Digital biomarkers of mobility and quality of life in Parkinson's disease based on a wearable motion analysis LAB.

BACKGROUND AND OBJECTIVE: Functional mobility, an indicator of the quality of life (QoL), requires fast and flexible changes during motion, which are limited in Parkinson's disease (PD). Recent body-worn sensors have emerged in the last decades as potential solutions to produce digital biomarkers able to quantify mobility outside routine consultations and during real-life scenarios for multiple days at a time. The proposed research aims to study the ability of a wearable motion analysis lab, developed by our team, to produce digital biomarkers of mobility and QoL levels in patients with PD. METHODS: A cross-sectional study was followed, including 40 patients stratified into three subgroups according to a clinic motor examination and a QoL questionnaire. RESULTS: The achieved outcomes demonstrate the ability of the proposed high-tech solution to measure prototypical gait impairments and discriminate motor condition (AUC=0,890) and patients' QoL levels (AUC=0,950). Also, from the measured multiple gait-associated parameters, we identified the variables with the most potential to be applied as digital biomarkers of mobility (67 % of the metrics) and QoL (72 % of the metrics) in PD. CONCLUSIONS: Overall, we confirmed our hypothesis of using our body-worn sensor-based solution for passive or active monitoring of mobility and QoL in PD to produce objective, feasible, and continuous digital biomarkers.

Handicap as a Measure of Perceived-Health Status in Parkinson's Disease.

Background: Handicap is a patient-centered measure of health status that encompasses the impact of social and physical environment on daily living, having been assessed in advanced and late-stage Parkinson's Disease (PD). Objective: To characterize the handicap of a broader sample of patients. Methods: A cross-sectional study of 405 PD patients during the MDS-UPDRS Portuguese validation study, using the MDS-UPDRS, Unified Dyskinesias Rating Scale, Nonmotor symptoms questionnaire, PDQ-8 and EQ-5D-3L. Handicap was measured using the London Handicap Scale (LHS). Results: Mean age was 64.42 (±10.3) years, mean disease duration 11.30 (±6.5) years and median HY 2 (IQR, 2-3). Mean LHS was 0.652 (±0.204); "Mobility," "Occupation" and "Physical Independence" were the most affected domains. LHS was significantly worse in patients with longer disease duration, older age and increased disability. In contrast, PDQ-8 did not differentiate age groups. Handicap was significantly correlated with disease duration (r = -0.35), nonmotor experiences of daily living (EDL) (MDS-UPDRS-I) (r = -0.51), motor EDL (MDS-UPDRS-II) (r = -0.69), motor disability (MDS-UPDRS-III) (r = -0.49), axial signs of MDS-UPDRS-III (r = -0.55), HY (r = -0.44), presence of nonmotor symptoms (r = -0.51) and PDQ-8 index (r = -0.64) (all P < 0.05). Motor EDL, MDS-UPDRS-III and PDQ-8 independently predicted Handicap (adjusted R 2 = 0.582; P = 0.007). Conclusions: The LHS was easily completed by patients and caregivers. Patients were mild-moderately handicapped, which was strongly determined by motor disability and its impact on EDL, and poor QoL. Despite correlated, handicap and QoL seem to differ in what they measure, and handicap may have an added value to QoL. Handicap seems to be a good measure of perceived-health status in a broad sample of PD.

New Reports on the Portuguese Endemic Species, Santolina impressa: Secretory Structures, Essential Oil Composition and Antiviral Activity.

Santolina impressa is an aromatic Asteraceae species endemic to Portugal, traditionally used for its anti-inflammatory properties. The aim of this study was to characterize S. impressa secretory structures, analyze the essential oil (EO) from the aerial organs, and evaluate its antiviral activity against herpes simplex viruses HSV-1 and HSV-2. Secretory structures were investigated by light and scanning microscopy, and the secretion was histochemically characterized. The EO from the aerial organs in full blooming was analyzed by gas chromatography with flame ionization detection and gas chromatography-mass spectrometry. Antiviral assays were performed by direct contact with viral suspensions (virucidal effect), and in infected Vero E6 cells, at different time periods during the viral replication cycle. Two types of secretory structures were described, biseriate glandular trichomes and secretory ducts, producing an oleoresin and a resin rich in flavonoids, respectively. Fifty compounds were identified in S. impressa EO, accounting for 87% of the total constituents. Monoterpenes constituted the main EO fraction (82%), with ß-pinene (13%) and ß-phellandrene (10%) being their major components. The EO interacted with HSV-1 and HSV-2 in a dose-dependent manner, thereby inactivating both viral infections. The EO did not evidence a virucidal effect but inhibited the HSV-1 and HSV-2 infection in Vero cells in a dose-dependent manner. However, further studies are needed to investigate the mode of action in the replication cycle.

Clinical Evolution of Tardive Cervical Dystonia from Antecollis to Retrocollis.

Tardive dystonia occurs after exposure, over months to years, to antipsychotics and other drugs that block dopaminergic receptors. Anterocollis is a rare form of cervical dystonia which is usually disabling for the patient. Here, we present the case of a 61-year-old woman with Alzheimer's dementia diagnosed eight years ago who was previously medicated with antipsychotics. Two years before admission, she was medicated with olanzapine. She presented to the emergency room with a sustained flexion posture of the neck that was difficult to feed. She had a marked and fixed anterocollis and severe akathisia. After the administration of propofol to perform computerized tomography, the abnormal posture disappeared. Subsequently, she was started on biperiden without improvement. One week later, olanzapine was suspended, and she was progressively started on propranolol, trihexyphenidyl, and tetrabenazine. Cervical posture improved, but two weeks later, she presented with a left laterocollis, which allowed feeding, and improvement of akathisia. We present a case of tardive dystonia supported by the beginning of dystonia five months after olanzapine administration and improvement after its suspension. The coexistence of degenerative pathology is a risk factor for dystonia, which often persists despite the suspension of the causative agent. Therefore, non-pharmacological treatment and approach with antipsychotics with a better profile of extrapyramidal effects should be preferred in patients with dementia.

Vibrotactile biofeedback devices in Parkinson's disease: a narrative review.

Parkinson's disease (PD) is often associated with a vast list of gait-associated disabilities, for which there is still a limited pharmacological/surgical treatment efficacy. Therefore, alternative approaches have emerged as vibrotactile biofeedback systems (VBS). This review aims to focus on the technologies supporting VBS and identify their effects on improving gait-associated disabilities by verifying how VBS were applied and validated with end-users. It is expected to furnish guidance to researchers looking to enhance the effectiveness of future vibrotactile cueing systems. The use of vibrotactile cues has proved to be relevant and attractive, as positive results have been obtained in patients' gait performance, suitability in any environment, and easy adherence. There seems to be a preference in developing VBS to mitigate freezing of gait, to improve balance, to overcome the risk of fall, and a prevalent use to apply miniaturized wearable actuators and sensors. Most studies implemented a biofeedback loop able to provide rescue strategies during or after the detection of a gait-associated disability. However, there is a need of more clinical evidence and inclusion of experimental sessions to evaluate if the biofeedback was effectively integrated into the patients' motor system.

Mass spectrometry-based forest tree metabolomics.

Research in forest tree species has advanced slowly when compared with other agricultural crops and model organisms, mainly due to the long-life cycles, large genome sizes, and lack of genomic tools. Additionally, trees are complex matrices, and the presence of interferents (e.g., oleoresins and cellulose) challenges the analysis of tree tissues with mass spectrometry (MS)-based analytical platforms. In this review, advances in MS-based forest tree metabolomics are discussed. Given their economic and ecological significance, particular focus is given to Pinus, Quercus, and Eucalyptus forest tree species to better understand their metabolite responses to abiotic and biotic stresses in the current climate change scenario. Furthermore, MS-based metabolomics technologies produce large and complex datasets that require expertize to adequately manage, process, analyze, and store the data in dedicated repositories. To ensure that the full potential of forest tree metabolomics data are translated into new knowledge, these data should comply with the FAIR principles (i.e., Findable, Accessible, Interoperable, and Re-usable). It is essential that adequate standards are implemented to annotate metadata from forest tree metabolomics studies as is already required by many science and governmental agencies and some major scientific publishers. © 2019 John Wiley & Sons Ltd. Mass Spec Rev 40:126-157, 2021.

[Portuguese Consensus on the Diagnosis and Management of Lewy Body Dementia (PORTUCALE)]. / Consenso Português para o Diagnóstico e Gestão Clínica da Demência com Corpos de Lewy (PORTUCALE).

Lewy body dementia is a common cause of dementia leading to the progressive deterioration of cognitive function and motor skills, behavioral changes, and loss of autonomy, impairing the quality of life of patients and their families. Even though it is the second leading cause of neurodegenerative dementia, diagnosis is still challenging, due to its heterogenous clinical presentation, especially in the early stages of the disease. Accordingly, Lewy body dementia is often misdiagnosed and clinically mismanaged. The lack of diagnostic accuracy has important implications for patients, given their increased susceptibility to the adverse effects of certain drugs, such as antipsychotics, which may worsen some symptoms associated with Lewy body dementia. Therefore, a specialist consensus based on the analysis of the most updated and relevant literature, and on clinical experience, is useful to all professionals involved in the care of these patients. This work aims to inform and provide recommendations about the best diagnostic and therapeutic approaches in Lewy body dementia in Portugal. Moreover, we suggest some strategies in order to raise the awareness of physicians, policy makers, and the society at large regarding this disease.

A demência com corpos de Lewy é uma causa comum de demência, provocando a perda progressiva de funções cognitivas e capacidades motoras, alterações comportamentais, e perda de autonomia, com compromisso da qualidade de vida dos doentes e seus familiares. Apesar de ser a segunda causa mais frequente de demência neurodegenerativa, o diagnóstico mantém-se um desafio, devido à sua apresentação clínica heterogénea, sobretudo nas fases iniciais da doença. Por conseguinte, a demência com corpos de Lewy é frequentemente mal diagnosticada e clinicamente gerida de forma insuficiente. A falta de acuidade diagnóstica tem implicações significativas para os doentes, dada a maior suscetibilidade aos efeitos adversos de determinados fármacos, tais como os antipsicóticos, que podem agravar alguns sintomas associados à demência com corpos de Lewy. Por conseguinte, um consenso de especialistas, baseado na análise da literatura mais atual e relevante, e na experiência clínica, é útil para todos os profissionais envolvidos no cuidado destes doentes. O objetivo deste trabalho é informar e gerar recomendações acerca das melhores abordagens diagnóstica e terapêutica da demência com corpos de Lewy em Portugal. Além disso, sugerimos estratégias para aumentar a sensibilização dos médicos, dos decisores políticos e da sociedade em geral em relação a esta doença.

Pinus Susceptibility to Pitch Canker Triggers Specific Physiological Responses in Symptomatic Plants: An Integrated Approach.

Fusarium circinatum, the causal agent of pine pitch canker (PPC), is an emergent and still understudied risk that threatens Pinus forests worldwide, with potential production and sustainability losses. In order to explore the response of pine species with distinct levels of susceptibility to PPC, we investigated changes in physiology, hormones, specific gene transcripts, and primary metabolism occurring in symptomatic Pinus pinea, Pinus pinaster, and Pinus radiata upon inoculation with F. circinatum. Pinus radiata and P. pinaster exhibiting high and intermediate susceptibility to PPC, respectively, suffered changes in plant water status and photosynthetic impairment. This was associated with sink metabolism induction, a general accumulation of amino acids and overexpression of pathogenesis-related genes. On the other hand, P. pinea exhibited the greatest resistance to PPC and stomatal opening, transpiration increase, and glycerol accumulation were observed in inoculated plants. A stronger induction of pyruvate decarboxylase transcripts and differential hormones regulation were also found for inoculated P. pinea in comparison with the susceptible Pinus species studied. The specific physiological changes reported herein are the first steps to understand the complex Pinus-Fusarium interaction and create tools for the selection of resistant genotypes thus contributing to disease mitigation.

Aphid infestation in the phyllosphere affects primary metabolic profiles in the arbuscular mycorrhizal hyphosphere.

While effects of (a)biotic stress events in the phyllosphere have been studied intensively, possible influences of stress on the arbuscular mycorrhizal hyphosphere has scarcely been investigated. We hypothesised that stress challenge in the phyllosphere could alter primary metabolite profiles of the hyphosphere - the mycelial network connecting plants. Donor plants, connected to receiver plants by mycelial networks, were aphid-challenged during 84 h. Primary metabolite profiles in the hyphosphere were investigated. Gene-expression of plant defence gene PR1 was measured in one of the receiver plants during the challenge. Hexose levels in the hyphosphere increased when donor plants were aphid-challenged. This change in metabolic profile was influenced by leaf sampling from receiver plant. PR1 expression increased in donor plants 48 h after challenge, and consequently 60 h after, in receiver plants. We conclude that aphid infestation of donor plants modified primary carbon metabolism in the hyphosphere. Plant defence response in receiver plants, occurred 12 h after detection of response in the aphid-challenged donor plants. While this work is the first to reveal primary metabolic profiles of the AM hyphosphere, more work is needed to elucidate the possible role of transient changes of hexose metabolism in stress response and signalling processes in the hyphosphere of connected plants.

Standard Key Steps in Mass Spectrometry-Based Plant Metabolomics Experiments: Instrument Performance and Analytical Method Validation.

Studies of the plant metabolome include the analysis of a wide range of chemical species with very diverse physicochemical properties requiring powerful analytical tools for the separation, characterization, and quantification of this vast compound diversity present in plant matrices. In quantitative metabolomics studies, major efforts are put into optimizing sample extraction and separation as well as instrument conditions to measure specific plant metabolites. Here, challenges in the use of mass spectrometry (MS) as a quantitative tool in plant metabolomics experiments are discussed, and an overview of the most critical steps in the development and validation of MS-based analytical methods is presented.

The quantification of lipid and protein oxidation in stallion spermatozoa and seminal plasma: seasonal distinctions and correlations with DNA strand breaks, classical seminal parameters and stallion fertility.

The goal of this work was to correlate oxidative stress caused by reactive oxygen species (ROS) and DNA damage with classic semen parameters in spermatozoa and seminal plasma of fertile and subfertile stallions. Oxidation was measured in both lipids and proteins, using the thiobarbituric acid reactive species (TBARS) assay and the DNPH carbonyl groups assay, respectively. Sperm DNA damage was monitored using the TUNEL assay. These parameters were monitored in samples obtained during the breeding and the non-breeding seasons. In general, fertile stallions showed better classical semen parameters, and those parameters improved from the non-breeding to the breeding season, although an increase in sperm production was accompanied by a decrease in the semen quality from subfertile stallions in the breeding season. In terms of oxidation levels we found that there were clear differences whether lipids or proteins were considered. In the breeding season there seemed to be a tendency towards normalizing lipid oxidation in spermatozoa and seminal plasma, and protein oxidation in the seminal plasma, of both fertile and subfertile animals. Thus, differences monitored in the non-breeding season were no longer visible. Interestingly, a higher level of protein oxidation was found in the sperm of fertile animals in the breeding season. Considering that there were positive correlations between sperm protein oxidation and sperm motility and vitality, these results suggests that the oxidation of semen proteins may be important for sperm function. On the other hand, lipid oxidation in the seminal plasma seemed to be a general indicator for sperm damage. In the non-breeding season positive correlations between lipid and protein oxidation levels in both sperm and seminal plasma and several defects in sperm function were found, but only for subfertile animals, thus suggesting that lipid and protein oxidation may aid in the identification of subfertile stallions during the non-breeding season. Levels of ROS production never seemed to result in compromised sperm DNA integrity, indicating that measurements were within physiological levels and/or that there is an efficient antioxidant activity in stallion sperm cells.