Metabolic activity grows in human cancers pushed by phenotypic variability.

Different evolutionary processes push cancers to increasingly aggressive behaviors, energetically sustained by metabolic reprogramming. The collective signature emerging from this transition is macroscopically displayed by positron emission tomography (PET). In fact, the most readily PET measure, the maximum standardized uptake value (SUVmax), has been found to have prognostic value in different cancers. However, few works have linked the properties of this metabolic hotspot to cancer evolutionary dynamics. Here, by analyzing diagnostic PET images from 512 patients with cancer, we found that SUVmax scales superlinearly with the mean metabolic activity (SUVmean), reflecting a dynamic preferential accumulation of activity on the hotspot. Additionally, SUVmax increased with metabolic tumor volume (MTV) following a power law. The behavior from the patients data was accurately captured by a mechanistic evolutionary dynamics model of tumor growth accounting for phenotypic transitions. This suggests that non-genetic changes may suffice to fuel the observed sustained increases in tumor metabolic activity.

A systematic review about the role of preoperative 18F-FDG PET/CT for prognosis and risk stratification in patients with endometrial cancer.

OBJECTIVE: To analyse the available literature on the prognostic value of preoperative 18F-FDG PET/CT metabolic parameters and their usefulness in risk stratification in patients with endometrial cancer (EC). MATERIAL AND METHODS: Pubmed searches used "(endometr* OR uter*) AND (PET OR FDG)" as keywords from January-2000 to June-2020. References in included articles were checked for possible publications not included in the first search. Studies evaluating the prognostic value of preoperative 18F-FDG PET/CT and its role for risk stratification in patients with EC were included. Non-original articles (reviews, editorials, letters, legal cases, interviews, case reports, etc.) were not included. RESULTS: Twenty-six studies (1918 patients) were selected according to the inclusion criteria in this review. Thirteen studies (939 patients) related to the prognostic role of preoperative 18F-FDG PET/CT and 14 studies (1036 patients) related to its role in risk stratification were included. Parameters such as SUVmax, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of the primary tumour were analysed. CONCLUSIONS: Preoperative SUVmax is useful for non-invasive diagnosis and for deciding the appropriate therapeutic strategy, as it could be used as an independent prognostic marker for recurrence and survival in EC. In addition, both preoperative VTM and GTL could be independent prognostic factors for predicting recurrence and survival, but there is still insufficient scientific evidence. The usefulness of SUVmax for risk stratification is limited (there is insufficient literature that 18F-FDG PET/CT can replace surgical staging), although VTM and GTL are more accurate and have a valuable role in risk stratification of EC. However, larger multicentre studies with adequate follow-up time are needed to confirm these findings.

Management of Patients with Metastatic Bladder Cancer in the Real-World Setting from the Multidisciplinary Team: Current Opinion of the SOGUG Multidisciplinary Working Group.

Based on the discussion of current state of research of relevant topics of metastatic bladder cancer (mBC) among a group of experts of a Spanish Oncology Genitourinary (SOGUG) Working Group, a set of recommendations were proposed to overcome the challenges posed by the management of mBC in clinical practice. First-line options in unfit patients for cisplatin are chemotherapy with carboplatin and immunotherapy in PD-L1 positive patients. FDG-PET/CT may be a useful imaging technique in the initial staging or re-staging. In patients with oligometastatic disease, it is important to consider not only the number of metastatic lesions, but also the tumor biology and the clinical course. The combination of stereotactic body radiotherapy and immunotherapy with anti-PD-L1 monoclonal antibodies is under investigation and could improve the results of systemic treatment in patient with oligometastatic disease. Rescue treatment with curative intent could be considered in patients with oligometastatic disease after complete response on FDG-PET/CT. Metastatic disease should be evaluated using the same imaging modality over the course of the disease from diagnosis until rescue treatment. For improving the outcome of patients with mBC, the involvement of a dedicated multidisciplinary team, including urologists, pathologists, oncologists, radiologists and other specialists is of outmost importance in the daily care of these patients.

Diagnostic methodology in labelled leukocyte scan for prosthetic / non-prosthetic osteoarticular infection: Visual or semi-quantitative analysis? One- or two-day protocol?

OBJECTIVE: as scarce literature on the topic is available, we aimed to compare diagnostic utility of semi-quantitative versus visual analysis in labelled white blood cell scintigraphy (WBCS) for osteoarticular infection. One-day and two-day protocols were assessed, particularly in orthopaedic devices. MATERIAL AND METHODS: prospective study of 79 consecutive patients with suspected osteoarticular infection. In all patients, WBCS were performed at 30min, 4h, 8h and 24h. Images were analysed by grouping in two protocols: one-day-protocol (experts evaluated 30min, 4h and 8h planar images) and two-day-protocol (experts evaluated 30min, 4h and 24h planar images). Planar images were interpreted qualitative and semiquantitatively and also were compared grouping patients with and without orthopaedic devices. To find which cut-off value of the percentage variation could predict of osteoarticular infection, multiple cut-off values were calculated in both protocols from the Youden index. Three blinded readers analysed the images. RESULTS: Comparing final diagnosis visual analysis of the one-day-protocol provided better results with sensitivity of 95.5%, specificity of 93% and diagnostic accuracy of 93.7% (p<001) than the two-day-protocol with values of 86.4%, 94.7% and 92.4%, respectively (p<001). For semi-quantitative analysis, the one-day-protocol also obtained better results with sensitivity of 72.7%, specificity of 78.9% and accuracy of 77.2% (p<001) than two-day-protocol (no significant results; p=0.14), especially in the group of patients with orthopaedic devices (sensitivity of 100%, specificity of 79.5% and accuracy of 82.7%; p<001). CONCLUSIONS: most accurate approach in the diagnosis of osteoarticular infection corresponded to visual analysis in one-day-protocol that showed greater sensitivity and specificity than semi-quantitative analysis. Semi-quantitative analysis only could be useful when visual analysis is doubtful. In patients with joint prostheses, an increase in percentage variation above 9% obtained maximum sensitivity and negative predictive value.

Management of Localized Muscle-Invasive Bladder Cancer from a Multidisciplinary Perspective: Current Position of the Spanish Oncology Genitourinary (SOGUG) Working Group.

This review presents challenges and recommendations on different aspects related to the management of patients with localized muscle-invasive bladder cancer (MIBC), which were discussed by a group of experts of a Spanish Oncology Genitourinary (SOGUG) Working Group within the framework of the Genitourinary Alliance project (12GU). It is necessary to clearly define which patients are candidates for radical cystectomy and which are candidates for undergoing bladder-sparing procedures. In older patients, it is necessary to include a geriatric assessment and evaluation of comorbidities. The pathological report should include a classification of the histopathological variant of MIBC, particularly the identification of subtypes with prognostic, molecular and therapeutic implications. Improvement of clinical staging, better definition of prognostic groups based on molecular subtypes, and identification of biomarkers potentially associated with maximum benefit from neoadjuvant chemotherapy are areas for further research. A current challenge in the management of MIBC is improving the selection of patients likely to be candidates for immunotherapy with checkpoint inhibitors in the neoadjuvant setting. Optimization of FDG-PET/CT reliability in staging of MIBC and the selection of patients is necessary, as well as the design of prospective studies aimed to compare the value of different imaging techniques in parallel.

Fingerprinting and emission rates of particulate organic compounds from typical restaurants in Portugal.

The aim of this study was a detailed chemical characterisation of the particles released during the preparation of popular Portuguese dishes. PM2.5 samples were collected from the exhaust stacks on the roofs of a university canteen, a charcoal-grilled chicken restaurant and a wood-oven roasted piglet restaurant. The speciation of organic compounds was carried out by gas chromatography-mass spectrometry. The canteen was responsible for the lowest emissions of PM2.5, while emissions from the roasted piglet restaurant were the highest. Naphthalene was quantified as the most abundant aromatic compound in particle emissions from the canteen, while phenanthrene, fluoranthene, pyrene and chrysene were the dominant polycyclic aromatic hydrocarbons in samples from the other establishments. Benzo[a]pyrene equivalent concentrations obtained for the charcoal-grilled chicken and piglet restaurant indicate a dangerous carcinogenic potential to human health. Cholesterol was the prevalent sterol. Its highest values were obtained in particles from the charcoal-grilled chicken restaurant (621 ± 233 µg g-1 PM2.5). Oleic and palmitoleic were the unsaturated fatty acids identified at highest concentrations (from trace levels to 34.4 and to 6.89 mg g-1 PM2.5, respectively). Resin acids, such as dehydroabietic and abietic, were detected in all samples from the wood-oven roasted piglet restaurant. Nicotinamide was the amide detected at highest amount in emissions from the university canteen during the preparation of stews (7.67 mg g-1 PM2.5). Levoglucosan and its isomers were identified in all samples from the roasted piglet restaurant, but only the first monosaccharide anhydride was present in emissions from the university canteen and the charcoal-grilled chicken restaurant. Additionally, emission rates were estimated for the most representative compounds, taking into account the specific activity of each restaurant.

Evolutionary dynamics at the tumor edge reveal metabolic imaging biomarkers.

Human cancers are biologically and morphologically heterogeneous. A variety of clonal populations emerge within these neoplasms and their interaction leads to complex spatiotemporal dynamics during tumor growth. We studied the reshaping of metabolic activity in human cancers by means of continuous and discrete mathematical models and matched the results to positron emission tomography (PET) imaging data. Our models revealed that the location of increasingly active proliferative cellular spots progressively drifted from the center of the tumor to the periphery, as a result of the competition between gradually more aggressive phenotypes. This computational finding led to the development of a metric, normalized distance from 18F-fluorodeoxyglucose (18F-FDG) hotspot to centroid (NHOC), based on the separation from the location of the activity (proliferation) hotspot to the tumor centroid. The NHOC metric can be computed for patients using 18F-FDG PET-computed tomography (PET/CT) images where the voxel of maximum uptake (standardized uptake value [SUV]max) is taken as the activity hotspot. Two datasets of 18F-FDG PET/CT images were collected, one from 61 breast cancer patients and another from 161 non-small-cell lung cancer patients. In both cohorts, survival analyses were carried out for the NHOC and for other classical PET/CT-based biomarkers, finding that the former had a high prognostic value, outperforming the latter. In summary, our work offers additional insights into the evolutionary mechanisms behind tumor progression, provides a different PET/CT-based biomarker, and reveals that an activity hotspot closer to the tumor periphery is associated to a worst patient outcome.

Cooking activities in a domestic kitchen: Chemical and toxicological profiling of emissions.

To obtain emission factors and cooking-related chemical signatures, a monitoring campaign was carried out in a modern kitchen where different dishes of the Latin cuisine were prepared. Particulate matter (PM10, PM2.5 and PM1) and total volatile organic compounds (TVOCs) were continuously measured. Passive tubes for carbonyls and a high volume PM10 sampler were simultaneously used. PM10 filters were analysed for organic and elemental carbon and for multiple organic compounds, including polyaromatic hydrocarbons (PAHs). The toxic potential of PM10 was evaluated using a bioluminescence inhibition bioassay. Acrolein was never detected, while formaldehyde and acetaldehyde levels were comparable to those in the background air. The protection limit for TVOCs was always exceeded. Fine particles comprised more than 86% of the PM10 mass concentrations. PM10 emission rates ranged from 124 to 369 µg min-1. Relatively low PAH concentrations were obtained. PM10 encompassed alcohols, acids, plasticisers, alkyl esters, sterols, sugars, polyols, glyceridic compounds, phenolics, among others. Total concentrations were 1.9-5.3 times higher during cooking than in the background air but, for some compounds, differences of tens or hundreds of times were registered. PM10 from grilled pork was found to contribute to non-negligible cancer risks and to be very toxic, while samples from other dishes were categorised as toxic.

Universal scaling laws rule explosive growth in human cancers.

Most physical and other natural systems are complex entities composed of a large number of interacting individual elements. It is a surprising fact that they often obey the so-called scaling laws relating an observable quantity with a measure of the size of the system. Here we describe the discovery of universal superlinear metabolic scaling laws in human cancers. This dependence underpins increasing tumour aggressiveness, due to evolutionary dynamics, which leads to an explosive growth as the disease progresses. We validated this dynamic using longitudinal volumetric data of different histologies from large cohorts of cancer patients. To explain our observations we put forward increasingly-complex biologically-inspired mathematical models that captured the key processes governing tumor growth. Our models predicted that the emergence of superlinear allometric scaling laws is an inherently three-dimensional phenomenon. Moreover, the scaling laws thereby identified allowed us to define a set of metabolic metrics with prognostic value, thus providing added clinical utility to the base findings.

Loadings, chemical patterns and risks of inhalable road dust particles in an Atlantic city in the north of Portugal.

Road dust resuspension has a significant contribution to the atmospheric particulate matter levels in urban areas, but loadings, emission factors, and chemical source profiles vary geographically, hampering the accuracy of emission inventories and source contribution estimates. Given the dearth of studies on the variability of road dust, in the present study, an in-situ resuspension chamber was used to collect PM10 samples from seven representative streets in Viana do Castelo, the northernmost coastal city in Portugal. PM10 samples were analysed for organic and elemental carbon by a thermo-optical technique, elemental composition by ICP-MS and ICP-AES, and organic constituents by GC-MS. Emission factors were estimated to be, on average, 340 and 41.2 mg veh-1 km-1 for cobbled and asphalt pavements, respectively. Organic carbon accounted for 5.56 ± 1.24% of the PM10 mass. Very low concentrations of PAHs and their alkylated congeners were detected, denoting a slight predominance of petrogenic compounds. Si, Al, Fe, Ca and K were the most abundant elements. The calculation of various geochemical indices (enrichment factor, geoaccumulation index, pollution index and potential ecological risk) showed that road dust was extremely enriched and contaminated by elements from tyre and brake wear (e.g. Sb, Sn, Cu, Bi and Zn), while lithophile elements showed no enrichment. For As, the geochemical and pollution indices reached their maximum in the street most influenced by agricultural activities. Sb, Cd, Cu and As can pose a very high ecological risk. Sb can be regarded as the pollutant of highest concern, since it represented 57% of the total ecological risk. Hazard indices higher than 1 for some anthropogenic elements indicate that non-carcinogenic effects may occur. Except for a street with more severe braking, the total carcinogenic risks can be considered insignificant.

Usefulness of CA125 and its kinetic parameters and positron emission tomography/computed tomography (PET/CT) with fluorodeoxyglucose ([18F] FDG) in the detection of recurrent ovarian cancer / Utilidad del CA125 y sus parámetros cinéticos y de la tomografía por emisión de positrones/tomografía computarizada (PET/TC) con fluorodesoxiglucosa ([18F]FDG) en la detección de la recidiva del cáncer de ovario

Background and objective: To assess the usefulness of cancer antigen 125 (CA125) serum levels and kinetic values, velocity (CA125vel) and doubling time (CA125dt), as well as fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT), in the detection of ovarian cancer recurrence. To assess the optimal cut-off for CA125, CA125vel and CA125dt to detect relapse with [18F]FDG-PET/CT. Material and methods: A retrospective analysis was performed of 59 [18F]FDG-PET/CT (48 patients) for suspected recurrence of ovarian cancer. Receiver operating characteristic (ROC) curves were plotted and area-under-the curve (AUC) statistics were computed for CA125, CA125vel and CA125dt. The results obtained in the group with normal and high (>35U/ml) CA125 levels were compared. Results: Forty-four cases of recurrence were diagnosed (7 had CA125 ≤35U/ml), whereas 15 showed no disease. All of them were correctly catalogued by PET/CT. In ROC analysis, the discriminatory power of CA125 was relatively high (AUC 0.835) and the optimal cut-off point to reflect active disease was 23.9U/ml. The ROC analyses for the CA125vel and CA125dt showed an AUC of 0.849 and 0.728, respectively, with an optimal cut-off point of 1.96U/ml/month and 0.76 months, respectively. In patients with normal CA125 and recurrence of ovarian cancer, the CA125vel was significantly higher than in patients without recurrence (p=0.029). Conclusion: [18F]FDG-PET/CT is more accurate than CA125 parameters in the detection of ovarian cancer recurrence. CA125 serum levels are essential; nevertheless, CA125 kinetic values must be considered to detect relapse. Particularly in patients with CA125 within normal values, in which a higher CA125vel is indicative of recurrence

Fundamento y objetivo: Valorar en la recidiva del cáncer de ovario la utilidad del CA125 y sus parámetros cinéticos, velocidad (CA125vel) y tiempo de duplicación (CA125td), y de la tomografía por emisión de positrones/tomografía computarizada (PET/TC) con fluorodesoxiglucosa ([18F]FDG). Determinar el valour óptimo del CA125, CA125vel y CA125td para detectar recidiva con [18F]FDG-PET/TC. Material y métodos: Análisis retrospectivo de 59 estudios [18F]FDG-PET/TC en 48 pacientes con sospecha de recidiva de cáncer de ovario platino-sensible. Realizamos un análisis ROC (Receiver operating characteristic) y el área bajo la curva (AUC) para el CA125, CA125vel, CA125td. Comparamos los resultados entre los grupos con CA125 dentro de la normalidad y CA125 patológico (>35U/ml). Resultados: Fueron diagnosticados de recidiva 44 casos (7 con CA125 ≤35U/ml), mientras que 15 no mostraron recurrencia. Todos ellos fueron correctamente catalogados mediante la PET/TC. La curva ROC demostró una capacidad discriminatoria del CA125 relativamente alta (AUC 0.835), con un valour óptimo de referencia de 23.9U/ml. El análisis ROC para la CA125vel y el CA125td mostró un AUC de 0.849 y 0.728, con un valour de referencia de 1.96U/ml/mes y 0.76 meses, respectivamente. En las pacientes con CA125 en límites normales la CA125vel fue significativamente mayor en las pacientes con recidiva que en aquellas sin enfermedad (p=0.029). Conclusión: La [18F]FDG-PET/TC es más exacta que los parámetros de CA125 en la detección de recurrencia de cáncer de ovario. Los niveles séricos de CA125 resultan esenciales, no obstante, los parámetros cinéticos deben ser tenidos en cuenta en la detección de la recidiva

Usefulness of CA125 and its kinetic parameters and positron emission tomography/computed tomography (PET/CT) with fluorodeoxyglucose ([18F] FDG) in the detection of recurrent ovarian cancer.

BACKGROUND AND OBJECTIVE: To assess the usefulness of cancer antigen 125 (CA125) serum levels and kinetic values, velocity (CA125vel) and doubling time (CA125dt), as well as fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT), in the detection of ovarian cancer recurrence. To assess the optimal cut-off for CA125, CA125vel and CA125dt to detect relapse with [18F]FDG-PET/CT. MATERIAL AND METHODS: A retrospective analysis was performed of 59 [18F]FDG-PET/CT (48 patients) for suspected recurrence of ovarian cancer. Receiver operating characteristic (ROC) curves were plotted and area-under-the curve (AUC) statistics were computed for CA125, CA125vel and CA125dt. The results obtained in the group with normal and high (>35U/ml) CA125 levels were compared. RESULTS: Forty-four cases of recurrence were diagnosed (7 had CA125 ≤35U/ml), whereas 15 showed no disease. All of them were correctly catalogued by PET/CT. In ROC analysis, the discriminatory power of CA125 was relatively high (AUC 0.835) and the optimal cut-off point to reflect active disease was 23.9U/ml. The ROC analyses for the CA125vel and CA125dt showed an AUC of 0.849 and 0.728, respectively, with an optimal cut-off point of 1.96U/ml/month and 0.76 months, respectively. In patients with normal CA125 and recurrence of ovarian cancer, the CA125vel was significantly higher than in patients without recurrence (p=0.029). CONCLUSION: [18F]FDG-PET/CT is more accurate than CA125 parameters in the detection of ovarian cancer recurrence. CA125 serum levels are essential; nevertheless, CA125 kinetic values must be considered to detect relapse. Particularly in patients with CA125 within normal values, in which a higher CA125vel is indicative of recurrence.

Polycyclic aromatic hydrocarbons and their derivatives (nitro-PAHs, oxygenated PAHs, and azaarenes) in PM2.5 from Southern European cities.

Atmospheric particulate matter (PM2.5) samples were collected over two one month periods during winter and summer in three Southern European cities (Oporto - traffic site, Florence - urban background, Athens - suburban). Concentrations of 27 polycyclic aromatic hydrocarbons (PAHs), 15 nitro-PAHs (NPAHs), 15 oxygenated-PAHs (OPAHs) and 4 azaarenes (AZAs) were determined. On average, the winter-summer concentrations of ΣPAHs were 16.3-5.60, 7.75-3.02 and 3.44-0.658ngm-3 in Oporto, Florence and Athens, respectively. The corresponding concentrations of ΣNPAHs were 15.8-9.15, 10.9-3.36 and 15.9-2.73ngm-3, whilst ΣOPAHs varied in the ranges 41.8-19.0, 11.3-3.10 and 12.6-0.704ngm-3. Concentrations of ΣAZAs were always below 0.5ngm-3. Irrespective of the city, the dominant PAHs were benzo[b+j+k]fluoranthene, retene, benzo[ghi]perylene and indeno[1,2,3-cd]pyrene. The most abundant OPAH in all cities was 1,8-naphthalic anhydride, whereas 5-nitroacenaphthene was the prevailing NPAH. The ΣOPAHs/ΣPAHs and ΣNPAHs/ΣPAHs were higher in summer than in winter, suggesting increasing formation of derivatives by photochemical degradation of PAHs. Molecular diagnostic ratios suggested that, after traffic, biomass burning was the dominant emission source. Apart from being influenced by seasonal sources, the marked differences between winter and summer may indicate that these diagnostic ratios are particularly sensitive to photodegradation, and thus should be applied and interpreted cautiously. The lifetime excess cancer risk from inhalation was, in part, attributable to PAH derivatives, acclaiming the need to include these compounds in regular monitoring programmes. On average, 206, 88 and 26 cancer cases per million people were estimated, by the World Health Organisation method, for the traffic-impacted, urban background and suburban atmospheres of Oporto, Florence and Athens, respectively.

Mutagenicity assessment of aerosols in emissions from domestic combustion processes.

Domestic biofuel combustion is one of the major sources of regional and local air pollution, mainly regarding particulate matter and organic compounds, during winter periods. Mutagenic and carcinogenic activity potentials of the ambient particulate matter have been associated with the fraction of polycyclic aromatic hydrocarbons (PAH) and their oxygenated (OPAH) and nitrogenated (NPAH) derivatives. This study aimed at assessing the mutagenicity potential of the fraction of this polycyclic aromatic compound in particles (PM10) from domestic combustion by using the Ames assays with Salmonella typhimurium TA98 and TA100. Seven biofuels, including four types of pellets and three agro-fuels (olive pit, almond shell and shell of pine nuts), were tested in an automatic pellet stove, and two types of wood (Pinus pinaster, maritime pine, and Eucalyptus globulus, eucalypt) were burned in a traditional wood stove. For this latter appliance, two combustion phases­Devolatilisation and flaming/smouldering­Were characterised separately. A direct-acting mutagenic effect for the devolatilisation phase of pine combustion and for both phases of eucalypt combustion was found. Almond shell revealed a weak direct-acting mutagenic effect, while one type of pellets, made of recycled wastes, and pine (devolatilisation) presented a cytotoxic effect towards strain TA100. Compared to the manually fired appliance, the automatic pellet stove promoted lower polyaromatic mutagenic emissions. For this device, only two of the studied biofuels presented a weak mutagenic or cytotoxic potential.

Direct and indirect dorsolateral striatum pathways reinforce different action strategies.

The basal ganglia, and the striatum in particular, are critical for action reinforcement [1,2]. The dorsal striatum, which can be further subdivided into dorsomedial (DMS) and dorsolateral (DLS) striatum, is mainly composed of two subpopulations of striatal medium spiny projection neurons (MSNs): dopamine D1 receptor-expressing MSNs that constitute the striatonigral or direct pathway (dMSNs); and dopamine D2 receptor-expressing MSNs that constitute the striatopallidal or indirect pathway (iMSNs) [3]. It has been suggested that each pathway has opposing roles in reinforcement, with dMSNs being important to learn positive reinforcement and iMSNs to learn to avoid undesired actions (Go/No-Go) [1]. Furthermore, optogenetic self-stimulation of dMSNs in DMS leads to reinforcement of actions, while self-stimulation of iMSNs leads to avoidance of actions [2]. However, in DLS, which has been implicated in the consolidation of well-trained actions and habits in mice [4,5], both pathways are active during lever-pressing for reward [6]. Furthermore, extensive skill training leads to long-lasting potentiation of glutamatergic inputs into both dMSNs and iMSNs [4]. We report here that, in DLS, both dMSNs and iMSNs are involved in positive reinforcement, but support different action strategies.

Mutagenicity assessment of aerosols in emissions from domestic combustion processes.

Domestic biofuel combustion is one of the major sources of regional and local air pollution, mainly regarding particulate matter and organic compounds, during winter periods. Mutagenic and carcinogenic activity potentials of the ambient particulate matter have been associated with the fraction of polycyclic aromatic hydrocarbons (PAH) and their oxygenated (OPAH) and nitrogenated (NPAH) derivatives. This study aimed at assessing the mutagenicity potential of the fraction of this polycyclic aromatic compound in particles (PM10) from domestic combustion by using the Ames assays with Salmonella typhimurium TA98 and TA100. Seven biofuels, including four types of pellets and three agro-fuels (olive pit, almond shell and shell of pine nuts), were tested in an automatic pellet stove, and two types of wood (Pinus pinaster, maritime pine, and Eucalyptus globulus, eucalypt) were burned in a traditional wood stove. For this latter appliance, two combustion phases-devolatilisation and flaming/smouldering-were characterised separately. A direct-acting mutagenic effect for the devolatilisation phase of pine combustion and for both phases of eucalypt combustion was found. Almond shell revealed a weak direct-acting mutagenic effect, while one type of pellets, made of recycled wastes, and pine (devolatilisation) presented a cytotoxic effect towards strain TA100. Compared to the manually fired appliance, the automatic pellet stove promoted lower polyaromatic mutagenic emissions. For this device, only two of the studied biofuels presented a weak mutagenic or cytotoxic potential.

An integrative assessment to determine the genotoxic hazard of estuarine sediments: combining cell and whole-organism responses.

The application of the Comet assay in environmental monitoring remains challenging in face of the complexity of environmental stressors, e.g., when dealing with estuarine sediments, that hampers the drawing of cause-effect relationships. Although the in vitro Comet assay may circumvent confounding factors, its application in environmental risk assessment (ERA) still needs validation. As such, the present work aims at integrating genotoxicity and oxidative DNA damage induced by sediment-bound toxicants in HepG2 cells with oxidative stress-related effects observed in three species collected from an impacted estuary. Distinct patterns were observed in cells exposed to crude mixtures of sediment contaminants from the urban/industrial area comparatively to the ones from the rural/riverine area of the estuary, with respect to oxidative DNA damage and oxidative DNA damage. The extracts obtained with the most polar solvent and the crude extracts caused the most significant oxidative DNA damage in HepG2 cells, as measured by the formamidopyrimidine-DNA glycosylase (FPG)-modified Comet assay. This observation suggests that metals and unknown toxicants more hydrophilic than polycyclic aromatic hydrocarbons may be important causative agents, especially in samples from the rural part of the estuary, where oxidative DNA damage was the most significant. Clams, sole, and cuttlefish responded differentially to environmental agents triggering oxidative stress, albeit yielding results accordant with the oxidative DNA damage observed in HepG2 cells. Overall, the integration of in vivo biomarker responses and Comet assay data in HepG2 cells yielded a comparable pattern, indicating that the in vitro FPG-modified Comet assay may be an effective and complementary line-of-evidence in ERA even in particularly challenging, natural, scenarios such as estuarine environments.

Looking at the trees in the central forest: a new pallidal-striatal cell type.

The glopus pallidus is a central nucleus of the basal ganglia, pivotal to their function in health and disease. In this issue of Neuron, Mallet et al. (2012) reveal that this structure is more diverse than previously thought, and identify a novel cell type that projects from pallidum to striatum providing massive GABAergic innervation. These findings invite new views on basal ganglia processing.

Essential oils from plants and in vitro shoots of Hypericum androsaemum L.

The essential oil yields obtained by hydrodistillation of the aerial parts of Hypericum androsaemum cultivated plants varied from 0.94 to 4.09 mg/g of biomass dry weight, depending of the harvest time. The respective analyses performed by gas chromatography and gas chromatography-mass spectrometry revealed more than 80 compounds, 72 of which were identified. Most of the compounds were sesquiterpene hydrocarbons, which, depending of the harvest time, corresponded to 43-78% of the total essential oil. The other compounds were distributed as monoterpene hydrocarbons, oxygen-containing sesquiterpenes, n-alkanes, 1-alkenes, and oxygen-containing monoterpenes, these being a minor group. In H. androsaemum in vitro shoots, sesquiterpene hydrocarbons represented >80% of the respective essential oil. Differences in the essential oil composition were found depending on the harvest time and origin, in vivo versus in vitro, of the plant material. The essential oil sampled in November was characterized by the highest levels of sesquiterpene hydrocarbons and a high number of n-alkanes and 1-alkenes, from C(18) to C(28), whereas that sampled in June of the following year showed the highest levels of n-nonane and 1-octene as well as monoterpene hydrocarbons, the second most representative group.