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1.
Gastrointest Endosc ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38777277

RESUMO

BACKGROUND AND AIMS: Juvenile Polyposis Syndrome (JPS) is a rare hereditary autosomal dominant cancer-predisposition syndrome caused by germline pathogenic variants (PV) located in SMAD4 or BMPR1A genes. Precise clinical and endoscopic presentation as the evolution of gastric lesions remain ill-known. METHODS: Clinical, endoscopic, genetic, pathological data from patients with SMAD4 or BMPR1A PVs included between 2007 and 2020 in the French network on rare digestive polyposis (RENAPOL) database were prospectively collected to address uncertainties regarding gastric involvement. RESULTS: Thirty-six patients were included: 25 (69.5%) had SMAD4 PVs, 11 had BMPR1A PVs. For SMAD4 PV carriers, median age at inclusion was 43.0 years [range 10-78]. At baseline esophagogastroduodenoscopy (EGD), 22/25 (88%) exhibited at least one gastric juvenile polyp, 5/25 (20%) had macroscopic signs of inflammatory gastritis. Early gastric disease was mostly located under the cardia, then progressed to gastric antrum and body. During a mean follow-up period of 55.0 months, 12/25 had gastric disease progression (i.e. new juvenile polyps (91.6%), diffuse gastric involvement (41.6%), inflammatory flat progression (25%)). Among 62 biopsies, low-grade dysplasia was observed in 5 (7.5%) samples from 2 patients. Nine carriers (36%) underwent gastrectomy (mean age of 47.2 years) due to diffuse gastric involvement or worsening clinical symptoms. Gastric adenocarcinoma (T1) was found in one gastrectomy specimen. Among the 11 patients with BMPR1A PVs, 2 had gastric hamartomatomas at baseline EGD, none with dysplasia or symptoms. CONCLUSION: Gastric involvement in JPS appears to be progressive during life, initiating in the cardia area, and mostly concerns SMAD4 PV carriers.

2.
Anaesthesia ; 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38789407

RESUMO

BACKGROUND: It is not certain whether the blade geometry of videolaryngoscopes, either a hyperangulated or Macintosh shape, affects glottic view, success rate and/or tracheal intubation time in patients with expected difficult airways. We hypothesised that using a hyperangulated videolaryngoscope blade would visualise a higher percentage of glottic opening compared with a Macintosh videolaryngoscope blade in patients with expected difficult airways. METHODS: We conducted an open-label, patient-blinded, randomised controlled trial in adult patients scheduled to undergo elective ear, nose and throat or oral and maxillofacial surgery, who were anticipated to have a difficult airway. All airway operators were consultant anaesthetists. Patients were allocated randomly to tracheal intubation with either hyperangulated (C-MAC D-BLADE™) or Macintosh videolaryngoscope blades (C-MAC™). The primary outcome was the percentage of glottic opening. First attempt success was designated a key secondary outcome. RESULTS: We assessed 2540 adults scheduled for elective head and neck surgery for eligibility and included 182 patients with expected difficult airways undergoing orotracheal intubation. The percentage of glottic opening visualised, expressed as median (IQR [range]), was 89 (69-99 [0-100])% with hyperangulated videolaryngoscope blades and 54 (9-90 [0-100])% with Macintosh videolaryngoscope blades (p < 0.001). First-line hyperangulated videolaryngoscopy failed in one patient and Macintosh videolaryngoscopy in 12 patients (13%, p = 0.002). First attempt success rate was 97% with hyperangulated videolaryngoscope blades and 67% with Macintosh videolaryngoscope blades (p < 0.001). CONCLUSIONS: Glottic view and first attempt success rate were superior with hyperangulated videolaryngoscope blades compared with Macintosh videolaryngoscope blades when used by experienced anaesthetists in patients with difficult airways.

3.
BMC Biol ; 21(1): 164, 2023 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-37525144

RESUMO

BACKGROUND: Individual functional modifications shape the ability of wildlife populations to cope with anthropogenic environmental changes. But instead of adaptive response, human-altered environments can generate a succession of deleterious functional changes leading to the extinction of the population. To study how persistent anthropogenic changes impacted local species' population status, we characterised population structure, genetic diversity and individual response of gene expression in the tree frog Hyla orientalis along a gradient of radioactive contamination around the Chernobyl nuclear power plant. RESULTS: We detected lower effective population size in populations most exposed to ionizing radiation in the Chernobyl Exclusion Zone that is not compensated by migrations from surrounding areas. We also highlighted a decreased body condition of frogs living in the most contaminated area, a distinctive transcriptomics signature and stop-gained mutations in genes involved in energy metabolism. While the association with dose will remain correlational until further experiments, a body of evidence suggests the direct or indirect involvement of radiation exposure in these changes. CONCLUSIONS: Despite ongoing migration and lower total dose rates absorbed than at the time of the accident, our results demonstrate that Hyla orientalis specimens living in the Chernobyl Exclusion Zone are still undergoing deleterious changes, emphasizing the long-term impacts of the nuclear disaster.


Assuntos
Acidente Nuclear de Chernobyl , Animais , Humanos , Densidade Demográfica , Animais Selvagens , Radiação Ionizante , Anuros/genética
4.
J Ultrasound Med ; 42(2): 309-344, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35993596

RESUMO

Following the innovations and new discoveries of the last 10 years in the field of lung ultrasound (LUS), a multidisciplinary panel of international LUS experts from six countries and from different fields (clinical and technical) reviewed and updated the original international consensus for point-of-care LUS, dated 2012. As a result, a total of 20 statements have been produced. Each statement is complemented by guidelines and future developments proposals. The statements are furthermore classified based on their nature as technical (5), clinical (11), educational (3), and safety (1) statements.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Consenso , Pulmão/diagnóstico por imagem , Testes Imediatos , Ultrassonografia
5.
Proc Natl Acad Sci U S A ; 117(12): 6866-6874, 2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-32161130

RESUMO

Increasing evidence suggests that amyloid polymorphism gives rise to different strains of amyloids with distinct toxicities and pathology-spreading properties. Validating this hypothesis is challenging due to a lack of tools and methods that allow for the direct characterization of amyloid polymorphism in hydrated and complex biological samples. Here, we report on the development of 11-mercapto-1-undecanesulfonate-coated gold nanoparticles (NPs) that efficiently label the edges of synthetic, recombinant, and native amyloid fibrils derived from different amyloidogenic proteins. We demonstrate that these NPs represent powerful tools for assessing amyloid morphological polymorphism, using cryogenic transmission electron microscopy (cryo-EM). The NPs allowed for the visualization of morphological features that are not directly observed using standard imaging techniques, including transmission electron microscopy with use of the negative stain or cryo-EM imaging. The use of these NPs to label native paired helical filaments (PHFs) from the postmortem brain of a patient with Alzheimer's disease, as well as amyloid fibrils extracted from the heart tissue of a patient suffering from systemic amyloid light-chain amyloidosis, revealed a high degree of homogeneity across the fibrils derived from human tissue in comparison with fibrils aggregated in vitro. These findings are consistent with, and strongly support, the emerging view that the physiologic milieu is a key determinant of amyloid fibril strains. Together, these advances should not only facilitate the profiling and characterization of amyloids for structural studies by cryo-EM, but also pave the way to elucidate the structural basis of amyloid strains and toxicity, and possibly the correlation between the pathological and clinical heterogeneity of amyloid diseases.


Assuntos
Amiloide/genética , Amiloide/metabolismo , Encéfalo/metabolismo , Microscopia Crioeletrônica/métodos , Ouro/química , Nanopartículas Metálicas/química , Polimorfismo Genético , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Amiloide/química , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/genética , Amiloidose de Cadeia Leve de Imunoglobulina/metabolismo , Amiloidose de Cadeia Leve de Imunoglobulina/patologia , Emaranhados Neurofibrilares
7.
Rev Med Suisse ; 19(834): 1306-1310, 2023 Jul 05.
Artigo em Francês | MEDLINE | ID: mdl-37403952

RESUMO

As a result of the Ukraine conflict, more than 6.3 million refugees had to flee to neighbouring countries, among them the Republic of Moldova (RoM), triggering a social and humanitarian crisis. From our assessment of the general health situation and upon request of the RoM Ministry of Health, Swiss Humanitarian Aid module "mother and child" has been deployed to refugee transit centres to deliver primary health care of mothers and children. Due to the specific refugee population consisting mainly of mothers and children, the module showed to be very beneficial, extremely flexible and was highly appreciated. Simultaneously, strategic hospitals were revisited for contingency planning, but also in view of logistical support. We organized a "train the trainer" course together with the National Centre of pre-hospital assistance.


En raison du conflit en Ukraine, plus de 6,3 millions de réfugiés ont dû fuir vers les pays voisins, dont la Moldavie, déclenchant une crise sociale et humanitaire. Sur la base de notre évaluation et à la demande du ministère de la Santé de Moldavie, le module « Mère-Enfant ¼ de l'Aide humanitaire suisse a été déployé dans les centres de transit pour réfugiés afin de fournir des soins de santé primaires aux mères et aux enfants. La population spécifique de réfugiés étant composée principalement de mères et d'enfants, le module s'est avéré très bénéfique, flexible et très apprécié. Dans le même temps, les hôpitaux stratégiques ont été revisités pour la planification d'urgence, mais aussi pour le soutien logistique. Nous avons organisé des « formations des formateurs ¼ en collaboration avec le Centre national d'assistance préhospitalière.


Assuntos
Refugiados , Socorro em Desastres , Feminino , Criança , Humanos , Mães , Moldávia , Suíça , Etnicidade
8.
Adv Exp Med Biol ; 1364: 177-196, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35508876

RESUMO

Recent advances in imaging of bone microstructure have led to a growing recognition of the role of cortical microstructure in osteoporosis. It is now accepted that the assessment of the microstructure of cortical porosity is essential to assess bone mechanical competence and predict fracture risk. Cortical porosity affects the propagation of ultrasound waves because pores act as ultrasound scatterers. Scattering by the porosity is an opportunity that should be leveraged to extract quantitative information about cortical microstructure. Scattering by the pores affects a number of ultrasound parameters that should be quantified, including attenuation, backscatter coefficient, ultrasound diffusivity, and their frequency dependence. Measuring these ultrasound parameters and developing models that describe their dependence upon parameters of cortical microstructure is the key to solve inverse problems that will allow the quantitative assessment of cortical porosity and ultimately will improve the non-invasive ultrasound-based evaluation of bone mechanical competence and fracture risk. In this chapter, we present recent advances in measuring and modeling those parameters in cortical bone.


Assuntos
Fraturas Ósseas , Osteoporose , Densidade Óssea , Osso e Ossos/diagnóstico por imagem , Osso Cortical/diagnóstico por imagem , Fraturas Ósseas/diagnóstico por imagem , Humanos , Osteoporose/diagnóstico por imagem , Porosidade , Ultrassonografia
9.
Vet Res ; 52(1): 56, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33853678

RESUMO

ELISA methods are the diagnostic tools recommended for the serological diagnosis of Coxiella burnetii infection in ruminants but their respective diagnostic performances are difficult to assess because of the absence of a gold standard. This study focused on three commercial ELISA tests with the following objectives (1) assess their sensitivity and specificity in sheep, goats and cattle, (2) assess the between- and within-herd seroprevalence distribution in these species, accounting for diagnostic errors, and (3) estimate optimal sample sizes considering sensitivity and specificity at herd level. We comparatively tested 1413 cattle, 1474 goat and 1432 sheep serum samples collected in France. We analyzed the cross-classified test results with a hierarchical zero-inflated beta-binomial latent class model considering each herd as a population and conditional dependence as a fixed effect. Potential biases and coverage probabilities of the model were assessed by simulation. Conditional dependence for truly seropositive animals was high in all species for two of the three ELISA methods. Specificity estimates were high, ranging from 94.8% [92.1; 97.8] to 99.2% [98.5; 99.7], whereas sensitivity estimates were generally low, ranging from 39.3 [30.7; 47.0] to 90.5% [83.3; 93.8]. Between- and within-herd seroprevalence estimates varied greatly among geographic areas and herds. Overall, goats showed higher within-herd seroprevalence levels than sheep and cattle. The optimal sample size maximizing both herd sensitivity and herd specificity varied from 3 to at least 20 animals depending on the test and ruminant species. This study provides better interpretation of three widely used commercial ELISA tests and will make it possible to optimize their implementation in future studies. The methodology developed may likewise be applied to other human or animal diseases.


Assuntos
Doenças dos Bovinos/diagnóstico , Coxiella burnetii/isolamento & purificação , Ensaio de Imunoadsorção Enzimática/veterinária , Doenças das Cabras/diagnóstico , Febre Q/veterinária , Doenças dos Ovinos/diagnóstico , Animais , Bovinos , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/microbiologia , Feminino , França/epidemiologia , Doenças das Cabras/epidemiologia , Doenças das Cabras/microbiologia , Cabras , Análise de Classes Latentes , Prevalência , Febre Q/diagnóstico , Febre Q/epidemiologia , Febre Q/microbiologia , Estudos Soroepidemiológicos , Ovinos , Doenças dos Ovinos/epidemiologia , Doenças dos Ovinos/microbiologia , Carneiro Doméstico
10.
J Acoust Soc Am ; 150(6): 4151, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34972307

RESUMO

The potential of lung ultrasound (LUS) has become manifest in the light of the recent COVID-19 pandemic. The need for a point-of care, quantitative, and widely available assessment of lung condition is critical. However, conventional ultrasound imaging was never designed for lung assessment. This limits LUS to the subjective and qualitative interpretation of artifacts and imaging patterns visible on ultrasound images. A number of research groups have begun to tackle this limitation, and this special issue reports on their most recent findings. Through in silico, in vitro, and in vivo studies (preclinical animal studies and pilot clinical studies on human subjects), the research presented aims at understanding and modelling the physical phenomena involved in ultrasound propagation, and at leveraging these phenomena to extract semi-quantitative and quantitative information relevant to estimate changes in lung structure. These studies are the first steps in unlocking the full potential of lung ultrasound as a relevant tool for lung assessment.


Assuntos
COVID-19 , Pandemias , Humanos , Pulmão/diagnóstico por imagem , SARS-CoV-2 , Ultrassonografia
11.
J Acoust Soc Am ; 150(6): 4095, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34972282

RESUMO

Although X-Ray Computed Tomography (CT) is widely used for detecting pulmonary nodules inside the parenchyma, it cannot be used during video-assisted surgical procedures. Real-time, non-ionizing, ultrasound-based techniques are an attractive alternative for nodule localization to ensure safe resection margins during surgery. Conventional ultrasound B-mode imaging of the lung is challenging due to multiple scattering. However, the multiple scattering contribution can be exploited to detect regions inside the lung containing no scatterers. Pulmonary nodules are homogeneous regions in contrast to the highly scattering parenchyma containing millions of air-filled alveoli. We developed a method relying on mapping the multiple scattering contribution inside the highly scattering lung to detect and localize pulmonary nodules. Impulse response matrices were acquired in ex-vivo pig and dog lungs using a linear array transducer to semi-locally investigate the backscattered field. Extracting the multiple-scattering contribution using singular-value decomposition and combining it with a depression detection algorithm allowed us to detect and localize regions with less multiple scattering, associated with the nodules. The feasibility of this method was demonstrated in five ex-vivo lungs containing a total of 20 artificial nodules. Ninety-five percent of the nodules were detected. Nodule depth and diameter significantly correlated with their ex-vivo CT-estimated counterparts (R = 0.960, 0.563, respectively).


Assuntos
Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Animais , Cães , Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/cirurgia , Suínos , Cirurgia Torácica Vídeoassistida , Tomografia Computadorizada por Raios X/métodos
12.
J Acoust Soc Am ; 150(1): 183, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34340489

RESUMO

Quantitative ultrasound methods based on the backscatter coefficient (BSC) and envelope statistics have been used to quantify disease in a wide variety of tissues, such as prostate, lymph nodes, breast, and thyroid. However, to date, these methods have not been investigated in the lung. In this study, lung properties were quantified by BSC and envelope statistical parameters in normal, fibrotic, and edematous rat lungs in vivo. The average and standard deviation of each parameter were calculated for each lung as well as the evolution of each parameter with acoustic propagation time within the lung. The transport mean free path and backscattered frequency shift, two parameters that have been successfully used to assess pulmonary fibrosis and edema in prior work, were evaluated in combination with the BSC and envelope statistical parameters. Multiple BSC and envelope statistical parameters were found to provide contrast between control and diseased lungs. BSC and envelope statistical parameters were also significantly correlated with fibrosis severity using the modified Ashcroft fibrosis score as the histological gold standard. These results demonstrate the potential for BSC and envelope statistical parameters to improve the diagnosis of pulmonary fibrosis and edema as well as monitor pulmonary fibrosis.


Assuntos
Fibrose Pulmonar , Roedores , Animais , Edema , Pulmão/diagnóstico por imagem , Masculino , Fibrose Pulmonar/diagnóstico por imagem , Ratos , Ultrassonografia
13.
J Acoust Soc Am ; 150(6): 4118, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34972274

RESUMO

Ultrasound in point-of-care lung assessment is becoming increasingly relevant. This is further reinforced in the context of the COVID-19 pandemic, where rapid decisions on the lung state must be made for staging and monitoring purposes. The lung structural changes due to severe COVID-19 modify the way ultrasound propagates in the parenchyma. This is reflected by changes in the appearance of the lung ultrasound images. In abnormal lungs, vertical artifacts known as B-lines appear and can evolve into white lung patterns in the more severe cases. Currently, these artifacts are assessed by trained physicians, and the diagnosis is qualitative and operator dependent. In this article, an automatic segmentation method using a convolutional neural network is proposed to automatically stage the progression of the disease. 1863 B-mode images from 203 videos obtained from 14 asymptomatic individual,14 confirmed COVID-19 cases, and 4 suspected COVID-19 cases were used. Signs of lung damage, such as the presence and extent of B-lines and white lung areas, are manually segmented and scored from zero to three (most severe). These manually scored images are considered as ground truth. Different test-training strategies are evaluated in this study. The results shed light on the efficient approaches and common challenges associated with automatic segmentation methods.


Assuntos
COVID-19 , Humanos , Processamento de Imagem Assistida por Computador , Pulmão/diagnóstico por imagem , Pandemias , SARS-CoV-2 , Tomografia Computadorizada por Raios X
14.
Int J Mol Sci ; 22(16)2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34445335

RESUMO

Protein inhibition is a natural regulatory process to control cellular metabolic fluxes. PII-family signal-transducing effectors are in this matter key regulators of the nitrogen metabolism. Their interaction with their various targets is governed by the cellular nitrogen level and the energy charge. Structural studies on GlnK, a PII-family inhibitor of the ammonium transporters (Amt), showed that the T-loops responsible for channel obstruction are displaced upon the binding of 2-oxoglutarate, magnesium and ATP in a conserved cleft. However, GlnK from Methanocaldococcus jannaschii was shown to bind 2-oxoglutarate on the tip of its T-loop, causing a moderate disruption to GlnK-Amt interaction, raising the question if methanogenic archaea use a singular adaptive strategy. Here we show that membrane fractions of Methanothermococcus thermolithotrophicus released GlnKs only in the presence of Mg-ATP and 2-oxoglutarate. This observation led us to structurally characterize the two GlnK isoforms apo or in complex with ligands. Together, our results show that the 2-oxoglutarate binding interface is conserved in GlnKs from Methanococcales, including Methanocaldococcus jannaschii, emphasizing the importance of a free carboxy-terminal group to facilitate ligand binding and to provoke the shift of the T-loop positions.


Assuntos
Compostos de Amônio/metabolismo , Ácidos Cetoglutáricos/metabolismo , Methanococcales/metabolismo , Proteínas PII Reguladoras de Nitrogênio , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Sequência Conservada , Cristalografia por Raios X , Transporte de Íons , Redes e Vias Metabólicas , Modelos Moleculares , Nitrogênio/metabolismo , Proteínas PII Reguladoras de Nitrogênio/química , Proteínas PII Reguladoras de Nitrogênio/metabolismo , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas/fisiologia , Análise de Sequência de Proteína
15.
Br J Cancer ; 123(2): 288-297, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32424150

RESUMO

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) patients frequently develop treatment resistance to cetuximab, a monoclonal antibody against EGFR, as well as radiotherapy. Here we addressed extracellular signal-regulated kinase 1/2 (ERK1/2) regulation by cetuximab or fractionated irradiation (IR) and conducted in silico prognostic evaluation of the EGFR-MAPK axis in HNSCC. METHODS: Expression of ERK1/2 phosphorylation (pERK1/2) was determined in HNSCC cell lines, which were treated with cetuximab or fractionated-IR. Furthermore, the effect of fractionated IR on pERK1/2 was confirmed in an ex vivo HNSCC tissue culture model. Expression and prognostic significance of EGFR-ERK axis was evaluated in a cohort of radiotherapy plus cetuximab-treated HNSCC. Correlations among EGFR-MAPK signalling components and association between transcript and protein expression profiles and patient survival in HNSCC were analysed using publicly available databases. RESULTS: ERK1/2 phosphorylation was rebounded by prolonged cetuximab administration and was induced by fractionated IR, which could be suppressed by a MEK inhibitor as a radiosensitiser. In silico assessments suggested that EGFR-MAPK cascade genes and proteins could predict HNSCC patients' survival as a prognostic signature. CONCLUSIONS: Activation of ERK1/2 signalling contributes to the cellular defence of HNSCC against cetuximab and fractionated IR treatment. EGFR-MAPK axis has a prognostic significance in HNSCC.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Proteína Quinase 1 Ativada por Mitógeno/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Animais , Linhagem Celular Tumoral , Cetuximab/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Receptores ErbB/genética , Humanos , Proteínas de Insetos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Prognóstico , Inibidores de Proteínas Quinases/farmacologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Ecotoxicol Environ Saf ; 200: 110722, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32460047

RESUMO

Species Sensitivity Distributions (SSD) are widely used in environmental risk assessment to predict the concentration of a contaminant that is hazardous for 5% of species (HC5). They are based on monospecific bioassays conducted in the laboratory and thus do not directly take into account ecological interactions. This point, among others, is accounted for in environmental risk assessment through an assessment factor (AF) that is applied to compensate for the lack of environmental representativity. In this study, we aimed to assess the effects of interspecific competition on the responses towards isoproturon of plant species representative of a vegetated filter strip community, and to assess its impact on the derived SSD and HC5 values. To do so, we realized bioassays confronting six herbaceous species to a gradient of isoproturon exposure in presence and absence of a competitor. Several modelling approaches were applied to see how they affected the results, using different critical effect concentrations and investigating different ways to handle multiple endpoints in SSD. At the species level, there was a strong trend toward organisms being more sensitive to isoproturon in presence of a competitor than in its absence. At the community level, this trend was also observed in the SSDs and HC5 values were always lower in presence of a competitor (1.12-11.13 times lower, depending on the modelling approach). Our discussion questions the relevance of SSD and AF as currently applied in environmental risk assessment.


Assuntos
Fenômenos Fisiológicos Vegetais , Plantas/efeitos dos fármacos , Estresse Fisiológico , Bioensaio , Ecossistema , Compostos de Fenilureia/toxicidade , Medição de Risco
17.
Rev Med Suisse ; 16(709): 1881-1885, 2020 Oct 07.
Artigo em Francês | MEDLINE | ID: mdl-33026732

RESUMO

Prevalence of burnout in physicians is increasing, affecting their health and satisfaction at work as well as quality and security of healthcare. Several causes have been identified, of which growing intensity of work, loss of meaning and feeling that healthcare structure reforms prevent one's job being done properly are the main reasons. New data shows an association between burnout and use of the yet widespread electronic health record. It has a proven impact on the multiple aspects of physician's work, and users' satisfaction is often mediocre. Hence, among the broad prevention field of physicians' burnout, specific measures related to the digital domain are needed.


La prévalence du burnout chez les médecins est en augmentation, affectant leur santé, leur satisfaction au travail ainsi que la qualité et la sécurité des soins. Diverses causes sont identifiées, les principales étant l'intensification du travail, le sentiment de perte de sens du travail et de ne pas faire son travail correctement dans un environnement (celui des organisations de soins) en changement. Des données récentes montrent aussi une association entre burnout et utilisation du dossier médical informatisé, désormais largement répandue. La satisfaction des utilisateurs est souvent médiocre et l'impact sur de multiples facettes du travail des médecins avéré. À la lumière de ces résultats, des actions de prévention spécifiques sont nécessaires, à intégrer dans le champ plus vaste de la prévention du burnout des médecins.


Assuntos
Esgotamento Profissional , Registros Eletrônicos de Saúde , Satisfação no Emprego , Médicos/psicologia , Esgotamento Psicológico , Humanos
18.
Clin Genet ; 96(6): 579-584, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31432501

RESUMO

The rate of genetic diagnosis of French patients with familial pancreatic ductal adenocarcinoma (PDAC) is not known. We report germline genetic testing data from 133 index cases meeting criteria for familial pancreatic cancer (FPC) as well as 87 'FPC-like' index cases who did not fulfilled strict FPC definition but were evocative for a PDAC predisposition. The overall rate of genetic diagnosis (in BRCA1, BRCA2, CDKN2A, and ATM genes) was 8.3% in FPC patients and 4.6% in FPC-like patients, consistent with the literature in other populations. Genetic variants were also identified in FANCA and BAP1 genes, as well as in the CDKN2A p12 transcript. This pancreas-specific transcript is a known key player in driving pancreatic oncogenesis. This might be the first described case of a PDAC genetic predisposition due to a variant in this specific transcript.


Assuntos
Carcinoma/genética , Testes Genéticos , Células Germinativas/metabolismo , Neoplasias Pancreáticas/genética , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Adulto Jovem
19.
Breast J ; 25(1): 16-19, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30414230

RESUMO

BACKGROUND: Invasive lobular carcinoma (ILC) of the breast has epidemiological, molecular and clinical specificities, and should likely be considered a unique entity. As for genetic susceptibility, CDH1 germline mutations predispose exclusively to ILC. Data are however scarce regarding ILC in women with BRCA1/2 (Hereditary Breast and Ovarian Cancer) and TP53 (Li-Fraumeni syndrome) germline mutations. METHODS: We included all breast cancers from female patients tested at our institute between 1992 and 2016 (n = 3469) for which pathology data were available. ILC proportion comparison according to mutational status was performed by a chi-squared test. The impact of susceptibility genes on ILC proportion was investigated by univariate logistic regression with wild-type patients as reference. RESULTS AND DISCUSSION: There were 265 (7.64%) ILC: 2/342 (0.58%) in BRCA1 patients, 24/238 (10%) in BRCA2 patients, 1/57 (1.75%) in TP53 patients and 238/2832 (8.4%) in non-carriers. The majority of breast cancers in all groups were invasive ductal and ductal in situ carcinomas. The difference in ILC proportion was highly significant (P < 0.001). Compared to wild-type patients, BRCA1 was associated with a lower ILC proportion (OR 0.064 [95% CI 0.016;0.259], P < 0.0001). BRCA2 OR was 1.222 [95%CI 0.785;1.902] (P = 0.374), TP53 OR was 0.195 [95%CI 0.027;1.412] (P = 0.105). ILC are therefore underrepresented in BRCA1 and TP53 mutation carriers. Formal significance (P = 0.05) was not reached for TP53, but statistical power was only 38%. Based on ILC incidence in the general population, we make the hypothesis that BRCA1 and TP53 do not predispose to ILC, as the few occurrences of ILC in mutation carriers could be attributed to chance and not to germline mutations. Our observations will be useful to clinical cancer geneticists managing patients with ILC, as a BRCA1 or TP53 mutation in these patients would be unlikely. Genetic counseling should be adapted accordingly.


Assuntos
Proteína BRCA1/genética , Neoplasias da Mama/genética , Carcinoma Lobular/genética , Mutação em Linhagem Germinativa , Proteína Supressora de Tumor p53/genética , Proteína BRCA2/genética , Carcinoma Intraductal não Infiltrante/genética , Feminino , Predisposição Genética para Doença , Heterozigoto , Humanos
20.
J Acoust Soc Am ; 146(2): 1015, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31472561

RESUMO

While osteoporosis assessment has long focused on the characterization of trabecular bone, the cortical bone micro-structure also provides relevant information on bone strength. This numerical study takes advantage of ultrasound multiple scattering in cortical bone to investigate the effect of pore size and pore density on the acoustic diffusion constant. Finite-difference time-domain simulations were conducted in cortical microstructures that were derived from acoustic microscopy images of human proximal femur cross sections and modified by controlling the density (Ct.Po.Dn) ∈[5-25] pore/mm2 and size (Ct.Po.Dm) ∈[30-100] µm of the pores. Gaussian pulses were transmitted through the medium and the backscattered signals were recorded to obtain the backscattered intensity. The incoherent contribution of the backscattered intensity was extracted to give access to the diffusion constant D. At 8 MHz, significant differences in the diffusion constant were observed in media with different porous micro-architectures. The diffusion constant was monotonously influenced by either pore diameter or pore density. An increase in pore size and pore density resulted in a decrease in the diffusion constant (D =285.9Ct.Po.Dm-1.49, R2=0.989 , p=4.96×10-5,RMSE=0.06; D=6.91Ct.Po.Dn-1.01, R2=0.94, p=2.8×10-3 , RMSE=0.09), suggesting the potential of the proposed technique for the characterization of the cortical microarchitecture.


Assuntos
Condução Óssea , Osso Cortical/fisiologia , Modelos Teóricos , Osso Cortical/ultraestrutura , Fêmur/ultraestrutura , Humanos , Microscopia Acústica , Porosidade , Espalhamento de Radiação , Ondas Ultrassônicas
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