Search

Background: The heightened risk of dementia resulting from multiple comorbid conditions calls for innovative strategies. Engaging in physical and cognitive activities emerges as a protective measure against cognitive decline. This protocol aims to discuss a multidomain intervention targeting individuals with dementias secondary to cerebrovascular or other medical diseases, emphasizing an often underrepresented demographic. Methods: This study primary objectives are: a) to identify patients affected by Neurocognitive disorder due to vascular disease or multiple etiologies (screening and diagnostic phase) and b) to evaluate the effectiveness of distinct rehabilitation protocols (intervention phase): motor training alone, paper-based cognitive rehabilitation combined with motor training, digital-based cognitive rehabilitation coupled with motor training. Discussion: Identifying cognitive impairment beyond rigid neurological contexts can facilitate timely and targeted interventions. This protocol strives to address the complex interplay of cognitive decline and comorbidities through a multidimensional approach, providing insights that can shape future interventions and enhancing overall well-being in this vulnerable population. Trial registration: The study has been registered on July 13, 2023 with the ClinicalTrials.gov NCT05954741 registration number (https://classic.clinicaltrials.gov/ct2/show/NCT05954741). [ABSTRACT FROM AUTHOR]

Temporal asymmetry is a peculiar aspect of heart period (HP) variability (HPV). HPV asymmetry (HPVA) is reduced with aging and pathology, but its origin is not fully elucidated. Given the impact of respiration on HPV resulting in the respiratory sinus arrhythmia (RSA) and the asymmetric shape of the respiratory pattern, a possible link between HPVA and RSA might be expected. In this study we tested the hypothesis that HPVA is significantly associated with RSA and asymmetry of the respiratory rhythm. We studied 42 middle-aged healthy (H) subjects, and 56 chronic heart failure (CHF) patients of whom 26 assigned to the New York Heart Association (NYHA) class II (CHF-II) and 30 to NYHA class III (CHF-III). Electrocardiogram and lung volume were monitored for 8 minutes during spontaneous breathing (SB) and controlled breathing (CB) at 15 breaths/minute. The ratio of inspiratory (INSP) to expiratory (EXP) phases, namely the I/E ratio, and RSA were calculated. HPVA was estimated as the percentage of negative HP variations, traditionally measured via the Porta's index (PI). Departures of PI from 50% indicated HPVA and its significance was tested via surrogate data. We found that RSA increased during CB and I/E ratio was smaller than 1 in all groups and experimental conditions. In H subjects the PI was about 50% during SB and it increased significantly during CB. In both CHF-II and CHF-III groups the PI was about 50% during SB and remained unmodified during CB. The PI was uncorrelated with RSA and I/E ratio regardless of the experimental condition and group. Pooling together data of different experimental conditions did not affect conclusions. Therefore, we conclude that the HPVA cannot be explained by RSA and/or I/E ratio, thus representing a peculiar feature of the cardiac control that can be aroused in middle-aged H individuals via CB.

BACKGROUND:The association among psychological, neuropsychological dysfunctions and functional/clinical variables in Chronic Heart Failure (CHF) has been extensively addressed in literature. However, only a few studies investigated those associations in the older population. PURPOSE:To evaluate the psychological/neuropsychological profile of older CHF patients, to explore the interrelation with clinical/functional variables and to identify potential independent predictors of patients' functional status. METHODS:This study was conducted with a multi-center observational design. The following assessments were performed: anxiety (Hospital Anxiety and Depression Scale, HADS), depression (Geriatric Depression Scale, GDS), cognitive impairment (Addenbrooke's Cognitive Examination Revised, ACE-R), executive functions (Frontal Assessment Battery, FAB), constructive abilities (Clock Drawing Test, CDT), psychomotor speed and alternated attention (Trail Making Test, TMT-A/B), functional status (6-minute walking test, 6MWT) and clinical variables (New York Heart Association, NYHA; Brain Natriuretic Peptide, BNP; left ventricular ejection fraction, LVEF; left ventricular end diastolic diameter, LVEDD; left ventricular end diastolic volume, LVEDV; tricuspid annular plane systolic excursion, TAPSE). RESULTS:100 CHF patients (mean age: 74.9±7.1 years; mean LVEF: 36.1±13.4) were included in the study. Anxious and depressive symptoms were observed in 16% and 24,5% of patients, respectively. Age was related to TMT-A and CDT (r = 0.49, p

BackgroundThis retrospective study had two main aims: (1) to document possible correlations between plasma Amino Acids (AAs) and circulating Albumin (Alb) and Haemoglobin (Hb); and (2) to identify which AAs were predictors of Alb and Hb.MethodsThe study considered 125 stroke subjects (ST) (61.6% males; 65.6 +/- 14.9 years) who met the eligibility criteria (absence of co morbidities associated with altered plasma AAs and presence of plasma AAs determined after overnight fasting). Fifteen matched healthy subjects with measured plasma AAs served as controls.ResultsThe best correlations of Alb were with tryptophan (Trp) and histidine (His) (r = + 0.53; p < 0.0001), and those of Hb were with histidine (r = +0.47) and Essential AAs (r = +0.47) (both pConclusionsThe study shows that the majority of plasma AAs were positively correlated with Alb and Hb. The best predictors of circulating Alb and Hb were the levels of tryptophan and glutamine, respectively.

INTRODUCTION:Chronic obstructive pulmonary disease (COPD) is a complex multi-component disorder characterized by progressive irreversible respiratory symptoms and extrapulmonary comorbidities, including anxiety-depression and mild cognitive impairment (MCI). However, the prevalence of these impairments is still uncertain, due to non-optimal screening methods. This observational cross-sectional multicentre study aimed to evaluate the prevalence of anxiety-depressive symptoms and MCI in COPD patients, identify the most appropriate cognitive tests to screen MCI, and investigate specific cognitive deficits in these patients and possible predictive factors. MATERIALS AND METHODS:Sixty-five stable COPD inpatients (n = 65, aged 69.9±7.6 years, mainly stage III-IV GOLD) underwent the following assessments: Hospital Anxiety and Depression Scale (HADS), Geriatric Depression Scale (GDS) or Beck Depression Inventory-II (BDI-II), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and a complete neuropsychological battery (ENB-2) including different cognitive domains (attention, memory, executive functions, and perceptive and praxis abilities). RESULTS:Moderate-severe anxiety was present in 18.5% of patients and depressive symptoms in 30.7%. The prevalence of MCI varied according to the test: 6.2% (MMSE), 18.5% (MoCA) and 50.8% (ENB-2). In ENB-2, patients performed significantly worse compared to Italian normative data on digit span (5.11±0.9 vs. 5.52±1.0, p = 0.0004), trail making test-B (TMT-B) (176.31±99.5 vs. 135.93±58.0, p = 0.004), overlapping pictures (26.03±8.9 vs. 28.75±8.2, p = 0.018) and copy drawing (1.370.6 vs. 1.61±0.5, p = 0.002). At logistic regression analysis, only COPD severity (p = 0.012, odds ratio, OR, 4.4 [95% CI: 1.4-14.0]) and anxiety symptoms (p = 0.026, OR 4.6 [1.2-17.7]) were significant and independent predictors of the deficit in copy drawing, which assesses visuospatial and praxis skills. CONCLUSION:Given the prevalence of neuropsychological impairments in COPD patients, the routine adoption in rehabilitation of screening tools for mood and cognitive function, including digit span, TMT-B and copy drawing, may be useful to detect psychosocial comorbidities and personalize the rehabilitative program.

Spines, or modified hairs, have evolved multiple times in mammals, particularly in rodents. In this study, we investigated the evolution of spines in six rodent families. We first measured and compared the morphology and physical properties of hairs between paired spiny and non-spiny sister lineages. We found two distinct hair morphologies had evolved repeatedly in spiny rodents: hairs with a grooved cross-section and a second near cylindrical form. Compared to the ancestral elliptical-shaped hairs, spiny hairs had higher tension and stiffness, and overall, hairs with similar morphology had similar functional properties. To examine the genetic basis of this convergent evolution, we tested whether a single amino acid change (V370A) in the Ectodysplasin A receptor (Edar) gene is associated with spiny hair, as this substitution causes thicker and straighter hair in East Asian human populations. We found that most mammals have the common amino acid valine at position 370, but two species, the kangaroo rat (non-spiny) and spiny pocket mouse (spiny), have an isoleucine. Importantly, none of the variants we identified are associated with differences in rodent hair morphology. Thus, the specific Edar mutation associated with variation in human hair does not seem to play a role in modifying hairs in wild rodents, suggesting that different mutations in Edar and/or other genes are responsible for variation in the spiny hair phenotypes we observed within rodents.

In the last decade robotic devices have been applied in rehabilitation to overcome walking disability in neurologic diseases with promising results. Robot assisted gait training (RAGT) using the Lokomat seems not only to improve gait parameters but also the perception of well-being. Data on the psychosocial patient-robot impact are limited, in particular in the real-world of RAGT, in the rehabilitation setting. During rehabilitation training, the Lokomat can be considered an "assistive device for movement". This allowed the use of the Psychosocial Impact of Assistive Device Scale- PIADS to describe patient interaction with the Lokomat. The primary aim of this pilot study was to evaluate the psychosocial impact of the Lokomat in an in-patient rehabilitation setting using the PIADS; secondary aims were to assess whether the psychosocial impact of RAGT is different between pathological sub-groups and if the Lokomat influenced functional variables (Functional Independence Measure scale-FIM and parameters provided by the Lokomat itself). Thirty-nine consecutive patients (69% males, 54.0±18.0 years) eligible for Lokomat training, with etiologically heterogeneous walking disabilities (Parkinson's Disease, n = 10; Spinal Cord Injury, n = 21; Ictus Event, n = 8) were enrolled. Patients were assessed with the FIM before and after rehabilitation with Lokomat, and the PIADS was administered after the rehabilitative period with Lokomat. Overall the PIADS score was positive (35.8±21.6), as well as the three sub-scales, pertaining to "ability", "adaptability" and "self-esteem" (17.2±10.4, 8.9±5.5 and 10.1±6.6 respectively) with no between-group differences. All patients significantly improved in gait measure and motor FIM scale (difference after-before treatment values: 11.7±9.8 and 11.2±10.3 respectively), increased treadmill speed (0.4 ± 0.2m/s), reduced body weight support (-14.0±9.5%) and guidance force (-13.1 ± 10.7%). This pilot study indicates that Lokomat, in a real-world in-patient setting, may have a generalised approval, independent of disease, underlining the importance of the psycho-social framework for patients training with assistive robotic-devices.

BACKGROUND:to date, there are no medical or surgical treatments for progressive supranuclear palsy (PSP). It is possible to speculate that patients with PSP could benefit from rehabilitative treatments designed for Parkinson's disease, including the use of robot-assisted walking training. OBJECTIVE:to evaluate whether the use of the robotic device Lokomat® is superior in PSP patients to the use of treadmill with visual cues and auditory feedbacks (treadmill-plus) in the context of an aerobic, multidisciplinary, intensive, motor-cognitive and goal-based rehabilitation treatment (MIRT) conceived for Parkinsonian patients. METHODS:we enrolled twenty-four PSP patients. Twelve subjects underwent a 4-week MIRT exploiting the use of the treadmill-plus (MIRT group). Twelve subjects underwent the same treatment, but replacing the treadmill-plus with Lokomat® (MIRT-Lokomat group). Subjects were evaluated with clinical and functional scales at admission and discharge. The primary outcomes were the total PSP Rating Scale (PSPRS) score and its "limb" and "gait" sub-scores. Secondary outcomes were Berg Balance Scale (BBS), Six Minutes Walking test (6MWT) and the number of falls. RESULTS:total PSPRS, PSPRS-gait sub-score, BBS, 6MWT and number of falls improved significantly in both groups (p ≤ 0.003 all, except 6MWT, p = 0.032 and p = 0.018 in MIRT-Lokomat and MIRT group respectively). The PSPRS-limb sub-score improved significantly only in the MIRT group (p = 0.002). A significant difference between groups was observed only for total PSPRS, indicating a slightly better improvement for patients in the MIRT group (p = 0.047). No differences between groups were revealed for the other outcomes, indicating that the effect of rehabilitation was similar in both groups. CONCLUSIONS:Lokomat® training, in comparison with treadmill-plus training, does not provide further benefits in PSP patients undergoing MIRT. Our findings suggest the usefulness of an aerobic, multidisciplinary, intensive, motor-cognitive and goal-based approach for the rehabilitation of patients suffering from such a complex disease as PSP. TRIAL REGISTRATION:This trial was registered on ClinicalTrials.gov, NCT02109393.

Pleistocene climatic oscillations favoured the expansion of grassland ecosystems and open vegetation landscapes throughout the Neotropics, and influenced the evolutionary history of species adapted to such environments. In this study, we sampled populations of the rodent Oxymycterus nasutus endemic to open areas in the Pampas and Atlantic Forest biomes to assess the tempo and mode of population divergence using an integrative approach, including coalescence theory, ecological niche models, and morphometry. Our results indicated that these O. nasutus populations exhibited high levels of genetic structure. Six major mtDNA clades were found, structuring these biomes into distinct groups. Estimates of their divergence times was indicated to be 0.571 myr. The high degree of genetic structure is reflected in the analyses of geometric morphometric; skull differences between lineages in the two ecoregions were detected. During the last glacial maximum, there was a strong increase in suitable abiotic conditions for O. nasutus. Distinct molecular markers revealed a population expansion over time, with a possible demographic retraction during the post-glacial period. Considering that all clades coalesce with the last interglacial maximum, our results indicated that reduction in suitable conditions during this period may have resulted in a possible vicariance associated with refuge isolation.

Sleep-related problems are known risk factors for road accidents. However, very few studies have investigated the role played by insomnia and its components, and no data are available for a population of occupational drivers at risk, such as the truck driver category.To measure the prevalence and impact of insomnia on motor vehicle accidents (MVAs) and near-miss accidents (NMAs) in 949 truck drivers.Cross-sectional survey.Insomnia affected 27.5% of the sample. Compared to other drivers, in the 3 years prior to the study, truck drivers with insomnia had reported a significantly higher number of MVAs; they had also reported a greater number of NMAs in the previous 6 months. After correction for the presence of obstructive sleep apnea, excessive daytime sleepiness, short sleep duration, and other concurrent diseases, insomniac truck drivers had an almost two-fold risk of driving accidents (OR: 1.82, CI 95%:1.33-2.49) and a more than three-fold increased risk of near-miss accidents (OR: 3.35, CI95%:2.06-5.45) compared to non-insomniac drivers.Insomnia emerged as an independent risk factor for MVAs and NMAs. We strongly advise screening commercial drivers for signs and symptoms of insomnia in order to improve health and safety on the road.

Understanding the spatial distribution of species sheds light on the group's biogeographical history, offers clues to the drivers of diversity, and helps to guide conservation strategies. Here, we compile geographic range information for South America's diverse rodents, whose 14 families comprise ~50% of the continent's mammalian species. The South American rodent fauna is dominated by independent and temporally staggered radiations of caviomorph and sigmodontine groups. We mapped species richness and turnover of all rodents and the principal clades to identify the main predictors of diversity patterns. Species richness was highest in the Andes, with a secondary hotspot in Atlantic Forest and some regions of considerable richness in Amazonia. Differences in richness were evident between the caviomorphs and sigmodontines, the former showing the greatest richness in tropical forests whereas the latter show-and largely determine-the all-rodent pattern. Elevation was the main predictor of sigmodontine richness, whereas temperature was the principal variable correlated with richness of caviomorphs. Across clades, species turnover was highest along the Andes and was best explained by elevational relief. In South America, the effects of the familiar latitudinal gradient in species richness are mixed with a strong longitudinal effect, triggered by the importance of elevation and the position of the Andes. Both latitudinal and elevational effects help explain the complicated distribution of rodent diversity across the continent. The continent's restricted-range species-those seemingly most vulnerable to localized disturbance-are mostly distributed along the Andes and in Atlantic Forest, with the greatest concentration in Ecuador. Both the Andes and Atlantic Forest are known hotspots for other faunal and floral components. Contrasting patterns of the older caviomorph and younger sigmodontine radiations underscore the interplay of both historical and ecological factors in determining present-day diversity patterns.

Verticalization was reported to improve the level of arousal and awareness in patients with severe acquired brain injury (ABI) and to be safe in ICU. We evaluated the effectiveness of a very early stepping verticalization protocol on their functional and neurological outcome.Consecutive patients with Vegetative State or Minimally Conscious State were enrolled in ICU on the third day after an ABI. They were randomized to undergo conventional physiotherapy alone or associated to fifteen 30-minute sessions of verticalization, using a tilt table with robotic stepping device. Once stabilized, patients were transferred to our Neurorehabilitation unit for an individualized treatment. Outcome measures (Glasgow Coma Scale, Coma Recovery Scale revised -CRSr-, Disability Rating Scale-DRS- and Levels of Cognitive Functioning) were assessed on the third day from the injury (T0), at ICU discharge (T1) and at Rehab discharge (T2). Between- and within-group comparisons were performed by the Mann-Whitney U test and Wilcoxon signed-rank test, respectively.Of the 40 patients enrolled, 31 completed the study without adverse events (15 in the verticalization group and 16 in the conventional physiotherapy). Early verticalization started 12.4±7.3 (mean±SD) days after ABI. The length of stay in ICU was longer for the verticalization group (38.8 ± 15.7 vs 25.1 ± 11.2 days, p = 0.01), while the total length of stay (ICU+Neurorehabilitation) was not significantly different (153.2 ± 59.6 vs 134.0 ± 61.0 days, p = 0.41). All outcome measures significantly improved in both groups after the overall period (T2 vs T0, p

Different host genetic variants may be related to the virulence and transmissibility of pandemic Influenza A(H1N1)pdm09, influencing events such as binding of the virus to the entry receptor on the cell of infected individuals and the host immune response. In the present study, two genetic variants of the ST3GAL1 gene, which encodes the Siaα2-3Galβ1- receptor to which influenza A(H1N1)pdm09 virus binds for entry into the host cell, were investigated in an admixed Brazilian population. First, the six exons encoding the ST3GAL1 gene were sequenced in 68 patients infected with strain A(H1N1)pdm09. In a second phase of the study, the rs113350588 and rs1048479 polymorphisms identified in this sample were genotyped in a sample of 356 subjects from the northern and northeastern regions of Brazil with a diagnosis of pandemic influenza. Functional analysis of the polymorphisms was performed in silico and the influence of these variants on the severity of infection was evaluated. The results suggest that rs113350588 and rs1048479 may alter the function of ST3GAL1 either directly through splicing regulation alteration and/or indirectly through LD with SNP with regulatory function. In the study the rs113350588 and rs1048479 polymorphisms were in linkage disequilibrium in the population studied (D' = 0.65). The GC haplotype was associated with an increased risk of death in subjects with influenza (OR = 4.632, 95% CI = 2.10;1.21). The AT haplotype was associated with an increased risk of severe disease and death (OR = 1.993, 95% CI = 1.09;3.61 and OR 4.476, 95% CI = 2.37;8.44, respectively). This study demonstrated for the first time the association of ST3GAL1 gene haplotypes on the risk of more severe disease and death in patients infected with Influenza A(H1N1)pdm09 virus.

Muscular weakness is a frequent cause of instability that contributes to falls in Parkinson's disease (PD). Isokinetic dynamometry is a method of muscle assessment useful to measure the muscular strength giving a quantification of the weakness, but only few studies about isokinetic assessment were performed in PD. The aims of the study were to evaluate the muscle strength in PD and to investigate the differences in patients affected on the right and left side.Knee flexor and extensor muscles strength was assessed using an isokinetic dynamometer in 25 patients in stage 3 H&Y and in 15 healthy controls. Subjects were tested in both legs at three fixed angular velocities: 90°/s, 120°/s, 180°/s.Considering the whole population of Parkinsonians, no difference in strength was observed with respect to controls. Considering the side, patients affected on the right side showed a clear tendency to be weaker than patients affected on the left side and controls.PD patients affected on the right side, but not those affected on the left side, had a reduction in muscle strength as compared to controls. We postulate a central origin deficit in muscle strength in PD. It is known that dopamine transporter binding is more severely reduced in the left posterior putamen and our results suggest that the control of the muscle strength in PD is linked to the right-left hemispheric asymmetry of the functional organization of basal ganglia and with their connections to cortical motor and pre-motor areas.

For conservation purposes, it is important to take into account the suitability of a species to particular habitats; this information may predict the long-term survival of a species. In this sense, morphological measures of developmental stress, such as fluctuating asymmetry, can be proxies for an individual's performance in different regions. In this study, we conducted tests to determine whether areas with different levels of suitability for a species (generated by ecological niche models) were congruent with morphological markers that reflect environmental stress and morphological variance. We generated a Maxent niche model and compared the suitability assessments of several areas with the skull morphology data (fluctuating asymmetry and morphological disparity) of populations of the Atlantic forest endemic to Brazil rodent Akodon cursor. Our analyses showed a significant negative relationship between suitability levels and fluctuating asymmetry levels, which indicates that in less suitable areas, the individuals experience numerous disturbances during skull ontogeny. We have not found an association between morphological variance and environmental suitability. As expected, these results suggest that in environments with a lower suitability, developmental stress is increased. Such information is helpful in the understanding of the species evolution and in the selection of priority areas for the conservation of species.

Retinal arterial narrowing is associated with higher office blood pressure (BP) and ambulatory blood pressure monitoring, and increased incidence of cardiovascular disease, but it is still unknown if the vessel caliber is associated with BP measured at the time of retinography acquisition.Retinal arteriolar and venular calibers were measured by the microdensitometric method in 448 patients with hypertension. Participants underwent 24-hours ambulatory blood pressure (24-h ABP) monitoring simultaneously with the retinography acquisition. Association between arteriolar and venular calibers with increase of 10 mmHg in the mean 24-hours, daily, and nightly BP, and with BP measured at the time of retinography, was evaluated by ANOVA and multivariate analyses.Mean 24-hours, daytime and nighttime systolic and diastolic BP were inversely associated with the arteriolar caliber, but not with the venular caliber. Arteriolar caliber decreased -0.8 (95% CI -1.4 to -0.2) μm per 10-mmHg increase in 24-hours mean systolic BP, adjusted for age, gender, fellow vessel, and duration of hypertension (P = 0.01). The corresponding decreasing in arteriolar caliber by 10 mmHg of increasing in mean diastolic BP was -1.1 μm (-2.0 to -0.2, P = 0.02). The decrease of arteriolar caliber by the same increasing of BP measured at the time of retinography was lower and not statistically significant, particularly for mean diastolic BP and outer arterioles calibers: -1.0 (-1.8 to -0.2) μm in the daytime BP average versus -0.3 (-0.9 to 0.3) at the moment of retinography acquisition.These findings suggest that the caliber of arteriolar retinal vessels in patients with uncontrolled hypertension are not significantly influenced by blood pressure measured at the time of retinography acquisition.

The increasing number of casting shows and talent contests in the media over the past years suggests a public interest in rating the quality of vocal performances. In many of these formats, laymen alongside music experts act as judges. Whereas experts' judgments are considered objective and reliable when it comes to evaluating singing voice, little is known about laymen's ability to evaluate peers. On the one hand, layman listeners-who by definition did not have any formal training or regular musical practice-are known to have internalized the musical rules on which singing accuracy is based. On the other hand, layman listeners' judgment of their own vocal skills is highly inaccurate. Also, when compared with that of music experts, their level of competence in pitch perception has proven limited. The present study investigates laypersons' ability to objectively evaluate melodies performed by untrained singers. For this purpose, laymen listeners were asked to judge sung melodies. The results were compared with those of music experts who had performed the same task in a previous study. Interestingly, the findings show a high objectivity and reliability in layman listeners. Whereas both the laymen's and experts' definition of pitch accuracy overlap, differences regarding the musical criteria employed in the rating task were evident. The findings suggest that the effect of expertise is circumscribed and limited and supports the view that laypersons make trustworthy judges when evaluating the pitch accuracy of untrained singers.

INTRODUCTION: Information on benefits and risks of drugs is a key element affecting doctors' prescribing decisions. Outreach visits promoting independent information have proved moderately effective in changing prescribing behaviours. OBJECTIVES: Testing the short and long-term effectiveness on general practitioners' prescribing of small groups meetings led by pharmacists. METHODS: Two cluster open randomised controlled trials (RCTs) were carried out in a large scale NHS setting. Ad hoc prepared evidence based material were used considering a therapeutic area approach--TEA, with information materials on osteoporosis or prostatic hyperplasia--and a single drug oriented approach--SIDRO, with information materials on me-too drugs of 2 different classes: barnidipine or prulifloxacin. In each study, all 115 Primary Care Groups in a Northern Italy area (2.2 million inhabitants, 1737 general practitioners) were randomised to educational small groups meetings, in which available evidence was provided together with drug utilization data and clinical scenarios. Main outcomes were changes in the six-months prescription of targeted drugs. Longer term results (24 and 48 months) were also evaluated. RESULTS: In the TEA trial, one of the four primary outcomes showed a reduction (prescription of alfuzosin compared to tamsulosin and terazosin in benign prostatic hyperplasia: prescribing ratio -8.5%, p = 0.03). Another primary outcome (prescription of risedronate) showed a reduction at 24 and 48 months (-7.6%, p = 0.02; and -9,8%, p = 0.03), but not at six months (-5.1%, p = 0.36). In the SIDRO trial both primary outcomes showed a statistically significant reduction (prescription of barnidipine -9.8%, p = 0.02; prescription of prulifloxacin -11.1%, p = 0.04), which persisted or increased over time. INTERPRETATION: These two cluster RCTs showed the large scale feasibility of a complex educational program in a NHS setting, and its potentially relevant long-term impact on prescribing habits, in particular when focusing on a single drug. National Health systems should invest in independent drug information programs. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN05866587.

Increased mobilization of circulating endothelial progenitor cells may represent a new biological hallmark of myeloproliferative neoplasms. We measured circulating endothelial colony forming cells (ECFCs) in 106 patients with primary myelofibrosis, fibrotic stage, 49 with prefibrotic myelofibrosis, 59 with essential thrombocythemia or polycythemia vera, and 43 normal controls. Levels of ECFC frequency for patient's characteristics were estimated by using logistic regression in univariate and multivariate setting. The sensitivity, specificity, likelihood ratios, and positive predictive value of increased ECFC frequency were calculated for the significantly associated characteristics. Increased frequency of ECFCs resulted independently associated with history of splanchnic vein thrombosis (adjusted odds ratio = 6.61, 95% CI = 2.54-17.16), and a summary measure of non-active disease, i.e. hemoglobin of 13.8 g/dL or lower, white blood cells count of 7.8×10(9)/L or lower, and platelet count of 400×10(9)/L or lower (adjusted odds ratio = 4.43, 95% CI = 1.45-13.49) Thirteen patients with splanchnic vein thrombosis non associated with myeloproliferative neoplasms were recruited as controls. We excluded a causal role of splanchnic vein thrombosis in ECFCs increase, since no control had elevated ECFCs. We concluded that increased frequency of ECFCs represents the biological hallmark of a non-active myeloproliferative neoplasm with high risk of splanchnic vein thrombosis. The recognition of this disease category copes with the phenotypic mimicry of myeloproliferative neoplasms. Due to inherent performance limitations of ECFCs assay, there is an urgent need to arrive to an acceptable standardization of ECFC assessment.

When we perceive a visual object, we implicitly or explicitly associate it with an object category we know. Recent research has shown that the visual system can use local, informative image fragments of a given object, rather than the whole object, to classify it into a familiar category. We have previously reported, using human psychophysical studies, that when subjects learn new object categories using whole objects, they incidentally learn informative fragments, even when not required to do so. However, the neuronal mechanisms by which we acquire and use informative fragments, as well as category knowledge itself, have remained unclear. Here we describe the methods by which we adapted the relevant human psychophysical methods to awake, behaving monkeys and replicated key previous psychophysical results. This establishes awake, behaving monkeys as a useful system for future neurophysiological studies not only of informative fragments in particular, but also of object categorization and category learning in general.

Introduction: Information on benefits and risks of drugs is a key element affecting doctors’ prescribing decisions. Outreach visits promoting independent information have proved moderately effective in changing prescribing behaviours. Objectives: Testing the short and long-term effectiveness on general practitioners’ prescribing of small groups meetings led by pharmacists. Methods: Two cluster open randomised controlled trials (RCTs) were carried out in a large scale NHS setting. Ad hoc prepared evidence based material were used considering a therapeutic area approach - TEA, with information materials on osteoporosis or prostatic hyperplasia - and a single drug oriented approach - SIDRO, with information materials on me-too drugs of 2 different classes: barnidipine or prulifloxacin. In each study, all 115 Primary Care Groups in a Northern Italy area (2.2 million inhabitants, 1737 general practitioners) were randomised to educational small groups meetings, in which available evidence was provided together with drug utilization data and clinical scenarios. Main outcomes were changes in the six-months prescription of targeted drugs. Longer term results (24 and 48 months) were also evaluated. Results: In the TEA trial, one of the four primary outcomes showed a reduction (prescription of alfuzosin compared to tamsulosin and terazosin in benign prostatic hyperplasia: prescribing ratio −8.5%, p = 0.03). Another primary outcome (prescription of risedronate) showed a reduction at 24 and 48 months (−7.6%, p = 0.02; and −9,8%, p = 0.03), but not at six months (−5.1%, p = 0.36). In the SIDRO trial both primary outcomes showed a statistically significant reduction (prescription of barnidipine −9.8%, p = 0.02; prescription of prulifloxacin −11.1%, p = 0.04), which persisted or increased over time. Interpretation: These two cluster RCTs showed the large scale feasibility of a complex educational program in a NHS setting, and its potentially relevant long-term impact on prescribing habits, in particular when focusing on a single drug. National Health systems should invest in independent drug information programs. Trial Registration: Controlled-Trials.com [ABSTRACT FROM AUTHOR]