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1.
Curr Pain Headache Rep ; 27(11): 737-745, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37740879

RESUMO

PURPOSE OF REVIEW: In the present review, various categories of pain, clinician-observed pain scales, and patient-reported pain scales are evaluated to better understand factors that impact patient pain perceptions. Additionally, the expansion of areas that require further research to determine the optimal way to evaluate pain scale data for treatment and management are discussed. RECENT FINDINGS: Electronic health record (EHR) data provides a starting point for evaluating whether patient predictors influence postoperative pain. There are several ways to assess pain and choosing the most effective form of pain treatment. Identifying individuals at high risk for severe postoperative pain enables more effective pain treatment. However, there are discrepancies in patient pain reporting dependent on instruments used to measure pain and their storage in the EHR. Additionally, whether administered by a physician or another healthcare practitioner, differences in patient pain perception occur. While each scale has distinct advantages and limitations, pain scale data is a valuable therapeutic tool for assisting clinicians in providing patients with optimal pain control. Accurate assessment of patient pain perceptions by data extraction from electronic health records provides a potential for pain alleviation improvement. Predicting high-risk postoperative pain syndromes is a difficult clinical challenge. Numerous studies have been conducted on factors that impact pain prediction. Postoperative pain is significantly predicted by the kind of operation, the existence of prior discomfort, patient anxiety, and age.


Assuntos
Registros Eletrônicos de Saúde , Percepção da Dor , Humanos , Dor Pós-Operatória/diagnóstico
2.
J Biol Chem ; 298(9): 102282, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35863431

RESUMO

The synthesis of proinflammatory leukotrienes implicated in asthma, allergic rhinitis, and atherosclerosis is initiated by the enzyme 5-lipoxygenase (5-LOX). The crystal structure of human Stable-5-LOX revealed a conformation where the catalytic iron was inaccessible to bulk solvent as two aromatic residues on a conserved helix-α2 (Hα2) plugged the substrate access portal. Whether 5-LOX can also adopt a more open conformation has not been resolved. Here, we present a new conformation of 5-LOX where Hα2 adopts an elongated conformation equivalent to that described in other animal lipoxygenase structures. Our observation of the sigmoidal kinetic behavior of 5-LOX, which is indicative of positive cooperativity, is consistent with a substrate-induced conformational change that shifts the ensemble of enzyme populations to favor the catalytically competent state. Strategic point mutations along Hα2 designed to unlock the closed conformation and elongate Hα2 resulted in improved kinetic parameters, altered limited proteolysis data, and a drastic reduction in the length of the lag phase yielding the most active Stable-5-LOX to date. Structural predictions by AlphaFold2 of these variants statistically favor an elongated Hα2 and reinforce a model in which improved kinetic parameters correlate with a more readily adopted open conformation. Taken together, these data provide valuable insights into the synthesis of leukotrienes.


Assuntos
Araquidonato 5-Lipoxigenase , Leucotrienos , Animais , Araquidonato 5-Lipoxigenase/química , Araquidonato 5-Lipoxigenase/genética , Humanos , Ferro/química , Cinética , Leucotrienos/biossíntese , Modelos Moleculares , Mutação Puntual , Conformação Proteica em alfa-Hélice , Solventes
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