Study of aerobic granular sludge stability in a continuous-flow membrane bioreactor

A granular continuous-flow membrane bioreactor with a novel hydrodynamic configuration was developed to evaluate the stability of aerobic granular sludge (AGS). Under continuous-flow operation (Period I), AGS rapidly lost their structural integrity resulting in loose and fluffy microbial aggregates in which filamentous bacteria were dominant. The intermittent feeding (Period II) allowed obtaining the succession of feast and famine conditions that favored the increase in AGS stability. Although no further breakage occurred, the formation of new granules was very limited, owing to the absence of the hydraulic selection pressure. These results noted the necessity to ensure, on the one hand the succession of feast/famine conditions, and on the other, the hydraulic selection pressure that allows flocculent sludge washout. This preliminary study shows that the proposed configuration could meet the first aspect; in contrast, biomass selection needs to be improved

Epidemiology of intensive care unit-acquired sepsis in Italy: results of the SPIN-UTI network

BACKGROUND: Sepsis is the major cause of mortality from any infectious disease worldwide. Sepsis may be the result of a healthcare associated infection (HAI): the most frequent adverse events during care delivery especially in Intensive Care Units (ICUs). The main aim of the present study was to describe the epidemiology of ICU-acquired sepsis and related outcomes among patients enrolled in the framework of the Italian Nosocomial Infections Surveillance in ICUs - SPIN-UTI project. STUDY DESIGN: Prospective multicenter study. METHODS: The SPIN-UTI network adopted the European protocols for patient-based HAI surveillance. RESULTS: During the five editions of the SPIN-UTI project, from 2008 to 2017, 47.0% of HAIs has led to sepsis in 832 patients. Overall, 57.0% episodes were classified as sepsis, 20.5% as severe sepsis and 22.5% as septic shock. The most common isolated microorganisms from sepsis episodes were Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa. The case fatality rate increased with the severity of sepsis and the mean length of ICU-stay was significantly higher in patients with ICU-acquired sepsis than in patients without. CONCLUSION: Our study provides evidence that ICU-acquired sepsis occurs frequently in Italian ICU patients and is associated with a high case fatality rate and increased length of stay. However, in order to explain these findings further analyses are needed in this population of ICU patient

Cytochrome c Reduction by H2S Potentiates Sulfide Signaling.

This is the author accepted manuscript. The final version is available from American Chemical Society via the DOI in this record.Hydrogen sulfide (H2S) is an endogenously produced gas that is toxic at high concentrations. It is eliminated by a dedicated mitochondrial sulfide oxidation pathway, which connects to the electron transfer chain at the level of complex III. Direct reduction of cytochrome c (Cyt C) by H2S has been reported previously but not characterized. In this study, we demonstrate that reduction of ferric Cyt C by H2S exhibits hysteretic behavior, which suggests the involvement of reactive sulfur species in the reduction process and is consistent with a reaction stoichiometry of 1.5 mol of Cyt C reduced/mol of H2S oxidized. H2S increases O2 consumption by human cells (HT29 and HepG2) treated with the complex III inhibitor antimycin A, which is consistent with the entry of sulfide-derived electrons at the level of complex IV. Cyt C-dependent H2S oxidation stimulated protein persulfidation in vitro, while silencing of Cyt C expression decreased mitochondrial protein persulfidation in a cell culture. Cyt C released during apoptosis was correlated with persulfidation of procaspase 9 and with loss of its activity. These results reveal a potential role for the electron transfer chain in general, and Cyt C in particular, for potentiating sulfide-based signaling.This work was supported by the French State in the frame of the “Investments for the future” Programme IdEx Bordeaux, reference ANR-10-IDEX-03-02, and by an ATIP-AVENIR grant (to M.R.F.), the National Institutes of Health (GM112455 to R.B. and R01GM113030 to M.D.P.), the Medical Research Council, UK (MR/M022706/1 to M.W.), the National Science Foundation (DGE-1309047 to A.K.S.), and the Brian Ridge Scholarship (R.T.). The authors are grateful to M.-F. Giraud for the help with purification of mitochondria

Hydrogen sulfide protects renal grafts against prolonged cold ischemia-reperfusion injury via specific mitochondrial actions

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/ajt.14080 This article is protected by copyright. All rights reserved.Accepted manuscript online: 15 October 2016Ischemia-reperfusion injury (IRI) is unavoidably caused by loss and subsequent restoration of blood flow during organ procurement and prolonged IRI results in increased rates of delayed graft function and early graft loss. The endogenously produced gasotransmitter, hydrogen sulfide (H2 S), is a novel molecule that mitigates hypoxic tissue injury. The current study investigates the protective mitochondrial effects of H2 S during in vivo cold storage and subsequent renal transplantation (RTx) and in vitro cold hypoxic renal injury. Donor allografts from Brown Norway rats treated with University of Wisconsin (UW) solution + H2 S (150 μM NaSH) during prolonged (24-hour) cold (4°C) storage exhibited significantly (p1000-fold compared to similar levels of the non-specific H2 S donor, GYY4137 and also improved syngraft function and survival following prolonged cold storage compared to UW. H2 S treatment mitigates cold IRI-associated renal injury via mitochondrial actions and could represent a novel therapeutic strategy to minimize the detrimental clinical outcomes of prolonged cold IRI during RTx.This work was supported by grants from Physicians Services Incorporated and the Canadian Urological Association (AS) and by a Frederick Banting and Charles Best Canada Graduate Scholarships Doctoral Award from the Canadian Institutes of Health Research (IL). MW and MEW would like to thank the Medical Research Council UK (MR/M022706/1) for their generous research support. RT would like to acknowledge the Brian Ridge Scholarship for support

GYY4137, a slow-releasing hydrogen sulfide donor, ameliorates renal damage associated with chronic obstructive uropathy.

PURPOSE: Chronic obstructive uropathy can cause irreversible kidney injury, atrophy, and inflammation, which can ultimately lead to fibrosis. Epithelial-mesenchymal transition (EMT) is a key trigger of fibrosis and is caused by upregulation of transforming growth factor beta 1 (TGF-β1) and angiotensin II (ANGII). Hydrogen sulfide (H2S) is an endogenously produced gasotransmitter with cytoprotective properties. The present study aims to elucidate the effects of the slow-releasing H2S donor GYY4137 on chronic ureteral obstruction and evaluate potential mechanisms. MATERIALS AND METHODS: Following unilateral ureteral obstruction (UUO), male Lewis rats were given daily intraperitoneal (IP) administration of phosphate buffered saline (PBS) vehicle (UUO group) or PBS+200μmol/kg GYY4137 (UUO+GYY4137 group) for 30 days. Urine and serum samples were collected to determine physiological parameters of renal function and injury. Kidneys were removed on post-operative day 30 for evaluation of histopathology and protein expression. EMT in pig kidney epithelial cells (LLC-PK1) was induced with TGF-β1 and treated with GYY4137 to evaluate potential mechanisms via in vitro scratch wound assays. RESULTS: H2S treatment decreased serum creatinine and urine protein/creatinine excretion ratio following UUO. In addition, H2S mitigated cortical loss, inflammatory damage, and tubulointerstitial fibrosis. Tissues exhibited decreased expression of EMT markers upon H2S treatment. EMT progression in LLC-PK1 was alleviated upon in vitro administration of GYY4137. CONCLUSIONS: Our findings demonstrate, for the first time, the protective effects of H2S in chronic obstructive uropathy and may represent a potential therapeutic solution to ameliorate renal damage and improve clinical outcomes of urinary obstruction.This work was supported by a grant from the Lawson Health Research Foundation

Lung recurrence of papillary thyroid cancer diagnosed with antithyroglobulin antibodies after 10 years from initial treatment.

Introduction: Papillary thyroid cancer (PTC) is the most common endocrine malignancy. More than 98% of patients achieve an excellent response with no evidence of clinical, biochemical, or structural disease after initial treatment. In these patients structural recurrence is rare, more frequently diagnosed in the first 5 years from initial treatment and almost invariably localized in neck lymph nodes. Patient: We report the case of a woman affected by PTC who presented with rapidly rising anti-thyroglobulin antibodies (TgAb) level after 10 years from clinical, morphological and biochemical remission. Diagnosis and Treatment: In 2003, a 56 year old patient was treated with total thyroidectomy and radioiodine remnant ablation (RRA) for a PTC (2 cm) with minimal extrathyroidal extension (T3N1aM0 according to the 6th AJCC TNM staging system) associated with diffuse lymphocytic thyroiditis. In 2004 the patient was free of disease defined as undetectable Tg after recombinant human TSH administration in the absence of TgAb and structural disease. Since February 2012 the appearance and progressive increase of TgAb titer was observed and in 2014 a18FDG-PET scan documented three hypermetabolic lesions suggestive of lung micrometastases. The lung lesions were cytologically confirmed as PTC metastases. Both the primary tissue and the lung metastasis were positive for BRAF V600E mutation. The patient was treated with 131-radioiodine that showed radioiodine avid lung lesions that lose the ability to take up iodine at the following treatment. The patient is still alive and the lung lesions are growing slowly. Conclusions: Structural recurrence in patients that demonstrated an excellent response after initial treatment for PTC is extremely rare, and distant metastases exceptional but possible. This case is peculiar because recurrence was early identified after 10 years from initial treatment for the presence of detectable TgAb in a patient that had an histological diagnosis of lymphocytic thyroiditis but with an atypical clinical presentation (normal thyroid at neck ultrasound and undetectable TgAb and anti-thyroid peroxidase antibodies). For this reason TgAb should be tested with Tg in patients with a history of lymphocytic thyroiditis, either histological or humoral, also when TgAb is in the normal range and not suggestive of autoimmune thyroiditis

MicroRNA expression profiling of RAS-mutant thyroid tumors with follicular architecture: microRNA signatures to discriminate benign from malignant lesions

Purpose: RAS mutations represent common driver alterations in thyroid cancer. They can be found in benign, low-risk and malignant thyroid tumors with follicular architecture, which are often diagnosed as indeterminate nodules on preoperative cytology. Therefore, the detection of RAS mutations in preoperative setting has a suboptimal predictive value for malignancy. In this study, we investigated differentially expressed microRNA (miRNA) in benign and malignant thyroid tumors with follicular architecture carrying mutations in RAS genes. Methods: Total RNA was purified from 60 RAS-mutant follicular-patterned thyroid tumors, including follicular adenoma (FA), noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), papillary and follicular thyroid carcinoma cases (PTC, FTC); 22 RAS-negative FAs were used as controls. The expression analysis of 798 miRNAs was performed by digital counting (nCounter nanoString platform). Results: Comparing RAS-mutant and RAS-negative FAs, 12 miRNAs showed significant deregulation, which was likely related to the oncogenic effects of RAS mutations. Twenty-two miRNAs were differentially expressed in RAS-mutant benign versus malignant tumors. Considering the tumor type, 24 miRNAs were deregulated in PTC, 19 in NIFTP, and seven in FTC and compared to FA group; among these, miR-146b-5p, miR-144-3p, and miR-451a showed consistent deregulation in all the comparisons with the highest fold change. Conclusions: The miRNA expression analysis of follicular-patterned thyroid tumors demonstrated that RAS mutations influences miRNA profile in benign tumors. In addition, several miRNAs showed a histotype-specific deregulation and could discriminate between RAS-mutant benign and RAS-mutant malignant thyroid lesions, thus deserving further investigation as potential diagnostic markers