Synthetic Colors in Food: A Warning for Children's Health.

This study addressed the harmful effects of artificial colors in pediatric populations, including children diagnosed with Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD), as well as those without behavioral disorders. There is a consensus that synthetic food colorings have several impacts on consumers, especially pediatrics, due to their influence on sensory appeal, which can encourage preference for certain foods. The results revealed that these color additives are directly linked to a series of health problems, with a greater impact on children, including a predisposition to pathological conditions such as carcinogenic, allergenic, mutagenic, cytotoxic, and clastogenic activities, as well as gastrointestinal and respiratory problems, in addition to behavioral changes in children with and without diagnosed disorders. The harms of synthetic dyes in children with or without comorbidities are worrying and require a careful and proactive approach from parents, caregivers and public authorities.

Fungal Endocarditis: A Rare Case of Multiple Arterial Embolization.

Fungal endocarditis is a rare and fatal condition, with a mortality of up to 75%, affecting immunocompromised hosts with a predisposing condition, namely, a history of previous cardiac or noncardiac surgery. Embolization is frequent, accounting for 44% of cases, and as the most common site is the brain, it can cause leptomeningitis, parenchymal granulomas, or abscesses. This case report describes a man with aortic valve replacement one year ago and a recent carotid endarterectomy who was admitted with fever and neurological deficits. The workup permitted a diagnosis of fungal endocarditis, and the patient underwent a combined and aggressive treatment approach with antifungal therapy and surgery, with a successful replacement of the aortic valve. During hospitalization, the patient's neurological status deteriorated, and a cerebral abscess was discovered on the left frontal lobe. Despite the poor prognosis, the patient recovered slowly and was discharged from the hospital three months later. The present case highlights the high index of suspicion needed for the diagnosis and the need for a multidisciplinary team to approach these patients to achieve a positive outcome.

Semaphorin3B promotes an anti-inflammatory and pro-resolving phenotype in macrophages from rheumatoid arthritis patients in a MerTK-dependent manner.

Previous works from our group show that Semaphorin3B (Sema3B) is reduced in RA and plays a protective role in a mouse arthritis model. In turn, MerTK plays a protective function in murine arthritis models, is expressed by synovial tissue macrophages and is linked to remission in patients with RA. In this study, we examined the role of Sema3B in the phenotypic characteristics of RA macrophages and the implication of MerTK. Peripheral blood monocytes from RA patients were differentiated into IFN-γ (RA MØIFN-γ) or M-CSF (RA MØM-CSF) macrophages and stimulated with LPS, Sema3B or their combination. Alternatively, RA fibroblast like synoviocytes (FLS) were stimulated with RA MØIFN-γ and RA MØM-CSF supernatants. Gene expression was determined by qPCR and protein expression and activation by flow cytometry, ELISA and western blot. Sema3B down-regulated the expression of pro-inflammatory mediators, in both RA MØIFN-γ and RA MØM-CSF. We observed a similar reduction in RA FLS stimulated with the supernatant of Sema3B-treated RA MØIFN-γ and RA MØM-CSF. Sema3B also modulated cell surface markers in macrophages towards an anti-inflammatory phenotype. Besides, MerTK expression and activation was up-regulated by Sema3B, just as GAS6 expression, Resolvin D1 secretion and the phagocytic activity of macrophages. Importantly, the inhibition of MerTK and neuropilins 1 and 2 abrogated the anti-inflammatory effect of Sema3B. Our data demonstrate that Sema3B modulates the macrophage characteristics in RA, inducing a skewing towards an anti-inflammatory/pro-resolving phenotype in a MerTK-dependant manner. Therefore, here we identify a new mechanism supporting the protective role of Sema3B in RA pathogenesis.

Mechanical regulation of the early stages of angiogenesis.

Favouring or thwarting the development of a vascular network is essential in fields as diverse as oncology, cardiovascular disease or tissue engineering. As a result, understanding and controlling angiogenesis has become a major scientific challenge. Mechanical factors play a fundamental role in angiogenesis and can potentially be exploited for optimizing the architecture of the resulting vascular network. Largely focusing on in vitro systems but also supported by some in vivo evidence, the aim of this Highlight Review is dual. First, we describe the current knowledge with particular focus on the effects of fluid and solid mechanical stimuli on the early stages of the angiogenic process, most notably the destabilization of existing vessels and the initiation and elongation of new vessels. Second, we explore inherent difficulties in the field and propose future perspectives on the use of in vitro and physics-based modelling to overcome these difficulties.

A 3D Digital Analysis of the Hard Palate Wound Healing after Free Gingival Graft Harvest: A Pilot Study in the Short Term.

Purpose: Within this context, this pilot study aimed to evaluate the healing dynamics process of the hard palate after free gingival graft harvesting in the short term (3 months), utilizing digital imaging technology and tridimensional analysis software. Furthermore, assessing the results found to verify the existence of a relationship between gender or age with tissue loss. Materials and Methods: For connective-tissue harvesting, fifteen patients with gingival recessions type (RT) 1 and RT2 were selected. On the surgery day (before the procedure) and after three months, palatal impressions were taken in all patients, and cast models were done for posterior model scanning. The following variables were analyzed: mean thickness alterations (x¯ TA), maximum thickness loss (MTL), mean maximum thickness loss (x¯ MTL), and volume alterations (VA). A descriptive and bivariate analysis of the data was done. The data were submitted for statistical evaluation and were significant if p < 0.05. Results: Fifteen patients were analyzed, 11 females (73.3%) and four males (26.7%). The patients' average age was 28 ± 8.52 years (ranging between 16 and 48 years old). The palatal wound region's mean thickness and volume changes were −0.26 mm (±0.31) and 46.99 mm3 (±47.47 mm3) at three months. There was no statistically significant result correlating age/gender with any variable evaluated. Conclusions: Connective tissue graft harvesting promoted changes with a standard volume and thickness loss of palatal soft tissue. A 3D digital evaluation was a non-invasive method with a reproducible technique for measuring thickness or volume after connective tissue is collected. There was no relationship between age/gender and any variables analyzed.

Monocytes and Macrophages in Spondyloarthritis: Functional Roles and Effects of Current Therapies.

Spondyloarthritis (SpA) is a family of chronic inflammatory diseases, being the most prevalent ankylosing spondylitis (AS) and psoriatic arthritis (PsA). These diseases share genetic, clinical and immunological features, such as the implication of human leukocyte antigen (HLA) class I molecule 27 (HLA-B27), the inflammation of peripheral, spine and sacroiliac joints and the presence of extra-articular manifestations (psoriasis, anterior uveitis, enthesitis and inflammatory bowel disease). Monocytes and macrophages are essential cells of the innate immune system and are the first line of defence against external agents. In rheumatic diseases including SpA, the frequency and phenotypic and functional characteristics of both cell types are deregulated and are involved in the pathogenesis of these diseases. In fact, monocytes and macrophages play key roles in the inflammatory processes characteristics of SpA. The aim of this review is analysing the characteristics and functional roles of monocytes and macrophages in these diseases, as well as the impact of different current therapies on these cell types.

An Improved LC-MS/MS Method for the Analysis of Thirteen Cytostatics on Workplace Surfaces.

Cytostatics are drugs used in cancer treatment, which pose serious risks to healthcare workers. Dermal absorption via surface contamination is the key exposure route; thus, rapid, reliable, and validated analytical methods for multicomponent detection are crucial to identify the exposure risk. A surface-wipe-sampling technique compatible with hospitals' safety requirements (gauze, 1 mL isopropanol) and a fast and simple extraction method (1 mL acetonitrile, 20 min ultrasonic bath, evaporation, reconstitution in 200 µL acetonitrile), coupled with liquid chromatography-tandem mass spectrometry analysis, were developed. It allowed identification and quantification of 13 cytostatics on surfaces: cyclophosphamide, doxorubicin, etoposide, ifosfamide, paclitaxel, bicalutamide, capecitabine, cyproterone, flutamide, imatinib, megestrol, mycophenolate mofetil, prednisone. Good linearity, sensitivity, and precision were achieved (R2 > 0.997, IDLs < 4.0 pg/cm2, average CV 16%, respectively). Accuracy for four model surfaces (melamine-coated wood, phenolic compact, steel 304, steel 316) was acceptable (80 ± 12%), except for capecitabine and doxorubicin. Global uncertainty is below 35% for concentrations above 100 pg/cm2 (except for capecitabine and doxorubicin)-a guidance value for relevant contamination. Method application in a Portuguese university hospital (28 samples) identified the presence of seven cytostatics, at concentrations below 100 pg/cm2, except for three samples. The widespread presence of cyclophosphamide evinces the necessity to review implemented procedures.

Analytical methodology to screen UV-filters and synthetic musk compounds in market tomatoes.

A Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) methodology followed by gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis was developed to extract thirteen synthetic musk compounds (SMCs: cashmeran, celestolide, phantolide, traseolide, galaxolide, tonalide, musk ambrette, musk xylene, musk ketone, musk tibetene, musk moskene, ethylene brassylate and exaltolide) and six ultraviolet-filters (UVFs: 2-ethylhexyl 4-dimethylaminobenzoate, 3-(4'-methylbenzylidene) camphor, 2-ethylhexyl 4-methoxycinnamate, 2-ethylhexyl 2-cyano-3,3-diphenylacrylate, benzophenone and drometrizole trisiloxane) from tomatoes. The proposed methodology was optimized: 2 g of freeze-dried tomato was extracted with 4 mL of water and 10 mL of ethyl acetate, adding 6 g of MgSO4 and 1.5 g of NaCl, then a dispersive solid-phase extraction was performed using 3 g of MgSO4, 300 mg of primary-secondary amino adsorbent (PSA) and 300 mg of octadecyl-silica (C18). Validation delivered recoveries between 81 (celestolide) and 119% (musk tibetene), with relative standard deviations <10%. The instrumental limit of detection varied from 0.02 (2-ethylhexyl 4-methoxycinnamate) to 3.00 pg (exaltolide and musk xylene). Regarding the method quantification limits, it ranged between 0.4 (celestolide) and 47.9 ng g-1 dw (exaltolide). The method was applied to different varieties of tomatoes (Solanum lycopersicum), revealing UVFs and SMCs between 1 and 210 ng g-1 dw. Higher concentrations were found for benzophenone (29-210 ng g-1 dw) and galaxolide (9-53 ng g-1 dw). The risk associated to the ingestion of contaminated tomatoes has also been estimated, showing that a potential health risk is unlikely.

Utility of the Brain Injury Screening Index in Identifying Female Prisoners With a Traumatic Brain Injury and Associated Cognitive Impairment.

There is a high prevalence of traumatic brain injury (TBI) in prisoners, but screening tools for identifying TBI in female prisoners are not readily available. Using a cross-sectional design, the psychometric properties of the Brain Injury Screening Index (BISI) were investigated in a closed United Kingdom female prison. Purposive sampling comprised 56 females. Assessment included clinical interview, the BISI, self-report measures of mood, and a battery of measures of cognitive functioning. Seven of the 10 clinical indicators on the BISI met test-retest reliability criteria. Two of the three BISI summary variables demonstrated correlations with questionnaires in the hypothesized directions; however, only two BISI variables were associated with cognitive functioning. Findings support further investigation into the validity and reliability of the BISI with a larger sample.

Perineal reconstruction using an inferior gluteal artery perforator flap after abdominoperineal resection.

The abdominoperineal resection is a surgical procedure which implies the removal of rectum, anal canal and the creation of a terminal colostomy. The most frequent complications of this type of surgery are haemorrhage, surgical wound complications, persistent perineal sinus and perineal hernia. Intraoperative haemorrhage or contamination and neoadjuvant radiotherapy are risk factors for the development of perineal complications. Perineal wound infection, with subsequent healing delay, has multifactorial aetiology and its incidence can reach up to 66% according to literature. The prevention of these complications requires adequate surgical technique to avoid or minimise the known risk factors. The treatment of a perineal wound complication depends on the clinical and radiographic findings. When there is no wound resolution in 6 months, it is considered a persistent sinus and treatment will probably require a flap. Several options of surgical treatment are available however, there are no randomised studies to determine which one is the best.

Fournier's Gangrene: 10-Year Experience of a Plastic Surgery and Burns Department at a Tertiary Hospital.

INTRODUCTION: Fournier gangrene is a polymicrobial life threatening infection of perineal subcutaneous soft tissues with its point of origin in urologic, colorectal or skin diseases. Although more frequent in elderly and men, it can affect all genders and age groups. Perianal abscess, diabetes mellitus and Escherichia coli are the most frequent cause, predisposing comorbidity, and microorganism found in tissue culture analysis respectively. The objective of this study was to describe the experience of a Plastic Surgery Department of a tertiary Hospital in reconstructing Fournier's gangrene perineal defects and its detailed demography. MATERIAL AND METHODS: The sample is composed of all patients with Fournier gangrene admitted in the Plastic Surgery and Burns Department. The authors retrospectively collected and analyzed demographic and clinical data during a period of 10 years including gender, age, length of stay, cause, number of debridements, predisposing factors, microbial culture results, surgical reconstructive techniques and its associated complications, additional surgical procedures and outcomes. RESULTS: Fifteen patients were identified: 14 males (93%) and one female (7%); mean age was 66.9 years (range: 46 - 86); mean, length of stay was 46.8 days (range: 20 - 71 days) and mean number of debridements was 3.3 (range: 1 - 4). The most frequent predisposing factor was diabetes mellitus, the major cause was perianal (n = 2) and skin abscess (n = 2). Eight (53.3%) patients had no identifiable source of Fournier gangrene. Various types of reconstructive techniques were employed; and 5 additional surgical interventions (33.3%) were undertaken (one cystostomy, two orchidectomy, two ileostomy); six patients (40%) presented reconstructive technique complications with adequate final outcome. DISCUSSION: In contrast with the literature, where Escherichia coli was the most frequently isolated agent, Staphylococcus aureus was the most frequent microorganism found in tissue biopsy/pus collection analysis. A higher than expected number of patients (n = 8) had no identifiable source of Fournier gangrene. This findings can be explained by the retrospective non-multicentre study limitation, with a potencial source of bias patients that were transferred from other hospitals in advanced stage, without point of origin of Fournier's gangrene identified. CONCLUSION: Early recognition and extensive necrotic tissue debridement, along with prompt and adequate antimicrobial treatment, are the mainstay of Fournier gangrene management, thus reducing morbidity and mortality in these patients. Surgical reconstruction challenges derived from this condition should be addressed by specialized teams due to the risk of dysfunctional sequelae and conspicuous deformities. Taking in account the single-center and retrospective observational character of the present study, these premises require proper validation from a multicenter prospective study.

Introdução: A gangrena de Fournier é uma infeção polimicrobiana potencialmente fatal que afeta os tecidos moles do períneo com ponto de origem em patologias urológicas, coloretais ou cutâneas. Apesar de ser mais frequente no sexo masculino e em idosos, pode afetar ambos os géneros e qualquer idade. O abcesso perianal, a diabetes mellitus e a Escherichia coli são respetivamente a causa, a co-morbilidade e o micro-organismo mais frequentemente encontrados. Este estudo teve como objetivo descrever a experiência de um Serviço de Cirurgia Plástica e Queimados de um Hospital terciário no tratamento e reconstrução de defeitos perineais causados por gangrena de Fournier, disponibilizando detalhes sobre a sua demografia. Material e Métodos: A amostra é constituída por todos os doentes internados no serviço de Cirurgia Plástica e Queimados com o diagnóstico de gangrena de Fournier. Os autores realizaram uma colheita e análise retrospetiva de dados clínicos e demográficos durante um período de 10 anos incluindo género, idade, tempo de internamento, causa, número de desbridamentos, fatores predisponentes, resultados microbiológicos de culturas de pus, técnicas reconstrutivas cirúrgicas e suas complicações, intervenções cirúrgicas adicionais e o resultado final. Resultados: Foram identificados 15 doentes: 14 homens (93%) e uma mulher (7%); a idade média foi 66,9 anos (amplitude: 46 - 86); tempo médio de internamento foi 46,8 dias (amplitude: 20 - 71 dias) e o número médio de desbridamentos foi 3,3 (amplitude: 1 - 4). O fator predisponente mais frequente foi a diabetes mellitus, e as causas mais frequentes o abcesso perianal (n = 2) e o abcesso cutâneo (n = 2). Em oito (53,3%) doentes não foi identificada a causa da gangrena de Fournier. Foram utilizadas várias técnicas reconstrutivas e realizadas conco (33,3%) intervenções cirúrgicas adicionais (uma cistostomia, duas orquidectomias, duas ileostomias); seis doentes (40%) apresentaram complicações de técnicas reconstrutivas com resultado final adequado. Discussão: O micro-organismo mais frequentemente isolado nas culturas de pus foi o Staphylococcus aureus, o que contrasta com a literatura onde a Escherichia coli é o agente mais frequentemente isolado. Foi identificado um número superior ao esperado de doentes sem causa identificável (n = 8) de gangrena de Fournier. Estes achados podem ser explicados pelo facto de se tratar de um estudo retrospetivo multicêntrico, com um potencial viés por existirem doentes que foram transferidos de outras institucões em estado avançado de doença, sem foco de origem de gangrena de Fournier identificado. Conclusão: O precoce reconhecimento e extenso desbridamento do tecido necrosado, em conjunto com um adequado tratamento antibiótico, são os pilares do tratamento da gangrena de Fournier reduzindo assim a morbilidade e mortalidade destes doentes. Os desafios cirúrgicos reconstrutivos que advêm desta patologia devem ser abordados por uma equipa especializada, pelo risco de sequelas funcionais e estéticas. Tendo em conta o carater observacional, retrospetivo e unicêntrico do presente estudo, estas premissas requerem uma validação adequada através de um estudo prospetivo e multicêntrico.

Simultaneous determination of synthetic musks and UV-filters in water matrices by dispersive liquid-liquid microextraction followed by gas chromatography tandem mass-spectrometry.

An analytical method was developed for the simultaneous analysis of 19 emergent compounds in water matrices, six UV-filters (UVFs), five nitro, six polycyclic and two macrocyclic musks. The target compounds were extracted by a dispersive liquid-liquid microextraction (DLLME) approach, using 2-propanol as the dispersive solvent and 1,1,2-trichloroethane as the extractant solvent. The extracts were then analysed by gas chromatography tandem mass-spectrometry (GC-MS/MS). This methodology was successfully validated for the analyses of the target compounds in five types of aqueous samples (tap, river and sea water and influent and effluent wastewater). Recoveries of the analytes based on the surrogate correction ranged from 80 to 120%, with a good repeatability (relative standard deviations less than 10%). The method limit of detection ranges from 0.1 ng L-1 (octocrylene (OC), celestolide (ADBI)) to 20.0 ng L-1 (benzophenone (BZ)). Both UVFs and synthetic musk compounds (SMCs) were detected in all matrices. Higher concentrations were found in wastewaters (total mean concentration in influents of 6248 ng L-1 and 3856 ng L-1 in effluents), followed by river water (159 ng L-1). Only BZ was detected in one of the analysed seawater samples and none of the compounds were detected in tap water. The most detected UVFs among all matrices were BZ and drometrizole (DTS) and tonalide (AHTN) and galaxolide (HHCB) within the SMCs class. Among all matrices, wastewater was the one with higher number of compounds found per sample (both UVFs and SMCs).

Development and optimization of a QuEChERS-GC-MS/MS methodology to analyse ultraviolet-filters and synthetic musks in sewage sludge.

A Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) methodology followed by gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) analysis was developed to extract synthetic musk compounds (SMCs) (6 polycyclic, 2 macrocyclic and 5 nitro musks) and ultraviolet-filters (UVFs) (6 compounds) from sludge. This methodology fills a gap in the literature, since the proposed technique does not require specific equipment, nor large amounts of solvents, sorbents and time to extract SMCs and UVFs from sludge. To optimize this new methodology, a design of experiments (DoE) approach was used, applying first a screening design (SD) and then a central composite design (CCD). The best conditions achieved to extract these 19 compounds simultaneously were: 500 mg freeze dried sludge, 2.5 min of vortex and 15 min ultrasound and the use of a QuEChERS for the dispersive solid-phase extraction (d-SPE) containing 500 mg MgSO4, 410 mg C18 and 315 mg PSA. Then, this methodology was successfully validated. Recoveries of the target compounds ranged from 75% (cashmeran, DPMI) to 122% (2­ethylhexyl 4­methoxycinnamate, EHMC), with good repeatability (relative standard deviation < 10%). The instrumental detection limits (IDLs) and quantification (IQLs) varied from 0.001 pg (musk moskene, MM) to 7.5 pg (musk xylene, MX) and from 0.003 (MM) to 25 pg (MX), respectively. The method detection and quantification limits (MDLs and MQLs) ranged between 0.5 (DPMI) and 1394 (exaltolide, EXA) ng/g dw and 2 and 4648 ng/g-dw, respectively. Both SMCs and UVFs were detected in all sludge samples analysed. Higher concentrations were found for octocrylene (OC: maximum value of 115,486 ng/g-dw) followed by galaxolide (HHCB: 81,771 ng/g-dw). Only the nitro musks ambrette, xylene, moskene and tibetene and macrocyclic musk ethylene brassylate (EB) were not detected in any sample.

Percepção dos riscos profissionais em trabalhadores de transporte de valores / Perceived occupational hazards among cash-in-transit guards

Introdução: Realizou-se um estudo no setor de vigilância privada com vigilantes de transporte de valores (VTVA) diante da presença de queixas de saúde a uma organização sindical do setor. Objetivos: Diagnosticar a situação de trabalho desses profissionais, do ponto de vista da saúde e segurança, caracterizando as condições de trabalho e as tarefas desses trabalhadores, identificando elementos da atividade de trabalho com influência em sua saúde e segurança e apontando os principais problemas de saúde autorreportados em três empresas que operam em Portugal. Métodos: Efetivou-se um estudo exploratório, de natureza descritiva, recorrendo a um questionário dirigido a trabalhadores com três dimensões, de acordo com os objetivos no contexto da saúde e segurança do trabalho (SST). O questionário foi aplicado nas empresas pelos representantes do sindicato e sem qualquer participação das direções das empresas. Resultados: A atividade desses funcionários apresenta exigências diversas, nomeadamente de concentração e precisão, carga física elevada, horários atípicos, exposição a situações emocionalmente fortes e ainda violência. Evidencia­se, por parte dos trabalhadores, influência negativa do trabalho em sua saúde e segurança, tanto no nível físico como no psicológico. Conclusão: Identifica-se uma importante variabilidade de condições e exigências do trabalho nas empresas observadas, que determina a necessidade de intervenção no contexto da SST, designadamente por meio de sensibilização sobre a legislação existente no sentido da prevenção das doenças ligadas ao trabalho e também dos acidentes de trabalho

Background: Given reports of health complaints by cash-in-transit (CIT) guards to their trade union, we conducted a study at private security companies. Objectives: To establish the health and safety at work (HSW) conditions to which employees from three companies in Portugal were subjected, characterize their working conditions and tasks, and identify aspects of their activity with influence on their health and safety, as well as self-reported health problems. Methods: We performed an exploratory and descriptive study based on a questionnaire with three dimensions corresponding to the study aims. The questionnaire was applied by workers' representatives in the workplace without any participation of employers. Results: The job of CIT guards poses several demands as concentration and precision, involves high physical load, atypical schedules, and exposure to emotionally disturbing situations and violence. The workers rated negative the influence of work on their physical and mental health and safety. Conclusion: We found considerable variability in working conditions and work demands between the analyzed companies. Such diversity points to the need to intervention on HSW through sensitization toward the legislation in force for the prevention of work related diseases and accidents

Clinical whole-genome sequencing from routine formalin-fixed, paraffin-embedded specimens: pilot study for the 100,000 Genomes Project.

PURPOSE: Fresh-frozen (FF) tissue is the optimal source of DNA for whole-genome sequencing (WGS) of cancer patients. However, it is not always available, limiting the widespread application of WGS in clinical practice. We explored the viability of using formalin-fixed, paraffin-embedded (FFPE) tissues, available routinely for cancer patients, as a source of DNA for clinical WGS. METHODS: We conducted a prospective study using DNAs from matched FF, FFPE, and peripheral blood germ-line specimens collected from 52 cancer patients (156 samples) following routine diagnostic protocols. We compared somatic variants detected in FFPE and matching FF samples. RESULTS: We found the single-nucleotide variant agreement reached 71% across the genome and somatic copy-number alterations (CNAs) detection from FFPE samples was suboptimal (0.44 median correlation with FF) due to nonuniform coverage. CNA detection was improved significantly with lower reverse crosslinking temperature in FFPE DNA extraction (80 °C or 65 °C depending on the methods). Our final data showed somatic variant detection from FFPE for clinical decision making is possible. We detected 98% of clinically actionable variants (including 30/31 CNAs). CONCLUSION: We present the first prospective WGS study of cancer patients using FFPE specimens collected in a routine clinical environment proving WGS can be applied in the clinic.

A rabbit model of progressive chronic right ventricular pressure overload.

OBJECTIVES: Right ventricular (RV) failure from increased pressure loading is a frequent consequence of acquired and congenital heart diseases. However, the mechanisms involved in their pathophysiology are still unclear, and few data exist on RV pressure-loading models and early versus late effects on RV and left ventricular responses. We characterized a rabbit model of chronic RV pressure overload and early-late effects on biventricular function. METHODS: Twenty-one New Zealand white rabbits were randomized into 3 groups: (i) sham, (ii) pulmonary artery (PA) banding (PAB) for 3 weeks (PAB3W) and (iii) PAB for 6 weeks (PAB6W). Progressive RV pressure overload was created by serial band inflation using an adjustable device. Molecular, echocardiographic and haemodynamic studies were performed. RESULTS: RV pressure overload was achieved with clinical manifestations of RV failure. Heart and liver weights were significantly higher after PAB. PAB-induced echocardiographic ventricular remodelling increased wall thickness and stress and ventricular dilation. Cardiac output (ml/min) (sham 172.4 ± 42.86 vs PAB3W 103.1 ± 23.14 vs PAB6W 144 ± 60.9, P = 0.0027) and systolic and diastolic functions decreased; with increased RV end-systolic and end-diastolic pressures (mmHg) (sham 1.6 ± 0.66 vs PAB3W 3.9 ± 1.8 vs PAB6W 5.2 ± 2.2, P = 0.0103), despite increased contractility [end-systolic pressure-volume relationship (mmHg/ml), sham 3.76 ± 1.76 vs PAB3W 12.21 ± 3.44 vs PAB6W 19.4 ± 6.88, P < 0.0001]. Functional parameters further worsened after PAB6W versus PAB3W. LV contractility increased in both the PAB groups, despite worsening of other invasive measures of systolic and diastolic functions. CONCLUSIONS: We describe a novel, unique model of chronic RV pressure overload leading to early biventricular dysfunction and fibrosis with further progression at 6 weeks. These findings can aid in guiding management.

Oral etoposide in Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a very infrequent and aggressive skin tumor with high recurrence and metastasis rates. MCC treatment is currently not well defined. CASE PRESENTATION: We present the case of a 75-year-old woman who was diagnosed with MCC in 2010 and suffered a third relapse in 2012 which could not be treated surgically. RESULTS: The patient began oral etoposide treatment reaching complete response after eight cycles and receiving a total of 11 cycles. As side effects, the patient suffered from neutropenia, candidiasis and mucositis, but after reducing the dosage to 50% it was well tolerated. DISCUSSION: Chemotherapy treatment in this setting is poorly defined. In this case, monotherapy treatment with oral etoposide was decided due to the patient's age and comorbidities, achieving a very positive outcome.

A review of organic UV-filters in wastewater treatment plants.

UV-filters are a group of compounds which have been massively used in the past years due to the recent concerns with sunburns, premature skin ageing and the risk of developing skin cancer, related to sun exposure. At the moment, these compounds have been identified by the scientific community as emerging pollutants, due to their persistence in the environment, potential to accumulate in biota and potential threat as endocrine disruptors. At some point, the majority of sunscreens will find their way into wastewater (due to bathing and washing activities) and because wastewater treatment plants (WWTPs) are not able to remove and/or degrade them, consequently they find their way into rivers, lakes and ocean, so it is not surprising that UV-filters are found in the environment. Therefore, wastewater treatment plants should be the focus of the scientific community aiming to better understand the fate of the UV-filters and develop new technologies to remove them from wastewater and sludge. This review, aims to provide the current state of the art in the occurrence and fate of UV-filters in wastewater treatment plants and how the technologies that are being used are successfully removing these compounds from both wastewater and sludge.

Toxic epidermal necrolysis: the experience of Coimbra's burn unit.

INTRODUCTION: Toxic Epidermal Necrolysis is a drug-induced life-threatening systemic disease, characterized by extensive dermoepidermal detachment and mucositis. At least 95% of cases are believed to be drug-induced. SCORTEN is a scoring system used to stratify severity and predict mortality. Treatment demands immediate withdrawal of the causative drug and early transfer to a burn centre for specific and intensive care. MATERIAL AND METHODS: Authors have performed a retrospective study of 21 consecutive patients with SJS/ Toxic Epidermal Necrolysis admitted in the Burn Centre of Coimbra's University Hospital, between January 1999 and December 2010, and have compared the actual mortality rate with that predicted by SCORTEN, in order to assess the predictive capacity of SCORTEN. Analysis of results and treatment options were conducted. Data were analysed in SPSS 17.0®. RESULTS: Thirteen females (61.9%) and 8 males (38.1%) were treated, mean age 55.6 ± 23.7 years and with a mean of 51% ± 22.4% epidermal detachment. The overall observed mortality rate was 47.6% and the one predicted by SCORTEN 42.2%. Immediate withdrawal of the causative drug and early transfer of the patient to our burn centre were the basis of treatment. CONCLUSION: Toxic Epidermal Necrolysis pathophysiology remains to be clarified and no specific treatment has unequivocally proven to be effective. SCORTEN seems to be an accurate scoring system for estimation of mortality rate.

Introdução: A necrólise epidérmica tóxica é uma doença sistémica grave, potencialmente fatal, caracterizada por febre, descolamento dermoepidérmico extenso e erosão das mucosas. Em 95% dos casos, consiste numa reacção idiossincrática à administração de fármacos. A gravidade da doença é estratificada através da aplicação de uma escala de previsão da mortalidade, denominada SCORTEN. O tratamento obriga à suspensão imediata do fármaco suspeito e à referenciação do doente a uma Unidade de Queimados capaz de assegurar um tratamento específico.Material e Métodos: Estudo retrospectivo de 21 doentes internados com SJS/ Necrólise Epidérmica Tóxica na Unidade de Queimados dos Hospitais da Universidade de Coimbra, entre Janeiro de 1999 e Dezembro de 2010 com avaliação dos resultados e das opções terapêuticas. Comparação das taxas de mortalidade desses doentes com as previstas pelo SCORTEN, no sentido de avaliar a capacidade preditiva desta escala. Os dados foram analisados no programa SPSS 17.0®.Resultados: Foram internados 13 doentes do sexo feminino (61,9%) e 8 do sexo masculino (38,1%), com média de idades de 55,6 ± 23,7 anos e com 51% ± 22,4% de superfície corporal atingida. A taxa de mortalidade dos doentes internados foi de 47,6% e a prevista pelo SCORTEN foi de 42,2%. %. O tratamento instituído centrou-se na remoção imediata do fármaco suspeito e na referenciação precoce do doente para a unidade.Conclusão: A fisiopatologia da necrólise epidérmica tóxica não está completamente esclarecida, pelo que não existe actualmente uma terapêutica específica, comprovadamente eficaz. A utilização do SCORTEN permite uma previsão adequada da taxa de mortalidade nestes doentes.