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value analysis over the first-year episode-of-care. With healthcare transitioning towards value-based delivery, PLVA offers a quantitative tool to measure the value of individual patient care delivery over the entire episode-of-care.

Muscle atrophy (MA) and fatty infiltration (FI) are degenerative processes of rotator cuff musculature that have incompletely understood relationships with the development of eccentric glenoid wear in the setting of primary glenohumeral osteoarthritis (GHOA).

All patients between 2015 and 2020 with GHOA and an intact rotator cuff that underwent both MRI and CT scans of the affected shoulder prior to total shoulder arthroplasty were identified from a prospectively maintained registry. Rotator cuff MA was measured quantitatively on sequential sagittal MRI images, whereas FI was assessed on sagittal MRI slices using the Goutallier classification. Preoperative CT scans were reconstructed utilizing automated 3-dimensional software in order to determine glenoid retroversion, inclination, and humeral head subluxation. Glenoid deformity was classified according to the Walch classification. Univariate and multivariable regression analyses were performed to characterize associations between age, sex, muscle area, fcle atrophy and fatty infiltration should be considered as two discrete processes in the natural history of GHOA.

Coronal shear fractures of the capitellum and trochlea are relatively uncommon and can be challenging to treat because of variable articular comminution and poor bone stock. Classification is valuable to help guide surgical decision making and prognosis. The aim of this study was to present a large series of coronal shear fractures treated according to the Modified Dubberley Classification System (MDCS).

45 patients with a coronal shear fracture were followed up (12-93 months, mean 28 months) after surgical intervention. Fractures were classified according to the MDCS by 3 observers and outcome data collected included Oxford Elbow Score (OES), Visual Analogue Pain Score (VAS), range of motion (ROM), complications, and radiographic findings.

There were 10 type 1; 12 type 2; 8 type 3 and 15 type 4 fractures. There were 26 subtype B fractures (posterior comminution). 37 patients had open reduction and internal fixation (ORIF) and 8 underwent primary arthroplasty. The median OES and VAS were 43(16-48) and 2hould be considered for arthroplasty because of the higher risk of complications with ORIF.

Consistently good outcomes can be achieved by classification and management according to the MDCS. It is recommended that type B fractures undergo combined plate and screw fixation and that type 4 fractures should be considered for arthroplasty because of the higher risk of complications with ORIF.

While numerous preoperative factors that influence postoperative outcomes after anatomic total shoulder arthroplasty (aTSA) have been identified, preoperative shoulder strength has not been studied. The purpose of this study was to determine if preoperative shoulder strength is predictive of postoperative outcomes and improvement after primary aTSA.

A retrospective review was conducted of prospectively-collected data from 160 shoulders with minimum 2-year follow-up after primary aTSA. Preoperative external rotation (ER) strength, supraspinatus strength, and abduction strength score were analyzed to determine their correlation with postoperative outcomes and improvement in shoulder strength, range of motion (ROM), and outcome scores. Multiple linear regression models were subsequently used to adjust for covariates and determine the preoperative measures of shoulder strength that most influenced postoperative outcomes and improvement.

Preoperative ER strength, supraspinatus strength, and abduction strengttcome scores. The results from our study demonstrate abduction strength may be a useful indicator of patient outcomes after aTSA. Our findings will provide surgeons with useful prognostic insight to aid in guiding patient expectations.

Preoperative shoulder strength is moderately associated with postoperative outcomes and improvements in shoulder strength, ROM, and outcome scores after primary aTSA. Importantly, we identified preoperative strength values that led to a decrease in strength postoperatively, but not ROM or outcome scores. The results from our study demonstrate abduction strength may be a useful indicator of patient outcomes after aTSA. Our findings will provide surgeons with useful prognostic insight to aid in guiding patient expectations.In Parkinson's disease (PD), the second most common neurodegenerative disorder, non-motor symptoms often precede the development of debilitating motor symptoms and present a severe impact on the quality of life. Lewy bodies containing misfolded α-synuclein progressively develop in neurons throughout the peripheral and central nervous system, which may be correlated with the early development of non-motor symptoms. Among those, increased fear and anxiety is frequent in PD and thought to result from pathology outside the dopaminergic system, which has been the focus of symptomatic treatment to alleviate motor symptoms. Alpha-synuclein accumulation has been reported in the amygdala of PD patients, a brain region critically involved in fear and anxiety. Here we asked whether α-synuclein overexpression alone is sufficient to induce an enhanced fear phenotype in vivo and which pathological mechanisms are involved. Transgenic mice expressing human wild-type α-synuclein (Thy1-aSyn), a well-established model of PD, wer therapeutic options and further early biomarker research.

α-synuclein (α-syn) aggregation can lead to degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) as invariably observed in patients with Parkinson's Disease (PD). The co-chaperone DNAJB6 has previously been found to be expressed at higher levels in PD patients than in control subjects and was also found in Lewy bodies. Our previous experiments showed that knock out of DNAJB6 induced α-syn aggregation in cellular level. However, effects of overexpression of DNAJB6 against α-syn aggregation remains to be investigated.

We used a α-syn CFP/YFP HEK293 FRET cell line to investigate the effects of overexpression of DNAJB6 in cellular level. α-syn aggregation was induced by transfection α-syn preformed fibrils (PPF), then was measured FRET analysis. We proceeded to investigate if DNAJB6b can impair α-syn aggregation and toxicity in an animal model and used adeno associated vira (AAV6) designed to overexpress of human wt α-syn, GFP-DNAJB6 or GFP in rats. These vectors were injected ints and that this results in a suppression of dopaminergic cell death and PD related motor deficits in an animal model of PD.The huntingtin-associated protein 40 (HAP40) is an abundant interactor of huntingtin (HTT). In complexes of these proteins, HAP40 tightly binds to HTT in a cleft formed by two larger domains rich in HEAT repeats, and a smaller bridge domain connecting the two. We show that HAP40 steady-state protein levels are directly dependent on HTT (both normal and mutant HTT) and that HAP40 is strongly stabilized by the interaction with HTT resulting in an at least 5-fold increase in HAP40's half-life when bound to HTT. Cellular HAP40 protein levels were reduced in primary fibroblasts and lymphoblasts of Huntington Disease (HD) patients and in brain tissue of a full-length HTT mouse model of HD, concomitant with decreased soluble HTT levels in these cell types. This data and our previous demonstration of coevolution between HTT and HAP40 and evolutionary conservation of their interaction suggest that HAP40 is an obligate interaction partner of HTT. Our observation of reduced HAP40 levels in HD invites further studies, whether HAP40 loss-of-function contributes to the pathophysiology of HD.Idiopathic Parkinson's disease is the second most common neurodegenerative disease and is estimated to be approximately 30% heritable. Genome wide association studies have revealed numerous loci associated with risk of development of Parkinson's disease. The majority of genes identified in these studies are expressed in glia at either similar or greater levels than their expression in neurons, suggesting that glia may play a role in Parkinson's disease pathogenesis. The role of individual glial risk genes in Parkinson's disease development or progression is unknown, however. We hypothesized that some Parkinson's disease risk genes exert their effects through glia. We developed a Drosophila model of α-synucleinopathy in which we can independently manipulate gene expression in neurons and glia. Human wild type α-synuclein is expressed in all neurons, and these flies develop the hallmarks of Parkinson's disease, including motor impairment, death of dopaminergic and other neurons, and α-synuclein aggregation. In these flies, we performed a candidate genetic screen, using RNAi to knockdown 14 well-validated Parkinson's disease risk genes in glia and measuring the effect on locomotion in order to identify glial modifiers of the α-synuclein phenotype. We identified 4 modifiers aux, Lrrk, Ric, and Vps13, orthologs of the human genes GAK, LRRK2, RIT2, and VPS13C, respectively. Knockdown of each gene exacerbated neurodegeneration as measured by total and dopaminergic neuron loss. Knockdown of each modifier also increased α-synuclein oligomerization. These results suggest that some Parkinson's disease risk genes exert their effects in glia and that glia can influence neuronal α-synuclein proteostasis in a non-cell-autonomous fashion. Further, this study provides proof of concept that our novel Drosophila α-synucleinopathy model can be used to study glial modifier genes, paving the way for future large unbiased screens to identify novel glial risk factors that contribute to PD risk and progression.From the first illustrations of neuronal morphology by Ramón y Cajal to the recent three-dimensional reconstruction of synaptic connections, the development of modern neuroscience has greatly benefited from breakthroughs in imaging technology. This also applies specifically to the study of neurodegenerative diseases. Much of the research into these diseases relies on the direct visualisation of intracellular structures and their dynamics in degenerating neural cells, which cannot be fully resolved by diffraction-limited microscopes. Progress in the field has therefore been closely linked to the development of super-resolution imaging methods. Their application has greatly advanced our understanding of disease mechanisms, ranging from the structural progression of protein aggregates to defects in organelle morphology. selleck inhibitor Recent super-resolution studies have specifically implicated the disruption of inter-organelle interactions in multiple neurodegenerative diseases. In this article, we describe some of the key super-resolution techniques that have contributed to this field. We then discuss work to visualise changes in the structure and dynamics of organelles and associated dysfunctions. Finally, we consider what future developments in imaging technology may further our knowledge of these processes.Group I metabotropic glutamate receptors (mGluRs), mGluR1 and mGluR5, in the spinal cord are implicated in nociceptive transmission and plasticity through G protein-mediated second messenger cascades leading to the activation of various protein kinases such as extracellular signal-regulated kinase (ERK). In this study, we demonstrated that cytohesin-2, a guanine nucleotide exchange factor for ADP ribosylation factors (Arfs), is abundantly expressed in subsets of excitatory interneurons and projection neurons in the superficial dorsal horn. Cytohesin-2 is enriched in the perisynapse on the postsynaptic membrane of dorsal horn neurons and forms a protein complex with mGluR5 in the spinal cord. Central nervous system-specific cytohesin-2 conditional knockout mice exhibited reduced mechanical allodynia in inflammatory and neuropathic pain models. Pharmacological blockade of cytohesin catalytic activity with SecinH3 similarly reduced mechanical allodynia and inhibited the spinal activation of Arf6, but not Arf1, in both pain models.