Growth Hormone (GH)-Releasing Peptide Stimulation of GH Release from Human Somatotroph Adenoma Cells: Interaction with GH-Releasing Hormone, Thyrotropin- Releasing Hormone, and Octreotide.

The synthetic hexapeptide GH-releasing peptide (GHRP; His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) specifically stimulates GH secretion in humans in vivo and in animals in vitro and in vivo via a still unknown receptor and mechanism. To determine the effect of GHRP on human somatotroph cells in vitro, we stimulated cell cultures derived from 12 different human somatotroph adenomas with GHRP alone and in combination with GH-releasing hormone (GHRH), TRH, and the somatostatin analog octreotide. GH secretion of all 12 adenoma cultures could be stimulated with GHRP, whereas GHRH was active only in 6 adenoma cultures. In GHRH-responsive cell cultures, simultaneous application of GHRH and GHRP had an additive effect on GH secretion. TRH stimulated GH release in 4 of 7 adenoma cultures; in TRH-responsive cell cultures there was also an additive effect of GHRP and TRH on GH secretion. In 5 of 9 adenoma cultures investigated, octreotide inhibited basal GH secretion. In these cell cultures, GHRP-induced GH release was suppressed by octreotide. In 5 of 5 cases, the protein kinase-C inhibitor phloretin partly inhibited GHRP-stimulated GH release, but not basal GH secretion. In summary, GH secretion was stimulated by GHRP in all somatotroph adenomas investigated, indicating that its unknown receptor and signaling pathway are expressed more consistently in somatotroph adenoma cells than those for GHRH, TRH, and somatostatin. Our data give further evidence that GHRP-stimulated GH secretion is mediated by a receptor different from that for GHRH or TRH, respectively, and that protein kinase-C is involved in the signal transduction pathway. Because human somatotroph adenoma cell cultures respond differently to various neuropeptides (GHRH, TRH, somatostatin, and others), they provide a model for further investigation of the mechanism of action of GHRP-induced GH secretion

Susceptibility of swine to H5 and H7 low pathogenic avian influenza viruses

Citation: Balzli, C., Lager, K., Vincent, A., Gauger, P., Brockmeier, S., Miller, L., . . . Swayne, D. E. (2016). Susceptibility of swine to H5 and H7 low pathogenic avian influenza viruses. Influenza and other Respiratory Viruses. doi:10.1111/irv.12386Background: The ability of pigs to become infected with low pathogenic avian influenza (LPAI) viruses and then generate mammalian adaptable influenza A viruses is difficult to determine. Yet, it is an important link to understanding any relationship between LPAI virus ecology and possible epidemics among swine and/or humans. Objectives: Assess susceptibility of pigs to LPAI viruses found within the United States and their direct contact transmission potential. Methods: Pigs were inoculated with one of ten H5 or H7 LPAI viruses selected from seven different bird species to test infectivity, virulence, pathogenesis, and potential to transmit virus to contact pigs through histological, RRT-PCR and seroconversion data. Results: Although pigs were susceptible to infection with each of the LPAI viruses, no clinical disease was recognized in any pig. During the acute phase of the infection, minor pulmonary lesions were found in some pigs and one or more pigs in each group were RRT-PCR-positive in the lower respiratory tract, but no virus was detected in upper respiratory tract (negative nasal swabs). Except for one group, one or more pigs in each LPAI group developed antibody. No LPAI viruses transmitted to contact pigs. Conclusions: LPAI strains from various bird populations within the United States are capable of infecting pigs. Although adaptability and transmission of individual strains seem unlikely, the subclinical nature of the infections demonstrates the need to improve sampling and testing methods to more accurately measure incidence of LPAI virus infection in pigs, and their potential role in human-zoonotic LPAI virus dynamics. © 2016 John Wiley & Sons Ltd

A Music-Related Quality of Life measure to guide music rehabilitation for adult CI users

Purpose: A music-related quality of life (MuRQoL) questionnaire was developed for the evaluation of music rehabilitation for adult cochlear implant (CI) users. The present studies were aimed at refinement and validation. Method: Twenty-four experts reviewed the MuRQoL items for face validity. A refined version was completed by 147 adult CI users and psychometric techniques were used for item selection, assessment of reliability and definition of the factor structure. The same participants completed the Short Form Health Survey for construct validation. MuRQoL responses from 68 CI users were compared with those of a matched group of normal-hearing (NH) adults. Results: Eighteen items measuring music perception & engagement and 18 items measuring their importance were selected; they grouped together into two domains. The final questionnaire has high internal consistency and repeatability. Significant differences between CI users and NH adults and a correlation between music engagement and quality of life (QoL) support construct validity. Scores of music perception & engagement and importance for the 18 items can be combined to assess the impact of music on the QoL. Conclusion: The MuRQoL questionnaire is a reliable and valid measure of self-reported music perception, engagement and their importance for adult CI users with potential to guide music aural rehabilitation

Efficacy in Pigs of Inactivated and Live Attenuated Influenza Virus Vaccines against Infection and Transmission of an Emerging H3N2 Similar to the 2011-2012 H3N2v

Vaccines provide a primary means to limit disease but may not be effective at blocking infection and pathogen transmission. The objective of the present study was to evaluate the efficacy of commercial inactivated swine influenza A virus (IAV) vaccines and experimental live attenuated influenza virus (LAIV) vaccines against infection with H3N2 virus and subsequent indirect transmission to naive pigs. The H3N2 virus evaluated was similar to the H3N2v detected in humans during 2011-2012, which was associated with swine contact at agricultural fairs. One commercial vaccine provided partial protection measured by reduced nasal shedding; however, indirect contacts became infected, indicating that the reduction in nasal shedding did not prevent aerosol transmission. One LAIV vaccine provided complete protection, and none of the indirect-contact pigs became infected. Clinical disease was not observed in any group, including nonvaccinated animals, a consistent observation in pigs infected with contemporary reassortant H3N2 swine viruses. Serum hemagglutination inhibition antibody titers against the challenge virus were not predictive of efficacy; titers following vaccination with a LAIV that provided sterilizing immunity were below the level considered protective, yet titers in a commercial vaccine group that was not protected were above that level. While vaccination with currently approved commercial inactivated products did not fully prevent transmission, certain vaccines may provide a benefit by limitating shedding, transmission, and zoonotic spillover of antigenically similar H3N2 viruses at agriculture fairs when administered appropriately and used in conjunction with additional control measures

High-dose Vitamin D Supplementation in Multiple Sclerosis - Results From the Randomized EVIDIMS (Efficacy of Vitamin D Supplementation in Multiple Sclerosis) Trial

Background: Epidemiological, preclinical, and non-interventional studies link vitamin D (VD) serum levels and disease activity in multiple sclerosis (MS). It is unclear whether high-dose VD supplementation can be used as an intervention to reduce disease activity. Objectives: The study aimed to compare the effects of every other day high- (20,400 IU) versus low-dose (400 IU) cholecalciferol supplementation on clinical and imaging markers of disease activity in patients with relapsing-remitting MS or clinically isolated syndrome. Methods: The EVIDIMS (efficacy of vitamin D supplementation in multiple sclerosis) trial was a multicentre randomized/stratified actively controlled explorative phase 2a pilot trial with a double-blind intervention period of 18 months, add on to interferon-β1b. Results: Fifty-three patients were randomized, and 41 patients completed the study. Cholecalciferol supplementation was well tolerated and safe in both arms. After 18 months, clinical (relapse rates, disability progression) and radiographical (T2-weighted lesion development, contrast-enhancing lesion development, brain atrophy) did not differ between both treatment arms. Post-study power calculations suggested that the sample size was too low to prove the hypothesis. Conclusions: The results neither support nor disprove a therapeutic benefit of high-dose VD supplementation but provide a basis for sound sample size estimations in future confirmatory studies. www.clinicaltrials.gov/NCT01440062

The narrative self, distributed memory, and evocative objects

In this article, I outline various ways in which artifacts are interwoven with autobiographical memory systems and conceptualize what this implies for the self. I first sketch the narrative approach to the self, arguing that who we are as persons is essentially our (unfolding) life story, which, in turn, determines our present beliefs and desires, but also directs our future goals and actions. I then argue that our autobiographical memory is partly anchored in our embodied interactions with an ecology of artifacts in our environment. Lifelogs, photos, videos, journals, diaries, souvenirs, jewelry, books, works of art, and many other meaningful objects trigger and sometimes constitute emotionally-laden autobiographical memories. Autobiographical memory is thus distributed across embodied agents and various environmental structures. To defend this claim, I draw on and integrate distributed cognition theory and empirical research in human-technology interaction. Based on this, I conclude that the self is neither defined by psychological states realized by the brain nor by biological states realized by the organism, but should be seen as a distributed and relational construct

Generation and evaluation of a Glaesserella (Haemophilus) parasuis capsular mutant

Glaesserella (Haemophilus) parasuis is a commensal of the upper respiratory tract in pigs and also the causative agent of Glässer's disease, which causes significant morbidity and mortality in pigs worldwide. Isolates are characterized into 15 serovars by their capsular polysaccharide, which has shown a correlation to isolate pathogenicity. To investigate the role capsule plays in G. parasuis virulence and host interaction, a capsule mutant of the serovar 5 strain HS069 was generated (HS069Δcap) through allelic exchange following natural transformation. HS069Δcap was unable to cause signs of systemic disease during a pig challenge study and had increased sensitivity to complement killing and phagocytosis by alveolar macrophages. When compared to the parent strain, HS069Δcap produced more robust biofilm and adhered equivalently to 3D4/31 cells; however, it was unable to persistently colonize the nasal cavity of inoculated pigs, with all pigs clearing HS069Δcap by 5 days post-challenge. Our results indicate the importance of capsular polysaccharide to G. parasuis virulence as well as nasal colonization in pigs

Physicians' messages in problematic sickness certification: a narrative analysis of case reports

<p>Abstract</p> <p>Background</p> <p>Many physicians find sickness certification tasks problematic. There is some knowledge about situations that are experienced as problematic, whereas less is understood about how physicians respond to the problems they face. One way to acquire such knowledge is to consider "reflection-in-action", aspects of which are expressed in the physician's interpretation of the patient's story. The aim of this study was to gain knowledge about the meaning content of case reports about problematic sickness certification. Specifically, we looked for possible messages to the colleagues intended to read the reports.</p> <p>Methods</p> <p>A narrative approach was used to analyse reports about problematic sickness certification cases that had been written by GPs and occupational health service physicians as part of a sickness insurance course. The analysis included elements from both thematic and structural analysis. Nineteen case reports were used in the actual analysis and 25 in the validation of the results. Main narrative qualities and structural features of the written case reports were explored.</p> <p>Results</p> <p>Five types of messages were identified in the case reports, here classified as "a call for help", "a call for understanding", "hidden worries", "in my opinion", and "appearing neutral". In the reports, the physicians tried to achieve neutrality in their writing, and the patients' stories tended to be interpreted within a traditional biomedical framework. In some cases there was an open request for help, in others it was not obvious that the physician had any problems. Overall, the messages were about having problems as such, rather than the specific features of the problems.</p> <p>Conclusions</p> <p>The case reports clearly demonstrated different ways of writing about problems that arise during sickness certification, from being neutral and not mentioning the problems to being emotionally involved and asking for help. The general character of the messages suggests that they are also relevant for case reports in problematic areas other than sickness certification. If pertinent relationships can be found between reflection-in-practice and the narrative writing about practice, they will provide an approach to further research concerning consultations perceived as problematic and also to medical education.</p