Unbiased high-throughput sequencing of whole metagenome shotgun DNA libraries is a promising new approach to identifying microbes in clinical specimens, which, unlike other techniques, is not limited ...to known sequences. Unlike most sequencing applications, it is highly sensitive to laboratory contaminants as these will appear to originate from the clinical specimens. To assess the extent and diversity of sequence contaminants, we aligned 57 "1000 Genomes Project" sequencing runs from six centers against the four largest NCBI BLAST databases, detecting reads of diverse contaminant species in all runs and identifying the most common of these contaminant genera (Bradyrhizobium) in assembled genomes from the NCBI Genome database. Many of these microorganisms have been reported as contaminants of ultrapure water systems. Studies aiming to identify novel microbes in clinical specimens will greatly benefit from not only preventive measures such as extensive UV irradiation of water and cross-validation using independent techniques, but also a concerted effort to sequence the complete genomes of common contaminants so that they may be subtracted computationally.
L’intégration des caméras dans les objets de la mobilité (ordinateur portable, appareil photo, smartphone, tablette) a conduit à l’émergence de l’autoproduction audiovisuelle comme activité sociale ...(YouTube) et la didactique des langues s’approprie ces nouvelles pratiques. Les apprenants peuvent se filmer facilement en dehors de la classe dans des environnements variés et transmettre leur production orale numérique à l’enseignant. En nous appuyant sur un corpus de tutoriels audiovisuels réalisés par des étudiants en français langue étrangère, nous montrerons comment les objets de la vie quotidienne participent à la construction du sens dans l’action et constituent ainsi des ressources qui aident l’apprenant à élaborer son discours et l’enseignant à évaluer la production orale. Les apprenants choisissent de se montrer en train d’agir dans des lieux qui étaient jusque-là réservés à l’apprentissage informel (salle de bain, magasin, cuisine etc.) et réalisent un produit audiovisuel en dehors de la salle de classe. L’enseignant peut intervenir sur la vidéo par exemple en repérant des erreurs dans la production orale et en insérant des annotations sur l’image. La vidéo numérique constitue une trace sur laquelle l’enseignant et l’apprenant peuvent agir de façon différée.
The integration of cameras in the objects of mobility (laptop, camera, smartphone, tablet) led to the emergence of audiovisual self production as a social activity and the didactics of languages appropriates these new social practices. Learners can easily film themself outside the classroom in varied contexts and send their digital oral production to their teacher. Using a corpus of video tutorials produced by students in French as a foreign language, we will show how objects of everyday life participate in the construction of meaning in action and thus constitute resources shared by learners and the teacher. Learners choose to show themself in places that were previously reserved for informal learning (bathroom, kitchen, shop, etc.) and produce an audiovisual product outside the classroom. Teachers can use the video as a teaching tool by identifying learners errors and by inserting annotations on the image. Digital video then becomes a trace on which teacher and learners can act together.
Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system. Infectious triggers of MS are being actively investigated. Substantial evidence supports the involvement of ...the Epstein-Barr virus (EBV), though other viruses, bacteria, protists, and fungi are also being considered. Many links between fungi and diseases involving chronic inflammation have been found recently. Evidence linking MS and fungi is reviewed here. The HLA-DRB1*15 allele group is the most important genetic risk factor of MS, and is a risk factor in several other conditions linked to fungal infections. Many biomarkers of MS are consistent with fungal infections, such as IL-17, chitotriosidase, and antibodies against fungi. Dimethyl fumarate (DMF), first used as an industrial fungicide, was recently repurposed to reduce MS symptoms. Its mechanisms of action in MS have not been firmly established. The low risk of MS during childhood and its moderate association with herpes simplex virus type 2 suggest genital exposure to microbes (including fungi) should be investigated as a possible trigger. Molecular and epidemiological evidence support a role for infections such as EBV in MS. Though fungal infections have not been widely studied in MS, many lines of evidence are consistent with a fungal etiology. Future microbiome and serological studies should consider fungi as a possible risk factor for MS, and future clinical studies should consider the effect of fungicides other than DMF on MS symptoms.
Malassezia and Parkinson's Disease Laurence, Martin; Benito-León, Julián; Calon, Frédéric
Frontiers in neurology,
07/2019, Volume:
10
Journal Article
Peer reviewed
Open access
Parkinson's disease (PD) is a common debilitating neurodegenerative disease caused by a loss of dopamine neurons in the substantia nigra within the central nervous system (CNS). The process leading ...to this neuronal loss is poorly understood. Seborrheic dermatitis (SD) is a common benign inflammatory condition of the skin which mainly affects lipid-rich regions of the head and trunk. SD is caused by over proliferation of the lipophilic fungus
. PD and SD are strongly associated. The increased PD risk following an SD diagnosis (OR = 1.69, 95% CI 1.36, 2.1;
< 0.001) reported by Tanner and colleagues remains unexplained.
were historically considered commensals confined to the skin. However, many recent studies report finding
in internal organs, including the CNS. This raises the possibility that
might be directly contributing to PD. Several lines of evidence support this hypothesis. AIDS is causally associated with both parkinsonism and SD, suggesting that weak T cell-mediated control of commensal microbes such as
might contribute to both. Genetic polymorphisms associated with PD (
) increase availability of lipids within human cells, providing a suitable environment for
. Four
polymorphisms which increase PD risk also increase Crohn's disease risk; Crohn's disease is strongly associated with an immune response against fungi, particularly
. Finally,
hypha formation and melanin synthesis are stimulated by L-DOPA, which could promote
invasiveness of dopamine neurons, and contribute to the accumulation of melanin in these neurons. Although
's presence in the substantia nigra remains to be confirmed, if
play a role in PD etiology, antifungal drugs should be tested as a possible therapeutic intervention.
Background & Aims Ligand-gated calcium channels have been reported to be involved in the pathogenesis of inflammatory bowel disease. One family member, transient receptor potential vanilloid 4 ...(TRPV4), is activated by arachidonic acid derivatives that might be released on inflammation, yet its role in gastrointestinal inflammation has not been characterized. We investigated whether TRPV4 activation participates in intestinal inflammation and its expression and functions in the gastrointestinal tract. Methods TRPV4 expression was studied in human colon samples, human intestinal epithelial cell lines (Caco-2 and T84), and inflamed colons of mice. Calcium mobilization and cytokine release were analyzed in intestinal epithelial cells exposed to the selective TRPV4 agonist 4α-phorbol-12,13-didecanoate (4αPDD). Mice were killed 3, 6, or 24 hours after intracolonic administration of 4αPDD; inflammatory parameters were measured in their colon tissues, and paracellular colonic permeability was measured by the passage of51 Cr-EDTA from the colon lumen to the blood. Results High levels of TRPV4 were detected in Caco-2 cells and in epithelial cells of human colon tissue samples; its expression was up-regulated in colons from inflamed mice compared with noninflamed control mice. Administration of 4αPDD to Caco-2 and T84 cells caused a dose-dependent increase in intracellular calcium concentration and chemokine release. In mice, intracolonic administration of 4αPDD caused colitis to develop 3 to 6 hours later; inflammation resolved by 24 hours. Increased colonic permeability was observed in vivo 3 hours after intracolonic administration of 4αPDD. Conclusions TRPV4 is expressed and functional in intestinal epithelial cells; its activation in the gastrointestinal tract causes increases in intracellular calcium concentrations, chemokine release, and colitis.
This study investigated the effect of decaffeinated green tea extract (dGTE), with or without antioxidant nutrients, on fat oxidation, body composition and cardio-metabolic health measures in ...overweight individuals engaged in regular exercise. Twenty-seven participants (20 females, 7 males; body mass: 77.5 ± 10.5 kg; body mass index: 27.4 ± 3.0 kg·m
; peak oxygen uptake (O
): 30.2 ± 5.8 mL·kg
·min
) were randomly assigned, in a double-blinded manner, either: dGTE (400 mg·d
(-)-epigallocatechin-3-gallate (EGCG),
= 9); a novel dGTE+ (400 mg·d
EGCG, quercetin (50 mg·d
) and α-lipoic acid (LA, 150 mg·d
),
= 9); or placebo (PL,
= 9) for 8 weeks, whilst maintaining standardised, aerobic exercise. Fat oxidation ('FAT
' and steady state exercise protocols), body composition, cardio-metabolic and blood measures (serum glucose, insulin, leptin, adiponectin, glycerol, free fatty acids, total cholesterol, high HDL-c and low-density lipoprotein cholesterol LDL-c, triglycerides, liver enzymes and bilirubin) were assessed at baseline, week 4 and 8. Following 8 weeks of dGTE+, maximal fat oxidation (MFO) significantly improved from 154.4 ± 20.6 to 224.6 ± 23.2 mg·min
(
= 0.009), along with a 22.5% increase in the exercise intensity at which fat oxidation was deemed negligible (FAT
; 67.6 ± 3.6%O
,
= 0.003). Steady state exercise substrate utilisation also improved for dGTE+ only, with respiratory exchange ratio reducing from 0.94 ± 0.01 at week 4, to 0.89 ± 0.01 at week 8 (
= 0.004). This corresponded with a significant increase in the contribution of fat to energy expenditure for dGTE+ from 21.0 ± 4.1% at week 4, to 34.6 ± 4.7% at week 8 (
= 0.006). LDL-c was also lower (normalised fold change of -0.09 ± 0.06) for dGTE+ by week 8 (
= 0.038). No other significant effects were found in any group. Eight weeks of dGTE+ improved MFO and substrate utilisation during exercise, and lowered LDL-c. However, body composition and cardio-metabolic markers in healthy, overweight individuals who maintained regular physical activity were largely unaffected by dGTE.
The
genus comprises lipid-dependent yeasts that have long been associated with common skin diseases, and have recently been linked with Crohn's disease and certain cancers. Understanding
...susceptibility to diverse antimicrobial agents is crucial for identifying effective antifungal therapies. Here, we tested the efficacy of isavuconazole, itraconazole, terbinafine, and artemisinin against three
species:
,
and
. Using broth microdilution, we found antifungal properties for the two previously unstudied antimicrobials: isavuconazole and artemisinin. Overall, all
species were particularly susceptible to itraconazole, with a MIC range from 0.007 to 0.110 μg/mL.
The
genus is known to be involved in a variety of skin conditions and has recently been associated with diseases such as Crohn's disease, pancreatic ductal carcinoma, and breast cancer. This work was completed to assess susceptibility to a variety of antimicrobial drugs on three
species, in particular
, which is an abundant
species both on human skin and internal organs and has been implicated in Crohn's disease. We tested two previously unstudied drugs and developed a new testing method to overcome current limitations for measuring growth inhibition of slow-growing
strains.
Commensal gut bacteria are essential for the development and maintenance of the gut's immune system. Some bacteria strains, such as
Lactobacillus and
Bifidobacterium species, have been reported to ...provide protection from allergic and inflammatory bowel diseases. However, the interactions between these commensal bacteria and the immune system are largely unknown.
We studied the effects of a supernatant from the culture of
B breve C50 (BbC50) on the maturation, activation, and survival of human dendritic cells (DCs).
DCs were differentiated from human monocytes with IL-4 and GM-CSF for 5 days and cultured with BbC50 supernatant (BbC50
SN) or LPS for 2 days.
BbC50
SN induced DC maturation, with increase in CD83, CD86, and HLA-DR expression. We also showed, for the first time, that BbC50
SN prolonged DC survival, with high IL-10 and low IL-12 production compared with that seen in LPS-DCs. Moreover, BbC50
SN inhibited the effects of LPS on DCs, both in terms of IL-12 production and in terms of survival. The prolonged DC survival was independent of IL-10 production and nuclear factor κB pathway but was associated with an upregulation of Bcl-x
L and Phospho-Bad. Finally, BbC50
SN induced activation of Toll-like receptor 2 (TLR2)–transfected cells in contrast to TLR4-, TLR7-, and TLR9-transfected cells.
The supernatant of
B breve C50 can induce DC maturation and prolonged DC survival through TLR2, with high IL-10 production. These properties might correspond to a regulatory DC profile, which could limit the excessive T
H1 response and control the excessive T
H2 polarization observed in atopic newborns.
Backgrounds
Many autosomal dominant polycystic kidney disease (ADPKD) patients undergo nephrectomy and subsequent renal transplantation. We report our outcomes after hand‐assisted laparoscopic ...nephrectomy (HALN) where a Rutherford‐Morrison incision is used as a hand‐port site and kidney extraction site, as well the future incision site for staged transplantation.
Methods
A retrospective review was performed on all adult nephrectomies for ADPKD by the Transplant Surgery department at Westmead Hospital between June 2011 and June 2021. Outcomes were compared between HALN, laparoscopic nephrectomy (LN) and open nephrectomy (ON) including operation time, hospital length of stay (LOS), post‐operative complications, subsequent transplantation and post‐transplantation wound complications.
Results
Twenty‐two HALN, 8 LN and 5 ON were performed during the study period. Median kidney weights for HALN, LN and ON were significantly different (1575, 403, 3420 g respectively, P = 0.001). There was a significant difference in LOS between the HALN and ON (5.8 versus 9.8 days, P = 0.04), but not between HALN and LN (5.8 versus 5.1, P = 0.06). There was no significant difference for operation time (P = 0.34) and major complication rates (P = 0.58). There were 8 HALN, 5 LN and 2 ON who have had subsequent renal transplantation with one wound complication, an incisional hernia in the HALN group.
Conclusion
Our HALN is associated with a shorter LOS and similar complication rate to ON and can be efficiently performed for significantly larger kidneys than LN without a significant difference in operation time or LOS. The same Rutherford‐Morrison incision site can be used for transplantation.
We report our outcomes after hand‐assisted laparoscopic nephrectomy (HALN) where a Rutherford‐Morrison incision is used as a hand‐port site and kidney extraction site, as well the future incision site for staged transplantation. Our HALN is associated with a shorter length of stay and similar complication rate to open nephrectomy and can be efficiently performed for significantly larger kidneys than laparoscopic nephrectomy without a significant difference in operation time or length of stay. The same Rutherford‐Morrison incision site can be used for transplantation.