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BACKGROUND: The function of polymorphonuclear neutrophils (PMNs) decreases with age, which results in infectious and inflammatory complications in older individuals. The underlying causes are not fully understood. ATP release and autocrine stimulation of purinergic receptors help PMNs combat microbial invaders. Excessive extracellular ATP interferes with these mechanisms and promotes inflammatory PMN responses. Here, we studied whether dysregulated purinergic signaling in PMNs contributes to their dysfunction in older individuals. RESULTS: Bacterial infection of C57BL/6 mice resulted in exaggerated PMN activation that was significantly greater in old mice (64 weeks) than in young animals (10 weeks). In contrast to young animals, old mice were unable to prevent the systemic spread of bacteria, resulting in lethal sepsis and significantly greater mortality in old mice than in their younger counterparts. We found that the ATP levels in the plasma of mice increased with age and that, along with the extracellular accumulation of ATP, the PMNs of old mice became increasingly primed. Stimulation of the formyl peptide receptors of those primed PMNs triggered inflammatory responses that were significantly more pronounced in old mice than in young animals. However, bacterial phagocytosis and killing by PMNs of old mice were significantly lower than that of young mice. These age-dependent PMN dysfunctions correlated with a decrease in the enzymatic activity of plasma ATPases that convert extracellular ATP to adenosine. ATPases depend on divalent metal ions, including Ca2+, Mg2+, and Zn2+, and we found that depletion of these ions blocked the hydrolysis of ATP and the formation of adenosine in human blood, resulting in ATP accumulation and dysregulation of PMN functions equivalent to those observed in response to aging. CONCLUSIONS: Our findings suggest that impaired hydrolysis of plasma ATP dysregulates PMN function in older individuals. We conclude that strategies aimed at re

Superficial lymphadenectomy is an easy-to-perform and cost-effective routine technique. Despite its simplicity, it remains underutilized in veterinary medicine, with most practitioners being oncological surgeons. This study aims to enhance accessibility to the surgical procedure by providing anatomical representations of superficial lymphadenectomy in the carcasses of dogs and cats. A preliminary study involving two canines and two felines was conducted, with each group comprising a dog and a cat. Group A was designated to superficial lymphadenectomy techniques to create an illustrated step-by-step procedure, while group B underwent anatomical dissection to expose lymph nodes and their adnexa. The approach to superficial lymph nodes in dogs and cats is simple, allowing for the demonstration of superficial lymphadenectomy techniques in the corpses of dogs and cats without complications. This includes the dissection and presentation of anatomical structures adjacent to the lymph nodes. In conclusion, the techniques applied to subjects in groups A and B proved effective, successfully demonstrating and excising all superficial lymph nodes in the corpses of dogs and cats. These findings suggest that the developed set of techniques developed for lymph node excision holds promise for safe and effective application in live animals., A linfadenectomia superficial é uma técnica de rotina de fácil execução e custo-benefício. Apesar da sua simplicidade, continua subutilizado na medicina veterinária, sendo a maioria dos profissionais cirurgiões oncológicos. Este estudo visa melhorar a acessibilidade ao procedimento cirúrgico, fornecendo representações anatômicas de linfadenectomia superficial em carcaças de cães e gatos. Foi realizado um estudo preliminar envolvendo dois cães e dois gatos, sendo cada grupo composto por um exemplar de cada espécie. O grupo A foi designado para técnicas de linfadenectomia superficial para criar um procedimento passo a passo ilustrado, enquanto o grupo B foi submetido à dissecção anatômica para expor os linfonodos e seus anexos. A abordagem dos linfonodos superficiais em cães e gatos é simples, permitindo a demonstração de técnicas de linfadenectomia superficial em cadáveres de cães e gatos sem complicações. Isto inclui a dissecção e apresentação de estruturas anatômicas adjacentes aos gânglios linfáticos. Concluindo, as técnicas aplicadas aos indivíduos dos grupos A e B mostraram-se eficazes, demonstrando e extirpando com sucesso todos os linfonodos superficiais nos cadáveres de cães e gatos. Essas descobertas sugerem que o conjunto desenvolvido de técnicas para excisão de linfonodos é promissor para aplicação segura e eficaz em animais vivos.

Superficial lymphadenectomy is an easy-to-perform and cost-effective routine technique. Despite its simplicity, it remains underutilized in veterinary medicine, with most practitioners being oncological surgeons. This study aims to enhance accessibility to the surgical procedure by providing anatomical representations of superficial lymphadenectomy in the carcasses of dogs and cats. A preliminary study involving two canines and two felines was conducted, with each group comprising a dog and a cat. Group A was designated to superficial lymphadenectomy techniques to create an illustrated step-by-step procedure, while group B underwent anatomical dissection to expose lymph nodes and their adnexa. The approach to superficial lymph nodes in dogs and cats is simple, allowing for the demonstration of superficial lymphadenectomy techniques in the corpses of dogs and cats without complications. This includes the dissection and presentation of anatomical structures adjacent to the lymph nodes. In conclusion, the techniques applied to subjects in groups A and B proved effective, successfully demonstrating and excising all superficial lymph nodes in the corpses of dogs and cats. These findings suggest that the developed set of techniques developed for lymph node excision holds promise for safe and effective application in live animals., A linfadenectomia superficial é uma técnica de rotina de fácil execução e custo-benefício. Apesar da sua simplicidade, continua subutilizado na medicina veterinária, sendo a maioria dos profissionais cirurgiões oncológicos. Este estudo visa melhorar a acessibilidade ao procedimento cirúrgico, fornecendo representações anatômicas de linfadenectomia superficial em carcaças de cães e gatos. Foi realizado um estudo preliminar envolvendo dois cães e dois gatos, sendo cada grupo composto por um exemplar de cada espécie. O grupo A foi designado para técnicas de linfadenectomia superficial para criar um procedimento passo a passo ilustrado, enquanto o grupo B foi submetido à dissecção anatômica para expor os linfonodos e seus anexos. A abordagem dos linfonodos superficiais em cães e gatos é simples, permitindo a demonstração de técnicas de linfadenectomia superficial em cadáveres de cães e gatos sem complicações. Isto inclui a dissecção e apresentação de estruturas anatômicas adjacentes aos gânglios linfáticos. Concluindo, as técnicas aplicadas aos indivíduos dos grupos A e B mostraram-se eficazes, demonstrando e extirpando com sucesso todos os linfonodos superficiais nos cadáveres de cães e gatos. Essas descobertas sugerem que o conjunto desenvolvido de técnicas para excisão de linfonodos é promissor para aplicação segura e eficaz em animais vivos.

In the past decade, research on measuring and assessing the environmental impact of software has gained significant momentum in science and industry. However, due to the large number of research groups, measurement setups, procedure models, tools, and general novelty of the research area, a comprehensive research framework has yet to be created. The literature documents several approaches from researchers and practitioners who have developed individual methods and models, along with more general ideas like the integration of software sustainability in the context of the UN Sustainable Development Goals, or science communication approaches to make the resource cost of software transparent to society. However, a reference measurement model for the energy and resource consumption of software is still missing. In this article, we jointly develop the Green Software Measurement Model (GSMM), in which we bring together the core ideas of the measurement models, setups, and methods of over 10 research groups in four countries who have done pioneering work in assessing the environmental impact of software. We briefly describe the different methods and models used by these research groups, derive the components of the GSMM from them, and then we discuss and evaluate the resulting reference model. By categorizing the existing measurement models and procedures and by providing guidelines for assimilating and tailoring existing methods, we expect this work to aid new researchers and practitioners who want to conduct measurements for their individual use cases.

Progressing digitalization and increasing demand and use of software cause rises in energy- and resource consumption from information and communication technologies (ICT). This raises the issue of sustainability in ICT, which increasingly includes the sustainability of the software products themselves and the art of creating sustainable software. To this end, we conducted an analysis to gather and present existing literature on three research questions relating to the production of ecologically sustainable software ("Green Coding") and to provide orientation for stakeholders approaching the subject. We compile the approaches to Green Coding and Green Software Engineering (GSE) that have been published since 2010. Furthermore, we considered ways to integrate the findings into existing industrial processes and higher education curricula to influence future development in an environmentally friendly way., Comment: This document is the extended version of the literature report published at the German Informatik Conference titled "Potentials of Green Coding - Findings and Recommendations for Industry, Education and Science". This document has since been updated and expanded to include relevant sources

Det svenska demokratiska samhället strävar ständigt mot att alla människor ska ha lika värde och rättigheter. I såväl lagar som skolans styrdokument framgår det att jämställdhet ska råda och att ingen ska diskrimineras på grund av sitt kön. Trots detta förmedlas normer och värden genom olika medier, däribland skolans läromedel, som elever möter dagligen. Läseböcker kan därmed förmedla synliga såväl som dolda budskap till eleverna. Syftet med studien är att undersöka hur genus och jämställdhet gestaltas i läseböcker som används i undervisningen i svenskämnet för årskurs 1-3, med avsikt att senare även kunna jämföra respektive läseboks innehåll i relation till dess samtida läroplan. Den teoretiska grund som används i studien är Hirdmans (2003) genusteori samt Nikolajevas (2017) schema för ”manliga” respektive ”kvinnliga” egenskaper. I vår analys av läseböcker används ideologikritisk analys som metod för att kunna analysera läseböckernas såväl framskrivna som dolda värderingar. De tre läseböckerna som analyseras är Djurspanarna (Norlin & Södergren 2001), Nyckeln till skatten (Wänblad & Nygård 2013) och Den gåtfulla tavlan (Genar & Sjölin 2021). Studiens resultat visar att läseböckerna över tid blir allt mer jämställda och fria från könsstereotyper. Även om det i den nyaste läseboken finns några exempel på stereotyper är utvecklingen från den äldsta läseboken stor. Läroplanerna följer även samma utveckling, från Lpo 94 (Utbildningsdepartementet 1994) till Lgr 11 (Skolverket 2011) och Lgr 22 (Skolverket 2022) har det skett en stor utveckling när det kommer till jämställdhets- och genusperspektivet. När läseböckernas innehåll sätts i relation till dess samtida läroplan kan slutsatsen dras att ingen läsebok helt förhåller sig till det som framgår i läroplanen, men att läseböckerna kronologiskt förhåller sig mer och mer till läroplanernas innehåll.

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Contains fulltext : 293272.pdf (Publisher’s version ) (Open Access), Leber congenital amaurosis (LCA) is a group of inherited retinal diseases characterized by early-onset, rapid loss of photoreceptor cells. Despite the discovery of a growing number of genes associated with this disease, the molecular mechanisms of photoreceptor cell degeneration of most LCA subtypes remain poorly understood. Here, using retina-specific affinity proteomics combined with ultrastructure expansion microscopy, we reveal the structural and molecular defects underlying LCA type 5 (LCA5) with nanoscale resolution. We show that LCA5-encoded lebercilin, together with retinitis pigmentosa 1 protein (RP1) and the intraflagellar transport (IFT) proteins IFT81 and IFT88, localized at the bulge region of the photoreceptor outer segment (OS), a region crucial for OS membrane disc formation. Next, we demonstrate that mutant mice deficient in lebercilin exhibited early axonemal defects at the bulge region and the distal OS, accompanied by reduced levels of RP1 and IFT proteins, affecting membrane disc formation and presumably leading to photoreceptor death. Finally, adeno-associated virus-based LCA5 gene augmentation partially restored the bulge region, preserved OS axoneme structure and membrane disc formation, and resulted in photoreceptor cell survival. Our approach thus provides a next level of assessment of retinal (gene) therapy efficacy at the molecular level.

Contains fulltext : 290085.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 289452.pdf (Publisher’s version ) (Open Access)

[EN] The marine microbiome, including prokaryotes and minute unicellular eukaryotes, stands for a great part of biodiversity and is essential for ocean food webs and global biogeochemical cycles. Yet, investigating their diversity and ecology was challenging due to sampling and methodological constraints. Modern molecular and bioinformatic tools together with recent large-scale oceanographic sampling cruises (e.g. Tara Oceans and Malaspina) have helped the scientific community to assess the ocean’s microbial diversity with an unprecedented depth of analysis. Recent studies have revealed that microbial communities display latitudinal, seasonal, and depthrelated patterns. However, there is still a limited understanding of the mechanisms underlying these biogeographical patterns. In this thesis, I have applied theoretical ecology on DNA sequencing data to disentangle the main ecological processes shaping the ocean’s microbiome across space and time. To do so, I have combined molecular data from two global oceanographic cruises (Tara Oceans and Malaspina), one regional cruise (HotMix Cruise) in the Mediterranean Sea, and from microbial observatories located in different latitudes. First, I demonstrate the high impact of the Theory of Ecological Communities (Vellend 2010, 2016) on the field of microbial ecology using a scientometric approach. Second, I investigated the relative importance of ecological processes (selection, dispersal limitation and ecological drift) shaping picoplankton communities inhabiting different ocean layers. To accomplish this goal, I analyzed 16S- and 18S-rRNA-gene amplicon sequence variants (ASVs) from samples (N=688) covering the epi- (0-200 m), meso- (200-1,000 m) and bathypelagic (1,000-4,000 m) layers of the ocean. I found that the role of selection decreased with depth due to a potential decrease in habitat heterogeneity. Conversely, the relative importance of dispersal limitation increased with depth due to dispersal barriers such as the, [BR] O microbioma marinho, incluindo procariontes e minúsculos eucariontes unicelulares, representa uma grande parte da biodiversidade e é essencial em teias tróficas e ciclos biogeoquímicos globais. No entanto, investigar a diversidade e ecologia microbiana em escala global era um desafio por limitações metodológicas e amostrais. A combinação de ferramentas moleculares e bioinformáticas modernas à grandes expedições oceanográficas (ex.: Tara Oceans e Malaspina) permitiram a descoberta de padrões de diversidade microbiana em escala global. Estudos recentes revelaram que as comunidades microbianas apresentam padrões latitudinais, sazonais e de profundidade. No entanto, ainda há uma compreensão limitada dos mecanismos ecológicos que estão por trás destes padrões biogeográficos. Nesta tese, apliquei ecologia teórica à dados de sequenciamento de DNA para investigar os principais processos ecológicos que moldam comunidades microbianas em diferentes camadas de profundidade e regiões latitudinais do oceano. Para isso, combinei dados moleculares de duas expedições oceanográficas globais (Tara Oceans e Malaspina), de uma expedição regional (HotMix Cruise) no Mar Mediterrâneo e de observatórios microbianos localizados em diferentes latitudes. Primeiro, demonstro o alto impacto da Teoria das Comunidades Ecológicas (Vellend 2010, 2016) no campo da ecologia microbiana utilizando uma abordagem cienciométrica. Em segundo lugar, investiguei a importância relativa dos processos ecológicos (seleção, limitação de dispersão e deriva ecológica) na montagem de comunidades microbianas que habitam diferentes camadas oceânicas. Para atingir este objetivo, analisei variantes únicas de sequências de amplicons (ASVs) dos genes 16S- e 18S-rRNA de amostras (N=688) cobrindo as camadas epi- (0-200 m), meso- (200-1.000 m) e batipelágicas (1.000-4.000 m) do oceano. Enquanto a importância relativa da seleção diminuiu com a profundidade devido a um potencial diminuição da heterogeneidade do habitat, a

Various animal models are used for research; however, non-human primates are well suited for biomedical research owing to their genetic homology with humans. The objective of this research was the anatomical characterization of red howler’s kidneys in view of the scarcity of information in the literature. Protocols were approved by the Committee for Ethics in the Use of Animals at the Federal Rural University of Rio de Janeiro (number 018/2017). The study was conducted at the Laboratory of Teaching and Research in Domestic and Wild Animal Morphology, Federal Rural University of Rio de Janeiro. Specimens of Alouatta guariba clamitans were collected from the Serra dos Órgãos National Park road in Rio de Janeiro and subsequently frozen. Four adult cadavers (two males and two females) were used, identified, and injected with a 10% formaldehyde solution. Later, the specimens were dissected, and measurements and topography of the kidneys and renal vessels were recorded. The kidneys of A. g. clamitans resemble a “bean seed,” with a smooth surface. The longitudinal section shows two distinct regions, cortical and medullary; in addition, the kidneys are unipyramidal. The renal arteries emerged from the abdominal aorta as a single vessel posterior to the renal veins. The renal veins drained directly into the caudal vena cava as a single vessel in all specimens., Vários modelos animais são usados para pesquisa, no entanto, primatas não humanos são adequados para pesquisas biomédicas devido à sua homologia genética com humanos. O objetivo desta pesquisa foi a caracterização anatômica dos rins do Bugio, tendo em vista a escassez de informações na literatura. Os protocolos foram aprovados pelo Comitê de Ética no Uso de Animais da Universidade Federal Rural do Rio de Janeiro (número 018/ 2017). O estudo foi realizado no Laboratório de Ensino e Pesquisa em Morfologia de Animais Domésticos e Silvestres da Universidade Federal Rural do Rio de Janeiro. Espécimes de Alouatta guariba clamitans foram coletados da estrada para o Parque Nacional da Serra dos Órgãos no Rio de Janeiro, e posteriormente congelados. Foram utilizados quatro cadáveres adultos (dois machos e duas fêmeas), identificados e injetados com solução de formaldeído a 10%. Os rins de A. g. clamitans assemelham-se a uma “semente de feijão”, com superfície lisa. Ao corte longitudinal apresenta duas regiões distintas, cortical e medular, além disso, apresenta-se unipiramidal. As artérias renais emergiram da aorta abdominal como um único vaso, posteriormente às veias renais. As veias renais drenaram diretamente para a veia cava caudal como um único vaso em todos os espécimes.

Establishment and maintenance of the primary cilium as a signaling-competent organelle requires a high degree of fine tuning, which is at least in part achieved by a variety of post-translational modifications. One such modification is ubiquitination. The small and highly conserved ubiquitin protein possesses a unique versatility in regulating protein function via its ability to build mono and polyubiquitin chains onto target proteins. We aimed to take an unbiased approach to generate a comprehensive blueprint of the ciliary ubiquitinome by deploying a multi-proteomics approach using both ciliary-targeted ubiquitin affinity proteomics, as well as ubiquitin-binding domain-based proximity labelling in two different mammalian cell lines. This resulted in the identification of several key proteins involved in signaling, cytoskeletal remodeling and membrane and protein trafficking. Interestingly, using two different approaches in IMCD3 and RPE1 cells, respectively, we uncovered several novel mechanisms that regulate cilia function. In our IMCD3 proximity labeling cell line model, we found a highly enriched group of ESCRT-dependent clathrin-mediated endocytosis-related proteins, suggesting an important and novel role for this pathway in the regulation of ciliary homeostasis and function. In contrast, in RPE1 cells we found that several structural components of caveolae (CAV1, CAVIN1, and EHD2) were highly enriched in our cilia affinity proteomics screen. Consistently, the presence of caveolae at the ciliary pocket and ubiquitination of CAV1 specifically, were found likely to play a role in the regulation of ciliary length in these cells. Cilia length measurements demonstrated increased ciliary length in RPE1 cells stably expressing a ubiquitination impaired CAV1 mutant protein. Furthermore, live cell imaging in the same cells revealed decreased CAV1 protein turnover at the cilium as the possible cause for this phenotype. In conclusion, we have generated a comprehensive li

Demographic trends across Europe indicate that many regions face sustained population decline due to aging and out-migration. Rural regions are often prone to flood hazards and have repeatedly been affected by damaging events in the past. However, we lack in-depth knowledge about how demographic trends challenge their capacities, abilities, and plans to manage flood risks. In this paper, we aim to close this gap. We employed a mixed-methods approach in the Gailtal-region in Carinthia (Austria), which combines the assessment of exposure to flood risk, social vulnerability, coping ability and adaptation capacity, as well as a discourse analysis. This comprehensive approach was designed to assess how demographic change impacts flood risk management. The findings do not support the hypothesis that population decline increases communities’ social vulnerability and reduces their coping ability and adaptation capacity. Additionally, the selected municipalities showed a strong increase in exposure. This is an example of the exposure paradox, which describes the phenomenon that settlement and population dynamics are not interconnected at all, especially in regions with a limited share of suitable land. Finally, our results show that current flood risk management and the corresponding social and political discourse mainly neglect the challenge of population decline. Overall, this study indicates that public administrations need to address the challenges of weak communities in flood risk management and consider how they might empower local authorities and citizens to adapt to future events – in full consideration of the demographic trends they have to expect.

Demographic trends across Europe indicate that many regions face sustained population decline due to aging and out-migration. Rural regions are often prone to flood hazards and have repeatedly been affected by damaging events in the past. However, we lack in-depth knowledge about how demographic trends challenge their capacities, abilities, and plans to manage flood risks. In this paper, we aim to close this gap. We employed a mixed-methods approach in the Gailtal-region in Carinthia (Austria), which combines the assessment of exposure to flood risk, social vulnerability, coping ability and adaptation capacity, as well as a discourse analysis. This comprehensive approach was designed to assess how demographic change impacts flood risk management. The findings do not support the hypothesis that population decline increases communities’ social vulnerability and reduces their coping ability and adaptation capacity. Additionally, the selected municipalities showed a strong increase in exposure. This is an example of the exposure paradox, which describes the phenomenon that settlement and population dynamics are not interconnected at all, especially in regions with a limited share of suitable land. Finally, our results show that current flood risk management and the corresponding social and political discourse mainly neglect the challenge of population decline. Overall, this study indicates that public administrations need to address the challenges of weak communities in flood risk management and consider how they might empower local authorities and citizens to adapt to future events – in full consideration of the demographic trends they have to expect.

Demographic trends across Europe indicate that many regions face sustained population decline due to aging and out-migration. Rural regions are often prone to flood hazards and have repeatedly been affected by damaging events in the past. However, we lack in-depth knowledge about how demographic trends challenge their capacities, abilities, and plans to manage flood risks. In this paper, we aim to close this gap. We employed a mixed-methods approach in the Gailtal-region in Carinthia (Austria), which combines the assessment of exposure to flood risk, social vulnerability, coping ability and adaptation capacity, as well as a discourse analysis. This comprehensive approach was designed to assess how demographic change impacts flood risk management. The findings do not support the hypothesis that population decline increases communities’ social vulnerability and reduces their coping ability and adaptation capacity. Additionally, the selected municipalities showed a strong increase in exposure. This is an example of the exposure paradox, which describes the phenomenon that settlement and population dynamics are not interconnected at all, especially in regions with a limited share of suitable land. Finally, our results show that current flood risk management and the corresponding social and political discourse mainly neglect the challenge of population decline. Overall, this study indicates that public administrations need to address the challenges of weak communities in flood risk management and consider how they might empower local authorities and citizens to adapt to future events – in full consideration of the demographic trends they have to expect.

Establishment and maintenance of the primary cilium as a signaling-competent organelle requires a high degree of fine tuning, which is at least in part achieved by a variety of post-translational modifications. One such modification is ubiquitination. The small and highly conserved ubiquitin protein possesses a unique versatility in regulating protein function via its ability to build mono and polyubiquitin chains onto target proteins. We aimed to take an unbiased approach to generate a comprehensive blueprint of the ciliary ubiquitinome by deploying a multi-proteomics approach using both ciliary-targeted ubiquitin affinity proteomics, as well as ubiquitin-binding domain-based proximity labelling in two different mammalian cell lines. This resulted in the identification of several key proteins involved in signaling, cytoskeletal remodeling and membrane and protein trafficking. Interestingly, using two different approaches in IMCD3 and RPE1 cells, respectively, we uncovered several novel mechanisms that regulate cilia function. In our IMCD3 proximity labeling cell line model, we found a highly enriched group of ESCRT-dependent clathrin-mediated endocytosis-related proteins, suggesting an important and novel role for this pathway in the regulation of ciliary homeostasis and function. In contrast, in RPE1 cells we found that several structural components of caveolae (CAV1, CAVIN1, and EHD2) were highly enriched in our cilia affinity proteomics screen. Consistently, the presence of caveolae at the ciliary pocket and ubiquitination of CAV1 specifically, were found likely to play a role in the regulation of ciliary length in these cells. Cilia length measurements demonstrated increased ciliary length in RPE1 cells stably expressing a ubiquitination impaired CAV1 mutant protein. Furthermore, live cell imaging in the same cells revealed decreased CAV1 protein turnover at the cilium as the possible cause for this phenotype. In conclusion, we have generated a comprehensive li

Društva za tjelovježbu u Hrvatskoj se osnivaju od kraja 19. stoljeća, točnije, od 1874, kada je osnovano prvo sokolsko društvo u Zagrebu. Uz osnivanje društva potrebno je donijeti pravila po kojima bi ono funkcioniralo. No, samo manji je broj pravila sačuvan. U ovom su članku prvi put objavljena Pravila Društva za tjelovježbu Hrvatski sokol u Čazmi. Napisana su 1912, a potvrđena 21. siječnja 1913. od strane Kraljevske hrvatsko-slavonsko-dalmatinske zemaljske vlade, Odjela za unutarnje poslove u Zagrebu., The beginnings of the Sokol movement are tied to Bohemia, whence it spread inside the Habsburg Monarchy. In Croatia, its beginnings are associated with the end of Bach’s absolutism and the elevation of Ivan Mažuranić to the post of ban (royal governor) in 1873. With the passage of the Public School and Teacher Training College Organization Act, physical education became a mandatory course in all primary and secondary schools and teacher training colleges, and the members of the Croatian Sokol were placed in charge of instruction. The Sokol idea thus expanded into the smallest communities that had schools and physical education classes. This idea also made its way to Čazma. Rules were drawn up to govern the functioning of the Sokol associations. The first rules were compiled in 1874 by the Zagreb association, since this was the first to be established in Croatia. The “Rules of the Croatian Sokol Zagreb Gymnastics Association” were ratified at the end of that year. To ensure that the associations established later would have their own rules, Hinko Mašek Bosnodolski released a booklet called Sokolsko vježbanje. Prva uputa za sokolska društva [Sokol Exercise. First Instructions for Sokol Associations] in 1894 which contained the “Basic Rules for Sokol Associations Organized According to the Zagreb Sokol Rules.” The rules of the Croatian Sokol Gymnastics Association in Čazma were written in 1912, and ratified on 21 January 1913. The activities of the Croatian Sokol in Čazma were essential to the development of sports and the establishment of sports clubs and associations in the wider Čazma area.

Det svenska demokratiska samhället strävar ständigt mot att alla människor ska ha lika värde och rättigheter. I såväl lagar som skolans styrdokument framgår det att jämställdhet ska råda och att ingen ska diskrimineras på grund av sitt kön. Trots detta förmedlas normer och värden genom olika medier, däribland skolans läromedel, som elever möter dagligen. Läseböcker kan därmed förmedla synliga såväl som dolda budskap till eleverna. Syftet med studien är att undersöka hur genus och jämställdhet gestaltas i läseböcker som används i undervisningen i svenskämnet för årskurs 1-3, med avsikt att senare även kunna jämföra respektive läseboks innehåll i relation till dess samtida läroplan. Den teoretiska grund som används i studien är Hirdmans (2003) genusteori samt Nikolajevas (2017) schema för ”manliga” respektive ”kvinnliga” egenskaper. I vår analys av läseböcker används ideologikritisk analys som metod för att kunna analysera läseböckernas såväl framskrivna som dolda värderingar. De tre läseböckerna som analyseras är Djurspanarna (Norlin & Södergren 2001), Nyckeln till skatten (Wänblad & Nygård 2013) och Den gåtfulla tavlan (Genar & Sjölin 2021). Studiens resultat visar att läseböckerna över tid blir allt mer jämställda och fria från könsstereotyper. Även om det i den nyaste läseboken finns några exempel på stereotyper är utvecklingen från den äldsta läseboken stor. Läroplanerna följer även samma utveckling, från Lpo 94 (Utbildningsdepartementet 1994) till Lgr 11 (Skolverket 2011) och Lgr 22 (Skolverket 2022) har det skett en stor utveckling när det kommer till jämställdhets- och genusperspektivet. När läseböckernas innehåll sätts i relation till dess samtida läroplan kan slutsatsen dras att ingen läsebok helt förhåller sig till det som framgår i läroplanen, men att läseböckerna kronologiskt förhåller sig mer och mer till läroplanernas innehåll.

BACKGROUND: In vitro studies using nucleus pulposus (NP) cells are commonly used to investigate disc cell biology and pathogenesis, or to aid in the development of new therapies. However, lab-to-lab variability jeopardizes the much-needed progress in the field. Here, an international group of spine scientists collaborated to standardize extraction and expansion techniques for NP cells to reduce variability, improve comparability between labs and improve utilization of funding and resources. METHODS: The most commonly applied methods for NP cell extraction, expansion, and re-differentiation were identified using a questionnaire to research groups worldwide. NP cell extraction methods from rat, rabbit, pig, dog, cow, and human NP tissue were experimentally assessed. Expansion and re-differentiation media and techniques were also investigated. RESULTS: Recommended protocols are provided for extraction, expansion, and re-differentiation of NP cells from common species utilized for NP cell culture. CONCLUSIONS: This international, multilab and multispecies study identified cell extraction methods for greater cell yield and fewer gene expression changes by applying species-specific pronase usage, 60-100 U/ml collagenase for shorter durations. Recommendations for NP cell expansion, passage number, and many factors driving successful cell culture in different species are also addressed to support harmonization, rigor, and cross-lab comparisons on NP cells worldwide.

The aerobic anoxygenic phototrophic (AAP) bacteria are common in most marine environments but their global diversity and biogeography remain poorly characterized. Here, we analyzed AAP communities across 113 globally-distributed surface ocean stations sampled during the Malaspina Expedition in the tropical and subtropical ocean. By means of amplicon sequencing of the pufM gene, a genetic marker for this functional group, we show that AAP communities along the surface ocean were mainly composed of members of the Halieaceae (Gammaproteobacteria), which were adapted to a large range of environmental conditions, and of different clades of the Alphaproteobacteria, which seemed to dominate under particular circumstances, such as in the oligotrophic gyres. AAP taxa were spatially structured within each of the studied oceans, with communities from adjacent stations sharing more taxonomic similarities. AAP communities were composed of a large pool of rare members and several habitat specialists. When compared to the surface ocean prokaryotic and picoeukaryotic communities, it appears that AAP communities display an idiosyncratic global biogeographical pattern, dominated by selection processes and less influenced by dispersal limitation. Our study contributes to the understanding of how AAP communities are distributed in the horizontal dimension and the mechanisms underlying their distribution across the global surface ocean.

Axonemal dynein ATPases direct ciliary and flagellar beating via adenosine triphosphate (ATP) hydrolysis. The modulatory effect of adenosine monophosphate (AMP) and adenosine diphosphate (ADP) on flagellar beating is not fully understood. Here, we describe a deficiency of cilia and flagella associated protein 45 (CFAP45) in humans and mice that presents a motile ciliopathy featuring situs inversus totalis and asthenospermia. CFAP45-deficient cilia and flagella show normal morphology and axonemal ultrastructure. Proteomic profiling links CFAP45 to an axonemal module including dynein ATPases and adenylate kinase as well as CFAP52, whose mutations cause a similar ciliopathy. CFAP45 binds AMP in vitro, consistent with structural modelling that identifies an AMP-binding interface between CFAP45 and AK8. Microtubule sliding of dyskinetic sperm from Cfap45−/− mice is rescued with the addition of either AMP or ADP with ATP, compared to ATP alone. We propose that CFAP45 supports mammalian ciliary and flagellar beating via an adenine nucleotide homeostasis module., source:https://www.nature.com/articles/s41467-020-19113-0#rightslink

Aufgrund seines hervorragenden Verhaltens gegenüber verschiedenen Beanspruchungen ist hochduktiler Beton (engl.: Strain-hardening cement-based composite, SHCC) ein vielversprechender Baustoff für eine Vielzahl an Anwendungen unter statischen, stoßartigen und zyklischen Belastungen. Für einen sicheren Materialeinsatz ist ein tieferes Verständnis des zyklischen Verhaltens erforderlich. Dazu wurden zyklische Belastungsversuche an hochfestem SHCC mit Polyethylen (PE)- Fasern unter Variation des Belastungsregimes durchgeführt. Anhand der Versuche und der morphologischen Analysen konnte gezeigt werden, dass PE-SHCC eine große Sensitivität gegenüber der Variation der mechanischen Einwirkung zeigt.

Axonemal dynein ATPases direct ciliary and flagellar beating via adenosine triphosphate (ATP) hydrolysis. The modulatory effect of adenosine monophosphate (AMP) and adenosine diphosphate (ADP) on flagellar beating is not fully understood. Here, we describe a deficiency of cilia and flagella associated protein 45 (CFAP45) in humans and mice that presents a motile ciliopathy featuring situs inversus totalis and asthenospermia. CFAP45-deficient cilia and flagella show normal morphology and axonemal ultrastructure. Proteomic profiling links CFAP45 to an axonemal module including dynein ATPases and adenylate kinase as well as CFAP52, whose mutations cause a similar ciliopathy. CFAP45 binds AMP in vitro, consistent with structural modelling that identifies an AMP-binding interface between CFAP45 and AK8. Microtubule sliding of dyskinetic sperm from Cfap45−/− mice is rescued with the addition of either AMP or ADP with ATP, compared to ATP alone. We propose that CFAP45 supports mammalian ciliary and flagellar beating via an adenine nucleotide homeostasis module., source:https://www.nature.com/articles/s41467-020-19113-0#rightslink

The aerobic anoxygenic phototrophic (AAP) bacteria are common in most marine environments but their global diversity and biogeography remain poorly characterized. Here, we analyzed AAP communities across 113 globally-distributed surface ocean stations sampled during the Malaspina Expedition in the tropical and subtropical ocean. By means of amplicon sequencing of the pufM gene, a genetic marker for this functional group, we show that AAP communities along the surface ocean were mainly composed of members of the Halieaceae (Gammaproteobacteria), which were adapted to a large range of environmental conditions, and of different clades of the Alphaproteobacteria, which seemed to dominate under particular circumstances, such as in the oligotrophic gyres. AAP taxa were spatially structured within each of the studied oceans, with communities from adjacent stations sharing more taxonomic similarities. AAP communities were composed of a large pool of rare members and several habitat specialists. When compared to the surface ocean prokaryotic and picoeukaryotic communities, it appears that AAP communities display an idiosyncratic global biogeographical pattern, dominated by selection processes and less influenced by dispersal limitation. Our study contributes to the understanding of how AAP communities are distributed in the horizontal dimension and the mechanisms underlying their distribution across the global surface ocean

Automne 1991 : une véritable fin d'été indien. Et soudain, c'est la tempête du siècle. Terrible, impitoyable, avec des vents de plus de cent n?uds et des vagues de vingt à trente mètres. « The perfect storm » ? la tempête parfaite comme dira un météorologiste américain? À Gloucester, dans le Massachusetts, Bobby Shatford a longuement hésité avant d'embarquer sur l'Andrea Gail, un bateau de pêche à l'espadon, pourtant réputé pour sa robustesse, son efficacité et la compétence de son capitaine. Bobby Shatford et les cinq autres hommes constituant l'équipage de l'Andrea Gail ne reviendront jamais, broyés, dévorés par la tempête. C'est leur histoire et celle des autres équipages que Sebastian Junger a choisi de reconstituer fidèlement, pièce à pièce, à travers les témoignages des survivants et des proches des disparus comme à travers la méticuleuse analyse des données techniques et des rapports officiels. Et la vigueur de son style aidant, ce gigantesque travail, débouche à la fois sur un sommet du reportage et sur une authentique et puissante oeuvre littéraire, tirant de la simple et cruelle réalité des faits un récit digne des plus grands livres de fiction.

Automne 1991 : une véritable fin d'été indien. Et soudain, c'est la tempête du siècle. Terrible, impitoyable, avec des vents de plus de cent n?uds et des vagues de vingt à trente mètres. « The perfect storm » ? la tempête parfaite comme dira un météorologiste américain? À Gloucester, dans le Massachusetts, Bobby Shatford a longuement hésité avant d'embarquer sur l'Andrea Gail, un bateau de pêche à l'espadon, pourtant réputé pour sa robustesse, son efficacité et la compétence de son capitaine. Bobby Shatford et les cinq autres hommes constituant l'équipage de l'Andrea Gail ne reviendront jamais, broyés, dévorés par la tempête. C'est leur histoire et celle des autres équipages que Sebastian Junger a choisi de reconstituer fidèlement, pièce à pièce, à travers les témoignages des survivants et des proches des disparus comme à travers la méticuleuse analyse des données techniques et des rapports officiels. Et la vigueur de son style aidant, ce gigantesque travail, débouche à la fois sur un sommet du reportage et sur une authentique et puissante oeuvre littéraire, tirant de la simple et cruelle réalité des faits un récit digne des plus grands livres de fiction.

Automne 1991 : une véritable fin d'été indien. Et soudain, c'est la tempête du siècle. Terrible, impitoyable, avec des vents de plus de cent n?uds et des vagues de vingt à trente mètres. « The perfect storm » ? la tempête parfaite comme dira un météorologiste américain? À Gloucester, dans le Massachusetts, Bobby Shatford a longuement hésité avant d'embarquer sur l'Andrea Gail, un bateau de pêche à l'espadon, pourtant réputé pour sa robustesse, son efficacité et la compétence de son capitaine. Bobby Shatford et les cinq autres hommes constituant l'équipage de l'Andrea Gail ne reviendront jamais, broyés, dévorés par la tempête. C'est leur histoire et celle des autres équipages que Sebastian Junger a choisi de reconstituer fidèlement, pièce à pièce, à travers les témoignages des survivants et des proches des disparus comme à travers la méticuleuse analyse des données techniques et des rapports officiels. Et la vigueur de son style aidant, ce gigantesque travail, débouche à la fois sur un sommet du reportage et sur une authentique et puissante oeuvre littéraire, tirant de la simple et cruelle réalité des faits un récit digne des plus grands livres de fiction.

A number of malicious activities, such as cyberbullying, disinformation, and phishing, are becoming increasingly serious, affecting the wellbeing of Internet users both financially and psychologically. These malicious activities are inherently socio-technical, and therefore effective countermeasures against them must draw not only from engineering and computer science, but also from other disciplines. To discuss these topics and find appropriate countermeasures, we assembled a group of researchers from a number of disciplines such as computer science, criminology, crime science, psychology, and education. Through five days of brainstorming and discussion, the participants developed a roadmap for future research on these topics, along four directions: modelling the attackers, measuring human behavior, detection and prevention approaches for online threats to adolescents, and understanding unintended consequences of mitigation techniques.

Automne 1991 : une véritable fin d'été indien. Et soudain, c'est la tempête du siècle. Terrible, impitoyable, avec des vents de plus de cent n?uds et des vagues de vingt à trente mètres. « The perfect storm » ? la tempête parfaite comme dira un météorologiste américain? À Gloucester, dans le Massachusetts, Bobby Shatford a longuement hésité avant d'embarquer sur l'Andrea Gail, un bateau de pêche à l'espadon, pourtant réputé pour sa robustesse, son efficacité et la compétence de son capitaine. Bobby Shatford et les cinq autres hommes constituant l'équipage de l'Andrea Gail ne reviendront jamais, broyés, dévorés par la tempête. C'est leur histoire et celle des autres équipages que Sebastian Junger a choisi de reconstituer fidèlement, pièce à pièce, à travers les témoignages des survivants et des proches des disparus comme à travers la méticuleuse analyse des données techniques et des rapports officiels. Et la vigueur de son style aidant, ce gigantesque travail, débouche à la fois sur un sommet du reportage et sur une authentique et puissante oeuvre littéraire, tirant de la simple et cruelle réalité des faits un récit digne des plus grands livres de fiction.

A number of malicious activities, such as cyberbullying, disinformation, and phishing, are becoming increasingly serious, affecting the wellbeing of Internet users both financially and psychologically. These malicious activities are inherently socio-technical, and therefore effective countermeasures against them must draw not only from engineering and computer science, but also from other disciplines. To discuss these topics and find appropriate countermeasures, we assembled a group of researchers from a number of disciplines such as computer science, criminology, crime science, psychology, and education. Through five days of brainstorming and discussion, the participants developed a roadmap for future research on these topics, along four directions: modelling the attackers, measuring human behavior, detection and prevention approaches for online threats to adolescents, and understanding unintended consequences of mitigation techniques.

BackgroundHistopathological analysis of intervertebral disc (IVD) tissues is a critical domain of back pain research. Identification, description, and classification of attributes that distinguish abnormal tissues form a basis for probing disease mechanisms and conceiving novel therapies. Unfortunately, lack of standardized methods and nomenclature can limit comparisons of results across studies and prevent organizing information into a clear representation of the hierarchical, spatial, and temporal patterns of IVD degeneration. Thus, the following Orthopaedic Research Society (ORS) Spine Section Initiative aimed to develop a standardized histopathology scoring scheme for human IVD degeneration.MethodsGuided by a working group of experts, this prospective process entailed a series of stages that consisted of reviewing and assessing past grading schemes, surveying IVD researchers globally on current practice and recommendations for a new grading system, utilizing expert opinion a taxonomy of histological grading was developed, and validation performed.ResultsA standardized taxonomy was developed, which showed excellent intra-rater reliability for scoring nucleus pulposus (NP), annulus fibrosus (AF), and cartilaginous end plate (CEP) regions (interclass correlation [ICC] > .89). The ability to reliably detect subtle changes varied by IVD region, being poorest in the NP (ICC: .89-.95) where changes at the cellular level were important, vs the AF (ICC: .93-.98), CEP (ICC: .97-.98), and boney end plate (ICC: .96-.99) where matrix and structural changes varied more dramatically with degeneration.ConclusionsThe proposed grading system incorporates more comprehensive descriptions of degenerative features for all the IVD sub-tissues than prior criteria. While there was excellent reliability, our results reinforce the need for improved training, particularly for novice raters. Future evaluation of the proposed system in real-world settings (eg, at the microscope) will be n

Two distinct genetically defined entities of ependymoma arising in the supratentorial compartment are characterized by the presence of either a C11orf95-RELA or a YAP-MAMLD1 fusion, respectively. There is growing evidence that supratentorial ependymomas without these genetic features exist. In this study, we report on 18 pediatric non-RELA/non-YAP supratentorial ependymomas that were systematically characterized by means of their histology, immunophenotype, genetics, and epigenomics. Comprehensive molecular analyses included high-resolution copy number analysis, methylation profiling, analysis of fusion transcripts by Nanostring technology, and RNA sequencing. Based upon histological and immunohistochemical features two main patterns were identified-RELA-like (n = 9) and tanycytic ependymomas (n = 6). In the RELA-like group histologically assigned to WHO grade III and resembling RELA-fused ependymomas, tumors lacked nuclear expression of p65-RelA as a surrogate marker for a pathological activation of the NF-kappa B pathway. Three tumors showed alternative C11orf95 fusions to MAML2 or NCOA1. A methylation-based brain tumor classifier assigned two RELA-like tumors to the methylation class EP, RELA-fusion; the others demonstrated no significant similarity score. Of the tanycytic group, 5/6 tumors were assigned a WHO grade II. No gene fusions were detected. Methylation profiling did not show any association with an established methylation class. We additionally identified two astroblastoma-like tumors that both presented with chromothripsis of chromosome 22 but lacked MN1 breaks according to FISH analysis. They revealed novel fusion events involving genes in chromosome 22. One further tumor with polyploid cytogenetics was interpreted as PFB ependymoma by the brain tumor methylation classifier but had no relation to the posterior fossa. Clinical follow-up was available for 16/18 patients. Patients with tanycytic and astroblastoma-like tumors had no relapse, while 2 patie

In patients with brain metastases (BM), advanced age is considered a negative prognostic factor. To address the potential reasons for that, we assessed 807 patients who had undergone BM resection; 315 patients aged at least 65 years (group A) were compared with 492 younger patients (group B). We analyzed the impact of the pre- and postoperative Karnofsky performance status (KPS), postoperative treatment structure and post-treatment survival. BM resection significantly improved KPS scores in both groups (p = 0.0001). Median survival after BM resection differed significantly between the groups (A: 5.81 vs. B: 8.12 months; p = 0.0015). In both groups, patients who received postoperative systemic treatment showed significantly longer overall survival (p = 0.00001). However, elderly patients less frequently received systemic treatment (p = 0.0001) and the subgroup of elderly patients receiving such therapies had a significantly higher postsurgical KPS score (p = 0.0007). In all patients receiving systemic treatment, age was no longer a negative prognostic factor. Resection of BM improves the functional status of elderly patients, thus enhancing the likeliness to receive systemic treatment, which, in turn, leads to longer overall survival. In the context of such a treatment structure, age alone is no longer a prognostic factor for survival.

Simple Summary In this monocentric retrospective analysis, the extent of resection of singular/solitary brain metastases has no impact on local recurrence and overall survival rates in patients receiving multidisciplinary adjuvant treatment. Since systemic disease progression is the leading cause of death, and an uncontrolled systemic disease status, along with adjuvant treatment, present independent predictors of overall survival, a comprehensive, multidisciplinary treatment concept is essential for patients with brain metastases. Background and Purpose: The value of gross-total surgical resection remains debatable in patients with brain metastases (BMs) as most patients succumb to systemic disease progression. In this study, we evaluated the impact of the extent of resection of singular/solitary BM on in-brain recurrence (iBR), focusing on local recurrence (LR) and overall survival (OS) in an interdisciplinary adjuvant treatment setting. Patients and Methods: In this monocentric retrospective analysis, we included patients receiving surgery of one BM and subsequent adjuvant treatment. A radiologist and a neurosurgeon determined in consensus the extent of resection based on magnetic resonance imaging. The OS was calculated using Kaplan-Meier estimates; prognostic factors for LR and OS were analysed by Log rank test and Cox proportional hazards. Results: We analyzed 197 patients. Gross-total resection was achieved in 123 (62.4%) patients. All patients were treated with adjuvant radiotherapy, and 130 (66.0%) received systemic treatment. Ninety-six (48.7%) patients showed iBR with an LR rate of 23.4%. LR was not significantly influenced by the extent of resection (p = 0.139) or any other parameter. The median OS after surgery was 18 (95%CI 12.5-23.5) months. In univariate analysis, the extent of resection did not influence OS (p = 0.6759), as opposed to adjuvant systemic treatment (p < 0.0001) and controlled systemic disease (p = 0.039). Systemic treatment and control

BackgroundHistopathological analysis of intervertebral disc (IVD) tissues is a critical domain of back pain research. Identification, description, and classification of attributes that distinguish abnormal tissues form a basis for probing disease mechanisms and conceiving novel therapies. Unfortunately, lack of standardized methods and nomenclature can limit comparisons of results across studies and prevent organizing information into a clear representation of the hierarchical, spatial, and temporal patterns of IVD degeneration. Thus, the following Orthopaedic Research Society (ORS) Spine Section Initiative aimed to develop a standardized histopathology scoring scheme for human IVD degeneration.MethodsGuided by a working group of experts, this prospective process entailed a series of stages that consisted of reviewing and assessing past grading schemes, surveying IVD researchers globally on current practice and recommendations for a new grading system, utilizing expert opinion a taxonomy of histological grading was developed, and validation performed.ResultsA standardized taxonomy was developed, which showed excellent intra-rater reliability for scoring nucleus pulposus (NP), annulus fibrosus (AF), and cartilaginous end plate (CEP) regions (interclass correlation [ICC] > .89). The ability to reliably detect subtle changes varied by IVD region, being poorest in the NP (ICC: .89-.95) where changes at the cellular level were important, vs the AF (ICC: .93-.98), CEP (ICC: .97-.98), and boney end plate (ICC: .96-.99) where matrix and structural changes varied more dramatically with degeneration.ConclusionsThe proposed grading system incorporates more comprehensive descriptions of degenerative features for all the IVD sub-tissues than prior criteria. While there was excellent reliability, our results reinforce the need for improved training, particularly for novice raters. Future evaluation of the proposed system in real-world settings (eg, at the microscope) will be n

Two distinct genetically defined entities of ependymoma arising in the supratentorial compartment are characterized by the presence of either a C11orf95-RELA or a YAP-MAMLD1 fusion, respectively. There is growing evidence that supratentorial ependymomas without these genetic features exist. In this study, we report on 18 pediatric non-RELA/non-YAP supratentorial ependymomas that were systematically characterized by means of their histology, immunophenotype, genetics, and epigenomics. Comprehensive molecular analyses included high-resolution copy number analysis, methylation profiling, analysis of fusion transcripts by Nanostring technology, and RNA sequencing. Based upon histological and immunohistochemical features two main patterns were identified-RELA-like (n = 9) and tanycytic ependymomas (n = 6). In the RELA-like group histologically assigned to WHO grade III and resembling RELA-fused ependymomas, tumors lacked nuclear expression of p65-RelA as a surrogate marker for a pathological activation of the NF-kappa B pathway. Three tumors showed alternative C11orf95 fusions to MAML2 or NCOA1. A methylation-based brain tumor classifier assigned two RELA-like tumors to the methylation class EP, RELA-fusion; the others demonstrated no significant similarity score. Of the tanycytic group, 5/6 tumors were assigned a WHO grade II. No gene fusions were detected. Methylation profiling did not show any association with an established methylation class. We additionally identified two astroblastoma-like tumors that both presented with chromothripsis of chromosome 22 but lacked MN1 breaks according to FISH analysis. They revealed novel fusion events involving genes in chromosome 22. One further tumor with polyploid cytogenetics was interpreted as PFB ependymoma by the brain tumor methylation classifier but had no relation to the posterior fossa. Clinical follow-up was available for 16/18 patients. Patients with tanycytic and astroblastoma-like tumors had no relapse, while 2 patie

In patients with brain metastases (BM), advanced age is considered a negative prognostic factor. To address the potential reasons for that, we assessed 807 patients who had undergone BM resection; 315 patients aged at least 65 years (group A) were compared with 492 younger patients (group B). We analyzed the impact of the pre- and postoperative Karnofsky performance status (KPS), postoperative treatment structure and post-treatment survival. BM resection significantly improved KPS scores in both groups (p = 0.0001). Median survival after BM resection differed significantly between the groups (A: 5.81 vs. B: 8.12 months; p = 0.0015). In both groups, patients who received postoperative systemic treatment showed significantly longer overall survival (p = 0.00001). However, elderly patients less frequently received systemic treatment (p = 0.0001) and the subgroup of elderly patients receiving such therapies had a significantly higher postsurgical KPS score (p = 0.0007). In all patients receiving systemic treatment, age was no longer a negative prognostic factor. Resection of BM improves the functional status of elderly patients, thus enhancing the likeliness to receive systemic treatment, which, in turn, leads to longer overall survival. In the context of such a treatment structure, age alone is no longer a prognostic factor for survival.

Simple Summary In this monocentric retrospective analysis, the extent of resection of singular/solitary brain metastases has no impact on local recurrence and overall survival rates in patients receiving multidisciplinary adjuvant treatment. Since systemic disease progression is the leading cause of death, and an uncontrolled systemic disease status, along with adjuvant treatment, present independent predictors of overall survival, a comprehensive, multidisciplinary treatment concept is essential for patients with brain metastases. Background and Purpose: The value of gross-total surgical resection remains debatable in patients with brain metastases (BMs) as most patients succumb to systemic disease progression. In this study, we evaluated the impact of the extent of resection of singular/solitary BM on in-brain recurrence (iBR), focusing on local recurrence (LR) and overall survival (OS) in an interdisciplinary adjuvant treatment setting. Patients and Methods: In this monocentric retrospective analysis, we included patients receiving surgery of one BM and subsequent adjuvant treatment. A radiologist and a neurosurgeon determined in consensus the extent of resection based on magnetic resonance imaging. The OS was calculated using Kaplan-Meier estimates; prognostic factors for LR and OS were analysed by Log rank test and Cox proportional hazards. Results: We analyzed 197 patients. Gross-total resection was achieved in 123 (62.4%) patients. All patients were treated with adjuvant radiotherapy, and 130 (66.0%) received systemic treatment. Ninety-six (48.7%) patients showed iBR with an LR rate of 23.4%. LR was not significantly influenced by the extent of resection (p = 0.139) or any other parameter. The median OS after surgery was 18 (95%CI 12.5-23.5) months. In univariate analysis, the extent of resection did not influence OS (p = 0.6759), as opposed to adjuvant systemic treatment (p < 0.0001) and controlled systemic disease (p = 0.039). Systemic treatment and control

Understanding how microbiomes are spatio-temporally structured and how their structure affects ecosystem function are central questions in aquatic microbial ecology that so far have been partially answered. A particular challenge is to attain a mechanistic understanding of microbial community assembly. Recent works have investigated how ecological processes (i.e. selection, drift, and dispersal) shape microbial communities over spatio-temporal scales in distinct aquatic ecosystems. However, much less is known about the connections between the processes that structure communities, the microbial assemblages that are formed, and the ultimate effects of structuring mechanisms on ecosystem function across variable spatial (from micrometers to thousands of kilometers) and temporal scales (e.g. hourly, diel, seasonal, inter-annually and over decades). Microbial features, such as minute organismal size, high dispersal, potential dormancy, high reproductive rates, huge population sizes and potentially high adaptability to environmental change need to be considered when investigating the links between ecological processes, microbial community composition, and indicators of overall ecosystem function (e.g. primary production, organic matter decomposition, nutrient cycling and gas emissions). A major goal is to comprehend how the composition of microbiomes will be affected by changes in abiotic and biotic drivers induced by global change, and how these changes will affect main ecosystem processes. We welcome abstracts investigating the structure of aquatic microbiomes, the underlying processes shaping them, and the potential effects in ecosystem function across diverse spatio-temporal scales in freshwater or marine ecosystems

Aims Evidence regarding the health burden of chronic venous insufficiency (CVI), its clinical determinants, and impact on outcome is scarce.Methods and results Systematic phenotyping of CVI according to established CEAP (Clinical-Etiologic-Anatomic-Pathophysiologic) classification was performed in 12 423 participants (age range: 40-80years) of the Gutenberg Health Study from April 2012 to April 2017. Prevalence was calculated age- and sex-specifically. Multivariable Poisson regression models were calculated to evaluate the relation of CVI with cardiovascular comorbidities. Survival analyses were carried out to assess the CVI-associated risk of death. Replication of findings was done in an independent cohort study (MyoVasc, NCT04064450). The prevalence of telangiectasia/reticular, varicose veins, and CVI was 36.5% [95% confidence interval (CI), 35.6-37.4%], 13.3% [12.6-13.9%], and 40.8% [39.9-41.7%], respectively. Age, female sex, arterial hypertension, obesity, smoking, and clinically overt cardiovascular disease were identified as clinical determinants of CVI. Higher CEAP classes were associated with a higher predicted 10-year risk for incident cardiovascular disease in individuals free of cardiovascular disease (n=9923). During a mean follow-up of 6.41.6years, CVI was a strong predictor of all-cause death independent of the concomitant clinical profile and medication [hazard ratio (HR) 1.46 (95% CI 1.19-1.79), P=0. 0003]. The association of CVI with an increased risk of all-cause death was externally validated in the MyoVasc cohort [HR 1.51 (95% CI 1.11-2.05), P=0.009].Conclusion Chronic venous insufficiency is highly prevalent in the population and is associated with the presence of cardiovascular risk factors and disease. Individuals with CVI experience an elevated risk of death, which is independent of age and sex, and present cardiovascular risk factors and comorbidities.