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Posts Tagged ‘Harvard School of Public Health’


In Two-thirds of Waking Hours Older Women are Sedentary

Reporter: Aviva Lev-Ari, PhD, RN

 

Older women sedentary two-thirds of waking hours

By: MARY ANN MOON, Family Practice News Digital Network

Older women are sedentary for approximately two-thirds of their waking hours, usually in bouts lasting about 30 minutes each punctuated by brief periods of activity, according to a report published Dec. 18, 2013 in JAMA.

Recent studies suggest a high volume of sedentary behavior may be a risk factor for adverse health outcomes. However, few data exist on how this behavior is patterned (for example, does most sedentary behavior occur in a few long bouts or in many short bouts?)

In a research letter to the editor, investigators presented data collected from 7,247 older women (mean age, 71 years) participating in an ancillary study of the Women’s Health Study who wore accelerometers for 1 week to track their physical activity. Overall, the women spent 65.5% of their waking hours – the equivalent of 9.7 hours per day – in sedentary behavior, said Eric J. Shiroma of Harvard School of Public Health, Boston, and his associates.

The mean number of sedentary intervals was 85.9/day, with a mean of 9 breaks per sedentary hour. Most sedentary time occurred in short rather than long intervals, with approximately one-third of the sedentary bouts lasting roughly 30 minutes, the researchers said (JAMA 2013;310:2562-3).

Accelerometers cannot convey whether the women were sitting, standing, or lying down during sedentary periods, but it is most likely that they were sitting. “If future studies confirm the health hazards of sedentary behavior and guidelines are warranted, these data may be useful to inform recommendations on how to improve such behavior,” Mr. Shiroma and his associates said.

They noted that most participants in the Women’s Health Study were white and of higher socioeconomic statusso these findings may not apply to women of other backgrounds.

This study was supported by the National Institutes of Health. No relevant financial conflicts of interest were reported.

SOURCE

http://www.familypracticenews.com/single-view/older-women-sedentary-two-thirds-of-waking-hours/0e9af152ff0d6f3fb1f085ae175489e3.html

 

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The Young Surgeon and The Retired Pathologist: On Science, Medicine and HealthCare Policy – The Best Writers Among the WRITERS

Curator: Aviva Lev-Ari, PhD, RN

Updated on 2/18/2016

Since January 2005, I am a Reader, Curator and Author of scientific articles in Life Sciences and Medicine.

On 2/18/2016, the Open Access Online Scientific Journal launched in 4/2012,

Open Access Online Scientific Journal

http://pharmaceuticalintelligence.com

Site Statistics

Date

Views to Date

# of articles

NIH Clicks

Nature Clicks

6/24/2013

199,857

1,034

1,275

661

 7/29/2013  217,356  1,138  1,389  705
       12/11/2013  293,694  1,464  1,693  828
10/17/2015  765,762  3,444  2,726 1,683 
02/18/2016  886,454 4,162  2,911 1,813 

By 2/18/2016, I have curated 2,333 articles, the list of titles is on 109 pages on http://pharmaceuticalintelligence.com

Links to each article to be found at

https://pharmaceuticalintelligence.com/?s=Aviva+Lev-Ari%2C+PhD%2C+RN

Frontiers in Cardiology – 653 articles

https://pharmaceuticalintelligence.com/?s=Frontiers+in+Cardiology

These articles have been viewed, since the first article was published on 4/30/2012, by +886,454 viewers.

Author and Curator e-Readers since

4/30/2012

Journal Articles

on

2/18/2016

Aviva Lev-Ari, PhD, RN 248,163 2,333
Larry H Bernstein, MD, FCAP  

155,253

 

1,183

Of all the readings and reviews I completed to date, my appreciation got bonded to two Science and Medicine writers:

and

I am inviting the e-Readers to join me on a language immersion during a LITERARY TOUR in Science, Medicine and HealthCare Policy. 

Part One: The Young Surgeon

Eric J. Topol, MD: Editor’s Note on The Young Surgeon

Atul Gawande, MD, MPH, wears many hats, including that of a surgeon, researcher, journalist, and author. In this segment of Medscape One-on-One, Dr. Gawande talks with Eric J. Topol, MD, about what inspires him, his plans for the future, and why he’s secretly a frustrated rock singer.

WATCH the INTERVIEW of December 06, 2013 on VIDEO

Eric Topol on Medscape > Medscape One-on-One

Atul Gawande on the Secrets of a Puzzle-Filled Career

, Atul Gawande, MD, MPH

http://www.medscape.com/viewarticle/815241?nlid=41903_2105&src=wnl_edit_medp_card&uac=93761AJ&spon=2

Atul Gawande is a surgeon, writer, and public health researcher. He practices general and endocrine surgery at Brigham and Women’s Hospital in Boston, and is Director of Ariadne Labs, a joint center for health systems innovation. He is Professor in the Department of Health Policy and Management at the Harvard School of Public Health and Professor of Surgery at Harvard Medical School. And he is also co-founder and chairman of Lifebox, an international not-for-profit implementing systems and technologies to reduce surgical deaths globally.

Soon after he began his residency, his friend Jacob Weisberg, editor of Slate, asked him to contribute to the online magazine. His pieces on the life of a surgical resident caught the eye of The New Yorker which published several pieces by him before making him a staff writer in 1998.

A June 2009 New Yorker essay by Gawande[12] compared the health care of two towns in Texas to show why health care was more expensive in one town compared to the other. Using the town of McAllen, Texas, as an example, it argued that a revenue-maximizing businessman-like culture (which can provide substantial amounts of unnecessary care) was an important factor in driving up costs, unlike a culture of low-cost high-quality care as provided by the Mayo Clinic and other efficient health systems.

Ezra Klein of The Washington Post called it “the best article you’ll see this year on American health care—why it’s so expensive, why it’s so poor, [and] what can be done.”[13] The article was cited by Pres. Barack Obama during Obama’s attempt to get health care reform legislation passed by the United States Congress. The article “made waves”[14] and according to Senator Ron Wyden, the article “affected [Obama’s] thinking dramatically”, and was shown to a group of senators by Obama, who said, “This is what we’ve got to fix.”[15] After reading the New Yorker article, Warren Buffett‘s long-time business partner Charlie Mungermailed a check to Gawande in the amount of $20,000 as a thank you to Dr. Gawande for providing something so socially useful.[16] Gawande donated the $20,000 to the Brigham and Women’s Hospital Center for Surgery and Public Health.[17]

In addition to his popular writing, Gawande has published studies on topics including military surgery techniques and error in medicine, included in the New England Journal of Medicine. He is also the director of theWorld Health Organization‘s Global Patient Safety Challenge. His essays have appeared in The Best American Essays 2003, The Best American Science Writing 2002, The Best American Science Writing 2009 andBest American Science and Nature Writing 2011.

He has been a staff writer for the New Yorker magazine since 1998. He has written three bestselling books: Complications, which was a finalist for the National Book Award in 2002; Better, which was selected as one of the ten best books of 2007 by Amazon.com; and The Checklist Manifesto. He has won two National Magazine Awards, AcademyHealth’s Impact Award for highest research impact on health care, a MacArthur Fellowship, and he has been named one of the world’s hundred most influential thinkers by Foreign Policy and TIME.

ADDITIONAL LINKS

http://gawande.com/about

RESEARCH by Dr. Atul Gawande

Tsai TC, Joynt KE, Orav EJ, Gawande AA, Jha AK. Variation in Surgical-Readmission Rates and Quality of Hospital CareNew England Journal of Medicine Published online September, 2013.

Funk LM, Conley DM, Berry WR, Gawande AA. Hospital Management Practices and Availability of Surgery in Sub-Saharan Africa: A Pilot Study of Three HospitalsWorld Journal of Surgery Published online August, 2013.

Nehs MA, Ruan DT, Gawande AA, Moore FD Jr, Cho NL.Bilateral neck exploration decreases operative time compared to minimally invasive parathyroidectomy in patients with discordant imagingWorld Journal of SurgeryPublished online July, 2013.

Joynt KE, Gawande AA, Orav EJ, Jha AK.Contribution of Preventable Acute Care Spending to Total Spending for High-Cost Medicare PatientsJAMA Published online June 24, 2013.

McCrum ML, Joynt KE, Orav EJ, Gawande AA, Jha AK.Mortality for Publicly Reported Conditions and Overall Hospital Mortality RatesJAMA Published online June 24, 2013.

Spector JM, Lashoher A, Agrawal P, Lemer C, Dziekan G, Bahl R, Mathai M, Merialdi M, Berry W, and Gawande AA.Designing the WHO Safe Childbirth Checklist Program to Improve Quality of Care at ChildbirthInternational Journal of Gynecology & Obstetrics Published online June 5, 2013.

Barnet CS, Arriaga AF, Hepner DL, Correll DJ, Gawande AA, Bader AM. Surgery at the End of LifeThe Journal of the American Society of Anathesiologists Published online June, 2013.

Bowman KG, Jovic G, Rangel S, Berry WR, Gawande AA.Pediatric emergency and essential surgical care in Zambian hospitals: A nationwide studyJournal of Pediatric Surgery Published online June, 2013.

Rice-Townsend S, Gawande A, Lipsitz S, Rangel SJ.Relationship between unplanned readmission and total treatment-related hospital days following management of complicated appendicitis at 31 children’s hospitalsJournal of Pediatric Surgery Published online June, 2013.

Eappen S, Lane BH, Rosenberg B, Lipsitz SA, Sadoff D, Matheson D, Berry WR, Lester M, Gawande AA. Relationship Between Occurrence of Surgical Complications and Hospital FinancesJAMA April 17, 2013;309:1599-1606.

Kwok AC, Funk LM, Baltaga R, Lipsitz SR, Merry AF, Dziekan G, Ciobanu G, Berry WR, Gawande AA. Implementation of the World Health Organization Surgical Safety Checklist, Including Introduction of Pulse Oximetry, in a Resource-Limited SettingAnnals of Surgery April 4, 2013.

Molina G, Funk LM, Rodriguez V, Lipsitz SR, Gawande A.Evaluation of Surgical Care in El Salvador Using the WHO Surgical Vital StatisticsWorld Journal of Surgery Published online, March 2013.

Arriaga AF, Bader AM, Wong JM, Lipsitz SR, Berry WR, Ziewacz JE, Hepner DL, Boorman DJ, Pozner CN, Smink DS, Gawande AA. Simulation-Based Trial of Surgical-Crisis ChecklistsNew England Journal Of Medicine 2013;368:246-53.

Spector JM, Reisman J, Lipsitz S, Desai P, and Gawande AA.Access to Essential Technologies for Safe Childbirth: A Survey of Health Workers in Africa and AsiaBMC Pregnancy and Childbirth February 20, 2013;13:43-49.

Wong JM, Panchmatia JR, Ziewacz JE, Bader AM, Dunn IF, Laws ER, Gawande AA. Patterns in neurosurgical adverse events: intracranial neoplasm surgeryJournal of Neurosurgery 2012;33(5):E16.

Wong JM, Ziewacz JE, Ho AL, Panchmatia JR, Kim AH, Bader AM, Thompson BG, Du R, Gawande AA. Patterns in neurosurgical adverse events: open cerebrovascular neurosurgeryJournal of Neurosurgery 2012;33(5):E15.

GO TO the First article

http://gawande.com/articles

FIRST ARTICLE

Nanevicz TM, Prince MR, Gawande AA, Puliafito CA. Excimer laser ablation of the lens.Archives of Ophthalmology. 1986;104(12):1825-9.

Selected References

  1. Dr Atul Gawande – 2014 Reith Lectures. BBC Radio 4. Retrieved October 18, 2014.
  2. Atul Gawande on Twitter
  3.  Atul Gawande: ‘If I haven’t succeeded in making you itchy, disgusted or cry I haven’t done my job’, The Guardian
  4.  Former Policymaker Opts for Hands-On Health Care – International Herald Tribune
  5. MacArthur Fellows 2006. Atul Gawand
  6. “Atul Gawande Named MacArthur Fellow”. Press release by Brigham and Women’s Hospital. September 19, 2006. Retrieved February 25, 2010
  7. “Q&A with Atul Gawande, Part 2” H&HN. June 30, 2011. Retrieved July 7, 2011.
  8. Why Do Doctors Fail?The Reith Lectures, Dr Atul Gawande: The Future of Medicine Episode 1 of 4, BBC
  9. “Atul Gawande: surgeon, health policy scholar, and writer”.Harvard Magazine. Sep–Oct 2009
  10. Bates, D. W.; Gawande, A. A. (2003). “Improving Safety with Information Technology”. New England Journal of Medicine 348 (25): 2526. doi:10.1056/NEJMsa020847.
  11. Weiser, T. G.; Regenbogen, S. E.; Thompson, K. D.; Haynes, A. B.; Lipsitz, S. R.; Berry, W. R.; Gawande, A. A. (2008). “An estimation of the global volume of surgery: A modelling strategy based on available data”. The Lancet 372 (9633): 139. doi:10.1016/S0140-6736(08)60878-8.
  12. Gawande, A. A.; Studdert, D. M.; Orav, E. J.; Brennan, T. A.; Zinner, M. J. (2003). “Risk factors for retained instruments and sponges after surgery”. New England Journal of Medicine 348 (3): 229–35. doi:10.1056/NEJMsa021721. PMID 12529464.
  13. Gawande, A. A.; Thomas, E. J.; Zinner, M. J.; Brennan, T. A. (1999). “The incidence and nature of surgical adverse events in Colorado and Utah in 1992”. Surgery 126 (1): 66–75.doi:10.1067/msy.1999.98664. PMID 10418594.

Dr. Atul Gawande’s Articles in the New Yorker

States of Health
New Yorker
October 7, 2013

Slow Ideas
New Yorker
July 29, 2013

Why Boston’s Hospitals Were Ready
New Yorker
April 17, 2013

Big Med
New Yorker
August 6, 2012

Something Wicked This Way Comes
New Yorker
June 28, 2012

Failure and Rescue
New Yorker
June 4, 2012

200 Years of Surgery
New England Journal of Medicine
May 2, 2012
Documentary

Personal Best
The New Yorker
September 26, 2011

A Townie Speaks
Ohio University Commencement Address
June 11, 2011

Cowboys and Pit Crews
2011 Harvard Medical School Commencement Address
May 26, 2011

The Hot Spotters
The New Yorker
January 17, 2011

Seeing Spots
The New Yorker News Desk
January 27, 2011

Letting Go
The New Yorker
July 26, 2010
(citations)

Now What?
The New Yorker
Apr 5, 2010

Testing, Testing 
The New Yorker
Dec 14, 2009

The Cost Conundrum Redux
The New Yorker
News Desk Blog
Jun 23, 2009

The Cost Conundrum 
The New Yorker
Jun 1, 2009

Hellhole
The New Yorker
Mar 30, 2009

Getting There from Here 
The New Yorker
Jan 26, 2009

The Itch 
The New Yorker
Jun 30, 2008

A Lifesaving Checklist 
The New York Times
Dec 30, 2007

The Checklist 
The New Yorker
Dec 10, 2007

Sick and Twisted
The New Yorker
Jul 23, 2007

The Obama Health Plan
The New York Times
May 31, 2007

A Katrina Health Care System 
The New York Times
May 26, 2007

Rethinking Old Age
The New York Times
May 24, 2007

Let’s Talk About Sex 
The New York Times
May 19, 2007

Doctors, Drugs, and the Poor 
The New York Times
May 17, 2007

Bad Medicine, Sneaking In 
The New York Times
May 12, 2007

Curing the System
The New York Times
May 10, 2007

Can This Patient Be Saved? 
The New York Times
May 5, 2007

The Power of Negative Thinking
The New York Times
May 1, 2007

The Way We Age Now 
The New Yorker
Apr 30, 2007

The Score
The New Yorker
Oct 9, 2006

The Malpractice Mess
The New Yorker
Nov 14, 2005

Piecework
The New Yorker
Apr 4, 2005

The Bell Curve
The New Yorker
Dec 6, 2004

The Mop-Up
The New Yorker
Jan 12, 2004

Desperate Measures
The New Yorker
May 5, 2003

Cold comfort
The New Yorker
Mar 11, 2002

The learning curve
The New Yorker
Jan 28, 2002

The man who couldn’t stop eating
The New Yorker
Jul 9, 2001

Final cut
The New Yorker
Mar 19, 2001

Crimson tide

The New Yorker

Feb 12, 2001

Under suspicion
The New Yorker
Jan 8, 2001

When good doctors go bad
The New Yorker
Aug 7, 2000

GO TO the First article

FIRST ARTICLE
The Gist: Persian Gulf War Syndrome
The Gist
Slate
Oct 25, 1996
BOOKS

THE CHECKLIST MANIFESTO

A New York Times Bestseller and an Amazon Best Book of the Month: December 2009

http://gawande.com/the-checklist-manifesto

BETTER
One of Amazon.com’s 10 Best Books of 2007
Complications
“Essential Reading For Anyone Involved In Medicine”–Amazon.com –  2002

Overkill
An avalanche of unnecessary medical care is harming patients physically and financially. What can we do about it?
Annals of Health Care MAY 11, 2015
http://www.newyorker.com/magazine/2015/05/11/overkill-atul-gawande

It was lunchtime before my afternoon surgery clinic, which meant that I was at my desk, eating a ham-and-cheese sandwich and clicking through medical articles. Among those which caught my eye: a British case report on the first 3-D-printed hip implanted in a human being, a Canadian analysis of the rising volume of emergency-room visits by children who have ingested magnets, and a Colorado study finding that the percentage of fatal motor-vehicle accidents involving marijuana had doubled since its commercial distribution became legal. The one that got me thinking, however, was a study of more than a million Medicare patients. It suggested that a huge proportion had received care that was simply a waste.
tests, drugs, and operations

tests, drugs, and operations

Millions of Americans get tests, drugs, and operations that won’t make them better, may cause harm, and cost billions.
Our medical systems are broken. Doctors are capable of extraordinary (and expensive) treatments, but they are losing their core focus: actually treating people. Doctor and writer Atul Gawande suggests we take a step back and look at new ways to do medicine — with fewer cowboys and more pit crews.

Being Mortal: Medicine and What Matters in the End – Deckle Edge, Oct 7, 2014

Part Two: The Retired Pathologist 

On Science, Medicine and HealthCare Policy – The Best Writers Among the WRITERS

Roles at http://pharmaceuticalintelligence.com

Chief Scientific Officer, Member of the Board

Research Categories OWNER:

  • Biomarkers & medical diagnosis in Pathology (Co-Owner)
  • Clinical Trials and IRB related Issues
  • Acute and Chronic Disease Classifications
  • Biomarker Discovery and Validation
  • Cardiovascular Research
  • Clinical Laboratory-Related Issues
  • Healthcare and Hospital Costs
  • Health Information Technology  and Workflow Redesign
  • Metabolomics
  • Metabolic Derangements
  • Nutraceuticals
  • Nutrigenomics
  • Nutrition
  • Nutrition and Phytochemistry
  • Proteomics
  • Statistical Methods for Research Evaluation
  • Systemic Inflammatory Response Related Disorders

 

Larry H. Bernstein, M.D., FCAP – My Life in Medicine 

www.linkedin.com/pub/larry-h-bernstein/a/599/50

I retired from a five year position as Chief of the Division of Clinical Pathology (Laboratory Medicine) at  New York Methodist Hospital-Weill Cornell Affiliate, Park Slope, Brooklyn in 2008 folowed by an interim consultancy at Norwalk Hospital in 2010.  I then became engaged with a medical informatics project called “Second Opinion” with Gil David and Ronald CoifmanEmeritus Professor and Chairman of the Department of Mathematics in the Program in Applied Mathematics at Yale.  I went to Prof. Coifman with a large database of 30,000 hemograms that are the most commonly ordered test in medicine because of the elucidation of red cell, white cell and platelet populations in the blood.  The problem boiled down to a level of noise that exists in such data, and developing a primary evidence-based classification that technology did not support until the first decade of the 21st century.

Realtime Clinical Expert Support and Validation System

Gil David and Larry Bernstein have developed, in consultation with Prof. Ronald Coifman, in the Yale University Applied Mathematics Program, a software system that is the equivalent of an intelligent Electronic Health Records Dashboard that provides empirical medical reference and suggests quantitative diagnostics options.

Our dashboard is a visual display of essential metrics. The primary purpose is to gather medical information, generate metrics, analyze them in realtime and provide a differential diagnosis, meeting the highest standard of accuracy. The diagnosis provides a risk assessment to the patient’s medical condition, while locating and presenting similar cases of other patients with the same anomalous profile and their corresponding treatment and followup. Given medical information of a patient, the system builds its unique characterization and provides a list of other patients that share this unique profile, therefore utilizing the vast aggregated knowledge (diagnosis, analysis, treatment, etc.) of the medical community.

The main mathematical breakthroughs are provided by accurate patient profiling and inference methodologies in which anomalous subprofiles are extracted and compared to potentially relevant cases. Our methodologies organize numerical medical data profiles into demographics and characteristics relevant for inference and case tracking. As the model grows and its knowledge database is extended, the diagnostic and the prognostic become more accurate and precise.

We anticipate that the effect of implementing this diagnostic amplifier would result in higher physician productivity at a time of great human resource limitations, safer prescribing practices, rapid identification of unusual patients, better assignment of patients to observation, inpatient beds, intensive care, or referral to clinic, shortened length of patients ICU and bed days.

[Second Opinion 2009-2011 Proprietary]

As an example, inputs from test data such as Hematology results are processed for anomaly characterization and compared with similar anomalies in a data base of 30,000 patients, provide diagnostic statistics, warning flags , and risk assessment . These are based on past prior experience , including ,diagnostics and treatment outcomes (collective experience). The system was trained on this database of patients, built the learning knowledge base and used to analysis and diagnosis 5,000 new patients. Our system identified successfully the main risks with very high accuracy (more than 96%) and very low false rate (less than 0.5%).

The main benefit is a real time assessment as well as diagnostic options based on

comparable cases, flags for risk and potential problems as illustrated in the following case acquired on 04/21/10. The patient was diagnosed by our system with severe SIRS at a grade of .61 .

The patient was treated for SIRS and the blood tests were repeated during the following week. Following treatment, the SIRS risk as a major concern was eliminated and the system provides a positive feedback for the treatment of the physician.

To experiment with our demo system using our existing database or your own data it  resides online at:

http://netlab2.math.yale.edu:30049/cgi-bin/second opinion.py

[Second Opinion 2009-2011 Proprietary]

I have been reviewing manuscripts somewhat frequently for Nutrition, Clin Chem Lab Med, Clin Biochem, and J Ped Hem Oncol., and serve on the Editorial Advisory Board of Nutrition.

I was the Chief, Clinical Pathology at NY Methodist Hospital, a 600+ bed hospital in Park Slope, Brooklyn, 2 hours from Bridgeport, CT, where I worked for 5 years,  and was previously Chief of Clinical Chemistry and Chief of Blood Bank at Bridgeport Hospital for 20 years, and Acting Chairman of Yale University Department of Pathology at Bridgeport Hospital for one year prior to my experience at NY Methodist Hospital Weill-Cornell.

My work with nutrition is extensive as a consulting pathologist on the Nutritional Support Team and I worked closely with the Burn Unit at Bridgeport Hospital, led by Dr. Walter Pleban, the first physician expert in burn and wound care to use TPN in Connecticut.  I rejected the dependence on serum albumin and implemented the first use of prealbumin (transthyretin)(half-life of 2 days) to follow the return to anabolic status of severely stressed patients, starting with Immunodiffusion plates from Behring Diagnostics, then converting to running batch turbidimetric assays on the Roche centrifugal analyzer, and finally running on a Beckman. My lab was the only one to get down to reliable measurements of 20 mg/L.  I co-chaired the First International Transthyretin Congress in Strasbourg, chaired the 14th and was an invited participant in the 17th Ross Roundtable on Nutrition, Organized and Chaired the Beckman Roundtable on Prealbumin in Los Angeles, was responsible for the AACC first document of Standards of Clinical Laboratory Practice with Lawrence Kaplan, and was recipient of the Labbe/Garry award of the Nutrition Division of AACC).  I did some of the earliest work on point of care diagnostics in neonatal care. My work with Creatine kinase isoenzyme MB and the isonzyme 1 of LD goes back to my residency and my long term contact with Burton Sobel. The improved use of troponins and NT-proBNP and have  been ongoing projects for the last 10 years, some of which was supported by Roche Diagnostics on the recommendation of Pauline Lau and Bernard Statland. The projects in normalizing the NT-proBNP for age and estimated glomerular filtration rate (eGFR), was successful, but widespread implementation is even more gradual than was TTR.

I have served on the Board of Directors of NAACLS and the American Library Association Commission on Accreditation, am listed in America’s Top Physicians, Marquis Who’s Who in Science and Engineering and Marquis’ Who’s Who in Medicine, Who’s Who in Pathology, Continental Who’s Who, Strathmore’s Who’s Who, and have 3 patents.

BIO
Selected Peer Reviewed publications

1. Rosser A. Rudolph, Larry H. Bernstein,and Joseph Babb. Information Induction for
Predicting Acute Myocardial Infarction. CLIN CHEM 1988; 34(10): 2031-2038.

2. Zarich SW, Bradley K, Mayall ID, Bernstein LH. Minor elevations in troponin T values enhance risk assessment in emergency department patients with suspected myocardial ischemia: analysis of novel troponin T cut-off values. Clin Chim Acta 2004; 343:223-29.

3. Bernstein, L.H.; Devakonda, A.; Engelman, E.; Pancer, G.; Ferrara, J.; Rucinski, J.; Raoof, S.; George, L.; Melniker, L. The Role of Procalcitonin in the Diagnosis of Sepsis and Patient Assignment to Medical Intensive Care.  J Clinical Ligand Assay, 2007; 30 (3-4):98-104

Older patients, make up a large part of the ICU population and tend to have an acute stressful condition superimposed on chronic illness.  The effects of anorexia, hypermetabolism, and malabsorption on these patients lead to substantial nitrogen losses. The most widely used methods for assessing malnutrition are the Subjective Global Assessment (SGA); TTR, and a combination of laboratory and biochemical features. The simplest of these, transthyretin (TTR) has become a commonly assayed protein in assessing PEM status. Clinical studies indicate that determination of the TTR level may allow for earlier recognition of malnutrition risk and timely intervention. Since TTR has a relatively short circulating half-life, it is expected to respond rapidly in response to metabolic support. TTR production decreases after 14 days of consuming a diet that provides only 60% of required proteins. Rapid turnover proteins, such as transthyretin (half-life < 2 days) respond early to nutrition support, and reflect a delayed return to anabolic status.It is particularly helpful in removing interpretation bias, and it is an excellent measure of the systemic inflammatory response concurrent with a preexisting state of chronic inanition. In the ICU patients we studied, TTR removed interpretation bias because the sickest patients experienced an uncommon delayed return of TTR to normal levels with adequate nutritional support.
DevakondaA, et al,Transthyretin as a marker to predict outcome in critically ill patients,ClinBiochem(2008),doi:10.1016/j.clinbiochem.2008.06.016
Protein energy malnutrition; Critically ill patients; Stress hypermetabolism; Transthyretin;  Multivariate classification.

4. Bernstein LH, Zions MY, Haq SA, Zarich S, Rucinski J, Seamonds B, Berger S, Lesley DY, Fleischman W, Heitner JF: Effect of renal function loss on NT-proBNP level variations. Clin Biochem; 2009;42(10-11):1091-8 [PMID: 19298805]

OBJECTIVE: NT-proBNP level is used for the detection of acute CHF and as a predictor of survival. However, a number of factors, including renal function, may affect the NT-proBNP levels. This study aims to provide a more precise way of interpreting NT-proBNP levels based on GFR, independent of age. METHODS: This study includes 247 pts in whom CHF and known confounders of elevated NT-proBNP were excluded, to show the relationship of GFR in association with age. The effect of eGFR on NT-proBNP level was adjusted by dividing 1000 x log(NT-proBNP) by eGFR then further adjusting for age in order to determine a normalized NT-proBNP value. RESULTS: The normalized NT-proBNP levels were affected by eGFR independent of the age of the patient. CONCLUSION: A normalizing function based on eGFR eliminates the need for an age-based reference ranges for NT-proBNP.
Kidney Function Tests. Natriuretic Peptide, Brain / blood. Peptide

5. David G, Bernstein LH, Coifman RR.  Generating Evidence Based Interpretation of Hematology Screens via Anomaly Characterization. The Open Clinical Chemistry Journal, 2011; 4:10-16. ISSN 1874-2416/11. Bentham Journal.
Introduction: We propose an automated nutritional assessment (ANA) algorithm that provides a method for malnutrition risk prediction with high accuracy and reliability. Materials  and Methods: The database used for this study is a file of 432 patients, where each patient is described by 4 laboratory parameters and 11 clinical parameters. A malnutrition risk assessment of low (1), moderate (2) or high (3) was assigned by a dietitian for each patient. An algorithm for data organization and classification via characteristic metrics is proposed.  For each patient, the algorithm characterizes its unique profile and builds a characteristic metric to identify similar patients who are mapped into a classification. Results: The algorithm assigned a malnutrition risk level for each patient based on different training sizes that were taken out of the data. Our method resulted in an average error (distance between the automated score and the real score) of 0.386, 0.3507, 0.3454, 0.34 and 0.2907 for 10%, 30%, 50%, 70% and 90% training sizes, respectively. Our method outperformed the compared method even when our method used a smaller training set then the compared method. In addition, we show that the laboratory parameters themselves are sufficient for the automated risk prediction and adding the clinical parameters does not improve the accuracy. We present an organization of the patients into several clusters and sub-clusters. These  clusters  correspond to low risk areas, low-moderate risk areas, moderate risk areas, moderate-high risk areas and high risk areas. The organization and visualization methods provide a tool for exploration and navigation of the data points. Discussion: The problem of rapidly identifying risk and severity of malnutrition is crucial for minimizing medical and
surgical complications associated with previsit under-nutrition, chronic illness affecting swallowing, eating, and weight loss.

6. Brugler L, Stankovic AK, Schlefer M, Bernstein L. A simplified nutrition screen for hospitalized patients using readily available laboratory and patient information. Nutrition 2005; 21(6): 650-658

Results:  The analysis demonstrated the characteristics that correlated best with MRC risk level assignment were: the occurrence of a wound (p=2.5e14), poor oral intake (p=3.2e-14), malnutrition related admission diagnosis (p=3.9e-9), serum albumin value (p=1.4e-31), hemoglobin value (p=3.3e-10), and total lymphocyte count   (p=1.4e-29). The 6 variable model had an R2 of 0.773 and p = 4.6e-116. A second model had 4 variables (malnutrition related admission diagnosis, serum albumin value, hemoglobin value and total lymphocyte count) and 3 (high, moderate and low) versus 4 (high, moderate, low and no) MRC risk levels with an R2 of 0.721 and p = 1.6e-104. Discussion: The ability of admission information to accurately reflect MRC risk is crucial to early initiation of restorative medical nutrition therapy (MNT), the efficient utilization of nutrition care resources and compliance with regulatory requirements. There is currently no uniform or proved standard for identifying MRC risk within 24 hours of acute care admission. The ideal nutrition screen correlates well with the occurrence of MRCs and also contains parameters that can be quickly and routinely obtained at admission. The six and even four parameter models described above meet both criteria and they can be uniformly used by hospitals to screen patients for MRC risk.7. Larry H. Bernstein, and James Rucinski. The relationship between granulocyte maturation and theseptic state measurement of granulocyte maturation may improve the early  diagnosis of the septic state,   Clin Chem Lab Med 2011;49   DOI 10.1515/CCLM.2011.688

Methods: This study calibrates and validates the measurement of granulocyte maturation with Immature granulocytes (IG) to the identification of sepsis, a study carried out on a
Sysmex Analyzer, model XE 2100 (Kobe, Japan). The Sysmex IG parameter is a crucial measure of immature granulocyte counts and includes metamyelocytes and myelocytes,
but not band neutrophils. Results and conclusions: We found agreement with previous work that designated an IG measurement cut-off of 3.2  as optimal. The analysis was then carried a step further with a multivariable discriminator.

8. Larry H Bernstein and Johannes Everse. Studies on the Mechanism of the Malate Dehydrogenase Reaction. J Biol Chemistry.  Dec 25, 1978; 253(24): 8702-8707.

These studies determine the levels of malate dehydrogenase isoenzymes in cardiac muscle by a steady state kinetic method which depends on the differential inhibition of these isoenzyme forms by high concentrations of oxaloacetate. This inhibition is similar to that exhibited by lactate dehydrogenase in the presence of high concentrations of pyruvate. The results obtained by this method are comparable in resolution to those obtained by CM-Sephadex fractionation and by differential centrifugation for the analyses of mitochondrial malate dehydrogenase and cytoplasmic malate dehydrogenase in tissues. The use of standard curves of percent inhibition of malate dehydrogenase activity plotted against the ratio of mitochondrial MDH activity to the total of mMDH and cMDH activities [ malate dehydrogenase ratio] (percent m-type) is introduced for studies of comparative mitochondrial function in heart muscle of different species or in different tissues of the same species.

9. MB Grisham, LH Bernstein, J Everse. The cytoplasmic malate dehydrogenase in neoplastic tissues” presence of a novel isoenzyme? Br J Cancer 1983; 47: 727-731

Malate dehydrogenase (MDH,EC1.1.1.37) catalyzes the reversible reduction of oxaloacetate tomalate in the presence of NADH. In eukaryotic cells the enzyme is generally found to be present as two distinct isoenzymes; one form is present in the cellular cytosol and the other is present exclusively in the mitochondria. These 2 isoenzymes form part of a shuttle system (the malate-aspartate shuttle) that functions as the major mechanism for the transportation of reducing equivalents between the cytosol and the mitochondria. As part of our ongoing studies on the mechansim of action and metabolic function of the malate dehydrogenases (Bernstein,etal. 1978; Bernstein & Everse, 1978; Bernstein & Grisham 1978), we recently
investigated the kinetic properties of the 2 isoenzymes present in rat Novikoff hepatoma tissues.These studies were initiated to evaluate whether or not the enzymes in the malate-asparate shuttle of tumour tissues are structurally and functionally identical to those of normal tissues. Fresh tumour or liver was homogenized with a glass tissue homogenizer in 0.1M potassium phosphate buffer, pH 7.5, containing 0.25M sucrose, centrifuged to remove tissue debris, and the supernatant was then centrifuged to obtain a supernatant that contained the cytoplasmic enzymes. The supernatantant did not contain any isocitrate dehydrogenase activity or transhydrogenase activity and was therefore judged to be free of mitochondrial enzymes.This high-speed supernatant was used without further fractionation for the determination of the cytoplasmic MDH activity. Mitochondria were prepared by suspending the pellet in 0.1M phosphate buffer, pH7.5, containing 0.25M sucrose and centrifuging the suspension at 600 g,  and re-centrifuged at 20,000 g for 30 min, and the precipitate was collected and washed, then suspended in phosphate buffer and sonicated for 1 min. The resulting solution was used for the assays for the mitochondrial enzyme. The assays were performed in 0.1M phosphate buffer, pH 7.0, at room temperature with a Beckman Model 24 recording spectrophotometer. We found that the Km values of the mitochondrial enzyme from the hepatoma tissue were identical with the values obtained with the enzyme from normal liver mitochondria. The cytoplasmic enzymes also have identical Km values for the coenzyme; however,the Lineweaver-Burk plots for oxaloacetate were non-identical. Whereas the Km value for oxaloacetate obtained with the liver enzyme was- 55 M, the Lineweaver-Burk plot obtained with the hepatoma enzyme displayed 2 slopes. One of the slopes corresponded with a Km value that is approximately identical to that of the liver enzyme, whereas the other slope yielded a Km value for oxaloacetate of-1mM. We interpret these data to indicate that Novikoff hepatoma tissue contains 2 cytoplasmic enzymes that possess MDH activity, one of which closely resembles that present in the rat liver cytoplasm. The other enzyme, having a Km of-1mM, is not found in normal liver tissue.

Is the Warburg Effect the Cause or the Effect of Cancer: A 21st Century View?

Author: Larry H. Bernstein, MD, FCAP  

Article Published 10/17/2012 — 4,111 VIEWS on 12/10/2013

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Electronic Books EDITORIAL 

Series A: e-Books on Cardiovascular Diseases

Content Consultant: Justin D Pearlman, MD, PhD, FACC

Volume One: Perspectives on Nitric Oxide

Sr. Editor: Larry Bernstein, MD, FCAP, Editor: Aviral Vatsa, PhD and Content Consultant: Stephen J Williams, PhD

available on Kindle Store @ Amazon.com

http://www.amazon.com/dp/B00DINFFYC

Volume Two: Cardiovascular Original Research: Cases in Methodology Design for Content Co-Curation

Curators: Justin D Pearlman, MD, PhD, FACC, Larry H Bernstein, MD, FCAP, Aviva Lev-Ari, PhD, RN

  • Causes
  • Risks and Biomarkers
  • Therapeutic Implications

Volume Three: Etiologies of CVD: Epigenetics, Genetics & Genomics

Curators: Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

  • Causes
  • Risks and Biomarkers
  • Therapeutic Implications

Genomics and Medicine by Prof. Marcus Feldman, Stanford University

Volume Four: Therapeutic Promise: CVD, Regenerative & Translational Medicine

Curators: Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

  • Causes
  • Risks and Biomarkers
  • Therapeutic Implications

Volume Five: Pharmaco-Therapies for CVD

Curators: Justin D Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

  • Causes
  • Risks and Biomarkers
  • Therapeutic Implications

Volume Six: Interventional Cardiology and Cardiac Surgery

Curators: Justin D Pearlman, MD, PhD, FACC, Larry H Bernstein, MD, FCAP, Aviva Lev-Ari, PhD, RN

  • Causes
  • Risks and Biomarkers
  • Therapeutic Implications

Series B: e-Books on Genomics & Medicine

Content Consultant: Larry H Bernstein, MD, FCAP

Volume 1: Genomics and Individualized Medicine

Sr. Editor: Stephen J Williams, PhD

Editors: Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

Volume 2: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS & BioInformatics, Simulations and the Genome Ontology

Editor: Stephen J Williams and Aviva Lev-Ari, PhD, RN

Volume 3: Institutional Leadership in Genomics

Editors: Marcus Feldman, PhD and Aviva Lev-Ari, PhD, RN 

Series C: e-Books on Cancer & Oncology

Content Consultant: Larry H Bernstein, MD, FCAP

Volume 1: Cancer and Genomics

Sr. Editor: Stephen J Williams, PhD

Editors: Ritu Saxena, PhD, Tilda Barliya, PhD

Volume 2: Radiation Oncology & Immunotherapy in Cancer

Editor: Larry H Bernstein, MD, FCAP

Volume 3: Nanotechnology and Drug Delivery

Editor and Author: Tilda Barliya, PhD

Series D: e-Books on BioMedicine

Volume 1: Metabolomics

Sr. Editors: Larry H Bernstein, MD, FCAP

Series E: Patient-Centered Medicine

Expert, Author, Writer: Larry H Bernstein, MD, FCAP

Editor: Larry H Bernstein, MD, FCAP

Editor: Larry H Bernstein, MD, FCAP

Expert, Author, Writer: Larry H Bernstein, MD, FCAP

ARTICLES on http://pharmaceuticalintelligence.com

12/10/2013: 276 Scientific Articles
FIRST Article on This Open Access Scientific Journal, 7/28/2013, 569 Views:
  • Vegan Diet is Sulfur Deficient and Heart Unhealthy
  • Erythropoietin (EPO) and Intravenous Iron (Fe) as Therapeutics for Anemia in Severe and Resistant CHF: The Elevated N-terminal proBNP Biomarker

Selected citations to peer reviewed publications

 Clinical value of NT-proBNP assay in the emergency department for the diagnosis of heart f…
Archives of gerontology and geriatrics 05/2015; 61(2). DOI:10.1016/j.archger.2015.05.001
 Diagnostic Yield of Targeted Next-Generation Sequencing in Various Cancer Types: An Inform…
Cancer Genetics 05/2015; 208(9). DOI:10.1016/j.cancergen.2015.05.030
Information induction for predicting acute myocardial infarction…in –
The economic cost of hospital malnutrition in Europe; a narrative review
e-SPEN the European e-Journal of Clinical Nutrition and Metabolism 04/2015; DOI:10.1016/j.clnesp.2015.04.003

Plasma Transthyretin as a Biomarker of Lean Body Mass and Catabolic States

Sep 2015 · Advances in Nutrition  Yves Ingenbleek  Larry H Bernstein

Transthyretin as a marker to predict outcome in critically ill patients
Devakonda, A., George, L., Raoof, S., Esan, A., Saleh, A., Bernstein, L.H.
Clinical Biochemistry  2008; 41(14-15):1126 – 1130

Biomarkers in critically ill patients with systemic inflammatory response syndrome or sepsis supplemented with high-dose selenium
Brodska, H., Valenta, J., Malickova, K., Kohout, P., Kazda, A., Drabek, T.
Journal of Trace Elements in Medicine and Biology 2015; 31:25-32View all citations to your article in Scopus

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Larry H. Bernstein, MD, Reviewer and Curator
Leaders in Pharmaceutical Intelligence
https://pharmaceuticalintelligence.com/2013/06/20/Naked Mole Rats Cancer-Free/lhbern

This discussion is a novel piece of investigations now and earlier  published in the Proceedings of the National Academy of Sciences, and another in Nature pertaining to aging, longevity, and cancer.  The blind mole rat has an unexpected lifespan compared to other rodents.  There are also findings of a related naked mole rat that comes into the picture.  They are related, but not exactly the same. In both cases, the moles are cold-blooded, live underground with a queen and workers and they don’t develop cancer. The naked mold rates don’t develop cancer because of the presence of an imbalance in the intercellular matrix caused by abundant naturally produced, sticky complex carbohydrate also found in human joints that repels the cells at their interstices.

This is fascinating because it is also an important aspect of joint mobility.  In the situation of chondomalacia before erosion of the articular cartilage, the movement and shearing stresses initially induced production of more chondrocytes and with that, a thickened cartilage that becomes taxed until it loses matrix fluid, followed by loss of matrix and loss of collagen by shearing stress.  This type of motion and shear stress plays no part in the life of the naked mole rat, which has a rough skin.  The property of the cellular matrix seems to be characterized by both the production of the intercellular goo…called hyalurenan (like hyaluronic acid) and sparse hyaluronidase to remove and remodel the cell architecture.  How this is related to extreme aging and no loss of cellular growth control, having sparce ubiqitination that is involve in cell death and repair is unclear.

The hyaluronidases (EC 3.2.1.35) are a family of enzymes that degrade hyaluronic acid.  In humans, there are six associated genes, including HYAL1, HYAL2, HYAL3, and PH-20/SPAM1. By catalyzing the hydrolysis of hyaluronan, a constituent of the extracellular matrix (ECM), hyaluronidase lowers the viscosity of hyaluronan.  http://upload.wikimedia.org/wikipedia/commons/2/2f/Hyaluronidase-1OJN.png

The blind mole rat is closely related, but it differs in that it has a mechanism by which the cells have limited proliferation and don’t proliferate to the point of getting out of control.  This is because after several generations of cellular proliferation they produce a protein,  IFN-β.  This protein induces massive apoptosis, limiting the size of the sell population. There are findings in these investigations that might be relevant to understanding cancer resistance, and perhaps it could provide clues to treatment approaches.  If that is too much to ask for, it gives us great insight into how cells organize.

Cancer resistance in the blind mole rat is mediated by concerted necrotic cell death mechanism

Gorbunovaa V, Hinea C, Tiana X, Ablaevaa J, Gudkovb AV, Nevoc E, and Seluanova A.
Contributed by Eviatar Nevo, October 3, 2012 (sent for review August 28, 2012)

Abstract

Blind mole rats Spalax (BMR) are small subterranean rodents common in the Middle East. BMR is distinguished by its adaptations to life underground, remarkable longevity (with a maximum documented lifespan of 21 y), and resistance to cancer. Spontaneous tumors have never been observed in spalacids. To understand the mechanisms responsible for this resistance, we examined the growth of BMR fibroblasts in vitro of the species Spalax judaei and Spalax golani. BMR cells proliferated actively for 7–20 population doublings, after which the cells began secreting IFN-β, and the cultures underwent massive necrotic cell death within 3 d. The necrotic cell death phenomenon was independent of culture conditions or telomere shortening. Interestingly, this cell behavior was distinct from that observed in another long-lived and cancer-resistant African mole rat, Heterocephalus glaber, the naked mole rat in which cells display hypersensitivity to contact inhibition. Sequestration of p53 and Rb proteins using SV40 large T antigen completely rescued necrotic cell death. Our results suggest that cancer resistance of BMR is conferred by massive necrotic response to overproliferation mediated by p53 and Rb pathways, and triggered by the release of IFN-β. Thus, we have identified a unique mechanism that contributes to cancer resistance of this subterranean mammal extremely adapted to life underground.

Source:

1To whom correspondence may be addressed. E-mail:  vera.gorbunova@rochester.edu, nevo@research.haifa.ac.il, or andrei.seluanov@rochester.edu.

2Present address: Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115.

http://www.pnas.org/content/early/2012/10/31/1217211109

naked mole rat

Image: Greg Goebel/Flickr


Long-Lived Rat May Hold Clues to Combating Aging

BY BRANDON KEIM02.17.09

The extraordinarily durable proteins in the world’s longest-lived rodent may contain a vital piece of the puzzle of aging.

  • Like short-lived mice, the cells of naked mole rats are suffused with free-floating, cell-damaging oxygen free radicals. 
  • Unlike the mice — and every other species that appears compromised by oxidative deterioration, including humans — they’ve found a way to live with it.

“When we compare the lab mouse with the naked mole rat, we find a striking difference in their systems,” said study co-author Asish Chaudhuri, a University of Texas Health Science Center biochemist. “Their proteins are still working. Even when damaged, the functions are maintained.”

The findings, published Monday in the Proceedings of the National Academy of Sciences, represent a new wrinkle in the oxidative-stress theory of aging. According to the theory, mitochondria — cellular machines that produce our bodies’ energy — pump out highly reactive oxygen molecules during respiration. Called free radicals, these molecules bind easily with other molecules, including DNA. Over time, DNA breaks down, compromising cellular function. Eventually whole tissues and organs no longer function.  Multiple studies have found evidence of mitochondrial malfunction in a range of diseases that become more common with age, from heart disease to neurodegeneration to cancer. Drugs designed to rejuvenate mitochondria have shown promise in treating diabetes, and are celebrated as possible therapies for other conditions.

DNA repair rate is an important determinant of...

DNA repair rate is an important determinant of cell pathology (Photo credit: Wikipedia)

Chaudhuri’s team’s findings don’t contradict the role of mitochondria, but expand the theory to include cellular proteins other than DNA. They also explain a condundrum: some long-lived species display plenty of oxidative damage. “We’ve studied a dozen species, half short-lived and the others long-lived. One long-lived species would have lots of oxidative damage, and another would have little. The one thing that seemed to be consistent was protein stability,” said University of Texas Health Sciences Center gerontologist Steven Austad, who was not involved in the current study. “Until recently I’ve focused on DNA damage and repair, but this strikes me as even more fundamental. For DNA repair to work, you need all the repair proteins to work properly.”  Mole rats caught the researchers’ attention because they can live for 30 years, or ten times longer than lab mice, even though the two are similarly sized.

They found that mole rats do have efficient mitochondria that release fewer free radicals than expected. But their mitochondria aren’t perfect. Free radicals still gather and cause damage. Two-year-old mole rats show just as much oxidative stress two-year-old mice — and then live for another quarter-century.  The key appears to be their proteins, which continue to function despite damage. Study co-author Rochelle Buffenstein, a University of Texas Health Sciences Center physiologist, likened the phenomena to rusting cars: in other species, the axles rust, but in naked mole rats, it’s just the doors.  With heat and urea — both of which typically cause complex protein spools to unfold — the researchers tried to break down the proteins, but to no avail.  “You can basically hit them with a sledgehammer, and the proteins don’t unfold,” said Buffenstein. “Something makes them inherently more stable. There might be small molecules that tack on to proteins and help them retain structure in the face of cellular stress.”

Mole rats also appear to delay protein repair until the last possible moment, thus saving energy and resources. When proteins finally do break down, mole rats do an especially efficient job of cleaning them up. Only a tiny bit of ubiquitin — the chemical tag used to label damaged proteins for disposal — is required.  Finally, specialized protein-disposal structures, called proteosomes (tied to ubiqitination), don’t appear to break down with age in mole rats.

English: Damaraland mole-rat (Fukomys damarensis)

English: Damaraland mole-rat (Fukomys damarensis) (Photo credit: Wikipedia)

The researchers will next try to determine what maintains the mole rat’s proteins and proteosome. If, as Buffenstein suspects, it turns out to be an as-yet-unidentified protein protectant, scientists could apply the findings to people. “If we can identify those proteins, we can use them to study aging and age-related diseases. These animals don’t have any symptoms of neurodegeneration, even in old age,” said Chaudhuri. “Then we can design peptides that act like the protein, and take it as a drug.”

Citation:

Protein stability and resistance to oxidative stress are determinants of longevity in the longest-living rodent, the naked mole-rat.

By Viviana I. Perez, Rochelle Buffenstein, Venkata Masamsetti, Shanique Leonard, Adam B. Salmon, James Meleb, Blazej Andziak, Ting Yang, Yael Edrey, Bertrand Friguet, Walter Ward, Arlan Richardson and Asish Chaudhuri. Proceedings of the National Academy of Sciences, Vol. 106 No. 7, Feb. 16, 2009.

Why Blind Mole Rats Don’t Get Cancer

By Ian Steadman, Wired UK

Blind mole rats don’t get cancer. in 2011 it was found they have a gene that stops cancerous cells from forming. The same team thought that two other cancer-proof mole rat species might have similar genes, but instead it turns out that they do develop cancerous cells. It’s just that those cells are programmed to destroy themselves if they become dangerous.

The blind mole rat (Spalax typhlus) has tiny e...

The blind mole rat (Spalax typhlus) has tiny eyes completely covered by a layer of skin. (Photo credit: Wikipedia)

Mole rats, which live in underground burrows throughout Southern and Eastern Africa, and the Middle East, are fascinating creatures. The naked mole rat, in particular, is the only cold-blooded mammal known to man, doesn’t experience pain, and is also arguably the only mammal (along with the Damaraland mole rat) to demonstrate eusociality — that is, they live in large hierarchical communities with a queen and workers, like ants or bees.

The two species examined by the University of Rochester’s Vera Gorbunova and her team were the Judean Mountains blind mole rat (Spalax judaei) and the Golan Heights blind mole rat (Spalax golani), which live within small regions of Israel. The team took cells from the rodents and put them in a culture that would force them to multiply beyond what would happen within the animals’ bodies. For the first seven to 20 multiplications, things looked fine, but beyond 20 multiplications the cells started rapidly dying off.  Examining the cells as they died revealed that they had started to produce a protein, IFN-β, that caused them to undergo “massive necrotic cell death within three days”. In effect, once the cells had detected that they had multiplied beyond a certain point, they killed themselves. The cells of naked mole rats have a self-preservation mechanism tied to a hypersensitivity to overcrowding, which stops them from multiplying too much.  On the one hand (blind mole rat) you have self-destruction at a point at which there is crowding due to IFN-β.  On the other hand, you find an aversion to overcrowding (naked mole rat).

In the Proceedings of the National Academy of Sciences, Gorbunova hypothesizes that the blind mole rats’ unique habitat — almost entirely underground — might mean that they “could perhaps afford to evolve a long lifespan, which includes developing efficient anti-cancer defences”. Blind mole rats have extremely long lifespans by rodent standards, often living beyond 20 years at a time.

The reasons why this is, though, are still all hypothetical, as the precise mechanism that triggers the production of the IFN-β is still unknown. The hope is that this research could eventually lead to new therapies for cancer in humans.

Super Sugar Keeps Naked Mole Rats Cancer-Free

BY ELIZABETH PENNISI, SCIENCENOW 06.20.13

Although they are quite ugly and confined to a life underground, naked mole rats have at least one attribute that other animals, even humans, might aspire to: They don’t get cancer. Now, researchers have discovered that the secret to this rodent’s good health is a complex sugar that helps keeps cells from clumping together and forming tumors.  It exists in the spaces between cells called the extracellular matrix, “the work underlines the very important regulatory role of [the] extracellular matrix in cancer,” says Bryan Toole, a cancer biologist at the Medical University of South Carolina in Charleston who was not involved with the study. Molecular and cell biologist Vera Gorbunova of the University of Rochester in New York wanted to take a different tack and focus on animals that seem protected from tumors. So she tracked down the lifespans of 20 different rodents, looking for the ones that live a long time. Beavers and gray squirrels last a couple of decades, but naked mole rats outlive those larger animals by 10 years.  Furthermore, naked mole rats have a unique social structure, with one queen that produces all the young for an underground colony full of helpers. Thanks to these studies, scientists know for sure that this species doesn’t get cancer. Given that naked mole rats live long and are resistant to cancer, “we fell in love with them right away,” Gorbunova says.

At first, she and her colleagues did not know where to look for the source of animals’ cancer resistance. But when they grew naked mole rat cells in a lab dish, they noticed that cells wouldn’t get too close together. Furthermore, the dish contents got very gooey, and when they eliminated the goo, the cells would clump together. The researchers tracked the stickiness to a complex sugar called hyaluronan, which cells make and release into the extracellular matrix.  Hyaluronan exists in all animals, helping lubricate joints and serving as an essential component in skin and cartilage. However, naked mole rat hyaluronan is unusual in that each molecule is about 5 times the size of hyaluronan molecules from mice, rats, and humans. In addition, the researchers discovered that the enzyme that breaks down this sugar (hyaluronidase) is not very active in naked mole rats, allowing the compound to accumulate to higher concentrations than it does in other animals. The researchers think that this sugar evolved to make naked mole rat skin more elastic and able to cope with the tight squeeze of the narrow underground tunnels.

But does it prevent cancer? Gorbunova and her colleagues tried to stimulate naked mole rat cells to form tumors by exposing them to viral proteins that in mice lead to tumor growth. These proteins inactivate genes that suppress cancer, yet still naked mole rat cells did not show uncontrolled growth. However, when the researchers interfered with the production of hyaluronan or revved up the activity of the enzyme that breaks the sugar down, thereby reducing its concentrations, tumors did form in live animals, they report online today in Nature.

The work is “very thought-provoking [and] adds an interesting wrinkle to the role of the extracellular matrix in cancer,” says Roy Zent, a cell biologist at Vanderbilt University Medical Center in Nashville. Toole agrees. “It pushes our thoughts forward [about hyaluronan] in a very dramatic way,” he notes. “It establishes hyaluronan as an important player in cancer.”  “If we could alter our [hyaluronan] or stabilize it somehow, we may be able to suppress cancers,” suggests Carlo Maley, an evolutionary cancer biologist at the University of California, San Francisco, who was not involved with the work. The next step, he adds, is to “put the naked mole rat [hyaluronan] gene into mice and test if they are cancer resistant.”

English: Naked mole rats. Cropped version of F...

English: Naked mole rats. Cropped version of File:Naked Mole Rats.jpg. (Photo credit: Wikipedia)

Naked Mole rat baby

Naked Mole rat baby (Photo credit: Wikipedia)

English: Spalax leucodon, syn. Nannospalax leu...

English: Spalax leucodon, syn. Nannospalax leucodon Magyar: Földikutya (Photo credit: Wikipedia)

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Reporters: Aviva Lev-Ari, PhD, RN and Pnina Abir-Am, PhD
Jeffrey L. Sturchio

Senior Partner, Rabin Martin

Jeffrey L. Sturchio is senior partner at Rabin Martin, a global health strategy firm in New York. Prior to joining the firm, he served as president and CEO of the Global Health Council. Before joining the Council, Dr. Sturchio was vice president of Corporate Responsibility at Merck & Co. Inc., president of the Merck Company Foundation and chairman of the U. S. Corporate Council on Africa, whose 150 member companies represent some 85 percent of total US private sector investment in Africa. He is a visiting scholar at the Institute for Applied Economics and the Study of Business Enterprise at Johns Hopkins University, a Fellow of the American Association for the Advancement of Science and a member of the Council on Foreign Relations. He received an AB in history from Princeton University and a PhD in the history and sociology of science from the University of Pennsylvania.

World Cancer Day: Treatment Should Not Be a Luxury
Posted: 02/04/2013 10:20 am
Huffington Post IMPACT
Author: Jeffrey L. Sturchio, Senior Partner, Rabin Martin

co-authored by Cary Adams.

All of us have been touched by cancer, whether personally or through the experience of our families and friends. For those of us living in the developed world, many types of cancer have ceased to be the “dread disease” they once were: Given the remarkable advances in basic science and oncology, it’s more a question of what the best course of treatment is, rather than one of availability or affordability. But for most of the world, access to cancer screening, detection, diagnosis and oncology care is still an unattainable luxury. Considering that nearly half of cancer cases — and 55 percent of the deaths — occur in less developed countries, we need to make progress now.

If left unchecked, the annual economic burden of cancer will be an estimated $458 billion by 2030, according to a study by the World Economic Forum and Harvard School of Public Health. But the human cost of 21.4 million new cases per year by 2030 is, quite simply, unacceptable. In commemoration of World Cancer Day (Today, February 4), we call for the global community to step-up its efforts to address cancer and other NCDs.

Cancers, along with other non-communicable diseases (NCDs) such as diabetes, upper respiratory infections and cardiovascular disease, are the leading causes of mortality around the world. Indeed, the number of cancer deaths alone surpasses those attributed to AIDS, tuberculosis and malaria combined. Once considered illnesses of the wealthy, 80 percent of the estimated 36 million NCD-related deaths actually occur in low- to middle- income countries, according to the World Health Organization. And while a global movement for action on NCDs has been gathering momentum in recent years, much remains to be done.

The Institute for Applied Economics, Global Health and the Study of Business Enterprise at Johns Hopkins University recently released a set of policy briefs that present recommendations for Addressing the Gaps in Global Policy and Research for Non-Communicable Disease. The publication compiles the findings of a Working Group of leading experts in the field and offers a road map of actionable recommendations for reducing the global burden of these diseases.

The report echoes many of the themes put forth by the global cancer community for achieving the goals articulated in the World Cancer Declaration. For starters, there needs to be a multi-sectoral approach to cancer. Governments, civil society, academe and the private sector must work together to leverage strengths and efficiencies to advance efforts to reduce the burden of cancer.

Greater participation by the private sector in a transparent and open way will improve efforts against the disease in coming years. Certainly, private-public partnerships to tackle cancer exist, but greater collaboration among stakeholders is needed. One suggestion may be to develop a knowledge exchange network for oncology researchers in industry and academe to accelerate the rate of progress in discovering and developing new vaccines, personalized medicines, pharmaceuticals and other essential medical technologies. While their most significant role is — and will continue to be — in R&D, the private sector can also lend considerable expertise in systems efficiencies, human resource development and supply chain management, to name just a few areas in which their capabilities can improve the global response to cancer.

Governments need to play a more active role in actively reducing and raising awareness about risk factors for cancer and other NCDs. They need to work with civil society and industry to reduce tobacco and excessive alcohol use, while promoting healthier diets and physical activity at the national and community levels. Again the private sector can play a lead role in improving the health impacts of their products to reduce the global growth in NCDs.

Countries need to make greater investments in building the capacity of local health workers so they are more capable of educating patients about reducing their cancer risk through behavior modification as well as immunization against human papilloma virus (HPV) and hepatitis B (HBV) infections (which can lead to cervical cancer and primary liver cancer, respectively). Health workers are the first line of defense, detecting hallmarks of disease and providing cancer screening, treatment and, when necessary, long-term care. Moreover, countries need to re-evaluate how they can retain health workers who are trained in cancer care. Without them, all interventions become impossible.

Finally, there needs to be greater focus on providing equitable access to screening, early diagnosis and treatment. Self-exams and visual inspection with acetic acid for breast cancer and cervical cancer screening respectively, are two excellent examples of effective, inexpensive, life-saving innovations that can be implemented even in low-resource settings. Integrating these methods into existing primary, reproductive and maternal health service models would help reduce the 750,000 deaths from cervical and breast cancer each year.

It’s a lot of work, but for many of us, cancer hits very close to home. By working together to combat cancer, each doing our part, we can begin to make a difference in the lives of millions — making cancer care and treatment not a luxury, but a reality.

Cary Adams is CEO of the Union for International Cancer Control (UICC), which helps the global health community accelerate the fight against cancer. Its growing membership of over 700 organisations in 155 countries features the world’s major cancer societies, ministries of health and patient groups and includes influential policy makers, researchers and experts in cancer prevention and control. Adams and his team focus on global advocacy to deliver the World Cancer Declaration targets by 2020, running global programs that address key cancer issues and use their membership reach to bring about the exchange of best practice globally. He recently became Chair of the NCD Alliance, a coalition of around 2,000 NGOs working on non-communicable diseases.

 SOURCE:
Jeffrey L. Sturchio
Doug Ulman

The Global Burden of Cancer

Posted: 02/04/2011 11:44 am
Most of us in developed countries have dwelled in the shadow of cancer. We’ve anxiously awaited a test result, become intimate with chemotherapy for ourselves or a loved one or held vigil at a bedside.

During those intense and often tragic periods, we usually have options — education, treatment, pain relief and sometimes, blessedly, remission and recovery — that is, if we happen to reside in a wealthy country. Not so for millions of others, adults and children alike, in poorer countries where more than 70 percent of all cancer deaths occur yet five percent or less of cancer resources are allocated to the people living there, despite the growing cancer burden.

Cancer is a growing cause of death worldwide. The cancer burden in low- and middle-income countries is increasingly disproportionate. Globally in 2009, there were an estimated 12.9 million cases of cancer, a number expected to double by 2020, with 60 percent of new cases occurring in low- and middle-income countries.

Not only do these countries carry more than half the disease burden, they lack the resources for cancer awareness and prevention, early detection, treatment or palliative options to relieve the staggering pain and human suffering if the disease is untreated — an unthinkable outcome for people who have cancer in rich nations.

Cancer also has the most devastating economic impact of any cause of death in the world, according to the recent landmark report, “The Global Economic Cost of Cancer,” released by the American Cancer Society and Livestrong. Premature deaths and disability from cancer cost the global economy nearly 1 trillion dollars a year. The data from this study provides compelling evidence that balancing the world’s global health agenda to address cancer more effectively will save not only millions of lives, but also billions of dollars.

By making cancer a global priority, as with many other non-communicable diseases, cancer deaths can be prevented an estimated 40 percent or more. This goal is a particular focus of this year’s World Cancer Day(today, February 4). But prevention can only be achieved through investments in awareness and education. Neglect of prevention leads to unaffordable treatment.

Even though tobacco use is the most preventable cause of cancer, lung cancer still kills more people worldwide than any other — a trend likely to surge unless efforts for global tobacco control are greatly accelerated. Tobacco use is responsible for 1.8 million cancer deaths per year, 60 percent in low- and middle-income nations, thanks to the tobacco industry’s unrelenting country-by-country approach to marketing their addictive product, including to youth. Last year, the Australian Broadcasting Corporation won a Global Health Council Excellence in Media Award for its hard-hitting and poignant exposé of tobacco marketing in Indonesia, “80 Million a Day: Big Tobacco’s New Frontier.” We need to cast more light on this invisible killer.

Other preventable risk factors for all cancers are unhealthy lifestyles (including alcohol abuse, inadequate diet and physical inactivity), exposure to occupational (e.g., asbestos) or environmental carcinogens (e.g., indoor air pollution), radiation (e.g., ultraviolet and ionizing radiation) and infections.

Cancers due to infectious diseases account for 8-10 percent of cases in high income countries, but 20-26 percent in developing countries. The human-to-human spread of viruses and bacteria can lead to liver and stomach cancers, lymphomas and leukemia. In addition to infections, many reproductive health diseases are linked to cancer. Strengthening the health systems of developing countries will pave the way for improved vaccine delivery and wider coverage of immunizations that will save lives and protect people’s health.

The Global Health Council and Livestrong call on global partners, allies, donors, policymakers, communities and individuals to work collaboratively to address the treatment expenditure gap and change the trajectory of this tidal wave of cancer. We have a choice – invest now or pay later with significant government spending and the loss of millions of lives and lessened productivity.

Capacity building is essential. Ministries of health, education and finance need to be engaged in developing and supporting plans that include both training of personnel to diagnose and treat cancer patients and strategies to reduce costs and strengthen health systems.

We need to focus on cancer surveillance to set standards to understand better the burden of cancer and the impacts of interventions. We need to implement relevant interventions at scale, including those that draw on successful models that address other diseases. We must rapidly expand information and awareness campaigns on a global scale to reach deeply into affected communities of developing countries. And we need continued investments in research and development for improved knowledge of the science of cancer and better drugs, vaccines and new tools for cancer prevention and control.

Starting today, advocates, governments, non-profits and the private sector must drive new and effective policies, programs and investments. Patients and survivors around the world cannot wait a moment longer for us to advance the global fight against cancer. Failing to act is indefensible — the human and economic costs are too high.

See more information at “Cancer in Developing Countries,” Global Health Council.

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Around the globe, from Cape Town to Kathmandu, from Manila to Mexico City, millions will be celebrating the 100th anniversary of International Women’s Day on March 8 — a day to honor the achievements made by and for women. Looking at this milestone through a global health lens, we see an increasingly positive picture, but the view is far from perfect. In fact, we stand at a crossroads.

Globally, we’ve seen a notable decline in maternal deaths from half a million women to 342,000 annually. This is still far too many, but it is an important step in the right direction. Yet this progress is at risk, with mounting efforts underway to deny access to one of the best investments in women’s health: family planning.

In Bangladesh, just last month, a national survey showed a 40 percent drop in maternal deaths during the last decade. One of the contributing factors? Family planning. That is an unprecedented step forward.

Tanzania achieved a 21.5 percent drop in maternal deaths during the last five years, precipitated in part by increased access to and enthusiastic use of modern contraception. Another step forward.

In places like Ghana and Ethiopia, women every day have access to more contraceptive options — another step forward — as they endeavor to plan their families and define their futures. Women like Ayera Kabele, an ambitious 30-year old in Addis Ababa. She married in her early 20s and had a child soon thereafter. But she was also a student who wanted to finish college — a dream achieved because she was able to delay having another child by using an IUD. Four years later, degree in hand, Ayera and her husband were ready for their second child — another dream achieved. Yet another step forward.

This scenario between couples plays out every day around the world — including here in the United States. These are universal conversations about when to start a family and how many children to have. Anyone who has been a party to one can appreciate how vital they are to the health and well-being not only of women, but also of their families as well.

Why is that? In addition to saving women from death and injury during pregnancy or childbirth, saving mothers’ lives saves babies’ lives. Family planning also boosts women’s economic empowerment and creates an environment where children have a better chance not only to survive, but also to thrive. Strong and healthy families lead to stronger and more stable communities, in a virtuous cycle toward prosperity for nations.

We know that up to one-third of maternal deaths could be prevented if every woman who wanted to use contraception to limit or space her births was able to do so. In part, this is due to fewer unwanted pregnancies — especially when women have no other options — and thus to fewer women seeking abortion to end them. Mostly, though, it’s because every pregnancy and childbirth poses risks, especially where medical care is inadequate, if it exists at all. This is how family planning saves lives — and more.

Yet flying in the face of mounting evidence, there is a real risk that the United States foreign assistance budget will include drastic cuts to international family planning — the catalyst to so much good in countless communities worldwide. Indeed, at a moment when every budget dollar must be used as efficiently and effectively as possible, few investments pay better long-term dividends than family planning.

Just four years remain until the deadline for achieving the Millennium Development Goals (MDGs) set by the United Nations. A report released last year rated access to reproductive health care as low or moderate in 70 percent of the regions surveyed. This is not acceptable.

There have been strong policy and funding commitments made in the United States’ Global Health Initiative as well as at the United Nations (U.N.) to bolster access to and support for family planning as vital investments to improve the lives of women and families worldwide. The year 2010 also saw the launch of the first-ever U.N.’s Global Strategy for Women’s and Children’s Health and ongoing efforts by the State Department’s Office on Global Women’s Issues to link foreign policy with women’s rights. There is much reason for optimism.

As we mark the centennial of International Women’s Day, supporters of women’s health worldwide must continue to advocate for family planning and reproductive health services, which have done so much for women and girls in the U.S. and in so many countries around the world.

See the Global Health Council position paper on Maternal, Newborn, Child and Reproductive Health.

 Follow Jeffrey L. Sturchio on Twitter: www.twitter.com/globalhealthorg
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