Indoxyl-sulfate activation of the AhR- NF-κB pathway promotes interleukin-6 secretion and the subsequent osteogenic differentiation of human valvular interstitial cells from the aortic valve.

Background: Calcific aortic stenosis (CAS) is more prevalent, occurs earlier, progresses faster and has worse outcomes in patients with chronic kidney disease (CKD). The uremic toxin indoxyl sulfate (IS) is powerful predictor of cardiovascular mortality in these patients and a strong promoter of ectopic calcification whose role in CAS remains poorly studied. The objective of this study was to evaluate whether IS influences the mineralization of primary human valvular interstitial cells (hVICs) from the aortic valve.

Decreased monocyte calcium sensing receptor expression in patients with chronic kidney disease is associated with impaired monocyte ability to reduce vascular calcification.

In chronic kidney disease (CKD), calcium-sensing receptor (CaSR) expression and function have been extensively studied in parathyroid tissue and vascular tissues. To examine whether similar changes occurred in other tissues, we measured total and surface CaSR expression in monocytes of patients with various stages of CKD and healthy volunteers respectively in cross-sectional studies. We further explored in vitro the impact of uremic serum on CaSR expression in monocytes (U937 and THP-1 cell lines), and whether human peripheral blood mononuclear cells or U937 and THP-1 monocytes might modify vascular calcium deposition in rat carotid arteries in vitro.

Rationale for COVID-19 Treatment by Nebulized Interferon-β-1b-Literature Review and Personal Preliminary Experience.

The inflammatory response to COVID-19 is specifically associated with an impaired type I interferon (IFN) response and complete blockade of IFN-β secretion. Clinically, nebulization of IFN-α-2b has been historically used in China to treat viral pneumonia associated with SARS-CoV. Very recent data show that the use of inhaled type I IFN is associated with decreased mortality in Chinese COVID-19 patients.

Role of the community pharmacist in detecting frailty and spatio-temporal disorientation among community-dwelling older people in France.

Background: Many older community-dwelling subjects may be frail and/or disoriented, putting them at risk of adverse outcomes. We investigated the prevalence of frailty and spatiotemporal disorientation among patients aged > 65 years collecting regular medication at a community pharmacy.

Methods: Prospective, cross-sectional study of geriatric evaluation in 218 community pharmacies in France.

Reviewing the womb.

Throughout most of human history women have been defined by their biological role in reproduction, seen first and foremost as gestators, which has led to the reproductive system being subjected to outside interference. The womb was perceived as dangerous and an object which husbands, doctors and the state had a legitimate interest in controlling. In this article, we consider how notions of conflict surrounding the womb have endured over time.

Aortic stenosis in patients with kidney failure: Is there an advantage for a ?

Aortic stenosis (AS) is the most common valvular disease. It is twice as prevalent in patients with kidney failure as compared to the general population. In addition, AS progresses at a faster rate and is associated with a higher risk of death and poorer quality of life in patients on dialysis.

The Metabolism of Epoxyeicosatrienoic Acids by Soluble Epoxide Hydrolase Is Protective against the Development of Vascular Calcification.

This study addressed the hypothesis that soluble epoxide hydrolase (sEH), which metabolizes endothelium-derived epoxyeicosatrienoic acids, plays a role in vascular calcification. The sEH inhibitor -4-(4-(3-adamantan-1-yl-ureido)-cyclohexyloxy)-benzoic acid (-AUCB) potentiated the increase in calcium deposition of rat aortic rings cultured in high-phosphate conditions. This was associated with increased tissue-nonspecific alkaline phosphatase activity and mRNA expression level of the osteochondrogenic marker Runx2.

The CaSR in Pathogenesis of Breast Cancer: A New Target for Early Stage Bone Metastases.

The Ca-sensing receptor (CaSR) is a class-C G protein-coupled receptor which plays a pivotal role in calciotropic processes, primarily in regulating parathyroid hormone secretion to maintain systemic calcium homeostasis. Among its non-calciotropic roles, where the CaSR sits at the intersection of myriad processes, it has steadily garnered attention as an oncogene or tumor suppressor in different organs. In maternal breast tissues the CaSR promotes lactation but in breast cancer it acts as an oncoprotein and has been shown to drive the pathogenesis of skeletal metastases from breast cancer.

New Insights into the Roles of Monocytes/Macrophages in Cardiovascular Calcification Associated with Chronic Kidney Disease.

Cardiovascular disease (CVD) is an important cause of death in patients with chronic kidney disease (CKD), and cardiovascular calcification (CVC) is one of the strongest predictors of CVD in this population. Cardiovascular calcification results from complex cellular interactions involving the endothelium, vascular/valvular cells (i.e.

Activation of the calcium-sensing receptor in human valvular interstitial cells promotes calcification.

Introduction And Aims: Calcific aortic valve disease (CAVD) is the most common heart valve disease in western countries. It has been reported that activation of the calcium-sensing receptor(CaSR) expressed by vascular smooth muscle cells prevents vascular calcification. However, to date, the CaSR's expression and function in cardiac valves have not been studied.

Mobile Phone Text Messages and Effect on Treatment Adherence in Patients Taking Methotrexate for Rheumatoid Arthritis: A Randomized Pilot Study.

Objective: To assess the impact of weekly text messages on adherence in patients taking methotrexate (MTX) for rheumatoid arthritis (RA).

Methods: This prospective, randomized pilot, single-site study included patients with RA stabilized using MTX alone or combined with biologics. Participants were randomized to 3 interventions: a standard consultation (controls), a 15-minute pharmacist-led counseling session, or the receipt of text message reminders.

Legally Human? 'Novel Beings' and English Law.

Novel beings-intelligent, conscious life-forms sapient in the same way or greater than are human beings-are no longer the preserve of science fiction. Through technologies such as artificial general intelligence, synthetic genomics, gene printing, cognitive enhancement, advanced neuroscience, and more, they are becoming ever more likely and by some definitions may already be emerging. Consideration of the nature of intelligent, conscious novel beings such as those that may result from these technologies requires analysis of the concept of the 'reasonable creature in being' in English law, as well as of the right to life as founded in the European Convention on Human Rights and the attempts to endow human status on animals in recent years.

Memories of Ken Mason.

John Kenyon Mason (19 December 1919-26 January 2017), CBE, MD, LLD, FRCPath, DMJ, FRCPE, FRSE, and known as Ken Mason to us all, was Regius Professor of Forensic Medicine at the University of Edinburgh from 1973-1985 and thereafter Emeritus Professor of Forensic Medicine and Honorary Fellow in the School of Law at the University of Edinburgh. A formal obituary to Professor Mason is published in the Scotsman (http://www.scotsman.

Expression of the calcium-sensing receptor in monocytes from synovial fluid is increased in osteoarthritis.

Objectives: We assessed calcium-sensing receptor (CaSR) expression in monocytes isolated from synovial fluid of patients with different types of rheumatisms and explored whether CaSR expression was related to the inflammatory nature of synovial fluid.

Methods: Forty-one patients were included: osteoarthritis (n=10), microcristallin rheumatisms (n=10), rheumatoid arthritis (n=12) and other inflammatory rheumatisms (n=9). Surface and total CaSR expressions in monocytes isolated from synovial fluid and blood were assessed by flow cytometry analysis.

Efficacy and safety of nicotinamide in haemodialysis patients: the NICOREN study.

Background: Nicotinamide (NAM) has been proposed as an alternative treatment to phosphate binders for hyperphosphataemia in chronic kidney disease.

Methods: The NICOREN multicentre, open-label and randomized study was designed to examine non-inferiority and safety of NAM when compared with sevelamer (SEV) in chronic haemodialysis patients. One hundred patients were randomized to either NAM or SEV treatment for 24 weeks.

Not so new directions in the law of consent? Examining Montgomery v Lanarkshire Health Board.

This paper examines the UK Supreme Court decision in Montgomery v Lanarkshire Health Board, which deals with consent and information disclosure in medical treatment and care. It signaled a move away from a 'doctor knows best' approach to one that focuses on disclosing information to which particular patients would attach significance. Notwithstanding concerns about increased litigation and loss of professional autonomy, the reality is that the decision will make little difference to healthcare practice and consent in the UK.

Trabecular Bone Score: Where are we now?

The Trabecular Bone Score is a rather new index obtained at the lumbar spine at the same time as a real bone mineral density. It was developed to reflect bone microarchitecture. It was proposed to be easily used in everyday practice as a surrogate of bone strength.

Calcitriol prevents in vitro vascular smooth muscle cell mineralization by regulating calcium-sensing receptor expression.

Vascular calcification (VC) is a degenerative disease that contributes to cardiovascular morbidity and mortality. A negative relationship has been demonstrated between VC and calcium sensing receptor (CaSR) expression in the vasculature. Of interest, vitamin D response elements, which allow responsiveness to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], are present in the promoters of the CaSR gene.