Retinal Vein Occlusion in a Patient on Dabrafenib and Trametinib Therapy for Metastatic Melanoma.

The purpose of this case report is to highlight the ocular complications of dabrafenib and trametinib treatment. We discuss the case of an 81-year-old female treated with dabrafenib and trametinib for metastatic melanoma, who developed a retinal branch vein occlusion with macular edema in the right eye. The other eye was healthy. The treatment was discontinued and her macular edema was managed with a loading dose of three injections of anti-vascular endothelial growth factor (anti-VEGF) medication with a good response. The use of BRAF and MEK inhibitors is increasingly becoming widespread, and hence it is important to report cases of these adverse effects to achieve earlier diagnoses and initiate fast and effective treatments.

Searching for Novel Air Pollutants Inducers of Toxicity in the Respiratory and Immune Systems.

Many contaminants may pollute the indoor or outdoor environment in a variety of ways [...].

Abundance of Ganoderma sp. in Europe and SW Asia: modelling the pathogen infection levels in local trees using the proxy of airborne fungal spore concentrations.

Ganoderma comprises a common bracket fungal genus that causes basal stem rot in deciduous and coniferous trees and palms, thus having a large economic impact on forestry production. We estimated pathogen abundance using long-term, daily spore concentration data collected in five biogeographic regions in Europe and SW Asia. We hypothesized that pathogen abundance in the air depends on the density of potential hosts (trees) in the surrounding area, and that its spores originate locally. We tested this hypothesis by (1) calculating tree cover density, (2) assessing the impact of local meteorological variables on spore concentration, (3) computing back trajectories, (4) developing random forest models predicting daily spore concentration. The area covered by trees was calculated based on Tree Density Datasets within a 30 km radius from sampling sites. Variations in daily and seasonal spore concentrations were cross-examined between sites using a selection of statistical tools including HYSPLIT and random forest models. Our results showed that spore concentrations were higher in Northern and Central Europe than in South Europe and SW Asia. High and unusually high spore concentrations (> 90th and > 98th percentile, respectively) were partially associated with long distance transported spores: at least 33% of Ganoderma spores recorded in Madeira during days with high concentrations originated from the Iberian Peninsula located >900 km away. Random forest models developed on local meteorological data performed better in sites where the contribution of long distance transported spores was lower. We found that high concentrations were recorded in sites with low host density (Leicester, Worcester), and low concentrations in Kastamonu with high host density. This suggests that south European and SW Asian forests may be less severely affected by Ganoderma. This study highlights the effectiveness of monitoring airborne Ganoderma spore concentrations as a tool for assessing local Ganoderma pathogen infection levels.

Airborne pollen calendar of Portugal: a 15-year survey (2002-2017)

INTRODUCTION: Data about the occurrence of airborne pollen enables the creation of pollen calendars with an approximation of flowering periods for the most common allergenic plant species in a specific area. The aim of this work is to provide pollen calendar for each of the seven monitoring regions of Portugal based on 15 years of airborne sampling, in order to chart the seasonal behaviour of the main allergenic pollen types. MATERIAL AND METHODS: Airborne pollen monitoring (2002-2017) was carried out by the Portuguese Aerobiology Network (RPA), using Hirst-type volumetric spore traps, following well-established guidelines. RESULTS: A total of 14 airborne pollen types were recorded at RPA monitoring stations, of which 64.2% belong to trees, 28.5% to herbs and 7.1% to weeds. The airborne pollen spectrum is dominated by important allergenic pollen types such as Poaceae, Quercus spp., Urticaceae and Cupressaceae. The average pollen index was 42.557 in mainland Portugal and 3.818 in the Islands. There was an increased trend in the airborne pollen levels over the years, namely in Coimbra, Évora and Porto, compared to the remaining regions. CONCLUSION: This report provides accessible information about the main allergenic airborne pollen types occurring in the course of the year. The pollen calendars charted for each Portuguese region showed that the occurrence of most allergenic taxa was centred from March to July. Pollen peak concentrations were detected earlier in the Centre and Lisbon and Tagus Valley regions, and later in the remaining regions

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Airborne pollen calendar of Portugal: a 15-year survey (2002-2017).

INTRODUCTION: Data about the occurrence of airborne pollen enables the creation of pollen calendars with an approximation of flowering periods for the most common allergenic plant species in a specific area. The aim of this work is to provide pollen calendar for each of the seven monitoring regions of Portugal based on 15 years of airborne sampling, in order to chart the seasonal behaviour of the main allergenic pollen types. MATERIAL AND METHODS: Airborne pollen monitoring (2002-2017) was carried out by the Portuguese Aerobiology Network (RPA), using Hirst-type volumetric spore traps, following well-established guidelines. RESULTS: A total of 14 airborne pollen types were recorded at RPA monitoring stations, of which 64.2% belong to trees, 28.5% to herbs and 7.1% to weeds. The airborne pollen spectrum is dominated by important allergenic pollen types such as Poaceae, Quercus spp., Urticaceae and Cupressaceae. The average pollen index was 42.557 in mainland Portugal and 3.818 in the Islands. There was an increased trend in the airborne pollen levels over the years, namely in Coimbra, Évora and Porto, compared to the remaining regions. CONCLUSION: This report provides accessible information about the main allergenic airborne pollen types occurring in the course of the year. The pollen calendars charted for each Portuguese region showed that the occurrence of most allergenic taxa was centred from March to July. Pollen peak concentrations were detected earlier in the Centre and Lisbon and Tagus Valley regions, and later in the remaining regions.

Airborne Alternaria and Cladosporium fungal spores in Europe: Forecasting possibilities and relationships with meteorological parameters.

Airborne fungal spores are prevalent components of bioaerosols with a large impact on ecology, economy and health. Their major socioeconomic effects could be reduced by accurate and timely prediction of airborne spore concentrations. The main aim of this study was to create and evaluate models of Alternaria and Cladosporium spore concentrations based on data on a continental scale. Additional goals included assessment of the level of generalization of the models spatially and description of the main meteorological factors influencing fungal spore concentrations. Aerobiological monitoring was carried out at 18 sites in six countries across Europe over 3 to 21 years depending on site. Quantile random forest modelling was used to predict spore concentrations. Generalization of the Alternaria and Cladosporium models was tested using (i) one model for all the sites, (ii) models for groups of sites, and (iii) models for individual sites. The study revealed the possibility of reliable prediction of fungal spore levels using gridded meteorological data. The classification models also showed the capacity for providing larger scale predictions of fungal spore concentrations. Regression models were distinctly less accurate than classification models due to several factors, including measurement errors and distinct day-to-day changes of concentrations. Temperature and vapour pressure proved to be the most important variables in the regression and classification models of Alternaria and Cladosporium spore concentrations. Accurate and operational daily-scale predictive models of bioaerosol abundances contribute to the assessment and evaluation of relevant exposure and consequently more timely and efficient management of phytopathogenic and of human allergic diseases.

Determination of potential childhood asthma biomarkers using a powerful methodology based on microextraction by packed sorbent combined with ultra-high pressure liquid chromatography. Eicosanoids as case study.

Leukotrienes and prostaglandins are arachidonic acid bioactive derived eicosanoids and key mediators of bronchial inflammation and response modulation in the airways contributing to the pathophysiology of asthma. An easy-to-use ultra-high pressure liquid chromatography (UHPLC)-based strategy was developed to characterize biomarkers of lipid peroxidation: leukotrienes E (LTE4) and B4 (LTB4) and 11ß-prostaglandin F2α (11ßPGF2α), present in urine of asthmatic patients (N = 27) and healthy individuals (N = 17). A semi-automatic eVol®-microextraction by packed sorbent (MEPS) was used to isolate the target analytes. Several experimental parameters with influence on the extraction efficiency and on the chromatographic resolution, were evaluated and optimized. The method was fully validated under optimal extraction (R-AX sorbent, 3 conditioning-equilibration cycles with 250 µL of ACN-water at 0.1% FA, 10 extract-discard cycles of 250 µL of sample at a pH of 5.1, elution with 2 times 50 µL of MeOH and concentration of the eluate until half of its volume) and chromatographic conditions (14-min analysis at a flow rate of 300 µL min-1 in an UHPLC-PDA equipped with a BEH C18 column), according to IUPAC guidelines. The findings indicated good recoveries (>95%) in addition to excellent extraction efficiency (>95%) at three concentration levels (low mid and high) with precision (RSDs) less than 11%. The lack-of-fit test, goodness-of-fit test and Mandel's fitting test, revealed good linearity within the concentration range. Good selectivity and sensitivity were achieved with a limits of detection ranging from 0.04 µg L-1 for LTB4 to 1.12 µg L-1 for 11ßPGF2α, and limits of quantification from 0.10 µg L-1 for the LTB4 to 2.11 µg L-1 for 11ßPGF2α. The successful application of the fully validated method shows that, on average, the asthmatic patients had significantly higher concentrations of 11ßPGF2α (112.96 µg L-1vs 62.56 µg L-1 in normal controls), LTE4 (1.27 µg L-1vs 0.89 µg L-1 in normal controls), and LTB4 (1.39 µg L-1vs 0.76 µg L-1 in normal controls). The results suggest the potential of the target eicosanoids on asthma diagnosis, however, a larger and more extensive study will be necessary to confirm the data obtained and to guarantee a greater robustness to the approach.

Domiciliary VR-Based Therapy for Functional Recovery and Cortical Reorganization: Randomized Controlled Trial in Participants at the Chronic Stage Post Stroke.

BACKGROUND: Most stroke survivors continue to experience motor impairments even after hospital discharge. Virtual reality-based techniques have shown potential for rehabilitative training of these motor impairments. Here we assess the impact of at-home VR-based motor training on functional motor recovery, corticospinal excitability and cortical reorganization. OBJECTIVE: The aim of this study was to identify the effects of home-based VR-based motor rehabilitation on (1) cortical reorganization, (2) corticospinal tract, and (3) functional recovery after stroke in comparison to home-based occupational therapy. METHODS: We conducted a parallel-group, controlled trial to compare the effectiveness of domiciliary VR-based therapy with occupational therapy in inducing motor recovery of the upper extremities. A total of 35 participants with chronic stroke underwent 3 weeks of home-based treatment. A group of subjects was trained using a VR-based system for motor rehabilitation, while the control group followed a conventional therapy. Motor function was evaluated at baseline, after the intervention, and at 12-weeks follow-up. In a subgroup of subjects, we used Navigated Brain Stimulation (NBS) procedures to measure the effect of the interventions on corticospinal excitability and cortical reorganization. RESULTS: Results from the system's recordings and clinical evaluation showed significantly greater functional recovery for the experimental group when compared with the control group (1.53, SD 2.4 in Chedoke Arm and Hand Activity Inventory). However, functional improvements did not reach clinical significance. After the therapy, physiological measures obtained from a subgroup of subjects revealed an increased corticospinal excitability for distal muscles driven by the pathological hemisphere, that is, abductor pollicis brevis. We also observed a displacement of the centroid of the cortical map for each tested muscle in the damaged hemisphere, which strongly correlated with improvements in clinical scales. CONCLUSIONS: These findings suggest that, in chronic stages, remote delivery of customized VR-based motor training promotes functional gains that are accompanied by neuroplastic changes. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number NCT02699398 (Archived by ClinicalTrials.gov at https://clinicaltrials.gov/ct2/show/NCT02699398?term=NCT02699398&rank=1).

Inhalant Allergens in Portugal.

This review aims to present in a simple manner the work performed in Portugal regarding the identification of the most prevalent aeroallergens in the country and the sensitization levels in Portuguese patients. Much of the data was summarized in tables and illustrated on maps, enabling the community of clinicians, researchers, and patient organizations to access the knowledge about the research performed. This study provides an overview about the distribution of aeroallergens in Portugal, signaling regions and critical periods of exposure of the sensitized population. The illustrated data can help the community of allergy specialists to view the temporal and spatial distribution of aeroallergens across the country. In addition, this information can guide clinicians to select the most appropriate allergens for allergy diagnostic testing, treatment, and allergen avoidance.

Madeira-a tourist destination for asthma sufferers.

Madeira Island is a famous tourist destination due to its natural and climatic values. Taking into account optimal weather conditions, flora richness and access to various substrates facilitating fungal growth, we hypothesised a very high risk of elevated fungal spore and pollen grain concentrations in the air of Funchal, the capital of Madeira. Concentration levels of the most allergenic taxa were measured from 2003 to 2009, using a 7-day volumetric air sampler, followed by microscopy analysis. Dependence of bioaerosols on the weather conditions and land use were assessed using spatial and statistical tools. Obtained results were re-visited by a comparison with hospital admission data recorded at the Dr. Nélio Mendonça Hospital in Funchal. Our results showed that despite propitious climatic conditions, overall pollen grain and fungal spore concentrations in the air were very low and did not exceed any clinically established threshold values. Pollen and spore peak concentrations also did not match with asthma outbreaks in the winter. Identification of places that are "free" from biological air pollution over the summer, such as Madeira Island, is very important from the allergic point of view.

Airborne pollen in Funchal city, (Madeira Island, Portugal) - First pollinic calendar and allergic risk assessment.

INTRODUCTION: Nowadays, pollen calendars are useful tools for clinical guidance intended for allergy sufferers, because they can be used to prevent and manage allergic respiratory diseases, thus improving the quality of life. OBJECTIVES: An aeropalinological study was performed in the city of Funchal with the purpose of establishing a pollen calendar and determining allergic risk, based on a seven year study (2003-2009). MATERIAL AND METHODS: The airborne pollen monitoring was carried out with a Hirst type volumetric spore trap, following well-established guidelines. RESULTS: The mean annual pollen index was 1,635.09 and comprised 42 different pollen types. Airborne pollen levels were higher between March - June, accounting for 57.9% of the annual counts. Arboreal pollen grains (52.72%) prevailed in the atmosphere together with herbs and grasses (44.64%), while fern spores (2.29%) and unidentified pollen (0.35%) were scarce. The main pollen types were Urticaceae (20.64%), Poaceae (16.02%), Cupressaceae (13.61%), Pinaceae (9.07%), Myrtaceae (5.93%) and Ericaceae (5.02%). The pollen calendar comprised a total of 14 taxa and is similar to Mediterranean regions, with the exception of Olea europaea, Quercus sp., Betula sp. and Alnus sp. pollen types which are rare or absent. The main pollen season of major pollen taxa is significantly longer in Funchal (on average 239 days) than other European sites, especially for Urticaceae and Poaceae, but the pollen peaks were substantially lower. CONCLUSIONS: The pollen calendar for Funchal is the first ever created for Madeira region. Taking into account the low pollen index and number of allergy-risk days recorded (39 days in 7 years), the air quality of Funchal can be considered good.

Exploring the potentialities of an improved ultrasound-assisted quick, easy, cheap, effective, rugged, and safe-based extraction technique combined with ultrahigh pressure liquid chromatography-fluorescence detection for determination of Zearalenone in cereals.

Zearalenone (ZEA), a secondary metabolite from Fusarium graminearum fungi that invade crops and grow during blooming in moist cool field conditions, is a nonsteroidal oestrogen, biologically very potent, although hardly toxic. Different analytical methods, among which a quick, easy, cheap, effective, rugged, and safe (QuEChERS) strategy, combined with or liquid chromatography, have been proposed for ZEA determination in foods. However, this extraction procedure has the disadvantage of using large amount of organic solvents, partitioning salts and sample volume, which limits the technique application on the fields where the sample amount is critical. Therefore in this work an improved sample preparation step based on the original QuEChERS (O-QuEChERS) approach, the µ-QuEChERS, combined with ultrasound-assisted extraction (USAE) and ultrahigh pressure liquid chromatography (UHPLC) analysis with fluorescence detection (FLR) is proposed for the sensitive and high-throughput quantification of ZEA in cereals. The proposed analytical strategy, µ-QuEChERSUSAE, uses up to 32 times lower amounts of partitioning salts, lower sample amount and lower extraction solvents, in comparison with O-QuEChERS technique. The performance of the analytical approach was assessed by studying the selectivity, specificity, limits of detection and quantification, linear dynamic range, matrix effect and precision. Good linearity (r(2)>0.99) was achieved for ZEA, and limits of detection (LOD=3.4µgkg(-1)) and limits of quantification (LOQ=4.7µgkg(-1)) were found below the tolerance levels set by European Commission. Good recoveries were obtained with different spiked concentrations, ranged from 80.2% to 109.7%, with relative standard deviations (RSD) lower than 5.0%. The comparison of the analytical performance of the proposed µ-QuEChERSUSAE with O-QuEChERS showed the powerful ability of the proposed strategy since it gives comparable results but using lower amounts of sample, partitioning salts and volume of the organic solvent, revealing of great potential and improvement of the proposed method.