The cytosolic hyperoxidation-sensitive and -robust Leishmania peroxiredoxins cPRX1 and cPRX2 are both dispensable for parasite infectivity.

Typical two-cysteine peroxiredoxins (2-Cys-PRXs) are H2O2-metabolizing enzymes whose activity relies on two cysteine residues. Protists of the family Trypanosomatidae invariably express one cytosolic 2-Cys-PRX (cPRX1). However, the Leishmaniinae sub-family features an additional isoform (cPRX2), almost identical to cPRX1, except for the lack of an elongated C-terminus with a Tyr-Phe (YF) motif. Previously, cytosolic PRXs were considered vital components of the trypanosomatid antioxidant machinery. Here, we shed new light on the properties, functions and relevance of cPRXs from the human pathogen Leishmania infantum. We show first that LicPRX1 is sensitive to inactivation by hyperoxidation, mirroring other YF-containing PRXs participating in redox signaling. Using genetic fusion constructs with roGFP2, we establish that LicPRX1 and LicPRX2 can act as sensors for H2O2 and oxidize protein thiols with implications for signal transduction. Third, we show that while disrupting the LicPRX-encoding genes increases susceptibility of L. infantum promastigotes to external H2O2in vitro, both enzymes are dispensable for the parasites to endure the macrophage respiratory burst, differentiate into amastigotes and initiate in vivo infections. This study introduces a novel perspective on the functions of trypanosomatid cPRXs, exposing their dual roles as both peroxidases and redox sensors. Furthermore, the discovery that Leishmania can adapt to the absence of both enzymes has significant implications for our understanding of Leishmania infections and their treatment. Importantly, it questions the conventional notion that the oxidative response of macrophages during phagocytosis is a major barrier to infection and the suitability of cPRXs as drug targets for leishmaniasis.

Utilidad de la neuromonitorización vagal continua en cirugía tiroidea: experiencia y resultados en un hospital de tercer nivel / The role of continuous vagal intraoperative nerve monitoring in thyroid surgery: experience and results in a third-level hospital

Resumen Objetivo: La lesión del nervio laríngeo recurrente es una grave complicación en cirugía tiroidea. El propósito del presente estudio es analizar la utilidad de la neuromonitorización vagal continua intraoperatoria en un hospital terciario. Materiales y Método: Estudio observacional, analítico y retrospectivo que recoge pacientes intervenidos de cirugía tiroidea con neuromonitorización en un período de 14 meses. La pérdida de señal se define como amplitud final nerviosa < 100 ^V, realizándose laringoscopia postquirúrgica ante la sospecha de lesión nerviosa. El análisis estadístico se realizó con el programa SPSS® V25,0, con p < 0,05. Resultados: Se incluyeron 120 pacientes intervenidos, registrándose en el 24,2% pérdida de señal. Factores de riesgo para lesión fueron bocio intratorácico (OR 5,31; IC 95% 1,56-17,99; p = 0,007), cirugía cervical previa (OR 5,76; IC 95% 0,64-51,97; p = 0,119) y patología maligna (OR 1,44; IC 95% 0,16-12,79; p = 0,743). Fue posible el cambio de estrategia quirúrgica en 7 casos. En el seguimiento posterior se cuantificó parálisis recurrencial transitoria en 27 pacientes y permanente en 4. Discusión: La neuromonitorización parece reducir la incidencia de parálisis laríngea porque aumenta la seguridad en la identificación del nervio recurrente y reduce su manipulación durante la cirugía. Conclusiones: La neuromonitorización intraoperatoria es útil para identificar el nervio laríngeo recurrente y advierte del riesgo potencial de lesión, permitiendo cambiar la estrategia quirúrgica para evitar la parálisis bilateral de cuerdas vocales.

Aim: Recurrent laryngeal nerve injury is a serious complication in thyroid surgery. The purpose of the present study is to analyze the use of intraoperative continuous vagal neuromonitoring in a tertiary hospital. Materials and Method: Observational, analytical and retrospective study that includes patients who underwent thyroid surgery with neuromonitoring in a period of 14 months. Loss of signal is defined as final nerve amplitude < 100 ^V, and postsurgical laryngoscopy is performed due to suspicion of nerve injury. Statistical analysis was performed with the SPSS® V25.0 program, with p < 0.05. Results: 120 operated patients were included, registering loss of signal in 24.2%. Risk factors for injury were intrathoracic goiter (OR 5.31; 95% CI 1.56-17.99; p = 0.007), previous cervical surgery (OR 5.76; 95% CI 0.64-51.97; p = 0.119) and malignant pathology (OR 1.44; 95% CI 0.16-12.79; p = 0.743). A change in surgical strategy was possible in 7 cases. In the subsequent follow-up, transient recurrent paralysis was quantified in 27 patients and permanent in 4. Discussion: Neuromonitoring seems to reduce the incidence of laryngeal paralysis because it increases the security in the identification of the recurrent nerve and reduces its manipulation during surgery. Conclusions: Intraoperative neuromonitoring is useful to identify the recurrent laryngeal nerve and warns of the potential risk of injury, allowing to change the surgical strategy to avoid bilateral vocal cord paralysis.