Mercury Isotopic Fractionation during Pedogenesis in a Tropical Forest Soil Catena (French Guiana): Deciphering the Impact of Historical Gold Mining.

We used natural mercury (Hg) stable isotopes to investigate the Hg cycle in a rainforest soil catena (French Guiana) partially gold-mined during the early 1950s. Litterfall showed homogeneous Δ199Hg values [-0.18 ± 0.05‰, i.e., a modern gaseous elemental Hg (GEM) isotopic signature]. After litter decomposition, Hg bound to organic matter (OM) is mixed with Hg from pristine (-0.55 ± 0.22‰) or gold-mined (-0.09 ± 0.16‰) mineral materials. Negative Δ199Hg values in deep pristine mineral horizons (-0.60 ± 0.16‰) suggest the transfer of Hg bound to dissolved OM depleted in odd isotopes due to mass-independent fractionation during Hg abiotic reduction. Perennial palm tree leaves collected above gold-mined and pristine soil recorded contrasting Δ199Hg signatures likely resulting from GEM re-emission processes from soils and leaf surfaces. Upslope, soil δ202Hg signatures showed a negative shift (ε ∼ -1‰) with depth attributed to mass-dependent fractionation during Hg sorption and complexation onto iron oxides and dissolved OM. Downslope, higher δ202Hg values in soils resulted from hydromorphy [lower humification, greater Hg(II) reduction, etc.]. The unique Hg isotopic signatures of Amazonian soils probably result in multistep fractionation processes during pedogenesis (millions of years) and in a potentially different Hg isotopic signature of preanthropogenic background GEM.

CPAP by helmet for treatment of acute respiratory failure after pediatric liver transplantation.

ARF after pediatric liver transplantation accounts for high rate of morbidity and mortality associated with this procedure. The role of CPAP in postoperative period is still unknown. The aim of the study was to describe current practice and risk factors associated with the application of helmet CPAP. In this retrospective observational cohort study, 119 recipients were divided into two groups based on indication to CPAP after extubation. Perioperative variables were studied, and determinants of CPAP application were analyzed in a multivariate logistic model. Sixty patients (60/114) developed ARF and were included in the CPAP group. No differences were found between the two groups for primary disease, graft type, and blood product transfused. At multivariate analysis, weight <11 kg (OR = 2.9; 95% CI = 1.1-7.3; P = .026), PaO2 /FiO2 <380 before extubation (OR = 5.4; 95% CI = 2.1-13.6; P < .001), need of vasopressors (OR = 2.6; 95% CI = 1.1-6.4; P = .038), and positive fluid balance >148 mL/kg (OR = 4.0; 95% CI = 1.6-10.1; P = .004) were the main determinants of CPAP application. In the CPAP group, five patients (8.4%) needed reintubation. Pediatric liver recipients with lower weight, higher need of inotropes/vasopressors, higher positive fluid balance after surgery, and lower PaO2 /FiO2 before extubation were at higher odds of developing ARF needing CPAP application.

Shift in skin microbiota of Western European women across aging.

AIMS: The objective of our study was to compare the microbiota diversity between two different age groups of Western European women. METHODS AND RESULTS: Skin-swab samples were collected directly on the forehead of 34 healthy Western European women: 17 younger (21-31 years old) and 17 older individuals (54-69 years old). Bacterial communities were evaluated using the 16S rRNA gene sequencing. Data revealed a higher alpha diversity on the skin of older individuals compared with younger ones. Overall microbiota structure was different between the two age groups, as demonstrated by beta diversity analysis, which also highlighted a high interpersonal variation within older individuals. Furthermore, taxonomic composition analysis showed both an increase in Proteobacteria and a decrease in Actinobacteria on the older skin. At the genus level, older skin exhibited a significant increase in Corynebacterium and a decrease in Propionibacterium relative abundance. CONCLUSIONS: Our study revealed a shift in the distribution of skin microbiota during chronological aging in Western European women. SIGNIFICANCE AND IMPACT OF STUDY: Altogether these results could become the basis to develop new approaches aiming to rebalance the skin microbiota, which is modified during the aging process.

Early responses to deep brain stimulation in depression are modulated by anti-inflammatory drugs.

Deep brain stimulation (DBS) in the subgenual cingulated gyrus (SCG) is a promising new technique that may provide sustained remission in resistant major depressive disorder (MDD). Initial studies reported a significant early improvement in patients, followed by a decline within the first month of treatment, an unexpected phenomenon attributed to potential placebo effects or a physiological response to probe insertion that remains poorly understood. Here we characterized the behavioural antidepressant-like effect of DBS in the rat medial prefrontal cortex, focusing on modifications to rodent SCG correlate (prelimbic and infralimbic (IL) cortex). In addition, we evaluated the early outcome of DBS in the SCG of eight patients with resistant MDD involved in a clinical trial. We found similar antidepressant-like effects in rats implanted with electrodes, irrespective of whether they received electrical brain stimulation or not. This effect was due to regional inflammation, as it was temporally correlated with an increase of glial-fibrillary-acidic-protein immunoreactivity, and it was blocked by anti-inflammatory drugs. Indeed, inflammatory mediators and neuronal p11 expression also changed. Furthermore, a retrospective study indicated that the early response of MDD patients subjected to DBS was poorer when they received anti-inflammatory drugs. Our study demonstrates that electrode implantation up to the IL cortex is sufficient to produce an antidepressant-like effect of a similar magnitude to that observed in rats receiving brain stimulation. Moreover, both preclinical and clinical findings suggest that the use of anti-inflammatory drugs after electrode implantation may attenuate the early anti-depressive response in patients who are subjected to DBS.

Roux-en-Y hepatico-jejunostomy for a left segmental graft: Do not twist the loop, stick it!

Biliary complications remain a major challenge for long-term success after LT, as it is, as a rule, the most common technical - early and late - complication that occurs, and because these complications contribute to a significant number of late graft losses and retransplantations. In the pediatric age group, both biliary atresia, as the patient's condition, and the use of a left liver graft, obtained by a liver division technique, make it necessary for the use of a Roux-en-Y jejunal loop for the biliary reconstruction in the majority of cases. A slight modification of the technique is presented, consisting of a straight positioning along the cut surface (rather than the conventional position that results in a harpoon shape). A favorable outcome in terms of a technical complication and graft survival was observed. This way of doing this is an interesting variation and adds to the surgical armamentarium.

Splitting livers: Trans-hilar or trans-umbilical division? Technical aspects and comparative outcomes.

UNLABELLED: Controversy remains about the best line of division for liver splitting, through Segment IV or through the umbilical fissure. Both techniques are currently used, with the choice varying between surgical teams in the absence of an evidence-based choice. We conducted a single-center retrospective analysis of 47 left split liver grafts that were procured with two different division techniques: "classical" (N = 28, Group A) or through the umbilical fissure and plate (N = 19, Group B). The allocation of recipients to each group was at random; a single transplant team performed all transplantations. Demographics, characteristics, technical aspects, and outcomes were similar in both groups. The grafts in Group A, prepared with the classical technique, were procured more often with a single BD orifice compared with the grafts in Group B; however, this was not associated with a higher incidence of biliary problems in this series of transplants (96% actual graft survival rate [median ± s.d. FOLLOW-UP: 26 ± 20 months]). Both techniques provide good quality split grafts and an excellent outcome; surgical expertise with a given technique is more relevant than the technique itself. The classical technique, however, seems to be more flexible in various ways, and surgeons may find it to be preferable.

Cytokine release assays: current practices and future directions.

As a result of the CD28 superagonist biotherapeutic monoclonal antibody (TGN 1412) "cytokine storm" incident, cytokine release assays (CRA) have become hazard identification and prospective risk assessment tools for screening novel biotherapeutics directed against targets having a potential risk for eliciting adverse pro-inflammatory clinical infusion reactions. Different laboratories may have different strategies, assay formats, and approaches to the reporting, interpretation, and use of data for either decision making or risk assessment. Additionally, many independent contract research organizations (CROs), academic and government laboratories are involved in some aspect of CRA work. As a result, while some pharmaceutical companies are providing CRA data as part of the regulatory submissions when necessary, technical and regulatory practices are still evolving to provide data predictive of cytokine release in humans and that are relevant to safety. This manuscript provides an overview of different approaches employed by the pharmaceutical industry and CROs, for the use and application of CRA based upon a survey and post survey follow up conducted by ILSI-Health and Environmental Sciences Institute (HESI) Immunotoxicology Committee CRA Working Group. Also discussed is ongoing research in the academic sector, the regulatory environment, current limitations of the assays, and future directions and recommendations for cytokine release assays.

Resilience to periodic disturbances and the long-term genetic stability in Acropora coral.

Climate change is restructuring natural ecosystems. The direct impacts of these events on biodiversity and community structure are widely documented, but the impacts on the genetic variation of populations remains largely unknown. We monitored populations of Acropora coral on a remote coral reef system in northwest Australia for two decades and through multiple cycles of impact and recovery. We combined these demographic data with a temporal genetic dataset of a common broadcast spawning corymbose Acropora to explore the spatial and temporal patterns of connectivity underlying recovery. Our data show that broad-scale dispersal and post-recruitment survival drive recovery from recurrent disturbances, including mass bleaching and mortality. Consequently, genetic diversity and associated patterns of connectivity are maintained through time in the broader metapopulation. The results highlight an inherent resilience in these globally threatened species of coral and showcase their ability to cope with multiple disturbances, given enough time to recover is permitted.

Liver transplantation for refractory severe pruritus related to widespread multifocal hepatic focal nodular hyperplasia (FNH) in a child: case report and review of literature.

FNH is a rare and benign tumor of the liver. It is not a conventional indication for liver transplantation, and no transplant for FNH in a child has been reported to date. Multifocal FNH growing in adolescent age to a widespread tumor invading the whole liver and associated with severe refractory pruritus was an unusual indication for transplantation in a 13-yr-old girl. The operation and the follow-up were uneventful, allowing full recovery and disappearance of pruritus.

Tunneling conductivity in composites of attractive colloids.

In conductor-insulator nanocomposites in which conducting fillers are dispersed in an insulating matrix, the electrical connectedness is established by inter-particle tunneling or hopping processes. These systems are intrinsically non-percolative and a coherent description of the functional dependence of the conductivity σ on the filler properties, and in particular of the conductor-insulator transition, requires going beyond the usual continuum percolation approach by relaxing the constraint of a fixed connectivity distance. In this article, we consider dispersions of conducting spherical particles which are connected to all others by tunneling conductances and which are subjected to an effective attractive square-well potential. We show that the conductor-insulator transition at low contents φ of the conducting fillers does not determine the behavior of σ at larger concentrations, in striking contrast to what is predicted by percolation theory. In particular, we find that at low φ the conductivity is governed almost entirely by the stickiness of the attraction, while at larger φ values σ depends mainly on the depth of the potential well. As a consequence, by varying the range and depth of the potential while keeping the stickiness fixed, composites with similar conductor-insulator transitions may display conductivity variations of several orders of magnitude at intermediate and large φ values. By using a recently developed effective medium theory and the critical path approximation, we explain this behavior in terms of dominant tunneling processes which involve inter-particle distances spanning different regions of the square-well fluid structure as φ is varied. Our predictions could be tested in experiments by changing the potential profile with different depletants in polymer nanocomposites.

The fluctuating phenotype of the lymphohematopoietic stem cell with cell cycle transit.

The most primitive engrafting hematopoietic stem cell has been assumed to have a fixed phenotype, with changes in engraftment and renewal potential occurring in a stepwise irreversible fashion linked with differentiation. Recent work shows that in vitro cytokine stimulation of murine marrow cells induces cell cycle transit of primitive stem cells, taking 40 h for progression from G0 to mitosis and 12 h for subsequent doublings. At 48 h of culture, progenitors are expanded, but stem cell engraftment is markedly diminished. We have investigated whether this effect on engraftment was an irreversible step or a reversible plastic feature correlated with cell cycle progression. Long-term engraftment (2 and 6 mo) of male BALB/c marrow cells exposed in vitro to interleukin (IL)-3, IL-6, IL-11, and steel factor was assessed at 2-4-h intervals of culture over 24-48 h using irradiated female hosts; the engraftment phenotype showed marked fluctuations over 2-4-h intervals, with engraftment nadirs occurring in late S and early G2. These data show that early stem cell regulation is cell cycle based, and have critical implications for strategies for stem cell expansion and engraftment or gene therapy, since position in cell cycle will determine whether effective engraftment occurs in either setting.

Primary Prophylaxis for Gastrointestinal Bleeding in Children With Biliary Atresia and Portal Hypertension Candidates for Liver Transplantation: A Single-Center Experience.

BACKGROUND: Cirrhosis for biliary atresia (BA) is associated with risk of gastrointestinal bleeding (GB) from gastroesophageal varices due to portal hypertension. Primary prophylaxis of GB is controversial in children who are candidates for liver transplantation (LT). The aim of the study was to define the management of gastroesophageal varices and to identify the benefit of primary prophylaxis for GB in BA children waiting for LT. METHODS: A retrospective single-center study including all BA children listed for LT in 2008-2016. Clinical, endoscopical, and biochemical data were analyzed. RESULTS: Of 82 children, 50 (61%) did not receive primary prophylaxis and did not present any episode of bleeding, 16 (19.5%) underwent primary prophylaxis, and 16 (19.5%) presented spontaneous GB and received secondary prophylaxis. Children without primary prophylaxis and GB were younger than patients with primary prophylaxis and those with GB (7.7 years [range, 4.1-37.9 years] vs 11.2 years [range, 5.1-43 years]; P = .03 vs 10.7 years [range, 6.9-39.9 years], respectively; P = .004). Seventy-five percent of GB occurred in children older than 8 months. Fifteen (93.8%) children with GB presented esophageal varices (grade III = 10 [62.5%]) and 10 (62.5%) required endoscopic treatments, consisting mainly of sclerotherapy. Median time to LT was similar for children with or without bleeding (2 months [range, 0-17.7 months] vs 2.2 months [0-17.9 months], respectively; P = .89). After 45.5 months (range, 13.7-105.5 months) of follow-up, the overall patient survival was 97.6%. At the intention-to-treat analysis, the survival rate was 100% for patients without bleeding episode and 87.5% for children with GB (P = .16). CONCLUSIONS: Despite the risk of GB being not clinically predictable in children with BA waiting for LT, our experience suggests that primary prophylaxis of GB might be unnecessary in children younger than 6 months, while it should be considered in older children. Thus, the occurrence of GB does not delay the timing of transplantation.

Thoracic ultrasound accuracy for the investigation of initial neonatal respiratory distress.

Thoracic ultrasound (TUS) is increasingly studied in neonatal respiratory distress but chest x-ray (CXR) remains the first-line exam. We aimed to evaluate its diagnostic performance for the investigation of unselected causes of neonatal respiratory distress in daily practice. We conducted a descriptive, prospective, and single-center diagnostic accuracy study in a tertiary hospital, including term and preterm newborns who needed a CXR because of respiratory conditions occurring at birth or during the first 24h of life. TUS was compared to the reference diagnosis, which was the association between the CXR results, the clinical initial context, and the patient's outcome. Fifty-two newborns were included and 104 hemi-thorax ultrasounds were analyzed. Sensitivity, specificity, positive and negative predictive values (PPV, NPV), diagnosis accuracy, as well as the positive and negative likelihood ratio of TUSs were 100% for respiratory distress syndrome (RDS), transient tachypnea of newborn (TTN), pneumomediastinum, meconium aspiration syndrome, and absence of pulmonary disease. TUS also showed 100% sensitivity and NPV for pneumothorax, but specificity was 97% and PPV was 50%. Kappa concordance between TUS and either CXR alone or the radiological/clinical gold standard was 0.79 and 0.95, respectively. CONCLUSION: TUS at the newborn's bedside is efficient for investigating the main neonatal respiratory diseases, especially for the confirmation of RDS or TTN and for the exclusion of differential diagnosis or complications.

Ab initio Everolimus-based Versus Standard Calcineurin Inhibitor Immunosuppression Regimen in Liver Transplant Recipients.

AIM: We designed a retrospective case-control study to determine the efficacy and feasibility of everolimus (EVR) combined with low-dose tacrolimus (Tac) ab initio versus standard-dose Tac after liver transplantation (LT). METHODS: Seventy-one adult LT patients, receiving EVR and low-dose Tac without corticosteroids or induction therapy from postoperative day 1 (EVR group) were compared with a well-matched control group of 61 recipients treated with standard-dose Tac in association with antimetabolite. RESULTS: Baseline characteristics for the two groups were comparable. The overall patient and graft survival rates were similar (P = .908). Liver function was stable during the follow-up. In the EVR group, biopsy-proven acute rejection occurred in two cases (2.8%), whereas chronic rejection occurred in one (1.4%). The EVR group experienced a better renal function already after 2 weeks (estimated glomerular filtration rate: 89.85 [36.46 to 115.3] mL/min/1.73 m2 vs. 68.77 [16.11 to 115.42] mL/min/1.73 m2; P = .013), which was also observed after a median time of 27 months (range, 0 to 82 months) from LT (estimated glomerular filtration rate: 80 [45 to 118.3] mL/min/1.73 m2 vs. 70.9 [45 to 88.4] mL/min/1.73 m2; P = .04). After a median time of 27 months, the EVR group showed lower incidence of arterial hypertension and insulin-dependent diabetes mellitus. CONCLUSION: Ab initio EVR-based immunosuppression could be a valid option immediately after surgery in recipients at high-risk for post-LT renal impairment.

Bromocriptine restores tolerance in estrogen-treated mice.

Estrogen can modulate autoimmunity in certain models of systemic lupus erythematosus. Recently, we have shown that it can mediate survival and activation of anti-DNA B cells in a mouse transgenic for the heavy chain of a pathogenic anti-DNA antibody. To identify whether estrogen effects reflect increased prolactin secretion, we characterized B-cell autoreactivity in transgenic mice given both bromocriptine (an inhibitor of prolactin secretion) and estradiol. Treatment of mice with estradiol plus bromocriptine led to reduced titers of anti-DNA antibodies and diminished IgG deposition in kidneys compared with treatment with estradiol alone. However, mice treated with estradiol plus bromocriptine showed an expansion of transgene-expressing B cells and enhanced Bcl-2 expression, similar to those of estradiol-treated mice. We identified anergic high-affinity anti-DNA B cells in mice treated with estradiol plus bromocriptine, and we showed by molecular analysis of anti-DNA hybridomas that their B cells derive from a naive repertoire. Thus, the estradiol-induced breakdown in B-cell tolerance can be abrogated by bromocriptine, which induces anergy in the high-affinity DNA-reactive B cells. These studies demonstrate that some of the effects of estrogen on naive autoreactive B cells require the presence of prolactin and, thus, suggest potential therapeutic interventions in lupus.

Sex hormones and SLE: influencing the fate of autoreactive B cells.

The prevalence of systemic lupus erythematosus (SLE) is far higher in females than in males and numerous investigations to understand this gender bias have been conducted. While it is plausible that some sex-linked genes may contribute to the genetic predisposition for the disease, other likely culprits are the sex hormones estrogen and prolactin. In this chapter we review studies that have addressed the influence of sex hormones in SLE activity and discuss the recent data established in a BALB/c mouse transgenic for the heavy chain of an anti-DNA antibody. These mice are prone to develop lupus following exposure to exogenous sex hormones. We describe how estrogen and prolactin influence B cell maturation and selection, permitting B cells to mature to immunocompetence. Finally, we discuss the relevance and implications of these data for human disease.

The French Muskoka Fund: origin, objectives, and implementation.

Through its Priority Solidarity Fund, France set up a partnership with four United Nations agencies, WHO, UNICEF, UNFPA, and UN WOMEN for the years 2011-2015 with an annual budget of 19 M €. An additional sixth year supplementary is underway. The program was developed through a common framework of actions coordinated and harmonized at the level of the target countries: integrated management of childhood diseases, mother-child nutrition, prenatal, perinatal, and postpartum follow-up, sexual and reproductive health, and adolescent health. The contribution of WHO was based on its normative role; UNICEF offered its operational capacity in the field, and UNFPA its focus on reproductive health, while UN WOMEN dealt with gender questions. The countries targeted specifically were: Benin, Burkina Faso, Côte d'Ivoire, Guinea, Haiti, Mali, Nigeria, Central Africa Republic, Democratic Republic of the Congo, Senegal, Chad, and Togo.

After Muskoka.

Substantial progress has been accomplished in reducing maternal, neonatal, and infant mortality, but the work to meet the Millennium Development Goals, boosted by numerous initiatives, including Muskoka, is far from finished. Since 2016, the Sustainable Development Goals, as well as the International Strategy for Women's, Children's, and Adolescent Health 2016 - 2030, have provided to the countries and development partners a consistent framework for action enlarged to all of the dimensions of human development, while keeping women, children, and adolescents at its heart. In this context, the Muskoka program, after an initial 5-year cycle, will continue in 2017.

Evaluation of antiandrogen therapy in unresectable hepatocellular carcinoma: results of a European Organization for Research and Treatment of Cancer multicentric double-blind trial.

PURPOSE: The aim of the study was to evaluate the efficacy of antiandrogen therapy on overall survival and response in unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: A total of 244 patients with unresectable HCC were included in this multicentric double-blind trial. According to a two-by-two factorial design, patients were randomly assigned to receive one of the following treatments: pure antiandrogen plus placebo (A+P group, 60 patients); luteinizing hormone-releasing hormone (LHRH) agonist plus placebo (LHRH+P group, 62 patients); pure antiandrogen plus LHRH agonist (A+LHRH group, 62 patients); or placebo plus placebo (P+P group, 60 patients). Pure antiandrogen consisted of Anandron (Roussel-Uclaf Laboratory, Romainville, France) administered orally (300 mg daily for 1 month, then 150 mg daily). LHRH consisted of goseriline acetate (3.6 mg) or triptoreline (3.75 mg) administered monthly by subcutaneous injection. Treatment was given until death. Response was evaluated every 8 weeks according to World Health Organization (WHO) criteria. RESULTS: Six patients were considered ineligible. One patient had a complete response (A+P arm) and three had a partial response (two in the LHRH+P arm and one in the A+LHRH arm). An overall log-rank test did not demonstrate any significant difference in survival among the four arms. Taking the factorial design into account, comparison of survival showed no significant difference between Anandron-containing regimens and others, or between LHRH-containing regimens and others. No serious side effects occurred for any regimen. CONCLUSION: This controlled study shows clearly the lack of efficacy of androgen treatment in unresectable HCC.