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Introduction. In a degenerative disorder such as Parkinson’s disease (PD), it is important to establish clinical stages that allow to know the course of the disease. Our aim was to analyze whether a scale combining Hoehn and Yahr’s motor stage (H&Y) and the nonmotor symptoms burden (NMSB) (assessed by the nonmotor symptoms scale (NMSS)) provides information about the disability and the patient’s quality of life (QoL) with regard to a defined clinical stage. Materials and Methods. Cross-sectional study in which 603 PD patients from the COPPADIS cohort were classified according to H&Y (1, stage I; 2, stage II; 3, stage III; 4, stage IV/V) and NMSB (A: NMSS = 0–20; B: NMSS = 21–40; C: NMSS = 41–70; D: NMSS ≥ 71) in 16 stages (HY.NMSB, from 1A to 4D). QoL was assessed with the PDQ-39SI, PQ-10, and EUROHIS-QOL8 and disability with the Schwab&England ADL (Activities of Daily Living) scale. Results. A worse QoL and greater disability were observed at a higher stage of H&Y and NMSB (p

The cancer-associated fibroblast (CAF) marker podoplanin (PDPN) is generally correlated with poor clinical outcomes in cancer patients and thus represents a promising therapeutic target. Despite its biomedical relevance, basic aspects of PDPN biology such as its cellular functions and cell surface ligands remain poorly uncharacterized, thus challenging drug development. Here, we utilize a high throughput platform to elucidate the PDPN cell surface interactome, and uncover the neutrophil protein CD177 as a new binding partner. Quantitative proteomics analysis of the CAF phosphoproteome reveals a role for PDPN in cell signaling, growth and actomyosin contractility, among other processes. Moreover, cellular assays demonstrate that CD177 is a functional antagonist, recapitulating the phenotype observed in PDPN-deficient CAFs. In sum, starting from the unbiased elucidation of the PDPN co-receptome, our work provides insights into PDPN functions and reveals the PDPN/CD177 axis as a possible modulator of fibroblast physiology in the tumor microenvironment.

Social distancing measures due to the COVID-19 pandemic have accelerated the adoption and implementation of digital mental health tools. Psychiatry and therapy sessions are being conducted via videoconferencing platforms, and the use of digital mental health tools for monitoring and treatment has grown. This rapid shift to telehealth during the pandemic has given added urgency to the ethical challenges presented by digital mental health tools. Regulatory standards have been relaxed to allow this shift to socially distanced mental health care. It is imperative to ensure that the implementation of digital mental health tools, especially in the context of this crisis, is guided by ethical principles and abides by professional codes of conduct. This paper examines key areas for an ethical path forward in this digital mental health revolution: privacy and data protection, safety and accountability, and access and fairness.

Objective: The aim of the present study was to analyze the progression of non-motor symptoms (NMS) burden in Parkinson’s disease (PD) patients regarding the development of motor fluctuations (MF). Methods: PD patients without MF at baseline, who were recruited from January 2016 to November 2017 (V0) and evaluated again at a 2-year follow-up (V2) from 35 centers of Spain from the COPPADIS cohort, were included in this analysis. MF development at V2 was defined as a score ≥ 1 in the item-39 of the UPDRS-Part IV, whereas NMS burden was defined according to the Non-motor Symptoms Scale (NMSS) total score. Results: Three hundred and thirty PD patients (62.67 ± 8.7 years old; 58.8% males) were included. From V0 to V2, 27.6% of the patients developed MF. The mean NMSS total score at baseline was higher in those patients who developed MF after the 2-year follow-up (46.34 ± 36.48 vs. 34.3 ± 29.07; p = 0.001). A greater increase in the NMSS total score from V0 to V2 was observed in patients who developed MF (+16.07 ± 37.37) compared to those who did not develop MF (+6.2 ± 25.8) (p = 0.021). Development of MF after a 2-year follow-up was associated with an increase in the NMSS total score (β = 0.128; p = 0.046) after adjustment to age, gender, years from symptoms onset, levodopa equivalent daily dose (LEDD) and the NMSS total score at baseline, and the change in LEDD from V0 to V2. Conclusions: In PD patients, the development of MF is associated with a greater increase in the NMS burden after a 2-year follow-up.

Functional nanoporous materials are categorized as an important class of nanostructured materials because of their tunable porosity and pore geometry (size, shape, and distribution) and their unique chemical and physical properties as compared with other nanostructures and bulk counterparts. Progress in developing a broad spectrum of nanoporous materials has accelerated their use for extensive applications in catalysis, sensing, separation, and environmental, energy, and biomedical areas. The purpose of this review is to provide recent advances in synthesis strategies for designing ordered or hierarchical nanoporous materials of tunable porosity and complex architectures. Furthermore, we briefly highlight working principles, potential pitfalls, experimental challenges, and limitations associated with nanoporous material fabrication strategies. Finally, we give a forward look at how digitally controlled additive manufacturing may overcome existing obstacles to guide the design and development of next-generation nanoporous materials with predefined properties for industrial manufacturing and applications.

Background: Cognitive impairment is one of the most frequent and disabling non-motor symptoms in Parkinson disease (PD) and encompasses a continuum from mild cognitive impairment (PD-MCI) to dementia (PDD). The risk factors associated with them are not completely elucidated.Objective: To characterize the presence and clinical presentation of PD-MCI and PDD in patients with idiopathic PD, examining motor and non-motor features and determining factors associated with cognitive impairment.Methods: Multicenter, cross-sectional study in 298 PD patients who underwent clinical [Hoehn and Yahr (HY) staging and Clinical Impression of Severity Index for Parkinson Disease], neurological [Scales for Outcomes in Parkinson's Disease (SCOPA)-Motor], neuropsychological (Mini Mental State Examination, SCOPA-Cognition, Frontal Assessment Battery and Clinical Dementia Rating Scale), neuropsychiatric [SCOPA-Psychiatric complications, SCOPA-Psychosocial (SCOPA-PS), and Hospital Anxiety and Depression Scale (HADS)], and health-related quality of life [Parkinson Disease Questionnaire for quality of life (PDQ-8)] assessment. Movement Disorders Society criteria were applied to classify patients as normal cognition (NC), PD-MCI, and PDD. The association between variables was explored using multivariate binary and multinomial logistic regression models.Results: Seventy-two patients (24.2%) were classified as NC, 82 (27.5%) as PD-MCI, and 144 (48.3%) as PDD. These last two groups reported more psychosocial problems related with the disease (mean SCOPA-PS, 16.27 and 10.39, respectively), compared with NC (7.28) and lower quality-of-life outcomes (PDQ-8 48.98 and 28.42, respectively) compared to NC (19.05). The logistic regression analysis showed that both cognitive impaired groups had a more severe stage of PD measured by HY [odds ratio (OR) for MCI-PD, 2.45; 95% confidence interval (CI), 1.22–4.90; OR for PDD 2.64; 95% CI, 1.17–5.98]. Specifically, age (OR, 1.30; 95% CI, 1.16–1.47), years of education (OR, 0.91; 95% CI, 0.83–0.99), disease duration (OR, 1.19; 95% CI, 1.07–1.32), HADS-D (OR, 1.20; 95% CI, 1.06–1.35), and hallucinations (OR, 2.98; 95% CI, 1.16–7.69) were related to PDD.Conclusions: Cognitive impairment in PD is associated with more severe disease stage, resulting in a global, neuropsychiatric, psychosocial, and quality-of-life deterioration. This study provides a better understanding of the great impact that cognitive impairment has within the natural history of PD and its relationship with the rest of motor and non-motor symptoms in the disease.

Shame and embarrassment related to Parkinson's disease (PD) are rarely addressed in clinical practice nor studied in neuroscience research, partly because no specific tool exists to detect them in PD.Objective: To develop a self-applied assessment tool of shame and embarrassment specifically related to PD or its treatment, to promptly identify the presence and severity of these two emotions in PD.Methods: Identification and selection of relevant items were obtained from the collection of PD patients' opinions during support groups and interviews. Several further items were added following a literature review. Subsequently, a two-phase pilot study was performed for identification of ambiguous items and omissions, and to obtain preliminary data on acceptability, reliability, validity and relevance of the new scale (SPARK).Results: A total of 105 PD patients were enrolled in the study. Embarrassment was reported in 85% of patients, while shame was present in 26%. Fifteen percent of patients did not describe any shame or embarrassment. On average, the intensity of these two emotions was low with a marked floor effect in SPARK items and subscales. However, SPARK total score inter-individual variability was important (range 1–84 out of 99). Acceptability and quality of data were satisfactory with no floor or ceiling effects (2.9% each) or missing data. Internal consistency (Cronbach's alpha) was 0.94 for total score and 0.73–0.87 for subscales. The scale correlated ≥0.60 with instruments measuring related constructs. Content validity was satisfactory. SPARK total score strongly correlated with impaired health-related quality of life (rS = 0.81), the propensity to feel embarrassed or ashamed (rS = 0.68 and 0.66, respectively), and anxiety (rS = 0.72) and depression (rS = 0.63) levels. Moderate to high correlations were observed between SPARK total score and apathy (rS = 0.46) and a more pronounced personality trait directed toward harm avoidance (rS = 0.46). No significant differences in SPARK scores were found by sex, education level, PD duration, Hoehn and Yahr stages or PD phenotype.Conclusion: Preliminary analysis of psychometric properties suggests that SPARK could be an acceptable and reliable instrument for assessing shame and embarrassment in PD. SPARK could help healthcare professionals to identify and characterize PD-induced shame and embarrassment.

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.

ObjectiveThe 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.MethodsOne 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.ResultsResults 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).ConclusionsOur 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.

Antihypertensive treatment of patients with diabetes should include those drugs with a positive effect on metabolic parameters. Most patients with diabetes require at least two antihypertensive agents. Combining a dihydropyridine calcium channel blocker with a renin-angiotensin-aldosterone system inhibitor is a rational approach. However, not all dihydropyridines are equal with respect to their effects on metabolic parameters. Thus, manidipine exerts a positive effect on insulin resistance. However, this effect has not been observed with amlodipine. On the other hand, the excessive activation of sympathetic nervous system has been related with an increase of insulin resistance, pulse pressure, and ankle edema rates. Compared with amlodipine, manidipine activates sympathetic nervous system to a lesser extent. As a result, treatment with manidipine represents a good option in hypertensive patients with diabetes.

Background and objective: Diplopia is relatively common in Parkinson’s disease (PD) but is still understudied. Our aim was to analyze the frequency of diplopia in PD patients from a multicenter Spanish cohort, to compare the frequency with a control group, and to identify factors associated with it. Patients and Methods: PD patients who were recruited from January 2016 to November 2017 (baseline visit; V0) and evaluated again at a 2-year ± 30 days follow-up (V2) from 35 centers of Spain from the COPPADIS cohort were included in this longitudinal prospective study. The patients and controls were classified as “with diplopia” or “without diplopia” according to item 15 of the Non-Motor Symptoms Scale (NMSS) at V0, V1 (1-year ± 15 days), and V2 for the patients and at V0 and V2 for the controls. Results: The frequency of diplopia in the PD patients was 13.6% (94/691) at V0 (1.9% in controls [4/206]; p < 0.0001), 14.2% (86/604) at V1, and 17.1% (86/502) at V2 (0.8% in controls [1/124]; p < 0.0001), with a period prevalence of 24.9% (120/481). Visual hallucinations at any visit from V0 to V2 (OR = 2.264; 95%CI, 1.269–4.039; p = 0.006), a higher score on the NMSS at V0 (OR = 1.009; 95%CI, 1.012–1.024; p = 0.015), and a greater increase from V0 to V2 on the Unified Parkinson’s Disease Rating Scale–III (OR = 1.039; 95%CI, 1.023–1.083; p < 0.0001) and Neuropsychiatric Inventory (OR = 1.028; 95%CI, 1.001–1.057; p = 0.049) scores were independent factors associated with diplopia (R2 = 0.25; Hosmer and Lemeshow test, p = 0.716). Conclusions: Diplopia represents a frequent symptom in PD patients and is associated with motor and non-motor severity.