Development of a hierarchical electrospun scaffold for ligament replacement

2018 Spring.Includes bibliographical references.The anterior cruciate ligament (ACL) is a dense collagenous structure that connects the femur to the tibia and is vital for joint stability. The ACL possesses complex time-dependent viscoelastic properties and functions primarily to prevent excessive translations and rotations of the tibia relative to the femur. It is estimated that 400,000 ACL tears occur in the United States annually and the monetary burden of these injuries and their subsequent treatment is approximately $1 billion annually. After injury allografts and autografts are commonly implanted to reconstruct the torn ACL in an attempt to restore joint stability, prevent pain, and limit damage to surrounding tissues. However surgical reconstructions fail to completely restore knee functionality or prevent additional injury and regardless of intervention technique radiographic osteoarthritis is present in 13% of patients 10 years after ACL rupture. Drawbacks to traditional treatments for ACL ruptures motivate the development of a synthetic ACL replacement. Tissue engineering is the use of a scaffold, cells, and signaling molecules to create a replacement for damaged tissue. The goal of this work is to develop a polymer scaffold that can be utilized as a replacement for the ACL. A tissue engineered ACL replacement should replicate the hierarchical structure of the native ACL, possess reasonable time zero mechanical properties, and promote the deposition of de novo collagenous tissue in vitro. Additionally, the scaffold should be implantable using standard surgical techniques and should maintain in situ tibiofemoral contact mechanics. Thus, four specific aims are proposed: 1) Fabricated and characterize an aligned 3-dimensional electrospun scaffold for ACL replacement. 2) Assess the in vitro behavior of ovine bone marrow-derived stems cells seeded on the scaffold in the presence of conjugated growth factor. 3) Evaluate the performance of the electrospun scaffold using uniaxial mechanical testing. 4) Assess the effect of the electrospun scaffold on ovine stifle joint contact mechanics. Development of a tissue engineered ACL replacement that mimics the structure and function of the native ACL would provide a novel treatment to improve outcomes of ACL injuries

Restoration of the striatal circuitry: from developmental aspects toward clinical applications

In the basal ganglia circuitry, the striatum is a highly complex structure coordinating motor and cognitive functions and it is severely affected in Huntington's disease (HD) patients. Transplantation of fetal ganglionic eminence (GE) derived precursor cells aims to restore neural circuitry in the degenerated striatum of HD patients. Pre-clinical transplantation in genetic and lesion HD animal models has increased our knowledge of graft vs. host interactions, and clinical studies have been shown to successfully reduce motor and cognitive effects caused by the disease. Investigating the molecular mechanisms of striatal neurogenesis is a key research target, since novel strategies aim on generating striatal neurons by differentiating embryonic stem cells or by reprogramming somatic cells as alternative cell source for neural transplantation

Les motivations à l’achat de pâtes alimentaires pour une filière blé dur française durable

Dans un contexte de préoccupations environnementales et sociétales croissantes, la filière « blé dur » française s’interroge sur de nouvelles motivations d’achat pour les consommateurs. Le blé dur est le composant quasi exclusif des pâtes, produits de base largement consommés. Cet article a pour objectif d’analyser le consentement à payer des consommateurs français pour des pâtes présentant des qualités spécifiques en matière environnementale et géographique (lien au local). Il mobilise une enquête exclusive sur internet auprès d’un échantillon de 1 000 personnes. Des modèles d’estimation (logit ordonné et régression par intervalle) permettent d’apprécier différents déterminants du consentement à payer des consommateurs relatifs aux attributs des pâtes. Les résultats montrent une prédominance des attributs locaux sur ceux environnementaux et confirment la diversité des registres de valeurs associés aux comportements d’achat.In a context of growing environmental and societal concerns, the French “durum wheat” sector is looking into new consumer purchasing motivations. Durum wheat is the almost exclusive component of pasta, a widely consumed basic product. This article aims to analyze the willingness of French consumers to pay for pasta with specific environmental and local-based qualities. It mobilizes an exclusive internet survey with a sample of 1000 people. Ordered logit and interval regression models were used to estimate the determinants of consumers’ willingness to pay for the addition attributes to pasta. The results show a predominance of local attributes over environmental attributes and confirm the importance of purchasing behaviors related to practices and values

Beyond Admissibility: Dominance Between Chains of Strategies

Admissible strategies, i.e. those that are not dominated by any other strategy, are a typical rationality notion in game theory. In many classes of games this is justified by results showing that any strategy is admissible or dominated by an admissible strategy. However, in games played on finite graphs with quantitative objectives (as used for reactive synthesis), this is not the case. We consider increasing chains of strategies instead to recover a satisfactory rationality notion based on dominance in such games. We start with some order-theoretic considerations establishing sufficient criteria for this to work. We then turn our attention to generalised safety/reachability games as a particular application. We propose the notion of maximal uniform chain as the desired dominance-based rationality concept in these games. Decidability of some fundamental questions about uniform chains is established

Determinants of patient-reported functional mobility in people with Parkinson's disease: A systematic review.

peer reviewed[en] BACKGROUND: Information on determinants of patient-reported functional mobility is lacking but would inform the planning of healthcare, resources and strategies to promote functional mobility in people with Parkinson's disease (PD). RESEARCH QUESTION: To identify the determinants of patient-reported functional mobility of people with PD. METHODS: Eligible: Randomized Controlled Trials, cohort, case-control, or cross-sectional analyses in people PD without date or setting restrictions, published in English, German, or French. Excluded: instruments with under 50 % of items measuring mobility. On August 9th 2023 we last searched Medline, CINAHL and PsychInfo. We assessed risk of bias using the mixed-methods appraisal tool. Results were synthesized by tabulating the determinants by outcomes and study designs. RESULTS: Eleven studies published 2012-2023 were included (most in Swedish outpatient settings). Samples ranged from 9 to 255 participants. Follow-up varied from 1.5 to 36 months with attrition of 15-42 %. Heterogenic study designs complicated results synthesis. However, determinants related to environment seem to associate the strongest with patient-reported functional mobility, although determinants related to body structures and functions were most investigated. We identified disease duration, the ability to drive, caregiving, sex, age, cognitive impairment, postural instability and social participation as determinants of patient-reported functional mobility. DISCUSSION: Methodological quality of the studies was limited. No study reported an a priori power calculation. Three studies controlled for confounders. The included studies lack representativeness of the population of people living with PD. Standardized sets of outcomes could enable more systematic research synthesis. CONCLUSIONS: Future research should focus on activities, participation and environmental factors and improve methodological quality

Determinants of Self-Stigma in People with Parkinson's Disease: A Mixed Methods Scoping Review

Background: Self-stigma in people with Parkinson's disease (PD) can substantially impact quality of life and possibilities for social participation. An integrative analysis of determinants of self-stigma has been lacking. Objective: We sought to explore which complementary insights from qualitative and quantitative studies, as well as from expert consultation, could be gained. Methods: An established mixed methods study design was employed to first conduct a mixed methods scoping review of published qualitative and quantitative literature, and then consult with experts to arrive at an exhaustive list of determinants of self-stigma after a thematic synthesis. Results: A total of 87 unique determinants of self-stigma were identified. Quantitative studies and expert consultations mainly identified personal determinants of people with self-stigma (e.g., age, anxiety, or apathy). In contrast, qualitative studies identified social situations associated with self-stigma (e.g., joint meals of people with typical PD with others). Notably, self-stigma of people with PD was found to be particularly salient in unfamiliar places, at the working place or in contact with people without PD. Across methods, cognitive impairment, tremor, and abnormal walk and unsteady gait, respectively, were associated with self-stigma. Conclusion: The mixed method study design yielded complementary insights, but also factors commonly associated with self-stigma across methods. Future prioritization exercises may gain further insights into self-stigma of people with PD. Facilitating social encounters by both addressing needs of affected people and raising knowledge and public awareness may improve quality of life in people with P

Luxembourg Parkinson’s study -comprehensive baseline analysis of Parkinson’s disease and atypical parkinsonism

BackgroundDeep phenotyping of Parkinson’s disease (PD) is essential to investigate this fastest-growing neurodegenerative disorder. Since 2015, over 800 individuals with PD and atypical parkinsonism along with more than 800 control subjects have been recruited in the frame of the observational, monocentric, nation-wide, longitudinal-prospective Luxembourg Parkinson’s study.ObjectiveTo profile the baseline dataset and to explore risk factors, comorbidities and clinical profiles associated with PD, atypical parkinsonism and controls.MethodsEpidemiological and clinical characteristics of all 1,648 participants divided in disease and control groups were investigated. Then, a cross-sectional group comparison was performed between the three largest groups: PD, progressive supranuclear palsy (PSP) and controls. Subsequently, multiple linear and logistic regression models were fitted adjusting for confounders.ResultsThe mean (SD) age at onset (AAO) of PD was 62.3 (11.8) years with 15% early onset (AAO < 50 years), mean disease duration 4.90 (5.16) years, male sex 66.5% and mean MDS-UPDRS III 35.2 (16.3). For PSP, the respective values were: 67.6 (8.2) years, all PSP with AAO > 50 years, 2.80 (2.62) years, 62.7% and 53.3 (19.5). The highest frequency of hyposmia was detected in PD followed by PSP and controls (72.9%; 53.2%; 14.7%), challenging the use of hyposmia as discriminating feature in PD vs. PSP. Alcohol abstinence was significantly higher in PD than controls (17.6 vs. 12.9%, p = 0.003).ConclusionLuxembourg Parkinson’s study constitutes a valuable resource to strengthen the understanding of complex traits in the aforementioned neurodegenerative disorders. It corroborated several previously observed clinical profiles, and provided insight on frequency of hyposmia in PSP and dietary habits, such as alcohol abstinence in PD.Clinical trial registration: clinicaltrials.gov, NCT05266872

Sex-specific progression of Parkinson’s disease: A longitudinal mixed-models analysis

BACKGROUND: Despite its relevance, the clinical progression of motor- and non-motor symptoms associated with Parkinson’s disease (PD) is poorly described and understood, particularly in relation to sex-specific differences in clinical progression.OBJECTIVES: Identification of differential aspects in disease progression in men and women with PD.METHODS: Linear mixed-model analyses of a total of 802 people with typical PD from the Luxembourg Parkinson’s study’s prospective cohort, stratified by sex. Marginal effects of disease duration on the outcomes (disease duration averaged over random effects) in analyses stratified by sex were estimated and illustrated for the following outcomes: MDS-UPDRS I-IV, apathy, depression, global cognition, olfaction, bodily discomfort, rapid eye movement sleep behaviour disorder, quality of sleep, dysphagia, patient-reported functional mobility, postural instability and gait disturbances and tremor. Men and women had similar age and median time of follow-up was 3 years.RESULTS: Compared to men, we observed slower disease progression in women for cognition, apathy, quality of sleep and MDS-UPDRS II and significantly worse scores for depression and pain at baseline. Only bodily discomfort and depression (in the first ten years since diagnosis) progressed faster in women. Intensity of tremor decreased over time for both groups.CONCLUSION: Differential progression of symptoms in men and women with PD exists and needs to be explored further. To enhance well-being in PD, we recommend considering a sex-specific approach to managing PD symptoms.</p