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1.
Int J Med Inform ; 136: 104090, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32045743

RESUMO

BACKGROUND AND OBJECTIVES: The examination of the fundus allows to evaluate retinal the microcirculation in vivo. We assess the reliability and validity of ALTAIR software, and to evaluate its clinical relevance by the association of thickness, area and length of the retinal vessels with other measures of vascular structure and function, target organ damage and cardiovascular risk. METHODS: Cross-sectional study involving a total of 250 subjects aged 62 ±â€¯9 years, 51 % males. In a random subsample of 60 subjects (118 retinographies), we estimated the intraobserver, interobserver and interdevice intraclass correlation coefficients (ICC) of the measurements of retinal vascular thickness, area and length in 3 concentric circles. Concurrent validity was assessed with all 250 subjects (495 retinographies), analysing the relationship to age, blood pressure, target organ damage, vascular structure and function, and cardiovascular risk. RESULTS: Of the sample, 69 % were diagnosed with hypertension and 17 % with diabetes. Intraobserver ICC ranged from 0.640 for venous length to 0.906 for arterial area. Interobserver ICC ranged from 0.809 for arterial length to 0.916 for venous area, and interdevice ICC for arteriovenous ratio (AVR) was 0.887, thickness of arteries 0.590 and vein thickness 0.677. We found a moderate correlation between retinal vascular parameters and vascular structure and function, and target organ damage. In multiple linear regression analysis, the association with blood pressure, albumin/creatinine ratio, carotid intima-media thickness and cardiovascular risk is maintained. CONCLUSION: The ALTAIR tool has been useful for analysing the thickness, area and length of retinal vessels, with adequate reliability and a concomitant association of retinal vessel measurements with other cardiovascular parameters and cardiovascular risk. Therefore, in addition to thickness, the area and length of retinal vessels could also play a role in the prediction of cardiovascular risk.

2.
J Virol ; 94(2)2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31645448

RESUMO

Low-virulence classical swine fever virus (CSFV) strains make CSF eradication particularly difficult. Few data are available on the molecular determinants of CSFV virulence. The aim of the present study was to assess a possible role for CSFV virulence of a unique, uninterrupted 36-uridine (poly-U) sequence found in the 3' untranslated region (3' UTR) of the low-virulence CSFV isolate Pinar de Rio (PdR). To this end, a pair of cDNA-derived viruses based on the PdR backbone were generated, one carrying the long poly-U insertion in the 3' UTR (vPdR-36U) and the other harboring the standard 5 uridines at this position (vPdR-5U). Two groups of 20 5-day-old piglets were infected with vPdR-36U and vPdR-5U. Ten contact piglets were added to each group. Disease progression, virus replication, and immune responses were monitored for 5 weeks. The vPdR-5U virus was significantly more virulent than the vPdR-36U virus, with more severe disease, higher mortality, and significantly higher viral loads in serum and body secretions, despite similar replication characteristics in cell culture. The two viruses were transmitted to all contact piglets. Ninety percent of the piglets infected with vPdR-36U seroconverted, while only one vPdR-5U-infected piglet developed antibodies. The vPdR-5U-infected piglets showed only transient alpha interferon (IFN-α) responses in serum after 1 week of infection, while the vPdR-36U-infected piglets showed sustained IFN-α levels during the first 2 weeks. Taken together, these data show that the 3' UTR poly-U insertion acquired by the PdR isolate reduces viral virulence and activates the innate and humoral immune responses without affecting viral transmission.IMPORTANCE Classical swine fever (CSF), a highly contagious viral disease of pigs, is still endemic in some countries of Asia and Central and South America. Considering that the 3' untranslated region (3' UTR) plays an important role in flavivirus replication, the present study showed for the first time that a long polyuridine sequence acquired in the 3' UTR by an endemic CSFV isolate can activate immunity, control viral replication, and modulate disease in piglets. Our findings provide new avenues for the development of novel vaccines against infections with CSF virus and other flaviviruses. Knowledge of molecular virulence determinants is also relevant for future development of rapid and efficient diagnostic tools for the prediction of the virulence of field isolates and for efficient CSF control.

3.
Hisp Health Care Int ; : 1540415319881755, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674199

RESUMO

INTRODUCTION: To determine the prevalence of prescription opioid (PO) use among Hispanics/Latinos with arthritis symptoms and to characterize how demographic and cultural factors are associated with PO use. METHOD: Cross-sectional analysis of baseline visit data during 2008 to 2011 from the Hispanic Community Health Study/Study of Latinos, a population-based cohort study of 16,415 Hispanics/Latinos living in Chicago, Illinois, Miami, Florida, Bronx, New York, and San Diego, California. Included participants self-reported painful inflammation or swelling in one or more joints. Multivariate models controlling for physical and mental health scores were constructed to assess how demographic and cultural factors were associated with PO use. RESULTS: A total of 9.3% were using POs at the time of the baseline visit. In multivariate models, persons of Cuban background (adjusted odds ratio [AOR] = 0.42, 95% confidence interval [CI; 0.21, 0.81]) and of Dominican background (AOR = 0.38, 95% CI [0.18, 0.80]) were significantly less likely to use POs compared with a reference group of persons of Mexican background. Greater language acculturation was also negatively associated with PO use (AOR = 0.68, 95% CI [0.53, 0.87]). CONCLUSION: POs were used relatively uncommonly, and use showed marked variation between Hispanic/Latino groups. Future study should determine mechanisms for why greater use of English among Hispanics/Latinos might influence PO use.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31707749

RESUMO

AIM: As suggested by the Shared Vulnerability Model, impairment in executive functions could lead to worse creative performance among individuals with schizophrenia. Another impaired function in schizophrenia, previously related to creativity in healthy people, is theory of mind. However, little is known about the effect of theory of mind in creativity in schizophrenia. Therefore, the aim of this study was to analyze differences in creativity among patients with schizophrenia compared to healthy controls (HC) and to explore the potential role of executive functions and theory of mind as mediators of this relation. METHODS: Forty-five patients with schizophrenia and 45 HC underwent a neuropsychological assessment, including executive functions (cognitive flexibility and working memory), theory of mind, and verbal and figural creativity. RESULTS: As expected, patients with schizophrenia obtained lower scores in creativity, cognitive flexibility, working memory, and theory of mind compared to HC. Path analysis showed that theory of mind mediated the relation between group (schizophrenia or HC) and both figural (Z = 2.075, P = 0.037) and verbal creativity (Z = 2.570, P = 0.010). Working memory mediated the relation between group and figural creativity (Z = 2.034, P = 0.041) and was marginally significant for verbal creativity (Z = 1.930, P = 0.053). Finally, cognitive flexibility mediated between group and figural creativity (Z = 2.454, P = 0.014). CONCLUSION: Results suggest that the lower performance in creativity among patients with schizophrenia was partly due to an impairment in executive functions and theory of mind. The involvement of theory of mind opens up a new field of research as a possible risk factor in the Shared Vulnerability Model.

5.
Reg Anesth Pain Med ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31694933

RESUMO

BACKGROUND/OBJECTIVE: The role of caregiver psychosocial characteristics and their relation to postsurgical caregiving capability remains unclear. The objective of this study was to explore caregiver psychosocial variables following surgery of patients undergoing total joint arthroplasty and spine surgery. METHODS: A prospective observational study was conducted where questionnaires were administered to caregivers preoperatively and 1 week/2 weeks/1 month postoperatively. Measures included demographics, caregiver activities and National Institutes of Health Patient Reported Outcomes Measurement Information System (NIH PROMIS) item banks. Bivariate analysis assessed differences between participants reporting baseline pain and those reporting no baseline pain. Generalized estimating equation models examined PROMIS T-scores across time. RESULTS: 190 caregivers were enrolled and completed surveys. 18% of caregivers reported experiencing a painful condition where they experienced pain during most days of the week. Across all time points, the majority of caregivers reported no worse than mild impairment across PROMIS scores. Compared with baseline, caregivers reported lower PROMIS satisfaction with social roles across all postoperative time points (p<0.001) and higher depression and fatigue at postoperative day 7 (p=0.002) and 14 (p=0.006). PROMIS sleep disturbance was only higher at day 7 (p=0.01). Caregivers reporting a baseline pain condition reported PROMIS scores indicative of higher anxiety (p=0.02), depression (p=0.003), sleep disturbances (p<0.001) and fatigue (p<0.001) and lower levels of satisfaction with social roles (p=0.002) compared with those caregivers without baseline pain. CONCLUSION: While there were transient worsening in PROMIS scores, it is unclear whether these were clinically meaningful. Postsurgical caregivers reporting baseline pain were characterized by worse functioning across all PROMIS scales.

6.
Nat Struct Mol Biol ; 26(10): 970-979, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31582854

RESUMO

Cohesin is a regulator of genome architecture with roles in sister chromatid cohesion and chromosome compaction. The recruitment and mobility of cohesin complexes on DNA is restricted by nucleosomes. Here, we show that the role of cohesin in chromosome organization requires the histone chaperone FACT ('facilitates chromatin transcription') in Saccharomyces cerevisiae. We find that FACT interacts directly with cohesin, and is dynamically required for its localization on chromatin. Depletion of FACT in metaphase cells prevents cohesin accumulation at pericentric regions and causes reduced binding on chromosome arms. Using the Hi-C technique, we show that cohesin-dependent TAD (topological associated domain)-like structures in G1 and metaphase chromosomes are reduced in the absence of FACT. Sister chromatid cohesion is intact in FACT-depleted cells, although chromosome segregation failure is observed. Our data show that FACT contributes to the formation of cohesin-dependent TADs, thus uncovering a new role for this complex in nuclear organization during interphase and mitotic chromosome folding.

7.
8.
Viruses ; 11(9)2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31487968

RESUMO

Classical swine fever virus (CSFV) remains a highly important pathogen, causing major losses in the swine industry. Persistent infection is highly relevant for CSFV maintenance in the field; however, this form of infection is not fully understood. An increase in the granulocyte population has been detected in CSFV persistently infected animals. The aim of this work was to evaluate the possible immunosuppressive role of these cells in CSFV persistent infection. The phenotype of peripheral blood and bone marrow cells from persistently infected and naïve animals was evaluated by flow cytometry, and the capacity of specific cell subsets to reduce the interferon gamma (IFN-γ) response against unspecific and specific antigen was determined using co-culture assays. The frequency of granulocytic cells was increased in cells from CSFV persistently infected pigs and they showed a phenotype similar to immunosuppressive cell populations found in persistent infection in humans. These cells from persistently infected animals were able to reduce the IFN-γ response against unspecific and specific antigen. Our results suggest that immature immunosuppressive cell populations play a role in CSFV persistent infection in swine. The information obtained by studying the role of myeloid derived suppressor cells (MDSC) during CSFV persistent infection may extrapolate to other viral persistent infections in mammals.

9.
Sensors (Basel) ; 19(15)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31370149

RESUMO

The Internet of Things (IoT) has become one of the most widely research paradigms, having received much attention from the research community in the last few years. IoT is the paradigm that creates an internet-connected world, where all the everyday objects capture data from our environment and adapt it to our needs. However, the implementation of IoT is a challenging task and all the implementation scenarios require the use of different technologies and the emergence of new ones, such as Edge Computing (EC). EC allows for more secure and efficient data processing in real time, achieving better performance and results. Energy efficiency is one of the most interesting IoT scenarios. In this scenario sensors, actuators and smart devices interact to generate a large volume of data associated with energy consumption. This work proposes the use of an Edge-IoT platform and a Social Computing framework to build a system aimed to smart energy efficiency in a public building scenario. The system has been evaluated in a public building and the results make evident the notable benefits that come from applying Edge Computing to both energy efficiency scenarios and the framework itself. Those benefits included reduced data transfer from the IoT-Edge to the Cloud and reduced Cloud, computing and network resource costs.

10.
Biores Open Access ; 8(1): 129-138, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31367477

RESUMO

Skeletal muscle has a remarkable regenerative capacity in response to mild injury. However, when muscle is severely injured, muscle regeneration is impaired due to the loss of muscle-resident stem cells, known as satellite cells. Fibrotic tissue, primarily comprising collagen I (COL), is deposited with this critical loss of muscle. In recent studies, supplementation of laminin (LM)-111 has been shown to improve skeletal muscle regeneration in several models of disease and injury. Additionally, electrical stimulation (E-stim) has been investigated as a possible rehabilitation therapy to improve muscle's functional recovery. This study investigated the role of E-stim and substrate in regulating myogenic response. C2C12 myoblasts were allowed to differentiate into myotubes on COL- and LM-coated polydimethylsiloxane molds. The myotubes were subjected to E-stim and compared with nonstimulated controls. While E-stim resulted in increased myogenic activity, irrespective of substrate, LM supported increased proliferation and uniform distribution of C2C12 myoblasts. In addition, C2C12 myoblasts cultured on LM showed higher Sirtuin 1, mammalian target of rapamycin, desmin, nitric oxide, and vascular endothelial growth factor expression. Taken together, these results suggest that an LM substrate is more conducive to myoblast growth and differentiation in response to E-stim in vitro.

11.
BMC Vet Res ; 15(1): 247, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307464

RESUMO

BACKGROUND: Recent studies have hypothesized that circulation of classical swine fever virus (CSFV) variants when the immunity induced by the vaccine is not sterilizing might favour viral persistence. Likewise, in addition to congenital viral persistence, CSFV has also been proven to generate postnatal viral persistence. Under experimental conditions, postnatal persistently infected pigs were unable to elicit a specific immune response to a CSFV live attenuated vaccine via the mechanism known as superinfection exclusion (SIE). Here, we study whether subclinical forms of classical swine fever (CSF) may be present in a conventional farm in an endemic country and evaluate vaccine efficacy under these types of infections in field conditions. RESULTS: Six litters born from CSF-vaccinated gilts were randomly chosen from a commercial Cuban farm at 33 days of age (weaning). At this time, the piglets were vaccinated with a lapinized live attenuated CSFV C-strain vaccine. Virological and immunological analyses were performed before and after vaccination. The piglets were clinically healthy at weaning; however, 82% were viraemic, and the rectal swabs in most of the remaining 18% were positive. Only five piglets from one litter showed a specific antibody response. The tonsils and rectal swabs of five sows were CSFV positive, and only one of the sows showed an antibody response. After vaccination, 98% of the piglets were unable to clear the virus and to seroconvert, and some of the piglets showed polyarthritis and wasting after 36 days post vaccination. The CSFV E2 glycoprotein sequences recovered from one pig per litter were the same. The amino acid positions 72(R), 20(L) and 195(N) of E2 were identified in silico as positions associated with adaptive advantage. CONCLUSIONS: Circulation of chronic and persistent CSF infections was demonstrated in field conditions under a vaccination programme. Persistent infection was predominant. Here, we provide evidence that, in field conditions, subclinical infections are not detected by clinical diagnosis and, despite being infected with CSFV, the animals are vaccinated, rather than diagnosed and eliminated. These animals are refractory to vaccination, likely due to the SIE phenomenon. Improvement of vaccination strategies and diagnosis of subclinical forms of CSF is imperative for CSF eradication.


Assuntos
Vírus da Febre Suína Clássica/imunologia , Peste Suína Clássica/imunologia , Peste Suína Clássica/patologia , Vacinas Atenuadas/imunologia , Vacinas Virais/imunologia , Sequência de Aminoácidos , Animais , Peste Suína Clássica/virologia , Vírus da Febre Suína Clássica/isolamento & purificação , Cuba , Feminino , Superinfecção/veterinária , Superinfecção/virologia , Suínos , Vacinação/veterinária
12.
Rev. bras. orientac. prof ; 20(1): 31-44, jan.-jun. 2019. tab
Artigo em Espanhol | LILACS, Index Psicologia - Periódicos técnico-científicos | ID: biblio-1042395

RESUMO

Este artículo expone los resultados de un estudio centrado en el desarrollo de competencias prácticas autopercibidas por los estudiantes de pedagogía. El objetivo es conocer si el nivel de autopercepción en la adquisición de competencias generales y específicas para el ejercicio de la profesión pedagógica, varía tras la realización de las prácticas y verificar la existencia de diferencias significativas en la autopercepción del estudiante en función de las variables: año de finalización de estudios, rendimiento académico, mención cursada y titularidad del centro de prácticas. La metodología utilizada es cuantitativa, el diseño de investigación de tipo pre-experimental, con aplicación de pre-test y post-test. Se empleó un método descriptivo-inferencial, por medio del estudio de encuesta electrónica. Los resultados muestran que la valoración de los futuros pedagogos sobre la adquisición de diferentes competencias del Grado de Pedagogía, es muy positiva tanto antes como después del periodo de prácticas externas; así como la existencia de diferencias significativas en función de las variables estudiadas.


Este artigo expõe os resultados de um estudo centrado no desenvolvimento de competências práticas autopercebidas pelos estudantes de Pedagogia. O objetivo é saber se o nível de autopercepção na aquisição de competências gerais e específicas para o exercício da profissão pedagógica varia após a realização das práticas e verificar a existência de diferenças significativas na autopercepção do aluno de acordo com as variáveis: ano de conclusão dos estudos, desempenho acadêmico, especialização matriculada e tipo de instituição de estágio. A metodologia empregada é quantitativa, o desenho de investigação de tipo pre-experimental, com aplicação de pré-teste e pós-teste. Utilizou-se um método descritivo-inferencial, por meio do estudo de pesquisas eletrônicas de opinião. Os resultados mostram que a valoração dos futuros pedagogos sobre a aquisição de diferentes competências do curso de Pedagogia, é muito positiva antes e depois do período de práticas externas; assim como a existência de diferenças significativas em função das variáveis estudadas.


This article presents the results of a study focused on the development of self - perceived practical skills by Pedagogy majors. The objective is to know if the level of self-perception in the acquisition of general and specific competences for the exercise of the pedagogical profession varies after the accomplishment of the teacher training period and verify the existence of significant differences in the student´s self-perception according to the variables: year of studies completion, academic performance, specialization enrollment and type of internship institution. The methodology used is quantitative, the research design is of the pre-experimental type, with application of pre-test and post-test. A descriptive-inferential method was used, through the study of electronic opinion surveys. The results reveal that the future teachers´ evaluation of the acquisition of different competences in the Degree Program in Pedagogy is very positive, both before and after the period of external teaching training; as well as the existence of significant differences according to the studied variables.


Assuntos
Competência Profissional , Estudantes , Ensino , Mobilidade Ocupacional
13.
Int J Food Sci Nutr ; 70(8): 977-985, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31084381

RESUMO

Type 2 diabetes mellitus (T2DM) is associated with premature atherosclerosis and arterial stiffening due to the accumulation of advanced glycation end-products in vessel walls. Green tea polyphenols are considered cardio-protective substances. In this randomised double-blind placebo-controlled trial (NCT02627898), we evaluated the effect of Green tea extract on arterial stiffness parameters, lipids, body composition and sRAGE levels. Twenty normotensive patients with T2DM treated with the standard therapy and statins, mean age 53.2 ± 9.4 years and mean BMI 30.1 ± 4.5 kg/m2, were randomised to receive a daily dose of 400 mg of green tea extract (polyphenols ≥90%, EGCG ≥45%) or placebo for 12 weeks. Compared to placebo, administration of green tea extract decreased central augmentation index (-3.05 ± 10.8% vs. 6.7 ± 0.1%, p = .04). These findings suggest that green tea extract could be used as an adjunct to the standard therapy to improve arterial stiffness in T2DM.

14.
Enferm Clin ; 2019 Apr 24.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31029552

RESUMO

OBJECTIVES: To determine the quality of life related to health, functional capacity and mood to hip fracture and one month after surgery. METHOD: Prospective and descriptive study developed from January 2015 to January 2016 in Campo Arañuelo Hospital (Navalmoral de la Mata, Cáceres, Spain). Sociodemographic variables, functional capacity (Barthel Index), dependence (Lawton and Brody Scale), quality of life related to health (Questionnaire Euroqol-5D) and on mood (Yesavage geriatric depression scale GDS15) were collected, prior to the hip fracture and one month after the intervention. RESULTS: Significant decrease in functional capacity (Barthel), the mean score was 86.66 before the fracture, compared to 58.72 at the month after surgery (P<.001). Regarding the Lawton and Brody Scale, the mean was 4.95 and at 2.24months (P<.001). The mean scores on health related quality of life, baseline and post-intervention in the analog visual scale of the EQ-5D questionnaire were 72.95 vs 59.45 respectively (P=.004). Although before the fracture, 94.10% had no alteration in mood, one month after the intervention there was a possible depression of 20.50% and an established depression of 11%. CONCLUSIONS: The fracture of the head affects the functionality of the elderly, causing dependence for the basic and instrumental activities of daily life. It also affects the quality of life related to health and this decreases significantly in the month after surgery. Depressive mood is inversely related to perceived perceived quality of life.

15.
Polymers (Basel) ; 11(2)2019 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-30960343

RESUMO

In the European Union, the demand for polyurethane is continually growing. In 2017, the estimated value of polyurethane production was 700,400 Tn, of which 27.3% is taken to landfill, which causes an environmental problem. In this paper, the behaviour of various polyurethane foams from the waste of different types of industries will be analyzed with the aim of assessing their potential use in construction materials. To achieve this, the wastes were chemically tested by means of CHNS, TGA, and leaching tests. They were tested microstructurally by means of SEM. The processing parameters of the waste was calculated after identifying its granulometry and its physical properties i.e., density and water absorption capacity. In addition, the possibility of incorporating these wastes in plaster matrices was studied by determining their rendering in an operational context, finding out their mechanical resistance to flexion and compression at seven days, their reaction to fire as well as their weight per unit of area, and their thermal behaviour. The results show that in all cases, the waste is inert and does not undergo leaching. The generation process of the waste determines the foam's microstructure in addition to its physical-chemical properties, which directly affect building materials in which they are included, thus offering different ways in which they can be applied.

16.
Int J Cancer ; 145(10): 2682-2691, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-30927264

RESUMO

Multigene panels provide a powerful tool for analyzing several genes simultaneously. We evaluated the frequency of pathogenic variants (PV) in customized predefined panels according to clinical suspicion by phenotype and compared it to the yield obtained in the analysis of our clinical research gene panel. We also investigated mutational yield of opportunistic testing of BRCA1/2 and mismatch repair (MMR) genes in all patients. A total of 1,205 unrelated probands with clinical suspicion of hereditary cancer were screened for germline mutations using panel testing. Overall, 1,048 females and 157 males were analyzed, mean age at cancer diagnosis was 48; 883 had hereditary breast/ovarian cancer-suspicion, 205 hereditary nonpolyposis colorectal cancer (HNPCC)-suspicion, 73 adenomatous-polyposis-suspicion and 44 with other/multiple clinical criteria. At least one PV was found in 150 probands (12%) analyzed by our customized phenotype-driven panel. Tumoral MMR deficiency predicted for the presence of germline MMR gene mutations in patients with HNPCC-suspicion (46/136 vs. 0/56 in patients with and without MMR deficiency, respectively). Opportunistic testing additionally identified five MSH6, one BRCA1 and one BRCA2 carriers (0.6%). The analysis of the extended 24-gene panel provided 25 additional PVs (2%), including in 4 out of 51 individuals harboring MMR-proficient colorectal tumors (2 CHEK2 and 2 ATM). Phenotype-based panels provide a notable rate of PVs with clinical actionability. Opportunistic testing of MMR and BRCA genes leads to a significant straightforward identification of MSH6, BRCA1 and BRCA2 mutation carriers, and endorses the model of opportunistic testing of genes with clinical utility within a standard genetic counseling framework.

17.
Radiat Environ Biophys ; 58(2): 237-245, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30689023

RESUMO

Osteosarcoma is the most common primary malignant tumour of bone in young patients. The survival of these patients has largely been improved due to adjuvant and neo-adjuvant chemotherapy in addition to surgery. Boron neutron capture therapy (BNCT) is proposed as a complementary therapy, due to its ability to inactivate tumour cells that may survive the standard treatment and that may be responsible for recurrences and/or metastases. BNCT is based on neutron irradiation of a tumour enriched in 10B with a boron-loaded drug. Low-energy neutron capture in 10B creates charged particles that impart a high dose to tumour cells, which can be calculated only knowing the boron concentration. Charged particle spectrometry is a method that can be used to quantify boron concentration. This method requires acquisition of the energy spectra of charged particles such as alpha particles produced by neutron capture reactions in thin tissue sections irradiated with low-energy neutrons. Boron concentration is then determined knowing the stopping power of the alpha particles in the sample material. This paper describes the adaptation of this method for bone, with emphasis on sample preparation, experimental set-up and stopping power assessment of the involved alpha particles. The knowledge of boron concentration in healthy bones is important, because it allows for any dose limitation that might be necessary to avoid adverse effects such as bone fragility. The measurement process was studied through Monte Carlo simulations and analytical calculations. Finally, the boron content of bone samples was measured by alpha spectrometry at the TRIGA reactor in Pavia, Italy, and compared to that obtained by neutron autoradiography. The agreement between the results obtained with these techniques confirms the suitability of alpha spectrometry to measure boron in bone.

18.
Int J Radiat Biol ; 95(5): 646-654, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30601686

RESUMO

PURPOSE: Boron neutron capture therapy (BNCT) combines selective accumulation of 10B carriers in tumor tissue with subsequent neutron irradiation. BNCT has been proposed for the treatment of multiple, non-resectable, diffuse tumors in lung. The aim of the present study was to evaluate the therapeutic efficacy and toxicity of BNCT in an experimental model of lung metastases of colon carcinoma in BDIX rats and perform complementary survival studies. MATERIALS AND METHODS: We evaluated tumor control and toxicity in lung 2 weeks post-BNCT at 2 dose levels, including 5 experimental groups per dose level: T0 (euthanized pre-treatment), Boronophenylalanine-BNCT (BPA-BNCT), BPA + Sodium decahydrodecaborate-BNCT ((BPA + GB-10)-BNCT), Beam only (BO) and Sham (no treatment, same manipulation). Tumor response was assessed employing macroscopic and microscopic end-points. An additional experiment was performed to evaluate survival and oxygen saturation in blood. RESULTS AND CONCLUSIONS: No dose-limiting signs of short/medium-term toxicity were observed in lung. All end-points revealed statistically significant BNCT-induced tumor control vs Sham at both dose levels. The survival experiment showed a statistically significant 45% increase in post-treatment survival time in the BNCT group (48 days) versus Sham (33 days). These data consistently revealed growth suppression of lung metastases by BNCT with no manifest lung toxicity. Highlights Boron Neutron Capture Therapy suppresses growth of experimental lung metastases No BNCT-induced short/medium-term toxicity in lung is associated with tumor control Boron Neutron Capture Therapy increased post-treatment survival time by 45.


Assuntos
Terapia por Captura de Nêutron de Boro , Neoplasias Pulmonares/radioterapia , Pesquisa Médica Translacional , Animais , Terapia por Captura de Nêutron de Boro/efeitos adversos , Linhagem Celular Tumoral , Neoplasias do Colo/secundário , Relação Dose-Resposta à Radiação , Neoplasias Pulmonares/patologia , Radiometria , Ratos , Análise de Sobrevida
19.
J Med Genet ; 56(8): 521-525, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30580288

RESUMO

IMPORTANCE: Genetic testing of hereditary cancer using comprehensive gene panels can identify patients with more than one pathogenic mutation in high and/or moderate-risk-associated cancer genes. This phenomenon is known as multilocus inherited neoplasia alleles syndrome (MINAS), which has been potentially linked to more severe clinical manifestations. OBJECTIVE: To determine the prevalence and clinical features of MINAS in a large cohort of adult patients with hereditary cancer homogeneously tested with the same gene panel. PATIENTS AND METHODS: A cohort of 1023 unrelated patients with suspicion of hereditary cancer was screened using a validated panel including up to 135 genes associated with hereditary cancer and phakomatoses. RESULTS: Thirteen (1.37%) patients harbouring two pathogenic mutations in dominant cancer-predisposing genes were identified, representing 5.7% (13/226) of patients with pathogenic mutations. Most (10/13) of these cases presented clinical manifestations associated with only one of the mutations identified. One case showed mutations in MEN1 and MLH1 and developed tumours associated with both cancer syndromes. Interestingly, three of the double mutants had a young age of onset or severe breast cancer phenotype and carried mutations in moderate to low-risk DNA damage repair-associated genes; two of them presented biallelic inactivation of CHEK2. We included these two patients for the sake of their clinical interest although we are aware that they do not exactly fulfil the definition of MINAS since both mutations are in the same gene. CONCLUSIONS AND RELEVANCE: Genetic analysis of a broad cancer gene panel identified the largest series of patients with MINAS described in a single study. Overall, our data do not support the existence of more severe manifestations in double mutants at the time of diagnosis although they do confirm previous evidence of severe phenotype in biallelic CHEK2 and other DNA repair cancer-predisposing genes.

20.
Sci Total Environ ; 654: 190-196, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30445320

RESUMO

Reports of enteric bacteria in Antarctic wildlife have suggested its spread from people to seabirds and seals, but evidence is scarce and fragmentary. We investigated the occurrence of zoonotic enteric bacteria in seabirds across the Antarctic and subantarctic region; for comparison purposes, in addition to seabirds, poultry in a subantarctic island was also sampled. Three findings suggest reverse zoonosis from humans to seabirds: the detection of a zoonotic Salmonella serovar (ser. Enteritidis) and Campylobacter species (e.g. C. jejuni), typical of human infections; the resistance of C. lari isolates to ciprofloxacin and enrofloxacin, antibiotics commonly used in human and veterinary medicine; and most importantly, the presence of C. jejuni genotypes mostly found in humans and domestic animals but rarely or never found in wild birds so far. We also show further spread of zoonotic agents among Antarctic wildlife is facilitated by substantial connectivity among populations of opportunistic seabirds, notably skuas (Stercorarius). Our results highlight the need for even stricter biosecurity measures to limit human impacts in Antarctica.


Assuntos
Animais Selvagens/microbiologia , Doenças das Aves/microbiologia , Campylobacter/isolamento & purificação , Microbioma Gastrointestinal , Salmonella/isolamento & purificação , Zoonoses/microbiologia , Animais , Regiões Antárticas , Antibacterianos/farmacologia , Campylobacter/efeitos dos fármacos , Monitoramento Ambiental , Fezes/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Oceanos e Mares , Salmonella/efeitos dos fármacos
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