Semantic variant primary progressive aphasia: Practical recommendations for treatment from 20 years of behavioural research

People with semantic variant primary progressive aphasia (svPPA) present with a char-acteristic progressive breakdown of semantic knowledge. There are currently no pharmacological interventions to cure or slow svPPA, but promising behavioural approaches are increasingly reported. This article offers an overview of the last two decades of research into interventions to support language in people with svPPA including recommendations for clinical practice and future research based on the best available evidence. We offer a lay summary in English, Spanish and French for education and dissemination purposes. This paper discusses the implications of right-versus left-predominant atrophy in svPPA, which naming therapies offer the best outcomes and how to capitalise on preserved long-term memory systems. Current knowledge regarding the maintenance and generalisation of language therapy gains is described in detail along with the development of compensatory approaches and educational and support group programmes. It is concluded that there is evidence to support an integrative framework of treatment and care as best practice for svPPA. Such an approach should combine rehabilitation interventions addressing the language impairment, compensatory approaches to support activities of daily living and provision of education and support within the context of dementia

Harnessing Naturally Occurring Tumor Immunity: A Clinical Vaccine Trial in Prostate Cancer

International audienceBACKGROUND:Studies of patients with paraneoplastic neurologic disorders (PND) have revealed that apoptotic tumor serves as a potential potent trigger for the initiation of naturally occurring tumor immunity. The purpose of this study was to assess the feasibility, safety, and immunogenicity of an apoptotic tumor-autologous dendritic cell (DC) vaccine.METHODS AND FINDINGS:We have modeled PND tumor immunity in a clinical trial in which apoptotic allogeneic prostate tumor cells were used to generate an apoptotic tumor-autologous dendritic cell vaccine. Twenty-four prostate cancer patients were immunized in a Phase I, randomized, single-blind, placebo-controlled study to assess the safety and immunogenicity of this vaccine. Vaccinations were safe and well tolerated. Importantly, we also found that the vaccine was immunogenic, inducing delayed type hypersensitivity (DTH) responses and CD4+ and CD8+ T cell proliferation, with no effect on FoxP3+ regulatory T cells. A statistically significant increase in T cell proliferation responses to prostate tumor cells in vitro (p = 0.002), decrease in prostate specific antigen (PSA) slope (p = 0.016), and a two-fold increase in PSA doubling time (p = 0.003) were identified when we compared data before and after vaccination.CONCLUSIONS:An apoptotic cancer cell vaccine modeled on naturally occurring tumor immune responses in PND patients provides a safe and immunogenic tumor vaccine

First Evidence for Adoption in California Sea Lions

Demographic parameters such as birth and death rates determine the persistence of populations. Understanding the mechanisms that influence these rates is essential to developing effective management strategies. Alloparental behavior, or the care of non-filial young, has been documented in many species and has been shown to influence offspring survival. However, the role of alloparental behavior in maintaining population viability has not been previously studied. Here, we provide the first evidence for adoption in California sea lions and show that adoption potentially works to maintain a high survival rate of young and may ultimately contribute to population persistence. Alloparental behavior should have a positive effect on the population growth rate when the sum of the effects on fitness for the alloparent and beneficiary is positive

Challenge and promise: the role of miRNA for pathogenesis and progression of malignant melanoma

microRNAs are endogenous noncoding RNAs that are implicated in gene regulation. More recently, miRNAs have been shown to play a pivotal role in multiple cellular processes that interfere with tumorigenesis. Here we summarize the essential role of microRNAs for human cancer with special focus on malignant melanoma and the promising perspectives for cancer therapies

BeadArray Expression Analysis Using Bioconductor

Illumina whole-genome expression BeadArrays are a popular choice in gene profiling studies. Aside from the vendor-provided software tools for analyzing BeadArray expression data (GenomeStudio/BeadStudio), there exists a comprehensive set of open-source analysis tools in the Bioconductor project, many of which have been tailored to exploit the unique properties of this platform. In this article, we explore a number of these software packages and demonstrate how to perform a complete analysis of BeadArray data in various formats. The key steps of importing data, performing quality assessments, preprocessing, and annotation in the common setting of assessing differential expression in designed experiments will be covered

Sports, morality and body. The voices of sportswomen under Franco's dictatorship

The aim of this research is to study sportswomen's perceptions and experiences of women's sport in Francoist Spain (1939-1975). The main objective is to analyse the social, moral and aesthetic elements that are present in the experience of these athletes. This study was carried out with an intentional sample of 24 women from Andalusia, Aragon, Asturias, Basque Country, Catalonia and Valencia. They were interviewed by a network of researchers from six universities. Outstanding results show the existence of social limitations to start sports practice (particularly in the post-war period); the importance of sport as a character-building aspect; sport's remarkable influence on their body self-concept; and the incidence on sports of the mainstream moral discourse, which created a female model that even affected sports clothing. The main conclusion is that sportswomen in that period were pioneers and had to fight against most of society in order to develop their facet as athletes, as they would not follow the established model

Use of anthropogenic material affects bird nest arthropod community structure: influence of urbanisation, and consequences for ectoparasites and fledging success

Nests are a critically important factor in determining the breeding success of many species of birds. Nevertheless, we have surprisingly little understanding of how local environment helps shape materials used in construction, how this differs among related species using similar nest sites, or if materials used directly or indirectly influence the numbers of offspring successfully reared. We also have little understanding of any potential links between nest construction and the assemblage of invertebrates which inhabit the nest and in particular, with ectoparasites. We addressed these questions by monitoring the success rates of nest-box using Blue Tits Cyanistes caeruleus and Great Tits Parus major, from rural, urban greenspace and urban garden settings. We collected used nests, identified arthropods present, and measured the proportions of highly processed anthropogenic materials used in their construction. Some 25% of Great Tit nest materials were of an anthropogenic source and this was consistent across habitats, while Blue Tits used little (1-2%) except in gardens (~16%), suggesting that Great Tits preferentially sought out these materials. In fledged nests, increasing use of anthropogenic material was associated with lower general arthropod diversity and ectoparasite predator abundance (Blue Tits only) but higher levels of Siphonapterans (fleas). Higher arthropod diversity was associated with lower flea numbers, suggesting that increased diversity played a role in limiting flea numbers. No direct link was found between breeding success and either anthropogenic material usage, or arthropod diversity and abundance. However, breeding success declined with increasing urbanisation in both species and increased with nest weight in Blue Tits. The interplay between urbanisation and bird ecology is complex; our work shows that subtle anthropogenic influences may have indirect and unexpected consequences for urban birds

Neonatal mortality risk for vulnerable newborn types in 15 countries using 125.5 million nationwide birth outcome records, 2000-2020.

OBJECTIVE: To compare neonatal mortality associated with six novel vulnerable newborn types in 125.5 million live births across 15 countries, 2000-2020. DESIGN: Population-based, multi-country study. SETTING: National data systems in 15 middle- and high-income countries. METHODS: We used individual-level data sets identified for the Vulnerable Newborn Measurement Collaboration. We examined the contribution to neonatal mortality of six newborn types combining gestational age (preterm [PT] versus term [T]) and size-for-gestational age (small [SGA], 90th centile) according to INTERGROWTH-21st newborn standards. Newborn babies with PT or SGA were defined as small and T + LGA was considered as large. We calculated risk ratios (RRs) and population attributable risks (PAR%) for the six newborn types. MAIN OUTCOME MEASURES: Mortality of six newborn types. RESULTS: Of 125.5 million live births analysed, risk ratios were highest among PT + SGA (median 67.2, interquartile range [IQR] 45.6-73.9), PT + AGA (median 34.3, IQR 23.9-37.5) and PT + LGA (median 28.3, IQR 18.4-32.3). At the population level, PT + AGA was the greatest contributor to newborn mortality (median PAR% 53.7, IQR 44.5-54.9). Mortality risk was highest among newborns born before 28 weeks (median RR 279.5, IQR 234.2-388.5) compared with babies born between 37 and 42 completed weeks or with a birthweight less than 1000 g (median RR 282.8, IQR 194.7-342.8) compared with those between 2500 g and 4000 g as a reference group. CONCLUSION: Preterm newborn types were the most vulnerable, and associated with the highest mortality, particularly with co-existence of preterm and SGA. As PT + AGA is more prevalent, it is responsible for the greatest burden of neonatal deaths at population level

A Novel Xenogeneic Co-Culture System to Examine Neuronal Differentiation Capability of Various Adult Human Stem Cells

Background: Targeted differentiation of stem cells is mainly achieved by the sequential administration of defined growth factors and cytokines, although these approaches are quite artificial, cost-intensive and time-consuming. We now present a simple xenogeneic rat brain co-culture system which supports neuronal differentiation of adult human stem cells under more in vivo-like conditions. Methods and Findings: This system was applied to well-characterized stem cell populations isolated from human skin, parotid gland and pancreas. In addition to general multi-lineage differentiation potential, these cells tend to differentiate spontaneously into neuronal cell types in vitro and are thus ideal candidates for the introduced co-culture system. Consequently, after two days of co-culture up to 12% of the cells showed neuronal morphology and expressed corresponding markers on the mRNA and protein level. Additionally, growth factors with the ability to induce neuronal different iation in stem cells could be found in the media supernatants of the co-cultures. Conclusions: The co-culture system described here is suitable for testing neuronal differentiation capability of numerous types of stem cells. Especially in the case of human cells, it may be of clinical relevance for future cell-based therapeutic applications