The oral mucosal and salivary microbial community of Behçet's syndrome and recurrent aphthous stomatitis.

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.Behçet's syndrome (BS) is a multisystem immune-related disease of unknown etiology. Recurrent aphthous stomatitis (RAS) is characterized by the presence of idiopathic oral ulceration without extraoral manifestation. The interplay between the oral microbial communities and the immune response could play an important role in the etiology and pathogenesis of both BS and RAS

Parents' Experiences Discussing Pediatric Vaccination with Healthcare Providers: A Survey of Canadian Naturopathic Patients

Parents who choose to selectively vaccinate or avoid vaccination for their children may do so at risk of compromising relations with their family physician or pediatrician. Groups that are associated with reduced rates of pedicatic vaccination, such as parents who access naturopathic care, may be particularly vulnerable to this issue.In March through September 2010, we administered a 26-item cross-sectional survey to 129 adult patients, all of whom were parents with children ≤ 16 years of age, presenting for naturopathic care in Ontario, Canada. Ninety-five parents completed the survey (response rate 74%), and only 50.5% (48 of 95) reported that their children had received all recommended vaccines. Most parents (50.5%; 48 of 95) reported feeling pressure to vaccinate from their allopathic physician and, of those who discussed vaccination with their physician, 25.9% (21 of 81) were less comfortable continuing care as a result. Five percent (4 of 81) of respondents were advised by their physician that their children would be refused care if they decided against vaccination. In our adjusted generalized linear model, feeling pressure to vaccinate (odds ratio [OR] = 3.07; 95% confidence interval [CI] = 1.14 to 8.26) or endorsing a naturopathic physician as their most trusted source of information regarding vaccination (OR = 3.57; 95% CI = 1.22 to 10.44) were associated with greater odds of having a partially vaccinated or unvaccinated child. The majority (69.6%; 32 of 46) of parent's with partially vaccinated or unvaccinated children reported a willingness to re-consider this decision.Use of naturopathic care should be explored among parents in order to identify this high-risk group and engage them in discussion regarding pediatric vaccination to encourage evidence-based, shared decision making. Physicians should ensure that discussions regarding vaccination are respectful, even if parents are determined not to vaccinate their children

Unchanged muscle fiber conduction velocity relates to mild acidosis during exhaustive bicycling

Muscle fiber conduction velocity (MFCV) has often been shown to decrease during standardized fatiguing isometric contractions. However, several studies have indicated that the MFCV may remain constant during fatiguing dynamic exercise. It was investigated if these observations can be related to the absence of a large decrease in pH and if MFCV can be considered as a good indicator of acidosis, also during dynamic bicycle exercise. High-density surface electromyography (HDsEMG) was combined with read-outs of muscle energetics recorded by in vivo 31P magnetic resonance spectroscopy (MRS). Measurements were performed during serial exhausting bouts of bicycle exercise at three different workloads. The HDsEMG recordings revealed a small and incoherent variation of MFCV during all high-intensity exercise bouts. 31P MRS spectra revealed a moderate decrease in pH at the end of exercise (~0.3 units down to 6.8) and a rapid ancillary drop to pH 6.5 during recovery 30 s post-exercise. This additional degree of acidification caused a significant decrease in MFCV during cycling immediately after the rest period. From the data a significant correlation between MFCV and [H+] ([H+] = 10−pH) was calculated (p < 0.001, Pearson’s R = −0.87). Our results confirmed the previous observations of MFCV remaining constant during fatiguing dynamic exercise. A constant MFCV is in line with a low degree of acidification, considering the presence of a correlation between pH and MFCV after further increasing acidification

Validation of the ADAMO Care Watch for step counting in older adults

Background: Accurate measurement devices are required to objectively quantify physical activity. Wearable activity monitors, such as pedometers, may serve as affordable and feasible instruments for measuring physical activity levels in older adults during their normal activities of daily living. Currently few available accelerometer-based steps counting devices have been shown to be accurate at slow walking speeds, therefore there is still lacking appropriate devices tailored for slow speed ambulation, typical of older adults. This study aimed to assess the validity of step counting using the pedometer function of the ADAMO Care Watch, containing an embedded algorithm for measuring physical activity in older adults. Methods: Twenty older adults aged ≥ 65 years (mean ± SD, 75±7 years; range, 68–91) and 20 young adults (25±5 years, range 20–40), wore a care watch on each wrist and performed a number of randomly ordered tasks: walking at slow, normal and fast self-paced speeds; a Timed Up and Go test (TUG); a step test and ascending/descending stairs. The criterion measure was the actual number of steps observed, counted with a manual tally counter. Absolute percentage error scores, Intraclass Correlation Coefficients (ICC), and Bland–Altman plots were used to assess validity. Results: ADAMO Care Watch demonstrated high validity during slow and normal speeds (range 0.5–1.5 m/s) showing an absolute error from 1.3% to 1.9% in the older adult group and from 0.7% to 2.7% in the young adult group. The percentage error for the 30-metre walking tasks increased with faster pace in both young adult (17%) and older adult groups (6%). In the TUG test, there was less error in the steps recorded for older adults (1.3% to 2.2%) than the young adults (6.6% to 7.2%). For the total sample, the ICCs for the ADAMO Care Watch for the 30-metre walking tasks at each speed and for the TUG test were ranged between 0.931 to 0.985. Conclusion: These findings provide evidence that the ADAMO Care Watch demonstrated highly accurate measurements of the steps count in all activities, particularly walking at normal and slow speeds. Therefore, these data support the inclusion of the ADAMO Care Watch in clinical applications for measuring the number of steps taken by older adults at normal, slow walking speeds

NOD2, RIP2 and IRF5 Play a Critical Role in the Type I Interferon Response to Mycobacterium tuberculosis

While the recognition of microbial infection often occurs at the cell surface via Toll-like receptors, the cytosol of the cell is also under surveillance for microbial products that breach the cell membrane. An important outcome of cytosolic recognition is the induction of IFNα and IFNβ, which are critical mediators of immunity against both bacteria and viruses. Like many intracellular pathogens, a significant fraction of the transcriptional response to Mycobacterium tuberculosis infection depends on these type I interferons, but the recognition pathways responsible remain elusive. In this work, we demonstrate that intraphagosomal M. tuberculosis stimulates the cytosolic Nod2 pathway that responds to bacterial peptidoglycan, and this event requires membrane damage that is actively inflicted by the bacterium. Unexpectedly, this recognition triggers the expression of type I interferons in a Tbk1- and Irf5-dependent manner. This response is only partially impaired by the loss of Irf3 and therefore, differs fundamentally from those stimulated by bacterial DNA, which depend entirely on this transcription factor. This difference appears to result from the unusual peptidoglycan produced by mycobacteria, which we show is a uniquely potent agonist of the Nod2/Rip2/Irf5 pathway. Thus, the Nod2 system is specialized to recognize bacteria that actively perturb host membranes and is remarkably sensitive to mycobacteria, perhaps reflecting the strong evolutionary pressure exerted by these pathogens on the mammalian immune system

Mycobacterium tuberculosis Transcriptional Adaptation, Growth Arrest and Dormancy Phenotype Development Is Triggered by Vitamin C

BACKGROUND: Tubercle bacilli are thought to persist in a dormant state during latent tuberculosis (TB) infection. Although little is known about the host factors that induce and maintain Mycobacterium tuberculosis (M. tb) within latent lesions, O(2) depletion, nutrient limitation and acidification are some of the stresses implicated in bacterial dormancy development/growth arrest. Adaptation to hypoxia and exposure to NO/CO is implemented through the DevRS/DosT two-component system which induces the dormancy regulon. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that vitamin C (ascorbic acid/AA) can serve as an additional signal to induce the DevR regulon. Physiological levels of AA scavenge O(2) and rapidly induce the DevR regulon at an estimated O(2) saturation of <30%. The kinetics and magnitude of the response suggests an initial involvement of DosT and a sustained DevS-mediated response during bacterial adaptation to increasing hypoxia. In addition to inducing DevR regulon mechanisms, vitamin C induces the expression of selected genes previously shown to be responsive to low pH and oxidative stress, triggers bacterial growth arrest and promotes dormancy phenotype development in M. tb grown in axenic culture and intracellularly in THP-1 cells. CONCLUSIONS/SIGNIFICANCE: Vitamin C mimics multiple intracellular stresses and has wide-ranging regulatory effects on gene expression and physiology of M. tb which leads to growth arrest and a 'dormant' drug-tolerant phenotype, but in a manner independent of the DevRS/DosT system. The 'AA-dormancy infection model' offers a potential alternative to other models of non-replicating persistence of M. tb and may be useful for investigating host-'dormant' M. tb interactions. Our findings offer a new perspective on the role of nutritional factors in TB and suggest a possible role for vitamin C in TB

Suboptimal Activation of Antigen-Specific CD4+ Effector Cells Enables Persistence of M. tuberculosis In Vivo

Adaptive immunity to Mycobacterium tuberculosis controls progressive bacterial growth and disease but does not eradicate infection. Among CD4+ T cells in the lungs of M. tuberculosis-infected mice, we observed that few produced IFN-γ without ex vivo restimulation. Therefore, we hypothesized that one mechanism whereby M. tuberculosis avoids elimination is by limiting activation of CD4+ effector T cells at the site of infection in the lungs. To test this hypothesis, we adoptively transferred Th1-polarized CD4+ effector T cells specific for M. tuberculosis Ag85B peptide 25 (P25TCRTh1 cells), which trafficked to the lungs of infected mice and exhibited antigen-dependent IFN-γ production. During the early phase of infection, ∼10% of P25TCRTh1 cells produced IFN-γ in vivo; this declined to <1% as infection progressed to chronic phase. Bacterial downregulation of fbpB (encoding Ag85B) contributed to the decrease in effector T cell activation in the lungs, as a strain of M. tuberculosis engineered to express fbpB in the chronic phase stimulated P25TCRTh1 effector cells at higher frequencies in vivo, and this resulted in CD4+ T cell-dependent reduction of lung bacterial burdens and prolonged survival of mice. Administration of synthetic peptide 25 alone also increased activation of endogenous antigen-specific effector cells and reduced the bacterial burden in the lungs without apparent host toxicity. These results indicate that CD4+ effector T cells are activated at suboptimal frequencies in tuberculosis, and that increasing effector T cell activation in the lungs by providing one or more epitope peptides may be a successful strategy for TB therapy

Defective folliculogenesis in female mice lacking Vaccinia-related kinase 1

The Vaccinia-related kinase 1(VRK1), which is generally implicated in modulating cell cycle, plays important roles in mammalian gametogenesis. Female infertility in VRK1-deficient mice was reported to be caused by defective meiotic progression in oocyte at postovulatory stage. VRK1 roles in folliculogenesis, however, remain largely unknown. Here, accurate quantification of folliculogenesis is performed by a direct visualization of ‘intact’ ovary in 3-dimensions (3-D) using a synchrotron X-ray microtomography. In VRK1-deficient ovaries, the numbers of pre-antral and antral follicles are significantly reduced by 38% and 46%, respectively, comparing to control. The oocytes volumes in antral and Graffian follicles also decrease by 42% and 37% in the mutants, respectively, indicating defects in oocyte quality at preovulatory stage. Genetic analysis shows that gene expressions related to folliculogenesis are down-regulated in VRK1-deficient ovaries, implying defects in folliculogenesis. We suggest that VRK1 is required for both follicle development and oocyte growth in mammalian female reproduction system