Patients with rosacea have increased risk of dementia.

OBJECTIVE:

Rosacea is a common chronic inflammatory skin disorder where upregulation of matrix metalloproteinases (MMPs) and peptides
 (AMPs) is observed. Notably, inflammation, MMPs, and AMPs are also involved in the etiopathogenesis of neurodegenerative disorders including certain forms of dementia such as Alzheimer disease (AD). Based on several clinical observations, we investigated the association between rosacea and dementia, including AD in Danish registers.

METHODS:

All Danish citizens aged ≥18 years between January 1, 1997 and December 31, 2012 were linked at the individual level through administrative registers. Cox regression was used to calculate unadjusted and adjusted hazard ratios (HRs).

RESULTS:

The study comprised a total of 5,591,718 individuals, including 82,439 patients with rosacea. A total of 99,040 individuals developed dementia (any form) in the study period, of whom 29,193 were diagnosed with AD. The adjusted HRs of dementia and AD were 1.07 (95% confidence interval [CI] = 1.01-1.14), and 1.25 (95% CI = 1.14-1.37), respectively, in patients with rosacea. Stratified by sex, the HRs of AD were 1.28 (95% CI = 1.15-1.45) and 1.16 (95% CI = 1.00-1.35) in women and men, respectively. When results were stratified by age at study entry, the risk of AD was only significantly increased in individuals ≥60 years old (adjusted HR = 1.20, 95% CI = 1.08-1.32). When analyses were limited to patients with a hospital dermatologist diagnosis of rosacea only, the adjusted HRs of dementia and AD were 1.42 (95% CI = 1.17-1.72) and 1.92 (95% CI = 1.44-2.58), respectively.

INTERPRETATION:

Rosacea is significantly associated with dementia, particularly AD. Increased focus on symptoms of cognitive dysfunction in older patients with rosacea may be relevant.

Aerial pesticide exposure increases the risk of developmental delay and Autism spectrum disorder

BACKGROUND:

Pesticides are one environmental factor implicated in developmental delay (DD) and autism spectrum disorder (ASD). The influence of the timing and route of pesticide exposure on the risk of ASD/DD is not well defined.

OBJECTIVE: We identified an area of Central New York (NY) with unique pyrethroid pesticide (PP) exposure to study these factors. Each summer, to combat mosquito-borne encephalitis in the Cicero Swamp region, the Department of Health uses airplanes to apply PPs. In contrast, surrounding areas are exposed to standard methods of pesticide application, such as controlled droplet application, by commercial applicators. The objective of this study was to determine if the amount, route or gestational timing of pesticide exposure influenced the risk of ASD/DD.

DESIGN/METHODS: A retrospective review of records from a tertiary referral center was used to estimate the number of children with ASD/DD from 24 zip codes within Central NY from March, 2010 to March, 2015. Cases were identified using ICD-9 codes for ASD or DD at 6 affiliated pediatric clinics. To control for referral bias, rates of 4 common diagnoses were calculated for each zip code. Publicly available mandated reporting data from the Department of Environmental Conservation were used to quantify pesticide exposure (kg) among zip codes. The 2013 American Community Survey was used to quantify demographic data. Data from the 8 zip codes exposed to yearly aerial PPs were compared with 16 control zip codes.

RESULTS: There was no significant difference between aerial-exposed and control groups in number of children, overall births, premature births, poverty level, or child sex. The referral rate from aerial-exposed zip codes was lower for all 4 control diagnoses. The aerial-exposed zip codes had higher levels of total pesticide exposure (p = 0.047), but no difference in pesticide use per square km (p = 0.10). The relative risk of ASD/DD for children in zip codes with aerial spraying was 1.25 (95% CI = 1.025-1.506). ASD/DD prevalence correlated with aerial PP exposure (r = 0.58) and total pesticide exposure (r = 0.41). There was no correlation between gestational age during aerial spraying and ASD/DD prevalence (r = -0.034).

CONCLUSIONS: Exposure to pesticides is correlated with increased risk of ASD/DD. The relative risk of ASD/DD increases when PP exposure occurs through aerial application, but the gestational timing of this exposure does not influence ASD/DD risk."



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Even a little air pollution may have long-term health effects on developing fetus

 Even small amounts of air pollution appear to raise the risk of a condition in pregnant women linked to premature births and lifelong neurological and respiratory disorders in their children, new Johns Hopkins Bloomberg School of Public Health research suggests.
Fine particles from car exhaust, power plants and other industrial sources are breathed into the lungs, but the scientists have now found evidence of the effects of that pollution in the pregnant women's placentas, the organ that connects her to her fetus and provides blood, oxygen and nutrition. They found that the greater the maternal exposure to air pollution, the more likely the pregnant women suffered from a condition called intrauterine inflammation, which can increase the risk of a number of health problems for her child from the fetal stage well into childhood.



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Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment: Immunity

Highlights
•Viruses induce depressive behavior and ISG15 expression at the blood-brain barrier
•IFNAR1 expression on neural cells is not involved in IFN-β-induced sickness behavior
•IFNAR1 expression on brain endothelial and epithelial cells drives behavioral changes
•Brain endothelia- and epithelia-derived CXCL10 inhibits hippocampal synaptic plasticity

Sickness behavior and cognitive dysfunction occur frequently by unknown mechanisms in virus-infected individuals with malignancies treated with type I interferons (IFNs) and in patients with autoimmune disorders. We found that during sickness behavior, single-stranded RNA viruses, double-stranded RNA ligands, and IFNs shared pathways involving engagement of melanoma differentiation-associated protein 5 (MDA5), retinoic acid-inducible gene 1 (RIG-I), and mitochondrial antiviral signaling protein (MAVS), and subsequently induced IFN responses specifically in brain endothelia and epithelia of mice. Behavioral alterations were specifically dependent on brain endothelial and epithelial IFN receptor chain 1 (IFNAR). Using gene profiling, we identified that the endothelia-derived chemokine ligand CXCL10 mediated behavioral changes through impairment of synaptic plasticity. These results identified brain endothelial and epithelial cells as natural gatekeepers for virus-induced sickness behavior, demonstrated tissue specific IFNAR engagement, and established the CXCL10-CXCR3 axis as target for the treatment of behavioral changes during virus infection and type I IFN therapy."



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Body’s defenses against common viruses may mess up neurons, spark depression | Ars Technica

Getting sick is definitely a bummer. But besides feeling icky and being stuck in bed, viral infections may cause us to actually be depressed. While scientists have been clued into this connection for a while, there was little data on how everyday viral infections, like the flu, might mess with our moods.

Now, data from a new mouse study shows that common viruses may spur sadness by causing the cells that line the blood-brain barrier to release signals that hush the chatter between neurons in the area of the brain responsible for mood. The findings, published this week in the journal Immunity, may finally explain the link between infections and mental health problems, and it could point researchers towards new strategies for treating depression and other mood disorders.

Researchers have been collecting hints of the connection between mental health and infections for years. Though it was first dismissed as people simply being blue about getting sick, doctors now accept that there is a condition called “sickness behavior.” This condition is marked by cognitive deficits, drowsiness, general malaise, and other depression-like symptoms in those with an infection. Moreover, in a 2013 Danish study, researchers found that people who had been treated for a severe infection were 62 percent more likely to suffer from mood disorders. Perhaps related, those that had an autoimmune disease were 45 percent more likely to have such a mental health issue."



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Fructose alters hundreds of brain genes, which can lead to a wide range of diseases | UCLA

Fructose alters hundreds of brain genes, which can lead to a wide range of diseases | UCLA: "A range of diseases — from diabetes to cardiovascular disease, and from Alzheimer’s disease to attention deficit hyperactivity disorder — are linked to changes to genes in the brain. A new study by UCLA life scientists has found that hundreds of those genes can be damaged by fructose, a sugar that’s common in the Western diet, in a way that could lead to those diseases.

However, the researchers discovered good news as well: An omega-3 fatty acid known as docosahexaenoic acid, or DHA, seems to reverse the harmful changes produced by fructose."



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Pancreatic cancer risk linked to changes in mouth bacteria - Medical News Today

The participants were taking part in larger, ongoing studies of cancer risk, where they had been given mouthwash samples when they joined the studies. They were followed for nearly 10 years, during which any cancer diagnoses were noted.

When they analyzed the results, Prof. Ahn and colleagues found that participants whose mouth bacteria contained either of two certain types had a higher risk of developing pancreatic cancer, compared with participants whose oral microbiome showed no evidence of the microorganisms.

Specifically, they found presence of Porphyromonas gingivalis was linked to a 59% overall higher risk of developing pancreatic cancer. Similarly, presence of Aggregatibacter actinomycetemcomitans was linked to a 50% overall higher risk. Both types of bacteria are known to be associated with gum disease or periodontitis."


A Systematic Review and Meta-Analysis of the Association between Helicobacterpylori Infection and Dementia - IOS Press

A positive association between Helicobacter pylori infection and dementia has been reported, yet findings are inconsistent.

Objective:To examine the association between H. pylori infection and dementia. Methods:A literature search was performed using the databases OVID-Medline, Institute of Scientific Information Web of Science, and EMBASE. The meta-analysis was conducted using the random effects model. The primary analysis included studies in which the exposure variable was presence of H. pylori infection (yes versus no) and the outcome was incident dementia (yes versus no), which was pre-selected as the end-result of gradual cognitive decline overtime. Publication bias was explored using funnel plot and the Egger regression intercept.

Results:A total of 260 records were identified; 13 addressed cognition and/or dementia in relation to H. pylori infection, of which only seven were included in the meta-analysis. The primary analysis showed a significant positive association between H. pylori infection and dementia; pooled odds ratio 1.71 (95% CI 1.17–2.49) (pv = 0.01). No significant evidence of publication bias was found. Conclusions:H. pylori may play a role in the etiology of dementia. Identification of the biological mechanisms of such association is needed, as well as assessment of the impact of H. pylori therapy on the risk and progression of dementia."



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Bisphenol A in low doses can affect the reproductive system , obesity, and behaviour

"If rats are exposed to bisphenol A in low doses during early development it can lead to reduced sperm count, obesity and changes to breast development and behaviour. These are some of the findings of a new study from the National Food Institute, Technical University of Denmark. The results support previous animal studies, which have shown that low doses of bisphenol A can affect development of the metabolism as well as the reproductive and nervous systems."



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Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment: Immunity

 Highlights 

•Viruses induce depressive behavior and ISG15 expression at the blood-brain barrier
•IFNAR1 expression on neural cells is not involved in IFN-β-induced sickness behavior
•IFNAR1 expression on brain endothelial and epithelial cells drives behavioral changes
•Brain endothelia- and epithelia-derived CXCL10 inhibits hippocampal synaptic plasticity

Summary 

Sickness behavior and cognitive dysfunction occur frequently by unknown mechanisms in virus-infected individuals with malignancies treated with type I interferons (IFNs) and in patients with autoimmune disorders. We found that during sickness behavior, single-stranded RNA viruses, double-stranded RNA ligands, and IFNs shared pathways involving engagement of melanoma differentiation-associated protein 5 (MDA5), retinoic acid-inducible gene 1 (RIG-I), and mitochondrial antiviral signaling protein (MAVS), and subsequently induced IFN responses specifically in brain endothelia and epithelia of mice. Behavioral alterations were specifically dependent on brain endothelial and epithelial IFN receptor chain 1 (IFNAR). Using gene profiling, we identified that the endothelia-derived chemokine ligand CXCL10 mediated behavioral changes through impairment of synaptic plasticity. These results identified brain endothelial and epithelial cells as natural gatekeepers for virus-induced sickness behavior, demonstrated tissue specific IFNAR engagement, and established the CXCL10-CXCR3 axis as target for the treatment of behavioral changes during virus infection and type I IFN therapy."



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Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host|[rsquo]|s metabolism : Molecular Psychiatry

"Major depressive disorder (MDD) is the result of complex gene–environment interactions. According to the World Health Organization, MDD is the leading cause of disability worldwide, and it is a major contributor to the overall global burden of disease. However, the definitive environmental mechanisms underlying the pathophysiology of MDD remain elusive. The gut microbiome is an increasingly recognized environmental factor that can shape the brain through the microbiota-gut-brain axis. We show here that the absence of gut microbiota in germ-free (GF) mice resulted in decreased immobility time in the forced swimming test relative to conventionally raised healthy control mice. Moreover, from clinical sampling, the gut microbiotic compositions of MDD patients and healthy controls were significantly different with MDD patients characterized by significant changes in the relative abundance of Firmicutes, Actinobacteria and Bacteroidetes. Fecal microbiota transplantation of GF mice with ‘depression microbiota’ derived from MDD patients resulted in depression-like behaviors compared with colonization with ‘healthy microbiota’ derived from healthy control individuals. Mice harboring ‘depression microbiota’ primarily exhibited disturbances of microbial genes and host metabolites involved in carbohydrate and amino acid metabolism. This study demonstrates that dysbiosis of the gut microbiome may have a causal role in the development of depressive-like behaviors, in a pathway that is mediated through the host’s metabolism."



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Drop in dementia rates suggests disease can be prevented, researchers say | Society | The Guardian

Pollutants in fish inhibit human's natural defense system

 "In a new study, environmental pollutants found in fish were shown to obstruct the human body's natural defense system to expel harmful toxins. The Scripps Institution of Oceanography at UC San Diego-led research team suggests that this information should be used to better assess the human health risks from eating contaminated seafood. The study was published in the April 15 issue of the journal Science Advances."



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Recent Fast Food Consumption and Bisphenol A and Phthalates Exposures among the U.S. Population in NHANES, 2003–2010

Background:

Phthalates and bisphenol A (BPA) are widely used industrial chemicals that may adversely impact human health. Human exposure is ubiquitous and can occur through diet, including consumption of processed or packaged food.

Objective:

To examine associations between recent fast food intake and BPA and urinary metabolites of di(2-ethylhexyl) phthalate (ΣDEHPm) and diisononyl phthalate (DiNPm) among the US population.

Methods:

We combined data on 8877 participants from the National Health and Nutrition Examination Survey (NHANES 2003-2010). Using 24-hour dietary recall data, we quantified: 1) fast food intake (percent of total energy intake (TEI) from fast food); 2) fast food-derived fat intake (percent of TEI from fat in fast food); and 3) fast food intake by food group (dairy, eggs, grains, meat, and other). We examined associations between dietary exposures and urinary chemical concentrations using multivariate linear regression.

Results:

We observed evidence of a positive, dose-response relationship between fast food intake and exposure to phthalates (p-trend<0.0001) but not BPA; participants with high consumption (≥34.9% TEI from fast food) had 23.8% (95% CI: 11.9%, 36.9%) and 39.0% (95% CI: 21.9%, 58.5%) higher levels of ΣDEHPm and DiNPm, respectively, than non-consumers. Fast food-derived fat intake was also positively associated with ΣDEHPm and DiNPm (p-trend <0.0001). After adjusting for other food groups, ΣDEHPm was associated with grain and other intake, and DiNPm was associated with meat and grain intake.

Conclusion: Fast food may be a source of exposure to DEHP and DiNP. These results, if confirmed, could inform individual and regulatory exposure reduction strategies."



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Oral activity of a nature-derived cyclic peptide for the treatment of multiple sclerosis

 "Multiple sclerosis (MS) is the most common autoimmune disease affecting the central nervous system. It is characterized by auto-reactive T cells that induce demyelination and neuronal degradation. Treatment options are still limited and several MS medications need to be administered by parenteral application but are modestly effective. Oral active drugs such as fingolimod have been weighed down by safety concerns. Consequently, there is a demand for novel, especially orally active therapeutics. Nature offers an abundance of compounds for drug discovery. Recently, the circular plant peptide kalata B1 was shown to silence T-cell proliferation in vitro in an IL-2–dependent mechanism. Owing to this promising effect, we aimed to determine in vivo activity of the cyclotide [T20K]kalata B1 using the MS mouse model experimental autoimmune encephalomyelitis (EAE). Treatment of mice with the cyclotide resulted in a significant delay and diminished symptoms of EAE by oral administration. Cyclotide application substantially impeded disease progression and did not exhibit adverse effects. Inhibition of lymphocyte proliferation and the reduction of proinflammatory cytokines, in particular IL-2, distinguish the cyclotide from other marketed drugs. Considering their stable structural topology and oral activity, cyclotides are candidates as peptide therapeutics for pharmaceutical drug development for treatment of T-cell-mediated disorders."



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Mild Infection May Raise Risk for Severe Mental Illness

 "FLORENCE, Italy — Even mild infections significantly increase the risk of later developing schizophrenia and mood disorders, results of a large, population-based registry study indicate (from the Danish Register).

Regarding the prescribing of anti-infective medications as a proxy for mild infections, the team found that any prior prescription increased the risk for schizophrenia by 37% and the risk for mood disorders by 64%, fitting dose-response and temporal relationships."




Gum disease opens up the body to a host of infections | Science News

When Salomon Amar, a periodontal specialist at Boston University, began exploring links between oral bacteria and heart disease in animal studies in the late 1990s, reactions were lukewarm. “Many cardiologists thought we were a bit crazy,” he says. Skepticism still abounds, but the same molecular tools that have dramatically changed understanding of the gut microbiome are now allowing scientists to track and examine bacteria in the mouth. Advocates of a connection between the artery disease atherosclerosis and microbes are hoping to find convincing proof of their suspicions, while exploring links between ailing gums and other conditions, including cancer, arthritis, diabetes and even Alzheimer’s disease.

Antiobesity effect of Pediococcus pentosaceus LP28 on overweight subjects: a randomized, double-blind, placebo-controlled clinical trial : European Journal of Clinical Nutrition

Background/Objectives:
The population of the obese is increasing worldwide. Prevention and improvement of obesity are indispensable for decreasing the risk of metabolic disorders. We have recently shown that obesity and fatty liver are reduced by a plant-derived lactic acid bacterium, Pediococcus pentosaceus LP28 (LP28), in high-fat diet-induced obese mice. The aim of the present clinical study is to prove that LP28 is effective for reducing body fat and body weight, as shown in the experiment using mice.

Subjects/Methods:

The clinical trial was carried out as a double-blind, randomized, placebo-controlled study comprising 62 subjects (20–70 years of age, BMI 25–30 kg/m2). These subjects were randomly assigned to three groups that received living LP28, heat-killed LP28 or a placebo powder, administered orally once a day for 12 weeks.

Results:

Heat-killed LP28 reduced BMI (0.45 kg/m2, 95% CI (0.04, 0.86), P=0.035), body fat percentage (1.11%, (0.39, 1.82), P=0.002), body fat mass (1.17 kg (0.43, 1.92), P=0.004) and waist circumference (2.84 cm (0.74, 4.93), P=0.009) when compared with a placebo group. Fasting plasma glucose, HbA1c, fasting insulin, HOMA-IR and serum lipids levels did not change by either living LP28 or heat-killed LP28 intake.

Conclusions:

Heat-killed LP28 displays an antiobesity effect that reduces BMI, body fat and waist circumference, suggesting that the plant-derived lactic acid bacterium LP28 would be a promising preventive of metabolic syndrome."



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Translational Psychiatry - Regulation of prefrontal cortex myelination by the microbiota

 "The prefrontal cortex (PFC) is a key region implicated in a range of neuropsychiatric disorders such as depression, schizophrenia and autism. In parallel, the role of the gut microbiota in contributing to these disorders is emerging. Germ-free (GF) animals, microbiota-deficient throughout life, have been instrumental in elucidating the role of the microbiota in many aspects of physiology, especially the role of the microbiota in anxiety-related behaviours, impaired social cognition and stress responsivity. Here we aim to further elucidate the mechanisms of the microbial influence by investigating changes in the homeostatic regulation of neuronal transcription of GF mice within the PFC using a genome-wide transcriptome profiling approach. Our results reveal a marked, concerted upregulation of genes linked to myelination and myelin plasticity. This coincided with upregulation of neural activity-induced pathways, potentially driving myelin plasticity. Subsequent investigation at the ultrastructural level demonstrated the presence of hypermyelinated axons within the PFC of GF mice. Notably, these changes in myelin and activity-related gene expression could be reversed by colonization with a conventional microbiota following weaning. In summary, we believe we demonstrate for the first time that the microbiome is necessary for appropriate and dynamic regulation of myelin-related genes with clear implications for cortical myelination at an ultrastructural level. The microbiota is therefore a potential therapeutic target for psychiatric disorders involving dynamic myelination in the PFC."



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