Targeting n-myristoyltransferases promotes a pan-Mammarenavirus inhibition through the degradation of the Z matrix protein.

Several Old World and New World Mammarenavirus are responsible for hemorrhagic fever in humans. These enveloped viruses have a bi-segmented ambisense RNA genome that encodes four proteins. All Mammarenavirus identified to date share a common dependency on myristoylation: the addition of the C14 myristic acid on the N-terminal G2 residue on two of their proteins.

Cellular N-Myristoyl Transferases Are Required for Mammarenavirus Multiplication.

The mammarenavirus matrix Z protein plays critical roles in virus assembly and cell egress. Meanwhile, heterotrimer complexes of a stable signal peptide (SSP) together with glycoprotein subunits GP1 and GP2, generated via co-and post-translational processing of the surface glycoprotein precursor GPC, form the spikes that decorate the virion surface and mediate virus cell entry via receptor-mediated endocytosis. The Z protein and the SSP undergo N-terminal myristoylation by host cell N-myristoyltransferases (NMT1 and NMT2), and G2A mutations that prevent myristoylation of Z or SSP have been shown to affect the Z-mediated virus budding and GP2-mediated fusion activity that is required to complete the virus cell entry process.

Manganese transporter SLC30A10 and iron transporters SLC40A1 and SLC11A2 impact dietary manganese absorption.

SLC30A10 deficiency is a disease of severe manganese excess attributed to loss of SLC30A10-dependent manganese excretion via the gastrointestinal tract. Patients develop dystonia, cirrhosis, and polycythemia. They are treated with chelators but also respond to oral iron, suggesting that iron can outcompete manganese for absorption in this disease.

Complications of Nasal Tip Stabilizing Grafts with Autologous Versus Irradiated Homologous Costal Cartilage in Septorhinoplasty: A Systematic Review.

Complications associated with the use of autologous and homologous costal cartilage for nasal tip stabilizing grafts in septorhinoplasty are not well understood. The authors review current literature to evaluate complications associated with autologous and irradiated homologous costal cartilage (IHCC) used for septal extension and columellar strut grafts in rhinoplasty. A comprehensive literature search was conducted in PubMed, Embase, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.

Hepatic HIF2 is a key determinant of manganese excess and polycythemia in SLC30A10 deficiency.

Manganese is an essential yet potentially toxic metal. Initially reported in 2012, mutations in SLC30A10 are the first known inherited cause of manganese excess. SLC30A10 is an apical membrane protein that exports manganese from hepatocytes into bile and from enterocytes into the lumen of the gastrointestinal tract.

Limb Length Discrepancy After Intraosseous Line Malpositioning: A Case Report.

Case: We will present the case of a 6-year-old girl who presented with a 3-cm limb length discrepancy after intraosseous line placement at age 14 months without other known history of trauma or infection to account for the growth arrest. Imaging revealed a left proximal tibial physeal bar amenable to surgical resection with autologous lipotransfer. At 10 months postoperatively, physical examination and imaging demonstrated a stable 3-cm leg length discrepancy with an interval increase in the length of the left tibia in proportion to the growth of the right side with an increase in valgus alignment that will continue to be monitored and addressed as indicated.

Aichivirus A1 replicates in human intestinal epithelium and bronchial tissue: Lung-gut axis?

The role of aichivirus A1 (AiV-A1) in acute gastroenteritis remains controversial and in vitro data illustrating its pathogenesis in suitable human models are scarce. Here, we demonstrate that AiV-A1 isolate A846/88 replicates in ApoA1- (absorptive) and Ki-67-positive (proliferative) enterocytes in stem cell-derived human small intestinal epithelium (HIE) as well as in patient biopsy samples, but not in any of the tested human cell lines. The infection did not result in tissue damage and did not trigger type I and type III interferon (IFN) signalling, whereas the control, human coxsackievirus B3 (strain Nancy), triggered both IFNs.

A Dedicated Simulator Training Curriculum Improves Resident Performance in Surgical Management of Pediatric Supracondylar Humerus Fractures.

Background: The primary goal of including simulation in residency training is to improve technical skills while working outside of the operating room. Such simulation-related skill improvements have seldom been measured in the operating room. This is largely because uncontrolled variables, such as injury severity, patient comorbidity, and anatomical variation, can bias evaluation of an operating surgeon's skill.

Pig-to-human heart xenotransplantation in two recently deceased human recipients.

Genetically modified xenografts are one of the most promising solutions to the discrepancy between the numbers of available human organs for transplantation and potential recipients. To date, a porcine heart has been implanted into only one human recipient. Here, using 10-gene-edited pigs, we transplanted porcine hearts into two brain-dead human recipients and monitored xenograft function, hemodynamics and systemic responses over the course of 66 hours.

Orthopedic Manifestations of Hereditary Sensory and Autonomic Neuropathy IV in a 10-Year-Old Patient.

Hereditary sensory and autonomic neuropathy type IV (HSAN) is a rare and debilitating disorder highlighted by congenital absence of pain and anhidrosis. Orthopedic sequelae include physeal fractures, Charcot joint development, excessive joint laxity, soft tissue infections and recurrent painless dislocations, all of which often present in a delayed fashion. While there is no accepted guideline on management of these patients, several case studies have highlighted the importance of early diagnosis and cautioned against surgical intervention in these patients due to their inability to perceive pain and comply with post-operative restriction.

Stabilization of the Quadruplex-Forming G-Rich Sequences in the Rhinovirus Genome Inhibits Uncoating-Role of Na and K.

Rhinoviruses (RVs) are the major cause of common cold, a respiratory disease that generally takes a mild course. However, occasionally, RV infection can lead to serious complications in patients debilitated by other ailments, e.g.

Hypoxia-inducible factor 2 is a key determinant of manganese excess and polycythemia in SLC30A10 deficiency.

Manganese is an essential yet potentially toxic metal. Initially reported in 2012, mutations in SLC30A10 are the first known inherited cause of manganese excess. SLC30A10 is an apical membrane transport protein that exports manganese from hepatocytes into bile and from enterocytes into the lumen of the gastrointestinal tract.

Current Presurgical Infant Orthopedics Practices Among American Cleft Palate Association-Approved Cleft Teams in North America.

Presurgical infant orthopedic (PSIO) therapy has evolved in both its popularity and focus of treatment since its advent. Nasoalveolar molding, nasal elevators, the Latham appliance, lip taping, and passive plates are the modern treatment options offered by cleft teams. Many cleft surgeons also employ postsurgical nasal stenting (PSNS) after the primary lip repair procedure.

Targeting Protein Interaction Hotspots Using Structured and Disordered Chimeric Peptide Inhibitors.

The main challenge in inhibiting protein-protein interactions (PPI) for therapeutic purposes is designing molecules that bind specifically to the interaction hotspots. Adding to the complexity, such hotspots can be within both structured and disordered interaction interfaces. To address this, we present a strategy for inhibiting the structured and disordered hotspots of interactions using chimeric peptides that contain both structured and disordered parts.

Identifying Barriers: Current Breastfeeding Policy in Orthopedic Surgery Residency.

Background: Family planning is a challenge for physicians at all stages of their careers but can be particularly difficult during residency. As the field of orthopedic surgery strives to increase diversity and recruit exceptional female candidates, barriers to entry should be identified. For many women, successful family planning including pregnancy, breast-feeding, and childcare, presents a daunting endeavor during residency training and a difficult topic to broach with superiors when planning future careers.

A Vision for Using Simulation & Virtual Coaching to Improve the Community Practice of Orthopedic Trauma Surgery.

Background: Many orthopedic surgeries involve the challenging integration of fluoroscopic image interpretation with skillful tool manipulation to enable procedures to be performed through less invasive approaches. Simulation has proved beneficial for teaching and improving these skills for residents, but similar benefits have not yet been realized for practicing orthopedic surgeons. A vision is presented to elevate community orthopedic practice and improve patient safety by advancing the use of simulators for training and assessing surgical skills.

nanoDSF: Label-Free Method to Monitor Picornavirus Uncoating and Test Compounds Affecting Particle Stability.

Thermal shift assays measure the stability of macromolecules and macromolecular assemblies as a function of temperature. The Particle Stability Thermal Release Assay (PaSTRy) of picornaviruses is based on probes becoming strongly fluorescent upon binding to hydrophobic patches of the protein capsid (e.g.

Catching Common Cold Virus with a Net: Pyridostatin Forms Filaments in Tris Buffer That Trap Viruses-A Novel Antiviral Strategy?

The neutrophil extracellular trap (ET) is a eukaryotic host defense machinery that operates by capturing and concentrating pathogens in a filamentous network manufactured by neutrophils and made of DNA, histones, and many other components. Respiratory virus-induced ETs are involved in tissue damage and impairment of the alveolar-capillary barrier, but they also aid in fending off infection. We found that the small organic compound pyridostatin (PDS) forms somewhat similar fibrillary structures in Tris buffer in a concentration-dependent manner.

Behavioral Activation as a Treatment for Posttraumatic Stress Disorder Among Returning Veterans: A Randomized Trial.

Objective: Although evidence-based, trauma-processing treatments exist for posttraumatic stress disorder (PTSD), many individuals do not seek out, complete, or fully respond to these treatments, pointing to the need for alternative treatments. In this study, the authors evaluated the effectiveness of behavioral activation therapy modified to address PTSD among veterans.

Methods: In a randomized trial, behavioral activation was compared with treatment as usual (referral to PTSD "standard care") among a sample of 80 veterans of the wars in Iraq and Afghanistan who were enrolled at the U.

Ruptured Appendicitis and Retrocecal Abscess Masquerading as Knee Pain in a Pediatric Patient: A Case Report.

Background: Knee pain has a variety of etiologies in the pediatric population, including septic arthritis, osteomyelitis, fracture, ligamentous injury, and neoplasms. Extrinsic sources of knee pain may also be intra-abdominal, although abdominal pathology is much more likely to manifest as hip or proximal thigh musculature pain.

Case Report: A 5-year-old healthy male presented with atraumatic right knee pain, discomfort with weightbearing, fever, and elevated inflammatory laboratory markers.