Evaluation of an Opt-Out Protocol for Antibiotic De-Escalation in Patients With Suspected Sepsis: A Multicenter, Randomized, Controlled Trial.

Background: Sepsis guidelines recommend daily review to de-escalate or stop antibiotics in appropriate patients. This randomized, controlled trial evaluated an opt-out protocol to decrease unnecessary antibiotics in patients with suspected sepsis.

Methods: We evaluated non-intensive care adults on broad-spectrum antibiotics despite negative blood cultures at 10 US hospitals from September 2018 through May 2020.

Why scientific societies should involve more early-career researchers.

Early-career researchers (ECRs) make up a large portion of the academic workforce. Yet, most leadership positions in scientific societies are held by senior scientists, and ECRs have little to no say over the decisions that will shape the future of research. This article looks at the level of influence ECRs have in 20 scientific societies based in the US and UK, and provides guidelines on how societies can successfully include ECRs in leadership roles.

Actionable recommendations from trainees to improve science training.

Over the past 20 years, a series of reports written by groups of senior researchers and administrators have recommended changes to improve the training environments for graduate students and postdoctoral researchers in the United States. However, academic institutions and departments have largely failed to implement these recommendations, which has exacerbated the problems faced by these trainees. Here, based on input from trainees at different career stages, we outline seven practical changes that academic institutions and departments can make to improve their training environments.

Effective Self-Management for Early Career Researchers in the Natural and Life Sciences.

Early career researchers (ECRs) are faced with a range of competing pressures in academia, making self-management key to building a successful career. The Organization for Human Brain Mapping undertook a group effort to gather helpful advice for ECRs in self-management.

Autophagy is essential for oligodendrocyte differentiation, survival, and proper myelination.

Deficient myelination, the spiral wrapping of highly specialized membrane around axons, causes severe neurological disorders. Maturation of oligodendrocyte progenitor cells (OPC) to myelinating oligodendrocytes (OL), the sole providers of central nervous system (CNS) myelin, is tightly regulated and involves extensive morphological changes. Here, we present evidence that autophagy, the targeted isolation of cytoplasm and organelles by the double-membrane autophagosome for lysosomal degradation, is essential for OPC/OL differentiation, survival, and proper myelin development.

Changing the Culture of Science Communication Training for Junior Scientists.

Being successful in an academic environment places many demands on junior scientists. Science communication currently may not be adequately valued and rewarded, and yet communication to multiple audiences is critical for ensuring that it remains a priority in today's society. Due to the potential for science communication to produce better scientists, facilitate scientific progress, and influence decision-making at multiple levels, training junior scientists in both effective and ethical science communication practices is imperative, and can benefit scientists regardless of their chosen career path.

Blocking Autophagy in Oligodendrocytes Limits Functional Recovery after Spinal Cord Injury.

Autophagy mechanisms are well documented in neurons after spinal cord injury (SCI), but the direct functional role of autophagy in oligodendrocyte (OL) survival in SCI pathogenesis remains unknown. Autophagy is an evolutionary conserved lysosomal-mediated catabolic pathway that ensures degradation of dysfunctional cellular components to maintain homeostasis in response to various forms of stress, including nutrient deprivation, hypoxia, reactive oxygen species, DNA damage, and endoplasmic reticulum (ER) stress. Using pharmacological gain and loss of function and genetic approaches, we investigated the contribution of autophagy in OL survival and its role in the pathogenesis of thoracic contusive SCI in female mice.

Monitoring the compliance of the academic enterprise with the Fair Labor Standards Act.

: On December 1, 2016, the Fair Labor Standards Act (FLSA) was due to be updated by the U.S. Department of Labor.

Active Cdk5 Immunoprecipitation and Kinase Assay.

Cdk5 activity is regulated by the amounts of two activator proteins, p35 and p39 (Tsai , 1994; Zheng , 1998; Humbert , 2000). The p35-Cdk5 and p39-Cdk5 complexes have differing sensitivity to salt and detergent concentrations (Hisanaga and Saito, 2003; Sato , 2007; Yamada , 2007; Asada , 2008). Cdk5 activation can be directly measured by immunoprecipitation of Cdk5 with its bound activator, followed by a Cdk5 kinase assay.

p39 Is Responsible for Increasing Cdk5 Activity during Postnatal Neuron Differentiation and Governs Neuronal Network Formation and Epileptic Responses.

Unlabelled: Two distinct protein cofactors, p35 and p39, independently activate Cyclin-dependent kinase 5 (Cdk5), which plays diverse roles in normal brain function and the pathogenesis of many neurological diseases. The initial discovery that loss of p35 impairs neuronal migration in the embryonic brain prompted intensive research exploring the function of p35-dependent Cdk5 activity. In contrast, p39 expression is restricted to the postnatal brain and its function remains poorly understood.

Does the preclinical evidence for functional remyelination following myelinating cell engraftment into the injured spinal cord support progression to clinical trials?

This article reviews all historical literature in which rodent-derived myelinating cells have been engrafted into the contused adult rodent spinal cord. From 2500 initial PubMed citations identified, human cells grafts, bone mesenchymal stem cells, olfactory ensheathing cells, non-myelinating cell grafts, and rodent grafts into hemisection or transection models were excluded, resulting in the 67 studies encompassed in this review. Forty five of those involved central nervous system (CNS)-derived cells, including neural stem progenitor cells (NSPCs), neural restricted precursor cells (NRPs) or oligodendrocyte precursor cells (OPCs), and 22 studies involved Schwann cells (SC).

Remyelinating Oligodendrocyte Precursor Cell miRNAs from the Sfmbt2 Cluster Promote Cell Cycle Arrest and Differentiation.

Unlabelled: Oligodendrocyte (OL) loss contributes to the functional deficits underlying diseases with a demyelinating component. Remyelination by oligodendrocyte progenitor cells (OPCs) can restore these deficits. To understand the role that microRNAs (miRNAs) play in remyelination, 2',3'-cyclic-nucleotide 3'-phosphodiesterase-EGFP(+) mice were treated with cuprizone, and OPCs were sorted from the corpus callosum.

p39, the primary activator for cyclin-dependent kinase 5 (Cdk5) in oligodendroglia, is essential for oligodendroglia differentiation and myelin repair.

Cyclin-dependent kinase 5 (Cdk5) plays key roles in normal brain development and function. Dysregulation of Cdk5 may cause neurodegeneration and cognitive impairment. Besides the well demonstrated role of Cdk5 in neurons, emerging evidence suggests the functional requirement of Cdk5 in oligodendroglia (OL) and CNS myelin development.

Oligodendroglia and neurotrophic factors in neurodegeneration.

Myelination by oligodendroglial cells (OLs) enables the propagation of action potentials along neuronal axons, which is essential for rapid information flow in the central nervous system. Besides saltatory conduction, the myelin sheath also protects axons against inflammatory and oxidative insults. Loss of myelin results in axonal damage and ultimately neuronal loss in demyelinating disorders.

The star family member QKI and cell signaling.

The family of Signal Transduction and Activators of RNA (STAR) is named based on the intriguing potential for these proteins to connect cell signaling directly to the homeostasis of their mRNA ligands. Besides the commonly shared single RNA binding domain that displays heterogeneous nuclear ribonucleoprotein K homology (KH), STAR proteins also harbor domains predicted to bind critical components in signal transduction pathways, in particular the Src-family protein tyrosine kinases (Src-PTKs). Indeed, accumulating evidence in recent years has demonstrated that the RNA-binding activity and the homeostasis of downstream mRNA targets of STAR proteins can be regulated by phosphorylation in response to various extracellular signals.

Building integrated mental health and medical programs for vulnerable populations post-disaster: connecting children and families to a medical home.

Introduction: Hurricane Katrina, a Category 3 hurricane, made landfall in August 2005. Approximately 1,500 deaths have been directly attributed to the hurricane, primarily in Louisiana and Mississippi. In New Orleans, Louisiana, most of the healthcare infrastructure was destroyed by flooding, and > 200,000 residents became homeless.

Polyethylene wear in total hip arthroplasty.

Polyethylene wear increasingly has been blamed for osteolysis and granuloma formation after total joint arthroplasty. The authors evaluated the wear difference between bearing surfaces of stainless steel, cobalt chrome, and titanium alloy. They also compared cemented all-polyethylene molded cups with cemented metal-backed molded acetabular cups.

Comparison of polyethylene wear in machined versus molded polyethylene.

Polyethylene wear debris has been identified as a cause of osteolysis, granuloma formation, and loosening in total hip arthroplasty. This study was designed to evaluate differences in polyethylene wear rates between acetabular cups machined from extruded bar stock and those direct compression molded. Two hundred thirty-six hip prostheses underwent radiographic evaluation using the technique of Livermore et al.

Intramedullary screw fixation of lateral malleolus fractures.

A biomechanical evaluation of intramedullary versus buttress plate and lag screw fixation of lateral malleolus fractures is combined with a clinical evaluation of 44 patients with lateral malleolus fractures who underwent intramedullary screw fixation. The biomechanical study was performed in experimentally produced, Weber B, supination-eversion ankle fractures. The fractures were fixed with one of the two above fixation methods and then placed under a torsional load to failure.

Measurement of polyethylene thickness in total hip arthroplasty. A technique analysis.

Accurate radiographic measurement techniques are necessary to evaluate wear characteristics of different metals, ceramics, and plastics. This study evaluated a standard technique for radiographic measurement of acetabular component thickness. Twenty-one acetabular components retrieved after revision surgery were studied.

Polyethylene wear in total hip arthroplasty in patient-matched groups. A comparison of stainless steel, cobalt chrome, and titanium-bearing surfaces.

Osteolysis and component loosening secondary to polyethylene (PE) debris are of paramount concern to today's joint replacement surgeon. This retrospective clinical study measures linear wear in 568 implanted total hip prostheses in which three different metals were used as bearing surfaces (307 stainless steel T-28 [Zimmer, Warsaw, IN], 162 cobalt chrome Tr-28 [Zimmer], and 99 nonion implanted titanium Miami Orthopedic Surgical Consultants [Biomet, Warsaw, IN] prostheses) implanted by a single surgeon over an 8-year period. The acetabular component in all cases was nonmetal-backed compression-molded PE, and all components were cemented.

The biomechanical evaluation of intramedullary nails in distal femoral shaft fractures.

The biomechanical parameters (torsional rigidity and compressive strength) for three different intramedullary femoral nails, Küntscher (K), Brooker-Wills (BW), and Küntscher Interlocking (KI) were compared in this study. Fractures were created in the femoral shaft distal to the isthmus with sections removed so that pure torsional rigidity and resistance to compression could be measured. The standard K nail provided no torsional rigidity and only minimal resistance to longitudinal compression.