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OBJECTIVE: The aim of this study was to develop an initial valid tool to measure attitudes toward cancer-related cognitive changes. SUBJECTS AND METHODS: After revising the literature, three main dimensions were hypothesized. Eight judges were contacted to obtain content validity evidence. A robust Exploratory Factor Analysis (EFA) was performed via a parallel analysis with an Unweighted Least Squares (ULS) estimator and polychoric correlations. The results were crossed with sociodemographic variables to find possible statistical differences and estimate the size effect. Analysis was performed in the software Factor and the statistical package R. RESULTS: A sample of 374 participants was obtained, involving oncology patients, their caregivers, and people from the general community. A statistical fit was found in two dimensions: Awareness and Judgments [root mean squared error of approximation (RMSEA) = 0.042, standardized root mean square residual (SRMR) = 0.02, comparative fit index (CFI) = 0.99, Tucker-Lewis index (TLI) = 0.98] with a moderate correlation between them (r = 0.612). Optimal reliability indices were obtained for the total scale and its dimensions. No real statistical difference was found between sociodemographic variables; the interpretation norms were established via the quartiles. CONCLUSIONS: The first attempt to measure the construct of interest was developed with two primary validity evidence based on the content and its internal structure. This instrument could help strengthen the prevention of cancer-related cognitive changes. More research is needed to adhere more valid evidence to the scale.
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Oncologia , Neoplasias , Humanos , Colômbia , Reprodutibilidade dos Testes , Software , CogniçãoRESUMO
Precision oncology research is challenging outside the contexts of oncogenic addiction and/or targeted therapies. We previously showed that phosphoproteomics is a powerful approach to reveal patient subsets of interest characterized by the activity of a few kinases where the underlying genomics is complex. Here, we conduct a phosphoproteomic screening of samples from HER2-negative female breast cancer receiving neoadjuvant paclitaxel (N = 130), aiming to find candidate biomarkers of paclitaxel sensitivity. Filtering 11 candidate biomarkers through 2 independent patient sets (N = 218) allowed the identification of a subgroup of patients characterized by high levels of CDK4 and filamin-A who had a 90% chance of achieving a pCR in response to paclitaxel. Mechanistically, CDK4 regulates filamin-A transcription, which in turn forms a complex with tubulin and CLIP-170, which elicits increased binding of paclitaxel to microtubules, microtubule acetylation and stabilization, and mitotic catastrophe. Thus, phosphoproteomics allows the identification of explainable factors for predicting response to paclitaxel.
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Neoplasias da Mama , Paclitaxel , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Quinase 4 Dependente de Ciclina , Genômica , Paclitaxel/farmacologia , Medicina de PrecisãoRESUMO
The inter-mountainous region of central Honduras has been experiencing abrupt urban drinking water shortages during the last decade. Land use fragmentation and rainfall deficits have rapidly reduced surface water quality and quantity in this region. Here we present a 3-yr (2018-2020) tracer study within the headwaters of the Choluteca River basin (2949 km2). We sampled rainfall (weekly N = 156; daily N = 270), drilled wells (N = 166; up to ~300 m depth), boreholes (N = 70; ~4-12 m depth), and springs (N = 128) to assess the spatiotemporal connectivity between rainfall and mean groundwater recharge elevations (MREs). Clear W-shaped incursions characterized rainfall isotopic seasonality from the dry to the wet season. Air mass back trajectory analysis revealed three primary moisture sources: 73 % (east, Caribbean Sea), 17 % (southwest, Pacific Ocean), and 10 % (north; Gulf of Mexico). Groundwater sources exhibited a strong meteoric origin with evidence of secondary evaporation evolution, characterized by low d-excess values. MREs for the drilled wells ranged from 821 to 2018 m asl with a mean value of 1570 ± 150 m asl. Seasonal isotopic variability during dry-wet transitions and the influence of rapid infiltration limited the performance of the MRE method in springs and boreholes. MREs coincided primarily with coniferous forests, pasture, and crop areas, within regions of moderate to high transmissivity. These results are intended to guide the mapping and delineation of critical recharge areas in central Honduras to enhance municipal water regulations, effective environmental protection, and long-term conservation practices.
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Monitoramento Ambiental , Água Subterrânea , Monitoramento Ambiental/métodos , Honduras , Isótopos/análise , Isótopos de Oxigênio/análise , RiosRESUMO
Although optical hyperthermia could be a promising anticancer therapy, the need for high concentrations of light-absorbing metal nanoparticles and high-intensity lasers, or large exposure times, could discourage its use due to the toxicity that they could imply. In this article, we explore a possible role of silica microparticles that have high biocompatibility and that scatter light, when used in combination with conventional nanoparticles, to reduce those high concentrations of particles and/or those intense laser beams, in order to improve the biocompatibility of the overall procedure. Our underlying hypothesis is that the scattering of light caused by the microparticles would increase the optical density of the irradiated volume due to the production of multiple reflections of the incident light: the nanoparticles present in the same volume would absorb more energy from the laser than without the presence of silica particles, resulting either in higher heat production or in the need for less laser power or absorbing particles for the same required temperature rise. Testing this new optical hyperthermia procedure, based on the use of a mixture of silica and metallic particles, we have measured cell mortality in vitro experiments with murine glioma (CT-2A) and mouse osteoblastic (MC3T3-E1) cell lines. We have used gold nanorods (GNRs) that absorb light with a wavelength of 808 nm, which are conventional in optical hyperthermia, and silica microparticles spheres (hereinafter referred to as SMSs) with a diameter size to scatter the light of this wavelength. The obtained results confirm our initial hypothesis, because a high mortality rate is achieved with reduced concentrations of GNR. We found a difference in mortality between CT2A cancer cells and cells considered non-cancer MC3T3, maintaining the same conditions, which gives indications that this technique possibly improves the efficiency in the cell survival. This might be related with differences in the proliferation rate. Since the experiments were carried out in the 2D dimensions of the Petri dishes, due to sedimentation of the silica particles at the bottom, whilst light scattering is a 3D phenomenon, a large amount of the energy provided by the laser escapes outside the medium. Therefore, better results might be expected when applying this methodology in tissues, which are 3D structures, where the multiple reflections of light we believe will produce higher optical density in comparison to the conventional case of no using scattering particles. Accordingly, further studies deserve to be carried out in this line of work in order to improve the optical hyperthermia technique.
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Glioblastoma/terapia , Hipertermia Induzida , Nanopartículas Metálicas/administração & dosagem , Osteoblastos/citologia , Dióxido de Silício/química , Animais , Sobrevivência Celular , Células Cultivadas , Glioblastoma/patologia , Lasers , Nanopartículas Metálicas/química , CamundongosRESUMO
OBJECTIVE: To assess the determinants of the participation rate in breast cancer screening programs by conducting a systematic review of reviews. METHODS: We conducted a systematic search in PubMed via Medline, Scopus, Embase, and Cochrane identifying the literature up to April 2019. Out of 2258 revealed unique abstracts, we included 31 reviews, from which 25 were considered as systematic. We applied the Walsh & McPhee Systems Model of Clinical Preventive Care to systematize the determinants of screening participation. RESULTS: The reviews, mainly in high-income settings, reported a wide range for breast cancer screening participation rate: 16-90%. The determinants of breast cancer screening participation were simple low-cost interventions such as invitation letters, basic information on screening, multiple reminders, fixed appointments, prompts from healthcare professionals, and healthcare organizational factors (e.g. close proximity to screening facility). More complex interventions (such as face-to-face counselling or home visits), mass media or improved access to transport should not be encouraged by policy makers unless other information appears. The repeated participation in mammography screening was consistently high, above 62%. Previous positive experience with screening influenced the repeated participation in screening programs. The reviews were inconsistent in the use of terminology related to breast cancer screening participation, which may have contributed to the heterogeneity in the reported outcomes. CONCLUSIONS: This study shows that consistent findings of systematic reviews bring more certainty into the conclusions on the effects of simple invitation techniques, fixed appointments and prompts, as well as healthcare organizational factors on promoting participation rate in screening mammography.
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Neoplasias da Mama , Neoplasias da Mama/diagnóstico , Detecção Precoce de Câncer , Feminino , Humanos , Mamografia , Programas de Rastreamento , Revisões Sistemáticas como AssuntoRESUMO
Groundwater plays an important role in the economic development of the Chaco-Pampean Plain (Argentina), where industry, agriculture and cattle farming are the main economic activities. The 66% of the country's population lives in this area. The low slopes of this region condition the water movement and the occurrence of physical and chemical processes. The aim of this work is to update the hydrological conceptual model of the Del Azul Creek basin (Buenos Aires Province), a sub-humid and continental plain, using environmental tracers. In total, the study was based on the analysis of 201 samples (stable isotopes) and 184 samples (chemical data) including rainwater, surface water and groundwater. The temporal and spatial variation in the isotopic composition of rainfall and the hydrological physical-processes, evaporation, surface water-groundwater interaction and recharge were studied. Isotopic compositions of rainfall revealed a seasonal variation across the basin. Low δ18O rainfalls occur during the coldest seasons, while high δ18O rainfalls occur during the warmest seasons. The isotopic compositions of rainfall varied only during the cold period in the upper basin. At this time, the lowest δ18O rainfall fell in the upper basin, while in the other areas and during the warmer seasons, no differences were observed. Evaporation was a relevant process in the flatter area of the basin, mainly during the warmest seasons. Samples taken from the wetlands and from the lower section of the Del Azul Creek were strongly evaporated. In the first 30 m depth of the aquifer, groundwater reflected the isotopic composition of rainfall from the warmest seasons, thus revealing seasonal preferential recharge and a good hydraulic connection. This study provides direct evidence showing that both evaporation and the surface water-groundwater interaction are processes that play a key role in the control of the isotopic and chemical composition of water.
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PURPOSE: To describe the results of MRI (magnetic resonance image) guided ROLL (radioguided occult lesion localization) and SNOLL (sentinel node occult lesion localization) in the localization of residual disease after neoadjuvant chemotherapy for breast cancer, as well as assessing the surgical results obtained and disease free survival. METHODS: Prospective observational analysis of 132 patients with 136 tumors, treated with neoadjuvant chemotherapy at our hospital between 2011-2017. Residual disease was located presurgically with MRI guided ROLL/SNOLL technique. We analyzed technical aspects of localization, and variables corresponding to surgical procedures and events occurred during follow-up. RESULTS: The median tumor size was of 20.5mm (interquartilic range [IQR]: 14-28). The majority (96.3%) were invasive ductal carcinomas. Sentinel lymph node detection rate was 98.9%. Complete pathological response (CPR) in the breast was achieved in 58.1% of cases. The rate of affected margins in 89 cases operated by conservative surgery was 2.2%. With a median follow-up of 50 months (IQR: 37-61) we found a 7.4% rate of relapses. Of these, seven were loco-regional and three at distant sites. The estimated mean of disease-free survival time was 83.2 months (Confidence Interval [CI] 95%: 79.6-86.6). CONCLUSIONS: MRI guided ROLL/SNOLL is a great tool for breast cancer residual disease localization following neoadjuvant chemotherapy. In addition, this technique attains good loco-regional control of the diseases and has excellent surgical results.
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Groundwater pollution in tropical and human-altered coastal landscapes is receiving novel attention due to decreasing in annual recharge as a consequence of recurrent droughts and overexploitation, whereby saline intrusion, point and diffuse source contamination, and water conflicts are common denominators. This study presents a detailed groundwater evaluation in a coastal aquifer within the central Pacific coast of Costa Rica. Three sampling campaigns including major ions, heavy metals, and fecal coliform analyses were conducted between July 2013 and March 2014 across 17 wells within the alluvial and fissured units of the Jacó aquifer. The groundwater system is classified as mixed HCO3--Ca2+-Mg2+ type. Coliforms presence was found in two wells, nearby Mona Creek headwaters and near the coastal line. Heavy metal concentrations were below quantification limits in most of the wells; however, chromium concentrations up to 6.56 µg/L were quantified within the coastal line and central portion of the alluvial aquifer in 20 out of the 48 samples. The spatial distribution of major ions (K+, Na+, Ca2+, Mg2+, Cl-, SO42-, and HCO3-) exhibited an increasing trend towards the central portion of the alluvial aquifer, which may be potentially associated with the large unregulated urban expansion, invoking a need of a continuous water quality monitoring program in this touristic hot spot. This study provides useful information for other similar coastal aquifers in Central America, whereby increasing population growth and unregulated touristic, industrial, and agricultural activities are posing a truly challenge to ensure water security and sustainability parallel to the economic development in a changing climate.
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Água Subterrânea/análise , Água Subterrânea/química , Poluentes Químicos da Água/análise , Agricultura , Costa Rica , Enterobacteriaceae , Monitoramento Ambiental , Fezes/microbiologia , Água Subterrânea/microbiologia , Humanos , Metais Pesados/análise , Oceano Pacífico , Microbiologia da Água , Qualidade da Água , Poços de ÁguaRESUMO
Metallic nanorods are promising agents for a wide range of biomedical applications. We report an optical hyperthermia method capable of inducing slowdown tumor progression of an experimental in vivo CT-2A glioblastoma tumor. The tumor model used in this research is based on the transplantation of mouse astrocytoma CT-2A cells in the striatum of mice by intracranial stereotaxic surgery. Two weeks after cell implant, the resulting tumor is treated by irradiating intratumoral injected gold nanorods, biofunctionalized with CD133 antibody (B-GNRs), using a continuous wave laser. Nanoparticles convert the absorbed light into localized heat (reaching up to 44 °C) due to the effect of surface plasmon resonance. A significant slowdown in CT-2A tumor progression is evident, by histology and magnetic resonance imaging, at one (p = 0.03) and two weeks (p = 0.008) after irradiation treatment. A notable deceleration in tumor size (15%-75%) as compared to the control untreated groups, it is observed. Thus, laser irradiation of B-GNRs is found to be effective for the treatment of CT-2A tumor progression. Similarities between the pre-clinical CT-2A tumor model and the human astrocytoma disease, in terms of anatomy, metastatic behavior and histopathology, suggest that hyperthermic treatment by laser irradiation of B-GNRs administered into high-grade human astrocytoma might constitute a promising alternative treatment to limit the progression of this deadly disease.
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Astrocitoma/terapia , Neoplasias Encefálicas/terapia , Ouro/farmacologia , Hipertermia Induzida/métodos , Terapia a Laser/métodos , Nanotubos/química , Antígeno AC133/antagonistas & inibidores , Antígeno AC133/imunologia , Animais , Anticorpos Neutralizantes/farmacologia , Astrocitoma/imunologia , Astrocitoma/patologia , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Progressão da Doença , Ouro/administração & dosagem , Ouro/química , Humanos , Injeções Intralesionais , Lasers , Camundongos , Camundongos Endogâmicos C57BL , Nanotubos/ultraestrutura , Transplante de Neoplasias , Técnicas Estereotáxicas , Ressonância de Plasmônio de Superfície , Carga Tumoral/efeitos da radiaçãoRESUMO
Congenital lipomatous overgrowth with vascular, epidermal, and skeletal (CLOVES) anomalies and Klippel-Trenaunay (KTS) syndromes are caused by somatic gain-of-function mutations in PIK3CA, encoding a catalytic subunit of phosphoinositide 3-kinase. Affected tissue is needed to find mutations, as mutant alleles are not detectable in blood. Because some patients with CLOVES develop Wilms tumor, we tested urine as a source of DNA for mutation detection. We extracted DNA from the urine of 17 and 24 individuals with CLOVES and KTS, respectively, and screened 5 common PIK3CA mutation hotspots using droplet digital polymerase chain reaction. Six of 17 CLOVES participants (35%) had mutant PIK3CA alleles in urine. Among 8 individuals in whom a mutation had been previously identified in affected tissue, 4 had the same mutant allele in the urine. One study participant with CLOVES had been treated for Wilms tumor. We detected the same PIK3CA mutation in her affected tissue, urine, and tumor, indicating Wilms tumors probably arise from PIK3CA mutant cells in patients with CLOVES. No urine sample from a participant with KTS had detectable PIK3CA mutations. We suggest that urine, which has the advantage of being collected non-invasively, is useful when searching for mutations in individuals with CLOVES syndrome.
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Classe I de Fosfatidilinositol 3-Quinases/genética , Síndrome de Klippel-Trenaunay-Weber/genética , Lipoma/genética , Anormalidades Musculoesqueléticas/genética , Nevo/genética , Malformações Vasculares/genética , Tumor de Wilms/genética , Adolescente , Adulto , Alelos , Criança , Pré-Escolar , DNA/genética , DNA/urina , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Síndrome de Klippel-Trenaunay-Weber/patologia , Síndrome de Klippel-Trenaunay-Weber/urina , Lipoma/patologia , Lipoma/urina , Masculino , Pessoa de Meia-Idade , Anormalidades Musculoesqueléticas/patologia , Anormalidades Musculoesqueléticas/urina , Mutação , Nevo/patologia , Nevo/urina , Fenótipo , Malformações Vasculares/patologia , Malformações Vasculares/urina , Tumor de Wilms/patologia , Tumor de Wilms/urinaRESUMO
Bioorthogonal dissociative reactions boast diverse potential applications in chemical biology and drug delivery. The reaction of benzonorbornadienes with tetrazines to release amines from carbamate leaving groups was recently introduced as a bioorthogonal bond-cleavage reaction. The present study aimed at investigating the scope of leaving groups that are compatible with benzonorbornadienes. Synthesis of several benzonorbornadienes with different releasable groups is reported, and the reaction of these molecules with tetrazine was found to be rapid and afforded high release yields. The tetrazine-induced release of molecules proceeds in a cascade of steps including inverse-electron demand cycloaddition and cycloreversion reactions that form unstable isoindoles/isobenzofuran intermediates and spontaneously eliminate a leaving group of interest. In the case of oxygen-bridged BNBDs at room temperature, we observed the formation of an unproductive byproduct.
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BACKGROUND: Multiple reviews demonstrated high variability in effectiveness and cost-effectiveness outcomes among studies on breast cancer screening (BCS) programmes. No study to our knowledge has summarized the current evidence on determinants of effectiveness and cost-effectiveness of the most used BCS approaches or tried to explain differences in conclusions of systematic reviews on this topic. Based on published reviews, this systematic review aims to assess the degree of variability of determinants for (a) effectiveness and (b) cost-effectiveness of BCS programmes using mammography, clinical breast examination, breast self-examination, ultrasonography, or their combinations among the general population. METHODS: We will perform a comprehensive systematic literature search in Cochrane, Scopus, Embase, and Medline (via Pubmed). The search will be supplemented with hand searching of references of the included reviews, with hand searching in the specialized journals, and by contacting prominent experts in the field. Additional search for grey literature will be conducted on the websites of international cancer associations and networks. Two trained research assistants will screen titles and abstracts of publications independently, with at least random 10% of all abstracts being also screened by the principal researcher. The full texts of the systematic reviews will then be screened independently by two authors, and disagreements will be solved by consensus. The included reviews will be grouped by publication year, outcomes, designs of original studies, and quality. Additionally, for reviews published since 2011, transparency in reporting will be assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist for the review on determinants of effectiveness and a modified PRISMA checklist for the review on determinants for cost-effectiveness. The study will apply the Assessing the Methodological Quality of Systematic Reviews checklist to assess the methodological quality of systematic reviews. We will report the data extracted from the systematic reviews in a systematic format. Meta-meta-analysis of extracted data will be conducted when feasible. DISCUSSION: This systematic review of reviews will examine the degree of variability in the effectiveness and cost-effectiveness of BCS programmes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016050764 and CRD42016050765.
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Neoplasias da Mama/diagnóstico , Análise Custo-Benefício , Detecção Precoce de Câncer/economia , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Literatura de Revisão como Assunto , Revisões Sistemáticas como AssuntoRESUMO
This study describes four multiple nucleocapsid nucleopolyhedrovirus isolates recovered from infected larvae of beet armyworm, Spodoptera exigua (Hübner) (Lepidoptera: Noctuidae), on crops in two different geographical regions of Mexico. Molecular and biological characterization was compared with characterized S. exigua multiple nucleopolyhedrovirus (SeMNPV) isolates from the United States (SeUS1 and SeUS2) and Spain (SeSP2). Restriction endonuclease analysis of viral DNA confirmed that all Mexican isolates were SeMNPV isolates, but molecular differences between the Mexican and the reference isolates were detected using PCR combined with restriction fragment length polymorphism (RFLP). Amplification of the variable region V01 combined with RFLP distinguished the two Mexican isolates, SeSLP6 and SeSIN6. BglII digestions showed that the majority of the isolates contained submolar bands, indicating the presence of genetic heterogeneity. Amplification of the variable regions V04 and V05 distinguished between American and the Spanish isolates. Biological characterization was performed against two laboratory colonies of S. exigua, one from Mexico, and another from Switzerland. Insects from the Mexican colony were less susceptible to infection than insects from Se-Swiss colony. In the Se-Mex colony, SeSP2 was the most pathogenic isolate followed by SeSIN6, although their virulence was similar to most of the isolates tested. In Se-Swiss colony, similar LD50 values were observed for the five isolates, although the virulence was higher for the SeSLP6 isolate, which also had the highest OB (occlusion body) yield. We conclude that the Mexican isolates SeSIN6 and SeSLP6 possess insecticidal traits of value for the development of biopesticides for the control of populations of S. exigua.
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DNA Viral/genética , Nucleopoliedrovírus/fisiologia , Controle Biológico de Vetores , Spodoptera/virologia , Animais , Larva/crescimento & desenvolvimento , Larva/virologia , México , Nucleopoliedrovírus/genética , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Spodoptera/crescimento & desenvolvimentoRESUMO
CASE REPORT: We report the case of a 55-year-old patient who pre- sented a pelvic mass, ascites and elevated serum CA125. Suspecting a malignant process she underwent surgery and a total hysterectomy with bilateral salpigo-oforectomy was performed. Pathologic report revealed a bilateral ovarian fibroma and non-tumoral ascites. The presence of elevated serum CA125 levels in a postmenopausal woman with a pelvic mass and ascites suggest an ovarian malignant disease. However, in case of Meigs'syndrome, all symptoms will diappear after removal of the pelvic tumor, so a fast surgical management of the patients is mandatory.
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Fibroma/diagnóstico , Síndrome de Meigs/diagnóstico , Neoplasias Ovarianas/diagnóstico , Ascite/etiologia , Antígeno Ca-125/sangue , Feminino , Fibroma/patologia , Fibroma/cirurgia , Humanos , Histerectomia/métodos , Síndrome de Meigs/etiologia , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Pós-MenopausaRESUMO
This study aims to verify the effects of coconut oil supplementation (COS) in the body composition and lipid profile of rats submitted to physical exercise. The animals (n=6 per group) were randomly assigned to: G1=Sedentary and Non-supplemented (Control Group), G2=Sedentary and Supplemented, G3=Exercised and Non-supplemented and G4=Exercised and Supplemented. The COS protocol used was 3 mL/Kg of body mass by gavage for 28 days. The physical exercise was the vertical jumping training for 28 days. It was determined the body mass parameters, Lee Index, blood glucose and lipid profile. The COS did not interfere with body mass, but the lean body mass was lower in G3 compared to G2. The final Lee Index classified G1 and G2 as obese (>30g/cm). The lipid profile showed total cholesterol was decreased in G3, LDL-c concentration was decreased in G2, triglycerides, VLDL-c and HDL-c concentrations were increased in G2 and G4 in relation to G1 and G3. The COS decreased LDL-c/HDL-c ratio. In conclusion, the COS associated or not to physical exercise worsen others lipid parameters, like triglycerides and VLDL-c level, showing the care with the use of lipid supplements.
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Composição Corporal/efeitos dos fármacos , Óleo de Coco/farmacologia , Animais , Óleo de Coco/administração & dosagem , Lipídeos/análise , Obesidade/diagnóstico , Condicionamento Físico Animal , Distribuição Aleatória , Ratos , Triglicerídeos/análiseRESUMO
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy that preferentially affects children and adolescents. Over 50% of human T-ALLs possess activating mutations of Notch1. The clerodane diterpene casearin J (CJ) is a natural product that inhibits the sarcoendoplasmatic reticulum calcium ATPase (SERCA) pump and induces cell death in leukemia cells, but the molecular mechanism of cytotoxicity remains poorly understood. Here we show that owing to SERCA pump inhibition, CJ induces depletion of the endoplasmic reticulum calcium pools, oxidative stress, and apoptosis via the intrinsic signaling pathway. Moreover, Notch1 signaling is reduced in T-ALL cells with auto-activating mutations in the HD-domain of Notch1, but not in cells that do not depend on Notch1 signaling. CJ also provoked a slight activation of NF-κB, and consistent with this notion a combined treatment of CJ and the NF-κB inhibitor parthenolide (Pt) led to a remarkable synergistic cell death in T-ALL cells. Altogether, our data support the concept that inhibition of the SERCA pump may be a novel strategy for the treatment of T-ALL with HD-domain-mutant Notch1 receptors and that additional treatment with the NF-κB inhibitor parthenolide may have further therapeutic benefits.
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Diterpenos Clerodânicos/farmacologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Receptor Notch1/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Bovinos , Linhagem Celular Tumoral , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Células HEK293 , Humanos , Células Jurkat , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Transdução de SinaisRESUMO
El tratamiento de la alergia alimentaria consiste en educar al paciente para evitar la ingestión y, cuando ello no es posible, emplear, entre otros procedimientos, la inmunoterapia con el alimento causal. El objetivo de esta revisión es presentar evidencias sobre eficacia y seguridad de la inmunoterapia en alergia alimentaria y las vías recomendadas para su aplicación. Se accedió a las bases de datos con los descriptores inmunoterapia, alergia alimentaria, vías, desensibilización, eficacia y seguridad. La inmunoterapia oral (ITO) a partir de leche caliente por microondas fue eficaz con buen perfil de seguridad en niños con alergia a leche de vaca (ALV). La quimotripsina inhibe la formación de ßLg y es un nuevo candidato para la inmunoterapia oral en ALV. La ITO con leche y omalizumab ha demostrado mejoría significativa en las medidas de seguridad, pero no en los resultados de eficacia. ITO en niños con alergia al huevo desarrollan tolerancia disminuyendo el riesgo de reacciones alérgicas. También ha aumentado la tolerancia al huevo sin cocinar. En alergia al maní la ITO indujo desensibilización en niños y dio lugar a un aumento significativo en la tolerancia con buen perfil de seguridad. La coadministración del probiótico Lactobacillus rhamnosus a ITO con maní fue eficaz en la inducción de la falta de respuesta y cambios inmunes sostenidos. Se concluye que la ITO puede ser una vía eficaz y segura para la alergia a la leche, huevo y maní. Los protocolos muestran resultados diferentes en eficacia y seguridad, por lo que se requieren más ensayos clínicos.(AU)
The treatment of food allergy is to educate the patient to avoid ingestion and, when it is not possible, to use, among other procedures, the immunotherapy with the offending food. The objective of this review is to present evidence on efficacy and safety of immunotherapy in food allergy and recommended for implementation pathways. It was accessed databases with describer's immunotherapy, food allergy, pathways, desensitization, efficacy and safety. The OIT from microwave hot milk was effective with good safety profile in children with CM. Chymotrypsin inhibits the formation of ßLg and is a new candidate for oral immunotherapy CM. The OIT with milk and omalizumab has shown significant improvement in security measures, but not in the efficacy results. OIT in children with egg allergy develop tolerance decreasing the risk of allergic reactions. It has also increased tolerance uncooked egg. In peanut allergy desensitization induced OIT in children and resulted in a significant increase in tolerance with good safety profile. The co-administration of probiotic Lactobacillus rhamnosus with peanut OIT was effective in inducing immune unresponsiveness and sustained changes. It is concluded that the OIT can be an effective and safe for allergy to milk, egg and peanut route. Protocols show different results in efficacy and safety so more clinical trials are required.(AU)
Assuntos
Humanos , Masculino , Feminino , Criança , Dessensibilização Imunológica , Hipersensibilidade Alimentar/diagnóstico , Segurança , Eficácia , ImunoterapiaRESUMO
El término alergia alimentaria se refiere a los eventos adversos a alimentos originados por mecanismo inmunológico. La alergia alimentaria puede aparecer en cualquier etapa de la vida. Es un padecimiento que, en general, se manifiesta en el lactante por llanto excesivo, cólicos, vómitos, diarreas, acompañadas de sangre y eccema en la piel. El objetivo de la investigación es demostrar la sensibilización del lactante a los alérgenos alimentarios que recibió en el útero de la madre y a través de la lactancia materna exclusiva. La metodología fue reporte de un caso al que se le suspendió la lactancia materna exclusiva y se introdujo leche en polvo hipoalergénica Puramino. La IgE total fue de 1.136 kU/l y los valores de IgE alérgeno específico para leche, el huevo y el maní mayores de 100 kU/l y para el trigo 24,4 kU/l. Se concluye así que la leche de vaca, el huevo, el maní y el trigo pueden sensibilizar al niño durante el embarazo y a través del seno materno. El uso de una dieta hipoalergénica durante el período de lactante puede revertir el proceso.(AU)
The term food allergy refers to adverse events caused by immunologic mechanism. Food allergy may appear at any stage of life, it is a condition that generally manifests itself in the baby's excessive crying, colic, vomiting, diarrhea accompanied by blood and skin eczema. The objective of the research is to demonstrate awareness infant to food allergens received in the mother's womb and through the exclusive breastfeeding. The methodology was a case report that was suspended exclusive breastfeeding and milk powder was introduced into hypoallergenic Puramino. The total IgE was 1.136 kU/L and allergen specific IgE values for milk, egg and peanut higher than 100 kU/L and wheat: 24. 4 kU/L. It is concluded that cow's milk, egg, peanuts and wheat can sensitize the child during pregnancy and through the womb. The use of a hypoallergenic diet during the infant can reverse the process.(AU)
Assuntos
Humanos , Masculino , Feminino , Gravidez , Lactente , Hipersensibilidade Alimentar , Lactente , Arachis , Triticum , Aleitamento Materno , Teste de Radioalergoadsorção , Micronutrientes , Substitutos do Leite Humano , Sistema ImunitárioRESUMO
Para evaluar la efi cacia y seguridad de la inmunoterapia subcutánea (ITSC) con extractos de ácaros, se realizó un ensayo clínico doble ciego controlado con placebo en 154 pacientes mayores de 18 años con rinoconjuntivitis alérgica y/o asma bronquial. La ITSC se administró en una fase de incremento de dosis durante 13 semanas y una fase de mantenimiento con inyecciones mensuales. Como placebo se dieron inyecciones de solución diluyente. Se evaluó la efi cacia según calidad de vida, consumo de medicamentos y frecuencia de las crisis. Se aplicaron los cuestionarios de calidad de vida para rinoconjuntivitis (RQLQ) y cuestionario de calidad de vida para asma (AQLQ). La seguridad se midió según eventos adversos locales y sistémicos. Concluyeron el estudio 136 pacientes (77 con tratamiento y 59 controles). En ambos grupos hubo incremento de la puntuación de los cuestionarios de calidad de vida, mayores en el grupo de estudio (p=0,010). El consumo de medicamentos descendió en rinoconjuntivitis y asma, tanto en el grupo de estudio como en el grupo placebo, sin diferencias signifi cativas entre ambos (p=0,083). La frecuencia de las crisis de rinitis y asma disminuyeron en la muestra, con más reducción en el grupo de tratamiento (p= 0,027). Se reportaron reacciones locales y sistémicas ligeras en ITSC, no así en el grupo placebo, p=0,0003. Los resultados revelan que la inmunoterapia subcutánea con ácaros es efi caz y segura en pacientes con rinoconjuntivitis alérgica y asma(AU)
To evaluate the effi cacy and safety of subcutaneous immunotherapy (SCIT) a double-blind placebo controlled clinical trial was performed with mite extracts in 154 patient's 18-years elders, with allergic rhinoconjunctivitis and/or bronchial asthma. The SCIT was administered in an increased dosage phase for a 13 week period followed by a maintenance phase with monthly injections. Diluted solution injections were given as placebo. Effi cacy was evaluated according to quality of life, medication use, and frequency of crisis. Rhinoconjunctivitis quality of life questionnaire (RQLQ) and asthma quality of life questionnaire (AQLQ) were applied. Safety was measured according to local and systemic adverse events. 136 patients completed the study (77 with SCIT and 59 with placebo). In both groups there was an increase in the score of quality of life questionnaires, score was higher in SCIT (p = 0.010). Medication use declined in both rhinitis and asthma in the SCIT group as in the placebo group with no signifi - cant difference between them (p=0,083). The frequency of rhinoconjunctivitis and asthma crisis decreased in the study group, with a greater reduction in the treatment group (p=0.027). Slight local and systemic reactions were reported in SCIT, none in the placebo group, p=0.0003. The results indicate that subcutaneous immunotherapy with mites is effective and safe in patients with allergic rhinoconjunctivitis and asthma(AU)
Assuntos
Humanos , Masculino , Feminino , Imunoterapia , Ácaros/imunologia , Asma , Conjuntivite Alérgica , RiniteRESUMO
AIM: This work describes the human papillomavirus (HPV) prevalence and the HPV type distribution in a large series of vaginal intraepithelial neoplasia (VAIN) grades 2/3 and vaginal cancer worldwide. METHODS: We analysed 189 VAIN 2/3 and 408 invasive vaginal cancer cases collected from 31 countries from 1986 to 2011. After histopathological evaluation of sectioned formalin-fixed paraffin-embedded samples, HPV DNA detection and typing was performed using the SPF-10/DNA enzyme immunoassay (DEIA)/LiPA25 system (version 1). A subset of 146 vaginal cancers was tested for p16(INK4a) expression, a cellular surrogate marker for HPV transformation. Prevalence ratios were estimated using multivariate Poisson regression with robust variance. RESULTS: HPV DNA was detected in 74% (95% confidence interval (CI): 70-78%) of invasive cancers and in 96% (95% CI: 92-98%) of VAIN 2/3. Among cancers, the highest detection rates were observed in warty-basaloid subtype of squamous cell carcinomas, and in younger ages. Concerning the type-specific distribution, HPV16 was the most frequently type detected in both precancerous and cancerous lesions (59%). p16(INK4a) overexpression was found in 87% of HPV DNA positive vaginal cancer cases. CONCLUSIONS: HPV was identified in a large proportion of invasive vaginal cancers and in almost all VAIN 2/3. HPV16 was the most common type detected. A large impact in the reduction of the burden of vaginal neoplastic lesions is expected among vaccinated cohorts.