Firefighters' Occupational Exposure in Preparation for Wildfire Season: Addressing Biological Impact.

The characterization of wildland firefighters' occupational exposure must consider different exposures, including those at the fire station. The present study aimed to characterize the occupational exposure of 172 Northern Portuguese wildland firefighters in fire stations during the pre-wildfire season of 2021. The biological impact of estimated inhaled doses of PM10 and PM2.5 (indoor/outdoor) was accessed through a buccal micronucleus cytome (BMCyt) assay in exfoliated buccal cells of a subgroup of 80 firefighters. No significant association was found between estimated inhaled doses of PM10 and PM2.5 (mean 1.73 ± 0.43 µg kg-1 and 0.53 ± 0.21 µg kg-1, respectively) and biological endpoints. However, increased frequencies of cell death parameters were found among subjects of the Permanent Intervention Teams (full-time firefighters). The intake of nutritional supplements was associated with a significant decrease in micronucleus frequencies (i.e., DNA damage or chromosome breakage). In addition, our findings showed a significantly increased frequency of cell death endpoints (i.e., nuclear fragmentation) with coffee consumption, while daily consumption of vegetables significantly decreased it (i.e., nuclear shrinkage). Our results provide data on the occupational exposure of wildland firefighters while working in fire stations during the pre-wildfire season, providing the essential baseline for further studies throughout the wildfire season.

Drug delivery in glioblastoma therapy: a review on nanoparticles targeting MGMT-mediated resistance.

INTRODUCTION: Glioblastoma multiforme (GBM) is the deadliest type of brain cancer with poor response to the available therapies, mainly due to intrinsic resistance mechanisms. Chemotherapy is based on alkylating agents, but DNA-repair mechanisms can revert this cytotoxic effect. O6-methylguanine-DNA methyltransferase (MGMT) protein is the primary mechanism for GBM resistance. Therefore, different strategies to suppress its activity have been explored. However, their clinical use has been hindered due to the high toxicity of MGMT inhibitors verified in clinical trials. AREAS COVERED: This review article aims to provide the current progress in the development of novel drug delivery systems (DDS) to overcome this resistance. Here, we also review the current knowledge on MGMT-mediated resistance and the clinical outcomes and potential risks of using MGMT inhibitors. EXPERT OPINION: To overcome therapeutic limitations, nano-based approaches have been proposed as a suitable solution to improve drug accumulation in the brain tumor tissue and decrease systemic toxicity. DDS to overcome MGMT-mediated resistance in GBM have been mostly developed to deliver MGMT inhibitors and for gene therapy to modulate MGMT gene expression.

Biosensors on the road to early diagnostic and surveillance of Alzheimer's disease.

Alzheimer's disease is a debilitating and largely untreatable condition with subtle onset and slow progression over an extensive period of time, which culminate in increasing levels of disability. As Alzheimer's disease prevalence is expected to grow exponentially in the upcoming decades, there is an urgency to develop analytical technologies for the sensitive, reliable and cost-effective detection of Alzheimer's disease biomarkers. Biosensors are powerful analytical devices that translate events of biological recognition on physical or chemical transducers into electrical, thermal or optical signals. The high sensitivity and selectivity of biosensors associated with easy, rapid and low-cost determination of analytes have made this discipline one of the most intensively studied in the past decades. This review centers on recent advances, challenges and trends of Alzheimer's disease biosensing particularly in the effort to combine the unique properties of nanomaterials with biorecognition elements. In the last decade, impressive progresses have been made towards the development of biosensors, mainly electrochemical and optical, for detection of Alzheimer's disease biomarkers in the pico- and femto-molar range. Nonetheless, advances in multiplexed detection, robustness, stability and specificity are still necessary to ensure an accurate and differentiated diagnosis of this disease.

Firefighters exposure to fire emissions: Impact on levels of biomarkers of exposure to polycyclic aromatic hydrocarbons and genotoxic/oxidative-effects.

Firefighters represent one of the riskiest occupations, yet due to the logistic reasons, the respective exposure assessment is one of the most challenging. Thus, this work assessed the impact of firefighting activities on levels of urinary monohydroxyl-polycyclic aromatic hydrocarbons (OHPAHs; 1-hydroxynaphthalene, 1-hydroxyacenaphthene, 2-hydroxyfluorene, 1-hydroxyphenanthrene, 1-hydroxypyrene, 3-hydroxybenzo(a)pyrene) and genotoxic/oxidative-effect biomarkers (basal DNA and oxidative DNA damage) of firefighters from eight firehouses. Cardiac frequency, blood pressure and arterial oxygen saturation were also monitored. OHPAHs were determined by liquid-chromatography with fluorescence detection, while genotoxic/oxidative-effect biomarkers were assessed by the comet assay. Concentrations of total OHPAHs were up to 340% higher (p ≤ 0.05) in (non-smoking and smoking) exposed workers than in control subjects (non-smoking and non-exposed to combat activities); the highest increments were observed for 1-hydroxynaphthalene and 1-hydroxyacenaphthene (82-88% of ∑OHPAHs), and for 2-hydroxyfluorene (5-15%). Levels of biomarker for oxidative stress were increased in non-smoking exposed workers than in control group (316%; p ≤ 0.001); inconclusive results were found for DNA damage. Positive correlations were found between the cardiac frequency, ∑OHPAHs and the oxidative DNA damage of non-smoking (non-exposed and exposed) firefighters. Evidences were raised regarding the simultaneous use of these biomarkers for the surveillance of firefighters' health and to better estimate the potential short-term health risks.

Nanotechnology to improve the Alzheimer's disease therapy with natural compounds.

Alzheimer's disease (AD) is a form of dementia with high impact worldwide, accounting with more than 46 million cases. It is estimated that the number of patients will be four times higher in 2050. The initial symptoms of AD are almost imperceptible and typically involve lapses of memory in recent events. However, the available medicines still focus on controlling the symptoms and do not cure the disease. Regarding the advances in the discovery of new treatments for this devastating disease, natural compounds are gaining increasing relevance in the treatment of AD. Nevertheless, they present some limiting characteristics such as the low bioavailability and the low ability to cross the blood-brain barrier (BBB) that hinder the development of effective therapies. To overcome these issues, the delivery of natural products by targeting nanocarriers has aroused a great interest, improving the therapeutic activity of these molecules. In this article, a review of the research progress on drug delivery systems (DDS) to improve the therapeutic activity of natural compounds with neuroprotective effects for AD is presented. Graphical abstract.

(Ultra) Fine particle concentrations and exposure in different indoor and outdoor microenvironments during physical exercising.

Although regular exercise improves overall well-being, increased physical activity results in enhanced breathing which consequently leads to elevated exposure to a variety of air pollutants producing adverse effects. It is well-known that one of these ambient air contaminants is ultrafine particles (UFP). Thus, this study aimed to (1) examine exposure to particle number concentrations (PNC) in size ranging from N20-1000 nm in different sport environments and (2) estimate the respective inhalation doses across varying activity scenarios based upon the World Health Organization recommendations for physical activity. PNC were continuously monitored (TSI P-Trak™ condensation particle counter) outdoors (Out1-Out2) and indoors (Ind1-Ind2; fitness clubs) over 4 weeks. Outdoor PNC (total median 12 563 # cm-3; means of 20 367 # cm-3 at Out1 and 7 122 # cm-3 at Out2) were approximately 1.6-fold higher than indoors (total median 7 653 # cm-3; means of 11 861 # cm-3 at Ind1 and 14 200 # cm-3 at Ind2). The lowest doses were inhaled during holistic group classes (7.91 × 107-1.87 × 108 # per kg body weight) whereas exercising with mixed cardio and strength training led to approximately 1.8-fold higher levels. In order to optimize the health benefit of exercises, environmental characteristics of the locations at which physical activities are conducted need to be considered.

Wood smoke exposure of Portuguese wildland firefighters: DNA and oxidative damage evaluation.

Portugal is among the European Union countries most devastated by forest fires each year. In the last three decades, more than 3.8 million hectares of forest were burned. Wildland firefighters are exposed to a variety of hazards, including many toxic combustion products that may lead to deleterious health effects. Epidemiological studies showed a positive association between firefighting and several chronic diseases, including cancer. Results from biomonitoring studies in firefighters, particularly concerning genotoxicity evaluation, constitute a valuable tool for investigating important occupational hazards. Thus, the aim of this study was to assess genotoxicity in a group of wildland firefighters using the comet assay for DNA damage and oxidative stress. Both parameters were increased in firefighters compared to controls, but significance was only found for basal DNA damage. No significant influence was found regarding major confounding variables on the genotoxic endpoints studied, with the exception of age. Data obtained provide preliminary information on human health effects of wildland firefighting exposure at genetic and molecular levels. These findings may also provide new important data to serve as public awareness to the potential adverse health risks involving wildland firefighting. Implementation of security and hygiene measures in this sector as well as good practices campaigns may be crucial to decrease risk.

Individual and cumulative impacts of fire emissions and tobacco consumption on wildland firefighters' total exposure to polycyclic aromatic hydrocarbons.

There is limited information about wildland firefighters' exposure to polycyclic aromatic hydrocarbons (PAHs), being scarce studies that included the impact of tobacco consumption. Thus, this work evaluated the individual and cumulative impacts of firefighting activities and smoking on wildland firefighters' total exposure to PAHs. Six urinary PAH metabolites (1-hydroxynaphthalene (1OHNaph), 1-hydroxyacenaphthene (1OHAce), 2-hydroxyfluorene (2OHFlu), 1-hydroxyphenanthrene (1OHPhen), 1-hydroxypyrene (1OHPy), and 3-hydroxybenzo[a]pyrene (3OHB[a]P)) were quantified by high-performance liquid chromatography with fluorescence detection. Firefighters from three fire stations were characterized and organized in three groups: non-smoking and non-exposed to fire emissions (NSNExp), smoking non-exposed (SNExp), and smoking exposed (SExp) individuals. 1OHNaph+1OHAce were the most predominant OH-PAHs (66-91% ∑OH-PAHs), followed by 2OHFlu (2.8-28%), 1OHPhen (1.3-7%), and 1OHPy (1.4-6%). 3OHB[a]P, the carcinogenicity PAH biomarker, was not detected. Regular consumption of tobacco increased 76-412% ∑OH-PAHs. Fire combat activities promoted significant increments of 158-551% ∑OH-PAHs. 2OHFlu was the most affected compound by firefighting activities (111-1068%), while 1OHNaph+1OHAce presented the more pronounced increments due to tobacco consumption (22-339%); 1OHPhen (76-176%) and 1OHPy (20-220%) were the least influenced ones. OH-PAH levels of SExp firefighters were significantly higher than in other groups, suggesting that these subjects may be more vulnerable to develop and/or aggravate diseases related with PAHs exposure.

Polycyclic aromatic hydrocarbons in primary school environments: Levels and potential risks.

Although polycyclic aromatic hydrocarbons (PAHs) are priority air pollutants that strongly affect human health, information concerning the indoor exposures is still limited. This study characterized PAH levels in primary schools and evaluated risk for the respective students (aged 8-10years) in comparison with school personnel. During January-April 2014, eighteen particulate-bound (PM2.5) PAHs (16 USEPA priority compounds, dibenzo[a,l]pyrene, benzo[j]fluoranthene) were collected (indoors and outdoors) at ten primary urban schools in Portugal. Total mean concentrations (ΣPAHs) ranged 2.8-54ngm-3 in indoor air, whereas corresponding outdoor levels were 7.1-48ngm-3. Indoor/outdoor ratios of lighter congeners (2-3 aromatic rings) demonstrated a contribution from indoor origin while heavier PAHs (4-6 aromatic rings) originated mostly from infiltration of ambient air indoors; traffic (both from diesel and gasoline fuelled vehicles) was the predominant source of indoor PAHs. Total cancer risk of 8-10years old children exceeded (up to 22 times) USEPA recommended guideline of 10-6, and 7-87 times WHO health-based threshold of 10-5. Risk due to indoor exposure in schools was 2-10 times higher than outdoors, mainly because of the higher amount of time that students spent indoors.

Assessment of exposure to polycyclic aromatic hydrocarbons in preschool children: Levels and impact of preschool indoor air on excretion of main urinary monohydroxyl metabolites.

The present work aimed to assess exposure of preschool children to polycyclic aromatic hydrocarbons (PAHs) by environmental monitoring (eighteen compounds in air) and biomonitoring (six urinary biomarkers of exposure (OH-PAHs)). The impact of preschool indoor air on excretion of urinary monohydroxyl metabolites was also evaluated. Gaseous and particulate-bound PAHs were simultaneously collected indoors and outdoors in two Portuguese preschools. PAHs and OH-PAHs were quantified by high-performance liquid chromatography with fluorescence and photodiode array detection. Total air (gaseous+total suspended particles) levels of PAHs (ΣPAHs) were higher indoors than outdoors. Gaseous phase (composed by ≥98% of 2-3 rings compounds) and particulate-bound PAHs (90-99% of 5-6 rings) accounted for 93-95% and 5-7% of ΣPAHs in indoor air, respectively. Total (including probable/possible) carcinogenic PAHs represented 26-45% of ΣPAHs; naphthalene and dibenz[a,h]anthracene were the strongest contributors. A similar distribution profile was observed between airborne PAHs and urinary OH-PAHs. Urinary 1-hydroxynaphthalene+1-hydroxyacenaphthene represented more than 78% of ΣOH-PAHs, being followed by 2-hydroxyfluorene, 1-hydroxypyrene, and 1-hydroxyphenanthrene. 3-hydroxybenzo[a]pyrene (PAH biomarker of carcinogenicity) was not detected. Results suggest that children had preschool indoor air as their major exposure source of naphthalene and acenaphthene, while no conclusion was reached regarding fluorene, phenanthrene and pyrene.

Immunoliposomes doubly targeted to transferrin receptor and to α-synuclein.

AIM: The present study was designed to test the cellular uptake of PEGylated liposomes targeted to transferrin receptor and to α-synuclein by a cell model of the blood-brain barrier (BBB). MATERIALS & METHODS: PEGylated immunoliposomes were prepared with anti-transferrin receptor OX26 and anti-α-synuclein LB509 antibodies to overcome the BBB in Parkinson's disease. RESULTS: The doubly targeted immunoliposomes bind to transferrin receptor and to α-synuclein protein, as assessed by ELISA assays. We establish that 40% of an encapsulated tested drug (epigallocatechin-3-gallate) is released in a time frame of 44 h, which is reasonable for sustained release. The cellular uptake of doubly targeted immunoliposomes in cultured brain endothelial cells hCMEC/D3 was two-times more efficient than that of PEGylated liposomes. CONCLUSION: Immunoliposomes targeted to BBB receptors and to α-synuclein could potentially enable the transport of drugs across the BBB and reach one of the drug targets in Parkinson's disease.

Ultrafine particles in ambient air of an urban area: dose implications for elderly.

Due to their detrimental effects on human health, the scientific interest in ultrafine particles (UFP) has been increasing, but available information is far from comprehensive. Compared to the remaining population, the elderly are potentially highly susceptible to the effects of outdoor air pollution. Thus, this study aimed to (1) determine the levels of outdoor pollutants in an urban area with emphasis on UFP concentrations and (2) estimate the respective dose rates of exposure for elderly populations. UFP were continuously measured over 3 weeks at 3 sites in north Portugal: 2 urban (U1 and U2) and 1 rural used as reference (R1). Meteorological parameters and outdoor pollutants including particulate matter (PM10), ozone (O3), nitric oxide (NO), and nitrogen dioxide (NO2) were also measured. The dose rates of inhalation exposure to UFP were estimated for three different elderly age categories: 64-70, 71-80, and >81 years. Over the sampling period levels of PM10, O3 and NO2 were in compliance with European legislation. Mean UFP were 1.7 × 10(4) and 1.2 × 10(4) particles/cm(3) at U1 and U2, respectively, whereas at rural site levels were 20-70% lower (mean of 1 ×10(4) particles/cm(3)). Vehicular traffic and local emissions were the predominant identified sources of UFP at urban sites. In addition, results of correlation analysis showed that UFP were meteorologically dependent. Exposure dose rates were 1.2- to 1.4-fold higher at urban than reference sites with the highest levels noted for adults at 71-80 yr, attributed mainly to higher inhalation rates.

Targeting nanoparticles across the blood-brain barrier with monoclonal antibodies.

Development of therapeutics for brain disorders is one of the more difficult challenges to be overcome by the scientific community due to the inability of most molecules to cross the blood-brain barrier (BBB). Antibody-conjugated nanoparticles are drug carriers that can be used to target encapsulated drugs to the brain endothelial cells and have proven to be very promising. They significantly improve the accumulation of the drug in pathological sites and decrease the undesirable side effect of drugs in healthy tissues. We review the systems that have demonstrated promising results in crossing the BBB through receptor-mediated endocytic mechanisms for the treatment of neurodegenerative disorders such as Alzheimer's and Parkinson's disease.

Lipid/particle assemblies based on maltodextrin-gum arabic core as bio-carriers.

A novel system to carry and protect epigallocatechin gallate (EGCG), an antioxidant from the green tea, is reported. The system consists of maltodextrin and gum arabic nanoparticles coated with egg-yolk l-alpha-phosphatidylcholine (Egg-PC)/stearylamine (SA) bilayers. In this study, the polysaccharide core was produced by homogenization followed by spray-drying. The lipid coating was performed by the lipid film hydration method. The polysaccharide core revealed negative zeta potential, which changed to opposite signs after lipid coating. The presence of lipid layers was evidenced by cryogenic-transmission (cryo-TEM) and scanning (cryo-SEM) electron microscopy studies. An increase in size was observed after lipid coating as determined by dynamic light scattering (DLS). Atomic force microscopy (AFM) demonstrated that the polysaccharide core provides high resistance to mechanical strength. The lipid/particle assemblies show high retention efficiency of EGCG at physiological pH, opening the possibility of their use for delivery and controlled release of tea catechins.

Analysis of polycyclic aromatic hydrocarbons in atmospheric particulate samples by microwave-assisted extraction and liquid chromatography.

A methodology based on microwave-assisted extraction (MAE) and LC with fluorescence detection (FLD) was investigated for the efficient determination of 15 polycyclic aromatic hydrocarbons (PAHs) regarded as priority pollutants by the US Environmental Protection Agency and dibenzo(a,l)pyrene in atmospheric particulate samples. PAHs were successfully extracted from real outdoor particulate matter (PM) samples with recoveries ranging from 81.4 +/- 8.8 to 112.0 +/- 1.1%, for all the compounds except for naphthalene (62.3 +/- 18.0%) and anthracene (67.3 +/- 5.7%), under the optimum MAE conditions (30.0 mL of ACN for 20 min at 110 degrees C). No clean-up steps were necessary prior to LC analysis. LOQs ranging from 0.0054 ng/m(3 )for benzo(a)anthracene to 0.089 ng/m(3) for naphthalene were reached. The validated MAE methodology was applied to the determination of PAHs from a set of real world PM samples collected in Oporto (north of Portugal). The sum of particulate-bound PAHs in outdoor PM ranged from 2.5 and 28 ng/m(3).