Epidemiology of traumatic spinal cord injury in Galicia, Spain: trends over a 20-year period

[Abstract] Study design: Observational study with prospective and retrospective monitoring. Objective: To describe the epidemiological and demographic characteristics of traumatic spinal cord injury (TSCI), and to analyze its epidemiological changes. Setting: Unidad de Lesionados Medulares, Complejo Hospitalario Universitario A Coruña, in Galicia (Spain). Methods: The study included patients with TSCI who had been hospitalized between January 1995 and December 2014. Relevant data were extracted from the admissions registry and electronic health record. Results: A total of 1195 patients with TSCI were admitted over the specified period of time; 76.4% male and 23.6% female. Mean patient age at injury was 50.20 years. Causes of injury were falls (54.2%), traffic accidents (37%), sports/leisure-related accidents (3.5%) and other traumatic causes (5.3%). Mean patient age increased significantly over time (from 46.40 to 56.54 years), and the number of cases of TSCI related to traffic accidents decreased (from 44.5% to 23.7%), whereas those linked to falls increased (from 46.9% to 65.6%). The most commonly affected neurological level was the cervical level (54.9%), increasing in the case of levels C1–C4 over time, and the most frequent ASIA (American Spinal Injury Association) grade was A (44.3%). The crude annual incidence rate was 2.17/100 000 inhabitants, decreasing significantly over time at an annual percentage rate change of −1.4%. Conclusions: The incidence rate of TSCI tends to decline progressively. Mean patient age has increased over time and cervical levels C1–C4 are currently the most commonly affected ones. These epidemiological changes will eventually result in adjustments in the standard model of care for TSCI

Adaptive Immunity against Leishmania Nucleoside Hydrolase Maps Its C-Terminal Domain as the Target of the CD4+ T Cell–Driven Protective Response

Nucleoside hydrolases (NHs) show homology among parasite protozoa, fungi and bacteria. They are vital protagonists in the establishment of early infection and, therefore, are excellent candidates for the pathogen recognition by adaptive immune responses. Immune protection against NHs would prevent disease at the early infection of several pathogens. We have identified the domain of the NH of L. donovani (NH36) responsible for its immunogenicity and protective efficacy against murine visceral leishmaniasis (VL). Using recombinant generated peptides covering the whole NH36 sequence and saponin we demonstrate that protection against L. chagasi is related to its C-terminal domain (amino-acids 199–314) and is mediated mainly by a CD4+ T cell driven response with a lower contribution of CD8+ T cells. Immunization with this peptide exceeds in 36.73±12.33% the protective response induced by the cognate NH36 protein. Increases in IgM, IgG2a, IgG1 and IgG2b antibodies, CD4+ T cell proportions, IFN-γ secretion, ratios of IFN-γ/IL-10 producing CD4+ and CD8+ T cells and percents of antibody binding inhibition by synthetic predicted epitopes were detected in F3 vaccinated mice. The increases in DTH and in ratios of TNFα/IL-10 CD4+ producing cells were however the strong correlates of protection which was confirmed by in vivo depletion with monoclonal antibodies, algorithm predicted CD4 and CD8 epitopes and a pronounced decrease in parasite load (90.5–88.23%; p = 0.011) that was long-lasting. No decrease in parasite load was detected after vaccination with the N-domain of NH36, in spite of the induction of IFN-γ/IL-10 expression by CD4+ T cells after challenge. Both peptides reduced the size of footpad lesions, but only the C-domain reduced the parasite load of mice challenged with L. amazonensis. The identification of the target of the immune response to NH36 represents a basis for the rationale development of a bivalent vaccine against leishmaniasis and for multivalent vaccines against NHs-dependent pathogens

Membrane fluidity matters: Hyperthermia from the aspects of lipids and membranes

Hyperthermia is a promising treatment modality for cancer in combination both with radio- and chemotherapy. In spite of its great therapeutic potential, the underlying molecular mechanisms still remain to be clarified. Due to lipid imbalances and 'membrane defects' most of the tumour cells possess elevated membrane fluidity. However, further increasing membrane fluidity to sensitise to chemo-or radiotherapy could have some other effects. In fact, hyperfluidisation of cell membrane induced by membrane fluidiser initiates a stress response as the heat shock protein response, which may modulate positively or negatively apoptotic cell death. Overviewing some recent findings based on a technology allowing direct imaging of lipid rafts in live cells and lipidomics, novel aspects of the intimate relationship between the 'membrane stress' of tumour cells and the cellular heat shock response will be highlighted. Our findings lend support to both the importance of membrane remodelling and the release of lipid signals initiating stress protein response, which can operate in tandem to control the extent of the ultimate cellular thermosensitivity. Overall, we suggest that the fluidity variable of membranes should be used as an independent factor for predicting the efficacy of combinational cancer therapies