Genetic causes of hypercalciuric nephrolithiasis

Renal stone disease (nephrolithiasis) affects 3–5% of the population and is often associated with hypercalciuria. Hypercalciuric nephrolithiasis is a familial disorder in over 35% of patients and may occur as a monogenic disorder that is more likely to manifest itself in childhood. Studies of these monogenic forms of hypercalciuric nephrolithiasis in humans, e.g. Bartter syndrome, Dent’s disease, autosomal dominant hypocalcemic hypercalciuria (ADHH), hypercalciuric nephrolithiasis with hypophosphatemia, and familial hypomagnesemia with hypercalciuria have helped to identify a number of transporters, channels and receptors that are involved in regulating the renal tubular reabsorption of calcium. Thus, Bartter syndrome, an autosomal disease, is caused by mutations of the bumetanide-sensitive Na–K–Cl (NKCC2) co-transporter, the renal outer-medullary potassium (ROMK) channel, the voltage-gated chloride channel, CLC-Kb, the CLC-Kb beta subunit, barttin, or the calcium-sensing receptor (CaSR). Dent’s disease, an X-linked disorder characterized by low molecular weight proteinuria, hypercalciuria and nephrolithiasis, is due to mutations of the chloride/proton antiporter 5, CLC-5; ADHH is associated with activating mutations of the CaSR, which is a G-protein-coupled receptor; hypophosphatemic hypercalciuric nephrolithiasis associated with rickets is due to mutations in the type 2c sodium–phosphate co-transporter (NPT2c); and familial hypomagnesemia with hypercalciuria is due to mutations of paracellin-1, which is a member of the claudin family of membrane proteins that form the intercellular tight junction barrier in a variety of epithelia. These studies have provided valuable insights into the renal tubular pathways that regulate calcium reabsorption and predispose to hypercalciuria and nephrolithiasis

The TFOS International Workshop on Contact Lens Discomfort: Executive Summary

Contact lens discomfort (CLD) is a frequently experienced problem, with most estimates suggesting that up to half of contact lens wearers experience this problem with some frequency or magnitude. This condition impacts millions of contact lens wearers worldwide. Yet, there is a paucity of consensus and standardization in the scientific and clinical communities on the characterization of the condition, including the definition, classification, epidemiology, pathophysiology, diagnosis, management, influence of contact lens materials, designs and care, and the proper design of clinical trials. \ud \ud The Tear Film & Ocular Surface Society (TFOS), which is a nonprofit organization, has conducted two prior international, consensus building workshops, including the Dry Eye WorkShop (DEWS; available in the public domain at http://www.tearfilm.org/tearfilm-reports-dews-report.php) and the Meibomian Gland Dysfunction Workshop (MGD; available in the public domain at http://www.tearfilm.org/tearfilm-reports-mgdreport.php). To that end, TFOS initiated the process of conducting a similar workshop in January 2012—a process that took approximately 18 months to complete and included 79 experts in the field. These experts participated in one or more topical subcommittees, and were assigned with taking an evidence-based approach at evaluating CLD. Eight topical subcommittees were formed, with each generating a related report, all of which were circulated for presentation, review, and input of the entire workshop membership. \ud \ud The entire workshop originally is being published in this issue of IOVS, in English, with subsequent translations into numerous other languages. All of this information is intended to be available and accessible online, free of charge. This article is intended to serve as an Executive Summary of the eight subcommittee reports, and all information contained here was abstracted from the full reports