Role of CD163 in PRRSV infection.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly infectious agent that poses a significant economic threat to the global swine industry. Efficient viral entry relies on interactions with cellular receptors, with CD163-a cysteine-rich scavenger receptor found on porcine alveolar macrophages (PAMs)-playing a critical role. Extensive evidence supports CD163's essential function in PRRSV infection.

Development of Tunable Mechanism-Based Carbasugar Ligands that Stabilize Glycoside Hydrolases through the Formation of Transient Covalent Intermediates.

Mutations in many members of the set of human lysosomal glycoside hydrolases cause a wide range of lysosomal storage diseases. As a result, much effort has been directed toward identifying pharmacological chaperones of these lysosomal enzymes. The majority of the candidate chaperones are active site-directed competitive iminosugar inhibitors but these have met with limited success.

Dual-mobility with modular components for primary total hip arthroplasty in bilateral bony ankylosis of the hips: A case report.

Introduction And Importance: Primary total hip arthroplasty (THA) is a procedure performed in the United States for a variety of indications, with operation rates slated to increase over 275 % by 2040 when compared to 2014 (Thilak et al., 2015). Dual-mobility (DM) implants have gained popularity in the United States since gaining approval in the early 2010s (Heckmann et al.

Guest Editorial - Ambulatory Care: Turning Urgent and Emergency Care inside out.

Emergency departments are under year-round pressure, driven by high hospital bed occupancy and compounded by increasing attendances and admissions. In 2023, 1.5 million people waited 12 hours or more for a bed.

Cryo-EM structure of the CDK2-cyclin A-CDC25A complex.

The cell division cycle 25 phosphatases CDC25A, B and C regulate cell cycle transitions by dephosphorylating residues in the conserved glycine-rich loop of CDKs to activate their activity. Here, we present the cryo-EM structure of CDK2-cyclin A in complex with CDC25A at 2.7 Å resolution, providing a detailed structural analysis of the overall complex architecture and key protein-protein interactions that underpin this 86 kDa complex.

The neonatal Fc receptor (FcRn) is a pan-arterivirus receptor.

Arteriviruses infect a variety of mammalian hosts, but the receptors used by these viruses to enter cells are poorly understood. We identified the neonatal Fc receptor (FcRn) as an important pro-viral host factor via comparative genome-wide CRISPR-knockout screens with multiple arteriviruses. Using a panel of cell lines and divergent arteriviruses, we demonstrate that FcRn is required for the entry step of arterivirus infection and serves as a molecular barrier to arterivirus cross-species infection.

Role of N-linked glycosylation in porcine reproductive and respiratory syndrome virus (PRRSV) infection.

Porcine reproductive and respiratory syndrome (PRRSV) is an enveloped single-stranded positive-sense RNA virus and one of the main pathogens that causes the most significant economical losses in the swine-producing countries. PRRSV is currently divided into two distinct species, PRRSV-1 and PRRSV-2. The PRRSV virion envelope is composed of four glycosylated membrane proteins and three non-glycosylated envelope proteins.

Comparing internal and external stabilization for traumatic elbow instability: a systematic review.

Background: Despite surgical reestablishment of the supporting structures, instability may often persist in traumatic elbow injury. In these cases, a temporary internal or external fixator may be indicated to unload the repaired structures and maintain joint concentricity. Aggregate data are needed to characterize the risk of complication between external fixation (ExFix) and the internal joint stabilizer (IJS) when used for traumatic elbow instability.

Methylone is a rapid-acting neuroplastogen with less off-target activity than MDMA.

Background: Post-traumatic stress disorder (PTSD) is a highly prevalent psychiatric disorder that can become chronic and debilitating when left untreated. Available pharmacotherapies are limited, take weeks to show modest benefit and remain ineffective for up to 40% of patients. Methylone is currently in clinical development for the treatment of PTSD.

Review of machine learning for optical imaging of burn wound severity assessment.

Significance: Over the past decade, machine learning (ML) algorithms have rapidly become much more widespread for numerous biomedical applications, including the diagnosis and categorization of disease and injury.

Aim: Here, we seek to characterize the recent growth of ML techniques that use imaging data to classify burn wound severity and report on the accuracies of different approaches.

Approach: To this end, we present a comprehensive literature review of preclinical and clinical studies using ML techniques to classify the severity of burn wounds.

Generation of a Commercial-Scale Founder Population of Porcine Reproductive and Respiratory Syndrome Virus Resistant Pigs Using CRISPR-Cas.

Disease resistance genes in livestock provide health benefits to animals and opportunities for farmers to meet the growing demand for affordable, high-quality protein. Previously, researchers used gene editing to modify the porcine CD163 gene and demonstrated resistance to a harmful virus that causes porcine reproductive and respiratory syndrome (PRRS). To maximize potential benefits, this disease resistance trait needs to be present in commercially relevant breeding populations for multiplication and distribution of pigs.

Genetically modified pigs lacking CD163 PSTII-domain-coding exon 13 are completely resistant to PRRSV infection.

CD163 expressed on cell surface of porcine alveolar macrophages (PAMs) serves as a cellular entry receptor for porcine reproductive and respiratory syndrome virus (PRRSV). The extracellular portion of CD163 contains nine scavenger receptor cysteine-rich (SRCR) and two proline-serine-threonine (PST) domains. Genomic editing of pigs to remove the entire CD163 or just the SRCR5 domain confers resistance to infection with both PRRSV-1 and PRRSV-2 viruses.

Local adiposity may be a more reliable predictor for infection than body mass index following total knee arthroplasty: a systematic review.

Purpose: Improved understanding of the factors that predispose TKA patients to infection has considerable economic and medical impact. BMI is commonly used as a proxy for obesity to determine the risk of postoperative infection. However, this metric appears to be fraught with inconsistency in this application.

A Dual Center Experience with a Locking Intramedullary Nail for Wrist Fusion.

 In aggregate, there is varied efficacy for total wrist fusion (TWF) with a locking intramedullary (IM) nail which indicates the need for further investigation. It remains unclear whether preparation of the third carpometacarpal joint (CMCJ) will reduce the risk of complications including distal screw loosening.  Our objectives were (a) to report clinical outcomes for wrist arthrodesis using a locking IM nail and (b) to determine whether maintenance of the native third CMCJ articulation would contribute to short-term complications.

Hop to It! The Relationship Between Hop Tests and The Anterior Cruciate Ligament - Return to Sport Index After Anterior Cruciate Ligament Reconstruction in NCAA Division 1 Collegiate Athletes.

Background: Outcomes after anterior cruciate ligament reconstruction (ACLR) may not be optimal, with poor physical and psychological function potentially affecting return to sport (RTS) ability. Understanding the relationship between commonly used hop tests and the Anterior Cruciate Ligament - Return to Sport Index (ACL-RSI) may improve rehabilitation strategies and optimize patient outcomes.

Hypothesis/purpose: The purpose of this study was to examine the relationship between ACL-RSI scores and limb symmetry index (LSI) for the single hop for distance (SHD), triple hop for distance (THD), crossover hop for distance (CHD), timed 6-meter hop (T6H), and single leg vertical hop (SLVH) in a cohort of National Collegiate Athletic Association (NCAA) Division 1 collegiate athletes after ACLR.

COVID-19 Disease Characterization and Outcomes Comparison in Pediatrics.

Background: It has been reported that children experience less severe COVID-19 symptoms than adults; however, the literature that supports this idea is evolving. The purpose of this study was to retrospectively characterize hospitalized COVID-19-positive pediatric patients with a focus on the assessment of risk factors for poorer outcomes, mortality, and evaluation of interventions utilized and associated clinical outcomes.

Methods: We conducted a multi-center retrospective chart review of patients 18 years old or younger who were COVID-19 positive and admitted to any US HCA Healthcare Pediatric service line between January 1, 2020, and November 30, 2020.

Fluorescence polarisation activity-based protein profiling for the identification of deoxynojirimycin-type inhibitors selective for lysosomal retaining alpha- and beta-glucosidases.

Lysosomal exoglycosidases are responsible for processing endocytosed glycans from the non-reducing end to produce the corresponding monosaccharides. Genetic mutations in a particular lysosomal glycosidase may result in accumulation of its particular substrate, which may cause diverse lysosomal storage disorders. The identification of effective therapeutic modalities to treat these diseases is a major yet poorly realised objective in biomedicine.

Cryo-EM structure of SKP1-SKP2-CKS1 in complex with CDK2-cyclin A-p27KIP1.

p27KIP1 (cyclin-dependent kinase inhibitor 1B, p27) is a member of the CIP/KIP family of CDK (cyclin dependent kinase) regulators that inhibit cell cycle CDKs. p27 phosphorylation by CDK1/2, signals its recruitment to the SCF (S-phase kinase associated protein 1 (SKP1)-cullin-SKP2) E3 ubiquitin ligase complex for proteasomal degradation. The nature of p27 binding to SKP2 and CKS1 was revealed by the SKP1-SKP2-CKS1-p27 phosphopeptide crystal structure.

Current and Emerging Imaging Techniques for Neurofibromatosis Type 1-Associated Cutaneous Neurofibromas.

A consistent set of measurement techniques must be applied to reliably and reproducibly evaluate the efficacy of treatments for cutaneous neurofibromas (cNFs) in people with neurofibromatosis type 1 (NF1). cNFs are neurocutaneous tumors that are the most common tumor in people with NF1 and represent an area of unmet clinical need. This review presents the available data regarding approaches in use or development to identify, measure, and track cNFs, including calipers, digital imaging, and high-frequency ultrasound sonography.

Morbidly Obese Patients Undergoing Unicompartmental Knee Arthroplasty Compared to Total Knee Arthroplasty: A Retrospective Case-Controlled Analysis.

Background: In this study, we assess the effects that morbid obesity (body mass index (BMI) ≥ 40) has on: (1) Ninety-day medical complications and readmission rates; (2) costs of care and lengths of stay (LOS); and (3) 2-year implant complications in patients undergoing unicompartmental knee arthroplasty (UKA) versus total knee arthroplasty (TKA).

Methods: A retrospective query of TKA and UKA patients were identified using a national database. Morbidly obese UKA patients were matched 1:5 to morbidly obese TKA patients by demographic and comorbidity profiles.

Reprogramming viral immune evasion for a rational design of next-generation vaccines for RNA viruses.

Type I interferons (IFNs-α/β) are antiviral cytokines that constitute the innate immunity of hosts to fight against viral infections. Recent studies, however, have revealed the pleiotropic functions of IFNs, in addition to their antiviral activities, for the priming of activation and maturation of adaptive immunity. In turn, many viruses have developed various strategies to counteract the IFN response and to evade the host immune system for their benefits.