$1 Million Prize for Alzheimer’s Disease Germ Announced by Dr. Leslie Norins on ALZgerm.org

Leslie Norins, MD, PhD, CEO of Alzheimer’s Germ Quest, Inc., announces a
$1 million challenge award for the scientist who provides persuasive
evidence that an infectious agent is the root cause of Alzheimer’s
disease. The three-year contest begins January 16, 2018. Details are
provided at ALZgerm.org..

Benefits of a healthy diet greater in people at high genetic risk for obesity: Genetic predisposition to obesity is no barrier to successful weight management -- ScienceDaily

The benefits of sticking to a healthy diet to prevent long term weight gain are greater in people at high genetic risk for obesity than in those with low genetic risk, finds a study in The BMJ today.
The researchers say their findings indicate that improving dietquality over time might lead to greater weight loss for people who are genetically susceptible to obesity. The study also indicates that the
genetic risk of weight gain is attenuated by improving diet quality.

Comment: In other words, certain susceptibility genes are no longer susceptibility genes when unhealthy eating is replaced by healthy eating.  

The paper is published in The British Medical Journal

Improving adherence to healthy dietary patterns, genetic risk, and long term weight gain: gene-diet interaction analysis in two prospective cohort studies

Monocyte activation detected prior to a diagnosis of schizophrenia in the US Military New Onset Psychosis Project (MNOPP)

 : Low-grade inflammation is present in some cases of schizophrenia, particularly in
the early stages of this disorder. The inflammation source is not known but may be
the result of dysbiotic processes occurring in the gut. We examined peripheral biomarkers
of bacterial translocation, soluble CD14 (sCD14) and lipopolysaccharide binding protein
(LBP), and of general inflammation, C-reactive protein (CRP), in a unique, pre-onset
study of schizophrenia. This sample was composed of 80 case-control matched pairs
of US military service members from whom blood samples were obtained at time of entry
to service, before a psychiatric diagnosis was made.

Defective cholesterol clearance limits remyelination in the aged central nervous system | Science

Age-associated decline in regeneration capacity limits the restoration of nervous system functionality after injury. In a model for demyelination, we found that old mice fail to resolve the inflammatory response initiated after myelin damage. Aged phagocytes accumulated excessive amounts of myelin debris, which triggered cholesterol crystal formation, phagolysosomal membrane rupture, and stimulated inflammasomes. Myelin debris clearance required cholesterol transporters including apolipoprotein E. Remarkably, stimulation of reverse cholesterol transport was sufficient to restore the capacity of old mice to remyelinate lesioned tissue. Thus, cholesterol-rich myelin debris can overwhelm the efflux capacity of phagocytes, resulting in a phase transition of cholesterol into crystals thereby inducing a maladaptive immune response that impedes tissue regeneration.

Artificial Sugar Trehalose Linked to Clostridium difficile Epidemics | Medicine | Sci-News.com

An artificial sugar called trehalose enhances the virulence of epidemic lineages of Clostridium difficile, a Gram-positive spore forming bacterium that causes life-threatening inflammation of the colon, according to a new study published in the journal Nature.

Hydraulic fracturing negatively impacts infant health -- ScienceDaily

Health risks increase for infants born to mothers living within 2 miles
of a hydraulic fracturing site, according to a study published Dec. 13
in Science Advances. The research team found that infants born
within a half a mile from a fracking site were 25 percent more likely to
be born at low birth weights, leaving them at greater risk of infant
mortality, ADHD, asthma, lower test scores, lower schooling attainment
and lower lifetime earnings.




Hydraulic fracturing and infant health: New evidence from Pennsylvania
Science Advances  13 Dec 2017:
Vol. 3, no. 12, e1603021

Frontiers | The Porphyromonas gingivalis/host interactome shows enrichment in GWASdb genes related to Alzheimer’s disease, diabetes and cardiovascular diseases | Frontiers in Aging Neuroscience

Periodontal disease is of established aetiology in which polymicrobial
synergistic ecology has become dysbiotic under the influence of
Porphyromonas gingivalis. Following breakdown of the host’s protective
oral tissue barriers, P. gingivalis migrates to developing inflammatory
pathologies that associate with Alzheimer’s disease (AD). Periodontal
disease is a risk factor for cardiovascular disorders (CVD), type II
diabetes mellitus (T2DM), AD and other chronic diseases, whilst T2DM
exacerbates periodontitis. This study analysed the relationship between
the P. gingivalis/host interactome and the genes identified in
genome-wide association studies (GWAS) for the aforementioned conditions
using data from GWASdb (P<1E-03) and, in some cases, from the
NCBI/EBI GWAS database (P< 1E-05). Gene expression data from
periodontitis or P. gingivalis microarray was compared to microarray
datasets from the AD hippocampus and/or from carotid artery plaques. The
results demonstrated that the host genes of the P. gingivalis
interactome were significantly enriched in genes deposited in GWASdb
genes related to cognitive disorders, AD and dementia, and its co-morbid
conditions T2DM, obesity, and CVD. The P. gingivalis/host interactome
was also enriched in GWAS genes from the more stringent NCBI-EBI
database for AD, atherosclerosis and T2DM. The misregulated genes in
periodontitis tissue or P. gingivalis infected macrophages also matched
those in the AD hippocampus or atherosclerotic plaques. Together, these
data suggest important gene/environment interactions between P.
gingivalis and susceptibility genes or gene expression changes in
conditions where periodontal disease is a contributory factor.

Building Bridges Between Infectious Disease Physicians and Psychiatrists

Complex problems require complex solutions with interdisciplinary cooperation.
When state mental hospitals were filled with mentally ill patients who
had syphilis, everyone recognized the close association between
infectious disease and psychiatric illness. In fact, in 1927, the first
Nobel prize in Psychiatry was awarded to Dr. Julius Wagner-Jauregg who
recognized the association between infections and mental illness and
introduced malaria inoculation, which proved to be very successful in
treating dementia paralytica. After the introduction of penicillin, the
gap between these two specialties widened with specialization and
fragmentation in medicine resulting in few physicians maintaining
updated capability in both infectious disease and psychiatry. Most
infectious disease physicians have very little current training in
neurochemistry, psychoimmunology, or the pathophysiology of mental
illness. Likewise, many psychiatrists have little current training in
infectious diseases and psychoimmunology.

More recently, this gap has been bridged by advances in evolutionary
medicine, a growing recognition of the significance of the microbiome,
improved brain imaging and testing capabilities and discoveries in
psychoimmunology which have greatly expanded our knowledge of the
pathophysiology of mental illness. Now, many, including the Center for
Disease and Prevention recognize chronic diseases and the mental
illnesses can stem from infectious agents.

Evidence of increased exposure to Toxoplasma gondii in individuals with recent onset psychosis but not with established schizophrenia. - PubMed - NCBI

A possible role for Toxoplasma gondii in the etiopathogenesis of
schizophrenia is supported by epidemiological studies and animal models
of infection. However, recent studies attempting to link Toxoplasma to
schizophrenia have yielded mixed results. We performed a nested
case-control study measured serological evidence of exposure to
Toxoplasma gondii in a cohort of 2052 individuals. Within this cohort, a
total of 1481 individuals had a psychiatric disorder and 571 of were
controls without a psychiatric disorder. We found an increased odds of
Toxoplasma exposure in individuals with a recent onset of psychosis (OR
2.44, 95% Confidence Interval 1.4-4.4, p < .003). On the other hand,
an increased odds of Toxoplasma exposure was not found in individuals
with schizophrenia or other psychiatric disorder who did not have a
recent onset of psychosis. By identifying the timing of evaluation as a
variable, these findings resolve discrepancies in previous studies and
suggest a temporal relationship between Toxoplasma exposure and disease
onset.

Exposure to BPA during pregnancy may cause health problems for offspring

Bisphenol A -- BPA -- used in plastic packaging and in the linings of food and beverage cans, may be passed from a mother to her offspring during pregnancy and cause changes in the gut bacteria of the offspring, according to an international team of researchers.
In a study on rabbits, the researchers observed that exposure to BPA during pregnancy caused chronic inflammation in the offspring's intestines and liver. The researchers also noted signs of increased gut permeability -- or leaky gut -- and a decrease in the diversity of gut bacteria and anti-inflammatory bacterial metabolites, such as short-chain fatty acids, said Jairam K.P. Vanamala, associate professor of food sciences, Penn State.
Leaky gut and decreased gut-bacteria diversity and metabolites are considered biomarkers -- or indicators -- of inflammation-related chronic diseases, he added.
"Obesity and inflammation-promoted chronic diseases like colon cancer and type 2 diabetes are increasing not just in America, but worldwide," said Vanamala. "We know that many types of cancers are inflammation-promoted, like colon cancer. But, we have not understood what causes inflammation in the intestine and liver. We have previously shown that food is a double-edge sword. Some foods can promote inflammation in the intestine, whereas bright-colored fruits and vegetables, like purple potatoes, can suppress intestinal inflammation. This study shows that we also need to think about the toxins in the environment."

Sulfites inhibit the growth of four species of beneficial gut bacteria at concentrations regarded as safe for food

Sulfites and other preservatives are considered food additives to limit
bacterial contamination, and are generally regarded as safe for
consumption by governmental regulatory agencies at concentrations up to
5000 parts per million (ppm). Consumption of bactericidal and
bacteriostatic drugs have been shown to damage beneficial bacteria in
the human gut and this damage has been associated with several diseases.
In the present study, bactericidal and bacteriostatic effects of two
common food preservatives, sodium bisulfite and sodium sulfite, were
tested on four known beneficial bacterial species common as probiotics
and members of the human gut microbiota. Lactobacillus species casei, plantarum and rhamnosus, and Streptococcus thermophilus
were grown under optimal environmental conditions to achieve early log
phase at start of experiments. Bacterial cultures were challenged with
sulfite concentrations ranging between 10 and 3780 ppm for six hours. To
establish a control, a culture of each species was inoculated into
media containing no sulfite preservative. By two hours of exposure, a
substantial decrease (or no increase) of cell numbers (based on OD600
readings) were observed for all bacteria types, in concentrations of
sulfites between 250–500 ppm, compared to cells in sulfite free media.
Further testing using serial dilution and drop plates identified
bactericidal effects in concentrations ranging between 1000–3780 ppm on
all the Lactobacillus species by 4 hours of exposure and bactericidal effects on S. thermophilus in 2000ppm NaHSO3 after 6 hours of exposure.

Could lupus raise dementia risk?

 The researchers identified 4,886 individuals who had received a
diagnosis of systemic lupus erythematosus , and these were matched by age and sex in a 1:5 ratio
to 24,430 people without the condition (the controls). The incidence of
dementia was assessed for each group.
The study revealed that people with SLE were 51 percent more
likely to develop dementia than people without SLE, and this association
persisted across all age groups.
Based on their results, the researchers conclude that "systemic lupus erythematosus is significantly associated with dementia."

Two new studies support the link between the gut microbiome and multiple sclerosis

Previous research has found that multiple sclerosis (MS) patients may
have a specific microbial signature in their gut microbiota that could
impact disease pathogenesis. However, it is
not known to what extent structural and functional changes in the gut
microbiota are primary contributors to MS pathogenesis and which
underlying mechanisms are involved.


A new study, led by Dr. Sergio Baranzini from the Department of
Neurology at the University of California San Francisco (USA), has found
that specific gut bacteria from multiple sclerosis patients regulate
immune responses and exacerbate MS-like symptoms in mice.


The researchers used 16S ribosomal ribonucleic acid (rRNA) gene
sequencing of stool samples from 71 untreated relapsing-remitting MS
patients and 71 healthy controls.


Although they did not find shifts in the gut microbiota structure,
specific bacterial taxa were significantly associated with MS. Both
Akkermansia muciniphila and Acinetobacter calcoaceticus were increased
in MS patients. Although the role of A. muciniphila has been extensively
studied in the context of metabolism, little is known about its role in
regulating immune responses and these results are in agreement with
previous research supporting A. muciniphila as a bacterial species that
exacerbates inflammation during infection. In contrast, MS patients
exhibited decreased levels of Parabacteroides distasonis.

Immune Cells Mistake Heart Attacks for Viral Infections

 What is it about dying cells in the heart that stimulates the immune
system? To answer this, researchers looked deep inside thousands of
individual cardiac immune cells and mapped their individual
transcriptomes using a method called single cell RNA-Seq. This led to
the discovery that after a heart attack, DNA from dying cells
masquerades as a virus and activates an ancient antiviral program called
the type I interferon response in specialized immune cells. ¬¬ The
researchers named these "interferon inducible cells (IFNICs)."


When investigators blocked the interferon response, either
genetically or with a neutralizing antibody given after the heart
attack, there was less inflammation, less heart dysfunction, and
improved survival. Specifically, blocking antiviral responses in mice
improved survival from 60 percent to over 95 percent. These findings
reveal a new potential therapeutic opportunity to prevent heart attacks
from progressing to heart failure in patients.

Here's the paper:-

IRF3 and type I interferons fuel a fatal response to myocardial infarction

Clemastine fumarate as a remyelinating therapy for multiple sclerosis (ReBUILD): a randomised, controlled, double-blind, crossover trial - The Lancet

 Background
Multiple sclerosis is a degenerative inflammatory disease of the CNS characterised by immune-mediated destruction of myelin and progressive neuroaxonal loss. Myelin in the CNS is a specialised extension of the oligodendrocyte plasma membrane and clemastine fumarate can stimulate differentiation of oligodendrocyte precursor cells in vitro, in animal models, and in human cells. We aimed to analyse the efficacy and safety of clemastine fumarate as a treatment for patients with multiple sclerosis.

Methods
We did this single-centre, 150-day, double-blind, randomised, placebo-controlled, crossover trial (ReBUILD) in patients with relapsing multiple sclerosis with chronic demyelinating optic neuropathy on stable immunomodulatory therapy. Patients who fulfilled international panel criteria for diagnosis with disease duration of less than 15 years were eligible. Patients were randomly assigned (1:1) via block randomisation using a random number generator to receive either clemastine fumarate (5·36 mg orally twice daily) for 90 days followed by placebo for 60 days (group 1), or placebo for 90 days followed by clemastine fumarate (5·36 mg orally twice daily) for 60 days (group 2). The primary outcome was shortening of P100 latency delay on full-field, pattern-reversal, visual-evoked potentials. We analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT02040298.

Findings
Between Jan 1, 2014, and April 11, 2015, we randomly assigned 50 patients to group 1 (n=25) or group 2 (n=25). All patients completed the study. The primary efficacy endpoint was met with clemastine fumarate treatment, which reduced the latency delay by 1·7 ms/eye (95% CI 0·5–2·9; p=0·0048) when analysing the trial as a crossover. Clemastine fumarate treatment was associated with fatigue, but no serious adverse events were reported.

Interpretation
To our knowledge, this is the first randomised controlled trial to document efficacy of a remyelinating drug for the treatment of chronic demyelinating injury in multiple sclerosis. Our findings suggest that myelin repair can be achieved even following prolonged damage."



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Frontiers | Selective Essential Oils from Spice or Culinary Herbs Have High Activity against Stationary Phase and Biofilm Borrelia burgdorferi | Medicine

 Although the majority of patients with acute Lyme disease can be cured with the standard 2–4 week antibiotic treatment, about 10–20% of patients continue suffering from chronic symptoms described as posttreatment Lyme disease syndrome. While the cause for this is debated, one possibility is that persister bacteria are not killed by the current Lyme antibiotics and remain active in the system. It has been reported that essential oils have antimicrobial activities and some have been used by patients with persisting Lyme disease symptoms. However, the activity of essential oils against the causative agent Borrelia burgdorferi (B. burgdorferi) has not been well studied. Here, we evaluated the activity of 34 essential oils against B. burgdorferi stationary phase culture as a model for persister bacteria. We found that not all essential oils had activity against the B. burgdorferi stationary phase culture, with top five essential oils (oregano, cinnamon bark, clove bud, citronella, and wintergreen) at a low concentration of 0.25% showing high anti-persister activity that is more active than the known persister drug daptomycin. Interestingly, some highly active essential oils were found to have excellent anti-biofilm ability as shown by their ability to dissolve the aggregated biofilm-like structures. The top three hits, oregano, cinnamon bark, and clove bud completely eradicated all viable cells without any regrowth in subculture in fresh medium, whereas but not citronella and wintergreen did not have this effect. Carvacrol was found to be the most active ingredient of oregano oil showing excellent activity against B. burgdorferi stationary phase cells, while other ingredients of oregano oil p-cymene and α-terpinene had no apparent activity. Future studies are needed to characterize and optimize the active essential oils in drug combination studies in vitro and in vivo and to address their safety and pharmacokinetic properties before they can be considered as a novel treatment of persistent Lyme disease."



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Selective Activation of Basal Forebrain Cholinergic Neurons Attenuates Polymicrobial Sepsis-Induced Inflammation via the Cholinergic Anti-Inflammat... - PubMed - NCBI

 OBJECTIVES:
Basal forebrain cholinergic neurons are proposed as a major neuromodulatory system in inflammatory modulation. However, the function of basal forebrain cholinergic neurons in sepsis is unknown, and the neural pathways underlying cholinergic anti-inflammation remain unexplored.
SUBJECTS:
Male wild-type C57BL/6 mice and ChAT-ChR2-EYFP (ChAT) transgenic mice.
INTERVENTIONS:
The cholinergic neuronal activity of the basal forebrain was manipulated optogenetically. Cecal ligation and puncture was produced to induce sepsis. Left cervical vagotomy and 6-hydroxydopamine injection to the spleen were used.

MEASUREMENTS AND MAIN RESULTS:
Photostimulation of basal forebrain cholinergic neurons induced a significant decrease in the levels of tumor necrosis factor-α and interleukin-6 in the serum and spleen. When cecal ligation and puncture was combined with left cervical vagotomy in photostimulated ChAT mice, these reductions in tumor necrosis factor-α and interleukin-6 were partly reversed. Furthermore, photostimulating basal forebrain cholinergic neurons induced a large increase in c-Fos expression in the basal forebrain, the dorsal motor nucleus of the vagus, and the ventral part of the solitary nucleus. Among them, 35.2% were tyrosine hydroxylase positive neurons. Furthermore, chemical denervation showed that dopaminergic neurotransmission to the spleen is indispensable for the anti-inflammation.

CONCLUSIONS:
These results are the first to demonstrate that selectively activating basal forebrain cholinergic neurons is sufficient to attenuate systemic inflammation in sepsis. Specifically, photostimulation of basal forebrain cholinergic neurons activated dopaminergic neurons in dorsal motor nucleus of the vagus/ventral part of the solitary nucleus, and this dopaminergic efferent signal was further transmitted by the vagus nerve to the spleen. This cholinergic-to-dopaminergic neural circuitry, connecting central cholinergic neurons to the peripheral organ, might have mediated the anti-inflammatory effect in sepsis."



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Confronted with bacteria, infected cells die so others can live, study finds -- ScienceDaily

 The immune system is contantly performing surveillance to detect foreign organisms that might do harm. But pathogens, for their part, have evolved a number of strategies to evade this detection, such as secreting proteins that hinder a host's ability to mount an immune response.

In a new study, a team of researchers led by Igor E. Brodsky of the University of Pennsylvania, identified a "back-up alarm" system in host cells that responds to a pathogen's attempt to subvert the immune system.

"In the context of an infection, the cells that are dying are talking to the other cells that aren't infected," said Brodsky, an assistant professor in the Department of Pathobiology in Penn's School of Veterinary Medicine and senior author on the study. "I don't think of it as altruistic, exactly, but it's a way for the cells that can't respond any longer to still alert their neighbors that a pathogen is present.""



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Genetic, Transcriptome, Proteomic, and Epidemiological Evidence for Blood-Brain Barrier Disruption and Polymicrobial Brain Invasion as Determinant Factors in Alzheimer’s Disease - IOS Press

Diverse pathogens are detected in Alzheimer’s disease (AD) brains. A bioinformatics survey showed that AD genome-wide association study (GWAS) genes (localized in bone marrow, immune locations and microglia) relate to multiple host/pathogen interactomes (Candida albicans, Cryptococcus neoformans, Bornavirus, Borrelia burgdorferri, cytomegalovirus, Ebola virus, HSV-1, HERV-W, HIV-1, Epstein-Barr, hepatitis C, influenza, Chlamydia pneumoniae, Porphyrymonas gingivalis, Helicobacter pylori, Toxoplasma gondii, Trypanosoma cruzi). These interactomes also relate to the AD hippocampal transcriptome and to plaque or tangle proteins. Upregulated AD hippocampal genes match those upregulated by multiple bacteria, viruses, fungi, or protozoa in immunocompetent cells. AD genes are enriched in GWAS datasets reflecting pathogen diversity, suggesting selection for pathogen resistance, as supported by the old age of AD patients, implying resistance to earlier infections. APOE4 is concentrated in regions of high parasitic burden and protects against childhood tropical infections and hepatitis C. Immune/inflammatory gain of function applies to APOE4, CR1, and TREM2 variants. AD genes are also expressed in the blood-brain barrier (BBB), which is disrupted by AD risk factors (age, alcohol, aluminum, concussion, cerebral hypoperfusion, diabetes, homocysteine, hypercholesterolemia, hypertension, obesity, pesticides, pollution, physical inactivity, sleep disruption, smoking) and by pathogens, directly or via olfactory routes to basal-forebrain BBB control centers. The BBB benefits from statins, NSAIDs, estrogen, melatonin, memantine, and the Mediterranean diet. Polymicrobial involvement is supported by upregulation of bacterial, viral, and fungal sensors/defenders in the AD brain, blood, or cerebrospinal fluid. AD serum amyloid-β autoantibodies may attenuate its antimicrobial effects favoring microbial survival and cerebral invasion leading to activation of neurodestructive immune/inflammatory processes, which may also be augmented by age-related immunosenescence. AD may thus respond to antibiotic, antifungal, or antiviral therapy."



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