Extracellular Vesicle-Associated Aβ Mediates Trans-Neuronal Bioenergetic and Ca\u3csup\u3e2+\u3c/sup\u3e-Handling Deficits in Alzheimer\u27s Disease Models

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder in which aggregation-prone neurotoxic amyloid β-peptide (Aβ) accumulates in the brain. Extracellular vesicles (EVs), including exosomes, are small 50–150 nm membrane vesicles that have recently been implicated in the prion-like spread of self-aggregating proteins. Here we report that EVs isolated from AD patient cerebrospinal fluid and plasma, from the plasma of two AD mouse models, and from the medium of neural cells expressing familial AD presenilin 1 mutations, destabilize neuronal Ca2+ homeostasis, impair mitochondrial function, and sensitize neurons to excitotoxicity. EVs contain a relatively low amount of Aβ but have an increased Aβ42/ Aβ40 ratio; the majority of Aβ is located on the surface of the EVs. Impairment of lysosome function results in increased generation of EVs with elevated Aβ42 levels. EVs may mediate transcellular spread of pathogenic Aβ species that impair neuronal Ca2+ handling and mitochondrial function, and may thereby render neurons vulnerable to excitotoxicity

Characterization and outcomes of 414 patients with primary SS who developed haematological malignancies

Objective: To characterize 414 patients with primary SS who developed haematological malignancies and to analyse how the main SS- and lymphoma-related features can modify the presentation patterns and outcomes. Methods: By January 2021, the Big Data Sjögren Project Consortium database included 11 966 patients fulfilling the 2002/2016 classification criteria. Haematological malignancies diagnosed according to the World Health Organization (WHO) classification were retrospectively identified. Results: There were 414 patients (355 women, mean age 57 years) with haematological malignancies (in 43, malignancy preceded at least one year the SS diagnosis). A total of 376 (91%) patients had mature B-cell malignancy, nearly half had extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT lymphoma) (n = 197), followed by diffuse large B-cell lymphoma (DLBCL) (n = 67), nodal MZL lymphoma (n = 29), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (n = 19) and follicular lymphoma (FL) (n = 17). Rates of complete response, relapses and death were 80%, 34% and 13%, respectively, with a 5-year survival rate of 86.5% after a mean follow-up of 8 years. There were significant differences in age at diagnosis (younger in MALT, older in CLL/SLL), predominant clinical presentation (glandular enlargement in MALT lymphoma, peripheral lymphadenopathy in nodal MZL and FL, constitutional symptoms in DLBCL, incidental diagnosis in CLL/SLL), therapeutic response (higher in MALT lymphoma, lower in DLBCL) and survival (better in MALT, nodal MZL and FL, worse in DLBCL). Conclusion: In the largest reported study of haematological malignancies complicating primary SS, we confirm the overwhelming predominance of B-cell lymphomas, especially MALT, with the salivary glands being the primary site of involvement. This highly-specific histopathological scenario is linked with the overall good prognosis with a 5-year survival rate of nearly 90%

Evaluando "en clave pública" : guía de instrumentos e indicadores para la medición de capacidades estatales

La presente Guía ensaya una definición de capacidades estatales para este tiempo y este sur continental. A partir de esta definición, se intenta contribuir al desarrollo de sistemas de indicadores e instrumentos que permitan medir estas capacidades

Tasso di abbandono fra i lanciatori finalisti dei campionati mondiali juniores

Scopo dello studio \ue8 stato quello di indagare il fenomeno del drop-out nelle specialit\ue0 dei lanci nell\u2019atletica leggera. Sono stati monitorati quali e quanti atleti finalisti delle quattro edizioni dei campionati del mondo juniores dal 2002 al 2008 siano riusciti a rimanere nella top-10 del ranking mondiale assoluto fino al 2010. Sono stati presi in considerazione i 10 finalisti delle specialit\ue0 dei lanci divisi per genere che hanno partecipato ai mondiali juniores nelle edizioni di Kingston 2002, Grosseto 2004, Beijing 2008 e Bydygoszcz 2008. Tramite un calcolatore elettronico e il programma di Excel per l\u2019elaborazione dei dati \ue8 stata monitorata l\u2019et\ue0 e la posizione nel ranking mondiale assoluto a partire dall\u2019anno del mondiale fino al 2010. Per dropout \ue8 stata considerata l\u2019assenza dell\u2019atleta nella graduatoria internazionale assoluta per due anni successivi. Di tutti gli atleti presi in considerazione verranno presentati i risultati relativi ai tassi di drop-out suddivisi per mondiale juniores. Questi poi verranno distinti per genere e specialit\ue0. In generale si assiste ad un incremento del tasso di abbandono nella specialit\ue0 in cui il passaggio da una categoria a quella successiva comporta un aumento significativo del peso dell\u2019attrezzo, rendendo gli adattamenti riguardanti sia gli aspett

Does the junior IAAF athletic world championship represent a springboard for the success in the throwing events? : a retrospective study

Aim. The aim of the present study was to analyze how many finalists of the IAAF World Junior Championships (WJC) in the throwing events were present in the senior IAAF ranking at the end of 2012. Methods. The results of the 8 male and the 8 female finalists of all throwing events of the last 5 editions of the WJC from the 2002 edition were gathered. We analyzed how many ath- letes were missing from the IAAF ranking in 2012. For those athletes that did not drop out we monitored their progression in performance comparing their WJC and their 2012 per- formance. Moreover, we evaluated if the relative age effects (RAE) influenced drop out rate. Results. Drop out rate was 58% in 2002, 59% in 2004, 39% in 2006, and 28% in 2008 and in 2010. The female javelin throwers showed the highest drop out rate (100%) in 2002, while the female hammer throwers showed the lowest drop out rate (0%) in 2008. Performance decreased for all male shot putters, discus and hammer throwers (P<0.001). For fe- males and for male javelin throwers, performance increased (P<0.001). RAEs showed no significant influence on drop out rate Conclusion. Even if 8 of the finalists won a medal at the Olympic Games or at the World Championships, it is still not clear if participation at the WJC is a prerequisite to success at a senior level, given the elevated drop out rate observed in the present study

Concurrent strength and endurance training effects on running economy in master endurance runners

Running economy (RE) has been seen to improve with concurrent strength and endurance training in young and elite endurance athletes. The purpose of the present study was to evaluate the effects of 2 different strength training protocols on RE and strength parameters in a group of regularly training master marathon runners. Sixteen participants were randomly assigned to a maximal strength training program (MST; n = 6; 44.2 \ub1 3.9 yrs), a resistance training (RT; n = 5; 44.8 \ub1 4.4 yrs) and a control group (CG; n = 5; 43.2 \ub1 7.9 yrs). Before and after the experimental period, resting metabolic rate, body composition, 1 repetition maximum, squat jump, countermovement jump and RE were evaluated. The MST group showed significant increases (p 0.05). Anthropometric data were unchanged after the training intervention (p > 0.05). Taken together, the results of this preliminary study indicate that master endurance athletes seem to benefit from concurrent strength and endurance training because the rate of force development may be crucial for RE improvement, one of the major determinants of endurance performance

Breathable hydrogel dressings containing natural antioxidants for management of skin disorders

Traditional wound dressings are not effective enough to regulate the moisture content and remove excessive exudate from the environment. Wet wound dressings formed from hydrogels such as alginate are widely used in clinical practice for treatment of skin disorders. Here, we functionalize alginate dressings with natural antioxidants such as curcumin and t-resveratrol to render them both anti-inflammatory and antibacterial. The hydrogel maintains excellent mechanical properties and oxygen permeability over time. The release rate of the compounds from the hydrogels is assessed and their impact on bacterial and cellular growth is evaluated. The antioxidant compounds act as bactericidal agents and improve cell viability. The optimal concentration of active compounds in the engineered alginate-based dressings is determined