Plos One
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Vaccination against tuberculosis (TB) should provide long-term protective immunity against Mycobacterium tuberculosis (M.tb). The current TB vaccine, Bacille Calmette-Guerin (BCG), protects against disseminated childhood TB, but protection against lung TB in adolescents and adults is variable and mostly poor. One potential reason for the limited durability of protection may be waning of immunity through gradual attrition of BCG-induced T cells. We determined if a MVA85A viral-vector boost could enhance the durability of mycobacteria-specific T cell responses above those induced by BCG alone. ⋯ MVA85A induces remarkably durable T cell responses in immunocompetent persons. However, results from a recent phase IIb trial of MVA85A, conducted in infants from the same geographic area and study population, showed no vaccine efficacy, suggesting that these durable T cell responses do not enhance BCG-induced protection against TB in infants.
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Randomized Controlled Trial
Effects of pressure support ventilation mode on emergence time and intra-operative ventilatory function: a randomized controlled trial.
We tested the hypothesis that pressure-support ventilation (PSV) allows a reduction in emergence time and laryngeal mask airway (LMA) removal time after general anesthesia compared to volume-controlled mechanical ventilation (CMV). Because spontaneous breathing (SB) is often used with LMA under general anesthesia, patients were allocated randomly to three groups (CMV, SB and PSV). Thirty-six consecutive ASA I-II patients scheduled for knee arthroscopic surgery under general anesthesia with a LMA and breathing throughout the ventilator circuit were included. Hemodynamic and ventilatory variables were recorded before and 10-min after general anesthesia-induction, at the surgical incision, at the end of anaesthetic drugs infusion and when the patient was totally awake (which defines emergence time). LMA removal time, drug consumption were recorded at the end of the surgical procedure. Leak fraction around the LMA was also evaluated. LMA removal time was significantly higher in the CMV-group (18 ± 6 min) compared to both SB (8 ± 4 min) and PSV (7 ± 4 min, P < 0.05) groups as well as for emergence time: CMV-group (32 ± 12 min), SB (17 ± 7 min) and PSV (13 ± 6 min, P < 0.05) groups. Total propofol consumption was significantly lower in the PSV-group (610 ± 180 mg) than in both CMV (852 ± 330 mg) and SB (734 ± 246 mg, P < 0.05) groups. Air leaks around the LMA was significantly higher in the CMV-group than in the SB and PSV groups (16% vs 3% and 7%, all P<0.05). In conclusion, in knee arthroscopic surgery, in comparison to CMV, PSV use during general anesthesia in unparalyzed patients decreases LMA removal time, propofol consumption and leaks around LMA while improving ventilatory variables without adverse effects.
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The canonical Wnt signaling pathway controls normal embryonic development, cellular proliferation and growth, and its aberrant activity results in human carcinogenesis. The core component in regulation of this pathway is β-catenin, but molecular regulation mechanisms of β-catenin stability are not completely known. Here, our recent studies have shown that KCTD1 strongly inhibits TCF/LEF reporter activity. ⋯ Moreover, KCTD1 suppressed the expression of endogenous Wnt downstream genes and transcription factor AP-2α. Finally, we found that Wnt pathway member APC and tumor suppressor p53 influence KCTD1-mediated downregulation of β-catenin. These results suggest that KCTD1 functions as a novel inhibitor of Wnt signaling pathway.
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The complex regional pain syndrome (CRPS) is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. ⋯ The same test applied to the "flipped" data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control.
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HIV sensory neuropathy and distal neuropathic pain (DNP) are common, disabling complications associated with combination antiretroviral therapy (cART). We previously associated iron-regulatory genetic polymorphisms with a reduced risk of HIV sensory neuropathy during more neurotoxic types of cART. We here evaluated the impact of polymorphisms in 19 iron-regulatory genes on DNP in 560 HIV-infected subjects from a prospective, observational study, who underwent neurological examinations to ascertain peripheral neuropathy and structured interviews to ascertain DNP. ⋯ Several of the same iron-regulatory-gene polymorphisms, including ACO1 rs2026739, were also associated with severity of DNP (all p<0.05). Common polymorphisms in iron-management genes are associated with DNP and with DNP severity in HIV-infected persons receiving cART. Consistent risk estimates across population subgroups and persistence of the ACO1 rs2026739 association after adjustment for multiple testing suggest that genetic variation in iron-regulation and transport modulates susceptibility to DNP.