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The stability and resilience of the Earth system and human well-being are inseparably linked1-3, yet their interdependencies are generally under-recognized; consequently, they are often treated independently4,5. Here, we use modelling and literature assessment to quantify safe and just Earth system boundaries (ESBs) for climate, the biosphere, water and nutrient cycles, and aerosols at global and subglobal scales. We propose ESBs for maintaining the resilience and stability of the Earth system (safe ESBs) and minimizing exposure to significant harm to humans from Earth system change (a necessary but not sufficient condition for justice)4. The stricter of the safe or just boundaries sets the integrated safe and just ESB. Our findings show that justice considerations constrain the integrated ESBs more than safety considerations for climate and atmospheric aerosol loading. Seven of eight globally quantified safe and just ESBs and at least two regional safe and just ESBs in over half of global land area are already exceeded. We propose that our assessment provides a quantitative foundation for safeguarding the global commons for all people now and into the future.
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Cambio Climático , Planeta Tierra , Justicia Ambiental , Internacionalidad , Seguridad , Humanos , Aerosoles/metabolismo , Clima , Agua/metabolismo , Nutrientes/metabolismo , Seguridad/legislación & jurisprudencia , Seguridad/normasRESUMEN
Gene expression assays (GEAs) can guide treatment for early-stage breast cancer. Several large prospective randomized clinical trials, and numerous additional studies, now provide new information for selecting an appropriate GEA. This systematic review builds upon prior reviews, with a focus on five widely commercialized GEAs (Breast Cancer Index®, EndoPredict®, MammaPrint®, Oncotype DX®, and Prosigna®). The comprehensive dataset available provides a contemporary opportunity to assess each GEA's utility as a prognosticator and/or predictor of adjuvant therapy benefit.
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Neoplasias de la Mama , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Femenino , Quimioterapia Adyuvante , Perfilación de la Expresión Génica , Biomarcadores de Tumor/genética , Estadificación de Neoplasias , PronósticoRESUMEN
This study aimed to evaluate the effect of chemical gasification and HEPES as alternative systems to pH control during in vitro maturation on bovine oocytes competence. Groups of 20 bovine cumulus oocytes complexes (COCs) were randomly distributed and cultured for 24 h in one of the following experimental groups: (i) chemical reaction (ChRG) system: CO2 generated from sodium bicarbonate and citric acid reaction (ii) culture media TCM-HEPES (HEPES-G); and (iii) control group (CNTG) in conventional incubator. After in vitro maturation (IVM), the COCs were in vitro fertilized (IVF), and in vitro cultivated (IVC) in a conventional incubator. We evaluated oocyte nuclear maturation, cleavage and blastocyst rates, in addition to the relative mRNA expression of BAX, BMP-15, AREG and EREG genes in oocytes and cumulus cells. The proportion of oocytes in metaphase II was higher in CNTG and ChRG (77.57% and 77.06%) than in the HEPES-G (65.32%; p = .0408 and .0492, respectively). The blastocyst production was similar between CNTG and ChRG (26.20% and 28.47%; p = .4232) and lower (p = .001) in the HEPES-G (18.71%). The relative mRNA expression of BAX gene in cumulus cells was significantly higher (p = .0190) in the HEPES-G compared to the CNTG. Additionally, the relative mRNA expression of BMP-15 gene was lower (p = .03) in oocytes from HEPES-G compared to the CNTG. In conclusion, inadequate atmosphere control has a detrimental effect on oocyte maturation. Yet, the use of chemical gasification can be an efficient alternative to bovine COCs cultivation.
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Fertilización In Vitro , Técnicas de Maduración In Vitro de los Oocitos , Oocitos , Animales , Bovinos , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Técnicas de Maduración In Vitro de los Oocitos/métodos , Oocitos/efectos de los fármacos , Fertilización In Vitro/veterinaria , Femenino , Medios de Cultivo , Blastocisto/efectos de los fármacos , Células del Cúmulo/efectos de los fármacos , Dióxido de Carbono/farmacología , Bicarbonato de Sodio/farmacología , Ácido Cítrico/farmacología , Técnicas de Cultivo de Embriones/veterinariaRESUMEN
OBJECTIVE: To assess SARS-CoV-2 antibody prevalence and titers in people living with HIV (PLWHIV) on antiretroviral treatment (ART) enrolled at a tertiary reference hospital in Mexico. METHODS: Two plasma aliquots per person, used for HIV viral load follow-up between 01/2020 and 09/2021, were used to assess total anti-N and neutralizing SARS-CoV-2 antibodies. Sociodemographic, clinical, and SARS-CoV-2 exposure risk information were collected. The risk associated with SARS-CoV-2 exposure and associations with antibody titers were analyzed with logistic, Cox, and linear multivariable models. RESULTS: 803 PLWHIV participated; 233 had detectable SARS-CoV-2 antibodies (prevalent cases), and 132 seroconverted (incident cases). Overall, the adjusted prevalence was 46.45%, with an incidence rate of 3.78 cases/100 person-months. Factors associated with prevalent cases included lower age, location (western zone of Mexico City and the neighboring Mexico State), use of public transport, attendance at meetings without social distancing, and higher CD4 + T cell counts (p < 0.05; multivariable logistic model). BNT162b2 vaccination reduced incident cases (Cox adjusted HR = 0.4; p = 0.013). Notably, previously infected and vaccinated individuals showed maximization of neutralizing activity (p < 0.001). No associations between SARS-CoV-2 neutralization and HIV-related variables (CD4 + T cell counts, viral load, number of years in viral suppression, ART regimen) were found in multivariable analysis. CONCLUSIONS: SARS-CoV-2 infection was associated with community risk rather than HIV-associated variables in PLWH on ART and clinical follow-up. Antibody neutralization activity in vaccinated participants was maximized with previous SARS-CoV-2 infection.
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COVID-19 , Infecciones por VIH , Humanos , Vacuna BNT162 , México/epidemiología , Prevalencia , Anticuerpos Antivirales , Antirretrovirales , COVID-19/epidemiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Anticuerpos Neutralizantes , VacunaciónRESUMEN
Growth traits are economically important characteristics for the genetic improvement of local cattle breeds. Genome-wide association studies (GWAS) provide valuable information to enhance the understanding on the genetics of complex traits. The aim of this study was to perform a GWAS to identify genomic regions and genes associated to birth weight, weaning weight adjusted for 240 days, 16 months, and 24 months weight in Romosinuano (ROMO) and Blanco Orejinegro (BON) cattle. A single-step genomic-BLUP was implemented using 596 BON and 569 ROMO individuals that were genotyped with an Illumina BovineSNP50 BeadChip. There were 25 regions of interest identified on different chromosomes, with few of them simultaneously associated with two or more growth traits and some were common to both breeds. The gene mapping allowed to find 173 annotations on these regions, from which 49 represent potential candidate genes with known growth-related functions in cattle and other species. Among the regions that were associated with several growth traits, that at 24 - 27 MB of BTA14, has important candidate genes such as LYPLA1, XKR4, TMEM68 and PLAG1. Another region of interest at 0.40-0.77 Mb of BTA23 was identified in both breeds, containing KHDRBS2 as a potential candidate gene influencing body weight. Future studies targeting these regions could provide more knowledge to uncover the genetic architecture underlying growth traits in BON and ROMO cattle. The genomic regions and genes identified in this study could be used to improve the prediction of genetic merit for growth traits in these creole cattle breeds.
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Estudio de Asociación del Genoma Completo , Genoma , Humanos , Bovinos/genética , Animales , Estudio de Asociación del Genoma Completo/veterinaria , Fenotipo , Genotipo , Destete , Polimorfismo de Nucleótido SimpleRESUMEN
Analyses of the genetic diversity of indigenous cattle are essential for implementing conservation programs, promoting their sustainable use and maintaining productive advantages offered by these breeds in local conditions. The aim of this study was to investigate the genetic diversity and population structure of six Colombian cattle breeds: Blanco Orejinegro (BON), Costeño con Cuernos (CCC), Romosinuano (ROM), Sanmartinero (SAM), Casanareño (CAS), and Hartón del Valle (HDV). Two additional breed groups were included for comparison: Zebu (CEB) and a crossbreed of Colombian cattle breeds × Zebu. Genetic diversity within breeds was analyzed using expected heterozygosity (He), inbreeding coefficient (f), and runs of homozygosity (ROH). Population structure was assessed using model-based clustering (ADMIXTURE) and principal components analysis (PCA). Zebu cattle showed the lowest genetic diversity (He = 0.240). Breeds with the highest genetic diversity level were HDV and BON (He = 0.350 and 0.340, respectively). Inbreeding was lower for Colombian cattle breeds ranging between 0.005 and 0.045. Overall, the largest average genetic distance was found among the group of Colombian cattle breeds and Zebu, while the smallest was found between ROM and CCC. Model-based clustering revealed some level of admixture among HDV and CAS cattle which is consistent with their recent history. The results of the present study provide a useful insight on the genetic structure of Colombian cattle breeds.
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Genoma , Endogamia , Bovinos/genética , Animales , Colombia , Genómica , Hibridación Genética , Polimorfismo de Nucleótido Simple , Variación GenéticaRESUMEN
Manual wheelchair dance is an artistic recreational and sport activity for people with disabilities that is becoming more and more popular. It has been reported that a significant part of the dance is dedicated to propulsion. Furthermore, wheelchair dance professionals such as Gladys Foggea highlight the need for monitoring the quantity and timing of propulsions for assessment and learning. This study addresses these needs by proposing a wearable system based on inertial sensors capable of detecting and characterizing propulsion gestures. We called the system WISP. Within our initial configuration, three inertial sensors were placed on the hands and the back. Two machine learning classifiers were used for online bilateral recognition of basic propulsion gestures (forward, backward, and dance). Then, a conditional block was implemented to rebuild eight specific propulsion gestures. Online paradigm is intended for real-time assessment applications using sliding window method. Thus, we evaluate the accuracy of the classifiers in two configurations: "three-sensor" and "two-sensor". Results showed that when using "two-sensor" configuration, it was possible to recognize the propulsion gestures with an accuracy of 90.28%. Finally, the system allows to quantify the propulsions and measure their timing in a manual wheelchair dance choreography, showing its possible applications in the teaching of dance.
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Personas con Discapacidad , Dispositivos Electrónicos Vestibles , Silla de Ruedas , Fenómenos Biomecánicos , Gestos , Mano , HumanosRESUMEN
Extracts of Hibiscus sabdariffa L. (commonly called Rosselle or "Jamaica flower" in Mexico) have been shown to have antibiotic and antivirulence properties in several bacteria. Here, an organic extract of H. sabdariffa L. is shown to inhibit motility in Salmonella enterica serovars Typhi and Typhimurium. The compound responsible for this effect was purified and found to be the hibiscus acid. When tested, this compound also inhibited motility and reduced the secretion of both flagellin and type III secretion effectors. Purified hibiscus acid was not toxic in tissue-cultured eukaryotic cells, and it was able to reduce the invasion of Salmonella Typhimurium in epithelial cells. Initial steps to understand its mode of action showed it might affect membrane proton balance.
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Antibacterianos/farmacología , Citratos/farmacología , Flagelos/fisiología , Flores/química , Hibiscus/química , Extractos Vegetales/farmacología , Salmonella enterica/efectos de los fármacos , Flagelos/efectos de los fármacosRESUMEN
BACKGROUND: The American College of Surgeon (ACS) Surgical Risk Calculator is an online tool that helps surgeons estimate the risk of postoperative complications for numerous surgical procedures across several surgical specialties. METHODS: We evaluated the predictive performance of the calculator in 385 cancer patients undergoing breast surgery. Calculator-predicted complication rates were compared with observed complication rates; calculator performance was evaluated using calibration and discrimination analyses. RESULTS: The mean calculator-predicted rates for any complication (4.1%) and serious complication (3.2%) were significantly lower than the observed rates (11.2% and 5.2%, respectively). The area under the curve was 0.617 for any complication and 0.682 for serious complications. p Values for the Hosmer-Lemeshow test were significant (<.05) for both outcomes. Brier scores were 0.102 for any complication and 0.048 for serious complication. CONCLUSIONS: The ACS risk calculator is not an ideal tool for predicting individual risk of complications following breast surgery in a Mexican cohort. The most valuable use of the calculator may reside in its role as an aid for patient-led surgery planning. The possibility of introducing breast surgery-specific data could improve the performance of the calculator. Furthermore, a disease-specific calculator could provide more accurate predictions and include complications more frequently found in breast cancer surgery.
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Neoplasias de la Mama/cirugía , Mastectomía/efectos adversos , Complicaciones Posoperatorias/diagnóstico , Mejoramiento de la Calidad , Medición de Riesgo/normas , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Femenino , Estudios de Seguimiento , Humanos , Complicaciones Posoperatorias/etiología , Pronóstico , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND: In Mexico, up to 15% of breast cancer (BC) patients are 40 years or younger. Therefore, fertility preservation and pregnancy after cancer treatment are major concerns in this population. However, no data are available regarding Mexican physicians' knowledge and attitudes toward these issues. OBJECTIVE: The objective of the study was to describe physicians' attitudes, knowledge, and perceived barriers toward fertility preservation among young women with BC (YWBC) in a developing country. METHODS: A cross-sectional study was conducted among physicians attending the 2016 Mexican Society of Oncology (SMeO) Annual Meeting or affiliated to SMeO. Chi-squared tests were used to assess factors associated with a higher likelihood of disclosing infertility risks, discussing fertility preservation methods, referring to specialists, and effective counseling. RESULTS: Of the 314 participants, 83% reported a high sense of responsibility about informing treatment-related infertility risks, 58% always informed patients about those risks, 38% always discussed fertility preservation procedures, 52% always referred interested patients to fertility specialists, and 24% wrongly considered pregnancy and GnRH analogs detrimental in YWBC. Barriers for discussing fertility preservation were costs, lack of specialists, and prognosis. CONCLUSIONS: It is crucial to promote physicians' knowledge and to endorse policies to overcome barriers obstructing universal access to fertility preservation for YWBC in Mexico.
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BACKGROUND: Older patients with breast cancer treated in high-income countries often present with early-stage disease, leading to a lack of information on the use of neoadjuvant chemotherapy in this population. We analyzed the real-world outcomes of older women with breast cancer treated with neoadjuvant chemotherapy at a single institution in Mexico. MATERIALS AND METHODS: The study included 2,216 patients treated with neoadjuvant chemotherapy. Regarding achievement of pathologic complete response (defined as no invasive residual tumor in the breast and lymph nodes), 243 patients aged ≥65 years were compared with 1,973 patients aged <65 years. Disease-free survival and overall survival were compared between groups according to pathologic complete response and subtype, defined by hormone receptor and human epidermal growth receptor 2 (HER2) status. RESULTS: Older women were less likely to have a pathologic complete response than their younger counterparts (26.3 vs. 35.3%, p < .001). When response rates by subtype were analyzed, this difference was significant only for women with triple-negative tumors. Achieving less than a pathologic complete response was associated with a greater chance of recurrence, but age was not an independent factor for recurrence for any subtype. Reaching a pathologic complete response was significantly associated with improved survival among older women with breast cancer, with the exception of those with hormone receptor-positive, HER2- disease. CONCLUSION: Although older women have fewer pathological complete responses, their outcomes after neoadjuvant chemotherapy are comparable to those of younger patients. This is particularly relevant for the treatment of older adults with breast cancer in developing countries, who present in advanced stages and more often need neoadjuvant therapy. IMPLICATIONS FOR PRACTICE: The majority of older patients with breast cancer in high-income countries present with early-stage disease, leading to a lack of information regarding the use of neoadjuvant chemotherapy in real-world settings. This article reports the outcomes of older Mexican women with breast cancer who received neoadjuvant chemotherapy compared with their younger counterparts. Although older women (particularly those with triple-negative tumors) were less likely to have a pathologic complete response after neoadjuvant treatment, age was not an independent factor for recurrence. Achieving a pathologic complete response was associated with improved survival, regardless of age.
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Neoplasias de la Mama , Terapia Neoadyuvante , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante , Femenino , Humanos , México , Recurrencia Local de Neoplasia/tratamiento farmacológico , Receptor ErbB-2/uso terapéutico , Resultado del TratamientoRESUMEN
Chagas disease, caused by Trypanosoma cruzi (T. cruzi), affects nearly eight million people worldwide. There are currently only limited treatment options, which cause several side effects and have drug resistance. Thus, there is a great need for a novel, improved Chagas treatment. Bifunctional enzyme dihydrofolate reductase-thymidylate synthase (DHFR-TS) has emerged as a promising pharmacological target. Moreover, some human dihydrofolate reductase (HsDHFR) inhibitors such as trimetrexate also inhibit T. cruzi DHFR-TS (TcDHFR-TS). These compounds serve as a starting point and a reference in a screening campaign to search for new TcDHFR-TS inhibitors. In this paper, a novel virtual screening approach was developed that combines classical docking with protein-ligand interaction profiling to identify drug repositioning opportunities against T. cruzi infection. In this approach, some food and drug administration (FDA)-approved drugs that were predicted to bind with high affinity to TcDHFR-TS and whose predicted molecular interactions are conserved among known inhibitors were selected. Overall, ten putative TcDHFR-TS inhibitors were identified. These exhibited a similar interaction profile and a higher computed binding affinity, compared to trimetrexate. Nilotinib, glipizide, glyburide and gliquidone were tested on T. cruzi epimastigotes and showed growth inhibitory activity in the micromolar range. Therefore, these compounds could lead to the development of new treatment options for Chagas disease.
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Enfermedad de Chagas/enzimología , Antagonistas del Ácido Fólico/farmacología , Tripanocidas/farmacología , Enfermedad de Chagas/tratamiento farmacológico , Simulación por Computador , Reposicionamiento de Medicamentos , Antagonistas del Ácido Fólico/química , Glipizida/química , Glipizida/farmacología , Gliburida/química , Gliburida/farmacología , Humanos , Ligandos , Simulación del Acoplamiento Molecular , Estructura Molecular , Pirimidinas/química , Pirimidinas/farmacología , Relación Estructura-Actividad , Compuestos de Sulfonilurea/química , Compuestos de Sulfonilurea/farmacología , Tripanocidas/química , Trypanosoma cruzi/efectos de los fármacosRESUMEN
AIM: The goal of this study was to determine whether a delay in starting treatment via surgery or neoadjuvant chemotherapy is related to a decrease in cancer-specific survival (CSS) in women with operable breast cancer (BrCr). BACKGROUND: Limited medical infrastructure and a lack of cancer prevention awareness in low- and middle-income countries have caused high BrCr incidence and mortality rates. METHODS: We analyzed a retrospective cohort of 720 women treated at a single center from 2005 to 2012. CSS estimates were obtained by the Kaplan-Meier method. A Cox model of proportional risks was performed to obtain the risk of dying from BrCr. We also obtained the risk according to the category of treatment initiation. RESULTS: Women with locally advanced stages and without hormone receptor expression were more likely to initiate treatment after 45 days. Patients in Stage IIIA had a 78.1% survival if treatment was initiated before 45 days (95% CI, 0.70-0.84) and 63.6% survival if treatment was started after 45 days (95% CI, 0.44-0.78; p < 0.001). Patients in Stage IIIB had a 62.9% survival if treatment was initiated before 45 days (95% CI, 0.53-0.72) and 57.4% survival if treatment started after 45 days (95% CI, 0.31-0.89; p < 0.001). Prognostic factors in which lower survival was recognized were Stage IIIA, Stage IIIB, treatment initiation after 45 days, and triple-negative tumors. CONCLUSIONS: The initiation of treatment within the first 45 days of diagnosis of BrCr in women portends better survival compared with those who began treatment longer than 45 days from diagnosis.
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BACKGROUND: Breast surgery is considered a clean surgery. However, surgical-site infection (SSI) rates are currently higher than predicted. Postoperative drains remain in situ for several days, with inevitable bacterial colonization and increased SSI risk. METHODS: This randomized controlled trial from October 2016 to January 2018 analyzed patients undergoing breast cancer surgery. The patients were randomized to either the standard drain care group or the antiseptic dressing group (3M® Tegaderm® CHG). Drain samples taken on postoperative days (PODs) 7 and 14 were cultured as standardized in the laboratory. Colonization rates and SSI were compared between the two groups. RESULTS: The study enrolled 104 patients with 167 surgical drains. The patients' clinical characteristics were similar in the two groups, with no statistically significant differences. Bulb fluid cultures at postoperative week (POW) 1 were positive for 42.9% of the control group and 28.9% of the antiseptic group (p = 0.06). Cultures from the POW 2 assessment were positive for 79.7% of the control group versus 54.9% of the antiseptic group (p = 0.001). Cultures from drain tubes were positive for 79.8% of the control group and 50.7% of the antiseptic group (p = < 0.001). In 11 patients, an SSI developed, 3 (5.8%) from the intervention and 8 (15.4%) from the control procedure (p = 0.11). CONCLUSION: The study findings demonstrated that the use of antiseptics at the drain exit site significantly reduced bacterial colonization of the closed drainage system in breast cancer surgery. Semi-permeable occlusive chlorhexidine-impregnated dressings provide an opportunity to test simple, safe, and low-cost interventions that may reduce drain bacterial colonization and SSI after breast surgery.
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Vendajes/estadística & datos numéricos , Neoplasias de la Mama/cirugía , Clorhexidina/uso terapéutico , Drenaje/métodos , Mastectomía/efectos adversos , Cuidados Posoperatorios , Infección de la Herida Quirúrgica/prevención & control , Antiinfecciosos Locales/uso terapéutico , Neoplasias de la Mama/patología , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/patologíaRESUMEN
The linkage disequilibrium (LD) between molecular markers affects the accuracy of genome-wide association studies and genomic selection application. High-density genotyping platforms allow identifying the genotype of thousands of single nucleotide polymorphisms (SNPs) distributed throughout the animal genomes, which increases the resolution of LD evaluations. This study evaluated the distribution of minor allele frequencies (MAF) and the level of LD in the Colombian Creole cattle breeds Blanco Orejinegro (BON) and Romosinuano (ROMO) using a medium density SNP panel (BovineSNP50K_v2). The LD decay in these breeds was lower than those reported for other taurine breeds, achieving optimal LD values (r2 ≥ 0.3) up to a distance of 70 kb in BON and 100 kb in ROMO, which is possibly associated with the conservation status of these cattle populations and their effective population size. The average MAF for both breeds was 0.27 ± 0.14 with a higher SNP proportion having high MAF values (≥ 0.3). The LD levels and distribution of allele frequencies found in this study suggest that it is possible to have adequate coverage throughout the genome of these breeds using the BovineSNP50K_v2, capturing the effect of most QTL related with productive traits, and ensuring an adequate prediction capacity in genomic analysis.
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Risk stratification of patients with early stage breast cancer may support adjuvant chemotherapy decision-making. This review details the development and validation of six multi-gene classifiers, each of which claims to provide useful prognostic and possibly predictive information for early stage breast cancer patients. A careful assessment is presented of each test's analytical validity, clinical validity, and clinical utility, as well as the quality of evidence supporting its use.
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Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Perfilación de la Expresión Génica/métodos , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Femenino , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND AND OBJECTIVES: The low availability and poor access to external beam radiotherapy (EBRT) in developing countries makes it hard for women with breast cancer to receive breast conservation. We studied the effect of providing intraoperative radiotherapy (IORT) on the travel time, distance, and costs of in the Mexico City Metropolitan Area (MCMA). METHODS: Sixty-nine patients treated between January 2013 and September 2014 were analyzed. Travel distance and transit time was calculated using Google Maps. The time and distance patients living in the MCMA treated with IORT would have spent if they had received EBRT was calculated. Cost analysis for each modality was performed. RESULTS: 71% (n = 49) lived in the MCMA. Sixteen (33%) received additional EBRT and 33 (66%) received IORT only. Mean driving distance and transit time of those 33 women was 132.6 km (SD 25.7) and 66 min (SD 32.9). Patients from the MCMA receiving IORT alone avoided 990 visits, 43 700 km and 65 400 min in transit. IORT led to a 12% reduction in costs per patient. CONCLUSIONS: By reducing costs and time needed for patients to receive radiotherapy, IORT could potentially enhance access to breast conservation in resource-limited developing countries.
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Neoplasias de la Mama/economía , Neoplasias de la Mama/terapia , Accesibilidad a los Servicios de Salud/economía , Viaje/economía , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Terapia Combinada , Países en Desarrollo , Femenino , Costos de la Atención en Salud , Humanos , Cuidados Intraoperatorios/economía , Cuidados Intraoperatorios/métodos , México , Persona de Mediana Edad , Radioterapia/economía , Radioterapia/métodos , Factores de TiempoRESUMEN
In order to obtain gold electrode surfaces modified with Human Papillomavirus L1 protein (HPV L1)-derived peptides, two sequences, SPINNTKPHEAR and YIK, were chosen. Both have been recognized by means of sera from patients infected with HPV. The molecules, Fc-Ahx-SPINNTKPHEAR, Ac-C-Ahx-(Fc)KSPINNTKPHEAR, Ac-C-Ahx-SPINNTKPHEAR(Fc)K, C-Ahx-SPINNTKPHEAR, and (YIK)2-Ahx-C, were designed, synthesized, and characterized. Our results suggest that peptides derived from the SPINNTKPHEAR sequence, containing ferrocene and cysteine residues, are not stable and not adequate for electrode surface modification. The surface of polycrystalline gold electrodes was modified with the peptides C-Ahx-SPINNTKPHEAR or (YIK)2-Ahx-C through self-assembly. The modified polycrystalline gold electrodes were characterized via infrared spectroscopy and electrochemical measurements. The thermodynamic parameters, surface coverage factor, and medium pH effect were determined for these surfaces. The results indicate that surface modification depends on the peptide sequence (length, amino acid composition, polyvalence, etc.). The influence of antipeptide antibodies on the voltammetric response of the modified electrode was evaluated by comparing results obtained with pre-immune and post-immune serum samples.
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Proteínas de la Cápside/química , Diseño de Fármacos , Electrodos , Oro , Proteínas Oncogénicas Virales/química , Péptidos/química , Secuencia de Aminoácidos , Animales , Oro/química , Estructura Molecular , Péptidos/síntesis química , Estabilidad Proteica , Conejos , Espectroscopía Infrarroja por Transformada de Fourier , TermodinámicaRESUMEN
Chagas, or American trypanosomiasis, remains an important public health problem in developing countries. In the last decade, trans-sialidase has become a pharmacological target for new anti-Chagas drugs. In this work, the aims were to design and find a new series of benzoic acid derivatives as trans-sialidase (TS) inhibitors and anti-trypanosomal agents. Three compounds (14, 18, and 19) sharing a para-aminobenzoic acid moiety showed more potent trypanocidal activity than the commercially available drugs nifurtimox and benznidazole in both strains: the lysis concentration of 50% of the population (LC50) was <0.15 µM on the NINOA strain, and LC50 < 0.22 µM on the INC-5 strain. Additionally, compound 18 showed a moderate inhibition (47%) on the trans-sialidase enzyme and a binding model similar to DANA (pattern A).
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Benzoatos/farmacología , Inhibidores Enzimáticos/farmacología , Glicoproteínas/química , Neuraminidasa/química , Tripanocidas/farmacología , Animales , Benzoatos/síntesis química , Benzoatos/química , Diseño de Fármacos , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Glicoproteínas/antagonistas & inhibidores , Ratones , Modelos Moleculares , Simulación del Acoplamiento Molecular , Estructura Molecular , Neuraminidasa/antagonistas & inhibidores , Relación Estructura-Actividad , Tripanocidas/síntesis química , Tripanocidas/química , Trypanosoma cruzi/efectos de los fármacosRESUMEN
Chagas disease or American trypanosomiasis is a worldwide public health problem. In this work, we evaluated 26 new propyl and isopropyl quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives as potential trypanocidal agents. Additionally, molecular docking and enzymatic assays on trypanothione reductase (TR) were performed to provide a basis for their potential mechanism of action. Seven compounds showed better trypanocidal activity on epimastigotes than the reference drugs, and only four displayed activity on trypomastigotes; T-085 was the lead compound with an IC50 = 59.9 and 73.02 µM on NINOA and INC-5 strain, respectively. An in silico analysis proposed compound T-085 as a potential TR inhibitor with better affinity than the natural substrate. Enzymatic analysis revealed that T-085 inhibits parasite TR non-competitively. Compound T-085 carries a carbonyl, a CF3, and an isopropyl carboxylate group at 2-, 3- and 7-position, respectively. These results suggest the chemical structure of this compound as a good starting point for the design and synthesis of novel trypanocidal derivatives with higher TR inhibitory potency and lower toxicity.