E.coli outbreak hits polygamist Utah town

Two chidren died in the city of Hildale, Utah, which is home to the polygamous Fundamentalist Church of Latter-Day Saints

From: http://www.cbsnews.com/news/e-coli-outbreak-hits-polygamist-utah-town/

Yemen's civil war fuels cholera outbreak

The two-year civil war in Yemen has devastated much of the nation and left millions on the brink of starvation. It has also spawned a health emergency: cholera. Jonathan Vigliotti has the story from London.

From: http://www.cbsnews.com/videos/yemens-civil-war-fuels-cholera-outbreak/

Yemen suffering from world's largest cholera outbreak

The war has also made it difficult for aid groups to deliver food and fresh water, and the nation's infrastructure -- including hospitals -- are on the brink of collapse

From: http://www.cbsnews.com/news/yemen-suffering-from-worlds-largest-cholera-outbreak/

Repealing Obamacare without replacement would be "very messy"

Margot Sanger-Katz, who covers health care for The New York Times, joins "CBS This Morning: Saturday" to discuss the impact of President Trump's suggestion to repeal the Affordable Care Act first and replace it later.

From: http://www.cbsnews.com/videos/repealing-obamacare-without-replacement-would-be-very-messy/

Heart transplant survivor dies after giving birth to first child

The couple spent six hours with their newborn before she started to experience complications

From: http://www.cbsnews.com/news/megan-johnson-heart-transplant-survivor-dies-after-giving-birth/

Pregnant or trying? Don't let Zika guard down

While cases of the birth defect-causing virus have dropped sharply from last year's peak, Zika hasn't disappeared from the region, experts warn

From: http://www.cbsnews.com/news/science-says-pregnant-or-trying-dont-let-zika-guard-down/

Brain-eating amoeba detected in water system

The Centers for Disease Control and Prevention says residents who use the water system should not let water go up the nose when bathing or swimming in small pools

From: http://www.cbsnews.com/news/brain-eating-amoeba-detected-in-louisiana-water-system/

Teen birth rate drops again to all-time low, CDC says

New government data looks at trends in birth across the United States

From: http://www.cbsnews.com/news/teen-birth-rate-drops-again-to-all-time-low-cdc/

Backlash after councilman asks city to ignore drug overdose calls

"We need to put a fear about overdosing​ in Middletown,"City Council member Dan Picard said

From: http://www.cbsnews.com/news/councilman-asks-if-city-can-stop-responding-to-overdoses/

Studies shed light on teen mental health after concussions

Two new studies look at depression in young athletes in the months and years after head injury

From: http://www.cbsnews.com/news/concussion-studies-shed-light-on-teen-athlete-mental-health-depression/

Trendy new mom practice led to infant's infection

Doctors traced the infection to unlikely source

From: http://www.cbsnews.com/news/new-mom-pregnancy-placenta-pills-led-to-infant-infection/

Trump says Congress should repeal Obamacare now, replace it later

The president said after the election that Obamacare would be repealed and replaced "simultaneously" so millions wouldn't lose coverage

From: http://www.cbsnews.com/news/trump-says-congress-should-repeal-obamacare-now-replace-it-later/

Medicaid cuts in Senate bill could have dire effects at Ohio opioid clinic

CBS News has learned that Senate Republicans, hoping to win support for the Obamacare replacement, have added another $45 billion for the treatment of opioid addiction. However, that is just a fraction of what Medicaid currently covers. So, what happens if Medicaid is cut drastically? Adriana Diaz reports.

From: http://www.cbsnews.com/videos/medicaid-cuts-in-senate-bill-could-have-dire-effects-at-ohio-opioid-clinic/

Cuts in Senate bill could have dire effects on opioid crisis

Proposal in the Senate rolls back Medicaid expansion, and that could potentially cut one treatment center's Medicaid funding by 75 percent

From: http://www.cbsnews.com/news/medicaid-cuts-in-senate-bill-could-have-dire-effects-at-ohio-opioid-clinic/

Laurie Hernandez on grandmother’s battle with Alzheimer’s

The Olympic gymnast and gold medal winner shares her family's story to bring awareness to the memory-robbing disease

From: http://www.cbsnews.com/news/olympic-gymnast-laurie-hernandez-on-her-grandmothers-battle-with-alzheimers/

Repealing Obamacare without replacement would be "very messy"

Margot Sanger-Katz, who covers health care for The New York Times, joins "CBS This Morning: Saturday" to discuss the impact of President Trump's suggestion to repeal the Affordable Care Act first and replace it later.

From: http://www.cbsnews.com/videos/repealing-obamacare-without-replacement-would-be-very-messy/

Pregnancy and bile acid disorders

During pregnancy, extensive adaptations in maternal metabolic and immunological physiology occur. Consequently, preexisting disease may be exacerbated or attenuated, and new disease susceptibility may be unmasked. Cholestatic diseases, characterized by a supraphysiological raise in bile acid levels, require careful monitoring during pregnancy. This review describes the latest advances in the knowledge of intrahepatic cholestasis of pregnancy (ICP), the most common bile acid disorder specific to pregnancy, with a focus on the disease etiology and potential mechanisms of ICP-associated adverse pregnancy outcomes, including fetal demise. The course of preexisting cholestatic conditions in pregnancy is considered, including primary sclerosing cholangitis, primary biliary cholangitis, biliary atresia, and Alagille syndrome. The currently accepted treatments for cholestasis in pregnancy and promising new therapeutics for the condition are described.

From: Pataia, V., Dixon, P. H., Williamson, C. http://ajpgi.physiology.org/cgi/content/abstract/313/1/G1?rss=1

From sensing to shaping microbiota: insights into the role of NOD2 in intestinal homeostasis and progression of Crohns disease

NOD2 was the first susceptibility gene identified for Crohn’s disease (CD), one of the major forms of inflammatory bowel disease (IBD). The field of NOD2 research has opened up many questions critical to understanding the complexities of microbiota-host interactions. In addition to sensing its specific bacterial components as a cytosolic pattern recognition receptor, NOD2 also appears to shape the colonization of intestinal microbiota. Activated NOD2 triggers downstream signaling cascades exampled by the NF-B pathway to induce antimicrobial activities, however, defective or loss of NOD2 functions incur a similarly activated inflammatory response. Additional studies have identified the involvement of NOD2 in protection against non-microbiota-related intestinal damages as well as extraintestinal infections. We survey recent molecular and genetic studies of NOD2-mediated bacterial sensing and immunological modulation, and integrate evidence to suggest a highly reciprocal but still poorly understood cross talk between enteric microbiota and host cells.

From: Balasubramanian, I., Gao, N. http://ajpgi.physiology.org/cgi/content/abstract/313/1/G7?rss=1

A new role for microbiota? Dulling the thrust of serotonin and 5-HT3 signaling cascade

From: Chang, E. B., Rao, M. C. http://ajpgi.physiology.org/cgi/content/full/313/1/G14?rss=1

Expression and localization of VPAC1, the major receptor of vasoactive intestinal peptide along the length of the intestine

Vasoactive intestinal peptide (VIP) is an endogenous neuropeptide with a broad array of physiological functions in many organs including the intestine. Its actions are mediated via G protein-coupled receptors, and vasoactive intestinal peptide receptor 1 (VPAC1) is the key receptor responsible for majority of VIP’s biological activity. The distribution of VPAC1 along the length of the gastrointestinal tract and its subcellular localization in intestinal epithelial cells have not been fully characterized. The current studies were undertaken to determine VPAC1 distribution and localization so that VIP-based therapies can be targeted to specific regions of the intestine. The results indicated that the mRNA levels of VPAC1 showed an abundance pattern of colon > ileum > jejunum in the mouse intestine. In parallel, the VPAC1 protein levels were higher in the mouse colon, followed by the ileum and jejunum. Immunofluorescence studies in mouse colon demonstrated that the receptor was specifically localized to the luminal surface, as was evident by colocalization with the apical marker villin but not with the basolateral marker Na⁺/K⁺-ATPase. In the human intestine, VPAC1 mRNA expression exhibited a distribution similar to that in mouse intestine and was highest in the sigmoid colon. Furthermore, in the human colon, VPAC1 also showed predominantly apical localization. The physiological relevance of the expression and apical localization of VPAC1 remains elusive. We speculate that apical VPAC1 in intestinal epithelial cells may have relevance in recognizing secreted peptides in the intestinal lumen and therefore supports the feasibility of potential therapeutic and targeting use of VIP formulations via oral route to treat gastrointestinal diseases.

NEW & NOTEWORTHY These studies for the first time present comprehensive data on the relative characterization of vasoactive intestinal peptide (VIP) receptors in the intestinal mucosa. Vasoactive intestinal peptide receptor 1 (VPAC1) was identified as the predominant receptor with higher levels in the colon compared with the small intestine and was mainly localized to the apical membrane. In addition, the findings in the human tissues were consistent with VPAC1 expression in the mouse intestine and open possibilities to target colonic tissues with VIP for treating diseases such as inflammatory bowel disease.

From: Jayawardena, D., Guzman, G., Gill, R. K., Alrefai, W. A., Onyuksel, H., Dudeja, P. K. http://ajpgi.physiology.org/cgi/content/abstract/313/1/G16?rss=1

Absence of the NOD2 protein renders epithelia more susceptible to barrier dysfunction due to mitochondrial dysfunction

Irregular mitochondria structure and reduced ATP in some patients with IBD suggest that metabolic stress contributes to disease. Loss-of-function mutation in the nucleotide-binding oligomerization domain (NOD)-2 gene is a major susceptibility trait for IBD. Hence, we assessed if loss of NOD2 further impairs the epithelial barrier function instigated by disruption of mitochondrial ATP synthesis via the hydrogen ionophore dinitrophenol (DNP). NOD2 protein (virtually undetectable in epithelia under basal conditions) was increased in T84 (human colon cell line) cells treated with noninvasive Escherichia coli + DNP (16 h). Increased intracellular bacteria in wild-type (WT) and NOD2 knockdown (KD) cells and colonoids from NOD2^–/– mice were mediated by reactive oxygen species (ROS) and the MAPK ERK1/2 pathways as determined by cotreatment with the antioxidant mitoTEMPO and the ERK inhibitor U0126: ROS was upstream of ERK1/2 activation. Despite increased E. coli in DNP-treated NOD2 KD compared with WT cells, there were no differences in the internalization of fluorescent inert beads or dead E. coli particles. This suggests that lack of killing in the NOD2 KD cells was responsible for the increased numbers of viable intracellular bacteria; a conclusion supported by evidence of reduced autophagy in NOD2 KD T84 epithelia. Thus, in a two-hit hypothesis, decreased barrier function due to dysfunctional mitochondrial is amplified by lack of NOD2 in transporting enterocytes: subsequently, greater numbers of bacteria entering the mucosa would be a significant inflammatory threat especially since individuals with NOD2 mutations have compromised macrophage and Paneth cell responses to bacteria.

NEW & NOTEWORTHY Increased internalization of bacteria by epithelia with dysfunctional mitochondria (reduced ATP) is potentiated if the cells lack nucleotide-binding oligomerization domain 2 (NOD2), mutations in which are inflammatory bowel disease-susceptibility traits. Uptake of bacteria was dependent on reactive oxygen species and MAP-kinase activity, and the increased viable intracellular bacteria in NOD2^–/– cells likely reflect a reduced ability to recognize and kill bacteria. Thus a significant barrier defect occurs with NOD2 deficiency in conjunction with metabolic stress that could contribute to inflammation.

From: Saxena, A., Lopes, F., Poon, K. K. H., McKay, D. M. http://ajpgi.physiology.org/cgi/content/abstract/313/1/G26?rss=1

Targeted inactivation of copper transporter Atp7b in hepatocytes causes liver steatosis and obesity in mice

Copper-transporting ATPase 2 (ATP7B) is essential for mammalian copper homeostasis. Mutations in ATP7B result in copper accumulation, especially in the liver, and cause Wilson disease (WD). The major role of hepatocytes in WD pathology is firmly established. It is less certain whether the excess Cu in hepatocytes is solely responsible for development of WD. To address this issue, we generated a mouse strain for Cre-mediated deletion of Atp7b and inactivated Atp7b selectively in hepatocytes. Atp7b^Hep mice accumulate copper in the liver, have elevated urinary copper, and lack holoceruloplasmin but show no liver disease for up to 30 wk. Liver inflammation is muted and markedly delayed compared with the age-matched Atp7b^–/– null mice, which show a strong type1 inflammatory response. Expression of metallothioneins is higher in Atp7b^Hep livers than in Atp7b^–/– mice, suggesting better sequestration of excess copper. Characterization of purified cell populations also revealed that nonparenchymal cells in Atp7b^Hep liver maintain Atp7b expression, have normal copper balance, and remain largely quiescent. The lack of inflammation unmasked metabolic consequences of copper misbalance in hepatocytes. Atp7b^Hep animals weigh more than controls and have higher levels of liver triglycerides and 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase. By 45 wk, all animals develop liver steatosis on a regular diet. Thus copper misbalance in hepatocytes dysregulates lipid metabolism, whereas development of inflammatory response in WD may depend on copper status of nonparenchymal cells. The implications of these findings for the cell-targeting WD therapies are discussed.

NEW & NOTEWORTHY Targeted inactivation of copper-transporting ATPase 2 (Atp7b) in hepatocytes causes steatosis in the absence of inflammation.

From: Muchenditsi, A., Yang, H., Hamilton, J. P., Koganti, L., Housseau, F., Aronov, L., Fan, H., Pierson, H., Bhattacharjee, A., Murphy, R., Sears, C., Potter, J., Wooton-Kee, C. R., Lutsenko, S. http://ajpgi.physiology.org/cgi/content/abstract/313/1/G39?rss=1

Phosphatidylcholine transfer protein/StarD2 promotes microvesicular steatosis and liver injury in murine experimental steatohepatitis

Mice fed a methionine- and choline-deficient (MCD) diet develop steatohepatitis that recapitulates key features of nonalcoholic steatohepatitis (NASH) in humans. Phosphatidylcholine is the most abundant phospholipid in the surfactant monolayer that coats and stabilizes lipid droplets within cells, and choline is required for its major biosynthetic pathway. Phosphatidylcholine-transfer protein (PC-TP), which exchanges phosphatidylcholines among membranes, is enriched in hepatocytes. PC-TP also regulates fatty acid metabolism through interactions with thioesterase superfamily member 2. We investigated the contribution of PC-TP to steatohepatitis induced by the MCD diet. Pctp^–/– and wild-type control mice were fed the MCD diet for 5 wk and were then euthanized for histopathologic and biochemical analyses, as well as determinations of mRNA and protein expression. Whereas all mice developed steatohepatitis, plasma alanine aminotransferase and aspartate aminotransferase activities were only elevated in wild-type mice, indicating that Pctp^–/– mice were protected from MCD diet-induced hepatocellular injury. Reduced hepatotoxicity due to the MCD diet in the absence of PC-TP expression was further evidenced by decreased activation of c-Jun and reduced plasma concentrations of fibroblast growth factor 21. Despite similar total hepatic concentrations of phosphatidylcholines and other lipids, the relative abundance of microvesicular lipid droplets within hepatocytes was reduced in Pctp^–/– mice. Considering that the formation of larger lipid droplets may serve to protect against lipotoxicity in NASH, our findings suggest a pathogenic role for PC-TP that could be targeted in the management of this condition.

NEW & NOTEWORTHY Phosphatidylcholine-transfer protein (PC-TP) is a highly specific phosphatidylcholine-binding protein that we previously showed to regulate hepatocellular nutrient metabolism through its interacting partner thioesterase superfamily member 2 (Them2). This study identifies a pathogenic role for PC-TP, independent of Them2, in the methionine- and choline-deficient diet model of experimental steatohepatitis. Our current observations suggest that PC-TP promotes liver injury by mediating the intermembrane transfer of phosphatidylcholines, thus stabilizing more pathogenic microvesicular lipid droplets.

From: Nicholls, H. T., Hornick, J. L., Cohen, D. E. http://ajpgi.physiology.org/cgi/content/abstract/313/1/G50?rss=1

Gastroparesis and lipid metabolism-associated dysbiosis in Wistar-Kyoto rats

Altered gastric accommodation and intestinal morphology suggest impaired gastrointestinal (GI) transit may occur in the Wistar-Kyoto (WKY) rat strain, as common in stress-associated functional GI disorders. Because changes in GI transit can alter microbiota composition, we investigated whether these are altered in WKY rats compared with the resilient Sprague-Dawley (SD) rats under basal conditions and characterized plasma lipid and metabolite differences. Bead transit was tracked by X-ray imaging to monitor gastric emptying (4 h), small intestine (SI) transit (9 h), and large intestine transit (12 h). Plasma extracts were analyzed by lipid and hydrophilic interaction liquid chromatography (HILIC) and liquid chromatography-mass spectrometry (LC-MS). Cecal microbial composition was determined by Illumina MiSeq 16S rRNA amplicon sequencing and analysis using the QIIME pipeline. Stomach retention of beads was 77% for WKY compared with 35% for SD rats. GI transit was decreased by 34% (9 h) and 21% (12 h) in WKY compared with SD rats. Excluding stomach retention, transiting beads moved 29% further along the SI over 4–9 h for WKY compared with SD rats. Cecal Ruminococcus, Roseburia, and unclassified Lachnospiraceae genera were less abundant in WKY rats, whereas the minor taxa Dorea, Turicibacter, and Lactobacillus were higher. Diglycerides, triglycerides, phosphatidyl-ethanolamines, and phosphatidylserine were lower in WKY rats, whereas cholesterol esters and taurocholic acids were higher. The unexpected WKY rat phenotype of delayed gastric emptying, yet rapid SI transit, was associated with altered lipid and metabolite profiles. The delayed gastric emptying of the WKY phenotype suggests this rat strain may be useful as a model for gastroparesis.

NEW & NOTEWORTHY This study reveals that the stress-prone Wistar-Kyoto rat strain has a baseline physiology of gastroparesis and rapid small intestine transit, together with metabolic changes consistent with lipid metabolism-associated dysbiosis, compared with nonstress-prone rats. This suggests that the Wistar-Kyoto rat strain may be an appropriate animal model for gastroparesis.

From: Dalziel, J. E., Fraser, K., Young, W., McKenzie, C. M., Bassett, S. A., Roy, N. C. http://ajpgi.physiology.org/cgi/content/abstract/313/1/G62?rss=1

Elevated intrabolus pressure identifies obstructive processes when integrated relaxation pressure is normal on esophageal high-resolution manometry

Elevated integrated relaxation pressure (IRP) on esophageal high-resolution manometry (HRM) identifies obstructive processes at the esophagogastric junction (EGJ). Our aim was to determine whether intrabolus pressure (IBP) can identify structural EGJ processes when IRP is normal. In this observational cohort study, adult patients with dysphagia and undergoing HRM were evaluated for endoscopic evidence of structural EGJ processes (strictures, rings, hiatus hernia) in the setting of normal IRP. HRM metrics [IRP, distal contractile integral (DCI), distal latency (DL), IBP, and EGJ contractile integral (EGJ-CI)] were compared among 74 patients with structural EGJ findings (62.8 ± 1.6 yr, 67.6% women), 27 patients with normal EGD (52.9 ± 3.2 yr, 70.3% women), and 21 healthy controls (27.6 ± 0.6 yr, 52.4% women). Findings were validated in 85 consecutive symptomatic patients to address clinical utility. In the primary cohort, mean IBP (18.4 ± 0.9 mmHg) was higher with structural EGJ findings compared with dysphagia with normal EGD (13.5 ± 1.1 mmHg, P = 0.002) and healthy controls (10.9 ± 0.9 mmHg, P < 0.001). However, mean IRP, DCI, DL, and EGJ-CI were similar across groups (P > 0.05 for each comparison). During multiple rapid swallows, IBP remained higher in the structural findings group compared with controls (P = 0.02). Similar analysis of the prospective validation cohort confirmed IBP elevation in structural EGJ processes, but correlation with dysphagia could not be demonstrated. We conclude that elevated IBP predicts the presence of structural EGJ processes even when IRP is normal, but correlation with dysphagia is suboptimal.

NEW & NOTEWORTHY Integrated relaxation pressure (IRP) above the upper limit of normal defines esophageal outflow obstruction using high-resolution manometry. In patients with normal IRP, elevated intrabolus pressure (IBP) can be a surrogate marker for a structural restrictive or obstructive process at the esophagogastric junction (EGJ). This has the potential to augment the clinical value of esophageal HRM by raising suspicion for a structural EGJ process when IBP is elevated.

From: Quader, F., Reddy, C., Patel, A., Gyawali, C. P. http://ajpgi.physiology.org/cgi/content/abstract/313/1/G73?rss=1

Human-derived gut microbiota modulates colonic secretion in mice by regulating 5-HT3 receptor expression via acetate production

Serotonin [5-hydroxytryptamine (5-HT)], an important neurotransmitter and a paracrine messenger in the gastrointestinal tract, regulates intestinal secretion by its action primarily on 5-HT₃ and 5-HT₄ receptors. Recent studies highlight the role of gut microbiota in 5-HT biosynthesis. In this study, we determine whether human-derived gut microbiota affects host secretory response to 5-HT and 5-HT receptor expression. We used proximal colonic mucosa-submucosa preparation from age-matched Swiss Webster germ-free (GF) and humanized (HM; ex-GF colonized with human gut microbiota) mice. 5-HT evoked a significantly greater increase in short-circuit current (I_sc) in GF compared with HM mice. Additionally, 5-HT₃ receptor mRNA and protein expression was significantly higher in GF compared with HM mice. Ondansetron, a 5-HT₃ receptor antagonist, inhibited 5-HT-evoked I_sc in GF mice but not in HM mice. Furthermore, a 5-HT₃ receptor-selective agonist, 2-methyl-5-hydroxytryptamine hydrochloride, evoked a significantly higher I_sc in GF compared with HM mice. Immunohistochemistry in 5-HT_3A-green fluorescent protein mice localized 5-HT₃ receptor expression to enterochromaffin cells in addition to nerve fibers. The significant difference in 5-HT-evoked I_sc between GF and HM mice persisted in the presence of tetrodotoxin (TTX) but was lost after ondansetron application in the presence of TTX. Application of acetate (10 mM) significantly lowered 5-HT₃ receptor mRNA in GF mouse colonoids. We conclude that host secretory response to 5-HT may be modulated by gut microbiota regulation of 5-HT₃ receptor expression via acetate production. Epithelial 5-HT₃ receptor may function as a mediator of gut microbiota-driven change in intestinal secretion.

NEW & NOTEWORTHY We found that gut microbiota alters serotonin (5-HT)-evoked intestinal secretion in a 5-HT₃ receptor-dependent mechanism and gut microbiota metabolite acetate alters 5-HT₃ receptor expression in colonoids.

View this article's corresponding video summary at https://www.youtube.com/watch?v=aOMYJMuLTcw&feature=youtu.be.

From: Bhattarai, Y., Schmidt, B. A., Linden, D. R., Larson, E. D., Grover, M., Beyder, A., Farrugia, G., Kashyap, P. C. http://ajpgi.physiology.org/cgi/content/abstract/313/1/G80?rss=1

Dr Tedros takes office as WHO Director-General

1 July 2017 | GENEVA – Today, Dr Tedros Adhanom Ghebreyesus takes office as Director-General of the World Health Organization. The Director-General is WHO's chief technical and administrative officer and oversees the policy for the Organization's international health work.

From: http://www.who.int/entity/mediacentre/news/releases/2017/tedros-director-general/en/index.html