Intra-datacenter links exploiting PCI express generation 4 interconnections

We demonstrate few-km reaches for PCIe-based optical fiber interconnections according to latency limitations, characterizing 16-Gb/s per lane Generation4 up to 10 km and confirming the Generation3 compliance of 2-km links employing suitable PCIe cards

Left Ventricular Unloading in Extracorporeal Membrane Oxygenation:A Clinical Perspective Derived from Basic Cardiovascular Physiology

Purpose of Review: To present an abridged overview of the literature and pathophysiological background of adjunct interventional left ventricular unloading strategies during veno-arterial extracorporeal membrane oxygenation (V-A ECMO). From a clinical perspective, the mechanistic complexity of such combined mechanical circulatory support often requires in-depth physiological reasoning at the bedside, which remains a cornerstone of daily practice for optimal patient-specific V-A ECMO care. Recent Findings: Recent conventional clinical trials have not convincingly shown the superiority of V-A ECMO in acute myocardial infarction complicated by cardiogenic shock as compared with medical therapy alone. Though, it has repeatedly been reported that the addition of interventional left ventricular unloading to V-A ECMO may improve clinical outcome. Novel approaches such as registry-based adaptive platform trials and computational physiological modeling are now introduced to inform clinicians by aiming to better account for patient-specific variation and complexity inherent to V-A ECMO and have raised a widespread interest. Summary: To provide modern high-quality V-A ECMO care, it remains essential to understand the patient's pathophysiology and the intricate interaction of an individual patient with extracorporeal circulatory support devices. Innovative clinical trial design and computational modeling approaches carry great potential towards advanced clinical decision support in ECMO and related critical care.</p

Which laboratory technique is used for the blood sodium analysis in clinical research? A systematic review

Circulating sodium is analyzed by flame spectrometry and indirect or direct potentiometry. The differences between estimates returned by the three techniques are often relevant. It is unknown whether peer-reviewed international publications focusing on this parameter provide information about the technique. Objectives of the study were to ascertain if information about the employed technique is provided. A search in the National Library of Medicine for articles whose title contains "hyponatr[a]emia"was performed. We restricted the search to clinical reports including 10 or more humans published in the 2013-2015 and 2017-2019 periods. Authors of papers not reporting the technique were contacted to obtain this information. The study design and journal quartile ranking of each article were also evaluated. For the final analysis, we included 361 articles (2013-2015, n=169; 2017-2019, n=192). Information about the laboratory technique was given in 61(17%) articles. Thanks to our inquiry, we collected this information for 116(32%) further reports. Indirect potentiometry was the most frequently used technique, followed by direct potentiometry. Spectrometry was used in a small minority of studies. Study design, journal ranking and study period did not modulate the mentioned frequency. Most articles focusing on hyponatremia do not provide information on the laboratory technique. This parameter is nowadays analyzed by indirect or, less frequently, direct potentiometry. The figures are similar for high and low impact factor journals and for the 2013-2015 and the 2017-2019 periods. Many authors, reviewers and editors likely assume that the results of this parameter are not influenced by the technique

Which laboratory technique is used for the blood sodium analysis in clinical research? A systematic review.

Circulating sodium is analyzed by flame spectrometry and indirect or direct potentiometry. The differences between estimates returned by the three techniques are often relevant. It is unknown whether peer-reviewed international publications focusing on this parameter provide information about the technique. Objectives of the study were to ascertain if information about the employed technique is provided. A search in the National Library of Medicine for articles whose title contains "hyponatr[a]emia" was performed. We restricted the search to clinical reports including 10 or more humans published in the 2013-2015 and 2017-2019 periods. Authors of papers not reporting the technique were contacted to obtain this information. The study design and journal quartile ranking of each article were also evaluated. For the final analysis, we included 361 articles (2013-2015, n=169; 2017-2019, n=192). Information about the laboratory technique was given in 61(17%) articles. Thanks to our inquiry, we collected this information for 116(32%) further reports. Indirect potentiometry was the most frequently used technique, followed by direct potentiometry. Spectrometry was used in a small minority of studies. Study design, journal ranking and study period did not modulate the mentioned frequency. Most articles focusing on hyponatremia do not provide information on the laboratory technique. This parameter is nowadays analyzed by indirect or, less frequently, direct potentiometry. The figures are similar for high and low impact factor journals and for the 2013-2015 and the 2017-2019 periods. Many authors, reviewers and editors likely assume that the results of this parameter are not influenced by the technique

Sodium assessment in neonates, infants, and children: a systematic review

Hyponatremia is a common disorder in childhood. The indirect and the direct potentiometry are currently the most popular techniques employed for sodium assessment, although discrepancies between the two techniques may be &gt; 10 mmol/L. It is known that &lt; 20% of the recently published articles report information about the technique used for sodium analysis, but no data are available on pediatric studies. This study aimed at investigating the laboratory technique employed for sodium measurement in studies conducted in childhood. A systematic literature search in PubMed, Embase, and Web of Science was undertaken to identify articles containing the word "hyponatremia" in the title between 2013 and 2020. Papers with &lt; 10 subjects were excluded. A total of 565 articles were included. Information on the laboratory technique used for sodium analysis was more commonly (p = 0.035) reported in pediatric (n = 15, 28%) than in non-pediatric (n = 81, 16%) reports. The frequency of reports with and without information on the technique for sodium assessment was not different with respect to the study characteristics, the quartile of the journal where the paper was published, the country income setting, and the inclusion of neonates among the 54 pediatric studies.Conclusion: Most pediatric papers do not report any information on the technique used for sodium analysis. Although international authorities have recommended the implementation of direct potentiometry, a low awareness on this issue is still widespread in pediatric research

Targeting the hedgehog transcription factors GLI1 and GLI2 restores sensitivity to vemurafenib-resistant human melanoma cells

BRAF inhibitor (BRAFi) therapy for melanoma patients harboring the V600E mutation is initially highly effective, but almost all patients relapse within a few months. Understanding the molecular mechanisms underpinning BRAFi-based therapy is therefore an important issue. Here we identified a previously unsuspected mechanism of BRAFi resistance driven by elevated Hedgehog (Hh) pathway activation that is observed in a cohort of melanoma patients after vemurafenib treatment. Specifically, we demonstrate that melanoma cell lines, with acquired in vitro-induced vemurafenib resistance, show increased levels of glioma-associated oncogene homolog 1 and 2 (GLI1/GLI2) compared with naive cells. We also observed these findings in clinical melanoma specimens. Moreover, the increased expression of the transcription factors GLI1/GLI2 was independent of canonical Hh signaling and was instead correlated with the noncanonical Hh pathway, involving TGF beta/SMAD (transforming growth factor-beta/Sma- and Mad-related family) signaling. Knockdown of GLI1 and GLI2 restored sensitivity to vemurafenib-resistant cells, an effect associated with both growth arrest and senescence. Treatment of vemurafenib-resistant cells with the GLI1/GLI2 inhibitor Gant61 led to decreased invasion of the melanoma cells in a three-dimensional skin reconstruct model and was associated with a decrease in metalloproteinase (MMP2/MMP9) expression and microphthalmia transcription factor upregulation. Gant61 monotherapy did not alter the drug sensitivity of naive cells, but could reverse the resistance of melanoma cells chronically treated with vemurafenib. We further noted that alternating dosing schedules of Gant61 and vemurafenib prevented the onset of BRAFi resistance, suggesting that this could be a potential therapeutic strategy for the prevention of therapeutic escape. Our results suggest that targeting the Hh pathway in BRAFi-resistant melanoma may represent a viable therapeutic strategy to restore vemurafenib sensitivity, reducing or even inhibiting the acquired chemoresistance in melanoma patients.Fapesp-grant number 2012/04194-1, 2013/05172-4, 2014/24400-0 and 2015/10821-7, CNPq-grant number 150447/2013-2 and 471512/2013-3 and PRODOC-grant no 3193-32/2010. Work in the lab of KS Smalley was supported by the National Institutes of Health grants R01 CA161107, R21 CA198550, and Skin SPORE grant P50 CA168536info:eu-repo/semantics/publishedVersio

Impact of loop diuretic dosage in a population of patients with acute heart failure: a retrospective analysis

BackgroundLoop diuretics are essential for managing congestion in acute heart failure (AHF) patients, but concerns exist about their dosing and administration. This study aims to explore the relationship between aggressive diuretic treatment and clinical outcomes in AHF patients.MethodsWe randomly selected 370 AHF patients from admissions at Maastricht University Medical Center between January 2011 and March 2017. Patients were divided into four quartiles based on diuretic doses administrated during index hospitalization. The primary endpoint was a composite of cardiovascular (CV) rehospitalization or death at 1 year.Results42.4% of patients experimented the primary outcome The composite endpoint rates were 35.4%, 41.6%, 38.5%, and 54.9%, respectively, from lowest to highest dose quartiles (p = 0.033). In univariate analysis, the outcome was significantly lower in the first three quartiles as compared to the fourth quartile. One-year CV mortality was 9.1%, 10.1%, 20.9% and 27.2%, respectively (p = 0.002). After adjusting for confounders, the association between loop diuretic dosage disappeared for both the primary outcome and one-year CV mortality. Most secondary outcomes and endpoints at 3 months, including worsening renal function, showed no significant differences between groups, while hypokaliemia occurrence, length of hospital stay and weight loss at index admission were higher in the fourth quartile compared to the first one.ConclusionsHigh loop diuretic doses are associated with poor outcomes in AHF patients, reflecting disease severity rather than harm from aggressive diuretic use. Furthermore, high diuretic doses do not seem to negatively affect kidney function

Sfrp5 Modulates Both Wnt and BMP Signaling and Regulates Gastrointestinal Organogensis in the Zebrafish, Danio rerio

Sfrp5 belongs to the family of secreted frizzled related proteins (Sfrp), secreted inhibitors of Wingless-MMTV Integration Site (Wnt) signaling, which play an important role in cancer and development. We selected sfrp5 because of its compelling expression profile in the developing endoderm in zebrafish, Danio rerio. In this study, overexpression of sfrp5 in embryos results in defects in both convergent extension (CE) by inhibition of non-canonical Wnt signaling and defects in dorsoventral patterning by inhibition of Tolloid-mediated proteolysis of the BMP inhibitor Chordin. From 25 hours post fertilization (hpf) to 3 days post fertilization (dpf), both overexpression and knockdown of Sfrp5 decrease the size of the endoderm, significantly reducing liver cell number. At 3 dpf, insulin-positive endodermal cells fail to coalesce into a single pancreatic islet. We show that Sfrp5 inhibits both canonical and non-canonical Wnt signaling during embryonic and endodermal development, resulting in endodermal abnormalities. © 2013 Stuckenholz et al