Occupational risks associated with chronic kidney disease of non-traditional origin (CKDnt) in Brazil: it is time to dig deeper into a neglected problem / Riscos ocupacionais associados à doença renal crônica de origem não tradicional (DRCnt) no Brasil: é hora de nos aprofundarmos em um problema negligenciado

Abstract In the past decades, an epidemic of chronic kidney disease (CKD) has been associated with environmental and occupational factors (heat stress from high workloads in hot temperatures and exposure to chemicals, such as pesticides and metals), which has been termed CKD of non-traditional origin (CKDnt). This descriptive review aims to present recent evidence about heat stress, pesticides, and metals as possible causes of CKDnt and provide an overview of the related Brazilian regulation, enforcement, and health surveillance strategies. Brazilian workers are commonly exposed to extreme heat conditions and other CKDnt risk factors, including increasing exposure to pesticides and metals. Furthermore, there is a lack of adequate regulation (and enforcement), public policies, and strategies to protect the kidney health of workers, considering the main risk factors. CKDnt is likely to be a significant cause of CKD in Brazil, since CKD's etiology is unknown in many patients and several conditions for its development are present in the country. Further epidemiological studies may be conducted to explore causal associations and estimate the impact of heat, pesticides, and metals on CKDnt in Brazil. Moreover, public policies should prioritize reducing workers´ exposure and promoting their health and safety.

Resumo Nas últimas décadas, uma epidemia de doença renal crônica (DRC) tem sido associada a fatores ambientais e ocupacionais (estresse térmico decorrente de cargas de trabalho elevadas em altas temperaturas e exposição a produtos químicos, como agrotóxicos e metais), denominada DRC de origem não tradicional (DRCnt). Esta revisão descritiva tem como objetivo apresentar evidências recentes sobre estresse térmico, agrotóxicos e metais como possíveis causas de DRCnt e fornecer uma visão geral das estratégias brasileiras de regulamentação, fiscalização e vigilância sanitária relacionadas. Os trabalhadores brasileiros são comumente expostos a condições extremas de calor e outros fatores de risco de DRCnt, incluindo o aumento da exposição a agrotóxicos e metais. Além disso, há uma falta de regulamentação e fiscalização, políticas públicas e estratégias adequadas para proteger a saúde renal dos trabalhadores em relação aos principais fatores de risco. É provável que a DRCnt seja uma causa significativa de DRC no Brasil, uma vez que a etiologia da doença é desconhecida em muitos pacientes e diversas condições para seu desenvolvimento estão presentes no país. Estudos epidemiológicos devem ser realizados para explorar associações causais e estimar o impacto do calor, dos agrotóxicos e dos metais na DRCnt no Brasil. Além disso, as políticas públicas devem priorizar a redução da exposição dos trabalhadores e a promoção de sua saúde e segurança.

The impact of norepinephrine dose reporting heterogeneity on mortality prediction in septic shock patients.

BACKGROUND: Norepinephrine (NE) is a cornerstone drug in the management of septic shock, with its dose being used clinically as a marker of disease severity and as mortality predictor. However, variations in NE dose reporting either as salt formulations or base molecule may lead to misinterpretation of mortality risks and hinder the process of care. METHODS: We conducted a retrospective analysis of the MIMIC-IV database to assess the impact of NE dose reporting heterogeneity on mortality prediction in a cohort of septic shock patients. NE doses were converted from the base molecule to equivalent salt doses, and their ability to predict 28-day mortality at common severity dose cut-offs was compared. RESULTS: 4086 eligible patients with septic shock were identified, with a median age of 68 [57-78] years, an admission SOFA score of 7 [6-10], and lactate at diagnosis of 3.2 [2.4-5.1] mmol/L. Median peak NE dose at day 1 was 0.24 [0.12-0.42] µg/kg/min, with a 28-day mortality of 39.3%. The NE dose showed significant heterogeneity in mortality prediction depending on which formulation was reported, with doses reported as bitartrate and tartrate presenting 65 (95% CI 79-43)% and 67 (95% CI 80-47)% lower ORs than base molecule, respectively. This divergence in prediction widened at increasing NE doses. When using a 1 µg/kg/min threshold, predicted mortality was 54 (95% CI 52-56)% and 83 (95% CI 80-87)% for tartrate formulation and base molecule, respectively. CONCLUSIONS: Heterogeneous reporting of NE doses significantly affects mortality prediction in septic shock. Standardizing NE dose reporting as base molecule could enhance risk stratification and improve processes of care. These findings underscore the importance of consistent NE dose reporting practices in critical care settings.

phoenix: an R package and Python module for calculating the Phoenix pediatric sepsis score and criteria.

Objectives: The publication of the Phoenix criteria for pediatric sepsis and septic shock initiates a new era in clinical care and research of pediatric sepsis. Tools to consistently and accurately apply the Phoenix criteria to electronic health records (EHRs) is one part of building a robust and internally consistent body of research across multiple research groups and datasets. Materials and Methods: We developed the phoenix R package and Python module to provide researchers with intuitive and simple functions to apply the Phoenix criteria to EHR data. Results: The phoenix R package and Python module enable researchers to apply the Phoenix criteria to EHR datasets and derive the relevant indicators, total scores, and sub-scores. Discussion: The transition to the Phoenix criteria marks a major change in the conceptual definition of pediatric sepsis. Applicable across differentially resourced settings, the Phoenix criteria should help improve clinical care and research. Conclusion: The phoenix R package and Python model are freely available on CRAN, PyPi, and GitHub. These tools enable the consistent and accurate application of the Phoenix criteria to EHR datasets.

Loss-of-function/gain-of-function polymorphisms of the ATP sensitive P2X7R influence sepsis, septic shock, pneumonia, and survival outcomes.

Introduction: Extracellular ATP (eATP) released from damaged cells activates the P2X7 receptor (P2X7R) ion channel on the surface of surrounding cells, resulting in calcium influx, potassium efflux and inflammasome activation. Inherited changes in the P2X7R gene (P2RX7) influence eATP induced responses. Single nucleotide polymorphisms (SNPs) of P2RX7 influence both function and signaling of the receptor, that in addition to ion flux includes pathogen control and immunity. Methods: Subjects (n = 105) were admitted to the ICU at the University Hospital Ulm, Germany between June 2018 and August 2019. Of these, subjects with a diagnosis of sepsis (n = 75), were also diagnosed with septic shock (n = 24), and/or pneumonia (n = 42). Subjects with pneumonia (n = 43) included those without sepsis (n = 1), sepsis without shock (n = 29) and pneumonia with septic shock (n = 13). Out of the 75 sepsis/septic shock patients, 33 patients were not diagnosed with pneumonia. Controls (n = 30) were recruited to the study from trauma patients and surgical patients without sepsis, septic shock, or pneumonia. SNP frequencies were determined for 16 P2RX7 SNPs known to affect P2X7R function, and association studies were performed between frequencies of these SNPs in sepsis, septic shock, and pneumonia compared to controls. Results: The loss-of-function (LOF) SNP rs17525809 (T253C) was found more frequently in patients with septic shock, and non-septic trauma patients when compared to sepsis. The LOF SNP rs2230911 (C1096G) was found to be more frequent in patients with sepsis and septic shock than in non-septic trauma patients. The frequencies of these SNPs were even higher in sepsis and septic patients with pneumonia. The current study also confirmed a previous study by our group that showed a five SNP combination that included the GOF SNPs rs208294 (C489T) and rs2230912 (Q460R) that was designated #21211 was associated with increased odds of survival in severe sepsis. Discussion: The results found an association between expression of LOF P2RX7 SNPs and presentation to the ICU with sepsis, and septic shock compared to control ICU patients. Furthermore, frequencies of LOF SNPs were found to be higher in sepsis patients with pneumonia compared to those without pneumonia. In addition, a five SNP GOF combination was associated with increased odds of survival in severe sepsis. These results suggest that P2RX7 is required to control infection in pneumonia and that inheritance of LOF variants increases the risk of sepsis when associated with pneumonia. This study confirms that P2RX7 genotyping in pneumonia may identify patients at risk of developing sepsis. The study also identifies P2X7R as a target in sepsis associated with an excessive immune response in subjects with GOF SNP combinations.

Predicting severe outcomes in pediatric trauma patients: Shock index pediatric age-adjusted vs. age-adjusted tachycardia.

INTRODUCTION: When an injured patient arrives in the Emergency Department (ED), timely and appropriate care is crucial. Shock Index Pediatric Age-Adjusted (SIPA) has been shown to accurately identify pediatric patients in need of emergency interventions. However, no study has evaluated SIPA against age-adjusted tachycardia (AT). This study aims to compare SIPA with AT in predicting outcomes such as mortality, severe injury, and the need for emergent intervention in pediatric trauma patients. MATERIAL AND METHODS: This is a retrospective cross-sectional analysis of patient data abstracted from the Trauma Quality Improvement Program Participant Use Files (TQIP PUFs) for years 2013-2020. Patients aged 4-16 with blunt mechanism of injury and injury severity score (ISS) > 15 were included. 36,517 children met this criteria. Sensitivity, specificity, overtriage, and undertriage rates were calculated to compare the effectiveness of AT and elevated SIPA as predictors of severe injuries and need for emergent intervention. Emergent interventions included craniotomy, endotracheal intubation, thoracotomy, laparotomy, or chest tube placement within 24 h of arrival. RESULTS: AT classified 59% of patients as "high risk," while elevated SIPA identified 26%. Compared to AT patients, a greater proportion of patients with elevated SIPA required a blood transfusion within 24 h (22% vs. 12%, respectively; p < 0.001). In-hospital mortality was higher for the elevated SIPA group than AT (10% vs. 5%, respectively; p < 0.001) as well as the need for emergent operative interventions (43% vs. 32% respectively; p < 0.001). Grade 3 or higher liver/spleen lacerations requiring blood transfusion were also more common among elevated SIPA patients than AT patients (8% vs. 4%, respectively; p < 0.001). AT demonstrated greater sensitivity but lower specificity compared to SIPA across all outcomes. AT showed improved overtriage and undertriage rates compared to SIPA, but this is attributed to identifying a large proportion of the sample as "high risk." CONCLUSIONS: AT outperforms SIPA in sensitivity for mortality, injury severity and emergent interventions in pediatric trauma patients while the specificity of SIPA is high across these outcomes.

Plastid HSP90C C-terminal extension region plays a regulatory role in chaperone activity and client binding.

HSP90Cs are essential molecular chaperones localized in the plastid stroma that maintain protein homeostasis and assist the import and thylakoid transport of chloroplast proteins. While HSP90C contains all conserved domains as an HSP90 family protein, it also possesses a unique feature in its variable C-terminal extension (CTE) region. This study elucidated the specific function of this HSP90C CTE region. Our phylogenetic analyses revealed that this intrinsically disordered region contains a highly conserved DPW motif in the green lineages. With biochemical assays, we showed that the CTE is required for the chaperone to effectively interact with client proteins PsbO1 and LHCB2 to regulate ATP-independent chaperone activity and to effectuate its ATP hydrolysis. The CTE truncation mutants could support plant growth and development reminiscing the wild type under normal conditions except for a minor phenotype in cotyledon when expressed at a level comparable to wild type. However, higher HSP90C expression was observed to correlate with a stronger response to specific photosystem II inhibitor DCMU, and CTE truncations dampened the response. Additionally, when treated with lincomycin to inhibit chloroplast protein translation, CTE truncation mutants showed a delayed response to PsbO1 expression repression, suggesting its role in chloroplast retrograde signaling. Our study therefore provides insights into the mechanism of HSP90C in client protein binding and the regulation of green chloroplast maturation and function, especially under stress conditions.

Factors Influencing Successful Weaning From Venoarterial Extracorporeal Membrane Oxygenation: A Systematic Review.

With advancements in extracorporeal life support (ECLS) technologies, venoarterial extracorporeal membrane oxygenation (VA-ECMO) has emerged as a crucial cardiopulmonary support mechanism. This review explores the significance of VA-ECMO system configuration, cannulation strategies, and timing of initiation. Through an analysis of medication management strategies, complication management, and comprehensive preweaning assessments, it aims to establish a multidimensional evaluation framework to assist clinicians in making informed decisions regarding weaning from VA-ECMO, thereby ensuring the safe and effective transition of patients.

Circulatory support with triple cannulation V-PaA ECMO in a patient with acute right ventricular failure and refractory hypoxemia secondary to diffuse alveolar hemorrhage: A case report.

A 48-year-old woman presented to the emergency department with a one-week history of progressive dyspnea. During her hospitalization, the diagnosis of diffuse alveolar hemorrhage was made. She subsequently developed respiratory failure and acute right ventricular failure. Despite medical treatment, she continued to experience distributive shock due to a generalized inflammatory response. Circulatory support with ECMO was needed. We opted for triple cannulation to manage the multiorgan failure as a bridge to recovery. We describe our experience with an uncommon cannulation technique: veno-pulmonary-arterial cannulation, which enabled us to address cardiogenic shock, refractory hypoxemia, and distributive shock, leading to the successful recovery of the patient.

The Efficacy of Montelukast in Reducing the Risk of Warning Signs and Subsequent Dengue Shock Syndrome in Adult Dengue Fever Patients.

BACKGROUND: Dengue fever continues to pose significant health challenges globally, with recent outbreaks in Bihar, India, prompting a search for effective therapeutic interventions. This study assesses the effectiveness of Montelukast, traditionally used for asthma, in mitigating the severity of dengue fever symptoms and its progression to dengue shock syndrome (DSS). OBJECTIVE: To evaluate the impact of Montelukast on the prevalence of dengue warning signs and the incidence of DSS in adult patients. METHODS: A prospective observational study was conducted at the Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, India, from August 2022 to October 2023, enrolling 500 patients diagnosed with dengue fever. Participants were divided into two groups. About 250 were treated with Montelukast and 250 received standard care. Outcomes measured included the incidence of warning signs, DSS, length of hospital stay, and 30-day mortality. RESULTS: The Montelukast group exhibited a 24% lower prevalence of dengue warning signs compared to the control group, with 90 out of 250 patients (36%) in the Montelukast group versus 150 out of 250 patients (60%) in the control group (p < 0.001). The incidence of DSS was significantly reduced in the Montelukast group, with 4 out of 250 patients (1.6%) compared to 21 out of 250 patients (8.4%) in the control group (odds ratio: 0.178, p < 0.001). Furthermore, Montelukast users experienced shorter hospital stays (average 4.52 days vs. 6.54 days, T-statistic: -7.59, p = 1.58×10-13) and a reduced 30-day mortality rate, with 5 out of 250 patients (2%) in the Montelukast group versus 12 out of 250 patients (5%) in the control group (p < 0.03). CONCLUSION: Montelukast significantly lowers the incidence of dengue warning signs and DSS, shortens hospital stays, and decreases mortality rates among dengue patients, supporting its potential integration into existing dengue treatment protocols. This study highlights the need for further clinical trials to confirm these findings and fully understand the therapeutic mechanisms of Montelukast in dengue management.

Central Venous Catheter Misplacement Into Pleural Cavity Causing Hypertensive Pleural Effusion: A Case Report.

Central venous catheter (CVC) insertion is a routine procedure in the management of critically ill patients. We report a clinical case of inadvertent placement of an internal jugular vein CVC into the right pleural cavity, despite employing clinical and imaging-based techniques to ensure proper catheter positioning. Infusion of fluids and vasopressors through this misplaced catheter led to hypertensive pleural effusion and subsequent cardiorespiratory arrest. Return of spontaneous circulation was achieved after two cycles of cardiopulmonary resuscitation. While multiple imaging modalities are recommended for confirming appropriate CVC placement, each method has inherent limitations. This case highlights the imperative need for a high index of suspicion to avert such complications and pretends to review some of each method's limitations.

Takotsubo Cardiomyopathy in a Young Patient Presenting as Cardiac Arrest and Cardiogenic Shock.

Takotsubo cardiomyopathy (TC) is a reversible cardiac disorder that rarely results in serious morbidity and mortality. Cardiogenic shock and cardiac arrest can occur in patients with TC. In this case report, we present the case of a 31-year-old woman with no significant comorbidities who suffered cardiac arrest due to TC and subsequent cardiogenic shock that required inotropic and vasopressor support. The patient's condition progressively improved, and her cardiac function recovered within a few weeks. This case illustrates the importance of recognizing TC as a significant cause of otherwise unexplained cardiac arrest and highlights the need for evidence-based guidelines for treating cardiogenic shock in this setting.

Safety and utility of mechanical circulatory support in patients with acute myocardial infarction complicated by cardiogenic shock: A systematic review and meta-analysis.

BACKGROUND: Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) is a major cause of morbidity and mortality. Although mechanical circulatory support (MCS) is an increasingly utilized therapeutic option in AMI-CS, studies evaluating the efficacy and safety of different forms of MCS have yielded conflicting results. This systematic review and meta-analysis aims to evaluate the safety and efficacy of different forms of MCS. METHODS: A database search was performed for studies reporting on the association of different forms of MCS with clinical outcomes in patients with AMI-CS. The primary efficacy endpoints were short term (≤30 days) and long term (>30 days) all-cause mortality. Secondary efficacy endpoints included recurrent AMI, cardiovascular (CV) mortality, device-related limb complications, moderate to severe bleeding events, and cerebrovascular accidents (CVA). RESULTS: 2752 patients with AMI-CS met inclusion criteria. Results were available comparing ECMO to other MCS or medical therapy alone, comparing IABP to medical therapy alone, and comparing pLVAD to IABP. Use of ECMO was not associated with lower risk of 30-day or long-term mortality compared to pVAD or standard medical therapy with or without IABP placement but was associated with higher risk of device-related limb complications and moderate to severe bleeding compared to pVAD. IABP use was not associated with a lower risk of 30 day or long-term mortality but was associated with higher risk of recurrent AMI and moderate to severe bleeding compared to medical therapy. Compared to IABP, pVAD use was associated with lower risk of CV mortality but not recurrent AMI. pVAD was associated with a higher risk of device-related limb complications and moderate to severe bleeding compared to IABP use. CONCLUSION: Use of ECMO or IABP in patients with AMI-CS is not associated with significant improvement in mortality. pVAD is associated with a lower risk of CV mortality. All MCS types are associated with increased risk of complications. Additional high-quality studies are needed to determine the optimal MCS therapy for patients with AMI-CS.

Predictive factors for size change of aorta in patients with acute blunt traumatic aortic injury.

OBJECTIVE: We aimed to investigate the changes in aorta size, the factors affecting size changes in patients with acute blunt traumatic aortic injury and to evaluate the adequacy of the current 120% thoracic endovascular aortic repair graft oversizing policy. DESIGN AND METHODS: This retrospective review study was conducted using the prospectively collected medical records of 45 patients (mean age: 53.5 years, male: 39 patients) with blunt traumatic aortic injury treated at a level 1 trauma center between 2012 and 2021. Aortic diameter was measured by computed tomography angiographic images at four different levels [ascending aorta (A), isthmus (B), descending thoracic aorta (C), and infrarenal aorta (D)] on arrival and follow-up (median time interval, 13 days). Associated factors including patient characteristics and hemodynamic parameters on arrival and follow-up were collected to determine their influence on changes in the aorta. RESULTS: The mean diameter of all four aortic levels increased on follow-up computed tomography compared to initial computed tomography (A: + 11.77%, B: + 10.19%, C: + 7.71%, D: + 12.04%). Patient age and injury severity score influenced changes in the diameter of the ascending aorta (P < 0.05). Patient age and blunt traumatic aortic injury grade were significantly associated with changes in the infrarenal aortic diameter (P < 0.05). Three cases of type 1 endoleak were observed at follow-up but all were spontaneously resolved without further intervention at next computed tomography follow-up. CONCLUSIONS: In patients with acute blunt traumatic aortic injury, aortic diameter is significantly smaller by about 10% under shock and is not considered a basis for oversizing the currently implemented 120% thoracic endovascular aortic repair graft sizing. However, in young patients under the age of 40, the change is significantly large and subsequent computed tomography follow-up is required.

International medical learners and their adjustment after returning to their countries of origin: a qualitative study.

INTRODUCTION: International medical trainees, including residents and fellows, must cope with many challenges, such as differences in cultural hierarchical systems, languages, and acceptance. Nonetheless, the need for adjustment perpetuates even after training is completed abroad. When some international trainees return to their countries of origin, they continue to face adjustment challenges due to reverse culture shock. Others must make many further readjustments. This study presents an exploration of the adjustment and coping strategies of international medical learners after returning to their countries of origin upon completion of their programs. METHOD: This study employed a qualitative approach grounded in interpretivism and utilised inductive thematic analysis following Braun and Clarke's method. Semi-structured, in-depth individual interviews were employed to explore the participants' coping strategies. Participants included international medical learners who were (1) international medical graduates who had already returned to their countries of origin, (2) non-Canadian citizens or nonpermanent residents by the start of the programs, and (3) previously enrolled in a residency or fellowship training programme at the University of Toronto, Ontario, Canada. RESULTS: Seventeen participants were included. Three main themes and seven subthemes were created from the analysis and are represented by the Ice Skater Landing Model. According to this model, there are three main forces in coping processes upon returning home: driving, stabilising, and situational forces. The sum and interaction of these forces impact the readjustment process. CONCLUSION: International medical learners who have trained abroad and returned to their countries of origin often struggle with readjustment. An equilibrium between the driving and stabilising forces is crucial for a smooth transition. The findings of this study can help stakeholders better understand coping processes. As healthy coping processes are related to job satisfaction and retention, efforts to support and shorten repatriation adjustment are worthwhile.

Reversal of cognitive deficits in FUSR521G amyotrophic lateral sclerosis mice by arimoclomol and a class I histone deacetylase inhibitor independent of heat shock protein induction.

Protein misfolding and mislocalization are common to both familial and sporadic forms of amyotrophic lateral sclerosis (ALS). Maintaining proteostasis through induction of heat shock proteins (HSP) to increase chaperoning capacity is a rational therapeutic strategy in the treatment of ALS. However, the threshold for upregulating stress-inducible HSPs remains high in neurons, presenting a therapeutic obstacle. This study used mouse models expressing the ALS variants FUSR521G or SOD1G93A to follow up on previous work in cultured motor neurons showing varied effects of the HSP co-inducer, arimoclomol, and class I histone deacetylase (HDAC) inhibitors on HSP expression depending on the ALS variant being expressed. As in cultured neurons, neither expression of the transgene nor drug treatments induced expression of HSPs in cortex, spinal cord or muscle of FUSR521G mice, indicating suppression of the heat shock response. Nonetheless, arimoclomol, and RGFP963, restored performance on cognitive tests and improved cortical dendritic spine densities. In SOD1G93A mice, multiple HSPs were upregulated in hindlimb skeletal muscle, but not in lumbar spinal cord with the exception of HSPB1 associated with astrocytosis. Drug treatments improved contractile force but reduced the increase in HSPs in muscle rather than facilitating their expression. The data point to mechanisms other than amplification of the heat shock response underlying recovery of cognitive function in ALS-FUS mice by arimoclomol and class I HDAC inhibition and suggest potential benefits in counteracting cognitive impairment in ALS, frontotemporal dementia and related disorders.

Comparing the clinical characteristics and outcomes of septic shock children with and without malignancies: a retrospective cohort study.

OBJECTIVE: There is an amelioration in mortality rates of septic shock patients with malignancies over time, but it remains uncertain in children. Therefore, the authors endeavored to compare the clinical characteristics, treatment needs, and outcomes of septic shock children with or without malignancies. METHODS: The authors retrospectively analyzed the data of children admitted to the PICU due to septic shock from January 2015 to December 2022 in a tertiary pediatric hospital. The main outcome was in-hospital mortality. RESULTS: A total of 508 patients were enrolled. The proportion of Gram-negative bacteria and fungal infections in children with malignancies was significantly higher than those without malignancies. Septic shock children with malignancies had a longer length of stay (LOS) in the hospital (21 vs. 11 days, p<0.001). However, there were no statistically significant differences in the LOS of PICU (5 vs. 5 days, p = 0.591), in-hospital mortality (43.0 % vs. 49.4 %, p = 0.276), and 28-day mortality (49.2 % vs. 44.7 %, p = 0.452). The 28-day survival analysis (p = 0.314) also showed no significant differences. CONCLUSION: Although there are significant differences in the bacterial spectrum of infections, the septic shock children with or without malignancies showed a similar mortality rate. The septic shock children with malignancies had longer LOS of the hospital.

Double-Phase-Networking Polyimide Hybrid Aerogel with Exceptional Dimensional Stability for Superior Thermal Protection System.

Polyimide aerogels have been extensively used in thermal protection domain because they possess a combination of intrinsic characteristics of aerogels and unique features of polyimide. However, polyimide aerogels still suffer significant thermally induced shrinkage at temperatures above 200 °C, restricting their application at high temperature. Here, a novel "double-phase-networking" strategy is proposed for fabricating a lightweight and mechanically robust polyimide hybrid aerogel by forming silica-zirconia-phase networking skeletons, which possess exceptional dimensional stability in high-temperature environments and superior thermal insulation. The rational mechanism responsible for the formation of double-phase-networking aerogel is further explained, generally attributing to chemical crosslinking reactions and supramolecular hydrogen bond interactions derived from the main chains of polyimide and silane/zirconia precursor/sol. The as-prepared aerogels exhibit excellent high-temperature (270 °C) dimensional stability (5.09% ± 0.16%), anti-thermal-shock properties, and low thermal conductivity. Moreover, the hydrophobic treatment provides aerogels high water resistance with water contact angle of 136.9°, further suggestive of low moisture content of 3.6% after exposure to 70 °C and 85% relative humidity for 64 h. The proposed solution for significantly enhancing high-temperature dimensional stability and thermal insulation provides a great supporting foundation for fabricating high-performance organic aerogels as thermal protection materials in aerospace.

Inflicting, Monitoring, Visualizing, and Quantitating Various Sterile Membrane Damages and the Repair Response in Dictyostelium discoideum.

Eukaryotic cells have been constantly challenged throughout their evolution by pathogens, mechanical stresses, or toxic compounds that induce plasma membrane (PM) or endolysosomal membrane damage. The survival of the wounded cells depends on damage detection and repair machineries that are evolutionary conserved between protozoan, plants, and animals. We use the social amoeba Dictyostelium discoideum as a model system to study bacteria, mechanical or sterile membrane damage that allows us to identify and monitor factors involved in PM, endolysosomal damage response (ELDR), and endolysosomal homeostasis. Importantly, the sterile damage techniques presented here homogenously affect cell populations, which allows to phenotype mutant strains and quantify various aspects of cell fitness using live cell microscopy. This is instrumental to functionally assess genes involved in the repair of damaged plasma membrane or intracellular compartments and the degradation of extensively damaged compartments. Here, we describe how to inflict sterile PM or endolysosomal membrane damage, how to monitor the cell-intrinsic response to damage, and how to proxy proton leakage from damaged acidic compartments and quantify cell viability.

The effect of high-dose selenium on mortality and postoperative organ dysfunction in post-cardiotomy cardiogenic shock patients supported with mechanical circulatory support - A post-hoc analysis of the SUSTAIN CSX trial.

PURPOSE: Cardiac surgery, post-cardiotomy cardiogenic shock (PCCS), and temporary mechanical circulatory support (tMCS) provoke substantial inflammation. We therefore investigated whether a selenium-based, anti-inflammatory strategy would benefit PCCS patients treated with tMCS in a post-hoc analysis of the sustain CSX trial. METHODS: Post-hoc analysis of patients receiving tMCS for PCCS in the Sustain CSX trial, which investigated the effects of high-dose selenium on postoperative organ dysfunction in cardiac surgery patients. PRIMARY OUTCOME: duration of tMCS therapy. SECONDARY OUTCOMES: postoperative organ dysfunction and 30-day mortality. RESULTS: Thirty-nine patients were treated with tMCS for PCCS. There was no difference in the median duration of tMCS between the selenium and the placebo group (3 days [IQR: 1-6] vs. 2 days [IQR: 1-7], p = 0.52). Median dialysis duration was longer in the selenium group (1.5 days [0-21.8] vs. 0 days [0-1.8], p = 0.048). There was no difference in 30-day mortality (53% vs. 41%, OR 1.44, 95% CI 0.32-6.47, p = 0.62). CONCLUSION: In this explorative study, a perioperative high-dose selenium-supplementation did not show beneficial effects on organ dysfunctions and mortality rates in patients with PCCS receiving tMCS.