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Background: VPS35 is part of the retromer complex and is responsible for the trafficking and recycling of proteins implicated in autophagy and lysosomal degradation, but also takes part in the degradation of mitochondrial proteins via mitochondria-derived vesicles. The p.D620N mutation of VPS35 causes an autosomal-dominant form of Parkinson’s disease (PD), clinically representing typical PD. Objective: Most of the studies on p.D620N VPS35 were performed on human tumor cell lines, rodent models overexpressing mutant VPS35, or in patient-derived fibroblasts. Here, based on identified target proteins, we investigated the implication of mutant VPS35 in autophagy, lysosomal degradation, and mitochondrial function in induced pluripotent stem cell-derived neurons from a patient harboring the p.D620N mutation. Methods: We reprogrammed fibroblasts from a PD patient carrying the p.D620N mutation in the VPS35 gene and from two healthy donors in induced pluripotent stem cells. These were subsequently differentiated into neuronal precursor cells to finally generate midbrain dopaminergic neurons. Results: We observed a decreased autophagic flux and lysosomal mass associated with an accumulation of α-synuclein in patient-derived neurons compared to controls. Moreover, patient-derived neurons presented a mitochondrial dysfunction with decreased membrane potential, impaired mitochondrial respiration, and increased production of reactive oxygen species associated with a defect in mitochondrial quality control via mitophagy. Conclusion: We describe for the first time the impact of the p.D620N VPS35 mutation on autophago-lysosome pathway and mitochondrial function in stem cell-derived neurons from an affected p.D620N carrier and define neuronal phenotypes for future pharmacological interventions

Supplemental material, Online_ressource_2-_Bland_Altmann_Plots_EDITS for Interrater Reliability of Dynamic Muscle Testing After Breast Cancer Surgery in Women at High Risk of Lymphedema: To Improve Quality in Clinical Practice by Tina Korsholm-Rosfort, Simone Larsen, Thomas Aagaard, Gunn Ammitzbøll and Susanne O. Dalton in Integrative Cancer Therapies

The purpose of the thesis is to investigate what circumstances supports inherited responsibility to afford reparations. The general arguments for and against inherited obligations are presented and discussed. Hereafter, Denmark and Australia’s forced assimilation policies are examined in order to establish their responsibilities to correct the past injustice. The general arguments are applied when scrutinizing the cases. It is visible that it remains difficult to determine a nation’s responsibilities to correct past injustices, however, once considering the continuance of communities as well as inherited benefits and desert-claims, it seems justified that nations also inherit liabilities. The thesis is argumentative and normative in nature, entailing suggestions both for and against inherited responsibility. Once nations recognize that the purpose is to correct an injustice, and not take responsibility for its occurrence, it becomes clear that nations ought to accept inherited responsibility to afford reparations.

Supplemental material, Online_ressource_1_-_Test_protocol_EDITS for Interrater Reliability of Dynamic Muscle Testing After Breast Cancer Surgery in Women at High Risk of Lymphedema: To Improve Quality in Clinical Practice by Tina Korsholm-Rosfort, Simone Larsen, Thomas Aagaard, Gunn Ammitzbøll and Susanne O. Dalton in Integrative Cancer Therapies

Background: Researchers and clinicians within the field of trauma have to choose between different diagnostic descriptions of posttraumatic stress disorder (PTSD) in the DSM-5 and the proposed ICD-11. Several studies support different competing models of the PTSD structure according to both diagnostic systems; however, findings show that the choice of diagnostic systems can affect the estimated prevalence rates. Objectives: The present study aimed to investigate the potential impact of using a large (i.e. the DSM-5) compared to a small (i.e. the ICD-11) diagnostic description of PTSD. In other words, does the size of PTSD really matter? Methods: The aim was investigated by examining differences in diagnostic rates between the two diagnostic systems and independently examining the model fit of the competing DSM-5 and ICD-11 models of PTSD across three trauma samples: university students (N = 4213), chronic pain patients (N = 573), and military personnel (N = 118). Results: Diagnostic rates of PTSD were significantly lower according to the proposed ICD-11 criteria in the university sample, but no significant differences were found for chronic pain patients and military personnel. The proposed ICD-11 three-factor model provided the best fit of the tested ICD-11 models across all samples, whereas the DSM-5 seven-factor Hybrid model provided the best fit in the university and pain samples, and the DSM-5 six-factor Anhedonia model provided the best fit in the military sample of the tested DSM-5 models. Conclusions: The advantages and disadvantages of using a broad or narrow set of symptoms for PTSD can be debated, however, this study demonstrated that choice of diagnostic system may influence the estimated PTSD rates both qualitatively and quantitatively. In the current described diagnostic criteria only the ICD-11 model can reflect the configuration of symptoms satisfactorily. Thus, size does matter when assessing PTSD. Planteamiento: Los investigadores y clínicos del campo del trauma pronto decidirán entre dos descripciones diagnósticas diferentes del trastorno de estrés postraumático (TEPT) en el DSM-5 y la propuesta CIE-11. Varios estudios apoyan diferentes modelos en competencia sobre la estructura del TEPT en función de ambos sistemas de diagnóstico; sin embargo, los resultados demuestran que la elección de los sistemas de diagnóstico puede afectar las tasas de prevalencia estimadas. Objetivos: y métodos. El presente estudio tenía como objetivo investigar el impacto potencial de usar una descripción del TEPT amplia (es decir, el DSM-5) en comparación con una pequeña (es decir, la CIE-11). En otras palabras, ¿el tamaño del TEPT importa realmente? El objetivo se investigó mediante el examen de las diferencias en las frecuencias de diagnóstico entre los dos sistemas de diagnóstico y examinando de forma independiente cómo se ajustaban los modelos en competencia para el TEPT del DSM-5 y la CIE-11 en tres muestras de trauma: estudiantes universitarios (N = 4213), pacientes con dolor crónico (N = 573) y personal militar (N = 118). Resultados: Las tasas diagnósticas del TEPT fueron significativamente más bajas según los criterios de la propuesta CIE-11 en la muestra universitaria, pero no se encontraron diferencias significativas para los pacientes con dolor crónico y el personal militar. El modelo de tres factores propuesto por la CIE-11 proporcionó el mejor ajuste de los modelos de la CIE-11 que fueron probados en todas las muestras. En cambio, el modelo híbrido de siete factores del DSM-5 proporcionó el mejor ajuste en las muestras universitaria y del dolor, y el modelo de Anhedonia de seis factores del DSM-5 en la muestra militar de los modelos probados del DSM-5. Conclusiones: Se pueden debatir las ventajas y desventajas de utilizar un conjunto amplio o reducido de síntomas para el TEPT; sin embargo, este estudio demostró que la elección del sistema de diagnóstico puede influir en las tasas estimadas del TEPT, tanto cualitativa como cuantitativamente. Al mismo tiempo, parece que, dados los criterios diagnósticos descritos actualmente, solo el modelo de la CIE-11 puede reflejar satisfactoriamente la configuración de los síntomas. Por lo tanto, el tamaño importa cuando se evalúa el TEPT. 背景：在创伤领域的研究者和临床工作者很快要在DSM-5和ICD-11提案种对两个不同的创伤后应激障碍(PTSD)诊断描述做出选择。一些研究根据不同的诊断系统支持不同的PTSD症状结构的竞争模型，但是研究发现显示不同的诊断系统的选择会影响对发生率的估计。 目标和方法：本研究旨在探究使用大量（如DSM-5）或者少量（如ICD-11）PTSD症状描述的潜在影响。换言之，PTSD的症状量是否真的重要？我们考察在两个不同诊断系统里的诊断率的差别，并分别在三个创伤样本里考察DSM-5和ICD-11 的PTSD竞争模型的拟合性：大学生样本（N=4213），长期疼痛病人（N=573）和军人样本（N=118）。 结果：在大学生样本里根据ICD-11提案的PTSD的诊断率显著更低，但是对长期疼痛病人和军人样本没有显著差别。ICD-11提案的三因子模型跨样本拟合最好，但DSM-5七因子混合模型在大学生和疼痛样本中拟合最好，DSM-5 六因子快感缺失模型在军人样本中拟合最好。 结论：使用一个广泛或者狭窄的PTSD症状集的优劣是可以争论的，但是本研究显示对诊断体系的选择可以从质性和量化角度影响对PTSD患病率的估计。同时，在目前的诊断标准中只有ICD-11模型可以令人满意地反映症状结果。因此在评估PTSD时，症状数量是重要的。