Brofunder1596
Clostridioides difficile is a gram-positive, spore-forming anaerobic bacterium, and the leading cause of antibiotic-associated diarrhea worldwide. During C. difficile infection, spores germinate in the presence of bile acids into vegetative cells that subsequently colonize the large intestine and produce toxins. In this study, we demonstrated that C. difficile spores can universally adhere to, and be phagocytosed by, murine macrophages. Only spores from toxigenic strains were able to significantly stimulate the production of inflammatory cytokines by macrophages and subsequently induce significant cytotoxicity. Spores from the isogenic TcdA and TcdB double mutant induced significantly lower inflammatory cytokines and cytotoxicity in macrophages, and these activities were restored by pre-exposure of the spores to either toxins. These findings suggest that during sporulation, spores might be coated with C. difficile toxins from the environment, which could affect C. difficile pathogenesis in vivo.The relevance of contextual factors in shaping neural mechanisms underlying visceral pain-related fear learning remains elusive. However, benign interoceptive sensations, which shape patients' clinical reality, may context-dependently become conditioned predictors of impending visceral pain. In a novel context-dependent interoceptive conditioning paradigm, we elucidated the putative role of the central fear network in the acquisition and extinction of pain-related fear induced by interoceptive cues and pain-predictive contexts. In this fMRI study involving rectal distensions as a clinically-relevant model of visceroception, N = 27 healthy men and women underwent differential conditioning. During acquisition training, visceral sensations of low intensity as conditioned stimuli (CS) predicted visceral pain as unconditioned stimulus (US) in one context (Con+), or safety from pain in another context (Con-). During extinction training, interoceptive CS remained unpaired in both contexts, which were operationalizedvoidance behavior, with implications for disorders of the gut-brain axis.Conceptual knowledge allows the categorisation of items according to their meaning beyond their physical similarities. This ability to respond to different stimuli (e.g., a leek, a cabbage, etc.) based on similar semantic representations (e.g., belonging to the vegetable category) is particularly important for language processing, because word meaning and the stimulus form are unrelated. The neural basis of this core human ability is debated and is complicated by the strong reliance of most neural measures on explicit tasks, involving many non-semantic processes. Here we establish an implicit method, i.e., fast periodic visual stimulation (FPVS) coupled with electroencephalography (EEG), to study neural conceptual categorisation processes with written word stimuli. Fourteen neurotypical participants were presented with different written words belonging to the same semantic category (e.g., different animals) alternating at 4 Hz rate. Words from a different semantic category (e.g., different cities) appeared every 4 stimuli (i.e., at 1 Hz). Following a few minutes of recording, objective electrophysiological responses at 1 Hz, highlighting the human brain's ability to implicitly categorize stimuli belonging to distinct conceptual categories, were found over the left occipito-temporal region. Topographic differences were observed depending on whether the periodic change involved living items, associated with relatively more ventro-temporal activity as compared to non-living items associated with relatively more dorsal posterior activity. Overall, this study demonstrates the validity and high sensitivity of an implicit frequency-tagged marker of word-based semantic memory abilities.Olfaction could prove to be an early marker of neurodegenerative diseases, including Alzheimer's and Parkinson's diseases. To use olfaction for disease diagnosis, elucidating the standard olfactory functions in healthy humans is necessary. However, the olfactory function in the human brain is less frequently assessed because of methodological difficulties associated with olfactory-related cerebral areas. Using ultra-high fields (UHF), functional magnetic resonance imaging (fMRI) with high spatial resolution and sensitivity may allow for the measurement of activation in the cerebral areas. Perifosine inhibitor This study aimed to apply 7-Tesla fMRI to assess olfactory function in the human brain by exposing individuals to four different odorants for 8 s. We found that olfactory stimulation mainly activated the piriform and orbitofrontal cortex in addition to the amygdala. Among these regions, univariate fMRI analysis indicated that subjective odor intensity significantly correlated with the averaged fMRI signals in the piriform cortex but not with subjective hedonic tone in any region. In contrast, multivariate fMRI analysis showed that subjective hedonic tone could be discriminated from the fMRI response patterns in the posterior orbitofrontal cortex. Thus, the piriform cortex is mainly associated with subjective odor intensity, whereas the posterior orbitofrontal cortex are involved in the discrimination of the subjective hedonic tone of the odorant. UHF-fMRI may be useful for assessing olfactory function in the human brain.Many magnetic resonance imaging (MRI) measures are being studied longitudinally to explore topics such as biomarker detection and clinical staging. A pertinent concern to longitudinal work is MRI scanner upgrades. When upgrades occur during the course of a longitudinal MRI neuroimaging investigation, there may be an impact on the compatibility of pre- and post-upgrade measures. Similarly, subject motion is another issue that may be detrimental to MRI work and embedding volumetric navigators (vNavs) within acquisition sequences has emerged as a technique that allows for prospective motion correction. Our research group recently underwent an upgrade from a Siemens MAGNETOM 3T Tim Trio system to a Siemens MAGNETOM 3T Prisma Fit system. The goals of the current work were to 1) investigate the impact of this upgrade on commonly used structural imaging measures and proton magnetic resonance spectroscopy indices ("Prisma Upgrade protocol") and 2) examine structural imaging measures in a sequence with vNavs alongside a standard acquisition sequence ("vNav protocol"). While high reliability was observed for most of the investigated MRI outputs, suboptimal reliability was observed for certain indices. Across the scanner upgrade, increases in frontal, temporal, and cingulate cortical thickness (CT) and thalamus volume, along with decreases in parietal CT and amygdala, globus pallidus, hippocampus, and striatum volumes, were observed. No significant impact of the upgrade was found in 1H-MRS analyses. Further, CT estimates were found to be larger in MPRAGE acquisitions compared to vNav-MPRAGE acquisitions mainly within temporal areas, while the opposite was found mostly in parietal brain regions. The results from this work should be considered in longitudinal study designs and comparable prospective motion correction investigations are warranted in cases of marked head movement.
This study evaluated the prognostic significance of cardiac magnetic resonance myocardial feature tracking (CMR-FT) in patients with Brugada syndrome (BrS) to detect subclinical alterations and predict major adverse events (MAE).
CMR was performed in 106 patients with BrS and 25 healthy controls. Biventricular global strain analysis was assessed using CMR-FT. Patients were followed over a median of 11.6 [8.8±13.8] years.
The study cohort was subdivided according to the presence of a spontaneous type 1 ECG (sECG) into sBrS (BrS with sECG, n=34 (32.1%)) and diBrS (BrS with drug-induced type 1 ECG, n=72 (67.9%)). CMR-FT revealed morphological differences between sBrS and diBrS patients with regard to right ventricular (RV) strain (circumferential (%) (sBrS-7.9±2.9 vs diBrS - 9.5±3.1, p=0.02) and radial (%) (sBrS 12.0±4.3 vs diBrS 15.4±5.4, p=0.004)). During follow-up, MAE occurred in 11 patients (10.4%). Multivariable analysis was performed to identify independent predictors for the occurrence of events duh reflects electrical vulnerability.
To analyze the spectrum of ophthalmologic manifestations in a large sample of children with congenital Zika syndrome (CZS) in Brazil.
The medical records of infants born in the states of Pernambuco, Bahia, and Rio de Janeiro, Brazil, between December 2015 and December 2016 with clinical manifestations of CZS and positive reverse transcription polymerase-chain-reaction (RT-PCR) and/or serology for the Zika virus were reviewed retrospectively. Data were collected from the record of the first ophthalmological assessment, performed on admission. Children with other congenital infectious diseases, genetic conditions, and incomplete medical records were excluded.
A total of 469 infants (242 female [51.6%]) were included. Mean age at examination was 5.0±7.1months (range, 0.0-36.0months). Of the 469 infants, 197 (42.0%) were from Rio de Janeiro, 144 (30.7%) from Pernambuco, and 128 (27.3%) from Bahia States. Microcephaly at birth was detected in 214 (45.6%) children; 62 cases (29.0%) were severe. Pernambuco had significantly more children born with microcephaly compared with Bahia and Rio de Janeiro (P<0.001). Ocular manifestations were found in 269 of 938 eyes (28.7%; 148/469 children [31.6%]). The main ocular alterations were optic nerve pallor in 122 of 938 eyes (13.0%), focal pigment mottling in 112 eyes (11.9%), and chorioretinal scars in 101 eyes (10.8%). A higher prevalence of ocular manifestations was seen in Pernambuco (P<0.001). No microcephaly was observed in 252 of 466 children (54.1%); of these, 19 children (7.5%) had funduscopic findings.
One-third of children with CZS had ocular manifestations. Children from Pernambuco were more affected. Ocular abnormalities were found in 7.5% of children without microcephaly.
One-third of children with CZS had ocular manifestations. Children from Pernambuco were more affected. Ocular abnormalities were found in 7.5% of children without microcephaly.
The flipped-classroom involves watching prerecorded lectures at home followed by group learning exercises within the classroom. This study compares the flipped classroom approach with the traditional classroom for teaching horizontal strabismus didactics in ophthalmology residency.
In this multicenter, randomized controlled survey study from October 2017 to July 2018, 110 ophthalmology residents were taught esotropia and exotropia sequentially, randomized by order and classroom style. Flipped classroom participants were assigned a preclass video lecture prior to the in-class case-based activity. The traditional classroom included a preparatory reading assignment and an in-person lecture. Residents completed three identical 5-question assessments (pretest, post-test, and 3-month retention) and surveys for each classroom. The primary outcome measured residents' preferences for classroom styles; the secondary outcome compared knowledge acquisition.
In our study cohort, the flipped classroom resulted in greater at-home preparation than the traditional classroom (P=0.
