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

The Dually Acylated NH2-terminal Domain of Gi1α Is Sufficient to Target a Green Fluorescent Protein Reporter to Caveolin-enriched Plasma Membrane Domains: PALMITOYLATION OF CAVEOLIN-1 IS REQUIRED FOR THE RECOGNITION OF DUALLY ACYLATED G-PROTEIN α SUBUNITS IN VIVO

Here we investigate the molecular mechanisms that govern the targeting of G-protein α subunits to the plasma membrane. For this purpose, we used Gi1α as a model dually acylated G-protein. We fused full-length Gi1α or its extreme NH2-terminal domain (residues 1–32 or 1–122) to green fluorescent protein (GFP) and analyzed the subcellular localization of these fusion proteins. We show that the first 32 amino acids of Gi1α are sufficient to target GFP to caveolin-enriched domains of the plasma membrane in vivo, as demonstrated by co-fractionation and co-immunoprecipitation with caveolin-1. Interestingly, when dual acylation of this 32-amino acid domain was blocked by specific point mutations (G2A or C3S), the resulting GFP fusion proteins were localized to the cytoplasm and excluded from caveolin-rich regions. The myristoylated but nonpalmitoylated (C3S) chimera only partially partitioned into caveolin-containing fractions. However, both nonacylated GFP fusions (G2A and C3S) no longer co-immunoprecipitated with caveolin-1. Taken together, these results indicate that lipid modification of the NH2-terminal of Gi1α is essential for targeting to its correct destination and interaction with caveolin-1. Also, a caveolin-1 mutant lacking all three palmitoylation sites (C133S, C143S, and C156S) was unable to co-immunoprecipitate these dually acylated GFP-G-protein fusions. Thus, dual acylation of the NH2-terminal domain of Gi1α and palmitoylation of caveolin-1 are both required to stabilize and perhaps regulate this reciprocal interaction at the plasma membrane in vivo. Our results provide the first demonstration of a functional role for caveolin-1 palmitoylation in its interaction with signaling molecules

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

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

Abstract Background 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. Content 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. Summary 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. Outlook 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

Granular cell tumor of the breast: a multidisciplinary challenge

Granular cell tumors are rare soft tissue tumors; they are almost never malignant, but can mimic a carcinoma clinically, radiologically and microscopically. The finding of a suspicious lump often entails subsequent diagnostic procedures that can pose significant anxiety on patients before reaching a challenging differential diagnosis. The physical and psychological burden is even more significant when such findings occur during the follow up of a previous oncologic condition. Sometimes the fear for a potential local or distant recurrence can be responsible for a misdiagnosis and lead to patient overtreatment

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

Association of Gray Matter Atrophy Patterns with Clinical Phenotype and Progression in Multiple Sclerosis

OBJECTIVES: Grey matter (GM) involvement is clinically relevant in multiple sclerosis (MS). Using source-based morphometry (SBM), we characterized GM atrophy and its 1-year evolution across different MS phenotypes. METHODS: Clinical and MRI data were obtained at 8 European sites from 170 healthy controls (HCs) and 398 MS patients (34 clinically isolated syndromes [CIS], 226 relapsing-remitting [RR], 95 secondary progressive [SP] and 43 primary progressive [PP] MS). Fifty-seven HC and 144 MS underwent 1-year follow-up. Baseline GM loss, atrophy progression and correlations with disability and 1-year clinical worsening were assessed. RESULTS: SBM identified 26 cerebellar, subcortical, sensory, motor and cognitive GM components. GM atrophy was found in MS vs HC in almost all components (p=range<0.001-0.04). Compared to HCs, CIS patients showed circumscribed subcortical, cerebellar, temporal and salience GM atrophy, while RRMS patients exhibited widespread GM atrophy. Cerebellar, subcortical, sensorimotor, salience and fronto-parietal GM atrophy was found in PPMS patients vs HCs, and SPMS vs RRMS. At 1-year, 21 (15%) patients had clinically worsened. GM atrophy progressed in MS in subcortical, cerebellar, sensorimotor, and fronto-temporo-parietal components. Baseline higher disability was associated (R2=0.65) with baseline lower normalized brain volume (beta=-0.13, p=0.001), greater sensorimotor GM atrophy (beta=-0.12, p=0.002) and longer disease duration (beta=0.09, p=0.04). Baseline normalized GM volume (odds ratio=0.98, p=0.008) and cerebellar GM atrophy (odds ratio=0.40, p=0.01) independently predicted clinical worsening (area-under-the-curve=0.83). CONCLUSION: GM atrophy differed across disease phenotypes and progressed at 1-year in MS. In addition to global atrophy measures, sensorimotor and cerebellar GM atrophy explained baseline disability and clinical worsening

Development of a novel nomogram-based online tool to predict axillary status after neoadjuvant chemotherapy in cN+ breast cancer: A multicentre study on 1,950 patients

Background: Type of axillary surgery in breast cancer (BC) patients who convert from cN + to ycN0 after neoadjuvant chemotherapy (NAC) is still debated. The aim of the present study was to develop and validate a preoperative predictive nomogram to select those patients with a low risk of residual axillary disease after NAC, in whom axillary surgery could be minimized. Patients and methods: 1950 clinically node-positive BC patients from 11 Breast Units, treated by NAC and subsequent surgery, were included from 2005 to 2020. Patients were divided in two groups: those who achieved nodal pCR vs. those with residual nodal disease after NAC. The cohort was divided into training and validation set with a geographic separation criterion. The outcome was to identify independent predictors of axillary pathologic complete response (pCR). Results: Independent predictive factors associated to nodal pCR were axillary clinical complete response (cCR) after NAC (OR 3.11, p &lt; 0.0001), ER-/HER2+ (OR 3.26, p &lt; 0.0001) or ER+/HER2+ (OR 2.26, p = 0.0002) or ER-/HER2- (OR 1.89, p = 0.009) BC, breast cCR (OR 2.48, p &lt; 0.0001), Ki67 &gt; 14% (OR 0.52, p = 0.0005), and tumor grading G2 (OR 0.35, p = 0.002) or G3 (OR 0.29, p = 0.0003). The nomogram showed a sensitivity of 71% and a specificity of 73% (AUC 0.77, 95%CI 0.75\u20130.80). After external validation the accuracy of the nomogram was confirmed. Conclusion: The accuracy makes this freely-available, nomogram-based online tool useful to predict nodal pCR after NAC, translating the concept of tailored axillary surgery also in this setting of patients