A minimally invasive endovascular approach to the cerebellopontine angle cistern enables broad CNS biodistribution of scAAV9-CB-GFP.

Neurological disorders pose a challenge for targeted therapy due to restricted access of therapeutic agents to the central nervous system (CNS). Current methods are limited by procedure-related risks, invasiveness, and insufficient CNS biodistribution. A novel percutaneous transvenous technology, currently in clinical trials for communicating hydrocephalus, offers a minimally invasive approach by providing endovascular access to the cerebrospinal fluid-filled cerebellopontine angle (CPA) cistern. We hypothesized that drug delivery to the CPA cistern could yield widespread CNS distribution. Using an ovine model, we compared the biodistribution of scAAV9-CB-GFP following CPA cistern infusion with previously reported cisterna magna (CM) administration. Targeting both the CPA cistern and CM in sheep, we employed a lumbar spine-inserted microcatheter under fluoroscopy. CPA delivery of AAV9 demonstrated biodistribution and transduction in the cerebral cortices, striatum, thalamus, midbrain, cerebellum, and spinal cord, with minor liver distribution comparable to CM. The favorable safety profile in humans with hydrocephalus suggests that percutaneous endovascular injection into the CPA could offer a clinically safer and minimally invasive delivery system for CNS gene and cell-based therapies.

Awake intracerebroventricular delivery and safety assessment of oligonucleotides in a large animal model.

Oligonucleotide therapeutics offer great promise in the treatment of previously untreatable neurodegenerative disorders; however, there are some challenges to overcome in pre-clinical studies. (1) They carry a well-established dose-related acute neurotoxicity at the time of administration. (2) Repeated administration into the cerebrospinal fluid may be required for long-term therapeutic effect. Modifying oligonucleotide formulation has been postulated to prevent acute toxicity, but a sensitive and quantitative way to track seizure activity in pre-clinical studies is lacking. The use of intracerebroventricular (i.c.v.) catheters offers a solution for repeated dosing; however, fixation techniques in large animal models are not standardized and are not reliable. Here we describe a novel surgical technique in a sheep model for i.c.v. delivery of neurotherapeutics based on the fixation of the i.c.v. catheter with a 3D-printed anchorage system composed of plastic and ceramic parts, compatible with magnetic resonance imaging, computed tomography, and electroencephalography (EEG). Our technique allowed tracking electrical brain activity in awake animals via EEG and video recording during and for the 24-h period after administration of a novel oligonucleotide in sheep. Its anchoring efficiency was demonstrated for at least 2 months and will be tested for up to a year in ongoing studies.

Endoparasites of capybaras (Hydrochoerus hydrochaeris) from anthropized and natural areas of Brazil.

This study aimed to evaluate the occurrence of endoparasites in fecal samples of capybaras from anthropized areas in seven cities in the state of São Paulo, southeastern Brazil, and natural areas in two locations in the Pantanal biome. For the parasitological evaluation of samples, feces were subjected to centrifugal sedimentation in water-ether and centrifugal flotation in sucrose solution. Out of the 113 samples examined, 97.3% (110/113) were positive for the presence of helminth eggs and/or protozoan oocysts, with 96.7% (89/92) and 100% (21/21) in capybaras from anthropized and natural areas, respectively. Helminth eggs belonging to the Class Cestoda (Monoecocestus spp.), Class Digenea, and Class Nematoda (Trichostrongyloidea, Strongyloides chapini, Protozoophaga obesa, and Capillaria hydrochoeri) were detected. Coccidia oocysts of Eimeria spp. and Cryptosporidium spp. were detected. The difference found was in the occurrence of S. chapini between anthropized and natural areas, as S. chapini was not detected in natural areas. Capybaras from anthropized areas showed a greater species richness of endoparasites, including species such as Fasciola hepatica and Cryptosporidium spp., that might have zoonotic potential.

Molecular survey of Leishmania spp. in skin samples of capybaras (Hydrochoerus hydrochaeris) from different areas of Brazil / Investigação molecular de Leishmania spp. em amostras de pele de capivaras (Hydrochoerus hydrochaeris) de diferentes regiões do Brasil

Leishmaniases comprise a spectrum of diseases caused by protozoan parasites of the genus Leishmania, with some species of rodents being incriminated as reservoirs. The capybara is the largest extant rodent species in the world and is widely distributed in South America. The occurrence of infection by Leishmania spp. was investigated in capybaras captured in Brazil during 2015­2019 from established populations in five highly anthropic areas of the state of São Paulo and two natural areas of the states of Mato Grosso and Mato Grosso do Sul. A total of 186 individuals were captured and subjected to abdominal skin biopsy. All skin samples were Leishmania kDNA-negative, suggesting that capybaras have no role in the transmission cycles of Leishmania species in the studied areas despite the well-known role of other rodents in the life cycle of Leishmania spp.(AU)

As leishmanioses compreendem um espectro de doenças causadas por protozoários do gênero Leishmania e algumas espécies de roedores são incriminadas como reservatórios de Leishmania spp. As capivaras compreendem a maior espécie de roedores existentes e são amplamente distribuídas na América do Sul. Para investigar a ocorrência de infecção por Leishmania spp. em capivaras, durante os anos de 2015-2019 capivaras foram capturadas em cinco áreas antrópicas do estado de São Paulo e em duas áreas naturais dos estados do Mato Grosso e do Mato Grosso do Sul, todos esses ambientes com populações de capivaras estabelecidas. Um total de 186 indivíduos foram capturados e submetidos à biópsia de pele abdominal. Todas as amostras de pele foram negativas para o alvo kDNA, assim, os dados sugerem que nas áreas estudadas as capivaras não têm papel no ciclo de transmissão de espécies de Leishmania spp., apesar do papel bem conhecido de outros roedores no ciclo de vida de Leishmania spp.(AU)

Human-modified landscape acts as refuge for mammals in Atlantic Forest / Paisagem antropicamente modificada atua como refúgio para mamíferos na Mata Atlântica

Abstract: Human-modified landscapes (HMLs) are composed by small, isolated and defaunated forest fragments, which are surrounded by agricultural and urban areas. Information on species that thrives in these HMLs is essential to direct conservation strategies in local and regional scales. Since HMLs are dominant in the Atlantic Forest, we aimed to assess the mammalian diversity in a HML in southeastern Brazil and to propose conservation strategies. We collected data of terrestrial (small-, medium- and large-sized) and volant mammals in three small forest fragments (10, 14 and 26 ha) and adjacent areas, between 2003 and 2016, using complementary methods: active search, camera trapping, live-traps, mist nets and occasional records (i.e., roadkills). In addition, we used secondary data to complement our species list. We recorded 35 native mammal species (6 small-sized, 16 medium- and large-sized, and 13 bats) and seven exotic species in the HML. The recorded mammal assemblage (non-volant and volant), although mainly composed of common and generalist species, includes three medium- and large-sized species nationally threatened (Leopardus guttulus, Puma concolor and Puma yagouaroundi) and two data deficient species (Galictis cuja and Histiotus velatus), highlighting the importance of this HML for the maintenance and conservation of mammal populations. Despite highly impacted by anthropogenic disturbances, the study area harbors a significant richness of medium- and large-sized mammals, being an important biodiversity refuge in the region. However, this biodiversity is threatened by the low quality of the habitats, roadkills and abundant populations of domestic cats and dogs. Therefore, we stress the need of conservation strategies focusing on the medium- and large-sized mammals as an umbrella group, which could benefit all biodiversity in the landscape. We recommend actions that promotes biological restoration, aiming to increase structural composition and connectivity of the forest fragments, reducing roadkills and controlling the domestic cats and dogs' populations, in order to maintain and improve the diversity of mammals in long-term.

Resumo: Paisagens antropicamente modificadas (HMLs) são compostas por fragmentos florestais pequenos, isolados e defaunados, imersos em áreas agrícolas e/ou urbanas. Informações sobre as espécies que habitam essas paisagens são importantes para o direcionamento de estratégias de conservação em escalas local e regional. Uma vez que as HMLs são as paisagens dominantes na Mata Atlântica, o objetivo deste trabalho foi avaliar a diversidade de mamíferos em uma HML do sudeste do Brasil e propor estratégias para sua conservação. Foram coletados dados de mamíferos terrestres (pequenos, médios e grandes) e voadores em três fragmentos florestais (10, 14 e 26 ha) e áreas adjacentes, entre 2003 e 2016, usando métodos complementares: busca ativa, armadilhamento fotográfico, armadilhas de captura e redes de neblina. Adicionalmente, foram utilizados dados de literatura para complementar a lista de espécies. Foram registradas 35 espécies de mamíferos nativos (6 de pequenos, 16 de médios e grandes e 13 de morcegos) e sete espécies exóticas. A assembleia de mamíferos registrada (terrestres e voadores), embora composta por espécies generalistas, apresentou três espécies de médio e grande porte ameaçadas de extinção nacionalmente (Leopardus guttulus, Puma concolor and Puma yagouaroundi) e duas deficientes em dados (Galictis cuja and Histiotus velatus), destacando a importância dessa HML para conservação e manutenção das populações de mamíferos. Embora inserida em uma paisagem extremamente modificada, a área de estudo abriga uma riqueza significativa de mamíferos de médio e grande porte, sendo um importante refúgio para a biodiversidade na região. Entretanto, essa biodiversidade está ameaçada pela baixa qualidade dos habitats, por atropelamentos e por abundantes populações de cães e gatos domésticos. Portanto, enfatizamos a necessidade de estratégias de conservação focadas nos mamíferos de médio e grande porte como grupo "guarda-chuva", o que pode beneficiar as demais espécies na paisagem. Recomendamos ações de conservação visando a restauração biológica, para melhorar a composição estrutural e conectividade dos fragmentos florestais, reduzir o número de atropelamentos e controlar as populações de cães e gatos domésticos, afim de manter e aumentar a diversidade local de mamíferos em longo prazo.