Basal procalcitonin, C-reactive protein, interleukin-6, and presepsin for prediction of mortality in critically ill septic patients: a systematic review and meta-analysis

Biomarkers; Mortality; SepsisBiomarcadores; Mortalidad; SepsisBiomarcadors; Mortalitat; SèpsiaBackground Numerous biomarkers have been proposed for diagnosis, therapeutic, and prognosis in sepsis. Previous evaluations of the value of biomarkers for predicting mortality due to this life-threatening condition fail to address the complexity of this condition and the risk of bias associated with prognostic studies. We evaluate the predictive performance of four of these biomarkers in the prognosis of mortality through a methodologically sound evaluation. Methods We conducted a systematic review a systematic review and meta-analysis to determine, in critically ill adults with sepsis, whether procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), and presepsin (sCD14) are independent prognostic factors for mortality. We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials up to March 2023. Only Phase-2 confirmatory prognostic factor studies among critically ill septic adults were included. Random effects meta-analyses pooled the prognostic association estimates. Results We included 60 studies (15,681 patients) with 99 biomarker assessments. Quality of the statistical analysis and reporting domains using the QUIPS tool showed high risk of bias in > 60% assessments. The biomarker measurement as a continuous variable in models adjusted by key covariates (age and severity score) for predicting mortality at 28–30 days showed a null or near to null association for basal PCT (pooled OR = 0.99, 95% CI = 0.99–1.003), CRP (OR = 1.01, 95% CI = 0.87 to 1.17), and IL-6 (OR = 1.02, 95% CI = 1.01–1.03) and sCD14 (pooled HR = 1.003, 95% CI = 1.000 to 1.006). Additional meta-analyses accounting for other prognostic covariates had similarly null findings. Conclusion Baseline, isolated measurement of PCT, CRP, IL-6, and sCD14 has not been shown to help predict mortality in critically ill patients with sepsis. The role of these biomarkers should be evaluated in new studies where the patient selection would be standardized and the measurement of biomarker results.Instituto de Salud Carlos III, Spain and European Union (“Fondo Europeo de Desarrollo Regional, Una manera de hacer Europa”), grant number [PI 19/0048]

Ion mobility action spectroscopy of flavin dianions reveals deprotomer-dependent photochemistry

The intrinsic optical properties and photochemistry of flavin adenine dinucleotide (FAD) dianions are investigated using a combination of tandem ion mobility spectrometry and action spectroscopy. Two principal isomers are observed, the more stable form being deprotonated on the isoalloxazine group and a phosphate (N-3,PO4 deprotomer), and the other on the two phosphates (PO4,PO4 deprotomer). Ion mobility data and electronic action spectra suggest that photo-induced proton transfer occurs from the isoalloxazine group to a phosphate group, converting the PO4,PO4 deprotomer to the N-3,PO4 deprotomer. Comparisons of the isomer selective action spectra of FAD dianions and flavin monoanions with solution spectra and gas-phase photodissociation action spectra suggests that solvation shifts the electronic absorption of the deprotonated isoalloxazine group to higher energy. This is interpreted as evidence for significant charge transfer in the lowest optical transition of deprotonated isoalloxazine. Overall, this work demonstrates that the site of deprotonation of flavin anions strongly affects their electronic absorptions and photochemistry

El Aborto En Las Menores De Edad En La Ciudad De Bogotá En Los Últimos 3 años

s/

Insights from ion mobility-mass spectrometry, infrared spectroscopy, and molecular dynamics simulations on nicotinamide adenine dinucleotide structural dynamics: NAD + vs. NADH

International audienc

Validación de la STANFORD PRESENTEEISM SCALE - SPS 6 para instituciones del sector salud en Colombia

Introducción: El Presentismo es un fenómeno organizacional que implica la permanencia en el trabajo, pero con factores físicos como enfermedades no tratadas y/o emocionales como el estrés, situaciones familiares entre otros distractores. Estas condiciones representan un reto para las empresas debido a que impacta directamente la productividad y el logro de objetivos institucionales, es por ello que en los últimos años se ha convertido en un tema de interés en las investigaciones a nivel mundial.   Objetivo: validar la Stanford Presenteeism Scale SPS-6 en entidades de salud mediante su adaptación al contexto colombiano. Métodos: Se realizó un estudio de adaptación cultural y validación del instrumento SPS-6 con 301 enfermeros, el proceso de validación comprendió: traducción y contra traducción del inglés - español - inglés del instrumento, aplicación método Delphi, prueba piloto y cálculo del coeficiente alfa de Cronbach. Resultados: el índice alfa de Cronbach fue de 0.637, la adaptación lingüística y el método Delphi favorecen la confiabilidad del instrumento y su validez, este proceso permitió la comprensión de la finalidad del instrumento por parte de los encuestados. Conclusiones: La SPS-6 en población de enfermería arrojó que aquellas personas que manifiestan Presentismo tienen una condición de salud física o emocional de base. El proceso investigativo demuestra que la SPS-6 es un instrumento válido y confiable para ser aplicado en instituciones del sector salud en Colombia

Characterization of Intramolecular Interactions of Cytochrome <i>c</i> Using Hydrogen–Deuterium Exchange-Trapped Ion Mobility Spectrometry–Mass Spectrometry and Molecular Dynamics

Globular proteins, such as cytochrome <i>c</i> (cyt <i>c</i>), display an organized native conformation, maintained by a hydrogen bond interaction network. In the present work, the structural interrogation of kinetically trapped intermediates of cyt <i>c</i> was performed by correlating the ion-neutral collision cross section (CCS) and charge state with the starting solution conditions and time after desolvation using collision induced activation (CIA), time-resolved hydrogen/deuterium back exchange (HDX) and trapped ion mobility spectrometry–mass spectrometry (TIMS-MS). The high ion mobility resolving power of the TIMS analyzer allowed the identification of new ion mobility bands, yielding a total of 63 mobility bands over the +6 to +21 charge states and 20 mobility bands over the −5 to −10 charge states. Mobility selected HDX rates showed that for the same charge state, conformers with larger CCS present faster HDX rates in both positive and negative ion mode, suggesting that the charge sites and neighboring exchange sites on the accessible surface area define the exchange rate regardless of the charge state. Complementary molecular dynamic simulations permitted the generation of candidate structures and a mechanistic model of the folding transitions from native (N) to molten globule (MG) to kinetic intermediates (U) pathways. Our results suggest that cyt <i>c</i> major structural unfolding is associated with the distancing of the N- and C-terminal helices and subsequent solvent exposure of the hydrophobic, heme-containing cavity

Flavin Adenine Dinucleotide Structural Motifs: From Solution to Gas Phase

Flavin adenine dinucleotide (FAD) is involved in important metabolic reactions where the biological function is intrinsically related to changes in conformation. In the present work, FAD conformational changes were studied in solution and in gas phase by measuring the fluorescence decay time and ion-neutral collision cross sections (CCS, in a trapped ion mobility spectrometer, TIMS) as a function of the solvent conditions (i.e., organic content) and gas-phase collisional partner (i.e., N₂ doped with organic molecules). Changes in the fluorescence decay suggest that FAD can exist in four conformations in solution, where the abundance of the extended conformations increases with the organic content. TIMS-MS experiments showed that FAD can exist in the gas phase as deprotonated (M = C₂₇H₃₁N₉O₁₅P₂) and protonated forms (M = C₂₇H₃₃N₉O₁₅P₂) and that multiple conformations (up to 12) can be observed as a function of the starting solution for the [M + H]⁺ and [M + Na]⁺molecular ions. In addition, changes in the relative abundances of the gas-phase structures were observed from a “stack” to a “close” conformation when organic molecules were introduced in the TIMS cell as collision partners. Candidate structures optimized at the DFT/B3LYP/6-31G­(d,p) were proposed for each IMS band, and results showed that the most abundant IMS band corresponds to the most stable candidate structure. Solution and gas-phase experiments suggest that the driving force that stabilizes the different conformations is based on the interaction of the adenine and isoalloxazine rings that can be tailored by the “solvation” effect created with the organic molecules

Characterization of the Photophysical, Thermodynamic, and Structural Properties of the Terbium(III)–DREAM Complex

DREAM (also known as K⁺ channel interacting protein 3 and calsenilin) is a calcium binding protein and an active modulator of K_V4 channels in neuronal cells as well as a novel Ca²⁺-regulated transcriptional modulator. DREAM has also been associated with the regulation of Alzheimer’s disease through the prevention of presenilin-2 fragmentation. Many interactions of DREAM with its binding partners (Kv4, calmodulin, DNA, and drugs) have been shown to be dependent on calcium. Therefore, understanding the structural changes induced by binding of metals to DREAM is essential for elucidating the mechanism of signal transduction and biological activity of this protein. Here, we show that the fluorescence emission and excitation spectra of the calcium luminescent analogue, Tb³⁺, are enhanced upon binding to the EF-hands of DREAM due to a mechanism of energy transfer between Trp and Tb³⁺. We also observe that unlike Tb³⁺-bound calmodulin, the luminescence lifetime of terbium bound to DREAM decays as a complex multiexponential (τ_average ∼ 1.8 ms) that is sensitive to perturbation of the protein structure and drug (NS5806) binding. Using isothermal calorimetry, we have determined that Tb³⁺ binds to at least three sites with high affinity (<i>K</i>_d = 1.8 μM in the presence of Ca²⁺) and displaces bound Ca²⁺ through an entropically driven mechanism (Δ<i>H</i> ∼ 12 kcal mol^–1, and <i>T</i>Δ<i>S</i> ∼ 22 kcal mol^–1). Furthermore, the hydrophobic probe 1,8-ANS shows that Tb³⁺, like Ca²⁺, triggers the exposure of a hydrophobic surface on DREAM, which modulates ligand binding. Analogous to Ca²⁺ binding, Tb³⁺ binding also induces the dimerization of DREAM. Secondary structural analyses using far-UV circular dichroism and trapped ion mobility spectrometry–mass spectrometry reveal that replacement of Ca²⁺ with Tb³⁺ preserves the folding state with minimal changes to the overall structure of DREAM. These findings pave the way for further investigation of the metal binding properties of DREAM using lanthanides as well as the study of DREAM–protein complexes by lanthanide resonance energy transfer or nuclear magnetic resonance