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Objective: To analyze the effects of neuromuscular electrical stimulation of the femoral quadriceps associated or not with whey protein supplementation on the electromyographic activity and body mass distribution in volunteers undergoing anterior cruciate ligament reconstruction. Methods: 24 volunteers were randomly divided into three groups: basal control, whey protein in association with neuromuscular electrical stimulation, and neuromuscular electrical stimulation alone. Results: In the postoperative evaluation, during the mini squat, the basal group showed a decrease in the electromyographic activity of the vastus medialis (p = 0.005, eyes open; p = 0.003, eyes closed), vastus lateralis (p = 0.005, eyes open; p = 0.020; eyes closed) and rectus femoris (p = 0.075, eyes open; p = 0.074, eyes closed) and of body mass distribution in the injured limb (p < 0.001, eyes open; p < 0.001, eyes closed), and in the healthy limb (p < 0.001, eyes open; p < 0.001, eyes closed). Conclusion: The early use of neuromuscular electrical stimulation of the quadriceps femoris maintained the electromyographic activity of the vastus medialis and vastus lateralis muscles and prevented asymmetries in body mass distribution 15 days after anterior cruciate ligament reconstruction. Level of Evidence I, High quality randomized trial. RESUMO Objetivo: Analisar os efeitos da estimulação elétrica neuromuscular do quadríceps femoral associado ou não à suplementação com whey protein na atividade eletromiográfica e distribuição de massa corporal em voluntários submetidos à reconstrução do ligamento cruzado anterior. Métodos: 24 voluntários foram divididos em três grupos: controle basal, whey protein associado com estimulação elétrica neuromuscular e estimulação elétrica neuromuscular isolada. Resultados: Na avaliação pós-operatória, durante o miniagachamento, o grupo controle basal demonstrou diminuição da atividade eletromiográfica do vasto medial (p = 0,005, olhos abertos; p = 0,003, olhos fechados), vasto lateral (p = 0,005, olhos abertos; p = 0,020, olhos fechados) e reto femoral (p = 0,075, olhos abertos; p = 0,074, olhos fechados) e da distribuição de massa corporal no membro operado (p < 0,001, olhos abertos; p < 0,001, olhos fechados) e membro lesionado (p < 0,001, olhos abertos; p < 0,001, olhos fechados). Conclusão: O uso precoce de estimulação elétrica neuromuscular do quadríceps femoral, independentemente do uso de whey protein, foi eficaz para manter a atividade eletromiográfica dos músculos vasto medial e vasto lateral, e prevenir assimetrias na distribuição de massa corporal 15 dias após a reconstrução do ligamento cruzado anterior. Nível de Evidência I, Ensaio randomizado de alta qualidade.

Background: In Alzheimer’s disease (AD), the abnormal aggregation of hyperphosphorylated tau leads to synaptic dysfunction and neurodegeneration. Recently developed tau PET imaging tracers are candidate biomarkers for diagnosis and staging of AD. Objective: We aimed to investigate the discriminative ability of 18F-THK5317 and 18F-flortaucipir tracers and brain atrophy at different stages of AD, and their respective associations with cognition. Methods: Two cohorts, each including 29 participants (healthy controls [HC], prodromal AD, and AD dementia patients), underwent 18F-THK5317 or 18F-flortaucipir PET, T1-weighted MRI, and neuropsychological assessment. For each subject, we quantified regional 18F-THK5317 and 18F-flortaucipir uptake within six bilateral and two composite regions of interest. We assessed global brain atrophy for each individual by quantifying the brain volume index, a measure of brain volume-to-cerebrospinal fluid ratio. We then quantified the discriminative ability of regional 18F-THK5317, 18F-flortaucipir, and brain volume index between diagnostic groups, and their associations with cognition in patients. Results: Both 18F-THK5317 and 18F-flortaucipir outperformed global brain atrophy in discriminating between HC and both prodromal AD and AD dementia groups. 18F-THK5317 provided the highest discriminative ability between HC and prodromal AD groups. 18F-flortaucipir performed best at discriminating between prodromal and dementia stages of AD. Across all patients, both tau tracers were predictive of RAVL learning, but only 18F-flortaucipir predicted MMSE. Conclusion: Our results warrant further in vivo head-to-head and antemortem-postmortem evaluations. These validation studies are needed to select tracers with high clinical validity as biomarkers for early diagnosis, prognosis, and disease staging, which will facilitate their incorporation in clinical practice and therapeutic trials.

We investigated whether cerebrovascular disease contributes to neurodegeneration and clinical phenotype in dementia with Lewy bodies (DLB). Regional cortical thickness and subcortical gray matter volumes were estimated from structural magnetic resonance imaging (MRI) in 165 DLB patients. Cortical and subcortical infarcts were recorded and white matter hyperintensities (WMHs) were assessed. Subcortical only infarcts were more frequent (13.3%) than cortical only infarcts (3.1%) or both subcortical and cortical infarcts (2.4%). Infarcts, irrespective of type, were associated with WMHs. A higher WMH volume was associated with thinner orbitofrontal, retrosplenial, and posterior cingulate cortices, smaller thalamus and pallidum, and larger caudate volume. A higher WMH volume was associated with the presence of visual hallucinations and lower global cognitive performance, and tended to be associated with the absence of probable rapid eye movement sleep behavior disorder. Presence of infarcts was associated with the absence of parkinsonism. We conclude that cerebrovascular disease is associated with gray matter neurodegeneration in patients with probable DLB, which may have implications for the multifactorial treatment of probable DLB.

The clavicle is the most frequently fractured bone in humans. General anesthesia with or without Regional Anesthesia (RA) is most frequently used for clavicle surgeries due to its complex innervation.

BACKGROUND: The COVID-19 pandemic forced the implementation of social distancing and circulation restrictions. This affected all aspects of society including health care. In the field of chronic neurological disorders such as Parkinson's disease (PD), teleneurology is employed in scenarios where face-to-face interactions are not possible. A growing number of clinicians and institutions are turning to teleneurology in order to providing medical care. AIMS OF THE ARTICLE: In this manuscript, we present a practical, 'how we do it in real life', example of a teleneurology appointment with a person with PD (PwP). METHODS: We elaborated a step-by-step approach of the main aspects of a consultation with a PwP and provide video illustration. RESULTS: The key aspects of a teleneurology appointment were separated into: (1) In the office, before the appointment; (2) History taking; (3) Examination; and (4) Finishing up. CONCLUSIONS: We discuss the strengths and weaknesses of this approach and provide our experience in overcoming commonly encountered difficulties.

Subjective cognitive decline (SCD) has been proposed as a risk factor for future cognitive decline and dementia. Given the heterogeneity of SCD and the lack of consensus about how to classify this condition, different operationalization approaches still need to be compared. In this study, we used the same sample of individuals to compare different SCD operationalization approaches. We included 399 cognitively healthy individuals from a community-based cohort. SCD was assessed through nine questions about memory and non-memory subjective complaints. We applied four approaches to operationalize SCD: two hypothesis-driven approaches and two data-driven approaches. We characterized the resulting groups from each operationalization approach using multivariate methods on comprehensive demographic, clinical, cognitive, and neuroimaging data. We identified two main phenotypes: an amnestic phenotype characterized by an Alzheimer’s Disease (AD) signature pattern of brain atrophy; and an anomic phenotype, which was mainly related to cerebrovascular pathology. Furthermore, language complaints other than naming helped to identify a subgroup with subclinical cognitive impairment and difficulties in activities of daily living. This subgroup also showed an AD signature pattern of atrophy. The identification of SCD phenotypes, characterized by different syndromic and biomarker profiles, varies depending on the operationalization approach used. In this study we discuss how these findings may be used in clinical practice and research.

ObjectiveIn a multicenter cohort of probable dementia with Lewy bodies (DLB), we tested the hypothesis that β-amyloid and tau biomarker positivity increases with age, which is modified by APOE genotype and sex, and that there are isolated and synergistic associations with the clinical phenotype.MethodsWe included 417 patients with DLB (age 45–93 years, 31% women). Positivity on β-amyloid (A+) and tau (T+) biomarkers was determined by CSF β-amyloid1-42 and phosphorylated tau in the European cohort and by Pittsburgh compound B and AV-1451 PET in the Mayo Clinic cohort. Patients were stratified into 4 groups: A−T−, A+T−, A−T+, and A+T+.ResultsA−T− was the largest group (39%), followed by A+T− (32%), A+T+ (15%), and A−T+ (13%). The percentage of A−T− decreased with age, and A+ and T+ increased with age in both women and men. A+ increased more in APOE ε4 carriers with age than in noncarriers. A+ was the main predictor of lower cognitive performance when considered together with T+. T+ was associated with a lower frequency of parkinsonism and probable REM sleep behavior disorder. There were no significant interactions between A+ and T+ in relation to the clinical phenotype.ConclusionsAlzheimer disease pathologic changes are common in DLB and are associated with the clinical phenotype. β-Amyloid is associated with cognitive impairment, and tau pathology is associated with lower frequency of clinical features of DLB. These findings have important implications for diagnosis, prognosis, and disease monitoring, as well as for clinical trials targeting disease-specific proteins in DLB.Classification of evidenceThis study provides Class II evidence that in patients with probable DLB, β-amyloid is associated with lower cognitive performance and tau pathology is associated with lower frequency of clinical features of DLB.

Objectives This study examined the effects of sacubitril/valsartan on N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels and determined patient characteristics associated with favorable NT-proBNP reduction response. Background NT-proBNP levels reflect cardiac wall stress and predict event risk in patients with acute decompensated heart failure (ADHF). Methods Post-hoc analysis of the TRANSITION (Comparison of Pre- and Post-discharge Initiation of Sacubitril/Valsartan Therapy in HFrEF Patients After an Acute Decompensation Event) study, including stabilized ADHF patients with reduced ejection fraction, randomized to open-label sacubitril/valsartan initiation in-hospital (pre-discharge) versus post-discharge. NT-proBNP was measured at randomization (baseline), discharge, and 4 and 10 weeks post-randomization. A favorable NT-proBNP response was defined as reduction to ≤1,000 pg/ml or >30% from baseline. Results In patients receiving sacubitril/valsartan in-hospital, NT-proBNP was reduced by 28% at discharge, with 46% of patients obtaining favorable NT-proBNP reduction response compared with a 4% reduction and 18% favorable response rate in patients initiated post-discharge (p Conclusions In-hospital initiation of sacubitril/valsartan produced rapid reductions in NT-proBNP, statistically significant at discharge. A favorable NT-proBNP response over time was associated with a better prognosis and predicted by higher starting dose and predisposing clinical profile. (Comparison of Pre- and Post-discharge Initiation of LCZ696 Therapy in HFrEF Patients After an Acute Decompensation Event [TRANSITION]; NCT02661217)

Background The heterogeneity within Alzheimer’s disease (AD) seriously challenges the development of disease-modifying treatments. We investigated volume of the basal forebrain, hippocampus, and precuneus in atrophy subtypes of AD and explored the relevance of subtype stratification in a small clinical trial on encapsulated cell biodelivery (ECB) of nerve growth factor (NGF) to the basal forebrain. Methods Structural MRI data was collected for 90 amyloid-positive patients and 69 amyloid-negative healthy controls at baseline, 6-, 12-, and 24-month follow-up. The effect of the NGF treatment was investigated in 10 biopsy-verified AD patients with structural MRI data at baseline and at 6- or 12-month follow-up. Patients were classified as typical, limbic-predominant, hippocampal-sparing, or minimal atrophy AD, using a validated visual assessment method. Volumetric analyses were performed using a region-of-interest approach. Results All AD subtypes showed reduced basal forebrain volume as compared with the healthy controls. The limbic-predominant subtype showed the fastest basal forebrain atrophy rate, whereas the minimal atrophy subtype did not show any significant volume decline over time. Atrophy rates of the hippocampus and precuneus also differed across subtypes. Our preliminary data from the small NGF cohort suggest that the NGF treatment seemed to slow the rate of atrophy in the precuneus and hippocampus in some hippocampal-sparing AD patients and in one typical AD patient. Conclusions The cholinergic system is differentially affected in distinct atrophy subtypes of AD. Larger studies in the future should confirm that this differential involvement of the cholinergic system may contribute to subtype-specific response to cholinergic treatment. Our preliminary findings suggest that future clinical trials should target specific subtypes of AD, or at least report treatment effects stratified by subtype. Trial registration ClinicalTrials.gov identifier: NCT01163825. Registered 14 July 2010.

Central retinal artery occlusion (CRAO) is a neuro-ophthalmological emergency. There is a finite time window for acute interventions such as revascularization (e.g. intravenous thrombolysis-IVT) and retinal oxygenation (e.g. hyperbaric oxygen therapy-HBOT) therapies. Case 1: A 35-year-old female presented with CRAO in the right eye (OD) confirmed by fluorescein angiography (FA) and optical coherence tomography (OCT). She underwent 4 sessions of HBOT (100% O2 at 2.4 atmosphere absolute for 90 min). Afterwards, visual defect on the nasal field was kept but visual acuity (VA) improved from counting fingers to 1.0. Case 2: A 65-year-old male presented with CRAO in his left eye (OS) with 1.5 h of evolution. Orbital sonography and OCT confirmed the presence of an embolus and he underwent IVT with rTPA (0.9 mg/kg). VA improved from light perception to 0.1. Case 3: A 21-year-old male presented acute visual loss in his OD with 2.5 h of evolution. OCT and retinography identified CRAO. He was submitted to IVT (rTPA-0.9 mg/kg) followed by 12 sessions of HBOT. VA improved from hand motion to 1.0. Our case series depicts the approaches and possible outcomes in acute management of an infrequent, but highly morbid, cerebroretinovascular disorder. Future clinical trials are warranted to tackle current difficulties in CRAO treatment.

Purpose The serotonin transporter (SERT) is a biochemical marker for monoaminergic signaling in brain and has been suggested to be involved inthe pathophysiology of Parkinson’s disease (PD). The aim of this PET study was to examine SERT availability in relevant brain regions in early stages ofnon-depressed PD patients. Methods In a cross-sectional study, 18 PD patients (13 M/5F, 64 ± 7 years, range 46–74 years, disease duration 2.9 ± 2.6 years; UPDRS motor 21.9 ± 5.2) and 20 age- and gender-matched healthy control (HC) subjects (15 M/5F, 61 ± 7 years, range 50–72 years) were included. In a subsequent longitudinal phase, ten of the PD patients (7 M/3F, UPDRS motor 20.6 ± 6.9) underwent a second PET measurement after 18–24 months. After a 3-T MRI acquisition, baseline PET measurements were performed with [11C]MADAM using a high-resolution research tomograph. The non-displaceablebinding potential (BPND) was chosen as the outcome measure and was estimated at voxel level on wavelet-aided parametric images, by using the Logan graphical analysis and the cerebellum as reference region. A molecular template was generated to visualize and define different subdivisions of the raphe nuclei in the brainstem. Subortical and cortical regions of interest were segmented using FreeSurfer. Univariate analyses and multivariate network analyses were performed on the PET data. Results The univariate region-based analysis showed no differences in SERT levels when the PD patients were compared with the HC neither at baseline or after 2 years of follow-up. The multivariate network analysis also showed no differences at baseline. However, prominent changes in integration and segregation measures were observed at follow-up, indicating a disconnection of the cortical and subcortical regions from the three nuclei of the raphe. Conclusion We conclude that the serotoninergic system in PD patients seems to become involved with a network dysregulation as the disease progresses, suggesting a disturbed serotonergic signaling from raphe nuclei to target subcortical and cortical regions.

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (V(T)). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients. OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference. DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries. MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as V(T) of 8 ml kg(−1) or less predicted bodyweight (PBW). A V(T) was deemed ‘default’ if the set V(T) was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation. RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default V(T) was often set, both in women and men; mode V(T) was 500 ml. Median [IQR] V(T) was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg(−1) PBW, P*** < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P*** < 0.001]. In the mediation analysis, patients’ height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default V(T). CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher V(T) than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV. TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

ObjectivesTo investigate whether antemortem atrophy-based subtypes of Alzheimer’s disease (AD) may be differentially susceptible to individual or concomitance of AD and non-AD (co)-pathologies, assessed neuropathologically at postmortem.MethodsWe selected 31 individuals from the AD neuroimaging initiative with: an antemortem magnetic resonance imaging scan evaluating brain atrophy available within two years before death; an antemortem diagnosis of AD dementia or prodromal AD; and postmortem neuropathological confirmation of AD. Antemortem atrophy-based subtypes was modeled as a continuous phenomenon in terms of two recently proposed dimensions: typicality (ranging from limbic-predominant AD to hippocampal-sparing AD subtypes) and severity (ranging from typical AD to minimal atrophy AD subtypes). Postmortem neuropathological evaluation included global and regional outcomes: AD hallmark pathologies of amyloid-beta and tau; non-AD co-pathologies of alpha-synuclein Lewy body and TDP-43; and the overall concomitance across these four (co)-pathologies. Partial correlation and linear regression models were used to assess the association between antemortem atrophy-based subtypes and postmortem neuropathological outcomes.ResultsWe observed significant global and regional associations between antemortem typicality and postmortem (co)-pathologies including tau, alpha-synuclein Lewy bodies and TDP-43. Antemortem typicality demonstrated stronger regional associations with concomitance of multiple postmortem (co)-pathologies in comparison to antemortem severity. Our findings suggest the following susceptibilities of atrophy-based subtypes: limbic-predominant AD towards higher burden of tau and TDP-43 pathologies while hippocampal-sparing AD towards lower burdens; limbic-predominant AD and typical AD towards higher burden of alpha-synuclein Lewy body pathology while hippocampal-sparing AD and minimal-atrophy AD towards lower burdens.DiscussionThrough a direct antemortem-to-postmortem validation, our study highlights the importance of understanding heterogeneity in AD in relation to concomitance of AD and non-AD pathologies. Our findings provide a deeper understanding of both global and regional vulnerabilities of the biological subtypes of AD brain towards (co)-pathologies. Relative involvement of both AD hallmark and non-AD (co)-pathologies will enhance prevailing knowledge of biological heterogeneity in AD and could thus, contribute towards tracking disease progression and designing clinical trials in the future.

INTRODUCTIONDifferent subtypes/patterns have been defined using tau-PET and structural-MRI in Alzheimer’s disease (AD), but the relationship between tau pathology and atrophy remains unclear. Our goals were twofold: (a) investigate the association between baseline tau-PET patterns and longitudinal atrophy in the AD continuum; (b) characterizeheterogeneityas a continuous phenomenon over the conventional notion using discrete subgroups.METHODSIn 366 individuals (amyloid-beta-positive: cognitively normal, prodromal AD, AD dementia; amyloid-beta-negative healthy), we examined the association between tau-PET patterns (operationalized as a continuous phenomenon and a discrete phenomenon) and longitudinal sMRI.RESULTSWe observed a differential association between tau-PET patterns and longitudinal atrophy. Heterogeneity, measured continuously, may offer an alternative characterization, sharing correspondence with the conventional subgrouping.DISCUSSIONSite and the rate of atrophy are modulated differentially by tau-PET patterns in the AD continuum. We postulate thatheterogeneitybe treated as a continuous phenomenon for greater sensitivity over the current/conventional discrete subgrouping.

The aim of the study was to assess the protocols of balance assessment in baropodometer in healthy individuals throu-gh a systematic review of the literature. The search was performed following the PRISMA guidelines. Relevant keywords were used for the search through PubMed/MEDLINE, SciELO and PEDro. The review included publications made up to August 2018, in English, Portuguese or Spanish, studies with human beings and relevance to the theme of baropodometry. Studies with children and individuals with associated disorders were not included. In all articles, information regarding the assessment protocol in baropodometry were screened, extracting positioning data of feet, arms and mouth, eye fixation, data acquisition time, rest time and number of collections.In the initial search a total of 98 articles were found, in the final sample 12 articles were included. Regarding the type of study, six were clinical trials, four were cross-sectional studies, a methodological study and an experimental one. Although results of relevant literature are limited, there is no methodological standardization in the assessment in baropodometry. Objetivo: Avaliar os protocolos de avaliação do equilíbrio em baropodômetro em indivíduos saudáveis por meio de uma revisão sistemática da literatura. Materiais e Métodos: A revisão incluiu publicações realizadas até junho de 2020, nos idiomas inglês, português ou espanhol, estudos com seres humanos, com idade a partir de 18 anos, sem doenças prévias, estudos relevantes sobre baropodometria na avaliação do equilíbrio postural.Resultados: Em todos os artigos foram triadas as informações referentes ao protocolo de avaliação em baropodometria, extraindo-se dados de posicionamento de pés, braços e boca, fixação ocular, tempo de aquisição de dados, tempo de descanso e número de coletas. Na busca inicial foi encontrado um total de 130 artigos, na amostra final 18 artigos foram incluídos.Conclusão: Por meio desta revisão, sugere-se para uma utilização mais efetiva do baropodômetro, protocolos que utilizam orientações para o posicionamento do pé, considerando uma posição confortável e a largura do quadril; manter a boca entreaberta ou fechada para que não haja pegada; mantenha os olhos fixos em um ponto marcado ao nível dos olhos; tempo de coleta entre 30 segundos a 60 segundos, com duas a três repetições e 30 a 60 segundos de descanso entre elas.

The aim of this work is an evaluation of different turbulence models applied in Computational Fluid Dynamics (CFD) techniques in the turbomachinery area, in this case, in an axial turbine stage used in turbopump (TP) application. The tip clearance region was considered in this study because it has a high influence in turbomachinery performance. In this region, due to its geometry and the relative movement between the rotor row and casing, there are losses associated with vortices and secondary flow making the flowfield even more turbulent and complex. Moreover, the flow that leaks in the tip region does not participate in the energy transfer between the fluid and rotor blades, degradating the machine efficiency and performance. In this work, the usual flat tip rotor blade geometry was considered. The modeling of turbulent flow based on Reynolds Averaged Navier-Stokes (RANS) equations predicts the variation of turbine operational characteristics that is sufficient for the present turbomachine and flow analysis. Therefore, the appropriate choice of the turbulence model for the study of a given flow is essential to obtain adequate results using numerical approximations. This comparison become important due to the fact that there is no general turbulence model for all engineering applications that has fluid and flow. The turbomachine considered in the present work, is the first stage of the hydraulic axial turbine used in the Low Pressure Oxidizer Turbopump (LPOTP) of the Space Shuttle Main Engine (SSME), considering the 3.0% tip clearance configuration relative to rotor blade height. The turbulence models evaluated in this work were the SST (Shear Stress Transport), the k-ε Standard and the k-ε RNG. The computational domain was discretized in several control volumes based on unstructured mesh. All the simulations were performed using the commercial software developed by ANSYS, CFX v15.0 (ANSYS). All numerical settings and how the boundary conditions were imposed at different surfaces are explained in the work. The boundary conditions settings follow the same rule used in the test facility and needs some attention during the simulations to vary the Blade-Jet-Speed ratio parameter adequately. The results from numerical simulations, were synthesized and compared with the experimental data published by National Aeronautics and Space Administration (NASA), in which the turbine efficiency and its jet velocity parameter are analyzed for each turbulence model result. The work fluid considered in this work was water, the same fluid used in the NASA test facility.

This study aimed to examine the prevalence rates of poor quality sleep and daytime sleepiness in health professionals and their association with socioeconomic, lifestyle, and anthropometric factors and psychosocial work conditions. This cross-sectional study was performed with health professionals from various public and private hospitals in Rio Verde, Goiás, Brazil. Daytime sleepiness and sleep quality were assessed using the Epworth Sleepiness Scale and the Pittsburgh Sleep Quality Index, respectively. The variables were analyzed using multiple hierarchical Poisson regression in the statistical package Stata version 13.0. A total of 244 health professionals participated in this study (women, 78.28%). The rates of abnormal daytime sleepiness and poor sleep quality were 50.41% (n = 123) and 55.74% (n = 136), respectively. Reduced physical activity was associated with poor sleep quality (prevalence ratio (PR) = 1.32, 95% confidence interval (CI) 1.02–1.70, p = 0.035). Age between 20 and 29 years (PR = 2.59, 95% CI 1.37–4.91, p = 0.021) and 30 and 49 years (PR = 2.09, 95% CI 1.12–3.91, p = 0.021), as well as excessive alcohol consumption (PR = 1.29, 95% CI 1.01–1.66, p = 0.048), were risk factors for daytime sleepiness. Conversely, adequate bodyweight (PR = 0.52, 95% CI 0.33–0.82, p = 0.005) was considered a protective factor. The present findings suggest high rates of abnormal daytime sleepiness and poor sleep quality among healthcare professionals. We emphasize the importance of physical activity, adequate weight, and healthy habits for better quality sleep and reduced daytime sleepiness.

The main objective of the present research is to identify the knowledge flows responsible for promoting the innovation capacity of Portuguese companies. Specifically, we intend to identify which variables influence Portuguese innovation capacity from a macro and micro perspective, so that we can establish possible ways to promote open innovation (OI) in Portugal since Portuguese companies have little maturity in terms of open innovation when compared to companies in other countries of the European Union. To achieve this goal, the methodological design used consisted of two phases. In the first phase, a literature review was conducted to identify the main variables associated with innovation performance. After identifying the most influential variables in the literature, in a second phase, data were collected through three distinct databases, namely Pordata, the Portuguese Tax and Customs Authority, and SABI. To identify the most influential variables in the Portuguese innovation capacity, the multivariate multiple regression technique based on the ordinary least square (OLS) method was applied. The results of the present research bring empirical evidence that researchers dedicated to R&amp, D from non-profit institutions (i.e., inbound OI) and researchers from firms (i.e., outbound OI) exert a significant influence on innovation capacity so the development of an optimal strategy for the strengthening of open innovation by Portuguese firms should take into account the use and combination of these two specific knowledge flows. In this sense, the originality of this research lies in the fact that it is the first attempt to understand the possible implications of the determinants of innovation capacity on open innovation, from an exploratory study concerning the flows of knowledge.

Background and purpose Gender bias is a known issue in healthcare and academia. We analysed the gender of patients reported in the literature with 'man-in-the-barrel' syndrome or equivalent semiological terms. Methods A search in the PubMed database was conducted using the terms 'man-in-the-barrel', 'person-in-the-barrel', 'woman-in-the-barrel', 'brachial diplegia', 'flail arm' and 'cruciate paralysis'. All articles published between 1969 and 2020 containing a detailed description compatible with the original description of man-in-the-barrel syndrome were included. Results Ninety-five patients with a clinical picture compatible with man-in-the-barrel syndrome were included. Up to 33% of patients were female. Overall, the proportion of female patients with man-in-the-barrel syndrome was 25%. Discussion and conclusions The term man-in-the-barrel may disenfranchise up to a third of women presenting with brachial diplegia with undesirable consequences. We propose a gender-neutral alternative such as 'person-in-the-barrel'.

Objective and Method: To investigate trends in the scientific evolution of the journal CNS & Neurological Disorders - Drug Targets in the neuroscience scope, we compared the contribution of publications between this journal and others from different geographical regions of the world. To track research output we conducted a bibliometric analysis of neuroscience research based on the SCimago Journal and Country Rank® from 2003 to 2017. Journal rankings were verified according to the following inclusion criteria: journals publishing the neuroscience scope and sub-areas; geographical location and journal trajectory. Additionally, the total number of original, peer-reviewed and conference articles was analyzed using bibliometric tools. Results: Results showed that Europe, North America and the Middle East have been the greatest contributors of neuroscience publications. Nevertheless, there is a huge discrepancy in the number of journals per region. Until 2017, Europe was on top with 85 journals in the neuroscience field. Moreover, research on neuroscience displayed a swift expanding trend, with significant growth in recent years. Conclusion:: In spite of CNS & Neurological Disorders - Drug Targets being a recent journal, it is an international journal emphasizing quality and innovations, and it is a hallmark on the scientific production in neuroscience. Research articles on the scope of the potential role of endocannabinoid systems in central appetite control and in obesity management and the potential of minocycline use in schizophrenia are paramount examples of innovation. Final results will help scientific researchers to know the current interests in neuroscience and provide useful information for further investigation and publication strategies.

Subjective cognitive complaints in cognitively normal individuals are a relevant predictor of Alzheimer's disease (AD), cerebrovascular disease, and age-related tauopathy. Complaints starting after the age of 60 increase the likelihood of preclinical AD. However, this criterion is arbitrary and current data show that neurodegenerative disorders likely start before that age. Further, data on the role of subjective complaints below the age of 60 in individuals qualifying for subjective cognitive decline (SCD) are lacking. We investigated the association of subjective cognitive complaints with an extensive number of neuroimaging, demographic, clinical, and cognitive measures in individuals fulfilling criteria for SCD below and above the age of 60. Nine complaints were scored in 416 individuals. Complaints were related to a higher load of white matter signal abnormalities, and this association was stronger the more subclinical changes in personality, interest, and drive were reported. In individuals

Introduction: We explored regional brain atrophy patterns and their clinical correlates in dementia with Lewy bodies (DLB). Methods: In this multicentre study, we included a total of 333 patients with DLB, 352 patients with Alzheimer's disease (AD), and 233 normal controls and used medial temporal lobe atrophy, posterior atrophy, and frontal atrophy (GCA-F) visual rating scales. Patients were classified according to four atrophy patterns. Results: Patients with DLB had higher scores on all the three atrophy scales than normal controls but had less medial temporal lobe atrophy than those with AD (all P values

Objective: This study comprises a systematic review and meta-analysis that aimed to estimate the prevalence of dementia in long-term care institutions (LTCIs). Methods: We used the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Original transversal and longitudinal articles published until July 2020 were eligible in this review. Databases PubMed/MedLine, Web of Science, Scopus and ScienceDirect were searched. Overall prevalence and confidence intervals were estimated. Heterogeneity was calculated according to the index of heterogeneity (I2). Results: One hundred seventy-five studies were found in all databases and 19 studies were meta-analyses, resulting in an overall prevalence of 53% (CI 46-59%; p < 0.01) of demented older adults living in LTCIs. Conclusion: Prevalence of dementia is higher in older adults living in LTCIs than those living in general communities. This data shows a worrying reality that needs to be changed. There is a need for a better understanding of the elements that cause this increase in dementia in LTCFs to direct actions to improve the quality of life and health of institutionalized elderly. RESUMO Objetivo: Esta revisão sistemática e metanálise objetiva estimar a prevalência de demência em instituições de longa permanência para idosos (ILPIs). Métodos: Utilizou-se o Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Artigos originais transversais e longitudinais publicados até julho de 2020 foram elegíveis para esta revisão. As buscas foram conduzidas por meio das bases de dados do PubMed/MedLine, Web of Science, Scopus e Science Direct. A prevalência geral e o intervalo de confiança foram estimados. A heterogeneidade foi calculada de acordo com o índice de heterogeneidade (I2). Resultados: Cento e setenta e cinco estudos foram encontrados em todas as bases de dados e 19 estudos foram analisados, resultando em uma prevalência geral de idosos com demência de 53% (IC 46-59%; p < 0,01) que habitam em ILPIs. Conclusão: A prevalência de demência é maior em idosos moradores de ILPIs que em idosos da população geral. Tal dado mostra uma realidade preocupante e que precisa ser modificada. Há necessidade de melhor entendimento dos elementos que causam esse aumento de demência nas ILPIs para direcionar ações para melhorar a qualidade de vida e a saúde dos idosos institucionalizados.

Alzheimer’s Disease Neuroimaging Initiative., [Background] Previous research has described distinct subtypes of Alzheimer’s disease (AD) based on the differences in regional patterns of brain atrophy on MRI. We conducted a data-driven exploration of distinct AD neurodegeneration subtypes using FDG-PET as a sensitive molecular imaging marker of neurodegenerative processes., [Methods] Hierarchical clustering of voxel-wise FDG-PET data from 177 amyloid-positive patients with AD dementia enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) was used to identify distinct hypometabolic subtypes of AD, which were then further characterized with respect to clinical and biomarker characteristics. We then classified FDG-PET scans of 217 amyloid-positive patients with mild cognitive impairment (“prodromal AD”) according to the identified subtypes and studied their domain-specific cognitive trajectories and progression to dementia over a follow-up interval of up to 72 months., [Results] Three main hypometabolic subtypes were identified: (i) “typical” (48.6%), showing a classic posterior temporo-parietal hypometabolic pattern; (ii) “limbic-predominant” (44.6%), characterized by old age and a memory-predominant cognitive profile; and (iii) a relatively rare “cortical-predominant” subtype (6.8%) characterized by younger age and more severe executive dysfunction. Subtypes classified in the prodromal AD sample demonstrated similar subtype characteristics as in the AD dementia sample and further showed differential courses of cognitive decline., [Conclusions] These findings complement recent research efforts on MRI-based identification of distinct AD atrophy subtypes and may provide a potentially more sensitive molecular imaging tool for early detection and characterization of AD-related neurodegeneration variants at prodromal disease stages., Michel J. Grothe is supported by the “Miguel Servet” program [CP19/00031] and a research grant [PI20/00613] of the Instituto de Salud Carlos III-Fondo Europeo de Desarrollo Regional (ISCIII-FEDER).

Alzheimer’s disease (AD) is a neurodegenerative disorder which spans several years from preclinical manifestations to dementia. In recent years, interest in the application of machine learning (ML) algorithms to personalized medicine has grown considerably, and a major challenge that such models face is the transferability from the research settings to clinical practice. The objective of this work was to demonstrate the transferability of the Subtype and Stage Inference (SuStaIn) model from well-characterized research data set, employed as training set, to independent less-structured and heterogeneous test sets representative of the clinical setting. The training set was composed of MRI data of 1043 subjects from the Alzheimer’s disease Neuroimaging Initiative (ADNI), and the test set was composed of data from 767 subjects from OASIS, Pharma-Cog, and ViTA clinical datasets. Both sets included subjects covering the entire spectrum of AD, and for both sets volumes of relevant brain regions were derived from T1-3D MRI scans processed with Freesurfer v5.3 cross-sectional stream. In order to assess the predictive value of the model, subpopulations of subjects with stable mild cognitive impairment (MCI) and MCIs that progressed to AD dementia (pMCI) were identified in both sets. SuStaIn identified three disease subtypes, of which the most prevalent corresponded to the typical atrophy pattern of AD. The other SuStaIn subtypes exhibited similarities with the previously defined hippocampal sparing and limbic predominant atrophy patterns of AD. Subject subtyping proved to be consistent in time for all cohorts and the staging provided by the model was correlated with cognitive performance. Classification of subjects on the basis of a combination of SuStaIn subtype and stage, mini mental state examination and amyloid-β1-42 cerebrospinal fluid concentration was proven to predict conversion from MCI to AD dementia on par with other novel statistical algorithms, with ROC curves that were not statistically different for the training and test sets and with area under curve respectively equal to 0.77 and 0.76. This study proves the transferability of a SuStaIn model for AD from research data to less-structured clinical cohorts, and indicates transferability to the clinical setting.

Background: Spatial navigation is a prodromal dementia marker. Exercise used alongside virtual reality improves many cognitive functions, but effects on spatial navigation are still unclear.Objective: To investigate the effect of virtual reality-based physical exercise with 2D exergames on spatial navigation in institutionalized non-robust older persons.Method: A total of 14 older persons (aged ≧ 60) were randomly allocated to the exergame (EG) and active control (ACG) groups. EG performed exercises with 2D exergames, while the ACG used the same movements as the EG, but without the use of virtual reality. Spatial navigation was assessed through the Floor Maze Test, where the immediate maze time (IMT) and delayed maze time (DMT) were recorded.Results: Spatial navigation was enhanced in EG participants compared to ACG individuals. A significant (p = 0.01) IMT reduction between groups was observed, while DMT time without prior planning was significantly different at the significance threshold (p = 0.07).Conclusions: Virtual reality-based exercise improves the spatial navigation of institutionalized non-robust older persons. This study should be replicated to confirm the findings reported herein.Clinical Trial Registration: This study was registered in the Brazilian Registry of Clinical Trials (Protocol RBR-8dv3kg - https://ensaiosclinicos.gov.br/rg/RBR-8dv3kg).

Fundac¸a˜o de Apoio a Pesquisa do Estado da Bahia (FAPESB), Bahia, Brazil, grant number 05/2015 and Conselho Nacional de Pesquisa (CNPq) grant number 401379/2014-0. DF received a CNPq fellowship (BJT_2014), and HA received a CNPq fellowship for undergraduate students. AB, VMB, EMC, LPC, DSZ, and CB are senior investigators of CNPq.

Introduction: General practitioners (GPs) play a key role in early identification of dementia, yet diagnosis is often missed or delayed in primary care. As part of the multinational Models of Patient Engagement for Alzheimer’s Disease project, we assess GPs’ attitude toward early and pre-dementia diagnosis of AD and explore barriers to early diagnosis. Methods: Our survey covered general attitude toward early diagnosis, diagnostic procedures, resources, and opinion on present and future treatment options across five European countries. Results: In total 343 GPs completed the survey; 74% of GPs indicated that an early diagnosis is valuable. There were country-specific differences in GPs’ perceptions of reimbursement and time available for the patient. If a drug were available to slow down the progression of AD, 59% of the GPs would change their implementation of early diagnosis. Discussion: Our findings provide insight into GPs’ attitudes by exploring differences in perception and management of early diagnosis. (Less)

Data is the basis for designing information. In the healthcare, the management of data can improve patients’ treatment and contribute to better provide healthcare services. This study aims to explore how health data are treated in the national health system in Mozambique.

Background: The heterogeneity in Alzheimer’s disease (AD) has recently become a topic of intensive research due to its implications in understanding the underlying pathophysiological mechanisms of AD. We aimed to assess whether AD atrophy subtypes reflect different disease stages or biologically distinct subtypes. Methods We used longitudinal magnetic resonance images of 1196 individuals (891 AD dementia patients and 305 cognitively unimpaired individuals) from ADNI, AIBL, J-ADNI, and AddNeuroMed cohorts. AD patients were divided in discovery and prediction datasets. In the discovery dataset we applied a novel longitudinal clustering model that estimates differential atrophy patterns from the age of clinical disease onset. We calculated cluster-specific cognitive trajectories and validated our model in the prediction dataset. Results We discovered five longitudinal atrophy patterns in 320 amyloid-β positive AD patients over 8 years, with different atrophy and cognitive trajectories. Our findings replicated the previously reported AD subtypes (typical, limbic predominant, hippocampal sparing, minimal atrophy), but featured only two distinct longitudinal neurodegeneration pathways (mediotemporal vs. cortical). AD subtypes with distinct atrophy trajectories converged in late disease stages. We found a substantial agreement between our model estimates and the prediction dataset’s (571 AD) atrophy levels. Conclusion: Two neurodegeneration pathways were defined, suggesting that some of the previously reported atrophy subtypes may reflect different disease stages rather than distinct subtypes. However, substantial heterogeneity exists within the two pathways with different rates of atrophy and cognitive decline, potentially caused by a complex combination of protective/risk factors and concomitant non-AD brain pathologies. Clearly distinct atrophy trajectories may converge in late disease stages. By shifting from the cross-sectional understanding of AD subtypes to the new perspective brought by longitudinal clustering, we set the ground to unravel the heterogeneity in AD, which may provide a platform for developing disease-modifying treatments in the future. Funding: No funding is declared. Declaration of Interest: None to declare. Ethical Approval: All participants provided written informed consent in accordance with the Helsinki declaration and approval for the studies was obtained by the local ethical committees.

Introduction: The amygdala is implicated in psychiatric illness. Even as the amygdala undergoes significant atrophy in mild dementia, amygdala volume is underexplored as a risk factor for neuropsychiatric symptoms (NPS).Objective: To analyze the association between baseline amygdala volume and the longitudinal trajectories of NPS and cognitive decline in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) over 5 years.Methods: Eighty-nine patients with mild dementia were included (AD = 55; DLB = 34). Amygdala volume was segmented from structural magnetic resonance images (sMRI) using a semi-automatic method (Freesurfer 6.0) and normalized by intracranial volumes. The intracranial volume-normalized amygdala was used as a predictor of the Neuropsychiatric Inventory (NPI) total score, ordinal NPI item scores (0 = absence of symptoms, 1–3 = mild symptoms, ≥4 = clinically relevant symptoms), and Mini-Mental State Examination (MMSE) as measured annually over 5 years using gamma, ordinal, and linear mixed-effects models, respectively. The models were adjusted for demographic variables, diagnosis, center of sMRI acquisition, and cognitive performance. Multiple testing-corrected p-values (q-values) are reported.Results: Larger intracranial volume-normalized amygdala was associated with less agitation/aggression (odds ratio (OR) = 0.62 [0.43, 0.90], p = 0.011, q = 0.038) and less MMSE decline per year (fixed effect = 0.70, [0.29, 1.03], p = 0.001, q = 0.010) but more depression (OR = 1.49 [1.09, 2.04], p = 0.013, q = 0.040).Conclusions: Greater amygdala volume in mild dementia is associated with lower odds of developing agitation/aggression, but higher odds of developing depression symptoms during the 5-year study period.