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Hypertension has been demonstrated to be a chief contributor to morbidity and mortality throughout the world. Although the cause of hypertension is multifactorial, emerging evidence, obtained in experimental studies, as well as observational studies in humans, points to the role of inflammation and immunity. Many aspects of immune function have now been implicated in hypertension and end-organ injury; this review will focus upon the recently-described role of Th17 cells in this pathophysiological response.
Studies in animal models and human genetic studies point to a role in the adaptive immune system as playing a contributory role in hypertension and renal tissue damage. Th17 cells, which produce the cytokine IL17, are strongly pro-inflammatory cells, which may contribute to tissue damage if expressed in chronic disease conditions. The activity of these cells may be enhanced by physiological factors associated with hypertension such as dietary salt or Ang II. This activity may culminate in the increased sodium retaining activity and exacerbation of inflammation and renal fibrosis via multiple cellular mechanisms.
Th17 cells are a distinct component of the adaptive immune system that may strongly enhance pathways leading to increased sodium reabsorption, elevated vascular tone and end-organ damage. Moreover, this pathway may lend itself towards specific targeting for treatment of kidney disease and hypertension.
Th17 cells are a distinct component of the adaptive immune system that may strongly enhance pathways leading to increased sodium reabsorption, elevated vascular tone and end-organ damage. Moreover, this pathway may lend itself towards specific targeting for treatment of kidney disease and hypertension.
Kidney stones are strongly associated with low bone density and bone fracture. Clinical management focuses on prevention of kidney stones and bone fracture. We reviewed literature of kidney stones and bone disease with a special focus on updates in therapeutic strategies. We will review the literature regarding dietary management, supplements, and medications and emphasize the recent studies on bisphosphonates and kidney stone management.
Bisphosphonate medications are commonly used in management of low bone density. Previous studies showed that they reduce urinary calcium. A recent large prospective study found that bisphosphonates may reduce the risk of kidney stones in individuals who have low bone density. In addition to lowering urinary calcium, a recent study found that bisphosphonates may act as an inhibitor in the urinary space.
There are multiple dietary and pharmacologic strategies that can be considered for kidney stones and bone disease, such as low salt and normal calcium diet, as well as thiazides, alkali, and bisphosphonate medications. Bisphosphonates may have an important role in reducing bone resorption and reducing overall risk of kidney stone and bone disease.
There are multiple dietary and pharmacologic strategies that can be considered for kidney stones and bone disease, such as low salt and normal calcium diet, as well as thiazides, alkali, and bisphosphonate medications. Bisphosphonates may have an important role in reducing bone resorption and reducing overall risk of kidney stone and bone disease.
This review focuses on recent efforts in identifying with-no-lysine kinase 4 (WNK4) as a physiological intracellular chloride sensor and exploring regulators of intracellular chloride concentration ([Cl-]i) in the distal convoluted tubule (DCT).
The discovery of WNK1's chloride-binding site provides the mechanistic details of the chloride-sensing regulation of WNK kinases. The subsequent in-vitro studies reveal that the chloride sensitivities of WNK kinases were variable. Because of its highest chloride sensitivity and dominant expression, WNK4 emerges as the leading candidate of the chloride sensor in DCT. The presentation of hypertension and increased sodium-chloride cotransporter (NCC) activity in chloride-insensitive WNK4 mice proved that WNK4 is inhibitable by physiological [Cl-]i in DCT. The chloride-mediated WNK4 regulation is responsible for hypokalemia-induced NCC activation but unnecessary for hyperkalemia-induced NCC deactivation. This chloride-sensing mechanism requires basolateral potassium and chloride channels or cotransporters, including Kir4.1/5.1, ClC-Kb, and possibly KCCs, to modulate [Cl-]i in response to the changes of plasma potassium.
WNK4 is both a master NCC stimulator and an in-vivo chloride sensor in DCT. The understanding of chloride-mediated regulation of WNK4 explains the inverse relationship between dietary potassium intake and NCC activity.
WNK4 is both a master NCC stimulator and an in-vivo chloride sensor in DCT. The understanding of chloride-mediated regulation of WNK4 explains the inverse relationship between dietary potassium intake and NCC activity.
The paper applies recent conceptualisations of predictive processing to the understanding of inequalities in mental health.
Social neuroscience has developed important ideas about the way the brain models the external world, and how the interface between cognitive and cultural processes interacts. These resonate with earlier concepts from cybernetics and sociology. These approaches could be applied to understanding some of the dynamics leading to the patterning of mental health problems in populations.
The implications for practice are the way such thinking might help illuminate how we think and act, and how these are anchored in the social world.
The implications for practice are the way such thinking might help illuminate how we think and act, and how these are anchored in the social world.
Alcohol is gaining increased recognition as an important risk factor for dementia. This review summarises recent evidence on the relationship between alcohol use and dementia, focusing on studies published from January 2019 to August 2020.
Epidemiological data continues to yield results consistent with protective effects of low-to-moderate alcohol consumption for dementia and cognitive function. However, recent literature highlights the methodological limitations of existing observational studies. The effects of chronic, heavy alcohol use are clearer, with excessive consumption causing alcohol-related brain damage. Several pathways to this damage have been suggested, including the neurotoxic effects of thiamine deficiency, ethanol and acetaldehyde.
Future research would benefit from greater implementation of analytical and design-based approaches to robustly model the alcohol use-dementia relationship in the general population, and should make use of large, consortia-level data. Telacebec inhibitor Early intervention to prevent dementia is critical thiamine substitution has shown potential but requires more research, and psychosocial interventions to treat harmful alcohol use have proven effective.
