CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice

Neuroinflammation and microglial activation are significant processes in Alzheimer's disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer's disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer's disease and other tau-mediated neurodegenerative diseases

Researching COVID to enhance recovery (RECOVER) pregnancy study: Rationale, objectives and design

Importance Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER-Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads. Methods RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators. Discussion RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero

Long-range Angular Correlations On The Near And Away Side In P-pb Collisions At √snn=5.02 Tev

7191/Mar294

Reporte de un caso de dracunculosis en un canino en la Provincia de Formosa - Argentina

Se comunica el hallazgo de Dracunculus sp. en un canino proveniente de la localidad de Fontana, Departamento Patiño, Provincia de Formosa, Argentina. El hallazgo constituye el cuarto caso de Dracunculosis registrado en animales en una misma área geográfica de Formosa

Infecção natural por Trypanosoma evansi em cavalos na região Central do Estado do Rio Grande do Sul Natural infection by Trypanosoma evansi in horses in the central area of the state of Rio Grande do Sul, Brazil

O objetivo deste trabalho foi avaliar a causa de mortalidade em cavalos de uma propriedade na região central do Rio Grande do Sul. Amostras de sangue de nove animais foram analisadas utilizando-se a técnica do micro-hematócrito e colorações da capa flogística sendo detectada a presença de Trypanosoma evansi em três amostras. Os sinais clínicos apresentados pelos animais foram anemia, edema das partes ventrais do corpo e incoordenação dos membros posteriores. As técnicas empregadas são de fundamental importância na triagem parasitológica a fim de aumentar as chances de observação dos protozoários.<br>The objective of the research was to evaluate the mortality cause in horses on a farm in the central area of the state of Rio Grande do Sul, Brazil. Blood samples of nine animals were analysed using the microhematocrit technique and stain of buffy coast where in three samples the presence of Trypanosoma evansi was detected. The clinical signs presented by the animals were anemia, edema of the ventral parts of the body and incoordenation of the subsequent members. The techniques used are of fundamental importance in parasitologics selection samples to increase the chances of finding the protozoan