Kinematic Analysis of Lateral Meniscal Oblique Radial Tears in the Anterior Cruciate Ligament-Deficient Knee.

Background: Lateral meniscal oblique radial tears (LMORT) occur frequently in conjunction with anterior cruciate ligament (ACL) disruption and are anatomically distinct from meniscus root tears.

Hypothesis/purpose: The purpose of this study was to characterize the effects of LMORT types 3 (LMORT3) and 4 (LMORT4) lesions on joint stability and meniscal extrusion in ACL-deficient knees. Our hypothesis was that both lesions would promote significant increases in anterior translation and meniscal extrusion, with the LMORT4 lesion having a greater effect.

A comprehensive tool box for large animal studies of intervertebral disc degeneration.

Preclinical studies involving large animal models aim to recapitulate the clinical situation as much as possible and bridge the gap from benchtop to bedside. To date, studies investigating intervertebral disc (IVD) degeneration and regeneration in large animal models have utilized a wide spectrum of methodologies for outcome evaluation. This paper aims to consolidate available knowledge, expertise, and experience in large animal preclinical models of IVD degeneration to create a comprehensive tool box of anatomical and functional outcomes.

Angiotensin II receptor blocker or angiotensin-converting enzyme inhibitor use and COVID-19-related outcomes among US Veterans.

Background: Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) may positively or negatively impact outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated the association of ARB or ACEI use with coronavirus disease 2019 (COVID-19)-related outcomes in US Veterans with treated hypertension using an active comparator design, appropriate covariate adjustment, and negative control analyses.

Methods And Findings: In this retrospective cohort study of Veterans with treated hypertension in the Veterans Health Administration (01/19/2020-08/28/2020), we compared users of (A) ARB/ACEI vs.

Histologic evidence for a humoral immune response in synovitis associated with cranial cruciate ligament disease in dogs.

Objective: To investigate histopathological features of synovium from dogs with cranial cruciate ligament disease (CCLD) to seek mechanisms of osteoarthritis (OA) associated with CCLD.

Study Design: Retrospective, single-institution case series.

Animals: Thirty client-owned dogs.

Airway macrophage-intrinsic TGF-β1 regulates pulmonary immunity during early-life allergen exposure.

Background: Early life represents a major risk window for asthma development. However, the mechanisms controlling the threshold for establishment of allergic airway inflammation in early life are incompletely understood. Airway macrophages (AMs) regulate pulmonary allergic responses and undergo TGF-β-dependent postnatal development, but the role of AM maturation factors such as TGF-β in controlling the threshold for pathogenic immune responses to inhaled allergens remains unclear.

Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals.

Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.

α6GABA Receptor Positive Modulators Alleviate Migraine-like Grimaces in Mice via Compensating GABAergic Deficits in Trigeminal Ganglia.

Migraine is caused by hyperactivity of the trigeminovascular system, where trigeminal ganglia (TG) play an important role. This hyperactivity might originate from an underfunctional GABAergic system in TG. To investigate this possibility, we adapted a mouse model of migraine by inducing migraine-like grimaces in male mice via repeated injections of nitroglycerin (NTG, 10 mg/kg, i.

BioCartilage augmentation of marrow stimulation procedures for cartilage defects of the knee: Two-year clinical outcomes.

Background: The present study evaluated short-term outcomes of microfracture augmented with micronized allograft cartilage matrix (BioCartilage) and platelet-rich plasma (PRP) for symptomatic focal femoral condyle or trochlea cartilage defects.

Methods: Patients who underwent microfracture augmented with BioCartilage and PRP for isolated contained chondral defects were evaluated. Magnetic resonance imaging (MRI) was performed at one year postoperatively.

Imidazodiazepine Anticonvulsant, KRM-II-81, Produces Novel, Non-diazepam-like Antiseizure Effects.

The need for improved medications for the treatment of epilepsy and chronic pain is essential. Epileptic patients typically take multiple antiseizure drugs without complete seizure freedom, and chronic pain is not fully managed with current medications. A positive allosteric modulator (PAM) of α2/3-containing GABA receptors (5-(8-ethynyl-6-(pyridin-2-yl)-4-benzo[]imidazole[1,5-α][1,4]diazepin-3-yl) oxazole or KRM-II-81 () is a lead compound in a series of imidazodiazepines.

Adenovirus 14p1 Immunopathogenesis during Lung Infection in the Syrian Hamster.

Adenovirus (Ad) infections are usually mild and self-limited, with minimal inflammatory responses. During worldwide outbreaks, Ad14p1, an emerging Ad14 variant, has caused severe pulmonary disease, including acute respiratory distress syndrome (ARDS). This increased pathogenicity of Ad14p1 is not completely understood.

Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction.

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.

miR-145a Regulation of Pericyte Dysfunction in a Murine Model of Sepsis.

Background: Sepsis is a life-threatening systemic disease with severe microvascular dysfunction. Pericytes preserve vascular homeostasis. To our knowledge, the potential roles of microRNAs in sepsis-induced pericyte dysfunction have not been explored.

Pathogen to commensal? Longitudinal within-host population dynamics, evolution, and adaptation during a chronic >16-year Burkholderia pseudomallei infection.

Although acute melioidosis is the most common outcome of Burkholderia pseudomallei infection, we have documented a case, P314, where disease severity lessened with time, and the pathogen evolved towards a commensal relationship with the host. In the current study, we used whole-genome sequencing to monitor this long-term symbiotic relationship to better understand B. pseudomallei persistence in P314's sputum despite intensive initial therapeutic regimens.

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure.

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls.

Dynamics of human monocytes and airway macrophages during healthy aging and after transplant.

The ontogeny of airway macrophages (AMs) in human lung and their contribution to disease are poorly mapped out. In mice, aging is associated with an increasing proportion of peripherally, as opposed to perinatally derived AMs. We sought to understand AM ontogeny in human lung during healthy aging and after transplant.

Impact of Medial Meniscotibial Ligament Disruption Compared to Peripheral Medial Meniscal Tear on Knee Biomechanics.

Medial meniscotibial ligament (MTL) lesions may go unrecognized and untreated and have detrimental impact on knee biomechanics and joint pathology. Therefore, this study was designed to compare the biomechanical impact of midbody MTL disruption to corresponding peripheral medial meniscal (PMM) tears in anterior cruciate ligament (ACL) intact and ACL-deficient cadaveric knees. Cadaveric knees ( = 12; 6 matched pairs) were tested for laxity and ACL strain under anterior, valgus, and external rotation loading at 0, 30, and 90 degree of flexion.

The Positive Allosteric Modulator of 2/3-Containing GABA Receptors, KRM-II-81, Is Active in Pharmaco-Resistant Models of Epilepsy and Reduces Hyperexcitability after Traumatic Brain Injury.

The imidizodiazepine, 5-(8-ethynyl-6-(pyridin-2-yl)-4-benzo[]imidazo[1,5-][1,4]diazepin-3-yl)oxazole (KRM-II-81), is selective for 2/3-containing GABA receptors. KRM-II-81 dampens seizure activity in rodent models with enhanced efficacy and reduced motor-impairment compared with diazepam. In the present study, KRM-II-81 was studied in assays designed to detect antiepileptics with improved chances of impacting pharmaco-resistant epilepsies.

T1ρ, T2 mapping, and EPIC-µCT Imaging in a Canine Model of Knee Osteochondral Injury.

The dog is the most commonly used large animal model for the study of osteoarthritis. Optimizing methods for assessing cartilage health would prove useful in reducing the number of dogs needed for a valid study of osteoarthritis and cartilage repair. Twelve beagles had critical-sized osteochondral defects created in the medial femoral condyle of both knees.

The value of human epileptic tissue in the characterization and development of novel antiepileptic drugs: The example of CERC-611 and KRM-II-81.

The need for improved antiepileptics is clearly mandated despite the existence of multiple existing medicines from different chemical and mechanistic classes. Standard of care agents do not fully control epilepsies and have a variety of side-effect and safety issues. Patients typically take multiple antiepileptic drugs and yet many continue to have seizures.

E1A oncogene induced sensitization to NK cell induced apoptosis requires PIDD and Caspase-2.

Expression of the adenovirus E1A oncogene sensitizes tumor cells to innate immune rejection by NK cells. This increased NK sensitivity is only partly explained by an E1A-induced increase in target cell surface expression of NKG2D ligands. The post-recognition mechanisms by which E1A sensitizes cells to the apoptotic cell death response to NK injury remains to be defined.

Do neoprene sleeves and prophylactic knee braces affect neuromuscular control and cutting agility?

Objectives: To evaluate the effects of neoprene sleeves (NSs) and prophylactic knee braces (PKBs) on neuromuscular control and cutting agility.

Design: Markerless motion-capture technology tracked subjects (1) without a brace as a control (2) with NSs and (3) with PKBs during single-leg drop vertical jump (SLDVJ), single-leg squat (SLS), Y-excursion, and cutting movements. Movements were recorded five times per bracing condition in three different sessions.

Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.