Nav1.7 is essential for nociceptor action potentials in the mouse in a manner independent of endogenous opioids.

Loss-of-function mutations in Nav1.7, a voltage-gated sodium channel, cause congenital insensitivity to pain (CIP) in humans, demonstrating that Nav1.7 is essential for the perception of pain.

Multi-ancestry genome-wide study in >2.5 million individuals reveals heterogeneity in mechanistic pathways of type 2 diabetes and complications.

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes. To characterise the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study (GWAS) data from 2,535,601 individuals (39.7% non-European ancestry), including 428,452 T2D cases.

Design of a Quantitative LC-MS Method for Residual Toxins Adenylate Cyclase Toxin (ACT), Dermonecrotic Toxin (DNT) and Tracheal Cytotoxin (TCT) in Vaccines.

The antigens for acellular pertussis vaccines are made up of protein components that are purified directly from bacterial fermentation. As such, there are additional toxins that must be monitored as residuals during process optimization. This paper describes a liquid chromatography mass spectrometry (LC-MS) method for simultaneous analysis of residual protein toxins adenylate cyclase toxin (ACT) and dermonecrotic toxin (DNT), as well as a small molecule glycopeptide, tracheal cytotoxin (TCT) in a Pertussis toxin vaccine antigen.

Updated APLAR consensus statements on care for patients with rheumatic diseases during the COVID-19 pandemic.

Aim: To update previous guidance of the Asia Pacific League of Associations for Rheumatology (APLAR) on the management of patients with rheumatic and musculoskeletal diseases (RMD) during the coronavirus disease 2019 (COVID-19) pandemic.

Methods: Research questions were formulated focusing on diagnosis and treatment of adult patients with RMD within the context of the pandemic, including the management of RMD in patients who developed COVID-19. MEDLINE was searched for eligible studies to address the questions, and the APLAR COVID-19 task force convened 2 meetings through video conferencing to discuss its findings and integrate best available evidence with expert opinion.

Adaptive Trial Designs in Rheumatology: Report from the OMERACT Special Interest Group.

Objective: Adaptive trial design was developed initially for oncology to improve trial efficiency. If optimized for rheumatology, it may improve trial efficiency by reducing sample size and time.

Methods: A systematic review assessed design of phase II clinical trials in rheumatoid arthritis.

Effect of Treat-to-target Strategies Aiming at Remission of Arterial Stiffness in Early Rheumatoid Arthritis: A Randomized Controlled Study.

Objective: To determine the efficacy of 2 tight control treatment strategies aiming at Simplified Disease Activity Score (SDAI) remission (SDAI ≤ 3.3) compared to 28-joint count Disease Activity Score (DAS28) remission (DAS28 < 2.6) in the prevention of arterial stiffness in patients with early rheumatoid arthritis (RA).

Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines.

mRNA represents a promising new vaccine technology platform with high flexibility in regard to development and production. Here, we demonstrate that vaccines based on sequence optimized, chemically unmodified mRNA formulated in optimized lipid nanoparticles (LNPs) are highly immunogenic and well tolerated in non-human primates (NHPs). Single intramuscular vaccination of NHPs with LNP-formulated mRNAs encoding rabies or influenza antigens induced protective antibody titers, which could be boosted and remained stable during an observation period of up to 1 year.

Synoviocytes-derived Interleukin 35 Potentiates B Cell Response in Patients with Osteoarthritis and Rheumatoid Arthritis.

Objective: Elevated expression of interleukin 35 (IL-35) is associated with autoimmune disease, including rheumatoid arthritis (RA). The present study was undertaken to determine the functional interaction among IL-35, B cells, and stromal cells residing in the synovium of patients with RA and osteoarthritis (OA).

Methods: IL-35 (EBI-3/p35) expression was investigated in RA and OA synovium using quantitative real-time PCR (qRT-PCR) and immunohistochemistry.

Underestimation of Risk of Carotid Subclinical Atherosclerosis by Cardiovascular Risk Scores in Patients with Psoriatic Arthritis.

Objective: To test the performances of established cardiovascular (CV) risk scores in discriminating subclinical atherosclerosis (SCA) in patients with psoriatic arthritis.

Methods: These scores were calculated: Framingham risk score (FRS), QRISK2, Systematic COronary Risk Evaluation (SCORE), 10-year atherosclerotic cardiovascular disease risk algorithm (ASCVD) from the American College of Cardiology and the American Heart Association, and the European League Against Rheumatism (EULAR)-recommended modified versions (by 1.5 multiplication factor, m-).

The Role of High-resolution Peripheral Quantitative Computed Tomography as a Biomarker for Joint Damage in Inflammatory Arthritis.

Since 2011, members of the SPECTRA Collaboration (Study grouP for xtrEme-Computed Tomography in Rheumatoid Arthritis) have investigated the validity, reliability, and responsiveness of high-resolution peripheral quantitative computed tomography (HR-pQCT) as a biomarker for joint damage in inflammatory arthritis. Presented in this series of articles are a systematic review of HR-pQCT-related findings to date, a review of selected images of cortical and subchondral trabecular bone of metacarpophalangeal (MCP) joints, results of a consensus process to standardize the definition of erosions and their quantification, as well as an examination of the effect of joint flexion on width and volume assessment of the joint space.

Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia.

Background: Chronic lymphocytic leukemia (CLL) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression. We conducted an international, open-label, randomized phase 3 trial to compare two oral agents, ibrutinib and chlorambucil, in previously untreated older patients with CLL or small lymphocytic lymphoma.

Methods: We randomly assigned 269 previously untreated patients who were 65 years of age or older and had CLL or small lymphocytic lymphoma to receive ibrutinib or chlorambucil.

Intrarenal and Urinary Th9 and Th22 Cytokine Gene Expression in Lupus Nephritis.

Objective: We studied the urinary sediment mRNA level of Th9- and Th22-related cytokines in patients with systemic lupus erythematosus (SLE).

Methods: We quantified urinary mRNA levels of interleukin (IL) 9, IL-10, IL-22, and their corresponding transcription factors in 73 patients with active lupus nephritis, 13 patients with hypertensive nephrosclerosis (HTN), and 25 healthy subjects.

Results: There was no detectable IL-9 mRNA in all samples.

Bone mineral density change in systemic lupus erythematosus: a 5-year followup study.

Objective: To determine changes of bone mineral density (BMD) over a 5-year period in a cohort of female patients with systemic lupus erythematosus (SLE) and to identify factors predictive of BMD loss.

Methods: Our longitudinal study involved 125 female patients with SLE with a mean (SD) age of 46.5 years (10.

Sulfur dioxide does not acutely increase nasal symptoms or nasal resistance in subjects with rhinitis or in subjects with bronchial responsiveness to sulfur dioxide.

We examined whether brief exposures to moderately high concentrations of sulfur dioxide (SO2) causes acute increases in nasal symptoms and nasal resistance in subjects with chronic rhinitis. We studied 19 subjects with allergic rhinitis and 3 subjects with chronic intermittent rhinorrhea, nasal congestion, and sneezing without any other manifestation of allergy. We found that the change in nasal resistance and symptoms caused by nasal inhalation of 4 ppm of SO2 for 10 min was no greater than the changes caused by nasal inhalation of conditioned room air.

Effect of eucapnic hypoxia on bronchomotor tone and on the bronchomotor response to dry air in asthmatic subjects.

Because hypoxia has been shown to cause bronchoconstriction and to potentiate bronchomotor responsiveness in animals, we investigated whether hypoxia has similar effects in subjects with asthma. We measured specific airway resistance (SRaw; the mean of 5 sequential readings taken 30 s apart) before and immediately after each of 15 asthmatic subjects breathed a mixture of 8% O2 in N2 until hemoglobin saturation (SaO2; by ear oximetry) fell to 80% or less for at least 2 min. We maintained end-tidal CO2 at resting levels, the temperature of the inspirate at 22.