822 research outputs found

    Neurobiological mechanisms of TENS-induced analgesia

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    Pain inhibition by additional somatosensory input is the rationale for the widespread use of Transcutaneous Electrical Nerve Stimulation (TENS) to relieve pain. Two main types of TENS produce analgesia in animal models: high-frequency (~50–100 Hz) and low-intensity ‘conventional’ TENS, and low-frequency (~2–4 Hz) and highintensity ‘acupuncture-like’ TENS. However, TENS efficacy in human participants is debated, raising the question of whether the analgesic mechanisms identified in animal models are valid in humans. Here, we used a shamcontrolled experimental design to clarify the efficacy and the neurobiological effects of ‘conventional’ and ‘acupuncture-like’ TENS in 80 human volunteers. To test the analgesic effect of TENS we recorded the perceptual and brain responses elicited by radiant heat laser pulses that activate selectively Aδ and C cutaneous nociceptors. To test whether TENS has a long-lasting effect on brain state we recorded spontaneous electrocortical oscillations. The analgesic effect of ‘conventional’ TENS was maximal when nociceptive stimuli were delivered homotopically, to the same hand that received the TENS. In contrast, ‘acupuncture-like’ TENS produced a spatially-diffuse analgesic effect, coupled with long-lasting changes both in the state of the primary sensorimotor cortex (S1/ M1) and in the functional connectivity between S1/M1 and the medial prefrontal cortex, a core region in the descending pain inhibitory system. These results demonstrate that ‘conventional’ and ‘acupuncture-like’ TENS have different analgesic effects, which are mediated by different neurobiological mechanisms

    Inflammatory cytokines and biofilm production sustain Staphylococcus aureus outgrowth and persistence: A pivotal interplay in the pathogenesis of Atopic Dermatitis

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    Individuals with Atopic dermatitis (AD) are highly susceptible to Staphylococcus aureus colonization. However, the mechanisms driving this process as well as the impact of S. aureus in AD pathogenesis are still incompletely understood. In this study, we analysed the role of biofilm in sustaining S. aureus chronic persistence and its impact on AD severity. Further we explored whether key inflammatory cytokines overexpressed in AD might provide a selective advantage to S. aureus. Results show that the strength of biofilm production by S. aureus correlated with the severity of the skin lesion, being significantly higher (P < 0.01) in patients with a more severe form of the disease as compared to those individuals with mild AD. Additionally, interleukin (IL)-β and interferon γ (IFN-γ), but not interleukin (IL)-6, induced a concentration-dependent increase of S. aureus growth. This effect was not observed with coagulase-negative staphylococci isolated from the skin of AD patients. These findings indicate that inflammatory cytokines such as IL1-β and IFN-γ, can selectively promote S. aureus outgrowth, thus subverting the composition of the healthy skin microbiome. Moreover, biofilm production by S. aureus plays a relevant role in further supporting chronic colonization and disease severity, while providing an increased tolerance to antimicrobials

    Synthetic long oligonucleotides to generate artificial templates for use as positive controls in molecular assays: drug resistance mutations in influenza virus as an example

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    <p>Abstract</p> <p>Background</p> <p>Positive controls are an integral component of any sensitive molecular diagnostic tool, but this can be affected, if several mutations are being screened in a scenario of a pandemic or newly emerging disease where it can be difficult to acquire all the necessary positive controls from the host. This work describes the development of a synthetic oligo-cassette for positive controls for accurate and highly sensitive diagnosis of several mutations relevant to influenza virus drug resistance.</p> <p>Results</p> <p>Using influenza antiviral drug resistance mutations as an example by employing the utility of synthetic paired long oligonucleotides containing complementary sequences at their 3' ends and utilizing the formation of oligonucleotide dimers and DNA polymerization, we generated ~170bp dsDNA containing several known specific neuraminidase inhibitor (NAI) resistance mutations. These templates were further cloned and successfully applied as positive controls in downstream assays.</p> <p>Conclusion</p> <p>This approach significantly improved the development of diagnosis of resistance mutations in terms of time, accuracy, efficiency and sensitivity, which are paramount to monitoring the emergence and spread of antiviral drug resistant influenza strains. Thus, this may have a significantly broader application in molecular diagnostics along with its application in rapid molecular testing of all relevant mutations in an event of pandemic.</p

    Chromosome 2p14 Is Linked to Susceptibility to Leprosy

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    BACKGROUND: A genetic component to the etiology of leprosy is well recognized but the mechanism of inheritance and the genes involved are yet to be fully established. METHODOLOGY: A genome-wide single nucleotide polymorphism (SNP) based linkage analysis was carried out using 23 pedigrees, each with 3 to 7 family members affected by leprosy. Multipoint parametric and non-parametric linkage analyses were performed using MERLIN 1.1.1. PRINCIPAL FINDINGS: Genome-wide significant evidence for linkage was identified on chromosome 2p14 with a heterogeneity logarithm of odds (HLOD) score of 3.51 (rs1106577) under a recessive model of inheritance, while suggestive evidence was identified on chr.4q22 (HLOD 2.92, rs1349350, dominant model), chr. 8q24 (HLOD 2.74, rs1618523, recessive model) and chr.16q24 (HLOD 1.93, rs276990 dominant model). Our study also provided moderate evidence for a linkage locus on chromosome 6q24-26 by non-parametric linkage analysis (rs6570858, LOD 1.54, p = 0.004), overlapping a previously reported linkage region on chromosome 6q25-26. CONCLUSION: A genome-wide linkage analysis has identified a new linkage locus on chromosome 2p14 for leprosy in Pedigrees from China

    Measurement of CP-violation asymmetries in D0 to Ks pi+ pi-

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    We report a measurement of time-integrated CP-violation asymmetries in the resonant substructure of the three-body decay D0 to Ks pi+ pi- using CDF II data corresponding to 6.0 invfb of integrated luminosity from Tevatron ppbar collisions at sqrt(s) = 1.96 TeV. The charm mesons used in this analysis come from D*+(2010) to D0 pi+ and D*-(2010) to D0bar pi-, where the production flavor of the charm meson is determined by the charge of the accompanying pion. We apply a Dalitz-amplitude analysis for the description of the dynamic decay structure and use two complementary approaches, namely a full Dalitz-plot fit employing the isobar model for the contributing resonances and a model-independent bin-by-bin comparison of the D0 and D0bar Dalitz plots. We find no CP-violation effects and measure an asymmetry of ACP = (-0.05 +- 0.57 (stat) +- 0.54 (syst))% for the overall integrated CP-violation asymmetry, consistent with the standard model prediction.Comment: 15 page

    Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

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    The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

    Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

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    The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO
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