Targeting prolonged short-term central venous catheters to reduce hospital-wide catheter days and CLABSI rates.

Background: The risk of central line-associated bloodstream infection (CLABSI) is associated with central venous catheter (CVC) dwelling time. We implemented a hospital-wide intervention aimed to alert physicians to CVC duration and necessity and to improve the monitoring of CLABSI prevention process measures outside the intensive care unit (ICU).

Methods: A retrospective, before-after study that evaluated short-term, nonhemodialysis CVCs in and out of the ICU.

A rapid host-protein test for differentiating bacterial from viral infection: Apollo diagnostic accuracy study.

Objectives: To determine the diagnostic accuracy of a rapid host-protein test for differentiating bacterial from viral infections in patients who presented to the emergency department (ED) or urgent care center (UCC).

Methods: This was a prospective multicenter, blinded study. MeMed BV (MMBV), a test based on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-inducible protein-10 (IP-10), and C-reactive protein (CRP), was measured using a rapid measurement platform.

Associations of High-Sensitive Cardiac Troponin T in Healthy Newborns and Prolonged Second Stage of Labor, Neonatal and Maternal Factors: A Prospective Study.

Introduction: High-sensitivity cardiac troponin T (hs-cTnT) is not used routinely as a diagnostic biomarker in newborns. The high precision of hs-cTnT assays increases the ability to determine small differences in cTnT over time and to detect troponin T elevation; thus, we believe that hs-cTnT assays might improve clinical care. We explored the plausible association between hs-cTnT levels (ng/L) in healthy newborns and prolonged second stage of labor, neonatal, and maternal factors.

Diagnostic Accuracy of a Real-Time Host-Protein Test for Infection.

Objective: Determining infection etiology can be difficult because viral and bacterial diseases often manifest similarly. A host protein test that computationally integrates the circulating levels of TNF-related apoptosis-induced ligand, interferon γ-induced protein-10, and C-reactive protein to differentiate between bacterial and viral infection (called MMBV) demonstrated high performance in multiple prospective clinical validation studies. Here, MMBV's diagnostic accuracy is evaluated in febrile children for whom physicians were uncertain about etiology when applied at the physician's discretion.

The Diagnostic Value of Human Neutrophilic Peptides 1-3 in Acute Pediatric Febrile Illness.

It is prudent to develop biomarkers that enhance the differentiation between viral and bacterial infection in order to support expeditious and judicious antimicrobial implementation in emergency department admissions. Human neutrophilic peptides 1-3 (HNP1-3) are the major neutrophilic peptides with potent antimicrobial activity. We tested the performance of the plasma HNP1-3 test in a prospective observational cohort of children admitted to the emergency department for fever.

An immune-protein score combining TRAIL, IP-10 and CRP for predicting severe COVID-19 disease.

COVID-19 patients are oftentimes over- or under-treated due to a deficit in predictive management tools. This study reports derivation of an algorithm that integrates the host levels of TRAIL, IP-10, and CRP into a single numeric score that is an early indicator of severe outcome for COVID-19 patients and can identify patients at-risk to deteriorate. 394 COVID-19 patients were eligible; 29% meeting a severe outcome (intensive care unit admission/non-invasive or invasive ventilation/death).

Comparison between School-Age Children with and without Obesity in Nutritional and Inflammation Biomarkers.

Childhood obesity is a major health problem. We examined differences between children with obesity and normal weight in nutritional and inflammation biomarkers. A cross-sectional study was conducted among healthy children aged 10-12 years from Arab villages in Israel.

BV score differentiates viral from bacterial-viral co-infection in adenovirus PCR positive children.

Background And Objectives: Adenovirus causes acute respiratory illness that can mimic bacterial infection, making it challenging to differentiate adenoviral infection from adenoviral-bacterial co-infection. A host-protein score (BV score) for differentiating bacterial from viral infection that combines the expression levels of TNF-related apoptosis-induced ligand, interferon gamma-induced protein-10, and C-reactive protein exhibited a negative predictive value (NPV) of 98% in prior studies. Here we evaluate BV score's diagnostic accuracy in pediatrics with adenovirus PCR detection.

Does mRNA SARS-CoV-2 vaccine in the follicular fluid impact follicle and oocyte performance in IVF treatments?

Problem: The COVID-19 pandemic has many clinical manifestations. Rapid vaccine development raised concerns and speculations about future fertility outcomes and vaccine safety. We evaluated the effect of Pfizer-BioNTech mRNA SARS-CoV-2 vaccine on IVF treatment, oocyte and embryo quality, and pregnancy outcomes.

Waning Humoral Response 3 to 6 Months after Vaccination with the SARS-COV-2 BNT162b2 mRNA Vaccine in Dialysis Patients.

Background And Objectives: The short-term reported antibody response to SARS-COV-2 vaccination in dialysis patients is high, with a seroconversion response rate up to 97%. Data on the long-term durability of this response are scarce. Our objective was to characterize the long-term anti-spike antibody level in dialysis patients.

Rapid identification of uropathogens by combining Alfred 60 system with matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry technology.

Rapid identification of uropathogens is needed to determine appropriate antimicrobial therapy. This study evaluated performance of the Alfred 60 system combined with matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) technology for rapid identification of uropathogens. The Alfred 60 system was used to screen urine cultures, followed by identifying the microbial pathogen in positive cultures using MALDI-TOF MS.

Serum separator tube method for matrix-assisted laser desorption/ionization time-of-flight analysis.

Background: Without appropriate treatment, bloodstream infections have a high mortality rate. Quicker identification of the microbial pathogen allows the clinician to develop an initial strategy of antimicrobial therapy. Sample preparation protocols for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS; Bruker Daltonics for Microflex LT spectrometer) technology were evaluated in an attempt to identify pathogens directly from positive blood culture bottles and thus shorten the time to identify them.

Automating a new host-protein assay for differentiating bacterial from viral infection to reduce operator hands-on time.

Distinguishing bacterial from viral infections is often challenging, leading to antibiotic misuse, and detrimental ramifications for the patient, the healthcare system and society. A novel ELISA-based assay that integrates the circulating levels of three host-response proteins (TRAIL, IP-10 and CRP) was developed to assist in differentiation between bacterial and viral etiologies. We developed a new protocol for measuring the host-based assay biomarkers using an automated ELISA workstation.

Correction to: The mTOR inhibitor rapamycin down-regulates the expression of the ubiquitin ligase subunit Skp2 in breast cancer cells.

After the publication of this work [1], an error was noticed in Fig. 2b, Fig. 3a and Fig.

Thrombin is a selective inducer of heparanase release from platelets and granulocytes via protease-activated receptor-1.

Heparanase, known to be involved in angiogenesis and metastasis, was shown to form a complex with tissue factor (TF) and to enhance the generation of factor Xa. Platelets and granulocytes contain abundant amounts of heparanase that may enhance the coagulation system upon discharge. It was the aim of this study to identify the inducer and pathway of heparanase release from these cells.

Regulation of APC/C (Cdh1) ubiquitin ligase in differentiation of human embryonic stem cells.

We have recently shown that Skp2 levels are high in undifferentiated human embryonic stem cells, but decline rapidly following induction of differentiation, thereby leading to accumulation of p27. Changes in Skp2 levels were found to be caused mainly by its rate of degradation. Here we show that the activity of APC/C (Cdh1), the ubiquitin ligase that targets Skp2 for degradation, increases markedly during the differentiation process of human embryonic stem cells.

Over-expression of Skp2 is associated with resistance to preoperative doxorubicin-based chemotherapy in primary breast cancer.

Introduction: Preoperative chemotherapy is often used in patients with locally advanced breast cancer. However, commonly used clinical and pathological parameters are poor predictors of response to this type of therapy. Recent studies have suggested that altered regulation of the cell cycle in cancer may be involved in resistance to chemotherapy.

Agonist-specific down regulation of mu-opioid receptors: Different cellular pathways are activated by different opioid agonists.

Opioid agonists are known to induce down regulation of opioid receptors through the classical pathway that involves phosphorylation, clathrin-dependent endocytosis and lysosomal/endosomal degradation of the internalized receptors. As expected, exposure of mu-opioid receptor (MOR)-transfected HEK-293 cells to either DAMGO (a specific mu-opioid agonist) or etorphine (a wide spectrum opioid agonist) resulted in down regulation of the receptors that was blocked by the kinase inhibitor staurosporine, by hypertonic sucrose and by the lysosomal and proteasomal inhibitors chloroquine and lactacystin. High concentration of etorphine, but not of DAMGO, induced an additional process of down regulation that was resistant to staurosporine, to hypertonic sucrose and to chloroquine-lactacystin.

Differential effects of doxorubicin treatment on cell cycle arrest and Skp2 expression in breast cancer cells.

Overexpression of Skp2, the ubiquitin ligase subunit that targets p27 for degradation, is often observed in cancers, and is associated with aggressive tumor proliferation and poor prognosis. As there is no drug at present that specifically targets Skp2, studies were undertaken to examine the effects of commonly used drugs on Skp2 regulation. Doxorubicin is among the most effective antitumor agents used for the management of breast cancer, but its effect on Skp2 expression is unknown.

Regulation of the cell cycle inhibitor p27 and its ubiquitin ligase Skp2 in differentiation of human embryonic stem cells.

Embryonic stem cells combine the features of robust proliferation with precise differentiation capacity. p27 is a cell cycle inhibitor that is involved in the regulation of proliferation and differentiation in many developing tissues. Recent studies in murine embryonic stem cells have suggested that p27 is involved in the progression of normal differentiation programs in these cells.

Expression of the ubiquitin ligase subunit cyclin kinase subunit 1 and its relationship to S-phase kinase protein 2 and p27Kip1 in prostate cancer.

Purpose: Loss of the cell cycle inhibitory protein p27Kip1 in cancer is associated with tumor aggressiveness and poor prognosis in the prostate. The decrease in p27(Kip1) results from increased proteasome dependent degradation, which is mediated by its specific ubiquitin ligase subunits S-phase kinase protein 2 and cyclin dependent kinase subunit 1. S-phase kinase protein 2 was found to be over expressed in aggressive prostate cancers but to our knowledge the role of cyclin dependent kinase subunit 1 in these cancers is unknown.