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1.
Biomed Pharmacother ; 158: 114070, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36526536

RESUMO

Stauprimide, a semi-synthetic derivative of staurosporine, is known mainly for its potent differentiation-enhancing properties in embryonic stem cells. Here, we studied the effects of stauprimide in cell growth and migration of triple-negative breast cancer cells in vitro, evaluating its potential antitumoral activity in an orthotopic mouse model of breast cancer in vivo. Our results from survival curves, EdU incorporation, cell cycle analysis and annexin-V detection in MDA-MB-231 cells indicated that stauprimide inhibited cell proliferation, arresting cell cycle in G2/M without induction of apoptosis. A decrease in the migratory capability of MDA-MB-231 was also assessed in response to stauprimide. In this work we pointed to a mechanism of action of stauprimide involving the modulation of ERK1/2, Akt and p38 MAPK signalling pathways, and the downregulation of MYC in MDA-MB-231 cells. In addition, orthotopic MDA-MB-231 xenograft and 4T1 syngeneic models suggested an effect of stauprimide in vivo, increasing the necrotic core of tumors and reducing metastasis in lung and liver of mice. Together, our results point to the promising role of stauprimide as a putative therapeutic agent in triple-negative breast cancer.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Feminino , Neoplasias de Mama Triplo Negativas/patologia , Linhagem Celular Tumoral , Ciclo Celular , Proliferação de Células , Neoplasias da Mama/tratamento farmacológico , Divisão Celular , Apoptose
2.
J Investig Allergol Clin Immunol ; 33(5): 383-391, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-36000827

RESUMO

BACKGROUND: Vine cultivation is widely distributed in La Rioja, Spain (37% of all crops) and is associated with exposure of the general population to vine pollen. The aims of this study were to investigate the prevalence of sensitization to Vitis vinifera pollen in persons with respiratory allergy in the general population and to identify the allergens involved. MATERIALS AND METHODS: The study population comprised patients who came to the hospital between September 2019 and January 2020 with suspected respiratory allergy. All patients underwent skin prick testing with a panel of standardized aeroallergens, profilin, lipid transfer protein (LTP), and V vinifera pollen extract and prick-prick testing with fresh grapes. The in vitro study included specific IgE by ImmunoCap and ELISA, allergenic profile by immunoblot with individual sera from patients positive to V vinifera pollen extract, and 2D immunoblot with a pool of sera. The spots recognized by IgE were identified using mass spectrometry. RESULTS: A total of 151 patients were included. Of these, 124 were positive to some of the allergens tested. Thirty-four (27.4%) were positive to vine pollen in the skin prick tests. The serology study revealed positive results in 20 patients. Five vine pollen allergens were identified, and profilin was the most prevalent (30%). The other 4 allergens could be considered specific to this pollen. CONCLUSIONS: Sensitization to vine pollen was frequent in the general population in a vine growing area. The clinical relevance of this finding is unknown owing to sensitization to other pollens in the vine pollen-positive patients. Five new vine pollen allergens were identified.

3.
J. investig. allergol. clin. immunol ; 33(5): 383-391, 2023. tab, graf
Artigo em Inglês | IBECS | ID: ibc-226552

RESUMO

Background: Vine cultivation is widely distributed in La Rioja, Spain (37% of all crops) and is associated with exposure of the general population to vine pollen. The aims of this study were to investigate the prevalence of sensitization to Vitis vinifera pollen in persons with respiratory allergy in the general population and to identify the allergens involved. Materials and Methods: The study population comprised patients who came to the hospital between September 2019 and January 2020 with suspected respiratory allergy. All patients underwent skin prick testing with a panel of standardized aeroallergens, profilin, lipid transfer protein (LTP), and V vinifera pollen extract and prick-prick testing with fresh grapes. The in vitro study included specific IgE by ImmunoCap and ELISA, allergenic profile by immunoblot with individual sera from patients positive to V vinifera pollen extract, and 2D immunoblot with a pool of sera. The spots recognized by IgE were identified using mass spectrometry. Results: A total of 151 patients were included. Of these, 124 were positive to some of the allergens tested. Thirty-four (27.4%) were positive to vine pollen in the skin prick tests. The serology study revealed positive results in 20 patients. Five vine pollen allergens were identified, and profilin was the most prevalent (30%). The other 4 allergens could be considered specific to this pollen. Conclusions: Sensitization to vine pollen was frequent in the general population in a vine growing area. The clinical relevance of this finding is unknown owing to sensitization to other pollens in the vine pollen–positive patients. Five new vine pollen allergens were identified (AU)


Antecedentes: El cultivo de la vid está ampliamente distribuido en La Rioja (37% de los cultivos), lo que supone una exposición de la población general al polen de esta planta. El objetivo de este estudio fue investigar la prevalencia de sensibilización al polen de Vitis vinifera en la población general con alergia respiratoria e identificar los alérgenos implicados. Materiales y métodos: Se incluyeron en el estudio pacientes que acudieron al hospital entre septiembre de 2019 y enero de 2020 con sospecha de alergia respiratoria. A todos ellos se les realizó una prueba cutánea con el panel de aeroalérgenos estandarizados, profilina, LTP, extracto de polen de V. vinifera y Prick prick con uva. El estudio in vitro incluyó IgE específica mediante ImmunoCap y ELISA, perfil alergénico por inmunoblot con sueros individuales de pacientes positivos al extracto de polen de V. vinifera e inmunoblot 2D con un pool de sueros. Las proteínas reconocidas por la IgE fueron identificadas por espectrometría de masas. Resultados: Se incluyeron un total de 151 pacientes. De ellos, 124 fueron positivos a algunos de los alérgenos analizados. 34 (27,4%) fueron positivos a polen de vid por prueba cutánea. 20 fueron positivos tras el estudio serológico. Se identificaron 5 alérgenos del polen de la vid, siendo la profilina el más prevalente (30%). Los otros 4 alérgenos podrían considerarse específicos de este polen. Conclusión: Se detectó una alta sensibilización al polen de vid en la población general en una zona de viñedos. Se desconoce la relevancia clínica debido a la sensibilización a otros pólenes en los pacientes positivos a polen de vid. Se identificaron 5 nuevos alérgenos del polen de la vid (AU)


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Rinite Alérgica Sazonal/diagnóstico , Vitis/efeitos adversos , Vitis/imunologia , Alérgenos , Ensaio de Imunoadsorção Enzimática
4.
Histopathology ; 81(3): 363-370, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35788982

RESUMO

OBJECTIVE: To describe the clinical findings in patients with incidental prostatic amyloidosis. PATIENTS AND METHODS: Retrospective search in the database of the Department of Pathology, Hospital de Bellvitge, for prostate specimens with amyloid. Congo red and immunohistochemical staining of the sections. Review of the patients' clinical charts for symptoms attributable to systemic amyloidosis. RESULTS: Amyloid deposition in the prostate was identified and reported in 40 patients between 2001 and 2022. Median age was 76.5 years (range = 62-90 years). Prostate cancer was diagnosed in 25 patients. Only four patients had a previous diagnosis of amyloidosis. In the remaining 36 the prostate sample (31 needle biopsies, two transurethral resections (TUR), two simple prostatectomies, one radical cystectomy for bladder cancer) provided the initial diagnosis. Amyloid deposits were mainly located in the wall of small vessels and rarely in the prostatic stroma. Immunohistochemistry was available in 32 cases, 26 of which were positive for TTR. All patients showed at least one symptom indicative of systemic amyloidosis, the most frequent being hearing loss (55%), carpal tunnel syndrome (42,5%) or other osteoarticular symptoms (tendinopathies, osteoarthritis), cataracts (37.5%) and cardiac symptoms (32.5%), among others. CONCLUSION: The prostate is a target tissue for amyloid deposition. The incidental finding of amyloid in prostate corresponds, in the majority of cases, to previously undiagnosed systemic TTR amyloidosis in patients lacking signs of heart involvement but having mainly osteoarticular symptoms, hearing and visual impairment.


Assuntos
Amiloidose , Amiloidose de Cadeia Leve de Imunoglobulina , Idoso , Idoso de 80 Anos ou mais , Amiloide , Amiloidose/diagnóstico , Amiloidose/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Próstata/patologia , Estudos Retrospectivos
5.
Malays J Pathol ; 44(1): 83-92, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35484890

RESUMO

INTRODUCTION: Data on pathological changes in COVID-19 are scarce. The aim of this study was to describe the histopathological and virological findings of postmortem biopsies, and the existing clinical correlations, in people who died of COVID-19. MATERIALS AND METHODS: We performed postmortem needle core biopsies of the chest in 11 people who died of COVID-19 pneumonia. Tissue examination was done by light microscopy and real-time polymerase chain reaction (RTPCR). RESULTS: The age of the patients were between 61 to 94 years. Of the 11 postmortem chest biopsies, lung tissue was obtained in 8, myocardium tissue in 7, and liver tissue in 5. Histologically of lung, the main findings pertaining to the lung were diffuse alveolar damage in proliferative phase (n = 4, 50%), diffuse alveolar damage in exudative and proliferative phase (n = 3, 37.5%), diffuse alveolar damage in exudative (n=1; 12.5%) and acute pneumonia (n = 2, 25%). Necrotising pneumonia, acute fibrinous and organising pneumonia, and neutrophils were detected in one sample each (12.5%). Another case presented myocarditis. RT-PCR showed RNA of SARS-CoV-2 in 7 of the 8 lung samples (87.5%), 2 of the 7 myocardial tissue samples (28.6%), and 1 of the 5 liver tissue samples (20%). CONCLUSION: The postmortem examinations show diffuse alveolar damage, as well as acute or necrotising pneumonia. RT-PCR of SARS-CoV-2 was positive in most lung samples.


Assuntos
COVID-19 , Pneumonia Necrosante , Pneumonia , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Humanos , Fígado/patologia , Pulmão/patologia , Pessoa de Meia-Idade , Pneumonia/patologia , Pneumonia Necrosante/patologia , SARS-CoV-2
6.
Rev Esp Quimioter ; 34(6): 618-622, 2021 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-34549577

RESUMO

OBJECTIVE: To assess the validity of SARS-CoV-2 Antigen (Ag) detection for the diagnosis of SARS-CoV-2 infection in mildly infected or asymptomatic patients. METHODS: Observational study to evaluate diagnostic tests. Non-hospitalized patients with indication for diagnostic testing for SARS-CoV-2 infection were included. The diagnostic test to be evaluated was the determination of Ag and as a reference standard to determine the presence of viral RNA the RT-PCR was used. RESULTS: A total of 494 patients were included. Of these 71.5% (353/494) had symptoms and 28.5% (141/494) were asymptomatic (presurgery screening (35/494) and confirmed case-contact (106/494). The overall sensitivity of the Ag test was 61.1% and the specificity was 99.7%. The sensitivity and specificity in the asymptomatic group were 40% and 100% respectively, and in the symptomatic group 63.5% and 99.6% respectively. In turn, the sensitivity and specificity in the group of symptomatic patients varied according to the time of symptom evolution: in patients with recent symptoms, they were 71.4% and 99.6% respectively, while in patients with symptoms of more than 5 days of evolution, they were 26.7% and 100% respectively. In all groups studied, the presence of antigen is associated with a high viral load (Ct<30 cycles). CONCLUSIONS: The use of Ag detection test is not indicated for the diagnosis of SARS-CoV-2 infection in asymptomatic patients or with symptoms of more than 5 days of evolution, but it could be useful in patients with symptoms of 1-5 days of evolution.


Assuntos
COVID-19 , SARS-CoV-2 , Reações Falso-Positivas , Humanos , Padrões de Referência , Sensibilidade e Especificidade
7.
Disabil Health J ; 14(3): 101095, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33840618

RESUMO

BACKGROUND: Overexposure to sunlight is the main cause of skin cancer. Outdoor sports increased sun exposure times. Sun protection behaviors and attitudes are utmost importance to reduce sun exposure. AIMS: To evaluate sun exposure habits, sun protection practices, and sun-related attitudes and knowledge among paralympic sailors. METHODS: This descriptive observational study analysed the answers of a validated self-reported questionnaire of habits, attitudes and knowledge related to sun exposure and skin cancer completed by 56 elite sailors with disabilities from 19 countries which taking part in 2019 Para World Sailing Championships. RESULTS: Three in four (76.8%) participants reported a history of sunburn in the previous season. Overall, participants showed an average for sport practice per week of 8.0 h (SD: 4.9). Participants reported a low adherence to sun protection practice, with the exception of using sunglasses (85.7%), sunscreen (83.9%) and hat (75%), having a very low rate (28.6%) of avoidance of midday sun and an inadequate sunscreen reapplication (33.9% reported "do not reapply" and 16.1% "reapply every one or 2 h"). Although 82.1% of participants reported to be worried about can get skin cancer out of the sun, they also presented excessive sun tanning attitudes (42.9% likes sunbathing and 57.1% sunbathing makes them feel well). The average score for sun-related knowledge was low (62.1 out 100 points; SD: 13.6). CONCLUSIONS: Awareness campaigns on sun risk are needed specifically directed at this target group, in order to improve their sun protection habits and reduce the rates of sunburn associated with sports practice.


Assuntos
Pessoas com Deficiência , Militares , Queimadura Solar , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Queimadura Solar/prevenção & controle , Luz Solar/efeitos adversos
9.
Orphanet J Rare Dis ; 14(1): 272, 2019 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-31779656

RESUMO

BACKGROUND: Congenital Pulmonary Airway Malformation (CPAM) has an estimated prevalence between 0.87 and 1.02/10,000 live births and little is know about their pathogenesis. To improve our knowledge on these rare malformations, we analyzed the cellular origin of the two most frequent CPAM, CPAM types 1 and 2, and compared these malformations with adjacent healthy lung and human fetal lungs. METHODS: We prospectively enrolled 21 infants undergoing surgical resection for CPAM. Human fetal lung samples were collected after termination of pregnancy. Immunohistochemistry and proteomic analysis were performed on laser microdissected samples. RESULTS: CPAM 1 and 2 express mostly bronchial markers, such as cytokeratin 17 (Krt17) or α-smooth muscle actin (ACTA 2). CPAM 1 also expresses alveolar type II epithelial cell markers (SPC). Proteomic analysis on microlaser dissected epithelium confirmed these results and showed distinct protein profiles, CPAM 1 being more heterogeneous and displaying some similarities with fetal bronchi. CONCLUSION: This study provides new insights in CPAM etiology, showing clear distinction between CPAM types 1 and 2, by immunohistochemistry and proteomics. This suggests that CPAM 1 and CPAM 2 might occur at different stages of lung branching. Finally, the comparison between fetal lung structures and CPAMs shows clearly different protein profiles, thereby arguing against a developmental arrest in a localized part of the lung.


Assuntos
Malformação Adenomatoide Cística Congênita do Pulmão/metabolismo , Proteômica/métodos , Actinas/metabolismo , Biomarcadores/metabolismo , Feminino , Feto/metabolismo , Humanos , Imuno-Histoquímica , Queratina-17/metabolismo , Pulmão/embriologia , Pulmão/metabolismo , Masculino , Gravidez , Estudos Prospectivos
10.
Acta pediatr. esp ; 76(11/12): 147-155, nov.-dic. 2018. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-177435

RESUMO

Introducción: Los síntomas de congestión nasal tienen una influencia negativa en la calidad de vida de los pacientes. Los tratamientos disponibles son parcialmente eficaces, por lo que es deseable el desarrollo de productos que ayuden a aliviar estos síntomas. El objetivo de este estudio fue investigar la efectividad y la tolerabilidad de un inhalador con ácido hialurónico en niños. Material y métodos: Se llevó a cabo un estudio piloto, prospectivo, multicéntrico, no comparativo, con un inhalador con ácido hialurónico al 0,2%, en niños de 2-11 años de edad que presentaban congestión nasal. El inhalador se administró durante 7 días, con dos visitas, una de inicio (día 0) y otra final (día 7), y un registro domiciliario diario de los síntomas. Se evaluaron la efectividad, la tolerabilidad, la facilidad de uso y la satisfacción de los usuarios. Resultados: El estudio se realizó en 99 pacientes. Se observaron mejoras estadísticamente significativas (p <0,001) entre la visita inicial y la final, así como en las valoraciones al tercer y sexto días, en cuanto a congestión nasal, dificultad para respirar por la nariz, moqueo, respiración bucal de día y de noche y dificultad para dormir, comer y realizar una actividad física. La satisfacción de los usuarios e investigadores fue mayor del 80%. Conclusiones: El inhalador con ácido hialurónico tuvo gran efectividad y buena tolerabilidad en niños con síntomas de congestión nasal, y fue valorado muy positivamente por parte de los investigadores, los padres y los niños mayores de 8 años


Background: Persistent congestive nasal symptoms have a negative influence on patients' quality of life, daily activities and sleep. The current available treatments are partly effective, and it would be desirable to develop products which help to relieve these symptoms. The purpose of this study was to research into the effectiveness and safety of a nasal spray with hyaluronic acid in children. Methods: This was a pilot, prospective, multicentric, uncontrolled study with a 0.2% hyaluronic acid nasal spray, tested in children aged from 2 to 11 with nasal congestion. The spray was used for 7 days, with two visits, basal (day 0) and final (day 7), and a daily record of symptoms by parents. Effectiveness, safety, ease of use and users’ satisfaction were assessed. Results: 99 patients were included. Statistically significant improvements (p <0.001) were observed in the parameters studied between basal and final visits, and at the third and sixth day: nasal congestion, difficulty in breathing through the nose, runny nose, breathing through the mouth during the day and during the night, and difficulty in sleeping, eating and performing physical activities. Satisfaction of users and researchers was greater than 80%. Conclusions: The nasal spray with hyaluronic acid had high effectiveness and safety in children with nasal congestion symptoms, and was evaluated very positively by researchers, parents and children older than 8


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Resultado do Tratamento , Ácido Hialurônico/uso terapêutico , Projetos Piloto , Administração Intranasal , Nebulizadores e Vaporizadores , Estudos Prospectivos , Satisfação do Paciente
11.
Science ; 361(6401): 482-485, 2018 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-29903886

RESUMO

Tidal disruption events (TDEs) are transient flares produced when a star is ripped apart by the gravitational field of a supermassive black hole (SMBH). We have observed a transient source in the western nucleus of the merging galaxy pair Arp 299 that radiated >1.5 × 1052 erg at infrared and radio wavelengths but was not luminous at optical or x-ray wavelengths. We interpret this as a TDE with much of its emission reradiated at infrared wavelengths by dust. Efficient reprocessing by dense gas and dust may explain the difference between theoretical predictions and observed luminosities of TDEs. The radio observations resolve an expanding and decelerating jet, probing the jet formation and evolution around a SMBH.

12.
J Chem Phys ; 147(22): 224902, 2017 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-29246037

RESUMO

Via computer simulation of a coarse-grained model of two-component lipid bilayers, we compare two methods of measuring the intrinsic curvatures of the constituting monolayers. The first one is a generalization of the swelling method that, in addition to the assumption that the spontaneous curvature linearly depends on the composition of the lipid mixture, incorporates contributions from its elastic energy. The second method measures the effective curvature-composition coupling between the apposing leaflets of bilayer structures (planar bilayers or cylindrical tethers) to extract the spontaneous curvature. Our findings demonstrate that both methods yield consistent results. However, we highlight that the two-leaflet structure inherent to the latter method has the advantage of allowing measurements for mixed lipid systems up to their critical point of demixing as well as in the regime of high concentration (of either species).

13.
Br J Cancer ; 117(9): 1314-1325, 2017 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-28881358

RESUMO

BACKGROUND: Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children. The Hedgehog (HH) pathway is known to develop an oncogenic role in RMS. However, the molecular mechanism that drives activation of the pathway in RMS is not well understood. METHODS: The expression of HH ligands was studied by qPCR, western blot and immunohistochemistry. Functional and animal model studies were carried out with cells transduced with shRNAs against HH ligands or treated with HH-specific inhibitors (Vismodegib and MEDI-5304). Finally, the molecular characterisation of an off-target effect of Vismodegib was also made. RESULTS: The results showed a prominent expression of HH ligands supporting an autocrine ligand-dependent activation of the pathway. A comparison of pharmacologic Smoothened inhibition (Vismodegib) and HH ligand blocking (MEDI-5304) is also provided. Interestingly, a first description of pernicious off-target effect of Vismodegib is also reported. CONCLUSIONS: The clarification of the HH pathway activation mechanism in RMS opens a door for targeted therapies against HH ligands as a possible alternative in the future development of better treatment protocols. Moreover, the description of a pernicious off-target effect of Vismodegib, via unfolded protein response activation, may mechanistically explain its previously reported inefficiency in several ligand-dependent cancers.


Assuntos
Carcinogênese/patologia , Proliferação de Células , Proteínas Hedgehog/metabolismo , Rabdomiossarcoma/patologia , Fatores de Transcrição/metabolismo , Animais , Apoptose , Carcinogênese/genética , Carcinogênese/metabolismo , Movimento Celular , Feminino , Proteínas Hedgehog/genética , Humanos , Ligantes , Camundongos , Camundongos SCID , Rabdomiossarcoma/genética , Rabdomiossarcoma/metabolismo , Transdução de Sinais , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Clin. transl. oncol. (Print) ; 19(1): 44-50, ene. 2017. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-159117

RESUMO

The use of preclinical models is essential in translational cancer research and especially important in pediatric cancer given the low incidence of each particular type of cancer. Cell line cultures have led to significant advances in cancer biology. However, cell lines have adapted to growth in artificial culture conditions, thereby undergoing genetic and phenotypic changes which may hinder the translational application. Tumor grafts developed in mice from patient tumor tissues, generally known as patient-derived xenografts (PDXs), are interesting alternative approaches to reproducing the biology of the original tumor. This review is focused on highlighting the interest of PDX models in pediatric cancer research and supporting strategies of personalized medicine. This review provides: (1) a description of the background of PDX in cancer, (2) the particular case of PDX in pediatric cancer, (3) how PDX can improve personalized medicine strategies, (4) new methods to increase engraftment, and, finally, (5) concluding remarks (AU)


No disponible


Assuntos
Humanos , Masculino , Feminino , Criança , Neoplasias/epidemiologia , Modelos Animais de Doenças , Modelos Animais , Técnicas In Vitro/métodos , Pesquisa Translacional Biomédica/métodos , Pesquisa Translacional Biomédica/organização & administração , Pesquisa Translacional Biomédica/normas , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Biópsia/métodos , Análise de Dados/métodos , RNA/efeitos adversos , RNA/genética , DNA/análise
15.
Clin Transl Oncol ; 19(1): 44-50, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27718156

RESUMO

The use of preclinical models is essential in translational cancer research and especially important in pediatric cancer given the low incidence of each particular type of cancer. Cell line cultures have led to significant advances in cancer biology. However, cell lines have adapted to growth in artificial culture conditions, thereby undergoing genetic and phenotypic changes which may hinder the translational application. Tumor grafts developed in mice from patient tumor tissues, generally known as patient-derived xenografts (PDXs), are interesting alternative approaches to reproducing the biology of the original tumor. This review is focused on highlighting the interest of PDX models in pediatric cancer research and supporting strategies of personalized medicine. This review provides: (1) a description of the background of PDX in cancer, (2) the particular case of PDX in pediatric cancer, (3) how PDX can improve personalized medicine strategies, (4) new methods to increase engraftment, and, finally, (5) concluding remarks.


Assuntos
Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Medicina de Precisão , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Humanos , Camundongos , Neoplasias/genética , Pesquisa Translacional Biomédica
17.
J Chem Phys ; 141(19): 194902, 2014 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-25416907

RESUMO

The coupling between local composition fluctuations in binary lipid membranes and curvature affects the lateral membrane structure. We propose an efficient method to compute the composition-curvature coupling in molecular simulations and apply it to two coarse-grained membrane models-a minimal, implicit-solvent model and the MARTINI model. Both the weak-curvature behavior that is typical for thermal fluctuations of planar bilayer membranes as well as the strong-curvature regime corresponding to narrow cylindrical membrane tubes are studied by molecular dynamics simulation. The simulation results are analyzed by using a phenomenological model of the thermodynamics of curved, mixed bilayer membranes that accounts for the change of the monolayer area upon bending. Additionally the role of thermodynamic characteristics such as the incompatibility between the two lipid species and asymmetry of composition are investigated.


Assuntos
Simulação por Computador , Lipídeos de Membrana , Termodinâmica
18.
Public Health ; 126(6): 535-40, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22546507

RESUMO

OBJECTIVE: Increasing overweight and obesity rates in Mexico have been associated with increases in mortality from cardiovascular disease (CVD). This study assessed changes in body mass index (BMI) and body weight over 1 year, and explored whether these were associated with changes in CVD risk factors of blood pressure and fasting glucose in a cohort of young Mexican adults. STUDY DESIGN: Longitudinal data were obtained from a cohort of young Mexican adults applying to college. METHODS: Data were collected from college applicants for the 2008 academic year who re-applied in 2009. In total, 795 college applicants aged 18-20 years, of both sexes (48% males and 52% females), were included in the study. The screen included height, weight, and systolic (SBP) and diastolic (DBP) blood pressure measurements plus a blood draw following an overnight fast for fasting glucose. RESULTS: At baseline, 31.8% of the participants were overweight or obese. The mean 1-year change in body weight and BMI were 0.80 kg and 0.35 kg/m(2), respectively. One-year changes in body weight and BMI were associated with increased SBP and DBP for both men and women (P < 0.05), independent of baseline BMI. A weight gain of 5% or more was positively associated with increases in blood pressure among women (P < 0.05), but not among men. A weight loss of 5% or more was associated with reductions in SBP among women. CONCLUSIONS: One-year changes in weight were associated with changes in blood pressure.


Assuntos
Pressão Sanguínea , Peso Corporal , Adulto , Glicemia , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , México/epidemiologia , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Fatores de Risco , Aumento de Peso , Redução de Peso , Adulto Jovem
19.
Comput Methods Programs Biomed ; 107(2): 218-32, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21908068

RESUMO

Most small-animal X-ray computed tomography (CT) scanners are based on cone-beam geometry with a flat-panel detector orbiting in a circular trajectory. Image reconstruction in these systems is usually performed by approximate methods based on the algorithm proposed by Feldkamp et al. (FDK). Besides the implementation of the reconstruction algorithm itself, in order to design a real system it is necessary to take into account numerous issues so as to obtain the best quality images from the acquired data. This work presents a comprehensive, novel software architecture for small-animal CT scanners based on cone-beam geometry with circular scanning trajectory. The proposed architecture covers all the steps from the system calibration to the volume reconstruction and conversion into Hounsfield units. It includes an efficient implementation of an FDK-based reconstruction algorithm that takes advantage of system symmetries and allows for parallel reconstruction using a multiprocessor computer. Strategies for calibration and artifact correction are discussed to justify the strategies adopted. New procedures for multi-bed misalignment, beam-hardening, and Housfield units calibration are proposed. Experiments with phantoms and real data showed the suitability of the proposed software architecture for an X-ray small animal CT based on cone-beam geometry.


Assuntos
Intensificação de Imagem Radiográfica/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Software , Tomografia Computadorizada por Raios X/métodos , Tomografia Computadorizada por Raios X/veterinária , Imagem Corporal Total/métodos , Imagem Corporal Total/veterinária , Algoritmos , Animais , Camundongos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
20.
Actas urol. esp ; 35(5): 296-301, mayo 2011. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-88837

RESUMO

Introducción: se describe la técnica y se presentan los resultados preliminares de la técnica decistectomía radical laparoscópica con confección extracorpórea de neovejiga ortotópica ileal en forma de ‘‘Y’’, usando una sutura mecánica no reabsorbible (Fontana). Material y método: se describe paso a paso la técnica y se presenta una serie de 15 pacientes sometidos a esta cirugía entre noviembre de 2005 y agosto de 2009, con especial énfasis en el tiempo de cirugía, tiempo de derivación urinaria, las complicaciones intraoperatorias y postoperatorias, la continencia diurna y nocturna y la frecuencia miccional postoperatoria. Resultados: la mediana de seguimiento de la serie es de 24 meses (6-32). El tiempo quirúrgico medio fue 280 (rango: 210-345) minutos y el tiempo medio de la derivación urinaria fue 54,5 (rango: 40-75) minutos. No se presentaron complicaciones intraoperatorias y el tiempo promedio de hospitalización fue de 7 días (rango: 5-15). Durante el seguimiento se presentaron 5complicaciones postoperatorias tardías, dos cuadros de infección urinaria con buena respuesta al tratamiento antibiótico y tres estenosis de la anastomosis uretero-neovesical, que se han manejado con una dilatación percutánea con balón con un buen resultado funcional. No se han encontrado litiasis en la neovejiga. Se obtuvo continencia diurna completa en 13 de 14 pacientes (92,9%) y nocturna completa en 6 de 14 (42,9%). Un paciente (6,7%) precisa autosondaje limpio intermitente por no presentar micción espontánea. Conclusiones: la neovejiga ortotópica ileal en forma de ‘‘Y’’ usando una sutura mecánica no reabsorbible es una técnica factible, rápida, segura y que permite resultados funcionales prometedores. Se necesita mayor seguimiento para determinar sus resultados a largo plazo (AU)


Introduction: We describe the technique and present the preliminary results of the laparoscopic radical cystectomy technique with the extracorporeal creation of a ‘‘y’’ shaped ileal orthotopicneo bladder using non-absorbable mechanical suture (Fontana). Materials and method: We describe the technique step by step and we present a series of 15 patients that underwent this surgery between November 2005 and August 2009, with special emphasis on the duration of the surgery, urinary diversion time, intraoperative and postoperative complications, daytime and night time continence and the frequency of postoperative micturition. Results: The mean follow-up of the series was 24 months (6-32). The mean duration of surgery was 280 (range 210-345) minutes and the mean urinary diversion time was 54.5 (range 40-75) minutes. There were no intraoperative complications and the average hospitalization time was 7 (range 5-15) days. During the follow-up, there were 5 late postoperative complications, 2cases of urinary infection with good response to antibiotic treatment and 3 uretero-neovesical anastomosis strictures, which were treated with percutaneous balloon dilation, with a good functional result. No lithiasis was found in the neobladder. Complete daytime continence wa sobtained in 13/14 patients (92.9%) and complete night time continence in 6/14 (42.9%). One patient (6.7%) required clean intermittent self-catheterization as the patient did not micturate spontaneously. Conclusions: The creation of a ‘‘Y’’ shaped ileal orthotopic neobladder using non-absorbable mechanical suture is a feasible, fast and safe technique and it provides promising functional results. Further follow-up is required to determine its long-term results (AU)


Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Cistectomia/história , Cistectomia/métodos , Cistectomia/estatística & dados numéricos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Cuidados Pós-Operatórios/psicologia , Cuidados Pós-Operatórios/reabilitação , Cistectomia/instrumentação , Cistectomia/reabilitação , Cistectomia/tendências , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/reabilitação , Cuidados Pós-Operatórios/ética , Cuidados Pós-Operatórios/enfermagem , Cuidados Pós-Operatórios/normas
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