Technology-enhanced multi-domain at home continuum of care program with respect to usual care for people with cognitive impairment: the Ability-TelerehABILITation study protocol for a randomized controlled trial.

BACKGROUND: According to the World Alzheimer Report (Prince, The Global Impact of Dementia: an Analysis of Prevalence, Incidence, Cost and Trends, 2015), 46.8 million people worldwide are nowadays living with dementia. And this number is estimated to approximate 131.5 million by 2050, with an increasing burden on society and families. The lack of medical treatments able to stop or slow down the course of the disease has moved the focus of interest toward the nonpharmacological approach and psychosocial therapies for people with/at risk of dementia, as in the Mild Cognitive Impairment (MCI) condition. The purpose of the present study is to test an individualized home-based multidimensional program aimed at enhancing the continuum of care for MCI and outpatients with dementia in early stage using technology. METHODS: The proposed study is a single blind randomized controlled trial (RCT) involving 30 subjects with MCI and Alzheimer's disease (AD) randomly assigned to the intervention group (Ability group), who will receive the "Ability Program", or to the active control group (ACG), who will receive "Treatment As Usual" (TAU). The protocol provides for three steps of assessment: at the baseline (T_0), after treatment, (T_1) and at follow-up (T_2) with a multidimensional evaluation battery including cognitive functioning, behavioral, functional, and quality of life measures. The Ability Program lasts 6 weeks, comprises tablet-delivered cognitive (5 days/week) and physical activities (7 days/week) combined with a set of devices for the measurement and monitoring from remote of vital and physical health parameters. The TAU equally lasts 6 weeks and includes paper and pencil cognitive activities (5 days/week), with clinician's prescription to perform physical exercise every day and to monitor selected vital parameters. DISCUSSION: Results of this study will inform on the efficacy of a technology-enhanced home care service to preserve cognitive and motor levels of functioning in MCI and AD, in order to slow down their loss of autonomy in daily life. The expected outcome is to ensure the continuity of care from clinical practice to the patient's home, enabling also cost effectiveness and the empowerment of patient and caregiver in the care process, positively impacting on their quality of life. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02746484 (registration date: 12/apr/2016 - retrospectively registered).

A century of oil and gas exploration in Albania: assessment of Naturally Occurring Radioactive Materials (NORMs).

The Naturally Occurring Radioactive Materials (NORMs) that are potentially generated from oil and gas extractions in Albania have been disposed of without regulations for many decades, and therefore, an extensive survey in one of the most productive regions (Vlora-Elbasan) was performed. A total of 52 gamma ray spectrometry measurements of soil, oil-sand, sludge, produced water and crude oil samples were performed. We discovered that relatively low activity concentrations of (226)Ra, (228)Ra, (228)Th and (40)K, with concentrations of 23±2Bq/kg, 23±2Bq/kg, 24±3Bq/kg and 549±12Bq/kg, respectively, came from the oil-sands produced by the hydrocarbon extraction of the molasses formations. The mineralogical characterizations and the (228)Ra/(40)K and (226)Ra/(40)K ratios of these Neogene deposits confirmed the predictions of the geological and geodynamic models of a dismantling of the Mesozoic source rocks. The average activity concentrations (±standard deviations) of the radium isotopes ((226)Ra and (228)Ra) and of the (228)Th and (40)K radionuclides in soil samples were 20±5Bq/kg, 25±10Bq/kg, 25±9Bq/kg and 326±83Bq/kg, respectively. Based on the measurements in this study, the future radiological assessments of other fields in the region should be strategically planned to focus on the oil-sands from the molasses sediments. Disequilibrium in the (228)Ra decay segment was not observed in the soil, sludge or oil-sand samples within the standard uncertainties. After a detailed radiological characterization of the four primary oil fields, we concluded that the outdoor absorbed dose rate never exceeded the worldwide population weighted average absorbed dose rate in outdoor air from terrestrial gamma radiation.

Dynamical transition in the D=3 Edwards-Anderson spin glass in an external magnetic field.

We study the off-equilibrium dynamics of the three-dimensional Ising spin glass in the presence of an external magnetic field. We have performed simulations both at fixed temperature and with an annealing protocol. Thanks to the Janus special-purpose computer, based on field-programmable gate array (FPGAs), we have been able to reach times equivalent to 0.01 s in experiments. We have studied the system relaxation both for high and for low temperatures, clearly identifying a dynamical transition point. This dynamical temperature is strictly positive and depends on the external applied magnetic field. We discuss different possibilities for the underlying physics, which include a thermodynamical spin-glass transition, a mode-coupling crossover, or an interpretation reminiscent of the random first-order picture of structural glasses.

Lifetimes of (214)Po and (212)Po measured with Counting Test Facility at Gran Sasso National Laboratory.

The decays of (214)Po into (210)Pb and of (212)Po into (208)Pb tagged by the previous decays from (214)Bi and (212)Bi have been studied inserting quartz vials inside the Counting Test Facility (CTF) at the underground laboratory in Gran Sasso (LNGS). We find that the mean lifetime of (214)Po is (236.00 ± 0.42(stat) ± 0.15(syst)) µs and that of (212)Po is (425.1 ± 0.9(stat) ± 1.2(syst)) ns. Our results are compatible with previous measurements, have a much better signal to background ratio, and reduce the overall uncertainties.

First characterisation of natural radioactivity in building materials manufactured in Albania.

This study focuses on the radiological characterisation of building materials manufactured in Albania by using a high-resolution gamma-ray spectrometer. The average activity concentrations of (40)K, (226)Ra and (232)Th were, respectively, 644.1±64.2, 33.4 ± 6.4 and 42.2 ± 7.6 Bq kg(-1) in the clay brick samples and 179.7 ± 48.9, 55.0 ± 5.8 and 17.0 ± 3.3 Bq kg(-1) in the cement samples. The calculated activity concentration index (ACI), varied from 0.48±0.02 to 0.63±0.04 in the clay brick samples and from 0.29±0.03 to 0.37±0.02 in the cement samples. Based on the ACI, all of the clay brick and cement samples were categorised as A1 materials. The authors can exclude (at 3σ level) any restriction of their use as bulk materials.

The prolyl-isomerase Pin1 activates the mitochondrial death program of p53.

In response to intense stress, the tumor protein p53 (p53) tumor suppressor rapidly mounts a direct mitochondrial death program that precedes transcription-mediated apoptosis. By eliminating severely damaged cells, this pathway contributes to tumor suppression as well as to cancer cell killing induced by both genotoxic drugs and non-genotoxic p53-reactivating molecules. Here we have explored the role had in this pathway by the prolyl-isomerase Pin1 (peptidylprolyl cis/trans isomerase, NIMA-interacting 1), a crucial transducer of p53's phosphorylation into conformational changes unleashing its pro-apoptotic activity. We show that Pin1 promotes stress-induced localization of p53 to mitochondria both in vitro and in vivo. In particular, we demonstrate that upon stress-induced phosphorylation of p53 on Ser46 by homeodomain interacting protein kinase 2, Pin1 stimulates its mitochondrial trafficking signal, that is, monoubiquitination. This pathway is induced also by the p53-activating molecule RITA, and we demonstrate the strong requirement of Pin1 for the induction of mitochondrial apoptosis by this compound. These findings have significant implications for treatment of p53-expressing tumors and for prospective use of p53-activating compounds in clinics.

A new FSA approach for in situ γ ray spectroscopy.

An increasing demand of environmental radioactivity monitoring comes both from the scientific community and from the society. This requires accurate, reliable and fast response preferably from portable radiation detectors. Thanks to recent improvements in the technology, γ spectroscopy with sodium iodide scintillators has been proved to be an excellent tool for in-situ measurements for the identification and quantitative determination of γ ray emitting radioisotopes, reducing time and costs. Both for geological and civil purposes not only (40)K, (238)U, and (232)Th have to be measured, but there is also a growing interest to determine the abundances of anthropic elements, like (137)Cs and (131)I, which are used to monitor the effect of nuclear accidents or other human activities. The Full Spectrum Analysis (FSA) approach has been chosen to analyze the γ spectra. The Non Negative Least Square (NNLS) and the energy calibration adjustment have been implemented in this method for the first time in order to correct the intrinsic problem related with the χ(2) minimization which could lead to artifacts and non physical results in the analysis. A new calibration procedure has been developed for the FSA method by using in situ γ spectra instead of calibration pad spectra. Finally, the new method has been validated by acquiring γ spectra with a 10.16 cm × 10.16 cm sodium iodide detector in 80 different sites in the Ombrone basin, in Tuscany. The results from the FSA method have been compared with the laboratory measurements by using HPGe detectors on soil samples collected particular, the (137)Cs isotopes has been implemented in the analysis since it has been found not negligible during the in-situ measurements.

Second-order closure in stratified turbulence: simulations and modeling of bulk and entrainment regions.

The parametrization of small-scale turbulent fluctuations in convective systems and in the presence of strong stratification is a key issue for many applied problems in oceanography, atmospheric science, and planetology. In the presence of stratification, one needs to cope with bulk turbulent fluctuations and with inversion regions, where temperature, density, or both develop highly nonlinear mean profiles due to the interactions between the turbulent boundary layer and the unmixed-stable-flow above or below it. We present a second-order closure able to cope simultaneously with both bulk and boundary layer regions, and we test it against high-resolution state-of-the-art two-dimensional numerical simulations in a convective and stratified belt for values of the Rayleigh number up to Ra∼10(10). Data are taken from a Rayleigh-Taylor system confined by the existence of an adiabatic gradient.

Numerical simulations of Rayleigh-Taylor front evolution in turbulent stratified fluids.

We present state-of-the-art numerical simulations of a two-dimensional Rayleigh-Taylor instability for a compressible stratified fluid. We describe the computational algorithm and its implementation on the QPACE supercomputer. High resolution enables the statistical properties of the evolving interface that we characterize in terms of its fractal dimension to be studied.

Serenoa repens in benign prostatic hypertrophy: analysis of 2 Italian studies.

AIM: Benign prostatic hypertrophy (BPH), which is characterized by a progressive swelling of the prostate causing symptoms of the lower urinary tract, is the second pathology as frequency among the diagnoses placed in men every year in Italy. The extract of Serenoa repens is an alternate therapeutic option to traditional drug therapies with a good profile of efficacy and safety for the management of the symptoms of BPH. The aim of this paper was to analyze systematically the results of two Italian studies carried out on patients with BPH treated with extract of serenoa repens (SABA. a product of Lampugnani Farmaceutici S.p.A.). METHODS: The studies were carried out on a total of 70 adult patients with diagnosis of benign prostatic hypertrophy. In one study the patients were treated with Serenoa repens 320 mg/day for 30 days; in the other study the patients received Serenoa repens 320 mg/day or Pygeum africanum (Tadenan) 4 capsules of 25 mg/day for 30 days. RESULTS: Both studies showed an improvement versus the baseline of about 50% of dysuria and pollakisuria, an about 50% increase in micturition rate with positive effects also in terms of reduction of the micturition rate and of prostate size. Also the tolerability profile was favorable. CONCLUSION: The extract of Serenoa repens (SABA Lampugnani Farmaceutici S.p.A.) administered at the dose of 320 mg/day to patients with benign prostatic hypertrophy, is effective in terms of improvement of the functional symptomatologic picture improvement and of the instrumental parameters with a good tolerability profile.

Functional living skills assessment: a standardized measure of high-order activities of daily living in patients with dementia.

AIM: Performance measures are tools aimed to directly evaluate social function in older adults. The authors present the standardization of a new direct performance measure for patients with dementia, the functional living skills assessment (FLSA). METHODS: FLSA was conceived to detect functional impairment in very mild to moderate patients and to pick up functional modification due to intervention. The patient is asked to perform an activity, and the performance is scored according to completeness and level of assistance required. Eight areas of interest are evaluated (Resources, Consumer Skills, Public Transportation, Time Management, Money management, Leisure, Telephone Skills, Self-Care and Health). Subjects included 54 patients with dementia and 36 normal controls. RESULTS: Total and partial FLSA scores significantly differed for the two groups (P<0.0001). Performance on FLSA could divide clinical dementia rating (CDR) 0 from CDR 1, CDR 2 e CDR 3 groups. Both sensitivity and specificity were 94%; inter-rater and test-retest reliability was good (P>0.9). Correction scores for education were calculated, while age influence was only marginally significant. Mini Mental State Examination (MMSE) and CDR highly influenced FLSA score (P< 0.0001); FLSA was highly correlated with another performance measure (the Direct Assessment of Functional Status; P=0.821), and with the Instrumental Activity of Daily Living (IADL) scale (P=-0.612), while no significant correlation was present with the Geriatric Depression Scale. CONCLUSION: FLSA evidences construct, concurrent and discriminative validity. We suggest that this tool could be possibly useful when a high sensibility to different levels of functional impairment is needed, as evaluation of treatment efficacy (both non-pharmacological and pharmacological) identification of relatively intact functional areas to plan cognitive rehabilitation, and confirmation of dementia in the initial phase when there are doubts about functional decline.

Static versus dynamic heterogeneities in the D = 3 Edwards-Anderson-Ising spin glass.

We numerically study the aging properties of the dynamical heterogeneities in the Ising spin glass. We find that a phase transition takes place during the aging process. Statics-dynamics correspondence implies that systems of finite size in equilibrium have static heterogeneities that obey finite-size scaling, thus signaling an analogous phase transition in the thermodynamical limit. We compute the critical exponents and the transition point in the equilibrium setting, and use them to show that aging in dynamic heterogeneities can be described by a finite-time scaling ansatz, with potential implications for experimental work.

Prospective evaluation of laparoscopic pancreatic biopsies in 11 healthy cats.

BACKGROUND: Definitive diagnosis of feline pancreatic disease is dependent on histologic examination of biopsies. HYPOTHESIS: Laparoscopic punch biopsy of the pancreas does not significantly affect pancreatic health or clinical status of healthy cats, and provides an adequate biopsy sample for histopathology. ANIMALS: Eleven healthy female domestic shorthair cats. METHODS: Effects of laparoscopic pancreatic visualization alone in 5 cats compared with laparoscopic pancreatic visualization and punch biopsy in 6 cats were studied. Temperature, pulse, and respiratory rate, physical examination, and daily caloric intake were evaluated for 1 week before and 1 week after the procedure. Pain scores (simple descriptive score and dynamic interactive visual assessment score) were evaluated hourly during the 1st 6 hours postprocedure. Complete blood cell counts, serum biochemical profiles, serum feline pancreatic lipase immunoreactivity, and urine specific gravity were evaluated before the procedure and at 6, 24, and 72 hours postprocedure. One month postprocedure, during sterilization, the pancreas was reassessed visually in all cats, and microscopically in the biopsy group. RESULTS: For all variables evaluated, there were no significant differences between biopsy and control cats. Re-evaluation of the pancreatic biopsy site 1 month later documented a normal tissue response to biopsy. The laparoscopic punch biopsy forceps provided high-quality pancreatic biopsy samples with an average size of 5 mm x 4 mm on 2-dimensional cut section. CONCLUSIONS AND CLINICAL IMPORTANCE: Laparoscopic pancreatic biopsy is a useful and safe technique in healthy cats.

Antinociceptive effects of epidural buprenorphine or medetomidine, or the combination, in conscious cats.

The aim of this study was to compare the antinociceptive effects of epidural buprenorphine (EB), epidural medetomidine (EM) or epidural buprenorphine-medetomidine (EBM). Eight cats were studied. Thermal thresholds (TT) were measured by increasing the temperature of a probe placed on the thorax. Mechanical thresholds (MT) were measured through inflation of a modified blood pressure bladder to the cat's forelimb. After baseline measurements, EB (0.02 mg/kg), EM (0.01 mg/kg) or half of the doses of each drug (EBM) were administered. Data were analysed using anova (P < 0.05) and 95% confidence interval (CI). TT increased from 30 min to 1 h after EB and at 45 min after EM. MT increased from 45 min to 2 h after EB, from 15 min to 1 h after EM and at 30, 45 min and at 2 h after EBM. MT were significantly lower after EB than EM at 30 min. TT were above the upper 95%CI from 15 min to 24 h after EB, from 15 min to 4 h after EM and from 15 min to 8 h after EBM. MT were above the upper 95%CI from 15 min to 5 h, and at 8, 12 and 24 h after EB, from 15 min to 6 h after EM and from 15 min to 6 h and at 12 and 24 h after EBM. All treatments had similar onset. Overall, EB presented longer period of action than EBM and EM. The same magnitude of analgesia was achieved, but with fewer side effects when EBM was compared with EM.

Frequency and clinical features of Lewy body dementia in Italian memory clinics.

BACKGROUND: The latest developments in Lewy Body Dementia (DLB) raise some controversies on clinical features, neuroimaging and therapy. The aim of our study is to determine clinical, neuropsychological, neuroimaging and EEG profile of DLB through retrospective and prospective data of 102 patients. METHODS: data were collected with an analytical form that was developed by an expertise of neurologists. RESULTS: DLB represented 4.8% of the dementia population, with no sex difference. Family history of dementia was common (24.5%), while familiarity for parkinsonism was rare (4.9%). Cognitive disturbances were the predominant clinical presentation at onset (49%), followed by behavioral symptoms (29.4%) and parkinsonism (21.6%). Clinical features at consultation were: memory disturbances (almost all cases), symmetrical (68.6%) or asymmetrical (18.6%) parkinsonism, cognitive fluctuations (49%), visuospatial deficits (53.9%), and visual hallucinations (44.1%). Autonomic signs were present in a third of the cases, while sleep disorders were present in 44.1%. Some clinical response to antiparkinsonian drugs was evident in half of the cases. MRI, SPET, EEG and Neuropsychiatric Inventory data were available in a subgroup of patients. CONCLUSIONS: Most of our data were in accordance with the previous literature. However, some data underline the relationship between DLB, Alzheimer's and Parkinson's disease.

Evaluation of the adverse effects of subcutaneous carprofen over six days in healthy cats.

This study evaluated the adverse effects of carprofen in seven healthy cats. Values for CBC, biochemical profiles and platelet aggregation were measured before and at seven days after SID treatment with subcutaneous carprofen: 4 mg/kg (day 1), 2mg/kg (day 2 and 3) and 1mg/kg (day 4 and 6) (CG) or 0.35 ml of saline (SG) for six days in a randomized, blinded, cross-over study with a four-week washout period. No treatment was given on day 5. Endoscopy of the GI tract was performed pre-treatment and on day 7 post-treatment. There were no significant changes in hematological profiles, biochemical profiles and endoscopy grading scores within nor between groups, except for lower albumin values at baseline than on day 7 (CG), and globulin and ALP values were higher at baseline than on day 7 in CG and SG. SC administration of carprofen over six days did not cause any adverse effects on gastrointestinal, hematological, or serum biochemical variables.

Nonequilibrium spin-glass dynamics from picoseconds to a tenth of a second.

We study numerically the nonequilibrium dynamics of the Ising spin glass, for a time spanning 11 orders of magnitude, thus approaching the experimentally relevant scale (i.e., seconds). We introduce novel analysis techniques to compute the coherence length in a model-independent way. We present strong evidence for a replicon correlator and for overlap equivalence. The emerging picture is compatible with noncoarsening behavior.

Evaluation of the adverse effects of oral firocoxib in healthy dogs.

This study evaluated the adverse effects of oral firocoxib in dogs. Six dogs (20.2+/-6.3 kg) were studied. Values for complete blood count (CBC), serum urea, creatinine, alanine transaminase, alanine phosphatase, gamma-glutamyl transferase, occult blood in feces, platelet aggregation, and buccal mucosal bleeding time were measured before and 7, 14, 21, and 29 days after SID treatment with firocoxib 5.3+/-0.34 mg/kg (FG) or lactose 1 mg/kg (LG) for 28 days, in a randomized crossover study. Gastrointestinal (GI) tract endoscopy was performed before treatment began and at 29 days. Lesions were scored from grade 0 to 6. Data were analyzed using anova and paired t-tests (P<0.05). None of the dogs presented adverse clinical effects. There were no significant changes in CBC, biochemical profiles within groups, or differences between groups. Pretreatment mean+/-SD bleeding time (LG, 70.7+/-32.1 sec; FG, 75.8+/-38.1 sec) and platelet aggregation (LG, 86.4+/-10.2%; FG, 85.6+/-9.2%) were not significantly different from readings at 29 days (LG, 95.2+/-25 sec; FG, 91.7+/-24 sec and LG, 73.2+/-15.1%; FG, 84+/-10.3%) nor the groups were different. None of the dogs had positive fecal occult blood tests, and endoscopic lesion scores were grade 0 both before treatment and at 29 days. Administration of firocoxib did not cause any adverse effects on GI, or hematological or serum biochemical variables and appears to have been well tolerated by dogs.

Evaluating two group programmes of cognitive training in mild-to-moderate AD: is there any difference between a 'global' stimulation and a 'cognitive-specific' one?

This study evaluated the efficacy of two different group procedures of non-pharmacological treatment in mild-to-moderate Alzheimer's disease (AD). Thirty-two patients entered the study and were divided in groups of four subjects. We compared recreational activities ('global' stimulation) with a combination of procedural memory training on activities of daily living and neuropsychological rehabilitation of 'residual' functions ('cognitive-specific'). All patients and caregivers were ensured psychological support. Both group treatments were delivered for six weeks. Multidimensional efficacy assessment of functional, behavioural and neuropsychological aspects was performed. Patients receiving 'global' stimulation showed a substantial reduction in behavioural disturbances (Neuropsychiatric Inventory [NPI]: frequency p = 0.034; severity p = 0.012); Revised Memory Behaviour Problems Checklist (frequency p = 0.008; reaction p = 0.027), and better performance in the Functional Living Skills Assessment (FLSA), a standardized direct measure of performance in everyday life (p = 0.021) and Verbal Fluency for Letters (p = 0.000). Patients receiving 'cognitive-specific' treatment improved only on the scale evaluating functional competence in daily living (Nurses' Observation Scale for Geriatric Patients [NOSGER] p = 0.018). At follow-up (six months later), compared with baseline, patients following the 'global' stimulation treatment showed an improvement at caregiver distress on NPI (p = 0.04). No other significant difference was detected. Our results support the contention that a 'global' treatment can lead to a significant improvement in AD patients, both for behavioural and functional aspects. The 'cognitive-specific' treatment we used in this research did not show better efficacy.