324 research outputs found
On isoperimetric inequalities with respect to infinite measures
We study isoperimetric problems with respect to infinite measures on .
In the case of the measure defined by , ,
we prove that, among all sets with given measure, the ball centered at
the origin has the smallest (weighted) perimeter. Our results are then
applied to obtain Polya-Szego-type inequalities, Sobolev embeddings theorems
and a comparison result for elliptic boundary value problems.Comment: 25 page
The isoperimetric problem for a class of non-radial weights and applications
We study a class of isoperimetric problems on R+ N where the densities of the weighted volume and weighted perimeter are given by two different non-radial functions of the type |x|kxN α. Our results imply some sharp functional inequalities, like for instance, Caffarelli-Kohn-Nirenberg type inequalities
Potential Use of MALDI-ToF Mass Spectrometry for Rapid Detection of Antifungal Resistance in the Human Pathogen Candida glabrata.
The echinocandins are relatively new antifungal drugs that represent, together with the older azoles, the recommended and/or preferred agents to treat candidaemia and other forms of invasive candidiasis in human patients. If "time is of the essence" to reduce the mortality for these infections, the administration of appropriate antifungal therapy could be accelerated by the timely reporting of laboratory test results. In this study, we attempted to validate a MALDI-ToF mass spectrometry-based assay for the antifungal susceptibility testing (AFST) of the potentially multidrug-resistant pathogen Candida glabrata against anidulafungin and fluconazole. The practical applicability of the assay, reported here as MS-AFST, was assessed with a panel of clinical isolates that were selected to represent phenotypically and genotypically/molecularly susceptible or resistant strains. The data show the potential of our assay for rapid detection of antifungal resistance, although the MS-AFST assay performed at 3 h of the in vitro antifungal exposure failed to detect C. glabrata isolates with echinocandin resistance-associated FKS2 mutations. However, cell growth kinetics in the presence of anidulafungin revealed important cues about the in vitro fitness of C. glabrata isolates, which may lead to genotypic or phenotypic antifungal testing in clinical practice
Robot-mediated therapy for paretic upper limb of chronic patients following neurological injury
Objective: To evaluate the effectiveness of robot-mediated therapy targeted at the motor recovery of the upper limb in chronic patients following neurological injury
Upregulation of the Adhesin Gene EPA1 Mediated by PDR1 in Candida glabrata Leads to Enhanced Host Colonization.
Candida glabrata is the second most common Candida species causing disseminated infection, after C. albicans. C. glabrata is intrinsically less susceptible to the widely used azole antifungal drugs and quickly develops secondary resistance. Resistance typically relies on drug efflux with transporters regulated by the transcription factor Pdr1. Gain-of-function (GOF) mutations in PDR1 lead to a hyperactive state and thus efflux transporter upregulation. Our laboratory has characterized a collection of C. glabrata clinical isolates in which azole resistance was found to correlate with increased virulence in vivo. Contributing phenotypes were the evasion of adhesion and phagocytosis by macrophages and an increased adhesion to epithelial cells. These phenotypes were found to be dependent on PDR1 GOF mutation and/or C. glabrata strain background. In the search for the molecular effectors, we found that PDR1 hyperactivity leads to overexpression of specific cell wall adhesins of C. glabrata. Further study revealed that EPA1 regulation, in particular, explained the increase in adherence to epithelial cells. Deleting EPA1 eliminates the increase in adherence in an in vitro model of interaction with epithelial cells. In a murine model of urinary tract infection, PDR1 hyperactivity conferred increased ability to colonize the bladder and kidneys in an EPA1-dependent way. In conclusion, this study establishes a relationship between PDR1 and the regulation of cell wall adhesins, an important virulence attribute of C. glabrata. Furthermore, our data show that PDR1 hyperactivity mediates increased adherence to host epithelial tissues both in vitro and in vivo through upregulation of the adhesin gene EPA1. IMPORTANCE Candida glabrata is an important fungal pathogen in human diseases and is also rapidly acquiring drug resistance. Drug resistance can be mediated by the transcriptional activator PDR1, and this results in the upregulation of multidrug transporters. Intriguingly, this resistance mechanism is associated in C. glabrata with increased virulence in animal models and also with increased adherence to specific host cell types. The C. glabrata adhesin gene EPA1 is a major contributor of virulence and adherence to host cells. Here, we show that EPA1 expression is controlled by PDR1 independently of subtelomeric silencing, a known EPA1 regulation mechanism. Thus, a relationship exists between PDR1, EPA1 expression, and adherence to host cells, which is critical for efficient virulence. Our results demonstrate that acquisition of drug resistance is beneficial for C. glabrata in fungus-host relationships. These findings further highlight the challenges of the therapeutic management of C. glabrata infections in human patients
Upper Limb Spasticity Reduction Following Active Training: A Robot-Mediated Study In Patients With Chronic Hemiparesis
sion of the arm. A 3-month follow-up was performed. Results: Statistically significant improvements were found in both groups after treatment. Some differences were found in elbow motor improvement between the 2 groups. Conclusion: Comparison between groups confirms that active movement training does not result in increased hypertonia, but results in spasticity reduction in antagonist muscles by activating the reciprocal inhibition mechanism. Furthermore, robot-mediated therapy contributes to a decrease in motor impairment of the upper limbs in subjects with chronic hemiparesis, resulting in a reduction in shoulder pain
Role of the (Mn)superoxide dismutase of Enterococcus faecalis in the in vitro interaction with microglia
Enterococcus faecalis is a significant human pathogen worldwide and is responsible for severenosocomial and community-acquired infections. Although enterococcal meningitis is rare,mortality is considerable, reaching 21 %. Nevertheless, the pathogenetic mechanisms of thisinfection remain poorly understood, even though the ability of E. faecalis to avoid or survivephagocytic attack in vivo may be very important during the infection process. We previouslyshowed that the manganese-cofactored superoxide dismutase (MnSOD) SodA of E. faecalis wasimplicated in oxidative stress responses and, interestingly, in the survival within mouse peritonealmacrophages using an in vivo\u2013in vitro infection model. In the present study, we investigated therole of MnSOD in the interaction of E. faecalis with microglia, the brain-resident macrophages. Byusing an in vitro infection model, murine microglial cells were challenged in parallel with the wildtypestrain JH2-2 and its isogenic sodA deletion mutant. While both strains were phagocytosedby microglia efficiently and to a similar extent, the DsodA mutant was found to be significantlymore susceptible to microglial killing than JH2-2, as assessed by the antimicrobial protectionassay. In addition, a significantly higher percentage of acidic DsodA-containing phagosomes wasfound and these also underwent enhanced maturation as determined by the expression ofendolysosomal markers. In conclusion, these results show that the MnSOD of E. faecaliscontributes to survival of the bacterium in microglial cells by influencing their antimicrobial activity,and this could even be important for intracellular killing in neutrophils and thus for E. faecalispathogenesis
Decompressive craniectomy in severe intracranial hypertension after brain injury: early or late?
Systematic review of outcome measures of walking training using electromechanical and robotic devices in patients with stroke
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