Aldosterone controls the final sodium reabsorption and potassium secretion in the kidney by regulating the activity of the epithelial sodium channel (ENaC) in the aldosterone-sensitive distal nephron (ASDN). ASDN consists of the last portion of the distal convoluted tubule (late DCT), the connecting tubule (CNT), and the collecting duct (CD) (i.e., the cortical CD [CCD] and the medullary CD [MCD]). It has been proposed that the control of sodium transport in the CCD is essential for achieving sodium and potassium balance. We have tested this hypothesis by inactivating the α subunit of ENaC in the CD but leaving ENaC expression in the late DCT and CNT intact. Under salt restriction or under aldosterone infusion, whole-cell voltage clamp of principal cells of CCD showed no detectable ENaC activity, whereas large amiloride-sensitive currents were observed in control littermates. The animals survive well and are able to maintain sodium and potassium balance, even when challenged by salt restriction, water deprivation, or potassium loading. We conclude that the expression of ENaC in the CD is not a prerequisite for achieving sodium and potassium balance in mice. This stresses the importance of more proximal nephron segments (late DCT/CNT) to achieve sodium and potassium balance. Isabelle Rubera, Johannes Loffing, and Edith Hummler contributed equally to this work. Conflict of interest:The authors have declared that no conflict of interest exists. Nonstandard abbreviations used: epithelial sodium channel (ENaC); aldosterone-sensitive distal nephron (ASDN); distal convoluted tubule (DCT); connecting tubule (CNT); collecting duct (CD); cortical CD (CCD); medullary CD (MCD); outer MCD (OMCD); inner MCD (IMCD); adrenalectomized (adx); glomerular filtration rate (GFR); pseudohypoaldosteronism type 1 (PHA-1); X-galactosidase (X-gal); aquaporin-2 (AQP2); sodium/calcium exchanger (NCX); calbindin D28K (CB); sodium thiazide-sensitive chloride cotransporter (NCC).
Aldosterone controls the final sodium reabsorption and potassium secretion in the kidney by regulating the activity of the epithelial sodium channel (ENaC) in the aldosterone-sensitive distal nephron (ASDN). ASDN consists of the last portion of the distal convoluted tubule (late DCT), the connecting tubule (CNT), and the collecting duct (CD) (i.e., the cortical CD [CCD] and the medullary CD [MCD]). It has been proposed that the control of sodium transport in the CCD is essential for achieving sodium and potassium balance. We have tested this hypothesis by inactivating the α subunit of ENaC in the CD but leaving ENaC expression in the late DCT and CNT intact. Under salt restriction or under aldosterone infusion, whole-cell voltage clamp of principal cells of CCD showed no detectable ENaC activity, whereas large amiloride-sensitive currents were observed in control littermates. The animals survive well and are able to maintain sodium and potassium balance, even when challenged by salt restriction, water deprivation, or potassium loading. We conclude that the expression of ENaC in the CD is not a prerequisite for achieving sodium and potassium balance in mice. This stresses the importance of more proximal nephron segments (late DCT/CNT) to achieve sodium and potassium balance. Isabelle Rubera, Johannes Loffing, and Edith Hummler contributed equally to this work. Conflict of interest:The authors have declared that no conflict of interest exists. Nonstandard abbreviations used: epithelial sodium channel (ENaC); aldosterone-sensitive distal nephron (ASDN); distal convoluted tubule (DCT); connecting tubule (CNT); collecting duct (CD); cortical CD (CCD); medullary CD (MCD); outer MCD (OMCD); inner MCD (IMCD); adrenalectomized (adx); glomerular filtration rate (GFR); pseudohypoaldosteronism type 1 (PHA-1); X-galactosidase (X-gal); aquaporin-2 (AQP2); sodium/calcium exchanger (NCX); calbindin D28K (CB); sodium thiazide-sensitive chloride cotransporter (NCC).
Mass media campaigns are a commonly used strategy in public health. However, no review has assessed whether the design and evaluation of overweight and obesity campaigns meets best practice recommendations. This study aimed to fill this gap. We systematically searched five databases for peer-reviewed articles describing adult-targeted obesity mass media campaigns published between 2000 and 2017, complemented by reference list searches and contact with authors and agencies responsible for the campaigns. We extracted data on campaign design, implementation, and evaluation from eligible publications and conducted a qualitative review of 29 publications reporting on 14 campaigns. We found a need for formative research with target audiences to ensure campaigns focus on the most salient issues. Further, we noted that most campaigns targeted individual behaviors, despite calls for campaigns to also focus upstream and to address social determinants of obesity. Television was the dominant communication channel but, with the rapid advance of digital media, evaluation of other channels, such as social media, is increasingly important. Finally, although evaluation methods varied in quality, the evidence suggests that campaigns can have an impact on intermediate outcomes, such as knowledge and attitudes. However, evidence is still limited as to whether campaigns can influence behavior change.
Let D be an open set in euclidean space Rm with non‐empty boundary ∂D, and let pD : D × D × [0,∞) → R be the Dirichlet heat kernel for the parabolic operator −Δ + ∂/∂t, where −Δ is the Dirichlet laplacian on L2(D). Since the Dirichlet heat kernel is non‐negative, we may define the (open) set function PD=∫0∞∫D∫DpD(x,y;t)dxdydt. (1.1) We say that D has finite torsional rigidity if PD < ∞. It is well known that if D has finite volume, then D has finite torsional rigidity [11]. As we shall see, the converse is not true. The main purpose of this paper is to obtain necessary and sufficient conditions on the geometry of D to guarantee finite torsional rigidity and to gain some understanding of the behaviour of the expected lifetime of brownian motion in a certain natural class of domains that do not have finite torsional rigidity.
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