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

Medical News Today: What causes boils on the inner thigh?

Medical News Today: What causes boils on the inner thigh?

Boils on the inner thigh can appear as red, swollen bumps. We take a look at these hair follicle infections, their risk factors, and home re...

This Months Highlights

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The Era of Human Developmental Nephrology

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Evolution and Kidney Development: A Rosetta Stone for Nephrology

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The Benefits of Tubular Proteinuria: An Evolutionary Perspective

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The UMOD Locus: Insights into the Pathogenesis and Prognosis of Kidney Disease

The identification of genetic factors associated with kidney disease has the potential to provide critical insights into disease mechanisms. Genome-wide association studies have uncovered genomic regions associated with renal function metrics and risk of CKD. UMOD is among the most outstanding loci associated with CKD in the general population, because it has a large effect on eGFR and CKD risk that is consistent across different ethnic groups. The relevance of UMOD for CKD is clear, because the encoded protein, uromodulin (Tamm–Horsfall protein), is exclusively produced by the kidney tubule and has specific biochemical properties that mediate important functions in the kidney and urine. Rare mutations in UMOD are the major cause of autosomal dominant tubulointerstitial kidney disease, a condition that leads to CKD and ESRD. In this brief review, we use the UMOD paradigm to describe how population genetic studies can yield insight into the pathogenesis and prognosis of kidney diseases.
 
 
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The UMOD Locus: Insights into the Pathogenesis and Prognosis of Kidney Disease

The identification of genetic factors associated with kidney disease has the potential to provide critical insights into disease mechanisms....

Salt-Losing Tubulopathies in Children: Whats New, Whats Controversial?

Renal tubulopathies provide insights into the inner workings of the kidney, yet also pose therapeutic challenges. Because of the central nature of sodium in tubular transport physiology, disorders of sodium handling may affect virtually all aspects of the homeostatic functions of the kidney. Yet, owing to the rarity of these disorders, little clinical evidence regarding treatment exists. Consequently, treatment can vary widely between individual physicians and centers and is based mainly on understanding of renal physiology, reported clinical observations, and individual experiences. Salt-losing tubulopathies can affect all tubular segments, from the proximal tubule to the collecting duct. But the more frequently observed disorders are Bartter and Gitelman syndrome, which affect salt transport in the thick ascending limb of Henle’s loop and/or the distal convoluted tubule, and these disorders generate the greatest controversies regarding management. Here, we review clinical and molecular aspects of salt-losing tubulopathies and discuss novel insights provided mainly by genetic investigations and retrospective clinical reviews. Additionally, we discuss controversial topics in the management of these disorders to highlight areas of importance for future clinical trials. International collaboration will be required to perform clinical studies to inform the treatment of these rare disorders.
 
 
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Salt-Losing Tubulopathies in Children: Whats New, Whats Controversial?

Renal tubulopathies provide insights into the inner workings of the kidney, yet also pose therapeutic challenges. Because of the central nat...

Targeting B Cells and Plasma Cells in Glomerular Diseases: Translational Perspectives

The unique contributions of memory B cells and plasma cells in kidney diseases remain unclear. In this review, we evaluate the clinical experience with treatments directed at B cells, such as rituximab, and at plasma cells, such as proteasome inhibition, to shed light on the role of these two B lineage compartments in glomerular diseases. Specifically, analysis of these targeted interventions in diseases such as ANCA-associated vasculitis, SLE, and antibody-mediated transplant rejection permits insight into the pathogenetic effect of these cells. Notwithstanding the limitations of preclinical models and clinical studies (heterogeneous populations, among others), the data suggest that memory B and plasma cells represent two engines of autoimmunity, with variable involvement in these diseases. Whereas memory B cells and plasma cells appear to be key in ANCA-associated vasculitis and antibody-mediated transplant rejection, respectively, SLE seems likely to be driven by both autoimmune compartments. These conclusions have implications for the future development of targeted therapeutics in immune-mediated renal disease.
 
 
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Targeting B Cells and Plasma Cells in Glomerular Diseases: Translational Perspectives

The unique contributions of memory B cells and plasma cells in kidney diseases remain unclear. In this review, we evaluate the clinical expe...

Differentiating Primary, Genetic, and Secondary FSGS in Adults: A Clinicopathologic Approach

FSGS describes a renal histologic lesion with diverse causes and pathogenicities that are linked by podocyte injury and depletion. Subclasses of FSGS include primary, genetic, and secondary forms, the latter comprising maladaptive, viral, and drug-induced FSGS. Despite sharing certain clinical and histologic features, these subclasses differ noticeably in management and prognosis. Without an accepted nongenetic biomarker that discriminates among these FSGS types, classification of patients is often challenging. This review summarizes the clinical and histologic features, including the onset and severity of proteinuria as well as the presence of nephrotic syndrome, that may aid in identifying the specific FSGS subtype. The FSGS lesion is characterized by segmental sclerosis and must be differentiated from nonspecific focal global glomerulosclerosis. No light microscopic features are pathognomonic for a particular FSGS subcategory. The characteristics of podocyte foot process effacement on electron microscopy, while helpful in discriminating between primary and maladaptive FSGS, may be of little utility in detecting genetic forms of FSGS. When FSGS cannot be classified by clinicopathologic assessment, genetic analysis should be offered. Next generation DNA sequencing enables cost-effective screening of multiple genes simultaneously, but determining the pathogenicity of a detected genetic variant may be challenging. A more systematic evaluation of patients, as suggested herein, will likely improve therapeutic outcomes and the design of future trials in FSGS.
 
 
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Differentiating Primary, Genetic, and Secondary FSGS in Adults: A Clinicopathologic Approach

FSGS describes a renal histologic lesion with diverse causes and pathogenicities that are linked by podocyte injury and depletion. Subclasse...

Reciprocal Spatiotemporally Controlled Apoptosis Regulates Wolffian Duct Cloaca Fusion

The epithelial Wolffian duct (WD) inserts into the cloaca (primitive bladder) before metanephric kidney development, thereby establishing the initial plumbing for eventual joining of the ureters and bladder. Defects in this process cause common anomalies in the spectrum of congenital anomalies of the kidney and urinary tract (CAKUT). However, developmental, cellular, and molecular mechanisms of WD-cloaca fusion are poorly understood. Through systematic analysis of early WD tip development in mice, we discovered that a novel process of spatiotemporally regulated apoptosis in WD and cloaca was necessary for WD-cloaca fusion. Aberrant RET tyrosine kinase signaling through tyrosine (Y) 1062, to which PI3K- or ERK-activating proteins dock, or Y1015, to which PLC docks, has been shown to cause CAKUT-like defects. Cloacal apoptosis did not occur in RetY1062F mutants, in which WDs did not reach the cloaca, or in RetY1015F mutants, in which WD tips reached the cloaca but did not fuse. Moreover, inhibition of ERK or apoptosis prevented WD-cloaca fusion in cultures, and WD-specific genetic deletion of YAP attenuated cloacal apoptosis and WD-cloacal fusion in vivo. Thus, cloacal apoptosis requires direct contact and signals from the WD tip and is necessary for WD-cloacal fusion. These findings may explain the mechanisms of many CAKUT.
 
 
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Reciprocal Spatiotemporally Controlled Apoptosis Regulates Wolffian Duct Cloaca Fusion

The epithelial Wolffian duct (WD) inserts into the cloaca (primitive bladder) before metanephric kidney development, thereby establishing th...

Conserved and Divergent Features of Human and Mouse Kidney Organogenesis

Human kidney function is underpinned by approximately 1,000,000 nephrons, although the number varies substantially, and low nephron number is linked to disease. Human kidney development initiates around 4 weeks of gestation and ends around 34–37 weeks of gestation. Over this period, a reiterative inductive process establishes the nephron complement. Studies have provided insightful anatomic descriptions of human kidney development, but the limited histologic views are not readily accessible to a broad audience. In this first paper in a series providing comprehensive insight into human kidney formation, we examined human kidney development in 135 anonymously donated human kidney specimens. We documented kidney development at a macroscopic and cellular level through histologic analysis, RNA in situ hybridization, immunofluorescence studies, and transcriptional profiling, contrasting human development (4–23 weeks) with mouse development at selected stages (embryonic day 15.5 and postnatal day 2). The high-resolution histologic interactive atlas of human kidney organogenesis generated can be viewed at the GUDMAP database (<a href="http://www.gudmap.org">www.gudmap.org</a>) together with three-dimensional reconstructions of key components of the data herein. At the anatomic level, human and mouse kidney development differ in timing, scale, and global features such as lobe formation and progenitor niche organization. The data also highlight differences in molecular and cellular features, including the expression and cellular distribution of anchor gene markers used to identify key cell types in mouse kidney studies. These data will facilitate and inform in vitro efforts to generate human kidney structures and comparative functional analyses across mammalian species.
 
 
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Conserved and Divergent Features of Human and Mouse Kidney Organogenesis

Human kidney function is underpinned by approximately 1,000,000 nephrons, although the number varies substantially, and low nephron number i...

Conserved and Divergent Features of Mesenchymal Progenitor Cell Types within the Cortical Nephrogenic Niche of the Human and Mouse Kidney

Cellular interactions among nephron, interstitial, and collecting duct progenitors drive mammalian kidney development. In mice, Six2+ nephron progenitor cells (NPCs) and Foxd1+ interstitial progenitor cells (IPCs) form largely distinct lineage compartments at the onset of metanephric kidney development. Here, we used the method for analyzing RNA following intracellular sorting (MARIS) approach, single-cell transcriptional profiling, in situ hybridization, and immunolabeling to characterize the presumptive NPC and IPC compartments of the developing human kidney. As in mice, each progenitor population adopts a stereotypical arrangement in the human nephron-forming niche: NPCs capped outgrowing ureteric branch tips, whereas IPCs were sandwiched between the NPCs and the renal capsule. Unlike mouse NPCs, human NPCs displayed a transcriptional profile that overlapped substantially with the IPC transcriptional profile, and key IPC determinants, including FOXD1, were readily detected within SIX2+ NPCs. Comparative gene expression profiling in human and mouse Six2/SIX2+ NPCs showed broad agreement between the species but also identified species-biased expression of some genes. Notably, some human NPC-enriched genes, including DAPL1 and COL9A2, are linked to human renal disease. We further explored the cellular diversity of mesenchymal cell types in the human nephrogenic niche through single-cell transcriptional profiling. Data analysis stratified NPCs into two main subpopulations and identified a third group of differentiating cells. These findings were confirmed by section in situ hybridization with novel human NPC markers predicted through the single-cell studies. This study provides a benchmark for the mesenchymal progenitors in the human nephrogenic niche and highlights species-variability in kidney developmental programs.
 
 
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Conserved and Divergent Features of Mesenchymal Progenitor Cell Types within the Cortical Nephrogenic Niche of the Human and Mouse Kidney

Cellular interactions among nephron, interstitial, and collecting duct progenitors drive mammalian kidney development. In mice, Six2 + neph...

Conserved and Divergent Molecular and Anatomic Features of Human and Mouse Nephron Patterning

The nephron is the functional unit of the kidney, but the mechanism of nephron formation during human development is unclear. We conducted a detailed analysis of nephron development in humans and mice by immunolabeling, and we compared human and mouse nephron patterning to describe conserved and divergent features. We created protein localization maps that highlight the emerging patterns along the proximal–distal axis of the developing nephron and benchmark expectations for localization of functionally important transcription factors, which revealed unanticipated cellular diversity. Moreover, we identified a novel nephron subdomain marked by Wnt4 expression that we fate-mapped to the proximal mature nephron. Significant conservation was observed between human and mouse patterning. We also determined the time at which markers for mature nephron cell types first emerge—critical data for the renal organoid field. These findings have conceptual implications for the evolutionary processes driving the diversity of mammalian organ systems. Furthermore, these findings provide practical insights beyond those gained with mouse and rat models that will guide in vitro efforts to harness the developmental programs necessary to build human kidney structures.
 
 
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Conserved and Divergent Molecular and Anatomic Features of Human and Mouse Nephron Patterning

The nephron is the functional unit of the kidney, but the mechanism of nephron formation during human development is unclear. We conducted a...

Tamm-Horsfall Protein Regulates Mononuclear Phagocytes in the Kidney

Tamm–Horsfall protein (THP), also known as uromodulin, is a kidney-specific protein produced by cells of the thick ascending limb of the loop of Henle. Although predominantly secreted apically into the urine, where it becomes highly polymerized, THP is also released basolaterally, toward the interstitium and circulation, to inhibit tubular inflammatory signaling. Whether, through this latter route, THP can also regulate the function of renal interstitial mononuclear phagocytes (MPCs) remains unclear, however. Here, we show that THP is primarily in a monomeric form in human serum. Compared with wild-type mice, THP–/– mice had markedly fewer MPCs in the kidney. A nonpolymerizing, truncated form of THP stimulated the proliferation of human macrophage cells in culture and partially restored the number of kidney MPCs when administered to THP–/– mice. Furthermore, resident renal MPCs had impaired phagocytic activity in the absence of THP. After ischemia-reperfusion injury, THP–/– mice, compared with wild-type mice, exhibited aggravated injury and an impaired transition of renal macrophages toward an M2 healing phenotype. However, treatment of THP–/– mice with truncated THP after ischemia-reperfusion injury mitigated the worsening of AKI. Taken together, our data suggest that interstitial THP positively regulates mononuclear phagocyte number, plasticity, and phagocytic activity. In addition to the effect of THP on the epithelium and granulopoiesis, this new immunomodulatory role could explain the protection conferred by THP during AKI.
 
 
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Tamm-Horsfall Protein Regulates Mononuclear Phagocytes in the Kidney

Tamm–Horsfall protein (THP), also known as uromodulin, is a kidney-specific protein produced by cells of the thick ascending limb of the loo...

GRHL2 Is Required for Collecting Duct Epithelial Barrier Function and Renal Osmoregulation

Collecting ducts make up the distal-most tubular segments of the kidney, extending from the cortex, where they connect to the nephron proper, into the medulla, where they release urine into the renal pelvis. During water deprivation, body water preservation is ensured by the selective transepithelial reabsorption of water into the hypertonic medullary interstitium mediated by collecting ducts. The collecting duct epithelium forms tight junctions composed of barrier-enforcing claudins and exhibits a higher transepithelial resistance than other segments of the renal tubule exhibit. However, the functional relevance of this strong collecting duct epithelial barrier is unresolved. Here, we report that collecting duct–specific deletion of an epithelial transcription factor, grainyhead-like 2 (GRHL2), in mice led to reduced expression of tight junction–associated barrier components, reduced collecting duct transepithelial resistance, and defective renal medullary accumulation of sodium and other osmolytes. In vitro, Grhl2-deficient collecting duct cells displayed increased paracellular flux of sodium, chloride, and urea. Consistent with these effects, Grhl2-deficient mice had diabetes insipidus, produced dilute urine, and failed to adequately concentrate their urine after water restriction, resulting in susceptibility to prerenal azotemia. These data indicate a direct functional link between collecting duct epithelial barrier characteristics, which appear to prevent leakage of interstitial osmolytes into urine, and body water homeostasis.
 
 
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GRHL2 Is Required for Collecting Duct Epithelial Barrier Function and Renal Osmoregulation

Collecting ducts make up the distal-most tubular segments of the kidney, extending from the cortex, where they connect to the nephron proper...

ApoL1 Overexpression Drives Variant-Independent Cytotoxicity

Coding variants in the APOL1 gene are associated with kidney diseases in African ancestral populations; yet, the underlying biologic mechanisms remain uncertain. Variant-dependent autophagic and cytotoxic cell death have been proposed as pathogenic pathways mediating kidney injury. To examine this possibility, we conditionally expressed APOL1-G0 (reference), -G1, and -G2 (variants) using a tetracycline-regulated system in HEK293 cells. Autophagy was monitored biochemically and cell death was measured using multiple assays. We measured intracellular Na+ and K+ content with atomic absorption spectroscopy and APOL1-dependent currents with whole-cell patch clamping. Neither reference nor variant APOL1s induced autophagy. At high expression levels, APOL1-G0, -G1, and -G2 inserted into the plasma membrane and formed pH-sensitive cation channels, causing collapse of cellular Na+ and K+ gradients, phosphorylation of p38 mitogen-activated protein kinase, and cell death, without variant-dependent differences. APOL1-G0 and -G2 exhibited similar channel properties in whole-cell patch clamp experiments. At low expression levels, neither reference nor variant APOL1s localized on the plasma membrane, Na+ and K+ gradients were maintained, and cells remained viable. Our results indicate that APOL1-mediated pore formation is critical for the trypanolytic activity of APOL1 and drives APOL1-mediated cytotoxicity in overexpression systems. The absence of cytotoxicity at physiologic expression levels suggests variant-dependent intracellular K+ loss and cytotoxicity does not drive kidney disease progression.
 
 
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ApoL1 Overexpression Drives Variant-Independent Cytotoxicity

Coding variants in the APOL1 gene are associated with kidney diseases in African ancestral populations; yet, the underlying biologic mechan...

Proteomic Profiling Reveals the Transglutaminase-2 Externalization Pathway in Kidneys after Unilateral Ureteric Obstruction

Increased export of transglutaminase-2 (TG2) by tubular epithelial cells (TECs) into the surrounding interstitium modifies the extracellular homeostatic balance, leading to fibrotic membrane expansion. Although silencing of extracellular TG2 ameliorates progressive kidney scarring in animal models of CKD, the pathway through which TG2 is secreted from TECs and contributes to disease progression has not been elucidated. In this study, we developed a global proteomic approach to identify binding partners of TG2 responsible for TG2 externalization in kidneys subjected to unilateral ureteric obstruction (UUO) using TG2 knockout kidneys as negative controls. We report a robust and unbiased analysis of the membrane interactome of TG2 in fibrotic kidneys relative to the entire proteome after UUO, detected by SWATH mass spectrometry. The data have been deposited to the ProteomeXchange with identifier PXD008173. Clusters of exosomal proteins in the TG2 interactome supported the hypothesis that TG2 is secreted by extracellular membrane vesicles during fibrosis progression. In established TEC lines, we found TG2 in vesicles of both endosomal (exosomes) and plasma membrane origin (microvesicles/ectosomes), and TGF-β1 stimulated TG2 secretion. Knockout of syndecan-4 (SDC4) greatly impaired TG2 exosomal secretion. TG2 coprecipitated with SDC4 from exosome lysate but not ectosome lysate. Ex vivo, EGFP-tagged TG2 accumulated in globular elements (blebs) protruding/retracting from the plasma membrane of primary cortical TECs, and SDC4 knockout impaired bleb formation, affecting TG2 release. Through this combined in vivo and in vitro approach, we have dissected the pathway through which TG2 is secreted from TECs in CKD.
 
 
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Proteomic Profiling Reveals the Transglutaminase-2 Externalization Pathway in Kidneys after Unilateral Ureteric Obstruction

Increased export of transglutaminase-2 (TG2) by tubular epithelial cells (TECs) into the surrounding interstitium modifies the extracellular...

Indoxyl Sulfate Upregulates Liver P-Glycoprotein Expression and Activity through Aryl Hydrocarbon Receptor Signaling

In patients with CKD, not only renal but also, nonrenal clearance of drugs is altered. Uremic toxins could modify the expression and/or activity of drug transporters in the liver. We tested whether the uremic toxin indoxyl sulfate (IS), an endogenous ligand of the transcription factor aryl hydrocarbon receptor, could change the expression of the following liver transporters involved in drug clearance: SLC10A1, SLC22A1, SLC22A7, SLC47A1, SLCO1B1, SLCO1B3, SLCO2B1, ABCB1, ABCB11, ABCC2, ABCC3, ABCC4, ABCC6, and ABCG2. We showed that IS increases the expression and activity of the efflux transporter P-glycoprotein (P-gp) encoded by ABCB1 in human hepatoma cells (HepG2) without modifying the expression of the other transporters. This effect depended on the aryl hydrocarbon receptor pathway. Presence of human albumin at physiologic concentration in the culture medium did not abolish the effect of IS. In two mouse models of CKD, the decline in renal function associated with the accumulation of IS in serum and the specific upregulation of Abcb1a in the liver. Additionally, among 109 heart or kidney transplant recipients with CKD, those with higher serum levels of IS needed higher doses of cyclosporin, a P-gp substrate, to obtain the cyclosporin target blood concentration. This need associated with serum levels of IS independent of renal function. These findings suggest that increased activity of P-gp could be responsible for increased hepatic cyclosporin clearance. Altogether, these results suggest that uremic toxins, such as IS, through effects on drug transporters, may modify the nonrenal clearance of drugs in patients with CKD.
 
 
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Indoxyl Sulfate Upregulates Liver P-Glycoprotein Expression and Activity through Aryl Hydrocarbon Receptor Signaling

In patients with CKD, not only renal but also, nonrenal clearance of drugs is altered. Uremic toxins could modify the expression and/or acti...

Exosomal CCL2 from Tubular Epithelial Cells Is Critical for Albumin-Induced Tubulointerstitial Inflammation

Albuminuria is a key instigator of tubulointerstitial inflammation associated with CKD, but the mechanism through which filtered albumin propagates renal injury remains unclear. In this study, we explored the role in this process of exosome mRNA released from tubular epithelial cells (TECs). Compared with control mice, acute and chronic kidney injury models had more exosomes containing inflammatory cytokine mRNA, particularly the chemokine CCL2, in kidneys and urine. In vitro stimulation of TECs with BSA recapitulated this finding. Notably, the internalization of purified TEC exosomes by cultured macrophages increased if TECs were exposed to BSA. Macrophage internalization of exosomes from BSA-treated TECs led to an enhanced inflammatory response and macrophage migration, but CCL2 silencing in TECs prevented these effects. Using a GFP-CCL2 fusion mRNA construct, we observed direct transfer of CCL2 mRNA from TEC exosomes to macrophages. Mice subjected to tail vein injection of purified BSA-treated TEC exosomes developed tubular injury with renal inflammatory cell infiltration. However, injection of exosomes from BSA-treated CCL2-deficient TECs induced less severe kidney inflammation. Finally, in patients with IgA nephropathy, the increase of proteinuria correlated with augmented urinary excretion of exosomes with exaggerated expression of CCL2 mRNA. Moreover, the level of CCL2 mRNA in urinary exosomes correlated closely with levels of renal interstitial macrophage infiltration in these patients. Our studies demonstrate that the increasing release of exosomes that transfer CCL2 mRNA from TECs to macrophages constitutes a critical mechanism of albumin-induced tubulointerstitial inflammation.
 
 
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Exosomal CCL2 from Tubular Epithelial Cells Is Critical for Albumin-Induced Tubulointerstitial Inflammation

Albuminuria is a key instigator of tubulointerstitial inflammation associated with CKD, but the mechanism through which filtered albumin pro...

CHIP Regulates Aquaporin-2 Quality Control and Body Water Homeostasis

The importance of the kidney distal convoluted tubule (DCT) and cortical collecting duct (CCD) is highlighted by various water and electrolyte disorders that arise when the unique transport properties of these segments are disturbed. Despite this critical role, little is known about which proteins have a regulatory role in these cells and how these cells can be regulated by individual physiologic stimuli. By combining proteomics, bioinformatics, and cell biology approaches, we found that the E3 ubiquitin ligase CHIP is highly expressed throughout the collecting duct; is modulated in abundance by vasopressin; interacts with aquaporin-2 (AQP2), Hsp70, and Hsc70; and can directly ubiquitylate the water channel AQP2 in vitro. shRNA knockdown of CHIP in CCD cells increased AQP2 protein t1/2 and reduced AQP2 ubiquitylation, resulting in greater levels of AQP2 and phosphorylated AQP2. CHIP knockdown increased the plasma membrane abundance of AQP2 in these cells. Compared with wild-type controls, CHIP knockout mice or novel CRISPR/Cas9 mice without CHIP E3 ligase activity had greater AQP2 abundance and altered renal water handling, with decreased water intake and urine volume, alongside higher urine osmolality. We did not observe significant changes in other water- or sodium-transporting proteins in the gene-modified mice. In summary, these results suggest that CHIP regulates AQP2 and subsequently, renal water handling.
 
 
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CHIP Regulates Aquaporin-2 Quality Control and Body Water Homeostasis

The importance of the kidney distal convoluted tubule (DCT) and cortical collecting duct (CCD) is highlighted by various water and electroly...

Pathogenicity of a Human Laminin {beta}2 Mutation Revealed in Models of Alport Syndrome

Pierson syndrome is a congenital nephrotic syndrome with eye and neurologic defects caused by mutations in laminin β2 (LAMB2), a major component of the glomerular basement membrane (GBM). Pathogenic missense mutations in human LAMB2 cluster in or near the laminin amino-terminal (LN) domain, a domain required for extracellular polymerization of laminin trimers and basement membrane scaffolding. Here, we investigated an LN domain missense mutation, LAMB2-S80R, which was discovered in a patient with Pierson syndrome and unusually late onset of proteinuria. Biochemical data indicated that this mutation impairs laminin polymerization, which we hypothesized to be the cause of the patient’s nephrotic syndrome. Testing this hypothesis in genetically altered mice showed that the corresponding amino acid change (LAMB2-S83R) alone is not pathogenic. However, expression of LAMB2-S83R significantly increased the rate of progression to kidney failure in a Col4a3–/– mouse model of autosomal recessive Alport syndrome and increased proteinuria in Col4a5+/– females that exhibit a mild form of X-linked Alport syndrome due to mosaic deposition of collagen α3α4α5(IV) in the GBM. Collectively, these data show the pathogenicity of LAMB2-S80R and provide the first evidence of genetic modification of Alport phenotypes by variation in another GBM component. This finding could help explain the wide range of Alport syndrome onset and severity observed in patients with Alport syndrome, even for family members who share the same COL4 mutation. Our results also show the complexities of using model organisms to investigate genetic variants suspected of being pathogenic in humans.
 
 
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Pathogenicity of a Human Laminin {beta}2 Mutation Revealed in Models of Alport Syndrome

Pierson syndrome is a congenital nephrotic syndrome with eye and neurologic defects caused by mutations in laminin β 2 ( LAMB2 ), a major co...

Potentiating Tissue-Resident Type 2 Innate Lymphoid Cells by IL-33 to Prevent Renal Ischemia-Reperfusion Injury

The IL-33-type 2 innate lymphoid cell (ILC2) axis has an important role in tissue homeostasis, inflammation, and wound healing. However, the relative importance of this innate immune pathway for immunotherapy against inflammation and tissue damage remains unclear. Here, we show that treatment with recombinant mouse IL-33 prevented renal structural and functional injury and reduced mortality in mice subjected to ischemia-reperfusion injury (IRI). Compared with control-treated IRI mice, IL-33–treated IRI mice had increased levels of IL-4 and IL-13 in serum and kidney and more ILC2, regulatory T cells (Tregs), and anti-inflammatory (M2) macrophages. Depletion of ILC2, but not Tregs, substantially abolished the protective effect of IL-33 on renal IRI. Adoptive transfer of ex vivo–expanded ILC2 prevented renal injury in mice subjected to IRI. This protective effect associated with induction of M2 macrophages in kidney and required ILC2 production of amphiregulin. Treatment of mice with IL-33 or ILC2 after IRI was also renoprotective. Furthermore, in a humanized mouse model of renal IRI, treatment with human IL-33 or transfer of ex vivo–expanded human ILC2 ameliorated renal IRI. This study has uncovered a major protective role of the IL-33–ILC2 axis in renal IRI that could be potentiated as a therapeutic strategy.
 
 
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Potentiating Tissue-Resident Type 2 Innate Lymphoid Cells by IL-33 to Prevent Renal Ischemia-Reperfusion Injury

The IL-33-type 2 innate lymphoid cell (ILC2) axis has an important role in tissue homeostasis, inflammation, and wound healing. However, the...

Plasma Potassium Determines NCC Abundance in Adult Kidney-Specific {gamma}ENaC Knockout

The amiloride-sensitive epithelial sodium channel (ENaC) and the thiazide-sensitive sodium chloride cotransporter (NCC) are key regulators of sodium and potassium and colocalize in the late distal convoluted tubule of the kidney. Loss of the αENaC subunit leads to a perinatal lethal phenotype characterized by sodium loss and hyperkalemia resembling the human syndrome pseudohypoaldosteronism type 1 (PHA-I). In adulthood, inducible nephron-specific deletion of αENaC in mice mimics the lethal phenotype observed in neonates, and as in humans, this phenotype is prevented by a high sodium (HNa+)/low potassium (LK+) rescue diet. Rescue reflects activation of NCC, which is suppressed at baseline by elevated plasma potassium concentration. In this study, we investigated the role of the ENaC subunit in the PHA-I phenotype. Nephron-specific ENaC knockout mice also presented with salt-wasting syndrome and severe hyperkalemia. Unlike mice lacking αENaC or βENaC, an HNa+/LK+ diet did not normalize plasma potassium (K+) concentration or increase NCC activation. However, when K+ was eliminated from the diet at the time that ENaC was deleted, plasma K+ concentration and NCC activity remained normal, and progressive weight loss was prevented. Loss of the late distal convoluted tubule, as well as overall reduced βENaC subunit expression, may be responsible for the more severe hyperkalemia. We conclude that plasma K+ concentration becomes the determining and limiting factor in regulating NCC activity, regardless of Na+ balance in ENaC-deficient mice.
 
 
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Plasma Potassium Determines NCC Abundance in Adult Kidney-Specific {gamma}ENaC Knockout

The amiloride-sensitive epithelial sodium channel (ENaC) and the thiazide-sensitive sodium chloride cotransporter (NCC) are key regulators o...

Magnesium and Risk of Hip Fracture among Patients Undergoing Hemodialysis

Magnesium is an essential mineral for bone metabolism. However, little is known about the relationship between magnesium and the risk of fractures. In this cohort study, we elucidated the association between serum magnesium level and the risk of incident hip fracture among patients undergoing hemodialysis. We identified 113,683 patients undergoing hemodialysis with no history of hip fracture from a nation-wide database of patients undergoing dialysis in Japan. During a 2-year follow-up, a total of 2305 (2%) new hip fractures occurred. The crude incidence rate was significantly higher among patients in the lower quartiles of serum magnesium levels (2.63%, 2.08%, 1.76%, and 1.49% in Q1–Q4, respectively; P<0.001 for trend). The range of serum magnesium levels (in milligrams per deciliter) in each quartile was as follows: Q1, <2.3; Q2, 2.4–2.6; Q3, 2.7–2.8, and Q4, >2.9. After adjustment for demographic and clinical factors, patients in Q1 had a 1.23-fold higher risk for hip fracture than those in Q4 (95% confidence interval, 1.06 to 1.44; P<0.01). Similarly, an inverse probability weighting analysis showed an increased risk of hip fracture among patients in the lower magnesium quartiles. We did not observe significant effect modifications in subgroup analyses. The population-attributable fraction of serum magnesium level for incident hip fractures was 13.7% (95% confidence interval, 3.7% to 22.7%), which was much higher than that of serum calcium, serum phosphate, and parathyroid hormone levels. Thus, mild hypermagnesemia is associated with a lower risk of hip fracture among patients undergoing hemodialysis.
 
 
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Magnesium and Risk of Hip Fracture among Patients Undergoing Hemodialysis

Magnesium is an essential mineral for bone metabolism. However, little is known about the relationship between magnesium and the risk of fra...

Causes of Death after a Hospitalization with AKI

Mortality after AKI is high, but the causes of death are not well described. To better understand causes of death in patients after a hospitalization with AKI and to determine patient and hospital factors associated with mortality, we conducted a population-based study of residents in Ontario, Canada, who survived a hospitalization with AKI from 2003 to 2013. Using linked administrative databases, we categorized cause of death in the year after hospital discharge as cardiovascular, cancer, infection-related, or other. We calculated standardized mortality ratios to compare the causes of death in survivors of AKI with those in the general adult population and used Cox proportional hazards modeling to estimate determinants of death. Of the 156,690 patients included, 43,422 (28%) died in the subsequent year. The most common causes of death were cardiovascular disease (28%) and cancer (28%), with respective standardized mortality ratios nearly six-fold (5.81; 95% confidence interval [95% CI], 5.70 to 5.92) and eight-fold (7.87; 95% CI, 7.72 to 8.02) higher than those in the general population. The highest standardized mortality ratios were for bladder cancer (18.24; 95% CI, 17.10 to 19.41), gynecologic cancer (16.83; 95% CI, 15.63 to 18.07), and leukemia (14.99; 95% CI, 14.16 to 15.85). Along with older age and nursing home residence, cancer and chemotherapy strongly associated with 1-year mortality. In conclusion, cancer-related death was as common as cardiovascular death in these patients; moreover, cancer-related deaths occurred at substantially higher rates than in the general population. Strategies are needed to care for and counsel patients with cancer who experience AKI.
 
 
from Journal of the American Society of Nephrology current issue http://ift.tt/2HQ9uci

Causes of Death after a Hospitalization with AKI

Mortality after AKI is high, but the causes of death are not well described. To better understand causes of death in patients after a hospit...

Long-Term Clinical Outcomes after Early Initiation of RRT in Critically Ill Patients with AKI

Whether earlier initiation of RRT in critically ill patients with AKI can improve outcomes remains debated. We examined follow-up data from a large clinical trial to prospectively investigate the long-term outcomes associated with the timing of RRT initiation in such patients. We extended the follow-up of patients in the Early Versus Delayed Initiation of RRT in Critically Ill Patients with AKI (ELAIN) Trial from 90 days to 1 year after randomization for 230 (99.6%) patients. The primary outcome was a composite of major adverse kidney events (persistent renal dysfunction, dialysis dependence, and mortality) at 1 year. Secondary outcomes included inflammatory markers. Overall, 72 of 111 (64.9%) and 106 of 119 (89.1%) patients met the primary outcome in the early (stage 2 AKI) and delayed (stage 3 AKI) initiation groups, respectively (odds ratio [OR] with early initiation, 0.23; 95% confidence interval [95% CI], 0.11 to 0.45; P< 0.001). The early initiation group had a 1-year all-cause mortality rate (56 of 111 [50.2%]) significantly lower than that of the delayed initiation group (83 of 119 [69.8%]; absolute difference, –19.6%; 95% CI, –32.0% to –7.2%; P<0.01). After 1 year, 16 of 55 (29.1%) and 23 of 36 (63.9%) surviving patients in the early and delayed groups, respectively, failed to recover renal function (absolute difference, –34.8%; 95% CI, –54.6% to –15.0%; P=0.001). In conclusion, early initiation of RRT in these critically ill patients with AKI significantly reduced the occurrence of major adverse kidney events, reduced mortality, and enhanced renal recovery at 1 year.
 
 
from Journal of the American Society of Nephrology current issue http://ift.tt/2FEA6w1

Long-Term Clinical Outcomes after Early Initiation of RRT in Critically Ill Patients with AKI

Whether earlier initiation of RRT in critically ill patients with AKI can improve outcomes remains debated. We examined follow-up data from ...

Maternal and Fetal Outcomes of Pregnancies in Women with Atypical Hemolytic Uremic Syndrome

Atypical HUS (aHUS) is a disorder most commonly caused by inherited defects of the alternative pathway of complement, or the proteins that regulate this pathway, and life-threatening episodes of aHUS can be provoked by pregnancy. We retrospectively and prospectively investigated 27 maternal and fetal pregnancy outcomes in 14 women with aHUS from the Vienna Thrombotic Microangiopathy Cohort. Seven pregnancies (26%) were complicated by pregnancy-associated aHUS (p-aHUS), of which three appeared to be provoked by infection, bleeding, and curettage, and three individuals were considered to have preeclampsia/HELLP syndrome before the definitive diagnosis of p-aHUS was made. Mutations in genes that encode the complement alternative pathway proteins or the molecules that regulate this pathway were detected in 71% of the women, with no relationship to pregnancy outcome. Twenty-one pregnancies (78%) resulted in a live birth, two preterm infants were stillborn, and four pregnancies resulted in early spontaneous abortions. Although short-term renal outcome was good in most women, long-term renal outcome was poor; among the 14 women, four had CKD stage 1–4, five had received a renal allograft, and three were dialysis-dependent at study end. We prospectively followed nine pregnancies of four women and treated six of these pregnancies with prophylactic plasma infusions (one pregnancy resulted in p-aHUS, one intrauterine fetal death occurred, and seven pregancies were uneventful). Our study emphasizes the frequency of successful pregnancies in women with aHUS. Close monitoring of such pregnancies for episodes of thrombotic microangiopathy is essential but, the best strategy to prevent these episodes remains unclear.
 
 
from Journal of the American Society of Nephrology current issue http://ift.tt/2oEkJf7

Maternal and Fetal Outcomes of Pregnancies in Women with Atypical Hemolytic Uremic Syndrome

Atypical HUS (aHUS) is a disorder most commonly caused by inherited defects of the alternative pathway of complement, or the proteins that r...

Fibrotic Venous Remodeling and Nonmaturation of Arteriovenous Fistulas

The frequency of primary failure in arteriovenous fistulas (AVFs) remains unacceptably high. This lack of improvement is due in part to a poor understanding of the pathobiology underlying AVF nonmaturation. This observational study quantified the progression of three vascular features, medial fibrosis, intimal hyperplasia (IH), and collagen fiber organization, during early AVF remodeling and evaluated the associations thereof with AVF nonmaturation. We obtained venous samples from patients undergoing two-stage upper-arm AVF surgeries at a single center, including intraoperative veins at the first-stage access creation surgery and AVFs at the second-stage transposition procedure. Paired venous samples from both stages were used to evaluate change in these vascular features after anastomosis. Anatomic nonmaturation (AVF diameter never ≥6 mm) occurred in 39 of 161 (24%) patients. Neither preexisting fibrosis nor IH predicted AVF outcomes. Postoperative medial fibrosis associated with nonmaturation (odds ratio [OR], 1.55; 95% confidence interval [95% CI], 1.05 to 2.30; P=0.03, per 10% absolute increase in fibrosis), whereas postoperative IH only associated with failure in those individuals with medial fibrosis over the population’s median value (OR, 2.63; 95% CI, 1.07 to 6.46; P=0.04, per increase of 1 in the intima/media ratio). Analysis of postoperative medial collagen organization revealed that circumferential alignment of fibers around the lumen associated with AVF nonmaturation (OR, 1.38; 95% CI, 1.03 to 1.84; P=0.03, per 10° increase in angle). This study demonstrates that excessive fibrotic remodeling of the vein after AVF creation is an important risk factor for nonmaturation and that high medial fibrosis determines the stenotic potential of IH.
 
 
from Journal of the American Society of Nephrology current issue http://ift.tt/2FFbraW

Fibrotic Venous Remodeling and Nonmaturation of Arteriovenous Fistulas

The frequency of primary failure in arteriovenous fistulas (AVFs) remains unacceptably high. This lack of improvement is due in part to a po...

Acidosis and Deafness in Patients with Recessive Mutations in FOXI1

Maintenance of the composition of inner ear fluid and regulation of electrolytes and acid-base homeostasis in the collecting duct system of the kidney require an overlapping set of membrane transport proteins regulated by the forkhead transcription factor FOXI1. In two unrelated consanguineous families, we identified three patients with novel homozygous missense mutations in FOXI1 (p.L146F and p.R213P) predicted to affect the highly conserved DNA binding domain. Patients presented with early-onset sensorineural deafness and distal renal tubular acidosis. In cultured cells, the mutations reduced the DNA binding affinity of FOXI1, which hence, failed to adequately activate genes crucial for normal inner ear function and acid-base regulation in the kidney. A substantial proportion of patients with a clinical diagnosis of inherited distal renal tubular acidosis has no identified causative mutations in currently known disease genes. Our data suggest that recessive mutations in FOXI1 can explain the disease in a subset of these patients.
 
 
from Journal of the American Society of Nephrology current issue http://ift.tt/2HVKfWc

Acidosis and Deafness in Patients with Recessive Mutations in FOXI1

Maintenance of the composition of inner ear fluid and regulation of electrolytes and acid-base homeostasis in the collecting duct system of ...

Control of Humoral Response in Renal Transplantation by Belatacept Depends on a Direct Effect on B Cells and Impaired T Follicular Helper-B Cell Crosstalk

Generation of de novo donor-specific antibodies (dnDSAs) after renal transplant is recognized as the leading cause of late transplant failure. Hence, the optimal immunosuppressive strategies to limit dnDSA development need to be defined. Recent clinical trials using the novel costimulatory blockade agent CTLA4-Ig (Belatacept) have shown that kidney transplant recipients (KTRs) treated with Belatacept have better graft survival and function and a lower proportion of dnDSAs than control-treated KTRs. Mechanisms involved in the control of humoral responses by Belatacept remain to be investigated. Here, we analyzed the effect of Belatacept on different steps of the B cell–mediated response in humans. In vitro, Belatacept reduced plasmablast differentiation, Ig production, and the expression of the major transcription factor involved in plasma cell function, Blimp-1, in a T cell–independent manner. Moreover, Belatacept induced activation of the STAT3 transcription factor in stimulated B cells and reduced the expression of CD86. Additionally, Belatacept blocked CD28-mediated activation of T follicular helper cells (Tfhs) in an autologous Tfh-memory B cells model. We then validated these observations in KTRs treated with Belatacept, who had a reduced proportion of blood effector B cells and activated Tfh (PD1+ICOS+) compared with control-treated KTRs. Our in vitro and in vivo results suggest that Belatacept modulates B cell function directly and at the level of B cell-Tfh interaction. These mechanisms likely account for the optimal control of humoral responses observed in KTRs treated with Belatacept.
 
 
from Journal of the American Society of Nephrology current issue http://ift.tt/2FCYFcM

Control of Humoral Response in Renal Transplantation by Belatacept Depends on a Direct Effect on B Cells and Impaired T Follicular Helper-B Cell Crosstalk

Generation of de novo donor-specific antibodies ( dn DSAs) after renal transplant is recognized as the leading cause of late transplant fai...

Uremic Solute-Aryl Hydrocarbon Receptor-Tissue Factor Axis Associates with Thrombosis after Vascular Injury in Humans

Individuals with CKD are particularly predisposed to thrombosis after vascular injury. Using mouse models, we recently described indoxyl sulfate, a tryptophan metabolite retained in CKD and an activator of tissue factor (TF) through aryl hydrocarbon receptor (AHR) signaling, as an inducer of thrombosis across the CKD spectrum. However, the translation of findings from animal models to humans is often challenging. Here, we investigated the uremic solute–AHR–TF thrombosis axis in two human cohorts, using a targeted metabolomics approach to probe a set of tryptophan products and high-throughput assays to measure AHR and TF activity. Analysis of baseline serum samples was performed from 473 participants with advanced CKD from the Dialysis Access Consortium Clopidogrel Prevention of Early AV Fistula Thrombosis trial. Participants with subsequent arteriovenous thrombosis had significantly higher levels of indoxyl sulfate and kynurenine, another uremic solute, and greater activity of AHR and TF, than those without thrombosis. Pattern recognition analysis using the components of the thrombosis axis facilitated clustering of the thrombotic and nonthrombotic groups. We further validated these findings using 377 baseline samples from participants in the Thrombolysis in Myocardial Infarction II trial, many of whom had CKD stage 2–3. Mechanistic probing revealed that kynurenine enhances thrombosis after vascular injury in an animal model and regulates thrombosis in an AHR-dependent manner. This human validation of the solute-AHR-TF axis supports further studies probing its utility in risk stratification of patients with CKD and exploring its role in other diseases with heightened risk of thrombosis.
 
 
from Journal of the American Society of Nephrology current issue http://ift.tt/2oFuOs6

Uremic Solute-Aryl Hydrocarbon Receptor-Tissue Factor Axis Associates with Thrombosis after Vascular Injury in Humans

Individuals with CKD are particularly predisposed to thrombosis after vascular injury. Using mouse models, we recently described indoxyl sul...

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In this article we look at what causes uncomfortable gas in the chest, how to tell it apart from a heart attack, and how to relieve symptoms...

Medical News Today: What foods should you eat if you have pancreatitis?

We take a look at how diet can help with pancreatitis, including foods to eat and foods to avoid. We also examine diet tips and treatment op...

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Fox News Breaking News Alert Trump defends call to arm teachers, wants to raise gun purchase age 02/22/18 9:01 AM

Medical News Today: What home remedies can help with a runny nose?

This article examines a number of simple ways to stop a runny nose that can be tried at home. We also provide tips on how to cope with a run...

Medical News Today: This specialized gel could improve cancer therapy

Researchers are testing a promising new gel-like medium capable of delivering a combination of therapeutic agents directly to the sites of p...

Medical News Today: Is social media ruining your social life?

A new study tests the theory that the more time you spend on social media, the less time you spend socializing with people in real life. f...

Medical News Today: What is aseptic meningitis?

Learn all about aseptic meningitis, a form of meningitis not caused by bacteria. We look at what does cause it, the symptoms, and treatment ...

Medical News Today: What is dependent edema?

A look at dependent edema, a condition where fluid pools in the lower parts of the body. Included is detail on treatment options and the war...

Medical News Today: What are lymphocytes and what are healthy levels to have?

Learn more about lymphocytes, a type of white blood cell. We look at their function, normal levels, and what happens if levels are too high ...

Medical News Today: What does the SGOT blood test mean?

A close look at the SGOT blood test, which is one part of a liver profile. We examine what the results mean and why the test is performed. ...

Medical News Today: Gout drug could help treat heart failure

A drug used for the treatment of gout has been found to improve heart functioning in a small number of people with heart failure, researcher...

Medical News Today: Marijuana: Good or bad?

More and more, marijuana is being legalized for medicinal or recreational purposes, but what are the health benefits and risks of the drug? ...

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Fox News Breaking News Alert Police officer shot dead in Maryland after intervening in domestic violence dispute 02/21/18 12:21 PM

Medical News Today: How one enzyme could stop the spread of cancer

A study reveals that activation of the enzyme RIPK1 can trigger cell death in cancer cells poised to migrate by causing them to degrade thei...

Medical News Today: The difference between dandruff and a dry scalp

We look at how the causes, symptoms, and treatment options for both dandruff and a dry scalp may differ, and what the link is between the tw...

Medical News Today: How can I lower my insulin levels?

In this article, we look at nine ways to lower high insulin levels. This can be achieved through diet, lifestyle changes, supplements, and m...

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Fox News Breaking News Alert The Rev. Billy Graham, prominent Christian evangelist, dead at 99, Fox News confirms 02/21/18 8:21 AM

Medical News Today: Why is my ankle itchy?

An itchy ankle is a complaint with a wide variety of causes. We discuss possible causes, means of prevention and when to see a doctor. fro...

Medical News Today: Do sad children overeat?

Many adults overeat when they feel low, and some binge when they are elated. A new study investigates whether children do the same. from F...

Medical News Today: Why do mosquito bites itch and swell up?

In this article we look at why mosquito bites itch, evidence-backed ways to reduce itching and swelling, and discuss when to see a doctor. ...

Medical News Today: Alcohol use disorder is a 'major risk factor' for dementia

In a large-scale study, links between alcohol use disorder and dementia are fleshed out. The relationship is stronger than previously though...

Medical News Today: Music makes us enjoy exercise more, finds brain study

If you find exercise dull, a new study suggests you might want to grab your headphones; listening to music can increase our enjoyment of phy...

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Fox News Breaking News Alert Alabama police officer killed in shooting 02/21/18 4:23 AM

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Fox News Breaking News Alert Alex Van Der Zwaan, lawyer linked to ex-Trump adviser Rick Gates, pleads guilty to lying to FBI 02/20/18 4:...

Medical News Today: How long will pain last after route canal?

A look at pain after a root canal, a common complaint that can last for some time. Included is detail on when to get help and managing root ...

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Fox News Breaking News Alert Alex Van Der Zwaan, lawyer linked to ex-Trump adviser Rick Gates, pleads guilty to lying to FBI 02/20/18 3:...

Medical News Today: How should you treat an ingrown hair cyst?

Learn about ingrown hair cysts, which develop when an ingrown hair becomes a fluid-filled lump. We look at treatment options and how a cyst ...

Medical News Today: Ten reasons why cramps happen after your period

In this article, we look at common causes of cramps that occur after your period ends. We also look at symptoms, and ways to manage period c...

Medical News Today: Type 1 diabetes: Does the gut hold the key to prevention?

Researchers suggest that targeting the gut microbiota could be a potential strategy for the prevention and treatment of type 1 diabetes. f...

Medical News Today: Low-fat vs. low-carb: Which diet is best for weight loss?

Dieters must often pick a side in the low-carb vs. low-fat diet question, but how can they know which is best for them? A new study weighs i...

Medical News Today: Fathers, your stress could affect your child's brain

The stress that fathers experience over their lifetime can alter their sperm in ways that influence brain development in their offspring, a ...

Medical News Today: How do you get rid of chest acne?

A look at chest acne, a condition where acne appears on the chest. Included is detail on when to see a doctor and lifestyle changes that mig...

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Fox News Breaking News Alert Special counsel Robert Mueller's team files new charge in Russia probe 02/20/18 9:53 AM

Medical News Today: How do you get rid of acne around your nose?

A look at nose acne, a common condition with a range of causes. Included is detail on the different types of nose acne and ways to prevent t...

Medical News Today: How to treat and prevent scalp acne

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Medical News Today: What causes pain under my left breast?

Learn about a number of digestive and heart-related causes of pain under the left breast. We also look at the treatment options available fo...

Medical News Today: Psoriasis drug may lower heart disease risk

A new study finds that a psoriasis drug might help to reduce heart disease risk. Overall, it reduced a particular risk marker by 19 percent....

Medical News Today: Even light exercise can increase men's lifespan

A study looked at the effects of a few minutes of light physical activity on senior men and found that modest levels of activity may improve...

Medical News Today: What causes a tilted uterus?

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As Some Got Free Health Care, Gwen Got Squeezed: An Obamacare Dilemma

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Medical News Today: What are the best foot exercises for healthy feet?

A look at foot exercises for strength, flexibility, and pain relief. Find detail on mobility and foot health, as well as safety tips to prev...

Medical News Today: Cutting back on carbs could help treat fatty liver disease

A new study reveals how reducing the intake of carbohydrates could help to reduce the buildup of liver fat in people who are obese. from F...

Medical News Today: Why does the penis change color?

A look at purple penis, a color change that most often occurs during arousal. Learn more about the other potential causes and what to do her...

Medical News Today: Can a vagina be too tight?

Sometimes women feel vaginal tightness, but can a vagina be too tight? Included is detail on how the vagina changes during the course of a w...

Medical News Today: New blood test predicts autism with 92 percent accuracy

Scientists have designed a test they believe is the first of its kind. Using blood and urine samples, the test correctly identified autism i...

Doctors Said Immunotherapy Would Not Cure Her Cancer. They Were Wrong.

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Medical News Today: 'Too much' brain calcium may cause Parkinson's

Calcium may affect how alpha-synuclein — a protein linked to Parkinson's — interacts with structures important for chemical signaling be...

Medical News Today: How to remove a pimple in your ear

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Medical News Today: What are the effects of an enlarged prostate on sex?

Learn about how benign prostatic hyperplasia can affect sexual function. We look at the effects and treatment options, including surgery, he...

Medical News Today: What are the symptoms of a broken foot?

A look at the symptoms that can be a sign that a foot bone is broken. Included is detail on the structure of the foot and how a broken bone ...

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Fox News Breaking News Alert At least 27 killed in ambush on Iraqi troops, officials say 02/19/18 5:56 AM

Medical News Today: Drinking soda daily may harm your fertility

Researchers have uncovered a link between conception and soda: drinking it daily could harm your chances of becoming pregnant. This goes for...

Medical News Today: It's official: Pets benefit our mental health

A systematic review of existing studies lists the many ways in which pets provide people with mental health issues some much-needed comfort....

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Fox News Breaking News Alert 4 people killed in shooting at church in Russia, Tass news agency reports 02/18/18 10:13 AM

Medical News Today: Osteoarthritis: Could researchers have found the key to prevention?

Researchers reveal how FoxO proteins are important for joint health, and how increasing the levels of these proteins could prevent or treat ...

Medical News Today: How making fun of yourself can make you happy

A new study has examined the psychological benefits and disadvantages of self-deprecating humor. The findings may come as a surprise for man...

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Fox News Breaking News Alert Vice President Mike Pence delivers remarks at America First Policies event 02/17/18 11:43 AM

America at Home: Grandparents in the Attic, Children in the Basement

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Medical News Today: Single dads twice as likely to die prematurely

Single fathers are more than twice as likely to die prematurely than their partnered counterparts or single moms, suggests a large-scale new...

Medical News Today: Just 1 hour of gaming may improve attention

Researchers found that playing a video game for just 1 hour led to an increase in brain activity and improved visual selective attention. ...

Medical News Today: How can I get rid of milia?

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Lassa Fever Erupts in Nigeria

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Fox News Breaking News Alert Deputy Attorney General Rod Rosenstein says no Americans were "knowing" participants in alleged ele...

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Fox News Breaking News Alert Deputy Attorney General Rod Rosenstein holds press conference 02/16/18 1:22 PM

Medical News Today: Common blood pressure drug may prevent type 1 diabetes

Researchers reveal that methyldopa — a drug commonly used to lower blood pressure — could also be used for the prevention and treatment of t...

Medical News Today: What is golfer's elbow and how is it treated?

In this article, we look at medial epicondylitis, its symptoms, and causes. We also provide information on treatment and exercises for it. ...

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Fox News Breaking News Alert FBI says it received tip in January regarding Nikolas Cruz 02/16/18 12:41 PM

Medical News Today: What side effects can result from interferon?

Interferon is used to treat several health conditions, but it has a range of side effects. We look at how these vary in severity and duratio...

Medical News Today: What are the health benefits of being creative?

From writing to dancing, creative activities can make our life more fun. Studies show that they can actually do wonders for our mental and p...

Medical News Today: How does exercise preserve the aging brain?

Higher cardiorespiratory fitness is tied to stronger white matter and better cognitive performance in a study of seniors with mild cognitive...

Medical News Today: What are the different types of poop?

A look at different types of poop, which has a range of consistencies and odors. Learn more about the different types and what they mean her...

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Fox News Breaking News Alert Mitt Romney announces US Senate run in Utah 02/16/18 8:28 AM

Medical News Today: Natural remedies for constipation

We look at some possible natural alternatives to laxatives for people looking to have a bowel movement. We also look at when to see a doctor...

Medical News Today: Stroke risk may depend on your height as a child

A new study from Denmark suggests that individuals who did not reach average height as children may be more exposed to stroke as adults. f...

Medical News Today: What causes a buildup of pressure behind the eyes?

In this article, we look at reasons for feelings of pressure behind the eye, including a migraine or sinus infection. When should you see a ...

Medical News Today: Ovarian cancer: How your father's genes can affect your risk

New research finds that fathers can pass their daughters a genetic mutation that can cause ovarian cancer. It can also cause prostate cancer...

The Flu Vaccine Is Working Better Than Expected, C.D.C. Finds

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Diplomats in Cuba Suffered Brain Injuries. Experts Still Don’t Know Why.

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Fox News Breaking News Alert Senate blocks immigration plans including bipartisan proposal slammed by Trump as 'total catastrophe'...

Medical News Today: How do I stop stress eating?

A look at emotional eating when people use food to cope with emotions, such as stress. Included is detail on the causes and common triggers ...

Transgender Woman Breast-Feeds Baby After Hospital Induces Lactation

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Fox News Breaking News Alert WATCH LIVE: Florida school gunman appears in court via videoconference 02/15/18 2:00 PM

Medical News Today: How to treat an infected hangnail

Find out how to treat an infected hangnail. In this article, we cover home remedies, how to drain an abscess, prevention methods, and sympto...

Medical News Today: The 10 things you should know about your vagina

Think you know all there is to know about your lady parts? Think again. Here, we take you through 10 things that you should know about the v...

Medical News Today: Have scientists found an anti-cancer vaccine?

Researchers used stem cells to create an anti-cancer vaccine, which they tested in 75 mice with various types of cancer. Here's what the...

Medical News Today: Running may protect your memory from stress

Chronic stress can affect our brain health, and particularly our memory. Not to worry, though; a new study has found that running could offs...

Medical News Today: What to do about tightness in the throat

A look at tightness in the throat, an uncomfortable feeling that has a range of causes. Included is detail on anxiety and the symptoms of th...

Medical News Today: Cancer: 'Ultra-processed' foods may increase risk

A new study suggests a possible link between the consumption of ultra-processed foods and raised risk of overall cancer, and breast cancer i...

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Fox News Breaking News Alert WATCH LIVE: President Trump addresses nation on Florida shooting 02/15/18 11:05 AM

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Fox News Breaking News Alert WATCH LIVE: Authorities hold press conference after school shooting 02/15/18 10:36 AM

Medical News Today: What is the apple cider vinegar detox?

A look at the apple cider vinegar detox, which is a popular cleansing diet. Included is detail on scientific studies and the potential adver...

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Fox News Breaking News Alert Trump to address nation after Florida school shooting 02/15/18 9:04 AM

Medical News Today: What is the best way to get rid of visceral fat?

A look at visceral fat, the fat stored in a person’s abdominal cavity. Included is detail on when to see a doctor and the outlook for people...

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Fox News Breaking News Alert Mug shot released of Nikolas Cruz, suspected gunman of Florida high school shooting 02/15/18 6:48 AM

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Fox News Breaking News Alert Federal judge rules toxic burn pits connected to service members’ lung disease 02/15/18 6:40 AM

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Fox News Breaking News Alert Aaron Feis, a football coach at Marjory Stoneman Douglas High School in Parkland, Fla., first fatality to be ...

Medical News Today: Can't keep the weight off? This may be why

Our bodies don't take well to repeated dieting, which they perceive as potentially dangerous. One protein, however, may be key to preven...

Medical News Today: What is an esophageal spasm?

A look at esophageal spasms, a condition where the food pipe in the throat twitches or convulses uncontrollably. Included is detail on diagn...

Medical News Today: Your partner's stress may change your brain

A new study examines how stress affects pairs of male and female mice. It reveals that not only is stress contagious, but it also leads to b...

Lena Dunham Says She Had Hysterectomy After Endometriosis

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New York Will Investigate Reports of Gay Men Denied Insurance

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First Blood Test to Detect Concussions Is Approved

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Fox News Breaking News Alert

Fox News Breaking News Alert At least 17 killed in Florida high school shooting, sheriff confirms 02/14/18 6:30 PM

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Fox News Breaking News Alert Florida high school shooting suspect identified as Nicolas Cruz, US official tells AP 02/14/18 5:35 PM

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Fox News Breaking News Alert Florida high school shooting suspect is former student, "multiple" deaths, sheriff confirms 02/14...

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Fox News Breaking News Alert 'At least 14 victims' in Florida high school shooting, sheriff says 02/14/18 4:30 PM

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Fox News Breaking News Alert Florida high school shooting suspect 'in custody,' sheriff says 02/14/18 4:15 PM

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Fox News Breaking News Alert South African President Jacob Zuma resigns from office 02/14/18 4:10 PM

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Fox News Breaking News Alert Trump reacts to shooting: Nobody should 'feel unsafe' in an American school 02/14/18 4:04 PM

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Fox News Breaking News Alert 'Many deaths' in Florida high school shooting, Sen. Nelson tells Fox News 02/14/18 3:59 PM

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Fox News Breaking News Alert At least 20 feared hurt in Florida high school shooting 02/14/18 3:45 PM

Medical News Today: What is an intercostal muscle strain?

Learn all about intercostal muscle strain, when the muscles between the ribs are damaged. We look at the signs, causes, and treatment option...

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Fox News Breaking News Alert Sen. Elizabeth Warren blasts Trump over nickname in speech to Native Americans, insists Cherokee heritage rea...

Medical News Today: How do penile implants work?

Penile implant surgery can help with erectile dysfunction that has not responded to other treatments. We look at the available types and how...

Medical News Today: Cholesterol-removing gene may prevent heart disease

Researchers have discovered that a gene once believed to be 'useless' actually helps to remove excess cholesterol from the blood ves...

Medical News Today: Blocking enzyme 'dramatically reverses' Alzheimer's in mice

For the first time, scientists achieve a 'dramatic reversal' of Alzheimer's-related brain damage in mice, offering hope for huma...

Medical News Today: Five health benefits of being single

Several studies cite the health benefits of living together or getting married, but how might staying single positively affect our health? W...

Medical News Today: Is there an average weight for men?

A look at the average weight for men, a statistic that depends on several factors. Included is detail on ideal weight and how to reach and m...

Medical News Today: Obesity: You don't have to lose weight to be fit

A study shows that obese people can have good cardiovascular health, as long as they are fit, and high fitness brings even more benefit in s...

Medical News Today: What is cholinergic urticaria and how is it treated?

Learn about cholinergic urticaria, a rash that can appear when the body gets warm and sweats. We look at symptoms, treatment, diagnosis, and...

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Fox News Breaking News Alert Shooting outside National Security Agency in Maryland, suspect held, AP reports 02/14/18 8:28 AM

Medical News Today: What is De Quervain's tenosynovitis?

A look at De Quervain’s tenosynovitis where the tendons of the thumb become inflamed. Included is detail on symptoms and exercises for the c...

Medical News Today: Are there any home remedies for ringworm?

A look at home remedies for ringworm, a condition that results in fungal infection on the skin. Included is detail on when to see a doctor a...

Medical News Today: Brain activity explains drunken aggression

A new study examines what goes on inside the brains of intoxicated young men. The findings may help to reduce alcohol-related crime. from ...

Medical News Today: Will your partner cheat? Look out for these signs

Is there a way to predict whether someone is likely to cheat on their romantic partner? New research says that there may be a few signs to l...

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Fox News Breaking News Alert Second judge rules against Trump administration on ending DACA 02/13/18 5:09 PM

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Fox News Breaking News Alert Chicago police officer dies after being shot multiple times, sources tell Fox News 02/13/18 4:36 PM

Medical News Today: Why does my stomach feel tight?

Learn about why your stomach feels tight. We take a look at the various causes, treatments, and conditions associated with a tight stomach. ...

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Fox News Breaking News Alert New York terror bomber sentenced to multiple life sentences for blast that injured 30 02/13/18 2:32 PM

Medical News Today: What is anasarca?

A look at anasarca, a condition that causes a general swelling of the body. Included is detail on how it is diagnosed and the outlook for th...

Medical News Today: Going vegan could prevent type 2 diabetes

Researchers have found that adopting a vegan diet has the potential to prevent type 2 diabetes in people who are overweight or obese. from...

Medical News Today: Should all women get screened for ovarian cancer?

The latest report from the United States Preventive Services Task Force examines whether ovarian cancer screening can reduce mortality among...

Medical News Today: What is Apert syndrome?

Learn about Apert syndrome, a genetic condition that causes abnormal head, hand, and foot development. We look at symptoms, treatment, and o...

Medical News Today: Huntington's 'super assassin' molecule could kill cancer

The gene that causes Huntington's disease is highly toxic to cancer cells, as revealed in tests on laboratory cells and mice with ovaria...

Medical News Today: What is the outlook for hydranencephaly?

Learn more about hydranencephaly, a condition where a baby is born with part of the brain missing. We examine the symptoms and prognosis. ...

Medical News Today: What is palmoplantar pustulosis?

Learn all about palmoplantar pustulosis, a condition that causes blisters to form on the palms and feet. Learn more about the symptoms and t...

Medical News Today: What happens during a testicular ultrasound?

Learn all about testicular ultrasound and its uses. This article explains the procedure, what to expect, and how to prepare for your scan. ...

Medical News Today: Why does my urine smell like ammonia?

A look at urine that smells like ammonia, which can have many causes. Included is detail on when to see a doctor and treatments for the cond...

Medical News Today: Why do some breast cancers become treatment-resistant?

A significant number of estrogen receptor-positive breast cancers are resistant to regular therapies. Why is that, and how can this obstacle...