECTIVES: In a French multicenter study, we investigated the clinical and epidemiological features of a new HCV genotype 1b strain bearing a wide insertion into the V3 domain. STUDY DESIGN: We studied NS5A gene sequences in 821 French patients infected with genotype 1b HCV. RESULTS: We identified an uncharacterized V3 insertion without ORF disruption in 3.05% of the HCV sequences. The insertion comprised 31 amino-acids for the majority of patients; 3 patients had 27 amino-acids insertions and 1 had a 12 amino-acids insertion. Sequence identity between the 31 amino-acids insertions and the V3 domain ranged from 48 to 96% with E-values above 4e(-5), thus illustrating sequence homology and a partial gene duplication event that to our knowledge has never been reported in HCV. Moreover we showed the presence of the duplication at the time of infection and its persistence at least during 12 years in the entire quasispecies. No association was found with extrahepatic diseases. Conversely, patients with cirrhosis were two times more likely to have HCV with this genetic characteristic (p=0.04). Moreover, its prevalence increased with liver disease severity (from 3.0% in patients without cirrhosis to 9.4% in patients with both cirrhosis and HCC, p for trend=0.045). CONCLUSIONS: We identified a duplicated V3 domain in the HCV-1b NS5A protein for the first time. The duplication may be associated with unfavorable evolution of liver disease including a possible involvement in liver carcinogenesis.

Consistency of species ranking based on functional leaf traits.

• Specific leaf area (leaf area to dry mass ratio), leaf dry matter content (leaf dry mass to saturated fresh mass ratio) and leaf nitrogen concentration (LNC) have been proposed as indicators of plant resource use in data bases of plant functional traits. • We tested whether species ranking based on these traits was repeatable by studying spatio-temporal variations in specific leaf area and leaf dry matter content of water-saturated leaves (SLASAT and LDMCSAT ), as well as in LNC, for 57 herbaceous and woody species (or subsets thereof) growing under the Mediterranean climate of southern France. • Interseason and intersite variations were more pronounced than interannual variations, but species ranking for a given trait remained mostly consistent in space and time. Classifications based on LDMCSAT were generally more repeatable across years and sites, whereas those based on SLASAT were more stable over seasons. LNC usually gave the least repeatable classifications. • Species rankings were not completely similar for the three traits. Discussion of reproducibility, ease of trait measurement, as well as trait-function relationships led us to propose that measurements of the leaf traits, SLASAT and/or LDMCSAT , were the most suitable in large screening programmes.

A one-step RT-PCR and a flow cytometry method as two specific tools for direct evaluation of human herpesvirus-6 replication.

In order to confirm the occurrence of active Human herpesvirus-6 (HHV-6) infection, two optimal procedures were developed to detect directly replicating virus. MT4 cells and peripheral blood mononuclear cells (PBMCs) infected with two different strains (HST and a patient strain GUI) were used. The first method consisted of a one-step reverse transcription PCR amplifying a part of the late alternatively spliced U100 gene which encode the gp 82-105 viral glycoprotein. Two extraction methods and two RT-PCR kits were evaluated, leading to the selection of TaKaRa mRNA selective PCR kit. The second procedure consisted in a flow cytometry method to analyze the expression of two late viral HHV-6 antigens using 7C7 and 10G6 monoclonal antibodies. Four fixation permeabilization procedures were compared and the preparation of cells with paraformaldehyde (PFA) 4% was found to be optimal. Evaluation of these methods was then realized during a sequential culture of HST strain on MT4 cells. This kinetic study confirmed that Mabs recognized late antigens and demonstrate that the U100 gene splicing starts at a late stage of multiplication whereas unspliced forms are detectable earlier in the cycle.

Variation in relative growth rate and its components in the annual Polygonum aviculare in relation to habitat disturbance and seed size.

Polygonum aviculare is an annual weedy species showing extensive genetic variation in seed and leaf size and colonizing various types of man-disturbed habitats. A growth analysis was conducted on 12 genotypes representative of three regimes of disturbance of natural habitat (trampling, weeding, and no disturbance in the course of the growing season), grown under productive conditions in order to test whether relative growth rate (RGR) varies at the intraspecific level and, if so, which growth parameters may explain its variation. RGR showed significant genotypic variation (0.355-0.452 g g-1 day-1), positively correlated with specific leaf area (SLA) and leaf mass ratio (LMR) and negatively correlated with unit leaf rate per unit leaf area (ULRA). Thus, the paramount importance of leaf area ratio (LAR=SLA×LMR) in determining growth rate variation between different herbaceous species is confirmed at the intraspecific level in this species. Genotypes originating from trampled habitats had smaller seeds and smaller leaves than genotypes from habitats subject to other disturbance regimes. Additionally, they showed a lower LAR, not entirely compensated for by a higher ULRA, which resulted in a positive allometric relationship between seed size and RGR. It is hypothesized that their lower SLA, correlated with a higher leaf dry matter content (possibly a consequence of a higher cell wall content per unit leaf area) and their lower LMR have been co-selected with small leaf size as adaptations promoting resistance to trampling stress. It is suggested that variation in cell size and/or gibberellin content might be the mediators of the correlation found between seed size, leaf size and growth parameters within this species.

Components of relative growth rate and sensitivity to nitrogen availability in annual and perennial species of Bromus.

Two grass species, the annual Bromus sterilis and the perennial Bromus erectus, were grown from seeds for 28 days in a hydroponic culture system at 1 and 100 µM NO3- in the nutrient solution. At 100 µM NO3-, the relative growth rate (RGR) of the perennial was 30% lower than that of the annual. This was only the consequence of the higher specific mass of its leaves, since its leaf mass ratio was higher than that of the annual and the unit leaf rates (ULR), calculated on an area basis, were similar for the two species. At 1 µM, the RGR of the annual was 50% lower than at 100 µM, while that of the perennial was not significantly lower. This was due mainly to a lower ULR for the annual. while for the perennial ULR was the same in both treatments. These differences between the two species were all the more striking in that the differences in total nitrogen concentrations and nitrate reductase activities between the two treatments were very similar for both species. These different responses together with differences in the nitrogen productivity of the two species suggest that the level of nutrient availability may play an important role in the distribution of these Bromus species in natural habitats.

Responses of wild plants to nitrate availability : Relationships between growth rate and nitrate uptake parameters, a case study with two Bromus species, and a survey.

Two annual species of Bromus, an invader (B. hordeaceus, ex B. mollis) and a non-invader (B. intermedius), were grown for 28 days in growth chambers, at 5 and 100 µM NO 3- in flowing nutrient solution. No differences between the two species were observed at either NO 3- level, in terms of relative growth rate (RGR) or its components, dry matter partitioning, specific NO 3- absorption rate, nitrogen concentration, and other characteristics of NO 3- uptake and photosynthesis. The effects of decreasing NO 3- concentration in the solution were mainly to decrease the NO 3- concentration in the plants through decreased absorption rate, and to decrease the leaf area ratio through increased specific leaf mass and decreased leaf mass ratio. Organic nitrogen concentration varied little between the two treatments, which may be the reason why photosynthetic rates were not altered. Consequently, RGR was only slightly decreased in the 5-µM treatment compared to the 100-µM treatment. This is in contrast with other species, where growth is reduced at much higher NO 3- concentrations. These discrepancies may be related to differences in RGR, since a log-linear relationship was found between RGR and the NO 3- concentration at which growth is first reduced. In addition, a strong linear relationship was found between the RGR of these species and their maximum absorption rate for nitrate, suggesting that the growth of species with low maximum RGR may be partly regulated by nutrient uptake.

Specific leaf area and leaf nitrogen concentration in annual and perennial grass species growing in Mediterranean old-fields.

Specific leaf area (the ratio of leaf area to leaf dry mass) and leaf nitrogen concentration were measured on ten annual and nine perennial grass species growing in two old-fields of southern France, under a sub-humid Mediterranean climate. Specific leaf area (SLA) was found to be significantly higher in annuals than in perennials, but leaf nitrogen concentration expressed on a dry mass basis (LNCm) was similar in both life-forms; expressed on an area basis, leaf nitrogen concentration (LNCa) was significantly higher in perennials. The correlation between SLA and LNCm was negative in annuals and positive in perennials, while that between the inverse of specific leaf area (1/SLA) and LNCa was positive in annuals and not significant in perennials. It is hypothesized that these contrasting patterns depend on whether the two components of SLA - leaf thickness and density - vary in opposite directions. For nine of the species studied (six annuals and three perennials), relative growth rate data obtained in the laboratory under non-limiting nutrient supply were available; positive correlations were found between these values and both SLA and LNCm obtained in the field, suggesting that the interspecific differences in structural and chemical characteristics of leaves are maintained under a wide range of growing conditions.

Preparation, composition and structure of some nickel and zinc ferrocyanides: Experimental results.

Several methods have been used for preparation of nickel and zinc ferrocyanides: precipitation, growth in a gel and a new method based on growth on a solid alkali-metal ferrocyanide. The granulometry, morphology, composition and structure of the compounds were studied. Only the last method of preparation gives products suitable for use as ion fixators in columns on a large scale. The nickel ferrocyanide compositions can be written as M(I)(2x)Ni(2-x)Fe(CN)(6).yH(2)O with M(I) Na, K, Cs, H and 0 < x < 0.8. They have a cubic lattice with a partial occupancy of iron sites. For zinc ferrocyanides, rhombohedral M(I)(2)Zn(3)[Fe(CN)(6)](2).xH(2)O, trigonal Zn(2)Fe(Cn)(6).2H(2)O and other cubic compounds were found. Products resulting from the fixation of caesium by ion-exchange were also studied.