Activin A circulating levels in patients with bone metastasis from breast or prostate cancer

Recent studies have highlighted that Activin A, a member of the transforming growth factor-beta (TGF-beta) superfamily, may be involved in the regulation of osteoblastic activity and in osteoclast differentiation. Therefore, we have investigated the clinical significance of its circulating levels in patients with bone metastasis. Activin A serum concentrations were determined, by a commercially available enzyme-linked immunosorbent assay kit, in 72 patients with breast cancer (BC) or prostatic cancer (PC) with (BM+) or without (BM-) bone metastases, in 15 female patients with age-related osteoporosis (OP), in 20 patients with benign prostatic hypertrophy (BPH) and in 48 registered healthy blood donors (HS) of both sex (25 female and 23 male). Activin A serum concentrations were significantly increased in BC or PC patients as compared to OP (P < 0.0001) or BPH (P = 0.045), respectively, or to sex matched HS (P < 0.0001). Additionally, these levels resulted more elevated in PC patients as compared to BC patients (P = 0.032). Interestingly, Activin A was significantly higher in BM+ patients than in BM- patients (BC, P = 0.047; PC, P = 0.016). In BC patients, a significant correlation was observed only between Activin A and number of bone metastases (P = 0.0065) while, in PC patients, Activin A levels were strongly correlated with the Gleason score (P = 0.011) or PSA levels (P = 0.0001) and, to a lessen extent, with the number of bone metastases (P = 0.056). Receiver operating characteristic curve (ROC) analysis showed a fair diagnostic accuracy of Activin A to discriminate between BM+ and BM- patients (BC: AUC = 0.71 +/- 0.09, P = 0.03; PC: AUC = 0.73 +/- 0.081, P = 0.005). These findings indicate that Activin A may be implicated in the pathogenesis of bone metastasis. Therefore, this cytokine may be considered a novel potential target for a more selective therapeutic approach in the treatment of skeletal metastasis and may be also useful as additional biochemical marker of metastatic bone disease

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

A survey by indicators on housing conditions in a city of Lazio, Italy

Introduction. To test the applicability, in a little town of central Italy, of an indicator set proposed by WHO to assess housing stock condition and wellbeing of its inhabitants. Methods. The indicator set created by WHO to evaluate housing conditions (LARES project) concerns affordability, accessibility, crowding, extremes of indoor air temperature, dampness and mould growth, household hygiene, housing safety and accidents, crime and fear of crime indicators. It was tested in Veroli (FR), a little town of Lazio, Italy. After a territory’s analysis, a questionnaire, formulated to obtain data for indicator values calculation, was administered to 310 voluntary subjects, corresponding to 17% of town’s residents, living in 98 different houses. At the same time, a visual inspection of the building was carried out to collect data about the dwelling’s quality, physical condition and technical equipments. Results. We obtained he necessary data for value calculation for all the proposed indicators except affordability and extremes of indoor air temperature, because this kind of information was not available at local level. Although available space is inadequate for only 1% of inhabitants (less than 14 m2 per person), overcrowding index (number of rooms available per person) is 16%, suggesting that spaces are not well distributed or are without adequate divisions. 94% of houses showed physical environmental barriers (such as narrow doors, staircase without lift, height differences within dwelling) and 39% of households included at least one person with functional limitations. 45% of houses presented mould and humidity inconvenience and/or presence of moulds on the walls. For 20% of houses water furniture was irregular. Discussion and conclusions. Study by indicators is a brief and effective analysis method to evaluate housing condition. It should represent an advantageous way for local Authorities which aim to extend on a large scale this analysis, to quantify urban decline and to identify intervention areas requesting priority. Nevertheless, this tool is not completely applicable in little towns where disaggregated data and adequate information systems are not existing

Metabolizing metabolism. Nakagin's capsules go rural

LAUREA MAGISTRALEA Tokyo, città in innovazione continua, anche un’ icona architettonica come la Nakagin Capsule Tower, non riesce a sottrarsi alle ferree regole che regolano il ciclo di vita degli edifici della città. La ricerca parte dal dibattito attuale riguardo le spinte immobiliari per la demolizione della nota torre dell’architetto metabolista Kisho Kurokawa. Ad oggi la torre si trova in uno stato di estremo abbandono: su 144 capsule iniziali, solo 20 sono quelle attualmente abitate. A questo si aggiungono le rigide regole del mercato immobiliare, secondo le quali non c’è più spazio per un edificio che riesca a sfruttare solo il 40% del rapporto superficie/volume in un’area dove il costo del suolo è tra i più elevati di Tokyo. Quello della Nakagin non è il primo fra gli esempi di demolizione di edifici simbolo, questo approccio nei confronti dell'architettura ha radici ben più profonde nella cultura giapponese: l’ abbattimento dello Ise Shrine ogni 20 anni ne è l'emblema. Assumendo quindi che la demolizione per la Nakagin sia una imminente e drammatica realtà, la ricerca si propone di trovare soluzioni alternative concrete. In conformità con il principio della capsula come elemento autonomo e rimovibile si prevede una terza via rispetto alla demolizione o musealizzazione della torre: il riutilizzo delle capsule. Ispirandosi all’ idea di Kurokawa di una declinazione extraurbana del vivere nella capsula, il progetto prevede lo spostamento delle 84 capsule ancora utilizzabili, passando da una verticalità urbana all'orizzontalità rurale della prefettura di Iwate. È infatti per questa comunità, distrutta degli effetti ancora presenti della catastrofe del maremoto del 2011, che è stato pensato il nuovo villaggio, basandosi sulle esigenze date della popolazione e dell’area in cui si insedia, tenendo conto delle tradizioni locali e dei pericoli del mare e della terra. Senza mettere in discussione il valore della Nakagin come manifesto, in risposta al modello individualista di abitazione pensata per l'homo movens, il progetto abbraccia i nascenti principi del vivere codividuale, sostenendo che, all'interno di un sistema più grande, sia possibile un futuro per le capsule.In Tokyo, everchanging city, even an architectural icon like the Nakagin Capsule Tower cannot escape the strict rules governing the life cycle of the city's buildings. The research starts from the actual debate about the real estate pressures for the demolition of the famous tower by the metabolist architect Kisho Kurokawa. Nowadays the tower is in a state of extreme abandonment: out of 144 initial capsules, only 20 are currently inhabited. Moreover, according the strict rules of the real estate market, there is no more space for a building that can exploit only 40% of the surface/volume ratio, expecially in an area where the cost of land is one of the highest in Tokyo. Nakagin is not the first example of the demolition of iconic buildings, this approach to architecture has much deeper roots in Japanese culture: the demolition of the Ise Shrine every 20 years is its emblem. Assuming therefore that the demolition for Nakagin is an imminent and dramatic reality, the research aims to find concrete alternative solutions. In accordance with the principle of the capsule as an autonomous and detachable element, a third way is proposed rather than the demolition or musealization of the tower: the reuse of the capsules. Inspired by Kurokawa's idea of a suburban declination the life in the capsules, the project provides the displacement of the still accessible 84 capsules, moving from the verticality of the city to a rural horizontality in the prefecture of Iwate. It’s in fact for this community, destroyed by the effects of the tsunami disaster in 2011, that the new village is designed, taking into account the needs and traditions of the population and dangers coming from the sea and the land. Without questioning the Nakagin's value as a manifesto, the project reacts to the individualist model of housing designed for the homo movens embracing the newborn principles of codividuaity, believing that, within a larger system, a future for the capsules is still possible