01/15/16

Friday, January 15, 2016

Gene Therapy for Cartilage Regeneration

From: Mayo Clinic http://www.youtube.com/watch?v=hK6CZdBiHVk

What you need to know about Zika virus

Travel alert issued for pregnant women over virus linked to birth defects; "We're seeing rapid spread of the virus and we need to act now," one expert says

From: http://www.cbsnews.com/news/zika-virus-what-you-need-to-know/

VP Joe Biden says politics are impeding cancer cure

"You're on the cusp of some phenomenal breakthroughs," vice president tells doctors and researchers in Philadelphia

From: http://www.cbsnews.com/news/vice-president-joe-biden-says-politics-are-impeding-cancer-cure/

Botched drug trial harms patients in France

Several volunteers were hospitalized with serious complications after something went wrong with a drug trial in France

From: http://www.cbsnews.com/videos/botched-drug-trial-harms-patients-in-france/

Could a healthier diet help you sleep better?

Small study suggests less saturated fat and sugar, and more fiber and protein, may make for sweeter dreams

From: http://www.cbsnews.com/news/could-a-healthier-diet-improve-sleep/

Zika Virus May Prompt CDC Travel Guidance

Exposure to mosquito-borne virus linked to birth defects, officials say

From: http://www.webmd.com/news/20160115/cdc-may-advise-pregnant-women-to-avoid-brazil?src=RSS_PUBLIC

WHO statements on Ebola

From: http://www.who.int/entity/mediacentre/news/ebola/statements/en/index.html

Effect of N-glycosylation on the transport activity of the peptide transporter PEPT1

Iron overload results in hepatic oxidative stress, immune cell activation, and hepatocellular ballooning injury, leading to nonalcoholic steatohepatitis in genetically obese mice

The aim of this study was to determine the effect of iron overload in the development of nonalcoholic steatohepatitis (NASH) in a genetically obese mouse model (Lepr^db/db). Leptin receptor-deficient mice were fed a normal or an iron-supplemented chow for 8 wk and switched to normal chow for 8 wk. All dietary iron (DI)-fed mice developed hepatic iron overload predominantly in the reticuloendothelial system. Hepatocellular ballooning injury was observed in the livers of 85% of DI mice, relative to 20% of chow-fed Lepr^db/db. Hepatic malonyldialdehyde levels and mRNA levels of antioxidant genes (Nrf2, Gpx1, and Hmox1) were significantly increased in the DI mice. Hepatic mRNA levels of mitochondrial biogenesis regulators Pgc1α, Tfam, Cox4, and Nrf1 were diminished in the DI mice. In addition, gene expression levels of cytokines (Il6, Tnfα) and several innate and adaptive immune cell markers such as Tlr4, Inos, CD11c, CD4, CD8, and Ifn were significantly increased in livers of the DI group. Strikingly, Nlrp3, a component of the inflammasome and Il18, a cytokine elicited by inflammasome activation, were significantly upregulated in the livers of DI mice. In addition, RAW 264.7 macrophages loaded with exogenous iron showed significantly higher levels of inflammatory markers (Inos, Tnfα, Mcp1, Tlr4). Thus dietary iron excess leads to hepatic oxidative stress, inflammasome activation, induction of inflammatory and immune mediators, hepatocellular ballooning injury, and therefore NASH in this model. Taken together, these studies indicate a multifactorial role for iron overload in the pathogenesis of NASH in the setting of obesity and metabolic syndrome.

From: Handa, P., Morgan-Stevenson, V., Maliken, B. D., Nelson, J. E., Washington, S., Westerman, M., Yeh, M. M., Kowdley, K. V. http://ajpgi.physiology.org/cgi/content/abstract/310/2/G117?rss=1

Glial cell line-derived neurotrophic factor protects against high-fat diet-induced hepatic steatosis by suppressing hepatic PPAR-{gamma} expression

Glial cell line-derived neurotrophic factor (GDNF) protects against high-fat diet (HFD)-induced hepatic steatosis in mice, however, the mechanisms involved are not known. In this study we investigated the effects of GDNF overexpression and nanoparticle delivery of GDNF in mice on hepatic steatosis and fibrosis and the expression of genes involved in the regulation of hepatic lipid uptake and de novo lipogenesis. Transgenic overexpression of GDNF in liver and other metabolically active tissues was protective against HFD-induced hepatic steatosis. Mice overexpressing GDNF had significantly reduced P62/sequestosome 1 protein levels suggestive of accelerated autophagic clearance. They also had significantly reduced peroxisome proliferator-activated receptor- (PPAR-) and CD36 gene expression and protein levels, and lower expression of mRNA coding for enzymes involved in de novo lipogenesis. GDNF-loaded nanoparticles were protective against short-term HFD-induced hepatic steatosis and attenuated liver fibrosis in mice with long-standing HFD-induced hepatic steatosis. They also suppressed the liver expression of steatosis-associated genes. In vitro, GDNF suppressed triglyceride accumulation in Hep G2 cells through enhanced p38 mitogen-activated protein kinase-dependent signaling and inhibition of PPAR- gene promoter activity. These results show that GDNF acts directly in the liver to protect against HFD-induced cellular stress and that GDNF may have a role in the treatment of nonalcoholic fatty liver disease.

From: Mwangi, S. M., Peng, S., Nezami, B. G., Thorn, N., Farris, A. B., Jain, S., Laroui, H., Merlin, D., Anania, F., Srinivasan, S. http://ajpgi.physiology.org/cgi/content/abstract/310/2/G103?rss=1

Corrigendum

From: http://ajpgi.physiology.org/cgi/content/full/310/2/G142?rss=1

Bile acids regulate intestinal cell proliferation by modulating EGFR and FXR signaling

Bile acids (BAs) are synthesized in the liver and secreted into the intestine. In the lumen, enteric bacteria metabolize BAs from conjugated, primary forms into more toxic unconjugated, secondary metabolites. Secondary BAs can be injurious to the intestine and may contribute to disease. The epidermal growth factor receptor (EGFR) and the nuclear farnesoid X receptor (FXR) are known to interact with BAs. In this study we examined the effects of BAs on intestinal epithelial cell proliferation and investigated the possible roles for EGFR and FXR in these effects. We report that taurine-conjugated cholic acid (TCA) induced proliferation, while its unconjugated secondary counterpart deoxycholic acid (DCA) inhibited proliferation. TCA stimulated phosphorylation of Src, EGFR, and ERK 1/2. Pharmacological blockade of any of these pathways or genetic ablation of EGFR abrogated TCA-stimulated proliferation. Interestingly, Src or EGFR inhibitors eliminated TCA-induced phosphorylation of both molecules, suggesting that their activation is interdependent. In contrast to TCA, DCA exposure diminished EGFR phosphorylation, and pharmacological or siRNA blockade of FXR abolished DCA-induced inhibition of proliferation. Taken together, these results suggest that TCA induces intestinal cell proliferation via Src, EGFR, and ERK activation. In contrast, DCA inhibits proliferation via an FXR-dependent mechanism that may include downstream inactivation of the EGFR/Src/ERK pathway. Since elevated secondary BA levels are the result of specific bacterial modification, this may provide a mechanism through which an altered microbiota contributes to normal or abnormal intestinal epithelial cell proliferation.

From: Dossa, A. Y., Escobar, O., Golden, J., Frey, M. R., Ford, H. R., Gayer, C. P. http://ajpgi.physiology.org/cgi/content/abstract/310/2/G81?rss=1

Intestinal NHE8 is highly expressed in goblet cells and its expression is subject to TNF-{alpha} regulation

While the intestine plays an important role in digestion and absorption, the mucus lining the epithelium represents a pivotal function in mucosal protection. Goblet cells are scattered in both the crypts and among enterocytes, and they secrete an important component of mucus, mucin. We have reported that sodium/hydrogen exchanger (NHE) 8 is a novel player in mucosal protection, since loss of NHE8 function resulted in reduced mucin production and increased bacterial adhesion. While NHE8 has been shown to be expressed in enterocytes and its expression is reduced during intestinal inflammation, nothing is known about the role of NHE8 in goblet cells. This current study is designed to define the expression of NHE8 and the role of TNF-α in the regulation of NHE8 in goblet cells. Using HT29-MTX cells as an in vitro model, we detected abundant NHE8 mRNA in goblet cells. Immunohistochemical staining localized NHE8 protein on the plasma membrane and in the intracellular compartments in goblet cells. Furthermore, NHE8 expression in goblet cells is regulated by the proinflammatory cytokine TNF-α. The expression of NHE8 in HT29-MTX cells was significantly reduced at both mRNA and protein levels in the presence of TNF-α. This inhibition of NHE8 mRNA expression could be blocked by the transcriptional inhibitor actinomycin D. Promoter reporter assay showed that NHE8 promoter activity was indeed reduced by TNF-α. Mechanistically, TNF-α reduced Sp3 protein binding to the human NHE8 basal promoter region. Therefore, NHE8 is expressed in goblet cells, and the inflammatory cytokine TNF-α downregulates NHE8 expression by a transcriptional mechanism.

From: Xu, H., Li, Q., Zhao, Y., Li, J., Ghishan, F. K. http://ajpgi.physiology.org/cgi/content/abstract/310/2/G64?rss=1

Ex vivo perfusion of the isolated rat small intestine as a novel model of Salmonella enteritis

Using an ex vivo perfused rat small intestinal model, we examined pathological changes to the tissue, inflammation induction, as well as dynamic changes to smooth muscle activity, metabolic competence, and luminal fluid accumulation during short-term infection with the enteropathogenic bacteria Salmonella enterica serovar Typhimurium and Yersinia enterocolitica. Although few effects were seen upon Yersinia infection, this system accurately modeled key aspects associated with Salmonella enteritis. Our results confirmed the importance of the Salmonella Pathogenicity Island 1 (SPI1)-encoded type 3 secretion system (T3SS) in pathology, tissue invasion, inflammation induction, and fluid secretion. Novel physiological consequences of Salmonella infection of the small intestine were also identified, namely, SPI-1-dependent vasoconstriction and SPI-1-independent reduction in the digestive and absorptive functions of the epithelium. Importantly, this is the first small animal model that allows for the study of Salmonella-induced fluid secretion. Another major advantage of this model is that one can specifically determine the contribution of resident cell populations. Accordingly, we can conclude that recruited cell populations were not involved in the pathological damage, inflammation induction, fluid accumulation, nutrient absorption deficiency, and vasoconstriction observed. Although fluid loss induced by Salmonella infection is hypothesized to be due to damage caused by recruited neutrophils, our data suggest that bacterial invasion and inflammation induction in resident cell populations are sufficient for fluid loss into the lumen. In summary, this model is a novel and useful tool that allows for detailed examination of the early physiopathological effects of Salmonella infection on the small intestine.

From: Boyle, E. C., Dombrowsky, H., Sarau, J., Braun, J., Aepfelbacher, M., Lautenschläger, I., Grassl, G. A. http://ajpgi.physiology.org/cgi/content/abstract/310/2/G55?rss=1

Young Investigator Perspectives. Choosing an intellectually generous mentor

From: Hoffman, J. M. http://ajpgi.physiology.org/cgi/content/full/310/2/G53?rss=1

Cellular chloride and bicarbonate retention alters intracellular pH regulation in Cftr KO crypt epithelium

Dysregulation of bile acid homeostasis in parenteral nutrition mouse model

Long-term parenteral nutrition (PN) administration can lead to PN-associated liver diseases (PNALD). Although multiple risk factors have been identified for PNALD, to date, the roles of bile acids (BAs) and the pathways involved in BA homeostasis in the development and progression of PNALD are still unclear. We have established a mouse PN model with IV infusion of PN solution containing soybean oil-based lipid emulsion (SOLE). Our results showed that PN altered the expression of genes involved in a variety of liver functions at the mRNA levels. PN increased liver gene expression of Cyp7a1 and markedly decreased that of Cyp8b1, Cyp7b1, Bsep, and Shp. CYP7A1 and CYP8B1 are important for synthesizing the total amount of BAs and regulating the hydrophobicity of BAs, respectively. Consistently, both the levels and the percentages of primary BAs as well as total non-12α-OH BAs increased significantly in the serum of PN mice compared with saline controls, whereas liver BA profiles were largely similar. The expression of several key liver-X receptor-α (LXRα) target genes involved in lipid synthesis was also increased in PN mouse livers. Retinoid acid-related orphan receptor-α (RORα) has been shown to induce the expression of Cyp8b1 and Cyp7b1, as well as to suppress LXRα function. Western blot showed significantly reduced nuclear migration of RORα protein in PN mouse livers. This study shows that continuous PN infusion with SOLE in mice leads to dysregulation of BA homeostasis. Alterations of liver RORα signaling in PN mice may be one of the mechanisms implicated in the pathogenesis of PNALD.

From: Zhan, L., Yang, I., Kong, B., Shen, J., Gorczyca, L., Memon, N., Buckley, B. T., Guo, G. L. http://ajpgi.physiology.org/cgi/content/abstract/310/2/G93?rss=1

Retail health clinics: The pros and cons

We moms tend to worry about our kids a fair amount, and think up ways to help them, even when they’re older. Case in point: I’m itching to tell my college-age son Chris about my latest helpful-because-I-care idea. It stems from an incident last year where Chris had the flu and wound up going to the local emergency room because the university clinic had a two-day wait. This year, I’m going to arm Chris with a back-up: retail health clinics.

Retail health clinics are part of the big trend to make health care more convenient. “Twenty years ago you had to go to an emergency department if you got sick and needed immediate care. Now we have an explosion of options, such as retail health clinics,” says Dr. Ateev Mehrotra, a researcher on the topic and an associate professor of health care policy at Harvard Medical School.

The clinics

Retail health clinics began showing up 15 years ago. Today, there are about 2,000 clinics across the United States, located mostly in drugstores, supermarkets, “big box” stores, and other large retail chain settings. The clinics are usually open from 7 a.m. to 7 p.m., seven days a week, and they’re staffed by a nurse practitioner or a physician assistant. They offer all kinds of health services: everything from treating minor illnesses like colds, pinkeye, and urinary tract infections, to complete physicals (including lab work and screenings), to vaccinations and even help with smoking cessation.

The pros

Retail health clinics have many perks. They’re easy to get into, with extended hours and no appointments necessary.

They have set prices for each service, which you can see in advance on their website. For example, a wellness visit is $59 at Walmart. A cholesterol screening at CVS is $59 to $69. “We have found in our data that clinics are 30% to 40% cheaper than a doctor’s office visit, and 80% cheaper than an emergency room visit,” says Dr. Mehrotra. The clinics also take private insurance and Medicare.

But does the lower price translate into poorer-quality care? “We’ve found that the quality of care at retail clinics is equal to or superior to some doctor’s offices, because the clinics are more likely to follow national guidelines of care,” says Dr. Mehrotra.

The cons

Despite all the perks, retail health clinics may not be right for everyone. “Health care is different for older adults. The care you’ll need for even a simple problem might be more complicated. For example, a urinary tract infection will affect an older woman much differently than a younger woman, putting the older woman at risk for dehydration, confusion, falls, and even sepsis,” says Dr. Mehrotra. And if you have a chronic health condition, a simple illness might signal something bigger that might only be caught by a clinician who sees you regularly, such as your primary care doctor.

Geriatrician Dr. Suzanne Salamon, an assistant professor at Harvard Medical School, is concerned that the details of a patient’s visit to a retail health clinic might not be sent to her. Although clinics offer this service, not everyone takes them up on it. “The risk with that is, scattered care from multiple places can lead to mix-ups,” says Dr. Salamon. “And if people don’t bring their complete medication lists to a clinic, the clinic may prescribe something that will interact with medications they’re taking.”

What you should do

A report from the American College of Physicians published recently in Annals of Internal Medicine maintains that retail clinics are fine for a short-term illness or as a back-up when you can’t see your doctor. But they should not replace a long-term relationship with a primary care physician. “Going to a retail clinic is fine for minor issues like a flu shot or a sore throat, particularly if you’re generally healthy,” says Dr. Mehrotra.

That means a retail health clinic would be a great option for my son Chris, or for anyone who’s generally healthy and needs to see a health care professional right away. But there are still a few things to keep in mind if you do visit a retail health clinic, even for a flu shot:

Bring a complete list of your medications with you.
Tell the clinician about your medical history and any other health conditions you have.
Ask the clinic to send details of the visit to your doctor.
Consider a follow-up appointment with your doctor when you have time, so that everyone is on the same page when it comes to keeping you healthy.

Follow that advice, and you’ll likely give yourself, your doctor, and even good ol’ Mom a little peace of mind. Right, Chris?

The post Retail health clinics: The pros and cons appeared first on Harvard Health Blog.

From: Heidi Godman http://www.health.harvard.edu/blog/retail-health-clinics-the-pros-and-cons-201601158979

Dog flu outbreak: How to protect your pet

Experts offer some advice to help keep your dog safe from illness that can spread "like wildfire"

From: http://www.cbsnews.com/media/dog-flu-how-to-protect-your-pet/

Trauma Workers at Risk for 'Compassion Fatigue'

Acknowledging it is a key to coping, researchers say

From: http://www.webmd.com/news/20160115/trauma-care-workers-at-risk-for-compassion-fatigue?src=RSS_PUBLIC

Chemo Nerve Damage Effects May Persist for Years

Symptoms associated with falls, researchers say

From: http://www.webmd.com/cancer/news/20160115/nerve-damage-from-chemo-may-affect-cancer-survivors-for-years?src=RSS_PUBLIC

New Ebola Case in West Africa

From: http://www.webmd.com/news/20160115/new-ebola-case-africa?src=RSS_PUBLIC

After a Prediabetes Diagnosis: How to Prevent Diabetes

WebMD offers 7 ways to prevent the onset of diabetes if you've been diagnosed with prediabetes.

From: http://www.webmd.com/diabetes/features/prediabetes-diagnosis-what-to-do?src=RSS_PUBLIC

Rise in Kidney Stones in Teens a Cause for Concern

Researchers also report growing number of cases among women, blacks and children

From: http://teens.webmd.com/news/20160115/rise-in-kidney-stones-in-teens-a-cause-for-concern-study?src=RSS_PUBLIC

Merck settles class-action case over Vioxx for $830M

Lawsuit involved shareholders; drugmaker pulled Vioxx from the market years ago over safety concerns

From: http://www.cbsnews.com/news/merck-settles-class-action-case-over-vioxx-for-830m/

Health benefits of chocolate milk? Doubts raised about study

University launches review of how study partially funded by milk company was handled

From: http://www.cbsnews.com/news/health-benefits-of-chocolate-milk-doubts-raised-about-study/

Skipping Breakfast May Raise Stroke Risk

Eating breakfast every day may help prevent strokes, particularly the brain hemorrhage type, new research suggests. WebMD has the details.

From: http://www.webmd.com/stroke/news/20160115/breakfast-stroke-risk?src=RSS_PUBLIC

Should You Eat Like Tom Brady?

Is Tom Brady's diet too strict? Or is it a healthy way to eat? WebMD asked two sports nutritionists for their take on this sports superstar's eating plan.

From: http://www.webmd.com/diet/20160115/tom-brady-gisele-bundchen-diet?src=RSS_PUBLIC

Some Spend 25% Of Income On Health Expenses

Urban Institute researchers found that premiums and out-of-pocket costs are still a major concern for people seeking coverage on the health care marketplaces.

From: http://www.webmd.com/health-insurance/20160115/study-some-marketplace-customers-spend-25-percent-of-income-on-health-expenses?src=RSS_PUBLIC

Agriculture Secretary Vilsack announces Expansion of USDA’s StrikeForce Initiative in Ohio

COLUMBUS, Ohio, Jan. 15, 2016 – Today, Agriculture Secretary Tom Vilsack announced the expansion of USDA’s StrikeForce for Rural Growth and Opportunity Initiative to 11 counties in Ohio. StrikeForce is a collaborative effort to bring targeted assistance to areas experiencing chronic poverty.

From: http://www.usda.gov/wps/portal/usda/usdahome?contentid=2016/01/0013.xml&contentidonly=true

USDA’s StrikeForce Initiative Invests $23.5 Billion in Rural Communities, Expands to Four New States

COLUMBUS, Ohio, Jan. 15, 2016 – Agriculture Secretary Tom Vilsack today announced the expansion of the Department's StrikeForce for Rural Growth and Opportunity Initiative into high-poverty counties in Florida, Missouri, Montana, and Ohio. Launched in 2010, more than 1,500 StrikeForce partnerships have already helped USDA support nearly 190,000 projects and invest $23.5 billion in high-poverty areas in rural America.

From: http://www.usda.gov/wps/portal/usda/usdahome?contentid=2016/01/0012.xml&contentidonly=true

Low Bicarbonate Levels May Be a Danger for Seniors

Healthy older people have greater risk of death if blood bicarbonate level too low, research suggests

From: http://www.webmd.com/healthy-aging/news/20160114/low-bicarbonate-levels-may-be-a-danger-for-seniors?src=RSS_PUBLIC

French drug trial reportedly leaves participant comatose

French media say prosecutor investigating "serious accident" in trial of cannabis-based drug as total of 6 people hospitalized

From: http://www.cbsnews.com/news/france-drug-trial-participant-coma-brain-dead/

New Ebola Case in Sierra Leone; WHO continues to stress risk of more flare-ups

A new case of Ebola has been confirmed in Sierra Leone, reflecting the ongoing risk of new flare-ups of the virus in affected countries.

The Sierra Leone government acted rapidly to respond to this new case. Through the country’s new emergency operations centre, a joint team of local authorities, WHO and partners are investigating the origin of the case, identifying contacts and initiating control measures to prevent further transmission.

From: http://www.who.int/entity/mediacentre/news/statements/2016/new-ebola-case/en/index.html

Friday, January 15, 2016

The clinics

The pros

The cons

What you should do

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