Associations of baroreflex sensitivity, heart rate variability, and initial orthostatic hypotension with prenatal and recent postnatal methylmercury exposure in the Seychelles Child Development Study at age 19 years.

BACKGROUND: A few studies have suggested an association between prenatal exposure to methylmercury and decreased heart rate variability (HRV) related to autonomic heart function, but no study has examined this association using baroreflex sensitivity (BRS). In this study we assessed the distribution of BRS and immediate orthostatic hypotension (IOH) in young Seychellois adults and their associations with exposure to prenatal and recent postnatal methylmercury. METHODS: Subjects in the Seychelles Child Development Study (SCDS) main cohort were evaluated at age 19 years. Non-invasive beat-to-beat blood pressure (BP) monitoring (Finapres, Ohmeda) was performed at rest and during active standing in 95 consecutive subjects. Recent postnatal mercury exposure was measured in subjects' hair at the age of 19 years and prenatal exposure in maternal hair grown during pregnancy. BRS was estimated by sequence analysis to identify spontaneous ascending and descending BP ramps. HRV was estimated by the following markers: PNN50 (relative numbers of normal-to-normal intervals which are shorter by more than 50 ms than the immediately following normal-to-normal intervals); rMSSD (root mean of the squared sum of successive interval differences); LF/HF (low frequency/high frequency component ratio); ratio of the mean expiratory/inspiratory RR intervals (EI ratio); and the ratio between the longest RR interval 30 s after active standing and the shortest RR interval at 15 s (Max30/Min15). IOH was estimated by the deepest BP fall within the first 15 s after active standing up. RESULTS: Prenatal MeHg exposures were similar in boys and girls (6.7±4.3, 6.7±3.8 ng/g) but recent postnatal mercury levels were higher in males than females (11.2±5.8 vs 7.9±4.3 ng/g, p=0.003). Markers of autonomic heart rate control were within the normal range (BRS: 24.8±7 ms/mm Hg, PNN50: 24.9±6.8%, rMSSD: 68±22, LF/HF: 0.61±0.28) in both sexes. After standing, 51.4% of subjects had a transient systolic BP drop>40 mm Hg, but only 5.3% reported dizziness or had syncope. Prenatal and recent postnatal MeHg levels, overall, were not associated with BRS, E/I ratio, PNN50, rMSSD, LF/HF ratio, Max30/Min15 ratio, and IOH. CONCLUSIONS: This study provides no support for the hypothesis that prenatal or recent postnatal MeHg exposure from fish consumption is associated with impaired autonomic heart rate control.

Dysfunctional SEMA3E signaling underlies gonadotropin-releasing hormone neuron deficiency in Kallmann syndrome.

Individuals with an inherited deficiency in gonadotropin-releasing hormone (GnRH) have impaired sexual reproduction. Previous genetic linkage studies and sequencing of plausible gene candidates have identified mutations associated with inherited GnRH deficiency, but the small number of affected families and limited success in validating candidates have impeded genetic diagnoses for most patients. Using a combination of exome sequencing and computational modeling, we have identified a shared point mutation in semaphorin 3E (SEMA3E) in 2 brothers with Kallmann syndrome (KS), which causes inherited GnRH deficiency. Recombinant wild-type SEMA3E protected maturing GnRH neurons from cell death by triggering a plexin D1-dependent (PLXND1-dependent) activation of PI3K-mediated survival signaling. In contrast, recombinant SEMA3E carrying the KS-associated mutation did not protect GnRH neurons from death. In murine models, lack of either SEMA3E or PLXND1 increased apoptosis of GnRH neurons in the developing brain, reducing innervation of the adult median eminence by GnRH-positive neurites. GnRH neuron deficiency in male mice was accompanied by impaired testes growth, a characteristic feature of KS. Together, these results identify SEMA3E as an essential gene for GnRH neuron development, uncover a neurotrophic function for SEMA3E in the developing brain, and elucidate SEMA3E/PLXND1/PI3K signaling as a mechanism that prevents GnRH neuron deficiency.

Climate change impacts on lakes: an integrated ecological perspective based on a multi-faceted approach, with special focus on shallow lakes

Freshwater ecosystems and their biodiversity are presently seriously threatened by global development and population growth, leading to increases in nutrient inputs and intensification of eutrophication-induced problems in receiving fresh waters, particularly in lakes. Climate change constitutes another threat exacerbating the symptoms of eutrophication and species migration and loss. Unequivocal evidence of climate change impacts is still highly fragmented despite the intensive research, in part due to the variety and uncertainty of climate models and underlying emission scenarios but also due to the different approaches applied to study its effects. We first describe the strengths and weaknesses of the multi-faceted approaches that are presently available for elucidating the effects of climate change in lakes, including space-for-time substitution, time series, experiments, palaeoecology and modelling. Reviewing combined results from studies based on the various approaches, we describe the likely effects of climate changes on biological communities, trophic dynamics and the ecological state of lakes. We further discuss potential mitigation and adaptation measures to counteract the effects of climate change on lakes and, finally, we highlight some of the future challenges that we face to improve our capacity for successful prediction.

Resilience and unmet supportive care needs in patients with cancer during early treatment: A descriptive study.

PURPOSE: The concept of resilience is gaining increasing importance as a key component of supportive care but to date has rarely been addressed in studies with adult cancer patients. The purpose of our study was to describe resilience and its potential predictors and supportive care needs in cancer patients during early treatment and to explore associations between both concepts. METHODS: This descriptive study included adult cancer patients under treatment in ambulatory cancer services of a Swiss hospital. Subjects completed the 25-item Connor-Davidson-Resilience Scale and the 34-item Supportive Care Needs Survey. Descriptive, correlational and regression analysis were performed. RESULTS: 68 patients with cancer were included in the study. Compared to general population, resilience scores were significantly lower (74.4 ± 12.6 vs. 80.4 ± 12.8, p = .0002). Multiple regression analysis showed predictors ("age", "metastasis", "recurrence" and "living alone") of resilience (adjusted R2 = .19, p < .001). Highest unmet needs were observed in the domain of psychological needs. Lower resilience scores were significantly and strongly associated with higher levels of unmet psychological needs (Rho = -.68, p < .001), supportive care needs (Rho = -.49, p < .001) and information needs (Rho = -.42, p = .001). CONCLUSION: Ambulatory patients with higher levels of resilience express fewer unmet needs. Further work is needed to elucidate the mechanism of the observed relationships and if interventions facilitating resilience have a positive effect on unmet needs.

The Interplay between NF-kappaB and E2F1 Coordinately Regulates Inflammation and Metabolism in Human Cardiac Cells

Pyruvate dehydrogenase kinase 4 (PDK4) inhibition by nuclear factor-κB (NF-κB) is related to a shift towards increased glycolysis during cardiac pathological processes such as cardiac hypertrophy and heart failure. The transcription factors estrogen-related receptor-α (ERRα) and peroxisome proliferator-activated receptor (PPAR) regulate PDK4 expression through the potent transcriptional coactivator PPARγ coactivator-1α (PGC-1α). NF-κB activation in AC16 cardiac cells inhibit ERRα and PPARβ/δ transcriptional activity, resulting in reduced PGC-1α and PDK4 expression, and an enhanced glucose oxidation rate. However, addition of the NF-κB inhibitor parthenolide to these cells prevents the downregulation of PDK4 expression but not ERRα and PPARβ/δ DNA binding activity, thus suggesting that additional transcription factors are regulating PDK4. Interestingly, a recent study has demonstrated that the transcription factor E2F1, which is crucial for cell cycle control, may regulate PDK4 expression. Given that NF-κB may antagonize the transcriptional activity of E2F1 in cardiac myocytes, we sought to study whether inflammatory processes driven by NF-κB can downregulate PDK4 expression in human cardiac AC16 cells through E2F1 inhibition. Protein coimmunoprecipitation indicated that PDK4 downregulation entailed enhanced physical interaction between the p65 subunit of NF-κB and E2F1. Chromatin immunoprecipitation analyses demonstrated that p65 translocation into the nucleus prevented the recruitment of E2F1 to the PDK4 promoter and its subsequent E2F1-dependent gene transcription. Interestingly, the NF-κB inhibitor parthenolide prevented the inhibition of E2F1, while E2F1 overexpression reduced interleukin expression in stimulated cardiac cells. Based on these findings, we propose that NF-κB acts as a molecular switch that regulates E2F1-dependent PDK4 gene transcription.

Methylmercury exposure and developmental neurotoxicity

Comment on: Global methylmercury exposure from seafood consumption and risk of developmental neurotoxicity: a systematic review. [Bull World Health Organ. 2014]

Mercury analysis in hair: comparability and quality assessment within the transnational COPHES/DEMOCOPHES project

Human biomonitoring (HBM) is an effective tool for assessing actual exposure to chemicals that takes into account all routes of intake. Although hair analysis is considered to be an optimal biomarker for assessing mercury exposure, the lack of harmonization as regards sampling and analytical procedures has often limited the comparison of data at national and international level. The European-funded projects COPHES and DEMOCOPHES developed and tested a harmonized European approach to Human Biomonitoring in response to the European Environment and Health Action Plan. Herein we describe the quality assurance program (QAP) for assessing mercury levels in hair samples from more than 1800 mother-child pairs recruited in 17 European countries. To ensure the comparability of the results, standard operating procedures (SOPs) for sampling and for mercury analysis were drafted and distributed to participating laboratories. Training sessions were organized for field workers and four external quality-assessment exercises (ICI/EQUAS), followed by the corresponding web conferences, were organized between March 2011 and February 2012. ICI/EQUAS used native hair samples at two mercury concentration ranges (0.20-0.71 and 0.80-1.63) per exercise. The results revealed relative standard deviations of 7.87-13.55% and 4.04-11.31% for the low and high mercury concentration ranges, respectively. A total of 16 out of 18 participating laboratories the QAP requirements and were allowed to analyze samples from the DEMOCOPHES pilot study. Web conferences after each ICI/EQUAS revealed this to be a new and effective tool for improving analytical performance and increasing capacity building. The procedure developed and tested in COPHES/DEMOCOPHES would be optimal for application on a global scale as regards implementation of the Minamata Convention on Mercury.

Utilização do índice de resistência vascular na diferenciação entre nódulos mamários benignos e malignos

OBJETIVO: O objetivo deste estudo foi avaliar o significado do Doppler espectral por meio da obtenção do índice de resistência vascular na diferenciação entre lesões mamárias benignas e malignas. MATERIAIS E MÉTODOS: Dezenove lesões malignas e 18 benignas, diagnosticadas por estudo histológico, foram submetidas previamente a análise de sua vascularização por meio do Doppler espectral para se obter o índice de resistência vascular. RESULTADOS: Observou-se diferença estatisticamente significante (p < 0,001) entre os valores médios do índice de resistência para os resultados benigno e maligno (0,62x 0,80, respectivamente), em nódulos maiores que 1 cm. Um índice de resistência 0,69 foi altamente associado a lesões malignas, com sensibilidade de 84,2%, especificidade de 88,9%, taxa de falso-positivo de 11,1% e taxa de falso-negativo de 15,8%. CONCLUSÃO: A análise do índice de resistência vascular pode fornecer grande auxílio na avaliação das lesões nodulares da mama maiores que 1 cm, em conjunto com as informações obtidas por meio da escala de cinzas, com elevada sensibilidade e especificidade.

Morbidade da biópsia da próstata transretal guiada por ultrassonografia

OBJETIVO: Avaliar a incidência de complicações pós-procedimento nos pacientes submetidos a biópsia prostática transretal guiada por ultrassom no setor de intervenção do Departamento de Diagnóstico por Imagem da Escola Paulista de Medicina - Universidade Federal de São Paulo. MATERIAIS E MÉTODOS: Foram avaliados, via contato telefônico, 132 pacientes submetidos a biópsia de próstata transretal guiada por ultrassom no período de abril/2011 a junho/2011, seguindo o protocolo padrão do nosso setor. RESULTADOS: As complicações pós-biópsia foram categorizadas em maiores e menores de acordo com a necessidade de avaliação médica adicional. Cinquenta e nove pacientes (61,8%) apresentaram complicações, e desses, grande parte (86,4%) apresentou sintomas leves e autolimitados, considerados menores. Oito pacientes (8,2%) apresentaram complicações maiores, sendo que apenas um deles necessitou de tratamento sob regime de internação hospitalar. A retenção urinária foi a complicação maior mais incidente no nosso estudo. CONCLUSÃO: Corroborando outros estudos da literatura, nosso trabalho demonstrou baixa prevalência de complicações maiores após a biópsia prostática transretal.

Laryngeal schwannoma: a case report with emphasis on sonographic findings

Schwannomas are benign nerve sheath tumors composed of Schwann cells, which normally produce the insulating myelin sheath covering peripheral, cranial and autonomic nerves. Twenty-five to forty-five percent of all schwannomas occur in the head and neck region, but location of such tumors in the larynx is rarely observed. The present report is aimed at describing a clinical case of laryngeal schwannoma, with emphasis on sonographic findings.

Radioterapia de intensidade modulada (IMRT) para pacientes do SUS: análise de 508 tratamentos em dois anos de instalação da técnica

Objetivo: A oferta de radioterapia de alta tecnologia para população atendida pelo Sistema Único de Saúde (SUS) é limitada, por não pertencer ao rol de procedimentos e, muitas vezes, pela capacidade instalada frente à demanda e dificuldade de retenção de recursos humanos especializados. Dessa forma, o acesso à radioterapia de intensidade modulada (IMRT) é restrito a poucos serviços no Brasil. Pretendemos apresentar as características dos primeiros 508 tratamentos de IMRT durante os primeiros anos de instalação da técnica em um hospital universitário. Materiais e Métodos: Foram analisados 508 tratamentos de IMRT, de maio de 2011 a setembro de 2013, que completaram a radioterapia. A técnica empregada foi multilâminas estático. Resultados: De um total de 4.233 pacientes tratados no período, 12,5% realizaram IMRT. As principais indicações foram para crânio, cabeça e pescoço, e próstata. Aproximadamente 30% das radioterapias de crânio e 50% das de próstata foram por IMRT. A toxicidade total foi 4%. Conclusão: Em razão das restrições de acesso à radioterapia e da não cobertura deste procedimento, as indicações de IMRT para pacientes do SUS devem ser apoiadas nos protocolos clínicos das instituições em acordo com sua realidade, com especial atenção à redução da toxicidade.

Landslide detection and monitoring capability of boat-based mobile laser scanning along Dieppe coastal cliffs, Normandy

Integrated in a wide research assessing destabilizing and triggering factors to model cliff dynamic along the Dieppe's shoreline in High Normandy, this study aims at testing boat-based mobile LiDAR capabilities by scanning 3D point clouds of the unstable coastal cliffs. Two acquisition campaigns were performed in September 2012 and September 2013, scanning (1) a 30-km-long shoreline and (2) the same test cliffs in different environmental conditions and device settings. The potentials of collected data for 3D modelling, change detection and landslide monitoring were afterward assessed. By scanning during favourable meteorological and marine conditions and close to the coast, mobile LiDAR devices are able to quickly scan a long shoreline with median point spacing up to 10cm. The acquired data are then sufficiently detailed to map geomorphological features smaller than 0.5m2. Furthermore, our capability to detect rockfalls and erosion deposits (>m3) is confirmed, since using the classical approach of computing differences between sequential acquisitions reveals many cliff collapses between Pourville and Quiberville and only sparse changes between Dieppe and Belleville-sur-Mer. These different change rates result from different rockfall susceptibilities. Finally, we also confirmed the capability of the boat-based mobile LiDAR technique to monitor single large changes, characterizing the Dieppe landslide geometry with two main active scarps, retrogression up to 40m and about 100,000m3 of eroded materials.