CD45 Isoform Expression in Microglia and Inflammatory Cells in HIV-1 Encephalitis

CD45 is a membrane tyrosine phosphatase that modulates the function of the hematopoietic cells. In vitro, agonist antibodies to CD45RO or CD45RB isoforms have been shown to suppress microglial activation, but whether microglia in vivo express these isoforms in HIV encephalitis (HIVE) is unknown. Brain sections from control and HIVE were immunostained for CD45 isoforms using exon-specific antibodies (RA, RB, RC and RO). RA and RC were limited to rare lymphocytes, while RB expression was robust in microglia and inflammatory cells. RO was low in control microglia, but increased in HIVE. RO was also localized to macrophages and CD8+ T cells. Targeting CD45 in vivo with isoform-specific antibodies remains a therapeutic option for neuroinflammatory diseases

A real world analysis of COVID-19 impact on hospitalizations in older adults with chronic conditions from an Italian region

Healthcare delivery reorganization during the COVID-19 emergency may have had a significant impact on access to care for older adults with chronic conditions. We investigated such impact among all adults with chronic conditions aged ≥ 65 years, identified through the electronic health databases of two local health agencies—ATS Brianza and ATS Bergamo—from the Lombardy region, Italy. We considered hospitalizations for 2020 compared to the average 2017–2019 and quantified differences using rate ratios (RRs). Overall, in 2017–2019 there were a mean of 374,855 older adults with ≥ 1 chronic condition per year in the two ATS and 405,371 in 2020. Hospitalizations significantly decreased from 84,624 (225.8/1000) in 2017–2019 to 78,345 (193.3/1000) in 2020 (RR 0.86). Declines were reported in individuals with many chronic conditions and for most Major Diagnostic Categories, except for diseases of the respiratory system. The strongest reductions were observed in hospitalizations for individuals with active tumours, particularly for surgical ones. Hospitalization rates increased in individuals with diabetes, likely due to COVID-19-related diseases. Although determinants of the decrease in demand and supply for care among chronic older adults are to be further explored, this raises awareness on their impacts on chronic patients’ health in the medium and long run

Origins of cattle on Chirikof Island, Alaska, elucidated from genome-wide SNP genotypes

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Non-reductivism and the Metaphilosophy of Mind

This paper discusses the metaphilosophical assumptions that have dominated analytic philosophy of mind, and how they gave rise to the central question that the best-known forms of non-reductivism available have sought to answer, namely: how can mind fit within nature? Its goal is to make room for forms of non-reductivism that have challenged the fruitfulness of this question, and which have taken a different approach to the so-called “placement” problem. Rather than trying to solve the placement problem, the forms of non-reductivism discussed in this paper have put pressure on the metaphilosophical assumptions that have given rise to the question of the place of mind in nature in the first instance

Targeting of the Arpc3 actin nucleation factor by miR-29a/b regulates dendritic spine morphology

Regulation of Arpc3 by miRNA alters dendritic spine morphology

Worldwide trends in population-based survival for children, adolescents, and young adults diagnosed with leukaemia, by subtype, during 2000–14 (CONCORD-3) : analysis of individual data from 258 cancer registries in 61 countries

Background Leukaemias comprise a heterogenous group of haematological malignancies. In CONCORD-3, we analysed data for children (aged 0–14 years) and adults (aged 15–99 years) diagnosed with a haematological malignancy during 2000–14 in 61 countries. Here, we aimed to examine worldwide trends in survival from leukaemia, by age and morphology, in young patients (aged 0–24 years). Methods We analysed data from 258 population-based cancer registries in 61 countries participating in CONCORD-3 that submitted data on patients diagnosed with leukaemia. We grouped patients by age as children (0–14 years), adolescents (15–19 years), and young adults (20–24 years). We categorised leukaemia subtypes according to the International Classification of Childhood Cancer (ICCC-3), updated with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes. We estimated 5-year net survival by age and morphology, with 95% CIs, using the non-parametric Pohar-Perme estimator. To control for background mortality, we used life tables by country or region, single year of age, single calendar year and sex, and, where possible, by race or ethnicity. All-age survival estimates were standardised to the marginal distribution of young people with leukaemia included in the analysis. Findings 164563 young people were included in this analysis: 121328 (73·7%) children, 22963 (14·0%) adolescents, and 20272 (12·3%) young adults. In 2010–14, the most common subtypes were lymphoid leukaemia (28205 [68·2%] patients) and acute myeloid leukaemia (7863 [19·0%] patients). Age-standardised 5-year net survival in children, adolescents, and young adults for all leukaemias combined during 2010–14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia. Individuals with lymphoid leukaemia had better age-standardised survival (from 43% in Ecuador to ≥80% in parts of Europe, North America, Oceania, and Asia) than those with acute myeloid leukaemia (from 32% in Peru to ≥70% in most high-income countries in Europe, North America, and Oceania). Throughout 2000–14, survival from all leukaemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries. Interpretation This study offers the first worldwide picture of population-based survival from leukaemia in children, adolescents, and young adults. Adolescents and young adults diagnosed with leukaemia continue to have lower survival than children. Trends in survival from leukaemia for adolescents and young adults are important indicators of the quality of cancer management in this age group.peer-reviewe

Global survival trends for brain tumors, by histology: analysis of individual records for 556,237 adults diagnosed in 59 countries during 2000–2014 (CONCORD-3)

Background: Survival is a key metric of the effectiveness of a health system in managing cancer. We set out to provide a comprehensive examination of worldwide variation and trends in survival from brain tumors in adults, by histology. Methods: We analyzed individual data for adults (15–99 years) diagnosed with a brain tumor (ICD-O-3 topography code C71) during 2000–2014, regardless of tumor behavior. Data underwent a 3-phase quality control as part of CONCORD-3. We estimated net survival for 11 histology groups, using the unbiased nonparametric Pohar Perme estimator. Results: The study included 556,237 adults. In 2010–2014, the global range in age-standardized 5-year net survival for the most common sub-types was broad: in the range 20%–38% for diffuse and anaplastic astrocytoma, from 4% to 17% for glioblastoma, and between 32% and 69% for oligodendroglioma. For patients with glioblastoma, the largest gains in survival occurred between 2000–2004 and 2005–2009. These improvements were more noticeable among adults diagnosed aged 40–70 years than among younger adults. Conclusions: To the best of our knowledge, this study provides the largest account to date of global trends in population-based survival for brain tumors by histology in adults. We have highlighted remarkable gains in 5-year survival from glioblastoma since 2005, providing large-scale empirical evidence on the uptake of chemoradiation at population level. Worldwide, survival improvements have been extensive, but some countries still lag behind. Our findings may help clinicians involved in national and international tumor pathway boards to promote initiatives aimed at more extensive implementation of clinical guidelines