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Big data and AI have enabled digital simulation for prediction of future health states or behaviors of specific individuals, populations or humans in general. "Digital simulacra" use multimodal datasets to develop computational models that are virtual representations of people or groups, generating predictions of how systems evolve and react to interventions over time. These include digital twins and virtual patients for in silico clinical trials, both of which seek to transform research and health care by speeding innovation and bridging the epistemic gap between population-based research findings and their application to the individual. Nevertheless, digital simulacra mark a major milestone on a trajectory to embrace the epistemic culture of data science and a potential abandonment of medical epistemological concepts of causality and representation. In doing so, "data first" approaches potentially shift moral attention from actual patients and principles, such as equity, to simulated patients and patient data. [ABSTRACT FROM AUTHOR]

Background: Caring for a partner or family member with Parkinson's disease (PD) negatively affects the caregiver's own physical and emotional well-being, especially those caring for people with advanced PD (APD). This study was designed to examine the impact of APD on caregiver perceived burden, quality of life (QoL), and health status. Methods: Dyads of people with PD and their primary caregivers were identified from the Adelphi Parkinson's Disease Specific Program (DSP™) using real-world data from the United States, Japan and five European countries. Questionnaires were used to capture measures of clinical burden (people with PD) and caregiver burden (caregivers). Results: Data from 721 patient-caregiver dyads in seven countries were captured. Caregivers had a mean age 62.6 years, 71.6% were female, and 70.4% were a spouse. Caregivers for people with APD had a greater perceived burden, were more likely to take medication and had lower caregiver treatment satisfaction than those caring for people with early or intermediate PD; similar findings were observed for caregivers of people with intermediate versus early PD. Caregivers for people with intermediate PD were also less likely to be employed than those with early PD (25.3% vs 42.4%) and spent more time caring (6.6 vs 3.2 h/day). Conclusions: This real-world study demonstrates that caregivers of people with APD experience a greater burden than those caring for people with early PD. This highlights the importance of including caregiver-centric measures in future studies, and emphasizes the need for implementing treatments that reduce caregiver burden in APD. Trial registration: N/A. [ABSTRACT FROM AUTHOR]

Patients with idiopathic Parkinson's disease (PD) suffer from different non-motor symptoms, including pain. The present study aimed to measure the psychometric properties of the Brief Pain Inventory (BPI) in patients with PD during ON- and OFF-states. We recruited 460 patients with PD and 100 non-PD controls. The pain was assessed by the BPI, King's Parkinson's disease Pain Scale (KPPS), Neuropathic Pain Symptom Inventory (NPSI), Visual Analogue Scale-Pain (VAS-pain), and short-form McGill Pain Questionnaire-2 (SF-MPQ-2) in both medication states. Internal consistency and test-retest reliability was examined using Cronbach's alpha coefficient and intra-class correlation coefficient (ICC). Dimensionality and convergent validity of BPI were also investigated. Diagnostic accuracy and discriminative validity were determined by Receiver Operating Characteristics (ROC) curve analysis and Area Under the Curve (AUC). Cronbach's alpha was satisfactory (α = 0.91–0.97) in both states. The ICC values were 0.85–0.96 in ON- and OFF-state. Factor analysis revealed two factors. A high correlation was obtained between BPI subscales and other scales. AUC >0.91, sensitivity, and specificity> 0.77 were observed for discriminating different pain levels. Furthermore, appropriate diagnostic accuracy was found (AUC, sensitivity, and specificity >0.67) between non-PD control and PD patients. The BPI has acceptable psychometric features as well as diagnostic accuracy for patients with PD. Pain as a non-motor symptom in PD can affect daily and social activities. The BPI is used to assess pain severity and interference in activities. For better treatment, pain should be assessed in off-state like to on-state. BPI has satisfactory reliability and validity in different medication states in PD. [ABSTRACT FROM AUTHOR]

The article focuses on ethical application of conversational artificial intelligence (CAI) in mental health therapy. Topics discussed include useful role of CAI in providing mental health support for diverse groups or those with specialized needs, funding and support for development of CAI and public funding of mental health services.

Background: The primary validation of the Movement Disorder Society Non-Motor Rating Scale was recently published, but 2 important structural analyses were not included. The objective of this study was to examine the structural characteristics of the Movement Disorder Society Non-Motor Rating Scale by factor and cluster analyses.Methods: Data came from the validation study, an international multicenter cross-sectional study of 402 Parkinson's disease patients. Demographic and clinical data, the Movement Disorder Society Non-Motor Rating Scale, and Hoehn and Yahr staging were used. Exploratory and confirmatory factor analysis and nonhierarchical cluster analysis were performed.Results: The exploratory factor analysis showed that all 13 domains of the Movement Disorder Society Non-Motor Rating Scale, except 1, and the Non-Motor Fluctuations subscale performed as unidimensional (variance explained: 0.36, sleep and wakefulness; -0.82, orthostatic hypotension). The confirmatory factor analysis could be carried out in 9 domains and showed that 6 of them and the Non-Motor Fluctuations subscale adjusted to the model satisfactorily according to the root mean square error of approximation. Furthermore, all domains had comparative fit index values >0.95, except depression and pain (both, 0.94) and sleep and wakefulness (0.90). The Non-Motor Fluctuations subscale showed satisfactory root mean square error of approximation (0.07), but a low comparative fit index value (0.91). A 5-cluster solution, correctly classifying 96% of the cases, was found.Conclusions: Overall, most subscales of the Movement Disorder Society Non-Motor Rating Scale are unidimensional, and although each subscale is distinct in terms of content covered, factors and clusters that are of clinical relevance are discernible and contribute to our understanding of possible nonmotor subtypes in Parkinson's disease. © 2020 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: The burden of Parkinson's disease (PD) worsens with disease progression. However, the lack of objective and uniform disease classification challenges our understanding of the incremental burden in patients with advanced Parkinson's disease (APD) and suboptimal medication control. The 5-2-1 criteria was proposed by clinical consensus to identify patients with advancing PD. Our objective was to evaluate the screening accuracy and incremental clinical burden, healthcare resource utilization (HCRU), and humanistic burden in PD patients meeting the 5-2-1 screening criteria.Methods: Data were drawn from the Adelphi Parkinson's Disease Specific Program (DSP™), a multi-country point-in-time survey (2017-2020). People with PD who were naive to device-aided therapy and on oral PD therapy were included. Patients meeting the 5-2-1 screening criteria had one or more of the three clinical indicators of APD: (i) ≥5 doses of oral levodopa/day, OR (ii) "off" symptoms for ≥2 h of waking day, OR (iii) ≥1 h of troublesome dyskinesia. Clinician assessment of PD stage was used as the reference in this study. Clinical screening accuracy of the 5-2-1 criteria was assessed using area under the curve and multivariable logistic regression models. Incremental clinical, HCRU, and humanistic burden were assessed by known-group comparisons between 5 and 2-1-positive and negative patients.Results: From the analytic sample (n = 4714), 33% of patients met the 5-2-1 screening criteria. Among physician-classified APD patients, 78.6% were 5-2-1 positive. Concordance between clinician judgment and 5-2-1 screening criteria was > 75%. 5-2-1-positive patients were nearly 7-times more likely to be classified as APD by physician judgment. Compared with the 5-2-1-negative group, 5-2-1-positive patients had significantly higher clinical, HCRU, and humanistic burden across all measures. In particular, 5-2-1-positive patients had 3.8-times more falls, 3.6-times higher annual hospitalization rate, and 3.4-times greater dissatisfaction with PD treatment. 5-2-1-positive patients also had significantly lower quality of life and worse caregiver burden.Conclusions: 5-2-1 criteria demonstrated potential as a screening tool for identifying people with APD with considerable clinical, humanistic, and HCRU burden. The 5-2-1 screening criteria is an objective and reliable tool that may aid the timely identification and treatment optimization of patients inadequately controlled on oral PD medications. [ABSTRACT FROM AUTHOR]

Cellular processes, in particular homeostasis and growth, require an intricate and complex exchange of matter between a cell and its surroundings. Yet experimental difficulties have prevented a detailed description of the dynamics of a cell's mass and volume along different cellular processes, limiting our understanding of cell physiology in health and disease. It has been recently observed that single mammalian cells fluctuate their mass in a timescale of seconds. This result challenges central and long-standing cell growth models, according to which cells increase their mass either linearly or exponentially throughout the cell cycle. However, it remains unclear to what extent cell mass fluctuations may be sustained in multicellular organisms. Here I provide a mathematical model for cell mass fluctuations and explore how such fluctuations can be successfully sustained in multicellular organisms. I postulate that cells do not synchronise their mass fluctuations, but they are executed with their phases uniformly distributed. I derive a mathematical expression to estimate the resulting mass shift between fluid compartments in an organism due to cell mass fluctuations. Together with a new estimate of 4 × 1013 human cells in the body, I demonstrate that my hypothesis leads to shifts of mass between the intracellular and extracellular fluid compartments in the human body that are approximately or smaller than 0.25 mg and, therefore, perfectly viable. The proposed model connects cell physiology with information theory and entropy. [ABSTRACT FROM AUTHOR]

Around 5% of the world population suffers from hearing impairment. One of its main barriers is communication with others since it could lead to their social exclusion and frustration. To overcome this issue, this paper presents a system to interpret the Spanish sign language alphabet which makes the communication possible in those cases, where it is necessary to sign proper nouns such as names, streets, or trademarks. For this, firstly, we have generated an image dataset of the signed 30 letters composing the Spanish alphabet. Then, given that there are static and in-motion letters, two different kinds of neural networks have been tested and compared: convolutional neural networks (CNNs) and recurrent neural networks (RNNs). A comparative analysis of the experimental results highlights the importance of the spatial dimension with respect to the temporal dimension in sign interpretation. So, CNNs obtain a much better accuracy, with 96.42% being the maximum value. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease is a progressive, disabling neurodegenerative disorder associated with significant economic burden for patients and caregivers. The objective of this study was to compare the direct and indirect economic burden of Parkinson's patients' caregivers with demographically matched controls in the United States, in the 5 years after first diagnosis of Parkinson's disease.Methods: Policyholders (18-64 years old) linked to a Parkinson's disease patient (≥2 diagnoses of Parkinson's disease; first diagnosis is the index date) from January 1, 1998 to March 31, 2014, were selected from a private-insurer claims database and categorized as Parkinson's caregivers. Eligible Parkinson's caregivers were matched 1:5 to policyholders with a non-Parkinson's dependent (controls). Multivariable regression adjusted for baseline characteristics estimated direct costs (all-cause insurer cost [medical and prescription] and comorbidity-related medical costs; patient out-of-pocket costs) and indirect costs (disability and medically related absenteeism costs). Income progression was also compared between cohorts.Results: A total of 1211 eligible Parkinson's caregivers (mean age, 56 years; 54% female) were matched to 6055 controls. In adjusted analyses, Parkinson's caregivers incurred significantly higher year 1 total all-cause insurer costs ($8999 vs $7117) and medical costs ($7081 vs $5568) (both P < 0.01) and higher prescription costs (range for years 1-5, $2506-2573 vs $1405-$1687) and total out-of-pocket costs ($1259-1585 vs $902-$1192) in years 1-5 (all P < 0.01). Parkinson's caregivers had significantly higher adjusted indirect costs in years 1-3 (range for years 1-3, $2054-$2464 vs $1681-$1857; all P < 0.05) and higher cumulative income loss over 5 years ($5967 vs $2634 by year 5; P for interaction = 0.03).Conclusions: Parkinson's caregivers exhibited higher direct and indirect costs and greater income loss compared with matched controls. © 2018 International Parkinson and Movement Disorder Society © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

The article presents the discussion on using the norms of evidence-based medicine (EBM) and clinical research. Topics include describing the epistemic divide between computer science and clinical research as coming down to a difference in methods between the disciplines; and advocating for rigorous evaluation of medical ML using clinical research norms and methods.

The Non‐Motor Symptoms Scale (NMSS) was developed and validated in 2007 as the first instrument for the comprehensive assessment of a range of non‐motor symptoms in Parkinson's disease (PD). Thirteen years have elapsed since its introduction and extensive international validation with good psychometric attributes has been carried out. Here, we review the validation data of the NMSS and its cross‐validity with other scales, and describe the key evidence derived from use of the NMSS in clinical studies. To date, over 100 clinical studies and trials have made use of it as an outcome measure, showing consistent and strong correlations between NMSS burden and health‐related quality of life measures. Moreover, the scale has shown to be capable of detecting longitudinal changes in non‐motor symptoms, where studies have shown differential changes over time of several of the NMSS domains. The scale has become a key outcome in several randomized clinical trials. Highlighting the prevalence and importance of non‐motor symptoms to quality of life in patients with PD, the development of NMSS has also been useful in signposting clinical and biomarker based research addressing non‐motor symptoms in PD. [ABSTRACT FROM AUTHOR]

Objective: The aims of the present study were: 1) to calculate the change of direction (COD) deficit (using a modified version of the 505 test and 10 m sprint time), and (2) to examine the differences in linear sprint, jump and COD performances, as well as COD deficit, between under-13 (U13) and under-15 (U15) male handball players. Methods: One hundred and nineteen young male handball players (under-13 [U13; n = 82] and under-15 [U15; n = 37]). Tests included anthropometric measurements, countermovement jump (CMJ), triple leg-hop for distance, linear sprint test (5, 10 and 20 m), and a modified version of the 505 COD test. Results: Results showed moderate to very large differences (P < 0.05) in age, predicted age at peak height velocity (APHV), distance from PHV (DPHV), height, and body mass between the age categories. Moreover, U15 players demonstrated higher performances in all jump tests and lower sprint times in 10- (ES = 0.84) and 20-m (ES = 0.51) and a higher 505 deficit (ES = 0.38) than the U13 players (P < 0.05). However, no significant differences were observed for the 505 COD test between groups (ES = 0.12; P > 0.05). Conclusions: Our results suggest that during the transition from pre- to post-puberty, young handball players should focus on transferring their progressive improvements in strength, speed, and power capacities to COD performance. [ABSTRACT FROM AUTHOR]

• The Barthel Index and modified Ranking Scale are valid and reliable outcome measures that can be used to assess level of disability in Parkinson disease (PD). • Along with PD specific assessments, the Barthel Index and modified Rankin Scale are accurate tools for patients in clinical settings. • The Barthel Index and modified Ranking Scale can be used in future research to measure level of disability in the ON and OFF medication phase, particularly. Independence in activities of daily living (ADL) is one of the most important aspects in planning treatment for people with Parkinson disease (PD). The Barthel Index (BI) and modified Rankin Scale (mRS) are commonly used in neurological diseases. This study was conducted to confirm the validity and reliability of the BI and mRS in PD during ON and OFF medication phases. We included 260 individuals with a diagnosis of idiopathic PD. The disability in ADL was measured by the BI, mRS, Parkinson's Disease Questionnaire-39 (PDQ-39), Unified Parkinson Disease Rating Scale-Activities of Daily Living (UPDRS-ADL), and Schwab and England ADL scale (SE). Test–retest, inter-rater reliability, and internal consistency were assessed by the intra-class correlation (ICC) and Cronbach α coefficients. Dimensionality was evaluated by factor analysis. Convergent validity was assessed by the SE, Berg Balance Scale (BBS), PDQ-39 and UPDRS-ADL. For the 260 participants (187 [71.9%] males; mean [SD] age 60.3 [12.3] years), both the BI and mRS achieved an acceptable level of test–retest and inter-rater reliability (ICC = 0.77 to 0.91) in ON and OFF medication phases. The Cronbach α for BI was 0.85 and 0.88, respectively. We found 1 and 2 factors for BI in ON and OFF phases, respectively. Investigation of convergent validity showed moderate to high correlation for the BI with the UPDRS-ADL, SE, PDQ-39 (ADL), BBS and mRS scores in ON and OFF phases (ρ = 0.51–0.74) and mRS with SE, UPDRS-ADL, PDQ-39 (ADL) and BBS scores (ρ = 0.48–0.82). The BI and mRS showed acceptable validity and reliability to measure the degree of disability in patients with PD in daily activities in both ON and OFF medication phases. [ABSTRACT FROM AUTHOR]

The EARLYSTIM Study compared deep brain stimulation (DBS) with best medical treatment (BMT) over 2-years, showing a between-group difference of 8.0 from baseline in favor of DBS in health-related quality of life (HRQoL), measured with the PDQ-39 SI (summary index). This study obtained complementary information about the importance of the change in HRQoL as measured by the PDQ-39, using anchor-based (Patient Global Impression of Change, PGIC) and distribution-based techniques (magnitude of change, effect size, thresholds, distribution of benefit) applied to the EARLYSTIM study data. Anchor-based techniques showed a difference follow-up–baseline for patients who reported "minimal improvement" of -5.8 [-9.9, -1.6] (mean [95%CI]) in the DBS group vs -2.9 [-9.0, 3.1] in the BMT group. As the vast majority (80.8%) of DBS patients reported "much or very much improvement", this difference was explored for the latter group and amounted to -8.7 for the DBS group and -6.5 in the BMT group. Distribution-based techniques that analyzed the relative change and treatment effect size showed a moderate benefit of the DBS on the HRQoL, whereas a slight worsening was observed in the BMT group. The change in the DBS group (-7.8) was higher than the MIC (Minimally Important Change) estimated value (-5.8 by the anchor; -6.3 by triangulation of thresholds), but not in the BMT (0.2 vs. -3.0 to -5.4, respectively). Almost 90% of the patients in the DBS group declared some improvement (58.3% and 56.7% beyond the estimated MIC), which was significantly different from the BMT group whose proportions were 32.0% and 30.3%, respectively. The number needed to treat to improve ≥1 MIC by DBS vs BMT was 3.8. Change in depression, disability and pain influenced the improvement of the DBS group. DBS improved HRQoL in a high proportion of patients to a significant and moderate degree, at 2 years follow-up. [ABSTRACT FROM AUTHOR]

This article argues that although electronic governance has been institutionalised as a public policy that promotes access to information, transparency and control of public institutions by citizens, the introduction of electronic governance has not immediately generated a positive impact on the reduction of corruption and that, consequently, other complementary actions are necessary in order to execute the public policies of electronic government. [ABSTRACT FROM AUTHOR]

Background and purpose: The objective was to determine the frequency, demographic and clinical correlates [such as age, sex, Parkinson's disease (PD) severity and dopaminergic treatment] of impulse control disorder (ICD) symptoms and related behaviors in patients with PD with (PD‐D) and without (PD‐ND) dementia. Methods: We analyzed historical data from a national, multi‐center, cross‐sectional database and assessed ICDs and related behaviors with the Scale for Evaluation of Neuropsychiatric Disorders in Parkinson's Disease administered as a semi‐structured interview to patients with PD‐D (n = 85) and PD‐ND (n = 444) and their informants. Results: Dopamine agonist therapy use was common and similar in the two groups (78.8% in PD‐D vs. 82.9% in PD‐ND), but ICDs (23.5% vs. 13.3%, P = 0.02), hobbyism‐punding (32.9% vs. 10.6%, P < 0.001) and dopaminergic medication abuse (8.2% vs. 3.2%, P = 0.03) were more common in the PD‐D group. Conclusions: The finding that ICDs and related behaviors are more common in patients with PD frequently treated with dopamine agonists who also have comorbid dementia suggests that the neural substrates associated with PD dementia may also predispose to development of compulsive behaviors. [ABSTRACT FROM AUTHOR]

Digital contact tracing, in combination with widespread testing, has been a focal point for many plans to "reopen" economies while containing the spread of Covid‐19. Most digital contact tracing projects in the United States and Europe have prioritized privacy protections in the form of local storage of data on smartphones and the deidentification of information. However, in the prioritization of privacy in this narrow form, there is not sufficient attention given to weighing ethical trade‐offs within the context of a public health pandemic or to the need to evaluate safety and effectiveness of software‐based technology applied to public health. [ABSTRACT FROM AUTHOR]

The authors explore the considerations for the equitable design of design bioethics (DB) that were not mentioned in the article "DB: A theoretical framework and argument for innovation in bioethics research," by G. Pavarini and her colleagues, which was published within the issue. Topics mentioned include the cause and effect of hegemonic design bias, the challenge of achieving equitable access to massive open online courses, and the equity-focused actions to prevent digital discrimination.

Health-related quality of life is a patient-reported outcome that complements clinical evaluation and provides information about disease activity and effects of the treatment. The objective of this review is to present the conceptual framework, the measures, and some of their most relevant applications in the field of Parkinson's disease and movement disorders. Health-related quality of life is a subjective, individual, and multidimensional construct, and its main dimensions are physical, mental, and social, besides global perceptions of health and personal domains. Health-related quality of life measurement is carried out by means of questionnaires or scales, ideally self-applied by patients, and has a diversity of important applications for clinical practice, research, and health policy. Movement disorders and Parkinson's disease are complex conditions impacting all components of patients' health-related quality of life. The use of health-related quality of life tools provides important information on a variety of aspects that are important to patients while complementing clinical evaluations. In particular, studies using this kind of assessment can identify and monitor the most important health-related quality of life determinant factors, allowing tailored assistance and prioritized interventions. In addition, maintaining or improving the patients' health-related quality of life is an objective of care for chronic diseases and, therefore, it has to be monitored over time and as an outcome of clinical trials. Several methods are available for the interpretation of the change in scores of health-related quality of life measures, although a definitive agreement on the most appropriate method is yet to be determined. Presently, health-related quality of life assessment is an important outcome for research and management of chronic conditions such as Parkinson's disease and other movement disorders. © 2016 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

The issue of public policy on accountability, transparency, and access to public information has now become a trend in most countries of the world. Among one of its objectives when evaluating institutions and public servants by their administrative and governmental decisions is to decrease corruption. Mexico is already a formal democracy, but the quality of its governments is still very low. Although these have been elected by the citizens, they continue without being accountable. In this paper, we analyze as a case study the State's last recourse to repair what bad management and privileges caused: the national anticorruption system, its formation, and operation. We enunciate the limits and scope it faces. [ABSTRACT FROM AUTHOR]

Background and purpose: A composite instrument able to rapidly and reliably assess the most relevant motor and non‐motor afflictions suffered by Parkinson's disease (PD) patients in a real world clinic setting is an unmet need. The recently validated PD Composite Scale (PDCS) was designed to fulfil this gap as a quick, comprehensive PD assessment. The objective of this study was extensive evaluation of the PDCS's clinimetric properties using a large international sample. Methods: This was a cross‐sectional study in which the PDCS, the Movement Disorder Society Unified Parkinson's Disease Rating Scale and the Clinical Impression of Severity Index for PD were applied. Basic clinimetric attributes of the PDCS were analysed. Results: In total, 776 PD patients were included. The PDCS total score showed negligible floor and ceiling effects. Three factors (54.5% of the variance) were identified: factor 1 included motor impairment, fluctuations and disability; factor 2, non‐motor symptoms; and factor 3, tremor and complications of therapy. Cronbach's alpha was from 0.66 to 0.79. Inter‐rater reliability showed weighted kappa values from 0.79 to 0.98 for items and intraclass correlation coefficient values from 0.95 (Disability) to 0.99 (Motor and total score). The Bland–Altmann method, however, showed irregular concordance. PDCS standard error of measurement and convergent validity with equivalent constructs of other measures were satisfactory (≥0.70). PDCS scores significantly differed by Hoehn and Yahr stage. Conclusion: Overall, in line with previous findings, the PDCS is a feasible, acceptable, valid, reliable and precise instrument for quickly and comprehensively assessing PD patients. [ABSTRACT FROM AUTHOR]

Background. The Parkinson's Disease Composite Scale (PDCS) is a recently developed easy-to-use tool enabling a timely but comprehensive assessment of Parkinson's disease (PD)-related symptoms. Although the PDCS has been extensively validated, its responsiveness to acute levodopa challenge has not been demonstrated yet. Objective. To investigate the correlation between changes in the motor examination part of the Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the PDCS motor scores during acute levodopa challenge and calculate a cutoff range on the PDCS indicating clinically relevant improvement. Methods. A consecutive series of 100 patients with parkinsonism were assessed using the motor examination sections of the MDS-UPDRS and the PDCS at least 12 hours after the last levodopa dose and after the administration of a single dose of a suprathreshold immediate formulation of levodopa/benserazide reaching the "best ON." Results. There was a high correlation between changes in the MDS-UPDRS and the PDCS motor scores (Spearman's rho = 0.73, p<0.001). Receiver operating characteristic analysis revealed that a 14.6%–18.5% improvement in the PDCS motor scores corresponds to a 20–30% improvement in the MDS-UPDRS motor examination. Conclusions. The PDCS can reliably and adequately respond to an acute levodopa challenge. Any improvements in PDCS motor scores exceeding the 14.6–18.5% threshold could represent a clinically relevant response to levodopa. [ABSTRACT FROM AUTHOR]

Introduction: In the elderly, functional balance, fear of falling, and independence in daily living activities are interrelated; however, this relationship may change under the influence of drug phase and the severity of disease in individuals with idiopathic Parkinson disease. This study aimed to investigate the association of functional balance, fear of falling, and independence in the Activities of Daily Living (ADL) with the drug on- and drug off-phases. Methods: A total of 140 patients with Parkinson disease (age: Mean±SD; 60.51±12.32 y) were evaluated in terms of their functional balance, fear of falling, and independence in their daily activities by the Berg Balance Scale (BBS), Fall Efficacy Scale-International (FES-I), and Unified Parkinson Disease Rating Scale-ADL (UPDRS-ADL), respectively, in drug on- and drug off-phases. The Hoehn and Yahr scale recorded global disease rating. The Spearman coefficient, Kruskal-Wallis, and Mann-Whitney tests were used to find out whether the distribution of scale scores differs with regard to functional balance or disease severity. Results: A strong correlation was found between the functional balance, fear of falling, and independence in ADL with both drug phases. The results also showed the significant difference in the distribution of the FES-I and UPDRS-ADL scores with regard to functional balance (except independence in ADL in drug off-phase). Also, the distribution of the scores of BBS, FES-I, and UPDRS-ADL showed significant differences with regard to disease severity. Conclusion: The study showed a strong correlation between functional balance, fear of falling, and independence in ADL that can be affected by the drug phase and severity of the disease. However, more studies are needed to understand this relationship precisely. [ABSTRACT FROM AUTHOR]

Rehabilitation is essential for disabled people to achieve the highest level of functional independence, reducing or preventing impairments. Nonetheless, this process can be long and expensive. This fact together with the ageing phenomenon has become a critical issue for both clinicians and patients. In this sense, technological solutions may be beneficial since they reduce the costs and increase the number of patients per caregiver, which makes them more accessible. In addition, they provide access to rehabilitation services for those facing physical, financial, and/or attitudinal barriers. This paper presents the state of the art of the assistive rehabilitation technologies for different recovery methods starting from in-person sessions to complementary at-home activities. [ABSTRACT FROM AUTHOR]

Background: Because of the prevalence and impact of sleep disorders in Parkinson's disease (PD), valid instruments for their evaluation and monitoring are necessary. However, some nocturnal sleep disorders may go unnoticed by patients themselves. Objectives: To validate a pan‐Spanish version of the Parkinson's Disease Sleep Scale Version 2 (PDSS‐2) and to test the relationships between the PDSS‐2 and a PDSS‐2 roommate version. Methods: PD patients (n = 399) from seven Spanish‐speaking countries were included. In addition to the tested PDSS‐2 scales, valid measures for sleep disorders and both motor and nonmotor manifestations were applied. Acceptability, dimensionality, reliability, precision, and construct validity were explored, as well as discrepancies and agreement between the PDSS‐2 and the roommate version. Results: PDSS‐2 showed negligible floor and ceiling effects. Four factors (57% of the variance) were identified. Reliability parameters were satisfactory: alpha = 0.84; item homogeneity coefficient = 0.27; corrected item total correlation = 0.28 to 0.61; and test‐retest reliability (average kappa = 0.70; intraclass correlation coefficient [ICC] = 0.83). The standard error of measurement was 5.84, and correlations with other scales assessing nocturnal sleep were high (rS = 0.62–0.56). In comparison to the patient‐based total score, the by proxy total score showed no significant difference, high correlation (rS = 0.70), and acceptable agreement (ICC = 0.69), but there were discrepancies in two or more points in 18% of item scores. Conclusions: The Spanish version of the PDSS‐2 has shown satisfactory clinimetric attributes. Acceptability and precision data are presented for the first time. The PDSS‐2 roommate version could be useful to complement the patient‐based evaluation, but additional studies are needed. [ABSTRACT FROM AUTHOR]

Objective: Real-life observational report of clinical efficacy of bilateral subthalamic stimulation (STN-DBS), apomorphine (APO), and intrajejunal levodopa infusion (IJLI) on quality of life, motor, and nonmotor symptoms (NMS) in Parkinson's disease (PD).Methods: In this prospective, multicenter, international, real-life cohort observation study of 173 PD patients undergoing STN-DBS (n = 101), IJLI (n = 33), or APO (n = 39) were followed-up using PDQuestionnaire-8, NMSScale (NMSS), Unified PD Rating Scale (UPDRS)-III, UPDRS-IV, and levodopa equivalent daily dose (LEDD) before and 6 months after intervention. Outcome changes were analyzed with Wilcoxon signed-rank or paired t test when parametric tests were applicable. Multiple comparisons were corrected (multiple treatments/scales). Effect strengths were quantified with relative changes, effect size, and number needed to treat. Analyses were computed before and after propensity score matching, balancing demographic and clinical characteristics.Results: In all groups, PDQuestionnaire-8, UPDRS-IV, and NMSS total scores improved significantly at follow-up. Levodopa equivalent daily dose was significantly reduced after STN-DBS. Explorative NMSS domain analyses resulted in distinct profiles: STN-DBS improved urinary/sexual functions, mood/cognition, sleep/fatigue, and the miscellaneous domain. IJLI improved the 3 latter domains and gastrointestinal symptoms. APO improved mood/cognition, perceptual problems/hallucinations, attention/memory, and the miscellaneous domain. Overall, STN-DBS and IJLI seemed favorable for NMSS total score, and APO favorable for neuropsychological/neuropsychiatric NMS and PDQuestionnaire-8 outcome.Conclusions: This is the first comparison of quality of life, nonmotor. and motor outcomes in PD patients undergoing STN-DBS, IJLI, and APO in a real-life cohort. Distinct effect profiles were identified for each treatment option. Our results highlight the importance of holistic nonmotor and motor symptoms assessments to personalize treatment choices. © 2019 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Non‐motor symptoms (NMS) are integral to Parkinson's disease (PD) and have a detrimental effect on patients and their caregivers. Clinical quantification has been aided by the development of comprehensive assessments such as the Non‐Motor Symptoms Questionnaire (NMSQuest) and Scale (NMSS). The NMSS has been widely used in clinical studies and trials; however, since its validation in 2007, our understanding of NMS has changed substantially. With the support of the International Parkinson and Movement Disorder Society (IPMDS), after a detailed peer review an initiative to develop an updated version of NMSS, the MDS‐NMS was launched in 2015. Objective: This paper encapsulates the data from the pre‐validation phases carried out under the auspices of the IPMDS Non‐Motor PD Study Group. Methods: Item selection and wording (formatted as a rater‐based tool) were based on the NMSS, literature review, and expert consensus. Neurologists, PD patients, and healthy controls were included in the cognitive pretesting and administration of the preliminary version of the MDS‐NMS. Primary data on acceptability and reliability were obtained. Results: The pilot study, carried out in English in the United Kingdom and the United States, demonstrated that the preliminary version of the MDS‐NMS was comprehensive, understandable, and appropriate. Data quality was excellent; moderate floor effect was present in patients for most MDS‐MNS domains, with some components showing weak internal consistency. The results led to additional instrument modifications. Conclusion: Qualitative and quantitative research results have led to an updated NMSS, the definitive version of the MDS‐NMS, which is currently being validated. [ABSTRACT FROM AUTHOR]

Applications of facial recognition technology (FRT) in health care settings have been developed to identify and monitor patients as well as to diagnose genetic, medical, and behavioral conditions. The use of FRT in health care suggests the importance of informed consent, data input and analysis quality, effective communication about incidental findings, and potential influence on patient-clinician relationships. Privacy and data protection are thought to present challenges for the use of FRT for health applications. [ABSTRACT FROM AUTHOR]

Purpose. Since fear of falling may be one of the main problems in people with Parkinson's disease (PD), its assessment with valid tools is necessary in both drug phases. This study was carried out to investigate the psychometric attributes of the Fall Efficacy Scale-International (FES-I) in people with PD, both in On and Off phases. Methods. One hundred twenty-four patients with PD (mean age ± standard deviation, 60.33 ± 12.59 years) were assessed with the FES-I, both in On- and Off-drug phases. Dimensionality, internal consistency, and test-retest reliability were, respectively, explored by means of factor analysis, Cronbach's alpha, and Intraclass Correlation Coefficient. Convergent validity of FES-I was established with Visual Analog Scale-Fear of Falling, Berg Balance Scale, and Functional Reach Test. Parkinson's Disease Questionnaire-39 and Unified Parkinson Disease Rating Scale-Activities of Daily Living were also applied. Discriminative validity was tested between patients with and without a history of falling. Results. Factor analysis showed two factors for On- and one factor for Off-drug phase. Internal consistency (α = 0.96, On phase; 0.98, Off phase) and test-retest reliability (0.94; 0.91) were satisfactory in both drug phases. There was a moderate/high correlation (rS = |0.50–0.70|) between FES-I and Visual Analog Scale-Fear of Falling, Berg Balance Scale, and Functional Reach Test. Parkinson's Disease Questionnaire-39 and Unified Parkinson Disease Rating Scale-Activities of Daily Living were achieved in both drug phases too. The sensitivity of FES-I to discriminate Parkinson's disease with and without falls showed moderate effect size in both phases. Conclusion. This study verified that FES-I is unidimensional, reliable, and valid to measure the Fear of Falling during On- and Off-drug phases in people with PD. [ABSTRACT FROM AUTHOR]

Background: Little research has been conducted regarding the relationship between sleep disorders and different pain types in Parkinson's disease (PD). Objective: To explore the influence of the various pain subtypes experienced by PD patients on sleep. Methods: Three hundred consecutive PD patients were assessed with the PD Sleep Scale‐Version 2 (PDSS‐2), King's PD Pain Scale (KPPS), King's PD Pain Questionnaire (KPPQ), Visual Analog Scales for Pain (VAS‐Pain), and Hospital Anxiety and Depression Scale. Results: According to the PDSS‐2, 99.3% of our sample suffered from at least one sleep issue. Those who reported experiencing any modality of pain suffered significantly more from sleep disorders than those who did not (all, P < 0.003). The PDSS‐2 showed moderate‐to‐high correlations with the KPPS (rS = 0.57), KPPQ (0.57), and VAS‐Pain (0.35). When PDSS‐2 items 10 to 12 (pain‐related) were excluded, the correlation values decreased to 0.50, 0.51, and 0.28, respectively, while these items showed moderate‐to‐high correlations with KPPS (0.56), KPPQ (0.54), and VAS‐Pain (0.42). Among the variables analyzed, multiple linear regression models suggested that KPPS and KPPQ were the most relevant predictors of sleep disorders (as per the PDSS‐2), although following exclusion of PDSS‐2 pain items, depression was the relevant predictor. Depression and anxiety were the most relevant predictors in the analysis involving the VAS‐Pain. Regression analysis, considering only the KPPS domains, showed that nocturnal and musculoskeletal pains were the best predictors of overall nocturnal sleep disorder. Conclusions: Pain showed a moderate association with nocturnal sleep dysfunction in PD. Some pain subtypes had a greater effect on sleep than others. [ABSTRACT FROM AUTHOR]

Background: Having an appropriate tool for assessment of the balance status during the drug off-phase in idiopathic Parkinson's disease (PD) is relevant for clinical and research settings. Our objective was to assess the clinimetric properties of the Berg balance scale (BBS) during drug off-phase in PD.Method: Balance of 98 PD patients (mean age ± SD, 59.19 ± 10.88 years) was evaluated with the BBS. Other assessments in the study included the Fall Efficacy Scale-International (FES-I), Functional Reach Test (FRT), Section II of the Unified Parkinson's Disease Rating Scale-3.0, Parkinson's Disease Questionnaire-39 (PDQ-39), and Schwab and England Activities of Daily Living Scale. All evaluations took place during the drug off-phase. Internal consistency and inter- and intra-rater reliability were evaluated by Cronbach's alpha coefficient and intraclass correlation coefficient, respectively. Dimensionality was explored by factor analysis. Discriminative validity was tested by comparing BBS score between PD patients with and without a history of falling.Results: Internal consistency was high (α = 0.98), as were intra- and inter-rater reliability (ICC = 0.98 and 0.95, respectively). Factor analysis identified only one dimension for the BBS, whose convergent validity with FES-I, FRT, and domain mobility of the PDQ-39 were moderate or high (rS = |0.60-0.74|). Correlation of BBS with functional scales and PDQ-39 Summary Index was moderate (rS = |0.45-0.62|). Finally, the BBS showed a moderate strength to discriminate between PD patients with and without a history of falling.Conclusion: Our study suggests that BBS has satisfactory internal consistency, reliability, and construct validity for measuring functional balance in people with PD during the drug off-phase. [ABSTRACT FROM AUTHOR]

The article explores the ethics of corporate surveillance of health-related data focusing on data protection and privacy. It considers research by Levinson et al. which discussed factors for assessing the ethical and legal duties of public health agencies involved in surveillance of a high-risk behavior raises, including the harm principle and the liberty-limiting continuum. It cites an artificial intelligence tool introduced by Facebook identifying users at high risk of suicide.

Background and purpose: Pain is highly prevalent in Parkinson's disease (PD), impacting patients’ ability, mood and quality of life. Detecting the presence of pain in its multiple modalities is necessary for adequate personalized management of PD. A 14‐item, PD‐specific, patient‐based questionnaire (the King's Parkinson's Disease Pain Questionnaire, KPPQ) was designed corresponding to the rater‐based KPP Scale (KPPS). The present multicentre study was aimed at testing the validity of this screening tool. Methods: First, a comparison between the KPPQ scores of patients and matched controls was performed. Next, convergent validity, reproducibility (test–retest) and diagnostic performance of the questionnaire were analysed. Results: Data from 300 patients and 150 controls are reported. PD patients declared significantly more pain symptoms than controls (3.96 ± 2.56 vs. 2.17 ± 1.39; P < 0.0001). The KPPQ convergent validity was high with KPPS total score (rS = 0.80) but weak or moderate with other pain assessments. Test–retest reliability was satisfactory with kappa values ≥0.65 except for item 5, Dyskinetic pains (κ = 0.44), and the intraclass correlation coefficient (ICC) for the KPPQ total score was 0.98. After the scores of the KPPS were adapted for screening (0, no symptom; ≥1, symptom present), a good agreement was found between the KPPQ and the KPPS (ICC = 0.88). A strong correlation (rS = 0.80) between the two instruments was found. The diagnostic parameters of the KPPQ were very satisfactory as a whole, with a global accuracy of 78.3%–98.3%. Conclusions: These results suggest that the KPPQ is a useful, reliable and valid screening instrument for pain in PD to advance patient‐related outcomes. [ABSTRACT FROM AUTHOR]

The article discusses the impact of the surveillance approach to medical nonadherence on the clinician-patient alliance. Topics covered include directly observed therapy's (DOT) violation of an individual's privacy and autonomy, the primarily financial and not public health benefits of smart pills, and the main reasons of side effects, cost, and forgetfulness, among others behind medication nonadherence. Also noted are ethical concerns on the data collection done in digital medicine.

Machine learning is a method for predicting clinically relevant variables, such as opportunities for early intervention, potential treatment response, prognosis, and health outcomes. This commentary examines the following ethical questions about machine learning in a case of a patient with new onset psychosis: (1) When is clinical innovation ethically acceptable? (2) How should clinicians communicate with patients about the ethical issues raised by a machine learning predictive model? [ABSTRACT FROM AUTHOR]

Aimed at building autonomous service robots, reasoning, perception, and action should be properly integrated. In this paper, the depth cue has been analysed as an early stage given its importance for robotic tasks. So, from neuroscience findings, a hierarchical four-level dorsal architecture has been designed and implemented. Mainly, from a stereo image pair, a set of complex Gabor filters is applied for estimating an egocentric quantitative disparity map. This map leads to a quantitative depth scene representation that provides the raw input for a qualitative approach. So, the reasoning method infers the data required to make the right decision at any time. As it will be shown, the experimental results highlight the robust performance of the biologically inspired approach presented in this paper. [ABSTRACT FROM AUTHOR]

Background: The relationship between Health-Related Quality of Life (HRQoL) and MDS-UPDRS has not been fully studied so far. The aim of this study was to evaluate the relationship between all MDS-UPDRS components and HRQoL in a representative international cohort of PD patients.Methods: We collected demographic and disease-related data as well as MDS-UPDRS and PDQ8 scales. Data were analyzed using correlations between PDQ8 and all MDS-UPDRS items, subsequently two hierarchical multiple regressions were performed, first between the scores of the MDS-UPDRS Parts and PDQ8 and second between individual items from those Parts demonstrating significant relationship to PDQ8 scores in the first regression. LASSO regression analyses were performed to evaluate the relationship between PDQ8 and all individual MDS-UPDRS items.Results: A total of 3206 PD patients were included in the study. In the first regression analysis, PDQ8 was significantly related to MDS-UPDRS parts I and II, but not to III and IV. In the second regression model, significant contributions to PDQ8 were found for Part I items Fatigue, Pain, Depressed mood, Apathy; and Part II items Dressing, Doing hobbies, Freezing, Speech and Tremor. In the LASSO analysis, six Part I, seven Part II, three Part III and one Part IV items contributed to PDQ8 scores. The five items most significantly related to the model were Depressed mood, Dressing, Apathy, Pain and Fatigue.Conclusions: This is so far the largest study related to HRQoL issues in PD. Restrictions in activities of daily living and non-motor symptoms significantly contribute to HRQoL in PD. [ABSTRACT FROM AUTHOR]

Holistic management of Parkinson's disease, now recognised as a combined motor and nonmotor disorder, remains a key unmet need. Such management needs relatively accurate definition of the various stages of Parkinson's from early untreated to late palliative as each stage calls for personalised therapies. Management also needs to have a robust knowledge of the progression pattern and clinical heterogeneity of the presentation of Parkinson's which may manifest in a motor dominant or nonmotor dominant manner. The 'advanced' stages of Parkinson's disease qualify for advanced treatments such as with continuous infusion or stereotactic surgery yet the concept of 'advanced Parkinson's disease' (APD) remains controversial in spite of growing knowledge of the natural history of the motor syndrome of PD. Advanced PD is currently largely defined on the basis of consensus opinion and thus with several caveats. Nonmotor aspects of PD may also reflect advancing course of the disorder, so far not reflected in usual scale based assessments which are largely focussed on motor symptoms. In this paper, we discuss the problems with current definitions of 'advanced' PD and also propose the term 'complex phase' Parkinson's disease as an alternative which takes into account a multimodal symptoms and biomarker based approach in addition to patient preference. [ABSTRACT FROM AUTHOR]

Psychiatry is rapidly adopting digital phenotyping and artificial intelligence/machine learning tools to study mental illness based on tracking participants' locations, online activity, phone and text message usage, heart rate, sleep, physical activity, and more. Existing ethical frameworks for return of individual research results (IRRs) are inadequate to guide researchers for when, if, and how to return this unprecedented number of potentially sensitive results about each participant's real-world behavior. To address this gap, we convened an interdisciplinary expert working group, supported by a National Institute of Mental Health grant. Building on established guidelines and the emerging norm of returning results in participant-centered research, we present a novel framework specific to the ethical, legal, and social implications of returning IRRs in digital phenotyping research. Our framework offers researchers, clinicians, and Institutional Review Boards (IRBs) urgently needed guidance, and the principles developed here in the context of psychiatry will be readily adaptable to other therapeutic areas. [ABSTRACT FROM AUTHOR]

Background The Movement Disorder Society Unified Parkinson's Disease Rating Scale ( MDS- UPDRS) is a newly developed tool to assess Parkinson's disease ( PD). Changes in scores on the scale over the course of PD, including increasing disease duration and Hoehn and Yahr ( HY) stages, have not been described. The objectives of this study were to analyze MDS- UPDRS scores on Parts I through IV and their differences based on HY stage and disease duration in a large cohort of patients with PD. Methods For this cross-sectional study, demographic data and MDS- UPDRS scores were collected, including HY stage. Subscores on MDS- UPDRS Parts I through IV were analyzed using 1-way analyses of variance for each HY stage and in 5-year increments of disease duration. Part III (motor assessment) scores were analyzed separately for on and off states. Results The mean age of the 3206 patients was 65.8 ± 10.6 years, 53.3% were men, the mean disease duration was 11.5 ± 4.6 years, and the median HY stage was 2 (range, 0-5); 2156 patients were examined in an on state and 987 were examined in an off state. Scores for all MDS- UPDRS parts increased significantly through HY stages 1 through 5, with an average increase of 3.8, 7.7, 14.6, and 2.0 points consecutively for parts I through IV, respectively. For the 5-year increments of disease duration, MDS- UPDRS subscores increased by an average of 1.6, 3.3, 4.2, and 1.4 points consecutively for parts I through IV, respectively. This increase was significant only during the first 15 years of disease for all 4 parts, including part III scores evaluated in both on and off states. Conclusions MDS- UPDRS scores for all 4 parts increase significantly with every HY stage and also with 5-year increments of disease duration in the first 15 years of the disease. [ABSTRACT FROM AUTHOR]

Parkinson's disease is a complex neurodegenerative disorder characterized by motor and non-motor symptoms, with neuropsychiatric manifestations among the most frequent non-motor symptoms. Health-related quality of life is a patient-reported outcome that reflects the impact of the disease on physical, mental, and social wellbeing, and on other aspects of patient’ life. Although older studies on health-related quality of life in Parkinson's disease mainly investigated the role of the motor impairment, recent research focused on non-motor symptoms has highlighted the critical role that behavioural disturbances due to neuropsychiatric symptoms play in determining health related quality of life. A considerable number of studies have demonstrated the importance of depression as a determinant of health-related quality of life in this population, but less evidence is available regarding the role of other neuropsychiatric symptoms such as anxiety, apathy, psychosis, and impulse control disorders. This narrative review analyses recent literature on this topic, focusing on studies in which neuropsychiatric symptoms were investigated as potential determinants of quality of life using regression techniques, including discussion of the assessment tools used. [ABSTRACT FROM AUTHOR]

Pathogens have evolved unique mechanisms to breach the cell surface barrier and manipulate the host immune response to establish a productive infection. Proteins exposed to the extracellular environment, both cell surface-expressed receptors and secreted proteins, are essential targets for initial invasion and play key roles in pathogen recognition and subsequent immunoregulatory processes. The identification of the host and pathogen extracellular molecules and their interaction networks is fundamental to understanding tissue tropism and pathogenesis and to inform the development of therapeutic strategies. Nevertheless, the characterization of the proteins that function in the host-pathogen interface has been challenging, largely due to the technical challenges associated with detection of extracellular protein interactions. This review discusses available technologies for the high throughput study of extracellular protein interactions between pathogens and their hosts, with a focus on mammalian viruses and bacteria. Emerging work illustrates a rich landscape for extracellular host-pathogen interaction and points towards the evolution of multifunctional pathogen-encoded proteins. Further development and application of technologies for genome-wide identification of extracellular protein interactions will be important in deciphering functional host-pathogen interaction networks, laying the foundation for development of novel therapeutics. [ABSTRACT FROM AUTHOR]

Parkinson's disease is a complex neurodegenerative disorder characterized by motor and non-motor symptoms, with neuropsychiatric manifestations among the most frequent non-motor symptoms. Health-related quality of life is a patient-reported outcome that reflects the impact of the disease on physical, mental, and social wellbeing, and on other aspects of patient’ life. Although older studies on health-related quality of life in Parkinson's disease mainly investigated the role of the motor impairment, recent research focused on non-motor symptoms has highlighted the critical role that behavioural disturbances due to neuropsychiatric symptoms play in determining health related quality of life. A considerable number of studies have demonstrated the importance of depression as a determinant of health-related quality of life in this population, but less evidence is available regarding the role of other neuropsychiatric symptoms such as anxiety, apathy, psychosis, and impulse control disorders. This narrative review analyses recent literature on this topic, focusing on studies in which neuropsychiatric symptoms were investigated as potential determinants of quality of life using regression techniques, including discussion of the assessment tools used. [ABSTRACT FROM AUTHOR]

Autophagy is important in a variety of cellular and pathophysiological situations; however, its role in immune responses remains elusive. Here, we show that among B cells, germinal center (GC) cells exhibited the highest rate of autophagy during viral infection. In contrast to mechanistic target of rapamycin complex 1 – dependent canonical autophagy, GC B cell autophagy occurred predominantly through a noncanonical pathway. B cell stimulation was sufficient to down-regulate canonical autophagy transiently while triggering noncanonical autophagy. Genetic ablation of WD repeat domain, phosphoinositide – interacting protein 2 in B cells alone enhanced this noncanonical autophagy, resulting in changes of mitochondrial homeostasis and alterations in GC and antibody-secreting cells. Thus, B cell activation prompts a temporal switch from canonical to noncanonical autophagy that is important in controlling B cell differentiation and fate. [ABSTRACT FROM AUTHOR]

Background: Due to the symptoms and the sleep disturbances it causes, Restless Legs Syndrome (RLS) has a negative impact on quality of life. Measurement of such impact can be performed by means of questionnaires, such as the Kohnen Restless Legs Syndrome-Quality of Life questionnaire (KRLS-QoL), a specific 12-item instrument that is self-applied by patients. The present study is aimed at performing a first formal validation study of this instrument.Methods: Eight hundred ninety-one patients were included for analysis. RLS severity was assessed by the International Restless Legs Scale (IRLS), Restless Legs Syndrome-6 scales (RLS-6), and Clinical Global Impression of Severity. In addition the Epworth Sleepiness Scale (ESS) was assessed. Acceptability, dimensionality, scaling assumptions, reliability, precision, hypotheses-related validity, and responsiveness were tested.Results: There were missing data in 3.58% patients. Floor and ceiling effects were low for the subscales, global evaluation, and summary index derived from items 1 to 11 after checking that scaling assumptions were met. Exploratory parallel factor analysis showed that the KRLS-QoL may be deemed unidimensional, ie, that all components of the scale are part of one overall general quality of life factor. Indexes of internal consistency (alpha = 0.88), item-total correlation (rS = 0.32-0.71), item homogeneity coefficient (0.41), and scale stability (ICC = 0.73) demonstrated a satisfactory reliability of the KRLS-QoL. Moderate or high correlations were obtained between KRLS-QoL scores and the IRLS, some components of the RLS-6, inter-KRLS-QoL domains, and global evaluations. Known-groups validity for severity levels grouping and responsiveness analysis results were satisfactory, the latter showing higher magnitudes of response for treated than for placebo arms.Conclusions: The KRLS-QoL was proven an acceptable, reliable, valid, and responsive measure to assess the impact of the RLS on quality of life. [ABSTRACT FROM AUTHOR]

Background Parkinson's disease (PD) is one of the factors which are associated with a higher risk of mortality during heat waves. The use of certain neuroleptic medications to control some of this disease's complications would appear to be related to an increase in heat-related mortality. Objective To analyse the relationship and quantify the short-term effect of high temperatures during heat wave episodes in Madrid on daily mortality and PD-related hospital admissions. Methods We used an ecological time-series study and fit Poisson regression models. We analysed the daily number of deaths due to PD and the number of daily PD-related emergency hospital admissions in the city of Madrid, using maximum daily temperature (°C) as the main environmental variable and chemical air pollution as covariates. We controlled for trend, seasonalities, and the autoregressive nature of the series. Results There was a maximum daily temperature of 30 °C at which PD-related admissions were at a minimum. Similarly, a temperature of 34 °C coincides with an increase in the number of admissions. For PD-related admissions, the Relative Risk (RR) for every increase of 1 °C above the threshold temperature was 1.13 IC95%:(1.03–1.23) at lags 1 and 5; and for daily PD-related mortality, the RR was 1.14 IC95%:(1.01–1.28) at lag 3. Conclusion Our results indicate that suffering from PD is a risk factor that contributes to the excess morbidity and mortality associated with high temperatures, and is relevant from the standpoint of public health prevention plans. [ABSTRACT FROM AUTHOR]

Background: The International Restless Legs Scale (IRLS) is the most widely used of the scales rating the severity of restless legs syndrome/Willis-Ekbom disease (RLS/WED). It has been well validated and is the primary end point for most of the therapeutic and nontherapeutic studies of RLS/WED. It has excellent psychometric properties, although it does not capture the severity of RLS under a wide variety of circumstances and times of day. Moreover, the IRLS has a large placebo effect.Methods: The Restless Legs Syndrome-6 Scale (RLS-6), however, takes another potentially valuable approach. Six items are rated on a 0-10 scale from no symptoms at 0 to very severe at 10. In addition to questions on satisfaction with sleep and sleepiness, the scale rates the severity of RLS for the past week under four separate circumstances: while falling asleep, during the night, during the day while sitting or lying, and during the day when moving around. The purpose of the current study is to report the validation of the RLS-6 under baseline and therapeutic conditions.Results: The RLS-6 seems to be an acceptable, reliable, precise, valid, and responsive instrument for the assessment of RLS severity in a specific and pragmatic manner.Conclusions: At present, we view the RLS-6 not as a replacement for the IRLS but as a supplement, as each scale provides information not captured by the other. [ABSTRACT FROM AUTHOR]

Parkinson's disease includes neuropsychiatric manifestations, such as depression, anxiety, apathy, psychosis, and impulse control disorders, which often are unreported by patients and caregivers or undetected by doctors. Given their substantial impact on patients and caregivers as well as the existence of effective therapies for some of these disorders, screening for neuropsychiatric symptoms is important. Instruments for screening have a particular methodology for validation, and their performance is expressed in terms of accuracy compared with formal diagnostic criteria. The present study reviews the attributes of the screening instruments applied for detection of the aforementioned major neuropsychiatric symptoms in Parkinson's disease. A quasi-systematic review (including predefined selection criteria, but not evaluating the quality of the reviewed studies) was carried out on the basis of previous systematic reviews (commissioned by the American Academy of Neurology and the Movement Disorder Society) and made current by conducting a literature search (2005-2014). For depression, 11 scales and questionnaires were shown to be valid for Parkinson's disease screening. The recently developed Parkinson Anxiety Scale and the Geriatric Anxiety Inventory demonstrate satisfactory properties as screening instruments for anxiety, and the Lille Apathy Rating Scale for detection of apathy. No scale adequately screens for psychosis, so a specific psychosis instrument should be developed. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (Questionnaire and Rating Scale) are valid for comprehensive screening of impulse control disorders, and the Parkinson's Disease-Sexual Addiction Screening Test for hypersexuality specifically. [ABSTRACT FROM AUTHOR]