Development of social behaviour and importance of social relations in calves

We concluded that the preference for peers met at two weeks of age can be seen in proximity of the calves. However, calves can form stable relations at least until the age of 14 weeks. These relations reduce aggressive behaviour, activity and frequency of vocalization, and help calves to cope with new and potentially stressful situations

Immunothrombosis and vascular heterogeneity in cerebral cavernous malformation

Cerebral cavernous malformation (CCM) is a neurovascular disease that results in various neurological symptoms. Thrombi have been reported in surgically resected CCM patient biopsies; but the molecular signatures of these thrombi remain elusive. Here, we investigated the kinetics of thrombi formation in CCM and how thrombi affect the vasculature and contribute to cerebral hypoxia. We used RNA-sequencing to investigate mouse brain endothelial cells with specific Ccm3 gene deletion (Ccm3-iECKO). We found that Ccm3 deficient brain endothelial cells had a higher expression of genes related to the coagulation cascade and hypoxia when compared to wild-type brain endothelial cells. Immunofluorescent assays identified key molecular signatures of thrombi such as fibrin, von Willebrand factor, and activated platelets in Ccm3-iECKO mice and human CCM biopsies. Notably, we identified polyhedrocytes in Ccm3-iECKO mice and human CCM biopsies and report it for the first time. We also found that the parenchyma surrounding CCM lesions is hypoxic and that more thrombi correlate with higher levels of hypoxia. Lastly, we created an in vitro model to study CCM pathology and found that human brain endothelial cells deficient for CCM3, expressed elevated levels of plasminogen activator inhibitor-1 and had a redistribution of von Willebrand factor. With transcriptomics, comprehensive imaging, and an in vitro CCM preclinical model this study provides experimental evidence that genes and proteins related to the coagulation cascade affect the brain vasculature and promote neurological side effects such as hypoxia in CCM. This study supports the concept that antithrombotic therapy may be beneficial for patients with CCM

Inflammation and neutrophil extracellular traps in cerebral cavernous malformation

Correction: Volume79, Issue7 Article Number: 388 DOI: 10.1007/s00018-022-04418-8Cerebral Cavernous Malformation (CCM) is a brain vascular disease with various neurological symptoms. In this study, we describe the inflammatory profile in CCM and show for the first time the formation of neutrophil extracellular traps (NETs) in rodents and humans with CCM. Through RNA-seq analysis of cerebellum endothelial cells from wild-type mice and mice with an endothelial cell-specific ablation of the Ccm3 gene (Ccm3(iECKO)), we show that endothelial cells from Ccm3(iECKO) mice have an increased expression of inflammation-related genes. These genes encode proinflammatory cytokines and chemokines, as well as adhesion molecules, which promote recruitment of inflammatory and immune cells. Similarly, immunoassays showed elevated levels of these cytokines and chemokines in the cerebellum of the Ccm3(iECKO) mice. Consistently, both flow cytometry and immunofluorescence analysis showed infiltration of different subsets of leukocytes into the CCM lesions. Neutrophils, which are known to fight against infection through different strategies, including the formation of NETs, represented the leukocyte subset within the most pronounced increase in CCM. Here, we detected elevated levels of NETs in the blood and the deposition of NETs in the cerebral cavernomas of Ccm3(iECKO) mice. Degradation of NETs by DNase I treatment improved the vascular barrier. The deposition of NETs in the cavernomas of patients with CCM confirms the clinical relevance of NETs in CCM.Peer reviewe

"Se oli elämän toiseksi parasta aikaa" : omaisen tukeminen kotisaattohoidossa

Opinnäytetyömme tarkoituksena oli selvittää, minkälaista tukea omaiset ovat saaneet kotisaattohoitotilanteissa ja minkälaista tukea he kokevat tarvitsevansa. Tavoitteenamme oli saada omaisten oma ääni kuuluviin, jolloin voitaisiin löytää uusia ratkaisuja omaisten tukemiseen. Opinnäytetyöstä saamiemme tulosten perusteella kotisairaala saa tietoa ja mahdollisuuden kehittää kotisaattohoitoa vastaamaan omaisten tuen tarpeita. Opinnäytetyömme työelämänkumppanina toimi pääkaupunkiseudulla toimiva kotisairaala. Opinnäytetyö toteutettiin kvalitatiivisen tutkimuksen menetelmin. Aineiston hankimme puolistrukturoidulla teemahaastattelulla ja litteroidun aineiston analysoimme teemoittelemalla. Opinnäytetyössä haastattelimme viittä omaishoitoperhettä; yhteensä kahdeksaa omaista, jotka olivat hoitaneet läheisensä kotona. Haastateltavista omaisista neljä oli tyttäriä ja toiset neljä leskeksi jääneitä puolisoita. Kaikki saattohoitotilanteet olivat tapahtuneet vuoden sisällä, mikä tuli ottaa huomioon haastattelutilanteissa. Tulosten mukaan omaiset kaipasivat erityisesti tiedollista tukea sairauden etenemisestä ja kuoleman kohtaamisesta. Omaiset tarvitsivat myös psykososiaalista tukea ja apua arjessa selviytymiseen. Omaisille oli tärkeää tietää, että hoitohenkilökunta on tavoitettavissa ympäri vuorokautisesti, mutta he eivät kuitenkaan halunneet häiritä hoitohenkilökuntaa ilman akuuttia hätää. Omaiset toivoivat, että yhteydenpito olisi vastavuoroista ja soittokynnys madaltuisi. Omaisilta tuli hyvää palautetta kotisairaalan henkilökunnalta saamasta tuesta. Omaisilta saimme ehdotuksia ja toivomuksia siihen, millä tavalla heitä tulisi huomioida saattohoidon aikana ja sen jälkeen. Kotisaattohoito vaatii ammattilaisilta herkkyyttä ja laaja-alaista osaamista, mikä korostuu kun toimitaan kotiympäristössä. Saattohoidossa ammattilaisten tulee muistaa, että omaisten tukeminen on tärkeää kuolevan asiakkaan hyvinvoinnin kannalta. Opinnäytetyömme tuloksista nousi vahvasti esille tarve informaatiopaketille, joka pitäisi sisällään kattavasti kaiken omaisten tarvitseman tiedon kotisaattohoidon aikana. Tämä informaatiopaketti toimisi omaisten sekä ammattilaisten apuna.The main purpose of this thesis was to investigate what kind of support relatives receive and what kind of support they feel they need at the end-of-life care at home. The target of our thesis was to get the relatives´ voice heard and find a new form to support the relatives. This study was carried out in cooperation with the hospital at home in the metropolitan area. The information that we gathered can be used in developing palliative care at home. The thesis was carried out using qualitative method. The collection of the data was carried out by interviewing relatives who have been taking care of their relatives at the end of their life at home. We interviewed members from five families: altogether eight relatives, of whom four were widowed spouses and four were children of the patient. Our aim was to map their needs and experiences of the carer at the end-of-life care in the home circum-stances. The results of the interviews suggest that family members had many positive experiences concerning end-of-life care at home, but also some shortcomings were mentioned. The central needs of the relatives were informational: providing the family members with infor-mation about the illness, symptoms and the changes in the patient when death approached. This was crucial information because end-of-life care happens at patient´s homes, not in the hospital environment. The relatives have different sorts of psychosocial, economical and practical needs, hence supporting the family was one of the main tasks of the staff. The carers gave lots of positive feedback from the staff of the hospital at home. They also gave good suggestions and wishes on how to take the relatives into consideration during and after the end-of-life care at home with the support of the hospital at home. Some complaints came up for example about how to reach the staff when needed. We suggest that in the future hospital at home should put more effort on carers; during the approaching death and how the carers survive after the death of their loved ones. Further developments in the end-of-life care could include an information package which would contain important information for the carers and family members

Axon Guidance-Related Factor FLRT3 Regulates VEGF-Signaling and Endothelial Cell Function

Vascular endothelial growth factors (VEGFs) are key mediators of endothelial cell (EC) function in angiogenesis. Emerging knowledge also supports the involvement of axon guidance-related factors in the regulation of angiogenesis and vascular patterning. In the current study, we demonstrate that fibronectin and leucine-rich transmembrane protein-3 (FLRT3), an axon guidance-related factor connected to the regulation of neuronal cell outgrowth and morphogenesis but not to VEGF-signaling, was upregulated in ECs after VEGF binding to VEGFR2. We found that FLRT3 exhibited a transcriptionally paused phenotype in non-stimulated human umbilical vein ECs. After VEGF-stimulation its nascent RNA and mRNA-levels were rapidly upregulated suggesting that the regulation of FLRT3 expression is mainly occurring at the level of transcriptional elongation. Blockage of FLRT3 by siRNA decreased survival of ECs and their arrangement into capillary-like structures but enhanced cell migration and wound closure in wound healing assay. Bifunctional role of FLRT3 in repulsive vs. adhesive cell signaling has been already detected during embryogenesis and neuronal growth, and depends on its interactions either with UNC5B or another FLRT3 expressed by adjacent cells. In conclusion, our findings demonstrate that besides regulating neuronal cell outgrowth and morphogenesis, FLRT3 has a novel role in ECs via regulating VEGF-stimulated EC-survival, migration, and tube formation. Thus, FLRT3 becomes a new member of the axon guidance-related factors which participate in the VEGF-signaling and regulation of the EC functions

Are long lasting social relationships significant for calves

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Vasikoiden sosiaalisen käyttäytymisen kehittyminen ja sosiaalisten suhteiden merkitys

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The formation of preferential relationships at early age in cattle

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