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BACKGROUND: Valve-sparing aortic root replacement with the David procedure is an alternative to the Bentall procedure in patients with aortic root aneurysm. The aim of this study was to describe our long-term experience with this technique and the predictive factors of late failure. METHODS: Between January 1998 and August 2019, 300 consecutive patients underwent a David procedure. Clinical and echocardiographic early- and long-term outcomes were analyzed. Median follow-up was 7.0 years (range, 4.1-11.5), with 98.3% complete. RESULTS: Early mortality was 1%. No early valve-related reoperations occurred. There were 9 cardiac-related deaths and 22 reinterventions (19 valve-related). All patients survived reoperation. In 3 patients reintervention consisted of transcatheter aortic valve implantation. Overall survival rates were 95.3% (95% confidence interval [CI], 92.0-97.2), 91.1% (95% CI, 86.5-94.2), and 82.9% (95% CI, 75.3-88.4) at 5, 10, and 15 years, respectively. Freedom from postoperative aortic insufficiency (AI) grade ≥ 2 was 84.8% (95% CI, 79.9-88.6) and 74.3% (95% CI, 67.4-79.9) at 5 and 10 years, respectively. Freedom from reintervention for aortic valve disease was 97.1% (95% CI, 94.2-98.5), 92.9% (95% CI, 88.2-95.7), and 92.5% (95% CI, 87.1-95.7) at 5, 10, and 15 years, respectively. Preoperative AI ≥ 2 (hazard ratio, 1.782; 95% CI, 1.352-2.350) and a ventriculoaortic junction ≥ 29 mm (hazard ratio, 3.379; 95% CI, 1.726-6.616) were predictive factors for postoperative AI ≥ 2 in a multivariate analysis (P < .001). CONCLUSIONS: Preoperative AI ≥ 2 and a ventriculoaortic junction ≥ 29 mm were identified as risk factors for late postoperative AI ≥ 2.
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Insuficiência da Valva Aórtica , Implante de Prótese de Valva Cardíaca , Humanos , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Resultado do Tratamento , Estudos Retrospectivos , Insuficiência da Valva Aórtica/etiologia , Aorta/cirurgia , Reoperação/efeitos adversos , Implante de Prótese de Valva Cardíaca/métodosRESUMO
Many older adults take benzodiazepines and sedative-hypnotics for the treatment of sleep disorders. With a view to considering the possible discontinuation of hypnotics, the objectives of the present study were to describe bedtime habits and sleep patterns in older adults and to identify the sleep medications taken. An expert group developed a structured interview guide for assessing the patients' bedtime habits, sleep patterns, and medications. During an internship in a community pharmacy, 103 sixth-year pharmacy students conducted around 10 interviews each with older adults (aged 65 or over) complaining of sleep disorders and taking at least one of the following medications: benzodiazepines, benzodiazepine derivatives ("Z-drugs"), antihistamines, and melatonin. A prospective, observational study was carried out from 4 January to 30 June 2016. The pharmacy students performed 960 interviews (with 330 men and 630 women; mean ± standard deviation age: 75.1 ± 8.8). The most commonly taken hypnotics were the Z-drugs zolpidem (n = 465, 48%) and zopiclone (n = 259, 27%). The vast majority of patients (n = 768, 80%) had only ever taken a single hypnotic medication. The median [interquartile range] prescription duration was 120 (48-180) months. About 75% (n = 696) of the patients had at least 1 poor sleep habit, and over 41% (n = 374) had 2 or more poor sleep habits. A total of 742 of the patients (77%) reported getting up at night-mainly due to nycturia (n = 481, 51%). Further, 330 of the patients (35%) stated that they were keen to discontinue their medication, of which 96 (29%) authorized the pharmacist to contact their family physician and discuss discontinuation. In France, pharmacy students and supervising community pharmacists can identify problems related to sleep disorders by asking simple questions about the patient's sleep patterns. Together with family physicians, community pharmacists can encourage patients to discuss their hypnotic medications.
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OBJECTIVE: The aim of this study was to provide a reliable instrument to assess evidence-based practice (EBP) dimensions in French-speaking dental students. To do so, a transcultural adaptation into French of the self-administered KACE questionnaire (Knowledge, Attitude, Access and Confidence Evaluation) and the evaluation of its psychometric properties in a sample of French dental students and teachers were performed. The effects of individual and academic factors on student performance in the KACE were also investigated. METHOD: Teachers and fourth-year students completed once the translated KACE and fifth-year students completed twice the questionnaire before and after an epidemiology course. Cronbach's alpha coefficient analysis, Kruskal-Wallis and post hoc Dunn's tests, paired samples Wilcoxon tests and a generalised linear mixed model were performed to assess the psychometric properties (reliability, internal consistency, discriminant validity and responsiveness) of the questionnaire and to identify the factors associated with KACE scores, respectively. RESULTS: 186 participants completed the survey. Cronbach's alpha ranged from 0.06 to 0.48 for Knowledge, 0.21 to 0.59 for Attitude, 0.42 to 0.76 for Access and 0.82 to 0.93 for Confidence. The discriminant value and sensitivity of the French KACE revealed significant differences amongst students and teachers and accurately identified the effect the training course had on the students who had completed it. Preparing for a residency programme or having received add-on modules in science improved the students' performance in the test. Being female negatively impacted the KACE Confidence score. CONCLUSION: This version of the KACE is appropriate to assess EBP dimensions in French dental students. Academic background and gender may affect test performance.
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Educação em Odontologia , Conhecimentos, Atitudes e Prática em Saúde , Prática Clínica Baseada em Evidências , Feminino , Humanos , Psicometria , Reprodutibilidade dos Testes , Estudantes de Odontologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The best valvular substitute remains controversial in young adults with active aortic valve endocarditis. The Ross procedure has gained interest because of its theoretical resistance to infection. We aimed to report our long-term outcomes of the Ross procedure in this indication. METHODS: Between March 1992 and January 2019, 511 patients underwent a Ross procedure in our institution. Among them, we included 38 patients who suffered from an active aortic valve infective endocarditis. The mean age was 33.9 ± 8.1 years. Six patients had emergent procedures and 17 patients had perivalvular involvement. A pulmonary autograft was implanted using the full root technique in 78.9% of patients. Median follow-up was 12 (interquartile range, 1.75-16.25) years. RESULTS: The hospital mortality rate was 5.3%. Estimated overall survival was 84.2% ± 6.6% at 10 years. There were 2 cases of recurrent endocarditis, both requiring reoperation. Six other patients required reoperation on an autograft or homograft. Estimated freedom from recurrent endocarditis or reoperation was 89.4% ± 5.9% at 10 years. CONCLUSIONS: In experienced centers, the Ross procedure is a reliable alternative to prosthetic or homograft valve replacement in young adults experiencing active aortic valve endocarditis, with a low operative risk and good long-term results.
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Valva Aórtica/diagnóstico por imagem , Endocardite/cirurgia , Previsões , Implante de Prótese de Valva Cardíaca/efeitos adversos , Adolescente , Adulto , Valva Aórtica/cirurgia , Endocardite/diagnóstico , Endocardite/epidemiologia , Feminino , Seguimentos , França/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Reoperação , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Resultado do Tratamento , Adulto JovemRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The plant species reported here are used in contemporary phytotherapies by native and neo-urban societies from the Iquitenian surroundings (district of Loreto, Peruvian Amazon) for ailments related to microbial infections. Inhabitants of various ethnic origins were interviewed and 81 selected extracts were evaluated for their antimicrobial properties against a panel of 36 sensitive and multi-resistant bacteria or yeast. Medicinal plant researches in the Peruvian Amazon are now significant, but none of them has focused on an exhaustive listing of identified species tested on so many microbes with standardized experiments (to obtain MIC value). AIM OF THE STUDY: The aim of the study was to inventory the plants used against infections in the Loreto, an Amazonian region of Peru. It led to the new identification of secondary metabolites in two plant species. MATERIALS AND METHODS: Ethnographic survey was carried out using "participant-observation" methodology and focus on bioprospecting of antimicrobial remedies. Selected plant extracts and antimicrobial drugs were tested in vitro with agar dilution method on 35 bacteria strains and 1 yeast to evaluate their Minimal Inhibitory Concentration (MIC). Microdilution methods using 96-well microtiter plates were used for the determination of MIC from isolated compounds, and cytotoxicity in HepG2 cells from some selected extracts were also evaluated. Activity-guided isolation and identification of compounds were performed by various chromatographic methods and structural elucidations were established using HRMS and NMR spectroscopy. RESULTS: This study outlined antimicrobial activities of 59 plant species from 33 families (72 single plant extracts and 2 fermented preparations), 7 mixtures, and one insect nest extract against 36 microorganisms. Of the 59 species analysed, 12 plants showed relevant antibacterial activity with MIC ≤0.15 mg/mL for one or several of the 36 micro-organisms (Aspidosperma excelsum, Brosimum acutifolium, Copaifera paupera, Erythrina amazonica, Hura crepitans, Myrciaria dubia, Ocotea aciphylla, Persea americana, Spondias mombin, Swartzia polyphylla, Virola pavonis, Vismia macrophylla). Examination by bioautography of E. amazonica, M. dubia and O. aciphylla extracts allowed the phytochemical characterization of antimicrobial fractions and compounds. CONCLUSION: This study suggested an a posteriori correlation of the plant extract antimicrobial activity with the chemosensory cues of the drugs and attested that those chemosensory cues may be correlated with the presence of antimicrobial compounds (alkaloids, tannins, saponosids, essential oil, oleoresin ). It also led to the first isolation and identification of three secondary metabolites from E. amazonica and M. dubia.
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Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Infecções Bacterianas/tratamento farmacológico , Fitoterapia/métodos , Extratos Vegetais/farmacologia , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Bactérias/efeitos dos fármacos , Infecções Bacterianas/microbiologia , Etnobotânica , Etnofarmacologia , Humanos , Testes de Sensibilidade Microbiana , Peru , Extratos Vegetais/uso terapêutico , Plantas Medicinais/químicaRESUMO
BACKGROUND: During their studies, pharmacy students must acquire the specific skills in clinical virology required for their subsequent professional practice. Recent experiments on teaching and learning in higher education have shown that hybrid courses strengthen the students' commitment to learning and enable high-quality knowledge acquisition. OBJECTIVE: This study concerned the design and deployment of a hybrid course that combines face-to-face and Web-based instruction in clinical virology for fourth-year pharmacy students. The study's objectives were to (1) measure the students' level of involvement in the course, (2) gauge their interest in this type of learning, and (3) highlight any associated difficulties. METHODS: The study included 194 fourth-year pharmacy students from the Lille Faculty of Pharmacy (University of Lille, Lille, France) between January and June 2017. The students followed a hybrid course comprising an online learning module and 5 tutorial sessions in which professional situations were simulated. The learning module and 3 online evaluation sessions were delivered via the Moodle learning management system. Each tutorial session ended with an evaluation. The number of Moodle log-ins, the number of views of learning resources, and the evaluation marks were recorded. The coefficient for the correlation between the marks in the online evaluation and those in the tutorials was calculated. The students' opinions and level of satisfaction were evaluated via a course questionnaire. RESULTS: The course's learning resources and Web pages were viewed 21,446 and 3413 times, respectively. Of the 194 students, 188 (96.9%) passed the course (ie, marks of at least 10 out of 20). There was a satisfactory correlation between the marks obtained in the online evaluations and those obtained after the tutorials. The course met the students' expectations in 53.2% of cases, and 57.4% of the students stated that they were able to work at their own pace. Finally, 26.6% of the students stated that they had difficulty organizing their work around this hybrid course. CONCLUSIONS: Our results showed that pharmacy students were strongly in favor of a hybrid course. The levels of attendance and participation were high. However, teachers must be aware that some students will encounter organizational difficulties.
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In a 12-month nationwide study on the prevalence of drug-resistant tuberculosis (TB) in Lebanon, we identified 3 multidrug-resistant cases and 3 extensively drug-resistant TB cases in refugees, migrants, and 1 Lebanon resident. Enhanced diagnostics, particularly in major destinations for refugees, asylum seekers, and migrant workers, can inform treatment decisions and may help prevent the spread of drug-resistant TB.
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Farmacorresistência Bacteriana Múltipla , Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adulto , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Feminino , Genes Bacterianos , Genótipo , História do Século XXI , Humanos , Líbano/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Repetições Minissatélites , Mutação , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/história , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adulto JovemRESUMO
This study is the first to examine the prognostic role of physician empathy in interaction with the type of consultation (TC) (TC, bad news versus follow-up consultations) in cancer patient survival. Between January 2015 and March 2016, 179 outpatients with thoracic cancer and a Karnofsky performance status ≥60 assessed their oncologist's empathy using the CARE questionnaire, which provides a general score and two sub-dimensions: listening/compassion and active/positive empathy. Survival was recorded until April 2018. Usual medical, social and psychological confounders were included in the Cox regression. The median follow-up time was 3.1 years. There was a statistical interaction between listening/compassion empathy and TC (p = 0.016) such that in bad news consultations, higher listening/compassion predicted a higher risk of death (hazard ratio (HR) = 1.13; 95% confidence interval (CI): 1.03â»1.23; p = 0.008). In follow-up consultations, listening/compassion did not predict survival (HR = 0.94; 95% CI: 0.85â»1.05; p = 0.30). The same results were found with the general score of empathy, but not with active/positive empathy. In bad news consultations, high patient-perceived physician compassion could worry patients by conveying the idea that there is no longer any hope, which could hasten death. Further studies are warranted to confirm these results and find out the determinants of patient perception of physician empathy.
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BACKGROUND: Global roll-out of rapid molecular assays is revolutionising the diagnosis of rifampicin resistance, predictive of multidrug-resistance, in tuberculosis. However, 30% of the multidrug-resistant (MDR) strains in an eSwatini study harboured the Ile491Phe mutation in the rpoB gene, which is associated with poor rifampicin-based treatment outcomes but is missed by commercial molecular assays or scored as susceptible by phenotypic drug-susceptibility testing deployed in South Africa. We evaluated the presence of Ile491Phe among South African tuberculosis isolates reported as isoniazid-monoresistant according to current national testing algorithms. METHODS: We screened records of 37â644 Mycobacterium tuberculosis positive cultures from four South African provinces, diagnosed at the National Health Laboratory Service-Dr George Mukhari Tertiary Laboratory, to identify isolates with rifampicin sensitivity and isoniazid resistance according to Xpert MTB/RIF, GenoType MTBDRplus, and BACTEC MGIT 960. Of 1823 isolates that met these criteria, 277 were randomly selected and screened for Ile491Phe with multiplex allele-specific PCR and Sanger sequencing of rpoB. Ile491Phe-positive strains (as well as 17 Ile491Phe-bearing isolates from the eSwatini study) were then tested by Deeplex-MycTB deep sequencing and whole-genome sequencing to evaluate their patterns of extensive resistance, transmission, and evolution. FINDINGS: Ile491Phe was identified in 37 (15%) of 249 samples with valid multiplex allele-specific PCR and sequencing results, thus reclassifying them as MDR. All 37 isolates were additionally identified as genotypically resistant to all first-line drugs by Deeplex-MycTB. Six of the South African isolates harboured four distinct mutations potentially associated with decreased bedaquiline sensitivity. Consistent with Deeplex-MycTB genotypic profiles, whole-genome sequencing revealed concurrent silent spread in South Africa of a MDR tuberculosis strain lineage extending from the eSwatini outbreak and at least another independently emerged Ile491Phe-bearing lineage. Whole-genome sequencing further suggested acquisition of mechanisms compensating for the Ile491Phe fitness cost, and of additional bedaquiline resistance following the introduction of this drug in South Africa. INTERPRETATION: A substantial number of MDR tuberculosis cases harbouring the Ile491Phe mutation in the rpoB gene in South Africa are missed by current diagnostic strategies, resulting in ineffective first-line treatment, continued amplification of drug resistance, and concurrent silent spread in the community. FUNDING: VLIR-UOS, National Research Foundation (South Africa), and INNOVIRIS.
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Erros de Diagnóstico/estatística & dados numéricos , Surtos de Doenças , Técnicas de Genotipagem/métodos , Técnicas de Diagnóstico Molecular/métodos , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adulto , RNA Polimerases Dirigidas por DNA/genética , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Mutantes/genética , Mutação de Sentido Incorreto , Reação em Cadeia da Polimerase , Sensibilidade e Especificidade , Análise de Sequência de DNA , África do Sul/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Etoposide phosphate (EP; single injection, 60 mg/kg) followed by total body irradiation (TBI) at 12 Gy has been used as an allogeneic stem cell transplantation (allo-SCT) conditioning regimen for children since 2010. In our institution, EP has been suspected of leading to acute nephrotoxicity. The aim of this study was to assess the potential renal toxicity of EP in this context. MATERIALS AND METHODS: A retrospective study was carried out on children hospitalized between 2007 and 2015 for allo-SCT with TBI-based myeloablative conditioning associated with cyclophosphamide (CY, 60 mg/kg/day × 2 days) or EP. The primary endpoint of the study was the occurrence of acute kidney injury (AKI). Additional endpoints were time to recovery for children with AKI, survival, and treatment-related mortality. RESULTS: Thirty-five patients were analyzed (CY: 22 vs. EP: 13). AKI occurred more frequently in the EP group than in the CY one (69% vs. 27%, adjusted odds ratio 6.0, 95% confidence interval [CI] [1.145; 31.445], P = 0.03). The median time to recovery was estimated at 3 days, 95% CI (2; 17), with CY and 11 days 95% CI (5; 18) with EP (adjusted hazard ratio of recovery for EP vs. CY 0.262, 95% CI [0.071; 0.969], P = 0.04). No significant difference was highlighted between the two treatments for survival or for treatment-related mortality. DISCUSSION: This study shows that EP at high dosage or one of its excipients is probably responsible for AKI, as compared to CY. Further studies are required to explore the origin of this adverse effect.
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Injúria Renal Aguda/induzido quimicamente , Antineoplásicos/efeitos adversos , Etoposídeo/análogos & derivados , Doença Enxerto-Hospedeiro/tratamento farmacológico , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Compostos Organofosforados/efeitos adversos , Condicionamento Pré-Transplante , Injúria Renal Aguda/mortalidade , Antineoplásicos/administração & dosagem , Criança , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Humanos , Masculino , Compostos Organofosforados/administração & dosagem , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Three molecular assays (FTD® Viral GE from Fast-track diagnostics, RIDA®GENE VSP1 from R-Biopharm, and Xpert Norovirus from Cepheid) were compared for virus detection in acute diarrhea samples. RIDA®GENE and FTD® Viral GE showed perfect/almost perfect agreement for Rotavirus, Sapovirus and Norovirus, substantial agreement for Adenovirus, and moderate agreement for Astrovirus.
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Infecções por Enterovirus/diagnóstico , Fezes/virologia , Técnicas de Diagnóstico Molecular/métodos , Norovirus/isolamento & purificação , Rotavirus/isolamento & purificação , Sapovirus/isolamento & purificação , Adenoviridae/genética , Adenoviridae/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Astroviridae/genética , Astroviridae/isolamento & purificação , Líquidos Corporais/virologia , Criança , Pré-Escolar , Diarreia/virologia , Infecções por Enterovirus/virologia , Feminino , Gastroenterite/virologia , Humanos , Lactente , Masculino , Mamastrovirus/genética , Mamastrovirus/isolamento & purificação , Pessoa de Meia-Idade , Norovirus/genética , RNA Viral , Rotavirus/genética , Sapovirus/genética , Adulto JovemRESUMO
PURPOSE: To quantify and compare the histological components and architectural patterns of Gleason grades in cancerous areas with restriction on apparent diffusion coefficient (ADC) maps. MATERIALS AND METHODS: Twelve consecutive cases with 14 separate ADC restriction areas, positive for cancer in the peripheral zone (PZ) and transition zone (TZ) were included. All had 3 Tesla MRI and radical prostatectomy. Ten regions of interest (ROIs) within and outside the 14 ADC restriction areas positive for cancer were selected. For each ROI, we performed quantitative analysis of (a) prostate benign and malignant histological component surface ratios, including stroma, glands, epithelium, lumen, cellular nuclei; (b) percent of Gleason grades and measures of ADC values. Means of histological components according to ADC restriction for cancerous area were compared with analyses of variance with repeated measures. RESULTS: Independent predictors of the probability of cancer were median epithelium/ROI ratio (P = 0.001) and nuclei/ROI ratio (P = 0.03). Independent predictors of the probability of ADC restriction were malignant glands/ROI and luminal space/ROI (P < 0.0001). Effect of malignant glands/ROI area was different according to the localization of the ROI (P = 0.03). We observed an overall difference between the means for all of the histological components for the comparison of true positive and false negative (P < 0.0001), except for the percent of Gleason grade 4 (P = 0.18). In TZ cancers, a predominant grade 3 pattern was associated with low ADC values. In PZ cancers, a predominant grade 4 pattern was associated with low ADC values. CONCLUSION: Determinants of low ADC were high ratio of malignant glands/ROI area which may be seen in Gleason grades 3 or 4 cancers. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1786-1796.
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Imagem de Difusão por Ressonância Magnética/métodos , Processamento de Imagem Assistida por Computador/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Idoso , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Gradação de Tumores , Próstata/diagnóstico por imagem , Próstata/patologia , Reprodutibilidade dos TestesRESUMO
[This corrects the article DOI: 10.1371/journal.pone.0120839.].
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To quantitatively assess the risk of contamination by Pneumocystis depending on the degree of immunosuppression (ID) of the exposed rat hosts, we developed an animal model, where rats went through different doses of dexamethasone. Then, natural and aerial transmission of Pneumocystis carinii occurred during cohousing of the rats undergoing gradual ID levels (receivers) with nude rats developing pneumocystosis (seeders). Following contact between receiver and seeder rats, the P. carinii burden of receiver rats was determined by toluidine blue ortho staining and by qPCR targeting the dhfr monocopy gene of this fungus. In this rat model, the level of circulating CD4(+) and CD8(+) T lymphocytes remained significantly stable and different for each dose of dexamethasone tested, thus reaching the goal of a new stable and gradual ID rat model. In addition, an inverse relationship between the P. carinii burden and the level of circulating CD4(+) or CD8(+) T lymphocytes was evidenced. This rat model may be used to study other opportunistic pathogens or even co-infections in a context of gradual ID.
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Microbiologia do Ar , Modelos Animais de Doenças , Hospedeiro Imunocomprometido , Pneumocystis carinii/fisiologia , Pneumonia por Pneumocystis/microbiologia , Pneumonia por Pneumocystis/transmissão , Aerossóis , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Contagem de Colônia Microbiana , Dexametasona/administração & dosagem , Genes Fúngicos , Pulmão/microbiologia , Masculino , Pneumocystis carinii/efeitos dos fármacos , Pneumocystis carinii/crescimento & desenvolvimento , Pneumocystis carinii/isolamento & purificação , RatosRESUMO
Bats are a reservoir for a diverse range of viruses, including coronaviruses (CoVs). To determine the presence of CoVs in French bats, fecal samples were collected between July and August of 2014 from four bat species in seven different locations around the city of Bourges in France. We present for the first time the presence of alpha-CoVs in French Pipistrellus pipistrellus bat species with an estimated prevalence of 4.2%. Based on the analysis of a fragment of the RNA-dependent RNA polymerase (RdRp) gene, phylogenetic analyses show that alpha-CoVs sequences detected in French bats are closely related to other European bat alpha-CoVs. Phylogeographic analyses of RdRp sequences show that several CoVs strains circulate in European bats: (i) old strains detected that have probably diverged a long time ago and are detected in different bat subspecies; (ii) strains detected in Myotis and Pipistrellus bat species that have more recently diverged. Our findings support previous observations describing the complexity of the detected CoVs in bats worldwide.
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Quirópteros/virologia , Infecções por Coronavirus/veterinária , Coronavirus/classificação , Coronavirus/genética , Filogeografia , Animais , Análise por Conglomerados , Coronavirus/isolamento & purificação , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Fezes/virologia , França/epidemiologia , Prevalência , RNA Viral/genética , RNA Polimerase Dependente de RNA/genética , Análise de Sequência de DNA , Homologia de SequênciaRESUMO
PURPOSE: Ensuring the correct administration of antineoplastic drugs is a constantly challenging task. Nowadays, several specific infusion devices have been marketed to decrease occupational exposure to these drugs through a post-administration rinsing step. As their impact on drug pharmacokinetics has never been evaluated, the objective of this study was to assess how the infusion process may alter the pharmacokinetics of antineoplastic drugs. METHODS: We developed a prospective randomized multicenter pharmacokinetic study (ONCOPERF01) to compare the influence of three infusion techniques (gravity-fed infusion-GFI, infusion pump-IP, and gravity-fed infusion with post-administration rinsing-PAR) to assess the impact of both flow rate and post-administration rinsing on gemcitabine pharmacokinetics during three consecutive administrations. Gemcitabine pharmacokinetics was determined with a two-compartment model after plasma dosing with an HPLC-UV method. Statistical comparisons of the three groups were made using repeated-measure analysis of variance (PROC MIXED). RESULTS: Patients received gemcitabine by gravity-fed infusion (GFI, n = 9; IP, n = 9; PAR, n = 7). Significant differences were noted between infusion duration (GFI = 30.0 ± 2.6 min, IP = 29.1 ± 1.2 min, PAR = 33.7 ± 3.5 min; p = 0.003) and AUCt (GFI = 23.5 ± 8.2 µM h, IP = 25.4 ± 9.1 µM h, PAR = 28.5 ± 6.3 µM h; p = 0.0009), which was significantly higher in the infusion group with post-administration rinsing than in the other groups. CONCLUSIONS: The ONCOPERF01 study indicates that post-administration rinsing leads to a significant increase in patient exposure to gemcitabine, whereas controlling flow rate has no significance. Further surveys are required to assess the impact of such infusion techniques on other antineoplastic drugs.
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Antimetabólitos Antineoplásicos/administração & dosagem , Desoxicitidina/análogos & derivados , Modelos Biológicos , Neoplasias/tratamento farmacológico , Idoso , Antimetabólitos Antineoplásicos/sangue , Antimetabólitos Antineoplásicos/farmacocinética , Antimetabólitos Antineoplásicos/uso terapêutico , Desoxicitidina/administração & dosagem , Desoxicitidina/sangue , Desoxicitidina/farmacocinética , Desoxicitidina/uso terapêutico , Feminino , Meia-Vida , Humanos , Bombas de Infusão , Infusões Intravenosas , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Neoplasias/sangue , Exposição Ocupacional/prevenção & controle , Cloreto de Sódio/administração & dosagem , Fatores de Tempo , GencitabinaRESUMO
OBJECTIVE: The purpose of this study was to compare renal outcomes (glomerular filtration rate [GFR] and renal volume) after endovascular aneurysm repair (EVAR) and open repair (OR) of abdominal aortic aneurysm (AAA). METHODS: All AAA repairs performed between November 2009 and July 2011 were included in this retrospective study. Patients requiring suprarenal clamping and renal bypass or reimplantation and patients requiring fenestrated endografting were excluded from the OR and EVAR groups, respectively. All EVARs were performed with transrenal proximal fixation. Renal volume (calculated with a three-dimensional workstation) and GFR (estimated with the Modification of Diet in Renal Disease formula) were evaluated before the procedure, at 12 months after the procedure, and yearly thereafter. RESULTS: The study included 90 patients (41 ORs and 49 EVARs). Both groups were comparable except for age at intervention, body mass index, smoking, peripheral arterial disease, arrhythmia, and vitamin K antagonist treatment. Median follow-up was 2.8 years for OR (2.5-2.9 years) and 3.2 years for EVAR (3.0-3.4 years). In both groups, we found a significant decrease when comparing postoperative estimated GFR with 1-year (14.4% decrease [3.8%-23.8%]; P = .002) and 3-year (12.8% decrease [3.8%-20.9%]; P = .0007) levels. In both groups, total renal volumes significantly diminished. Median preoperative total renal volume (372 cm(3) [311-349]) significantly decreased (6.7% [2.8%-10.5%]; P = .008) between 1 year and 2 years of follow-up. CONCLUSIONS: Renal function impairment is similar after open and endovascular AAA repair. It is associated with a decrease in total renal volume, which seems to be an early and constant marker of postoperative renal impairment.
Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Nefropatias/etiologia , Idoso , Aneurisma da Aorta Abdominal/diagnóstico , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/diagnóstico por imagem , Rim/fisiopatologia , Nefropatias/diagnóstico , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: Identification of the culprit genes underlying multifactorial diseases is one of the most important current challenges of molecular genetics. While recent advances in genomics research have accelerated the discovery of susceptibility genes, much remains to be learned about the functions of disease-associated genetic variants. Recently, Moore and co-workers identified, in the donor genome, an association between a common genetic variant (rs4730751) in the gene encoding caveolin-1 (CAV1), a major structural component of caveolae, and long-term allograft survival. METHODS: Four hundred seventy-five renal recipients consecutively transplanted were included in this study. Donor genomic DNA was extracted and used to genotype CAV1 rs4730751 Single Nucleotide Polymorphism. RESULTS: Patients receiving a graft carrying CAV1 rs4730751 AA genotype displayed a significant decrease in estimated glomerular filtration rate and a significant increase in serum creatinine in both univariate and multivariate analyzes. Moreover, patients receiving a graft with CAV1 AA genotype significantly developed more interstitial fibrosis lesions on systematic biopsies performed 3 months post-transplantation. CONCLUSIONS: Genotyping of CAV1 may be relevant to identify patients at risk of adverse renal transplant outcome.
RESUMO
Pneumocystis fungi represent a highly diversified biological group with numerous species, which display a strong host-specificity suggesting a long co-speciation process. In the present study, the presence and genetic diversity of Pneumocystis organisms was investigated in 203 lung samples from woodmice (Apodemus sylvaticus) collected on western continental Europe and Mediterranean islands. The presence of Pneumocystis DNA was assessed by nested PCR at both large and small mitochondrial subunit (mtLSU and mtSSU) rRNA loci. Direct sequencing of nested PCR products demonstrated a very high variability among woodmouse-derived Pneumocystis organisms with a total number of 30 distinct combined mtLSU and mtSSU sequence types. However, the genetic divergence among these sequence types was very low (up to 3.87%) and the presence of several Pneumocystis species within Apodemus sylvaticus was considered unlikely. The analysis of the genetic structure of woodmouse-derived Pneumocystis revealed two distinct groups. The first one comprised Pneumocystis from woodmice collected in continental Spain, France and Balearic islands. The second one included Pneumocystis from woodmice collected in continental Italy, Corsica and Sicily. These two genetic groups were in accordance with the two lineages currently described within the host species Apodemus sylvaticus. Pneumocystis organisms are emerging as powerful tools for phylogeographic studies in mammals.