Thomsengram4482

Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder after Alzheimer's disease. Increasing evidence highlights the role of age-related chronic inflammation, oxidative stress and mitochondrial dysfunction in the pathogenesis of PD. A combination of these factors impairs the crosstalk between mitochondria and lysosomes, resulting in compromised cell homeostasis. this website Apolipoprotein D (APOD), an ancient and highly conserved anti-inflammatory and antioxidant lipocalin, and the transcription factor EB (TFEB), a master regulator of mitophagy, autophagy and lysosomal biogenesis, play key roles in these processes. Both APOD and TFEB have attracted attention as therapeutic targets for PD. The aim of this study was to investigate if the selective cyclooxygenase-2 inhibitor celecoxib (CXB) exerts a direct neuroprotective effect in 6-hydroxydopamine (6-OHDA) and paraquat (PQ) PD models. We found that CXB rescued SH-SY5Y cells challenged by 6-OHDA- and PQ-induced toxicity. Furthermore, treatment with CXB led to a marked and sustained upregulation of APOD and the two microphthalmia transcription factors TFEB and MITF. In sum, this study highlights the clinically approved drug CXB as a promising neuroprotective therapeutic tool in PD research that has the potential to increase the survival rate of dopaminergic neurons that are still alive at the time of diagnosis.Significant efforts have been recently made to obtain the three-dimensional (3D) structure of the genome with the goal of understanding how structures may affect gene regulation and expression. Chromosome conformational capture techniques such as Hi-C, have been key in uncovering the quantitative information needed to determine chromatin organization. Complementing these experimental tools, co-polymers theoretical methods are necessary to determine the ensemble of three-dimensional structures associated to the experimental data provided by Hi-C maps. Going beyond just structural information, these theoretical advances also start to provide an understanding of the underlying mechanisms governing genome assembly and function. Recent theoretical work, however, has been focused on single chromosome structures, missing the fact that, in the full nucleus, interactions between chromosomes play a central role in their organization. To overcome this limitation, MiChroM (Minimal Chromatin Model) has been modified to become capable of performing these multi-chromosome simulations. It has been upgraded into a fast and scalable software version, which is able to perform chromosome simulations using GPUs via OpenMM Python API, called Open-MiChroM. To validate the efficiency of this new version, analyses for GM12878 individual autosomes were performed and compared to earlier studies. This validation was followed by multi-chain simulations including the four largest human chromosomes (C1-C4). These simulations demonstrated the full power of this new approach. Comparison to Hi-C data shows that these multiple chromosome interactions are essential for a more accurate agreement with experimental results. Without any changes to the original MiChroM potential, it is now possible to predict experimentally observed inter-chromosome contacts. This scalability of Open-MiChroM allow for more audacious investigations, looking at interactions of multiple chains as well as moving towards higher resolution chromosomes models.

Endoscopists experience upper extremity musculoskeletal injuries. The primary aim of this study was to compare distal upper extremity biomechanical risk factors during colonoscopy with established risk thresholds. Secondary aims were to determine which subtasks during colonoscopy are associated with the greatest risk and to evaluate an intervention to reduce risks.

Twelve endoscopists performed 2 to 4 colonoscopies while thumb pinch force and forearm muscle loads of extensor carpi radialis (ECR) and flexor digitorum superficialis (FDS) muscles were collected. Peak exertion values were analyzed using amplitude probability distribution functions. An endoscope support device was evaluated during simulated colonoscopy (n= 8).

Mean endoscopist age was 42.3 years; 67% were men. Peak thumb pinch force exceeded risk thresholds for pinch force (10 N) and percent of time spent in forceful pinch for all colonoscopy subtasks. Peak ECR and FDS muscle activity exceeded the action limit (10% maximum voluntary contraction [MVC]) in both forearms. Peak left FDS, left ECR, and right ECR activity exceeded the threshold limit value (>30% MVC). Peak left FDS and ECR activity were significantly greater during insertion than during withdrawal (P< .05). Peak right FDS and ECR activity were significantly greater during right colon insertion compared with withdrawal (P< .05). The endoscope support device reduced left ECR muscle activity (P= .02).

Thumb pinch forces and time spent in forceful pinch indicate high-risk exposures during colonoscopy. Left wrist extensor muscle activity exceeded established thresholds with the greatest risk occurring during insertion. An endoscope support device reduced loads to the left wrist extensors.

Thumb pinch forces and time spent in forceful pinch indicate high-risk exposures during colonoscopy. Left wrist extensor muscle activity exceeded established thresholds with the greatest risk occurring during insertion. An endoscope support device reduced loads to the left wrist extensors.

The American Society for Gastrointestinal Endoscopy (ASGE) 2010 guidelines for suspected choledocholithiasis were recently updated by proposing more specific criteria for selection of high-risk patients to undergo direct ERCP while advocating the use of additional imaging studies for intermediate- and low-risk individuals. We aim to compare the performance and diagnostic accuracy of 2019 versus 2010 ASGE criteria for suspected choledocholithiasis.

We performed a retrospective chart review of a prospectively maintained database (2013-2019) of over 10,000 ERCPs performed by 70 gastroenterologists in our 14-hospital system. We randomly selected 744 ERCPs in which the primary indication was suspected choledocholithiasis. Patients with a history of cholecystectomy or prior sphincterotomy were excluded. The same patient cohort was assigned as low, intermediate, or high risk according to the 2010 and 2019 guideline criteria. Overall accuracy of both guidelines was compared against the presence of stones and/or sludge on ERCP.