Majority of children affected by allergy-related diseases

A majority of children have one or more allergy-related diseases, including eczema, asthma, and rhinitis, according to research published in the April issue of Allergy.
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Circulating cells signal upcoming heart attack - FierceBiomarkers

Heart attacks can be devastating for the family and the patient, and around half of heart attacks or strokes can occur in people who don't seem to have any obvious risk factors. A blood test that detects abnormal cells in the blood could pinpoint people at risk of a heart attack, and has been described as the holy grail of cardiovascular medicine.

Role of amyloid beta as sensors and protectors in Alzheimer's and other diseases explored

Amyloid senses cellular environmental stress, such as elevation of 
reactive metabolites and oxidative products or metals, and then 
misfolds. This misfolding initiates a protective cellular response in 
the short term. Long-term or chronic stress such as metabolic 
dysfunction (diabetes) would lead to the pathological consequences of 
amyloid misfolding (as diabetes is a risk factor for Alzheimer's).
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Gastrointestinal inflammation and associated immune activation in schizophrenia.

Immune factors are implicated in normal brain development and in brain disorde pathogenesis. Pathogen infection and food antigen penetration across gastrointestinal barriers are means by which environmental factors might affect immune-related neurodevelopment. Here, we test if gastrointestinal inflammation is associated with schizophrenia and therefore, might contribute to bloodstream entry of potentially neurotropic milk and gluten exorphins and/or immune
activation by food antigens. IgG antibodies to Saccharomyces cerevisiae (ASCA, a marker of intestinal inflammation), bovine milk casein, wheat-derived gluten, and 6 infectious agents were assayed. Cohort 1 included 193 with non-recent onset schizophrenia, 67 with recent onset schizophrenia and 207 non-psychiatric controls. Cohort 2 included 103 with first episode schizophrenia, 40 of whom were antipsychotic-naïve. ASCA markers were significantly elevated and correlated with food antigen antibodies in recent onset and non-recent onset schizophrenia
compared to controls (p≤0.00001-0.004) and in unmedicated individuals with first episode schizophrenia compared to those receiving antipsychotics (p≤0.05-0.01). Elevated ASCA levels were especially evident in non-recent onset females (p≤0.009), recent onset males (p≤0.01) and in antipsychotic-naïve males (p≤0.03). Anti-food antigen antibodies were correlated to antibodies against Toxoplasma gondii, an intestinally-infectious pathogen, particularly in males with recent
onset schizophrenia (p≤0.002). In conclusion, gastrointestinal inflammation is a relevant pathology in schizophrenia, appears to occur in the absence of but may be modified by antipsychotics, and may link food antigen sensitivity and microbial infection as sources of immune activation in mental illness.
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Epigenetic changes in blood samples may point to schizophrenia

In a new study, researchers at the Swedish medical university Karolinska Institutet have identified epigenetic changes – known as DNA methylation – in the blood of patients with schizophrenia. The researchers were also able to detect differences depending on how old the patients were when they developed the disease and whether they had been treated with various drugs. In the future this new knowledge may be used to develop a simple test to diagnose patients with schizophrenia.
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Microbiome sequencing offers hope for diagnostics : Nature News & Comment

Microbes have hit the big time. Results from major projects that aim to sequence the metagenome — the trillions of microbial cells and genes in the human body — potentially offer new ways of diagnosing and treating a wide range of health problems. But some researchers are warning against the dangers of hyping the data too soon.
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Drug to Cut Cholesterol Level Tests Better Than Statins - NYTimes.com

The drug works by modifying the way cholesterol levels are naturally controlled. A protein produced in the liver ( PCSK9 )helps limit the amount of LDL, or “bad” cholesterol, that liver cells can remove from the bloodstream. The new drug, called REGN727, is a monoclonal antibody, made in a laboratory, that blocks the action of that protein.
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Toxoplasma gondii and Other Risk Factors for Schizophrenia: An Update.

The failure to find genes of major effect in schizophrenia has refocused attention on nongenetic, including infectious factors. 

METHOD

In a previous study, antibodies to Toxoplasma gondii were found to be elevated in 23 studies of schizophrenia (OR 2.73; 95% CI 2.10-3.60). 

RESULT

The current study replicates this finding with 15 additional studies (OR 2.71; 95% CI 1.93-3.80) and compares this with other identified schizophrenia risk factors. The highest risk factors are having an affected mother (relative risks [RR] 9.31; 95% CI 7.24-11.96), father (RR 7.20; 95% CI 5.10-10.16), or sibling (RR 6.99; 95% CI 5.38-9.08) or being the offspring of immigrants from selected countries (RR 4.5; 95% CI 1.5-13.1). Intermediate risk factors, in addition to infection with T. gondii, include being an immigrant from and to selected countries (RR 2.7; 95% CI 2.3-3.2), being born in (RR 2.24; 95% CI 1.92-2.61) or raised in (RR 2.75; 95% CI 2.31-3.28) an urban area, cannabis use (OR 2.10-2.93; 95% CI 1.08-6.13), having minor physical anomalies (OR 2.23; 95% CI 1.42-3.58), or having a father 55 or older (OR 2.21-5.92; 95% CI 1.46-17.02). 

CONCLUSION

Low-risk factors include a history of traumatic brain injury (OR 1.65; 95% CI 1.17-2.32), sex abuse in childhood (OR 1.46; 95% CI 0.84-2.52), obstetrical complications (OR 1.29-1.38; 95% CI 1.00-1.84), having a father 45 or older (OR 1.21-1.66; 95% CI 1.09-2.01), specific genetic polymorphisms (OR 1.09-1.24; 95% CI 1.06-1.45), birth seasonality (OR 1.07-1.95; 95% CI 1.05-2.91), maternal exposure to influenza (RR 1.05; 95% CI 0.98-1.12), or prenatal stress (RR 0.98-1.00; 95% CI 0.85-1.16).

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Multiplexing analysis of the polyspecific intrathecal immune viral response in multiple sclerosis.


OBJECTIVE

Intrathecal synthesis of the antibodies specific to neurotrofic viruses: measles (M), rubella (R), Varicella-Zoster (Z), and/or H. simplex (H), known as "MRZH-reaction" plays important diagnostic role in multiple sclerosis (MS). 

METHOD

Whereas the analysis of the oligoclonal IgG bands provides high sensitivity, the MRZH-reaction shows high specificity, and hence these methods complement each other. 

RESULT

For the first time we applied multiplexing bead-based technology to simultaneously analyze cerebrospinal fluid (CSF) and serum concentrations of antibodies against these viruses, and to calculate the antibody specific indices (ASI's). The method shows reasonable precision: intra-assay, 2.9-6.7%, and inter-assay, 2.0-3.2%. The results are comparable with these obtained with other methods (ELISAs), including two runs of the certified external quality control schemes. Eighty-one percent of the MS cases (n=27) and none of the sex- and age-matched controls (n=14), except one subject with "borderline" anti-measles ASI of 1.5, showed intrathecal synthesis of IgG against at least one of the viruses discussed. The ratios of the MRZH-positive cases in the MS group were: 12/22 for M, 12/19 for R, 13/26 for Z, and 7/26 for H. 

CONCLUSION

We conclude that the multiplexing technology can be applied as a tool to study the intrathecal immune response in the diagnosis of MS

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Attention-deficit/hyperactivity disorder after early exposure to procedures requiring general anesthesia.

To study the association between exposure to procedures performed under general anesthesia before age 2 years and development of attention-deficit hyperactivity disorder (ADHD).

PATIENTS AND METHODS:

Study patients included all children born between January 1, 1976, and December 31, 1982, in Rochester, MN, who remained in Rochester after age 5. Cases of ADHD diagnosed before age 19 years were identified by applying stringent research criteria. Cox proportional hazards regression assessed exposure to procedures requiring general anesthesia (none, 1, 2 or more) as a predictor of ADHD using a stratified analysis with strata based on a propensity score including comorbid health conditions.

RESULTS:

Among the 5357 children analyzed, 341 ADHD cases were identified (estimated cumulative incidence, 7.6%; 95% confidence interval [CI], 6.8%-8.4%). For children with no postnatal exposure to procedures requiring anesthesia before the age of 2 years, the cumulative incidence of ADHD at age 19 years was 7.3% (95% CI, 6.5%-8.1%). For single and 2 or more exposures, the estimates were 10.7% ( 95% CI, 6.8%-14.4%) and 17.9% ( 95% CI, 7.2%-27.4%), respectively. After adjusting for gestational age, sex, birth weight, and comorbid health conditions, exposure to multiple (hazard ratio, 1.95; 95% CI, 1.03-3.71), but not single (hazard ratio,1.18; 95% CI, 0.79-1.77), procedures requiring general anesthesia was associated with an increased risk for ADHD.

CONCLUSION:

Children repeatedly exposed to procedures requiring general anesthesia before age 2 years are at increased risk for the later development of ADHD even after adjusting for comorbidities.
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Chronic dichlorvos exposure: microglial activation, proinflammatory cytokines and damage to nigrostriatal dopaminergic system.


Dopaminergic cells in the substantia nigra are highly vulnerable to the neurodegenerative process of Parkinson's disease. Therefore, mechanisms that enhance their susceptibility to injury bear important implications for disease pathogenesis. We have previously shown that chronic dichlorvos exposure caused nigrostriatal dopaminergic degeneration and significant behavioral impairments. In this study, we analyzed the relationship between microglial activation and dopaminergic neurodegeneration to examine the possibility that neuroinflammation may induce dopaminergic neuronal loss in the nigrostriatal system. Chronic dichlorvos exposure causes microglial activation including induction of NADPH oxidase and a selective loss of dopaminergic neurons in rat. 

METHOD

Microglial marker expression was increased at transcription as well as translational levels in the substantia nigra (SN) and corpus striatum (CS) of rats exposed to dichlorvos. Activated microglia were seen in SN and CS of dichlorvos-treated animals but were rarely observed in controls. 

RESULT

Immunostaining revealed lesser number of TH-positive neurons and higher number of microglia in SN and CS regions after dichlorvos treatment. The mRNA and protein levels of the NADPH oxidase main subunit gp91(phox) were significantly increased after dichlorvos administration. Dichlorvos exposure also leads to increased level of microglial noxious mediators such as IL-1β, TNF-α and IL-6 in ventral midbrain and CS at transcription as well as translational levels. 

CONCLUSION

Data indicate that microglial activation and consequent induction of NADPH oxidase and proinflammatory cytokines such as TNF-α, IL-1β and IL-6 may act as risk factors for Parkinson's disease by increasing the vulnerability of dopaminergic cells to dichlorvos toxic injury.

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Antiherpes Virus-Specific Treatment and Cognition in Schizophrenia: A Test-of-Concept Randomized Double-Blind Placebo-Controlled Trial

To test our hypothesis that valacyclovir, an antiherpes virus-specific
medication, added to antipsychotics (APs) would improve cognitive performance and
psychopathology among schizophrenia subjects exposed to neurotropic herpes
simplex virus, type 1 (HSV1).Methods:Using a double-blind placebo-controlled
design, we randomized 24 HSV1-seropositive schizophrenia subjects to receive
either valacyclovir (n = 12) or placebo (n = 12) for 18 weeks in addition to
stable doses of APs. Valacyclovir dose was stabilized at 1.5 g twice daily
orally. At each visit, subjects were evaluated for severity of psychopathology
and side effects using standardized scales and a study-specific semistructured
checklist. A computerized neurocognitive battery validated on both schizophrenia
and healthy subjects was administered at baseline and follow-up. Intent-to-treat
analysis, using linear regression models that included all randomized subjects,
were used to examine differential changes in cognition and psychopathology scores
over 18 weeks between valacyclovir and placebo, accounting for placebo
response.Results:Valacyclovir group improved in verbal memory, working memory,
and visual object learning compared with placebo group. The effect sizes (Cohen's
d) were 0.79 for working memory, 1.14 for immediate verbal memory, and 0.97 for
the visual object learning. Psychotic symptom severity did not
improve.Conclusions:Supplemental valacyclovir may alleviate impairments in
cognitive domains that are often observed in schizophrenia but not psychotic
symptoms in those exposed to HSV1. If replicated, this approach could provide a
novel strategy to treat cognitive impairments in a subgroup of schizophrenia
subjects who can be reliably identified using a blood test.
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Genetic risk and stressful early infancy join to increase risk for schizophrenia

Working with genetically engineered mice and the genomes of thousands of people with schizophrenia, researchers at Johns Hopkins say they now better understand how both nature and nurture can affect one's risks for schizophrenia and abnormal brain development in general.
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Child-Proofing Drugs | The Scientist

When children need medications, getting the dosing and method of administration right is like trying to hit a moving target with an untried weapon.

Genome WEB; Genetic Architecture Analysis Suggests More Risk SNPs to be Discovered for Common Diseases | GenomeWeb Daily News | Informatics | GenomeWeb

The genetic risk for common, complex disease likely lies in many common SNPs combined with a few rare causal variants, according to a Nature Genetics study by an international team that developed a new statistical strategy for delving into the genetic architecture of such diseases.
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Dental plaque bacteria may trigger blood clots

Oral bacteria that escape into the bloodstream (Streptococcus gordonii ) are able to cause blood clots and trigger life-threatening endocarditis. Further research could lead to new drugs to tackle infective heart disease, say scientists presenting their work at the Society for General Microbiology's Spring Conference in Dublin this week.
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The body's bacteria affect intestinal blood vessel formation

Researchers at the Sahlgrenska Academy at the University of Gothenburg, Sweden,  have discovered a previously unknown mechanism which helps intestinal bacteria to affect the formation of blood vessels. The results, which are presented in Nature, may provide future treatments of intestinal diseases and obesity.
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Scientists Reprogram Cancer Cells With Low Doses Of Epigenetic Drugs - News Story - Biocompare Buyer's Guide For Life Scientists

Experimenting with cells in culture, researchers at the Johns Hopkins Kimmel Cancer Center have breathed possible new life into two drugs once considered too toxic for human cancer treatment. The drugs, azacitidine  and decitabine , are epigenetic-targeted drugs and work to correct cancer-causing alterations that modify DNA.
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Growth-promoting #Antibiotics: On The Way Out? - Science News

Inner weapons against allergies: Gut bacteria control allergic diseases

Commensal bacteria might play an important role in influencing and controlling allergic inflammation. The commensal relationship that develops between humans and internal bacteria is one in which both humans and bacteria derive benefits. The study -- appearing this week in Nature Medicine -- suggests that therapeutic targeting of immune cell responses to resident gut bacteria may be beneficial in treating allergic diseases.
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Researchers discover first-ever link between micro RNA and imminent heart attack risk

Researchers at the Intermountain Medical Center Heart Institute have, for the first time ever, made a connection between tiny genetic molecules called #microRNAs and the imminent threat of a #heart attack, according to a new study.
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Interventional radiologists see 'significant' symptom relief in MS patients

Researchers who investigated the connection between chronic cerebrospinal venous insufficiency (a reported condition characterized as a blockage in the veins that drain blood from the brain and spinal cord and returns it to the heart) and multiple sclerosis indicate that a minimally invasive endovascular treatment for CCSVI, is safe and may produce "significant," short-term improvement in physical- and mental health-related quality of life in individuals with MS. These findings were presented at the Society of Interventional Radiology's 37th Annual Scientific Meeting in San Francisco, Calif.
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Human Immunodeficiency Virus In Late-Stage AIDS Inhibited By Marijuana-Like Chemicals

Mount Sinai School of Medicine researchers have discovered that marijuana-like chemicals trigger receptors on human immune cells that can directly inhibit a type of human immunodeficiency virus (HIV) found in late-stage AIDS, according to new findings published online in the journal PLoS ONE.
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Prenatal exposure to combustion-related pollutants and anxiety, attention problems in young children

Mothers' exposure during pregnancy to a class of air pollutants called polycyclic aromatic hydrocarbons (PAH) can lead to behavioral problems in their children. PAH are released to air during incomplete combustion of fossil fuel such as diesel, gasoline, coal, and other organic material.
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Inflammatory effects of highly pathogenic H5N1 influenza virus infection in the CNS of mice.

The A/VN/1203/04 strain of the H5N1 influenza virus is capable of infecting the
CNS of mice and inducing a number of neurodegenerative pathologies. Here, we
examined the effects of H5N1 on several pathological aspects affected in
parkinsonism, including loss of the phenotype of dopaminergic neurons located in
the substantia nigra pars compacta (SNpc), expression of monoamines and
indolamines in brain, alterations in SNpc microglia number and morphology, and
expression of cytokines, chemokines, and growth factors. We find that H5N1
induces a transient loss of the dopaminergic phenotype in SNpc and now report
that this loss recovers by 90 d after infection. A similar pattern of loss and
recovery was seen in monoamine levels of the basal ganglia. The inflammatory
response in lung and different regions of the brain known to be targets of the
H5N1 virus (brainstem, substantia nigra, striatum, and cortex) were examined at
3, 10, 21, 60, and 90 d after infection. In each of these brain regions, we found
a significant increase in the number of activated microglia that lasted at least
90 d. We also quantified expression of IL-1α, IL-1β, IL-2, IL-6, IL-9, IL-10,
IL-12(p70), IL-13, TNF-α, IFN-γ, granulocyte-macrophage colony-stimulating
factor, granulocyte colony-stimulating factor, macrophage colony-stimulating
factor, eotaxin, interferon-inducible protein 10, cytokine-induced neutrophil
chemoattractant, monocyte chemotactic protein-1, macrophage inflammatory protein
(MIP) 1α, MIP-1β, and VEGF, and found that the pattern and levels of expression
are dependent on both brain region and time after infection. We conclude that
H5N1 infection in mice induces a long-lasting inflammatory response in brain and
may play a contributing factor in the development of pathologies in
neurodegenerative disorders.
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Protein Lounge - Pathway analysis and many more

The Ballooning Brain: Defective Genes May Explain Uncontrolled Brain Growth in Autism: Scientific American

Autistic children's brains may grow too big, too soon. A new study links this unusual growth to abnormal gene activity that fails to prune unnecessary neural connections. Autistic children's brains may grow too big, too soon. A new study links this unusual growth to abnormal gene activity that fails to prune unnecessary neural connections
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Combating Childhood Obesity, The Budget Case - Rep. Ron Kind and Donna Katen-Bahensky

Spend more on the problem  and reap the benefit of spending less on the problems.

Researchers find beta cell stress could trigger the development of type 1 diabetes

In all cells, there is a vital compartment known as the endoplasmic reticulum (ER) where secreted proteins, like insulin, are produced and processed before being released by the cell. Pancreatic beta cells are highly specialized for the production and secretion of insulin and therefore, the ER plays a critical role in their function, making them particularly sensitive to ER stress. The study by Tersey and colleagues show that an alteration of the beta cell ER stress response occurs early in the disease, and if the ER stress is not resolved properly, it can result in defects in insulin secretion, and ultimately death of the beta cell.
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Let Them Eat Dirt | It's good for you: The Scientist

Maybe it’s okay to let your toddler lick the swing set and kiss the dog. A new mouse study suggests early exposure to microbes is essential for normal immune development, supporting the so-called “hygiene hypothesis” which states that lack of such exposure leads to an increased risk of autoimmune diseases. Specifically, the study found that early-life microbe exposure decreases the number of inflammatory immune cells in the lungs and colon, lowering susceptibility to asthma and inflammatory bowel diseases later in life.
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HHMI News: Structure of Disease-Causing Amyloid Protein Solved : Novel Protein Structure at Heart of Toxic Amyloids

Mechanisms of Ageing and Development - Elsevier

Powerful Immunosupressant Cells Obtained From Cheek Tissue Could Be Key To Immune System Disease

Powerful new cells created by Cardiff University scientists from cheek lining tissue could offer the answer to disorders of the immune system.

While the body's immune system protects against many diseases, it can also be harmful. Using white blood cells (lymphocytes), the system can attack insulin-producing cells, causing diabetes, or cause the body to reject transplanted organs.
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Diet soda linked to increase in glucagon-like peptide 1 levels

Drinking a diet soda before a glucose load is associated with increased glucagon-like peptide 1 secretion in individuals with type 1 diabetes and healthy controls, but not in those with type 2 diabetes, according to research published online March 12 in Diabetes Care.
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Gut Microbes Keep Rare Immune Cells in Line

 The idea that exposure to microbes can be good for us—by tuning up our immune systems and preventing overreactions like asthma and autoimmune diseases—is catching. Now, a new study of this provocative notion, known as the hygiene hypothesis, suggests that microbes furnish some of their benefits in an unexpected way. Researchers have found that the typical intestinal bacteria in mice rein in a rare type of immune cell, curtailing asthma and colitis in the rodents. Scientists following the long-running discussion over the hygiene hypothesis give the new work, reported online in Science this week
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Can our genes be making us fat? Science Daily

While high-fat foods are thought to be of universal appeal, there is actually a lot of variation in the extent to which people like and consume fat. A new study in the March issue of the Journal of Food Science, published by the Institute of Food Technologists, reported that two specific genes (TAS2R38-a bitter taste receptor and CD36-a possible fat receptor), may play a role in some people's ability to taste and enjoy dietary fat. By understanding the role of these two genes, food scientists may be able to help people who have trouble controlling how much fat they eat.

Genetic influences on oral fat perception and preference: presented at the symposium "the taste for fat: new discoveries on the role of fat in sensory perception, metabolism, sensory pleasure and beyond" held at the institute of food technologists 2011 annual meeting, new orleans, la., june 12, 2011.


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Possible causes of sudden onset OCD in kids broadened, March 22, 2012 News Release - National Institutes of Health (NIH)

Criteria for a broadened syndrome of acute onset obsessive compulsive disorder (OCD) have been proposed by a National Institutes of Health scientist and her colleagues. The syndrome, Pediatric Acute-onset Neuropsychiatric Syndrome (PANS), includes children and teens that suddenly develop on-again/off-again OCD symptoms or abnormal eating behaviors, along with other psychiatric symptoms — without any known cause.
PANS expands on Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus (PANDAS), which is limited to a subset of cases traceable to an autoimmune process triggered by a strep infection. A clinical trial testing an immune-based treatment for PANDAS is currently underway at NIH and Yale University (see below).
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Translational Psychiatry - A novel blood-based biomarker for detection of autism spectrum disorders

Autism spectrum disorders (ASD) are classified as neurological developmental disorders. Several studies have been carried out to find a candidate biomarker linked to the development of these disorders, but up to date no reliable biomarker is available. Mass spectrometry techniques have been used for protein profiling of blood plasma of children with such disorders in order to identify proteins/peptides that may be used as biomarkers for detection of the disorders. Three differentially expressed peptides with mass–charge (m/z) values of 2020±1, 1864±1 and 1978±1Da in the heparin plasma of children with ASD that were significantly changed as compared with the peptide pattern of the non-ASD control group are reported here. This novel set of biomarkers allows for a reliable blood-based diagnostic tool that may be used in diagnosis and potentially, in prognosis of ASD.
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Alzheimer's Improvements Seen In Mice Infected With Toxoplasma gondii Parasite

Don't do this at home !

Bacteriophages and diffusion of genes encoding antimicrobial resistance in cystic fibrosis sputum microbiota.

The cystic fibrosis (CF) airway is now considered the site of a
complex microbiota, where cross-talking between microbes and lateral gene
transfer are believed to contribute to the adaptation of bacteria to this
specific environment and to the emergence of multidrug-resistant bacteria. The
objective of this study was to retrieve and analyse specific sequences associated
with antimicrobial resistance from the CF viromes database.
METHODS: Specific sequences from CF metagenomic studies related to the
'antibiotic and toxic compound resistance' dataset were retrieved from the
MG-RAST web site, assembled and functionally annotated for identification of the 
genes. Phylogenetic trees were constructed using a minimum parsimony starting
tree topology search strategy.
RESULTS: Overall, we found 1031 short sequences in the CF virome putatively
encoding resistance to antimicrobials versus only 3 reads in the non-CF virome
dataset (P = 0.001). Among them, we could confidently identify 66 efflux pump
genes, 15 fluoroquinolone resistance genes and 9 β-lactamase genes. Evolutionary 
relatedness determined using phylogenetic information demonstrates the different 
origins of these genes among the CF microbiota. Interestingly, among annotated
sequences within CF viromes, we also found matching 16S rDNA sequences from
Escherichia, Cyanobacteria and Bacteroidetes.
CONCLUSIONS: Our results suggest that phages in the CF sputum microbiota
represent a reservoir of mobilizable genes associated with antimicrobial
resistance that may spread in this specific niche. This phenomenon could explain 
the fantastic adaptation of CF strains to their niche and may represent a new
potential therapeutic target to prevent the emergence of multidrug-resistant
bacteria, which are responsible for most of the deaths in CF.
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Bacteriophages as vehicles of the resistome in cystic fibrosis.

Environmental microbial communities and human microbiota represent a huge
reservoir of mobilizable genes, the 'mobilome', including a pool of genes
encoding antimicrobial resistance, the 'resistome'. Whole-genome sequencing of
bacterial genomes from cystic fibrosis (CF) patients has demonstrated that
bacteriophages contribute significantly to bacterial genome alterations, and
metagenomic analysis of respiratory tract DNA viral communities has revealed the 
presence of genes encoding antimicrobial resistance in bacteriophages of CF
patients. CF airways should now be considered as the site of complex microbiota, 
where bacteriophages are vehicles for the adaptation of bacteria to this specific
environment and for the emergence and selection of multidrug-resistant bacteria
with chimeric repertoires. As phages are already known to be mobilized during
chronic infection of the lungs of patients with CF, it seems particularly
important to improve the understanding of the mechanisms of phage induction to
prevent the spread of virulence and/or antimicrobial resistance determinants
within the CF population as well as in the community. Such a modern point of view
may be a seminal reflection for clinical practice in the future since current
antimicrobial therapy guidelines in the context of CF may lead to the emergence
of genes encoding antimicrobial resistance.
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Chronic HCV infection is a risk of atherosclerosis. Role of HCV and HCV-related steatosis

Chronic hepatitis C  patients have an earlier and a higher prevalence of atherosclerosis than general population.. HCV RNA and HCV-related steatosis are the independent factors associated with atherosclerosis.  HCV and steatosis promote atherogenesis through inflammation and metabolic changes.  CHC patients should be screened routinely for asymptomatic atherosclerosis.
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Researchers uncover new evidence of cancer-causing agent present in gaseous phase of cigarette smoke

A team of researchers led by A. K. Rajasekaran, PhD, Director of the Nemours Center for Childhood Cancer Research, has shown that a key protein involved in cell function and regulation is stopped by a substance present in cigarette smoke. Their work is published online in the American Journal of Physiology - Lung Cell and Molecular Physiology.
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Curcumin shows promise in attacking Parkinson's disease

Identification of common biological pathways and drug targets across multiple respiratory viruses based on human host gene expression analysis.

Pandemic and seasonal respiratory viruses are a major global health
concern. Given the genetic diversity of respiratory viruses and the emergence of 
drug resistant strains, the targeted disruption of human host-virus interactions 
is a potential therapeutic strategy for treating multi-viral infections. The
availability of large-scale genomic datasets focused on host-pathogen
interactions can be used to discover novel drug targets as well as potential
opportunities for drug repositioning.
METHODS/RESULTS: In this study, we performed a large-scale analysis of microarray
datasets involving host response to infections by influenza A virus, respiratory 
syncytial virus, rhinovirus, SARS-coronavirus, metapneumonia virus,
coxsackievirus and cytomegalovirus. Common genes and pathways were found through 
a rigorous, iterative analysis pipeline where relevant host mRNA expression
datasets were identified, analyzed for quality and gene differential expression, 
then mapped to pathways for enrichment analysis. Possible repurposed drugs
targets were found through database and literature searches. A total of 67 common
biological pathways were identified among the seven different respiratory viruses
analyzed, representing fifteen laboratories, nine different cell types, and seven
different array platforms. A large overlap in the general immune response was
observed among the top twenty of these 67 pathways, adding validation to our
analysis strategy. Of the top five pathways, we found 53 differentially expressed
genes affected by at least five of the seven viruses. We suggest five new
therapeutic indications for existing small molecules or biological agents
targeting proteins encoded by the genes F3, IL1B, TNF, CASP1 and MMP9. Pathway
enrichment analysis also identified a potential novel host response, the
Parkin-Ubiquitin Proteasomal System (Parkin-UPS) pathway, which is known to be
involved in the progression of neurodegenerative Parkinson's disease.
CONCLUSIONS: Our study suggests that multiple and diverse respiratory viruses
invoke several common host response pathways. Further analysis of these pathways 
suggests potential opportunities for therapeutic intervention.
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New evidence links Alzheimer's disease and diabetes

An emerging body of research suggests that Alzheimer's disease may be linked to insulin resistance, constituting a third type of diabetes. This model is based on several observations including an increased risk of developing Alzheimer's disease for diabetic patients, and reduced insulin levels in the brain tissue of Alzheimer's disease patients.
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New Computer Program Improves Behavioral Symptoms and Brain Activity in Schizophrenia | Brain & Behavior Research Foundation

A hallmark symptom of schizophrenia is difficulty in distinguishing external reality from internal experiences. Whether or not this impairment is irreversible has long been debated. Now, a pilot study at the University of California, San Francisco, led by NARSAD Independent Investigator Grantee Sophia Vinogradov, M.D., has shown that targeted computer “brain training” can improve reality monitoring in people with schizophrenia.
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Prenatal antiepileptic exposure associates with neonatal DNA methylation differences.

Antiepileptic drugs (AEDs) are used to treat a variety of neuropsychiatric
illnesses commonly encountered in women during their reproductive years,
including epilepsy and bipolar disorder. Despite their widespread use, the impact
of prenatal exposure on fetal development remains obscure. To evaluate whether
AEDs taken by pregnant mothers influence DNA methylation patterns in their
neonates, DNA was extracted from the umbilical cord blood of 201 neonates whose
mothers were treated for neuropsychiatric illness during pregnancy and
interrogated across 27,578 CpG sites using the Illumina HumanMethylation27
BeadChip. The association of each methylation value with the cumulative duration 
of prenatal AED exposure was examined using a linear mixed model. The average
methylation level across all CpG sites was calculated for each subject, and this 
global methylation measure was evaluated similarly. Neonates with a longer
duration of AED exposure in pregnancy showed a decrease in average global
methylation (p = 0.0045). Further, DNA methylation of CpG sites in 14 genes
significantly decreased with the duration of prenatal AED exposure even after
adjusting for multiple comparisons (FDR < 0.05). For a small subset (n = 19) of
these neonates, a second tissue, placenta, was available, in addition to cord
blood. Methylation of 3 of these 14 CpG sites was also significantly decreased in
placental tissue. These novel data suggest decreased DNA methylation in neonates 
of mothers who took AEDs during pregnancy. The long-term stability and potential 
impact of these changes warrant further attention, and caution may be warranted
before prescribing AEDs to pregnant women.
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Aluminium overload after 5 years in skin biopsy following post-vaccination with subcutaneous pseudolymphoma.

Aluminium hydroxide is used as an effective adjuvant in a wide range of vaccines 
for enhancing immune response to the antigen. The pathogenic role of aluminium
hydroxide is now recognized by the presence of chronic fatigue syndrome,
macrophagic myofasciitis and subcutaneous pseudolymphoma, linked to intramuscular
injection of aluminium hydroxide-containing vaccines. The aim of this study is to
verify if the subcutaneous pseudolymphoma observed in this patient in the site of
vaccine injection is linked to an aluminium overload. Many years after
vaccination, a subcutaneous nodule was discovered in a 45-year-old woman with
subcutaneous pseudolymphoma. In skin biopsy at the injection site for vaccines,
aluminium (Al) deposits are assessed by Morin stain and quantification of Al is
performed by Zeeman Electrothermal Atomic Absorption Spectrophotometry. Morin
stain shows Al deposits in the macrophages, and Al assays (in μg/g, dry weight)
were 768.10±18 for the patient compared with the two control patients, 5.61±0.59 
and 9.13±0.057. Given the pathology of this patient and the high Al concentration
in skin biopsy, the authors wish to draw attention when using the Al salts known 
to be particularly effective as adjuvants in single or repeated vaccinations. The
possible release of Al may induce other pathologies ascribed to the well-known
toxicity of this metal.
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Genetic variation in human gut viruses could be raw material for inner evolution

A growing body of evidence underscores the importance of human gut bacteria in modulating human health, metabolism, and disease. Yet bacteria are only part of the story. Viruses that infect those bacteria also shape who we are. Frederic D. Bushman, PhD, professor of Microbiology at the Perelman School of Medicine at the University of Pennsylvania, led a study published this month in the Proceedings of the National Academy of Sciences that sequenced the DNA of viruses -- the virome -- present in the gut of healthy people.
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Novel therapy discovered for Crohn's disease

The Nutritional Immunology and Molecular Medicine Laboratory (NIMML) research team at Virginia Tech has discovered important new information on the efficacy of conjugated linoleic acid (CLA) in treating Crohn's disease, a form of inflammatory bowel disease (IBD). CLA is a naturally occurring acid found in meat and dairy products known for its anti-cancer and immune modulatory properties.
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Diagnosis of ADHD on the rise: 10 million American children diagnosed with ADHD during doctors' visits

The number of American children leaving doctors' offices with an attention deficit hyperactivity disorder (ADHD) diagnosis has risen 66 percent in 10 years, according to a new Northwestern Medicine study. Over this same timeframe, specialists, instead of primary care physicians, have begun treating an increasing number of these young patients, the study found.

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The effect of rosuvastatin on incident pneumonia

Statins may prevent pneumonia, according to a new study in CMAJ (Canadian Medical Association Journal). Researchers from Israel and the United States analyzed data from the JUPITER trial, a randomized, double-blind trial with placebo control groups conducted at 1315 sites in 26 countries to look at the use of the statin rosuvastatin in disease prevention. The trial involved 17 802 men aged 50 years or older and women aged 60 years or older without a history of heart disease or diabetes.
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Children whose minds wander 'have sharper brains' - Telegraph

So stop worrying about the apparent lack of concentration  !!

Immune Role in Brain Disorder? RETT syndrome The Scientist

Nature abstract

Rett syndrome is an X-linked autism spectrum disorder. The disease is characterized in most cases by mutation of the MECP2 gene, which encodes a methyl-CpG-binding protein1, 2, 3, 4, 5. Although MECP2 is expressed in many tissues, the disease is generally attributed to a primary neuronal dysfunction6. However, as shown recently, glia, specifically astrocytes, also contribute to Rett pathophysiology. Here we examine the role of another form of glia, microglia, in a murine model of Rett syndrome. Transplantation of wild-type bone marrow into irradiation-conditioned Mecp2-null hosts resulted in engraftment of brain parenchyma by bone-marrow-derived myeloid cells of microglial phenotype, and arrest of disease development. However, when cranial irradiation was blocked by lead shield, and microglial engraftment was prevented, disease was not arrested. Similarly, targeted expression of MECP2 in myeloid cells, driven by Lysmcre on an Mecp2-null background, markedly attenuated disease symptoms. Thus, through multiple approaches, wild-type Mecp2-expressing microglia within the context of an Mecp2-null male mouse arrested numerous facets of disease pathology: lifespan was increased, breathing patterns were normalized, apnoeas were reduced, body weight was increased to near that of wild type, and locomotor activity was improved. Mecp2+/− females also showed significant improvements as a result of wild-type microglial engraftment. These benefits mediated by wild-type microglia, however, were diminished when phagocytic activity was inhibited pharmacologically by using annexin V to block phosphatydilserine residues on apoptotic targets, thus preventing recognition and engulfment by tissue-resident phagocytes. These results suggest the importance of microglial phagocytic activity in Rett syndrome. Our data implicate microglia as major players in the pathophysiology of this devastating disorder, and suggest that bone marrow transplantation might offer a feasible therapeutic approach for it.
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Cell-signaling pathway (HGF) has key role in development of gestational diabetes

ScienceDaily (Mar. 16, 2012) — Researchers at the University of Pittsburgh School of Medicine have identified a cell-signaling pathway that plays a key role in increasing insulin secretion during pregnancy and, when blocked, leads to the development of gestational diabetes. Their findings are available online March 16 in Diabetes, one of the journals of the American Diabetes Association
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Depression: an inflammatory illness?

Major depressive disorder (MDD) is associated with significant morbidity and mortality. Findings from preclinical and clinical studies suggest that psychiatric illnesses, particularly MDD, are associated with inflammatory processes. While it is unlikely that MDD is a primary 'inflammatory' disorder, there is now evidence to suggest that inflammation may play a subtle role in the pathophysiology of MDD. Most of the evidence that links inflammation to MDD comes from three observations: (a) one-third of those with major depression show elevated peripheral inflammatory biomarkers, even in the absence of a medical illness; (b) inflammatory illnesses are associated with greater rates of MDD; and (c) patients treated with cytokines are at greater risk of developing major depressive illness. We now know that the brain is not an immune privileged organ. Inflammatory mediators have been found to affect various substrates thought to be important in the aetiopathogenesis of MDD, including altered monoamine and glutamate neurotransmission, glucocorticoid receptor resistance and adult hippocampal neurogenesis. At a higher level, inflammation is thought to affect brain signalling patterns, cognition and the production of a constellation of symptoms, termed 'sickness behaviour'. Inflammation may therefore play a role in the aetiology of depression, at least in a 'cohort' of vulnerable individuals. Inflammation may not only act as a precipitating factor that pushes a person into depression but also a perpetuating factor that may pose an obstacle to recovery. More importantly, inflammatory markers may aid in the diagnosis and prediction of treatment response, leading to the possibility of tailored treatments, thereby allowing stratification of what remains a heterogenous disorder.
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Study finds how to correct human mitochondrial mutations

Researchers at the UCLA stem cell center and the departments of chemistry and biochemistry and pathology and laboratory medicine have identified, for the first time, a generic way to correct mutations in human mitochondrial DNA by targeting corrective RNAs, a finding with implications for treating a host of mitochondrial diseases.
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Scientific Summary of the 5th HIV Persistence Workshop

The December 2011 5th International Workshop on HIV Persistence during Therapy addressed the issue of HIV persistence among 210 scientists from 10 countries involved in the study of HIV reservoirs and the search of an HIV cure. High quality abstracts were selected and discussed as oral or poster presentations. The aim of this review is to distribute the scientific highlights of this workshop outside the group as analyzed and represented by experts in retrovirology, immunology and clinical research.

GWAS central database

GWAS Central (previously the Human Genome Variation database of Genotype-to-Phenotype information) is a database of summary level findings from genetic association studies, both large and small. We actively gather datasets from public domain projects, and encourage direct data submission from the community.
GWAS Central is built upon a basal layer of Markers that comprises all known SNPs and other variants from public databases such as dbSNP and the DBGV. Allele and genotype frequency data, plus genetic association significance findings, are added on top of the Marker data, and organised the same way that investigations are reported in typical journal manuscripts. Critically, no individual level genotypes or phenotypes are presented in GWAS Central – only group level aggregated (summary level) data. The largest unit in a data submission is a Study, which can be thought of as being equivalent to one journal article. This may contain one or more Experiments, one or more Sample Panels of test subjects, and one or more Phenotypes. Sample Panels may be characterised in terms of various Phenotypes, and they also may be combined and/or split into Assayed Panels. The Assayed Panels are used as the basis for reporting allele/genotype frequencies (in `Genotype Experiments`) and/or genetic association findings (in ‘Analysis Experiments’). Environmental factors are handled as part of the Sample Panel and Assayed Panel data structures.
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Study shows how the breakup of two proteins interferes with the immune system

Autoimmune diseases, such as Type I diabetes and rheumatoid arthritis, are caused by an immune system gone haywire, where the body's defense system assaults and destroys healthy tissues. A mutant form of a protein called LYP has been implicated in multiple autoimmune diseases, but the precise molecular pathway involved has been unknown. Now, in a paper published March 18 in Nature Chemical Biology, researchers at Sanford-Burnham Medical Research Institute show how the errant form of LYP can disrupt the immune system. In doing so, they also found a potential new therapy for autoimmune diseases—a chemical compound that appears to inhibit this mutant protein.
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