Polymicrobial Infections In Brain Tissue From Alzheimer's Disease Patients.

Several studies have advanced the idea that the etiology of Alzheimer's disease (AD) could be microbial in origin. In the present study, we tested the possibility that polymicrobial infections exist in tissue from the entorhinal cortex/hippocampus region of patients with AD using immunohistochemistry (confocal laser scanning microscopy) and highly sensitive (nested) PCR. We found no evidence for expression of early (ICP0) or late (ICP5) proteins of herpes simplex virus type 1 (HSV-1) in brain sections. A polyclonal antibody against Borrelia detected structures that appeared not related to spirochetes, but rather to fungi. These structures were not found with a monoclonal antibody. Also, Borrelia DNA was undetectable by nested PCR in the ten patients analyzed. By contrast, two independent Chlamydophila antibodies revealed several structures that resembled fungal cells and hyphae, and prokaryotic cells, but most probably were unrelated to Chlamydophila spp. Finally, several structures that could belong to fungi or prokaryotes were detected using peptidoglycan and Clostridium antibodies, and PCR analysis revealed the presence of several bacteria in frozen brain tissue from AD patients. Thus, our results show that polymicrobial infections consisting of fungi and bacteria can be revealed in brain tissue from AD patients."



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Study on the Association among Mycotoxins and other Variables in Children with Autism.

 Environmental factors and genetic susceptibility are implicated in the increased risk of autism spectrum disorder (ASD). Mycotoxins are agricultural contaminants of fungal origin that represent real risk factors for human health and especially for children. Thus, the main hypothesis of this work is that the deterioration of the clinical manifestation of autism in children may result from the exposure to mycotoxins through the consumption of contaminated food. Within a cross-sectional study, a group of autistic children (n = 172) and a group of controls (n = 61) (siblings and non-parental) were recruited in North and South Italy. All children had blood and urine samples taken, for testing some mycotoxins by a LC-MS/MS validated method. Blood samples were also tested for assessing specific IgG against food and fungal antigens and cytokines. The analyses outputs highlighted statistically significant differences comparing mycotoxins levels between (i) children groups both in urine (deoxynivalenol and de-epoxydeoxynivalenol, p = 0.0141 and p = 0.0259, respectively) and serum (aflatoxin M1, ochratoxin A and fumonisin B1, p = 0.0072, p = 0.0141 and p = 0.0061, respectively); (ii) a group of selected fungal IgGs, and IgGs against wheat and gluten and (iii) cytokines. These results suggest the need for a deeper examination of the role that mycotoxins may have on the etiology of ASD."



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Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies

 BACKGROUND Nonnutritive sweeteners, such as aspartame, sucralose and stevioside, are widely consumed, yet their long-term health impact is uncertain. We synthesized evidence from prospective studies to determine whether routine consumption of non-nutritive sweeteners was associated with long-term adverse cardiometabolic effects. 

METHODS We searched MEDLINE, Embase and Cochrane Library (inception to January 2016) for randomized controlled trials (RCTs) that evaluated interventions for nonnutritive sweeteners and prospective cohort studies that reported on consumption of non-nutritive sweeteners among adults and adolescents. The primary outcome was body mass index (BMI). Secondary outcomes included weight, obesity and other cardiometabolic end points.

 RESULTS From 11 774 citations, we included 7 trials (1003 participants; median follow-up 6 mo) and 30 cohort studies (405 907 participants; median follow-up 10 yr). In the included RCTs, nonnutritive sweeteners had no significant effect on BMI (mean difference −0.37 kg/m2; 95% confidence interval [CI] −1.10 to 0.36; I2 9%; 242 participants). In the included cohort studies, consumption of nonnutritive sweeteners was associated with a modest increase in BMI (mean correlation 0.05, 95% CI 0.03 to 0.06; I2 0%; 21 256 participants). Data from RCTs showed no consistent effects of nonnutritive sweeteners on other measures of body composition and reported no further secondary outcomes. In the cohort studies, consumption of nonnutritive sweeteners was associated with increases in weight and waist circumference, and higher incidence of obesity, hypertension, metabolic syndrome, type 2 diabetes and cardiovascular events. Publication bias was indicated for studies with diabetes as an outcome.

 INTERPRETATION Evidence from RCTs does not clearly support the intended benefits of nonnutritive sweeteners for weight management, and observational data suggest that routine intake of nonnutritive sweeteners may be associated with increased BMI and cardiometabolic risk. Further research is needed to fully characterize the long-term risks and benefits of nonnutritive sweeteners. Protocol registration: PROSPERO-CRD42015019749"



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The association between total phthalate concentration and non-communicable diseases and chronic inflammation in South Australian urban dwelling men - ScienceDirect

 Objective
To investigate associations between urinary total phthalate concentration, chronic low-grade inflammation and non-communicable diseases in a cohort of South Australian men.
Methods
1504 men aged 39–84 years who provided a urinary sample at the follow-up visit of the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study, a randomly-selected group of urban-dwelling, community-based men from Adelaide, Australia (n = 2038; study participation rate: 78.1%). Total phthalate concentration was quantified in fasting morning urine samples. Chronic diseases were assessed through self-report questionnaire or directly measured using standardised clinical and laboratory procedures. Inflammatory biomarkers were assayed by ELISA or spectroscopy. Multivariable linear and logistic regression models were applied to determine associations of log-transformed urinary phthalate concentration with inflammation and chronic disease.
Results
Total phthalates were detected in 99.6% of urinary samples; geometric mean (95% CI) was 114.1 (109.5–118.9) µg/g creatinine. Higher total phthalate levels were associated with higher levels of hs-CRP, IL-6 (all p < 0.05) and TNF-α but not MPO. Urinary total phthalate concentrations were positively associated with cardiovascular disease, type-2-diabetes and hypertension. Comparing extreme quartiles of total phthalate, prevalence ratios were 1.78 (95% CI 1.17 – 2.71, p-trend = 0.001) for cardiovascular disease and 1.84 (95%CI 1.34 – 2.51, p-trend = 0.001) for type-2-diabetes and 1.14 (95%CI 1.01 – 1.29, p-trend = 0.013) for hypertension. Total phthalates and asthma and depression were not significantly associated.
Conclusion
A positive association between total phthalates and cardiovascular disease, type-2-diabetes, hypertension and increased levels of chronic low-grade inflammatory biomarkers was observed in urban-dwelling Australian men."



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Characterization of Adipogenic Activity of House Dust Extracts and Semi-Volatile Indoor Contaminants in 3T3-L1 Cells - Environmental Science & Technology (ACS Publications)

  "Obesity and metabolic disorders are of great societal concern and generate significant human health care costs. Recently, attention has focused on the potential for environmental contaminants to act as metabolic disruptors. This study sought to evaluate the adipogenic activity of indoor house dust extracts and a suite of semivolatile organic chemicals (SVOCs) that are often ubiquitously detected in indoor environments. 3T3-L1 cells were exposed to extracts of indoor dust or individual SVOCs and assessed for triglyceride accumulation and preadipocyte proliferation. Ten of 11 house dust extracts exhibited significant triglyceride accumulation and/or proliferation at environmentally relevant levels (<20 μg of dust/well), and significant adipogenic activity was also exhibited by 28 of the SVOCs. Notably, pyraclostrobin, dibutyl phthalate, tert-butyl-phenyl diphenyl phosphate, and the isopropylated triaryl phosphates (ITPs) exhibited near maximal or supra-maximal triglyceride accumulation relative to the rosiglitazone-induced maximum. The adipogenic activity in house dust occurred at concentrations below EPA estimated child exposure levels, and raises concerns for human health impacts, particularly in children. Our results delineate a novel potential health threat and identify putative causative SVOCs that are likely contributing to this activity."



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Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children

 "Viruses have long been considered potential triggers of autoimmune diseases. Here we defined the intestinal virome from birth to the development of autoimmunity in children at risk for type 1 diabetes (T1D). A total of 220 virus-enriched preparations from serially collected fecal samples from 11 children (cases) who developed serum autoantibodies associated with T1D (of whom five developed clinical T1D) were compared with samples from controls. Intestinal viromes of case subjects were less diverse than those of controls. Among eukaryotic viruses, we identified significant enrichment of Circoviridae-related sequences in samples from controls in comparison with cases. Enterovirus, kobuvirus, parechovirus, parvovirus, and rotavirus sequences were frequently detected but were not associated with autoimmunity. For bacteriophages, we found higher Shannon diversity and richness in controls compared with cases and observed that changes in the intestinal virome over time differed between cases and controls. Using Random Forests analysis, we identified disease-associated viral bacteriophage contigs after subtraction of age-associated contigs. These disease-associated contigs were statistically linked to specific components of the bacterial microbiome. Thus, changes in the intestinal virome preceded autoimmunity in this cohort. Specific components of the virome were both directly and inversely associated with the development of human autoimmune disease."



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Hidden herpes virus may play key role in MS, other brain disorders -- ScienceDaily

 "The ubiquitous human herpesvirus 6 (HHV-6) may play a critical role in impeding the brain's ability to repair itself in diseases like multiple sclerosis. The findings, which appear in the journal Scientific Reports, may help explain the differences in severity in symptoms that many people with the disease experience.

"While latent HHV-6 -- which can be found in cells throughout the brain -- has been associated with demyelinating disorders like multiple sclerosis it has not been clear what role, if any, it plays in these diseases," said Margot Mayer-Proschel, Ph.D., an associate professor at the University of Rochester Medical Center Department of Biomedical Genetics and co-author of the study. "These findings show that, while in the process of hiding from the immune system, the virus produces a protein that has the potential to impair the normal ability of cells in the brain to repair damaged myelin.""



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Sugar intake during pregnancy is associated with allergy and allergic asthma in children

 "High maternal sugar intake during pregnancy may increase the risk of allergy and allergic asthma in the offspring, according to an early study led by Queen Mary University of London (QMUL) involving almost 9,000 mother-child pairs."



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Rat Brain-Connectome

 ChemNetDB is an open access constantly evolving neurochemical connectivity database obtained from the rat brain. By utilizing advanced neuroinformatics methods, we have integrated over 50 years of neuroanatomical and neurochemical research on rat brain into a consistent, brain-wide, multi-scale neurochemical cerebral connectome. This connectome differs from the previously suggested neuronal networks of rat brain in two major aspects:

it integrates information on transmitter systems and receptors on the network topology;
it is unbiased and hypothesis-free as the connectome was obtained by consistent and systematic procedures without a priori assumptions."



New study links antibiotic resistance to common household disinfectant triclosan

 "Scientists from the University of Birmingham and Norwich Research Park have discovered a link between a major mechanism of antibiotic resistance and resistance to the disinfectant triclosan which is commonly found in domestic products."



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Study finds link between upper GI infections and protein (synuclein) implicated in Parkinson’s disease

 "Acute and chronic infections in a person's upper gastrointestinal tract appear to be linked to Parkinson's disease, say scientists at Georgetown University Medical Center and their collaborators at the National Institutes of Health and other institutions.

Their study, published in the Journal of Innate Immunity, finds that alpha-Synuclein (αS), the protein implicated in Parkinson's disease and other forms of neurodegenerative diseases, is released when an infection occurs in the upper GI tract (the esophagus, stomach, and duodenum) inducing an immune response as part of the body's innate immune system. The researchers say that these findings suggest that frequent or chronic upper GI infections could overwhelm the body's capacity to clear αS, leading to disease."



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Banned chemicals pass through umbilical cord from mother to baby, research finds

 "Trace amounts of flame retardants, banned in the U.S. for more than a decade, are still being passed through umbilical cord blood from mothers to their babies, according to new Indiana University research. The chemicals are linked to health concerns including hormone disruption and low birth weight.
PBDEs, or polybrominated diphenyl ethers, were commonly used flame retardants in building materials, electronics and textiles until they were banned in 2004. The chemicals leach into the environment, where they persist and are found today in virtually every population worldwide."



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What's on your skin? Archaea, that's what: Study on human skin microbiome finds archaea abundance associated with age -- ScienceDaily

 "It turns out your skin is crawling with single-celled microorganisms -- and they're not just bacteria. A study by the Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) and the Medical University of Graz has found that the skin microbiome also contains archaea, a type of extreme-loving microbe, and that the amount of it varies with age."



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Signalling through AMPA receptors on oligodendrocyte precursors promotes myelination by enhancing oligodendrocyte survival | eLife

 Myelin, made by oligodendrocytes, is essential for rapid information transfer in the central nervous system. Oligodendrocyte precursors (OPs) receive glutamatergic synaptic input from axons but how this affects their development is unclear. Murine OPs in white matter express AMPA receptor (AMPAR) subunits GluA2, GluA3 and GluA4. We generated mice in which OPs lack both GluA2 and GluA3, or all three subunits GluA2/3/4, which respectively reduced or abolished AMPAR-mediated input to OPs. In both double- and triple-knockouts OP proliferation and number were unchanged but ~25% fewer oligodendrocytes survived in the subcortical white matter during development. In triple knockouts, this shortfall persisted into adulthood. The oligodendrocyte deficit resulted in ~20% fewer myelin sheaths but the average length, number and thickness of myelin internodes made by individual oligodendrocytes appeared normal. Thus, AMPAR-mediated signalling from active axons stimulates myelin production in developing white matter by enhancing oligodendrocyte survival, without influencing myelin synthesis per se.



The effect of smallpox and BCG vaccination on the risk of HIV-1 infection in Guinea-Bissau and Denmark | Open Forum Infectious Diseases | Oxford Academic

Background:
The live smallpox and BCG vaccinations have been associated with better adult survival in both Guinea-Bissau and Denmark. In Guinea-Bissau, HIV-1 became an important cause of death after smallpox vaccination was phased out globally in 1980. We hypothesised that smallpox and BCG vaccinations were associated with a lower prevalence of HIV-1 infection, and tested this hypothesis both in Guinea-Bissau and in Denmark.

Methods:
We conducted two studies, a cross-sectional study of HIV infection and vaccination scars in Guinea-Bissau including 1,751 individuals, and a case-base study with a background population of 46,239 individuals in Denmark. In Guinea-Bissau, HIV-1 transmission is almost exclusively sexually transmitted, in Denmark we excluded intravenous drug users. Data was analysed using logistic regression.

Results:
BCG and/or smallpox vaccination compared with neither of these vaccines was associated with an adjusted odds ratio (aOR) for HIV-1 of 0.62 (95% confidence interval (CI) 0.36-1.07) in Guinea-Bissau and 0.70 (95%CI 0.43-1.15) in Denmark. Combining results from both settings in a meta-analysis gave an aOR of 0.66 (95%CI 0.46-0.96). Data from Guinea-Bissau indicated a stronger effect of multiple smallpox vaccination scars (aOR of 0.27 (95%CI 0.10-0.75); women: 0.18 (95%CI 0.05-0.64), men: 0.52 (95%CI 0.12-2.33), sex-differential effect, p-value = 0.29).


Conclusions:
The studies from Guinea-Bissau and Denmark, two very different settings, both suggest that the BCG and smallpox vaccines could be associated with a decreased risk of sexually transmitted HIV-1. It might be informative to pursue this observation and explore possible protective mechanisms as part of the search for an HIV-1 vaccine."


Related:- Cowpox Helped Against Smallpox; Will the Goat Lentivirus (Caprine Arthritis Encephalitis Virus) Help Against HIV-1?

Vaccinia and other viruses with available vaccines show marked homology with the HIV-1 envelope glycoprotein: the prospect of using existing vaccines to stem the AIDS pandemic.

Sick Building: Fungi Release Toxin Directly Into Air, Study Finds - NBC News

 "Jean-Denis Bailly of the University of Toulouse in France and colleagues tested three common types of fungi that can grow inside buildings and found that their mycotoxins could and did disperse into the air until normal conditions.

“These toxins can subsequently be aerosolized, at least partly, from moldy material,” they wrote in their report in the journal Applied and Environmental Microbiology, published by the American Society for Microbiology.

“This transfer to air requires air velocities that can be encountered in ‘real life conditions’ in buildings.

The three species they tested were Penicillium brevicompactum, Aspergillus versicolor and Stachybotrys chartarum, all of which grew on wallpaper in their lab.

They all also produce mycotoxins."



Here's the paper:-

Aerosolization of mycotoxins after growth of toxinogenic fungi on wallpaper


The joint effect of air pollution exposure and copy number variation on risk for autism - Kim - 2017 - Autism Research - Wiley Online Library

 Autism spectrum disorder is a complex trait with a high degree of heritability as well as documented susceptibility from environmental factors. In this study the contributions of copy number variation, exposure to air pollutants, and the interaction between the two on autism risk, were evaluated in the population-based case-control Childhood Autism Risks from Genetics and Environment (CHARGE) Study. For the current investigation, we included only those CHARGE children (a) who met criteria for autism or typical development and (b) for whom our team had conducted both genetic evaluation of copy number burden and determination of environmental air pollution exposures based on mapping addresses from the pregnancy and early childhood. This sample consisted of 158 cases of children with autism and 147 controls with typical development. Multiple logistic regression models were fit with and without environmental variable-copy number burden interactions. We found no correlation between average air pollution exposure from conception to age 2 years and the child's CNV burden. We found a significant interaction in which a 1SD increase in duplication burden combined with a 1SD increase in ozone exposure was associated with an elevated autism risk (OR 3.4, P < 0.005) much greater than the increased risks associated with either genomic duplication (OR 1.85, 95% CI 1.25–2.73) or ozone (OR 1.20, 95% CI 0.93–1.54) alone. Similar results were obtained when CNV and ozone were dichotomized to compare those in the top quartile relative to those having a smaller CNV burden and lower exposure to ozone, and when exposures were assessed separately for pregnancy, the first year of life, and the second year of life. No interactions were observed for other air pollutants, even those that demonstrated main effects; ozone tends to be negatively correlated with the other pollutants examined. While earlier work has demonstrated interactions between the presence of a pathogenic CNV and an environmental exposure [Webb et al., 2016], these findings appear to be the first indication that global copy number variation may increase susceptibility to certain environmental factors, and underscore the need to consider both genomics and environmental exposures as well as the mechanisms by which each may amplify the risks for autism associated with the other.



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Frontiers | 16S rRNA Next Generation Sequencing Analysis Shows Bacteria in Alzheimer’s Post-Mortem Brain | Frontiers in Aging Neuroscience

The neurological deterioration associated with Alzheimer’s disease (AD), involving accumulation of amyloid-beta peptides and neurofibrillary tangles, is associated with evident neuroinflammation. This is now seen to be a significant contributor to pathology. Recently the tenet of the privileged status of the brain, regarding microbial compromise, has been questioned, particularly in terms of neurodegenerative diseases. It is now being considered that microbiological incursion into the central nervous system could be either an initiator or significant contributor to these. This is a novel study using 16S ribosomal gene-specific Next generation sequencing (NGS) of extracted brain tissue. A comparison was made of the bacterial species content of both frozen and formaldehyde fixed sections of a small cohort of Alzheimer-affected cases with those of cognitively unimpaired (normal). Our findings suggest an increase in bacterial populations in Alzheimer brain tissue compared with normal."




Environmental Health Perspectives – The Florence Statement on Triclosan and Triclocarban

The Florence Statement on Triclosan and Triclocarban documents a consensus of more than 200 scientists and medical professionals on the hazards of and lack of demonstrated benefit from common uses of triclosan and triclocarban. These chemicals may be used in thousands of personal care and consumer products as well as in building materials. Based on extensive peer-reviewed research, this statement concludes that triclosan and triclocarban are environmentally persistent endocrine disruptors that bioaccumulate in and are toxic to aquatic and other organisms. Evidence of other hazards to humans and ecosystems from triclosan and triclocarban is presented along with recommendations intended to prevent future harm from triclosan, triclocarban, and antimicrobial substances with similar properties and effects. Because antimicrobials can have unintended adverse health and environmental impacts, they should only be used when they provide an evidence-based health benefit. Greater transparency is needed in product formulations, and before an antimicrobial is incorporated into a product, the long-term health and ecological impacts should be evaluated. "



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CRISPR Reverses Huntington’s Disease in Mice | GEN

  Huntington disease is an inherited, progressive brain disorder that causes uncontrolled movements, emotional problems, and loss of thinking ability (cognition). [NIH]
The potential of genome-editing techniques, such as CRISPR/Cas9, to alleviate disease burden has ignited the imagination for thousands of researchers looking for new therapeutic strategies. Scientists were very quickly able to show that this gene-altering technique could eliminate disease-causing mutations within a variety of tissues in vitro. More recently, CRISPR is being positioned to help treat patients directly, with clinical trials in humans already under way in China and soon to begin in the U.S. Yet, no current clinical trials feature drugs made using the technique for the treatment of neurodegenerative diseases.

Now, a group of investigators led by scientists at Emory University is hoping to open up new avenues of neurodegenerative research and rapidly move toward human trials after the release of their new findings. The research team showed that the CRISPR/Cas9 system could snip part of a gene that produces toxic protein aggregates in the brains of 9-month-old mice used as a model for Huntington’s disease. Moreover, the scientists noted that when they looked at the brain region where the vector was applied, some weeks later, the aggregated proteins had almost disappeared. Amazingly, the motor abilities of the mice had improved, although not to the level of control mice.            

Findings from the new study were published today in the Journal of Clinical Investigation through an article entitled, “CRISPR/Cas9-mediated gene editing ameliorates neurotoxicity in mouse model of Huntington’s disease.”"



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