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Eczema Fungus Found Everywhere Including Deep Hydrothermal Vents And Antarctic Soil

Posted in Infectious Disease & New Antibiotic Targets on September 2, 2014| Leave a Comment »

Eczema Fungus Found Everywhere Including Deep Hydrothermal Vents And Antarctic Soil

Reporter: Aviva Lev-Ari, PhD, RN

Professor Anthony Amend from the University of Hawaii at Manoa showed very recently that the fungus genus Malassezia is not only found on human skin with conditions such as dandruff and eczema, but has also been identified in marine environments such as deep-sea sediment, hydrothermal vents, corals, guts of lobster larvae, eel tissue, and Antarctica soils.

More remarkably, sequencing and tree building of species relatedness shows that the marine species and terrestrial (non-marine) species do not group together but “interdigitate”, or are spread randomly in the way they group together in their relatedness. The evidence suggests that the marine and terrestrial forms have jumped repeatedly between habitats.

The data was obtained from a number of sources, most of them “environmental sequencing” projects around the world which aim to do simultaneous sequencing of all DNA found in a sample. Done correctly the analysis yields in one try the identities of all organisms captured in a sample.

Prior to this analysis, it was thought that these fungus evolved to become optimally suited to mammalian skin. But the careful analysis of environmental sequencing efforts overturned that belief. One species could be spread out all over the globe, on land as well as in ocean. One example is Malassezia restricta, found on human skin but also in extreme habitats such as arctic soil and hydrothermal vents. Marine animals also carry this fungus, including higher order seals and lower order fish, lobsters, and corals.

One criticism is that sequencing is bound to become contaminated especially with a fungus endemic to human skin. However, the detection of completely novel species cannot be explained by contamination. And moreover, RNA is a fairly unstable molecule, so in the cases where detection occurred for some of the samples in which there was sufficient time for degradation suggests that microbes were actively generating RNA.

While it is associated with many skin conditions it is unclear as of yet whether the fungus is a causal factor. This is simply because disease etiology is a complex interplay of an individual immune system and disease agent.

Source: www.neomatica.com

See on Scoop.it – Cardiovascular and vascular imaging

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Plant-based Nutrition, Neutraceuticals and Alternative Medicine: Article Compilation the Journal PharmaceuticalIntelligence.com

Posted in Advanced Drug Manufacturing Technology, CANCER BIOLOGY & Innovations in Cancer Therapy, Diabetes Mellitus, Human Immune System in Health and in Disease, Infectious Disease & New Antibiotic Targets, Lipid metabolism, Nutrition, Nutrition and Phytochemistry, Nutritional Supplements: Atherogenesis, Pharmacotherapy and Cell Activity, Population Health Management, Proteomics, Systemic Inflammatory Response Related Disorders, Translational Effectiveness, Translational Science, tagged Biotechnology and Pharmaceuticals, Cancer research, Cardiovascular disease, Cardiovascular Disorders, Chemotherapy, Diabetes mellitus type 2, FDA, Nutrition on September 1, 2014| Leave a Comment »

Plant-based Nutrition, Neutraceuticals and Alternative Medicine: Article Compilation the Journal PharmaceuticalIntelligence.com

Curator: Larry H. Bernstein, MD, FCAP

Green tea polyphenols alleviate early BBB damage
http://pharmaceuticalintelligence.com/2013/07/31/green-tea-polyphenols-alleviate-early-bbb-damage-during/
What do you know about Plants and Neutraceuticals?

Author and Curator, Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2014/07/30/what-do-you-know-about-plants-and-neutraceuticals/

The Final Considerations of the Role of Platelets and Platelet Endothelial Reactions in Atherosclerosis and Novel Treatments

Author and Curator: Larry H Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2013/10/15/the-final-considerations-of-the-role-of-platelets-and-platelet-endothelial-reactions-in-atherosclerosis-and-novel-treatments/

Endothelial Function and Cardiovascular Disease

Author and Curator: Larry H Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2012/10/25/endothelial-function-and-cardiovascular-disease/

NO Nutritional remedies for hypertension and atherosclerosis. It’s 12 am: do you know where your electrons are?

Author and Reporter: Meg Baker, Ph.D., Registered Patent Agent

http://pharmaceuticalintelligence.com/2012/10/07/no-nutritional-remedies-for-hypertension-and-atherosclerosis-its-12-am-do-you-know-where-your-electrons-are/

Cocoa and Heart Health

Reporter: Larry H Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2013/11/17/cocoa-and-heart-health/

Metabolomics: its applications in food and nutrition research

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

http://pharmaceuticalintelligence.com/2013/05/12/metabolomics-its-applications-in-food-and-nutrition-research/

Japanese knotweed extract (Polygonum cuspidatum) Resveratrol 98%

Reporter: Larry H Bernstein, MD, FCAP Stanford Lee, Shanghai Natural Bio-engineering Co., Ltd
Key products: resveratrol, curcumin,artemisinin,artemether,artesunate,dihydroartemisinin,Lumefantrine,etc
https://www.linkedin.com/today/post/article/20140805055958-283555965-japanese-knotweed-extract-polygonum-cuspidatum-resveratrol-98?/

http://pharmaceuticalintelligence.com/2014/08/20/japanese-knotweed-extract-polygonum-cuspidatum-resveratrol-98/

Antimicrobial resistance
Reporter: Larry H Bernstein, MD, FCAP
http://pharmaceuticalintelligence.com/2014/08/18/antimicrobial-resistance/
Macrocycles in new drug discovery
Reporter: Larry H Bernstein, MD, FCAP Jamie Mallinson, Ian Collins
Future Medicinal Chemistry, Jul 2012, Vol. 4, No. 11, Pages 1409-1438.

Natural product macrocycles and their synthetic derivatives

http://pharmaceuticalintelligence.com/2014/08/16/macrocycles-in-new-drug-discovery/

Lipid Metabolism

ALA and LA, LCPUFAs (EPA, DHA, and AA), eicosanoids, delta-3-desaturase, prostaglandins, leukotrienes

Ginseng fights fatigue in cancer patients, Mayo Clinic-led study finds http://pharmaceuticalintelligence.com/2014/08/15/lipid-metabolism/

Ginseng fights fatigue in cancer patients, Mayo Clinic-led study finds

Reporter: Larry H Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2014/08/10/ginseng-fights-fatigue-in-cancer-patients-mayo-clinic-led-study-finds/

Scientists develop new cancer-killing compound from salad plant / 1,200 times more specific in killing certain kinds of cancer cells than currently available drugs
Reporter: Larry H Bernstein, MD, FCAP
http://pharmaceuticalintelligence.com/2014/07/17/scientists-develop-new-cancer-killing-compound-from-salad-plant-1200-times-more-specific-in-killing-certain-kinds-of-cancer-cells-than-currently-available-drugs/
Protein heals wounds, boosts immunity and protects from cancer – Lactoferrin
Reporter: Larry H Bernstein, MD, FCAP
http://pharmaceuticalintelligence.com/2014/07/17/protein-heals-wounds-boosts-immunity-and-protects-from-cancer-lactoferrin/
Inula helenium ( elecampane ) 100% Effective against MRSA in vitro, 200 Strains
Reporter: Larry H Bernstein, MD, FCAP
http://pharmaceuticalintelligence.com/2014/07/15/inula-helenium-elecampane-100-effective-against-mrsa-in-vitro-200-strains/
Thymoquinone, an extract of nigella sativa seed oil, blocked pancreatic cancer cell growth and killed the cells by enhancing the process of programmed cell death.
Reporter: Larry H Bernstein, MD, FCAP
http://pharmaceuticalintelligence.com/2014/07/15/thymoquinone-an-extract-of-nigella-sativa-seed-oil-blocked-pancreatic-cancer-cell-growth-and-killed-the-cells-by-enhancing-the-process-of-programmed-cell-death/
Cinnamon is lethal weapon against E. coli O157:H7
Reporter: Larry H Bernstein, MD, FCAP
http://pharmaceuticalintelligence.com/2014/07/15/cinnamon-is-lethal-weapon-against-e-coli-o157h7/
Garlic compound fights source of food-borne illness better than antibiotics (100 times more effective than two popular antibiotics )

Reporter: Larry H Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2014/07/15/garlic-compound-fights-source-of-food-borne-illness-better-than-antibiotics-100-times-more-effective-than-two-popular-antibiotics/

Reference Genes in the Human Gut Microbiome: The BGI Catalogue

Reporter: Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2014/07/14/reference-genes-in-the-human-gut-microbiome-the-bgi-catalogue/

Study suggests consuming whey protein before meals could help improve blood glucose control in people with diabetes
Reporter: Larry H Bernstein, MD, FCAP
http://pharmaceuticalintelligence.com/2014/07/12/study-suggests-consuming-whey-protein-before-meals-could-help-improve-blood-glucose-control-in-people-with-diabetes/
Omega-3 fatty acids, depleting the source, and protein insufficiency in renal disease
Larry H. Bernstein, MD, FCAP, Curator
http://pharmaceuticalintelligence.com/2014/07/06/omega-3-fatty-acids-depleting-the-source-and-protein-insufficiency-in-renal-disease/
Health benefit of anthocyanins from apples and berries noted for men
Larry H. Bernstein, MD, FCAP, Curator
http://pharmaceuticalintelligence.com/2014/07/06/health-benefit-of-anthocyanins-from-apples-and-berries-noted-for-men/
Carrots Cut Men’s Prostate Cancer Risk by 50%
Larry H. Bernstein, MD, FCAP, Reporter
http://pharmaceuticalintelligence.com/2014/07/03/carrots-cut-mens-prostate-cancer-risk-by-50/
A Recipe To Make Cannabis Oil For A Chemotherapy Alternative
Larry H. Bernstein, MD, FCAP, Reporter
http://pharmaceuticalintelligence.com/2014/07/02/a-recipe-to-make-cannabis-oil-for-a-chemotherapy-alternative/
Plant flavonoid found to reduce inflammatory response in the brain: luteolin
Larry H. Bernstein, MD, FCAP, Reporter
http://pharmaceuticalintelligence.com/2014/06/29/plant-flavonoid-found-to-reduce-inflammatory-response-in-the-brain-luteolin/
Omega-3 fatty acids protect eyes against retinopathy, study finds
Larry H. Bernstein, MD, FCAP, Reporter
http://pharmaceuticalintelligence.com/2014/06/28/omega-3-fatty-acids-protect-eyes-against-retinopathy-study-finds/
Scientists identify new pathogenic and protective microbes associated with severe diarrhea
Larry H. Bernstein, MD, FCAP, Reporter
http://pharmaceuticalintelligence.com/2014/06/28/scientists-identify-new-pathogenic-and-protective-microbes-associated-with-severe-diarrhea/
2,000-year-old herb regulates autoimmunity and inflammation / Chang Shan, from a type of hydrangea that grows in Tibet and Nepal
Larry H. Bernstein, MD, FCAP, Reporter
http://pharmaceuticalintelligence.com/2014/06/27/2000-year-old-herb-regulates-autoimmunity-and-inflammation-chang-shan-from-a-type-of-hydrangea-that-grows-in-tibet-and-nepal/
Turmeric-based drug effective on Alzheimer flies
Larry H. Bernstein, MD, FCAP, Reporter
http://pharmaceuticalintelligence.com/2014/06/27/turmeric-based-drug-effective-on-alzheimer-flies/
Plant flavonoid luteolin blocks cell signaling pathways in colon cancer cells
Larry H. Bernstein, MD, FCAP, Reporter
http://pharmaceuticalintelligence.com/2014/06/26/plant-flavonoid-luteolin-blocks-cell-signaling-pathways-in-colon-cancer-cells/
Study Finds Shu Gan Liang Xue Herbal Formula Has Breast Cancer Anti Tumor Effect
Larry H. Bernstein, MD, FCAP, Reporter
http://pharmaceuticalintelligence.com/2014/06/25/study-finds-shu-gan-liang-xue-herbal-formula-has-breast-cancer-anti-tumor-effect/
HMPC Q&A Documents on Herbal Medicinal Products published
Larry H. Bernstein, MD, FCAP, Reporter
http://pharmaceuticalintelligence.com/2014/06/25/hmpc-qa-documents-on-herbal-medicinal-products-published/
Garden Cress Extract Kills 97% of Breast Cancer Cells in Vitro
Larry H. Bernstein, MD, FCAP, Reporter
http://pharmaceuticalintelligence.com/2014/06/21/garden-cress-extract-kills-97-of-breast-cancer-cells-in-vitro/
Moringa Oleifera Kills 97% of Pancreatic Cancer Cells in Vitro
Larry H. Bernstein, MD, FCAP, Reporter
http://pharmaceuticalintelligence.com/2014/06/21/moringa-oleifera-kills-97-of-pancreatic-cancer-cells-in-vitro/

16. The Discovery and Properties of Avemar – Fermented Wheat Germ Extract: Carcinogenesis Suppressor
Larry H. Bernstein, MD, FCAP, Author and Curator
http://pharmaceuticalintelligence.com/2014/06/09/the-discovery-and-properties-of-avemar-fermented-wheat-germ-extract-carcinogenesis-suppressor-2/

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Proteomics, Metabolomics, Signaling Pathways, and Cell Regulation: a Compilation of Articles in the Journal http://pharmaceuticalintelligence.com

Posted in Biological Networks, Biomarkers & Medical Diagnostics, Biomedical Measurement Science, Calcium Signaling, CANCER BIOLOGY & Innovations in Cancer Therapy, Cardiovascular Research, Cell Biology, Chemical Biology and its relations to Metabolic Disease, Chemical Genetics, Coagulation Therapy and Internal Bleeding, Diabetes Mellitus, Disease Biology, FDA Regulatory Affairs, Frontiers in Cardiology and Cardiovascular Disorders, Gene Regulation and Evolution, Genetics & Pharmaceutical, Genome Biology, Genomic Expression, Genomic Testing: Methodology for Diagnosis, Infectious Disease & New Antibiotic Targets, Innovation in Immunology Diagnostics, Lipid metabolism, Liver & Digestive Diseases Research, Metabolomics, Molecular Genetics & Pharmaceutical, Myocardial adenine nucleotide metabolism, Myocardial Ischemia, Myocardial Metabolism, Nitric Oxide in Health and Disease, Nutritional Supplements: Atherogenesis, Pharmacotherapy and Cell Activity, Pharmacotherapy of Cardiovascular Disease, Population Health Management, Proteomics, Signaling, Signaling & Cell Circuits, Small Molecules in Development of Therapeutic Drugs, Systemic Inflammatory Response Related Disorders, Translational Research, Translational Science, tagged Alzheimers Disease, Apoptosis, Aviva Lev-Ari, bibliorgaphy, Biochemistry and Molecular Biology, biomarkers, breast cancer, Cancer research, Cardiovascular disease, Chemotherapy, compilation, Conditions and Diseases, curations, Diabetes mellitus type 2, DNA, Endothelium, gene, gene expression, Genome-wide association study, Human Genome Project, immune system, Leaders in Pharmaceutical Intelligence, Messenger RNA, Metabolism, Metabolomics, metastasis, MicroRNA, mitochondria, National Human Genome Research Institute, National Institutes of Health, Nitric oxide synthase, NO, Personalized medicine, Proceedings of the National Academy of Sciences of the United States of America, Proteomics, RNA, Signal transduction, Single-nucleotide polymorphism, Stanford University, Stem cell, Warburg Effect on September 1, 2014| Leave a Comment »

Compilation of References by Leaders in Pharmaceutical Business Intelligence in the Journal http://pharmaceuticalintelligence.com about
Proteomics, Metabolomics, Signaling Pathways, and Cell Regulation

Curator: Larry H Bernstein, MD, FCAP

Proteomics

The Human Proteome Map Completed

Reporter and Curator: Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2014/08/28/the-human-proteome-map-completed/

Proteomics – The Pathway to Understanding and Decision-making in Medicine

Author and Curator, Larry H Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2014/06/24/proteomics-the-pathway-to-
understanding-and-decision-making-in-medicine/

3. Advances in Separations Technology for the “OMICs” and Clarification of Therapeutic Targets

Author and Curator, Larry H Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2012/10/22/advances-in-separations-technology-for-the-omics-and-clarification- of-therapeutic-targets/

Expanding the Genetic Alphabet and Linking the Genome to the Metabolome

Author and Curator, Larry H Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2012/09/24/expanding-the-genetic-alphabet-and-linking-the-genome-to-the- metabolome/

5. Genomics, Proteomics and standards

Larry H Bernstein, MD, FCAP, Author and Curator

http://pharmaceuticalintelligence.com/2014/07/06/genomics-proteomics-and-standards/

6. Proteins and cellular adaptation to stress

Larry H Bernstein, MD, FCAP, Author and Curator

http://pharmaceuticalintelligence.com/2014/07/08/proteins-and-cellular-adaptation-to-stress/

Metabolomics

Extracellular evaluation of intracellular flux in yeast cells

Larry H. Bernstein, MD, FCAP, Reviewer and Curator

http://pharmaceuticalintelligence.com/2014/08/25/extracellular-evaluation-of-intracellular-flux-in-yeast-cells/

Metabolomic analysis of two leukemia cell lines. I.

Larry H. Bernstein, MD, FCAP, Reviewer and Curator

http://pharmaceuticalintelligence.com/2014/08/23/metabolomic-analysis-of-two-leukemia-cell-lines-_i/

Metabolomic analysis of two leukemia cell lines. II.

Larry H. Bernstein, MD, FCAP, Reviewer and Curator

http://pharmaceuticalintelligence.com/2014/08/24/metabolomic-analysis-of-two-leukemia-cell-lines-ii/

Metabolomics, Metabonomics and Functional Nutrition: the next step in nutritional metabolism and biotherapeutics

Reviewer and Curator, Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2014/08/22/metabolomics-metabonomics-and-functional-nutrition-the-next-step- in-nutritional-metabolism-and-biotherapeutics/

Buffering of genetic modules involved in tricarboxylic acid cycle metabolism provides homeomeostatic regulation

Larry H. Bernstein, MD, FCAP, Reviewer and curator

http://pharmaceuticalintelligence.com/2014/08/27/buffering-of-genetic-modules-involved-in-tricarboxylic-acid-cycle- metabolism-provides-homeomeostatic-regulation/

Metabolic Pathways

Pentose Shunt, Electron Transfer, Galactose, more Lipids in brief

Reviewer and Curator: Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2014/08/21/pentose-shunt-electron-transfer-galactose-more-lipids-in-brief/

Mitochondria: More than just the “powerhouse of the cell”

Ritu Saxena, PhD

http://pharmaceuticalintelligence.com/2012/07/09/mitochondria-more-than-just-the-powerhouse-of-the-cell/

Mitochondrial fission and fusion: potential therapeutic targets?

Ritu saxena

http://pharmaceuticalintelligence.com/2012/10/31/mitochondrial-fission-and-fusion-potential-therapeutic-target/

4. Mitochondrial mutation analysis might be “1-step” away

Ritu Saxena

http://pharmaceuticalintelligence.com/2012/08/14/mitochondrial-mutation-analysis-might-be-1-step-away/

Selected References to Signaling and Metabolic Pathways in PharmaceuticalIntelligence.com

Curator: Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2014/08/14/selected-references-to-signaling-and-metabolic-pathways-in- leaders-in-pharmaceutical-intelligence/

Metabolic drivers in aggressive brain tumors

Prabodh Kandal, PhD

http://pharmaceuticalintelligence.com/2012/11/11/metabolic-drivers-in-aggressive-brain-tumors/

Metabolite Identification Combining Genetic and Metabolic Information: Genetic association links unknown metabolites to functionally related genes

Writer and Curator, Aviva Lev-Ari, PhD, RD

http://pharmaceuticalintelligence.com/2012/10/22/metabolite-identification-combining-genetic-and-metabolic- information-genetic-association-links-unknown-metabolites-to-functionally-related-genes/

Mitochondria: Origin from oxygen free environment, role in aerobic glycolysis, metabolic adaptation

Larry H Bernstein, MD, FCAP, author and curator

http://pharmaceuticalintelligence.com/2012/09/26/mitochondria-origin-from-oxygen-free-environment-role-in-aerobic- glycolysis-metabolic-adaptation/

Therapeutic Targets for Diabetes and Related Metabolic Disorders

Reporter, Aviva Lev-Ari, PhD, RD

http://pharmaceuticalintelligence.com/2012/08/20/therapeutic-targets-for-diabetes-and-related-metabolic-disorders/

10. Buffering of genetic modules involved in tricarboxylic acid cycle metabolism provides homeomeostatic regulation

Larry H. Bernstein, MD, FCAP, Reviewer and curator

http://pharmaceuticalintelligence.com/2014/08/27/buffering-of-genetic-modules-involved-in-tricarboxylic-acid-cycle- metabolism-provides-homeomeostatic-regulation/

11. The multi-step transfer of phosphate bond and hydrogen exchange energy

Larry H. Bernstein, MD, FCAP, Curator:

http://pharmaceuticalintelligence.com/2014/08/19/the-multi-step-transfer-of-phosphate-bond-and-hydrogen- exchange-energy/

12. Studies of Respiration Lead to Acetyl CoA

http://pharmaceuticalintelligence.com/2014/08/18/studies-of-respiration-lead-to-acetyl-coa/

13. Lipid Metabolism

Author and Curator: Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2014/08/15/lipid-metabolism/

14. Carbohydrate Metabolism

Author and Curator: Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2014/08/13/carbohydrate-metabolism/

15. Update on mitochondrial function, respiration, and associated disorders

Larry H. Bernstein, MD, FCAP, Author and Curator

http://pharmaceuticalintelligence.com/2014/07/08/update-on-mitochondrial-function-respiration-and-associated- disorders/

16. Prologue to Cancer – e-book Volume One – Where are we in this journey?

Author and Curator: Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2014/04/13/prologue-to-cancer-ebook-4-where-are-we-in-this-journey/

17. Introduction – The Evolution of Cancer Therapy and Cancer Research: How We Got Here?

Author and Curator: Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2014/04/04/introduction-the-evolution-of-cancer-therapy-and-cancer-research- how-we-got-here/

18. Inhibition of the Cardiomyocyte-Specific Kinase TNNI3K

Author and Curator: Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2013/11/01/inhibition-of-the-cardiomyocyte-specific-kinase-tnni3k/

19. The Binding of Oligonucleotides in DNA and 3-D Lattice Structures

Author and Curator: Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2013/05/15/the-binding-of-oligonucleotides-in-dna-and-3-d-lattice-structures/

20. Mitochondrial Metabolism and Cardiac Function

Author and Curator: Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2013/04/14/mitochondrial-metabolism-and-cardiac-function/

21. How Methionine Imbalance with Sulfur-Insufficiency Leads to Hyperhomocysteinemia

Curator: Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2013/04/04/sulfur-deficiency-leads_to_hyperhomocysteinemia/

22. AMPK Is a Negative Regulator of the Warburg Effect and Suppresses Tumor Growth In Vivo

Author and Curator: Stephen J. Williams, PhD

http://pharmaceuticalintelligence.com/2013/03/12/ampk-is-a-negative-regulator-of-the-warburg-effect-and-suppresses- tumor-growth-in-vivo/

23. A Second Look at the Transthyretin Nutrition Inflammatory Conundrum

Author and Curator: Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2012/12/03/a-second-look-at-the-transthyretin-nutrition-inflammatory- conundrum/

24. Mitochondrial Damage and Repair under Oxidative Stress

Author and Curator: Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2012/10/28/mitochondrial-damage-and-repair-under-oxidative-stress/

25. Nitric Oxide and Immune Responses: Part 2

Author and Curator: Aviral Vatsa, PhD, MBBS

http://pharmaceuticalintelligence.com/2012/10/28/nitric-oxide-and-immune-responses-part-2/

26. Overview of Posttranslational Modification (PTM)

Writer and Curator: Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2014/07/29/overview-of-posttranslational-modification-ptm/

27. Malnutrition in India, high newborn death rate and stunting of children age under five years

Writer and Curator: Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2014/07/15/malnutrition-in-india-high-newborn-death-rate-and-stunting-of- children-age-under-five-years/

28. Update on mitochondrial function, respiration, and associated disorders

Writer and Curator: Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2014/07/08/update-on-mitochondrial-function-respiration-and-associated- disorders/

29. Omega-3 fatty acids, depleting the source, and protein insufficiency in renal disease

Larry H. Bernstein, MD, FCAP, Curator

http://pharmaceuticalintelligence.com/2014/07/06/omega-3-fatty-acids-depleting-the-source-and-protein-insufficiency- in-renal-disease/

30. Introduction to e-Series A: Cardiovascular Diseases, Volume Four Part 2: Regenerative Medicine

Larry H. Bernstein, MD, FCAP, writer, and Aviva Lev- Ari, PhD, RN

http://pharmaceuticalintelligence.com/2014/04/27/larryhbernintroduction_to_cardiovascular_diseases- translational_medicine-part_2/

31. Epilogue: Envisioning New Insights in Cancer Translational Biology
Series C: e-Books on Cancer & Oncology

Author & Curator: Larry H. Bernstein, MD, FCAP, Series C Content Consultant

http://pharmaceuticalintelligence.com/2014/03/29/epilogue-envisioning-new-insights/

32. Ca2+-Stimulated Exocytosis: The Role of Calmodulin and Protein Kinase C in Ca2+ Regulation of Hormone and Neurotransmitter

Writer and Curator: Larry H Bernstein, MD, FCAP and
Curator and Content Editor: Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/12/23/calmodulin-and-protein-kinase-c-drive-the-ca2-regulation-of- hormone-and-neurotransmitter-release-that-triggers-ca2-stimulated-exocy

33. Cardiac Contractility & Myocardial Performance: Therapeutic Implications of Ryanopathy (Calcium Release- related Contractile Dysfunction) and Catecholamine Responses

Author, and Content Consultant to e-SERIES A: Cardiovascular Diseases: Justin Pearlman, MD, PhD, FACC
Author and Curator: Larry H Bernstein, MD, FCAP
and Article Curator: Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/08/28/cardiac-contractility-myocardium-performance-ventricular-arrhythmias- and-non-ischemic-heart-failure-therapeutic-implications-for-cardiomyocyte-ryanopathy-calcium-release-related- contractile/

34. Role of Calcium, the Actin Skeleton, and Lipid Structures in Signaling and Cell Motility

Author and Curator: Larry H Bernstein, MD, FCAP Author: Stephen Williams, PhD, and Curator: Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/08/26/role-of-calcium-the-actin-skeleton-and-lipid-structures-in-signaling-and-cell-motility/

35. Identification of Biomarkers that are Related to the Actin Cytoskeleton

Larry H Bernstein, MD, FCAP, Author and Curator

http://pharmaceuticalintelligence.com/2012/12/10/identification-of-biomarkers-that-are-related-to-the-actin- cytoskeleton/

36. Advanced Topics in Sepsis and the Cardiovascular System at its End Stage

Author: Larry H Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2013/08/18/advanced-topics-in-Sepsis-and-the-Cardiovascular-System-at-its- End-Stage/

37. The Delicate Connection: IDO (Indolamine 2, 3 dehydrogenase) and Cancer Immunology

Demet Sag, PhD, Author and Curator

http://pharmaceuticalintelligence.com/2013/08/04/the-delicate-connection-ido-indolamine-2-3-dehydrogenase-and- immunology/

38. IDO for Commitment of a Life Time: The Origins and Mechanisms of IDO, indolamine 2, 3-dioxygenase

Demet Sag, PhD, Author and Curator

http://pharmaceuticalintelligence.com/2013/08/04/ido-for-commitment-of-a-life-time-the-origins-and-mechanisms-of- ido-indolamine-2-3-dioxygenase/

39. Confined Indolamine 2, 3 dioxygenase (IDO) Controls the Homeostasis of Immune Responses for Good and Bad

Curator: Demet Sag, PhD, CRA, GCP

http://pharmaceuticalintelligence.com/2013/07/31/confined-indolamine-2-3-dehydrogenase-controls-the-hemostasis- of-immune-responses-for-good-and-bad/

40. Signaling Pathway that Makes Young Neurons Connect was discovered @ Scripps Research Institute

Reporter: Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/06/26/signaling-pathway-that-makes-young-neurons-connect-was- discovered-scripps-research-institute/

41. Naked Mole Rats Cancer-Free

Writer and Curator: Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2013/06/20/naked-mole-rats-cancer-free/

42. Late Onset of Alzheimer’s Disease and One-carbon Metabolism

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

http://pharmaceuticalintelligence.com/2013/05/06/alzheimers-disease-and-one-carbon-metabolism/

43. Problems of vegetarianism

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

http://pharmaceuticalintelligence.com/2013/04/22/problems-of-vegetarianism/

44. Amyloidosis with Cardiomyopathy

Writer and Curator: Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2013/03/31/amyloidosis-with-cardiomyopathy/

45. Liver endoplasmic reticulum stress and hepatosteatosis

Larry H Bernstein, MD, FACP

http://pharmaceuticalintelligence.com/2013/03/10/liver-endoplasmic-reticulum-stress-and-hepatosteatosis/

46. The Molecular Biology of Renal Disorders: Nitric Oxide – Part III

Curator and Author: Larry H Bernstein, MD, FACP

http://pharmaceuticalintelligence.com/2012/11/26/the-molecular-biology-of-renal-disorders/

47. Nitric Oxide Function in Coagulation – Part II

Curator and Author: Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2012/11/26/nitric-oxide-function-in-coagulation/

48. Nitric Oxide, Platelets, Endothelium and Hemostasis

Curator and Author: Larry H Bernstein, MD, FACP

http://pharmaceuticalintelligence.com/2012/11/08/nitric-oxide-platelets-endothelium-and-hemostasis/

49. Interaction of Nitric Oxide and Prostacyclin in Vascular Endothelium

Curator and Author: Larry H Bernstein, MD, FACP

http://pharmaceuticalintelligence.com/2012/09/14/interaction-of-nitric-oxide-and-prostacyclin-in-vascular-endothelium/

50. Nitric Oxide and Immune Responses: Part 1

Curator and Author: Aviral Vatsa PhD, MBBS

http://pharmaceuticalintelligence.com/2012/10/18/nitric-oxide-and-immune-responses-part-1/

51. Nitric Oxide and Immune Responses: Part 2

Curator and Author: Aviral Vatsa PhD, MBBS

http://pharmaceuticalintelligence.com/2012/10/28/nitric-oxide-and-immune-responses-part-2/

52. Mitochondrial Damage and Repair under Oxidative Stress

Curator and Author: Larry H Bernstein, MD, FACP

http://pharmaceuticalintelligence.com/2012/10/28/mitochondrial-damage-and-repair-under-oxidative-stress/

53. Is the Warburg Effect the cause or the effect of cancer: A 21st Century View?

Curator and Author: Larry H Bernstein, MD, FACP

http://pharmaceuticalintelligence.com/2012/10/17/is-the-warburg-effect-the-cause-or-the-effect-of-cancer-a-21st- century-view/

54. Ubiquinin-Proteosome pathway, autophagy, the mitochondrion, proteolysis and cell apoptosis

Curator and Author: Larry H Bernstein, MD, FACP

http://pharmaceuticalintelligence.com/2012/10/30/ubiquinin-proteosome-pathway-autophagy-the-mitochondrion- proteolysis-and-cell-apoptosis/

55. Ubiquitin-Proteosome pathway, Autophagy, the Mitochondrion, Proteolysis and Cell Apoptosis: Part III

Curator and Author: Larry H Bernstein, MD, FACP

http://pharmaceuticalintelligence.com/2013/02/14/ubiquinin-proteosome-pathway-autophagy-the-mitochondrion- proteolysis-and-cell-apoptosis-reconsidered/

56. Nitric Oxide and iNOS have Key Roles in Kidney Diseases – Part II

Curator and Author: Larry H Bernstein, MD, FACP

http://pharmaceuticalintelligence.com/2012/11/26/nitric-oxide-and-inos-have-key-roles-in-kidney-diseases/

57. New Insights on Nitric Oxide donors – Part IV

Curator and Author: Larry H Bernstein, MD, FACP

http://pharmaceuticalintelligence.com/2012/11/26/new-insights-on-no-donors/

58. Crucial role of Nitric Oxide in Cancer

Curator and Author: Ritu Saxena, Ph.D.

http://pharmaceuticalintelligence.com/2012/10/16/crucial-role-of-nitric-oxide-in-cancer/

59. Nitric Oxide has a ubiquitous role in the regulation of glycolysis -with a concomitant influence on mitochondrial function

Curator and Author: Larry H Bernstein, MD, FACP

http://pharmaceuticalintelligence.com/2012/09/16/nitric-oxide-has-a-ubiquitous-role-in-the-regulation-of-glycolysis-with- a-concomitant-influence-on-mitochondrial-function/

60. Targeting Mitochondrial-bound Hexokinase for Cancer Therapy

Curator and Author: Ziv Raviv, PhD, RN 04/06/2013

http://pharmaceuticalintelligence.com/2013/04/06/targeting-mitochondrial-bound-hexokinase-for-cancer-therapy/

61. Biochemistry of the Coagulation Cascade and Platelet Aggregation – Part I

Curator and Author: Larry H Bernstein, MD, FACP

http://pharmaceuticalintelligence.com/2012/11/26/biochemistry-of-the-coagulation-cascade-and-platelet-aggregation/

Genomics, Transcriptomics, and Epigenetics

What is the meaning of so many RNAs?

Writer and Curator: Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2014/08/06/what-is-the-meaning-of-so-many-rnas/

RNA and the transcription the genetic code

Larry H. Bernstein, MD, FCAP, Writer and Curator

http://pharmaceuticalintelligence.com/2014/08/02/rna-and-the-transcription-of-the-genetic-code/

A Primer on DNA and DNA Replication

Writer and Curator: Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2014/07/29/a_primer_on_dna_and_dna_replication/

4. Synthesizing Synthetic Biology: PLOS Collections

Reporter: Aviva Lev-Ari

http://pharmaceuticalintelligence.com/2012/08/17/synthesizing-synthetic-biology-plos-collections/

5. Pathology Emergence in the 21st Century

Author and Curator: Larry Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2014/08/03/pathology-emergence-in-the-21st-century/

6. RNA and the transcription the genetic code

Writer and Curator, Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2014/08/02/rna-and-the-transcription-of-the-genetic-code/

7. A Great University engaged in Drug Discovery: University of Pittsburgh

Larry H. Bernstein, MD, FCAP, Reporter and Curator

http://pharmaceuticalintelligence.com/2014/07/15/a-great-university-engaged-in-drug-discovery/

8. microRNA called miRNA-142 involved in the process by which the immature cells in the bone marrow give rise to all the types of blood cells, including immune cells and the oxygen-bearing red blood cells

Aviva Lev-Ari, PhD, RN, Author and Curator

http://pharmaceuticalintelligence.com/2014/07/24/microrna-called-mir-142-involved-in-the-process-by-which-the- immature-cells-in-the-bone-marrow-give-rise-to-all-the-types-of-blood-cells-including-immune-cells-and-the-oxygen- bearing-red-blood-cells/

9. Genes, proteomes, and their interaction

Larry H. Bernstein, MD, FCAP, Writer and Curator

http://pharmaceuticalintelligence.com/2014/07/28/genes-proteomes-and-their-interaction/

10. Regulation of somatic stem cell Function

Larry H. Bernstein, MD, FCAP, Writer and Curator Aviva Lev-Ari, PhD, RN, Curator

http://pharmaceuticalintelligence.com/2014/07/29/regulation-of-somatic-stem-cell-function/

11. Scientists discover that pluripotency factor NANOG is also active in adult organisms

Larry H. Bernstein, MD, FCAP, Reporter

http://pharmaceuticalintelligence.com/2014/07/10/scientists-discover-that-pluripotency-factor-nanog-is-also-active-in- adult-organisms/

12. Bzzz! Are fruitflies like us?

Larry H Bernstein, MD, FCAP, Author and Curator

http://pharmaceuticalintelligence.com/2014/07/07/bzzz-are-fruitflies-like-us/

13. Long Non-coding RNAs Can Encode Proteins After All

Larry H Bernstein, MD, FCAP, Reporter

http://pharmaceuticalintelligence.com/2014/06/29/long-non-coding-rnas-can-encode-proteins-after-all/

14. Michael Snyder @Stanford University sequenced the lymphoblastoid transcriptomes and developed an
allele-specific full-length transcriptome

Aviva Lev-Ari, PhD, RN, Author and Curator

http://pharmaceuticalintelligence.com/014/06/23/michael-snyder-stanford-university-sequenced-the-lymphoblastoid- transcriptomes-and-developed-an-allele-specific-full-length-transcriptome/

15. Commentary on Biomarkers for Genetics and Genomics of Cardiovascular Disease: Views by Larry H Bernstein, MD, FCAP

Author: Larry H Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2014/07/16/commentary-on-biomarkers-for-genetics-and-genomics-of- cardiovascular-disease-views-by-larry-h-bernstein-md-fcap/

16. Observations on Finding the Genetic Links in Common Disease: Whole Genomic Sequencing Studies

Author an curator: Larry H Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2013/05/18/observations-on-finding-the-genetic-links/

17. Silencing Cancers with Synthetic siRNAs

Larry H. Bernstein, MD, FCAP, Reviewer and Curator

http://pharmaceuticalintelligence.com/2013/12/09/silencing-cancers-with-synthetic-sirnas/

18. Cardiometabolic Syndrome and the Genetics of Hypertension: The Neuroendocrine Transcriptome Control Points

Reporter: Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/12/12/cardiometabolic-syndrome-and-the-genetics-of-hypertension-the-neuroendocrine-transcriptome-control-points/

19. Developments in the Genomics and Proteomics of Type 2 Diabetes Mellitus and Treatment Targets

Larry H. Bernstein, MD, FCAP, Reviewer and Curator

http://pharmaceuticalintelligence.com/2013/12/08/developments-in-the-genomics-and-proteomics-of-type-2-diabetes- mellitus-and-treatment-targets/

20. Loss of normal growth regulation

Larry H Bernstein, MD, FCAP, Curator

http://pharmaceuticalintelligence.com/2014/07/06/loss-of-normal-growth-regulation/

21. CT Angiography & TrueVision™ Metabolomics (Genomic Phenotyping) for new Therapeutic Targets to Atherosclerosis

Reporter: Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/11/15/ct-angiography-truevision-metabolomics-genomic-phenotyping-for- new-therapeutic-targets-to-atherosclerosis/

22. CRACKING THE CODE OF HUMAN LIFE: The Birth of BioInformatics & Computational Genomics

Genomics Curator, Larry H Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2014/08/30/cracking-the-code-of-human-life-the-birth-of-bioinformatics- computational-genomics/

23. Big Data in Genomic Medicine

Author and Curator, Larry H Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2012/12/17/big-data-in-genomic-medicine/

24. From Genomics of Microorganisms to Translational Medicine

Author and Curator: Demet Sag, PhD

http://pharmaceuticalintelligence.com/2014/03/20/without-the-past-no-future-but-learn-and-move-genomics-of- microorganisms-to-translational-medicine/

25. Summary of Genomics and Medicine: Role in Cardiovascular Diseases

Author and Curator, Larry H Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2014/01/06/summary-of-genomics-and-medicine-role-in-cardiovascular-diseases/

26. Genomic Promise for Neurodegenerative Diseases, Dementias, Autism Spectrum, Schizophrenia, and Serious Depression

Author and Curator, Larry H Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2013/02/19/genomic-promise-for-neurodegenerative-diseases-dementias-autism- spectrum-schizophrenia-and-serious-depression/

27. BRCA1 a tumour suppressor in breast and ovarian cancer – functions in transcription, ubiquitination and DNA repair

Sudipta Saha, PhD

http://pharmaceuticalintelligence.com/2012/12/04/brca1-a-tumour-suppressor-in-breast-and-ovarian-cancer-functions- in-transcription-ubiquitination-and-dna-repair/

28. Personalized medicine gearing up to tackle cancer

Ritu Saxena, PhD

http://pharmaceuticalintelligence.com/2013/01/07/personalized-medicine-gearing-up-to-tackle-cancer/

29. Differentiation Therapy – Epigenetics Tackles Solid Tumors

Stephen J Williams, PhD

http://pharmaceuticalintelligence.com/2013/01/03/differentiation-therapy-epigenetics-tackles-solid-tumors/

30. Mechanism involved in Breast Cancer Cell Growth: Function in Early Detection & Treatment

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/01/17/mechanism-involved-in-breast-cancer-cell-growth-function-in-early- detection-treatment/

31. The Molecular pathology of Breast Cancer Progression

Tilde Barliya, PhD

http://pharmaceuticalintelligence.com/2013/01/10/the-molecular-pathology-of-breast-cancer-progression

32. Gastric Cancer: Whole-genome reconstruction and mutational signatures

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2012/12/24/gastric-cancer-whole-genome-reconstruction-and-mutational- signatures-2/

33. Paradigm Shift in Human Genomics – Predictive Biomarkers and Personalized Medicine – Part 1 (pharmaceuticalintelligence.com)

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalntelligence.com/2013/01/13/paradigm-shift-in-human-genomics-predictive-biomarkers-and-personalized-medicine-part-1/

34. LEADERS in Genome Sequencing of Genetic Mutations for Therapeutic Drug Selection in Cancer Personalized Treatment: Part 2

A Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/01/13/leaders-in-genome-sequencing-of-genetic-mutations-for-therapeutic- drug-selection-in-cancer-personalized-treatment-part-2/

35. Personalized Medicine: An Institute Profile – Coriell Institute for Medical Research: Part 3

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/01/13/personalized-medicine-an-institute-profile-coriell-institute-for-medical- research-part-3/

36. Harnessing Personalized Medicine for Cancer Management, Prospects of Prevention and Cure: Opinions of Cancer Scientific Leaders @http://pharmaceuticalintelligence.com

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/01/13/7000/Harnessing_Personalized_Medicine_for_ Cancer_Management- Prospects_of_Prevention_and_Cure/

37. GSK for Personalized Medicine using Cancer Drugs needs Alacris systems biology model to determine the in silico
effect of the inhibitor in its “virtual clinical trial”

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2012/11/14/gsk-for-personalized-medicine-using-cancer-drugs-needs-alacris- systems-biology-model-to-determine-the-in-silico-effect-of-the-inhibitor-in-its-virtual-clinical-trial/

38. Personalized medicine-based cure for cancer might not be far away

Ritu Saxena, PhD

http://pharmaceuticalintelligence.com/2012/11/20/personalized-medicine-based-cure-for-cancer-might-not-be-far-away/

39. Human Variome Project: encyclopedic catalog of sequence variants indexed to the human genome sequence

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2012/11/24/human-variome-project-encyclopedic-catalog-of-sequence-variants- indexed-to-the-human-genome-sequence/

40. Inspiration From Dr. Maureen Cronin’s Achievements in Applying Genomic Sequencing to Cancer Diagnostics

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/01/10/inspiration-from-dr-maureen-cronins-achievements-in-applying- genomic-sequencing-to-cancer-diagnostics/

41. The “Cancer establishments” examined by James Watson, co-discoverer of DNA w/Crick, 4/1953

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/01/09/the-cancer-establishments-examined-by-james-watson-co-discover- of-dna-wcrick-41953/

42. What can we expect of tumor therapeutic response?

Author and curator: Larry H Bernstein, MD, FACP

http://pharmaceuticalintelligence.com/2012/12/05/what-can-we-expect-of-tumor-therapeutic-response/

43. Directions for genomics in personalized medicine

Author and Curator: Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2013/01/27/directions-for-genomics-in-personalized-medicine/

44. How mobile elements in “Junk” DNA promote cancer. Part 1: Transposon-mediated tumorigenesis.

Stephen J Williams, PhD

http://pharmaceuticalintelligence.com/2012/10/31/how-mobile-elements-in-junk-dna-prote-cancer-part1-transposon- mediated-tumorigenesis/

45. mRNA interference with cancer expression

Author and Curator, Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2012/10/26/mrna-interference-with-cancer-expression/

46. Expanding the Genetic Alphabet and linking the genome to the metabolome

Aviva Lev-Ari, PhD, RD

http://pharmaceuticalintelligence.com/2012/09/24/expanding-the-genetic-alphabet-and-linking-the-genome-to-the- metabolome/

47. Breast Cancer, drug resistance, and biopharmaceutical targets

Author and Curator: Larry H Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2012/09/18/breast-cancer-drug-resistance-and-biopharmaceutical-targets/

48. Breast Cancer: Genomic profiling to predict Survival: Combination of Histopathology and Gene Expression Analysis

Aviva Lev-Ari, PhD, RD

http://pharmaceuticalintelligence.com/2012/12/24/breast-cancer-genomic-profiling-to-predict-survival-combination-of- histopathology-and-gene-expression-analysis

49. Gastric Cancer: Whole-genome reconstruction and mutational signatures

Aviva Lev-Ari, PhD, RD

http://pharmaceuticalintelligence.com/2012/12/24/gastric-cancer-whole-genome-reconstruction-and-mutational- signatures-2/

50. Genomic Analysis: FLUIDIGM Technology in the Life Science and Agricultural Biotechnology

Aviva Lev-Ari, PhD, RD

http://pharmaceuticalintelligence.com/2012/08/22/genomic-analysis-fluidigm-technology-in-the-life-science-and- agricultural-biotechnology/

51. 2013 Genomics: The Era Beyond the Sequencing Human Genome: Francis Collins, Craig Venter, Eric Lander, et al.

Aviva Lev-Ari, PhD, RD

http://pharmaceuticalintelligence.com/2013_Genomics

52. Paradigm Shift in Human Genomics – Predictive Biomarkers and Personalized Medicine – Part 1

Aviva Lev-Ari, PhD, RD

http://pharmaceuticalintelligence.com/Paradigm Shift in Human Genomics_/

Signaling Pathways

Proteins and cellular adaptation to stress

Larry H Bernstein, MD, FCAP, Curator

http://pharmaceuticalintelligence.com/2014/07/08/proteins-and-cellular-adaptation-to-stress/

A Synthesis of the Beauty and Complexity of How We View Cancer:
Cancer Volume One – Summary

Author and Curator: Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2014/03/26/a-synthesis-of-the-beauty-and-complexity-of-how-we-view-cancer/

Recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes in
serous endometrial tumors

Sudipta Saha, PhD

http://pharmaceuticalintelligence.com/2012/11/19/recurrent-somatic-mutations-in-chromatin-remodeling-ad-ubiquitin- ligase-complex-genes-in-serous-endometrial-tumors/

4. Prostate Cancer Cells: Histone Deacetylase Inhibitors Induce Epithelial-to-Mesenchymal Transition

Stephen J Williams, PhD

http://pharmaceuticalintelligence.com/2012/11/30/histone-deacetylase-inhibitors-induce-epithelial-to-mesenchymal- transition-in-prostate-cancer-cells/

5. Ubiquinin-Proteosome pathway, autophagy, the mitochondrion, proteolysis and cell apoptosis

Author and Curator: Larry H Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2012/10/30/ubiquinin-proteosome-pathway-autophagy-the-mitochondrion- proteolysis-and-cell-apoptosis/

6. Signaling and Signaling Pathways

Larry H. Bernstein, MD, FCAP, Reporter and Curator

http://pharmaceuticalintelligence.com/2014/08/12/signaling-and-signaling-pathways/

7. Leptin signaling in mediating the cardiac hypertrophy associated with obesity

Larry H. Bernstein, MD, FCAP, Reporter and Curator

http://pharmaceuticalintelligence.com/2013/11/03/leptin-signaling-in-mediating-the-cardiac-hypertrophy-associated- with-obesity/

Sensors and Signaling in Oxidative Stress

Larry H. Bernstein, MD, FCAP, Reporter and Curator

http://pharmaceuticalintelligence.com/2013/11/01/sensors-and-signaling-in-oxidative-stress/

The Final Considerations of the Role of Platelets and Platelet Endothelial Reactions in Atherosclerosis and Novel
Treatments

Larry H. Bernstein, MD, FCAP, Reporter and Curator

http://pharmaceuticalintelligence.com/2013/10/15/the-final-considerations-of-the-role-of-platelets-and-platelet- endothelial-reactions-in-atherosclerosis-and-novel-treatments

10. Platelets in Translational Research – Part 1

Larry H. Bernstein, MD, FCAP, Reporter and Curator

http://pharmaceuticalintelligence.com/2013/10/07/platelets-in-translational-research-1/

11. Disruption of Calcium Homeostasis: Cardiomyocytes and Vascular Smooth Muscle Cells: The Cardiac and
Cardiovascular Calcium Signaling Mechanism

Author and Curator: Larry H Bernstein, MD, FCAP, Author, and Content Consultant to e-SERIES A:
Cardiovascular Diseases: Justin Pearlman, MD, PhD, FACC and Curator: Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/09/12/disruption-of-calcium-homeostasis-cardiomyocytes-and-vascular- smooth-muscle-cells-the-cardiac-and-cardiovascular-calcium-signaling-mechanism/

12. The Centrality of Ca(2+) Signaling and Cytoskeleton Involving Calmodulin Kinases and
Ryanodine Receptors in Cardiac Failure, Arterial Smooth Muscle, Post-ischemic Arrhythmia,
Similarities and Differences, and Pharmaceutical Targets

Author and Curator: Larry H Bernstein, MD, FCAP, Author, and Content Consultant to
e-SERIES A: Cardiovascular Diseases: Justin Pearlman, MD, PhD, FACC and
Curator: Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/09/08/the-centrality-of-ca2-signaling-and-cytoskeleton-involving-calmodulin- kinases-and-ryanodine-receptors-in-cardiac-failure-arterial-smooth-muscle-post-ischemic-arrhythmia-similarities-and- differen/

13. Nitric Oxide Signalling Pathways

Aviral Vatsa, PhD, MBBS

http://pharmaceuticalintelligence.com/2012/08/22/nitric-oxide-signalling-pathways/

14. Immune activation, immunity, antibacterial activity

Larry H. Bernstein, MD, FCAP, Curator

http://pharmaceuticalintelligence.com/2014/07/06/immune-activation-immunity-antibacterial-activity/

15. Regulation of somatic stem cell Function

Larry H. Bernstein, MD, FCAP, Writer and Curator Aviva Lev-Ari, PhD, RN, Curator

http://pharmaceuticalintelligence.com/2014/07/29/regulation-of-somatic-stem-cell-function/

16. Scientists discover that pluripotency factor NANOG is also active in adult organisms

Larry H. Bernstein, MD, FCAP, Reporter

http://pharmaceuticalintelligence.com/2014/07/10/scientists-discover-that-pluripotency-factor-nanog-is-also-active-in-adult-organisms/

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Why did this occur? The matter of Individual Actions Undermining Trust, The Patent Dilemma and The Value of a Clinical Trials

Posted in Academic Publishing, Automated Cell Processing, BioBanking, Biomarkers & Medical Diagnostics, Biomedical Measurement Science, Cancer Prevention: Research & Programs, Cancer Screening, Cardiac and Cardiovascular Surgical Procedures, Clinical Diagnostics, Curation, Diagnostic Immunology, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Ecosystems & Industrial Concentration in the Medical Device Sector, Epigenetics and Cardiovascular Risks, FDA Regulatory Affairs, Frontiers in Cardiology and Cardiovascular Disorders, Health Economics and Outcomes Research, Health Law & Patient Safety, HealthCare IT, Healthcare Reform, Immunodiagnostics, Infectious Disease & New Antibiotic Targets, Intellectual Property, Innovations, Commercialization, Investment in technological breakthrough, Law and Medicine Conflicts, Leadership, Power, Social Interlocking Connections, Mass automation of plasma proteins, Medical Devices R&D and Inventions, Medical Devices R&D Investment, Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound, Open Access Journals, Origins of Cardiovascular Disease, Patents, Pharmaceutical Analytics, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Investment, Scientist: Career considerations, Statistical Methods for Research Evaluation, tagged academic advancement, impact factor, patents, pressure to publish, prestigious institution, RAP, retraction of published work, scientific discovery, standing in scientific community on July 18, 2014| Leave a Comment »

Why did this occur? The matter of Individual Actions Undermining Trust, The Patent Dilemma and The Value of a Clinical Trials

Reporter and Curator: Larry H. Bernstein, MD, FCAP

he large amount of funding tied to continued research and support of postdoctoral fellows leads one to ask how following the money can lead to discredited work in th elite scientific community.

Moreover, the pressure to publish in prestigious journals with high impact factors is a road to academic promotion. In the last twenty years, it is unusual to find submissions for review with less than 6-8 authors, with the statement that all contributed to the work. These factors can’t be discounted outright, but it is easy for work to fall through the cracks when a key investigator has over 200 publications and holds tenure in a great research environment. But that is where we find ourselves today.

There is another issue that comes up, which is also related to the issue of carrying out research, and then protecting the work for commercialization. It is more complicated in the sense that it is necessary to determine whether there is prior art, and then there is the possibility that after the cost of filing patent and a 6 year delay in obtaining protection, there is as great a cost in bringing the patent to finasl production.

I. Individual actions undermining trust.

II. The patent dilemma.

III. The value of a clinical trial.

IV. The value contributions of RAP physicians
(radiologists, anesthesiologists, and pathologists – the last for discussion)
Those who maintain and inform the integrity of medical and surgical decisions

I. Top heart lab comes under fire

Kelly Servick

Science 18 July 2014: Vol. 345 no. 6194 p. 254 DOI: 10.1126/science.345.6194.25

In the study of cardiac regeneration, Piero Anversa is among the heavy hitters. His research into the heart’s repair mechanisms helped kick-start the field of cardiac cell therapy (see main story). After more than 4 decades of research and 350 papers, he heads a lab at Harvard Medical School’s Brigham and Women’s Hospital (BWH) in Boston that has more than $6 million in active grant funding from the National Institutes of Health (NIH). He is also an outspoken voice in a field full of disagreement.

So when an ongoing BWH investigation of the lab came to light earlier this year, Anversa’s colleagues were transfixed. “Reactions in the field run the gamut from disbelief to vindication,” says Mark Sussman, a cardiovascular researcher at San Diego State University in California who has collaborated with Anversa. By Sussman’s account, Anversa’s reputation for “pushing the envelope” and “challenging existing dogma” has generated some criticism. Others, however, say that the disputes run deeper—to doubts about a cell therapy his lab has developed and about the group’s scientific integrity. Anversa told Science he was unable to comment during the investigation.

“People are talking about this all the time—at every scientific meeting I go to,” says Charles Murry, a cardiovascular pathologist at the University of Washington, Seattle. “It’s of grave concern to people in the field, but it’s been frustrating,” because no information is available about BWH’s investigation. BWH would not comment for this article, other than to say that it addresses concerns about its researchers confidentially.

In April, however, the journal Circulation agreed to Harvard’s request to retract a 2012 paper on which Anversa is a corresponding author, citing “compromised” data. The Lancet also issued an “Expression of Concern” about a 2011 paper reporting results from a clinical trial, known as SCIPIO, on which Anversa collaborated. According to a notice from the journal, two supplemental figures are at issue.

For some, Anversa’s status has earned him the benefit of the doubt. “Obviously, this is very disconcerting,” says Timothy Kamp, a cardiologist at the University of Wisconsin, Madison, but “I would be surprised if it was an implication of a whole career of research.”

Throughout that career, Anversa has argued that the heart is a prolific, lifelong factory for new muscle cells. Most now accept the view that the adult heart can regenerate muscle, but many have sparred with Anversa over his high estimates for the rate of this turnover, which he maintained in the retracted Circulation paper.

Anversa’s group also pioneered a method of separating cells with potential regenerative abilities from other cardiac tissue based on the presence of a protein called c-kit. After publishing evidence that these cardiac c-kit⁺cells spur new muscle growth in rodent hearts, the group collaborated in the SCIPIO trial to inject them into patients with heart failure. In The Lancet, the scientists reported that the therapy was safe and showed modest ability to strengthen the heart—evidence that many found intriguing and provocative. Roberto Bolli, the cardiologist whose group at the University of Louisville in Kentucky ran the SCIPIO trial, plans to test c-kit⁺ cells in further clinical trials as part of the NIH-funded Cardiovascular Cell Therapy Research Network.

But others have been unable to reproduce the dramatic effects Anversa saw in animals, and some have questioned whether these cells really have stem cell–like properties. In May, a group led by Jeffery Molkentin, a molecular biologist at Cincinnati Children’s Hospital Medical Center in Ohio, published a paper in Nature tracing the genetic lineage of c-kit⁺ cells that reside in the heart. He concluded that although they did make new muscle cells, the number is “astonishingly low” and likely not enough to contribute to the repair of damaged hearts. Still, Molkentin says that he “believe[s] in their therapeutic potential” and that he and Anversa have discussed collaborating.

Now, an anonymous blogger claims that problems in the Anversa lab go beyond controversial findings. In a letter published on the blog Retraction Watch on 30 May, a former research fellow in the Anversa lab described a lab culture focused on protecting the c-kit⁺ cell hypothesis: “[A]ll data that did not point to the ‘truth’ of the hypothesis were considered wrong,” the person wrote. But another former lab member offers a different perspective. “I had a great experience,” says Federica Limana, a cardiovascular disease researcher at IRCCS San Raffaele Pisana in Rome who spent 2 years of her Ph.D. work with the group in 1999 and 2000, as it was beginning to investigate c-kit⁺ cells. “In that period, there was no such pressure” to produce any particular result, she says.

Accusations about the lab’s integrity, combined with continued silence from BWH, are deeply troubling for scientists who have staked their research on theories that Anversa helped pioneer. Some have criticized BWH for requesting retractions in the midst of an investigation. “Scientific reputations and careers hang in the balance,” Sussman says, “so everyone should wait until all facts are clearly and fully disclosed.”

II. Trolling Along: Recent Commotion About Patent Trolls

July 17, 2014

PriceWaterhouseCoopers recently released a study about 2014 Patent Litigation. PwC’s ultimate conclusion was that case volume increased vastly and damages continue a general decline, but what’s making headlines everywhere is that “patent trolls” now account for 67% of all new patent lawsuits (see, e.g., Washington Post and Fast Company).

Surprisingly, looking at PwC’s study, the word “troll” is not to be found. So, with regard to patent trolls, what does this study really mean for companies, patent owners and casual onlookers?

First of all, who are these trolls?

“Patent Troll” is a label applied to patent owners who do not make or manufacture a product, or offer a service. Patent trolls live (and die) by suing others for allegedly practicing an invention that is claimed by their patents.

The politically correct term is Non-practicing Entity (NPE). PwC solely uses the term NPE, which it defines as an entity that does not have the capability to design, manufacture, or distribute products with features protected by the patent.

So, what’s so bad about them?

The common impression of an NPEs is a business venture looking to collect and monetize assets (i.e., patents). In the most basic strategy, an NPE typically buys patents with broad claims that cover a wide variety of technologies and markets, and then sues a large group of alleged patent infringers in the hope to collect a licensing royalty or a settlement. NPEs typically don’t want to spend money on a trial unless they have to, and one tactic uses settlements with smaller businesses to build a “war chest” for potential suits with larger companies.

NPEs initiating a lawsuit can be viewed positively, such as a just defense of the lowly inventor who sold his patent to someone (with deeper pockets) who could fund the litigation to protect the inventor’s hard work against a mega-conglomerate who ripped off his idea.

Or NPE litigation can be seen negatively, such as an attorney’s demand letter on behalf of an anonymous shell corporation to shake down dozens of five-figure settlements from all the local small businesses that have ever used a fax machine.

NPEs can waste a company’s valuable time and resources with lawsuits, yet also bring value to their patent portfolios by energizing a patent sales and licensing market. There are unscrupulous NPEs, but it’s hardly the black and white situation that some media outlets are depicting.

What did PwC say about trolls?

Well, the PwC study looked at the success rates and awards of patent litigation decisions. One conclusion is that damages awards for NPEs averaged more than triple those for practicing entities over the last four years. We’ll come back to this statistic.

Another key observation is that NPEs have been successful 25% of the time overall, versus 35% for practicing entities. This makes sense because of the burden of proof the NPEs carry as a plaintiff at trial and the relative lack of success for NPEs at summary judgment. However, PwC’s report states that both types of entities win about two-thirds of their trials.

But what about this “67% of all patent trials are initiated by trolls” discussion?

The 67% number comes from the RPX Corporation’s litigation report (produced January 2014) that quantified the percentage of NPE cases filed in 2013 as 67%, compared to 64% in 2012, 47% in 2011, 30% in 2010 and 28% in 2009.

PwC refers to the RPX statistics to accentuate that this new study indicates that only 20% ofdecisions in 2013 involved NPE-filed cases, so the general conclusion would be that NPE cases tend to settle or be dismissed prior to a court’s decision. Admittedly, this is indicative of the prevalent “spray and pray” strategy where NPEs prefer to collect many settlement checks from several “targets” and avoid the courtroom.

In this study, who else is an NPE?

If someone were looking to dramatize the role of “trolls,” the name can be thrown around liberally (and hurtfully) to anyone who owns and asserts a patent without offering a product or a service. For instance, colleges and universities fall under the NPE umbrella as their research and development often ends with a series of published papers rather than a marketable product on an assembly line.

In fact, PwC distinguishes universities and non-profits from companies and individuals within their NPE analysis, with only about 5% of the NPE cases from 1995 to 2013 being attributed to universities and non-profits. Almost 50% of the NPE cases are attributed to an “individual,” who could be the listed inventor for the patent or a third-party assignee.

The word “troll” is obviously a derogatory term used to connote greed and hiding (under a bridge), but the term has adopted a newer, meme-like status as trolls are currently depicted as lacking any contribution to society and merely living off of others’ misfortunes and fears. [Three Billy Goats Gruff]. This is not always the truth with NPEs (e.g., universities).

No one wants to be called a troll—especially in front of a jury—so we’ve even recently seen courts bar defendants from referring to NPEs as such colorful terms as a “corporate shell,” “bounty hunter,” “privateer,” or someone “playing the lawsuit lottery.” [Judge Koh Bans Use Of Term ” Patent Troll” In Apple Jury Trial]

Regardless of the portrayal of an NPE, most people in the patent world distinguish the “trolls” by the strength of the patent, merits of the alleged infringement and their behavior upon notification. Often these are expressed as “frivolity” of the case and “gamesmanship” of the attorneys. Courts are able to punish plaintiffs who bring frivolous claims against a party and state bar associations are tasked with monitoring the ethics of attorneys. The USPTO is tasked with working to strengthen the quality of patents.

What’s the take-away from this study regarding NPEs?

The study focuses on patent litigation that produced a decision, therefore the most important and relevant conclusion is that, over the last four years, average damages awards for NPEs are more than triple the damages for practicing entities. Everything else in these articles, such as the initiation of litigation by NPEs, settlement percentages, and the general behavior of patent trolls is pure inference beyond the scope of the study.

This may sound sympathetic to trolls, but keep in mind that the study highlights that NPEs have more than triple the damages on average compared to practicing entities and it is meant to shock the reader a bit. One explanation for this is that NPEs are in the best position to choose the patents they want to assert and choose the targets they wish to sue—especially when the NPE is willing to ride that patent all the way to the end of a long, expensive trial. Sometimes settling is not an option. Chart 2b indicates that the disparity in the damages awarded to NPEs relative to practicing entities has always been big (since 2000), but perhaps going from two-fold from 2000 – 2009 to three times as much in the past 4 years indicates that NPEs are improving at finding patents and/or picking battles to take all the way to a court decision. More than anything, this seems to reflect the growth in the concept of patents as a business asset.

The PwC report is chock full of interesting patterns and trends of litigation results, so it’s a shame that the 67% number makes the headlines—far more interesting are the charts comparing success rates by 4-year periods (Chart 6b) or success rates for NPEs and practicing entities in front of a jury verusin front of a bench (Chart 6c), as well as other tables that reveal statistics for specific districts of the federal courts. Even the stats that look at the success rates of each type of NPE are telling because the reader sees that universities and non-profits have a higher success rate than non-practicing companies or individuals.

What do we do about the trolls?

The White House has recently called for Congress to do something about the trolls as horror stories of scams and shake-downs are shared. A bill was gaining momentum in the Senate, when Senator Leahy took it off the agenda in early July. That bill had miraculously passed 325-91 in the House and President Obama was willing to sign it if the Senate were to pass it. The bill was opposed by trial attorneys, universities, and bio-pharmaceutical businesses who felt as though the law would severely inhibit everyone’s access to the courts in order to hinder just the trolls. Regardless, most people think that the sitting Congressmen merely wanted a “win” prior to the mid-term elections and that patent reform is unlikely to reappear until next term.

In the meantime, the Supreme Court has recently reiterated rules concerning attorney fee-shifting on frivolous patent cases, as well as clarifying the validity of software patents. Time will tell if these changes have any effects on the damages awards that PwC’s study examined or even if they cause a chilling of the number of patent lawsuit filings.

Furthermore, new ways to challenge the validity of asserted patents have been initiated via the America Invents Act. For example, the Inter Partes Review (IPR) has yielded frightening preliminary statistics as to slowing, if not killing, patents that have been asserted in a suit. While these administrative trials are not cheap, many view these new tools at the Patent Trial and Appeals Board as anti-troll measures. It will be interesting to watch how the USPTO implements these procedures in the near future, especially while former Google counsel, Acting Director Michelle K. Lee, oversees the office.

In the private sector, Silicon Valley has recently seen a handful of tech companies come together as the License on Transfer Network, a group hoping to disarm the “Patent Assertion Entities.” Joining the LOT Network comes via an agreement that creates a license for use of a patent by anyone in the LOT network once that patent is sold. The thought is that the NPEs who consider purchasing patents from companies in the LOT Network will have fewer companies to sue since the license to the other active LOT participants will have triggered upon the transfer and, thus, the NPE will not be as inclined to “troll.” For instance, if a member-company such as Google were to sell a patent to a non-member company and an NPE bought that patent, the NPE would not be able to sue any members of the LOT Network with that patent.

Other notes

NPEs are only as evil as the people who run them—that being said, there are plenty of horror stories of small businesses receiving phantom demand letters that threaten a patent infringement suit without identifying themselves or the patent. This is an out-and-out scam and a plague on society that results in wasted time and resource, and inevitably higher prices on the consumer end.

It is a sin and a shame that patent rights can be misused in scams and shake-downs of businesses around us, but there is a reason that U.S. courts are so often used to defend patent rights. The PwC study, at minimum, reflects the high stakes of the patent market and perhaps the fragility. Nevertheless, merely monitoring the courts may not keep the trolls at bay.

I’d love to hear your thoughts.

*This is provided for informational purposes only, and does not constitute legal or financial advice. The information expressed is subject to change at any time and should be checked for completeness, accuracy and current applicability. For advice, consult a suitably licensed attorney or patent agent.

III. Large-scale analysis finds majority of clinical trials don’t provide meaningful evidence

Ineffective Treatments, Medical Ethics • Tags: Center for Drug Evaluation and Research, Clinical trial, CTTI, Duke University Hospital, FDA, Food and Drug Administration, National Institutes of Health, United States National Library of Medicine

04 May 2012

DURHAM, N.C.— The largest comprehensive analysis of ClinicalTrials.gov finds that clinical trials are falling short of producing high-quality evidence needed to guide medical decision-making. The analysis, published today in JAMA, found the majority of clinical trials is small, and there are significant differences among methodical approaches, including randomizing, blinding and the use of data monitoring committees.

“Our analysis raises questions about the best methods for generating evidence, as well as the capacity of the clinical trials enterprise to supply sufficient amounts of high quality evidence to ensure confidence in guideline recommendations,” said Robert Califf, M.D., first author of the paper, vice chancellor for clinical research at Duke University Medical Center, and director of the Duke Translational Medicine Institute.

The analysis was conducted by the Clinical Trials Transformation Initiative (CTTI), a public private partnership founded by the Food and Drug Administration (FDA) and Duke. It extends the usability of the data in ClinicalTrials.gov for research by placing the data through September 27, 2010 into a database structured to facilitate aggregate analysis. This publically accessible database facilitates the assessment of the clinical trials enterprise in a more comprehensive manner than ever before and enables the identification of trends by study type.

The National Library of Medicine (NLM), a part of the National Institutes of Health, developed and manages ClinicalTrials.gov. This site maintains a registry of past, current, and planned clinical research studies.

“Since 2007, the Food and Drug Administration Amendment Act has required registration of clinical trials, and the expanded scope and rigor of trial registration policies internationally is producing more complete data from around the world,” stated Deborah Zarin, MD, director, ClinicalTrials.gov, and assistant director for clinical research projects, NLM. “We have amassed over 120,000 registered clinical trials. This rich repository of data has a lot to say about the national and international research portfolio.”

This CTTI project was a collaborative effort by informaticians, statisticians and project managers from NLM, FDA and Duke. CTTI comprises more than 60 member organizations with the goal of identifying practices that will improve the quality and efficiency of clinical trials.

“Since the ClinicalTrials.gov registry contains studies sponsored by multiple entities, including government, industry, foundations and universities, CTTI leaders recognized that it might be a valuable source for benchmarking the state of the clinical trials enterprise,” stated Judith Kramer, MD, executive director of CTTI.

The project goal was to produce an easily accessible database incorporating advances in informatics to permit a detailed characterization of the body of clinical research and facilitate analysis of groups of studies by therapeutic areas, by type of sponsor, by number of participants and by many other parameters.

“Analysis of the entire portfolio will enable the many entities in the clinical trials enterprise to examine their practices in comparison with others,” says Califf. “For example, 96% of clinical trials have ≤1000 participants, and 62% have ≤ 100. While there are many excellent small clinical trials, these studies will not be able to inform patients, doctors and consumers about the choices they must make to prevent and treat disease.”

The analysis showed heterogeneity in median trial size, with cardiovascular trials tending to be twice as large as those in oncology and trials in mental health falling in the middle. It also showed major differences in the use of randomization, blinding, and data monitoring committees, critical issues often used to judge the quality of evidence for medical decisions in clinical practice guidelines and systematic overviews.

“These results reinforce the importance of exploration, analysis and inspection of our clinical trials enterprise,” said Rachel Behrman Sherman, MD, associate director for the Office of Medical Policy at the FDA’s Center for Drug Evaluation and Research. “Generation of this evidence will contribute to our understanding of the number of studies in different phases of research, the therapeutic areas, and ways we can improve data collection about clinical trials, eventually improving the quality of clinical trials.”

Large-scale analysis finds majority of clinical trials don’t provide meaningful evidence (eurekalert.org)
Large-scale analysis finds majority of clinical trials don’t provide meaningful evidence (talesfromthelou.wordpress.com)
Clinical trials often fall short: US study(news.com.au.feedsportal.com)
Clinical trials often fall short: U.S. study (rawstory.com)

IV. Lawmakers urge CMS to extend MU hardship exemption for pathologists

Eighty-nine members of Congress have asked the Centers for Medicare & Medicaid Services to give pathologists a break and extend the hardship exemption they currently enjoy for all of Stage 3 of the Meaningful Use program.In the letter–dated July 10 and addressed to CMS Administrator Marilyn Tavenner–the lawmakers point out that CMS had recognized in its 2012 final rule implementing Stage 2 of the program that it was difficult for pathologists to meet the Meaningful Use requirements and granted a one year exception for 2015, the first year that penalties will be imposed. They now are asking that the exception be expanded to include the full five-year maximum allowed under the American Recovery and Reinvestment Act.

“Pathologists have limited direct contact with patients and do not operate in EHRs,” the letter states. “Instead, pathologists use sophisticated computerized laboratory information systems (LISs) to support the work of analyzing patient specimens and generating test results. These LISs exchange laboratory and pathology data with EHRs.”

Interestingly, the lawmakers’ exemption request is only on behalf of pathologists, even though CMS had granted the one-year hardship exception to pathologists, radiologists and anesthesiologists.

Rep. Tom Price (R-Ga.), one of the members spearheading the letter, had also introduced a bill (H.R. 1309) in March 2013 that would exclude pathologists from the incentives and penalties of the Meaningful Use program. The bill, which has 31 cosponsors, is currently sitting in committee. That bill also does not include relief for radiologists or anesthesiologists.

CMS has provided some flexibility about the hardship exceptions in the past, most recently by allowing providers to apply for one due to EHR vendor delays in upgrading to Stage 2 of the program.

However, CMS also noted in the 2012 rule granting the one-year exception that it was granting the exception in large part because of the then-current lack of health information exchange and that “physicians in these three specialties should not expect that this exception will continue indefinitely, nor should they expect that we will grant the exception for the full 5-year period permitted by statute.”

To learn more:
– read the letter (.pdf)

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Inula helenium ( elecampane ) 100% Effective against MRSA in vitro, 200 Strains

Posted in FDA Regulatory Affairs, Genome Biology, Genomic Testing: Methodology for Diagnosis, Infectious Disease & New Antibiotic Targets, Lipid metabolism, Nutrigenomics, Nutrition, Nutritional Supplements: Atherogenesis, tagged antibacterial resistance, FDA, Food and Drug Administration, MRSA, Nutrition, Plant extract on July 15, 2014| Leave a Comment »

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Cinnamon is lethal weapon against E. coli O157:H7

Posted in Chemical Biology and its relations to Metabolic Disease, Disease Biology, FDA Regulatory Affairs, Human Immune System in Health and in Disease, Infectious Disease & New Antibiotic Targets, Lipid metabolism, Nutrition, Nutrition and Phytochemistry, Nutritional Supplements: Atherogenesis, Population Health Management, Small Molecules in Development of Therapeutic Drugs, tagged antibacterial resistance, cinnamon, FDA, Food and Drug Administration, foods, Nutraceutical, Nutrition, research on July 15, 2014| Leave a Comment »

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Garlic compound fights source of food-borne illness better than antibiotics (100 times more effective than two popular antibiotics )

Posted in FDA Regulatory Affairs, Human Immune System in Health and in Disease, Infectious Disease & New Antibiotic Targets, Lipid metabolism, Nutrition, Nutrition and Phytochemistry, Nutritional Supplements: Atherogenesis, Population Health Management, Translational Effectiveness, Translational Research, Translational Science on July 15, 2014| Leave a Comment »

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Research on inflammasomes opens therapeutic ways for treatment of rheumatoid arthritis

Posted in Cell Biology, Signaling & Cell Circuits, Disease Biology, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Human Immune System in Health and in Disease, Infectious Disease & New Antibiotic Targets, Metabolomics, Population Health Management, Genetics & Pharmaceutical, Proteomics, Signaling, Signaling & Cell Circuits, Small Molecules in Development of Therapeutic Drugs, Systemic Inflammatory Response Related Disorders, Translational Research, Translational Science, tagged inflammasomes, RA on July 12, 2014| Leave a Comment »

Research on inflammasomes opens therapeutic ways for treatment of rheumatoid arthritis

Reporter: Larry H. Bernstein, MD, FCAP

One of the processes accounted for by inflammasomes is the production of interleukin-1, a protein with an important role in inflammatory reactions. Stopping the effects of interleukin-1 resulted in a cure for the mice. In this manner, Vande Walle and Lamkanfi demonstrated that the mouse model is perfectly suitable for studying the correlation between inflammasomes and RA.

RA is a syndrome rather than a single disease
Previous research has already demonstrated that other proteins in our immune system – such as TNF and IL-17 – could possibly play a role in RA
We could evolve towards a more personalized approach for RA

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Genomics, Proteomics and standards

Posted in BioBanking, Biomarkers & Medical Diagnostics, Biomedical Measurement Science, CANCER BIOLOGY & Innovations in Cancer Therapy, Cancer Screening, Cell Biology, Signaling & Cell Circuits, Computational Biology/Systems and Bioinformatics, Curation, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Epigenetics and Cardiovascular Risks, FDA Regulatory Affairs, Genome Biology, Genomic Testing: Methodology for Diagnosis, Hematology, Human Immune System in Health and in Disease, Imaging-based Cancer Patient Management, Immunodiagnostics, Infectious Disease & New Antibiotic Targets, Innovation in Immunology Diagnostics, Intellectual Property, Innovations, Commercialization, Investment in technological breakthrough, Medical and Population Genetics, Molecular Genetics & Pharmaceutical, Nephrology & Regenerative medicine, Neurodegenerative Diseases, Origins of Cardiovascular Disease, Personalized and Precision Medicine & Genomic Research, Pharmaceutical Analytics, Pharmaceutical Discovery, Pharmacogenomics, Population Health Management, Genetics & Pharmaceutical, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics, RNA Biology, Cancer and Therapeutics, tagged biomarkers, Computational Biology/Systems and Bioinformatics, genomics, Personalized medicine on July 6, 2014| Leave a Comment »

Larry H. Bernstein, MD, FCAP, Curator

http://pharmaceuticalintelligence/7/6/2014/Genomics, Proteomics and standards

This article is a look at where the biomedical research sciences are in developing standards for development in the near term.

Let’s Not Wait for the FDA: Raising the Standards of Biomarker Development – A New Series

published by Theral Timpson on Tue, 07/01/2014 – 15:03

We talk a lot on this show about the potential of personalized medicine. Never before have we learned at such breakneck speed just how our bodies function. The pace of biological research staggers the mind and hints at a time when we will “crack the code” of the system that is homo sapiens, going from picking the low hanging fruit to a more rational approach. The high tech world has put at the fingertips of biologists just the tools to do it. There is plenty of compute, plenty of storage available to untangle, or decipher the human body. Yet still, we talk of potential.

Chat with anyone heavily involved in the life science industry–be it diagnostics or pharma– and you’ll quickly hear that we must have better biomarkers.

Next week we launch a series, Let’s Not Wait for the FDA: Raising the Standards of Biomarker Development, where we will pursue the “hotspots” that are haunting those in the field.

The National Biomarker Development Alliance (NBDA) is a non profit organization based at Arizona State University and led by the formidable Anna Barker, former deputy director of the NCI. The aim of the NBDA is to identify problem areas in biomarker development–from the biospecimen and sampling issues to experiment design to bioinformatics challenges–and raise the standards in each area. This series of interviews is based on their approach. We will purse each of these topics with a special guest.

The place to start is with samples. The majority of researchers who are working on biomarker assays don’t give much thought to the “story” of their samples. Yet the quality of their research will never exceed the quality of the samples with which they start–a very scary thought according toCarolyn Compton, a former pathologist, now professor of pathology at ASU and Johns Hopkins. Carolyn worked originally as a clinical pathologist and knows first hand the the issues around sample degradation. She left the clinic when she was recruited to the NCI with the mission of bringing more awareness to the issue of bio specimens. She joins us as our first guest in the series.

That Carolyn has straddled the world of the clinic and the world of research is key to her message. And it’s key to this series. As we see an increased push to “translate” research into clinical applications, we find that these two worlds do not work enough together.

Researchers spend a lot of time analyzing data and developing causal relationships from certain biological molecules to a disease. But how often do these researchers consider how the history of a sample might be altering their data?

“Garbage in, garbage out,” says Carolyn, who links low quality samples with the abysmal non-reproducable rate of most published research.

Two of our guests in the series have worked on the adaptive iSpy breast cancer trials. These are innovative clinical trials that have been designed to “adapt” to the specific biology of those in the trial. Using the latest advances in genetics, the iSPY trials aim to match experimental drugs with the molecular makeup of tumors most likely to respond to them. And the trials are testing multiple drugs at once.

Don Berry is known for bringing statistics to clinical trials. He designed the iSpy trials and joins us to explain how these new trials work and of the promise of the adaptive design.

Laura Esserman is the director of the breast cancer center at UCSC and has been heavily involved in the implementation of the iSpy trials. Esserman is concerned that “if we keep doing conventional clinical trials, people are going to give up on doing them.” An MBA as well as an MD, Esserman brings what she learned about innovation in the high-tech industry to treatment for breast cancer.

From there we turn to the topic of “systems biology” where we will chat with George Poste, a tour de force when it comes to considering all of the various aspects of biology. Anyone who has ever been present for one of George’s presentations has no doubt come away scratching your head wondering if we’ll ever really glimpse the whole system that is a human being. If there is one brain that has seen all the rooms and hallways of our complex system, it’s George Poste.

We’ll finish the series by interviewing David Haussler from UCSC of Genome Browser fame. Recently Haussler has worked extensively on an NCI project, The Cancer Genome Atlas, to bring together data sets and connect cancer researchers around the world. What is the promise and pitfalls David sees with the latest bioinformatics tools?

George Poste says that in the literature we have identified 150,000 biomarkers that have causal linkage to disease. Yet only 100 of these have been commercialized and are used in the clinic. Why is the number so low? We hope to come up with some answers in this series.

Why Hasn’t Clinical Genetics Taken Off? (part 2)

published by Sultan Meghji on Fri, 06/20/2014 – 14:49

In my previous post, I made the broad comment that education of the patient and front line doctors was the single largest barrier to entry for clinical genetics. Here I look at the steps in the scientific process and where the biggest opportunities lie:

The Sequencing (still)

PCR is a perfectly reasonable technology for sequencing in the research lab today, but the current configuration of technologies need to change. We need to move away from an expert level skill set and a complicated chemistry process in the lab to a disposable, consumer friendly set of technologies. I’m not convinced PCR is the right technology for that and would love to see nanopore be a serious contender, but lack of funding for a broad spectrum of both physics-only as well as physical-electrical startups have slowed the progress of these technologies. And waiting in the wings, other technologies are spinning up in research labs around the world. Price is no longer a serious problem in the space – reliable, repeatable, easy to use sequencing technologies are. The complexity of the current technology (both in terms of sample preparation and machine operation) is a big hurdle.

The Analysis (compute)

Over the last few years, quite a bit of commentary and effort has been put into making the case that the compute is a significant challenge (including more than a few comments by yours truly in that vein!). Today, it can be said with total confidence that compute is NOT a problem. Compute has been commoditized. Through excellent new software to advanced platforms and new hardware, it is a trivial exercise to do the analysis and costs tiny amounts of money ($<25 per sample on a cloud provider appears to be the going rate for a clinical exome in terms of platform & infrastructure cost). Integration with the sequencer and downstream medical middleware is the biggest opportunity.

The Analysis (value)

The bigger challenge on the analysis is the specific things being analyzed as mapped to the needs of the patient. We are still in a world where the vast majority of the sequencing work is being done in support of a specific patient with a specific disease. There isn’t even broad consensus yet in the scientific community about the basics of the pipeline (see my blog posthere for an attempt at capturing what I’m seeing in the market). A movement away from the recent trend in studying specific indications (esp. cancer) is called for. Broadening the sample population will allow us to pick simpler, clearer and easier pipelines which will then make them more adoptable. It would be a massive benefit to the world if the scientific, medical and regulatory communities would get together and start creating, in a crowdsourced manner, a small number of databases that are specifically useful to healthy people. Targeting things like nutrition, athletics, metabolism, and other normal aspects of daily life. A dataset that could, when any one person’s DNA is references, would find something useful. Including the regulators is key so that we can begin to move away from the old fashioned model of clearances that still permeate the industry.

The Regulators

Beyond the broader issues around education I referenced in my previous post, there is a massive upgrade in the regulation infrastructure that is needed. We still live in a world of fax machines, overnight shipping of paper documents and personal relationships all being more important than the quality of the science you as an innovator are bringing to bear.

Consider the recent massive growth in wearables, fitness trackers and other instrumentation local to the human body. Why must we treat clinical genetics simply as a diagnostic and not, as it should be, as a fundamental set of quantitative data about your body that you can leverage in a myriad of ways. Direct to consumer (DTC) genetics companies, most notably 23andme, have approached this problem poorly – instead of making it valuable to the average consumer, what they’ve done is attempted to straddle the line between medical and not. The Fitbit model has shown very clearly that lifestyle activities can be directly harnessed to build commercial value in scaling health related activities without becoming a regulatory issue. It’s time for genetics to do the same thing.

Development and Role of the Human Reference Sequence in Personal Genomics

Posted by @finchtalk on July 3, 2014

A few weeks back, we published a review about the development and role of the human reference genome. A key point of the reference genome is that it is not a single sequence. Instead it is an assembly of consensus sequences that are designed to deal with variation in the human population and uncertainty in the data. The reference is a map and like a geographical maps evolves though increased understanding over time.

From the Wiley On Line site:

Abstract

Genome maps, like geographical maps, need to be interpreted carefully. Although maps are essential to exploration and navigation they cannot be completely accurate. Humans have been mapping the world for several millennia, but genomes have been mapped and explored for just a single century with the greatest advancements in making a sequence reference map of the human genome possible in the past 30 years. After the deoxyribonucleic acid (DNA) sequence of the human genome was completed in 2003, the reference sequence underwent several improvements and today provides the underlying comparative resource for a multitude genetic assays and biochemical measurements. However, the ability to simplify genetic analysis through a single comprehensive map remains an elusive goal.

Key Concepts:

Maps are incomplete and contain errors.
DNA sequence data are interpreted through biochemical experiments or comparisons to other DNA sequences.
A reference genome sequence is a map that provides the essential coordinate system for annotating the functional regions of the genome and comparing differences between individuals’ genomes.
The reference genome sequence is always product of understanding at a set point in time and continues to evolve.
DNA sequences evolve through duplication and mutation and, as a result, contain many repeated sequences of different sizes, which complicates data analysis.
DNA sequence variation happens on large and small scales with respect to the lengths of the DNA differences to include single base changes, insertions, deletions, duplications and rearrangements.
DNA sequences within the human population undergo continual change and vary highly between individuals.
The current reference genome sequence is a collection of sequences, an assembly, that include sequences assembled into chromosomes, sequences that are part of structurally complex regions that cannot be assembled, patches (fixes) that cannot be included in the primary sequence, and high variability sequences that are organised into alternate loci.
Genetic analysis is error prone and the data require validation because the methods for collecting DNA sequences create artifacts and the reference sequence used for comparative analyses is incomplete.

Keywords:DNA sequencing

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Immune activation, immunity, antibacterial activity

Posted in Biological Networks, Gene Regulation and Evolution, Federal Budget Appropriations, Genome Biology, Health Economics and Outcomes Research, Healthcare costs and reimbursement, Human Immune System in Health and in Disease, Infectious Disease & New Antibiotic Targets, Molecular Genetics & Pharmaceutical, Neutrophilia, Pharmaceutical Analytics, Pharmaceutical Discovery, Pharmaceutical Drug Discovery, Pharmaceutical R&D Investment, Pharmacogenomics, Platelet count disorder, Population Health Management, Genetics & Pharmaceutical, Prescription Drugs Costs, Proteomics, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Systemic Inflammatory Response Related Disorders, Technology Transfer: Biotech and Pharmaceutical, Translational Effectiveness, Translational Research, Translational Science, tagged 8-OXO dG, antimicrobial therapy, autoimmunity, cGAMP, DAMP, immune activation, innate immunity, microbiota, PAMPs, ribonuclease TREX1 on July 6, 2014| Leave a Comment »

Larry H. Bernstein, MD, FCAP, Curator

http://pharmaceuticalintelligence.com/6/7/2014/Immune activation, immunity, antibacterial activity

This segment is an update on activation of innate immunity, which has had a great amount of basic science resurgence in the last several decades. It also addresses the issue of antibiotic resistance, which shall be covered more fully in later segments. Antimicrobial resistance is a growing threat, and a challenge to the pharmaceutical industry. Moreover, worldwide travel increases the possibility of transfer of strains of virus and microbiota to distant communities.

8-OH-dG: A novel immune activator.

Innate immunity against viral or pathogenic infection involves sensing of non-self-molecules, otherwise known at pathogen-associated molecular patterns (PAMPs). This same sensing mechanism can be applied to damaged self-molecules, which are called damage-associated molecular patterns (DAMPs). One type of molecular pattern, for both groups, is cytosolic or extracellular DNA. However, there is not an extensive amount of research showing specifically what type of DAMP DNA molecule is best at activating this immune sensing response. A recent study investigated the mechanism behind how oxidized DNA from UV damage activates an immune sensing response.

A group of researchers found that, compared to a variety of types of cellular damage, damage from UV irradiation created a strong immune response (type I IFN response), seen across different types of immune regulatory cells. This was compared with freeze/thaw, physical damage and nutritional deprivation, each of which did not produce a noticeable immune response. Additionally, this immune response was seen when DNA was exposed to UV-A and UV-B (the type of radiation produced by our sun) and UV-C radiation.

DNA can be damaged by UV light directly, or through reactive oxygen species (ROS) caused by UV light. A well-known mark of DNA damaged by ROS is the oxidation of guanine to create 8-hydroxyguanine (8-OH-dG). These researchers saw an increase in 8-OH-dG dependant on the level of UV dose, and this also correlated with an increase in immune response; showing that DNA damage created by UV light in the form of 8-OH-dG is sufficient to activate an immune response. This study shows that 8-OH-dG can be classified at a DAMP.

Next, this group wanted to place a mechanism to these observations. They found that the ability of oxidation-damaged DNA to activate an immune response was dependant on cGAS and STING. Free DNA in the cytosol binds cGAS, a cGAMP synthase. This action produces a messenger molecule which proceeds to bind to and activate STING, an endoplasmic reticulum protein. STING activation will ultimately stimulate a type I IFN response.

When a cell’s own DNA is damaged, the cell’s machinery does all it can to repair it. This sometimes involves erasing, or degrading, the DNA that has been damaged. The enzyme, TREX1 exonuclease, has this job in a cell. However, this group found that when DNA was modified with an 8-OH-dG, it was resistant to this degradation by TREX1. This implies that the observed increase in immune response due to the presence of 8-OH-dG occurred because of an accumulation of damaged DNA, because it was not being degraded by TREX1 and could therefore sufficiently activate cGAS and STING.

This type of study has important implications for autoimmune diseases like lupus erythematosus (LE), which is characterized by its abnormally high number of autoantibodies against DNA. It is possible that this uncontrollable immune response is activated by oxidation-damaged DNA. Studies in this area, therefore, hold great importance.

– See more at: http://www.stressmarq.com/Blog/November-2013/8-OH-dG-A-novel-immune-activator.aspx#sthash.CvSdK0H1.dpuf

Oxidative Damage of DNA Confers Resistance to Cytosolic Nuclease TREX1 Degradation and Potentiates STING-Dependent Immune Sensing

Nadine Gehrke, Christina Mertens, Thomas Zillinger, Jörg Wenzel,…,Winfried Barchet

DOI: http://dx.doi.org/10.1016/j.immuni.2013.08.004

Highlights

•UV or ROS damage potentiates immunorecognition of DNA via cGAS and STING
•The oxidation product 8-OHG in DNA is sufficient for enhanced immunorecognition
•Oxidized self-DNA acts as a DAMP and induces skin lesions in lupus-prone mice
•Oxidized DNA is resistant to cytosolic nuclease TREX1-mediated degradation

Summary

Immune sensing of DNA is critical for antiviral immunity but can also trigger autoimmune diseases such as lupus erythematosus (LE). Here we have provided evidence for the involvement of a damage-associated DNA modification in the detection of cytosolic DNA. The oxidized base 8-hydroxyguanosine (8-OHG), a marker of oxidative damage in DNA, potentiated cytosolic immune recognition by decreasing its susceptibility to 3′ repair exonuclease 1 (TREX1)-mediated degradation. Oxidizative modifications arose physiologically in pathogen DNA during lysosomal reactive oxygen species (ROS) exposure, as well as in neutrophil extracellular trap (NET) DNA during the oxidative burst. 8-OHG was also abundant in UV-exposed skin lesions of LE patients and colocalized with type I interferon (IFN). Injection of oxidized DNA in the skin of lupus-prone mice induced lesions that closely matched respective lesions in patients. Thus, oxidized DNA represents a prototypic damage-associated molecular pattern (DAMP) with important implications for infection, sterile inflammation, and autoimmunity.

ribonuclease TREX1 and immunity

Immunity 19 Sep 2013;39(3), p482–495,

New Weapon in Fight Against ‘Superbugs’

Some harmful bacteria are increasingly resistant to treatment with antibiotics. A discovery might be able to help the antibiotics treat the disease.

By ANN LUKITS June 30, 2014 8:47 p.m. ET

Some harmful bacteria are increasingly resistant to treatment with antibiotics. This common fungus found in soil might be able to help the antibiotics combat diseases. Corbis

A soil sample from a national park in eastern Canada has produced a compound that appears to reverse antibiotic resistance in dangerous bacteria.

Scientists at McMaster University in Ontario discovered that the compound almost instantly turned off a gene in several harmful bacteria that makes them highly resistant to treatment with a class of antibiotics used to fight so-called superbug infections. The compound, called aspergillomarasmine A, or AMA, was extracted from a common fungus found in soil and mold.

Antibiotic resistance is a growing public-health threat. Common germs such asEscherichia coli, or E. coli, are becoming harder to treat because they increasingly don’t respond to antibiotics. Some two million people in the U.S. are infected each year by antibiotic-resistant bacteria and 23,000 die as a result, according to the Centers for Disease Control and Prevention. The World Health Organization has called antibiotic resistance a threat to global public health.

The Canadian team was able to disarm a gene—New Delhi Metallo-beta-Lactamase-1, or NDM-1—that has become “public enemy No. 1” since its discovery in 2009, says Gerard Wright, director of McMaster’s Michael G. DeGroote Institute for Infectious Disease Research and lead researcher on the study. The report appears on the cover of this week’s issue of the journal Nature.

“Discovery of a fungus capable of rendering these multidrug-resistant organisms incapable of further infection is huge,” says Irena Kenneley, a microbiologist and infectious disease specialist at Frances Payne Bolton School of Nursing at Cleveland’s Case Western Reserve University. “The availability of more treatment options will ultimately save many more lives,” says Dr. Kenneley, who wasn’t involved in the McMaster research.

The McMaster team plans further experiments to determine the safety and effective dosage of AMA. It could take as long as a decade to complete clinical trials on people with superbug infections, Dr. Wright says.

The researchers found that AMA, extracted from a strain of Aspergillus versicolor and combined with a carbapenem antibiotic, inactivated the NDM-1 gene in three drug-resistant superbugs—Enterobacteriaceae, a group of bacteria that includes E. coli;Acenitobacter, which can cause pneumonia and blood infections; and Pseudomonas, which often infect patients in hospitals and nursing homes. The NDM-1 gene encodes an enzyme that helps bacteria become resistant to antibiotics and that requires zinc to survive. AMA works by removing zinc from the enzyme, freeing the antibiotic to do its job, Dr. Wright says. Although AMA was only tested on carbapenem-resistant bacteria, he expects the compound would have a similar effect when combined with other antibiotics.

AMA was first identified in the 1960s in connection with leaf wilt in plants and later investigated as a potential drug for treating high blood pressure. The compound turned up in Dr. Wright’s lab a few years ago during a random screening of organisms derived from 10,000 soil samples stored at McMaster. The sample that produced AMA was collected by one of Dr. Wright’s graduate students during a visit to a Nova Scotia park. It was the only sample of 500 tested that inhibited NDM-1 in cell cultures.

“It was a lucky hit,” says Dr. Wright. “It tells us that going back to those environmental organisms, where we got antibiotics in the first place, is a really good idea.”

The McMaster team developed a purified form of AMA for experiments on mice injected with a lethal form of drug-resistant pneumonia. Treatment with either AMA or a carbapenem antibiotic alone proved ineffective. But combining the substances resulted in more than 95% of the mice still being alive after five days. The combination was also tested on 229 cell cultures from human patients infected with resistant superbugs. The treatment resensitized 88% of the samples to carbapenem.

Still, bacteria could someday find a way to outwit AMA. “I can’t imagine anything we could make where resistance would never be an issue,” he says. “At the end of the day, this is evolution and you can’t fight evolution.”

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New Weapon in Fight Against ‘Superbugs’

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12. The Centrality of Ca(2+) Signaling and Cytoskeleton Involving Calmodulin Kinases and
Ryanodine Receptors in Cardiac Failure, Arterial Smooth Muscle, Post-ischemic Arrhythmia,
Similarities and Differences, and Pharmaceutical Targets

Author and Curator: Larry H Bernstein, MD, FCAP, Author, and Content Consultant to
e-SERIES A: Cardiovascular Diseases: Justin Pearlman, MD, PhD, FACC and
Curator: Aviva Lev-Ari, PhD, RN