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Abstract Impulsive-compulsive behaviour (ICB) is a frequently observed non-motor symptom in early Parkinson’s disease after initiating dopamine replacement therapy. At the opposite end of the motivated behaviour spectrum, apathy occurs in early Parkinson’s disease even before dopamine replacement is started. The co-occurrence of these behavioural conditions in Parkinson’s disease raises questions about their relationship and underlying pathophysiological determinants. In previous imaging or genetic studies, both conditions have been associated with the limbic dopaminergic system. The risk variant of the Ser9Gly polymorphism of the dopamine receptor D3 (DRD3) is linked to increased dopamine affinity in the limbic striatum. With this in mind, we investigated how ICB expression is explained by apathy and DRD3 polymorphisms and their effects on grey matter volume and dopamine synthesis capacity. Fifty-four patients with early Parkinson’s disease took part in anatomical T1-weighted MRI. Forty of them also underwent dynamic PET imaging using [18F]DOPA to measure striatal dopamine synthesis capacity. Further, Ser9Gly (rs6280) gene polymorphism influencing the DRD3 dopamine-binding affinity was determined in all patients. The severity of impulsive-compulsive behaviour and apathy was assessed using the Questionnaire for Impulsive-Compulsive Disorders Rating Scale and the Apathy Evaluation Scale. ICB and the severity of apathy were indeed positively correlated. Apathy and the DRD3 polymorphism were interactive risk factors for ICB severity. Apathy was significantly linked to atrophy of the bilateral putamen. Patients with the DRD3 risk type had reduced dopamine synthesis capacity in the putamen and limbic striatum, apathy was associated with reduced dopamine synthesis capacity in the limbic striatum. The results of [18F]DOPA reached only trend significance. Apathy in drug-naïve PD patients might be a consequence of impaired striatal dopaminergic tone. This may represent a predisposing factor for the development of ICB after the initiation of dopamine replacement therapy. The risk type of DRD3 could further amplify this predisposition due to its higher affinity to dopamine.

Abstract Background Previous cross-sectional and longitudinal observational studies revealed positive relationships between contextual built environment components and walking behavior. Due to severe restrictions during COVID-19 pandemic lockdowns, physical activity was primarily performed within the immediate living area. Using this unique opportunity, we evaluated whether built environment components were associated with the magnitude of change in walking activity in adults during COVID-19 restrictions. Methods Data on self-reported demographic characteristics and walking behaviour were extracted from the prospective longitudinal Lifelines Cohort Study in the Netherlands of participants ≥ 18 years. For our analyses, we made use of the data acquired between 2014–2017 (n = 100,285). A fifth of the participants completed the questionnaires during COVID-19 restrictive policies in July 2021 (n = 20,806). Seven spatial components were calculated for a 500m and 1650m Euclidean buffer per postal code area in GIS: population density, retail and service destination density, land use mix, street connectivity, green space density, sidewalk density, and public transport stops. Additionally, the walkability index (WI) of these seven components was calculated. Using multivariable linear regression analyses, we analyzed the association between the WI (and separate components) and the change in leisure walking minutes/week. Included demographic variables were age, gender, BMI, education, net income, occupation status, household composition and the season in which the questionnaire was filled in. Results The average leisure walking time strongly increased by 127 min/week upon COVID-19 restrictions. All seven spatial components of the WI were significantly associated with an increase in leisure walking time; a 10% higher score in the individual spatial component was associated with 5 to 8 more minutes of leisure walking/week. Green space density at the 500m Euclidean buffer and side-walk density at the 1650m Euclidean buffer were associated with the highest increase in leisure walking time/week. Subgroup analysis revealed that the built environment showed its strongest impact on leisure walking time in participants not engaging in leisure walking before the COVID-19 pandemic, compared to participants who already engaged in leisure walking before the COVID-19 pandemic. Conclusions These results provide strong evidence that the built environment, corrected for individual-level characteristics, directly links to changes observed in leisure walking time during COVID-19 restrictions. Since this relation was strongest in those who did not engage in leisure walking before the COVID-19 pandemic, our results encourage new perspectives in health promotion and urban planning.

The relative inability to produce effortful movements is the most specific motor sign of Parkinson's disease, which is primarily characterized by loss of dopaminergic terminals in the putamen. The motor motivation hypothesis suggests that this motor deficit may not reflect a deficiency in motor control per se , but a deficiency in cost-benefit considerations for motor effort. For the first time, we investigated the quantitative effect of dopamine depletion on the motivation of motor effort in Parkinson's disease. A total of 21 early-stage, unmedicated patients with Parkinson's disease and 26 healthy controls were included. An incentivized force task was used to capture the amount of effort participants were willing to invest for different monetary incentive levels and dopamine transporter depletion in the bilateral putamen was assessed. Our results demonstrate that patients with Parkinson's disease applied significantly less grip force than healthy controls, especially for low incentive levels. Congruously, decrease of motor effort with greater loss of putaminal dopaminergic terminals was most pronounced for low incentive levels. This signifies that putaminal dopamine is most critical to motor effort when the trade-off with the benefit is poor. Taken together, we provide direct evidence that the reduction of effortful movements in Parkinson's disease depends on motivation and that this effect is associated with putaminal dopaminergic degeneration. [ABSTRACT FROM AUTHOR]

Recent studies in Parkinson's disease (PD) patients reported disruptions in dynamic functional connectivity (dFC, i.e., a characterization of spontaneous fluctuations in functional connectivity over time). Here, we assessed whether the integrity of striatal dopamine terminals directly modulates dFC metrics in two separate PD cohorts, indexing dopamine‐related changes in large‐scale brain network dynamics and its implications in clinical features. We pooled data from two disease‐control cohorts reflecting early PD. From the Parkinson's Progression Marker Initiative (PPMI) cohort, resting‐state functional magnetic resonance imaging (rsfMRI) and dopamine transporter (DaT) single‐photon emission computed tomography (SPECT) were available for 63 PD patients and 16 age‐ and sex‐matched healthy controls. From the clinical research group 219 (KFO) cohort, rsfMRI imaging was available for 52 PD patients and 17 age‐ and sex‐matched healthy controls. A subset of 41 PD patients and 13 healthy control subjects additionally underwent 18F‐DOPA‐positron emission tomography (PET) imaging. The striatal synthesis capacity of 18F‐DOPA PET and dopamine terminal quantity of DaT SPECT images were extracted for the putamen and the caudate. After rsfMRI pre‐processing, an independent component analysis was performed on both cohorts simultaneously. Based on the derived components, an individual sliding window approach (44 s window) and a subsequent k‐means clustering were conducted separately for each cohort to derive dFC states (reemerging intra‐ and interindividual connectivity patterns). From these states, we derived temporal metrics, such as average dwell time per state, state attendance, and number of transitions and compared them between groups and cohorts. Further, we correlated these with the respective measures for local dopaminergic impairment and clinical severity. The cohorts did not differ regarding age and sex. Between cohorts, PD groups differed regarding disease duration, education, cognitive scores and L‐dopa equivalent daily dose. In both cohorts, the dFC analysis resulted in three distinct states, varying in connectivity patterns and strength. In the PPMI cohort, PD patients showed a lower state attendance for the globally integrated (GI) state and a lower number of transitions than controls. Significantly, worse motor scores (Unified Parkinson's Disease Rating Scale Part III) and dopaminergic impairment in the putamen and the caudate were associated with low average dwell time in the GI state and a low total number of transitions. These results were not observed in the KFO cohort: No group differences in dFC measures or associations between dFC variables and dopamine synthesis capacity were observed. Notably, worse motor performance was associated with a low number of bidirectional transitions between the GI and the lesser connected (LC) state across the PD groups of both cohorts. Hence, in early PD, relative preservation of motor performance may be linked to a more dynamic engagement of an interconnected brain state. Specifically, those large‐scale network dynamics seem to relate to striatal dopamine availability. Notably, most of these results were obtained only for one cohort, suggesting that dFC is impacted by certain cohort features like educational level, or disease severity. As we could not pinpoint these features with the data at hand, we suspect that other, in our case untracked, demographical features drive connectivity dynamics in PD. Practitioner Points: Exploring dopamine's role in brain network dynamics in two Parkinson's disease (PD) cohorts, we unraveled PD‐specific changes in dynamic functional connectivity.Results in the Parkinson's Progression Marker Initiative (PPMI) and the KFO cohort suggest motor performance may be linked to a more dynamic engagement and disengagement of an interconnected brain state.Results only in the PPMI cohort suggest striatal dopamine availability influences large‐scale network dynamics that are relevant in motor control. [ABSTRACT FROM AUTHOR]

This study addresses concerns surrounding the transition program in Special Education (SPED) within the Philippines' Department of Education (DepEd), focusing on the competence of SPED teachers in facilitating smooth transitions for Learners with Special Educational Needs (LSENs). The research uses a mixed-method approach to evaluate 23 SPED teachers from 12 public elementary schools in the DepEd Camarines Norte Division. The findings revealed competencies in livelihood programs among the strength of SPED teachers and indicated room for improved vocational skills. While the teachers exhibit moderate competence in academics, enrichment, and pre-vocational skills, crucial for holistic transition planning, their profile factors such as age, service length, and education significantly influence their competence to facilitate successful transition programs. The thematic analysis of the focus group discussions uncovers challenges, which include insufficient support, financial constraints, and stereotypes. In conclusion, the study recommends a contextualized transition program tailored to support SPED teachers in guiding learners effectively. [ABSTRACT FROM AUTHOR]

Background Previous cross-sectional and longitudinal observational studies revealed positive relationships between contextual built environment components and walking behavior. Due to severe restrictions during COVID-19 pandemic lockdowns, physical activity was primarily performed within the immediate living area. Using this unique opportunity, we evaluated whether built environment components were associated with the magnitude of change in walking activity in adults during COVID-19 restrictions. Methods Data on self-reported demographic characteristics and walking behaviour were extracted from the prospective longitudinal Lifelines Cohort Study in the Netherlands of participants≥18 years. For our analyses, we made use of the data acquired between 2014–2017 (n=100,285). A ffth of the participants completed the questionnaires during COVID-19 restrictive policies in July 2021 (n=20,806). Seven spatial components were calculated for a 500m and 1650m Euclidean bufer per postal code area in GIS: population density, retail and service destination density, land use mix, street connectivity, green space density, sidewalk density, and public transport stops. Additionally, the walkability index (WI) of these seven components was calculated. Using multivariable linear regression analyses, we analyzed the association between the WI (and separate components) and the change in leisure walking minutes/week. Included demographic variables were age, gender, BMI, education, net income, occupation status, household composition and the season in which the questionnaire was flled in. Results The average leisure walking time strongly increased by 127 min/week upon COVID-19 restrictions. All seven spatial components of the WI were signifcantly associated with an increase in leisure walking time; a 10% higher score in the individual spatial component was associated with 5 to 8 more minutes of leisure walking/week. Green space density at the 500m Euclidean bufer and side-walk density at the 1650m Euclidean bufer were associated with the highest increase in leisure walking time/week. Subgroup analysis revealed that the built environment showed its strongest impact on leisure walking time in participants not engaging in leisure walking before the COVID-19 pandemic, compared to participants who already engaged in leisure walking before the COVID-19 pandemic. Conclusions These results provide strong evidence that the built environment, corrected for individual-level characteristics, directly links to changes observed in leisure walking time during COVID-19 restrictions. Since this relation was strongest in those who did not engage in leisure walking before the COVID-19 pandemic, our results encourage new perspectives in health promotion and urban planning. [ABSTRACT FROM AUTHOR]

We demonstrate the coupling of single color centers in diamond to plasmonic and dielectric photonic structures to realize novel nanophotonic devices. Nanometer spatial control in the creation of single color centers in diamond is achieved by implantation of nitrogen atoms through high-aspect-ratio channels in a mica mask. Enhanced broadband single-photon emission is demonstrated by coupling nitrogen–vacancy centers to plasmonic resonators, such as metallic nanoantennas. Improved photon-collection efficiency and directed emission is demonstrated by solid immersion lenses and micropillar cavities. Thereafter, the coupling of diamond nanocrystals to the guided modes of micropillar resonators is discussed along with experimental results. Finally, we present a gas-phase-doping approach to incorporate color centers based on nickel and tungsten, in situ into diamond using microwave-plasma-enhanced chemical vapor deposition. The fabrication of silicon–vacancy centers in nanodiamonds by microwave-plasma-enhanced chemical vapor deposition is discussed in addition.

Background: Depression and anxiety are two frequent neuropsychiatric symptoms in Alzheimer's disease (AD). Moreover, depressive symptoms and anxiety are frequently associated with greater amyloid deposition and risk of Alzheimer's dementia. The aim of the present study is to assess the association between anxiety and depression and amyloid burden. Method: In the AMPYAD study, participants with subjective cognitive decline (SCD+, n = 244), mild cognitive impairment (MCI, n = 341) and dementia (n = 255) were enrolled in eight European memory clinics between 2018 and 2020. They underwent three study visits (baseline, six months, thirteen months) with collection of cognitive data and symptoms of depression and anxiety (Hospital Anxiety and Depression Scale, HADS) as well as measures of quality of life and coping strategies. Amyloid burden was obtained as the standardized centiloid values (CL). Correlation analyses were carried out for HADS‐Scores and CL. We analyzed the progression of depressive and anxiety symptoms over time between patients with and without presence of amyloid (CL≥21) using mixed‐model‐ANOVA. All analyses were corrected for time of PET result disclosure. Result: A total of 840 patients (46.2% female; mean age of 70.9 (SD = 7.8)) were included. Among SCD+ patients, CL values were positively correlated with baseline anxiety scores (r(216) =.14, p =.038). In contrast, MCI and dementia patients showed a negative correlation between CL and depressive symptoms (r(296) = ‐.16, p =.005; r(209) = ‐.23, p<.001). In SCD+, there was no significant interaction between time and CL status for anxiety (p =.512), but a significant main effect of time (F(2,302) = 3.4, p =.036, η² =.02), indicating a decline in anxiety symptoms over time. A trend indicated higher anxiety for amyloid positive participants, but the effect missed statistical significance (p =.068). For depressive symptoms, we found no main effects and no significant interaction of time and CL status. Conclusion: The AMYPAD study contains a large amyloid‐PET data set of patients from eight European memory clinics. We observed an association of increased anxiety scores with amyloid load in SCD+, but reduced symptoms of depression with higher amyloid load in the MCI and dementia group. These findings and their longitudinal development over time will be put into a broader context of patient characteristics. [ABSTRACT FROM AUTHOR]

Background: Adequate animal-based protein intake can attenuate exercise induced-muscle damage (EIMD) in young adults. We examined the effects of 13 days plant-based (pea) protein supplementation compared to whey protein and placebo on EIMD in active older adults. Methods: 47 Physically active older adults (60+ years) were randomly allocated to the following groups: (I) whey protein (25 g/day), (II) pea protein (25 g/day) or (III) iso-caloric placebo. Blood concentrations of creatine kinase (CK) and lactate dehydrogenase (LDH), and skeletal muscle mass, muscle strength and muscle soreness were measured prior to and 24 h, 48 h and 72 h after a long-distance walking bout (20–30 km). Results: Participants walked 20–30 km and 2 dropped out, leaving n = 15 per subgroup. The whey group showed a significant attenuation of the increase in EIMD at 24 h post-exercise compared to the pea and placebo group (CK concentration: 175 ± 90 versus 300 ± 309 versus 330 ± 165, p = p < 0.001). No differences in LDH levels, muscle strength, skeletal muscle mass and muscle soreness were observed across groups (all p-values > 0.05). Conclusions: Thirteen days of pea protein supplementation (25 g/day) does not attenuate EIMD in older adults following a single bout of prolonged walking exercise, whereas the whey protein supplementation group showed significantly lower post-exercise CK concentrations. [ABSTRACT FROM AUTHOR]