Polydatin and Nicotinamide Rescue the Cellular Phenotype of Mitochondrial Diseases by Mitochondrial Unfolded Protein Response (mtUPR) Activation.

Primary mitochondrial diseases result from mutations in nuclear DNA (nDNA) or mitochondrial DNA (mtDNA) genes, encoding proteins crucial for mitochondrial structure or function. Given that few disease-specific therapies are available for mitochondrial diseases, novel treatments to reverse mitochondrial dysfunction are necessary. In this work, we explored new therapeutic options in mitochondrial diseases using fibroblasts and induced neurons derived from patients with mutations in the GFM1 gene. This gene encodes the essential mitochondrial translation elongation factor G1 involved in mitochondrial protein synthesis. Due to the severe mitochondrial defect, mutant GFM1 fibroblasts cannot survive in galactose medium, making them an ideal screening model to test the effectiveness of pharmacological compounds. We found that the combination of polydatin and nicotinamide enabled the survival of mutant GFM1 fibroblasts in stress medium. We also demonstrated that polydatin and nicotinamide upregulated the mitochondrial Unfolded Protein Response (mtUPR), especially the SIRT3 pathway. Activation of mtUPR partially restored mitochondrial protein synthesis and expression, as well as improved cellular bioenergetics. Furthermore, we confirmed the positive effect of the treatment in GFM1 mutant induced neurons obtained by direct reprogramming from patient fibroblasts. Overall, we provide compelling evidence that mtUPR activation is a promising therapeutic strategy for GFM1 mutations.

Endovascular therapy for posterior cerebral artery occlusion: systematic review with meta-analysis.

Endovascular therapy (EVT) is a highly effective stroke treatment, but trials validating this intervention did not include patients with posterior cerebral artery (PCA) occlusion. The aim of this systematic review with meta-analysis was to assess the efficacy and safety of EVT for acute PCA occlusion. PubMed, Scopus, ISI, and CENTRAL were searched for studies assessing EVT in adult patients with PCA occlusion. Outcomes of interest were recanalization, symptomatic intracerebral haemorrhage (sICH), mortality, functional independence, and excellent functional outcome at 90 days. Frequencies and odds ratios (ORs) were pooled using random effect models and heterogeneity was measured using the I2 statistic and explored by means of meta-regression. Fifteen studies were included, all observational. Recanalization rates were high [81%, 95% CI (73-88%)] and sICH rates low [2%, 95% CI (1-4%)]. Heterogeneity was high for recanalization (I2 = 80%) but not for sICH, and not accounted for by any of the moderators tested. Compared to best medical treatment, EVT was associated with higher chances of sICH [OR = 2.04, 95% CI (1.12-3.71)] and no effect in functional independence [OR = 0.98, 95% CI (0.63-1.54)], with a tendency to higher chances of excellent functional outcome [OR = 1.29, 95% CI (0.90-1.86)] and mortality [OR = 1.56, 95% CI (0.84-2.90)]. EVT for acute PCA occlusion is technically feasible but associated with higher chance of sICH. There is no evidence to support this treatment to achieve higher rates of functional independence, but other gains that can impact patients' quality of life cannot be excluded. More studies are required with robust design, better patient selection, and comprehensive outcome evaluation.

Bacteria isolated from Aedes aegypti with potential vector control applications.

Highly anthropophilic and adapted to urban environments, Aedes aegypti mosquitoes are the main vectors of arboviruses that cause human diseases such as dengue, zika, and chikungunya fever, especially in countries with tropical and subtropical climates. Microorganisms with mosquitocidal and larvicidal activities have been suggested as environmentally safe alternatives to chemical or mechanical mosquito control methods. Here, we analyzed cultivable bacteria isolated from all stages of the mosquito life cycle for their larvicidal activity against Ae. aegypti. A total of 424 bacterial strains isolated from eggs, larvae, pupae, or adult Ae. aegypti were analyzed for the pathogenic potential of their crude cultures against larvae of this same mosquito species. Nine strains displayed larvicidal activity comparable to the strain AM65-52, reisolated from commercial BTi-based product VectoBac® WG. 16S rRNA gene sequencing revealed that the set of larvicidal strains contains two representatives of the genus Bacillus, five Enterobacter, and two Stenotrophomonas. This study demonstrates that some bacteria isolated from Ae. aegypti are pathogenic for the mosquito from which they were isolated. The data are promising for developing novel bioinsecticides for the control of these medically important mosquitoes.

Biomonitoring of polycyclic aromatic hydrocarbons exposure and short-time health effects in wildland firefighters during real-life fire events.

Human biomonitoring data retrieved from real-life wildland firefighting in Europe and, also, worldwide are scarce. Thus, in this study, 176 Portuguese firefighters were biomonitored pre- and post- unsimulated wildfire combating (average:12-13 h; maximum: 55 h) to evaluate the impact on the levels of urinary polycyclic aromatic hydrocarbons hydroxylated metabolites (OHPAH; quantified by high-performance liquid chromatography with fluorescence detection) and the associated short-term health effects (symptoms, and total and differentiated white blood cells). Correlations between these variables and data retrieved from the self-reported questionnaires were also investigated. Firefighters were organized into four groups according to their exposure to wildfire emissions and their smoking habits: non-smoking non-exposed (NSNExp), non-smoking exposed (NSExp), smoking non-exposed (SNExp), and smoking and exposed (SExp). The most abundant metabolites were 1-hydroxynaphthalene and 1-hydroxyacenaphthene (1OHNaph + 1OHAce) (98-99 %), followed by 2-hydroxyfluorene (2OHFlu) (0.2-1.1 %), 1-hydroxyphenanthrene (1OHPhen) (0.2-0.4 %), and 1-hydroxypyrene (1OHPy) (0.1-0.2 %); urinary 3-hydroxybenzo(a)pyrene was not detected. The exposure to wildfire emissions significantly elevated the median concentrations of each individual and total OHPAH compounds in all groups, but this effect was more pronounced in non-smoking (1.7-4.2 times; p ≤ 0.006) than in smoking firefighters (1.3-1.6 times; p ≤ 0.03). The greatest discriminant of exposure to wildfire emissions was 1OHNaph + 1OHAce (increase of 4.2 times), while for tobacco smoke it was 2OHFlu (increase of 10 times). Post-exposure, white blood cells count significantly increased ranging from 1.4 (smokers, p = 0.025) to 3.7-fold (non-smokers, p < 0.001), which was accompanied by stronger significant correlations (0.480 < r < 0.882; p < 0.04) between individual and total OHPAH and total white blood cells (and lymphocytes > monocytes > neutrophils in non-smokers), evidencing the impact of PAH released from wildfire on immune cells. This study identifies Portuguese firefighters with high levels of biomarkers of exposure to PAH and points out the importance of adopting biomonitoring schemes, that include multiple biomarkers of exposure and biomarkers of effect, and implementing mitigations strategies.

Baseline data and associations between urinary biomarkers of polycyclic aromatic hydrocarbons, blood pressure, hemogram, and lifestyle among wildland firefighters.

Introduction: Available literature has found an association between firefighting and pathologic pathways leading to cardiorespiratory diseases, which have been linked with exposure to polycyclic aromatic hydrocarbons (PAHs). PAHs are highlighted as priority pollutants by the European Human Biomonitoring Initiative in occupational and non-occupational contexts. Methods: This cross-sectional study is the first to simultaneously characterize six creatinine-adjusted PAHs metabolites (OHPAHs) in urine, blood pressure, cardiac frequency, and hemogram parameters among wildland firefighters without occupational exposure to fire emissions (> 7 days), while exploring several variables retrieved via questionnaires. Results: Overall, baseline levels for total OHPAHs levels were 2 to 23-times superior to the general population, whereas individual metabolites remained below the general population median range (except for 1-hydroxynaphthalene+1-hydroxyacenaphtene). Exposure to gaseous pollutants and/or particulate matter during work-shift was associated with a 3.5-fold increase in total OHPAHs levels. Firefighters who smoke presented 3-times higher total concentration of OHPAHs than non-smokers (p < 0.001); non-smoker females presented 2-fold lower total OHPAHs (p = 0.049) than males. 1-hydroxypyrene was below the recommended occupational biological exposure value (2.5 µg/L), and the metabolite of carcinogenic PAH (benzo(a)pyrene) was not detected. Blood pressure was above 120/80 mmHg in 71% of subjects. Firefighters from the permanent intervention team presented significantly increased systolic pressure than those who performed other functions (p = 0.034). Tobacco consumption was significantly associated with higher basophils (p = 0.01-0.02) and hematocrit (p = 0.03). No association between OHPAHs and blood pressure was found. OHPAHs concentrations were positively correlated with monocyte, basophils, large immune cells, atypical lymphocytes, and mean corpuscular volume, which were stronger among smokers. Nevertheless, inverse associations were observed between fluorene and pyrene metabolites with neutrophils and eosinophils, respectively, in non-smokers. Hemogram was negatively affected by overworking and lower physical activity. Conclusion: This study suggests possible associations between urinary PAHs metabolites and health parameters in firefighters, that should be further assessed in larger groups.

Benchmarking the influence of pre-training on explanation performance in MR image classification.

Convolutional Neural Networks (CNNs) are frequently and successfully used in medical prediction tasks. They are often used in combination with transfer learning, leading to improved performance when training data for the task are scarce. The resulting models are highly complex and typically do not provide any insight into their predictive mechanisms, motivating the field of "explainable" artificial intelligence (XAI). However, previous studies have rarely quantitatively evaluated the "explanation performance" of XAI methods against ground-truth data, and transfer learning and its influence on objective measures of explanation performance has not been investigated. Here, we propose a benchmark dataset that allows for quantifying explanation performance in a realistic magnetic resonance imaging (MRI) classification task. We employ this benchmark to understand the influence of transfer learning on the quality of explanations. Experimental results show that popular XAI methods applied to the same underlying model differ vastly in performance, even when considering only correctly classified examples. We further observe that explanation performance strongly depends on the task used for pre-training and the number of CNN layers pre-trained. These results hold after correcting for a substantial correlation between explanation and classification performance.

A stronger antibody response in increased disease severity of SARS-CoV-2.

BACKGROUND: An assessment of the factors that interfere with serum levels and the persistence of anti-SARs-CoV-2 IgG antibodies is essential in order to estimate the risk of reinfection and to plan vaccination. We analyzed the impact of the severity of coronavirus disease 2019 (COVID-19) and the clinical and biological factors regarding the persistence of SARs-CoV-2 anti-spike protein (IgG-S) antibodies at 12 months. METHODS: This was an observational, longitudinal study with individuals who had recovered from COVID-19 between August 2020 and June 2021. Peripheral blood samples were collected from volunteers who were hospitalized (SERIOUS COVID-19) and those who required no hospitalization (COVID-19 LIGHT). Samples were grouped according to days after symptom onset: up to 90, between 91 and 180, ≥ 180 days after symptom onset. A semiquantitative test for IgG anti-spike protein S1(IgG-S1) was used. RESULTS: We analyzed 238 individuals who had recovered from COVID-19, of whom 87 had been hospitalized and 151 had not. They provided 148 and 220 samples, respectively. Among those hospitalized, males (65.5%), volunteers aged over 60 years (41.1%), comorbidities such as arterial hypertension (67.8%) and diabetes mellitus (37.9%) were most frequent. We observed higher median serum IgG-S1 titers among those who had recovered from COVID-19 and had been hospitalized, at all collection time intervals (p < 0.001). We observed a weak correlation of increasing age with humoral IgG-S1 response (Spearman correlation = 0.298). There was a greater probability of IgG-S1 antibody persistence over time among samples from hospitalized individuals compared to samples from non-hospitalized participants (p = 0.001). CONCLUSION: This study has revealed higher titers and a higher probability of the persistence of IgG-S1 in severe cases after SARs-CoV-2 primary infection in unvaccinated recovered patients. Thus, in this study, the severe clinical presentation of COVID-19 was the main factor influencing serum levels and the persistence of IgG-S1 antibodies in COVID-19.

Levels of soluble TNF receptors (sTNFR1 and sTNFR2) increase with clinical worsening of patients and are related to COVID-19 mortality.

The present study aimed to inspect the serum levels of the soluble receptors, sTNFR1 and sTNFR2, in patients with COVID-19. The large production of inflammatory cytokines is an essential process in the pathogenesis of COVID-19. TNF is a multifaceted proinflammatory cytokine which has soluble and membrane receptors. Thus, knowing the role of these receptors will help better understand this disease's immunopathogenesis. We included 131 patients confirmed for SARS-CoV-2, separated into three groups: ward patients without O2 support, group A (n = 14); ward patients with O2 support, group B (n = 85), and patients in an intensive care unit (ICU), group C (n = 32), making up the receptors dosed by flow cytometry. The results showed that sTNFR1 and sTNFR2 are associated with disease severity, being higher in group C when compared to group A. As for the levels of receptors and their relationship with the degree of lung involvement, we found higher values of sTNFR1 in patients in group 1 (pulmonary involvement < 25%), suggesting that inflammatory processes related to TNF are not necessarily associated with the primary site of infection. When we analysed the patients who passed away compared to those who recovered, both receptors significantly increased the mortality numbers. These findings suggest a relevant influence of soluble receptors in the inflammatory processes involved in the pathogenesis of COVID-19. Wherefore, we suggest using these receptors as biomarkers of severity and mortality of the disease.

A vivência da dor experienciada pela mulher durante o trabalho de parto/parto / Women's experience of pain during labor/childbirth

Introdução: A dor do trabalho de parto/parto (TP/P) é uma experiência individual. É uma dor desafiadora, emocional e significativa sendo muito diferente de outros tipos de dor. Fatores cognitivos, sociais e ambientais são determinantes e influenciam a dor do trabalho de parto/ parto. No decorrer da prática clínica, no âmbito da assistência à mulher durante o trabalho de parto/parto, inserida na família e comunidade, o Enfermeiro Especialista em Enfermagem de Saúde Materna e Obstétrica (EEESMO) confronta-se com o fenómeno experienciado pela mulher: a dor do seu trabalho de parto/ parto. A dor do trabalho de parto/ parto é um fenómeno transversal experienciado pelas mulheres, que fica gravado na sua memória e dele depende a qualidade da sua experiência no trabalho de parto/parto, qualidade essa, que tem impacto a longo prazo na vida da mulher. Objetivo: Descrever a vivência da dor experienciada pela mulher durante o seu trabalho de parto/parto. Metodologia: Estudo qualitativo de nível I, exploratório-descritivo. A amostra intencional, não probabilística por rede, tipo bola de neve, foi constituída por 22 mulheres, até 6 meses após o parto, que após consentimento informado participaram no estudo. A recolha de dados realizou-se através de entrevista semiestruturada com colheita de dados sociodemográficos e obstétricos, e questões semiabertas para exploração do fenómeno. Procedida a análise dos dados utilizando o método fenomenológico de Giorgi (Giorgi & Sousa, 2010). Resultados: Do discurso das participantes emergiram duas estruturas essenciais e que dizem respeito à qualidade das experiências vivenciadas, uma com características positivas e, a outra estrutura, com características negativas, tendo em consideração o foco deste estudo, a dor experienciada pela mulher durante o trabalho de parto/parto. Dos dados analisados emergiram quatro diferentes contextos: a vivência da dor do trabalho de parto/parto, necessidades da mulher, ?bagagem? e o papel dos profissionais de saúde. Conclusão: A vivência da dor experienciada pela mulher durante o trabalho de parto/parto é uma experiência individual e subjetiva. A dor pode ser vivida como positiva e como tendo um propósito. Surgiu como necessidades da mulher a presença de um acompanhaDor do parto; Trabalho de parto; Parto; Mulheres; Vivênciasnte, as estratégias de alívio da dor e conforto e um ambiente seguro. Realça-se a importância do papel dos EEESMO para uma assistência ao parto segura, promotora de experiências de parto positivas e um fator importante na forma como a mulher vivencia a dor do trabalho de parto/parto.

A rare case of skin metastasis from a chordoma.

Chordoma is an uncommon, indolent malignant tumor arising from notochordal remnants. The incidence of distant metastasis varies between 30 and 40% in different series. Even though local involvement of the skin by direct invasion of chordoma is common, distant skin metastasis are rare, with less than 30 cases reported in the literature. The present clinical case illustrates the slow-growing natural history of a sacral chordoma, which evolved with lung metastasis, followed three years later by skin metastasis, thus giving us the opportunity to review the diagnostic approach, as well as the clinical and histopathological characteristics of this rare tumor.

Mathematical and numerical analyses of cellular, molecular and angiogenic parameters of a rat skin wound healing model.

The inflammatory phase is an important event in the skin wound healing process. The deposition of granulation tissue in the wound bed and the rebuilding of the vascular network occur as inflammation diminishes. An angiogenic component in the formation of granulation tissue is the secretion of vascular endothelial growth factor, which assists in the chemotaxis, proliferation, and replication of fibroblasts. In this paper, we develop a mathematical model of skin wound healing angiogenic factors based on inflammatory cells (macrophages and neutrophils) and mediators (interleukin 6 and interleukin 10). We highlight the importance of this process in vascular endothelial growth factor release and in the formation of new capillary tips. We used a mathematical model of partial differential equations based on the reaction-diffusion-advection equations. In order to calibrate the parameters, we considered an in vivo model composed by four treatments: hydroalcoholic extract and oil-resin of Copaifera langsdorffii at 10% concentration, collagenase, and Lanette cream. Using the laboratory data for the wound edge, our mathematical model estimated the values of vascular endothelial growth factor concentration, and tips density in the center of the wound with a maximum error of 2.9%, and predicted healing time required for each treatment. The region of viability for the parameters, in the proposed model, was found through numerical simulations from the Interleukin 6 and 10 dysregulation and we obtained that, among the parameters analyzed, the greatest influencer in the dynamics of the system is the one, which represents the production of Interleukin 10 during phagocytosis.

Continent-based systematic review of the short-term health impacts of wildfire emissions.

This review systematically gathers and provides an analysis of pollutants levels emitted from wildfire (WF) and their impact on short-term health effects of affected populations. The available literature was searched according to Population, Exposure, Comparator, Outcome, and Study design (PECOS) database defined by the World Health Organization (WHO) and a meta-analysis was conducted whenever possible. Data obtained through PECOS characterized information from the USA, Europe, Australia, and some Asian countries; South American countries were seldom characterized, and no data were available for Africa and Russia. Extremely high levels of pollutants, mostly of fine fraction of particulate matter (PM) and ozone, were associated with intense WF emissions in North America, Oceania, and Asia and reported to exceed several-fold the WHO guidelines. Adverse health outcomes include emergency department visits and hospital admissions for cardiorespiratory diseases as well as mortality. Despite the heterogeneity among exposure and health assessment methods, all-cause mortality, and specific-cause mortality were significantly associated with WF emissions in most of the reports. Globally, a significant association was found for all-cause respiratory outcomes including asthma, but mixed results were noted for cardiovascular-related effects. For the latter, estimates were only significant several days after WF emissions, suggesting a more delayed impact on the heart. Different research gaps are presented, including the need for the application of standardized protocols for assessment of both exposure and adverse health risks. Mitigation actions also need to be strengthened, including dedicated efforts to communicate with the affected populations, to engage them for adoption of protective behaviors and measures.

From Testicle to Brain: A Case of Disseminated Tuberculosis.

Tuberculosis remains a major cause of death by infection in the world. Disseminated tuberculosis occurs most frequently in the context of reactivation of a previously latent infection and is invariably lethal if untreated. Age, late presentation, and serious underlying disease are strong death predictors. We report the case of a 72-year-old male patient who presented to the emergency room with sudden onset hemiparesis and aphasia, with no acute lesions on contrast CT. Two months prior to the current event, the patient had undergone surgery for a testicular abscess in a different hospital. Since the surgery, he had progressive and unexplained weight loss and dysphagia. The medical team reviewed patient records from this hospital and the one where the surgery took place and concluded that the histopathology results from the surgery were not reviewed in the post-surgery follow-up consult and that the diagnosis of genitourinary tuberculosis was never made. This disease, untreated, evolved into disseminated tuberculosis with central nervous system involvement, causing the neurological deficits the patient presented and leading to his death. Surveillance and notification systems exist for individual and public health safeguarding. In the present case, failure to review the pathology report after surgery, coupled with the absence of notification from the laboratory, delayed the diagnosis and led to patient death. This report suggests a need for continuous system improvement, with integrated healthcare records and interinstitutional communication channels, in order to minimize information loss, diagnostic delays, and public health risks.

Assessment of coarse, fine, and ultrafine particulate matter at different microenvironments of fire stations.

The concentrations of respirable particulate matter (PM) and the impact on indoor air quality in occupational settings remains poorly characterized. This study assesses, for the first time, the cumulative and non-cumulative concentrations of 14 fractions of coarse (3.65-9.88 µm), fine (0.156-2.47 µm), and ultrafine (0.015-0.095 µm) PM inside the garage of heavy vehicles, firefighting personal protective equipment' storage room, bar, and a common area of seven Portuguese fire stations. Sampling campaigns were performed during a regular work week at the fire stations. Levels of daily total cumulative PM ranged from 277.4 to 413.2 µg/m3 (maximum values of 811.4 µg/m3), with the bar (370.1 µg/m3) and the PPE' storage room (361.3 µg/m3) presenting slightly increased levels (p > 0.05) than the common area (324.8 µg/m3) and the garage (339.4 µg/m3). The location of the sampling site, the proximity to local industries and commercial activities, the layout of the building, the heating system used, and indoor sources influenced the PM concentrations. Fine (193.8-301.0 µg/m3) and ultrafine (41.3-78.2 µg/m3) particles were predominant in the microenvironments of all fire stations and accounted for 71.5% and 17.8% of daily total cumulative levels, respectively; coarse particles (23.3-47.1 µg/m3) represented 10.7% of total PM. The permissible exposure limit (5.0 mg/m3) defined by the Occupational Safety and Health Organization for respirable dust was not overcome in the evaluated fire stations. Results suggest firefighters' regular exposure to fine and ultrafine PM inside fire stations which will contribute to cardiorespiratory health burden. Further studies are needed to characterize firefighters' exposure to fine and ultrafine PM inside fire stations, identify main emission sources, and evaluate the contribution of exposures at fire stations to firefighters' occupational health risks.

Comparative assessment of the bacterial communities associated with Anopheles darlingi immature stages and their breeding sites in the Brazilian Amazon.

BACKGROUND: The neotropical anopheline mosquito Anopheles darlingi is a major malaria vector in the Americas. Studies on mosquito-associated microbiota have shown that symbiotic bacteria play a major role in host biology. Mosquitoes acquire and transmit microorganisms over their life cycle. Specifically, the microbiota of immature forms is largely acquired from their aquatic environment. Therefore, our study aimed to describe the microbial communities associated with An. darlingi immature forms and their breeding sites in the Coari municipality, Brazilian Amazon. METHODS: Larvae, pupae, and breeding water were collected in two different geographical locations. Samples were submitted for DNA extraction and high-throughput 16S rRNA gene sequencing was conducted. Microbial ecology analyses were performed to explore and compare the bacterial profiles of An. darlingi and their aquatic habitats. RESULTS: We found lower richness and diversity in An. darlingi microbiota than in water samples, which suggests that larvae are colonized by a subset of the bacterial community present in their breeding sites. Moreover, the bacterial community composition of the immature mosquitoes and their breeding water differed according to their collection sites, i.e., the microbiota associated with An. darlingi reflected that in the aquatic habitats where they developed. The three most abundant bacterial classes across the An. darlingi samples were Betaproteobacteria, Clostridia, and Gammaproteobacteria, while across the water samples they were Gammaproteobacteria, Bacilli, and Alphaproteobacteria. CONCLUSIONS: Our findings reinforce the current evidence that the environment strongly shapes the composition and diversity of mosquito microbiota. A better understanding of mosquito-microbe interactions will contribute to identifying microbial candidates impacting host fitness and disease transmission.

Pediatric Organ and Tissue Donation-A 10-Year Retrospective Study in Portugal.

Organ and tissue donation can transform lives. One donor can ensure the survival of up to 8 people through their organs and improve the quality of life for dozens more through tissue donation. Portugal has an excellent transplantation rate, but deaths still occur while waiting for an organ. The study aimed to analyze pediatric organ and tissue donors nationally and evaluate brain deaths in a pediatric intensive care unit (PICU) over the past 10 years to identify any potential lost donors. We conducted a retrospective descriptive study of pediatric organ and tissue donors and diagnosed brain deaths from January 2011 to December 2021. Demographic and clinical data were analyzed, including those provided by the National Transplant Coordination. Over the past 10 years in Portugal, 121 pediatric donors (11.7 per million population) were collected, and 569 organs and tissues were collected. During the same period in the PICU, there were 125 deaths, including 20 brain deaths. Of this group, 4 were organ and tissue donors. In the non-donor group (n = 16), a potential lost donor case stands out. Pediatric specialists need to be more familiar with the donation process, which would enable the identification and optimization of all potential donors, thus minimizing the number of potentially lost organs.

In vitro data for fire pollutants: contribution of studies using human cell models towards firefighters' occupational.

Firefighters are the principal line of defense against fires, being at elevated risk of exposure to health-relevant pollutants released during fires and burning processes. Although many biomonitoring studies exist, only a limited number of human in vitro investigations in fire risk assessment are currently available. In vitro studies stand out as valuable tools to assess the toxicity mechanisms involved following exposure to fire pollutants at a cellular level. The aim of the present review was to contextualize existing in vitro studies using human cell models exposed to chemicals emitted from fire emissions and wood smoke and discuss the implications of the observed toxic outcomes on adverse health effects detected in firefighters. Most of the reported in vitro investigations focused on monocultures respiratory models and exposure to particulate matter (PM) extracts collected from fire effluents. Overall, (1) a decrease in cellular viability, (2) enhanced oxidative stress, (3) increased pro-inflammatory cytokines levels and (4) elevated cell death frequencies were noted. However, limited information remains regarding the toxicity mechanisms initiated by firefighting activities. Hence, more studies employing advanced in vitro models and exposure systems using human cell lines are urgently needed taking into consideration different routes of exposure and health-related pollutants released from fires. Data are needed to establish and define firefighters' occupational exposure limits and to propose mitigation strategies to promote beneficial human health.

Acute kidney injury after endovascular therapy in acute stroke patients: systematic review with meta-analysis.

AIMS: Endovascular therapy (EVT) is a highly effective stroke treatment, but it requires the administration of contrast media which puts patients at risk of acute kidney injury (AKI). AKI is associated with increased morbidity and mortality in cardiovascular patients. METHODS: PubMed, Scopus, ISI and the Cochrane Library were systematically searched for observational and experimental studies assessing the occurrence of AKI in adult acute stroke patients submitted to EVT. Two independent reviewers collected study data regarding study setting, period, source of data, and AKI definition and predictors, the outcomes of interest being AKI incidence and 90-day death or dependency (modified Rankin Scale score ≥3). These outcomes were pooled using random effect models, and heterogeneity was measured using the I2 statistic. RESULTS: 22 studies were identified and included in the analysis, involving 32 034 patients. Pooled incidence of AKI was 7% (95% CI 5% to 10%), but heterogeneity was high across studies (I2=98%), and not accounted for by the definition of AKI used. The most frequently reported AKI predictors were impaired baseline renal function (5 studies) and diabetes (3 studies); 3 studies (2103 patients) reported data on death and 4 studies (2424 patients) reported data on dependency. Overall, AKI was associated with both outcomes, with ORs of 6.21 (95% CI 3.52 to 10.96) and 2.86 (95% CI 1.88 to 4.37), respectively. Heterogeneity was low for both analyses (I2=0%). CONCLUSIONS: AKI affects 7% of acute stroke patients submitted to EVT and identifies a subgroup of patients for which treatment outcomes are suboptimal, with an increased risk of death and dependency.

Biomonitoring of firefighting forces: a review on biomarkers of exposure to health-relevant pollutants released from fires.

Occupational exposure as a firefighter has recently been classified as a carcinogen to humans by International Agency for Research on Cancer (IARC). Biomonitoring has been increasingly used to characterize exposure of firefighting forces to contaminants. However, available data are dispersed and information on the most relevant and promising biomarkers in this context of firefighting is missing. This review presents a comprehensive summary and critical appraisal of existing biomarkers of exposure including volatile organic compounds such as polycyclic aromatic hydrocarbons, several other persistent other organic pollutants as well as heavy metals and metalloids detected in biological fluids of firefighters attending different fire scenarios. Urine was the most characterized matrix, followed by blood. Firefighters exhaled breath and saliva were poorly evaluated. Overall, biological levels of compounds were predominantly increased in firefighters after participation in firefighting activities. Biomonitoring studies combining different biomarkers of exposure and of effect are currently limited but exploratory findings are of high interest. However, biomonitoring still has some unresolved major limitations since reference or recommended values are not yet established for most biomarkers. In addition, half-lives values for most of the biomarkers have thus far not been defined, which significantly hampers the design of studies. These limitations need to be tackled urgently to improve risk assessment and support implementation of better more effective preventive strategies.