Progressive dementia associated with ataxia or obesity in patients with Tropheryma whipplei encephalitis

<p>Abstract</p> <p>Background</p> <p><it>Tropheryma whipplei</it>, the agent of Whipple's disease, causes localised infections in the absence of histological digestive involvement. Our objective is to describe <it>T. whipplei </it>encephalitis.</p> <p>Methods</p> <p>We first diagnosed a patient presenting dementia and obesity whose brain biopsy and cerebrospinal fluid specimens contained <it>T. whipplei </it>DNA and who responded dramatically to antibiotic treatment. We subsequently tested cerebrospinal fluid specimens and brain biopsies sent to our laboratory using <it>T. whipplei </it>PCR assays. PAS-staining and <it>T. whipplei </it>immunohistochemistry were also performed on brain biopsies. Analysis was conducted for 824 cerebrospinal fluid specimens and 16 brain biopsies.</p> <p>Results</p> <p>We diagnosed seven patients with <it>T. whipplei </it>encephalitis who demonstrated no digestive involvement. Detailed clinical histories were available for 5 of them. Regular PCR that targeted a monocopy sequence, PAS-staining and immunohistochemistry were negative; however, several highly sensitive and specific PCR assays targeting a repeated sequence were positive. Cognitive impairments and ataxia were the most common neurologic manifestations. Weight gain was paradoxically observed for 2 patients. The patients' responses to the antibiotic treatment were dramatic and included weight loss in the obese patients.</p> <p>Conclusions</p> <p>We describe a new clinical condition in patients with dementia and obesity or ataxia linked to <it>T. whipplei </it>that may be cured with antibiotics.</p

Molecular remodeling of cardiac sinus node associated with acute Chagas disease myocarditis

Chagas disease principally affects Latin-American people, but it currently has worldwide distribution due to migration. Death among those with Chagas disease can occur suddenly and without warning, even in those who may not have evidence of clinical or structural cardiac disease and who are younger than 60 years old. HCN4 channels, one of the principal elements responsible for pacemaker currents, are associated with cardiac fetal reprogramming and supraventricular and ventricular arrhythmias, but their role in chagasic arrhythmias is not clear. We found that a single-dose administration of ivabradine, which blocks HCN4, caused QTc and QRS enlargement and an increase in P-wave amplitude and was associated with ventricular and supraventricular arrhythmias in mice challenged with isoproterenol, a chronotropic/ionotropic positive agent. Continuous treatment with ivabradine did not alter the QTc interval, but P-wave morphology was deeply modified, generating supraventricular arrhythmias. In addition, we found that repolarization parameters improved with ivabradine treatment. These effects could have been caused by the high HCN4 expression observed in auricular and ventricular tissue in infected mice. Thus, we suggest, for the first time, that molecular remodeling by overexpression of HCN4 channels may be related to supraventricular arrhythmias in acute Chagas disease, causing ivabradine over-response. Thus, ivabradine treatment should be administered with caution, while HCN4 overexpression may be an indicator of heart failure and/or sudden death risk.Ministerio de Economía y competitividad and Fondo Europeo de Desarrollo Regional (SAF2015-63868-R (MINECO/FEDER) to N.G. and SAF2016-75988-R (MINECO/FEDER) to M.F.); Ministerio de Ciencia, Innovación y Universidades-Agencia Estatal de Investigación and Fondo Europeo de Desarrollo Regional (PGC2018-096132-B-I00 and PID2019- 104760RB-I00 (MICINN/FEDER) to N.G. and M.F., respectively); the Universidad Autónoma de Madrid-Banco de Santander Inter-University Cooperation Grant with Latin América (SN/2013 to M.F. and CEAL-AL/2015-12 to N.G.); Red de Investigación de Centros de Enfermedades Tropicales (RICET RD12/0018/0004 to M.F.); Comunidad de Madrid (S-2010/BMD-2332 to M.F.); and Instituto Venezolano de Investigaciones Científicas (IVIC-1365 to H.R.). CBMSO institutional grants from Fundación Ramón Areces and Banco de Santande

Pessoas com deficiência e trabalho: percepção de gerentes e pós-graduandos em Administração

A inserção de pessoas com deficiência no mercado de trabalho é recente nas organizações. Esta pesquisa analisou as diferenças nas concepções de deficiência e na avaliação sobre possibilidades de trabalho para pessoas com deficiência entre 163 gerentes (idade média: 43 anos; 73% homens; 91% com nível superior) que trabalhavam, em média, há 3,6 anos com essas pessoas, em 18 empresas nacionais (83%= >1.000 funcionários; 39% = 20-100 com deficiências), e entre 285 pós-graduandos em administração de três Estados, que nunca atuaram com elas. Aplicou-se um Inventário de Concepções de Deficiência, em escala Likert, especialmente elaborado para esse fim. Não houve diferença significativa entre as concepções de deficiência dos grupos analisados. Houve correlação positiva entre o tempo de trabalho dos gerentes de pessoas com deficiência e a percepção do desempenho dessas pessoas. Conclui-se que o contato com as pessoas com deficiência pode modificar a percepção sobre elas, melhorando suas possibilidades de inserção no mercado de trabalho