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August 2010 Briefing - Pathology

Here are what the editors at HealthDay consider to be the most important developments in Pathology for August 2010. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that are the most likely to affect clinical practice.

Diverse Veggie Intake May Lower Lung Cancer Risk

TUESDAY, Aug. 31 (HealthDay News) -- Eating a variety of vegetables and fruits may reduce the risk of lung cancer in current smokers, according to research published online Aug. 31 in Cancer Epidemiology, Biomarkers & Prevention.

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No Benefit Seen for Vitamin Use With Colon Cancer Chemo

TUESDAY, Aug. 31 (HealthDay News) -- Among patients with stage III colon cancer, the use of multivitamins during and after adjuvant chemotherapy is not associated with a lower recurrence rate or improved survival, according to a study published online Aug. 30 in the Journal of Clinical Oncology.

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Higher MS Activity Associated With Warmer Seasons

TUESDAY, Aug. 31 (HealthDay News) -- Multiple sclerosis (MS) activity -- both incidence and severity -- appears to be higher in the spring and summer, according to research published in the Aug. 31 issue of Neurology.

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Drinking Alcohol Appears to Increase Breast Cancer Risks

TUESDAY, Aug. 31 (HealthDay News) -- Among women who previously were diagnosed with early-stage breast cancer, alcohol drinking may increase the risks for disease recurrence and death, especially in postmenopausal and overweight and obese women, according to research published online Aug. 30 in the Journal of Clinical Oncology.

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Black Race Independent Predictor of Stent Thrombosis

MONDAY, Aug. 30 (HealthDay News) -- Black race is a distinct risk factor for developing stent thrombosis (ST) after drug-eluting stent (DES) implantation, according to a study published online Aug. 30 in Circulation.

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Screening Guidelines Offered for Urinary Tract Conditions

MONDAY, Aug. 30 (HealthDay News) -- The American Urological Association (AUA) has published new guidelines for the screening of siblings and offspring of index patients with vesicoureteral reflux (VUR) and infants with prenatal hydronephrosis (PNH) in the September issue of The Journal of Urology.

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Genetic Basis for Severe Asthma Identified

MONDAY, Aug. 30 (HealthDay News) -- Interleukin-17A (IL-17A) has been identified as a promoter of severe asthma-like symptoms in mice, a finding that may provide a basis for further research into therapeutic treatments for severe asthma in humans, according to research published online Aug. 29 in Nature Immunology.

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Post-Op Delirium Linked to Cerebral Vascular Disease

MONDAY, Aug. 30 (HealthDay News) -- Delirium after spinal fusion in elderly patients is more common in those with a history of cerebral vascular disease, low hemoglobin and hematocrit levels after surgery, and poor nutrition, according to a study in the Aug. 15 issue of Spine.

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BPA Exposure May Be Related to Male Endocrine Changes

FRIDAY, Aug. 27 (HealthDay News) -- Bisphenol A (BPA) exposure may have an impact on male sex hormones, according to research published online Aug. 25 in Environmental Health Perspectives.

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Study Finds Vitamin D Links to Disease-Associated Genes

FRIDAY, Aug. 27 (HealthDay News) -- Vitamin D receptor (VDR) binding sites are significantly enriched at genes that have been linked to several autoimmune diseases and cancer, suggesting that vitamin D deficiency may be linked to disease pathogenesis, according to research published online Aug. 24 in Genome Research.

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Myopathy Patients With Novel Autoantibodies Identified

FRIDAY, Aug. 27 (HealthDay News) -- Researchers have identified a subgroup of necrotizing myopathy patients with novel autoantibodies who are potential candidates for immunosuppressive therapy, according to a study in the September issue of Arthritis & Rheumatism.

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Factor in Inflammation May Be Linked to Diabetes Risk

FRIDAY, Aug. 27 (HealthDay News) -- Plasma protein growth arrest-specific 6 (Gas6) -- a growth factor-like molecule -- is associated with inflammation, endothelial dysfunction, and altered glucose tolerance, and it may be a risk factor for type 2 diabetes, according to research published in the August issue of Diabetes Care.

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PET/CT Imaging Restages Prostate Cancer After Surgery

FRIDAY, Aug. 27 (HealthDay News) -- Positron emission tomography/computerized tomography (PET/CT) to detect [11C]choline uptake appears to be useful for re-evaluating prostate cancer disease stage for men who have increasing prostate-specific antigen (PSA) levels after radical prostatectomy and no evidence of disease on conventional imaging, according to a study in the September issue of The Journal of Urology.

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New Mechanism Found for Viral Suppression of Cell Defenses

FRIDAY, Aug. 27 (HealthDay News) -- Researchers have discovered a mechanism by which adenoviruses breach cellular defenses, and this could help explain how p53 tumor-suppressor genes are disabled in cancer cells and point the way to the development of new, more effective targeted cancer therapies; these findings have been published in the Aug. 26 issue of Nature.

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Type 2 Diabetes Susceptibility Alleles Tied to BMI in Children

THURSDAY, Aug. 26 (HealthDay News) -- In children who were born large for gestational age, certain type 2 diabetes susceptibility alleles are linked to low body mass index (BMI) at age 8, according to research published in the August issue of Diabetes.

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Diabetes, Insulin Resistance Tied to Alzheimer's Pathology

THURSDAY, Aug. 26 (HealthDay News) -- Individuals with type 2 diabetes and insulin resistance may be at an increased risk of developing brain plaques that are linked to Alzheimer's disease, according to a study published online Aug. 25 in Neurology.

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Study Links Genetic Variants to Fuchs's Corneal Dystrophy

WEDNESDAY, Aug. 25 (HealthDay News) -- Researchers have identified genetic variants that substantially increase the risk for Fuchs's corneal dystrophy (FCD), and their research has been published online Aug. 25 by the New England Journal of Medicine.

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Novel Targeted Therapy for Melanoma Shows Promise

WEDNESDAY, Aug. 25 (HealthDay News) -- Therapy targeting the V600E BRAF mutation found in many melanoma tumors can result in complete or partial tumor regression in most patients, according to a study in the Aug. 26 issue of the New England Journal of Medicine.

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Berberine Linked to Impaired Muscle Metabolism in Mice

WEDNESDAY, Aug. 25 (HealthDay News) -- The herbal compound berberine stimulates the expression of atrogin-1, leading to protein degradation, suppression of protein synthesis, and muscle atrophy in a mouse model of type 2 diabetes, according to research published in the August issue of Diabetes.

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Elevated CRP Has Robust Link to Higher A-Fib Risk

WEDNESDAY, Aug. 25 (HealthDay News) -- Higher levels of plasma C-reactive protein (CRP) are robustly associated with a higher risk of atrial fibrillation, but elevated levels don't necessarily increase the risk, according to research published in the Aug. 31 issue of the Journal of the American College of Cardiology.

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Genetic Variants Associated With End-Stage Renal Disease

TUESDAY, Aug. 24 (HealthDay News) -- Genetic variants in protein kinase C-β 1 (PRKCB1) genes, the genes implicated in the development of complications in diabetes, are associated with the risk of end-stage renal disease (ESRD) in Chinese individuals with type 2 diabetes, according to a study in the Aug. 25 issue of the Journal of the American Medical Association.

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Virus May Be Associated With Chronic Fatigue Syndrome

TUESDAY, Aug. 24 (HealthDay News) -- Researchers have found evidence of the murine leukemia virus (MLV) in a group of patients with chronic fatigue syndrome (CFS); their findings were published online Aug. 23 in the Proceedings of the National Academy of Sciences.

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Researchers Isolate BRCA2 Protein for First Time

MONDAY, Aug. 23 (HealthDay News) -- For the first time, scientists have purified the entire protein encoded by BRCA2, allowing for a better understanding of the molecular mechanisms linking BRCA2 to cancer and DNA repair; the findings are reported in three articles published online Aug. 22 in Nature and Nature Structural & Molecular Biology.

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β Cells Still Functioning in Long-Time Diabetes Patients

MONDAY, Aug. 23 (HealthDay News) -- Some patients with type 1 diabetes mellitus (T1DM) still have functional pancreatic β cells after 50 years despite prolonged autoimmune and metabolic stress, suggesting that autoimmune stress reduction with stimulation of β cell regeneration could improve insulin production in individuals with diabetes, according to research published online Aug. 10 in Diabetes.

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High A1C Tied to Heart Failure in Those Without Diabetes

MONDAY, Aug. 23 (HealthDay News) -- Among middle-aged people without diabetes, elevated hemoglobin A1C is associated with risk of later heart failure, indicating that chronic hyperglycemia even before diabetes development may be a risk factor for heart failure, according to research published in the August issue of Diabetes.

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Hepatitis C, Hispanic Ethnicity Linked to HCC Mortality

FRIDAY, Aug. 20 (HealthDay News) -- Hepatitis C infection and Hispanic ethnicity are associated with a higher risk of hepatocellular carcinoma (HCC)-related mortality, according to research published in the August issue of Clinical Gastroenterology and Hepatology.

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Low Levels of Tobacco Smoke Exposure Tied to Lung Disease

FRIDAY, Aug. 20 (HealthDay News) -- Individuals exposed to even low levels of tobacco smoke may be at increased risk for developing lung diseases, according to a study published online Aug. 6 in the American Journal of Respiratory and Critical Care Medicine.

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Prenatal DDT Exposure Tied to Testicular Cancer Risk

FRIDAY, Aug. 20 (HealthDay News) -- In the early postpartum period, maternal serum DDT-related compounds appear to be associated with sons' risk of testicular cancer three decades later, according to a study in the July issue of the Archives of Environmental & Occupational Health.

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HIV Viral Populations in Semen Different Than in Blood

FRIDAY, Aug. 20 (HealthDay News) -- HIV-1 living in the genital tract displays genetic differences from HIV-1 in the bloodstream, suggesting three mechanisms leading to the virus getting into semen, according to a study published online Aug. 19 in PLoS Pathogens.

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Pesticide Exposure in Womb May Derail Attention Later

THURSDAY, Aug. 19 (HealthDay News) -- It remains to be determined what impact paraoxonase 1 (PON1) genotypes have on the influence of in utero organophosphate exposure on subsequent childhood mental and motor development, but such exposure does appear to affect attention levels in children, according to two studies published online Aug. 19 in Environmental Health Perspectives.

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Genetic Link With Advanced Fatty Liver Disease Confirmed

THURSDAY, Aug. 19 (HealthDay News) -- Carriers of an allele of the PNPLA3 gene who have non-alcoholic fatty liver disease (NAFLD) may be at increased risk for advanced disease; the allele is also associated with earlier presentation in pediatric patients, according to two studies published online May 14, ahead of the print issue of Hepatology.

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Basal Cell Carcinoma Risk Factors Identified

WEDNESDAY, Aug. 18 (HealthDay News) -- Individuals who have red hair, are of higher socioeconomic status, are relatively young upon initial basal cell carcinoma (BCC) diagnosis, and/or develop a BCC lesion on their upper extremities have an increased risk of developing multiple BCC lesions, according to a study in the August issue of the Archives of Dermatology.

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Vitamin D Insufficiency May Hurt Lymphoma Prognosis

TUESDAY, Aug. 17 (HealthDay News) -- In patients with two non-Hodgkin's lymphoma subtypes, vitamin D insufficiency is associated with inferior overall survival (OS) as well as inferior event-free survival (EFS), according to a study published online Aug. 16 in the Journal of Clinical Oncology.

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Nottingham Prognostic Index Accuracy Improved

TUESDAY, Aug. 17 (HealthDay News) -- The addition of progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) to the Nottingham Prognostic Index (NPI) in the classification of patients with primary operable breast cancer results in improved five-year prognostic accuracy, according to a study published online Aug. 16 in the Journal of Clinical Oncology.

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Single Genetic Factor Related to Pain at Many Body Sites

MONDAY, Aug. 16 (HealthDay News) -- A single, heritable pain factor underlies 46 percent of chronic musculoskeletal pain reported at many different anatomical sites, according to research published in the September issue of Rheumatology. This is in contrast to findings from previous research on osteoarthritis pain which showed that the propensity to report pain is determined by genetic factors specific to each anatomical site.

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Isotype Measurement May Increase RA Diagnosis

MONDAY, Aug. 16 (HealthDay News) -- The chance of serologically diagnosing rheumatoid arthritis (RA) could increase dramatically by measuring the presence of three rheumatoid factor (RF) isotypes, according to research published in the August issue of the Journal of Rheumatology.

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1,097 Foodborne Outbreaks Occurred in U.S. in 2007

FRIDAY, Aug. 13 (HealthDay News) -- In 2007, nearly 1,100 foodborne outbreaks were reported in the United States, resulting in 21,244 cases of illness and 18 deaths, according to data published in the Aug. 13 issue of the U.S. Centers for Disease Control and Prevention's Morbidity and Mortality Weekly Report.

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Cholesterol Levels Vary Across the Menstrual Cycle

FRIDAY, Aug. 13 (HealthDay News) -- Serum lipid levels are associated with endogenous estrogen levels in menstruating women, and vary throughout the cycle, according to research published online June 9 in the Journal of Clinical Endocrinology and Metabolism.

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Rheumatoid Arthritis Gets New Classification System

FRIDAY, Aug. 13 (HealthDay News) -- A revised system of classification for rheumatoid arthritis (RA) may allow for earlier identification of the disease, earlier treatment, and ultimately better patient outcomes; the new system has been published in the September issues of the Annals of the Rheumatic Diseases and Arthritis & Rheumatism.

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Mass Spectrometer Test IDs Cancer With High Accuracy

THURSDAY, Aug. 12 (HealthDay News) -- A novel method of mass spectrometer technology plus a computerized algorithm can identify ovarian cancer in blood sera with nearly 100 percent accuracy, according to research published online Aug. 10 in Cancer Epidemiology, Biomarkers & Prevention.

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Maternal High-Fat Diet Tied to Offspring's Gene Expression

THURSDAY, Aug. 12 (HealthDay News) -- Maternal consumption of a high-fat diet during pregnancy and lactation may alter gene expression among offspring, according to an animal study published online Aug. 4 in Endocrinology.

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Gestational Glucose Tolerance Status May Affect Diabetes Risk

THURSDAY, Aug. 12 (HealthDay News) -- β-cell dysfunction progresses in women with a history of gestational diabetes mellitus (GDM) and gestational impaired glucose tolerance (GIGT) in the first year after giving birth, and may contribute to subsequent development of type 2 diabetes, according to research published in the August issue of Diabetes Care.

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Bone Marrow Transplant May Treat Blistering Disease

WEDNESDAY, Aug. 11 (HealthDay News) -- Allogeneic bone marrow transplantation may help children with recessive dystrophic epidermolysis bullosa by increasing the deposition of type VII collagen (C7), the lack of which characterizes the disease, according to research published in the Aug. 12 issue of the New England Journal of Medicine.

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Modest Visceral Fat Gain Decreases Endothelial Function

WEDNESDAY, Aug. 11 (HealthDay News) -- Even modest gains in visceral fat are associated with decreased endothelial function in healthy young adults, according to research published in the Aug. 17 issue of the Journal of the American College of Cardiology.

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Longer HRT Duration Tied to Lower Colon Cancer Rate

WEDNESDAY, Aug. 11 (HealthDay News) -- Longer duration of hormone replacement therapy (HRT) use among women is linked to a greater reduction in distal large bowel cancer incidence, independent of race, according to a study published in the August issue of the American Journal of Gastroenterology.

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TP53 Mutation Indicates Poor Prognosis in Leukemia

WEDNESDAY, Aug. 11 (HealthDay News) -- TP53 mutations are linked with poor prognosis in people with chronic lymphocytic leukemia (CLL), regardless of whether 17p deletion is present, according to research published online Aug. 9 in the Journal of Clinical Oncology.

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Travel Linked to Spread of Antibiotic Resistance Gene

WEDNESDAY, Aug. 11 (HealthDay News) -- A gene that creates antibiotic resistance has been found to be widespread in Enterobacteriaceae of patients in India and Pakistan and in patients from the United Kingdom who have visited India or Pakistan for elective surgery; this could indicate an emerging public health threat, according to research published online Aug. 11 in The Lancet Infectious Diseases.

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Three Genotypes Confirmed as Alzheimer's Disease Risk Loci

TUESDAY, Aug. 10 (HealthDay News) -- Three specific genotypes at CLU, PICALM, and CR1 confer risk for Alzheimer's disease (AD), and an apolipoprotein E genotype, APOE ε4, interacts synergistically in those who also have the PICALM variant, according to a study published online Aug. 9 in the Archives of Neurology. A related study in the same issue clarifies the association between plasma β-amyloid (Aβ) and various aspects of cognition.

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Study Sheds More Light on Hormones, Breast Cancer Risk

TUESDAY, Aug. 10 (HealthDay News) -- Longer use of estrogen or estrogen-progestin therapy (EPT) is associated with a higher risk of breast cancer, with risks varying by body mass index (BMI) and tumor subtype, according to research published online Aug. 10 in Cancer Epidemiology, Biomarkers & Prevention.

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Risk Factors for Glaucoma Visual Field Changes Identified

TUESDAY, Aug. 10 (HealthDay News) -- Visual field change in glaucoma occurs faster in patients with abnormal anticardiolipin antibody levels and higher age, but the change can be slowed with modest reductions in intraocular pressure (IOP), according to research published online Aug. 9 in the Archives of Ophthalmology.

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Diverse Variables Affect Risk of Age-Related Cataracts

MONDAY, Aug. 9 (HealthDay News) -- The risk of cataracts can be increased by a combination of sun exposure and sun-sensitizing medications, by smoking, or even by socioeconomic factors, according to two studies in the August issue of the Archives of Ophthalmology.

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Endocrine Sensitivity Measure Predicts Breast Cancer Survival

MONDAY, Aug. 9 (HealthDay News) -- A patient's sensitivity to endocrine therapy (SET) index, a measure of estrogen receptor-related transcriptional activity, appears to be predictive of distant relapse-free survival in breast cancer patients who receive endocrine therapy alone or endocrine therapy after chemotherapy, but not in those who receive no adjuvant therapy, according to research published online Aug. 9 in the Journal of Clinical Oncology.

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Gene Variants Linked to Abnormal Lipids Identified

MONDAY, Aug. 9 (HealthDay News) -- Identification of 95 genetic variants implicated in lipoprotein metabolism may provide new targets for the prevention of coronary artery disease (CAD), according to research published in the Aug. 5 issue of Nature.

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Menstrual Phase Linked to Tracheal Intubation Response

MONDAY, Aug. 9 (HealthDay News) -- Menstrual cycle phase appears to influence the hemodynamic response to tracheal intubation (TI), according to research published in the August issue of Anesthesia & Analgesia.

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Strep Accounts for 37 Percent of Pharyngitis in Children

MONDAY, Aug. 9 (HealthDay News) -- Group A Streptococcus (GAS) accounts for 37 percent of pediatric pharyngitis cases, though prevalence varies by age, and clinical scoring systems could reduce unnecessary antibiotic prescribing for non-GAS pharyngitis in low-resource settings, according to research published online Aug. 9 in Pediatrics.

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Low Hep B Viral Load Linked to Surface Antigen Seroclearance

FRIDAY, Aug. 6 (HealthDay News) -- In patients with chronic hepatitis B virus (HBV) infection, a low viral load appears to predict the natural seroclearance of hepatitis B surface antigen (HBsAg), according to research published in the August issue of Gastroenterology.

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Assessment Found Useful in Inactive Hep B Carriers

FRIDAY, Aug. 6 (HealthDay News) -- Assessment of hepatitis B virus (HBV)-DNA and hepatitis B surface antigen provides identification of inactive carriers of hepatitis B with high diagnostic accuracy, according to research published in the August issue of Gastroenterology.

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Causal Hypothesis for Multiple Sclerosis Challenged

THURSDAY, Aug. 5 (HealthDay News) -- An emerging hypothesis suggests that the demyelination of cerebral veins that characterizes multiple sclerosis (MS) may be caused by chronic cerebrospinal venous insufficiency (CCSVI), but research published in the August issue of the Annals of Neurology does not concur with the hypothesis.

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Left Atrial Index Predicts Mitral Regurgitation Outcome

THURSDAY, Aug. 5 (HealthDay News) -- Left atrial volume indexed to body surface area (LA index) predicts mortality risk in patients with organic mitral regurgitation (MR), according to research published in the Aug. 10 issue of the Journal of the American College of Cardiology.

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Non-Hodgkin's Lymphoma Risk Higher With Chronic Hepatitis

THURSDAY, Aug. 5 (HealthDay News) -- Chronic hepatitis B virus (HBV) infection is associated with an increased risk of developing non-Hodgkin's lymphoma (NHL), according to research published online Aug. 4 in The Lancet Oncology.

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Stimulus for Myocardial Fibrosis Early Sign of Cardiomyopathy

WEDNESDAY, Aug. 4 (HealthDay News) -- Elevated levels of serum C-terminal propeptide of type I procollagen (PICP) are indicative of increased myocardial collagen synthesis in sarcomere-mutation carriers without overt hypertrophic cardiomyopathy, and often precede the development of left ventricular hypertrophy or fibrosis that is visible on imaging, according to a study in the Aug. 5 issue of the New England Journal of Medicine.

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CD31+ Peripheral Blood Cells Promote Angiogenesis

WEDNESDAY, Aug. 4 (HealthDay News) -- Peripheral blood (PB) cells which are positive for the endothelial marker CD31 promote angiogenesis in an ischemic animal model even without prior cell culture, according to research published in the Aug. 10 issue of the Journal of the American College of Cardiology.

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Pain in Fibromyalgia Patients Tied to Altered Brain Functions

WEDNESDAY, Aug. 4 (HealthDay News) -- In people with fibromyalgia, there appears to be an association between resting brain activity in multiple brain networks and spontaneous clinical pain, according to research published in the August issue of Arthritis & Rheumatism.

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Gene Variants, High BMI Linked to Prostate Cancer Mortality

WEDNESDAY, Aug. 4 (HealthDay News) -- Several single nucleotide polymorphisms (SNPs) in the gene for fatty acid synthase (FASN) are associated with lethal prostate cancer, particularly among overweight men, according to a study published online Aug. 2 in the Journal of Clinical Oncology.

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Environmental Traits, Mom's Obesity Tied to Type 1 Diabetes

TUESDAY, Aug. 3 (HealthDay News) -- Consistent with the hygiene and overload hypotheses, environmental factors associated with less antigenic exposure in early life and maternal obesity may be associated with risk for type 1 diabetes, according to a study published in the August issue of the Archives of Pediatrics & Adolescent Medicine.

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Industry-Funded Clinical Trials Yield More Positive Outcomes

TUESDAY, Aug. 3 (HealthDay News) -- Drug clinical trials supported by industry are more likely to produce favorable results than trials supported by government or nonprofit/nonfederal organizations, and they are less likely to be published within two years of the study being completed, according to research published in the Aug. 3 issue of the Annals of Internal Medicine.

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Diet Appears to Influence Gut Bacteria Types

TUESDAY, Aug. 3 (HealthDay News) -- Gut bacteria may be different in children who eat a high-fiber, vegetation-based diet than in those who consume a typically Western, high-fat, high-sugar, low-fiber diet, and the bacteria may play a role in vulnerability to obesity and allergies, according to research published online Aug. 2 in the Proceedings of the National Academy of Sciences.

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Use of Some Common Drugs May Lower PSA Levels

TUESDAY, Aug. 3 (HealthDay News) -- The use of nonsteroidal anti-inflammatory drugs (NSAIDs), statins, or thiazide diuretics can significantly lower tested levels of prostate-specific antigen (PSA), according to research published online Aug. 2 in the Journal of Clinical Oncology.

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Genetic Variant Affects MS Severity and Relapse

MONDAY, Aug. 2 (HealthDay News) -- A variant of the oligoadenylate synthetase 1 (OAS1) gene may increase the activity of multiple sclerosis (MS) and shorten time to relapse, according to a study in the Aug. 3 issue of Neurology.

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Vaccine May Block Tumor Growth in Some Cancers

MONDAY, Aug. 2 (HealthDay News) -- An experimental vaccine based on an encephalitis virus may be able to block tumor growth in some advanced cancers by stimulating an immune response -- even when an immune system has been suppressed, according to a study published online Aug. 2 in the Journal of Clinical Investigation.

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Fever Alone Unreliable Indicator of H1N1 Infection

MONDAY, Aug. 2 (HealthDay News) -- Standard diagnostic criteria used for the diagnosis of 2009 H1N1 influenza infection, based on the presence of fever, may fail to identify patients with the disease, and respiratory symptoms may be more reliable indicators, according to research published in the August issue of the American Journal of Infection Control.

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Specific Behaviors in NICU Grads Predictive of Autism

MONDAY, Aug. 2 (HealthDay News) -- Neurobehavioral testing during infancy in babies who are neonatal intensive care unit (NICU) graduates reveals specific abnormalities in those who are later diagnosed with autism spectrum disorder (ASD), according to research published online Aug. 2 in Pediatrics.

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