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1.
Cancer Immunol Immunother ; 71(4): 807-818, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34415404

RESUMEN

Histiocytic sarcoma (HS) is a rare and aggressive tumor in humans with no universally agreed standard of care therapy. Spontaneous canine HS exhibits increased prevalence in specific breeds, shares key genetic and biologic similarities with the human disease, and occurs in an immunocompetent setting. Previous data allude to the immunogenicity of this disease in both species, highlighting the potential for their successful treatment with immunotherapy. Quantification of CD3 tumor-infiltrating lymphocytes (TIL) in five cases of human HS revealed variable intra-tumoral T cell infiltration. Due to the paucity of human cases and lack of current model systems in which to appraise associations between anti-tumor immunity and treatment-outcome in HS, we analyzed clinical data and quantified TIL in 18 dogs that were previously diagnosed with localized HS and treated with curative-intent tumor resection with or without adjuvant chemotherapy. As in humans, assessment of TIL in biopsy tissues taken at diagnosis reveal a spectrum of immunologically "cold" to "hot" tumors. Importantly, we show that increased CD3 and granzyme B TIL are positively associated with favorable outcomes in dogs following surgical resection. NanoString transcriptional analyses revealed increased T cell and antigen presentation transcripts associated with prolonged survival in canine pulmonary HS and a decreased tumor immunogenicity profile associated with shorter survivals in splenic HS. Based on these findings, we propose that spontaneous canine HS is an accessible and powerful novel model to study tumor immunology and will provide a unique platform to preclinically appraise the efficacy and tolerability of anti-cancer immunotherapies for HS.


Asunto(s)
Enfermedades de los Perros , Sarcoma Histiocítico , Animales , Biopsia , Perros , Sarcoma Histiocítico/genética , Sarcoma Histiocítico/patología , Sarcoma Histiocítico/veterinaria , Linfocitos Infiltrantes de Tumor/patología , Bazo/patología
2.
Proc Natl Acad Sci U S A ; 116(52): 27074-27083, 2019 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-31843913

RESUMEN

Multiple sclerosis (MS) is a common cause of neurologic disease in young adults that is primarily treated with disease-modifying therapies which target the immune and inflammatory responses. Promotion of remyelination has opened a new therapeutic avenue, but how best to determine efficacy of remyelinating drugs remains unresolved. Although prolongation and then shortening of visual evoked potential (VEP) latencies in optic neuritis in MS may identify demyelination and remyelination, this has not been directly confirmed. We recorded VEPs in a model in which there is complete demyelination of the optic nerve, with subsequent remyelination. We examined the optic nerves microscopically during active disease and recovery, and quantitated both demyelination and remyelination along the length of the nerves. Latencies of the main positive component of the control VEP demonstrated around 2-fold prolongation during active disease. VEP waveforms were nonrecordable in a few subjects or exhibited a broadened profile which precluded peak identification. As animals recovered neurologically, the VEP latencies decreased in association with complete remyelination of the optic nerve but remained prolonged relative to controls. Thus, it has been directly confirmed that VEP latencies reflect the myelin status of the optic nerve and will provide a surrogate marker in future remyelination clinical trials.

3.
Matern Child Nutr ; 15(1): e12670, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30182474

RESUMEN

The Baby-friendly Hospital Initiative (BFHI) includes a set of 10 evidenced-based maternity practices that when used together have been shown to improve breastfeeding outcomes. In 2007, the Centers for Disease Control and Prevention launched the Maternity Practices in Infant Nutrition and Care (mPINC) survey to assess and monitor these and other evidenced-based maternity practices. The purpose of this study was to explore individual maternity practices measured in the 2013 mPINC survey, along with hospital demographic information, and their relationships with exclusive breastfeeding (EBF) rates, using a sample of United States (U.S.) hospitals. We obtained mPINC survey data from 69 BFHI hospitals and 654 non-BFHI hospitals in the U.S., and EBF rates from The Joint Commission, a leading hospital accreditation agency. On the basis of linear regression analysis, we found that most maternity practices studied were significantly associated with EBF rates (max adjusted R2  = 14.9%). We found a parsimonious model with an adjusted R2 of 47.3%. This study supports the need for a systematic approach in providing breastfeeding support as no one maternity care practice was able to explain the variability in EBF rates as well as a collection of maternity care practices.


Asunto(s)
Lactancia Materna/estadística & datos numéricos , Promoción de la Salud/métodos , Atención Posnatal/métodos , Femenino , Hospitales , Humanos , Recién Nacido , Embarazo , Estados Unidos/epidemiología
4.
Matern Child Nutr ; 14(3): e12589, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29411938

RESUMEN

In 2014, a leading hospital accreditation agency, mandated hospitals publicly report their exclusive breastfeeding (EBF) rates. This new regulation provided an opportunity to explore differences in EBF outcomes using a standardized definition across a large hospital sample in the United States. The purpose of this study was to examine the relationships between population demographics and the Baby-friendly (BF) hospital designation on EBF rates in hospitals throughout the United States. We obtained EBF rates from 121 BF hospitals and 1,608 hospitals without the BF designation. Demographic variables were computed using census tract data for the population surrounding each hospital. Relationships were explored using linear regression. We found that EBF rates were positively correlated with a bachelor's degree, log income, and those who identified as White or Asian and negatively correlated with those without college attendance, individuals living below the poverty line, and those who identified as African American or Hispanic. For all models, the BF designation of a hospital was associated with higher EBF rates (p < 0.01; effect sizes, 0.11-0.49) with the exception of the model containing log income. Using a multiple linear regression model that was allowed to contain more than one independent variable, we were able to explain 22% of the variability in EBF rates. The BF hospital designation was associated with significantly higher EBF rates independent of demographic variables. Support for hospitals to attain the BF hospital designation is a meaningful public health goal.


Asunto(s)
Lactancia Materna/psicología , Hospitales , Demografía , Femenino , Humanos , Lactante , Madres , Factores Socioeconómicos , Estados Unidos
5.
Ecol Appl ; 26(7): 2323-2338, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27755741

RESUMEN

Wildfire is globally an important ecological disturbance affecting biochemical cycles and vegetation composition, but also puts people and their homes at risk. Suppressing wildfires has detrimental ecological effects and can promote larger and more intense wildfires when fuels accumulate, which increases the threat to buildings in the wildland-urban interface (WUI). Yet, when wildfires occur, typically only a small proportion of the buildings within the fire perimeter are lost, and the question is what determines which buildings burn. Our goal was to examine which factors are related to building loss when a wildfire occurs throughout the United States. We were particularly interested in the relative roles of vegetation, topography, and the spatial arrangement of buildings, and how their respective roles vary among ecoregions. We analyzed all fires that occurred within the conterminous United States from 2000 to 2010 and digitized which buildings were lost and which survived according to Google Earth historical imagery. We modeled the occurrence as well as the percentage of buildings lost within clusters using logistic and linear regression. Overall, variables related to topography and the spatial arrangement of buildings were more frequently present in the best 20 regression models than vegetation-related variables. In other words, specific locations in the landscape have a higher fire risk, and certain development patterns can exacerbate that risk. Fire policies and prevention efforts focused on vegetation management are important, but insufficient to solve current wildfire problems. Furthermore, the factors associated with building loss varied considerably among ecoregions suggesting that fire policy applied uniformly across the United States will not work equally well in all regions and that efforts to adapt communities to wildfires must be regionally tailored.


Asunto(s)
Conservación de los Recursos Naturales , Incendios Forestales/estadística & datos numéricos , Humanos , Estados Unidos
6.
Vet Radiol Ultrasound ; 56(2): 144-52, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25154869

RESUMEN

Comprehensive evaluation of canine elbow joint dysfunction includes assessment of articular cartilage, which can noninvasively be performed with contrast arthrography. Aims of this prospective study were to compare positive contrast computed tomographic (CT) arthrography and histomorphometry measures of cartilage thickness in normal canine elbows, and to determine the optimal contrast medium concentration. Thirty-two canine cadaver elbows were examined using multidetector CT, before and after intra-articular administration of iohexol at one of three different concentrations. Articular cartilage thickness was measured on both the CT arthrography images and corresponding histologic specimens. Mean difference (bias) between the CT arthrography and histomorphologic measurements was 0.18 and 0.19 mm in the sagittal and dorsal planes, respectively. Mean bias and precision of CT arthrography measurements made in the sagittal or dorsal reformations were not significantly different from one another. Computed tomographic arthrography measurements from elbows with 75 mg I/ml were significantly larger and had greater bias compared to other contrast medium groups (150 and 37.5 mg I/ml). There was no significant difference in CT arthrography measurement precision between different contrast medium concentrations. Histomorphologic thickness of the articular cartilage overlying the cranial aspect of the ulna (mean 0.32 mm) was significantly thinner than cartilage of the radius (0.36 mm) or humerus (0.36 mm). Findings from this cadaver study indicated that CT arthrography delineates articular cartilage of the normal canine elbow; yields cartilage thickness measures slightly greater than histomorphometry measures; and provides high measurement precision regardless of image plane, contrast medium concentration, or anatomic zone.


Asunto(s)
Perros/anatomía & histología , Miembro Anterior/diagnóstico por imagen , Tomografía Computarizada por Rayos X/veterinaria , Animales , Artrografía/veterinaria , Cadáver , Cartílago Articular/anatomía & histología , Cartílago Articular/diagnóstico por imagen , Medios de Contraste/administración & dosificación , Miembro Anterior/anatomía & histología , Húmero/anatomía & histología , Húmero/diagnóstico por imagen , Yohexol/administración & dosificación , Estudios Prospectivos , Intensificación de Imagen Radiográfica/métodos , Cúbito/anatomía & histología , Cúbito/diagnóstico por imagen
7.
J Nutr ; 144(4): 533-7, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24500940

RESUMEN

Studies suggest a link between magnesium status and osteoporosis. One barrier to more conclusive research on the potential relation is measuring intestinal magnesium absorption (MgA), which requires the use of stable isotopes and a ≥6-d stool or 3-d urine collection. We evaluated alternative methods of measuring MgA. We administered 2 stable magnesium isotopes to 15 postmenopausal women (cohort 1) aged 62 ± 8 y with a dietary magnesium intake of 345 ± 72 mg/d. Participants fasted from 1200 h to 0700 h and then consumed breakfast with ∼23 mg of oral ²6Mg and ∼11 mg of i.v. ²5Mg. We measured magnesium isotope concentrations in 72-h urine, spot urine (36, 48, 60, and 72 h), and spot serum (1, 3, and 5 h) samples collected after isotope dosing. We calculated MgA using the dose-corrected fraction of isotope concentrations from the 72-h urine collection. We validated new methods in 10 postmenopausal women (cohort 2) aged 59 ± 5 y with a dietary magnesium intake of 325 ± 122 mg/d. In cohort 1, MgA based on the 72-h urine collection was 0.28 ± 0.08. The 72-h MgA correlated most highly with 0-24 h urine MgA value alone (ρ = 0.95, P < 0.001) or the mean of the 0-24 h urine and the 3-h (ρ = 0.93, P < 0.001) or 5-h (ρ = 0.96, P < 0.001) serum MgA values. In cohort 2, Bland-Altman bias was lowest (-0.003, P = 0.82) using means of the 0-24 h urine and 3-h serum MgA values. We conclude that means of 0-24 h urine and 3-h serum MgA provide a reasonable estimate of 72-h MgA. However, if researchers seek to identify small changes in MgA, we recommend a 3-d urine or extended stool collection.


Asunto(s)
Absorción Intestinal , Mucosa Intestinal/fisiopatología , Óxido de Magnesio , Magnesio/metabolismo , Síndromes de Malabsorción/diagnóstico , Administración Oral , Anciano , Desayuno , Estudios de Cohortes , Dieta , Femenino , Humanos , Infusiones Intravenosas , Mucosa Intestinal/fisiología , Isótopos , Magnesio/administración & dosificación , Magnesio/sangre , Magnesio/orina , Óxido de Magnesio/administración & dosificación , Síndromes de Malabsorción/sangre , Síndromes de Malabsorción/fisiopatología , Síndromes de Malabsorción/orina , Tamizaje Masivo/métodos , Persona de Mediana Edad , Posmenopausia , Periodo Posprandial , Valor Predictivo de las Pruebas , Espectrofotometría Atómica
8.
Ecol Appl ; 24(6): 1445-62, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-29160666

RESUMEN

Protected areas are a cornerstone for biodiversity conservation, but they also provide amenities that attract housing development on inholdings and adjacent private lands. We explored how this development affects biodiversity within and near protected areas among six ecological regions throughout the United States. We quantified the effect of housing density within, at the boundary, and outside protected areas, and natural land cover within protected areas, on the proportional abundance and proportional richness of three avian guilds within protected areas. We developed three guilds from the North American Breeding Bird Survey, which included Species of Greatest Conservation Need, land cover affiliates (e.g., forest breeders), and synanthropic species associated with urban environments. We gathered housing density data for the year 2000 from the U.S. Census Bureau, and centered the bird data on this year. We obtained land cover data from the 2001 National Land Cover Database, and we used single- and multiple-variable analyses to address our research question. In all regions, housing density within protected areas was positively associated with the proportional abundance or proportional richness of synanthropes, and negatively associated with the proportional abundance or proportional richness of Species of Greatest Conservation Need. These relationships were strongest in the eastern forested regions and the central grasslands, where more than 70% and 45%, respectively, of the variation in the proportional abundance of synanthropes and Species of Greatest Conservation Need were explained by housing within protected areas. Furthermore, in most regions, housing density outside protected areas was positively associated with the proportional abundance or proportional richness of synanthropes and negatively associated with the proportional abundance of land cover affiliates and Species of Greatest Conservation Need within protected areas. However, these effects were weaker than housing within protected areas. Natural land cover was high with little variability within protected areas, and consequently, was less influential than housing density within or outside protected areas explaining the proportional abundance or proportional richness of the avian guilds. Our results indicate that housing development within, at the boundary, and outside protected areas impacts avian community structure within protected areas throughout the United States.


Asunto(s)
Biodiversidad , Aves , Conservación de los Recursos Naturales , Vivienda , Animales , Actividades Humanas , Densidad de Población , Estados Unidos
9.
Conserv Biol ; 28(5): 1291-301, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24811862

RESUMEN

As people encroach increasingly on natural areas, one question is how this affects avian biodiversity. The answer to this is partly scale-dependent. At broad scales, human populations and biodiversity concentrate in the same areas and are positively associated, but at local scales people and biodiversity are negatively associated with biodiversity. We investigated whether there is also a systematic temporal trend in the relationship between bird biodiversity and housing development. We used linear regression to examine associations between forest bird species richness and housing growth in the conterminous United States over 30 years. Our data sources were the North American Breeding Bird Survey and the 2000 decennial U.S. Census. In the 9 largest forested ecoregions, housing density increased continually over time. Across the conterminous United States, the association between bird species richness and housing density was positive for virtually all guilds except ground nesting birds. We found a systematic trajectory of declining bird species richness as housing increased through time. In more recently developed ecoregions, where housing density was still low, the association with bird species richness was neutral or positive. In ecoregions that were developed earlier and where housing density was highest, the association of housing density with bird species richness for most guilds was negative and grew stronger with advancing decades. We propose that in general the relationship between human settlement and biodiversity over time unfolds as a 2-phase process. The first phase is apparently innocuous; associations are positive due to coincidence of low-density housing with high biodiversity. The second phase is highly detrimental to biodiversity, and increases in housing density are associated with biodiversity losses. The long-term effect on biodiversity depends on the final housing density. This general pattern can help unify our understanding of the relationship of human encroachment and biodiversity response.


Asunto(s)
Biodiversidad , Aves/fisiología , Bosques , Animales , Humanos , Dinámica Poblacional , Factores de Tiempo , Estados Unidos
10.
Public Health Nutr ; 17(4): 739-46, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23870503

RESUMEN

OBJECTIVE: Our objective was to determine whether a questionnaire can identify individuals with vitamin D insufficiency (VDI). DESIGN: Women completed the Vitamin D & Sun (VIDSUN) questionnaire and we measured their serum 25-hydrocyvitamin D (25(OH)D) levels. We assessed the sensitivity and specificity of the questionnaire to identify VDI (25(OH)D level <50 nmol/l). SETTING: Clinical Research Unit, University of Wisconsin-Madison. SUBJECTS: Postmenopausal women. RESULTS: We recruited 609 postmenopausal women with a mean age of 61 (sd 6 years), of whom 113 (19%) had VDI. Women with VDI were more likely to be black (17% v. 2%, P < 0.001), heavier (BMI 33.0 (sd 7) kg/m2 v. 29.0 (sd 7) kg/m2, P < 0.001) and less likely to tan in the past year (49% v. 72%, P < 0.001), use sunscreen (57% v. 72%, P < 0.001) or report sun exposure in the last 3 months. They consumed less vitamin D from supplements (2.15 (sd 5.24) µg/d (86 (sd 210) IU/d) v. 4.55 (sd 8.48) µg/d (188 (sd 344) IU/d), P = 0.003). In logistic regression models, black race, BMI, suntan within the past year, sun exposure in the past 3 months, sunscreen use and supplemental vitamin D intake were the most useful questions to identify VDI. From these six items, a composite score of ≤ 2.25 demonstrated ≥89% sensitivity but ≤35% specificity for VDI. CONCLUSIONS: The VIDSUN questionnaire provides an initial tool to identify postmenopausal women at high or low risk of VDI. Existing studies suggest that inclusion of physical activity and TAG levels might improve the performance of the VIDSUN questionnaire.


Asunto(s)
Posmenopausia/sangre , Encuestas y Cuestionarios , Vitamina D/sangre , Anciano , Índice de Masa Corporal , Suplementos Dietéticos , Femenino , Humanos , Modelos Logísticos , Persona de Mediana Edad , Estado Nutricional , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Luz Solar , Vitamina D/administración & dosificación , Deficiencia de Vitamina D/sangre
11.
Vet Immunol Immunopathol ; 271: 110741, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38520894

RESUMEN

Tumor-infiltrating lymphocyte (TIL) density plays an important role in anti-tumor immunity and is associated with patient outcome in various human and canine malignancies. As a first assessment of the immune landscape of the tumor microenvironment in canine renal cell carcinoma (RCC), we retrospectively analyzed clinical data and quantified CD3, FoxP3, and granzyme B immunostaining in formalin-fixed paraffin-embedded tumor samples from 16 dogs diagnosed with renal cell carcinoma treated with ureteronephrectomy. Cell density was low for all markers evaluated. Increased numbers of intratumoral FoxP3 labelled (+) cells, as well as decreased granzyme B+: FoxP3+ TIL ratio, were associated with poor patient outcomes. Our initial study of canine RCC reveals that these tumors are immunologically cold and Tregs may play an important role in immune evasion.


Asunto(s)
Complejo CD3 , Carcinoma de Células Renales , Enfermedades de los Perros , Factores de Transcripción Forkhead , Granzimas , Neoplasias Renales , Linfocitos Infiltrantes de Tumor , Animales , Perros , Carcinoma de Células Renales/veterinaria , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/enzimología , Complejo CD3/análisis , Complejo CD3/metabolismo , Enfermedades de los Perros/inmunología , Enfermedades de los Perros/enzimología , Factores de Transcripción Forkhead/análisis , Factores de Transcripción Forkhead/metabolismo , Granzimas/metabolismo , Granzimas/análisis , Inmunohistoquímica/veterinaria , Neoplasias Renales/veterinaria , Neoplasias Renales/inmunología , Neoplasias Renales/enzimología , Linfocitos Infiltrantes de Tumor/inmunología , Estudios Retrospectivos
12.
Ecol Appl ; 23(3): 565-82, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23734486

RESUMEN

National-scale analyses of fire occurrence are needed to prioritize fire policy and management activities across the United States. However, the drivers of national-scale patterns of fire occurrence are not well understood, and how the relative importance of human or biophysical factors varies across the country is unclear. Our research goal was to model the drivers of fire occurrence within ecoregions across the conterminous United States. We used generalized linear models to compare the relative influence of human, vegetation, climate, and topographic variables on fire occurrence in the United States, as measured by MODIS active fire detections collected between 2000 and 2006. We constructed models for all fires and for large fires only and generated predictive maps to quantify fire occurrence probabilities. Areas with high fire occurrence probabilities were widespread in the Southeast, and localized in the Mountain West, particularly in southern California, Arizona, and New Mexico. Probabilities for large-fire occurrence were generally lower, but hot spots existed in the western and south-central United States The probability of fire occurrence is a critical component of fire risk assessments, in addition to vegetation type, fire behavior, and the values at risk. Many of the hot spots we identified have extensive development in the wildland--urban interface and are near large metropolitan areas. Our results demonstrated that human variables were important predictors of both all fires and large fires and frequently exhibited nonlinear relationships. However, vegetation, climate, and topography were also significant variables in most ecoregions. If recent housing growth trends and fire occurrence patterns continue, these areas will continue to challenge policies and management efforts seeking to balance the risks generated by wildfires with the ecological benefits of fire.


Asunto(s)
Ecosistema , Incendios , Actividades Humanas , Modelos Estadísticos , Demografía , Humanos , Factores de Riesgo , Factores de Tiempo , Estados Unidos
13.
Front Vet Sci ; 10: 1240227, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37818390

RESUMEN

Many dairy operations uses a Brix refractometer to assess the quality of first-milking colostrum. This study investigated whether a digital Brix refractometer could be used in a model to predict colostrum IgG concentration and whether more than one %Brix threshold could be used for different colostrum IgG concentrations. Colostrum from 182 animals was tested using a digital Brix refractometer and by single radial immunodiffusion. Statistical analysis, using simple linear regression to relate %Brix results with corresponding colostral IgG concentration, and receiver operating characteristic (ROC) analysis were used to identify %Brix cutoffs that had no false positive results. Colostral IgG concentrations from digital Brix refractometry had a R2 value of 0.818 and a S-value of 21.7 g/L. The large S-value shows that a digital Brix refractometer should not be used in a model to predict colostrum IgG concentration. However, %Brix scores of 19.0, 22.0, 25.0 and 30.0 percent can be used to estimate minimum colostral IgG concentrations of 25, 50, 75 and 100 g/L. These four cutoffs can be used to strategically feed smaller volumes of colostrum to newborn calves. Smaller volumes may reduce unwanted side effects and shorten the time interval in which calves refuse to nurse, while still delivering an adequate mass of IgG to have successful transfer of passive immunity.

14.
Vet Comp Oncol ; 21(2): 339-348, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36929679

RESUMEN

Methods of calculating and reporting dose intensity (DI) of CHOP-based protocols in the veterinary literature vary. The goal of this retrospective study is to examine the prognostic significance of the average percentage of planned DI received in a cohort of canine T-cell lymphoma patients treated with a modified CHOP protocol with corresponding toxicity and efficacy data. Our data set of 40 dogs was analysed using various previously published methods for calculating DI. Median progression-free survival and overall survival were 91 and 196 days, respectively. Receiving a higher percentage of planned DI was not found to be associated with patient outcome. Outcomes remain poor for dogs with T-cell lymphoma treated with CHOP-based chemotherapy irrespective of received DI. Standard methods of DI calculation and reporting should be adopted in veterinary oncology to enable repeatable and rigorous comparisons of published chemotherapy protocols and to ascertain the potential prognostic relevance of DI in canine lymphoma patients.


Asunto(s)
Enfermedades de los Perros , Linfoma de Células T , Perros , Animales , Estudios Retrospectivos , Linfoma de Células T/tratamiento farmacológico , Linfoma de Células T/veterinaria , Prednisona/uso terapéutico , Vincristina , Ciclofosfamida , Protocolos de Quimioterapia Combinada Antineoplásica , Doxorrubicina , Pronóstico
15.
Vet Comp Oncol ; 21(3): 503-508, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37222086

RESUMEN

Multi-agent chemotherapy successfully induces remission in most naïve, high-grade canine lymphoma patients; however, disease recurrence is common. MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) is an effective rescue protocol used to re-induce remission, but is associated with gastrointestinal toxicity and can be a less desirable option for patients that previously failed vincristine-containing protocols. Therefore, alternative members of the vinca alkaloid family, such as vinblastine, could be potentially advantageous as substitutes for vincristine to reduce gastrointestinal toxicity and chemoresistance. The objective of this study was to report the clinical outcomes and toxicity of 36 dogs with relapsed or refractory multicentric lymphoma treated with a modified MOPP protocol whereby vincristine was replaced with vinblastine (MVPP). The overall response rate to MVPP was 25% with a median progression free survival of 15 days and a median overall survival of 45 days. MVPP at the prescribed doses resulted in modest and transient clinical benefit, but was well tolerated with no treatment delays or hospitalizations secondary to side effects. Given the minimal toxicity, dose intensification could be considered to improve clinical responses.


Asunto(s)
Enfermedades de los Perros , Linfoma no Hodgkin , Linfoma , Recurrencia Local de Neoplasia , Animales , Perros , Prednisona/uso terapéutico , Vinblastina/uso terapéutico , Mecloretamina/uso terapéutico , Mecloretamina/efectos adversos , Vincristina , Procarbazina/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/veterinaria , Enfermedades de los Perros/inducido químicamente , Linfoma/tratamiento farmacológico , Linfoma/veterinaria , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/veterinaria , Doxorrubicina/uso terapéutico
16.
Sci Rep ; 12(1): 7348, 2022 05 05.
Artículo en Inglés | MEDLINE | ID: mdl-35513694

RESUMEN

Zika virus (ZIKV) infection at the maternal-placental interface is associated with adverse pregnancy outcomes including fetal demise and pregnancy loss. To determine how infection impacts placental trophoblasts, we utilized rhesus macaque trophoblast stem cells (TSC) that can be differentiated into early gestation syncytiotrophoblasts (ST) and extravillous trophoblasts (EVT). TSCs and STs, but not EVTs, were highly permissive to productive infection with ZIKV strain DAK AR 41524. The impact of ZIKV on the cellular transcriptome showed that infection of TSCs and STs increased expression of immune related genes, including those involved in type I and type III interferon responses. ZIKV exposure altered extracellular vesicle (EV) mRNA, miRNA and protein cargo, including ZIKV proteins, regardless of productive infection. These findings suggest that early gestation macaque TSCs and STs are permissive to ZIKV infection, and that EV analysis may provide a foundation for identifying non-invasive biomarkers of placental infection in a highly translational model.


Asunto(s)
Vesículas Extracelulares , Complicaciones Infecciosas del Embarazo , Infección por el Virus Zika , Virus Zika , Animales , Vesículas Extracelulares/genética , Femenino , Expresión Génica , Humanos , Macaca mulatta , Placenta/metabolismo , Embarazo , Trofoblastos/metabolismo , Virus Zika/fisiología
17.
Am J Clin Nutr ; 115(4): 1059-1068, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-35030234

RESUMEN

BACKGROUND: Excessive vitamin A (VA) can cause bone resorption and impair growth. Government-mandated VA supplementation (VAS) and adequate intake through dietary fortification and liver consumption led to excessive VA in South African children. OBJECTIVES: We evaluated the relation between VAS and underlying hypervitaminosis A assessed by retinol isotope dilution (RID) with measures of growth and bone turnover in this cohort. METHODS: Primary outcomes in these children (n = 94, 36-60 mo) were anthropometric measurements [height-for-age (HAZ), weight-for-age (WAZ), and weight-for-height (WHZ) z scores], serum bone turnover markers [C-terminal telopeptide of type I collagen (CTX) and N-terminal propeptide of type I procollagen (P1NP)], and inflammation defined as C-reactive protein (CRP; ≥5 mg/L) and/or α1-acid glycoprotein (AGP; ≥1 g/L). VA status was previously measured by RID-estimated total body VA stores (TBSs) and total liver VA reserves (TLRs), and serum retinol and carotenoid concentrations, before and 4 wk after children were administered 200,000 IU VAS. Serum 25-hydroxyvitamin D3 was measured by ultra-performance LC. RESULTS: In this largely hypervitaminotic A cohort, HAZ, WAZ, and WHZ were negatively associated with increasing TLRs, where TLRs predicted 6-10% of the variation before VAS (P < 0.05), increasing to 14-19% 4 wk after VAS (P < 0.01). Bone resorption decreased after VAS (P < 0.0001), whereas formation was unaffected. Neither CTX nor P1NP were correlated with TLRs at either time. Serum carotenoids were low. One child at each time point was vitamin D deficient (<50 nmol/L). CRP and AGP were not associated with growth measurements. CONCLUSIONS: Excessive TLRs due to dietary VA intake and VAS are associated with lower anthropometric measures and bone resorption decreased after supplementation. VA supplementation programs should monitor VA status with biomarkers sensitive to TLRs to avoid causing negative consequences in children with hypervitaminosis A. This trial is registered at clinicaltrials.gov as NCT02915731.


Asunto(s)
Hipervitaminosis A , Deficiencia de Vitamina A , Preescolar , Dieta , Humanos , Sudáfrica , Vitamina A
18.
Conserv Biol ; 25(3): 514-25, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21453363

RESUMEN

Understanding the spatial dimensions of hunting and prey population dynamics is important in order to estimate the sustainability of hunting in tropical forests. We investigated how hunting offtake of vertebrates differed in mixed forest and monodominant forest (composed of Gilbertiodendron dewevrei) and over different spatial extents within the hunting catchment around the logging town of Kabo, Congo. In 9 months of recall surveys with hunters, we gathered information on over 1500 hunting trips in which ungulates were 65% of the species killed and 82% of harvested biomass. Hunters supplied information on animals killed and the hunting trip, including the area visited (i.e., hunting zone; 11 separate zones within a 506 km(2) catchment or commonly hunted area). Over 65% of all animals were killed in monodominant forest, which made up 28% of the hunting catchment, and zones with small amounts of monodominant forest were used most frequently by hunters. Given the large offtakes from monodominant forests, we suggest that animal dispersal may be maintaining high, localized harvests in these areas. We believe hunters preferred to hunt in monodominant forest because the understory was accessible and that areas with small amounts of monodominant forest and large amounts of mixed forest were more productive. The variation in hunting pressure we found between and within hunting zones differs from past examinations of spatial variation in hunting offtake, where entire hunting catchments were considered population sinks and areas with low to no hunting (no-take zones) were outside hunting catchments. Future use of no-take zones to manage hunting should incorporate variability in offtake within hunting catchments.


Asunto(s)
Conservación de los Recursos Naturales , Ambiente , Recreación , Rumiantes , Animales , Congo , Dinámica Poblacional , Árboles
19.
Breastfeed Med ; 16(10): 799-806, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34107777

RESUMEN

Background: Disparities in breastfeeding persist placing a greater burden of disease on non-Hispanic black and Hispanic women and infants. Targeted implementation of the Baby-Friendly Hospital Initiative (BFHI) in areas at risk for poor breastfeeding outcomes has been shown to improve disparities in breastfeeding. The area deprivation index (ADI), a measure of the relative socioeconomic disadvantage of a neighborhood, may be useful in exploring the accessibility of BFHI hospitals in highly deprived areas and the differences in exclusive breastfeeding (EBF) rates in hospitals with and without the BFHI designation across deprivation categories. Objective: To evaluate the geographical distribution of BFHI and non-BFHI hospitals across ADI categories and explore the differences in EBF rates in BFHI and non-BFHI hospitals across ADI categories. Methods: Hospital EBF rates obtained from the Joint Commission included 414 BFHI and 1,532 non-BFHI hospitals. State ADI rank scores were determined for each hospital's census block group. Descriptive statistics were used to describe the geographic distribution of BFHI hospitals across three ADI categories (low, medium, and high). EBF rates across ADI categories and BFHI designations were compared using multiway analysis of variance. Results: The distribution of BFHI was similar across all ADI categories, ranging from 18% to 24%. EBF rates were 4.9% lower in highly deprived areas compared to areas with lower deprivation (p < 0.01). BFHI was associated with significantly higher EBF rates across all ADI categories (6.9%-11.2%, p < 0.01). Conclusion: ADI may be a useful tool for targeting the implementation of BFHI in hospitals in highly deprived areas to reduce breastfeeding disparities.


Asunto(s)
Lactancia Materna , Hospitales , Femenino , Promoción de la Salud , Humanos , Lactante
20.
Vet Comp Oncol ; 19(3): 541-550, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33729654

RESUMEN

Despite high initial response rates, a subset of dogs with B-cell lymphoma responds less robustly to CHOP-based chemotherapy and experiences shorter survival. One hundred and four dogs with nodal B-cell lymphoma were treated with a response-based CHOP (RBCHOP) protocol modified based on response to individual drugs during the first chemotherapy cycle. Dogs achieving complete (CR) or partial response (PR) at week 3, following treatment with vincristine and cyclophosphamide, received RBCHOP 1 (n = 72), a protocol sequentially rotating vincristine, cyclophosphamide, and doxorubicin. Dogs without a detectable response at week 3 that subsequently achieved CR or PR following treatment with doxorubicin received RBCHOP 2 (n = 14), in which four doses of doxorubicin were given consecutively followed by vincristine and cyclophosphamide. Dogs that failed to respond at week 3 and then to doxorubicin at week 5 assessment were offered rescue chemotherapy (RBCHOP 3, n = 18). Median progression free survival (PFS) and overall survival time (OST) were similar between RBCHOP 1 (PFS 210 days, OST 354 days) and RBCHOP 2 (PFS 220 days, OST 456 days), but significantly shorter for RBCHOP 3 (PFS 34 days, OST 80.5 days, P < 0.001). No presenting signalment nor hematologic variable differentiated patient cohort, however, dogs in RBCHOP 2 and RBCHOP 3 were more likely to have a lymphocytosis at diagnosis (P = 0.02 and 0.04, respectively). Protocol modification based on response during the first cycle resulted in similar toxicity profiles and outcomes to previously published variants of CHOP, and prognosis remained poor for dogs failing to respond during the first treatment cycle.


Asunto(s)
Enfermedades de los Perros , Linfoma de Células B , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Perros , Doxorrubicina/uso terapéutico , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B/veterinaria , Prednisona/uso terapéutico , Vincristina/uso terapéutico
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