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Genetics of High Cholesterol

Researchers have found that ABCB4 gene, is defective in patients with high cholesterol thus leading to an impairment in the transport of fats from the liver into bile to facilitate removal of cholesterol from the body. Defective ABCB4 protein was found to impair cholesterol excretion & caused bad cholesterol to accumulate.

Reference:

Michael C. Mahaney, Ph.D., Rampratap S. Kushwaha, Ph.D., and Jane F. VandeBerg,Chan et al.. ABCB4 mediates diet-induced hypercholesterolemia in laboratory opossums. The Journal of Lipid Research

Smart bandages detect wound infections

A pH below 5 is a sign of healthy skin and healed wounds. A new technology allows doctors to know if a wound is healing or infected by changing color based on the pH. So if there is a shift from the acid to the alkaline, this is  a sign that there are complications in the healing of the wound. A pH value between 6.5 und 8.5 means an infection is present.

 

Reference:
ScienceDaily. from http://www.sciencedaily.com­ /releases/2010/11/101116093821.htm

Genetics of a Migraine

A new study has shown that the accumulation of brain glutamate levels in nerve cell junctions (synapses) causes the initiation of a migraine.

DNA variant on Chromosome 8 between two genes -- PGCP and MTDH/AEG-1 -- have a greater risk for developing migraine

MTDH/AEG-1 regulates the EAAT2 gene: the protein responsible for clearing glutamate from brain synapses.

Reference:
Verneri Anttila, Hreinn Stefansson, Mikko Kallela, Unda Todt, Gisela M Terwindt, M Stella Calafato, Dale R Nyholt, Antigone S Dimas, Tobias Freilinger, Bertram Müller-Myhsok, Ville Artto, Michael Inouye, Kirsi Alakurtti, Mari A Kaunisto, Eija Hämäläinen, Boukje de Vries, Anine H Stam, Claudia M Weller, Axel Heinze, Katja Heinze-Kuhn, Ingrid Goebel, Guntram Borck, Hartmut Göbel, Stacy Steinberg, Christiane Wolf, Asgeir Björnsson, Gretar Gudmundsson, Malene Kirchmann, Anne Hauge, Thomas Werge, Jean Schoenen, Johan G Eriksson, Knut Hagen, Lars Stovner, H-Erich Wichmann, Thomas Meitinger, Michael Alexander, Susanne Moebus, Stefan Schreiber, Yurii S Aulchenko, Monique M B Breteler, Andre G Uitterlinden, Albert Hofman, Cornelia M van Duijn, Päivi Tikka-Kleemola, Salli Vepsäläinen, Susanne Lucae, Federica Tozzi, Pierandrea Muglia, Jeffrey Barrett, Jaakko Kaprio, Markus Färkkilä, Leena Peltonen, Kari Stefansson, John-Anker Zwart, Michel D Ferrari, Jes Olesen, Mark Daly, Maija Wessman, Arn M J M van den Maagdenberg, Martin Dichgans, Christian Kubisch, Emmanouil T Dermitzakis, Rune R Frants, Aarno Palotie. Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1. Nature Genetics

New Atrial fibrillation Treatment Guide

Controlling the heart rate of patients provides no advantage over lenient control.

• Not a candidate for coumadin? Then clopidogrel and aspirin is recommended to prevent stroke or clots.
• Dronedarone –reduces hospitalizations for cardiovascular events but cannot be used in Stage IV ventricular dysfunction and  depressed ventricular function.
• Catheter Ablation (to maintain sinus rhythm)- a tube is inserted into a blood vessel and guided to the heart. Ablation is ideal if patients have not had success with drug treatment, don’t have severe lung disease.

References:

L. Samuel Wann, Anne B. Curtis, Craig T. January, Kenneth A. Ellenbogen, James E. Lowe, N.A. Mark Estes III, Richard L. Page, Michael D. Ezekowitz, David J. Slotwiner, Warren M. Jackman, William G. Stevenson, and Cynthia M. Tracy. 2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Updating the 2006 Guideline): A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation,

New Treatment of Hamstring tendinopathy

Hamstring tendinopathy is a common sports. Tiny microtears that characterize chronic tendinopathy are not easily diagnosed. A research study shows that Ultrasound-guided autologous blood injection in the hamstring, in combination with a local steroid and dry-needling, appears to be a more clinically effective alternative to the current standard, steroid therapy.

Reference:

Radiological Society of North America. Researchers use patient's own blood to treat hamstring injury. ScienceDaily

Is attention-deficit/hyperactivity disorder (ADHD) is a genetic condition?

New research shows that copy number variants (CNVs) are more common in ADHD patients. Certain genetic variants implicated in autism and schizophrenia resulting in missing or duplicated DNA segments along with overlaps on chromosome 16 shows that ADHD is a genetic and a shared biological basis exists between ADHD, autism, and other major psychiatric disorders.

References:

Nigel M Williams, Irina Zaharieva, Andrew Martin, Kate Langley, Kiran Mantripragada, Ragnheidur Fossdal, Hreinn Stefansson, Kari Stefansson, Pall Magnusson, Olafur O Gudmundsson, Omar Gustafsson, Peter Holmans, Michael J Owen, Michael O'Donovan, Anita Thapar. Rare chromosomal deletions and duplications in attention-deficit hyperactivity disorder: a genome-wide analysis. Lancet

Regular exercise and lower colon cancer incidence

A 30-minute walk every day reduces your risk of a number of diseases. The American Cancer Society Prevention Study II (CPS II) viewed whether physical activity reduced the incidence of colon cancer. The study found that regular exercise consistently for at least 10 years had the lowest risk of colon cancer incidence.

Reference:
K. Y. Wolin, A. V. Patel, P. T. Campbell, E. J. Jacobs, M. L. McCullough, G. A. Colditz, S. M. Gapstur. Change in Physical Activity and Colon Cancer Incidence. Cancer Epidemiology Biomarkers & Prevention

siRNA delivery system to treat inflammatory bowel disease

People with inflammatory bowel disease may benefit from a new experimental treatment in which tissues are treated with siRNA thioketal nanoparticles (new polymer -- poly-(1,4-phenyleneacetone dimethylene thioketal) (PPADT) PPADT siRNA that inhibits an inflammation-promoting cytokine called tumor necrosis factor -- alpha (TNF-α).

References:

Georgia Institute of Technology. siRNA delivery system to treat inflammatory bowel diseases developed.

Fibrinogen and Alzheimer's disease small molecule therapy

Researchers are studying small molecules therapies which can stop Aβ42-fibrinogen interaction to prevent clot structures result in less oxygen to brain cells as a potential therapy for AD disease (a type of amyloid-β, called Aβ42, reacts with fibrinogen leading to oligomeric clots and deterioration of memory and cognitive ability).

 

References:

H. J. Ahn, D. Zamolodchikov, M. Cortes-Canteli, E. H. Norris, J. F. Glickman, S. Strickland. Alzheimer's disease peptide  -amyloid interacts with fibrinogen and induces its oligomerization. Proceedings of the National Academy of Sciences,

APOE4 variant and amyloid deposits

The precuneus(a anatomical structure in the brain) develops amyloid deposits for patients with Alzheimer's disease and in pre-Alzheimer's . APOE4 is the major genetic risk factor for sporadic causes of developing Alzheimer's disease.

References:

Y. I. Sheline, J. C. Morris, A. Z. Snyder, J. L. Price, Z. Yan, G. D'Angelo, C. Liu, S. Dixit, T. Benzinger, A. Fagan, A. Goate, M. A. Mintun. APOE4 Allele Disrupts Resting State fMRI Connectivity in the Absence of Amyloid Plaques or Decreased CSF A 42. Journal of Neuroscience

Chronic granulomatous disease review

How can a person determine their risk for developing chronic granulomatous disease (CGD is a disease which causes bacteria from Staphylococcus aureus, Aspergillus, abscesses in the lungs, liver, spleen, granulomas causing urinary tract or bladder obstruction)?

Answer: The amount of super oxide produced is correlated with severity of CGD.

Antibiotics and interferon-gamma is the treatment for CGD.

Douglas B. Kuhns, W. Gregory Alvord, Theo Heller, Jordan J. Feld, Kristen M. Pike, Beatriz E. Marciano, Gulbu Uzel, Suk See DeRavin, Debra A. Long Priel, Benjamin P. Soule, Kol A. Zarember, Harry L. Malech, Steven M. Holland, John I. Gallin. Residual NADPH Oxidase and Survival in Chronic Granulomatous Disease. New England Journal of Medicine

Genetics of frontotemporal lobar degeneration (FTLD) type of dementia

A new research study has found that mutations in the progranulin gene (develops the progranulin protein and helps brain neurons), led to the development of frontotemporal lobar degeneration (FTLD) type of dementia. However, those individuals with a progranulin mutation who had copies of the protective TMEM106B allele did not develop FTLD immediately.

Reference:
N. Finch, M.M. Carrasquillo, M. Baker, N.J. Rutherford, G. Coppola, M. Dejesus-Hernandez, R. Crook, T. Hunter, R. Ghidoni, L. Benussi, J. Crook, E. Finger, K.J. Hantanpaa, A.M. Karydas, P. Sengdy, J. Gonzalez, W.W. Seeley, N. Johnson, T.G. Beach, M. Mesulam, G. Forloni, A. Kertesz, D.S. Knopman, R. Uitti, C.L. White III, R. Caselli, C. Lippa, E.H. Bigio, Z.K. Wszolek, G. Binetti, I.R. Mackenzie, B.L. Miller, B.F. Boeve, S.G. Younkin, D.W. Dickson, R.C. Petersen, N.R. Graff-Radford, D.H. Geschwind, R. Rademakers. TMEM106B regulates progranulin levels and the penetrance of FTLD in GRN mutation carriers. Neurology,

Increased Fibrocytes May Cause Inflammation of Graves disease

Fibrocytes are present in greater quantities in patients suffering from Graves' disease when measured in the bloodstream and in the orbital tissues. Fibrocytes express antigens: thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor-1 receptor (IGF-1R) that cause increases in the immune response.

References:

Douglas et al. Increased Generation of Fibrocytes in Thyroid-Associated Ophthalmopathy. Journal of Clinical Endocrinology & Metabolism,

C/EPB-beta expression gene and cardiomyopathies

Changes in the genetics causing reduced C/EPB-beta expression raised the activity of CITED4. As a result, heart cells called cardiomyocytes increasingly divide and grow in size to similar levels of an athlete. Lowering C/EPB-beta expression protected mice from developing heart failure.

References:

Pontus Boström, Nina Mann, Jun Wu, Pablo A. Quintero, Eva R. Plovie, Daniela Panáková, Rana K. Gupta, Chunyang Xiao, Calum A. MacRae, Anthony Rosenzweig, Bruce M. Spiegelman. C/EBPβ Controls Exercise-Induced Cardiac Growth and Protects against Pathological Cardiac Remodeling. Cell

What causes eczema?

A particular tight junction protein, claudin-1 is reduced in atopic dermatitis (a condition that causes dry, red, itchy skin). New research has found that the stratum corneum and cell-to-cell connections known as tight junctions in skin are faulty for people suffering from atopic dermatitis. Minimize allergens such as pollen, mold, pet dander, dust mites reduces the effect of atopic dermatitis.

Source:
http://www.urmc.rochester.edu/news/story/index.cfm?id=3076

P-Rex1: Breast Cancer Therapy Genetic Pathway Discovery

P-Rex1 is overexpressed breast cancer patients leading to increased chances of developing metastasis. Estrogen-receptor signaling and CXCR4 also also appears to rely on P-Rex1, indicating small molecule inhibitors that block proteins in the Rac pathway may help in developing medicines to treat breast cancer. For example, inhibition of P-Rex1 might improve responses tamoxifen efficacy.

Reference:
Maria Soledad Sosa, Cynthia Lopez-Haber, Chengfeng Yang, HongBin Wang, Mark A. Lemmon, John M. Busillo, Jiansong Luo, Jeffrey L. Benovic, Andres Klein-Szanto, Hiroshi Yagi, J. Silvio Gutkind, Ramon E. Parsons, Marcelo G. Kazanietz. Identification of the Rac-GEF P-Rex1 as an Essential Mediator of ErbB Signaling in Breast Cancer. Molecular Cell, Volume 40, Issue 6, 877-892, 22 December 2010

Garlic helps prevent hip osteoarthritis

A compound called diallyl disulphide in garlic limits the amount of cartilage-damaging enzymes. A new study shows that women who consume allium vegetables, such as garlic, onions and leeks, have lower levels of hip osteoarthritis.

Reference:
Frances MK Williams, Jane Skinner, Tim D Spector, Aedin Cassidy, Ian M Clark, Rose M Davidson, Alex J MacGregor. Dietary garlic and hip osteoarthritis: evidence of a protective effect and putative mechanism of action. BMC Musculoskeletal Disorders, 2010

Good clostridia prevents allergies and inflammatory bowel disease.

Good clostridia, prevents allergies and inflammatory bowel disease.While some species are harmful pathogens, such as C. difficile, many other Clostridia species are harmless or even beneficial. How? CD4⁺ T regulatory cells  have the the Foxp3 transcription factor that plays an important role in the maintenance of immune homeostasis.

Reference:
Induction of Colonic Regulatory T Cells by Indigenous Clostridium Species: Science December 2010

The process of wound healing

Preventing venous stasis ulcers, pressure sores and diabetic foot ulcers is achieved by bioactive peptides promote wound healing. The formation of new blood vessels (angiogenesis) and remodeling of extracellular matrices by collageneses from Clostridium histolyticum bacteria allows for wound healing.

Reference:
Demidova-Rice TN, Geevarghese A, Herman IM. Wound Repair and Regeneration. "Bioactive peptides derived from vascular endothelial cell extracellular matrices promote microvascular morphogenesis and wound healing in vitro.

The FOXO protein keeps you young!

Experiments show that an anti-aging gene, FOXO increases a cell’s ability to cope with damaged proteins(eg: Alzheimer’s disease and amyotrophic lateral sclerosis (ALS)). FOXO maintains the ability of the cell to dispose of bad proteins, which in turn keeps the cell young. Patients with increased FOXO in their muscles ate less, and in turn they release less insulin, which is well known to accelerate aging by putting a  brake on metabolism. Aging is multi-factorial and complex.

What is trans-palmitoleic acid?

Trans-palmitoleic acid, can cause lower insulin resistance, higher lipids and possible diabetes. The compound is a fatty acid found in milk, cheese, yogurt, and butter.

Dariush Mozaffarian, Haiming Cao, Irena B. King, Rozenn N. Lemaitre, Xiaoling Song, David S. Siscovick, and Gökhan S. Hotamisligil. Trans-Palmitoleic Acid, Metabolic Risk Factors, and New-Onset Diabetes in U.S. Adults. Annals of Internal Medicine

Do you have healthy vimentin?

Vimentin helps a cell handle mechanical stress in cartilage. Osteoarthritis is the most common joint disease in the United States. A degeneration of cartilage due to chondrocytes from osteoarthritic joints that have weaker vimentin structures than chondrocytes from normal joints causes the joint to be susceptible to fractures. Healthy vimentin is necessary to maintain cartilage’s vitality.

Reference:
Haudenschild, D. R., Chen, J., Pang, N., Steklov, N., Grogan, S. P., Lotz, M. K. and D'Lima, D. D. (2011), Vimentin contributes to changes in chondrocyte stiffness in osteoarthritis. Journal of Orthopaedic Research, 29: 20–25. doi: 10.1002/jor.21198

Genetics of Glioblastoma

Gene deletion of NFKBIA, on chromosome 14, causes Hodgkin’s lymphoma, multiple myeloma, melanoma, and breast, lung, colon cancer and glioblastoma. NFKBIA, deletions causes changes of the epidermal growth factor receptor, or EGFR. NFKBIA deletion causes increases in NF-kappa-B because it’s activity is not reduced by the lack of I-kappa-B in the cell. EGFR hyperactivity and NF-kappa-B activity results in glioblastoma formation.

Reference: http://www.nejm.org/doi/full/10.1056/NEJMoa1006312#t=abstract

Nephrotic syndrome–causes and new hope for treatment

New research has found that Angiopoietin-like 4 is increased in the podocytes of patients with nephrotic syndrome resulting in a reduction of the kidney's filtering ability. Loss of proteins through urine causes nephrotic syndrome. Other features of the disease include low levels of blood-protein, increased cholesterol, high triglycerides and swelling.

A research study found that inadequate amounts of sialic acid(a carb that affects adhesion) is not present in the angiopoietin-like 4 protein. Nephrotic syndrome includes diseases such as nephropathy in diabetics, minimal change disease, focal and segmental glomerulosclerosis and membranous nephropathy.

Attaching sialic acid precursor N-acetyl-D-mannosamine (ManNAc) decreased albuminuria by increased the sialylation of Angptl4.

Reference:

Podocyte-secreted angiopoietin-like-4 mediates proteinuria in glucocorticoid-sensitive nephrotic syndrome.
Clement LC, Avila-Casado C, Macé C, Soria E, Bakker WW, Kersten S, Chugh SS.
Glomerular Disease Therapeutics Laboratory, and Nephrology Research and Training Center, University of Alabama at Birmingham, Birmingham, Alabama, USA

What genes affect Amyotrophic lateral sclerosis (ALS)

New research has shown that a handful of genes may cause some cases of ALS. A new technique known as exome sequencing focuses on only the 1 percent to 2 percent of the genome that codes for proteins and simultaneously sequences thousands of genes at the same time, and is faster faster. Using exome sequencing scientists have found that mutations in the valosin-containing protein might lead to ALS. Valosin-containing protein affects ubiquination(a process which tags proteins for degradation) causing an imbalance in motor proteins in the body.

How hyperphosphorylation of the tau protein causes Alzheimer's disease and other tauopathies.

Normally tau is a soluble protein. It’s function is to stabilize microtubules (polymers of α- and β-tubulin dimers). Hyperphosphorylation can cause loss of normal tau function and insoluble tau aggregates leading to cause frontotemporal lobar degeneration. Tau inclusions on histology are seen in  Pick's disease, MAPT mutations, corticobasal degeneration, progressive supranuclear palsy.

Tau hyperphosphorylation reduces tau binding to microtubules and increases tau fibrillization. Currently, compounds that can stabilize microtubules; reduce tau hyperphosphorylation; inhibit tau formation of oligomers and fibrils; or enhance tau intracellular degradative pathways are under development to find cures for Alzheimer’s and other tauopathies.

Genetics of Parkinson’s Disease

Mutations in the LRRK2 gene, a protein that acts as a kinase, is a common cause of Parkinson’s disease. Researchers have discovered a broad spectrum of kinase inhibitors against LRRK2.  For example, indolinones are the most effective at reducing LRRK2's kinase activity.

The parkin and PINK1 genes clear damaged mitochondria from the brain. These genes are not functioning optimally in patients with Parkinson’s  disease. Moreover, genes for mitochondrial function are less active in people with Parkinson’s disease.  Researchers are studying how PGC-1alpha, a gene that regulates energy metabolism and mitochondrial biogenesis( the production of new mitochondrion)

Lee, B.D. et al.  "Inhibitors of leucine-rich repeat kinase-2 protect against models of Parkinson's disease."  Nature Medicine, Vol. 16(9), pp. 998-1000

Zheng B et al.  “PGC-1alpha, a potential therapeutic target for early intervention in Parkinson’s disease.”  Science Translational Medicine, October 6, 2010, Vol. 2 (52), pp. 1-14

Neuropeptide S role in the brain that boosts memory

Researchers observed that if neuropeptide S receptors in the brain were activated immediately after a learning experience, it could be recalled for much longer and with much greater accuracy. The discovery could provide important clues about how the brain stores memories and also lead to new treatments for Alzheimer’s disease, dementia and other cognitive impairments.

Journal: Neuropeptide S Enhances Memory During the Consolidation Phase and Interacts with Noradrenergic Systems in the Brain
http://www.nature.com/npp/journal/vaop/ncurrent/full/npp2010207a.html

Rosacea – Cathelicidin and Corneum Tryptic Enzymes

The peptide cathelicidin within the skin is processed differently in rosacea patients than in individuals not affected by rosacea and induces inflammation that may contribute to rosacea. Rosacea patients have elevated levels of enzymes called stratum corneum tryptic enzymes (SCTE).Patients have the following features:

• Redness on the cheeks, nose, chin or forehead
• Small visible blood vessels on the face
• Bumps or pimples on the face
• Watery or irritated eyes

Factors increasing the risk for rosacea are sun exposure, emotional stress, hot or cold weather, wind, heavy exercise, alcohol, spicy foods, heated beverages, humidity, certain skin-care products and many others.

Benefits of Yoga – Helps Promote Mindful Eating and Weight Maintenance

Mindful eating is a skill that augments the usual approaches to weight loss, such as dieting, counting calories and limiting portion sizes. Regular yoga practice promotes mindful eating, and people who eat mindfully are less likely to be obese. Adding yoga practice to a standard weight-loss program may make mindful eating more effective.

Reducing atherosclerosis progression for patients with rheumatoid arthritis

Inflammation and rheumatoid arthritis disease (a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints) activity may contribute to the progression of atherosclerosis in people with rheumatoid arthritis . Limiting inflammation would mean patients have fewer cardiovascular events like myocardial infarction and stroke. Patients who used anti-TNF treatment had lower rate of progression of intima thickness, a marker for atherosclerosis. Physicians found that prednisone is associated with progression of atherosclerosis. Therefore medications like TNF inhibitors and statins can be taken to lower cholesterol and atherosclerosis progression. A high c-reactive protein may suggest more risk for cholesterol plaque.

Study:
Longitudinal Predictors of Progression of Subclinical Carotid Atherosclerosis in Rheumatoid Arthritis.
http://www.jrheum.org/content/37/4/730.abstract

Reducing the risk of developing cardiovascular disease for people with diabetes

The ACCORD Study Group results summary:

1. Effective blood pressure control does not reduce CVD risk in people with type 2 diabetes at high risk for CVD.

2. A combination of a statin and a fibrate was no better at reducing risk than a statin alone in patients with type 2 diabetes at high risk for CVD.

3. For patients with low HDL and low triglycerides, the combination lipid therapy may be successful in reducing CVD risk in those with type 2 diabetes patients.

The ACCORD Study Group – New England Journal of Medicine, March 14,2010; N Engl J Med 2010;362:1575-85. N Engl J Med 2010; 362:1563-74. www.nejm.org;