Disentangling Neurodegeneration From Aging in Multiple Sclerosis Using Deep Learning: The Brain-Predicted Disease Duration Gap.

Background And Objectives: Disentangling brain aging from disease-related neurodegeneration in patients with multiple sclerosis (PwMS) is increasingly topical. The brain-age paradigm offers a window into this problem but may miss disease-specific effects. In this study, we investigated whether a disease-specific model might complement the brain-age gap (BAG) by capturing aspects unique to MS.

The translesion polymerase Pol Y1 is a constitutive component of the B. subtilis replication machinery.

Unrepaired DNA damage encountered by the cellular replication machinery can stall DNA replication, ultimately leading to cell death. In the DNA damage tolerance pathway translesion synthesis (TLS), replication stalling is alleviated by the recruitment of specialized polymerases to synthesize short stretches of DNA near a lesion. Although TLS promotes cell survival, most TLS polymerases are low-fidelity and must be tightly regulated to avoid harmful mutagenesis.

A clinical review of elbow ligament repairs and reconstructions in the acute and chronic settings.

Background: The ligamentous and osseous structures of the elbow joint are the major contributors to its inherent stability and damage to any of these structures can result in elbow instability. The aim of this study is to present objective and subjective outcomes following ligament repairs and/or reconstructions for acute elbow instability and chronic elbow instability.

Methods: This study included patients who underwent an elbow ligament repair and/or reconstruction for acute or chronic elbow instability.

Probing Isosteric Replacement for Immunoadjuvant Design: Bis-Aryl Triazole Trehalolipids are Mincle Agonists.

Herein, we report the modular synthesis and immunological activity of seven bis-aryl triazole trehalolipids (-) as Brartemicin analogs. The compounds comprised one or two octyloxy (C8) alkyl chains and were synthesized using the venerable CuAAc reaction between the respective aryl acetylenes and a trehalose diazide. A Mincle reporter cell assay revealed that all lipidated analogs activated Mincle.

Improving explanation of motor disability with diffusion-based graph metrics at onset of the first demyelinating event.

Background: Conventional magnetic resonance imaging (MRI) does not account for all disability in multiple sclerosis.

Objective: The objective was to assess the ability of graph metrics from diffusion-based structural connectomes to explain motor function beyond conventional MRI in early demyelinating clinically isolated syndrome (CIS).

Methods: A total of 73 people with CIS underwent conventional MRI, diffusion-weighted imaging and clinical assessment within 3 months from onset.

Large birth mark and unilateral swelling of the lower extremity in a young teenager.

We describe an early adolescent male who was diagnosed with vascular malformation associated with unilateral limb overgrowth based on the clinical findings of a persistent port-wine stain since birth and gradually progressing right lower limb oedema since early childhood. Clinicians should keep in mind to clinically evaluate such malformations in detail, as well as contemplate genetic testing in patients presenting with a large port-wine stain at birth, particularly if well demarcated and lateral in a lower extremity.

Comparative anatomy of the caudate nucleus in canids and felids: Associations with brain size, curvature, cross-sectional properties, and behavioral ecology.

The evolutionary history of canids and felids is marked by a deep time separation that has uniquely shaped their behavior and phenotype toward refined predatory abilities. The caudate nucleus is a subcortical brain structure associated with both motor control and cognitive, emotional, and executive functions. We used a combination of three-dimensional imaging, allometric scaling, and structural analyses to compare the size and shape characteristics of the caudate nucleus.

Effect of Varus-Producing Distal Femoral Osteotomy and High Tibial Osteotomy on Compartment Pressures and Contact Area at Varying Degrees of Knee Flexion.

Background: In patients with valgus alignment and degenerative changes in the lateral compartment, both distal femoral osteotomy (DFO) and high tibial osteotomy (HTO) can be used to unload the lateral compartment. Prior studies have shown that in valgus knees, the tibial wear is posterior and DFO exerts the greatest effect in extension; however, its effect is decreased as flexion angle rises.

Hypothesis: Medial closing-wedge (MCW) HTO would significantly decrease contact area, mean contact pressure (MCP), and peak contact pressure (PCP) in the lateral knee compartment through knee flexion to a greater extent compared with lateral opening-wedge (LOW) DFO.

Do maternal haemodynamics have a causal influence on treatment for gestational diabetes?

Background: Arterial stiffening is believed to contribute to the worsening of insulin resistance, and factors which are associated with needing pharmacological treatment of gestational diabetes (GDM), such as maternal obesity or advanced age, are associated with impaired cardiovascular adaptation to pregnancy. In this observational study, we aimed to investigate causal relationships between maternal haemodynamics and treatment requirement amongst women with GDM.

Methods: We assessed maternal haemodynamics in women with GDM, comparing those who remained on dietary treatment with those who required pharmacological management.

Associations between cortical lesions, optic nerve damage, and disability at the onset of multiple sclerosis: insights into neurodegenerative processes.

Background: Multiple sclerosis cortical lesions are areas of demyelination and neuroaxonal loss. Retinal layer thickness, measured with optical coherence tomography (OCT), is an emerging biomarker of neuroaxonal loss. Studies have reported correlations between cortical lesions and retinal layer thinning in established multiple sclerosis, suggesting a shared pathophysiological process.

Biomechanical Analysis Evaluating Meniscal Extrusion After Knotless Suture Anchor Fixation for Segmental Medial Meniscal Allograft Transplantation.

Background: Segmental medial meniscal allograft transplantation (MAT) has been shown to restore knee biomechanics; however, stable fixation of the transplantation is critical to avoid extrusion and maximize healing.

Purpose: To evaluate the degree of meniscal extrusion and biomechanical function of segmental medial MAT performed with meniscocapsular sutures versus repair augmentation with knotless suture anchors.

Study Design: Controlled laboratory study.

Outcomes of total shoulder arthroplasty in patients with prior anterior shoulder instability: minimum 5-year follow-up.

Background: Patients with a history of anterior shoulder instability (ASI) commonly progress to glenohumeral arthritis or even dislocation arthropathy and often require total shoulder arthroplasty (TSA). The purposes of this study were to (1) report patient-reported outcomes (PROs) after TSA in patients with a history of ASI, (2) compare TSA outcomes of patients whose ASI was managed operatively vs. nonoperatively, and (3) report PROs of TSA in patients who previously underwent arthroscopic vs.

Effects of maternal hypothyroidism on postnatal cardiomyocyte proliferation and cardiac disease responses of the progeny.

Maternal hypothyroidism (MH) could adversely affect the cardiac disease responses of the progeny. This study tested the hypothesis that MH reduces early postnatal cardiomyocyte (CM) proliferation so that the adult heart of MH progeny has a smaller number of larger cardiac myocytes, which imparts adverse cardiac disease responses following injury. Thyroidectomy (TX) was used to establish MH.

A collaborative approach to improving representation in viral genomic surveillance.

The lack of routine viral genomic surveillance delayed the initial detection of SARS-CoV-2, allowing the virus to spread unfettered at the outset of the U.S. epidemic.

Inflammatory and Immunologic Contributions in Femoroacetabular Impingement Syndrome.

Femoroacetabular impingement (FAI) is one of the most common causes of labral and early cartilage damage in the nondysplastic hip. FAI is increasingly recognized as a cause for hip and groin pain in the young, active patient, and the surgical treatment of FAI with hip arthroscopy has risen exponentially. Although our understanding of FAI and the progression to degenerative osteoarthritis of the hip has historically been considered a mechanical "wear-and-tear" disease of an imperfectly shaped, aspherical, femoral head within a deep or overcovering acetabulum leading to cartilage injury, our understanding of the intrinsic pathophysiologic mechanisms underlying the development of FAI and joint degeneration of the hip remains poor.

Advanced central nervous system imaging biomarkers in radiologically isolated syndrome: a mini review.

Radiologically isolated syndrome is characterised by central nervous system white-matter hyperintensities highly suggestive of multiple sclerosis in individuals without a neurological history of clinical demyelinating episodes. It probably represents the pre-symptomatic phase of clinical multiple sclerosis but is poorly understood. This mini review summarises our current knowledge regarding advanced imaging techniques in radiologically isolated syndrome that provide insights into its pathobiology and prognosis.

Use of Computed Tomography in the Evaluation of Anterior Shoulder Instability: Possible Effect on Surgical Management.

Background: Glenoid bone loss is a critical factor in the management of anterior shoulder instability (ASI). Computed tomography (CT) is often considered the gold standard to evaluate glenoid bone loss, but it is associated with negative factors such as radiation. Thus, interest exists as to when orthopaedic surgeons need a CT scan to guide decision-making when treating ASI.