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While dynamic ocular motor abnormalities (e.g., gaze-evoked nystagmus (GEN), low optokinetic nystagmus (OKN), pursuit and vestibulo-ocular reflex (VOR) gains, and dysmetric saccades) have been shown to be potential biomarkers in spinocerebellar ataxia type 3 (SCA3), the value of static abnormalities (e.g., convergent [esodeviation] and divergent strabismus [exodeviation]) is unknown. Moreover, studies on dynamic abnormalities in SCA3 usually do not take into account the existence of potential abduction-adduction asymmetries in patients with degenerative ataxia. Thirty-eight patients with genetically confirmed SCA3 (24 females; mean age ± SD, 49.8± 12.2 years) and 22 healthy controls (12 females, p = 0.589; mean age ± SD, 50.7± 12.5 years, p = 0.651) underwent clinical and video-oculographic assessment. A p value

Background and purpose: Clinical trials in spinocerebellar ataxia type 3 (SCA3) will require biomarkers for use as outcome measures. Methods: To evaluate total tau (t-tau), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCHL1) and neurofilament light-chain (NfL) as fluid biomarkers in SCA3, ATXN3 mutation carriers (n = 143) and controls (n = 172) were clinically assessed, and the plasma concentrations of the four proteins were analysed on the Simoa HD-1 platform. Eleven ATXN3 mutation carrier cerebrospinal fluid samples were analysed for t-tau and phosphorylated tau (p-tau181 ). A transgenic SCA3 mouse model (MJDTg) was used to measure cerebellar t-tau levels. Results: Plasma t-tau levels were higher in mutation carriers below the age of 50 compared to controls, and the Inventory of Non-Ataxia Signs was associated with t-tau in ataxic patients (p = 0.004). Pre-ataxic carriers showed higher cerebrospinal fluid t-tau and p-tau181 concentrations compared to ataxic patients (p = 0.025 and p = 0.014, respectively). Cerebellar t-tau was elevated in MJDTg mice compared to wild-type (p = 0.033) only in the early stages of the disease. GFAP and UCHL1 did not show higher levels in mutation carriers compared to controls. Plasma NfL concentrations were higher in mutation carriers compared to controls, and differences were greater for younger carriers. The Scale for the Assessment and Rating of Ataxia was the strongest predictor of NfL in ataxic patients (p < 0.001). Conclusion: Our results suggest that tau might be a marker of early disease stages in SCA3. NfL can discriminate mutation carriers from controls and is associated with different clinical variables. Longitudinal studies are required to confirm their potential role as biomarkers in clinical trials. Federal Ministry of Education and Research, Grant/Award Number: 01ED1602A/B; The Netherlands Organisation for Health Research and Development; Fundação para a Ciência e a Tecnologia (FCT); Medical Research Council, Grant/Award Number: MR/N028767/1; Department of Health’s National Institute for Health Research Biomedical Research Centre’s funding scheme; National Institute for Health Research University College London Hospitals Biomedical Research Centre UCLH; Swedish Research Council, Grant/Award Number: 2018-02532; European Research Council, Grant/Award Number: 681712; Swedish State Support for Clinical Research, Grant/Award Number: ALFGBG-720931; Alzheimer Drug Discovery Foundation (ADDF), Grant/Award Number: 201809-2016862; National Ataxia Foundation; Hertie Academy for Clinical Neuroscience; German Federal Ministry of Education and Research, Grant/Award Number: 01GQ1402 and 01DN18022; German Research Foundation, Grant/Award Number: IRTG 2150 and ZUK32/1; NIH/National Institute of Neurological Disorder and Stroke, Grant/Award Number: P01NS084974, R01NS088689, R35NS097273 and R21NS084528; Department of Defense, Grant/Award Number: ALSRP AL130125; Mayo Clinic Foundation; Amyotrophic Lateral Sclerosis Association; Robert Packard Center for ALS Research at Johns Hopkins; Target ALS Foundation; Mayo Clinic Center for Regenerative Medicine; Mayo Clinic Neuroscience Focused Research Team; Albertson Parkinson’s Research Foundation; European Union’s Horizon 2020 research and innovation programme, Grant/Award Number: 643417; CureSCA3; Regional Fund for Science and Technology (FRCT), PRO-SCIENTIA program, Azores Government; SCA-network, Sweden; Region Skåne, Sweden; Sol Goldman Charitable Trust; Donald G and Jodi P Heeringa Family; The Haworth Family Professorship in Neurodegenerative Diseases fund; Alzheimer Forschung Initiative e.V., Grant/Award Number: AFI13812 and NL-18002CB; Fundo Social Europeu (FSE); ALF, Sweden

Mitochondrial and autophagy dysfunction are mechanisms proposed to be involved in the pathogenesis of several neurodegenerative diseases. Huntington’s disease (HD) is a progressive neurodegenerative disorder associated with mutant Huntingtin-induced abnormalities in neuronal mitochondrial dynamics and quality control. Former studies suggest that the removal of defective mitochondria may be compromised in HD. The mitochondrial quality control is a complex, well-orchestrated pathway that can be compromised through mitophagy dysregulation or impairment in the mitochondrial-lysosomal axis. Another mitochondrial stress response is the generation of mitochondrial-derived vesicles that fuse with the endolysosomal system and form multivesicular bodies that are extruded from cells as extracellular vesicles (EVs).In this study, we comprehensively characterized the mitochondrial and autophagy alterations in premanifest and manifest HD patients and performed a proteomic and genomic EVs profile. We observed that manifest HD patients exhibit mitochondrial and autophagy impairment associated with enhanced EVs release. Further, we detected mitochondrial components in EVs released by HD cells and in neuron-derived EVs. The EV-associated mtDNA copies were elevated in manifest HD patients suggesting to be an alternative pathway for secretion of reactive mitochondrial components. This study provides a novel framework connecting EVs enhanced release of mitochondrial components to mitochondrial and lysosomal dysfunction in HD.

Patients with Parkinson’s and Huntington’s Disease (PD and HD) present impairments in cognitively challenging everyday activities. This study contrasts these two basal ganglia disorders on the ability to perform daily life- like tasks and their level of awareness regarding the disease impact on function. 19 controls, 10 early-onset PD, 20 early stage PD, and 15 early manifest HD patients were compared in the “EcoKitchen,” a virtual reality task with increasing executive load, the “Behavioural Assessment of Dysexecutive Syndrome battery – BADS,” and “The Adults and Older Adults Functional Assessment Inventory – IAFAI,” a self-report functional questionnaire. The EcoKitchen clinical correlates were investigated. All clinical groups presented slower EcoKitchen performance than controls, however, only HD patients showed decreased accuracy. HD and PD patients exhibited reduced BADS scores compared to the other study participants. Importantly, on the IAFAI, PD patients signalled more physically related incapacities and HD patients indicated more cognitively related incapacities. Accordingly, the EcoKitchen performance was significantly associated with PD motor symptom severity. Our findings suggest differential disease impact on cognition and function across PD and HD patients, with preserved awareness regarding disease- related functional sequelae. These observations have important implications for clinical management, research and rehabilitation.Implications for rehabilitationPatients with early stage Parkinson’s and Huntington’s disease have diagnosis-specific impairments in the performance of executively demanding everyday activities and, yet, show preserved awareness about the disease impact on their daily life.An active involvement of patients in the rehabilitation process should be encouraged, as their appraisal of the disease effects can help on practical decisions about meaningful targets for intervention, vocational choices, quality-of-life issues and/or specific everyday skills to boost.The EcoKitchen, a non-immersive virtual reality task, can detect and quantify early deficits in everyday-like tasks and is therefore a valuable tool for assessing the effects of rehabilitation strategies on the functional cognition of these patients.Rehabilitation efforts in the mild stages of Parkinson’s and Huntington’s disease should be aware of greater time needs from the patients in the performance of daily life tasks, target executive skills, and give a more prominent role to patients in symptoms report and management. Patients with early stage Parkinson’s and Huntington’s disease have diagnosis-specific impairments in the performance of executively demanding everyday activities and, yet, show preserved awareness about the disease impact on their daily life. An active involvement of patients in the rehabilitation process should be encouraged, as their appraisal of the disease effects can help on practical decisions about meaningful targets for intervention, vocational choices, quality-of-life issues and/or specific everyday skills to boost. The EcoKitchen, a non-immersive virtual reality task, can detect and quantify early deficits in everyday-like tasks and is therefore a valuable tool for assessing the effects of rehabilitation strategies on the functional cognition of these patients. Rehabilitation efforts in the mild stages of Parkinson’s and Huntington’s disease should be aware of greater time needs from the patients in the performance of daily life tasks, target executive skills, and give a more prominent role to patients in symptoms report and management.

Cognitive impairment is an essential feature of Huntington’s disease (HD) and dementia is a predictable outcome in all patients. However, validated instruments to assess global cognitive performance in the field of HD are lacking. We aimed to explore the utility of the Parkinson’s disease-Cognitive Rating Scale (PD-CRS) for the screening of global cognition in HD. A multicenter cohort of 132 HD patients at different disease stages and 33 matched healthy controls were classified as having preserved cognition, mild cognitive impairment (HD-MCI) or dementia (HD-Dem) according to the Clinical Dementia Rating and Functional Independence Score. The PD-CRS and the Mini-Mental State Examination were administered. Receiver operating characteristic curve analysis was used to determine optimal cutoffs to differentiate patients according to their cognitive status. A PD-CRS cutoff score ≤ 81/82 was optimal to detect HD-MCI (sensitivity = 93%; specificity = 80%; area under the curve (AUC) = 0.940), and ≤ 63/64 was optimal to detect HD-Dem (sensitivity = 90%; specificity = 87%; AUC = 0.933). MMSE scores failed to show robust psychometric properties in this context. The PD-CRS is a valid and reliable instrument to assess global cognition in HD in routine clinical care and clinical trials.

Movement disorders 37(2), 405-410 (2022). doi:10.1002/mds.28844, Published by Wiley, New York, NY

BackgroundThis study aims to test response inhibition in premanifest Huntington’s disease individuals (Pre-HD), in the context of a saccadic paradigm with working memory demands and fronto-executive load as a way to measure inhibitory control deficits and impulsive behavior in Huntington’s disease (HD).MethodsThe oculomotor function of 15 Pre-HD and 22 Control individuals was assessed using an experimental paradigm comprising four horizontal saccadic tasks: prosaccade (PS), antisaccade (AS), 1- or 2-back memory prosaccade (MPS), and 1- or 2-back memory antisaccade (MAS). Success rate, latency, directional and timing errors were calculated for each task. A comprehensive battery of neuropsychological tests was also used to assess the overall cognitive functioning of study participants. Statistical correlations between oculomotor, clinical and cognitive measures were computed for the Pre-HD group.ResultsPre-HD participants showed reduced success rate in the AS task, increased direction errors in the AS and MAS tasks and decreased latency in the MAS task when compared to Controls, despite presenting similar executive and memory scores in the conventional neuropsychological tests applied. Significant associations were identified between specific AS and MAS parameters and disease-related measures, cognitive skills and other oculomotor results of Pre-HD participants.ConclusionsOur results show that oculomotor performance in premanifest Huntington’s disease deteriorates once inhibitory control, working memory and/or fronto-executive load are added to the task. A more automatic pattern of performance, including a faster response time and directionally erroneous eye movements were detected in the oculomotor behavior of the Pre-HD group—these alterations were significantly correlated with disease stage and cognitive status. Our saccadic paradigm was able to capture impulsivity and inhibitory control deficits in a group of Pre-HD individuals on average far from symptom onset, thus holding the potential to identify the earliest disease-related changes.

We investigated the behavior of a Susceptible-Infected-Recovered seasonally forced model for endemic childhood infectious diseases in the case where the target population is not isolated and, moreover, fast weekly fluctuations of the social contacts occur. We considered some key scenarios of interplay of Susceptible subjects with the external world, leading to subharmonic resonances and chaos. Our simulations suggest that the above–mentioned fast oscillations of the contact rate can cause the suppression/reduction of chaos and of subharmonic resonances. Thus, far from being filtered, they have an important role. If one considers an opposition of phase of the pattern of external infections w.r.t. the pattern of internal transmission rate, they result remarkably different from a scenario of synchrony. In most scenarios, the chaotic behavior is not associated to the phenomenon of the ‘atom–infectious’, i.e. the proportion of infectious is small but not unrealistic for large populations. published

Objective.To explore the viability of developing a computer-aided diagnostic system for Parkinsonian syndromes using dynamic [11C]raclopride positron emission tomography (PET) and T1-weighted magnetic resonance imaging (MRI) data.Approach.The biological heterogeneity of Parkinsonian syndromes renders their statistical classification a challenge. The unique combination of structural and molecular imaging data allowed different classifier designs to be tested. Datasets from dynamic [11C]raclopride PET and T1-weighted MRI scans were acquired from six groups of participants. There were healthy controls (CTRLn= 15), patients with Parkinson’s disease (PDn= 27), multiple system atrophy (MSAn= 8), corticobasal degeneration (CBDn= 6), and dementia with Lewy bodies (DLBn= 5). MSA, CBD, and DLB patients were classified into one category designated as atypical Parkinsonism (AP). The distribution volume ratio (DVR) kinetic parameters obtained from the PET data were used to quantify the reversible tracer binding to D2/D3 receptors in the subcortical regions of interest (ROI). The grey matter (GM) volumes obtained from the MRI data were used to quantify GM atrophy across cortical, subcortical, and cerebellar ROI.Results.The classifiers CTRL vs PD and CTRL vs AP achieved the highest balanced accuracy combining DVR and GM (DVR-GM) features (96.7%, 92.1%, respectively), followed by the classifiers designed with DVR features (93.3%, 88.8%, respectively), and GM features (69.6%, 86.1%, respectively). In contrast, the classifier PD vs AP showed the highest balanced accuracy (78.9%) using DVR features only. The integration of DVR-GM (77.9%) and GM features (72.7%) produced inferior performances. The classifier CTRL vs PD vs AP showed high weighted balanced accuracy when DVR (80.5%) or DVR-GM features (79.9%) were integrated. GM features revealed poorer performance (59.5%).Significance.This work was unique in its combination of structural and molecular imaging features in binary and triple category classifications. We were able to demonstrate improved binary classification of healthy/diseased status (concerning both PD and AP) and equate performance to DVR features in multiclass classifications.

The study of how different breeds adapt to heat stress and the further understanding of mechanisms underlying pigs thermotolerance is of utmost importance to attenuate the negative effects of heat stress on pigs welfare, physiology, and performance. Therefore, this study aimed at evaluating the effects of ambient temperature on performance and thermoregulatory responses of Piau purebred pigs. The Brazilian native pig breed Piau is a fat-type breed characterized by adaptability and resistance to diseases. To achieve our goal, Piau purebred pigs (65 kg initial BW) were allocated to one of the two constant ambient temperature conditions: thermoneutral (22 °C; n = 11) and heat stress (30 °C; n = 11). The experimental period lasted 15 days (days 1 to 15). Pigs were individually weighed at the beginning and end of the experimental period. Body and rectal temperatures, respiratory rate and blood indicators of stress and metabolism were measured throughout the experiment. Piau purebred pigs exposed to 30 °C had lower (p 0.05) feed intake, body weight gain and final body weight than pigs at 22 °C. Feed conversion rate was not affected (p 0.05) by ambient temperature. Irrespective of ambient temperature, pigs had similar (p 0.05) backfat thickness and loin eye area. Piau pigs at 30 °C had increased (p 0.05) nape, dorsal, flank, and rectal temperatures and increased respiratory rate than their counterparts reared at 22 °C. In summary, our results show that Piau purebred pigs acclimation to 30 °C of ambient temperature is characterized by increased body skin temperature to optimize sensible heat loss to the environment; increased respiratory rate to promote latent heat loss; and by a concomitant reduced voluntary feed intake to reduce heat production associated with digestion and metabolic processes with negative effects on body weight gain.

While dynamic ocular motor abnormalities (e.g., gaze-evoked nystagmus (GEN), low optokinetic nystagmus (OKN), pursuit and vestibulo-ocular reflex (VOR) gains, and dysmetric saccades) have been shown to be potential biomarkers in spinocerebellar ataxia type 3 (SCA3), the value of static abnormalities (e.g., convergent [esodeviation] and divergent strabismus [exodeviation]) is unknown. Moreover, studies on dynamic abnormalities in SCA3 usually do not take into account the existence of potential abduction-adduction asymmetries in patients with degenerative ataxia. Thirty-eight patients with genetically confirmed SCA3 (24 females; mean age ± SD, 49.8± 12.2 years) and 22 healthy controls (12 females, p = 0.589; mean age ± SD, 50.7± 12.5 years, p = 0.651) underwent clinical and video-oculographic assessment. A p value 0.002 (between- and within-group analyses) and 0.001 (correlation analysis) was considered significant. Patients showed larger esodeviation at distance (p 0.001), became more esodeviated in lateral gaze (p 0.001), and their near exodeviation correlated with scale for the assessment and rating of ataxia (SARA) score (p = 0.004). Pursuit, OKN, and VOR gains were lower in patients, both for their adducting and abducting components (p 0.001). Saccades showed higher velocities (p 0.001), abducting saccades showed lower amplitude (p 0.001), and adducting saccades tended to show greater vertical bias (p = 0.018) in patients. Abducting saccades showed relatively lower velocity (p 0.001) and lower amplitude (p = 0.015) than abducting saccades within patients. All dynamic ocular motor abnormalities except saccades correlated with SARA score, CAG repeat number, and/or disease duration (p 0.001). Static and dynamic ocular motor abnormalities are potential biomarkers in SCA3. SCA3 studies using saccades should take into account the existence of potential abduction-adduction asymmetries.

The purpose of this study was to classify Huntington’s disease (HD) stage using support vector machines and measures derived from T1- and diffusion-weighted imaging. The effects of feature selection approach and combination of imaging modalities are assessed. Fourteen premanifest-HD individuals (Pre-HD; on average > 20 years from estimated disease onset), eleven early-manifest HD (Early-HD) patients, and eighteen healthy controls (HC) participated in the study. We compared three feature selection approaches: (i) whole-brain segmented grey matter (GM; voxel-based measure) or fractional anisotropy (FA) values; (ii) GM or FA values from subcortical regions-of-interest (caudate, putamen, pallidum); and (iii) automated selection of GM or FA values with the algorithm Relief-F. We assessed single- and multi-kernel approaches to classify combined GM and FA measures. Significant classifications were achieved between Early-HD and Pre-HD or HC individuals (accuracy: generally, 85% to 95%), and between Pre-HD and controls for the feature FA of the caudate ROI (74% accuracy). The combination of GM and FA measures did not result in higher performances. We demonstrate evidence on the high sensitivity of FA for the classification of the earliest Pre-HD stages, and successful distinction between HD stages.

Spinocerebellar ataxia type 3 (SCA3), caused by a CAG repeat expansion in the ataxin-3 gene (ATXN3), is characterized by neuronal polyglutamine (polyQ) ATXN3 protein aggregates. Although there is no cure for SCA3, gene-silencing approaches to reduce toxic polyQ ATXN3 showed promise in preclinical models. However, a major limitation in translating putative treatments for this rare disease to the clinic is the lack of pharmacodynamic markers for use in clinical trials. Here, we developed an immunoassay that readily detects polyQ ATXN3 proteins in human biological fluids and discriminates patients with SCA3 from healthy controls and individuals with other ataxias. We show that polyQ ATXN3 serves as a marker of target engagement in human fibroblasts, which may bode well for its use in clinical trials. Last, we identified a single-nucleotide polymorphism that strongly associates with the expanded allele, thus providing an exciting drug target to abrogate detrimental events initiated by mutant ATXN3. Gene-silencing strategies for several repeat diseases are well under way, and our results are expected to improve clinical trial preparedness for SCA3 therapies.

Background and Objectives: The medication process in the hospital environment is one of the most important activities to ensure efficacy in the patient's therapy. The objective of this study was to know the perception of the nursing team about the occurrence of adverse events related to drug administration in a hospital in Vale do Taquari, Rio Grande do Sul. Methods: This is a descriptive exploratory study with a qualitative approach-quantitative. Data were collected through the application of a questionnaire to nursing professionals, constituting a sample of fifty-eight interviewees. The analysis was made through descriptive statistics. Results: Of the participants, 96.6% knew the steps to avoid medication errors, and 79.3% had already made some mistake in their professional practices in the institution. The most frequent error was the erroneous administration dose of 43.5%, with 97.3% of the professionals already perceived some error in the medication process and 30% considered the work overload to be an aggravating factor for the occurrence of errors. Regarding the professional's behavior regarding the error, 80.4% communicated verbally to the supervising professional and as a consequence received verbal guidance 78.3% of the time. As for feelings about the error 36.8% revealed to feel fear of harming the patient. Conclusion: These findings point to serious potential errors that impair patient safety; however, it is noted that verbal guidelines are offered avoiding punishment, but the incentive for reporting the error is precarious, making it difficult for the team to identify potential errors and implement barriers to avoid them. Justificación y Objetivos: El proceso de medicación en el ambiente hospitalario es una de las actividades de mayor importancia para asegurar la eficacia en la terapéutica del paciente. El estudio tuvo como objetivo conocer la percepción del equipo de enfermería sobre la ocurrencia de eventos adversos relacionados con la administración de medicamentos en un hospital del Valle del Taquari, Rio Grande do Sul. Métodos: Se trata de un estudio exploratorio descriptivo, con abordaje cuali-quantitativo. Los datos fueron recolectados por medio de la aplicación de un cuestionario a los profesionales de la enfermería, constituyendo una muestra de cincuenta y ocho entrevistados. El análisis fue realizado por medio de estadística descriptiva. Resultados: De los participantes 96,6% conocían las etapas para evitar errores de medicación y el 79,3% ya cometieron algún error en sus prácticas profesionales en la institución. El error más frecuente fue la dosis de administración equivocada 43,5%, siendo que el 97,3% de los profesionales ya percibieron algún error en el proceso de medicación y el 30% considera la sobrecarga de trabajo un factor agravante para la ocurrencia de errores. En cuanto a la conducta del profesional frente al error 80,4% comunicaban verbalmente al profesional supervisor y como consecuencia recibieron orientación verbal el 78,3% de las veces. En cuanto a los sentimientos frente al error 36,8% revelaron sentir miedo de perjudicar al paciente. Conclusión: Tales hallazgos apuntan errores potenciales graves que perjudican la seguridad del paciente, pero se nota que las orientaciones verbales son ofrecidas evitando el castigo, pero el incentivo para el registro de notificación del error es precario, dificultando el equipo de identificar los errores potenciales e implementar barreras para evitarlos Justificativa e Objetivos: O processo de medicação no ambiente hospitalar é uma das atividades de maior importância para assegurar a eficácia na terapêutica do paciente. Este estudo teve como objetivo conhecer a percepção da equipe de enfermagem sobre a ocorrência de eventos adversos relacionados a administração de medicamentos em um hospital do Vale do Taquari, Rio Grande do Sul. Métodos: Trata-se de um estudo exploratório descritivo, com abordagem quali-quantitativa. Os dados foram coletados por meio da aplicação de um questionário aos profissionais da enfermagem, constituindo uma amostra de cinquenta e oito entrevistados. A análise foi feita por meio de estatística descritiva. Resultados: Dos participantes, 96,6% conheciam as etapas para evitar erros de medicação, e 79,3% já cometeram algum erro em suas práticas profissionais na instituição. O erro mais frequente foi a dose de administração errada, 43,5%, sendo que 97,3% dos profissionais já perceberam algum erro no processo de medicação e 30% consideram a sobrecarga de trabalho um fator agravante para a ocorrência de erros. Quanto à conduta do profissional frente ao erro, 80,4% comunicavam verbalmente ao profissional supervisor e como consequência receberam orientação verbal, 78,3% das vezes. Quanto aos sentimentos frente ao erro 36,8% revelaram sentir medo de prejudicar o paciente. Conclusão: Tais achados apontam erros potenciais graves que prejudicam a segurança do paciente, no entanto, nota-se que orientações verbais são oferecidas evitando a punição, mas o incentivo para o registro de notificação do erro é precário, dificultando a equipe de identificar os erros potenciais e implementar barreiras para evitá-los.

Motor impairment in Parkinson's disease (PD) is characterized by different signs that include bradykinesia, rigidity, tremor, and postural instability. Manifestations are heterogeneous among patients and progress throughout the course of the disease. There is evidence that tremor-dominant patients have a slower progression of motor impairment than akinetic-rigid ones. Some studies have identified predictors of disease progression. The presence of cognitive decline at baseline is associated with faster motor impairment, whereas late-onset disease, the presence of, gait disturbance and postural instability at baseline are associated with more disability. There is an increasing interest in defining a biomarker for disease progression. Some genetic, biochemical, and neuroimaging studies found potential biomarkers, but none has fulfilled all the required characteristics. Treatment of PD patients becomes more difficult at later stages of the disease, with a progressive loss of levodopa effectiveness and the development of motor fluctuations. Future investigations are needed to develop a disease-modifying drug that ensures better disease management.

Background/aimsNeurodegeneration with brain iron accumulation (NBIA) type I is a rare disease that can be divided into a classical or atypical variant, according to age of onset and clinical pattern. Neuro-ophthalmological involvement has been documented in the classical variant but only anecdotically in the atypical variant. We sought to describe the visual and ocular motor function in patients with atypical form of NBIA type I.MethodsCross-sectional study, including patients with genetically confirmed NBIA type I and classified as atypical variant, who underwent ophthalmological examination with best corrected visual acuity (BCVA), optical coherence tomography (OCT), fundus autofluorescence (FAF), electroretinography (ERG), visual evoked potentials (VEP) and video-oculography.ResultsSeven patients with a mean BCVA of 0.12±0.14 logMAR were included. Only two patients showed structural evidence of advanced retinopathy in OCT and FAF, and there were no cases of optic atrophy. ERG data, however, showed abnormal scotopic and/or photopic responses in all patients. VEP were normal in all three patients. Ocular fixation was markedly unstable (eg, increased rate of saccadic pulses) in the majority of patients (5). Additional mild ocular motor disturbances included low gain pursuit (2), hypermetric saccades (1), low gain optokinetic (2) and caloric and rotatory responses (3).ConclusionFunctional retinal changes associated with marked instability of ocular fixation should be included in the clinical spectrum of NBIA, particularly in the atypical form.

The studies of nonlinear models in epidemiology have generated a deep interest in gaining insight into the mechanisms that underlie AIDS-related cancers, providing us with a better understanding of cancer immunity and viral oncogenesis. In this article, we analyze an HIV-1 model incorporating the relations between three dynamical variables: cancer cells, healthy CD4 + T lymphocytes, and infected CD4 + T lymphocytes. Recent theoretical investigations indicate that these cells interactions lead to different dynamical outcomes, for instance to periodic or chaotic behavior. Firstly, we analytically prove the boundedness of the trajectories in the system’s attractor. The complexity of the coupling between the dynamical variables is quantified using observability indices. Our calculations reveal that the highest observable variable is the population of cancer cells, thus indicating that these cells could be monitored in future experiments in order to obtain time series for attractor’s reconstruction. We identify different dynamical behaviors of the system varying two biologically meaningful parameters: r 1, representing the uncontrolled proliferation rate of cancer cells, and k 1, denoting the immune system’s killing rate of cancer cells. The maximum Lyapunov exponent is computed to identify the chaotic regimes. Considering very recent developments in the literature related to the homotopy analysis method (HAM), we calculate the explicit series solutions of the cancer model and focus our analysis on the dynamical variable with the highest observability index. An optimal homotopy analysis approach is used to improve the computational efficiency of HAM by means of appropriate values for the convergence control parameter, which greatly accelerate the convergence of the series solution. The approximated analytical solutions are used to compute density plots, which allow us to discuss additional dynamical features of the model.

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder showing predominant brainstem involvement, characterized by marked slowing of rapid eye movements (saccades), particularly along the vertical plane. While the contribution of the brainstem damage for the saccadic disturbance in PSP has been extensively studied, much less is known about its cortical and subcortical pathomechanisms. We measured reflexive (prosaccades) and voluntary (antisaccades) saccades in the vertical and horizontal plane in PSP patients (n=8) and controls (n=10) in an eye tracking study, followed by the measurement of blood oxygenation-level dependent (BOLD) activation (PSP, n=6; controls, n=10) during similar saccade paradigms. Behaviorally, PSP patients evidenced slower and lower amplitude prosaccades (horizontal and vertical) and lower amplitude antisaccades (vertical) than controls. Functionally, patients showed decreased frontostriatal BOLD activation during prosaccades (horizontal and vertical) and antisaccades (vertical), relative to controls. Additionally, PSP patients showed less default mode network (DMN) deactivation than controls for all types of saccades. Within groups, controls showed no BOLD differences between horizontal and vertical prosaccades while PSP patients demonstrated greater DMN deactivation during vertical prosaccades. Both groups evidenced greater DMN deactivation during vertical antisaccades when compared to their horizontal counterpart and patients further showed relative frontostriatal BOLD hypoactivity during vertical antisaccades. We found fMRI evidence of frontostriatal hypoactivity in PSP patients relative to controls, especially during vertical saccades. These new findings highlight the impact of cortical impairment in saccadic disturbance of PSP.

Nonlinear systems are commonly able to display abrupt qualitative changes (or transitions) in the dynamics. A particular type of these transitions occurs when the size of a chaotic attractor suddenly changes. In this article, we present such a transition through the observation of a chaotic interior crisis in the Deng bursting-spiking model for the glucose-induced electrical activity of pancreatic $β $-cells. To this chaos-chaos transition corresponds precisely the change between the bursting and spiking dynamics, which are central and key dynamical regimes that the Deng model is able to perform. We provide a description of the crisis mechanism at the bursting-spiking transition point in terms of time series variations and based on certain amplitudes of invariant intervals associated with return maps. Using symbolic dynamics, we are able to accurately compute the points of a curve representing the transition between the bursting and spiking regimes in a biophysical meaningfully parameter space. The analysis of the chaotic interior crisis is complemented by means of topological invariants with the computation of the topological entropy and the maximum Lyapunov exponent. Considering very recent developments in the literature, we construct analytical solutions triggering the bursting-spiking transition in the Deng model. This study provides an illustration of how an integrated approach, involving numerical evidences and theoretical reasoning within the theory of dynamical systems, can directly enhance our understanding of biophysically motivated models.

Justificativa e Objetivos: O processo de medicação no ambiente hospitalar é uma das atividades de maior importância para assegurar a eficácia na terapêutica do paciente. Este estudo teve como objetivo conhecer a percepção da equipe de enfermagem sobre a ocorrência de eventos adversos relacionados a administração de medicamentos em um hospital do Vale do Taquari, Rio Grande do Sul. Métodos: Trata-se de um estudo exploratório descritivo, com abordagem quali-quantitativa. Os dados foram coletados por meio da aplicação de um questionário aos profissionais da enfermagem, constituindo uma amostra de cinquenta e oito entrevistados. A análise foi feita por meio de estatística descritiva. Resultados: Dos participantes, 96,6% conheciam as etapas para evitar erros de medicação, e 79,3% já cometeram algum erro em suas práticas profissionais na instituição. O erro mais frequente foi a dose de administração errada, 43,5%, sendo que 97,3% dos profissionais já perceberam algum erro no processo de medicação e 30% consideram a sobrecarga de trabalho um fator agravante para a ocorrência de erros. Quanto à conduta do profissional frente ao erro, 80,4% comunicavam verbalmente ao profissional supervisor e como consequência receberam orientação verbal, 78,3% das vezes. Quanto aos sentimentos frente ao erro 36,8% revelaram sentir medo de prejudicar o paciente. Conclusão: Tais achados apontam erros potenciais graves que prejudicam a segurança do paciente, no entanto, nota-se que orientações verbais são oferecidas evitando a punição, mas o incentivo para o registro de notificação do erro é precário, dificultando a equipe de identificar os erros potenciais e implementar barreiras para evitá-los.

Dopamine dysregulation syndrome is a rare complication of Parkinson’s disease (PD) treatment. We present a 70-year-old woman with a long-standing PD and a clinical picture compatible with dopaminergic dysregulation, which was ultimately revealed to be induced by her companion. Patient’s exuberant choreiform dyskinesia led to a potential financial advantage when performed outside the hospital but excessive dopamine intake also occurred during hospital admission, without any obvious reward for the abuser. Even in cases where there is no place for a definitive diagnosis, deceptive behaviours must be identified as their management is based on psychological and social support in parallel to the adjustment of PD therapy.