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Background: Most in vitro studies of potential osteoarthritis (OA) therapies have used cartilage monocultures, even though synovium is a key player in mediating joint inflammation and, thereby, cartilage degeneration. In the case of interleukin-1 (IL-1) inhibition using its receptor antagonist (IL-1Ra), like chondrocytes, synoviocytes also express IL-1 receptors that influence intra-articular IL-1

Incretin-based therapy is associated with low risk of hypoglycemia in type 2 diabetes mellitus (T2DM) possibly due to its glucose-dependency in stimulating insulin secretion and a sustained glucagon response during hypoglycemia. This is of special relevance when it is combined with insulin or given to elderly patients since both insulin therapy and high age are associated with impaired glucagon co

Introduction: The demographic changes with population ageing and a rapidly growing share of very old peoplewill put an increasing pressure on the health and social care system. In order to both restrict early retirement and force people to extend their working life reforms are changing pension systems in many European countries. Besides that older people have to extend their working life it is imp

IMPORTANCE The positron emission tomography (PET) tracer [18F]flortaucipir allows in vivo quantification of paired helical filament tau, a core neuropathological feature of Alzheimer disease (AD), but its diagnostic utility is unclear. OBJECTIVE To examine the discriminative accuracy of [18F]flortaucipir for AD vs non-AD neurodegenerative disorders. DESIGN, SETTING, AND PARTICIPANTS In this cross-

Importance: Preterm delivery has been associated with future cardiometabolic disorders in women. However, the long-term risks of chronic hypertension associated with preterm delivery and whether such risks are attributable to familial confounding are unclear. Such knowledge is needed to improve long-term risk assessment, clinical monitoring, and cardiovascular prevention strategies in women. Objec

Importance: The association between long sleep duration and mortality appears stronger in East Asian populations than in North American or European populations. Objectives: To assess the sex-specific association between sleep duration and all-cause and major-cause mortality in a pooled longitudinal cohort and to stratify the association by age and body mass index. Design, Setting, and Participants

The current plastic system is unsustainable and needs to change. Plastics are mainly produced from fossil feedstock, contributing to greenhouse gas emissions, and low rate of post-consumer recycling results in pollution on land and in oceans with high ecological impact, and huge loss of valuable material. There is an urgent need to find solutions for shifting the raw material base to renewable res

Importance: Patients with amnestic mild cognitive impairment (aMCI) may progress to clinical Alzheimer disease (AD), remain stable, or revert to normal. Earlier progression to AD among patients who were β-amyloid positive vs those who were β-amyloid negative has been previously observed. Current research now accepts that a combination of biomarkers could provide greater refinement in the assessmen

Background: Potent antithrombotic therapy has significantly improved prognosis for patients with acute myocardial infarction (AMI), however, at a price of increased bleeding risk. Chronic gastric infection with Helicobacter pylori (Hp) commonly causes upper gastrointestinal bleeding and is proposed as a risk factor for subsequent bleeding post AMI. The prevalence of active Hp in a current AMI popu

Background If carotid artery narrowing remains asymptomatic (ie, has caused no recent stroke or other neurological symptoms), successful carotid endarterectomy (CEA) reduces stroke incidence for some years. We assessed the long-term effects of successful CEA. Methods Between 1993 and 2003, 3120 asymptomatic patients from 126 centres in 30 countries were allocated equally, by blinded minimised rand

Importance: Soft drinks are frequently consumed, but whether this consumption is associated with mortality risk is unknown and has been understudied in European populations to date.Objective: To examine the association between total, sugar-sweetened, and artificially sweetened soft drink consumption and subsequent total and cause-specific mortality.Design, Setting, and Participants: This populatio

Colorectal cancer (CRC) is the third most common cancer worldwide. Increasing evidence suggests that CRC should be considered a heterogeneous disease, with multiple differences between proximal and distal tumours. The immune system may, depending on the context, promote or inhibit tumour growth, and different immune cell subsets have been found to be associated with impaired or improved prognosis

Importance: Better understanding is needed of the degree to which individuals tolerate Alzheimer disease (AD)-like pathological tau with respect to brain structure (brain resilience) and cognition (cognitive resilience). Objective: To examine the demographic (age, sex, and educational level), genetic (APOE-ϵ4 status), and neuroimaging (white matter hyperintensities and cortical thickness) factors

Background: Endometriosis and irritable bowel syndrome (IBS) have similar symptoms, pathogenesis, and risk factors. These diagnoses often coexist and are frequently misdiagnosed leading to diagnostic delays. This study of a population-based cohort aimed to investigate associations relating to endometriosis and IBS and to compare gastrointestinal symptoms between endometriosis and IBS. Method: The

Aims: Ventricular longitudinal function measured as basal-apical atrioventricular plane displacement (AVPD) or global longitudinal strain (GLS) is a potent predictor of mortality and could potentially be a predictor of heart failure-associated morbidity. We hypothesized that low AVPD and GLS are associated with the combined endpoint of cardiovascular mortality and heart failure-associated morbidit

The immune control of tuberculosis (TB) infection could be influenced by pregnancy. To elucidate this, we longitudinally characterized Mycobacterium tuberculosis (Mtb)-specific and nonspecific immune responses in women during pregnancy and postpartum. HIV-uninfected women without past or current active TB, and with blood samples available from the 1st/2nd trimester, 3rd trimester, and 9 months pos

IMPORTANCE: Chronic breathlessness is common in people with chronic obstructive pulmonary disease (COPD). Regular, low-dose, extended-release morphine may relieve breathlessness, but evidence about its efficacy and dosing is needed.OBJECTIVE: To determine the effect of different doses of extended-release morphine on worst breathlessness in people with COPD after 1 week of treatment.DESIGN, SETTING

BACKGROUND: Neuronal damage in systemic lupus erythematosus (SLE) is common, but the extent and mechanisms are unclear. Neurofilament light (NfL) concentrations rise in plasma and cerebrospinal fluid (CSF) during neuronal damage in various neurological disorders. In this cross-sectional study, plasma and CSF concentrations of NfL were explored as a marker of neuronal damage in SLE.METHODS: Seventy