Long-term prognosis and educational determinants of brain network decline in older adult individuals

Older adults with lower education are at greater risk for dementia. It is unclear which brain changes lead to these outcomes. Longitudinal imaging-based measures of brain structure and function were examined in adult individuals (baseline age, 45-86 years; two to five visits per participant over 1-9 years). College degree completion differentiates individual-based and neighborhood-based measures of socioeconomic status and disadvantage. Older adults (~65 years and over) without a college degree exhibit a pattern of declining large-scale functional brain network organization (resting-state system segregation) that is less evident in their college-educated peers. Declining brain system segregation predicts impending changes in dementia severity, measured up to 10 years past the last scan date. The prognostic value of brain network change is independent of Alzheimer\u27s disease (AD)-related genetic risk

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Decreased segregation of brain systems across the healthy adult lifespan

El señor Forel, autor de este interesante artículo, al terminarlo, invoca simpatía para los trabajos de la Comisión Internacional de los Ventisqueros, y solicita la colaboración de todos los trabajadores, físicos, naturalistas, alpinistas, ó exploradores de regiones polares, así como el apoyo de las academias y dé los gobiernos, y confía en que este concurso no le faltará. La iniciativa del señor Marshall-Hall ha encontrado eco en este Museo. Desde el primer momento de conocida, hemos procurado reunir todos los antecedentes sobre la cuestión glacial en este extremo de la América, donde tan grandes manifestaciones ha dejado de su paso el hielo y donde los gigantes ventisqueros y neveras de todos los tipos se cuentan por centenares. La acción glacial se ha hecho sentir en toda la extensión del territorio argentino desde el grado 23 hasta el 56, y las facilidades para el estudio de esa acción son grandes por su misma magnitud; además, este estudio tan importante está ligado, é íntimamente, con el de una de las cuestiones geográficas más interesantes de estas regiones: el divortia aquarum continental, producido en buena extensión por esa misma acción. La traducción del artículo del señor Forel, tiene pues su colocación justificada en esta Revista, y el personal técnico del Museo de La Plata va á ser un colaborador entusiasta de la Comisión Internacional de los Ventisqueros, cuyo programa de trabajo publicamos. (Presentación por Francisco P. Moreno)Facultad de Ciencias Naturales y Muse

Prevalence and clinical significance of anti-MDA5 antibodies in European patients with polymyositis/dermatomyositis

Polymyositis/dermatomyositis (PM/DM) is an autoimmune disease characterised by skin and muscle inflammation, internal organ involvement and serum disease-specific autoantibodies. The recently identified anti-MDA5 (melanoma differentiation-associated gene 5) antibodies are associated with clinically amyopathic DM (CADM), rapidly progressive interstitial lung disease, severe skin manifestations, and poor prognosis. Our objective was to examine the clinical significance of anti-MDA5 antibodies in a cohort of European Caucasian patients with PM/DM, considering that data on anti-MDA5 serology are limited to Asian and US cohorts

Tyrosine phosphatase SHP2 promotes breast cancer progression and maintains tumor-initiating cells via activation of key transcription factors and a positive feedback signaling loop

New cancer therapies are likely to arise from an in-depth understanding of the signaling networks influencing tumor initiation, progression and metastasis. We show a fundamental role for Src-homology 2 domain-containing phosphatase 2 (SHP2) in these processes in human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancers. Knockdown of SHP2 eradicated breast tumor-initiating cells in xenograft models, and SHP2 depletion also prevented invasion in three-dimensional cultures and in a transductal invasion assay in vivo. Notably, SHP2 knockdown in established breast tumors blocked their growth and reduced metastasis. Mechanistically, SHP2 activated stemness-associated transcription factors, including v-myc myelocytomatosis viral oncogene homolog (c-Myc) and zinc finger E-box binding homeobox 1 (ZEB1), which resulted in the repression of let-7 microRNA and the expression of a set of 'SHP2 signature' genes. We found these genes to be simultaneously activated in a large subset of human primary breast tumors that are associated with invasive behavior and poor prognosis. These results provide new insights into the signaling cascades influencing tumor-initiating cells as well as a rationale for targeting SHP2 in breast cancer