Mechanism of NACHO-mediated assembly of pentameric ligand-gated ion channels.

Pentameric ligand-gated ion channels (pLGICs) are cell surface receptors of crucial importance for animal physiology. This diverse protein family mediates the ionotropic signals triggered by major neurotransmitters and includes γ-aminobutyric acid receptors (GABARs) and acetylcholine receptors (nAChRs). Receptor function is fine-tuned by a myriad of endogenous and pharmacological modulators.

Evolution and host-specific adaptation of .

The major human bacterial pathogen causes multidrug-resistant infections in people with underlying immunodeficiencies or structural lung diseases such as cystic fibrosis (CF). We show that a few environmental isolates, driven by horizontal gene acquisition, have become dominant epidemic clones that have sequentially emerged and spread through global transmission networks over the past 200 years. These clones demonstrate varying intrinsic propensities for infecting CF or non-CF individuals (linked to specific transcriptional changes enabling survival within macrophages); have undergone multiple rounds of convergent, host-specific adaptation; and have eventually lost their ability to transmit between different patient groups.

The N1 domain of the peroxisomal AAA-ATPase Pex6 is required for Pex15 binding and proper assembly with Pex1.

The heterohexameric ATPases associated with diverse cellular activities (AAA)-ATPase Pex1/Pex6 is essential for the formation and maintenance of peroxisomes. Pex1/Pex6, similar to other AAA-ATPases, uses the energy from ATP hydrolysis to mechanically thread substrate proteins through its central pore, thereby unfolding them. In related AAA-ATPase motors, substrates are recruited through binding to the motor's N-terminal domains or N terminally bound cofactors.

The Pex6 N1 domain is required for Pex15 binding and proper assembly with Pex1.

The heterohexameric AAA-ATPase Pex1/Pex6 is essential for the formation and maintenance of peroxisomes. Pex1/Pex6, similar to other AAA-ATPases, uses the energy from ATP hydrolysis to mechanically thread substrate proteins through its central pore, thereby unfolding them. In related AAA-ATPase motors, substrates are recruited through binding to the motor's N-terminal domains or N-terminally bound co-factors.

Larger Perioperative Opioid Prescriptions Lead to Prolonged Opioid Use After Hand and Upper Extremity Surgery: A Multicenter Analysis.

Introduction: The opioid epidemic remains an ongoing public health crisis. The purpose of this study was to investigate whether surgeons' prescribing patterns of the initial postoperative opioid prescription predispose patients to prolonged opioid use after upper extremity surgery.

Methods: This multicenter retrospective study was done at three academic institutions.

Insights into the Structure and Function of the Pex1/Pex6 AAA-ATPase in Peroxisome Homeostasis.

The AAA-ATPases Pex1 and Pex6 are required for the formation and maintenance of peroxisomes, membrane-bound organelles that harbor enzymes for specialized metabolism. Together, Pex1 and Pex6 form a heterohexameric AAA-ATPase capable of unfolding substrate proteins via processive threading through a central pore. Here, we review the proposed roles for Pex1/Pex6 in peroxisome biogenesis and degradation, discussing how the unfolding of potential substrates contributes to peroxisome homeostasis.

Multiple Opioid Prescribers During the Perioperative Period Increases Opioid Consumption Following Upper Extremity Surgery: A Multicenter Analysis.

Background Opioid prescribing practices have been an area of interest for orthopedic surgeons in the wake of the opioid epidemic. Previous studies have investigated the effects of a multitude of patient-specific risk factors on prolonged opioid use postoperatively. However, to date, there is a lack of studies examining the effects of multiple prescribers during the perioperative period and their potential contribution to prolonged opioid use postoperatively.

Ten Years of : Authorship Characteristics and Levels of Evidence.

Context: , now 10 years into production, has been ranked a top-25 journal in sport sciences and has tripled its impact throughout its existence.

Objective: To evaluate authorship trends and levels of evidence (LOE) of articles published in from 2009 to 2018. The secondary aim was to analyze funding sources and internationalization throughout the journal's tenure.

Development of nursing quality care process metrics and indicators for intellectual disability services: a literature review and modified Delphi consensus study.

Background: Nursing process quality care metrics and indicators are quantifiable measures of the nursing care delivered to clients. They can be used to identify and support nurses' contribution to high quality, safe, client care and are lacking in specialist intellectual disability nursing. In a national Nursing Quality Care-Metrics project for Irish intellectual disability services, a set of nursing quality care process metrics and associated indicators were established for intellectual disability services.

Level of evidence and authorship trends of clinical studies in knee surgery, sports traumatology, arthroscopy, 1995-2015.

Purpose: There is increasing emphasis on publication quality and internationalization of author groups in orthopaedic literature. The purpose of this review was to evaluate the type of studies and the level of evidence (LOE) published in knee surgery, sports traumatology, arthroscopy (KSSTA) from 1995 to 2015. The secondary aim was to analyze trends in authorship characteristics in KSSTA.

Near-infrared operating lamp for intraoperative molecular imaging of a mediastinal tumor.

Background: Near-Infrared (NIR) intraoperative molecular imaging is a new diagnostic modality utilized during cancer surgery for the identification of tumors, metastases and lymph nodes. Surgeons typically use headlamps during an operation to increase visible light; however, these light sources are not adapted to function simultaneously with NIR molecular imaging technology. Here, we design a NIR cancelling headlamp and utilize it during surgery to assess whether intraoperative molecular imaging of mediastinal tumors is possible.

Quantification of tumor fluorescence during intraoperative optical cancer imaging.

Intraoperative optical cancer imaging is an emerging technology in which surgeons employ fluorophores to visualize tumors, identify tumor-positive margins and lymph nodes containing metastases. This study compares instrumentation to measure tumor fluorescence. Three imaging systems (Spectropen, Glomax, Flocam) measured and quantified fluorescent signal-to-background ratios (SBR) in vitro, murine xenografts, tissue phantoms and clinically.

Intraoperative Molecular Diagnostic Imaging Can Identify Renal Cell Carcinoma.

Purpose: Margin status can often be difficult to assess intraoperatively, particularly during partial nephrectomy given the time constraints related to renal hilar clamping. We hypothesized that a targeted molecular imaging approach could be used during surgery to identify tumor margins and confirm disease clearance.

Materials And Methods: EC17, a novel tracer targeting FRα, was used in murine models of renal cell carcinoma to identify positive margins after surgery.

Comparison of Folate Receptor Targeted Optical Contrast Agents for Intraoperative Molecular Imaging.

Background. Intraoperative imaging can identify cancer cells in order to improve resection; thus fluorescent contrast agents have emerged. Our objective was to do a preclinical comparison of two fluorescent dyes, EC17 and OTL38, which both target folate receptor but have different fluorochromes.

Optimization of the enhanced permeability and retention effect for near-infrared imaging of solid tumors with indocyanine green.

Surgery is the most effective method to cure patients with solid tumors. New techniques in near-infrared (NIR) cancer imaging are being used to identify surgical margins and residual tumor cells in the wound. Our goal was to determine the optimal time and dose for imaging solid tumors using Indocyanine Green.

Intraoperative Molecular Imaging of Lung Adenocarcinoma Can Identify Residual Tumor Cells at the Surgical Margins.

Purpose: During lung surgery, identification of surgical margins is challenging. We hypothesized that molecular imaging with a fluorescent probe to pulmonary adenocarcinomas could enhance residual tumor during resection.

Procedures: Mice with flank tumors received a contrast agent targeting folate receptor alpha.

Intraoperative molecular imaging can identify lung adenocarcinomas during pulmonary resection.

Background: More than 80,000 people undergo resection of a pulmonary tumor each year, and the only method to determine if the tumor is malignant is histologic analysis. We propose that a targeted molecular contrast agent could bind lung adenocarcinomas, which could be identified using real-time optical imaging at the time of surgery.

Methods: Fifty patients with a biopsy-proven lung adenocarcinoma were enrolled.

Molecular imaging to identify tumor recurrence following chemoradiation in a hostile surgical environment.

Surgical biopsy of potential tumor recurrence is a common challenge facing oncologists, surgeons, and cancer patients. Imaging modalities have limited ability to accurately detect recurrent cancer in fields affected by previous surgery, chemotherapy, or radiation. However, definitive tissue diagnosis is often needed to initiate treatment and to direct therapy.

Intraoperative near-infrared imaging can identify pulmonary nodules.

Background: Over 80,000 people undergo pulmonary resection for a lung nodule in the United States each year. Small nodules are frequently missed or difficult to find despite preoperative imaging. We hypothesized that near-infrared (NIR) imaging technology could be used to identify and locate lung nodules during surgery.

Intraoperative near-infrared imaging can distinguish cancer from normal tissue but not inflammation.

Introduction: Defining tumor from non-tumor tissue is one of the major challenges of cancer surgery. Surgeons depend on visual and tactile clues to select which tissues should be removed from a patient. Recently, we and others have hypothesized near-infrared (NIR) imaging can be used during surgery to differentiate tumors from normal tissue.

Adenoviral-based immunotherapy provides local disease control in an orthotopic murine model of esophageal cancer.

Despite recent advances in the development of novel therapies, esophageal carcinoma remains an aggressive cancer associated with a poor prognosis. The lack of a high throughput, reproducible syngeneic animal model that replicates human disease is partly responsible for the paucity of novel therapeutic approaches. In this report, we present the first successful syngeneic, orthotopic model for esophageal cancer.

Cognitive function, mental health, and health-related quality of life after lung transplantation.

Rationale: Cognitive and psychiatric impairments are threats to functional independence, general health, and quality of life. Evidence regarding these outcomes after lung transplantation is limited.

Objectives: Determine the frequency of cognitive and psychiatric impairment after lung transplantation and identify potential factors associated with cognitive impairment after lung transplantation.

Case series of lower-extremity chronic wounds managed with an antibacterial foam dressing bound with gentian violet and methylene blue.

Objective: To evaluate an antibacterial dressing for the management of lower-extremity chronic wounds with critical colonization.

Design: A case series of n = 15 patients with lower-extremity chronic wounds were treated with an antibacterial foam dressing consisting of polyvinyl alcohol (PVA) foam bound with gentian violet and methylene blue (Hydrofera Blue; Hydrofera, LLC, Willimantic, Connecticut).

Setting: An outpatient clinic in Ontario, Canada.