Abnormalities in Cortical GABAergic Interneurons of the Primary Motor Cortex Caused by Lis1 (Pafah1b1) Mutation Produce a Non-drastic Functional Phenotype.

LIS1 (PAFAH1B1) plays a major role in the developing cerebral cortex, and haploinsufficient mutations cause human lissencephaly type 1. We have studied morphological and functional properties of the cerebral cortex of mutant mice harboring a deletion in the first exon of the mouse Lis1 (Pafah1b1) gene, which encodes for the LisH domain. The Lis1/sLis1 animals had an overall unaltered cortical structure but showed an abnormal distribution of cortical GABAergic interneurons (those expressing calbindin, calretinin, or parvalbumin), which mainly accumulated in the deep neocortical layers. Interestingly, the study of the oscillatory activity revealed an apparent inability of the cortical circuits to produce correct activity patterns. Moreover, the fast spiking (FS) inhibitory GABAergic interneurons exhibited several abnormalities regarding the size of the action potentials, the threshold for spike firing, the time course of the action potential after-hyperpolarization (AHP), the firing frequency, and the frequency and peak amplitude of spontaneous excitatory postsynaptic currents (sEPSC's). These morphological and functional alterations in the cortical inhibitory system characterize the Lis1/sLis1 mouse as a model of mild lissencephaly, showing a phenotype less drastic than the typical phenotype attributed to classical lissencephaly. Therefore, the results described in the present manuscript corroborate the idea that mutations in some regions of the Lis1 gene can produce phenotypes more similar to those typically described in schizophrenic and autistic patients and animal models.

Shock wave and mesenchymal stem cells as treatment in the acute phase of spinal cord injury: A pilot study / Ondas de choque y células madre mesenquimales como tratamiento en la fase aguda de la lesión medular: un estudio piloto

Introduction: Spinal cord injury (SCI) is a complex pathology with thousands of patients worldwide. During the acute early phase, neural tissue shows some regenerative properties that disappear at the chronic phase. Shock Waves and Stem Cells have been proposed as a possible therapy. Methods: Here, we analyse Shock Waves’ immediate effect over spinal cord genetic response in the injured and healthy spinal cord and the effect of Shock Waves and combined Shock Waves plus Stem Cells distally grafted to treat the first month after spinal cord injury. Results: The immediate application of shock waves increases VEGF (Vascular Endothelial Growth Factor) but reduces the BDNF (Brain-Derived Growth Factor) RNA (Ribonucleic acid) response. Shock wave therapy increases GFAP (Glial fibrillary acidic protein) positive cells and vascularity during the treatment's acute phase. Conclusion: Shock wave treatment seems to be enough to produce benefits in the acute phase of spinal cord injury, with no accumulative positive effects when mesenchymal stem cell graft is applied together.(AU)

Introducción: La lesión medular es una afección compleja con miles de pacientes repartidos a lo largo del mundo. Durante la fase aguda temprana de la lesión, el tejido neural muestras ciertas propiedades regenerativas que desaparecen durante la fase crónica. Las ondas de choque y las células madre han sido propuestas como posibles terapias. Metodología: En este estudio analizamos el efecto inmediato de una sesión de ondas de choque sobre la médula espinal, tanto sana como lesionada, y si su efecto es sumatorio al que produce un tratamiento de células madre mesenquimales inyectadas distalmente, como se ha observado en estudios previos. Resultados: Se observa un efecto inmediato con las ondas de choque que promueve un incremento del efecto trófico vascular endotelial, y una disminución del factor trófico derivado del cerebro. La terapia prolongada con ondas de choque en la fase aguda incrementa la presencia de astrocitos y la vascularización local. No parece haber efecto sumatorio con el tratamiento de células madre, produciéndose efectos similares con o sin las células madre mesenquimales. Conclusiones: Las ondas de choque parecen tener un efecto positivo durante la fase aguda de una lesión medular por compresión, sin que el tratamiento distal de células madre mesenquimales parezca implicar un efecto sumatorio.(AU)

Shock wave and mesenchymal stem cells as treatment in the acute phase of spinal cord injury: A pilot study.

INTRODUCTION: Spinal cord injury (SCI) is a complex pathology with thousands of patients worldwide. During the acute early phase, neural tissue shows some regenerative properties that disappear at the chronic phase. Shock Waves and Stem Cells have been proposed as a possible therapy. METHODS: Here, we analyse Shock Waves' immediate effect over spinal cord genetic response in the injured and healthy spinal cord and the effect of Shock Waves and combined Shock Waves plus Stem Cells distally grafted to treat the first month after spinal cord injury. RESULTS: The immediate application of shock waves increases VEGF (Vascular Endothelial Growth Factor) but reduces the BDNF (Brain-Derived Growth Factor) RNA (Ribonucleic acid) response. Shock wave therapy increases GFAP (Glial fibrillary acidic protein) positive cells and vascularity during the treatment's acute phase. CONCLUSION: Shock wave treatment seems to be enough to produce benefits in the acute phase of spinal cord injury, with no accumulative positive effects when mesenchymal stem cell graft is applied together.

Clinical characteristics and outcomes of 1,331 patients with COVID-19: HM Spanish Cohort.

OBJECTIVE: Spain is one of the European countries most affected by the COVID-19 pandemic. Epidemiologic studies are warranted to improve the disease understanding, evaluate the care procedure and prepare for futures waves. The aim of the study was to describe epidemiologic characteristics associated with hospitalized patients with COVID-19. METHODS: This real-world, observational, multicenter and retrospective study screened all consecutive patients admitted to 8 Spanish private hospitals. Inclusion criteria: hospitalized adults (age≥18 years old) with clinically and radiologically findings compatible with COVID-19 disease from March 1st to April 5th, 2020. Exclusion criteria: patients presenting negative PCR for SARS-CoV-2 during the first 7 days from hospital admission, transfer to a hospital not belonging to the HM consortium, lack of data and discharge against medical advice in emergency departments. RESULTS: One thousand and three hundred thirty-one COVID-19 patients (medium age 66.9 years old; males n= 841, medium length of hospital stayed 8 days, non-survivors n=233) were analyzed. One hundred and fifteen were admitted to intensive care unit (medium length of stay 16 days, invasive mechanical ventilation n= 95, septic shock n= 37 and renal replacement therapy n= 17). Age, male gender, leukocytes, platelets, oxygen saturation, chronic therapy with steroids and treatment with hydroxychloroquine/azithromycin were independent factors associated with mortality. The proportion of patients that survive and received tocilizumab and steroids were lesser and higher respectively than those that die, but their association was not significant. CONCLUSIONS: Overall crude mortality rate was 17.5%, rising up to 36.5% in the subgroup of patients that were admitted to the intensive care unit. Seven factors impact in hospital mortality. No immunomodulatory intervention were associated with in-hospital mortality.

Re-emergence of leishmaniasis in Spain: community outbreak in Madrid, Spain, 2009 to 2012.

Since July 2009, there has been a community outbreak of leishmaniasis in the south-west area of the Madrid autonomous community, Spain, affecting residents from four towns that are geographically close together and share extensive park areas. As of December 2012, 446 cases were reported (6 in 2009, 97 in 2010, 196 in 2011 and 147 in 2012), a mean incidence rate of 22.2 per 100,000 inhabitants during July 2009 and December 2012. The mean age was 44 years (range: 2 months to 95 years); 61.0% were male. A total of 68 (15.2%) had immunosuppressive conditions; 160 (35.9%) had visceral leishmaniasis and 286 (64.1%) cutaneous. A total of 421 (94.4%) cases were confirmed. Leishmania infantum was identified as the agent. Monitoring revealed high densities of the vector Phlebotomus perniciosus. The surveillance system for canine leishmaniasis did not detect any increase in prevalence during the period. Environmental control measures have been taken, such as improvements in sanitation and disinsection in the risk areas and control of the overpopulation of Leporidae, as xenodiagnosis studies have shown that hares play a role as active reservoirs. This is the largest reported community outbreak of leishmaniasis in Europe. The discovery of the new reservoir stands out in the multifactorial aetiology of the outbreak. Epidemiological research and environmental intervention measures are continuing.