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Background: Despite controversy regarding its validity and clinical usefulness, manual examination findings still have an important role for manipulative therapies. As an example, somatic dysfunction (SD) remains central to osteopathic practice.This study aims to explore the experienced osteopaths' attitudes concerning SD and its role in osteopathic practice. This qualitative research could contribute to building a consistent paradigm for manual intervention in all musculoskeletal manipulations., Methods: A thematic analysis with grounded theory elements was used. Data were collected through semi-structured interviews carried out between February and April 2021. A purposive sample of twenty professional osteopaths with past experience in osteopathic care was chosen to reflect the phenomenon's variety. The data analysis was done inductively and in tandem with the recruiting to keep track of data saturation., Results: Eleven osteopaths participated in the study. Three main themes emerged from the data analysis: (1) SD as a safe tissue-touch-based communication tool between operator and person complex adaptive health system; (2) The treatment of SD is shareable between osteopaths, other health professionals, and the patients involved in the therapeutic pathway improving body awareness and health; (3) The development of the SD concept in research and practice to better clarify osteopathic profession identity and definition., Conclusions: A panel of expert osteopaths consider the concept of SD as a valuable tool integrated into the osteopathic evaluation and treatment process. The shared concept and clinical application of SD is informed by person-centered care concepts and from the fields of neuroscience, cognitive and complexity science. Our study reports a common need among osteopaths to develop an evidence-based framework of SD to allow the best development of the osteopathic profession., (© 2022. The Author(s).)

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common genetic cause of Parkinson's disease. Here, we investigated whether the G2019S LRRK2 mutation causes morphological and/or functional changes at nigro-striatal dopamine neurons. Density of striatal dopaminergic terminals, nigral cell counts, tyrosine hydroxylase protein levels as well as exocytotic dopamine release measured in striatal synaptosomes, or striatal extracellular dopamine levels monitored by in vivo microdialysis were similar between ≥12-month-old G2019S knock-in mice and wild-type controls. In vivo striatal dopamine release was insensitive to the LRRK2 inhibitor Nov-LRRK2-11, and was elevated by the membrane dopamine transporter blocker GBR-12783. However, G2019S knock-in mice showed a blunted neurochemical and motor activation response to GBR-12783 compared to wild-type controls. Western blot and dopamine uptake analysis revealed an increase in dopamine transporter levels and activity in the striatum of 12-month-old G2019S KI mice. This phenotype correlated with a reduction in vesicular monoamine transporter 2 levels and an enhancement of vesicular dopamine uptake, which was consistent with greater resistance to reserpine-induced hypolocomotion. These changes were not observed in 3-month-old mice. Finally, Western blot analysis revealed no genotype difference in striatal levels of endogenous α-synuclein or α-synuclein bound to DOPAL (a toxic metabolite of dopamine). However, Serine129-phosphorylated α-synuclein levels were higher in 12-month-old G2019S knock-in mice. Immunohistochemistry confirmed this finding, also showing no genotype difference in 3-month-old mice. We conclude that the G2019S mutation causes progressive dysfunctions of dopamine transporters, along with Serine129-phosphorylated α-synuclein overload, at striatal dopaminergic terminals, which are not associated with dopamine homeostasis dysregulation or neuron loss but might contribute to intrinsic dopaminergic terminal vulnerability. We propose G2019S knock-in mice as a presymptomatic Parkinson's disease model, useful to investigate the pathogenic interaction among genetics, aging, and internal or environmental factors leading to the disease.