Exogenous application of platelet-leukocyte gel during open subacromial decompression contributes to improved patient outcome

Background: Platelet-leukocyte gel (PLG) is being used during various surgical procedures in an attempt to enhance the healing process. We studied the effects of PLG on postoperative recovery of patients undergoing open subacromial decompression (OSD). Methods: PLG was produced from platelet-leukocyte-rich plasma (P-LRP), prepared from a unit of whole blood. Forty patients were included in the study. Self-assessed evaluations, using the American Shoulder and Elbow Surgeons scoring system of activities of daily living (ADL), joint instability, pain levels, pain medications, and clinical evaluations for range of motion were conducted. Results: Platelet and leukocyte counts were significantly increased in the P-LRP compared to baseline counts. Treated patients demonstrated decreased visual analog scales for pain and used significantly less pain medication, had an improved range of motion during passive forward elevation, external rotation, external rotation with arm at 90 degrees abduction, internal rotation, and cross body adduction compared to control patients (p < 0.001). No differences in the instability score were observed between the groups. Furthermore, treated patients performed more ADL (p < 0.05). Conclusion: In the PLG-treated group, recovery was faster and patients returned earlier to daily activities and also took less pain medication than control subjects

A Bayesian Approach to Risk Management in a World of High-Frequency Data

A Realised Volatility GARCH model using high-frequency data is developed within a Bayesian framework for the purpose of forecasting Value at Risk and Conditional Value at Risk. A Skewed Student-t return distribution is combined with a Student-t distribution in the measurement equation in a GARCH framework. Realised Volatility GARCH models show a marked improvement compared to ordinary GARCH. A Skewed Student-t Realised DCC copula model using Realised Volatility GARCH marginal functions is developed within a Bayesian framework for the purpose of forecasting portfolio tail risk. The use of copulas is implemented so that the marginal distributions can be separated from the dependence structure to produce tail forecasts. This is compared to using traditional GARCH-copula models, and GARCH on an aggregated portfolio. Copula models implementing a Realised Volatility GARCH framework show an improvement over traditional GARCH models. A Bayesian detection of regime changes utilizing high-frequency data is developed, once again for the purpose of forecasting portfolio tail risk. The use of high-frequency data improves the accuracy of regime change detection compared to daily data. Monte Carlo sampling schemes are employed for the estimation of these models

Protein-protein modelling using cryo-EM restraints

The recent improvements in cryo-electron microscopy (cryo-EM) in the past few years are now allowing to observe molecular complexes at atomic resolution. As a consequence, numerous structures derived from cryo-EM are now available in the Protein Data Bank. However, if for some complexes atomic resolution is reached, this is not true for all. This is also the case in cryo-electron tomography where the achievable resolution is still limited. Furthermore the resolution in a cryo-EM map is not a constant, with often outer regions being of lower resolution, possibly linked to conformational variability. Although those low to medium resolution EM maps (or regions thereof) cannot directly provide atomic structure of large molecular complexes, they provide valuable information to model the individual components and their assembly into them. Most approaches for this kind of modelling are performing rigid fitting of the individual components into the EM density map. While this would appear an obvious option, they ignore key aspects of molecular recognition, the energetics and flexibility of the interfaces. Moreover, these often restricts the modelling to a unique source of data, the EM density map. In this chapter, we describe a protocol where an EM map is used as restraint in HADDOCK to guide the modelling process.Comment: 28 pages including 7 figure

Protein kinase B (AKT) upregulation and Thy-1-α_vβ₃ integrin-induced phosphorylation of Connexin43 by activated AKT in astrogliosis.

In response to brain injury or inflammation, astrocytes undergo hypertrophy, proliferate, and migrate to the damaged zone. These changes, collectively known as "astrogliosis", initially protect the brain; however, astrogliosis can also cause neuronal dysfunction. Additionally, these astrocytes undergo intracellular changes involving alterations in the expression and localization of many proteins, including α &lt;sub&gt;v&lt;/sub&gt; β &lt;sub&gt;3&lt;/sub&gt; integrin. Our previous reports indicate that Thy-1, a neuronal glycoprotein, binds to this integrin inducing Connexin43 (Cx43) hemichannel (HC) opening, ATP release, and astrocyte migration. Despite such insight, important links and molecular events leading to astrogliosis remain to be defined. Using bioinformatics approaches, we analyzed different Gene Expression Omnibus datasets to identify changes occurring in reactive astrocytes as compared to astrocytes from the normal mouse brain. In silico analysis was validated by both qRT-PCR and immunoblotting using reactive astrocyte cultures from the normal rat brain treated with TNF and from the brain of a hSOD1 &lt;sup&gt;G93A&lt;/sup&gt; transgenic mouse model. We evaluated the phosphorylation of Cx43 serine residue 373 (S373) by AKT and ATP release as a functional assay for HC opening. In vivo experiments were also performed with an AKT inhibitor (AKTi). The bioinformatics analysis revealed that genes of the PI3K/AKT signaling pathway were among the most significantly altered in reactive astrocytes. mRNA and protein levels of PI3K, AKT, as well as Cx43, were elevated in reactive astrocytes from normal rats and from hSOD1 &lt;sup&gt;G93A&lt;/sup&gt; transgenic mice, as compared to controls. In vitro, reactive astrocytes stimulated with Thy-1 responded by activating AKT, which phosphorylated S373Cx43. Increased pS373Cx43 augmented the release of ATP to the extracellular medium and AKTi inhibited these Thy-1-induced responses. Furthermore, in an in vivo model of inflammation (brain damage), AKTi decreased the levels of astrocyte reactivity markers and S373Cx43 phosphorylation. Here, we identify changes in the PI3K/AKT molecular signaling network and show how they participate in astrogliosis by regulating the HC protein Cx43. Moreover, because HC opening and ATP release are important in astrocyte reactivity, the phosphorylation of Cx43 by AKT and the associated increase in ATP release identify a potential therapeutic window of opportunity to limit the adverse effects of astrogliosis

Chronic primary pain in the COVID-19 pandemic: how uncertainty and stress impact on functioning and suffering.

Health and self-regulatio

Radiofrequency Treatment of Facet-related Pain: Evidence and Controversies

Pain originating from the lumbar facet joints is estimated to represent about 15% of all low back pain complaints. The diagnostic block is considered to be a valuable tool for confirming facetogenic pain. It was demonstrated that a block of the ramus medialis of the ramus dorsalis is preferred over an intra-articular injection. The outcome of the consequent radiofrequency treatment is not different in patients reporting over 80% pain relief after the diagnostic block than in those who have between 50% and 79% pain relief. There is one well-conducted comparative trial assessing the value of one or two controlled diagnostic blocks to none. The results of the seven randomized trials on the use of radiofrequency treatment of facet joint pain demonstrate that good patient selection is imperative for good clinical outcome. Therefore, we suggest one block of the ramus medialis of the ramus dorsalis before radiofrequency treatment