Eur J Clin Microbiol Infect Dis
April 2020
The epidemiology of coagulase-negative staphylococcal (CNS) bacteremia among adult ICU patients remains unclear. Decontamination studies among ICU patients provide a unique opportunity to study the impacts of different diagnostic criteria, exposure to various decontamination interventions, and various other factors, on its incidence over three decades. Decontamination studies among ICU patients reporting CNS bacteremia incidence data were obtained mostly from recent systematic reviews.
View Article and Find Full Text PDFCircadian rhythms are 24-hour biological cycles that control daily molecular rhythms in many organisms. The cellular elements that fall under the regulation of the clock are often studied through the use of omics-scale data sets gathered over time to determine how circadian regulation impacts cellular physiology. Previously, we created the ECHO (Extended Circadian Harmonic Oscillator) tool to identify rhythms in these data sets.
View Article and Find Full Text PDFJ Appl Clin Med Phys
December 2019
We studied the dosimetry of single-isocenter treatment plans generated to treat a solitary intracranial lesion using linac-based stereotactic radiosurgery (SRS). A common metric for evaluating SRS plan quality is the volume of normal brain tissue irradiated by a dose of at least 12 Gy (V12), which is important because multiple studies have shown a strong correlation between V12 and incidence of radiation necrosis. Unrealistic expectations for values of V12 can lead to wasted planning time.
View Article and Find Full Text PDFTo understand the impact reduced mercury (Hg) loading and invasive species have had on methylmercury bioaccumulation in predator fish of Lake Michigan, we reconstructed bioaccumulation trends from a fish archive (1978 to 2012). By measuring fish Hg stable isotope ratios, we related temporal changes in Hg concentrations to varying Hg sources. Additionally, dietary tracers were necessary to identify food web influences.
View Article and Find Full Text PDFThe tumor suppressor folliculin (FLCN) enables nutrient-dependent activation of the mechanistic target of rapamycin complex 1 (mTORC1) protein kinase via its guanosine triphosphatase (GTPase) activating protein (GAP) activity toward the GTPase RagC. Concomitant with mTORC1 inactivation by starvation, FLCN relocalizes from the cytosol to lysosomes. To determine the lysosomal function of FLCN, we reconstituted the human lysosomal FLCN complex (LFC) containing FLCN, its partner FLCN-interacting protein 2 (FNIP2), and the RagA:RagC GTPases as they exist in the starved state with their lysosomal anchor Ragulator complex and determined its cryo-electron microscopy structure to 3.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
October 2019
Autophagy induction by starvation and stress involves the enzymatic activation of the class III phosphatidylinositol (PI) 3-kinase complex I (PI3KC3-C1). The inactive basal state of PI3KC3-C1 is maintained by inhibitory contacts between the VPS15 protein kinase and VPS34 lipid kinase domains that restrict the conformation of the VPS34 activation loop. Here, the proautophagic MIT domain-containing protein NRBF2 was used to map the structural changes leading to activation.
View Article and Find Full Text PDFBackground: Person-centred care (PCC) focusing on personalised goals and care plans derived from "What matters to you?" has an impact on single disease outcomes, but studies on multi-morbid elderly are lacking. Furthermore, the combination of PCC, Integrated Care (IC) and Pro-active care are widely recognised as desirable for multi-morbid elderly, yet previous studies focus on single components only, leaving synergies unexplored. The effect of a synergistic intervention, which implements 1) Person-centred goal-oriented care driven by "What matters to you?" with 2) IC and 3) pro-active care is unknown.
View Article and Find Full Text PDFThe accessory protein Nef of human immunodeficiency virus (HIV) is a primary determinant of viral pathogenesis. Nef is abundantly expressed during infection and reroutes a variety of cell surface proteins to disrupt host immunity and promote the viral replication cycle. Nef counteracts host defenses by sequestering and/or degrading its targets via the endocytic and secretory pathways.
View Article and Find Full Text PDFSoluble guanylate cyclase (sGC) is the primary receptor for nitric oxide (NO) in mammalian nitric oxide signaling. We determined structures of full-length sGC in both inactive and active states using cryo-electron microscopy. NO and the sGC-specific stimulator YC-1 induce a 71° rotation of the heme-binding β H-NOX and PAS domains.
View Article and Find Full Text PDFHeadache is a common complaint after mild traumatic brain injury (mTBI). Changes in the CNS lipidome were previously associated with acrolein-induced headache in rodents. mTBI caused similar headache-like symptoms in rats; therefore, we tested the hypothesis that mTBI might likewise alter the lipidome.
View Article and Find Full Text PDFA few-mode transmission system is proposed using 850 nm single-mode VCSEL based transceivers over graded-index single-mode fibers for high data rate data center applications. A graded-index single-mode fiber that supports two mode groups at 850 nm window with a high modal bandwidth of 48.3 GHz·km is realized for the first time.
View Article and Find Full Text PDFTetherin is a host defense factor that physically prevents virion release from the plasma membrane. The Nef accessory protein of simian immunodeficiency virus (SIV) engages the clathrin adaptor AP-2 to downregulate tetherin via its DIWK motif. As human tetherin lacks DIWK, antagonism of tetherin by Nef is a barrier to simian-human transmission of non-human primate lentiviruses.
View Article and Find Full Text PDFBackground: There are few studies that directly investigate disparities in outcome within the African diaspora in the US. We investigated the association between nativity of Black women diagnosed with breast cancer (Caribbean or USA place of birth) and ethnicity, age at diagnosis, treatment, tumor characteristics and outcome.
Methods: The data were obtained from the University of Miami Health System, and Jackson Health System.
Background: Persistent strength deficits secondary to Achilles tendinopathy (AT) have been postulated to account for difficulty engaging in tendon-loading movements, such as running and jumping, and may contribute to the increased risk of recurrence. To date, little consensus exists on the presence of strength deficits in AT. Consequently, researchers are uncertain about the appropriate methods of assessment that may inform rehabilitation in clinical practice.
View Article and Find Full Text PDFMotivation: Time courses utilizing genome scale data are a common approach to identifying the biological pathways that are controlled by the circadian clock, an important regulator of organismal fitness. However, the methods used to detect circadian oscillations in these datasets are not able to accommodate changes in the amplitude of the oscillations over time, leading to an underestimation of the impact of the clock on biological systems.
Results: We have created a program to efficaciously identify oscillations in large-scale datasets, called the Extended Circadian Harmonic Oscillator application, or ECHO.
Photoreceptors are specialized neurons that rely on Ca to regulate phototransduction and neurotransmission. Photoreceptor dysfunction and degeneration occur when intracellular Ca homeostasis is disrupted. Ca homeostasis is maintained partly by mitochondrial Ca uptake through the mitochondrial Ca uniporter (MCU), which can influence cytosolic Ca signals, stimulate energy production, and trigger apoptosis.
View Article and Find Full Text PDFBackground: Selective digestive decontamination (SDD) and selective oropharyngeal decontamination (SOD) regimens appear protective against ICU-acquired overall bacteraemia. These regimens can be factorized as topical antibiotic prophylaxis (TAP) with (SDD) or without (SOD) protocolized parenteral antibiotic prophylaxis (PPAP) using cephalosporins. Both TAP and cephalosporins are risk factors for enterococcal colonization although their impact on enterococcal bacteraemia within studies of SDD/SOD remains unclear.
View Article and Find Full Text PDFCytotoxic chemotherapy is the mainstay of cancer treatment. Conventional chemotherapeutic agents do not distinguish between normal and neoplastic cells. This leads to severe toxic side effects, which may necessitate the discontinuation of treatment in some patients.
View Article and Find Full Text PDFAim: Current International Association of the Diabetes and Pregnancy Study Groups/World Health Organization gestational diabetes mellitus (GDM) diagnostic thresholds are based on a landmark study in which the pre-analytical plasma glucose sampling methodology is unclear. Worldwide, plasma glucose pre-analytical sampling methodology practices are divergent. We considered the effects of pre-analytical plasma glucose sampling methodology on GDM prevalence and gestational outcomes.
View Article and Find Full Text PDFCluster-randomized trials (CRTs) are able to address research questions that randomized controlled trials (RCTs) of individual patients cannot answer. Of great interest for infectious disease physicians and infection control practitioners are research questions relating to the impact of interventions on infectious disease dynamics at the whole-of-population level. However, there are important conceptual differences between CRTs and RCTs relating to design, analysis, and inference.
View Article and Find Full Text PDFIntroduction: There is a paucity of published data on the clinical experience with trans-catheter aortic valve implantation (TAVI) in the Republic of Ireland. We sought to examine the clinical outcomes of patients with medium-term follow-up treated with TAVI at our institution.
Methods: A prospective TAVI registry was used to assess the baseline demographics, procedural variables and clinical outcomes of patients treated with TAVI between the inception of the programme in 2008 and November 2017.
Acute lymphoblastic leukemia and other aggressive lymphoid malignancies like Burkitt leukemia/lymphoma have high incidence of central nervous system (CNS) involvement. Various solid tumors, most notably breast cancer, can also metastasize into the CNS as a late stage complication causing devastating effects. Intrathecal (IT) chemotherapy consisting of methotrexate, cytarabine, or the two in combination is frequently used for the prophylaxis and treatment of CNS metastasis.
View Article and Find Full Text PDFThe environments in which nursing work is undertaken can be highly stressful and complex with resultant harmful outcomes for the health of both nurses and patients reported. Undergraduate nursing students are particularly challenged when on clinical placement through having only partially developed work capabilities, with wide claims that these nurses remain underprepared for work even upon graduation. Over time undergraduate nursing education has arguably not prioritized developing resilience and other non-technical skills required to respond effectively to these challenges.
View Article and Find Full Text PDFMacroautophagy/autophagy mediates the degradation of ubiquitinated aggregated proteins within lysosomes in a process known as aggrephagy. The cargo receptor SQSTM1/p62 condenses aggregated proteins into larger structures and links them to the nascent autophagosomal membrane (phagophore). How the condensation reaction and autophagosome formation are coupled is unclear.
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