Electrophysiological characterisation of envelope-following responses

IntroductionThe auditory ability to discriminate rapid changes in the envelope of language sounds is essential for speech comprehension. This ability is deteriorated in some neurological diseases such as multiple sclerosis, auditory neuropathy, sensorineural hearing loss, presbycusis and primary developmental language disorder. Envelope-following responses (EFRs) in humans are useful in objective measurement of temporal processing in the auditory nervous system.ObjectivesTo evaluate EFRs in healthy younger subjects and to investigate the effects of subject states on the EFRs recorded.MethodsEleven young subjects were included; six of them were awake and five were asleep. EFRs were evoked by white noise carrier stimuli with a sweep of modulation frequencies from 20 to 200 Hz presented at 50 dB HL.ResultsThe EFRs we recorded were similar in all subjects. There were two principal components. During both subject sleep and wakefulness, the first component (located between 30-50 Hz) was significantly larger than the second component (located between 80-110 Hz). There was also a significant effect of sleep on the EFR amplitude for the modulation frequencies between 88-110, 155-165 and 190-200 Hz. However, there were no significant effects of sleep on the principal EFR components.ConclusionsThese results corroborate the usefulness of the EFR technique for objective measurement of human auditory temporal processing.     

Multiple sclerosis: specificity of MR for diagnosis

The specificity of magnetic resonance (MR) imaging in the diagnosis of multiple sclerosis (MS) has not been measured systematically. Conventional MR head images with sagittal localizer and axial multiple-echo sequences with long repetition times were obtained in 92 patients with clinically verified MS (Schumacher criteria), 100 healthy volunteers, 60 subjects with hypertension, and eight patients with dementia. Two readers, without the aid of any clinical or demographic information, classified each of the 260 studies as MS or not MS. The readers classified the studies again after being supplied with the subjects' ages and sex. True-negative and true-positive diagnoses of MS were tabulated. The specificity of the MR diagnosis of MS (true-negative results in proportion to all non-MS studies) was 95%-99% with all the control groups included. There is a small risk of misinterpreting incidental periventricular white matter foci as plaques of MS in MR studies.     

In Vivo Discrimination of Type 3 Secretion System-Positive and -Negative Pseudomonas aeruginosa via a Caspase-1-Dependent Pathway

Microbe-associated molecular patterns are recognized by Toll-like receptors of the innate immune system. This recognition enables a rapid response to potential pathogens but does not clearly provide a way for the innate immune system to discriminate between virulent and avirulent microbes. We find that pulmonary infection of mice with type 3 translocation-competent Pseudomonas aeruginosa triggers a rapid inflammatory response, while infection with isogenic translocation-deficient mutants does not. Discrimination between translocon-positive and -negative bacteria requires caspase-1 activity in bone marrow-derived cells and interleukin-1 receptor signaling. Thus, the activation of caspase-1 by bacteria expressing type 3 secretion systems allows for rapid recognition of bacteria expressing conserved functions associated with virulence.The innate immune system provides a means for vertebrate and invertebrate animals to respond rapidly to potential bacterial, viral, or protozoan pathogens. Unlike the B- and T-cell receptors of the adaptive immune system, the receptors that trigger innate immune responses are germ line encoded and recognize molecular patterns common to microbes but absent from the host (20). Although these pattern recognition receptors, as exemplified by Toll-like receptors (TLRs), can discriminate between host and microbe, the microbial-associated molecular patterns that they recognize are expressed by both pathogenic microorganisms and minimally virulent commensal or environmental microbes. Much effort has been devoted, therefore, to understanding how hosts limit inflammatory responses to most microorganisms while retaining the ability to respond appropriately to a potential pathogen (45).Macrophages mount a proinflammatory response to a variety of Gram-negative and Gram-positive bacteria via inflammasome activation (4). Although the bacterial triggers of inflammasome activation are incompletely characterized, monomeric flagellin present in the macrophage cytosol strongly activates the inflammasome via the adaptor IPAF/Nlrc4 (29). However, flagellin-independent signaling pathways for inflammasome activation via IPAF/Nlrc4 and other cytosolic adaptors also exist, as nonflagellated bacteria trigger robust inflammasome activation (43, 44). The molecular trigger for inflammasome activation in this situation remains unknown. However, Gram-negative organisms lacking a functional type 3 secretion apparatus do not activate the macrophage inflammasome (4), suggesting that some component of this apparatus (or a ligand that it translocates into the cell) may be sensed directly or indirectly. As these specialized protein secretion/translocation systems are frequently required for bacterial virulence, the inflammasome response is thus directed to a broadly conserved bacterial structure or function that is linked to pathogenesis.The Gram-negative pathogen Pseudomonas aeruginosa is capable of both acutely infecting and persistently colonizing the human respiratory tract (28). Rapid neutrophil recruitment to the airways appears to be a critical determinant in controlling P. aeruginosa replication in the lungs following acute infection (22, 32). P. aeruginosa expresses a type 3 secretion system (T3SS) that has been associated with increased virulence in murine pneumonia models and with worse clinical outcomes in human patients with ventilator-associated pneumonia (15, 38). However, a substantial proportion of P. aeruginosa clinical strains recovered from patients (with or without cystic fibrosis) no longer express a functional T3SS (19, 34). We asked whether the presence or absence of a T3SS, in otherwise isogenic P. aeruginosa strains, affected the initial host response to bacterial infection.