Lysgaardmunoz4904
KEY POINTS The roles of the Na+ /HCO3 - cotransporters NBCn1 and NBCn2 as well as their activators IRBIT and L-IRBIT in the regulation of the mTAL transport of NH4 + , HCO3 - , and NaCl are investigated. Dietary challenges of NH4 Cl, NaHCO3 , or NaCl all increase the abundance of NBCn1 and NBCn2 in the outer medulla. The three challenges generally produce parallel increases in the abundance of IRBIT and L-IRBIT in the outer medulla. Both IRBIT and L-IRBIT powerfully stimulate the activities of the mTAL isoforms of NBCn1 and NBCn2 as expressed in Xenopus oocytes. Our findings surpport the hypothesis that NBCn1, NBCn2, IRBIT, and L-IRBIT appropriately promote NH4 + shunting but oppose HCO3 - and NaCl reabsorption in the mTAL, and thus are at the nexus of the regulation pathways for multiple renal transport processes. ABSTRACT The medullary thick ascending limb (mTAL) plays a key role in urinary acid and NaCl excretion. NBCn1 and NBCn2 are present in the basolateral mTAL, where NBCn1 promotes NH4 + shunting. IRBcal NH4 + uptake during MAc; (2) inhibits HCO3 - reabsorption during MAlk by opposing HCO3 - efflux via the basolateral anion exchanger AE2; and (3) inhibits NaCl reabsorption by mediating (with AE2) net NaCl backflux into the mTAL cell during HSD. Thus, NBCn1, NBCn2 and the IRBITs are at the nexus of the regulatory pathways for multiple renal transport processes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.This article seeks to outline the implementation of a longitudinal interprofessional education (IPE) program in the predoctoral curriculum at a U.S. dental school. The challenges of implementing the curriculum in a complex environment are reviewed, and an overview of the 4-year curriculum is offered, including exposure, immersion, and clinical readiness components. Results of developmental evaluations are reviewed. Respondents to surveys regarding the capstone case conference experiences overwhelmingly suggest the conferences were educationally rewarding as well as enriching for each of the health professions represented. While response was limited, alumni surveys also indicate satisfaction with the IPE experience. A discussion of challenges and suggestions regarding successful implementation and expansion of IPE programs from didactic to clinical settings are also included. © 2020 American Dental Education Association.Motile cilia propel directed cell movements and sweep fluids across the surface of tissues. Orthologs of Dynein Assembly Factor with WD Repeat Domains 1 (DAW1) support normal ciliary beating by enhancing delivery of dynein complexes to axonemal microtubules. DAW1 mutations in vertebrates result in multiple developmental abnormalities and early or prenatal lethality, complicating functional assessment of DAW1 in adult structures. Planarian flatworms maintain cellular homeostasis and regenerate through differentiation of adult pluripotent stem cells, and systemic RNA-interference (RNAi) can be induced to analyze gene function at any point after birth. A single ortholog of DAW1 was identified in the genome of the planarian Schmidtea mediterranea (Smed-daw1). Smed-DAW1 is composed of eight WD repeats, which are 55% identical to the founding member of this protein family (Chlamydomonas reinhardtii ODA16) and 58% identical to human DAW1. Smed-daw1 is expressed in the planarian epidermis, protonephridial excretory system, and testes, all of which contain cells functionally dependent on motile cilia. Smed-daw1 RNAi resulted in locomotion defects and edema, which are phenotypes characteristic of multiciliated epidermis and protonephridial dysfunction, respectively. Changes in abundance or length of motile cilia were not observed at the onset of phenotypic manifestations upon Smed-daw1 RNAi, corroborating with studies showing that DAW-1 loss of function leads to aberrant movement of motile cilia in other organisms, rather than loss of cilia per se. However, extended RNAi treatments did result in shorter epidermal cilia and decreased abundance of ciliated protonephridia, suggesting that Smed-daw1 is required for homeostatic maintenance of these structures in flatworms. This article is protected by copyright. All rights reserved.AIMS Right atrial (RA) function largely contributes to the maintenance of right ventricular (RV) function. This study investigated the effect of balloon pulmonary angioplasty (BPA) on RA functions in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) using cardiac magnetic resonance imaging (CMRI). METHODS AND RESULTS CMRI and RV catheterization were performed before BPA sessions and at the follow-up periods in 29 CTEPH patients. Reservoir [RA longitudinal strain (RA-LS)], passive conduit [RA early LS rate (LSR)], and active (RA late LSR) phases were assessed by using cine CMRI and a feature-tracking algorithm. The relationships between the changes in RA functions and in brain natriuretic peptide (BNP) were evaluated in both the dilated and non-dilated RA groups. RA-LS (32.4% vs. 42.7%), RA LSR (6.3% vs. 8.3%), and RA early LSR (-2.3% vs. -4.3%) were improved after BPA, whereas no significant change was seen in RA late LSR. The changes in RA peak LS and in RA early LSR were significantly correlated with the changes in BNP (ΔRA-LS r = -0.63, ΔRA-early LSR r = 0.65) and pulmonary vascular resistance (PVR) (ΔRA-LS r = -0.69, ΔRA-early LSR r = 0.66) in the nondilated RA group. Tacedinaline clinical trial CONCLUSION The RA reservoir and passive conduit functions were impaired in inoperable CTEPH, whereas RA active function was preserved. BPA markedly reversed these impaired functions. The improvements in RA reservoir and conduit functions were significantly correlated with the changes in BNP levels and PVR in CTEPH patients with normal RA sizes. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email journals.permissions@oup.com.The antiphospholipid antibody syndrome (APS), a chronic autoimmune thrombophilia with an increased mortality and morbidity, has been recognized for more than three decades. Unlike other autoimmune rheumatic conditions such as systemic lupus erythematosus, myositis and Sjögren's syndrome, relatively few attempts have been made to develop activity, damage or disease-specific quality of life indices for APS. In this review of the literature, we consider those attempts that have been made to develop assessment tools for patients with APS, but also reflect upon the nature of the condition, to discuss, in particular, whether an activity index is appropriate for this disease. © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email journals.permissions@oup.com.