Objective-To report clinical and immunological investigations of contactin-associated proteinlike 2 (Caspr2), an autoantigen of encephalitis and peripheral nerve hyperexcitability (PNH) previously attributed to voltage-gated potassium channels (VGKC).Methods-Clinical analysis of patients with encephalitis, PNH, or both. Immunoprecipitation and mass spectrometry were used to identify the antigen and to develop an assay with Caspr2-expressing cells. Immunoabsorption with Caspr2 and comparative immunostaining of brain and peripheral nerve of wild-type and Caspr2-null mice were used to assess antibody specificity.

Pulmonary congestion assessed by ultrasound is prevalent in ambulatory patients with chronic HF, is associated with other features of clinical congestion, and identifies those who have worse prognosis.

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This paper discusses the uptake of standardized terminology and definitions for texture modified foods and fluids. The Australian dietetic and speech-language pathology associations endorsed national standards in 2007. This project sought to determine the barriers and enablers for use of the national standards in clinical practice. Cross-sectional online surveys were developed, including open- and closed-response questions. The surveys targeted different professional groups in Australia including speech-language pathologists, dietitians, nurses, and food service personnel. Australian accredited universities were contacted to determine penetration of the standards. A total of 574 surveys were received. Sixty-five per cent of respondents indicated full implementation, 23% partial implementation, and 10% no implementation of the standards in their workplace. Speech-language pathologists and dietitians were most likely to have championed implementation of the standards. Barriers to implementation included: lack of knowledge about the standards, time, and resistance to change. Enablers included: encouragement to use the standards and 'buy-in' from stakeholders. Benefits of implementation included: consistent terminology and perceived improvements in patient safety. It was concluded that the standards have been successfully implemented in a majority of facilities and Australian universities. This study provides insight into the complexity of introducing and managing change in healthcare environments.

BackgroundNon-invasive measures that can accurately estimate cardiac output may help identify volume-responsive patients. This study seeks to compare two non-invasive measures (corrected carotid flow time and carotid blood flow) and their correlations with invasive reference measurements of cardiac output. Consenting adult patients (n = 51) at Massachusetts General Hospital cardiac catheterization laboratory undergoing right heart catheterization between February and April 2016 were included. Carotid ultrasound images were obtained concurrently with cardiac output measurements, obtained by the thermodilution method in the absence of severe tricuspid regurgitation and by the Fick oxygen method otherwise. Corrected carotid flow time was calculated as systole time/√cycle time. Carotid blood flow was calculated as π × (carotid diameter)2/4 × velocity time integral × heart rate. Measurements were obtained using a single carotid waveform and an average of three carotid waveforms for both measures.ResultsSingle waveform measurements of corrected flow time did not correlate with cardiac output (ρ = 0.25, 95% CI −0.03 to 0.49, p = 0.08), but an average of three waveforms correlated significantly, although weakly (ρ = 0.29, 95% CI 0.02–0.53, p = 0.046). Carotid blood flow measurements correlated moderately with cardiac output regardless of if single waveform or an average of three waveforms were used: ρ = 0.44, 95% CI 0.18–0.63, p = 0.004, and ρ = 0.41, 95% CI 0.16–0.62, p = 0.004, respectively.ConclusionsCarotid blood flow may be a better marker of cardiac output and less subject to measurements issues than corrected carotid flow time.Electronic supplementary materialThe online version of this article (doi:10.1186/s13089-017-0065-0) contains supplementary material, which is available to authorized users.

Objective CD4+CD25+FoxP3+ regulatory T cells (TR) are critical regulators of autoimmunity. Yet, TR are paradoxically increased in RA patients and show variable activity in human studies. Our objective is to characterize the expansion and function of TR during the initiation and progression of experimental arthritis. Methods To unequivocally identify TR, we crossed FoxP3gfp mice to K/BxN to generate arthritic mice in which TR express green fluorescence protein. We examined the expansion and function of TR and effector T cells (TE) during different stages of arthritis by flow cytometry and cell proliferation. Results In K/BxN mice, thymic selection of KRN T cells resulted in an enrichment of FoxP3+ TR. TR numbers increased during arthritis with significant increases in the spleen and draining lymph node, indicating selective tropism to sites of disease. In contrast to the in vitro unresponsiveness when cultured by themselves, substantial fractions of TR proliferated in both non-arthritic and arthritic mice. However, they also underwent greater apoptosis thereby maintaining equilibrium with TE. Similarly, enhanced TR suppressive activity during arthritis was offset by greater resistance by their TE counterparts and antigen presenting cells. Conclusion In this well established model of RA, the interplay of TE and TR in K/BxN mice recapitulated many features of human disease. We demonstrated an ordered expansion of TR during arthritis and the dynamic changes in TR and TE functions. By elucidating factors that govern TR and TE development in K/BxNgfp mice, we will gain insight into the pathophysiology and develop novel therapeutics for human RA.

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Atypical scrapie is a relatively recent discovery, and it was unknown whether it was a new phenomenon or whether it had existed undetected in the United Kingdom national flock. Before 1998, the routine statutory diagnosis of transmissible spongiform encephalopathy (TSE) in sheep relied on the presence of TSE vacuolation in the brainstem. This method would not have been effective for the detection of atypical scrapie. Currently, immunohistochemistry (IHC) and Western blot are commonly used for the differential diagnosis of classical and atypical scrapie. The IHC pattern of PrPd deposition in atypical scrapie is very different from that in classical scrapie using the same antibody. It is thus possible that because of a lack of suitable diagnostic techniques and awareness of this form of the disease, historic cases of atypical scrapie remain undiagnosed. Immunohistochemistry was performed on selected formalin-fixed, paraffin-embedded (FFPE) blocks of ovine brain from the Veterinary Laboratories Agency archives that were submitted for various reasons, including suspect neurological disorders, between 1980 and 1989. It was found that PrPd deposits in a single case were consistent with atypical scrapie. A method was developed to obtain a PrP genotype from FFPE tissues and was applied to material from this single case, which was shown to be AHQ/AHQ. This animal was a scrapie suspect from 1987, but diagnosis was not confirmed by the available techniques at that time.