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).

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.

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.

Comparing two programs of cognitive training in Alzheimer's disease: a pilot study.

OBJECTIVES: To evaluate the efficacy of two different procedures of individual cognitive training in mild to moderate Alzheimer's Disease (AD). MATERIAL AND METHODS: Twenty-two AD patients entered the study. We compared stimulation of procedural memory (group 1) with training of partially spared cognitive functions (group 2). Assessment included: neuropsychological tests, scales, and the Functional Living Skills Assessment (FLSA), a standardized battery built to directly evaluate patients' performance in everyday life. RESULTS: We observed a significant improvement for both groups after training in FLSA total score (P=0.005) and subscales. For group 1, we also found a slightly improved performance in two tests: Attentional Matrices (P=0.041), and Verbal Fluency for Letters (P=0.059). After 3 months, patients' results showed a tendency to regress to the pre-training level. CONCLUSION: Both AD groups showed a substantial improvement after training in a direct performance measure of everyday functioning. However, results at neuropsychological tests suggest that training activities of daily living (supported by procedural memory) may be more effective than stimulating "residual" cognitive functions.

Mycobacterium bovis: polymerase chain reaction identification in bovine lymphonode biopsies and genotyping in isolates from Southeast Brazil by spolygotyping and restriction fragment length polymorphism.

Diagnosis of the Mycobacterium tuberculosis complex by direct PCR of mediastinal lymphnode DNA and microbiological tests were compared in cattle suspicious of bearing tuberculous-like lesions detected during slaughter. The PCR procedure applied on DNA samples (n=54) obtained by adding alpha -casein into the thiocyanate extraction mix was positive in 70% of the samples. PCR confirmed the identification of 23 samples (100%) that grew in culture, 9 samples (60%) that failed to grow in culture, plus 6 (37.5%) samples that resulted in growth of bacterial contaminants. Genotyping by IS6110-RFLP and DR-spoligotyping analysis of seven samples revealed the presence of several polimorphisms. Seven of the isolates contained multiple copies of IS6110, thus defining the existence of five singular genotypes.

Mycobacterium bovis: polymerase chain reaction identification in bovine Lymphonode biopsies and genotyping in isolates from Southeast Brazil by spolygotyping and restriction fragment length polymorphism

Diagnosis of the Mycobacterium tuberculosis complex by direct PCR of mediastinal lymphnode DNA and microbiological tests were compared in cattle suspicious of bearing tuberculous-like lesions detected during slaughter. The PCR procedure applied on DNA samples (n=54) obtained by adding alpha -casein into the thiocyanate extraction mix was positive in 70 percent of the samples. PCR confirmed the identification of 23 samples (100 percent) that grew in culture, 9 samples (60 percent) that failed to grow in culture, plus 6 (37.5 percent) samples that resulted in growth of bacterial contaminants. Genotyping by IS6110-RFLP and DR-spoligotyping analysis of seven samples revealed the presence of several polimorphisms. Seven of the isolates contained multiple copies of IS6110, thus defining the existence of five singular genotypes

Building a pharmacophore model for a novel class of antitubercular compounds.

Starting from a set of 32 antitubercular compounds, for the first time a three-dimensional pharmacophore model has been derived through a computational approach based on CATALYST software. The model proved to be able to identify compounds belonging to classes of molecules already reported as antitubercular agents.

New pyrrole derivatives as antimycobacterial agents analogs of BM212.

During the course of our investigations in the field of azole antimicrobial agents, we have identified BM212 a pyrrole derivative with good in vitro activity against mycobacteria and candidae. These findings prompted us to prepare new pyrrole derivatives 2-6 in the hope of increasing the activity. The microbiological data showed interesting in vitro activity against Mycobacterium tuberculosis and atypical mycobacteria.

Smoluchowski dynamics of the vnd/NK-2 homeodomain from Drosophila melanogaster: first-order mode-coupling approximation.

This work is the first in a series devoted to applying mode coupling diffusion theory to the derivation of local dynamics properties of proteins in solution. The first-order mode-coupling approximation, or optimized Rouse-Zimm local dynamics (ORZLD), is applied here to derive the rotational dynamics of the bonds and compare the calculated with the experimental nmr 15N spin-lattice relaxation time behavior of the vnd/NK-2 homeodomain from Drosophila melanogaster. The starting point for the calculations is the experimental three-dimensional structure of the homeodomain determined by multidimensional nmr spectroscopy. The results of the computations are compared with experimentally measured 15N spin-lattice relaxation times T1, at 34.5 and 60.8 MHz, to check the first-order approximation. To estimate the relative importance of internal and overall rotation, both rigid and fluctuating dynamic models are examined, with fluctuations evaluated using molecular dynamics (MD) simulations. The correlation times for the fundamental bond vector time correlation function and for the second-order bond orientational TCF are obtained as a function of the residue number for vnd/NK-2. The stability of the corresponding local dynamics pattern for the fluctuating structure as a function of the length of the MD trajectory is presented. Diffusive dynamics, which is essentially free of model parameters even at first order in the mode-coupling diffusion approach, confirm that local dynamics of proteins can be described in terms of rotational diffusion of a fluctuating quasi-rigid structure. The comparison with the nmr data shows that the first-order mode coupling diffusion approximation accounts for the correct order of magnitude of the results and of important qualitative aspects of the data sensitive to conformational changes. Indications are obtained from this study to efficiently extend the theory to higher order in the mode-coupling expansion. These results demonstrate the promise of the mode-coupling approach, where the local dynamics of proteins is described in terms of rotational diffusion of a fluctuating quasi-rigid structure, to analyze nmr spin-lattice relaxation behavior.

Antimycobacterial activity of new ortho-, meta- and para-toluidine derivatives.

Novel toluidine derivatives are described. Some of them showed an interesting in vitro activity against Mycobacterium tuberculosis, M. smegmatis, M. marinum, M. gordonae, and M. avium. Some of them were more active than Streptomycin and Isoniazid, which were used as controls, against M. avium and M. gordonae. In particular, we confirm the good activity of biphenyl derivatives.

Bactericidal activities of the pyrrole derivative BM212 against multidrug-resistant and intramacrophagic Mycobacterium tuberculosis strains.

The pyrrole derivative BM212 [1, 5-diaryl-2-methyl-3-(4-methylpiperazin-1-yl)methyl-pyrrole] was shown to possess strong inhibitory activity against both Mycobacterium tuberculosis and some nontuberculosis mycobacteria. BM212 was inhibitory to drug-resistant mycobacteria and also exerted bactericidal activity against intracellular bacilli residing in the U937 human histiocytic lymphoma cell line.

Synthesis and microbiological evaluations of (N-heteroaryl) arylmethanamines and their Schiff bases.

The synthesis as well as the antimicrobial and antiviral activities of new (N-heteroaryl)arylmethanamines and their Schiff bases are reported. None of the tested compounds shown activity against Herpes simplex virus type 2 and against Gram positive and Gram negative bacteria. Weak or moderate activity on poliovirus Sabin type 1, on reverse transcriptase and against Cryptococcus neoformans was shown by some of the tested compounds. Viceversa several synthesized compounds exhibited a moderate or good activity against strains of Candida albicans, while only some of the tested compounds were found moderately active against strains of Candida sp. Instead numerous new compounds 3 or 4 were active as control against isolates of plant pathogenic fungi. The obtained results are discussed on the basis of structure-activity relationships.

Antifungal agents, Part 11. Biphenyl analogues of naftifine: synthesis and antifungal activities.

A series of naftifine analogues having the biphenyl instead of the naphthyl moiety have been synthesized in a search devoted to study bioanalogues of clinically efficacious antifungal agents. The new derivatives were tested against Candida albicans by the direct contact method. They were also assayed against Gram-positive and Gram-negative bacteria and against some isolates of plant pathogenic fungi. Derivatives 8a, 8c, and 9a were found to be active against Candida albicans, derivative 5a was active against E. coli, a very resistant species to antimycotic agents, and derivatives 8a and 8b inhibited the plant pathogenic Rhizoctonia solani.

Research on antibacterial and antifungal agents. XII--Synthesis and antimicrobial activity of some Mannich bases of diarylpyrroles.

The synthesis and antimicrobial activity of some Mannich bases of diarylpyrroles are reported. The obtained data show that activity is closely connected to molecular basicity. Results are discussed on the basis of structure activity relationships.

Study of the Mannich reaction: beta-amino-methylation of N-aryl and N-azaheteroaryl-substituted 2,5-dimethylpyrroles, compounds with potential biological activity.

Owing to the increasing need of drugs for the treatment of a variety of fungal and bacterial opportunistic infections, a study has been started with the aim of synthesizing structures amenable to a number of easily-to-perform structural modifications in order to meet the requirement of bypassing resistance phenomena. This paper reports on the synthesis of several N-(alpha-azaheteroaryl)-substituted 2,5-dimethyl-pyrroles bearing in one beta-position (or in both beta-positions) aminomethyl groups, introduced via a Mannich reaction. Electronic and steric effects by the N-(azaheteroaryl) substituents and the 2- and 5-methyl groups on the course of the Mannich reaction are discussed along with the results of in vitro tests against many Candida species, some bacteria, and several pathogenic plant fungi.

A study on retinal photoisomerization catalyzed by a protein from the honeybee visual system.

The photoisomerization of all-trans retinal catalyzed by an isomerase purified from the honeybee retina is stereospecifically directed toward the formation of 11-cis retinal, the isomer required for rhodopsin regeneration. A model of the enzymatic reactions was developed, which fits the experimental data. In a particular experiment where irradiation was performed with a LASER light, the rate constants of the photoisomerization of all-trans retinal were dependent on the light intensity and were therefore greatly enhanced.

Impairment of saccadic eye movements by scopolamine treatment.

The effects of Scopolamine on the dynamics of saccadic eye movements, stimulated over a random time interval, have been investigated in humans. A 0.5-mg dose of the drug (intramuscular injection) had various influences on the basic saccadic parameters. For all subjects duration increased and peak velocity decreased, while for 50% of the subjects saccades became hypometric and latency increased. Standard deviation increased consistently too. Moreover, the Scopolamine treatment affected postsaccadic fixation; at the end of many saccades, the eye drifted considerably, but stability was recovered after a few seconds.

Chemotherapeutic agents with an imidazole moiety. III. Synthesis and microbiological activity of new 1,4-diarylimidazole and 1,4-pyrrolimidazolphenylene derivatives.

New 1,4-diarylimidazole and 1,4-pyrrolimidazol-phenylene derivatives were prepared in attempt to deepen S.A.R. study on chemotherapeutic agents with an imidazole moiety. Antimicrobial data in comparison with antifungal antibiotic pyrrolnitrin showed that all tested compounds are practically inactive against blastomycetes but some derivatives exhibited selective activity against strains of gram-negative bacteria. The results obtained are discussed on the basis of structure-activity relationships.

Research on antibacterial and antifungal agents. IX--Synthesis and microbiological activity of new N-arylpyrroles.

The synthesis and antiblastomycete activity of new N-arylpyrrole derivatives are reported. Antimicrobial data in comparison with those obtained with pyrrolnitrin and miconazole showed that all tested compounds possess weak or poor activity. The obtained results are discussed on the basis of structure-activity relationships.