April 2018 | Health And News Articles - All about Health and Fitness

This Months Highlights

This Months Highlights

from Journal of the American Society of Nephrology current issue https://ift.tt/2rbO3M5

JASN this Month: Something Old, Something New

from Journal of the American Society of Nephrology current issue https://ift.tt/2w0dK7k

Repairing the GBM Step by Step

from Journal of the American Society of Nephrology current issue https://ift.tt/2vZ6yIy

WNKs on the Fly

from Journal of the American Society of Nephrology current issue https://ift.tt/2vWYcBi

Insights into CKD from Metabolite GWAS

from Journal of the American Society of Nephrology current issue https://ift.tt/2vZ6fNU

Using Large Datasets to Understand CKD

from Journal of the American Society of Nephrology current issue https://ift.tt/2vZ67ho

The Quest for Better Biomarkers of Bone Turnover in CKD

from Journal of the American Society of Nephrology current issue https://ift.tt/2vZ5RyW

HDL in CKD--The Devil Is in the Detail

The picture of HDL cholesterol (HDL-C) as the "good" cholesterol has eroded. This is even more surprising because there exists strong evidence that HDL-C is associated with cardiovascular disease (CVD) in the general population as well as in patients with impairment of kidney function and/or progression of CKD. However, drugs that dramatically increase HDL-C have mostly failed to decrease CVD events. Furthermore, genetic studies took the same line, as genetic variants that have a pronounced influence on HDL-C concentrations did not show an association with cardiovascular risk. For many, this was not surprising, given that an HDL particle is highly complex and carries >80 proteins and several hundred lipid species. Simply measuring cholesterol might not reflect the variety of biologic effects of heterogeneous HDL particles. Therefore, functional studies and the involvement of HDL components in the reverse cholesterol transport, including the cholesterol efflux capacity, have become a further focus of study during recent years. As also observed for other aspects, CKD populations behave differently compared with non-CKD populations. Although clear disturbances have been observed for the "functionality" of HDL particles in patients with CKD, this did not necessarily translate into clear-cut associations with outcomes.
 
 
from Journal of the American Society of Nephrology current issue https://ift.tt/2vZIYva

HDL in CKD--The Devil Is in the Detail

The picture of HDL cholesterol (HDL-C) as the "good" cholesterol has eroded. This is even more surprising because there exists str...

The Ebb and Flow of Echocardiographic Cardiac Function Parameters in Relationship to Hemodialysis Treatment in Patients with ESRD

Cardiovascular disease is the leading cause of mortality in patients receiving hemodialysis. Cardiovascular events in these patients demonstrate a day-of-week pattern; i.e., they occur more commonly during the last day of the long interdialytic interval and the first session of the week. The hemodialysis process causes acute decreases in cardiac chamber size and pulmonary circulation loading and acute diastolic dysfunction, possibly through myocardial stunning and other non–myocardial-related mechanisms; systolic function, in contrast, is largely unchanged. During interdialytic intervals volume overload, acid-base, and electrolyte shifts, as well as arterial and myocardial wall changes, result in dilatation of right cardiac chambers and pulmonary circulation overload. Recent studies suggest that these alterations are more extended during the long interdialytic interval or the first dialysis session of the week and are associated with excess volume overload or removal, respectively, thus adding a mechanism for the day-of-week pattern of mortality in patients receiving hemodialysis. This review summarizes the existing data from echocardiographic studies of cardiac morphology and function during the hemodialysis session, as well as during the interdialytic intervals.
 
 
from Journal of the American Society of Nephrology current issue https://ift.tt/2w00aAV

The Ebb and Flow of Echocardiographic Cardiac Function Parameters in Relationship to Hemodialysis Treatment in Patients with ESRD

Cardiovascular disease is the leading cause of mortality in patients receiving hemodialysis. Cardiovascular events in these patients demonst...

Renal Interstitial Platelet-Derived Growth Factor Receptor-{beta} Cells Support Proximal Tubular Regeneration

Protein S Protects against Podocyte Injury in Diabetic Nephropathy

Background Diabetic nephropathy (DN) is a leading cause of ESRD in the United States, but the molecular mechanisms mediating the early stages of DN are unclear.
Methods To assess global changes that occur in early diabetic kidneys and to identify proteins potentially involved in pathogenic pathways in DN progression, we performed proteomic analysis of diabetic and nondiabetic rat glomeruli. Protein S (PS) among the highly upregulated proteins in the diabetic glomeruli. PS exerts multiple biologic effects through the Tyro3, Axl, and Mer (TAM) receptors. Because increased activation of Axl by the PS homolog Gas6 has been implicated in DN progression, we further examined the role of PS in DN.
Results In human kidneys, glomerular PS expression was elevated in early DN but suppressed in advanced DN. However, plasma PS concentrations did not differ between patients with DN and healthy controls. A prominent increase of PS expression also colocalized with the expression of podocyte markers in early diabetic kidneys. In cultured podocytes, high-glucose treatment elevated PS expression, and PS knockdown further enhanced the high-glucose–induced apoptosis. Conversely, PS overexpression in cultured podocytes dampened the high-glucose– and TNF-α–induced expression of proinflammatory mediators. Tyro3 receptor was upregulated in response to high glucose and mediated the anti-inflammatory response of PS. Podocyte-specific PS loss resulted in accelerated DN in streptozotocin-induced diabetic mice, whereas the transient induction of PS expression in glomerular cells in vivo attenuated albuminuria and podocyte loss in diabetic OVE26 mice.
Conclusions Our results support a protective role of PS against glomerular injury in DN progression.
 
 
from Journal of the American Society of Nephrology current issue https://ift.tt/2w25ROw

Protein S Protects against Podocyte Injury in Diabetic Nephropathy

Background Diabetic nephropathy (DN) is a leading cause of ESRD in the United States, but the molecular mechanisms mediating the early stag...

Mechanism of Hyperkalemia-Induced Metabolic Acidosis

Background Hyperkalemia in association with metabolic acidosis that are out of proportion to changes in glomerular filtration rate defines type 4 renal tubular acidosis (RTA), the most common RTA observed, but the molecular mechanisms underlying the associated metabolic acidosis are incompletely understood. We sought to determine whether hyperkalemia directly causes metabolic acidosis and, if so, the mechanisms through which this occurs.
Methods We studied a genetic model of hyperkalemia that results from early distal convoluted tubule (DCT)–specific overexpression of constitutively active Ste20/SPS1-related proline-alanine–rich kinase (DCT-CA-SPAK).
Results DCT-CA-SPAK mice developed hyperkalemia in association with metabolic acidosis and suppressed ammonia excretion; however, titratable acid excretion and urine pH were unchanged compared with those in wild-type mice. Abnormal ammonia excretion in DCT-CA-SPAK mice associated with decreased proximal tubule expression of the ammonia-generating enzymes phosphate-dependent glutaminase and phosphoenolpyruvate carboxykinase and overexpression of the ammonia-recycling enzyme glutamine synthetase. These mice also had decreased expression of the ammonia transporter family member Rhcg and decreased apical polarization of H+-ATPase in the inner stripe of the outer medullary collecting duct. Correcting the hyperkalemia by treatment with hydrochlorothiazide corrected the metabolic acidosis, increased ammonia excretion, and normalized ammoniagenic enzyme and Rhcg expression in DCT-CA-SPAK mice. In wild-type mice, induction of hyperkalemia by administration of the epithelial sodium channel blocker benzamil caused hyperkalemia and suppressed ammonia excretion.
Conclusions Hyperkalemia decreases proximal tubule ammonia generation and collecting duct ammonia transport, leading to impaired ammonia excretion that causes metabolic acidosis.
 
 
from Journal of the American Society of Nephrology current issue https://ift.tt/2rbdm02

Mechanism of Hyperkalemia-Induced Metabolic Acidosis

Background Hyperkalemia in association with metabolic acidosis that are out of proportion to changes in glomerular filtration rate defines ...

Laminin-521 Protein Therapy for Glomerular Basement Membrane and Podocyte Abnormalities in a Model of Pierson Syndrome

Background Laminin α5β21 (LM-521) is a major component of the GBM. Mutations in LAMB2 that prevent LM-521 synthesis and/or secretion cause Pierson syndrome, a rare congenital nephrotic syndrome with diffuse mesangial sclerosis and ocular and neurologic defects. Because the GBM is uniquely accessible to plasma, which permeates endothelial cell fenestrae, we hypothesized that intravenous delivery of LM-521 could replace the missing LM-521 in the GBM of Lamb2 mutant mice and restore glomerular permselectivity.
Methods We injected human LM-521 (hLM-521), a macromolecule of approximately 800 kD, into the retro-orbital sinus of Lamb2–/– pups daily. Deposition of hLM-521 into the GBM was investigated by fluorescence microscopy. We assayed the effects of hLM-521 on glomerular permselectivity by urinalysis and the effects on podocytes by desmin immunostaining and ultrastructural analysis of podocyte architecture.
Results Injected hLM-521 rapidly and stably accumulated in the GBM of all glomeruli. Super-resolution imaging showed that hLM-521 accumulated in the correct orientation in the GBM, primarily on the endothelial aspect. Treatment with hLM-521 greatly reduced the expression of the podocyte injury marker desmin and attenuated the foot process effacement observed in untreated pups. Moreover, treatment with hLM-521 delayed the onset of proteinuria but did not prevent nephrotic syndrome, perhaps due to its absence from the podocyte aspect of the GBM.
Conclusions These studies show that GBM composition and function can be altered in vivo via vascular delivery of even very large proteins, which may advance therapeutic options for patients with abnormal GBM composition, whether genetic or acquired.
 
 
from Journal of the American Society of Nephrology current issue https://ift.tt/2HEGlnQ

Laminin-521 Protein Therapy for Glomerular Basement Membrane and Podocyte Abnormalities in a Model of Pierson Syndrome

Background Laminin α 5 β 21 (LM-521) is a major component of the GBM. Mutations in LAMB2 that prevent LM-521 synthesis and/or secretion ca...

Lipoxins Regulate the Early Growth Response-1 Network and Reverse Diabetic Kidney Disease

Background The failure of spontaneous resolution underlies chronic inflammatory conditions, including microvascular complications of diabetes such as diabetic kidney disease. The identification of endogenously generated molecules that promote the physiologic resolution of inflammation suggests that these bioactions may have therapeutic potential in the context of chronic inflammation. Lipoxins (LXs) are lipid mediators that promote the resolution of inflammation.
Methods We investigated the potential of LXA4 and a synthetic LX analog (Benzo-LXA4) as therapeutics in a murine model of diabetic kidney disease, ApoE–/– mice treated with streptozotocin.
Results Intraperitoneal injection of LXs attenuated the development of diabetes-induced albuminuria, mesangial expansion, and collagen deposition. Notably, LXs administered 10 weeks after disease onset also attenuated established kidney disease, with evidence of preserved kidney function. Kidney transcriptome profiling defined a diabetic signature (725 genes; false discovery rate P≤0.05). Comparison of this murine gene signature with that of human diabetic kidney disease identified shared renal proinflammatory/profibrotic signals (TNF-α, IL-1β, NF-B). In diabetic mice, we identified 20 and 51 transcripts regulated by LXA4 and Benzo-LXA4, respectively, and pathway analysis identified established (TGF-β1, PDGF, TNF-α, NF-B) and novel (early growth response–1 [EGR-1]) networks activated in diabetes and regulated by LXs. In cultured human renal epithelial cells, treatment with LXs attenuated TNF-α–driven Egr-1 activation, and Egr-1 depletion prevented cellular responses to TGF-β1 and TNF-α.
Conclusions These data demonstrate that LXs can reverse established diabetic complications and support a therapeutic paradigm to promote the resolution of inflammation.
 
 
from Journal of the American Society of Nephrology current issue https://ift.tt/2rbdkoW

Lipoxins Regulate the Early Growth Response-1 Network and Reverse Diabetic Kidney Disease

Background The failure of spontaneous resolution underlies chronic inflammatory conditions, including microvascular complications of diabet...

Intracellular Chloride and Scaffold Protein Mo25 Cooperatively Regulate Transepithelial Ion Transport through WNK Signaling in the Malpighian Tubule

Background With No Lysine kinase (WNK) signaling regulates mammalian renal epithelial ion transport to maintain electrolyte and BP homeostasis. Our previous studies showed a conserved role for WNK in the regulation of transepithelial ion transport in the Drosophila Malpighian tubule.
Methods Using in vitro assays and transgenic Drosophila lines, we examined two potential WNK regulators, chloride ion and the scaffold protein mouse protein 25 (Mo25), in the stimulation of transepithelial ion flux.
Results In vitro, autophosphorylation of purified Drosophila WNK decreased as chloride concentration increased. In conditions in which tubule intracellular chloride concentration decreased from 30 to 15 mM as measured using a transgenic sensor, Drosophila WNK activity acutely increased. Drosophila WNK activity in tubules also increased or decreased when bath potassium concentration decreased or increased, respectively. However, a mutation that reduces chloride sensitivity of Drosophila WNK failed to alter transepithelial ion transport in 30 mM chloride. We, therefore, examined a role for Mo25. In in vitro kinase assays, Drosophila Mo25 enhanced the activity of the Drosophila WNK downstream kinase Fray, the fly homolog of mammalian Ste20-related proline/alanine-rich kinase (SPAK), and oxidative stress-responsive 1 protein (OSR1). Knockdown of Drosophila Mo25 in the Malpighian tubule decreased transepithelial ion flux under stimulated but not basal conditions. Finally, whereas overexpression of wild-type Drosophila WNK, with or without Drosophila Mo25, did not affect transepithelial ion transport, Drosophila Mo25 overexpressed with chloride-insensitive Drosophila WNK increased ion flux.
Conclusions Cooperative interactions between chloride and Mo25 regulate WNK signaling in a transporting renal epithelium.
 
 
from Journal of the American Society of Nephrology current issue https://ift.tt/2HG292N

Intracellular Chloride and Scaffold Protein Mo25 Cooperatively Regulate Transepithelial Ion Transport through WNK Signaling in the Malpighian Tubule

Background With No Lysine kinase (WNK) signaling regulates mammalian renal epithelial ion transport to maintain electrolyte and BP homeosta...

Nephrin-Binding Ephrin-B1 at the Slit Diaphragm Controls Podocyte Function through the JNK Pathway

Background B-type ephrins are membrane-bound proteins that maintain tissue function in several organs. We previously reported that ephrin-B1 is localized at the slit diaphragm of glomerular podocytes. However, the function of ephrin-B1 at this location is unclear.
Methods We analyzed the phenotype of podocyte-specific ephrin-B1 knockout mice and assessed the molecular association of ephrin-B1 and nephrin, a key molecule of the slit diaphragm, in HEK293 cells and rats with anti-nephrin antibody-induced nephropathy.
Results Compared with controls, ephrin-B1 conditional knockout mice displayed altered podocyte morphology, disarrangement of the slit diaphragm molecules, and proteinuria. Ephrin-B1 expressed in HEK293 cells immunoprecipitated with nephrin, which required the basal regions of the extracellular domains of both proteins. Treatment of cells with an anti-nephrin antibody promoted the phosphorylation of nephrin and ephrin-B1. However, phosphorylation of ephrin-B1 did not occur in cells expressing a mutant nephrin lacking the ephrin-B1 binding site or in cells treated with an Src kinase inhibitor. The phosphorylation of ephrin-B1 enhanced the phosphorylation of nephrin and promoted the phosphorylation of c-Jun N-terminal kinase (JNK), which was required for ephrin-B1–promoted cell motility in wound-healing assays. Notably, phosphorylated JNK was detected in the glomeruli of control mice but not ephrin-B1 conditional knockout mice. In rats, the phosphorylation of ephrin-B1, JNK, and nephrin occurred in the early phase (24 hours) of anti-nephrin antibody-induced nephropathy.
Conclusions Through interactions with nephrin, ephrin-B1 maintains the structure and barrier function of the slit diaphragm. Moreover, phosphorylation of ephrin-B1 and, consequently, JNK are involved in the development of podocyte injury.
 
 
from Journal of the American Society of Nephrology current issue https://ift.tt/2rbwZpA

Nephrin-Binding Ephrin-B1 at the Slit Diaphragm Controls Podocyte Function through the JNK Pathway

Background B-type ephrins are membrane-bound proteins that maintain tissue function in several organs. We previously reported that ephrin-B...

Gpr97 Exacerbates AKI by Mediating Sema3A Signaling

Background G protein-coupled receptors (GPCRs) participate in a variety of physiologic functions, and several GPCRs have critical physiologic and pathophysiologic roles in the regulation of renal function. We investigated the role of Gpr97, a newly identified member of the adhesion GPCR family, in AKI.
Methods AKI was induced by ischemia–reperfusion or cisplatin treatment in Gpr97-deficient mice. We assessed renal injury in these models and in patients with acute tubular necrosis by histologic examination, and we conducted microarray analysis and in vitro assays to determine the molecular mechanisms of Gpr97 function.
Results Gpr97 was upregulated in the kidneys from mice with AKI and patients with biopsy-proven acute tubular necrosis compared with healthy controls. In AKI models, Gpr97-deficient mice had significantly less renal injury and inflammation than wild-type mice. Gpr97 deficiency also attenuated the AKI-induced expression of semaphorin 3A (Sema3A), a potential early diagnostic biomarker of renal injury. In NRK-52E cells subjected to oxygen–glucose deprivation, siRNA-mediated knockdown of Gpr97 further increased the expression of survivin and phosphorylated STAT3 and reduced toll-like receptor 4 expression. Cotreatment with recombinant murine Sema3A protein counteracted these effects. Finally, additional in vivo and in vitro studies, including electrophoretic mobility shift assays and luciferase reporter assays, showed that Gpr97 deficiency attenuates ischemia–reperfusion-induced expression of the RNA-binding protein human antigen R, which post-transcriptionally regulates Sema3A expression.
Conclusions Gpr97 is an important mediator of AKI, and pharmacologic targeting of Gpr97-mediated Sema3A signaling at multiple levels may provide a novel approach for the treatment of AKI.
 
 
from Journal of the American Society of Nephrology current issue https://ift.tt/2I5t5Z1

Gpr97 Exacerbates AKI by Mediating Sema3A Signaling

Background G protein-coupled receptors (GPCRs) participate in a variety of physiologic functions, and several GPCRs have critical physiolog...

Genome-Wide Mapping of DNA Accessibility and Binding Sites for CREB and C/EBP{beta} in Vasopressin-Sensitive Collecting Duct Cells

Background Renal water excretion is controlled by vasopressin, in part through regulation of the transcription of the aquaporin-2 gene (Aqp2).
Methods To identify enhancer regions likely to be involved in the regulation of Aqp2 and other principal cell–specific genes, we used several next generation DNA-sequencing techniques in a well characterized cultured cell model of collecting duct principal cells (mpkCCD). To locate enhancers, we performed the assay for transposase-accessible chromatin using sequencing (ATAC-Seq) to identify accessible regions of DNA and integrated the data with data generated by chromatin immunoprecipitation followed by next generation DNA-sequencing (ChIP-Seq) for CCCTC binding factor (CTCF) binding, histone H3 lysine-27 acetylation, and RNA polymerase II.
Results We identified two high-probability enhancers centered 81 kb upstream and 5.8 kb downstream from the Aqp2 transcriptional start site. Motif analysis of these regions and the Aqp2 promoter identified several potential transcription factor binding sites, including sites for two b-ZIP transcription factors: CCAAT/enhancer binding protein-β (C/EBPβ) and cAMP-responsive element binding protein (CREB). To identify genomic binding sites for both, we conducted ChIP-Seq using well characterized antibodies. In the presence of vasopressin, C/EBPβ, a pioneer transcription factor critical to cell-specific gene expression, bound strongly at the identified enhancer downstream from Aqp2. However, over multiple replicates, we found no detectable CREB binding sites within 390 kb of Aqp2. Thus, any role for CREB in the regulation of Aqp2 gene transcription is likely to be indirect.
Conclusions The analysis identified two enhancer regions pertinent to transcriptional regulation of the Aqp2 gene and showed C/EBPβ (but not CREB) binding.
 
 
from Journal of the American Society of Nephrology current issue https://ift.tt/2I5tDhx

Genome-Wide Mapping of DNA Accessibility and Binding Sites for CREB and C/EBP{beta} in Vasopressin-Sensitive Collecting Duct Cells

Background Renal water excretion is controlled by vasopressin, in part through regulation of the transcription of the aquaporin-2 gene ( Aq...

Similar Biophysical Abnormalities in Glomeruli and Podocytes from Two Distinct Models

Background FSGS is a pattern of podocyte injury that leads to loss of glomerular function. Podocytes support other podocytes and glomerular capillary structure, oppose hemodynamic forces, form the slit diaphragm, and have mechanical properties that permit these functions. However, the biophysical characteristics of glomeruli and podocytes in disease remain unclear.
Methods Using microindentation, atomic force microscopy, immunofluorescence microscopy, quantitative RT-PCR, and a three-dimensional collagen gel contraction assay, we studied the biophysical and structural properties of glomeruli and podocytes in chronic (Tg26 mice [HIV protein expression]) and acute (protamine administration [cytoskeletal rearrangement]) models of podocyte injury.
Results Compared with wild-type glomeruli, Tg26 glomeruli became progressively more deformable with disease progression, despite increased collagen content. Tg26 podocytes had disordered cytoskeletons, markedly abnormal focal adhesions, and weaker adhesion; they failed to respond to mechanical signals and exerted minimal traction force in three-dimensional collagen gels. Protamine treatment had similar but milder effects on glomeruli and podocytes.
Conclusions Reduced structural integrity of Tg26 podocytes causes increased deformability of glomerular capillaries and limits the ability of capillaries to counter hemodynamic force, possibly leading to further podocyte injury. Loss of normal podocyte mechanical integrity could injure neighboring podocytes due to the absence of normal biophysical signals required for podocyte maintenance. The severe defects in podocyte mechanical behavior in the Tg26 model may explain why Tg26 glomeruli soften progressively, despite increased collagen deposition, and may be the basis for the rapid course of glomerular diseases associated with severe podocyte injury. In milder injury (protamine), similar processes occur but over a longer time.
 
 
from Journal of the American Society of Nephrology current issue https://ift.tt/2I2lYjR

Similar Biophysical Abnormalities in Glomeruli and Podocytes from Two Distinct Models

Background FSGS is a pattern of podocyte injury that leads to loss of glomerular function. Podocytes support other podocytes and glomerular...

Genome-Wide Association Studies of Metabolites in Patients with CKD Identify Multiple Loci and Illuminate Tubular Transport Mechanisms

Background The kidneys have a central role in the generation, turnover, transport, and excretion of metabolites, and these functions can be altered in CKD. Genetic studies of metabolite concentrations can identify proteins performing these functions.
Methods We conducted genome-wide association studies and aggregate rare variant tests of the concentrations of 139 serum metabolites and 41 urine metabolites, as well as their pairwise ratios and fractional excretions in up to 1168 patients with CKD.
Results After correction for multiple testing, genome-wide significant associations were detected for 25 serum metabolites, two urine metabolites, and 259 serum and 14 urinary metabolite ratios. These included associations already known from population-based studies. Additional findings included an association for the uremic toxin putrescine and variants upstream of an enzyme catalyzing the oxidative deamination of polyamines (AOC1, P-min=2.4x10–12), a relatively high carrier frequency (2%) for rare deleterious missense variants in ACADM that are collectively associated with serum ratios of medium-chain acylcarnitines (P-burden=6.6x10–16), and associations of a common variant in SLC7A9 with several ratios of lysine to neutral amino acids in urine, including the lysine/glutamine ratio (P=2.2x10–23). The associations of this SLC7A9 variant with ratios of lysine to specific neutral amino acids were much stronger than the association with lysine concentration alone. This finding is consistent with SLC7A9 functioning as an exchanger of urinary cationic amino acids against specific intracellular neutral amino acids at the apical membrane of proximal tubular cells.
Conclusions Metabolomic indices of specific kidney functions in genetic studies may provide insight into human renal physiology.
 
 
from Journal of the American Society of Nephrology current issue https://ift.tt/2r6J53h

Genome-Wide Association Studies of Metabolites in Patients with CKD Identify Multiple Loci and Illuminate Tubular Transport Mechanisms

Background The kidneys have a central role in the generation, turnover, transport, and excretion of metabolites, and these functions can be...

Characterization of Coding/Noncoding Variants for SHROOM3 in Patients with CKD

Background Interpreting genetic variants is one of the greatest challenges impeding analysis of rapidly increasing volumes of genomic data from patients. For example, SHROOM3 is an associated risk gene for CKD, yet causative mechanism(s) of SHROOM3 allele(s) are unknown.
Methods We used our analytic pipeline that integrates genetic, computational, biochemical, CRISPR/Cas9 editing, molecular, and physiologic data to characterize coding and noncoding variants to study the human SHROOM3 risk locus for CKD.
Results We identified a novel SHROOM3 transcriptional start site, which results in a shorter isoform lacking the PDZ domain and is regulated by a common noncoding sequence variant associated with CKD (rs17319721, allele frequency: 0.35). This variant disrupted allele binding to the transcription factor TCF7L2 in podocyte cell nuclear extracts and altered transcription levels of SHROOM3 in cultured cells, potentially through the loss of repressive looping between rs17319721 and the novel start site. Although common variant mechanisms are of high utility, sequencing is beginning to identify rare variants involved in disease; therefore, we used our biophysical tools to analyze an average of 112,849 individual human genome sequences for rare SHROOM3 missense variants, revealing 35 high-effect variants. The high-effect alleles include a coding variant (P1244L) previously associated with CKD (P=0.01, odds ratio=7.95; 95% CI, 1.53 to 41.46) that we find to be present in East Asian individuals at an allele frequency of 0.0027. We determined that P1244L attenuates the interaction of SHROOM3 with 14–3-3, suggesting alterations to the Hippo pathway, a known mediator of CKD.
Conclusions These data demonstrate multiple new SHROOM3-dependent genetic/molecular mechanisms that likely affect CKD.
 
 
from Journal of the American Society of Nephrology current issue https://ift.tt/2rcy8MC

Characterization of Coding/Noncoding Variants for SHROOM3 in Patients with CKD

Background Interpreting genetic variants is one of the greatest challenges impeding analysis of rapidly increasing volumes of genomic data ...

The Most N-Terminal Region of THSD7A Is the Predominant Target for Autoimmunity in THSD7A-Associated Membranous Nephropathy

Background Thrombospondin type 1 domain–containing 7A (THSD7A) has been identified as a pathogenic autoantigen in membranous nephropathy (MN). However, the THSD7A epitopes targeted by patient autoantibodies are unknown.
Methods We performed an in silico analysis of the THSD7A multidomain structure, expressed the folded domains in HEK293 cells, and tested for domain reactivity with 31 serum samples from patients with THSD7A-associated MN using Western and native blotting. Immunogenicity of the antigen domains was further investigated by cDNA immunization of rabbits and mice.
Results We characterized the extracellular topology of THSD7A as a tandem string of 21 thrombospondin type 1 domains. Overall, 28 serum samples (90%) recognized multiple epitope domains along the molecule. Detailed epitope mapping revealed that the complex consisting of the first and second N-terminal domains (amino acids 48–192) was recognized by 27 of 31 patient serum samples (87%). Serum recognizing one or two epitope domains showed lower anti-THSD7A antibody levels than serum recognizing three or more epitope domains. During follow-up, a loss of epitope recognition was observed in seven of 16 patients, and it was accompanied by decreasing antibody levels and remission of proteinuria. In four of 16 patients, epitope recognition patterns changed during follow-up. Notably, immunization experiments in rabbits and mice revealed that induced antibodies, like patient autoantibodies, preferentially bound to the most N-terminal domains of THSD7A.
Conclusions Our data show that the immune response in THSD7A-associated MN is polyreactive and that autoantibodies predominantly target the most N-terminal part of THSD7A.
 
 
from Journal of the American Society of Nephrology current issue https://ift.tt/2rbwUSO

The Most N-Terminal Region of THSD7A Is the Predominant Target for Autoimmunity in THSD7A-Associated Membranous Nephropathy

Background Thrombospondin type 1 domain–containing 7A (THSD7A) has been identified as a pathogenic autoantigen in membranous nephropathy (M...

Biomarkers of AKI Progression after Pediatric Cardiac Surgery

Background As children progress to higher stages of AKI, the risk for adverse outcomes dramatically increases. No reliable methods exist to predict AKI progression in hospitalized children. To determine if biomarkers of inflammation and kidney injury can predict AKI progression, we conducted a three-center prospective cohort study of children undergoing cardiopulmonary bypass.
Methods On the first day of serum creatinine–defined AKI, we measured urine biomarkers (neutrophil gelatinase–associated lipocalin [NGAL], IL-18, kidney injury molecule 1, liver fatty acid binding protein [L-FABP], albumin, and cystatin C) and plasma biomarkers (IFN, IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, TNF-α, NGAL, and cystatin C). We defined AKI progression as a worsening of AKI stage or persisting stage 3 AKI (≥2 consecutive days).
Results In all, 176 of 408 (43%) children developed postoperative AKI. Among the children with AKI, we diagnosed stages 1, 2, and 3 AKI in 145 (82.5%), 25 (14%), and six (3.5%) children, respectively, on the first day of AKI; 28 (7%) children had AKI progression. On the first day of AKI, nine of 17 biomarkers were significantly higher in patients with than without AKI progression. Urine L-FABP (among injury biomarkers) and plasma IL-8 (among inflammatory biomarkers) had the highest discrimination for AKI progression: optimism-corrected area under the curve, 0.70; 95% confidence interval, 0.58 to 0.81 and optimism-corrected area under the curve, 0.80; 95% confidence interval, 0.69 to 0.91, respectively.
Conclusions If validated in additional cohorts, plasma IL-8 could be used to improve clinical care and guide enrollment in therapeutic trials of AKI.
 
 
from Journal of the American Society of Nephrology current issue https://ift.tt/2HD8WtT

Biomarkers of AKI Progression after Pediatric Cardiac Surgery

Background As children progress to higher stages of AKI, the risk for adverse outcomes dramatically increases. No reliable methods exist to...

Diagnostic Accuracy of Biomarkers and Imaging for Bone Turnover in Renal Osteodystrophy

Background Renal osteodystrophy is common in advanced CKD, but characterization of bone turnover status can only be achieved by histomorphometric analysis of bone biopsy specimens (gold standard test). We tested whether bone biomarkers and high-resolution peripheral computed tomography (HR-pQCT) parameters can predict bone turnover status determined by histomorphometry.
Methods We obtained fasting blood samples from 69 patients with CKD stages 4–5, including patients on dialysis, and 68 controls for biomarker analysis (intact parathyroid hormone [iPTH], procollagen type 1 N-terminal propeptide [PINP], bone alkaline phosphatase [bALP], collagen type 1 crosslinked C-telopeptide [CTX], and tartrate-resistant acid phosphatase 5b [TRAP5b]) and scanned the distal radius and tibia of participants by HR-pQCT. We used histomorphometry to evaluate bone biopsy specimens from 43 patients with CKD.
Results Levels of all biomarkers tested were significantly higher in CKD samples than control samples. For discriminating low bone turnover, bALP, intact PINP, and TRAP5b had an areas under the receiver operating characteristic curve (AUCs) of 0.82, 0.79, and 0.80, respectively, each significantly better than the iPTH AUC of 0.61. Furthermore, radius HR-pQCT total volumetric bone mineral density and cortical bone volume had AUCs of 0.81 and 0.80, respectively. For discriminating high bone turnover, iPTH had an AUC of 0.76, similar to that of all other biomarkers tested.
Conclusions The biomarkers bALP, intact PINP, and TRAP5b and radius HR-pQCT parameters can discriminate low from nonlow bone turnover. Despite poor diagnostic accuracy for low bone turnover, iPTH can discriminate high bone turnover with accuracy similar to that of the other biomarkers, including CTX.
 
 
from Journal of the American Society of Nephrology current issue https://ift.tt/2r6Jgvt

Diagnostic Accuracy of Biomarkers and Imaging for Bone Turnover in Renal Osteodystrophy

Background Renal osteodystrophy is common in advanced CKD, but characterization of bone turnover status can only be achieved by histomorpho...

Ischemia-Induced DNA Hypermethylation during Kidney Transplant Predicts Chronic Allograft Injury

Background Ischemia during kidney transplant causes chronic allograft injury and adversely affects outcome, but the underlying mechanisms are incompletely understood. In tumors, oxygen shortage reduces the DNA demethylating activity of the ten-11 translocation (TET) enzymes, yielding hypermethylated genomes that promote tumor progression. We investigated whether ischemia similarly induces DNA hypermethylation in kidney transplants and contributes to chronic injury.
Methods We profiled genome-wide DNA methylation in three cohorts of brain-dead donor kidney allograft biopsy specimens: a longitudinal cohort with paired biopsy specimens obtained at allograft procurement (preischemia; n=13), after implantation and reperfusion (postischemia; n=13), and at 3 or 12 months after transplant (n=5 each); a cross-sectional cohort with preimplantation biopsy specimens (n=82); and a cross-sectional cohort with postreperfusion biopsy specimens (n=46).
Results Analysis of the paired preischemia and postischemia specimens revealed that methylation increased drastically in all allografts on ischemia. Hypermethylation was caused by loss of 5-hydroxymethylcytosine, the product of TET activity, and it was stable 1 year after transplant. In the preimplantation cohort, CpG hypermethylation directly correlated with ischemia time and for some CpGs, increased 2.6% per additional hour of ischemia. Hypermethylation preferentially affected and reduced the expression of genes involved in suppressing kidney injury and fibrosis. Moreover, CpG hypermethylation in preimplantation specimens predicted chronic injury, particularly fibrosis and glomerulosclerosis, 1 year after transplant. This finding was validated in the independent postreperfusion cohort, in which hypermethylation also predicted reduced allograft function 1 year after transplant, outperforming established clinical variables.
Conclusions We highlight a novel epigenetic basis for ischemia-induced chronic allograft injury with biomarker potential.
 
 
from Journal of the American Society of Nephrology current issue https://ift.tt/2rbd9tM

Ischemia-Induced DNA Hypermethylation during Kidney Transplant Predicts Chronic Allograft Injury

Background Ischemia during kidney transplant causes chronic allograft injury and adversely affects outcome, but the underlying mechanisms a...

Antibodies Can Extenuate Polyomavirus Infections

from Journal of the American Society of Nephrology current issue https://ift.tt/2I2mr5B

Studying the Effect of Vitamin D Supplementation on Vascular Function in CKD: A Work in Progress

from Journal of the American Society of Nephrology current issue https://ift.tt/2HCit4t

The Authors Reply

from Journal of the American Society of Nephrology current issue https://ift.tt/2I2mLkP

The Authors Reply

from Journal of the American Society of Nephrology current issue https://ift.tt/2rdq12r

C.D.C. Director’s $375,000 Salary Will Be Cut

By PAM BELLUCK from NYT Health https://ift.tt/2rbspH1

Medical News Today: Alzheimer's: 'Music may make symptoms more manageable'

Alzheimer's disease can cause people living with it to experience severe anxiety as they try to navigate an unfamiliar world. Can music ...

Fox News Breaking News Alert

Fox News Breaking News Alert Israeli PM Netanyahu reveals Iranian nuke designs, blueprints, spreadsheets 04/30/18 1:27 PM

Fox News Breaking News Alert

Fox News Breaking News Alert Netanyahu set to reveal 'dramatic' intelligence about Iran nuke deal, report says 04/30/18 12:55 PM...

Medical News Today: Can a vitamin D deficiency cause hair loss?

People get vitamin D from a variety of foods and from spending time outdoors in sunlight. Vitamin D is an essential nutrient that plays a ro...

Medical News Today: Vitamin B-6 could help us to recall dreams

A new study suggests that taking a vitamin B-6 supplement before going to bed each night could help us to remember the details of our dreams...

Medical News Today: These five habits will lengthen your lifespan

Adopting five low-risk lifestyle factors in adulthood could raise life expectancy at age 50 by 14 years for women and 12 years for men, larg...

Medical News Today: What is a vaginal cuff and what are the risks?

A vaginal cuff is a closure made at the top of the vagina in the place of the cervix after a person has a hysterectomy. In this article, we ...

Medical News Today: Can a salt water flush help you lose weight?

A salt water flush is commonly used for weight loss and to avoid fluid retention. The effectiveness is highly debated, with many believing t...

Medical News Today: Why is my nose tingling inside?

There are many reasons for a tingling feeling in the nose. It is sometimes the effect of illness and may be caused by allergies. There are m...

Wheelchairs Prohibited in the Last Place You’d Expect

By PAULA SPAN from NYT Health https://ift.tt/2rgfkx9

Medical News Today: Vulvar varicosities: What to know about varicose veins on the vulva

Vulvar varicosities are varicose veins that appear on the vulva. These veins may appear misshapen and swollen and often occur during pregnan...

Medical News Today: Can jojoba oil treat acne?

Jojoba oil is a waxy substance that is commonly included in skin creams and gels. Its consistency and natural anti-inflammatory properties m...

Medical News Today: Can an iron deficiency cause hair loss?

Iron deficiency anemia occurs when a person does not have enough iron in their body or the body cannot use its supply properly. This can cau...

Medical News Today: Diaphoresis: What causes excessive sweating?

Diaphoresis refers to excessive sweating with no clear cause. In this article, we look at the possible reasons for diaphoresis, including hy...

Medical News Today: Is it safe to have sex during menstruation?

Many people wonder if having sex during menstruation has side effects. There is no health-related reason to avoid sex because someone is men...

Medical News Today: What happens in the brain during a 'eureka!' moment?

Neuroscientists recently studied that 'Aha!' moment you get when you finally solve a puzzle. It is linked to reward centers and our ...

Medical News Today: Mediterranean diet increases 'good' gut bacteria

In a study of monkeys, researchers found that a Mediterranean diet significantly increased levels of beneficial bacteria in the gut. from ...

Fox News Breaking News Alert

Fox News Breaking News Alert T-Mobile and Sprint announce plan to merge, form new company 04/29/18 12:26 PM

Fox News Breaking News Alert

Fox News Breaking News Alert Trump eager to meet with Kim Jong-Un, but won't until North Korea surrenders nuclear program: John Bolton...

Fox News Breaking News Alert

Fox News Breaking News Alert President Trump says comedian 'bombed' at White House Correspondents' Dinner, touts success of hi...

Injecting Drugs Can Ruin a Heart. How Many Second Chances Should a User Get?

By ABBY GOODNOUGH from NYT Health https://ift.tt/2I0Wvay

Medical News Today: Dark chocolate may boost vision

Researchers have set their sights on dark chocolate as a potential vision booster, after finding that the delicious treat may improve eyesig...

Medical News Today: How exercise tells the brain to curb appetite

Appetite decreases in the aftermath of a good workout, but why is that? A new study reveals the hidden brain mechanisms set in motion by exe...

Fox News Breaking News Alert

Fox News Breaking News Alert Man wanted in shooting death of Maine deputy caught 04/28/18 1:08 PM

Medical News Today: Do compression stockings help to treat varicose veins?

Doctors often recommend compression stockings to improve circulation, prevent varicose veins from becoming worse, and reduce pain and discom...

Medical News Today: How to treat esophageal spasms

Esophageal spasms can occur after a person eats certain foods, but can also be triggered by stress, medications, or GERD. Spasms of the esop...

Medical News Today: How long does it take to recover from a wisdom tooth extraction?

Removal of the wisdom teeth is a common dental surgery, and there is a variety of reasons for doing it. The most common reason is that there...

Medical News Today: Why does my urine feel hot?

Urine is normally warm because it comes from inside the body, which has a core temperature of 98.6°F. Hot urine occurs when urine is hotter ...

Medical News Today: Causes of stomach tightening during each trimester

There are a variety of reasons a woman may feel her stomach is tightening when she is pregnant, ranging from gas and constipation to round l...

Medical News Today: Predicting psychosis: Brain folds hold the key

Catching psychosis at an early stage is the key to successful treatment. Examining communication between folds on the cortex may predict tho...

Medical News Today: Latest CDC autism figures show 15 percent rise

After conducting the largest study of its kind, the CDC may revise their estimates for autism prevalence. Is autism on the rise, or is diagn...

Medical News Today: Is coconut oil a laxative?

Coconut oil has many different uses. Nutritionally, it is considered healthful in moderate amounts, so may be worth a try to relieve constip...

Fox News Breaking News Alert

Fox News Breaking News Alert Alfie Evans, UK toddler at center of legal battle, dies 04/28/18 3:10 AM

The Golden State Killer Is Tracked Through a Thicket of DNA, and Experts Shudder

By GINA KOLATA and HEATHER MURPHY from NYT Health https://ift.tt/2I2fjWS

New C.D.C. Director’s $375,000 Salary Under Scrutiny

By SHEILA KAPLAN from NYT Health https://ift.tt/2r5yvZn

Medical News Today: Is saturated or unsaturated fat better for you?

Saturated and unsaturated fat are the two main forms of dietary fat. The health impact of these different types of fat has been debated for ...

Medical News Today: Do BiPAP machines work for COPD?

A BiPAP machine is a small breathing device that can help a person with COPD to breathe more easily. It can be used at night or when symptom...

Medical News Today: What are delusions of grandeur?

A delusion of grandeur is a false belief in one’s importance or greatness. A person may believe, for instance, that they are famous, can end...

Medical News Today: Depression: Pioneering study pinpoints 44 genetic culprits

The authors of a large-scale new genome study have identified dozens of new genetic variants that can heighten the risk of major depression....

Medical News Today: Can CBD oil help with migraines?

Some researchers suggest that cannabidiol (CBD) oil can treat a range of complaints and conditions. While CBD is a compound in cannabis, the...

Medical News Today: High blood pressure? Drinking kefir could lower it

Kefir, a fermented milk drink, is known for its probiotic properties that help to rebalance gut bacteria. But how can this influence blood p...

Medical News Today: This 'genetic switch' could help to fight cancer

Scientists mobilize T cells inside tumors with a laser that remotely activates heat-sensitive gene switches to boost protein expression more...

Medical News Today: What causes a yellow vaginal discharge?

Yellow discharge before a period can have a range of potential causes. Diagnosis depends on the consistency, smell, and color of the dischar...

Medical News Today: What to know about sex during pregnancy

During a healthy pregnancy, it is typically safe to continue having sex. In fact, sex during pregnancy can have various benefits for the wom...

Medical News Today: What could cause chest pain?

Pain in the chest may cause people to worry. Although some causes are severe, such as heart attacks, many of the potential causes are less w...

Fox News Breaking News Alert

Fox News Breaking News Alert House Intel Committee releases final report on Russia probe 04/27/18 10:04 AM

Medical News Today: Which essential oils help get rid of wrinkles?

There are many lotions and creams that claim to help reduce the appearance of wrinkles, but some people may prefer a natural alternative. Ma...

Medical News Today: What does it mean when you have white gums?

Some conditions can make the gums appear white. The color change may occur in one part of the mouth or over the entire gums. There are many ...

Medical News Today: Can you remove a skin tag yourself?

Skin tags are harmless, but some people choose to eliminate large or noticeable tags for cosmetic reasons. There are many simple methods of ...

Medical News Today: What to know about a tibia fracture

$Medical News Today: What to know about a tibia fracture$

Medical News Today: What to know about a tibia fracture

The tibia or shinbone is the most common long bone in the body for someone to fracture. The severity of symptoms depends on how it breaks, w...

Fox News Breaking News Alert

Fox News Breaking News Alert Duke and Duchess of Cambridge name their third child 04/27/18 6:24 AM

Fox News Breaking News Alert

Fox News Breaking News Alert North, South Korea agree on denuclearization of peninsula 04/27/18 5:22 AM

Medical News Today: How dark chocolate could boost brain health, immunity

If ever you needed an excuse to eat chocolate, this is it. Researchers shed light on how dark chocolate can offer benefits for brain health ...

Medical News Today: Experimental glue could soon fix broken bones

Currently, fixing bone fractures is no easy feat in the absence of a suitable adhesive. But researchers from Sweden may have just solved thi...

Fox News Breaking News Alert

Fox News Breaking News Alert Kim Jong Un, South Korea's Moon Jae-in readying joint announcement 04/27/18 4:17 AM

Fox News Breaking News Alert

Fox News Breaking News Alert North Korea's Kim Jong Un crosses border into South Korea to meet Moon Jae-in for historic summit 04/26...

Fox News Breaking News Alert

Fox News Breaking News Alert Cleveland Browns select Baker Mayfield with No. 1 pick in NFL Draft 04/26/18 8:20 PM

Fox News Breaking News Alert

Fox News Breaking News Alert James Comey claims release of memo contents not a 'leak' in Fox News interview 04/26/18 6:59 PM

Trump’s Doctor Accused of Handing Out Ambien. D.E.A. Calls the Practice Illegal

By GINA KOLATA from NYT Health https://ift.tt/2Fk9j6s

Fox News Breaking News Alert

Fox News Breaking News Alert James Comey talks to Fox News live on 'Special Report' at 6 pm ET 04/26/18 5:20 PM

Medical News Today: How to safely flush your eye

If chemicals come into contact with the eye, it is essential to flush them out immediately. In this article, we describe how to flush the ey...

Medical News Today: The best carrier oils for essential oils

Carrier oils are used to dilute essential oils so that they do not irritate the skin of those who use them. There are many different plant-b...

Fox News Breaking News Alert

Fox News Breaking News Alert Bill Cosby lashes out in profane rant after being found guilty of sexual assault 04/26/18 2:21 PM

Fox News Breaking News Alert

Fox News Breaking News Alert Bill Cosby found guilty of sexual assault 04/26/18 1:52 PM

Medical News Today: Could hemp help to beat ovarian cancer?

Although hemp has fallen out of favor over the years, some scientists believe that a certain strain could help in the battle against ovarian...

Medical News Today: Fibromyalgia and chest pain: What is normal, symptoms, and treatment

Fibromyalgia causes widespread pain and tenderness. While symptoms differ, many people report intense pain in the chest and ribcage. Fibromy...

Medical News Today: What is Ureaplasma?

Ureaplasma is a form of bacteria that is often found in the urinary or genital tract and can be transmitted through sexual contact. In some ...

Fox News Breaking News Alert

Fox News Breaking News Alert Senate confirms Mike Pompeo as secretary of state in 57-42 vote 04/26/18 1:05 PM

Medical News Today: Researchers use light to battle chronic pain

An innovative technique uses pulses of light to trim oversensitive neurons. It could, one day, help in the treatment of neuropathic pain. ...

Fox News Breaking News Alert

Fox News Breaking News Alert Explosion at an oil refinery in Wisconsin results in at least 20 casualties 04/26/18 12:20 PM

Medical News Today: These common drugs may raise your risk of dementia

A new study links long-term anticholinergic use for depression, Parkinson's, and loss of bladder control to raised risk of dementia up t...

Medical News Today: What to know about trochanteric bursitis

Trochanteric bursitis is an inflammation of the bursa in the hip. The main symptom of trochanteric bursitis is pain outside the hip at the t...

Medical News Today: What should you do about a pimple on the penis?

Pimples can occur anywhere on the body, including the genitals, and a pimple on the penis can have a range of causes. Knowing the signs of a...

Medical News Today: What does it mean when you have a lot of clear watery discharge?

Vaginal discharge varies according to the menstrual cycle, and it often changes color and consistency. Clear, watery discharge is common and...

Medical News Today: What are the benefits of an Epsom salt detox?

Epsom salt can be added to a warm bath or foot soak to provide a variety of benefits, including soothing the skin, reducing stress, and reli...

Fox News Breaking News Alert

Fox News Breaking News Alert Trump says ex-FBI Director James Comey is 'guilty of crimes' 04/26/18 8:23 AM

Fox News Breaking News Alert

Fox News Breaking News Alert Trump says allegations against Dr. Ronny Jackson are 'false' 04/26/18 8:15 AM

Fox News Breaking News Alert

Fox News Breaking News Alert Dr. Ronny Jackson withdraws name from VA nomination 04/26/18 7:52 AM

Medical News Today: How do you stretch the latissimus dorsi?

The latissimus dorsi is a large muscle that stretches from the middle to lower back. While overuse can lead to pain, some movement may provi...

Medical News Today: What to know about cuboid syndrome

Cuboid syndrome is an injury related to a dislocation of the cuboid bone in the middle of the foot. Cuboid syndrome often results from injur...

‘Desperation Oncology’: When Patients Are Dying, Some Cancer Doctors Turn to Immunotherapy

By GINA KOLATA from NYT Health https://ift.tt/2Hwgv5t

Medical News Today: Alcohol promotes disease by altering oral bacteria

Drinking alcohol disrupts the fine balance of our oral bacteria, a new study shows. Thus, harmful types are fostered over helpful ones, prom...

Medical News Today: Baking soda: A safe, easy treatment for arthritis?

Baking soda is a kitchen staple and go-to home remedy for many conditions. But how and why might it help to treat inflammatory diseases such...

Fox News Breaking News Alert

Fox News Breaking News Alert Fox News Poll: Most Americans say Trump likely to fire Mueller 04/25/18 6:01 PM

A Lifesaving Pump for Cancer Patients Is Being Phased Out

By DENISE GRADY and SHEILA KAPLAN from NYT Health https://ift.tt/2HQ1ieM

Infant Deaths Fall Sharply in Africa With Routine Antibiotics

By DONALD G. McNEIL Jr. from NYT Health https://ift.tt/2vNkmWj

Medical News Today: Caring for a child with ADHD: 21 tips

Parenting or caring for a child with ADHD can be both challenging and rewarding. In this article, we give tips on how to encourage positive ...

Medical News Today: What is the cause of drooling?

A person usually drools while asleep, when they have less control over their mouth. Infections, neurological conditions, and other issues ca...

Medical News Today: How dogs could help us explore our own gut health

The proverbial best friends of humankind give us unconditional love and moments of joy. But can they also enrich our knowledge of our own gu...

Medical News Today: Macrocytic anemia: Symptoms and treatment

Macrocytic anemia is a type of anemia characterized by abnormally large red blood cells. The size of the red blood cells means there are few...

Medical News Today: Could this vitamin A derivative cure liver cancer?

Researchers reveal how a compound called acyclic retinoid, which is a synthetic form of vitamin A, can target and destroy liver cancer stem ...

Medical News Today: Letter from the Editor: Winds of change

The winds of change are blowing at Medical News Today. Read Managing Editor Marie Ellis' monthly update to learn about what's on the...

Medical News Today: Cognitive decline: Impaired sense of smell could be used as marker

The first population study of sense of smell and cognitive performance by age suggests that testing sense of smell could be a marker for cog...

Fox News Breaking News Alert

Fox News Breaking News Alert Dallas police officer injured in Home Depot shooting dies, mayor says 04/25/18 11:08 AM

Medical News Today: What are the possible causes of vaginal dryness?

Vaginal dryness is a common symptom for women transitioning to menopause. It is caused by a drop in levels of the hormone estrogen. Treatmen...

Medical News Today: What are the main functions of the muscular system?

The human muscular system is complex and has many functions in the body. These include mobility, stability, posture, circulation, digestion,...

Fox News Breaking News Alert

Fox News Breaking News Alert Maine officer shot and killed while responding to robbery, police say 04/25/18 10:04 AM

Medical News Today: What to do about a hyperextended elbow

A hyperextended elbow can occur when the elbow moves outside its normal range of motion. This can result in a variety of symptoms, such as p...

Medical News Today: What are the risks of breast implant surgery?

As with many medical procedures, breast implant surgery has a range of risks and complications for people to be aware of beforehand. These c...

Medical News Today: Causes and treatments for a nervous stomach

A nervous stomach usually refers to stomach problems that are caused by stress and anxiety. Despite having some of the same symptoms as some...

Medical News Today: What are the risks of being underweight?

A person is considered to be underweight if they have a body mass index (BMI) of under 18.5. Being underweight is associated with a range of...

Fox News Breaking News Alert

Fox News Breaking News Alert Kim Wall killer Peter Madsen sentenced to life in prison 04/25/18 7:07 AM

Medical News Today: Could 'one puff' of cannabis ease depression?

Researchers found that users of medical cannabis reported a reduction in depressive symptoms after just one puff of a high-CBD, low-THC form...

Medical News Today: Sheep disease toxin shines a light on multiple sclerosis

A sheep disease has parallels with multiple sclerosis. A study identifies antibodies to the toxin in humans, providing clues as to the condi...

With George H.W. Bush Hospitalized, the World Wonders: Is It a Broken Heart?

By GINA KOLATA and BENEDICT CAREY from NYT Health https://ift.tt/2FhjCsg

Medical News Today: What does it mean if you're born with more than five fingers on a hand?

Some people are born with extra fingers or toes. Known as polydactyly, the condition occurs genetically and can be inherited. If polydactyly...

Medical News Today: Can avocado oil strengthen my hair?

Oils play an important role in the health of a person’s hair. Avocado oil may have specific benefits due to its vitamin and mineral composit...

Medical News Today: What home remedies can stop flatulence?

Although passing gas is a normal bodily function, some people may be concerned that they do so excessively. There are many steps that can he...

Medical News Today: What is Crouzon syndrome?

Crouzon syndrome is relatively rare genetic condition that affects the features of a person's face and head. It impacts bone development...

Medical News Today: Essential oils for a sore throat: Lemon, peppermint, and more

Essential oils are a popular home remedy for many ailments, but can they soothe a sore throat? In this article, we look at the evidence behi...

Medical News Today: World's first penis and scrotum transplant complete

The first total penis and scrotum transplant has now been performed by a team of Johns Hopkins surgeons. The recipient, they say, 'is re...

Medical News Today: Could eating fish stave off Parkinson's disease?

We know that eating fish protects brain health. A new study identifies the protein responsible for this and explains how it fights 'Park...

F.D.A. Cracks Down on Sales of E-Cigarettes to Minors

By KATE ZERNIKE and SHEILA KAPLAN from NYT Health https://ift.tt/2qYcqMe

Medical News Today: ALS: Most physically active have '26 percent higher risk'

A large study conducted in three countries provides good evidence of a link between a history of vigorous physical activity and the risk of ...

Medical News Today: What causes a chronic cough?

A chronic cough is one that lasts for 8 weeks in adults or 4 weeks in children. It may produce mucus or be dry and tickle the throat. Common...

Medical News Today: What causes bumps on the eyeball?

Finding a bump on the eyeball can be alarming, but most causes are harmless and easily treatable. In this article, we look at issues that ca...

Fox News Breaking News Alert

Fox News Breaking News Alert Toronto van attack driver charged with first-degree murder 04/24/18 10:15 AM

Medical News Today: Why are my hands warm?

A person's hands may feel unusually warm for many reasons, ranging from recent exercise to medical conditions. In this article, we look ...

Medical News Today: What is a malar rash?

A malar rash is also known as a butterfly rash and appears on the face. It is usually red or purple and may be blotchy or solid. It can occu...

Medical News Today: What essential oils are good for preventing stretch marks?

Stretch marks can affect many areas of the body and are associated with changes in the body’s shape and appearance. This might be due to rap...

Medical News Today: Heart failure: Destroying gut bacteria could improve outcomes

In a new study, researchers demonstrate that immune molecules activated by gut bacteria could negatively impact cardiac health following hea...

Medical News Today: Over 10 percent of PMS cases linked to drinking habits

Many women have to deal with premenstrual syndrome, but the risk factors for this remain unclear. A new review suggests that we should look ...

Trump Administration Pushes Abstinence in Teen Pregnancy Programs

By PAM BELLUCK from NYT Health https://ift.tt/2Hm2nYt

Fox News Breaking News Alert

Fox News Breaking News Alert Former President George H.W. Bush hospitalized after contracting infection, spokesman says 04/23/18 6:50 PM...

Fox News Breaking News Alert

Fox News Breaking News Alert At least 9 dead, 16 hurt after driver plows van into Toronto crowd 04/23/18 4:53 PM

Medical News Today: Can essential oils treat a UTI?

Essential oils are popular home remedies for many ailments, but can they help to relieve the symptoms of a UTI? In this article, we look at ...

Medical News Today: What is the best thing for stiff joints?

Bones are heavy and moving them around can put strain on the joints. Overuse, injury, age, or a medical condition can cause joint strain and...

Medical News Today: Why do some people sneeze after eating?

If a person sneezes after eating all or certain foods, they may either have gustatory rhinitis, snatiation, or a food allergy. Hot or spicy ...

Medical News Today: Is telogen effluvium reversible?

Telogen effluvium is a form of temporary hair loss that usually happens several months after a person experiences a traumatic event or stres...

Medical News Today: What are phleboliths and are they safe?

Phleboliths are small, round lumps of calcium that form inside a person's veins. This type of vascular calcification often occurs in the...

Medical News Today: Best 40 foods for vitamin K

Vitamin K is an essential nutrient that helps the body clot blood, build strong bones, and keep the heart healthy. In this article, we look ...

Fox News Breaking News Alert

Fox News Breaking News Alert Suspected driver who plowed into pedestrians in Toronto in custody, cops say 04/23/18 2:25 PM

Fox News Breaking News Alert

Fox News Breaking News Alert Waffle House shooting suspect in custody, police say 04/23/18 2:08 PM

Fox News Breaking News Alert

Fox News Breaking News Alert Several people injured when van plows into pedestrians in Toronto: cops 04/23/18 1:52 PM

Medical News Today: Common allergic conditions linked to mental health

Although allergies might seem a world away from mental health, a new study finds that common allergic conditions increase the risk of psychi...

Medical News Today: What is calcific tendonitis and what causes it?

Calcific tendonitis is a condition where deposits of calcium build up in a tendon or muscle, which can lead to pain and reduced movement. It...

Fox News Breaking News Alert

Fox News Breaking News Alert Kate Middleton, Prince William leave hospital with baby boy 04/23/18 1:12 PM

Fox News Breaking News Alert

Fox News Breaking News Alert Waffle House shooter escaped police chase days before deadly rampage: police 04/23/18 1:06 PM

Medical News Today: Want better sleep? Leave your work at the office

Your work-related stress is mental baggage that you must learn not to drag home with you. If you hold on to it, both your sleep and health w...

‘Whole Again’: A Vet Maimed by an I.E.D. Receives a Transplanted Penis

By DENISE GRADY from NYT Health https://ift.tt/2qWoNIL

Medical News Today: How vitamin D protects against type 2 diabetes

A new study suggests that vitamin D deficiency is tied to a five times greater risk of type 2 diabetes compared with levels well above the h...

Medical News Today: Eczema during pregnancy: What to know

Many women experience eczema for the first time during pregnancy, while those who already have eczema may experience an increase or reductio...

Medical News Today: What are the benefits of barley water?

Barley is a great source of fiber and contains many other essential minerals, including magnesium, manganese, and selenium. In this article,...

Medical News Today: Is apple cider vinegar good or bad for diarrhea?

Apple cider vinegar has recently been touted as a cure-all for many ailments, including diarrhea. However, this common household ingredient ...

Fox News Breaking News Alert

Fox News Breaking News Alert Kate Middleton gives birth to baby boy 04/23/18 8:09 AM

Infinitesimal Odds: A Scientist Finds Her Child’s Rare Illness Stems From the Gene She Studies

By PAM BELLUCK from NYT Health https://ift.tt/2HUFk8n

Medical News Today: Artificial sweeteners may damage blood vessels

In the most detailed study of its type, researchers demonstrate that artificial sweeteners damage blood vessels and may increase diabetes ri...

Medical News Today: Diabetes: Body fat percentage, not BMI, predicts risk

A new study suggests that the standard body mass index cannot accurately predict someone's risk of developing type 2 diabetes or prediab...

Fox News Breaking News Alert

Fox News Breaking News Alert Waffle House shooting suspect may have 2 guns, was arrested by Secret Service near White House last year, pol...

Fox News Breaking News Alert

Fox News Breaking News Alert Devin Nunes tells Fox News that review of FBI, DOJ documents shows Russia probe was launched without supporti...

Fox News Breaking News Alert

Fox News Breaking News Alert Exclusive: French president Macron tells 'Fox News Sunday' he has a 'very special relationship...

Fox News Breaking News Alert

Fox News Breaking News Alert 4 dead, several others injured when gunman opens fire at Nashville Waffle House, police say 04/22/18 7:51 A...

Fox News Breaking News Alert

Fox News Breaking News Alert Waffle House shooting leaves 3 dead, 4 wounded; gunman sought 04/22/18 6:30 AM

Medical News Today: Parkinson's: Targeting new compound slows disease in rats

The results of a decade-long study are in: a new therapeutic target is found, and scientists manage to slow the progression of the disease i...

Medical News Today: What is cervicitis and what causes it?

Cervicitis refers to inflammation of the cervix, the narrow passage connecting the uterus and vagina. It can result in itching, pain, and bl...

Medical News Today: 'Biomedical tattoo' might catch cancer early

Medical research is reaching a new frontier with implants that can accurately spot early signs of cancer. Yet the road from laboratory to pa...

Medical News Today: What is cervical stimulation and is it safe?

Some people use the term cervix penetration to refer to cervical stimulation. With this, the small canal behind the vagina is stimulated whe...

Medical News Today: Why is my eyelash growing in the wrong direction?

Instead of becoming trapped under the skin, an ingrown eyelash may grow in the wrong direction, toward the eye. This is called trichiasis, a...

Medical News Today: What does it mean if your RDW is high?

A red cell distribution width (RDW) blood test can help detect the presence of anemia, along with what could be causing it. The test identif...

Fox News Breaking News Alert

Fox News Breaking News Alert Former first lady Barbara Bush laid to rest in Houston funeral 04/21/18 11:56 AM

Medical News Today: How are Dexedrine and Adderall different?

Dexedrine and Adderall are two medications that are commonly used to treat ADHD. Both drugs are similar, but there are some differences in h...

Medical News Today: Can essential oils reduce varicose veins?

Varicose veins occur when blood pools in the veins as it tries to return to the heart to pick up fresh oxygen. They are common in people...

Medical News Today: What causes blood in sputum?

Seeing blood in sputum or mucus can be worrying, but it is usually not a cause for concern. If a person is young or generally healthy, these...

Medical News Today: Why are my legs and feet numb?

There are many reasons why a person may feel numbness or tingling in their legs or feet. The most common is sitting in the same position for...

Medical News Today: How inflammation and gut bacteria influence autism

A recent study looks at the links between the immune system, gut bacteria, and autism spectrum disorders. It uncovers some interesting inter...

Medical News Today: Having an audience makes your brain perform better

New research examines what goes on in the brain when people perform a task in front of an audience versus when they are not being watched. ...

Fox News Breaking News Alert

Fox News Breaking News Alert North Korea suspends missile testing, closing nuclear test site, reports say 04/20/18 6:19 PM

Medical News Today: 15 ways to prevent pregnancy

A person can choose from a wide range of methods to avoid pregnancy. Non-hormonal methods include condoms and natural family planning, where...

Ethicists Call for More Scrutiny of ‘Human-Challenge’ Trials

By EMILY BAUMGAERTNER from NYT Health https://ift.tt/2JefATV

Medical News Today: Is fibromyalgia worse in women?

The defining feature of fibromyalgia is widespread pain. It is more common in women than men, who may experience this and other symptoms dif...

Medical News Today: Could gut bacteria cause joint pain?

A study looks at the relationship between diet, gut bacteria, and osteoarthritis. Surprisingly, it found that the microbiome is linked to jo...

Medical News Today: How to make yourself fart

Farting is an everyday term for the expulsion of gas that builds up in the body. Gas can cause uncomfortable bloating and pain, but many yog...

Fox News Breaking News Alert

Fox News Breaking News Alert Justice Dept. IG reportedly probing Comey memos over classified material 04/20/18 1:41 PM

Medical News Today: A waking nightmare: The enigma of sleep paralysis

In sleep paralysis, your mind wakes up, but your body does not. You may also experience frightening hallucinations. What is this, and how ca...

Medical News Today: Why all men 'should be concerned about declining testosterone'

A new study finds a strong link between low total testosterone and chronic diseases in men of all ages, especially in the under-40 and 60-pl...

Fox News Breaking News Alert

Fox News Breaking News Alert Democratic Party files lawsuit alleging conspiracy to disrupt 2016 election 04/20/18 11:29 AM

Medical News Today: How to get rid of greasy hair naturally

There are many ways to get rid of oily, greasy hair. These include changing how the hair is washed, the products used, and a number of natur...

Medical News Today: How long are you contagious with pink eye?

Pink eye is a relatively common eye condition. There are many potential causes, but one of the most significant problems is how not to sprea...

Bodies Remodeled for a Life at Sea

By CARL ZIMMER from NYT Health https://ift.tt/2qJNQj9

Medical News Today: Sebaceous hyperplasia: Treatment and home remedies

When sebaceous glands become enlarged, small bumps can appear under the skin, often on the face. These bumps are harmless, but some choose t...

Medical News Today: Have some humans evolved into real-life merfolk?

Can the human body adapt to fit different environments? Sea nomad people from Southeast Asia testify to humans' versatility and enduranc...

Medical News Today: What to eat and avoid on a low-fiber diet

Fiber is an essential part of a healthful diet, but some people may benefit from eating less fiber, especially if they have irritable bowel ...

Medical News Today: How to beat psoriasis at its own game

Harnessing the power of immune cells, researchers create a compound that successfully treats psoriasis in mice. The innovative approach may ...

F.D.A. Panel Recommends Approval of Cannabis-Based Drug for Epilepsy

By SHEILA KAPLAN from NYT Health https://ift.tt/2JbUV2L

Fox News Breaking News Alert

Fox News Breaking News Alert Rudy Giuliani to join Trump’s legal team 04/19/18 5:14 PM

Medical News Today: How can you unblock your ear?

A clogged ear can happen for a variety of reasons. It can be a buildup of wax or caused by a cold or sinus infection. Thankfully, many cases...

Fox News Breaking News Alert

Fox News Breaking News Alert Rosenstein told Trump he is not target of Cohen probe, source says 04/19/18 4:16 PM

Medical News Today: What causes mucus in the chest?

Mucus in the chest can cause discomfort and symptoms such as coughing, wheezing, sleep difficulties, and a sore throat. We describe simple, ...

Medical News Today: What can you eat on a low-carb diet?

Lots of people try to lose weight by reducing their intake of carbohydrates. To ensure the diet is a success, it is essential to understand ...

Medical News Today: Pancreatic cancer: Some blood pressure drugs put women at risk

A new study reveals that certain blood pressure drugs are linked with a high risk of pancreatic cancer among postmenopausal women. from Fe...

Fox News Breaking News Alert

Fox News Breaking News Alert No charges filed in Prince's death, prosecutor says 04/19/18 1:02 PM

Medical News Today: Is it lung cancer? This blood test can tell

To tell lung cancer from benign tumors, specialists often have to use invasive methods. Yet researchers say that a simple blood test can cha...

Fox News Breaking News Alert

Fox News Breaking News Alert Philadelphia police commissioner apologizes to 2 men arrested at Starbucks 04/19/18 12:41 PM

Fox News Breaking News Alert

Fox News Breaking News Alert One dead, several injured after TV station tower collapses in Missouri 04/19/18 11:55 AM

Medical News Today: Added to chemotherapy, this drug doubles lung cancer survival

Adding immunotherapy to chemotherapy doubled survival in a trial of metastatic nonsquamous non-small cell lung cancer lacking EGFR and ALK m...

Medical News Today: Eight benefits of avocado oil for the skin

Cooking with avocado oil has many well-known advantages, but the oil can also benefit the skin. Here, we look at the research behind its man...

Medical News Today: Is it safe to drink alcohol while taking Adderall?

There are risks and dangers to drinking alcohol alongside Adderall, a drug commonly used to treat ADHD. Here, we look at why it might be dan...

As Opioid Prescriptions Fall, Prescriptions for Drugs to Treat Addiction Rise

By ABBY GOODNOUGH from NYT Health https://ift.tt/2HbznXf

Medical News Today: How do you get rid of a butt rash?

A butt rash is common in babies, but adults can get them too. They have many causes, and sometimes the rash is accompanied by an itchy or pa...

Medical News Today: Surprisingly, opioids may increase risk of chronic pain

Opioids are routinely given after surgery to help minimize pain. However, according to new research, opioids may increase the risk of chroni...

Medical News Today: Do feminine hygiene products actually lead to a higher risk of infection?

Many women may view using intimate hygiene products, such as washes or wipes, as a necessity. But new research suggests that they may, in fa...

Medical News Today: Ways to stop heart palpitations

Heart palpitations can feel like a fluttering in the chest, a pounding heart, or a racing pulse. Smoking, exercise, and stress can cause the...

Fox News Breaking News Alert

Fox News Breaking News Alert Magnitude 5.5 quake strikes southern Iran, near nuclear plant 04/19/18 3:42 AM

Fox News Breaking News Alert

Fox News Breaking News Alert Magnitude 5.5 quake strikes southern Iran, near nuclear plant 04/19/18 3:42 AM

Fox News Breaking News Alert

Fox News Breaking News Alert Delta flight makes emergency landing after smoke pours from engine 1 day after Southwest disaster 04/18/18 ...

Fox News Breaking News Alert

Fox News Breaking News Alert Trump warns if he doesn't believe meeting with Kim Jong Un will be productive, 'we won't have it...

Fox News Breaking News Alert

Fox News Breaking News Alert Trump, Japanese PM Abe to hold joint news conference at 6 pm ET 04/18/18 5:33 PM

Medical News Today: How long can a person live with congestive heart failure?

Congestive heart failure is a progressive disease that causes the heart to weaken, making it difficult to pump blood around the body. In thi...

Fox News Breaking News Alert

Fox News Breaking News Alert Nanny convicted of murdering 2 NYC children in 2012 04/18/18 4:26 PM

Medical News Today: Does the 20-20-20 rule prevent eye strain?

The 20-20-20 rule says that after spending 20 minutes on the computer, a person should spend 20 seconds looking at an object 20 feet away. T...

Medical News Today: How to relieve fibromyalgia pain

Fibromyalgia is a condition that causes chronic pain. The pain caused by fibromyalgia may be treated with specific pain relief drugs, or wit...

Medical News Today: New drug halves previously untreatable migraine attacks

A new compound, called erenumab, was found to be successful in treating migraines for which other treatments had previously failed. from F...

Medical News Today: Type 2 diabetes: Late breakfast could drive obesity

New research suggests that eating breakfast later may drive a preference for late rising and retiring, which is linked to higher BMI in type...

Medical News Today: How to increase hemoglobin: Home remedies

A variety of conditions and lifestyle factors can lead to a reduction in hemoglobin. Common causes include anemia, pregnancy, and thyroid co...

Fox News Breaking News Alert

Fox News Breaking News Alert WWE Hall of Famer Bruno Sammartino dead at 82 04/18/18 10:46 AM

Medical News Today: What is the difference between polymyalgia and fibromyalgia?

Fibromyalgia is a nervous system condition that causes widespread pain in the body. Attacks can vary in severity. Polymyalgia is an autoimmu...

Medical News Today: Am I nonbinary?

Many people choose to define their gender outside of biological sex. They conceptualize their gender identity based on psychological and soc...

Fox News Breaking News Alert

Fox News Breaking News Alert Southwest Airlines flight forced to land after bird strike, spokesperson says 04/18/18 7:39 AM

Medical News Today: Nut lovers rejoice: Your favorite snack protects your heart

Nuts are widely considered beneficial to the heart. A new study dives deeper into the specifics and finds out exactly what nuts can do for o...

Medical News Today: Female pattern baldness: Treatment and genetics

While most women lose between 50 and 100 strands of hair per day, this hair is usually quickly replaced by new growth. When bald patches or ...

Medical News Today: Ketamine nasal spray could fight depression fast

Could a fast-acting new drug curb serious depression symptoms, including suicidal thoughts? A recent study says 'yes,' but questions...

Medical News Today: What are the signs of heart attack in a woman?

Symptoms of a heart attack can often vary between males and females. Being able to spot the early signs means that prompt treatment can be s...

Fox News Breaking News Alert

Fox News Breaking News Alert Exclusive interview with Sen. Mitch McConnell at 4 pm ET on ‘Your World with Neil Cavuto’ 04/17/18 3:45 PM

Medical News Today: How can I stabilize my blood pressure?

A wide range of factors influences blood pressure, including anxiety, stress, and medications. High blood pressure can have severe complicat...

Fox News Breaking News Alert

Fox News Breaking News Alert Trump says North Korea, South Korea have his 'blessing' to try ending decades-long war 04/17/18 3:3...

Fox News Breaking News Alert

Fox News Breaking News Alert One person dead after Southwest Airlines plane engine explosion, officials say 04/17/18 3:20 PM

Medical News Today: ALS: How 'toxic' proteins could protect neurons

Researchers have found that large, fibrous aggregates thought to drive Lou Gehrig's disease might actually help to protect motor neurons...

Medical News Today: Does menopause cause rashes?

Menopause causes a variety of familiar symptoms, such as hot flashes, mood swings, and vaginal dryness — but can it cause a rash? In this ar...

Medical News Today: How music helps the heart find its beat

A new study shows that listening to music can intensify the beneficial effects of hypertension medication in people with high blood pressure...

Medical News Today: Prostate cancer: Big data unlocks 80 new drug targets

In the largest study of its type, researchers find several new prostate cancer drug targets by harvesting and analyzing reams of genetic dat...

Fox News Breaking News Alert

Fox News Breaking News Alert Passenger hospitalized after Southwest Airlines plane engine reportedly explodes 04/17/18 12:22 PM

Medical News Today: Could this implant protect women from HIV?

A study suggests that a vaginal implant with drugs that keep T cells unresponsive and inaccessible to HIV may offer a new way to reduce tran...