The IgA nephropathy Biobank. An important starting point for the genetic dissection of a complex trait

BACKGROUND: IgA nephropathy (IgAN) or Berger's disease, is the most common glomerulonephritis in the world diagnosed in renal biopsied patients. The involvement of genetic factors in the pathogenesis of the IgAN is evidenced by ethnic and geographic variations in prevalence, familial clustering in isolated populations, familial aggregation and by the identification of a genetic linkage to locus IGAN1 mapped on 6q22–23. This study seems to imply a single major locus, but the hypothesis of multiple interacting loci or genetic heterogeneity cannot be ruled out. The organization of a multi-centre Biobank for the collection of biological samples and clinical data from IgAN patients and relatives is an important starting point for the identification of the disease susceptibility genes. DESCRIPTION: The IgAN Consortium organized a Biobank, recruiting IgAN patients and relatives following a common protocol. A website was constructed to allow scientific information to be shared between partners and to divulge obtained data (URL: ). The electronic database, the core of the website includes data concerning the subjects enrolled. A search page gives open access to the database and allows groups of patients to be selected according to their clinical characteristics. DNA samples of IgAN patients and relatives belonging to 72 multiplex extended pedigrees were collected. Moreover, 159 trios (sons/daughters affected and healthy parents), 1068 patients with biopsy-proven IgAN and 1040 healthy subjects were included in the IgAN Consortium Biobank. Some valuable and statistically productive genetic studies have been launched within the 5(th )Framework Programme 1998–2002 of the European project No. QLG1-2000-00464 and preliminary data have been published in "Technology Marketplace" website: . CONCLUSION: The first world IgAN Biobank with a readily accessible database has been constituted. The knowledge gained from the study of Mendelian diseases has shown that the genetic dissection of a complex trait is more powerful when combined linkage-based, association-based, and sequence-based approaches are performed. This Biobank continuously expanded contains a sample size of adequately matched IgAN patients and healthy subjects, extended multiplex pedigrees, parent-child trios, thus permitting the combined genetic approaches with collaborative studies

Geographical variation in therapy for bloodstream infections due to multidrug-resistant enterobacteriaceae: a post hoc analysis of the INCREMENT study

We aimed to describe regional differences in therapy for bloodstream infection (BSI) caused by extended-spectrum ?-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). 1,482 patients in 12 countries were included from an observational study of BSI caused by ESBL-E or CPE. Multivariate logistic regression was used to calculate adjusted odds ratios (aORs) for the influence of country of recruitment on empirical use of ?-lactam/?-lactamase inhibitors (BLBLI) or carbapenems, targeted use of BLBLI for ESBL-E and use of targeted combination therapy for CPE. The use of BLBLI for empirical therapy was least likely in sites from Israel (aOR 0.34, 95% CI 0.14-0.81), Greece (aOR 0.49, 95% CI 0.26-0.94) and Canada (aOR 0.31, 95% CI 0.11-0.88) but more likely in Italy (aOR 1.58, 95% CI 1.11-2.2) and Turkey (aOR 2.09, 95% CI 1.14-3.81), compared to Spain as a reference. Empirical carbapenems were more likely to be used in sites from Taiwan (aOR 1.73, 95% CI 1.03-2.92) and USA (aOR 1.89; 95% CI 1.05-3.39), and less likely in Italy (aOR 0.44, 95% CI 0.28-0.69) and Canada (aOR 0.10, 95% CI 0.01-0.74). Targeted BLBLI for ESBL-E was more likely in sites from Italy. Treatment at sites within Israel, Taiwan, Turkey and Brazil was associated with less combination therapy for CPE. Although this study does not provide precise data on the relative prevalence of ESBL-E or CPE, significant variation in therapy exists across countries even after adjustment for patient factors. A better understanding of what influences therapeutic choices for these infections will aid antimicrobial stewardship efforts.PH is supported by an Australian Postgraduate Award from the University of Queensland. The study was funded by the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III - co-financed by European Development Regional Fund "A way to achieve Europe" ERDF, Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015). BGG, JRB, APH and YC also received funds from the COMBACTE-CARE project (grant agreement 115620), Innovative Medicines Initiative (IMI), the European Union's Seventh Framework Programme (FP7/2007-2013) and in-kind contributions from EFPIA companies

Author Correction:A consensus protocol for functional connectivity analysis in the rat brain

International audienceNo abstract availabl

A consensus protocol for functional connectivity analysis in the rat brain

Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows for comparisons with data modalities collected under invasive or terminal procedures. Currently, animal acquisitions are performed with varying protocols and analyses that hamper result comparison and integration. Here we introduce StandardRat, a consensus rat functional magnetic resonance imaging acquisition protocol tested across 20 centers. To develop this protocol with optimized acquisition and processing parameters, we initially aggregated 65 functional imaging datasets acquired from rats across 46 centers. We developed a reproducible pipeline for analyzing rat data acquired with diverse protocols and determined experimental and processing parameters associated with the robust detection of functional connectivity across centers. We show that the standardized protocol enhances biologically plausible functional connectivity patterns relative to previous acquisitions. The protocol and processing pipeline described here is openly shared with the neuroimaging community to promote interoperability and cooperation toward tackling the most important challenges in neuroscience

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Boost type resonant LCL-T converter for autonomous power supply system from renewable sources

Актуальность. Проблеме автономного электропитания нефтегазового оборудования на возобновляемых источниках энергии оказывается все большее внимание ввиду экологической чистоты этого вида энергии. Требования, предъявляемые системой электропитания к преобразователю энергии солнечной батареи, заключаются в первую очередь в высоком КПД и широком диапазоне изменения нагрузки, меняющейся вплоть до холостого хода. Последнее требование является серьезной проблемой, учитывая, что солнечная батарея по своей природе является источником постоянного тока. При применении непосредственных преобразователей изменение нагрузки вызывает существенные затруднения и приводит к глубокому регулированию, необходимости формирования быстродействующих контуров обратной связи. В работе рассмотрены топологии резонансного преобразователя энергии солнечной батареи на основе LCL-T контура, обеспечивающего не только мягкое переключение транзисторов, но и параметрическую стабилизацию выходного напряжения в полном диапазоне изменения нагрузки за счет преобразования импеданса нагрузки. Цель работы: анализ энергетических характеристик вольтодобавочного резонансного LCL-T преобразователя энергии солнечной батареи и оценка его КПД. Методы исследования основаны на общих положениях теории электрических цепей, теории алгебраических уравнений, вычислительных методах и использовании современных инструментальных систем и методов математического моделирования. Результаты. Показано, что при питании от источника тока для реализации параметрической стабилизации выходного напряжения резонансным LCL-T преобразователем необходим активный выпрямитель, обеспечивающий рекуперацию энергии выходного фильтра в резонансный контур. При этом статические потери в преобразователе существенны, так как ток инвертора определяется током солнечной батареи. Построение резонансного преобразователя по вольтодобавочной топологии позволяет разделить ток солнечной батареи между мостовыми преобразователями и существенно уменьшить статические потери, что, учитывая одновременную реализацию мягкого переключения транзисторов, позволяет получить высокий КПД преобразования, свыше 98 % в номинальном режиме. Исследованы характеристики вольтодобавочного резонансного LCL-T преобразователя при широтно-импульсном регулировании. Во всем диапазоне регулирования параметры схемы не превышают номинальных значений, так как их увеличение за счет фазового сдвига тока относительно напряжения, неизбежного в процессе регулирования, компенсируется уменьшением тока солнечной батареи. Преобразователь с LCL-T контуром обеспечивает мягкую коммутацию транзисторов без частотной подстройки, необходимой в классическом последовательном преобразователе. Проведена экспериментальная проверка полученных результатов, сделаны выводы.Relevance. Autonomous electrical supply from renewable sources in oil-gas equipment is considered more and more due to ecology concerns. The requirements set by the power supply system to the converter include high efficiency and wide load range including idle. The latter is quite serious taking into account intrinsic property as a current source of photovoltaic. Direct conversion is impeded and required high loop gain as well as high speed in a control circuit. Current work examines resonant converter topologies for solar sources assuring soft commutation as well as parametric stabilization of the output voltage in full load range due to load impedance transformation. The aim of the research is the analysis of electrical properties of boost resonant LCL-T converter for photovoltaics along with efficiency of the one. Methods: basic electric circuit theory, algebraic equations, computational solving as well as modern instrumental systems and numerical simulation. Results. It is shown that current fed resonant LCL-T converter needs active rectifier to achieve parametric output voltage stabilization by recuperation energy out of output filter into resonant tank. That solution has high static losses because they are determined by the photovoltaic's current. Use of boost topology allowed divert source's current between bridge converters thus less static losses to achieve 98 % efficiency at nominal load. The authors have examined the properties of boost type resonant LCL-T converter controlled by PWM. Current and voltage values within the full control range do not exceed nominal ones due to mitigation of gain rise by declining source (solar battery) current. The gain increase is caused by the phase shift between current and voltage. LCL-T converter assures soft commutation of the transistors without frequency adjustment needed in typical series resonant converter. Validation of the result obtained is provided, conclusions are given

Management of STEC Gastroenteritis: Is There a Role for Probiotics?

Shiga toxin-producing Escherichia Coli (STEC) infections routinely run as a common gastroenteritis, but in many cases they may evolve towards hemolytic uremic syndrome (HUS). HUS is a rare disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Gut microorganisms have a fundamental impact on human physiology, because they modulate normal intestinal functions and play a pivotal role in influencing the local and systemic immune responses. Despite surveillance established in many countries and major progresses in the understanding of STEC-HUS mechanisms, no specific treatment is currently available. Targeting the gut microbiota could represent a new potential therapeutic strategy in STEC infection. In this paper, we reviewed the current knowledge about microbiota characteristics of patients with STEC infections, as well as in vitro and in vivo evidence of probiotic supplementation in managing STEC gastroenteritis and in HUS onset prevention.</jats:p

Low C3 Serum Levels Predict Severe Forms of STEC-HUS With Neurologic Involvement

Background: The correlation between the severity of hemolytic uremic syndrome related to Shiga toxin–producing Escherichia coli (STEC-HUS) and involvement of the complement system has been examined in a small number of studies, with conflicting results. In the present study, we investigated whether serum C3 levels on admission are associated with neurologic involvement. Methods: To this purpose, 68 consecutive STEC-HUS patients were recruited and main clinical and laboratory variables ad hospital admission were compared between those with or without neurologic involvement. Results: STEC-HUS patients who developed neurologic involvement (NI) showed significant higher leukocyte count, C-reactive protein and hemoglobin, and lower sodium levels as compared with those without. Interestingly, baseline serum levels of C3 were significantly lower in patients with NI as compared with those without (p &lt; 0.001). Moreover, when stratified according to need of Eculizumab rescue therapy due to severe NI, patients treated with this drug showed baseline C3 serum levels significantly lower than those who were not (p &lt; 0.001). Low C3 was independent risk factor for NI in our patients' population when entered as covariate in a multivariate logistic regression analysis including other major variables previously proposed as possible predictors of poor prognosis in STEC-HUS (for instance, leukocyte count, c-reactive protein, sodium levels) (HR 6.401, 95%CI 1.617–25.334, p = 0.008 for C3). To underline the role of complement in the worsening of STEC-HUS patients' clinical conditions and outcomes, all patients were divided into two groups according to the baseline lower vs. normal serum levels of C3 and the main data on care needs were assessed. Interestingly more patients with lower C3 serum levels required renal replacement therapy (p = 0.024), anti-hypertensive therapy (p = 0.011), Intensive Care Unit admission (p = 0.009), and longer hospitalization (p = 0.003), thus displaying significantly more severe disease features as compared with those with normal C3 serum levels. Conclusions: Our data suggests that children with STEC-HUS with decreased C3 concentrations at admission are more likely to develop neurologic involvement and are at increased risk of having severe clinical complications

Management of STEC Gastroenteritis: Is There a Role for Probiotics?

Shiga toxin-producing Escherichia Coli (STEC) infections routinely run as a common gastroenteritis, but in many cases they may evolve towards hemolytic uremic syndrome (HUS). HUS is a rare disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Gut microorganisms have a fundamental impact on human physiology, because they modulate normal intestinal functions and play a pivotal role in influencing the local and systemic immune responses. Despite surveillance established in many countries and major progresses in the understanding of STEC-HUS mechanisms, no specific treatment is currently available. Targeting the gut microbiota could represent a new potential therapeutic strategy in STEC infection. In this paper, we reviewed the current knowledge about microbiota characteristics of patients with STEC infections, as well as in vitro and in vivo evidence of probiotic supplementation in managing STEC gastroenteritis and in HUS onset prevention