Expression of the human Parkinson-disease-associated protein α-synuclein in all Drosophila neurons induces progressive locomotor deficits. Here, we identify a group of 15 dopaminergic neurons per hemisphere in the anterior medial region of the brain whose disruption correlates with climbing impairments in this model. These neurons selectively innervate the horizontal β and β' lobes of the mushroom bodies, and their connections to the Kenyon cells are markedly reduced when they express α-synuclein. Using selective mushroom body drivers, we show that blocking or overstimulating neuronal activity in the β' lobe, but not the β or γ lobes, significantly inhibits negative geotaxis behavior. This suggests that modulation of the mushroom body β' lobes by this dopaminergic pathway is specifically required for an efficient control of startle-induced locomotion in flies.

BackgroundBone metastases in thyroid cancer impair the patient's quality of life and prognosis. Interestingly, wide margins resection as the surgical treatment of bone metastases might improve the overall survival (OS). Nonetheless, data are lacking regarding the potential benefits of this strategy.MethodsIn order to assess the OS of patients with thyroid cancer after a bone metastases carcinologic resection, a retrospective multicentric study was performed, evaluating the 1, 5, 10 and 15 years-OS along with the potential prognosis associated factors.Results40 patients have been included in this multicentric study, with a mean follow-up after surgery of 46.6 ± 58 months. We observed 25 (62.5%) unimestastatic patients and 15 multimetastatic patients (37.5%). The median overall survival after resection was 48 ± 57.3 months. OS at 1, 5, 10, and 15 years was respectively 76.2%, 63.6%, 63.6%, and 31.8%. Survival for patients with a single bone metastasis at 15 year was 82.3%, compared with 0.0% (Log Rank, p = 0.022) for multi-metastatic bone patients.ConclusionsThis study advocates for an increased long term 10-year OS in patients with thyroid cancer, after resection of a single bone metastasis, suggesting the benefits of this strategy in this population.

Long bone pathological fractures very much reflect bone metastases morbidity in many types of cancer. Bearing in mind that they not only compromise patient function but also survival, identifying impending fractures before the actual event is one of the main concerns for tumor boards. Indeed, timely prophylactic surgery has been demonstrated to increase patient quality of life as well as survival. However, early surgery for long bone metastases remains controversial as the current fracture risk assessment tools lack accuracy. This review first focuses on the gold standard Mirels rating system. It then explores other unique imaging thresholds such as axial or circumferential cortical involvement and the merits of nuclear imaging tools. To overcome the lack of specificity, other fracture prediction strategies have focused on biomechanical models based on quantitative computed tomography (CT): computed tomography rigidity analysis (CT-RA) and finite element analysis (CT-FEA). Despite their higher specificities in impending fracture assessment, their limited availability, along with a need for standardization, have limited their use in everyday practice. Currently, the prediction of long bone pathologic fractures is a multifactorial process. In this regard, machine learning could potentially be of value by taking into account clinical survival prediction as well as clinical and improved CT-RA/FEA data.