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ABSTRACTThe toll-like receptor (TLR) family comprises both cell-surface and intracellular receptors that recognize different types of pathogen-associated molecular patterns (PAMPs) leading to the production of pro-inflammatory cytokines and subsequent development of adaptive immunity. TLR2 is a cell-surface receptor initially thought to act as a bacterial sentinel but also shown to recognize a number of viral glycoproteins. In this study, we sought to characterize the role of TLR2 in the activation of the immune response by peste des petits ruminants virus (PPRV), a morbillivirus of the Paramixoviridaefamily that causes an acute, highly contagious disease in goats and sheep. Using human embryonic kidney (HEK) 293 cells stably expressing human (h)TLR2 but lacking any other TLR, we found that PPRV induces IL-8 production in a dose-dependent manner. That activation is only observed in cells expressing hTLR2 and is greatly reduced when the receptor is blocked by pretreatment with specific antibody. We identified hemagglutinin (H) as the viral protein responsible of TLR2 activation by performing the same assays with purified recombinant mammalian-expressed H protein. Exogenous addition of recombinant H protein to cell culture induces high levels of interleukin (IL)-8 only in TLR2-expressing cells. Moreover, H engagement on TLR2 in the monocytic cell line THP-1 activates extracellular-signal-regulated kinase (ERK) signaling. Stimulation of primary ovine dendritic cells with either inactivated PPRV or purified recombinant H protein results in transcription of pro-inflammatory cytokines and the secretion of the Th1-polarizing cytokine IL-12. The role of these host immune mechanisms in the control of PPR is discussed.

Recent reports of patients with coronavirus disease 2019 (COVID-19) developing pneumothorax correspond mainly to case reports describing mechanically ventilated patients. The real incidence, clinical characteristics, and outcome of spontaneous pneumothorax (SP) as a form of COVID-19 presentation remain to be defined.

La creación de Unidades de Cuidados Paliativos Pediátricos (UCPP) podría optimizar el manejo de niños que tras ingreso en la unidad de cuidados intensivos pediátricos (UCIP) requieren enfoque paliativo. Este trabajo describe las características clínico-epidemiológicas de pacientes derivados por este hecho a la UCPP de la Comunidad Autónoma de Madrid (CAM). Se detallan el tratamiento global requerido, las reagudizaciones, los ingresos hospitalarios y las condiciones del fallecimiento, si se produjo.

Ticks are parasites of great medical and veterinary importance since they are vectors of numerous pathogens that affect humans, livestock and pets. Among the argasids, several species of the genus Ornithodorostransmit serious diseases such as tick-borne human relapsing fever (TBRF) and African Swine Fever (ASF). In particular, Ornithodoros erraticusis the main vector of these two diseases in the Mediterranean while O. moubatais the main vector in Africa. The presence of these Ornithodorosticks in domestic and peridomestic environments may greatly hinder the eradication of TBRF and ASF from endemic areas. In addition, there is a constant threat of reintroduction and spreading of ASF into countries from where it has been eradicated (Spain and Portugal) or where it was never present (the Caucasus, Russia and Eastern Europe). In these countries, the presence of Ornithodorosvectors could have a tremendous impact on ASF transmission and long-term maintenance. Therefore, elimination of these ticks from at least synanthropic environments would contribute heavily to the prevention and control of the diseases they transmit. Tick control is a difficult task and although several methods for such control have been used, none of them has been fully effective against all ticks and the problems they cause. Nevertheless, immunological control using anti-tick vaccines offers an attractive alternative to the traditional use of acaricides. The aim of the present paper is to offer a brief overview of the current status in control measure development for Ornithodorossoft ticks, paying special attention to the development of vaccines against O. erraticusand O. moubata. Thus, our contribution includes an analysis of the chief attributes that the ideal antigens for an anti-tick vaccine should have, an exhaustive compilation and analysis of the scant anti-soft tick vaccine trials carried out to date using both concealed and salivary antigens and, finally, a brief description of the new reverse vaccinology approaches currently used to identify new and more effective protective tick antigens.

The evolutionary dynamics of viruses must be taken into consideration in designing preventive and therapeutic treatments. Here we review mechanisms by which viruses adapt in response to antiviral interventions. We propose combination therapy and multiepitopic vaccines as adequate to circumvent virus adaptability. An alternative design, termed lethal mutagenesis or virus entry into error catastrophe is presented. It exploits the high error rates inherent in RNA virus replication, to provoke virus extinction through excess of mutations.

Tradicionalmente se ha reconocido que los enfermos con distrofia miotónica tipo 1 (DM-1), ó enfermedad de Steinert, presentan una conducta muy característica, dejando aparte aquellos casos en que existe patología mental o un retraso del neurodesarrollo. Se describe el sustrato neurológico de dicha conducta. El objetivo de este texto es doble. Por una parte, se pretende que los clínicos, ante un paciente con DM-1, consideren siempre los aspectos cognitivos de la enfermedad. Por otra, se busca desmontar ideas preconcebidas sobre el peculiar comportamiento de estos pacientes.

Up to a third of patients with radiologically isolated syndrome (RIS) exhibit lower-than-expected cognitive performances in neuropsychological evaluations, but the relationship between cognitive impairment (CI) and quantitative magnetic resonance (MRI) measures has not been stablished. Furthermore, the prognostic role of CI in RIS for conversion to MS is currently unknown. We assessed 17 patients with RIS and 17 matched healthy controls (HC) with a neurophychological battery and a 3T MRI. Six patients (35,3%) fulfilled our criterion for CI (scores 2 SDs below the mean of HC in at least two cognitive tests) (ci-RIS). The ci-RIS subgroup showed lower values of normalized brain and gray matter volumes when compared to HC. After a median follow-up time of 4.5 years, the ci-RIS subgroup presented a higher conversion rate to MS, suggesting that CI might be an independent risk factor for conversion to MS.

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