Clinicai characteristics and mortality in mechanically ventilated COVID-19 patients: prospective cohort study / Características clínicas y mortalidad en pacientes COVID-19 ventilados mecánicamente: estudio de cohorte prospectivo

Abstract Introduction: Factors associated with mortality among mechanically ventilated COVID-19 patients have been scarcely studied in Latin America. Objective: To identify factors associated with mortality in mechanically ventilated COVID-19 patients. Methods: This prospective study was undertaken in a single center between April and October 2020, recruiting COVID-19 patients managed with mechanical ventilation. We excluded patients who died within the first 24 hours after endotracheal intubation. Clinical characteristics, laboratory results, ventilation interventions, and outcomes were collected and compared between the deceased and surviving groups. The association between these factors and hospital death was examined, and relevant covariates were included in a multivariate logistic regression model. Results: A total of 273 patients were included (72.5% male), the mortality rate was 37% (95% CI 31% - 43%), and the median age was 63 years (IQR 52-72). The most frequent comorbidity was hypertension (45%). Factors associated with mortality were: older age (OR 1.08; 95% CI 1.051.11), male gender (OR 2.79; 95% CI 1.30-6.01), immunosuppression (OR 3.98; 95% CI 1.57-10.06), thrombocytopenia (OR 3.84; CI 95% 1.47-10.01), driving pressure (OR 1.20; 95% CI 1.07-1.34) and the use of dialysis (OR 4.94; 95% CI 2.56-9.51). Chronic hypertension (OR 0.35; 95% CI 0.17-0.71) and fever on admission (OR 0.51; 95% CI 0.27-0.98) were found to have a protective effect. Conclusions: Older age, male sex, immunosuppression, thrombocytopenia, increased driving pressure, use of dialysis, absence of fever, or arterial hypertension were associated with an increased risk of mortality among mechanically ventilated COVID-19 patients.

Resumen Introducción: Es poco lo que se han estudiado en América Latina los factores asociados con mortalidad en pacientes con COVID-19 ventilados mecánicamente. Objetivo: Identificar los factores asociados con mortalidad en pacientes con COVID-19 manejados con ventilación mecánica. Métodos: Este estudio prospectivo se adelantó en un solo centro entre los meses de abril y octubre de 2020 e incluyó pacientes con COVID-19 manejados con ventilación mecánica. Se excluyeron pacientes que fallecieron en las primeras 24 horas después de la intubación orotraqueal. Se recopilaron datos de las características clínicas, resultados de laboratorio, intervenciones ventilatorias y desenlaces, y se hizo una comparación entre el grupo de pacientes fallecidos y el grupo de sobrevivientes. Se examinó la asociación entre estos factores y la muerte intrahospitalaria, y las covariables relevantes se incluyeron en un modelo multivariable de regresión logística. Resultados: Se incluyó un total de 273 pacientes (72.5% hombres), la tasa de mortalidad fue del 37% (IC 95% 31% - 43%), la mediana de edad fue de 36 años (RIC 52-72) y la comorbilidad más frecuente fue la hipertensión (45%). Los factores asociados con mortalidad fueron: edad avanzada (OR 1.08; IC 95% 1.05-1.11), género masculino (OR 2.79; IC 95% 1.30-6.01), inmunosupresión (OR 3.98; IC 95% 1.57-10.06), trombocitopenia (OR 3.84; CI 95% 1.47-10.01), presión de distensión (OR 1.20; IC 95% 1.07-1.34) y el uso de diálisis (OR 4.94; IC 95% 2.56-9.51). La presencia de hipertensión (OR 0.35; IC 95% 0.17-0.71) y de fiebre (OR 0.51; IC 95% 0.27-0.98) al momento de la hospitalización demostraron tener un efecto protector. Conclusiones: Se encontró asociación entre la edad avanzada, el sexo masculino, la inmunosupresión, la trombocitopenia, una presión de distensión elevada, el uso de diálisis, la ausencia de fiebre o de hipertensión y un mayor riesgo de mortalidad en pacientes con COVID-19 ventilados mecánicamente.

Interacción de Tratamiento Ortodóncico, Fonoaudiológico y Kinesiológico. Reporte de caso

Se describe el caso clínico de una paciente de 8 años de edad, sexo femenino que presenta respiración oral, anomalía dentomaxilar, interposición lingual en deglución, fonación, lengua descendida en reposo y adaptaciones musculoesqueléticas por lo que requiere tratamiento de Ortodoncia, Fonoaudiología y Kinesiología. El presente reporte de caso describe la interacción de las especialidades requeridas para el manejo adecuado de la paciente y expone un flujograma sugerido para abordar casos similares.

The following is a clinical case of an eight-year-old female patient who presents oral respiration, dentomaxilar anomaly, tongue interposition during swallowing and phonation, lowered tongue at rest and musculoskeletal adaptations, hence requires orthodontics, speech and physical therapy. This case report describes the interaction of the specialties necessary for the proper management of the patient and presents a suggested flow chart to address similar cases.

Pneumatophore CO2 effluxes decrease with increased salinity in mangrove forests of Yucatan, Mexico.

Although mangrove forests are great carbon sinks, they also release carbon dioxide (CO2) from soil, plants, and water through respiration. Many studies have focused on CO2 effluxes only from soils, but the role of biogenic structures such as pneumatophore roots has been poorly studied. Hence, CO2 effluxes from pneumatophores were quantified at sediment-air (non-flooded sediment) and water-air (flooded sediment) interfaces along a salinity gradient in three mangrove types (fringe, scrub, and basin) dominated by Avicennia germinans during the dry and rainy seasons in Yucatan, Mexico. Pneumatophore abundance explained up to 91% of CO2 effluxes for scrub, 87% for fringe, and 83% for basin mangrove forests at the water-air interface. Overall, CO2 effluxes were inversely correlated with temperature and salinity. The highest CO2 effluxes were in the fringe and the lowest were in the scrub mangrove forests. Flooding decreased CO2 effluxes from the dry to the rainy season in all mangrove forests. These results highlight the contribution of pneumatophores to mangrove respiration, and the need to include them in our current carbon budgets and models, but considering different exchange interfaces, seasons, and mangrove ecotypes.

Environment and microbiome drive different microbial traits and functions in the macroscale soil organic carbon cycle.

Soil microbial traits and functions play a central role in soil organic carbon (SOC) dynamics. However, at the macroscale (regional to global) it is still unresolved whether (i) specific environmental attributes (e.g., climate, geology, soil types) or (ii) microbial community composition drive key microbial traits and functions directly. To address this knowledge gap, we used 33 grassland topsoils (0-10 cm) from a geoclimatic gradient in Chile. First, we incubated the soils for 1 week in favorable standardized conditions and quantified a wide range of soil microbial traits and functions such as microbial biomass carbon (MBC), enzyme kinetics, microbial respiration, growth rates as well as carbon use efficiency (CUE). Second, we characterized climatic and physicochemical properties as well as bacterial and fungal community composition of the soils. We then applied regression analysis to investigate how strongly the measured microbial traits and functions were linked with the environmental setting versus microbial community composition. We show that environmental attributes (predominantly the amount of soil organic matter) determined patterns of MBC along the gradient, which in turn explained microbial respiration and growth rates. However, respiration and growth normalized for MBC (i.e., specific respiration and growth) were more linked to microbial community composition than environmental attributes. Notably, both specific respiration and growth followed distinct trends and were related to different parts of the microbial community, which in turn resulted in strong effects on microbial CUE. We conclude that even at the macroscale, CUE is the result of physiologically decoupled aspects of microbial metabolism, which in turn is partially determined by microbial community composition. The environmental setting and microbial community composition affect different microbial traits and functions, and therefore both factors need to be considered in the context of macroscale SOC dynamics.

CCL2 and Lactate from Chemotherapeutics-Treated Fibroblasts Drive Malignant Traits by Metabolic Rewiring in Low-Migrating Breast Cancer Cell Lines.

While cytostatic chemotherapy targeting DNA is known to induce genotoxicity, leading to cell cycle arrest and cytokine secretion, the impact of these drugs on fibroblast-epithelial cancer cell communication and metabolism remains understudied. Our research focused on human breast fibroblast RMF-621 exposed to nonlethal concentrations of cisplatin and doxorubicin, revealing reduced proliferation, diminished basal and maximal mitochondrial respirations, heightened mitochondrial ROS and lactate production, and elevated MCT4 protein levels. Interestingly, RMF-621 cells enhanced glucose uptake, promoting lactate export. Breast cancer cells MCF-7 exposed to conditioned media (CM) from drug-treated stromal RMF-621 cells increased MCT1 protein levels, lactate-driven mitochondrial respiration, and a significantly high mitochondrial spare capacity for lactate. These changes occurred alongside altered mitochondrial respiration, mitochondrial membrane potential, and superoxide levels. Furthermore, CM with doxorubicin and cisplatin increased migratory capacity in MCF-7 cells, which was inhibited by MCT1 (BAY-8002), glutamate dehydrogenase (EGCG), mitochondrial pyruvate carrier (UK5099), and complex I (rotenone) inhibitors. A similar behavior was observed in T47-D and ZR-75-1 breast cancer cells. This suggests that CM induces metabolic rewiring involving elevated lactate uptake to sustain mitochondrial bioenergetics during migration. Treatment with the mitochondrial-targeting antioxidant mitoTEMPO in RMF-621 and the addition of an anti-CCL2 antibody in the CM prevented the promigratory MCF-7 phenotype. Similar effects were observed in THP1 monocyte cells, where CM increased monocyte recruitment. We propose that nonlethal concentrations of DNA-damaging drugs induce changes in the cellular environment favoring a promalignant state dependent on mitochondrial bioenergetics.

Enhancing biodegradation of aged hydrocarbon-contaminated soils through toluene addition: assessing effects on solid and slurry phase treatments.

The main challenge in treating aged soils highly contaminated with total petroleum hydrocarbons (TPH) is to enhance their bioavailability for microbial degradation. Hydrocarbons in soils undergo chemical changes that make them more resistant to biodegradation. This study investigates toluene's efficacy in enhancing the biodegradation of aged hydrocarbon-contaminated soil containing 292,000 mg TPH kg-1 dry soil. Toluene's effect was compared between solid phase (SOP) and slurry phase (SLP) treatments using a microbial consortium isolated from Cyperus laxus rhizosphere. TPH biodegradation and microbial respiration were measured, the latter to estimate the respiratory quotient (RQ, the ratio between moles of carbon dioxide released and moles of oxygen absorbed during respiration). Toluene significantly accelerated TPH biodegradation in both treatments, achieving ~ 30% higher removal than in a non-solvent control, possibly through improved bioavailability of aromatic compounds and other low molecular weight compounds. According to the RQ analysis, toluene enhanced microbial respiratory processes and hydrocarbon catabolism with higher hydrocarbon mineralization (RQ = ~ 0.5) in both SOP and SLP assays. Our results reveal toluene's potential to increase hydrocarbon availability and microbial degradation efficiency in aged contaminated soils; its use in various bioremediation techniques could be of broad applicability across diverse soil types and pollutants.

Sea butterflies in a pickle: reliable biomarkers and seasonal sensitivity of Limacina retroversa to ocean acidification in the Gulf of Maine.

The passive dissolution of anthropogenically produced CO2 into the ocean system is reducing ocean pH and changing a suite of chemical equilibria, with negative consequences for some marine organisms, in particular those that bear calcium carbonate shells. Although our monitoring of these chemical changes has improved, we have not developed effective tools to translate observations, which are typically of the pH and carbonate saturation state, into ecologically relevant predictions of biological risks. One potential solution is to develop bioindicators: biological variables with a clear relationship to environmental risk factors that can be used for assessment and management. Thecosomatous pteropods are a group of pelagic shelled marine gastropods, whose biological responses to CO2 have been suggested as potential bioindicators of ocean acidification owing to their sensitivity to acidification in both the laboratory and the natural environment. Using five CO2 exposure experiments, occurring across four seasons and running for up to 15 days, we describe a consistent relationship between saturation state, shell transparency and duration of exposure, as well as identify a suite of genes that could be used for biological monitoring with further study. We clarify variations in thecosome responses due to seasonality, resolving prior uncertainties and demonstrating the range of their phenotypic plasticity. These biomarkers of acidification stress can be implemented into ecosystem models and monitoring programmes in regions where pteropods are found, whilst the approach will serve as an example for other regions on how to bridge the gap between point-based chemical monitoring and biologically relevant assessments of ecosystem health.

Decreased mitochondrial respiration associates with frailty in community-dwelling older adults.

Aging population has led to an increased prevalence of chronic and degenerative pathologies. A manifestation of unhealthy aging is frailty, a geriatric syndrome that implies a non-specific state of greater vulnerability. Currently, methods for frailty diagnosis are based exclusively on clinical observation. The aim of this study is to determine whether the bioenergetic capacity defined as mitochondrial oxygen consumption rate (OCR) of peripheral circulation mononuclear cells (PBMC) associates with the frailty phenotype in older adults and with their nutritional status. This is a cross-sectional analytic study of 58 participants 70 years and older, 18 frail and 40 non-frail adults, from the ALEXANDROS cohort study, previously described. Participants were characterized through sociodemographic and anthropometric assessments. Frail individuals displayed a higher frequency of osteoporosis and depression. The mean age of the participants was 80.2 ± 5.2 years, similar in both groups of men and women. Regarding the nutritional status defined as the body mass index, most non-frail individuals were normal or overweight, while frail participants were mostly overweight or obese. We observed that OCR was significantly decreased in frail men (p < 0.01). Age was also associated with significant differences in oxygen consumption in frail patients, with lower oxygen consumption being observed in those over 80 years of age. Therefore, the use of PBMC can result in an accessible fingerprint that may identify initial stages of frailty in a minimally invasive way.

Activation of innate immunity selectively compromises mitochondrial complex I, proline oxidation, and flight activity in the major arbovirus vector Aedes aegypti.

Aedes aegypti females are natural vectors of important arboviruses such as dengue, zika, and yellow fever. Mosquitoes activate innate immune response signaling pathways upon infection, as a resistance mechanism to fight pathogens and limit their propagation. Despite the beneficial effects of immune activation for insect vectors, phenotypic costs ultimately affect their fitness. However, the underlying mechanisms that mediate these fitness costs remain poorly understood. Given the high energy required to mount a proper immune response, we hypothesized that systemic activation of innate immunity would impair flight muscle mitochondrial function, compromising tissue energy demand and flight activity. Here, we investigated the dynamic effects of activation of innate immunity by intra-thoracic zymosan injection on A. aegypti flight muscle mitochondrial metabolism. Zymosan injection significantly increased defensin A expression in fat bodies in a time-dependent manner that compromised flight activity. Although oxidant levels in flight muscle were hardly altered, ATP-linked respiratory rates driven by mitochondrial pyruvate+proline oxidation were significantly reduced at 24 h upon zymosan injection. Oxidative phosphorylation coupling was preserved regardless of innate immune response activation along 24 h. Importantly, rotenone-sensitive respiration and complex I-III activity were specifically reduced 24 h upon zymosan injection. Also, loss of complex I activity compromised ATP-linked and maximal respiratory rates mediated by mitochondrial proline oxidation. Finally, the magnitude of innate immune response activation negatively correlated with respiratory rates, regardless of the metabolic states. Collectively, we demonstrate that activation of innate immunity is strongly associated with reduced flight muscle complex I activity with direct consequences to mitochondrial proline oxidation and flight activity. Remarkably, our results indicate a trade-off between dispersal and immunity exists in an insect vector, underscoring the potential consequences of disrupted flight muscle mitochondrial energy metabolism to arbovirus transmission.

Cricothyrotomy - In Unanticipated Difficult Intubation Cases with Respiratory Compromise.

Introduction Cricothyrotomy, percutaneous dilation tracheostomy, and tracheostomy are all cost-effective and safe techniques used in the management of critically ill patients who need an artificial airway other than endotracheal tube ventilation. The present study focused on enlightening on elective and emergency procedures performed on conditions present with difficult airways and also attempts to shed light on the aspects of securing an airway in anticipated and unanticipated difficult intubation. Objective The objective of the study was to compare the three procedures conducted during difficult airway/failed intubation situations. Methods The present retrospective observational study was conducted collecting data from patient files obtained at a tertiary healthcare center from 2013 to 2018. The difficult intubation cases were managed by ear, nose, and throat (ENT) surgeons. The study compared three methods: Cricothyrotomy, percutaneous dilation tracheostomy, and tracheostomy based on factors such as procedure duration, complications, and the instruments required for each procedure. Results The study enrolled 85 patients, 61 males and 24 females, aged between 30 and 70 years old. To perform cricothyrotomy, only a simple blade was required. Cricothyrotomy had the shortest operating time (4.1±3.1 minutes) and the shortest time of full oxygen saturation (3 min). Percutaneous tracheostomy had the least amount of bleeding (1%). Cricothyrotomy significantly showed the least intraoperative bleeding than percutaneous dilation, tracheostomy, and tracheostomy ( p = 0.001). Conclusion Cricothyrotomy is preferable as it takes less time to perform, causes less bleeding, and takes the least time for full oxygen saturation than tracheostomy and percutaneous dilatational tracheostomy in "can't intubate, can't oxygenate" patients.

Implications of converting native forest areas to agricultural systems on the dynamics of CO2 emission and carbon stock in a Cerrado soil, Brazil.

The conversion of native vegetation to agricultural areas leads to a natural process of carbon loss but these systems can stabilize in terms of carbon dynamics depending on the management and conversion time, presenting potential to both store and stabilize this carbon in the soil, resulting in lower soil respiration rates. In this context, this study aimed to investigate the effect of converting native Cerrado forest areas to agricultural systems with a forest planted with Eucalyptus camaldulensis and silvopastoral systems on the dynamics of CO2 emission and carbon stock at different soil depths. The experimental sites are located in the Midwest of Brazil, in the coordinates 20°22'31″ S and 51°24'12″ W. Were evaluated soil CO2 emission (FCO2), soil organic carbon, the degree of humification of soil organic matter (HLIFS), soil temperature, soil moisture, and soil chemical and physical attributes. The soil of the area is classified as an Oxisol (Haplic Acrustox). Soil samples were collected at depths of 0.00-0.10, 0.10-0.20, 0.20-0.30, and 0.30-0.40 m. The lowest FCO2 values were found in the silvopastoral system (1.05 µmol m-2 s-1), followed by the native forest (1.65 µmol m-2 s-1) and the eucalyptus system (1.96 µmol m-2 s-1), indicating a 36% reduction in FCO2 compared to the conversion of the native forest to the silvopastoral system and an increase of 19% when converting the native forest to the eucalyptus system. The soil chemical attributes (N, K+, Ca2+, H++Al3+, CEC, and organic carbon) showed a decrease along the profile. The shallowest depths (0.00-0.10 and 0.10-0.20 m) presented no differences between systems but the subsequent depths (0.20-0.30 and 0.30-0.40 m) had a difference (95% confidence interval), relative to N, Ca2+, H++Al3, CEC, and organic carbon stock (OCS), and the soil under silvopastoral system showed a higher concentration of these attributes than the native forest. The multivariate analysis showed that the eucalyptus and silvopastoral systems did not differ from the forest in the shallowest soil layer but differed from each other. This behavior changed from the second assessed depth (0.10-0.20 m), in which the silvopastoral system stands out, differing both from the eucalyptus system and from the native forest, and this behavior is maintained at the following depths (0.20-0.30 and 0.30-0.40 m). OCS, H++Al3, CEC, and nitrogen are strongly related to land use change for silvopastoral system. Regarding the behavior/relationship of attributes as a function of depth, the silvopastoral system contributed to soil carbon accumulation and stability over consecutive years.

Inhibition of Crif1 protects fatty acid-induced POMC neuron-like cell-line damage by increasing CPT-1 function.

Hypothalamic proopiomelanocortin (POMC) neurons are sensors of signals that reflect the energy stored in the body. Inducing mild stress in proopiomelanocortin neurons protects them from the damage promoted by the consumption of a high-fat diet, mitigating the development of obesity; however, the cellular mechanisms behind these effects are unknown. Here, we induced mild stress in a proopiomelanocortin neuron cell line by inhibiting Crif1. In proopiomelanocortin neurons exposed to high levels of palmitate, the partial inhibition of Crif1 reverted the defects in mitochondrial respiration and ATP production; this was accompanied by improved mitochondrial fusion/fission cycling. Furthermore, the partial inhibition of Crif1 resulted in increased reactive oxygen species production, increased fatty acid oxidation, and reduced dependency on glucose for mitochondrial respiration. These changes were dependent on the activity of CPT-1. Thus, we identified a CPT-1-dependent metabolic shift toward greater utilization of fatty acids as substrates for respiration as the mechanism behind the protective effect of mild stress against palmitate-induced damage of proopiomelanocortin neurons.NEW & NOTEWORTHY Saturated fats can damage hypothalamic neurons resulting in positive energy balance, and this is mitigated by mild cellular stress; however, the mechanisms behind this protective effect are unknown. Using a proopiomelanocortin cell line, we show that under exposure to a high concentration of palmitate, the partial inhibition of the mitochondrial protein Crif1 results in protection due to a metabolic shift warranted by the increased expression and activity of the mitochondrial fatty acid transporter CPT-1.

Outcomes of Minimally Invasive Aortic Valve Replacement in Obese Patients: A Propensity-Matched Study.

INTRODUCTION: Obese patients are at risk of complications after cardiac surgery. The aim of this study is to investigate safety and efficacy of a minimally invasive approach via upper sternotomy in this setting. METHODS: We retrospectively reviewed 203 obese patients who underwent isolated, elective aortic valve replacement between January 2014 and January 2023 - 106 with minimally invasive aortic valve replacement (MIAVR) and 97 with conventional aortic valve replacement (CAVR). To account for baseline differences, a propensity-matching analysis was performed obtaining two balanced groups of 91 patients each. RESULTS: The 30-day mortality rate was comparable between groups (1.1% MIAVR vs. 0% CAVR, P=0.99). MIAVR patients had faster extubation than CAVR patients (6 ± 2 vs. 9 ± 2 hours, P<0.01). Continuous positive airway pressure therapy was less common in the MIAVR than in the CAVR group (3.3% vs. 13.2%, P=0.03). Other postoperative complications did not differ significantly. Intensive care unit stay (1.8 ± 1.2 vs. 3.2 ± 1.4 days, P<0.01), but not hospital stay (6.7 ± 2.1 vs. 7.2 ± 1.9 days, P=0.09), was shorter for MIAVR than for CAVR patients. Follow-up survival was comparable (logrank P-value = 0.58). CONCLUSION: MIAVR via upper sternotomy has been shown to be a safe and effective option for obese patients. Respiratory outcome was promising with shorter mechanical ventilation time and reduced need for post-extubation support. The length of stay in the intensive care unit was reduced. These advantages might be important for the obese patient to whom minimally invasive surgery should not be denied.

A practical and robust method to evaluate metabolic fluxes in primary pancreatic islets.

OBJECTIVE: Evaluation of mitochondrial oxygen consumption and ATP production is important to investigate pancreatic islet pathophysiology. Most studies use cell lines due to difficulties in measuring primary islet respiration, which requires specific equipment and consumables, is expensive and poorly reproducible. Our aim was to establish a practical method to assess primary islet metabolic fluxes using standard commercial consumables. METHODS: Pancreatic islets were isolated from mice/rats, dispersed with trypsin, and adhered to pre-coated standard Seahorse or Resipher microplates. Oxygen consumption was evaluated using a Seahorse Extracellular Flux Analyzer or a Resipher Real-time Cell Analyzer. RESULTS: We provide a detailed protocol with all steps to optimize islet isolation with high yield and functionality. Our method requires a few islets per replicate; both rat and mouse islets present robust basal respiration and proper response to mitochondrial modulators and glucose. The technique was validated by other functional assays, which show these cells present conserved calcium influx and insulin secretion in response to glucose. We also show that our dispersed islets maintain robust basal respiration levels, in addition to maintaining up to 89% viability after five days in dispersed cultures. Furthermore, OCRs can be measured in Seahorse analyzers and in other plate respirometry systems, using standard materials. CONCLUSIONS: Overall, we established a practical and robust method to assess islet metabolic fluxes and oxidative phosphorylation, a valuable tool to uncover basic ß-cell metabolic mechanisms as well as for translational investigations, such as pharmacological candidate discovery and islet transplantation protocols.

Parkin is a critical player in the effects of caffeine over mitochondrial quality control pathways during skeletal muscle regeneration in mice.

AIM: This study aimed to investigate the effects of caffeine on pathways associated with mitochondrial quality control and mitochondrial capacity during skeletal muscle regeneration, focusing on the role of Parkin, a key protein involved in mitophagy. METHODS: We used in vitro C2C12 myoblast during differentiation with and without caffeine in the medium, and we evaluated several markers of mitochondrial quality control pathways and myotube growth. In vivo experiments, we used C57BL/6J (WT) and Parkintm 1Shn lineage (Parkin-/- ) mice and injured tibial anterior muscle. The mice regenerated TA muscle for 3, 10, and 21 days with or without caffeine ingestion. TA muscle was used to analyze the protein content of several markers of mitochondrial quality pathways, muscle satellite cell differentiation, and protein synthesis. Furthermore, it analyzed mtDNA, mitochondrial respiration, and myofiber growth. RESULTS: C2C12 differentiation experiments showed that caffeine decreased Parkin content, potentially leading to increased DRP1 and PGC-1α content and altered mitochondrial population, thereby enhancing growth capacity. Using Parkin-/- mice, we found that caffeine intake during the regenerative process induces an increase in AMPKα phosphorylation and PGC-1α and TFAM content, changes that were partly Parkin-dependent. In addition, the absence of Parkin potentiates the ergogenic effect of caffeine by increasing mitochondrial capacity and myotube growth. Those effects are related to increased ATF4 content and activation of protein synthesis pathways, such as increased 4E-BP1 phosphorylation. CONCLUSION: These findings demonstrate that caffeine ingestion changes mitochondrial quality control during skeletal muscle regeneration, and Parkin is a central player in those mechanisms.

Decreased Photosynthetic Efficiency in Nicotiana tabacum L. under Transient Heat Stress.

Heat stress is an abiotic factor that affects the photosynthetic parameters of plants. In this study, we examined the photosynthetic mechanisms underlying the rapid response of tobacco plants to heat stress in a controlled environment. To evaluate transient heat stress conditions, changes in photochemical, carboxylative, and fluorescence efficiencies were measured using an infrared gas analyser (IRGA Licor 6800) coupled with chlorophyll a fluorescence measurements. Our findings indicated that significant disruptions in the photosynthetic machinery occurred at 45 °C for 6 h following transient heat treatment, as explained by 76.2% in the principal component analysis. The photosynthetic mechanism analysis revealed that the dark respiration rate (Rd and Rd*CO2) increased, indicating a reduced potential for carbon fixation during plant growth and development. When the light compensation point (LCP) increased as the light saturation point (LSP) decreased, this indicated potential damage to the photosystem membrane of the thylakoids. Other photosynthetic parameters, such as AMAX, VCMAX, JMAX, and ΦCO2, also decreased, compromising both photochemical and carboxylative efficiencies in the Calvin-Benson cycle. The energy dissipation mechanism, as indicated by the NPQ, qN, and thermal values, suggested that a photoprotective strategy may have been employed. However, the observed transitory damage was a result of disruption of the electron transport rate (ETR) between the PSII and PSI photosystems, which was initially caused by high temperatures. Our study highlights the impact of rapid temperature changes on plant physiology and the potential acclimatisation mechanisms under rapid heat stress. Future research should focus on exploring the adaptive mechanisms involved in distinguishing mutants to improve crop resilience against environmental stressors.

Microbiological attributes as indicators of soil quality in coffee growing systems in Southwest Bahia, Brazil.

Microorganisms are important indicators of soil quality due to their sensitivity to changes, reflecting the impacts caused by different land uses. The objective of this study was to evaluate the microbiological and physical-chemical attributes of the soil in areas cultivated with coffee under three different management systems (shaded coffee and full sun coffee with two spacings), as well as in adjacent areas under pasture and native forest, in Bahia, Brazil. The microbiological and physicochemical indicators evaluated were basal soil respiration (MBR), soil total organic carbon (TOC), microbial biomass carbon (MBC), metabolic quotient (qCO2), microbial quotient (qMic), enzyme activities (urease, acid phosphatase and fluorescein diacetate hydrolysis (FDA)). Physical and chemical indicators (particle size, texture, pH, P, K+, Ca2+, Mg2+, Al3+, and sum of bases) were also evaluated. Biological and chemical attributes were much more discriminative of study areas in the dry season. Microbial quotient (qMic) and metabolic quotient (qCO2) in the dry season showed that pasture is the most degraded land use. Conversely, nature forest and coffee with Grevillea were similar and were the best ones. In general, soil quality indicators were more sensitive to discriminate pasture and native forest from coffee systems, which, in turn, were not well discriminated among themselves.

Asociación entre impulso respiratorio y profundidad de sedación en sujetos bajo ventilación mecánica invasiva: estudio observacional / Association between respiratory drive and depth of sedation in subjects under invasive mechanical ventilation: an observational study

RESUMEN Objetivo: El objetivo de este estudio es determinar si existe asociación entre el impulso respiratorio, evaluado a través de la presión de oclusión (P0.1), y la profundidad de sedación, medida a través de la escala de agitación-sedación de Richmond (RASS, por sus siglas en inglés), en sujetos adultos sometidos a ventilación mecánica invasiva e internados en la unidad de cuidados intensivos del Hospital de Clínicas José de San Martín (HCJSM) en Buenos Aires. Como objetivo secundario, se planteó analizar el comportamiento de variables que pudieran tener impacto en el impulso respiratorio. Materiales y método: Se realizó un estudio observacional en un hospital universitario de la Ciudad Autónoma de Buenos Aires entre el 1 de abril de 2023 y el 28 de mayo de 2023. Las variables analizadas fueron P0.1, RASS, dolor, delirio, exposición a analgésicos y sedantes, estado ácido-base, presión arterial de oxígeno/fracción inspirada de oxígeno (PaO2/FiO2), evaluación de falla orgánica relacionada con la sepsis (SOFA, por sus siglas en inglés) e índice de masa corporal (IMC). Resultados: Se recolectaron 71 mediciones correspondientes a 33 sujetos. La mediana de P0.1 fue de 0,13 cmH20 (0-0,97). En el análisis univariado, se encontró una asociación inversamente proporcional entre la P0.1 y el puntaje RASS (β=-0,4068 y p=0,0435). Los resultados del análisis multivariado mostraron que ninguna de las variables contempladas se asoció con la P0.1 cuando fueron ajustadas entre sí. Conclusión: En este estudio, encontramos una asociación entre la P0.1 y el puntaje RASS, así como una asociación independiente entre la P0.1 y la exposición a la combinación de analgesia y sedación. Sin embargo, al ajustar estas variables en el análisis multivariado, no se encontró asociación.

ABSTRACT Objective: The objective of this study is to determine whether there is an association between respiratory drive, assessed through P0.1, and depth of sedation, measured through the Richmond agitation-sedation scale (RASS), in adult subjects undergoing invasive mechanical ventilation and admitted to the intensive care unit of Hospital de Clínicas José de San Martín (HCJSM) in Buenos Aires. As a secondary objective, we aim to analyze the behavior of variables that may have an impact on respiratory drive. Materials and method: An observational study was conducted at a university hospital in the Autonomous City of Buenos Aires between April 1, 2023, and May 28, 2023. The analyzed variables included P0.1, RASS, pain, delirium, exposure to analgesics and sedatives, acid-base status, pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FiO2), sepsis-related organ failure assessment (SOFA), and body mass index (BMI). Results: A total of 71 measurements were collected from 33 subjects. The median P0.1 was 0.13 cmH20 (0-0.97). In the univariate analysis, an inversely proportional association was found between P0.1 and RASS score (β=-0.4068 and p=0.0435). The results of the multivariate analysis showed no association between P0.1 and any of the considered variables when adjusted for each other. Conclusion: In this study, we found an association between P0.1 and RASS score, along with an independent association between P0.1 and exposure to the combination of analgesia and sedation. However, when adjusting these variables in the multivariate analysis, no association was found.

Embryo development is impaired by sperm mitochondrial-derived ROS.

BACKGROUND: Basal energetic metabolism in sperm, particularly oxidative phosphorylation, is known to condition not only their oocyte fertilising ability, but also the subsequent embryo development. While the molecular pathways underlying these events still need to be elucidated, reactive oxygen species (ROS) could have a relevant role. We, therefore, aimed to describe the mechanisms through which mitochondrial activity can influence the first stages of embryo development. RESULTS: We first show that embryo development is tightly influenced by both intracellular ROS and mitochondrial activity. In addition, we depict that the inhibition of mitochondrial activity dramatically decreases intracellular ROS levels. Finally, we also demonstrate that the inhibition of mitochondrial respiration positively influences sperm DNA integrity, most likely because of the depletion of intracellular ROS formation. CONCLUSION: Collectively, the data presented in this work reveals that impairment of early embryo development may result from the accumulation of sperm DNA damage caused by mitochondrial-derived ROS.