Primate cerebrospinal fluid CHI3L1 reflects brain TREM2 agonism.

Introduction: Triggering receptor expressed on myeloid cells 2 (TREM2) agonists are being clinically evaluated as disease-modifying therapeutics for Alzheimer's disease. Clinically translatable pharmacodynamic (PD) biomarkers are needed to confirm drug activity and select the appropriate therapeutic dose in clinical trials.

Methods: We conducted multi-omic analyses on paired non-human primate brain and cerebrospinal fluid (CSF), and stimulation of human induced pluripotent stem cell-derived microglia cultures after TREM2 agonist treatment, followed by validation of candidate fluid PD biomarkers using immunoassays.

Microfluidic Sample Preparation for Multiplexed Single-Cell Proteomics Using a Nested Nanowell Chip.

Mass spectrometry-based single-cell proteomics has undergone rapid progress and has become an active research area. However, because of the ultralow amount of proteins in single cells, it is still highly challenging to achieve efficient sample preparation and sensitive LC-MS detection. Here, we provide a detailed protocol for isobaric labeling-based single-cell proteomics relying on a microfluidic droplet-based sample processing technology.

Context-Specific Stress Causes Compartmentalized SARM1 Activation and Local Degeneration in Cortical Neurons.

Sterile alpha and TIR motif containing 1 (SARM1) is an inducible NADase that localizes to mitochondria throughout neurons and senses metabolic changes that occur after injury. Minimal proteomic changes are observed upon either SARM1 depletion or activation, suggesting that SARM1 does not exert broad effects on neuronal protein homeostasis. However, whether SARM1 activation occurs throughout the neuron in response to injury and cell stress remains largely unknown.

Polarized microtubule remodeling transforms the morphology of reactive microglia and drives cytokine release.

Microglial reactivity is a pathological hallmark in many neurodegenerative diseases. During stimulation, microglia undergo complex morphological changes, including loss of their characteristic ramified morphology, which is routinely used to detect and quantify inflammation in the brain. However, the underlying molecular mechanisms and the relation between microglial morphology and their pathophysiological function are unknown.

The Hong Kong Society of Rheumatology consensus recommendations for the management of gout.

Gout is one of the most common noncommunicable diseases in Hong Kong. Although effective treatment options are readily available, the management of gout in Hong Kong remains suboptimal. Like other countries, the treatment goal in Hong Kong usually focuses on relieving symptoms of gout but not treating the serum urate level to target.

Safety, Tolerability, and Pharmacokinetics of Benralizumab: A Phase 1, Randomized, Single-Blind Study of Healthy Chinese Participants.

Purpose: Biological therapies targeting eosinophils have been shown to be effective in treating patients with severe eosinophilic asthma. Benralizumab (Fasenra, AstraZeneca) is a humanized monoclonal antibody binding to the alpha subunit of the interleukin-5 receptor, which rapidly depletes eosinophils via antibody-dependent cellular cytotoxicity. The aim of this Phase 1 study was to assess the safety, tolerability, and pharmacokinetics of benralizumab in healthy Chinese individuals.

Five-year cardiovascular event risk in early rheumatoid arthritis patients who received treat-to-target management: a case-control study.

Objectives: This study explored whether the excess cardiovascular (CV) disease (CVD) risk in RA could be ameliorated by suppression of inflammation using a treat-to-target (T2T) approach. We compared the CV event (CVE) incidence among ERA patients managed by a T2T strategy with a CV risk factor-matched non-RA population and a historical RA cohort (HRA).

Methods: This was an observational study using the city-wide hospital data and the ERA registry.

Prevalence of Childhood Obesity in the United States in 1999-2018: A 20-Year Analysis.

Introduction: Obesity is a public health crisis in the USA. This study aimed to estimate the prevalence of obesity and severe obesity in US children and adolescents and identify novel targetable risk factors associated with childhood obesity.

Methods: From the US National Health and Nutrition Examination Survey from 1999 to 2018, 35,907 children aged 2-19 with body mass index (BMI) data were included.

The role of cytokeratin 7/20 coordination revisited-Machine learning identifies improved interpretative algorithms for cell block immunohistochemistry in aspirates of metastatic carcinoma.

Background: Fine-needle aspiration (FNA) is a robust diagnostic technique often used for tissue diagnosis of metastatic carcinoma. For interpretation of FNA cytology, cell block immunohistochemistry (IHC) and clinicocytologic parameters are indispensable. In this review of a large cohort, the current report: 1) describes clinicocytologic parameters and immunoprofiles of aspirates of metastatic carcinoma, 2) compares the predictivity of immunostains and classical approaches for IHC interpretation, and 3) describes machine learning-based algorithms for IHC interpretation.

Phase I Study of the Pharmacodynamics and Safety of Sodium Zirconium Cyclosilicate in Healthy Chinese Adults.

Sodium zirconium cyclosilicate (SZC) is an effective potassium binder for patients with hyperkalemia. This single-center, open-label, phase I study (NCT03283267) characterized the pharmacodynamics and safety of SZC in Chinese individuals. Twenty-two healthy Chinese adults (mean age, 33.

Shigella ubiquitin ligase IpaH7.8 targets gasdermin D for degradation to prevent pyroptosis and enable infection.

The pore-forming protein gasdermin D (GSDMD) executes lytic cell death called pyroptosis to eliminate the replicative niche of intracellular pathogens. Evolution favors pathogens that circumvent this host defense mechanism. Here, we show that the Shigella ubiquitin ligase IpaH7.

Nurse-Led Consultation for Patients With Rheumatoid Arthritis at Low Disease Activity: A Randomized Noninferiority Trial.

Objective: To determine the effectiveness of nurse-led consultations in patients with stable rheumatoid arthritis (RA) in Hong Kong.

Methods: The present work was a single-center, randomized, open-label, noninferiority trial. Patients who had rheumatoid arthritis (RA) with low disease activity (LDA) were randomized at a 1:1 ratio to attend a nurse-led consultation or rheumatologist follow-up visit for 2 years.

Blood lead level and risk of hypertension in the United States National Health and Nutrition Examination Survey 1999-2016.

Lead is a heavy metal without a biological role. High level of lead exposure is known to be associated with hypertension, but the risk at low levels of exposure is uncertain. In this study, data from US NHANES 1999-2016 were analyzed.

Defining the carrier proteome limit for single-cell proteomics.

Single-cell proteomics by mass spectrometry (SCoPE-MS) is a recently introduced method to quantify multiplexed single-cell proteomes. While this technique has generated great excitement, the underlying technologies (isobaric labeling and mass spectrometry (MS)) have technical limitations with the potential to affect data quality and biological interpretation. These limitations are particularly relevant when a carrier proteome, a sample added at 25-500× the amount of a single-cell proteome, is used to enable peptide identifications.

Prevalence and Impact of Reported Drug Allergies among Rheumatology Patients.

Background: Drug allergies (DA) are immunologically mediated adverse drug reactions and their manifestations depend on a variety of drug- and patient-specific factors. The dysregulated immune system underpinning rheumatological diseases may also lead to an increase in hypersensitivity reactions, including DA. The higher prevalence of reported DA, especially anti-microbials, also restricts the medication repertoire for these already immunocompromised patients.

Epidemiology of gout in Hong Kong: a population-based study from 2006 to 2016.

Objective: To determine the incidence and prevalence of gout in the general population and the utilisation of urate-lowering therapy (ULT) among patients with gout in Hong Kong.

Methods: A total of 2,741,862 subjects who attended any outpatient clinics or accident and emergency department (with or without hospitalisation) in 2005 and did not die before 2006 were identified from the Clinical Data Analysis and Reporting System (CDARS) of the Hospital Authority in Hong Kong. All subjects were followed until the end of 2016 or death.

Blood and Urine Inorganic and Organic Mercury Levels in the United States from 1999 to 2016.

Background: Mercury is an environmental hazard. Organic mercury is biologically more toxic than inorganic mercury. Therefore, we studied recent trends in the blood levels of organic and inorganic mercury in the United States.

Proteomic Analyses Identify a Novel Role for EZH2 in the Initiation of Cancer Cell Drug Tolerance.

Acquisition of drug resistance remains a chief impediment to successful cancer therapy, and we previously described a transient drug-tolerant cancer cell population (DTPs) whose survival is in part dependent on the activities of the histone methyltransferases G9a/EHMT2 and EZH2, the latter being the catalytic component of the polycomb repressive complex 2 (PRC2). Here, we apply multiple proteomic techniques to better understand the role of these histone methyltransferases (HMTs) in the establishment of the DTP state. Proteome-wide comparisons of lysine methylation patterns reveal that DTPs display an increase in methylation on K116 of PRC member Jarid2, an event that helps stabilize and recruit PRC2 to chromatin.

Management of rheumatoid arthritis: 2019 updated consensus recommendations from the Hong Kong Society of Rheumatology.

The expanding range of treatment options for rheumatoid arthritis (RA), from conventional synthetic disease-modifying antirheumatic drugs (DMARDs) to biological DMARDs (bDMARDs), biosimilar bDMARDs, and targeted synthetic DMARDs, has improved patient outcomes but increased the complexity of treatment decisions. These updated consensus recommendations from the Hong Kong Society of Rheumatology provide guidance on the management of RA, with a focus on how to integrate newly available DMARDs into clinical practice. The recommendations were developed based on evidence from the literature along with local expert opinion.

Cumulative Rheumatic Inflammation Modulates the Bone-Vascular Axis and Risk of Coronary Calcification.

Background Rheumatic diseases are related to both abnormal bone turnover and atherogenesis, but a mechanistic link was missing. Methods and Results We investigated the effect of cumulative rheumatic inflammation ( CRI ) on risk of coronary calcification in a retrospective cohort of 145 rheumatoid arthritis patients. A time-adjusted aggregate CRI score was derived by conglomerating all quarterly biomarker encounters of serum C-reactive protein over 60 months immediately preceding computed tomography coronary angiography.

Osteogenic circulating endothelial progenitor cells are linked to electrocardiographic conduction abnormalities in rheumatic patients.

Background: Osteogenic circulating endothelial progenitor cells (EPC) play a pathogenic role in cardiovascular system degeneration through promulgating vasculature calcification, but its role in conduction disorders as part of the cardiovascular degenerative continuum remained unknown.

Aim: To investigate the role of osteocalcin (OCN)-expressing circulating EPCs in cardiac conduction disorders in the unique clinical sample of rheumatoid arthritis (RA) susceptible to both abnormal bone metabolism and cardiac conduction disorders.

Methods: We performed flow cytometry studies in 134 consecutive asymptomatic patients with rheumatoid arthritis to derive osteogenic circulating OCN-positive (OCN+) CD34+KDR+ vs.