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Inflammasomes are multi-protein complexes expressed in immune cells that function as intracellular sensors of environmental, metabolic and cellular stress. Inflammasome activation in the brain, has been shown to drive neuropathology and disease progression by multiple mechanisms, making it one of the most attractive therapeutic targets for disease modification in Parkinson's Disease (PD). Extensive inflammasome activation is evident in the brains of people with PD at the sites of dopaminergic degeneration and synuclein aggregation. While substantial progress has been made on validating inflammasome activation as a therapeutic target for PD, the mechanisms by which inflammasome activation is triggered and sustained over the disease course remain poorly understood. A growing body of evidence point to environmental and occupational chemical exposures as possible triggers of inflammasome activation in PD. The involvement of the gastrointestinal system and gut microbiota in PD pathophysiology is beginning to be elucidated, especially the profound link between gut dysbiosis and immune activation. While large cohort studies confirmed specific changes in the gut microbiota in PD patients compared to age-matched healthy controls, recent research suggest that synuclein pathology could be initiated in the gastrointestinal tract. In this review, we present a summarized perspective on current understanding on inflammasome activation and the gut-brain-axis link during PD pathophysiology. We discuss multiple environmental toxicants that are implicated as the etiological agents in causing idiopathic PD and their mechanistic underpinnings during neuroinflammatory events. We additionally present future directions that needs to address the research questions related to the gut-microbiome-brain mechanisms in PD., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

An important aspect of managing a limited cognitive resource like attention is to use the reward value of stimuli to prioritize the allocation of attention to higher-value over lower-value stimuli. Recent evidence suggests this depends on dopaminergic signaling of reward. In Parkinson's disease, both reward sensitivity and attention are impaired, but whether these deficits are directly related to one another is unknown. We tested whether Parkinson's patients use reward information when automatically allocating their attention and whether this is modulated by dopamine replacement. We compared patients, tested both ON and OFF dopamine replacement medication, to older controls using a standard attention capture task. First, participants learned the different reward values of stimuli. Then, these reward-associated stimuli were used as distractors in a visual search task. We found that patients were generally distracted by the presence of the distractors but that the degree of distraction caused by the high-value and low-value distractors was similar. Furthermore, we found no evidence to support the possibility that dopamine replacement modulates the effect of reward on automatic attention allocation. Our results suggest a possible inability in Parkinson's patients to use the reward value of stimuli when automatically allocating their attention, and raise the possibility that reward-driven allocation of resources may affect the adaptive modulation of other cognitive processes., (© 2021. The Author(s).)

Brain-derived neurotrophic factor (BDNF) is implicated in the survival of striatal neurons. BDNF function is reduced in Huntington's disease (HD), possibly because mutant huntingtin impairs its cortico-striatal transport, contributing to striatal neurodegeneration. The BDNF trophic pathway is a therapeutic target, and blood BDNF has been suggested as a potential biomarker for HD, but BDNF has not been quantified in cerebrospinal fluid (CSF) in HD. We quantified BDNF in CSF and plasma in the HD-CSF cohort (20 pre-manifest and 40 manifest HD mutation carriers and 20 age and gender-matched controls) using conventional ELISAs and an ultra-sensitive immunoassay. BDNF concentration was below the limit of detection of the conventional ELISAs, raising doubt about previous CSF reports in neurodegeneration. Using the ultra-sensitive method, BDNF concentration was quantifiable in all samples but did not differ between controls and HD mutation carriers in CSF or plasma, was not associated with clinical scores or MRI brain volumetric measures, and had poor ability to discriminate controls from HD mutation carriers, and premanifest from manifest HD. We conclude that BDNF in CSF and plasma is unlikely to be a biomarker of HD progression and urge caution in interpreting studies where conventional ELISA was used to quantify CSF BDNF.

Lysosomes receive and degrade cargo from endocytosis, phagocytosis and autophagy. They also play an important role in sensing and instructing cells on their metabolic state. The lipid kinase PIKfyve generates phosphatidylinositol-3,5-bisphosphate to modulate lysosome function. PIKfyve inhibition leads to impaired degradative capacity, ion dysregulation, abated autophagic flux and a massive enlargement of lysosomes. Collectively, this leads to various physiological defects, including embryonic lethality, neurodegeneration and overt inflammation. The reasons for such drastic lysosome enlargement remain unclear. Here, we examined whether biosynthesis and/or fusion-fission dynamics contribute to swelling. First, we show that PIKfyve inhibition activates TFEB, TFE3 and MITF, enhancing lysosome gene expression. However, this did not augment lysosomal protein levels during acute PIKfyve inhibition, and deletion of TFEB and/or related proteins did not impair lysosome swelling. Instead, PIKfyve inhibition led to fewer but enlarged lysosomes, suggesting that an imbalance favouring lysosome fusion over fission causes lysosome enlargement. Indeed, conditions that abated fusion curtailed lysosome swelling in PIKfyve-inhibited cells., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Background: Extended thymectomy is indicated for patients with myasthenia gravis (MG) when drug-resistance or dependence is seen. We have employed a technique for subcostal thoracoscopic extended thymectomy (STET) on patients with MG., Methods: Clinical data of 15 eligible patients who underwent STET in our department from February 2015 to November 2015 by the same surgical team were retrospectively analyzed. The operation time, blood loss, duration of postoperative hospital stay, thoracic drainage periods were concerned., Results: All the surgeries were finished successfully without conversion to sternotomy. Mean operation time was 157.53±40.31 min (range, 73-275 min). Mean blood loss was 56.33±7.07 mL (range, 10-200 mL). Mean pleural drainage volume in the first 24 hours was 72.67±17.68 mL (range, 0-250 mL). Mean postoperative thoracic drainage periods were 1.20±0.71 days (range, 0-3 days). Mean duration of postoperative hospital stay was 6.13±0.71 days (range, 3-22 days)., Conclusions: This procedure showed satisfactory results for patients with MG. Moreover, the STET approach is more easily for surgeons to fully reveal the bilateral phrenic nerve and the upper thymic poles. We believe that STET is a satisfactory procedure for performing extended thymectomy in well selected patients.