Effectiveness of cognitive and physical training in slowing progression to dementia: a clinical and experimental study. Focus on relationship with cardiovascular fitness

Physical activity is beneficial to vascular health; on the other hand, vascular damage is associated with cognitive impairment. Both physical activity and a cognitively stimulating environment are known to delay the onset of dementia. The Train The Brain study evaluated the effectiveness of a comprehensive program of physical training and mental activity in delaying cognitive decline in elderly people with initial cognitive impairment, at the same time investigating the relationship between physical, vascular, neurological, and cognitive fitness. Elders age 65-89 with were recruited with the help of family physicians and territorial services. All participants underwent a neurological and cardiologic evaluation. Carotid-femoral pulse wave velocity and carotid pressure were measured with the SphygmoCor system (AtCor, Australia). Longitudinal ultrasound scans of the common carotid were performed and 10-second video clips were recorded to be analysed offline through the Cardiovascular Suite software (Quipu srl, Italy), with the computation of diameter, intima-media thickness, wall cross-sectional area, distensibility coefficient, and elastic modulus. The latter software was used also to measure endothelial function through flow mediated dilation (FMD) of the brachial artery. Subjects classified as mild cognitive impairment at the neurological examination were randomized either to standard care, or a 7-month program of physical training and environmental stimulation (lectures, games, music, social activities) three hours a week. The evaluation was then repeated. Data were obtained for 54 patients who underwent training and 36 controls. The intervention was successful in improving cognitive function as measured through the ADAS-Cog score: 11.95 (3.86) to 13.00 (4.73) for no training, 14.32 (4.27) to 12.85 (4.03) for training, time x treatment p<0.001. Pulse wave velocity showed no significant effect (p=0.5). FMD improved with intervention (no training: 3.20 (2.03) to 2.50 (1.77) %; training: from 2.82 (2.19) to 3.42 (1.82); p=0.014). All selected carotid parameters were influenced by the combination of time and treatment, in a diverging trend, at a statistically significant level, with intervention determining less dilated, less thick and less stiff vessels. None of the parameters measured analysing the vessels showed a correlation The proposed 7-months program improved cognitive function in elders with initial cognitive impairment. There was a significant difference in behaviour in time of the two groups as for endothelial function and carotid enlargement, wall thickening and arterial stiffening. The intervention seems to oppose the typical harmful effects of aging on vessels; at the same time, the positive effects on cognition and vascular health do not appear as directly correlated

Le determinanti nella scelta del sistema di costing: analisi di un caso aziendale.

La tesi è incentrata sullo studio delle variabili interne all'azienda e dei fattori esterni che possono esercitare un'influenza significativa sulla scelta del sistema di costing da implementare. Tale studio si avvale del contributo di un'ampia letteratura sulla materia. Nello specifico,viene concentrata l'attenzione sull'analisi della struttura organizzativa, del processo decisionale, delle finalità di utilizzo del sistema di costing e dell'ambiente competitivo in cui l'azienda muove i propri passi, al fine di valutare come tali fattori influenzano la scelta e l'adozione di sistemi di costing più o meno sofisticati. Le nozioni teoriche acquisite e argomentate sono poi impiegate per la valutazione dell'adeguatezza del sistema di costing adottato nell'azienda Alfa Srl (nome di fantasia), una società di progettazione e consulenza ingegneristica con sede a Pisa

Teoria efficace dell'inflazione con simmetria galileiana

La teoria dell'inflazione cosmologica nasce per fornire una spiegazione dell'estrema uniformità della temperatura della CMB e della geometria sostanzialmente piatta dell'Universo attuale che, all'interno della cosmologia relativistica standard, richiederebbero un “fine tuning” delle condizioni iniziali dell'Universo. Tali problemi vengono risolti in modo naturale se si ammette l'esistenza di un rapido ma intenso periodo di espansione accelerata nelle primissime fasi di vita dell'Universo, alla fine del quale l'evoluzione sarebbe proseguita come descritto dalla cosmologia standard. Un ottimo candidato a guidare l'inflazione è un campo scalare che in opportune condizioni simula gli effetti di una costante cosmologica e produce dunque un'espansione accelerata. Il più grande successo dell'inflazione sta comunque nella sua capacità di fornire una spiegazione della formazione delle perturbazioni di densità primordiali, i germi delle grandi strutture formate in seguito dal collasso gravitazionale. Le informazioni su tali perturbazioni primordiali provengono dallo studio delle piccole anisotropie nella radiazione di fondo, che rivela una loro distribuzione approssimativamente gaussiana con piccole deviazioni. Lo studio di queste ultime non-gaussianità ci permette di discriminare tra vari modelli di inflazione. Il modello più semplice di inflazione è quello di slow-roll, dove la dinamica di un campo scalare è guidata da un potenziale molto piatto che domina sul termine cinetico; tuttavia un modello di questo tipo predice non-gaussianità troppo piccole per essere osservabili nel prossimo futuro, giustificando così l'introduzione di modelli più complessi. In questo lavoro di tesi si prende in considerazione un modello di inflazione descritto da una teoria efficace con interazioni “higher derivative”, quindi con più di una derivata per campo, che restituisca però equazioni del moto del secondo ordine in modo da non contenere gradi di libertà ulteriori e instabili. Tale condizione è raggiungibile considerando una teoria per un campo scalare invariante sotto la simmetria interna detta galileiana. Si considera dapprima la situazione in assenza di gravità, dove la simmetria vincola molto la struttura della teoria, tanto che sono possibili solo un numero finito di termini lagrangiani. Le correzioni radiative sono in grado di generare solo operatori con almeno due derivate per campo (che rispettano quindi la simmetria) soppressi ad energie minori del cutoff della teoria, mentre i potenziali operatori dello stesso ordine di quelli originari, ma che non rispettano la simmetria galileiana, non vengono generati. Quando si estende la teoria al caso di spazio curvo attraverso il metodo di accoppiamento minimale, la simmetria ne risulta rotta, ma tale rottura è caratterizzata da una scala di energia molto maggiore del cutoff ultravioletto della teoria stessa. In questo senso si dirà che la simmetria galileiana è rotta solo debolmente e si parlerà di “weakly broken galileon (WBG) invariance”. Considereremo una classe di teorie WBG accoppiate alla gravità e studieremo le equazioni di Friedmann corrispondenti che governano la dinamica del background, mostrando l'esistenza di soluzioni cosmologiche inflazionarie. Per affrontare lo studio delle fluttuazioni attorno alla soluzione uniforme per il campo scalare galileonico (e di tipo FRW per la metrica), è conveniente utilizzare la gauge unitaria in cui il grado di libertà scalare proveniente dalla fluttuazione del campo è inglobato dalle fluttuazioni della metrica. Questa gauge rompe l'invarianza della teoria sotto diffeomorfismi richiesta dalla relatività generale, in quanto implica la scelta di una coordinata temporale ben precisa. Tuttavia l'invarianza può essere ripristinata mediante la reintroduzione di un grado di libertà scalare corrispondente al bosone di Goldstone che realizza i diffeomorfismi temporali. Con tale procedura lo studio delle conseguenze cosmologiche della teoria risulta semplificato grazie al disaccoppiamento della dinamica del Goldstone da quella della metrica al di sopra di una certa energia minore della scala H data dal parametro di Hubble durante l'inflazione. Possiamo dunque calcolare le non-gaussianità previste dal modello, le più rilevanti delle quali sono fornite dalla funzione di correlazione a tre punti. Le non-gaussianità sono calcolate in termini dei parametri della teoria e, sotto ipotesi naturali che vengono discusse, è possibile ottenere valori compatibili con i limiti attuali, dati dal satellite Planck, e abbastanza grandi da essere esplorati nel prossimo futuro

La criticità delle risorse umane nei processi di Turnaround: prime riflessioni sulla valutazione del loro "valore".

In un periodo di crisi globale come quello che stiamo vivendo, buona parte delle imprese è impegnata a ristudiare e reimpostare i propri sistemi di gestione, focalizzandosi principalmente sulle modalità di recupero dell’efficienza, sullo sviluppo di nuove opportunità e sul ripensamento delle proprie strategie e dei propri modelli di business al fine di sostenere la sopravvivenza dell’azienda nel dinamico e competitivo mercato di riferimento. Lo sviluppo tecnologico moderno non consente più, alle imprese, di ottenere un vantaggio competitivo duraturo nei confronti dei competitors, operando attraverso l’introduzione di miglioramenti nei prodotti e nei processi. Oggi, il successo delle imprese è merito delle risorse che operano al suo interno. Concetti come leadership, cultura aziendale, competenze e comunicazione, rappresentano oggi più che mai fattori sui quali far leva per avere successo. In questo mio lavoro cercherò di far comprendere l'importanza delle Risorse umane in termine di valore apportato in azienda. Inoltre il capitale umano può aiutare l'impresa nel capire il proprio Stato di Salute e prevenire future crisi aziendali. È in questo contesto, dunque, che trova sempre più spazio l’analisi del Capitale Umano presente in azienda, considerato come il nuovo fattore chiave per affermarsi ed essere competitivi sul mercato

Characteristics of misclassified ct perfusion ischemic core in patients with acute ischemic stroke

Background CT perfusion (CTP) is used to estimate the extent of ischemic core and penumbra in patients with acute ischemic stroke. CTP reliability, however, is limited. This study aims to identify regions misclassified as ischemic core on CTP, using infarct on follow-up noncontrast CT. We aim to assess differences in volumetric and perfusion characteristics in these regions compared to areas that ended up as infarct on follo

Forefoot pathology in rheumatoid arthritis identified with ultrasound may not localise to areas of highest pressure: cohort observations at baseline and twelve months

BackgroundPlantar pressures are commonly used as clinical measures, especially to determine optimum foot orthotic design. In rheumatoid arthritis (RA) high plantar foot pressures have been linked to metatarsophalangeal (MTP) joint radiological erosion scores. However, the sensitivity of foot pressure measurement to soft tissue pathology within the foot is unknown. The aim of this study was to observe plantar foot pressures and forefoot soft tissue pathology in patients who have RA.Methods A total of 114 patients with established RA (1987 ACR criteria) and 50 healthy volunteers were assessed at baseline. All RA participants returned for reassessment at twelve months. Interface foot-shoe plantar pressures were recorded using an F-Scan® system. The presence of forefoot soft tissue pathology was assessed using a DIASUS musculoskeletal ultrasound (US) system. Chi-square analyses and independent t-tests were used to determine statistical differences between baseline and twelve months. Pearson’s correlation coefficient was used to determine interrelationships between soft tissue pathology and foot pressures.ResultsAt baseline, RA patients had a significantly higher peak foot pressures compared to healthy participants and peak pressures were located in the medial aspect of the forefoot in both groups. In contrast, RA participants had US detectable soft tissue pathology in the lateral aspect of the forefoot. Analysis of person specific data suggests that there are considerable variations over time with more than half the RA cohort having unstable presence of US detectable forefoot soft tissue pathology. Findings also indicated that, over time, changes in US detectable soft tissue pathology are out of phase with changes in foot-shoe interface pressures both temporally and spatially.Conclusions We found that US detectable forefoot soft tissue pathology may be unrelated to peak forefoot pressures and suggest that patients with RA may biomechanically adapt to soft tissue forefoot pathology. In addition, we have observed that, in patients with RA, interface foot-shoe pressures and the presence of US detectable forefoot pathology may vary substantially over time. This has implications for clinical strategies that aim to offload peak plantar pressures

Recommendations for a core outcome set for measuring standing balance in adult populations: a consensus-based approach

Standing balance is imperative for mobility and avoiding falls. Use of an excessive number of standing balance measures has limited the synthesis of balance intervention data and hampered consistent clinical practice.To develop recommendations for a core outcome set (COS) of standing balance measures for research and practice among adults.A combination of scoping reviews, literature appraisal, anonymous voting and face-to-face meetings with fourteen invited experts from a range of disciplines with international recognition in balance measurement and falls prevention. Consensus was sought over three rounds using pre-established criteria.The scoping review identified 56 existing standing balance measures validated in adult populations with evidence of use in the past five years, and these were considered for inclusion in the COS.Fifteen measures were excluded after the first round of scoring and a further 36 after round two. Five measures were considered in round three. Two measures reached consensus for recommendation, and the expert panel recommended that at a minimum, either the Berg Balance Scale or Mini Balance Evaluation Systems Test be used when measuring standing balance in adult populations.Inclusion of two measures in the COS may increase the feasibility of potential uptake, but poses challenges for data synthesis. Adoption of the standing balance COS does not constitute a comprehensive balance assessment for any population, and users should include additional validated measures as appropriate.The absence of a gold standard for measuring standing balance has contributed to the proliferation of outcome measures. These recommendations represent an important first step towards greater standardization in the assessment and measurement of this critical skill and will inform clinical research and practice internationally

Interventions for preventing oral mucositis in patients with cancer receiving treatment:Oral cryotherapy

BACKGROUND: Oral mucositis is a side effect of chemotherapy, head and neck radiotherapy, and targeted therapy, affecting over 75% of high risk patients. Ulceration can lead to severe pain and difficulty eating and drinking, which may necessitate opioid analgesics, hospitalisation and nasogastric or intravenous nutrition. These complications may lead to interruptions or alterations to cancer therapy, which may reduce survival. There is also a risk of death from sepsis if pathogens enter the ulcers of immunocompromised patients. Ulcerative oral mucositis can be costly to healthcare systems, yet there are few preventive interventions proven to be beneficial. Oral cryotherapy is a low‐cost, simple intervention which is unlikely to cause side‐effects. It has shown promise in clinical trials and warrants an up‐to‐date Cochrane review to assess and summarise the international evidence. OBJECTIVES: To assess the effects of oral cryotherapy for preventing oral mucositis in patients with cancer who are receiving treatment. SEARCH METHODS: We searched the following databases: the Cochrane Oral Health Group Trials Register (to 17 June 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 5), MEDLINE via Ovid (1946 to 17 June 2015), EMBASE via Ovid (1980 to 17 June 2015), CANCERLIT via PubMed (1950 to 17 June 2015) and CINAHL via EBSCO (1937 to 17 June 2015). We searched the US National Institutes of Health Trials Registry, and the WHO Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching databases. SELECTION CRITERIA: We included parallel‐design randomised controlled trials (RCTs) assessing the effects of oral cryotherapy in patients with cancer receiving treatment. We used outcomes from a published core outcome set registered on the COMET website. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the results of electronic searches, extracted data and assessed risk of bias. We contacted study authors for information where feasible. For dichotomous outcomes, we reported risk ratios (RR) and 95% confidence intervals (CI). For continuous outcomes, we reported mean differences (MD) and 95% CIs. We pooled similar studies in random‐effects meta‐analyses. We reported adverse effects in a narrative format. MAIN RESULTS: We included 14 RCTs analysing 1280 participants. The vast majority of participants did not receive radiotherapy to the head and neck, so this review primarily assesses prevention of chemotherapy‐induced oral mucositis. All studies were at high risk of bias. The following results are for the main comparison: oral cryotherapy versus control (standard care or no treatment). Adults receiving fluorouracil‐based (5FU) chemotherapy for solid cancers Oral cryotherapy probably reduces oral mucositis of any severity (RR 0.61, 95% CI 0.52 to 0.72, 5 studies, 444 analysed, moderate quality evidence). In a population where 728 per 1000 would develop oral mucositis, oral cryotherapy would reduce this to 444 (95% CI 379 to 524). The number needed to treat to benefit one additional person (NNTB), i.e. to prevent them from developing oral mucositis, is 4 people (95% CI 3 to 5). The results were similar for moderate to severe oral mucositis (RR 0.52, 95% CI 0.41 to 0.65, 5 studies, 444 analysed, moderate quality evidence). NNTB 4 (95% CI 4 to 6). Severe oral mucositis is probably reduced (RR 0.40, 95% CI 0.27 to 0.61, 5 studies, 444 analysed, moderate quality evidence). Where 300 per 1000 would develop severe oral mucositis, oral cryotherapy would reduce this to 120 (95% CI 81 to 183), NNTB 6 (95% CI 5 to 9). Adults receiving high‐dose melphalan‐based chemotherapy before haematopoietic stem cell transplantation (HSCT) Oral cryotherapy may reduce oral mucositis of any severity (RR 0.59, 95% CI 0.35 to 1.01, 5 studies, 270 analysed, low quality evidence). Where 824 per 1000 would develop oral mucositis, oral cryotherapy would reduce this to 486 (95% CI reduced to 289 to increased to 833). The NNTB is 3, although the uncertainty surrounding the effect estimate means that the 95% CI ranges from 2 NNTB, to 111 NNTH (number needed to treat in order to harm one additional person, i.e. for one additional person to develop oral mucositis). The results were similar for moderate to severe oral mucositis (RR 0.43, 95% CI 0.17 to 1.09, 5 studies, 270 analysed, low quality evidence). NNTB 3 (95% CI 2 NNTB to 17 NNTH). Severe oral mucositis is probably reduced (RR 0.38, 95% CI 0.20 to 0.72, 5 studies, 270 analysed, moderate quality evidence). Where 427 per 1000 would develop severe oral mucositis, oral cryotherapy would reduce this to 162 (95% CI 85 to 308), NNTB 4 (95% CI 3 to 9). Oral cryotherapy was shown to be safe, with very low rates of minor adverse effects, such as headaches, chills, numbness/taste disturbance, and tooth pain. This appears to contribute to the high rates of compliance seen in the included studies. There was limited or no evidence on the secondary outcomes of this review, or on patients undergoing other chemotherapies, radiotherapy, targeted therapy, or on comparisons of oral cryotherapy with other interventions or different oral cryotherapy regimens. Therefore no further robust conclusions can be made. There was also no evidence on the effects of oral cryotherapy in children undergoing cancer treatment. AUTHORS' CONCLUSIONS: We are confident that oral cryotherapy leads to large reductions in oral mucositis of all severities in adults receiving 5FU for solid cancers. We are less confident in the ability of oral cryotherapy to reduce oral mucositis in adults receiving high‐dose melphalan before HSCT. Evidence suggests that it does reduce oral mucositis in these adults, but we are less certain about the size of the reduction, which could be large or small. However, we are confident that there is an appreciable reduction in severe oral mucositis in these adults. This Cochrane review includes some very recent and currently unpublished data, and strengthens international guideline statements for adults receiving the above cancer treatments

Airway branching morphogenesis in three dimensional culture

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldBACKGROUND: Lungs develop from the fetal digestive tract where epithelium invades the vascular rich stroma in a process called branching morphogenesis. In organogenesis, endothelial cells have been shown to be important for morphogenesis and the maintenance of organ structure. The aim of this study was to recapitulate human lung morphogenesis in vitro by establishing a three dimensional (3D) co-culture model where lung epithelial cells were cultured in endothelial-rich stroma. METHODS: We used a human bronchial epithelial cell line (VA10) recently developed in our laboratory. This cell line cell line maintains a predominant basal cell phenotype, expressing p63 and other basal markers such as cytokeratin-5 and -14. Here, we cultured VA10 with human umbilical vein endothelial cells (HUVECs), to mimic the close interaction between these cell types during lung development. Morphogenesis and differentiation was monitored by phase contrast microscopy, immunostainings and confocal imaging. RESULTS: We found that in co-culture with endothelial cells, the VA10 cells generated bronchioalveolar like structures, suggesting that lung epithelial branching is facilitated by the presence of endothelial cells. The VA10 derived epithelial structures display various complex patterns of branching and show partial alveolar type-II differentiation with pro-Surfactant-C expression. The epithelial origin of the branching VA10 colonies was confirmed by immunostaining. These bronchioalveolar-like structures were polarized with respect to integrin expression at the cell-matrix interface. The endothelial-induced branching was mediated by soluble factors. Furthermore, fibroblast growth factor receptor-2 (FGFR-2) and sprouty-2 were expressed at the growing tips of the branching structures and the branching was inhibited by the FGFR-small molecule inhibitor SU5402. DISCUSSION: In this study we show that a human lung epithelial cell line can be induced by endothelial cells to form branching bronchioalveolar-like structures in 3-D culture. This novel model of human airway morphogenesis can be used to study critical events in human lung development and suggests a supportive role for the endothelium in promoting branching of airway epithelium