SHP2 ablation mitigates osteoarthritic cartilage degeneration by promoting chondrocyte anabolism through SOX9.

Articular cartilage phenotypic homeostasis is crucial for life-long joint function, but the underlying cellular and molecular mechanisms governing chondrocyte stability remain poorly understood. Here, we show that the protein tyrosine phosphatase SHP2 is differentially expressed in articular cartilage (AC) and growth plate cartilage (GPC) and that it negatively regulates cell proliferation and cartilage phenotypic program. Postnatal SHP2 deletion in Prg4 AC chondrocytes increased articular cellularity and thickness, whereas SHP2 deletion in Acan pan-chondrocytes caused excessive GPC chondrocyte proliferation and led to joint malformation post-puberty.

Pandemic Action Plan: Phase 3-Lessons Learned from Implementation. "What Did We Learn?".

The COVID-19 pandemic created critical challenges for hospitals and health care providers. Suddenly clinics were forced to close; elective procedures were delayed; scheduled visits were canceled; emergency rooms were overcrowded; hospital beds, equipment, and personal protective equipment (PPE) were in short supply; and staff were faced with rapidly changing circumstances, care protocols, trauma, and personal risk. To better address challenges of the ongoing COVID-19 pandemic and prepare for future pandemics, the National Telemedicine Technology Assessment Resource Center (TTAC) was asked to develop a Pandemic Response Action Plan that would allow its users to address critical issues with available telemedicine and related technologies.

Floral scent changes in response to pollen removal are rare in buzz-pollinated Solanum.

One of seven Solanum taxa studied displayed associations between pollen presence and floral scent composition and volume, suggesting buzz-pollinated plants rarely use scent as an honest cue for foraging pollinators. Floral scent influences the recruitment, learning, and behaviour of floral visitors. Variation in floral scent can provide information on the amount of reward available or whether a flower has been visited recently and may be particularly important in species with visually concealed rewards.

Development of an implantable trapezium carpal bone replacement for measuring in vivo loads at the base of the thumb.

Understanding the loads that occur across musculoskeletal joints is critical to advancing our understanding of joint function and pathology, implant design and testing, as well as model verification. Substantial work in these areas has occurred in the hip and knee but has not yet been undertaken in smaller joints, such as those in the wrist. The thumb carpometacarpal (CMC) joint is a uniquely human articulation that is also a common site of osteoarthritis with unknown etiology.

Evaluation of the Toyota Human Support Robot (HSR) for Social Interaction and Learning.

Tele-operated social robots (telerobots) offer an innovative means of allowing children who are medically restricted to their homes (MRH) to return to their local schools and physical communities. Most commercially available telerobots have three foundational features that facilitate child-robot interaction: remote mobility, synchronous two-way vision capabilities, and synchronous two-way audio capabilities. We conducted a comparative analysis between the Toyota Human Support Robot (HSR) and commercially available telerobots, focusing on these foundational features.

Optimization of physicochemical properties of pyrrolidine GPR40 AgoPAMs results in a differentiated profile with improved pharmacokinetics and reduced off-target activities.

GPR40 AgoPAMs are highly effective antidiabetic agents that have a dual mechanism of action, stimulating both glucose-dependent insulin and GLP-1 secretion. The early lipophilic, aromatic pyrrolidine and dihydropyrazole GPR40 AgoPAMs from our laboratory were highly efficacious in lowering plasma glucose levels in rodents but possessed off-target activities and triggered rebound hyperglycemia in rats at high doses. A focus on increasing molecular complexity through saturation and chirality in combination with reducing polarity for the pyrrolidine AgoPAM chemotype resulted in the discovery of compound 46, which shows significantly reduced off-target activities as well as improved aqueous solubility, rapid absorption, and linear PK.

Bone morphological changes of the trapezium and first metacarpal with early thumb osteoarthritis progression.

Background: Thumb carpometacarpal osteoarthritis is characterized by osteophyte growth and changes in the curvature of the articular surfaces of the trapezium and first metacarpal. The aim of this longitudinal study was to quantify in-vivo bone morphology changes with osteoarthritis progression.

Methods: The study analyzed an observational dataset of 86 subjects with early thumb osteoarthritis and 22 age-matched asymptomatic controls.

Formalising the Pathways to Life Using Assembly Spaces.

Assembly theory (referred to in prior works as pathway assembly) has been developed to explore the extrinsic information required to distinguish a given object from a random ensemble. In prior work, we explored the key concepts relating to deconstructing an object into its irreducible parts and then evaluating the minimum number of steps required to rebuild it, allowing for the reuse of constructed sub-objects. We have also explored the application of this approach to molecules, as molecular assembly, and how molecular assembly can be inferred experimentally and used for life detection.

Evaluation of the PROMIS Upper Extremity Against Validated Patient-Reported Outcomes in Patients With Early Carpometacarpal Osteoarthritis.

Purpose: Internal consistency, construct, and criterion validity of the Patient-Reported Outcomes Measurement Information System (PROMIS) upper extremity (UE) v1.2 were evaluated in patients with early-stage carpometacarpal (CMC) osteoarthritis (OA). We hypothesized that in patients with early CMC OA, PROMIS UE scores would: (1) be lower than those in asymptomatic controls; (2) correlate with established patient-reported outcomes; (3) correlate with pinch and grip strengths; and (4) not correlate with radiographic disease progression.

Total Wrist Arthroplasty Alignment and Its Potential Association with Clinical Outcomes.

 There is a lack of quantitative research that describes the alignment and, more importantly, the effects of malalignment on total wrist arthroplasty (TWA). The main goal of this pilot study was to assess the alignment of TWA components in radiographic images and compare them with measures computed by three-dimensional analysis. Using these measures, we then determined if malalignment is associated with range of motion (ROM) or clinical outcomes (PRWHE, PROMIS, QuickDash, and grip strength).

Pandemic Telemedicine Technology Response Plan and Technology Assessment Phase 2: Pandemic Action Plan Key Issues and Technology Solutions for Health Care Delivery Organizations in a Pandemic.

The Covid-19 pandemic created critical challenges for hospitals and healthcare providers. Suddenly clinics were forced to close; scheduled visits were cancelled; emergency rooms were overcrowded; hospital beds, equipment and personal protective equipment (PPE) was in short supply; and staff were faced with rapidly changing circumstances, care protocols, trauma and personal risk. In order to better address the ongoing the Covid-19 pandemic and prepare for future pandemics, the National Telemedicine Technology Assessment resource Center (TTAC) was asked to develop an Pandemic Response Action Plan that would allow its user to address critical issues with available telemedicine and related technologies.

Pandemic Action Plan Policy and Regulatory Summary Telehealth Policy and Regulatory Considerations During a Pandemic.

Reports, studies, and surveys have demonstrated telehealth provides opportunities to make health care more efficient, better coordinated, convenient, and affordable. Telehealth can also help address health income and access disparities in underserved communities by removing location and transportation barriers, unproductive time away from work, childcare expenses, and so on. Despite evidence showing high-quality outcomes, satisfaction, and success rates (e.

The role of scapholunate interosseous, dorsal intercarpal, and radiolunate ligaments in wrist biomechanics.

Rupture to wrist ligaments predisposes the joint to degenerative changes. Scapholunate interosseous ligament (SLIL) rupture, especially when compounded by dorsal intercarpal ligament (DIC) and long radiolunate ligament (LRL) disruption, can cause carpal bone kinematic abnormalities. It is essential to delineate the role of these ligaments and their constraints on wrist range-of-motion (ROM) and center of rotation (COR).

Biomechanics of the Distal Radioulnar Joint During In Vivo Forearm Pronosupination.

 Ulnar variance (UV) and center of rotation (COR) location at the level of the distal radioulnar joint (DRUJ) change with forearm rotation. Nevertheless, these parameters have not been assessed dynamically during active in vivo pronosupination. This assessment could help us to improve our diagnosis and treatment strategies.

Multisystem inflammatory syndrome in adults: A rare sequela of SARS-CoV-2 infection.

Multisystem inflammatory syndrome in adults (MIS-A) came to attention back in June 2020, when the United States Center for Disease Control and Prevention (CDC) received initial reports regarding patients who had presented delayed and multisystem involvement of the disease, with clinical course resembling multisystem inflammatory syndrome in children (MIS-C). This study introduces a case of MIS-A, where the patient presented 3 weeks after initial COVID-19 exposure. His clinical course was consistent with the working definition of MIS-A as specified by the CDC.

Identifying molecules as biosignatures with assembly theory and mass spectrometry.

The search for alien life is hard because we do not know what signatures are unique to life. We show why complex molecules found in high abundance are universal biosignatures and demonstrate the first intrinsic experimentally tractable measure of molecular complexity, called the molecular assembly index (MA). To do this we calculate the complexity of several million molecules and validate that their complexity can be experimentally determined by mass spectrometry.

In vivo articular contact pattern of a total wrist arthroplasty design.

Total wrist arthroplasty (TWA) designs suffer from relatively high complication rates when compared to other arthroplasties. Understanding the contact pattern of hip and knee replacement has improved their design and function; however, the in vivo contact pattern of TWA has not yet been examined and is thus the aim of this study. We hypothesized that the center of contact (CoC) is located at the geometric centers of the carpal component and radial component in the neutral posture and that the CoC moves along the principal arcs of curvature throughout primary anatomical motions.

Optical motion capture accuracy is task-dependent in assessing wrist motion.

Optical motion capture (OMC) systems are commonly used to capture in-vivo three-dimensional joint kinematics. However, the skin-based markers may not reflect the underlying bone movement, a source of error known as soft tissue artifact (STA). This study examined STA during wrist motion by evaluating the agreement between OMC and biplanar videoradiography (BVR).

Biplanar Videoradiography to Study the Wrist and Distal Radioulnar Joints.

Accurate measurement of skeletal kinematics in vivo is essential for understanding normal joint function, the influence of pathology, disease progression, and the effects of treatments. Measurement systems that use skin surface markers to infer skeletal motion have provided important insight into normal and pathological kinematics, however, accurate arthrokinematics cannot be attained using these systems, especially during dynamic activities. In the past two decades, biplanar videoradiography (BVR) systems have enabled many researchers to directly study the skeletal kinematics of the joints during activities of daily living.

Sympathetic stimulation increases serum lactate concentrations in patients admitted with sepsis: implications for resuscitation strategies.

Background: Diametrically opposed positions exist regarding the deleterious effects of elevated lactate. There are data suggesting that it is a detrimental proxy for tissue hypoperfusion and anaerobic metabolism in sepsis and an alternative viewpoint is that some of the hyperlactatemia produced maybe adaptive. This study was conducted to explore the relationship between serum lactate levels, mean arterial blood pressure (MAP), and sympathetic stimulation in patients with sepsis.

Pulmonary Manifestations of Rheumatoid Arthritis.

To describe the case of an 88-yearold male with rheumatoid arthritis who developed pulmonary manifestations. Treatment for his RA previously included various biologics, while at the time of pulmonary consultation included meloxicam, methotrexate, and abatacept. Following chest scans, bronchoscopy, needle biopsy, pulmonary function testing, and a thoracentesis, the diagnosis of pleural effusion and nodules associated with rheumatoid arthritis was determined.

Targeted Ptpn11 deletion in mice reveals the essential role of SHP2 in osteoblast differentiation and skeletal homeostasis.

The maturation and function of osteoblasts (OBs) rely heavily on the reversible phosphorylation of signaling proteins. To date, most of the work in OBs has focused on phosphorylation by tyrosyl kinases, but little has been revealed about dephosphorylation by protein tyrosine phosphatases (PTPases). SHP2 (encoded by PTPN11) is a ubiquitously expressed PTPase.

Major Urological Cancer Surgery for Patients is Safe and Surgical Training Should Be Encouraged During the COVID-19 Pandemic: A Multicentre Analysis of 30-day Outcomes.

Unlabelled: COVID-19 has resulted in the deferral of major surgery for genitourinary (GU) cancers with the exception of cancers with a high risk of progression. We report outcomes for major GU cancer operations, namely radical prostatectomy (RP), radical cystectomy (RC), radical nephrectomy (RN), partial nephrectomy (PN), and nephroureterectomy performed at 13 major GU cancer centres across the UK between March 1 and May 5, 2020. A total of 598 such operations were performed.