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1.
Phys Med ; 106: 102525, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36621081

RESUMO

PURPOSE: The feasibility of machine learning (ML) techniques and their performance compared to the conventional χ2-minimization technique in the context of the proton energy-resolved dose imaging method are presented. MATERIALS AND METHOD: Various geometries resembling a wedge and varying gradients are simulated in GATE to obtain energy-resolved dose functions (ERDF) from proton beams of different energies. These ERDFs are used to predict the WEPL using a conventional technique and other ML-based methods. The results are compared to gain an understanding of the performance of ML models in proton radiography. RESULTS: The results obtained from the χ2-minimization technique indicate that it is robust and more reliable compared to the ML-based techniques. It is also observed that the ML-based techniques did not mitigate the effect of range-mixing but seem to be more affected by it compared to the χ2-minimization technique. Substantial data reduction was required in order to make the results of ML-based methods comparable to that of χ2-minimization. We also note that such data reduction might not be possible in a clinical setting. The only advantage in using the ML-based technique is the computational time required to generate a WEPL map which, in our case study, is 10-30 times shorter than the time required for the conventional χ2-minimization technique. CONCLUSIONS: The first results from this preliminary study indicate that the ML techniques failed to be on par with the conventional χ2-minimization technique in terms of the achievable accuracy in the predictions of WEPL and in the mitigation of range-mixing effects in the WEPL image. Modern strategies like the GAN-based models may be suitable for such applications.


Assuntos
Terapia com Prótons , Prótons , Radiografia , Aprendizado de Máquina , Terapia com Prótons/métodos
2.
Am J Primatol ; 84(4-5): e23376, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35384010

RESUMO

Wild nonhuman primates (NHP) are considered natural hosts of a protozoan parasite from the genus Leishmania, the etiological agent of leishmaniasis. It is important to study the population of this infectious agent in zoo animals to establish surveillance and control mechanisms in Sorocaba through the application of a One Health approach, this is where human-animal-environment health and disease interface and can aid in the protection of endangered species. This study aimed to identify Leishmania infantum and Leishmania braziliensis in NHP living in a city where leishmaniasis is endemic. DNA was extracted from 48 NHP and analyzed using polymerase chain reaction primers that are specific for the species L. infantum and L. braziliensis. The results of our research revealed the first report of L. infantum and L. braziliensis naturally infecting primates at Sorocaba zoo. One primate from the species Plecturocebus vieirai was positive for L. infantum and five primates (four Alouatta caraya and one Ateles chamek) were positive for L. braziliensis. This indicates a possible role of these animals on the maintenance of these parasites.


Assuntos
Leishmania braziliensis , Leishmania infantum , Leishmaniose , Animais , Brasil/epidemiologia , Leishmania braziliensis/genética , Leishmania infantum/genética , Leishmaniose/parasitologia , Primatas
3.
Curr Comput Aided Drug Des ; 17(2): 214-224, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32053077

RESUMO

BACKGROUND: Considering the interesting role in the peptidoglycan biosynthesis pathway, the enzyme UDP-N-acetylglucosamine enolpyruvyl transferase is an attractive target to develop new antibacterial agents. It catalyzes the first key step of this pathway and its inhibition leads to bacterial cell death. Fosfomycin is known as the natural inhibitor of MurA. OBJECTIVE: The study aimed to introduce new inhibitors of MurA by virtual screening of different chemical compounds libraries, and test the best scored "virtual hits" against three pathogenic bacteria: Escherichia coli, Bacillus subtilis and Staphylococcus aureus. METHODS: A virtual screening of the structural analogues of fosfomycin downloaded from the Pub- Chem database was performed. Moreover, French National Chemical Library and ZINC database were also utilized to identify new structures different from fosfomycin. FlexX was the software used for this study. The antibacterial testing was divided into two methods: disk diffusion and broth dilution. RESULTS: A set of virtual hits was found to have better energy score than that of fosfomycin, seven of them were tested in vitro. In addition, the disk diffusion method explored four compounds that exhibited antibacterial activity: CID-21680357 (fosfomycin analogue), AB-00005001, ZINC04658565, and ZINC901335. The testing was continued by broth dilution method for both compounds CID-21680357 and ZINC901335 to determine their minimum inhibitory concentrations, and ZINC901335 had the best value with 457µg/ml against Staphylococcus aureus. CONCLUSION: Four compounds were found and proven in silico and in vitro to have antibacterial activity, namely CID-21680357, AB-00005001, ZINC04658565, and ZINC901335.


Assuntos
Alquil e Aril Transferases/antagonistas & inibidores , Antibacterianos/química , Inibidores Enzimáticos/química , Fosfomicina/análogos & derivados , Simulação de Acoplamento Molecular/métodos , Alquil e Aril Transferases/metabolismo , Antibacterianos/farmacologia , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Inibidores Enzimáticos/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Fosfomicina/farmacologia , Testes de Sensibilidade Microbiana/métodos
4.
Biomed Phys Eng Express ; 6(6)2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-35102004

RESUMO

Purpose:Proton energy-resolved dose imaging (pERDI) is a recently proposed technique to generate water equivalent path length (WEPL) images using a single detector. Owing to its simplicity in instrumentation, analysis and the possibility of using the in-room x-ray flat panels as detectors, this technique offers a promising avenue towards a clinically usable imaging system for proton therapy using scanned beams. The purpose of this study is to estimate the achievable accuracy in WEPL and Relative Stopping Power (RSP) using the pERDI technique and to assess the minimum dose required to achieve such accuracy. The novelty of this study is the first demonstration of the feasibility of pERDI technique in the pencil beam scanning (PBS) mode.Methods:A solid water wedge was placed in front of a 2D detector (Lynx). A library of energy-resolved dose functions (ERDF) was generated from the dose deposited in the detector by 50 PBS layers of energy varying from 100 MeV to 225 MeV. This set-up is further used to image the following configurations using the pERDI technique: stair-case shaped solid water phantom (configuration 1), electron density phantom (configuration 2) and head phantom (configuration 3). The result from configuration 1 was used to determine the achievable WEPL accuracy. The result from configuration 2 was used to estimate the relative uncertainty in RSP. Configuration 3 was used to evaluate the effect of range mixing on the WEPL. In all three cases, the variation of the accuracy with respect to dose, by varying the number of scanning layers, was also studied.Results:An accuracy of 1 mm in WEPL was achieved using the Lynx detector with an imaging field of 10 PBS layers or more, which is equivalent to a total dose of 5 cGy. The RSP is measured with a precision better than 2% for all homogeneous inserts of tissue surrogates. The pERDI technique failed for tissues surrogates with total WEPL outside the calibration window (WEPL < 70 mm) like in the case of lung exhale and lung inhale. The imaging of an anthropomorphic head phantom, in the same condition, produced a WEPL radiograph and compared to the WEPL derived from CT using gamma index analysis. The gamma index failed in the heterogeneous areas due to range mixing.Conclusions:The pERDI technique is a promising clinically usable imaging modality for reducing range uncertainties and set-up errors in proton therapy. The first results have demonstrated that WEPL and RSP can be estimated with clinically acceptable accuracy using the Lynx detector. Similar accuracy is also expected with in-room flat-panel detectors but at significantly reduced imaging dose. Though the issue of range mixing is still to be addressed, we expect that a statistical moment analysis of the ERDFs can be implemented to filter out the regions with high gradient of range mixing.


Assuntos
Terapia com Prótons , Calibragem , Estudos de Viabilidade , Imagens de Fantasmas , Prótons
5.
J Thromb Haemost ; 17(6): 951-963, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30929299

RESUMO

Essentials Factor Xa (FXa)-targeting direct oral anticoagulants (DOACs) reduce venous thromboembolism (VTE) The effects of FXa-targeting DOACs on cancer progression remain to be studied In xenograft models, a FXa-targeting DOAC did not inhibit breast cancer growth and metastasis A thrombin-targeting DOAC, dabigatran, also did not inhibit breast cancer growth and metastasis ABSTRACT: Background Factor Xa-targeting DOACs were recently found to reduce recurrent VTE efficiently in cancer patients when compared to the standard treatment with low-molecular-weight heparins (LMWHs). While the anticancer effects of LMWHs have been extensively studied in preclinical cancer models, the effects of FXa-targeting DOACs on cancer progression remain to be studied. Objective We investigated whether the FXa-targeting DOAC rivaroxaban and the thrombin-targeting DOAC dabigatran etexilate (DE) affected human breast cancer growth and metastasis in orthotopic xenograft models. Methods/results Mice that were put on a custom-made chow diet supplemented with rivaroxaban (0.4 or 1.0 mg/g diet) or dabigatran etexilate (DE) (10 mg/g diet) showed prolonged ex vivo coagulation times (prothrombin time [PT] and activated partial thromboplastin time [aPTT] assay, respectively). However, rivaroxaban and DE did not inhibit MDA-MB-231 tumor growth and metastasis formation in lungs or livers of 7-week-old fully immunodeficient NOD/SCID/Æ´C-/- (NSG) mice. Comparable data were obtained for rivaroxaban-treated mice when using NOD-SCID mice. Rivaroxaban and DE treatment also did not significantly inhibit tumor growth and metastasis formation when using another human triple negative breast cancer (TNBC) cell line (HCC1806) in NOD-SCID mice. The FXa and thrombin-induced gene expression of the downstream target CXCL8 in both cell lines, but FXa and thrombin, did not significantly stimulate migration, proliferation, or stemness in vitro. Conclusion Although effectively inhibiting coagulation, the DOACs rivaroxaban and DE did not inhibit orthotopic growth and metastasis of human TNBC. It remains to be investigated whether DOACs exert antitumorigenic effects in other types of cancer.


Assuntos
Anticoagulantes/farmacologia , Neoplasias da Mama/tratamento farmacológico , Dabigatrana/farmacologia , Rivaroxabana/farmacologia , Animais , Antitrombinas/farmacologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Progressão da Doença , Inibidores do Fator Xa/farmacologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Metástase Neoplásica/tratamento farmacológico , Metástase Neoplásica/patologia , Metástase Neoplásica/prevenção & controle , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Tromboembolia Venosa/prevenção & controle , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Front Physiol ; 8: 155, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28382003

RESUMO

Aim: Survivors of neonatal chronic lung disease or bronchopulmonary dysplasia (BPD) suffer from compromised lung function and are at high risk for developing lung injury by multiple insults later in life. Because neonatal lysophosphatidic acid receptor-1 (LPAR1)-deficient rats are protected against hyperoxia-induced lung injury, we hypothesize that LPAR1-deficiency may protect adult survivors of BPD from a second hit response against lipopolysaccharides (LPS)-induced lung injury. Methods: Directly after birth, Wistar control and LPAR1-deficient rat pups were exposed to hyperoxia (90%) for 8 days followed by recovery in room air. After 7 weeks, male rats received either LPS (2 mg kg-1) or 0.9% NaCl by intraperitoneal injection. Alveolar development and lung inflammation were investigated by morphometric analysis, IL-6 production, and mRNA expression of cytokines, chemokines, coagulation factors, and an indicator of oxidative stress. Results: LPAR1-deficient and control rats developed hyperoxia-induced neonatal emphysema, which persisted into adulthood, as demonstrated by alveolar enlargement and decreased vessel density. LPAR1-deficiency protected against LPS-induced lung injury. Adult controls with BPD exhibited an exacerbated response toward LPS with an increased expression of pro-inflammatory mRNAs, whereas LPAR1-deficient rats with BPD were less sensitive to this "second hit" with a decreased pulmonary influx of macrophages and neutrophils, interleukin-6 (IL-6) production, and mRNA expression of IL-6, monocyte chemoattractant protein-1, cytokine-induced neutrophil chemoattractant 1, plasminogen activator inhibitor-1, and tissue factor. Conclusion: LPAR1-deficient rats have increased hyperoxia-induced BPD survival rates and, despite the presence of neonatal emphysema, are less sensitive to an aggravated "second hit" than Wistar controls with BPD. Intervening in LPA-LPAR1-dependent signaling may not only have therapeutic potential for neonatal chronic lung disease, but may also protect adult survivors of BPD from sequelae later in life.

7.
Mali Med ; 32(4): 33-36, 2017.
Artigo em Francês | MEDLINE | ID: mdl-30079648

RESUMO

We report two cases of primitive pleural hydatid cyst. These two boys aged 13 and 14 who were referred for suspected tuberculosis. Front of the x-rays showed, Fluid pleural effusions with lobulated internal limits. Ultrasound has helped highlight the patient of 13 years a multi-vesicular cystic mass (cluster of grapes) compatible with girls vesicles. CT has helped highlight the pleural headquarters multiloculated cystic mass. CT allowed to objectify the right mediastinal pleura and the small fissure of multiple cystic formations without wall or mural nodule. It is noted an extension of the lesions to the diaphragm and to adjacent soft parts. The diagnosis of primary pleural cyst was raised in both cases before the characteristic appearance of the images. The confirmation was made by the hydatid serology was positive and 8kDa 18kDa respectively. The curative treatment is surgical. The outcome was favorable.


Nous rapportons deux observations de kyste hydatique pleural primitif. Il s'agit de deux garçons de 13 ans et 14 ans qui nous ont été adressés pour suspicion de tuberculose. Les radiographies de face ont montré, des épanchements liquidiens pleuraux aux limites internes lobulées. L'échographie a permis de mettre en évidence chez le patient de 13 ans une masse kystique multi-vésiculaire (en grappe de raisin) compatible avec des vésicules filles. La TDM a permis de mettre en évidence le siège pleural de la masse kystique multiloculée. Chez celui de 14 ans, la TDM a permis d'objectiver dans la plèvre médiastinale droite et la petite scissure de multiples formations kystiques arrondies sans cloison ni nodule mural. Il est noté une extension des lésions au diaphragme et aux parties molles adjacentes.Le diagnostic de kyste pleural primitif était évoqué dans les deux cas devant l'aspect caractéristique des images. La confirmation a été faite grâce à la sérologie hydatique qui était positive respectivement à 18kDa et 8kDa. Le traitement curatif est essentiellement chirurgical. L'évolution a été favorable.

8.
Phys Med Biol ; 61(16): N386-93, 2016 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-27435446

RESUMO

Energy resolved dosimetry offers a potential path to single detector based proton imaging using scanned proton beams. This is because energy resolved dose functions encrypt the radiological depth at which the measurements are made. When a set of predetermined proton beams 'proton imaging field' are used to deliver a well determined dose distribution in a specific volume, then, at any given depth x of this volume, the behavior of the dose against the energies of the proton imaging field is unique and characterizes the depth x. This concept applies directly to proton therapy scanning delivery methods (pencil beam scanning and uniform scanning) and it can be extended to the proton therapy passive delivery methods (single and double scattering) if the delivery of the irradiation is time-controlled with a known time-energy relationship. To derive the water equivalent path length (WEPL) from the energy resolved dose measurement, one may proceed in two different ways. A first method is by matching the measured energy resolved dose function to a pre-established calibration database of the behavior of the energy resolved dose in water, measured over the entire range of radiological depths with at least 1 mm spatial resolution. This calibration database can also be made specific to the patient if computed using the patient x-CT data. A second method to determine the WEPL is by using the empirical relationships between the WEPL and the integral dose or the depth at 80% of the proximal fall off of the energy resolved dose functions in water. In this note, we establish the evidence of the fundamental relationship between the energy resolved dose and the WEPL at the depth of the measurement. Then, we illustrate this relationship with experimental data and discuss its imaging dynamic range for 230 MeV protons.


Assuntos
Prótons , Radiometria/métodos , Radiometria/normas , Calibragem , Humanos , Doses de Radiação , Radiometria/instrumentação , Água
9.
Med Phys ; 42(4): 1936-47, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25832084

RESUMO

PURPOSE: In-vivo dosimetry and beam range verification in proton therapy could play significant role in proton treatment validation and improvements. In-vivo beam range verification, in particular, could enable new treatment techniques one of which could be the use of anterior fields for prostate treatment instead of opposed lateral fields as in current practice. This paper reports validation study of an in-vivo range verification method which can reduce the range uncertainty to submillimeter levels and potentially allow for in-vivo dosimetry. METHODS: An anthropomorphic pelvic phantom is used to validate the clinical potential of the time-resolved dose method for range verification in the case of prostrate treatment using range modulated anterior proton beams. The method uses a 3 × 4 matrix of 1 mm diodes mounted in water balloon which are read by an ADC system at 100 kHz. The method is first validated against beam range measurements by dose extinction measurements. The validation is first completed in water phantom and then in pelvic phantom for both open field and treatment field configurations. Later, the beam range results are compared with the water equivalent path length (WEPL) values computed from the treatment planning system XIO. RESULTS: Beam range measurements from both time-resolved dose method and the dose extinction method agree with submillimeter precision in water phantom. For the pelvic phantom, when discarding two of the diodes that show sign of significant range mixing, the two methods agree with ±1 mm. Only a dose of 7 mGy is sufficient to achieve this result. The comparison to the computed WEPL by the treatment planning system (XIO) shows that XIO underestimates the protons beam range. Quantifying the exact XIO range underestimation depends on the strategy used to evaluate the WEPL results. To our best evaluation, XIO underestimates the treatment beam range between a minimum of 1.7% and maximum of 4.1%. CONCLUSIONS: Time-resolved dose measurement method satisfies the two basic requirements, WEPL accuracy and minimum dose, necessary for clinical use, thus, its potential for in-vivo protons range verification. Further development is needed, namely, devising a workflow that takes into account the limits imposed by proton range mixing and the susceptibility of the comparison of measured and expected WEPLs to errors on the detector positions. The methods may also be used for in-vivo dosimetry and could benefit various proton therapy treatments.


Assuntos
Terapia com Prótons/métodos , Radiometria/métodos , Dosagem Radioterapêutica , Humanos , Masculino , Modelos Biológicos , Pelve , Imagens de Fantasmas , Neoplasias da Próstata/radioterapia , Terapia com Prótons/instrumentação , Prótons , Radiometria/instrumentação , Planejamento da Radioterapia Assistida por Computador/instrumentação , Planejamento da Radioterapia Assistida por Computador/métodos , Incerteza , Água
10.
Orthod Craniofac Res ; 16(2): 87-96, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23324041

RESUMO

OBJECTIVE: To evaluate and compare three-dimensional pharyngeal airway changes in orthodontic patients treated with and without extractions. MATERIAL AND METHODS: Pharyngeal airway was analyzed for 31 subjects (15 males, 16 females) treated with extractions of four first premolars and 31 age- and gender-matched controls (15 males, 16 females) treated without extractions. The mean age of subjects was 12.97 ± 1.15 years at the beginning and 15.69 ± 1.28 years at the end of treatment. The mean age of controls was 12.86 ± 0.74 years at the beginning and 15.18 ± 0.86 years at the end of treatment. Nasopharyngeal (NP) and oropharyngeal (OP) volumes, area of maximum pharyngeal constriction (AMPC), and upper arch perimeter were measured on T0 and T1 cone beam computed tomography (CBCT) scans. Paired samples t-test was used for analyzing statistical significance of changes (p ≤ 0.05). RESULTS: There were no statistically significant differences in the pharyngeal airway values between the extraction and non-extraction groups at neither T0 nor T1. The extraction group showed a statistically significant increase for NP and OP volumes and AMPC values. Such increase was also noted in the non-extraction group, without statistical significance for AMPC values. CONCLUSIONS: The findings suggest that an extraction or non-extraction choice for orthodontic treatment would not affect the pharyngeal airway.


Assuntos
Má Oclusão/terapia , Ortodontia Corretiva/métodos , Faringe/anatomia & histologia , Ventilação Pulmonar , Extração Dentária , Adolescente , Cefalometria , Criança , Tomografia Computadorizada de Feixe Cônico , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional/métodos , Masculino , Cavidade Nasal/anatomia & histologia , Faringe/diagnóstico por imagem , Estudos Retrospectivos , Estatísticas não Paramétricas , Resultado do Tratamento
11.
Oncogene ; 31(21): 2627-39, 2012 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-22056873

RESUMO

Pancreatic cancer remains as one of the most deadly cancers, and responds poorly to current therapies. The prognosis is extremely poor, with a 5-year survival of less than 5%. Therefore, search for new effective therapeutic drugs is of pivotal need and urgency to improve treatment of this incurable malignancy. Synthetic alkyl-lysophospholipid analogs (ALPs) constitute a heterogeneous group of unnatural lipids that promote apoptosis in a wide variety of tumor cells. In this study, we found that the anticancer drug edelfosine was the most potent ALP in killing human pancreatic cancer cells, targeting endoplasmic reticulum (ER). Edelfosine was taken up in significant amounts by pancreatic cancer cells and induced caspase- and mitochondrial-mediated apoptosis. Pancreatic cancer cells show a prominent ER and edelfosine accumulated in this subcellular structure, inducing a potent ER stress response, with caspase-4, BAP31 and c-Jun NH(2)-terminal kinase (JNK) activation, CHOP/GADD153 upregulation and phosphorylation of eukaryotic translation initiation factor 2 α-subunit that eventually led to cell death. Oral administration of edelfosine in xenograft mouse models of pancreatic cancer induced a significant regression in tumor growth and an increase in apoptotic index, as assessed by TUNEL assay and caspase-3 activation in the tumor sections. The ER stress-associated marker CHOP/GADD153 was visualized in the pancreatic tumor isolated from edelfosine-treated mice, indicating a strong in vivo ER stress response. These results suggest that edelfosine exerts its pro-apoptotic action in pancreatic cancer cells, both in vitro and in vivo, through its accumulation in the ER, which leads to ER stress and apoptosis. Thus, we propose that the ER could be a key target in pancreatic cancer, and edelfosine may constitute a prototype for the development of a new class of antitumor drugs targeting the ER.


Assuntos
Antineoplásicos/uso terapêutico , Retículo Endoplasmático/efeitos dos fármacos , Neoplasias Pancreáticas/tratamento farmacológico , Inibidores de Fosfodiesterase/farmacologia , Éteres Fosfolipídicos/farmacologia , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/metabolismo , Retículo Endoplasmático/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Mitocôndrias/efeitos dos fármacos , Neoplasias Pancreáticas/metabolismo , Inibidores de Fosfodiesterase/uso terapêutico , Éteres Fosfolipídicos/uso terapêutico , Fatores de Transcrição de Fator Regulador X , Fatores de Transcrição/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Afr J Lab Med ; 1(1): 39, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-29062735

RESUMO

A regional external quality assessment scheme (REQAS) for anti-HIV serology aimed to objectively assess reliability and quality of HIV testing processes in the African region. This involved the distribution of proficiency testing (PT) panels to participating laboratories from 2002 to 2010. During the survey period, this included 16 distributions of PT panels to 49 laboratories in 30 countries, and the overall average score during the nine-year survey period was 98.9%, with a frequency of accurate detection, of anti-HIV-1 and/or anti-HIV-2 antibodies in the PT panels, ranging from 93% to 100%. Problems highlighted included lack of human resources and frequent stock outs of test kits, reagents and consumables for routine HIV testing. The design of the REQAS allowed appraisal of the reliability of anti-HIV serological testing methods utilised by laboratories for clinical assessment of patients and/or surveillance programmes. The REQAS was able to demonstrate that laboratories participating in the REQAS performed well and sustained their participation in the scheme. This bodes well for clinical diagnosis, surveillance and training activities at these reference laboratories.

13.
Genet Sel Evol ; 43: 41, 2011 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-22128882

RESUMO

BACKGROUND: Estimates of variance components for binary responses in presence of extreme case problems tend to be biased due to an under-identified likelihood. The bias persists even when a normal prior is used for the fixed effects. METHODS: A simulation study was carried out to investigate methods for the analysis of binary responses with extreme case problems. A linear mixed model that included a fixed effect and random effects of sire and residual on the liability scale was used to generate binary data. Five simulation scenarios were conducted based on varying percentages of extreme case problems, with true values of heritability equal to 0.07 and 0.17. Five replicates of each dataset were generated and analyzed with a generalized prior (g-prior) of varying weight. RESULTS: Point estimates of sire variance using a normal prior were severely biased when the percentage of extreme case problems was greater than 30%. Depending on the percentage of extreme case problems, the sire variance was overestimated when a normal prior was used by 36 to 102% and 25 to 105% for a heritability of 0.17 and 0.07, respectively. When a g-prior was used, the bias was reduced and even eliminated, depending on the percentage of extreme case problems and the weight assigned to the g-prior. The lowest Pearson correlations between true and estimated fixed effects were obtained when a normal prior was used. When a 15% g-prior was used instead of a normal prior with a heritability equal to 0.17, Pearson correlations between true and fixed effects increased by 11, 20, 23, 27, and 60% for 5, 10, 20, 30 and 75% of extreme case problems, respectively. Conversely, Pearson correlations between true and estimated fixed effects were similar, within datasets of varying percentages of extreme case problems, when a 5, 10, or 15% g-prior was included. Therefore this indicates that a model with a g-prior provides a more adequate estimation of fixed effects. CONCLUSIONS: The results suggest that when analyzing binary data with extreme case problems, bias in the estimation of variance components could be eliminated, or at least significantly reduced by using a g-prior.


Assuntos
Simulação por Computador , Modelos Genéticos , Algoritmos , Animais , Teorema de Bayes , Cruzamento , Funções Verossimilhança
14.
J Clin Invest ; 120(8): 2979-88, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20644255

RESUMO

Pulmonary metastasis remains the leading ca use of death for cancer patients. Opportunities to improve treatment outcomes for patients require new methods to study and view the biology of metastatic progression. Here, we describe an ex vivo pulmonary metastasis assay (PuMA) in which the metastatic progression of GFP-expressing cancer cells, from a single cell to the formation of multicellular colonies, in the mouse lung microenvironment was assessed in real time for up to 21 days. The biological validity of this assay was confirmed by its prediction of the in vivo behavior of a variety of high- and low-metastatic human and mouse cancer cell lines and the discrimination of tumor microenvironments in the lung that were most permissive to metastasis. Using this approach, we provide what we believe to be new insights into the importance of tumor cell interactions with the stromal components of the lung microenvironment. Finally, the translational utility of this assay was demonstrated through its use in the evaluation of therapeutics at discrete time points during metastatic progression. We believe that this assay system is uniquely capable of advancing our understanding of both metastasis biology and therapeutic strategies.


Assuntos
Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Progressão da Doença , Feminino , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos
15.
Planta Med ; 76(7): 708-12, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19937549

RESUMO

The new compounds guttiferone O ( 1) and 3-methoxycheffouxanthone ( 2) have been isolated from the seeds of Garcinia afzelii Engl., together with nine known compounds: 2-hydroxy-1,7-dimethoxyxanthone ( 3), smeathxanthone A ( 4), 1,5-dihydroxyxanthone ( 5), 1,6-dihydroxy-5-methoxyxanthone ( 6), cheffouxanthone ( 7), 1,3,5-trihydroxyxanthone ( 8), smeathxanthone B ( 9), isoxanthochymol ( 10) and guttiferone E ( 11). Their structures were elucidated by means of 1D and 2D-NMR techniques. All the isolates showed high cytotoxic activity and were found inactive when tested against HIV and influenza viruses.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Benzofenonas/isolamento & purificação , Garcinia/química , Xantonas/isolamento & purificação , Antivirais/isolamento & purificação , Avaliação Pré-Clínica de Medicamentos , Sementes/química
16.
J Egypt Soc Parasitol ; 39(1 Suppl): 371-81, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19621655

RESUMO

A cross-sectional study was conducted in a village in Menoufia Governorate, Egypt where the majority of people had individual trenches in the houses for sewage disposal with absence of public sewage system. Out of 2292 stool samples 47.8% had at least a single infection. Multiple infections occurred in 14.9%. Entamoeba histolytica was 20%, E. coli 10%, Giardia lamblia 10%, Ascaris lumbricoides 27.31%, Hymenolepis nana 2.96%, Schistosoma mansoni 2.45% and Ancylostoma duodenale 2.23%. Males were significantly infected with S. mansoni than females. Younger age groups were significantly infected by H. nana than older ones. Working in agriculture was significantly at risk with S. mansoni and A. duodenale infections. On multiple logistic regression analysis; the risk factor most strongly associated with infection was the presence of another infected family member.


Assuntos
Enteropatias Parasitárias/epidemiologia , População Rural , Adolescente , Adulto , Distribuição por Idade , Doenças dos Trabalhadores Agrícolas/epidemiologia , Doenças dos Trabalhadores Agrícolas/parasitologia , Criança , Estudos Transversais , Egito/epidemiologia , Fezes/parasitologia , Feminino , Humanos , Enteropatias Parasitárias/parasitologia , Masculino , Prevalência , Fatores de Risco , Distribuição por Sexo , Banheiros/normas , Adulto Jovem
17.
Acta Chir Belg ; 109(1): 117-8, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19341213

RESUMO

We present the case of a 12-year-old girl with familial hypercholesterolemia and coronary artery disease. She underwent triple-vessel coronary artery bypass grafting with bilateral pedicled internal mammary artery grafting without adverse events. Pediatric patients with familial hypercholesterolemia may present with premature coronary atherosclerosis requiring coronary artery bypass grafting. In situ internal mammary artery grafts should be the graft of choice.


Assuntos
Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/cirurgia , Hiperlipoproteinemia Tipo II/complicações , Anastomose de Artéria Torácica Interna-Coronária , Criança , Estenose Coronária/complicações , Estenose Coronária/cirurgia , Feminino , Humanos , Xantomatose/etiologia
18.
J Chir (Paris) ; 145(3): 244-6, 2008.
Artigo em Francês | MEDLINE | ID: mdl-18772732

RESUMO

OBJECTIVE: To evaluate the incidence of thyroid carcinoma in patients operated on for Graves' disease, to identify criteria which may predict malignancy, and to develop a practical approach to determine the extensiveness of thyroidectomy. PATIENTS AND METHODS: Retrospective study of all patients who underwent thyroidectomy for Graves' disease between 1995 and 2005. RESULTS: 547 patients underwent subtotal thyroidectomy for Graves' disease during this period. Post-operative pathology examination revealed six cases of thyroid cancer (1.1%). All six cases had differentiated thyroid carcinoma (papillary carcinoma in 3 cases, follicular carcinoma in 2 cases and papillo-follicular carcinoma in 1 case). The indication for initial thyroidectomy was a palpable thyroid nodule in 3 cases (50%), failure of medical treatment for Grave's disease in 2 cases (33%), and signs of goiter compression in 1 case (17%). Five patients underwent re-operative total thyroidectomy. CONCLUSION: This study shows that while malignancy in Grave's disease is uncommon, the presence of thyroid nodule(s) in patients with Grave's disease may be considered as an indication for radical surgery. The most adequate radical surgery in this situation is to perform a total thyroidectomy.


Assuntos
Doença de Graves/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico , Tireoidectomia , Adulto , Idoso , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/epidemiologia , Adulto Jovem
19.
Acta Chir Belg ; 108(6): 783-5, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19241943

RESUMO

Hydatid disease is a parasitic infection caused by the larvae of tapeworm Echinococcus Granulosus. Hydatid cyst of the heart is an uncommon presentation of human echinococcosis which may lead to life-threatening conditions. We present a rare case of recurrent pericardial cyst in a 42-year-old man presenting with chest pain and ECG findings. We were able to avoid risks of resternotomy with a limited anterolateral thoracotomy. A direct enucleation of the cyst was possible without the need for cardiopulmonary bypass. He was free of complications at 6-month follow-up. Diagnosis should be suspected in every case of anginal symptoms or cyst-like mass in persons coming from areas where echinococcus granulosus is endemic.


Assuntos
Angina Pectoris/parasitologia , Equinococose/diagnóstico , Cardiopatias/diagnóstico , Cardiopatias/parasitologia , Adulto , Equinococose/cirurgia , Cardiopatias/cirurgia , Ventrículos do Coração/parasitologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Recidiva
20.
J Chir (Paris) ; 145(3): 244-6, 2008 May.
Artigo em Francês | MEDLINE | ID: mdl-22805257

RESUMO

UNLABELLED: R. Mssrouri, S. Benamr, A. Essadel, J. Mdaghri, El H. Mohammadine, M.-K. Lahlou, A. Taghy, A. Belmahi, B. Chad Objective: To evaluate the incidence of thyroid carcinoma in patients operated on for Graves' disease, to identify criteria which may predict malignancy, and to develop a practical approach to determine the extensiveness of thyroidectomy. PATIENTS AND METHODS: Retrospective study of all patients who underwent thyroidectomy for Graves' disease between 1995 and 2005. RESULTS: 547 patients underwent subtotal thyroidectomy for Graves' disease during this period. Post-operative pathology examination revealed six cases of thyroid cancer (1.1%). All six cases had differentiated thyroid carcinoma (papillary carcinoma in 3 cases, follicular carcinoma in 2 cases and papillo-follicular carcinoma in 1 case). The indication for initial thyroidectomy was a palpable thyroid nodule in 3 cases (50%), failure of medical treatment for Grave's disease in 2 cases (33%), and signs of goiter compression in 1 case (17%). Five patients underwent re-operative total thyroidectomy. CONCLUSION: This study shows that while malignancy in Grave's disease is uncommon, the presence of thyroid nodule(s) in patients with Grave's disease may be considered as an indication for radical surgery. The most adequate radical surgery in this situation is to perform a total thyroidectomy.

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