Progetto di un complesso residenziale situato nel quartiere Pisanova-Via I. Bargagna, Pisa

Questo progetto nasce come risposta a indicazioni realmente presenti nel Regolamento Urbanistico del Comune di Pisa che prevede, per l’area in oggetto, l’edificazione di un complesso ad uso misto residenziale – commerciale articolato con aree verdi private e pubbliche Il lotto in esame è compreso tra Via I. Bargagna e Via Frascani nel quartiere di Pisanova e attualmente è costituito per la maggior parte da terreni liberi. Il progetto si inserisce all’interno di un contesto di residenza privata e aree libere in via di trasformazione. E’ finalizzato alla creazione di un centro di aggregazione pubblica che si articola su di un asse principale che taglia l’area di intervento diagonalmente da ovest verso est in direzione dei Monti Pisani. Su questo asse, in posizione quasi centrale, si pone un fulcro intorno al quale, in maniera concentrica, si sviluppano i vari edifici che mantengono il loro fronte principale rivolto verso la piazza ellittica posta al centro

SIRT1 Activity Is Linked to Its Brain Region-Specific Phosphorylation and Is Impaired in Huntington’s Disease Mice

Huntingtons disease (HD) is a neurodegenerative disorder for which there are no disease-modifying treatments. SIRT1 is a NAD+-dependent protein deacetylase that is implicated in maintaining neuronal health during development, differentiation and ageing. Previous studies suggested that the modulation of SIRT1 activity is neuroprotective in HD mouse models, however, the mechanisms controlling SIRT1 activity are unknown. We have identified a striatum-specific phosphorylation-dependent regulatory mechanism of SIRT1 induction under normal physiological conditions, which is impaired in HD. We demonstrate that SIRT1 activity is down-regulated in the brains of two complementary HD mouse models, which correlated with altered SIRT1 phosphorylation levels. This SIRT1 impairment could not be rescued by the ablation of DBC1, a negative regulator of SIRT1, but was linked to changes in the sub-cellular distribution of AMPK-α1, a positive regulator of SIRT1 function. This work provides insights into the regulation of SIRT1 activity with the potential for the development of novel therapeutic strategies

Therapy-induced antitumor vaccination in neuroblastomas by the combined targeting of IL-2 and TNF alpha

L19-IL2 and L19TNF are fusion proteins composed of L19(scFv), specific for the angiogenesis-associated ED-B containing fibronectin isoform and IL-2 or TNF. Because of the tumor targeting properties of L19, IL-2 and TNF concentrate at therapeutic doses at the tumor vascular level. To evaluate the therapeutic effects of L19-IL2 and L19mTNF in neuroblastoma (NB)-bearing mice, A/J mice bearing Neuro2A or NIE115 NB were systemically treated with L19-IL2 and L19mTNF, alone or in combination protocols. Seventy percent of Neuro2A- and 30% of NIE115-bearing mice were cured by the combined treatment with L19-IL2 and L19mTNF, and further rejected a homologous tumor challenge, indicating specific antitumor immune memory. The immunological bases of tumor cure and rejection were studied. A highly efficient priming of CD4+ T helper cells and CD8+ CTL effectors was generated, paralleled by massive infiltration in the tumor tissue of CD4+ and CD8+ T cells at day 16 after tumor cell implantation, when, after therapy, tumor volume was drastically reduced and tumor necrosis reached about 80%. The curative treatment resulted in a long-lasting antitumor immune memory, accompanied by a mixed Th1/Th2 type of response. Concluding, L19-IL2 and L19mTNF efficiently cooperate in determining a high percentage of NB cure that, in our experimental models, is strongly associated to the generation of adaptive immunity involving CD4+ and CD8+ T cells

Apartment Living and Community Care: Experiences of People With Intellectual Disability, Their Families, and Support Staff

Understanding how the design of urban infrastructure influences the independence and autonomy of people with intellectual disability has far-reaching implications for community inclusion and participation. This article explores how urban design elements of an apartment complex influence how a person with an intellectual disability receives support and participates in the wider community. The study reports on the post-occupancy evaluation of an Australian development of over 400 apartments in Sydney, where 25 people with intellectual disability received 24-hour support. Fifty-three interviews were conducted with people with intellectual disability, their families, and disability support staff. Participants with intellectual disability described what living in their new apartment was like and appreciated the outdoor gardens. However, they also explained that wayfinding was more difficult than in their previous homes—all free-standing group homes. Disability support staff discussed how providing community care for people with intellectual disability in an apartment differed from a suburban free-standing house. Findings were translated into design suggestions for improving service provision to people with disability through the urban design around multi-tower sites of mixed-tenure apartments. The article concludes with recommendations for urban design features to support safe, efficient, and quality care in a high-density urban setting. When viewed through a lens of social infrastructure, the results show how urban design has the potential to influence the collective independence and provision of care to diverse communities in urban centres and cities and is relevant to people with disability, older people, and other community groups who rely on community-care support to remain living independently at home

Protocol for a 1-year prospective, longitudinal cohort study of patients undergoing Roux-en-Y gastric bypass and sleeve gastrectomy: the BARI-LIFESTYLE observational study

INTRODUCTION: Roux-en-Y gastric bypass and sleeve gastrectomy are the two most common bariatric surgery performed in the UK that result in comparable weight loss and remission of obesity-associated comorbidities. However, there is a paucity of studies examining the impact of these procedures on body composition, physical activity levels, sedentary behaviour, physical function and strength, dietary intake, health-related quality of life and costs. METHODS AND ANALYSIS: The BARI-LIFESTYLE observational study is a 1-year prospective, longitudinal cohort study within a real-world routine clinical care setting aiming to recruit 100 patients with severe obesity undergoing either primary Roux-en-Y gastric bypass or sleeve gastrectomy from two bariatric centres in London, UK. Participants will be followed up four times during the study period; presurgery baseline (T0) and at 3 (T1), 6 (T2) and 12 months (T3) postsurgery. In addition to the standard follow-up investigations, assessments including dual-energy X-ray absorptiometry scan, bioelectric impedance analysis, 6 min walk test, sit-to-stand test and handgrip test will be undertaken together with completion of questionnaires. Physical activity levels and sedentary behaviour will be assessed using accelerometer, and dietary intake will be recorded using a 3-day food diary. Outcome measures will include body weight, body fat mass, lean muscle mass, bone mineral density, physical activity levels, sedentary behaviour, physical function and strength, dietary intake, health-related quality of life, remission of comorbidities, healthcare resource utilisation and costs. ETHICS AND DISSEMINATION: This study has been reviewed and given a favourable ethical opinion by London-Dulwich Research Ethics Committee (17/LO/0950). The results will be presented to stakeholder groups locally, nationally and internationally and published in peer-reviewed medical journals. The lay-person summary of the findings will be published on the Centre for Obesity Research, University College London website (http://www.ucl.ac.uk/obesity)

Ageing in place and the internet of things – how smart home technologies, the built environment and caregiving intersect

© 2018, The Author(s). Smart technologies and the Internet of Things (IoT), have the potential to play a significant role in enabling older people to age in place. Although there has been substantial development of new applications of sensor technology in the home, this has tended to be tele-health focused, and there has been less work done on the role of IoT and ageing in place that more broadly considers caregiving and the built environment. Research in the field of IoT development and evaluation has recognised a number of challenges and limitations associated with past smart technology developments to support Ageing in Place, calling for user centeredness and better integration with broader systems. Compounding this, research into Ageing in Place and home environments has focused on built environments and largely ignored the impact of technology in the lives of older people staying at home. Recognising a gap in acknowledging the potential impact of technology on Ageing in Place theories, the purpose of this paper is to conceptualise a way of framing smart technology within an Ageing in Place model that acknowledges the interaction of smart technology with the built environment and caregiving and to present a framework for visualising the interactions that take place. A review of Environmental Gerontology model development is undertaken and a new model is presented that recognises the role of technology in Ageing in Place. Based on this model, a template is developed and three case studies of older people’s experiences of smart home technology, home modifications and caregiving are mapped out. These are used to demonstrate “proof of concept” of the relationships put forward in the HAST model and the pre-curser for a template to help people map smart technology and its role in supporting caregiving and ageing in place. This paper’s position is that technologies such as IoT further support the role of the built environment and caregiving to produce outcomes that enable older people to remain autonomous, independent, safe and well at home. However, a number of risks were also identified through the case studies, the issues of maintenance, cost and ease of use, and willingness to use are considerations and potential barriers to the benefits of smart technology

Individualized Apartment Accommodation for People With Intellectual Disability: Protocol for a Qualitative Study Examining the Well-Being and Support Outcomes Linking Housing and Health.

BACKGROUND:Understanding the outcomes associated with both receiving and providing support to people with intellectual disability in specific settings can facilitate the alignment of health providers, community care providers, architects, and urban planners to strengthen levels of autonomy and community participation of people with intellectual disability living in the community. This study explores the impact of providing support (available 24 hours a day) for people with intellectual disability in a high-density apartment. It seeks the perspectives of people with intellectual disability who have moved into an apartment from a group home (where 4-6 people with disability live), their families, and support staff. It will enable comparison between two models of supported accommodation, group homes and individualized apartments, in a community setting. OBJECTIVE:The aims of this study are to explore the impact of an individualized apartment model of supported accommodation in a high-density setting on the well-being, autonomy, and participation of people with intellectual disability living and receiving support; the experience of providing care or support; and how this setting impacts the logistics of how quality support is provided. METHODS:Qualitative research methods were employed as the primary means of collecting and analyzing data. There are two main sources of data in this study: (1) semistructured interviews with participants in up to 3 waves (pre, post 1, and post 2) and (2) pre- and postoccupancy evaluation data on the design, layout, and location details of the built environments. Coded interview data will be paired with pre- and postoccupancy evaluations of the two accommodation settings. RESULTS:As of May 2020, we have recruited 55 participants. There have been 96 interviews conducted in 2 waves with people who have moved into supported accommodation, families, and staff. Collected data are currently being analyzed. We expect the results of the trial to be published in a peer-reviewed journal in late 2020. CONCLUSIONS:This paper sets out a study of an alternative housing and support model for people with intellectual disability. It will capture personal experiences of people with intellectual disability receiving support in an apartment compared to their experiences in a group home. It will also capture the experiences of support staff working in the new setting and reveal how this differs from a group home setting. The inclusion of pre (group home) and post (apartment integrated into a community setting) measures addresses evaluative and comparative questions around the nature and impacts of the small-scale apartment and support model for both those who live and receive support, and those who support them. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):DERR1-10.2196/18248

Effects of Pin1 Loss in HdhQ111 Knock-in Mice

Huntington’s disease (HD) is a fatal, dominantly inherited, neurodegenerative disorder due to a pathological expansion of the CAG repeat in the coding region of the HTT gene. In the quest for understanding the molecular basis of neurodegeneration, we have previously demonstrated that the prolyl isomerase Pin1 plays a crucial role in mediating p53-dependent apoptosis triggered by mutant huntingtin (mHtt) in vitro. To assess the effects of the lack of Pin1 in vivo, we have bred Pin1 knock-out mice with HdhQ111 knock-in mice, a genetically precise model of HD. We show that Pin1 genetic ablation modifies a portion of HdhQ111 phenotypes in a time-dependent fashion. As an early event, Pin1 activity reduces the DNA damage response (DDR). In midlife mice, by taking advantage of next-generation sequencing technology, we show that Pin1 activity modulates a portion of the alterations triggered by mHtt, extending the role of Pin1 to two additional HdhQ111 phenotypes: the unbalance in the “synthesis/concentration of hormones”, as well as the alteration of “Wnt/β-catenin signaling”. In aging animals, Pin1 significantly increases the number of mHtt-positive nuclear inclusions while it reduces gliosis. In summary, this work provides further support for a role of Pin1 in HD pathogenesis

Housing design and community care: How home modifications reduce care needs of older people and people with disability

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. The extent to which housing design can minimise levels of community caregiving has remained largely unmeasured. This paper reports the potential for home modifications to reduce caregiving in the peoples’ homes, particularly older people and people with a disability. It contributes to new knowledge in understanding how housing can play a role in community caregiving and acknowledges the role of the built environment in managing care levels in ageing societies. This paper analyses self-reported care data from 157 Australian community care recipients (average age: 72 years) who had received home modifications within the past 6 months. A before/after comparison of care provided revealed that home modifications reduced hours of care provided by 42% per week. More detailed analysis revealed that the positive association of home modifications with care reduction is stronger with informal care (46% reduction) followed by formal care (16% reduction). These results suggest the role that home modifications, and housing design in general, play in reducing care needs in a community setting