Mayo Clinic Minute: Revamping your plate to reduce processed meats

From: Mayo Clinic https://www.youtube.com/watch?v=85azZZywsbk

Patient records stolen from plastic surgery clinic

Officials say the records of 15,000 patients were stolen from an exclusive Rodeo Drive plastic surgery clinic in Beverly Hills, Calif.

From: http://www.cbsnews.com/news/beverly-hills-plastic-surgery-clinic-patient-records-stolen/

Type 2 Diabetes: How to Handle the News

You just learned you have type 2 diabetes. What now?

From: http://www.webmd.com/diabetes/features/type-2-diabetes-coping-with-news?src=RSS_PUBLIC

Wild 'Death Cap' Mushroom Sickens 14 in California

Foraging by novices tied to 3 people needing liver transplants and permanent brain damage in a child

From: http://www.webmd.com/food-recipes/food-poisoning/news/20170601/wild-death-cap-mushroom-seriously-sickens-14-in-california?src=RSS_PUBLIC

Elite High Schools May Increase Risk of Addiction

Rates are two to three times higher than national norms

From: http://www.webmd.com/mental-health/addiction/news/20170601/elite-high-schools-breed-higher-risk-of-addiction-study?src=RSS_PUBLIC

MS-Related Brain Changes May Affect Social Skills

Study might explain why some multiple sclerosis patients stop understanding what others are feeling

From: http://www.webmd.com/multiple-sclerosis/news/20170601/ms-related-brain-changes-may-affect-social-skills?src=RSS_PUBLIC

New Teen Drivers Face Triple the Risk of a Fatal Crash

Distractions, such as cell phones, and failure to buckle up are main causes

From: http://www.webmd.com/parenting/news/20170601/new-teen-drivers-face-triple-the-risk-of-a-fatal-crash?src=RSS_PUBLIC

Marijuana May Make Your Gums Go to Pot

People who use it frequently twice as likely to have periodontal disease, researchers say

From: http://www.webmd.com/oral-health/news/20170601/marijuana-may-make-your-gums-go-to-pot?src=RSS_PUBLIC

Addiction risk high at elite schools, study finds

Going to a prestigious high school doesn't protect teens from drug and alcohol abuse, according to new research

From: http://www.cbsnews.com/news/elite-high-schools-higher-risk-of-addiction-study/

MS-related brain changes may affect social skills

A new study might explain why some multiple sclerosis patients have trouble understanding what others are feeling

From: http://www.cbsnews.com/news/ms-multiple-sclerosis-brain-changes-may-affect-social-skills/

Kevin Hart Goes All In

Actor and comedian Kevin Hart talks fitness, family, and fans.

From: http://www.webmd.com/a-to-z-guides/features/kevin-hart-all-in?src=RSS_PUBLIC

Harmed by Sunscreen? What Parents Need to Know

Toddler's face was badly injured after using Banana Boat sunscreen. Dermatologists think it's a photo allergic reaction.

From: http://www.webmd.com/allergies/news/20170601/burned-by-sunscreen-what-parents-need-to-know?src=RSS_PUBLIC

Dr. Ruben Mesa: 10 tips for being a successful cancer survivor

From: Mayo Clinic https://www.youtube.com/watch?v=3AAJUYIIRcQ

10 Questions for Selenis Leyva

We chat with the Orange Is the New Black star about work, family, and her advocacy for the transgender community.

From: http://www.webmd.com/a-to-z-guides/features/selenis-leyva-10-questions?src=RSS_PUBLIC

Florida becomes first state to provide certificates for miscarriages

Gov. Rick Scott signed a bill Wednesday that will allow the state to start issuing "certificates of nonviable birth" beginning July 1

From: http://www.cbsnews.com/news/florida-becomes-first-state-to-provide-certificates-for-miscarriages-under-new-law/

Health hazards of pee in the pool

Swimming pool chemicals like chlorine can interact with urine in the water to cause potential health concerns. Tanae Howard of CBS Indianapolis station WTTV reports.

From: http://www.cbsnews.com/videos/health-hazards-of-pee-in-the-pool/

New drug kits save police dogs from opioid ODs

Accidentally inhaling powerful opioids can be deadly, so officers have a new tool to protect their four-legged partners

From: http://www.cbsnews.com/news/new-drug-kits-save-police-dogs-from-opioid-overdoses/

Top Republican says Senate will repeal and replace Obamacare "by the end of July"

Mitch McConnell said last week that he doesn't know how Senate Republicans will secure a majority of votes to pass legislation to repeal and replace Obamacare

From: http://www.cbsnews.com/news/top-republican-says-senate-will-repeal-and-replace-obamacare-by-the-end-of-july/

Magnesium Reduces Hepatic Lipid Accumulation in Yellow Catfish (Pelteobagrus fulvidraco) and Modulates Lipogenesis and Lipolysis via PPARA, JAK-STAT, and AMPK Pathways in Hepatocytes [Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions]

Background: Magnesium influences hepatic lipid deposition in vertebrates, but the underlying mechanism is unknown.

Objective: We used yellow catfish and their isolated hepatocytes to test the hypothesis that magnesium influences lipid deposition by modulating lipogenesis and lipolysis.

Methods: Juvenile yellow catfish (mean ± SEM weight: 3.43 ± 0.02 g, 3 mo old, mixed sex) were fed a 0.14- (low), 0.87- (intermediate) or 2.11- (high) g Mg/kg diet for 56 d. Primary hepatocytes were incubated for 48 h in control or MgSO₄-containing medium with or without 2-h pretreatment with an inhibitor (AG490, GW6471, or Compound C). Growth performance, cell viability, triglyceride (TG) concentrations, and expression of enzymes and genes involved in lipid metabolism were measured.

Results: Compared with fish fed low magnesium, those fed intermediate or high magnesium had lower hepatic lipids (18%, 22%) and 6-phosphogluconate dehydrogenase (6PGD; 3.7%, 3.8%) and malic enzyme (ME; 35%, 48%) activities and greater mRNA levels of the lipolytic genes adipose triacylglyceride lipase (atgl; 82% and 1.7-fold) and peroxisome proliferator-activated receptor (ppara; 18% and 1.0-fold), respectively (P < 0.05). Relative mRNA levels of AMP-activated protein kinase (ampk) a1, ampka2, ampkb1, ampkb2, ampkg1a, ampkg1b, Janus kinase (jak) 2a, jak2b, and signal transducers and activators of transcription (stat) 3 in fish fed high magnesium were higher (24% to 3.1-fold, P < 0.05) than in those fed low or intermediate magnesium. Compared with cells incubated with MgSO₄ alone, those incubated with MgSO₄ and pretreated with AG490, GW6471, or Compound C had greater TG concentrations (42%, 31%, or 56%), g6pd (98%, 59%, or 51%), 6pgd (68%, 73%, or 32%) mRNA expression, and activities of G6PD (35%, 45%, or 16%) and ME (1.5-fold, 1.3-fold, or 13%), and reduced upregulation (61%, 25%, or 45%) of the lipolytic gene, atgl (P < 0.05).

Conclusions: Magnesium reduced hepatic lipid accumulation in yellow catfish and the variation might be attributed to inhibited lipogenesis and increased lipolysis. PPARA, JAK-STAT, and AMPK pathways mediated the magnesium-induced changes in lipid deposition and metabolism. These results offer new insight into magnesium nutrition in vertebrates.

From: Wei, C.-C., Wu, K., Gao, Y., Zhang, L.-H., Li, D.-D., Luo, Z. http://jn.nutrition.org/cgi/content/short/147/6/1070?rss=1

Upregulation of Zinc Absorption Matches Increases in Physiologic Requirements for Zinc in Women Consuming High- or Moderate-Phytate Diets during Late Pregnancy and Early Lactation [Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions]

Background: Estimated physiologic requirements (PRs) for zinc increase in late pregnancy and early lactation, but the effect on dietary zinc requirements is uncertain.

Objective: The aim of this study was to determine changes in daily fractional absorbed zinc and total absorbed zinc (TAZ) from ad libitum diets of differing phytate contents in relation to physiologic zinc requirements during pregnancy and lactation.

Methods: This was a prospective observational study of zinc absorption at 8 (phase 1) and 34 (phase 2) wk of gestation and 2 (phase 3) and 6 (phase 4) mo of lactation. Participants were indigenous Guatemalan women of childbearing age whose major food staple was maize and who had been randomly assigned in a larger study to either of 2 ad libitum feeding groups: low-phytate maize (LP; 1.6 mg/g; n = 14) or control maize (C; 7.1 mg/g; n = 8). Total dietary zinc (milligrams per day, TDZ) and phytate (milligrams per day) were determined from duplicate diets and fractional absorption (FAZ) by dual isotope ratio technique (TAZ = TDZ x FAZ). All variables were examined longitudinally and by group and compared with PRs. TAZ values at later phases were compared with phase 1. Measured TAZ was compared with predicted TAZ for nonpregnant, nonlactating (NPNL) women.

Results: TAZ was greater in the LP group than in the C group at all phases. All variables increased from phase 1 to phases 2 and 3 and declined at phase 4. TAZ increased by 1.25 mg/d (P = 0.045) in the C group and by 0.81 mg/d (P = 0.058) in the LP group at phase 2. At phase 3, the increases were 2.66 mg/d (P = 0.002) in the C group and 2.28 mg/d (P = 0.0004) in the LP group, compared with a 1.37-mg/d increase in PR. Measured TAZ was greater than predicted values in phases 2–4.

Conclusions: Upregulation of zinc absorption in late pregnancy and early lactation matches increases in PRs of pregnant and lactating women, regardless of dietary phytate, which has implications for dietary zinc requirements of pregnant and lactating women.

From: Hambidge, K. M., Miller, L. V., Mazariegos, M., Westcott, J., Solomons, N. W., Raboy, V., Kemp, J. F., Das, A., Goco, N., Hartwell, T., Wright, L., Krebs, N. F. http://jn.nutrition.org/cgi/content/short/147/6/1079?rss=1

Zinc Absorption from Milk Is Affected by Dilution but Not by Thermal Processing, and Milk Enhances Absorption of Zinc from High-Phytate Rice in Young Dutch Women [Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions]

Background: Milk has been suggested to increase zinc absorption. The effect of processing and the ability of milk to enhance zinc absorption from other foods has not been measured directly in humans.

Objective: We aimed to assess zinc absorption from 1) milk undergoing various processing and preparatory steps and 2) from intrinsically labeled high-phytate rice consumed with milk or water.

Methods: Two randomized crossover studies were conducted in healthy young women [age:18–25 y; body mass index (in kg/m²): 20–25]: 1) a milk study (n = 19) comparing the consumption of 800 mL full-fat ultra-high temperature (UHT) milk [heat-treated milk (HTM)], full-fat UHT milk diluted 1:1 with water [heat-treated milk and water (MW)], water, or unprocessed (raw) milk (UM), each extrinsically labeled with ⁶⁷Zn, and 2) a rice study (n = 18) comparing the consumption of 90 g intrinsically ⁶⁷Zn-labeled rice with 600 mL of water [rice and water (RW)] or full-fat UHT milk [rice and milk (RM)]. The fractional absorption of zinc (FAZ) was measured with the double-isotope tracer ratio method. In vitro, we assessed zinc extraction from rice blended into water, UM, or HTM with or without phytate.

Results: FAZ from HTM was 25.5% (95% CI: 21.6%, 29.4%) and was not different from UM (27.8%; 95% CI: 24.2%, 31.4%). FAZ from water was higher (72.3%; 95% CI: 68.7%, 75.9%), whereas FAZ from MW was lower (19.7%; 95% CI: 17.5%, 21.9%) than HTM and UM (both P < 0.01). FAZ from RM (20.7%; 95% CI: 18.8%, 22.7%) was significantly higher than from RW (12.8%; 95% CI: 10.8%, 14.6%; P < 0.01). In vitro, HTM and UM showed several orders of magnitude higher extraction of zinc from rice with HTM than from rice with water at various phytate concentrations.

Conclusions: Milk enhanced human FAZ from high-phytate rice by 62% compared with water. Diluting milk with water decreases its absorption-enhancing proprieties, whereas UHT processing does not. This trial was registered at the Dutch trial registry as NTR4267 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4267).

From: Talsma, E. F., Moretti, D., Ly, S. C., Dekkers, R., van den Heuvel, E. G., Fitri, A., Boelsma, E., Stomph, T. J., Zeder, C., Melse-Boonstra, A. http://jn.nutrition.org/cgi/content/short/147/6/1086?rss=1

Combined Vitamin B-12 and Balanced Protein-Energy Supplementation Affect Homocysteine Remethylation in the Methionine Cycle in Pregnant South Indian Women of Low Vitamin B-12 Status [Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions]

Background: Low-quality dietary protein intake and vitamin B-12 deficiency could interact to decrease methionine transmethylation and remethylation rates during pregnancy and may affect epigenetic modifications of the fetal genome.

Objective: The objective of this randomized, partially open-labeled intervention trial was to examine the effect of supplemental high-quality protein and vitamin B-12 on third-trimester methionine kinetics in pregnant Indian women with a low vitamin B-12 status.

Methods: Pregnant women with low serum vitamin B-12 concentrations (<200 pmol/L) were randomly assigned to 1 of 3 groups: the first group received balanced protein-energy supplementation of 500 mL milk/d plus a 10-μg vitamin B-12 tablet/d (M+B-12 group; n = 30), the second group received milk (500 mL/d) plus a placebo tablet (M+P group; n = 30), and the third group received a placebo tablet alone (P group; n = 33). Third-trimester fasting plasma amino acid kinetics were measured by infusing 1-¹³C,methyl-²H₃-methionine, ring-²H₅-phenylalanine, ring-²H₄-tyrosine,1-¹³C-glycine, and 2,3,3-²H₃,¹⁵N-serine in a subset of participants. Placental mRNA expression of genes involved in methionine pathways, placental long interspersed nuclear elements 1 (LINE-1) methylation, and promoter methylation levels of vascular endothelial growth factor (VEGF) were analyzed.

Results: Remethylation rates in the M+B-12, M+P, and P groups were 5.1 ± 1.7, 4.1 ± 1.0, and, 5.0 ± 1.4 μmol ⋅ kg^–1 ⋅ h^–1, respectively (P = 0.057), such that the percentage of transmethylation remethylated to methionine tended to be higher in the M+B-12 group (49.5% ± 10.5%) than in the M+P group (42.3% ± 8.4%; P = 0.053) but neither differed from the P group (44.2% ± 8.1%; P > 0.1). Placental mRNA expression, LINE-1, and VEGF promoter methylation did not differ between groups.

Conclusions: Combined vitamin B-12 and balanced protein-energy supplementation increased the homocysteine remethylation rate in late pregnancy. Thus, vitamin B-12 along with balanced protein-energy supplementation is critical for optimal functioning of the methionine cycle in the third trimester of pregnancy in Indian women with low serum vitamin B-12 in early pregnancy. This trial was registered at clinicaltrials.gov as CTRI/2016/01/006578.

From: Devi, S., Mukhopadhyay, A., Dwarkanath, P., Thomas, T., Crasta, J., Thomas, A., Sheela, C., Hsu, J. W., Tang, G. J., Jahoor, F., Kurpad, A. V. http://jn.nutrition.org/cgi/content/short/147/6/1094?rss=1

Silicon Alleviates Nonalcoholic Steatohepatitis by Reducing Apoptosis in Aged Wistar Rats Fed a High-Saturated Fat, High-Cholesterol Diet [Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions]

Background: Lipoapoptosis has been identified as a key event in the progression of nonalcoholic fatty liver disease (NAFLD), and hence, antiapoptotic agents have been recommended as a possible effective treatment for nonalcoholic steatohepatitis (NASH). Silicon, included in meat as a functional ingredient, improves lipoprotein profiles and liver antioxidant defenses in aged rats fed a high–saturated fat, high-cholesterol diet (HSHCD). However, to our knowledge, the antiapoptotic effect of this potential functional meat on the liver has never been tested.

Objective: This study was designed to evaluate the effect of silicon on NASH development and the potential antiapoptotic properties of silicon in aged rats.

Methods: One-year-old male Wistar rats weighing ~500 g were fed 3 experimental diets containing restructured pork (RP) for 8 wk: 1) a high–saturated fat diet, as an NAFLD control, with 16.9% total fat, 0.14 g cholesterol/kg diet, and 46.8 mg SiO₂/kg (control); 2) the HSHCD as a model of NASH, with 16.6% total fat, 16.3 g cholesterol/kg diet, and 46.8 mg SiO₂/kg [high-cholesterol diet (Chol-C)]; and 3) the HSHCD with silicon-supplemented RP with amounts of fat and cholesterol identical to those in the Chol-C diet, but with 750 mg SiO₂/kg (Chol-Si). Detailed histopathological assessments were performed, and the NAFLD activity score (NAS) was calculated. Liver apoptosis and damage markers were evaluated by Western blotting and immunohistochemical staining.

Results: Chol-C rats had a higher mean NAS (7.4) than did control rats (1.9; P < 0.001). The score in Chol-Si rats (5.4) was intermediate and different from that in both other groups (P < 0.05). Several liver apoptosis markers—including hepatocyte terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate (dUTP) nick end labeling, cytosolic cytochrome c, apoptosis-inducing factor, caspases 9 and 3, and the mitochondrial Bcl-2-associated X protein (BAX)-to-B-cell lymphoma 2 (BCL2) ratio—were 9–45% lower in Chol-Si than in Chol-C rats (P < 0.05) and did not differ from values in the control group.

Conclusions: Supplemental silicon substantially affects NASH development in aged male Wistar rats fed an HSHCD by partially blocking apoptosis. These results suggest that silicon-enriched RP could be used as an effective nutritional strategy in preventing NASH.

From: Garcimartin, A., Lopez-Oliva, M. E., Santos-Lopez, J. A., Garcia-Fernandez, R. A., Macho-Gonzalez, A., Bastida, S., Benedi, J., Sanchez-Muniz, F. J. http://jn.nutrition.org/cgi/content/short/147/6/1104?rss=1

Excretion of Zinc and Copper Increases in Men during 3 Weeks of Bed Rest, with or without Artificial Gravity [Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions]

Background: Zinc and copper have many physiologic functions and little or no functional storage capability, so persistent losses of either element present health concerns, especially during extended-duration space missions.

Objectives: We evaluated the effects of short-term bed rest (BR), a spaceflight analog, on copper and zinc metabolism to better understand the role of these nutrients in human adaptation to (simulated) spaceflight. We also investigated the effect of artificial gravity on copper and zinc homeostasis.

Methods: Zinc and copper balances were studied in 15 men [mean ± SD age: 29 ± 3 y; body mass index (in kg/m²): 26.4 ± 2.2] before, during, and after 21 d of head-down tilt BR, during which 8 of the participants were subjected to artificial gravity (AG) by centrifugation for 1 h/d. Control subjects were transferred onto the centrifuge but were not exposed to centrifugation. The study was conducted in a metabolic ward; all urine and feces were collected. Data were analyzed by 2-factor repeated-measures ANOVA.

Results: Urinary zinc excretion values for control and AG groups were 33% and 14%, respectively, higher during BR than before BR, and fecal zinc excretion values for control and AG groups were 36% and 19%, respectively, higher during BR, resulting in 67% and 82% lower net zinc balances for controls and AG, respectively (both P < 0.01), despite lower nutrient intake during BR. Fecal copper values for control and AG groups were 40% and 33%, respectively, higher during BR than before BR (P < 0.01 for both). Urinary copper did not change during BR, but a 19% increase was observed after BR compared with before BR in the AG group (P < 0.05).

Conclusions: The increased fecal excretion of copper and zinc by men during BR suggests that their absorption of these minerals from the diet was reduced, secondary to the release of minerals from bone and muscle. These findings highlight the importance of determining dietary requirements for astronauts on space missions and ensuring provision and intake of all nutrients.

From: Heacox, H. N., Gillman, P. L., Zwart, S. R., Smith, S. M. http://jn.nutrition.org/cgi/content/short/147/6/1113?rss=1

Coughing canines? 6 things to know about dog flu

At least a dozen dogs in Florida have gotten sick and many other cases are suspected

From: http://www.cbsnews.com/news/coughing-canines-6-things-to-know-about-dog-flu/

Report reveals how many Americans have food allergies

Study shows which foods are most often linked to allergic reactions

From: http://www.cbsnews.com/news/food-allergies-in-america-new-report-shellfish-peanut-dairy/

Mayo Clinic Dolores Jean Lavins Arts at the Bedside Program

From: Mayo Clinic https://www.youtube.com/watch?v=Wr5TyOaNxR0

4 science-backed ways toward better learning (Hint: drop the highlighter)

We have all done it. We are reading something we want to remember later and out comes the highlighter. Green, yellow, blue, sometimes multiple colors at once to differentiate the importance of words in sentences.

Even though highlighting is a widespread practice to help us learn and remember information, it actually does very little. In fact, in some situations highlighting can prevent us from using knowledge to make inferences in the future. Highlighting, it turns out, isn’t the only common strategy that doesn’t really help you learn. Others include underlining and rereading, which are popular study tools but are not effective.

So, what is a learner to do? Recent journal articles and the book Make It Stick point us in the direction of effective learning strategies. Here are four of them.

1. Quiz yourself frequently on the material you read. Make flashcards of important topics you read. Generate questions and answers from the material and regularly quiz yourself. Keep retrieving knowledge from your memory. It will prevent forgetting and allow you to identify areas you do not know to focus future study.
2. Space out your studying and quizzes. Spread out when you quiz yourself by hours, days, weeks, and months. As you gain mastery over the material, keep spacing the quizzes further apart.
3. Quiz yourself on different topics in each study session. For example, if you are studying for a biology test, don’t just study the chapters in order. Mix in questions from different chapters as you study. Interleaving, or alternating topics, will improve your ability to remember and apply information in the future.
4. Ask yourself questions while you are reading. These can include “Why?” questions. Why is this happening? Why does this make sense? Or why does this not make sense? Asking why will help you process the information you are reading and apply it in future situations. Questions can also help you process and make meaning of the information you have just read. For example, you can ask yourself, “What new facts did I just learn?” after reading a paragraph. “How do these new facts relate to facts I already know?” “What were the main themes of what I read?” “Why are these themes important?” “What further questions do I have?”

So, keep this article handy and use it to practice these methods. Quiz yourself on what you’ve just read, space out self-quizzes, keep quizzing yourself on the definitions of different strategies along with other information you are trying to learn, and ask yourself questions about the content, meaning, and applicability of the material while you are reading.

But please, put down the highlighter!

Sources

Make It Stick: The Science of Successful Learning. Harvard University Press, 2014.

Improving students’ learning with effective learning techniques: Promising directions form cognitive and educational psychology. Psychological Science in the Public Interest, 2013.

Inexpensive techniques to improve education: Applying cognitive psychology to enhance educational practice. Journal of Applied Research in Memory and Cognition, December 2012.

The post 4 science-backed ways toward better learning (Hint: drop the highlighter) appeared first on Harvard Health Blog.

From: David R. Topor, PhD, MS-HPEd http://www.health.harvard.edu/blog/4-science-backed-ways-toward-better-learning-hint-drop-highlighter-2017060111775

Neurofibromatosis Type 1 and Type 2 – Mayo Clinic

From: Mayo Clinic https://www.youtube.com/watch?v=UFG-1UHoAy8

Fairweather Lab Tour

From: Mayo Clinic https://www.youtube.com/watch?v=yE9TQ2Uonqo

New Combo Pill Offers Hope to Hepatitis C Patients Who Fail Other Treatment

3-drug mixture was nearly 100 percent effective in drug company trials

From: http://www.webmd.com/hepatitis/news/20170531/new-combo-pill-offers-hope-to-hepatitis-c-patients-who-fail-other-treatment?src=RSS_PUBLIC

Drug Prolongs Survival for Some with Breast Cancer

It cut risk of relapse, death by 30 percent over 5 years, trial found

From: http://www.webmd.com/breast-cancer/news/20170531/drug-xeloda-prolongs-survival-for-some-breast-cancer-patients?src=RSS_PUBLIC

Did a 1980 Letter Help Spark the Opioid Crisis?

Doctors may have been misled by report calling painkiller addiction 'rare'

From: http://www.webmd.com/mental-health/addiction/news/20170531/did-a-1980-letter-help-spark-the-us-opioid-crisis?src=RSS_PUBLIC

Opioid epidemic’s unlikely, little-known spark

Researchers say drug companies pounced on 1980 letter from respected doctor to persuade physicians the powerful meds aren’t necessarily addictive

From: http://www.cbsnews.com/news/drug-companies-1980-doctors-letter-widespread-opioids-use/

Helminths in the gastrointestinal tract as modulators of immunity and pathology

Helminth parasites are highly prevalent in many low- and middle-income countries, in which inflammatory bowel disease and other immunopathologies are less frequent than in the developed world. Many of the most common helminths establish themselves in the gastrointestinal tract and can exert counter-inflammatory influences on the host immune system. For these reasons, interest has arisen as to how parasites may ameliorate intestinal inflammation and whether these organisms, or products they release, could offer future therapies for immune disorders. In this review, we discuss interactions between helminth parasites and the mucosal immune system, as well as the progress being made toward identifying mechanisms and molecular mediators through which it may be possible to attenuate pathology in the intestinal tract.

From: Varyani, F., Fleming, J. O., Maizels, R. M. http://ajpgi.physiology.org/cgi/content/abstract/312/6/G537?rss=1

Ursodeoxycholic acid and lithocholic acid exert anti-inflammatory actions in the colon

Ward JB, Lajczak NK, Kelly OB, O’Dwyer AM, Giddam AK, Ní Gabhann J, Franco P, Tambuwala MM, Jefferies CA, Keely S, Roda A, Keely SJ. Ursodeoxycholic acid and lithocholic acid exert anti-inflammatory actions in the colon. Am J Physiol Gastrointest Liver Physiol 312: G550–G558, 2017. First published March 30, 2017; doi:10.1152/ajpgi.00256.2016.—Inflammatory bowel diseases (IBD) comprise a group of common and debilitating chronic intestinal disorders for which currently available therapies are often unsatisfactory. The naturally occurring secondary bile acid, ursodeoxycholic acid (UDCA), has well-established anti-inflammatory and cytoprotective actions and may therefore be effective in treating IBD. We aimed to investigate regulation of colonic inflammatory responses by UDCA and to determine the potential impact of bacterial metabolism on its therapeutic actions. The anti-inflammatory efficacy of UDCA, a nonmetabolizable analog, 6α-methyl-UDCA (6-MUDCA), and its primary colonic metabolite lithocholic acid (LCA) was assessed in the murine dextran sodium sulfate (DSS) model of mucosal injury. The effects of bile acids on cytokine (TNF-α, IL-6, Il-1β, and IFN-) release from cultured colonic epithelial cells and mouse colonic tissue in vivo were investigated. Luminal bile acids were measured by gas chromatography-mass spectrometry. UDCA attenuated release of proinflammatory cytokines from colonic epithelial cells in vitro and was protective against the development of colonic inflammation in vivo. In contrast, although 6-MUDCA mimicked the effects of UDCA on epithelial cytokine release in vitro, it was ineffective in preventing inflammation in the DSS model. In UDCA-treated mice, LCA became the most common colonic bile acid. Finally, LCA treatment more potently inhibited epithelial cytokine release and protected against DSS-induced mucosal inflammation than did UDCA. These studies identify a new role for the primary metabolite of UDCA, LCA, in preventing colonic inflammation and suggest that microbial metabolism of UDCA is necessary for the full expression of its protective actions.

NEW & NOTEWORTHY On the basis of its cytoprotective and anti-inflammatory actions, the secondary bile acid ursodeoxycholic acid (UDCA) has well-established uses in both traditional and Western medicine. We identify a new role for the primary metabolite of UDCA, lithocholic acid, as a potent inhibitor of intestinal inflammatory responses, and we present data to suggest that microbial metabolism of UDCA is necessary for the full expression of its protective effects against colonic inflammation.

From: Ward, J. B. J., Lajczak, N. K., Kelly, O. B., ODwyer, A. M., Giddam, A. K., Ni Gabhann, J., Franco, P., Tambuwala, M. M., Jefferies, C. A., Keely, S., Roda, A., Keely, S. J. http://ajpgi.physiology.org/cgi/content/abstract/312/6/G550?rss=1

Changes in intestinal microbiota composition and metabolism coincide with increased intestinal permeability in young adults under prolonged physiological stress

The magnitude, temporal dynamics, and physiological effects of intestinal microbiome responses to physiological stress are poorly characterized. This study used a systems biology approach and a multiple-stressor military training environment to determine the effects of physiological stress on intestinal microbiota composition and metabolic activity, as well as intestinal permeability (IP). Soldiers (n = 73) were provided three rations per day with or without protein- or carbohydrate-based supplements during a 4-day cross-country ski-march (STRESS). IP was measured before and during STRESS. Blood and stool samples were collected before and after STRESS to measure inflammation, stool microbiota, and stool and plasma global metabolite profiles. IP increased 62 ± 57% (mean ± SD, P < 0.001) during STRESS independent of diet group and was associated with increased inflammation. Intestinal microbiota responses were characterized by increased α-diversity and changes in the relative abundance of >50% of identified genera, including increased abundance of less dominant taxa at the expense of more dominant taxa such as Bacteroides. Changes in intestinal microbiota composition were linked to 23% of metabolites that were significantly altered in stool after STRESS. Together, pre-STRESS Actinobacteria relative abundance and changes in serum IL-6 and stool cysteine concentrations accounted for 84% of the variability in the change in IP. Findings demonstrate that a multiple-stressor military training environment induced increases in IP that were associated with alterations in markers of inflammation and with intestinal microbiota composition and metabolism. Associations between IP, the pre-STRESS microbiota, and microbiota metabolites suggest that targeting the intestinal microbiota could provide novel strategies for preserving IP during physiological stress.

NEW & NOTEWORTHY Military training, a unique model for studying temporal dynamics of intestinal barrier and intestinal microbiota responses to stress, resulted in increased intestinal permeability concomitant with changes in intestinal microbiota composition and metabolism. Prestress intestinal microbiota composition and changes in fecal concentrations of metabolites linked to the microbiota were associated with increased intestinal permeability. Findings suggest that targeting the intestinal microbiota could provide novel strategies for mitigating increases in intestinal permeability during stress.

From: Karl, J. P., Margolis, L. M., Madslien, E. H., Murphy, N. E., Castellani, J. W., Gundersen, Y., Hoke, A. V., Levangie, M. W., Kumar, R., Chakraborty, N., Gautam, A., Hammamieh, R., Martini, S., Montain, S. J., Pasiakos, S. M. http://ajpgi.physiology.org/cgi/content/abstract/312/6/G559?rss=1

EAVK segment "c" sequence confers Ca2+-dependent changes to the kinetics of full-length human Ano1

Anoctamin1 (Ano1 and TMEM16A) is a calcium-activated chloride channel specifically expressed in the interstitial cells of Cajal (ICC) of the gastrointestinal tract muscularis propria. Ano1 is necessary for normal electrical slow waves and ICC proliferation. The full-length human Ano1 sequence includes an additional exon, exon "0," at the NH₂ terminus. Ano1 with exon 0 [Ano1₍₀₎] had a lower EC₅₀ for intracellular calcium ([Ca²⁺]_i) and faster chloride current (I_Cl) kinetics. The Ano1 alternative splice variant with segment "c" encoding exon 13 expresses on the first intracellular loop four additional amino acid residues, EAVK, which alter I_Cl at low [Ca²⁺]_i. Exon 13 is expressed in 75–100% of Ano1 transcripts in most human tissues but only 25% in the human stomach. Our aim was to determine the effect of EAVK deletion on Ano1₍₀₎ I_Cl parameters. By voltage-clamp electrophysiology, we examined I_Cl in HEK293 cells transiently expressing Ano1₍₀₎ with or without the EAVK sequence [Ano1₍₀₎EAVK]. The EC₅₀ values of activating and deactivating I_Cl for [Ca²⁺]_i were 438 ± 7 and 493 ± 9 nM for Ano1₍₀₎ but higher for Ano1₍₀₎EAVK at 746 ± 47 and 761 ± 26 nM, respectively. Meanwhile, the EC₅₀ values for the ratio of instantaneous to steady-state I_Cl were not different between variants. Congruently, the time constant of activation was slower for Ano1₍₀₎EAVK than Ano1₍₀₎ currents at intermediate [Ca²⁺]_i. These results suggest that EAVK decreases the calcium sensitivity of Ano1₍₀₎ current activation and deactivation by slowing activation kinetics. Differential expression of EAVK in the human stomach may function as a switch to increase sensitivity to [Ca²⁺]_i via faster gating of Ano1.

NEW & NOTEWORTHY Calcium-activated chloride channel anoctamin1 (Ano1) is necessary for normal slow waves in the gastrointestinal interstitial cells of Cajal. Exon 0 encodes the NH₂ terminus of full-length human Ano1 [Ano1₍₀₎], while exon 13 encodes residues EAVK on its first intracellular loop. Splice variants lack EAVK more often in the stomach than other tissues. Ano1₍₀₎ without EAVK [Ano1₍₀₎EAVK] has reduced sensitivity for intracellular calcium, attributable to slower kinetics. Differential expression of EAVK may function as a calcium-sensitive switch in the human stomach.

From: Strege, P. R., Gibbons, S. J., Mazzone, A., Bernard, C. E., Beyder, A., Farrugia, G. http://ajpgi.physiology.org/cgi/content/abstract/312/6/G572?rss=1

Glycans in the intestinal peptide transporter PEPT1 contribute to function and protect from proteolysis

Despite the fact that many membrane proteins carry extracellular glycans, little is known about whether the glycan chains also affect protein function. We recently demonstrated that the proton-coupled oligopeptide transporter 1 (PEPT1) in the intestine is glycosylated at six asparagine residues (N50, N406, N439, N510, N515, and N532). Mutagenesis-induced disruption of the individual N-glycosylation site N50, which is highly conserved among mammals, was detected to significantly enhance the PEPT1-mediated inward transport of peptides. Here, we show that for the murine protein the inhibition of glycosylation at sequon N50 by substituting N50 with glutamine, lysine, or cysteine or by replacing S52 with alanine equally altered PEPT1 transport kinetics in oocytes. Furthermore, we provide evidence that the uptake of [¹⁴C]glycyl-sarcosine in immortalized murine small intestinal (MODE-K) or colonic epithelial (PTK-6) cells stably expressing the PEPT1 transporter N50Q is also significantly increased relative to the wild-type protein. By using electrophysiological recordings and tracer flux studies, we further demonstrate that the rise in transport velocity observed for PEPT1 N50Q is bidirectional. In line with these findings, we show that attachment of biotin derivatives, comparable in weight with two to four monosaccharides, to the PEPT1 N50C transporter slows down the transport velocity. In addition, our experiments provide strong evidence that glycosylation of PEPT1 confers resistance against proteolytic cleavage by proteinase K, whereas a remarkable intrinsic stability against trypsin, even in the absence of N-linked glycans, was detected.

NEW & NOTEWORTHY This study highlights the role of N50-linked glycans in modulating the bidirectional transport activity of the murine peptide transporter PEPT1. Electrophysiological and tracer flux measurements in Xenopus oocytes have shown that removal of the N50 glycans increases the maximal peptide transport rate in the inward and outward directions. This effect could be largely reversed by replacement of N50 glycans with structurally dissimilar biotin derivatives. In addition, N-glycans were detected to stabilize PEPT1 against proteolytic cleavage.

From: Stelzl, T., Geillinger-Kästle, K. E., Stolz, J., Daniel, H. http://ajpgi.physiology.org/cgi/content/abstract/312/6/G580?rss=1

Nutrient sensing by absorptive and secretory progenies of small intestinal stem cells

Nutrient sensing triggers responses by the gut-brain axis modulating hormone release, feeding behavior and metabolism that become dysregulated in metabolic syndrome and some cancers. Except for absorptive enterocytes and secretory enteroendocrine cells, the ability of many intestinal cell types to sense nutrients is still unknown; hence we hypothesized that progenitor stem cells (intestinal stem cells, ISC) possess nutrient sensing ability inherited by progenies during differentiation. We directed via modulators of Wnt and Notch signaling differentiation of precursor mouse intestinal crypts into specialized organoids each containing ISC, enterocyte, goblet, or Paneth cells at relative proportions much higher than in situ as determined by mRNA expression and immunocytochemistry of cell type biomarkers. We identified nutrient sensing cell type(s) by increased expression of fructolytic genes in response to a fructose challenge. Organoids comprised primarily of enterocytes, Paneth, or goblet, but not ISC, cells responded specifically to fructose without affecting nonfructolytic genes. Sensing was independent of Wnt and Notch modulators and of glucose concentrations in the medium but required fructose absorption and metabolism. More mature enterocyte- and goblet-enriched organoids exhibited stronger fructose responses. Remarkably, enterocyte organoids, upon forced dedifferentiation to reacquire ISC characteristics, exhibited a markedly extended lifespan and retained fructose sensing ability, mimicking responses of some dedifferentiated cancer cells. Using an innovative approach, we discovered that nutrient sensing is likely repressed in progenitor ISCs then irreversibly derepressed during specification into sensing-competent absorptive or secretory lineages, the surprising capacity of Paneth and goblet cells to detect fructose, and the important role of differentiation in modulating nutrient sensing.

NEW & NOTEWORTHY Small intestinal stem cells differentiate into several cell types transiently populating the villi. We used specialized organoid cultures each comprised of a single cell type to demonstrate that 1) differentiation seems required for nutrient sensing, 2) secretory goblet and Paneth cells along with enterocytes sense fructose, suggesting that sensing is acquired after differentiation is triggered but before divergence between absorptive and secretory lineages, and 3) forcibly dedifferentiated enterocytes exhibit fructose sensing and lifespan extension.

From: Kishida, K., Pearce, S. C., Yu, S., Gao, N., Ferraris, R. P. http://ajpgi.physiology.org/cgi/content/abstract/312/6/G592?rss=1

Detection of human elastase isoforms by the ScheBo Pancreatic Elastase 1 Test

Determination of fecal pancreatic elastase content by ELISA is a reliable, noninvasive clinical test for assessing exocrine pancreatic function. Despite the widespread use of commercial tests, their exact molecular targets remain poorly characterized. This study was undertaken to clarify which human pancreatic elastase isoforms are detected by the ScheBo Pancreatic Elastase 1 Stool Test and whether naturally occurring genetic variants influence the performance of this test. Using recombinantly expressed and purified human pancreatic proteinases, we found that the test specifically measured chymotrypsin-like elastases (CELA) 3A and 3B (CELA3A and CELA3B), while CELA2A was not detected. Inactive proelastases, active elastases, and autolyzed forms were detected with identical efficiency. CELA3B elicited approximately four times higher ELISA signal than CELA3A, and we identified Glu¹⁵⁴ in CELA3B as the critical determinant of detection. Common genetic variants of CELA3A and CELA3B had no effect on test performance, with the exception of the CELA3B variant W79R, which increased detection by 1.4-fold. Finally, none of the human trypsin and chymotrypsin isoforms were detected. We conclude that the ScheBo Pancreatic Elastase 1 Stool Test is specific for human CELA3A and CELA3B, with most of the ELISA signal attributable to CELA3B.

NEW & NOTEWORTHY The ScheBo Pancreatic Elastase 1 Stool Test is widely used to assess pancreatic exocrine function, yet its molecular targets have been poorly defined. We demonstrate that, among the human pancreatic proteinases, the test measures the elastase isoform CELA3B and, to a lesser extent, CELA3A. Genetic variants of the human CELA3 isoforms have no significant effect on test performance.

From: Toth, A. Z., Szabo, A., Hegyi, E., Hegyi, P., Sahin-Toth, M. http://ajpgi.physiology.org/cgi/content/abstract/312/6/G606?rss=1

Barretts metaplasia develops from cellular reprograming of esophageal squamous epithelium due to gastroesophageal reflux

Gastroesophageal reflux disease (GERD) clinically predisposes to columnar Barrett’s metaplasia (BM) in the distal esophagus. We demonstrate evidence supporting the cellular origin of BM from reprograming or transcommitment of resident normal esophageal squamous (NES) epithelial cells in response to acid and bile (A + B) exposure using an in vitro cell culture model. The hTERT-immortalized NES cell line NES-B10T was exposed 5 min/day to an A + B mixture for 30 wk. Morphological changes, mRNA, and protein expression levels for the inflammatory marker cyclooxygenase-2; the lineage-determining transcription factors TAp63 (squamous), CDX2, and SOX9 (both columnar); and the columnar lineage markers Villin, Muc-2, CK8, and mAb Das-1 (incomplete phenotype of intestinal metaplasia) were assessed every 10 wk. Markers of columnar lineage and inflammation increased progressively, while squamous lineage-determining transcriptional factors were significantly decreased both at the mRNA and/or protein level in the NES-B10T cells at/after A + B treatment for 30 wk. Distinct modifications in morphological features were only observed at/after 30 wk of A + B exposure. These changes acquired by the NES-B10T 30-wk cells were retained even after cessation of A + B exposure for at least 3 wk. This study provides evidence that chronic exposure to the physiological components of gastric refluxate leads to repression of the discernable squamous transcriptional factors and activation of latent columnar transcriptional factors. This reflects the alteration in lineage commitment of the precursor-like biphenotypic, NES-B10T cells in response to A + B exposure as the possible origin of BM from the resident NES cells.

NEW & NOTEWORTHY This study provides evidence of the origins of Barrett’s metaplasia from lineage transcommitment of resident esophageal cells after chronic exposure to gastroesophageal refluxate. The preterminal progenitor-like squamous cells alter their differentiation and develop biphenotypic characteristics, expressing markers of incomplete-type columnar metaplasia. Development of these biphenotypic precursors in vitro is a unique model to study pathogenesis of Barrett’s metaplasia and esophageal adenocarcinoma.

From: Minacapelli, C. D., Bajpai, M., Geng, X., Cheng, C. L., Chouthai, A. A., Souza, R., Spechler, S. J., Das, K. M. http://ajpgi.physiology.org/cgi/content/abstract/312/6/G615?rss=1

Oral Health Month seeks to raise dental health in Hispanic communities

Share photos, video for campaign to benefit GKAS

From: By Kimber Solana http://www.ada.org/en/publications/ada-news/2017-archive/may/oral-health-month-in-hispanic-communities

The cuts to a major disability program within Trump's budget

The White House's proposed cuts to Social Security Disability Insurance are aimed at pushing some beneficiaries back into the workforce

From: http://www.cbsnews.com/news/the-cuts-to-a-major-disability-program-within-trumps-budget/