Validity of the Central Sensitization Inventory to Address Human Assumed Central Sensitization:Newly Proposed Clinically Relevant Values and Associations

Central sensitization cannot be directly demonstrated in humans and thus a gold standard is missing. Therefore, we used human assumed central sensitization (HACS) when associated with humans. The central sensitization inventory (CSI) is a screening questionnaire for addressing symptoms that are associated with HACS. This cross-sectional study compared patients with chronic pain and at least one central sensitivity syndrome with healthy, pain-free controls via ROC analyses. Analyses were performed for all participants together and for each sex separately. Regression analyses were performed on patients with chronic pain with and without central sensitivity syndromes. Based on 1730 patients and 250 healthy controls, cutoff values for the CSI for the total group were established at 30 points: women: 33 points; men: 25 points. Univariate and multivariate regression analyses were used to identify possible predictors for the CSI score in 2890 patients with chronic pain. The CSI score is associated with all independent factors and has a low association with pain severity in women and a low association with pain severity, age, and body mass index in men. The newly established CSI cutoff values are lower than in previous studies and different per sex, which might be of clinical relevance in daily practice and importance in research.</p

Changes in an Enzyme Ensemble During Catalysis Observed by High Resolution XFEL Crystallography

Enzymes populate ensembles of structures with intrinsically different catalytic proficiencies that are difficult to experimentally characterize. We use time-resolved mix-and-inject serial crystallography (MISC) at an X-ray free electron laser (XFEL) to observe catalysis in a designed mutant (G150T) isocyanide hydratase (ICH) enzyme that enhances sampling of important minor conformations. The active site exists in a mixture of conformations and formation of the thioimidate catalytic intermediate selects for catalytically competent substates. A prior proposal for active site cysteine charge-coupled conformational changes in ICH is validated by determining structures of the enzyme over a range of pH values. A combination of large molecular dynamics simulations of the enzyme in crystallo and timeresolved electron density maps shows that ionization of the general acid Asp17 during catalysis causes additional conformational changes that propagate across the dimer interface, connecting the two active sites. These ionization-linked changes in the ICH conformational ensemble permit water to enter the active site in a location that is poised for intermediate hydrolysis. ICH exhibits a tight coupling between ionization of active site residues and catalysis-activated protein motions, exemplifying a mechanism of electrostatic control of enzyme dynamics

The Downtown Area of Jonestown, Texas.

The objective was to assess Jonestown's value and potential using the Quadruple Net Value metrics.Three projects are focused on the city of Jonestown. The first being a Quadruple Net Value Analysis report generated by undergraduate Land and Property Development students. The second is a public sewer feasibility study to generate creative solutions to septic and environmental conditions by undergraduate capstone Civil Engineering students. Finally, a graduate student will complete a transportation plan for the city to address connectivity and walkability.Texas Target Communitie