Calcium selective channel TRPV6: Structure, function, and implications in health and disease.

Calcium-selective channel TRPV6 (Transient Receptor Potential channel family, Vanilloid subfamily member 6) belongs to the TRP family of cation channels and plays critical roles in transcellular calcium (Ca2+) transport, reuptake of Ca2+ into cells, and maintaining a local low Ca2+ environment for certain biological processes. Recent crystal and cryo-electron microscopy-based structures of TRPV6 have revealed mechanistic insights on how the protein achieves Ca2+ selectivity, permeation, and inactivation by calmodulin. The TRPV6 protein is expressed in a range of epithelial tissues such as the intestine, kidney, placenta, epididymis, and exocrine glands such as the pancreas, prostate and salivary, sweat, and mammary glands. The TRPV6 gene is a direct transcriptional target of the active form of vitamin D and is efficiently regulated to meet the body's need for Ca2+ demand. In addition, TRPV6 is also regulated by the level of dietary Ca2+ and under physiological conditions such as pregnancy and lactation. Genetic models of loss of function in TRPV6 display hypercalciuria, decreased bone marrow density, deficient weight gain, reduced fertility, and in some cases alopecia. The models also reveal that the channel plays an indispensable role in maintaining maternal-fetal Ca2+ transport and low Ca2+ environment in the epididymal lumen that is critical for male fertility. Most recently, loss of function mutations in TRPV6 gene is linked to transient neonatal hyperparathyroidism and early onset chronic pancreatitis. TRPV6 is overexpressed in a wide range of human malignancies and its upregulation is strongly correlated to tumor aggressiveness, metastasis, and poor survival in selected cancers. This review summarizes the current state of knowledge on the expression, structure, biophysical properties, function, polymorphisms, and regulation of TRPV6. The aberrant expression, polymorphisms, and dysfunction of this protein linked to human diseases are also discussed.

Addressing medically underserved populations through maternal-fetal transport: a geographic analysis.

Objective: Despite regionalization of maternal care in the USA, there is little contemporary information on characteristics and utilization of maternal-fetal transport. We used geographic analysis to investigate referral and transportation patterns of the maternal-fetal transport service at our institution.Methods: This is a retrospective cohort study of all calls taken by our maternal-fetal transfer service. Call logs were abstracted, and diagnoses, gestational ages, referring hospital, and mode of transportation were analyzed. The United States Health Resources and Services Administration's Medically Underserved Area (MUA) designations were used to identify hospitals in these areas. Geographic information system software was used to analyze and map geographic variables, including frequency of transfers from each hospital, distance traveled, mode of transfer, and MUAs.Results: From November 2012 to March 2017, there were 835 telephone consults without transfer and 1682 patients transferred from 103 hospitals. Preterm labor was the most common diagnosis (n = 338, 20%), followed by hypertensive disorders (n = 231, 14%). There were 738 transfers (44%) from MUAs, and 20 (19%) of hospitals were critical access hospitals, accounting for 121 (7%) transfers. One-way trips from a referring hospital accounted for 659 patients, and the transport team was dispatched in 1023 cases. The median distance traveled was 24 mi. For hospitals within 50 mi, the mean difference in transport time between air and ground was <1 h, yet there were 73 air round trips for hospitals <50 mi from our hospital.Conclusion: The transfer system is robust and supports underserved hospitals; however, the service could be deployed more efficiently.