[Recurring genital bleeding in an extreme premature infant]. / Sangrado genital recurrente en una lactante prematura extrema.

Mini-puberty refers to the transient activation of the hypothalamic-pituitary-gonadal axis during the first months of life. This activation in preterm infants could be more exaggerated and prolonged. Ob jective: To present a case of exaggerated mini-puberty in an extremely preterm infant, with recurrent genital bleeding. Clinical Case: A 25-week preterm newborn presented at 5 months old with breast buds, areolar pigmentation, and estrogenic effects on the vaginal mucosa, with recurrent genital blee ding in three consecutive months. Her laboratory evaluation showed elevated values of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2). An exaggerated mini-puber ty due to extreme prematurity was suspected, therefore a conservative approach was taken. During follow-up, the patient showed partial regression of breast buds and cessation of genital bleeding, and decreasing levels of gonadotropin and estradiol. Conclusion: Mini-puberty in preterm newborns can present exaggeratedly, simulating precocious puberty and even presenting, exceptionally, recurrent genital bleeding. Considering the increasing survival of extremely premature infants, it is important to know the spectrum of clinical and laboratory manifestations of this phenomenon, in order to carry out adequate management.

Inicio de un nuevo programa de cuidados paliativos pediátricos en un hospital general: características de la población y uso de recursos / Starting of a new pediatric palliative care program in a general hospital: characteristics of the population and use of resources

Se describen las características de los pacientes susceptibles de cuidados paliativos pediátricos (CPP) de un hospital de segundo nivel, así como la frecuencia de visitas a urgencias, de ingresos y de dispositivos tecnológicos empleados. Estudio retrospectivo de los pacientes atendidos desde el inicio del programa de CPP (enero 2017 a enero 2020) en un hospital de nivel secundario. Se incluyeron 29 niños, 58,6% varones y edad media a la entrada en el estudio de 2,3 años (DE: 2,4); el 44,8% procedían del ámbito rural. El 41% presentaron multimorbilidad, con mayor frecuencia de patología neurológica. La causa más frecuente de atención en urgencias (n = 360) y hospitalización (n = 145) fue la infeccioso-respiratoria. El 51,7% de los pacientes eran dependientes de dispositivos médicos. Conocer el uso de recursos de esta población puede ayudar a un mejor reparto de los mismos para poder ofrecer CPP con independencia del lugar de residencia.(AU)

This article sets out to describe the characteristics of patients at a second-level hospital who are likely to receive pediatric palliative care (PPC), the frequency of visits to the emergency room, admissions and technological devices used. A retrospective study was carried out of the patients who received care from the start of the PPC program (January 2017 to January 2020) at a secondary-level hospital. Twenty-nine patients were included, 58.6% male with mean age at entry into the study of 2.3 years (SD: 2.4); 44.8% of them were from rural areas. The prevalence of multimorbidity was 41%, with a higher frequency of neurological pathology. Respiratory infection was the most frequent cause of emergency care (n = 360) and hospitalization (n=145). Half of patients (51.7%) depended on medical devices. Better knowledge of the resources used by this population can lead to more effective distribution/management that in turn can enable PPC to be offered regardless of the place of residence.(AU)

[Starting of a new pediatric palliative care program in a general hospital: characteristics of the population and use of resources].

This article sets out to describe the characteristics of patients at a second-level hospital who are likely to receive pedi-atric palliative care (PPC), the frequency of visits to the emergency room, admissions and technological devices used. A retrospective study was carried out of the patients who received care from the start of the PPC program (January 2017 to January 2020) at a secondary-level hospital. Twenty-nine patients were included, 58.6% male with mean age at entry into the study of 2.3 years (SD: 2.4); 44.8% of them were from rural areas. The prevalence of multimorbidity was 41%, with a higher frequency of neurological patholo-gy. Respiratory infection was the most frequent cause of emergency care (n = 360) and hospitalization (n=145). Half of patients (51.7%) depended on medical devices. Better knowledge of the resources used by this population can lead to more effective distribution/management that in turn can enable PPC to be offered regardless of the place of residence.

OLA strategy for ARDS: Its effect on mortality depends on achieved recruitment (PaO2/FiO2) and mechanical power. Systematic review and meta-analysis with meta-regression / Estrategia OLA para el SDRA: su efecto en la mortalidad depende del reclutamiento alcanzado (PaO2/FiO2) y la potencia mecánica. Revisión sistemática y metaanálisis con metarregresión

Objective: The “Open Lung Approach” (OLA), that includes high levels of positive end-expiratory pressure coupled with limited tidal volumes, is considered optimal for adult patients with ARDS. However, many previous meta-analyses have shown only marginal benefits of OLA on mortality but with statistical heterogeneity. It is crucial to identify the most likely moderators of this effect. To determine the effect of OLA strategy on mortality of ventilated ARDS patients. We hypothesized that the degree of recruitment achieved in the control group (PaO2/FiO2 ratio on day 3 of ventilation), and the difference in Mechanical Power (MP) or Driving Pressure (DP) between experimental and control groups will be the most likely sources of heterogeneity. Design: A Systematic Review and Meta-analysis was performed according to PRISMA statement and registered in PROSPERO database. We searched only for randomized controlled trials (RCTs). GRADE guidelines were used for rating the quality of evidence. Publication bias was assessed. For the Meta-analysis, we used a Random Effects Model. Sources of heterogeneity were explored with Meta-Regression, using a priori proposed set of possible moderators. For model comparison, Akaike's Information Criterion with the finite sample correction (AICc) was used. Patients: Fourteen RCTs were included in the study. Results: Evidence of publication bias was detected, and quality of evidence was downgraded. Pooled analysis did not show a significant difference in the 28-day mortality between OLA strategy and control groups. Overall risk of bias was low. The analysis detected statistical heterogeneity. The two “best” explicative meta-regression models were those that used control PaO2/FiO2 on day 3 and difference in MP between experimental and control groups. The DP and MP models were highly correlated. Conclusions: There is no clear benefit of OLA strategy on mortality of ARDS patients, with significant heterogeneity among RCTs. ... (AU)

Objetivo: La Estrategia Open Lung (EOL), que incluye niveles elevados de presión positiva teleespiratoria junto con volumen corriente bajo, es considerada como el «patrón oro» para los pacientes adultos con SDRA. Sin embargo, varios metaanálisis previos han mostrado únicamente beneficios marginales de la EOL en la disminución de la mortalidad, aunque con gran heterogeneidad estadística. Es crucial identificar los moderadores más probables, así como determinar el efecto de la estrategia EOL en la mortalidad de los pacientes ventilados con SDRA. La hipótesis fue que el grado de reclutamiento alcanzado en el grupo control (cociente PaO2/FiO2 en el día3 de ventilación) y la diferencia en potencia mecánica (MP) o driving pressure (DP) entre el grupo experimental y el grupo control son la fuente más probable de heterogeneidad. Diseño Se realizó una revisión sistemática y metaanálisis de acuerdo con la declaración PRISMA, y se registró en la base de datos PROSPERO (N.° CRD42020179778). Se seleccionaron únicamente ensayos clínicos aleatorizados (ECA). Se estratificó la calidad de la evidencia de acuerdo con la metodología GRADE. Se evaluó el sesgo de publicación. Para el metaanálisis se utilizó el modelo de efectos aleatorios. Se exploraron las fuentes de heterogeneidad mediante metarregresión utilizando a priori un conjunto establecido de posibles moderadores. Para el modelo de comparación se utilizó el criterio de información de Akaike con la corrección para muestras pequeñas (AICc). Pacientes Se incluyeron 14 ECA en el estudio. Resultados Se detectó un sesgo de publicación, y la calidad fue degradada. El análisis combinado no mostró una diferencia estadísticamente significativa en la mortalidad en el día28 entre la estrategia EOL y los grupos control. El riesgo total de sesgo fue bajo. El análisis detectó heterogeneidad estadística. ... (AU)

OLA strategy for ARDS: Its effect on mortality depends on achieved recruitment (PaO2/FiO2) and mechanical power. Systematic review and meta-analysis with meta-regression.

OBJECTIVE: The "Open Lung Approach" (OLA), that includes high levels of positive end-expiratory pressure coupled with limited tidal volumes, is considered optimal for adult patients with ARDS. However, many previous meta-analyses have shown only marginal benefits of OLA on mortality but with statistical heterogeneity. It is crucial to identify the most likely moderators of this effect. To determine the effect of OLA strategy on mortality of ventilated ARDS patients. We hypothesized that the degree of recruitment achieved in the control group (PaO2/FiO2 ratio on day 3 of ventilation), and the difference in Mechanical Power (MP) or Driving Pressure (DP) between experimental and control groups will be the most likely sources of heterogeneity. DESIGN: A Systematic Review and Meta-analysis was performed according to PRISMA statement and registered in PROSPERO database. We searched only for randomized controlled trials (RCTs). GRADE guidelines were used for rating the quality of evidence. Publication bias was assessed. For the Meta-analysis, we used a Random Effects Model. Sources of heterogeneity were explored with Meta-Regression, using a priori proposed set of possible moderators. For model comparison, Akaike's Information Criterion with the finite sample correction (AICc) was used. SETTING: Not applicable. PATIENTS: Fourteen RCTs were included in the study. INTERVENTIONS: Not applicable. MAIN VARIABLES OF INTEREST: Not applicable. RESULTS: Evidence of publication bias was detected, and quality of evidence was downgraded. Pooled analysis did not show a significant difference in the 28-day mortality between OLA strategy and control groups. Overall risk of bias was low. The analysis detected statistical heterogeneity. The two "best" explicative meta-regression models were those that used control PaO2/FiO2 on day 3 and difference in MP between experimental and control groups. The DP and MP models were highly correlated. CONCLUSIONS: There is no clear benefit of OLA strategy on mortality of ARDS patients, with significant heterogeneity among RCTs. Mortality effect of OLA is mediated by lung recruitment and mechanical power.

OLA strategy for ARDS: Its effect on mortality depends on achieved recruitment (PaO2/FiO2) and mechanical power. Systematic review and meta-analysis with meta-regression.

OBJECTIVE: The "Open Lung Approach" (OLA), that includes high levels of positive end-expiratory pressure coupled with limited tidal volumes, is considered optimal for adult patients with ARDS. However, many previous meta-analyses have shown only marginal benefits of OLA on mortality but with statistical heterogeneity. It is crucial to identify the most likely moderators of this effect. To determine the effect of OLA strategy on mortality of ventilated ARDS patients. We hypothesized that the degree of recruitment achieved in the control group (PaO2/FiO2 ratio on day 3 of ventilation), and the difference in Mechanical Power (MP) or Driving Pressure (DP) between experimental and control groups will be the most likely sources of heterogeneity. DESIGN: A Systematic Review and Meta-analysis was performed according to PRISMA statement and registered in PROSPERO database. We searched only for randomized controlled trials (RCTs). GRADE guidelines were used for rating the quality of evidence. Publication bias was assessed. For the Meta-analysis, we used a Random Effects Model. Sources of heterogeneity were explored with Meta-Regression, using a priori proposed set of possible moderators. For model comparison, Akaike's Information Criterion with the finite sample correction (AICc) was used. SETTING: Not applicable. PATIENTS: Fourteen RCTs were included in the study. INTERVENTIONS: Not applicable. MAIN VARIABLES OF INTEREST: Not applicable. RESULTS: Evidence of publication bias was detected, and quality of evidence was downgraded. Pooled analysis did not show a significant difference in the 28-day mortality between OLA strategy and control groups. Overall risk of bias was low. The analysis detected statistical heterogeneity. The two "best" explicative meta-regression models were those that used control PaO2/FiO2 on day 3 and difference in MP between experimental and control groups. The DP and MP models were highly correlated. CONCLUSIONS: There is no clear benefit of OLA strategy on mortality of ARDS patients, with significant heterogeneity among RCTs. Mortality effect of OLA is mediated by lung recruitment and mechanical power.

Association of tyrosine hydroxylase expression in brain and tumor with increased tumor growth in sympathectomized mice.

OBJECTIVE: Lymphocytes express tyrosine hydroxylase (TH), the rate-limiting enzyme for the synthesis of dopamine, norepinephrine and epinephrine. This suggests a broader role for cathecholamines in lymphocyte function, as well as the potential secretion of catecholamines by tumors of lymphoid origin. Our aim was to evaluate the expression of Th by murine lymphoma cells in an in vivo mouse model. For this, L5178Y-R lymphoma cells were implanted in nerve-intact and sympathectomized male BALB/c mice. Relative Th gene expression in tumor and brain was determined by quantitative PCR. Body composition, tumor volume, and plasma TH1/TH2/TH17 cytokines were also evaluated as markers of tumor-host condition and anti-tumor immune response in absence of adrenergic innervation. RESULTS: We found a significant (p = 0.045) 3.3-fold decrease of Th gene expression in tumor and a non-significant (p = 0.60) 6.9-fold increase in brain after sympathectomy. Sympathectomized mice also showed a significant increase in tumor mass at days 18 (p = 0.032) and 28 (p = 0.022) and increased interscapular fat (p = 0.04). TH1/TH2 and TH17 cytokines levels in plasma from sympathectomized tumor-bearing mice were not different from control mice. CONCLUSION: The L5178Y-R lymphoma does not express Th during in vivo progression.

Covid-19 management by farmers and policymakers in Burkina Faso, Colombia and France: Lessons for climate action.

CONTEXT: During crises, adaptation or recovery measures or plans at local or national scales may not necessarily address longer-term or structural problems such as climate change mitigation. OBJECTIVE: This article describes farmers and policymakers' responses to mitigate the adverse effects of Covid-19 on the agricultural sector. We then assess the responses' possible effects on greenhouse gas (GHG) emissions. METHODS: The study is based on surveys conducted with farmers, traders, and extension staff in Burkina Faso, Colombia, and France, and literature. We used the Cool Farm Tool calculator to assess GHG emissions associated with fertilizer production, crop production and produce transportation to international markets for the three main cash crops in the three countries. RESULTS AND CONCLUSIONS: We identified contrasting responses by the agricultural sector mostly driven by changes in the consumption patterns at local or international levels. We also identified contrasting state responses to mitigate Covid-19. These responses at farm and policy scales led to similar trends in decreasing carbon dioxide (CO2) emissions across the studied countries. However, none of the studied countries linked Covid-19 response measures to long-term climate change mitigation actions. Therefore, an opportunity to sustain Covid-19 induced short-term decreases in GHG emissions was overlooked. SIGNIFICANCE: Analyzing the impacts that Covid-19 had on agricultural systems and the decision taken by policymakers to handle its direct and indirect effects can help society draw lessons on how to improve climate action.

Increased phagocytosis and growth inhibition of Encephalitozoon cuniculi by LPS-activated J774A.1 murine macrophages.

Encephalitozoon cuniculi is an obligate macrophage parasite of vertebrates that commonly infects rodents, monkeys, dogs, birds, and humans. In the present study, we aimed to assess the phagocytosis and intracellular survival of E. cuniculi spores using untreated and lipopolysaccharide (LPS)-activated J774A.1 murine macrophages and assess the macrophage viability. The experimental groups comprised untreated spores, spores killed by heat treatment at 90 °C, and spores killed by treatment with 10% formalin. LPS-activated macrophages significantly increased the phagocytosis of spores and reduced their intracellular growth after 24 and 48 h (P < 0.01); however, after 72 h, we observed an increase in spore replication but no detectable microbicidal activity. These results indicate that LPS activation enhanced E. cuniculi phagocytosis between 24 and 48 h of treatment, but the effect was lost after 72 h, enabling parasitic growth. This study contributes to the understanding of the phagocytosis and survival of E. cuniculi in murine macrophages.

Dispositivo de presión positiva continua en la vía aérea de Boussignac durante el transporte interhospitalario en lactantes menores de tres meses / Boussignac continuous positive airway pressure device during inter-hospital transportation in infants aged less than three months

Fundamento: El objetivo del presente estudio es evaluar la seguridad y efectividad del dispositivo de generación de presión positiva continua en la vía aérea de Boussignac(R) (CPAPB) durante su uso en el transporte en lactantes menores de tres meses con bronquiolitis. Material y métodos: Estudio observacional analítico transversal de cuatro años de duración. Se recogieron datos de 25 lactantes que precisaron trasladado interhospitalario a la Unidad de Cuidados Intensivos Pediátrica (UCIP) de referencia con CPAPB e interfase tipo Helmet. Se registraron las caracteristicas epidemiológicas, del traslado y de la evolución en UCIP, además de los parámetros cardiorrespiratorios y gasométricos previos al traslado y a su llegada a UCIP. Resultados: La mediana del nivel de presión contínua en la vía aérea (CPAP) utilizada durante el traslado fue de 7 cm H2O (6-7,25). Ningún paciente precisó de intubación endotraqueal durante el traslado y un paciente la precisó durante las primeras seis horas de ingreso en UCIP. Los siguientes parámetros cardiorrespiratorios presentaron una mejoría estadisticamente significativa a su llegada a UCIP: score de Wood-Downes modificado [8,40 (2,1) vs 5,29 (1,68)], frecuencia respiratoria [60,72 (12,73) vs 47,28 (10,31)], frecuencia cardiaca [167,28 (22,60) vs 154,48 (24,83)] y saturación de oxígeno [92,08 (5,63) vs 97,64 (2,27)]. Conclusiones: La aplicación de CPAPB resultó ser un método de soporte respiratorio seguro en lactantes menores de tres meses. Su uso durante el transporte suposo una mejoría en los parámetros cardiorrespiratoriosl

Background: The present study aims to evaluate the safety and effectiveness of the Boussignac continuous positive airway pressure device (CPAPB) when used during the transportation of infants under three months of age with bronchiolitis. Methods: Transversal analytical observational study of four years duration. Data was collected on 25 infants who needed inter-hospital transportation to the reference Paediatric Intensive Care Unit (PICU), with CPAPB and Helmet interface. The epidemiological characteristics of the transportation and evolution in the PICU were registered, as well as the cardiorespiratory gastronomic parameters prior to transfer and on arrival at the PICU. Results: The median level of continuous airway pressure (CPAP) used during the transfer was 7 cm H2O (6-7.25). No patient required endotracheal intubation during transportation, while one patient required this during the first six hours of admission in the PICU. The following cardiorespiratory parameters presented a statistically significant improvement on arrival at the PICU: modified Wood-Downes score [8.40 (2.1) vs 5.29 (1.68)], respiratory frequency [60.72 (12.73) vs 47.28 (10.31)], cardiac frequency [167.28 (22.60) vs 154.48 (24.83)] and oxygen saturation [92.08 (5.63) vs 97.64 (2.27)]. Conclusions: Application of CPAPB proved to be a safe method of respiratory support in infants under three months of age. Its use during transportation brought an improvement in cardiorespiratory parameters

[Boussignac continuous positive airway pressure device during inter-hospital transportation in infants aged less than three months]. / Dispositivo de presión positiva continua en la vía aérea de Boussignac durante el transporte interhospitalario en lactantes menores de tres meses.

BACKGROUND: The present study aims to evaluate the safety and effectiveness of the Boussignac continuous positive airway pressure device (CPAPB) when used during the transportation of infants under three months of age with bronchiolitis. METHODS: Transversal analytical observational study of four years duration. Data was collected on 25 infants who needed inter-hospital transportation to the reference Paediatric Intensive Care Unit (PICU), with CPAPB and Helmet interface. The epidemiological characteristics of the transportation and evolution in the PICU were registered, as well as the cardiorespiratory gastronomic parameters prior to transfer and on arrival at the PICU. RESULTS: The median level of continuous airway pressure (CPAP) used during the transfer was 7 cm H2O (6-7.25). No patient required endotracheal intubation during transportation, while one patient required this during the first six hours of admission in the PICU. The following cardiorespiratory parameters presented a statistically significant improvement on arrival at the PICU: modified Wood-Downes score [8.40 (2.1) vs 5.29 (1.68)], respiratory frequency [60.72 (12.73) vs 47.28 (10.31)], cardiac frequency [167.28 (22.60) vs 154.48 (24.83)] and oxygen saturation [92.08 (5.63) vs 97.64 (2.27)]. CONCLUSIONS: Application of CPAPB proved to be a safe method of respiratory support in infants under three months of age. Its use during transportation brought an improvement in cardiorespiratory parameters.

Fast optimized Monte Carlo phase-space generation and dose prediction for low energy x-ray intra-operative radiation therapy.

Low energy x-ray intra-operative radiation therapy (IORT) is used mostly for breast cancer treatment with spherical applicators. X-ray IORT treatment delivered during surgery (ex: INTRABEAM®, Carl Zeiss) can benefit from accurate and fast dose prediction in a patient 3D volume. However, full Monte Carlo (MC) simulations are time-consuming and no commercial treatment planning system (TPS) was available for this treatment delivery technique. Therefore, the aim of this work is to develop a dose computation tool based on MC phase space information, which computes fast and accurate dose distributions for spherical and needle INTRABEAM® applicators. First, a database of monoenergetic phase-space (PHSP) files and depth dose profiles (DDPs) in water for each applicator is generated at factory and stored for on-site use. During commissioning of a given INTRABEAM® unit, the proposed fast and optimized phase-space (FOPS) generation process creates a phase-space at the exit of the applicator considered, by fitting the energy spectrum of the source to a combination of the monoenergetic precomputed phase-spaces, by means of a genetic algorithm, with simple experimental data of DDPs in water provided by the user. An in-house hybrid MC (HMC) algorithm which takes into account condensed history simulations of photoelectric, Rayleigh and Compton interactions for x-rays up to 1 MeV computes the dose from the optimized phase-space file. The whole process has been validated against radiochromic films in water as well as reference MC simulations performed with penEasy in heterogeneous phantoms. From the pre-computed monoenergetic PHSP files and DDPs, building the PHSP file optimized to a particular depth-dose curve in water only takes a few minutes in a single core (i7@2.5 GHz), for all the applicators considered in this work, and this needs to be done only when the x-ray source (XRS) is replaced. Once the phase-space file is ready, the HMC code is able to compute dose distributions within 10 min. For all the applicators, more than 95% of voxels from dose distributions computed with the FOPS+hybrid code agreed within 7%-0.5 mm with both reference MC simulations and measurements. The method proposed has been fully validated and it is now implemented into radiance (GMV SA, Spain), the first commercial IORT TPS.

Pharmacometabolomics applied to zonisamide pharmacokinetic parameter prediction.

INTRODUCTION: Zonisamide is a new-generation anticonvulsant antiepileptic drug metabolized primarily in the liver, with subsequent elimination via the renal route. OBJECTIVES: Our objective was to evaluate the utility of pharmacometabolomics in the detection of zonisamide metabolites that could be related to its disposition and therefore, to its efficacy and toxicity. METHODS: This study was nested to a bioequivalence clinical trial with 28 healthy volunteers. Each participant received a single dose of zonisamide on two separate occasions (period 1 and period 2), with a washout period between them. Blood samples of zonisamide were obtained from all patients at baseline for each period, before volunteers were administered any medication, for metabolomics analysis. RESULTS: After a Lasso regression was applied, age, height, branched-chain amino acids, steroids, triacylglycerols, diacyl glycerophosphoethanolamine, glycerophospholipids susceptible to methylation, phosphatidylcholines with 20:4 FA (arachidonic acid) and cholesterol ester and lysophosphatidylcholine were obtained in both periods. CONCLUSION: To our knowledge, this is the only research study to date that has attempted to link basal metabolomic status with pharmacokinetic parameters of zonisamide.

Correction to: Pharmacometabolomics applied to zonisamide pharmacokinetic parameter prediction.

The original version of this article contains a mistake.

Alterations of antitumor and metabolic responses in L5178Y-R lymphoma-bearing mice after only 30-minute daily chronic stress exposure.

AIM: In stress research, reducing times of stress induction may contribute to improving the well-being of experimental animals, especially in cancer models, already under physiological distress. To support this idea, we evaluated the effects of a short-timed stress protocol on endocrine, metabolic and immune indicators in mice bearing the L5178Y-R lymphoma. MATERIALS AND METHODS: A 30-minute daily stress protocol was applied for 28 days to healthy and lymphoma-bearing BALB/c mice; body weight, plasma levels of corticosterone, norepinephrine, Th1/Th2 cytokines, insulin, and leptin, were measured. RESULTS: We found a 12% significant decrease in body weight in non-tumor bearing mice under stress (p < 0.007). The disruption of weight evolution was accompanied by a stress induced 85% decrease in plasmatic leptin (p < 0.01) and total reduction of insulin. Tumor burden alone was associated to an increase in more than two-fold of plasmatic levels of norepinephrine (p < 0.008). Neither stress nor tumor or their combination, resulted in an elevation of systemic IL-6. IFN-γ levels were 20 times higher in lymphoma-bearing animals when compared with non-tumor bearing mice (p < 0.01); however, under stress, this response was reduced by half, indicating a suppressing effect of chronic stress on the antitumor immune response. CONCLUSION: A short-timed stress induction is enough to cause significant alterations in the metabolism and immunity of healthy and tumor-bearing mice, supporting the use of short-timed protocols as an efficient way to induce chronic stress that also considers concerns regarding the well-being of experimental animals in biomedical research.