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1.
Osteoporos Int ; 32(3): 539-547, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32886188

RESUMEN

A study of 959 black and white women shows that the normal range for 24-h urine calcium excretion in white women is 30-300 mg and 10-285 mg in black women. Clinical laboratories use a normal range for 24-h urine calcium excretion of 100-300 mg; there is a need for them to update their age- and race-specific ranges. INTRODUCTION: Recommendations for a normal range for 24-h urine calcium vary from a low of 50 mg to a high of 400 mg; most "laboratory normal ranges" based on older literature are incorrect. The objective of this analysis is to define a normal range for young women age 25-45 years and older women age 55-90 years, white and black, for 24-h urine calcium and calcium/creatinine ratio, and to examine the relationship between 24-h urine calcium, calcium absorption, and vitamin D metabolites. METHODS: Data from 3 studies was collected on 959 normal black and white women, ages 25-87 years, for 24-h urine calcium, creatinine, calcium intake, serum 25-hydroxyvitamin D (25OHD),1,25 dihydroxyvitamin D (1,25(OH)2D), and calcium absorption. Urine calcium and creatinine were measured on an auto-analyzer. Calcium absorption was measured by a single isotope method. Serum 25OHD and 1,25(OH)2D were measured by competitive protein binding assay or radioimmunoassay. Because 24-h urine calcium did not fit a normal distribution, non-parametric methods were used to determine the 95% reference interval (RI) and 90% non-parametric confidence intervals (CI) calculated for groups. RESULTS: The 95% reference intervals for 24-h urine calcium for women were as follows: black older 7-225 mg, black younger 8-285 mg; white older 37-275 mg, and white younger 23-287 mg. In older white women, 24-h urine calcium was significantly correlated with serum 1,25(OH)2 D, r = 0.23, p < 0.001, calcium intake r = 0.12, p = 0.001, and calcium absorption r = 0.18, p = 0.003, but not serum 25OHD r = 0.07, p = 0.06. CONCLUSIONS: The normal reference interval for 24-h urine calcium for black women is lower than white women. Twenty-four-hour urine calcium was correlated with serum 1,25(OH)2 D calcium intake and calcium absorption, but not serum 25OHD. This range will be useful clinically for defining hypercalciuria and for following patients on vitamin D and calcium treatment.


Asunto(s)
Calcio de la Dieta , Calcio , Adulto , Anciano , Anciano de 80 o más Años , Creatinina , Femenino , Humanos , Persona de Mediana Edad , Hormona Paratiroidea , Valores de Referencia , Vitamina D
2.
Ecol Modell ; 440: 109358, 2020 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-34017153

RESUMEN

Changing patterns of land use, temperature, and precipitation are expected to impact ecosystem services, including water quality and quantity, buffering of extreme events, soil quality, and biodiversity. Scenario analyses that link such impacts on ecosystem services to human well-being may be valuable in anticipating potential consequences of change that are meaningful to people living in a community. Ecosystem services provide numerous benefits to community well-being, including living standards, health, cultural fulfillment, education, and connection to nature. Yet assessments of impacts of ecosystem services on human well-being have largely focused on human health or monetary benefits (e.g. market values). This study applies a human well-being modelling framework to demonstrate the potential impacts of alternative land use scenarios on multi-faceted components of human well-being through changes in ecosystem services (i.e., ecological benefits functions). The modelling framework quantitatively defines these relationships in a way that can be used to project the influence of ecosystem service flows on indicators of human well-being, alongside social service flows and economic service flows. Land use changes are linked to changing indicators of ecosystem services through the application of ecological production functions. The approach is demonstrated for two future land use scenarios in a Florida watershed, representing different degrees of population growth and environmental resource protection. Increasing rates of land development were almost universally associated with declines in ecosystem services indicators and associated indicators of well-being, as natural ecosystems were replaced by impervious surfaces that depleted the ability of ecosystems to buffer air pollutants, provide habitat for biodiversity, and retain rainwater. Scenarios with increases in indicators of ecosystem services, however, did not necessarily translate into increases in indicators of well-being, due to covarying changes in social and economic services indicators. The approach is broadly transferable to other communities or decision scenarios and serves to illustrate the potential impacts of changing land use on ecosystem services and human well-being.

3.
J Intern Med ; 286(6): 651-659, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31215092

RESUMEN

BACKGROUND: It is questionable as to whether total serum 25 hydroxyvitamin D (T25D) levels are lower in African Americans. We measured serum T25D, free 25hydroxyvitamin D (F25D) and serum parathyroid hormone (PTH) in African American and Caucasian women and studied the effect of vitamin D dosing to determine if differences by race or age occur. METHODS: Healthy young and older Caucasian and African American women who were vitamin D insufficient were randomized in two clinical trials to escalating daily doses of vitamin D from 400 to 4800 IU and placebo for 12 months. RESULTS: Baseline F25D and T25D were significantly lower in young but not older African American compared to Caucasian women. At baseline, the rate of change, or slope, in F25D with T25D was significantly greater in younger women than in older women, but difference in the rate of change in F25D with T25D is similar in African American and Caucasian women. After vitamin D supplementation, there was an increase in F25D, and the dose response was not significantly different by age or race. The ratio of F25D/T25D decreased in all groups once T25D exceeded ~60 nmol L-1 . There was a progressive decrease in serum PTH with increasing vitamin D doses and the per cent change was similar for F25D and T25D. CONCLUSION: Serum F25D and T25D are lower in younger African American women, and since dietary vitamin D is similar in the groups, it is likely that the cause of low serum 25OHD in African American women is due to reduced UV exposure and reduced skin production of vitamin D.


Asunto(s)
Negro o Afroamericano , Hormona Paratiroidea/sangre , Deficiencia de Vitamina D/tratamiento farmacológico , Vitamina D/análogos & derivados , Vitamina D/sangre , Población Blanca , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Vitamina D/uso terapéutico
4.
J Intern Med ; 284(6): 685-693, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30137647

RESUMEN

BACKGROUND: There are few controlled studies of the effect of different doses of vitamin D3 on bone mineral density (BMD). OBJECTIVES: We conducted a randomized placebo-controlled trial of increasing doses of vitamin D3 in 163 Caucasian and 31 African American women with serum 25-hydroxyvitamin D (25OHD) ≤50 nmol/L. This is an analysis of secondary outcome BMD to see if there is an association between percent change in BMD and dose of vitamin D3. METHODS: Participants were randomly assigned to placebo, vitamin D3 400, 800, 1600, 2400, 3200, 4000, or 4800 IU/day; calcium supplements, average 600mg, were given to provide a total calcium intake of 1200 mg/d. The primary outcome was 12-month serum 25OHD level. Analysis methods include ANOVA and Pearson correlations. RESULTS: The mean percent increase (±SD) in BMD at 12 months for all women was small; total body, 0.62% (± 2.72), femoral neck 0.59% (±3.58) and spine 0.43% (±2.80). There was no difference in BMD or serum N-telopeptide in response to vitamin D by dose or race. The increase in total body, spine and hip BMD in elderly women given vitamin D doses between 400 and 4800 IU daily and calcium supplementation is small, unrelated to dose or 12-month serum 25OHD, free 25OHD or 1,25(OH)2D. There was no evidence of a threshold change in BMD with increasing serum 25OHD or free 25OHD in this population. CONCLUSIONS: We found no significant effect of daily vitamin D dose ranging from 400 to 4800 IU/day on BMD or serum N-terminal telopeptides in elderly women with initially low serum 25OHD.


Asunto(s)
Densidad Ósea/efectos de los fármacos , Fosfopéptidos/sangre , Procolágeno/sangre , Vitamina D/administración & dosificación , Vitaminas/administración & dosificación , Anciano , Anciano de 80 o más Años , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Persona de Mediana Edad , Vitamina D/uso terapéutico , Vitaminas/uso terapéutico
5.
Genes Immun ; 18(2): 67-74, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-28123183

RESUMEN

Exposure to organic dust from agricultural environments is associated with inflammatory respiratory conditions. The putative causal agents in organic dust include viral, microbial and fungal components, which are recognized by the family of Toll-like receptors (TLRs) and drive host innate and adaptive responses. Our aim in this study was to determine whether responsiveness to organic dust among agricultural workers was dependent on polymorphisms in the TLR10-TLR1-TLR6 gene cluster. We stimulated whole blood from 509 agricultural workers with organic dust, triacyl lipopeptide N-palmitoyl-S-dipalmitoylglyceryl Cys-Ser-(Lys)4 (Pam3CSK4) and the diacyl-lipopeptide peptidoglycan. Several of the tagging polymorphisms and haplotypes conferred hyper-responsiveness to organic dust with an increase in interleukin-6 (IL-6; P<0.005), but not tumor necrosis factor-α (TNF-α), secretion. We conclude that genetic variation in the TLR10-TLR1-TLR6 gene cluster mediates responsiveness to organic dust, but indicates different signaling pathways for IL-6 and TNF-α. These studies provide new insight into the role of the TLR10-TLR1-TLR6 gene cluster and the innate immune response to organic dust.


Asunto(s)
Polvo , Epistasis Genética , Receptor Toll-Like 10/genética , Receptor Toll-Like 1/genética , Receptor Toll-Like 6/genética , Anciano , Crianza de Animales Domésticos , Animales , Femenino , Humanos , Inmunidad Innata , Interleucina-6/inmunología , Lipopéptidos/inmunología , Lipopéptidos/farmacología , Masculino , Persona de Mediana Edad , Exposición Profesional , Peptidoglicano/inmunología , Polimorfismo Genético , Polimorfismo de Nucleótido Simple , Porcinos , Receptor Toll-Like 1/inmunología , Receptor Toll-Like 10/inmunología , Receptor Toll-Like 6/inmunología , Factor de Necrosis Tumoral alfa/inmunología
6.
Bipolar Disord ; 19(6): 417-433, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28804990

RESUMEN

OBJECTIVES: The aim of the current study was to inform ongoing attempts to identify clinically meaningful subcategories of auditory verbal hallucination (AVH), and to evaluate evidence that might pertain to the suitability of current psychological interventions for people with bipolar disorder (BD) who experience psychotic symptoms. METHODS: A comprehensive synthesis of findings on the phenomenology of AVH and delusions in BD is included, alongside a critical review of clinical and cognitive correlates. Studies published in the previous 20 years, until December 2016, were retrieved from the following databases: Embase, CINAHL, MEDLINE, PsycINFO and Web of Science. Thirty-two articles were reviewed after applying a set of predetermined inclusion criteria. RESULTS: Psychotic symptoms were common in both manic and depressive phases, although higher frequencies were indicated in mania. Few detailed characterizations of AVH phenomenology were identified. Delusions with persecutory, grandiose and referential themes were the most common in BD. AVHs were associated with delusions and there was evidence to suggest that delusion subtype may vary according to mood state and type of AVH. Data on clinical correlates of AVH in BD were sparse. However, the results indicated that cognitive appraisals or interpretations of voices might be different in BD from those established to be predictive of clinical outcomes in schizophrenia spectrum disorders. CONCLUSIONS: Clear gaps exist in our current understanding of the first-person experience of AVH in BD and the potential relationship to co-occurring symptoms, including delusions. Further research into cognitive interpretations of AVH in BD might inform adapted psychological interventions for psychotic symptoms in this population.


Asunto(s)
Trastorno Bipolar , Deluciones , Alucinaciones , Trastornos Psicóticos , Trastorno Bipolar/complicaciones , Trastorno Bipolar/psicología , Deluciones/diagnóstico , Deluciones/etiología , Alucinaciones/diagnóstico , Alucinaciones/etiología , Humanos , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/etiología
7.
J Anim Physiol Anim Nutr (Berl) ; 100(2): 348-60, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25960083

RESUMEN

Our study investigated the effects of condensed tannins (CT) on rumen in vitro methane (CH4 ) production and fermentation characteristics by incubating lucerne in buffered rumen fluid in combination with different CT extracts at 0 (control), 40, 80 and 120 g CT/kg of substrate DM. Condensed tannins were extracted from four sainfoin accessions: Rees 'A', CPI63763, Cotswold Common and CPI63767. Gas production (GP) was measured using a fully automated GP apparatus with CH4 measured at distinct time points. Condensed tannins differed substantially in terms of polymer size and varied from 13 (Rees 'A') to 73 (CPI63767) mean degree of polymerization, but had relatively similar characteristics in terms of CT content, procyanidin: prodelphinidin (PC: PD) and cis:trans ratios. Compared to control, addition of CT from CPI63767 and CPI63763 at 80 and 120 g CT/kg of substrate DM reduced CH4 by 43% and 65%, and by 23% and 57%, respectively, after 24-h incubation. Similarly, CT from Rees 'A' and Cotswold Common reduced CH4 by 26% and 46%, and by 28% and 46% respectively. Addition of increasing level of CT linearly reduced the maximum rates of GP and CH4 production, and the estimated in vitro organic matter digestibility. There was a negative linear and quadratic (p < 0.01) relation between CT concentration and total volatile fatty acid (VFA) production. Inclusion of 80 and 120 g CT/kg of substrate DM reduced (p < 0.001) branched-chain VFA production and acetate: propionate ratio and was lowest for CPI63767. A decrease in proteolytic activity as indirectly shown by a change in VFA composition favouring a shift towards propionate and reduction in branched-chain VFA production varied with type of CT and was highest for CPI63767. In conclusion, these results suggest that tannin polymer size is an important factor affecting in vitro CH4 production which may be linked to the CT interaction with dietary substrate or microbial cells.


Asunto(s)
Fabaceae/química , Metano/metabolismo , Proantocianidinas/química , Alimentación Animal/análisis , Animales , Reactores Biológicos , Fermentación , Estructura Molecular , Rumen/metabolismo
8.
Haemophilia ; 20(3): 398-406, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24418368

RESUMEN

Few randomized studies have reported on the use of factor IX (FIX) for secondary prophylaxis in haemophilia B patients. This study aimed to evaluate the efficacy and safety of two secondary prophylaxis regimens of recombinant coagulation FIX, nonacog alfa, compared with on-demand therapy. Male subjects aged 6-65 years with severe or moderately severe haemophilia B (FIX:C ≤ 2, n = 50) and ≥12 bleeding episodes (including ≥6 haemarthroses episodes) within 12 months of study participation were enrolled in this multicentre, randomized, open-label, four-period crossover trial. The primary measure was the annualized bleeding rate (ABR) of two prophylactic regimens vs. on-demand therapy. In the intent-to-treat group, mean ABR values were 35.1, 2.6 and 4.6 for the first on-demand period, the 50 IU kg(-1) twice-weekly period, and the 100 IU kg(-1) once-weekly period respectively. Differences in ABR between the first on-demand period and both prophylaxis regimens were significant (P < 0.0001); no significant differences were observed between prophylaxis regimens (P = 0.22). Seven serious adverse events occurred in five subjects, none related to study drug. Results demonstrated that secondary prophylaxis therapy with nonacog alfa 50 IU kg(-1) twice weekly or 100 IU kg(-1) once weekly reduced ABR by 89.4% relative to on-demand treatment. Both prophylaxis regimens demonstrated favourable safety profiles in subjects with haemophilia B.


Asunto(s)
Factor IX/uso terapéutico , Hemofilia B/tratamiento farmacológico , Adolescente , Adulto , Anciano , Niño , Estudios Cruzados , Humanos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéutico , Adulto Joven
9.
Ambio ; 43(6): 718-28, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24402649

RESUMEN

A sustainable world is one in which human needs are met equitably and without sacrificing the ability of future generations to meet their needs. Human well-being is described by four primary elements-basic human needs, economic needs, environmental needs, and subjective well-being. These elements can interact in a myriad of ways to influence overall well-being. What makes changes in human well-being sustainable for a population or a nation? Two major interactional concepts can push changes in human well-being toward a sustainable state in space and time-social equity and intergenerational equity. The concept of social equity distributes well-being over space, ensuring the fair treatment of all members of society promoting spatial sustainability of a well-being decision. The concept of intergenerational equity distributes well-being through time, ensuring the well-being of present and future generations of a population or nation, promoting temporal sustainability of a well-being decision. The roles of social and intergenerational equity in terms of their influence on human well-being are examined with a focus on more sustainable decision-making.


Asunto(s)
Conservación de los Recursos Naturales , Toma de Decisiones , Cambio Social , Medio Social , Humanos
10.
Science ; 381(6665): 1440-1445, 2023 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-37769069

RESUMEN

Molecular clocks are the basis for dating the divergence between lineages over macroevolutionary timescales (~105 to 108 years). However, classical DNA-based clocks tick too slowly to inform us about the recent past. Here, we demonstrate that stochastic DNA methylation changes at a subset of cytosines in plant genomes display a clocklike behavior. This "epimutation clock" is orders of magnitude faster than DNA-based clocks and enables phylogenetic explorations on a scale of years to centuries. We show experimentally that epimutation clocks recapitulate known topologies and branching times of intraspecies phylogenetic trees in the self-fertilizing plant Arabidopsis thaliana and the clonal seagrass Zostera marina, which represent two major modes of plant reproduction. This discovery will open new possibilities for high-resolution temporal studies of plant biodiversity.

11.
bioRxiv ; 2023 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-36993545

RESUMEN

Molecular clocks are the basis for dating the divergence between lineages over macro-evolutionary timescales (~10 5 -10 8 years). However, classical DNA-based clocks tick too slowly to inform us about the recent past. Here, we demonstrate that stochastic DNA methylation changes at a subset of cytosines in plant genomes possess a clock-like behavior. This 'epimutation-clock' is orders of magnitude faster than DNA-based clocks and enables phylogenetic explorations on a scale of years to centuries. We show experimentally that epimutation-clocks recapitulate known topologies and branching times of intra-species phylogenetic trees in the selfing plant A. thaliana and the clonal seagrass Z. marina , which represent two major modes of plant reproduction. This discovery will open new possibilities for high-resolution temporal studies of plant biodiversity.

12.
Am J Transplant ; 12(11): 3069-75, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22883417

RESUMEN

Optimal therapy for posttransplant lymphoproliferative disease (PTLD) remains problematic. A phase II trial adding rituximab to a low-dose cyclophosphamide and prednisone regimen was conducted for pediatric patients with Epstein-Barr virus (EBV) (+), CD20 (+) PTLD. Fifty-five patients were enrolled. Toxicity was similar for cycles of therapy containing rituximab versus those without. The complete remission (CR) rate was 69% (95% confidence interval (CI); 57%-84%). Of 12 patients with radiographic evidence of persistent disease at the end of therapy, eight were in CR 28 weeks later without further PTLD therapy. There were 10 deaths, 3 due to infections while receiving therapy and 7 from PTLD. The 2-year event-free survival (alive with functioning original allograft and no PTLD) was 71% (95% CI: 57%-82%) and overall survival was 83% (95% CI: 69%-91%) with median follow-up of 4.8 years. Due to small numbers, we were unable to determine significance of tumor histology, stage of disease, allograft type or early response to treatment on outcome. These data suggest rituximab combined with low-dose chemotherapy is safe and effective in treating pediatric with EBV (+) PTLD following solid-organ transplantation.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Trastornos Linfoproliferativos/tratamiento farmacológico , Trasplante de Órganos/efectos adversos , Adolescente , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Niño , Preescolar , Intervalos de Confianza , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Infecciones por Virus de Epstein-Barr/etiología , Infecciones por Virus de Epstein-Barr/mortalidad , Infecciones por Virus de Epstein-Barr/patología , Femenino , Estudios de Seguimiento , Humanos , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/mortalidad , Trastornos Linfoproliferativos/patología , Masculino , Dosis Máxima Tolerada , Trasplante de Órganos/métodos , Prednisona/administración & dosificación , Prednisona/efectos adversos , Estudios Prospectivos , Medición de Riesgo , Rituximab , Análisis de Supervivencia , Trasplante Homólogo , Resultado del Tratamiento
13.
Ambio ; 41(4): 327-40, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22581385

RESUMEN

Natural ecosystems perform fundamental life-support services upon which human civilization depends. However, many people believe that nature provides these services for free and therefore, they are of little or no value. While we do not pay for them, we pay significantly for their loss in terms of wastewater treatment facilities, moratoriums on greenhouse gases, increased illnesses, reduced soil fertility and losses in those images of nature that contribute to our basic happiness. Little is understood about the well-being benefits of the natural environment and its ecosystem services. The interwoven relationship of ecosystems and human well-being is insufficiently acknowledged in the wider philosophical, social, and economic well-being literature. In this article, we discuss an approach to examine human well-being and the interactions of its four primary elements-basic human needs, economic needs, environmental needs, and subjective well-being-and ecosystem services.


Asunto(s)
Ecosistema , Calidad de Vida , Humanos
14.
Animal ; 16 Suppl 2: 100518, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35469753

RESUMEN

The projected rise in the global human population and the anticipated increase in demand for meat and animal products, albeit with a greatly reduced environmental footprint, offers a difficult set of challenges to the livestock sector. Primarily, how do we produce more, but in a way that is healthier for the animals, public, and the environment? Implementing a smart agri-systems approach, utilising multiplatform precision technologies, internet of things, data analytics, machine learning, digital twinning and other emerging technologies can support a more informed decision-making and forecasting position that will allow us to move towards greater sustainability in future. If we look to precision agronomy, there are a wide range of technologies available and examples of how digitalisation and integration of platform outputs can lead to advances in understanding the agricultural system and forecasting upcoming events and performance that have hitherto been impossible to achieve. There is much for the livestock sector and animal scientists to learn from the developments of precision technologies and smart agri-system approaches in the arable and horticultural contexts. However, there are several barriers the livestock sector must overcome: (i) the development and implementation of precision livestock farming technologies that can be easily integrated and analysed without the support of a dedicated data analyst in house; (ii) the lack of extensive validation of many developed and available precision livestock farming technologies means that reliability and accuracy are likely to be compromised when applied in commercial practice; (iii) the best smart agri-systems approaches are reliant on large quantities of data from across a wide variety of conditions, but at present the complications of data sharing, commercial sensitivities, data ownership, and permissions make it challenging to obtain or knit together data from different parts of the system into a comprehensive picture; and (iv) the high level of investment needed to develop and scale these technologies is substantial and represents significant risk for companies when a technology is emerging. Using a case study of the National Pig Centre (a flagship pig research facility in the UK) we discuss how a smart agri-systems approach can be applied in practice to investigate alternative future systems for production, and enable monitoring of these systems as a commercial demonstrator site for future pork production.


Asunto(s)
Agricultura , Ganado , Animales , Granjas , Carne , Reproducibilidad de los Resultados , Porcinos
15.
Br J Cancer ; 104(6): 1038-48, 2011 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-21364589

RESUMEN

BACKGROUND: Pancreatic cancer (PC) harbours an activated point mutation (Kras(G12D)) in the Kras proto-oncogene that has been demonstrated to promote the development of PC. METHODS: This study was designed to investigate the effect of the oncogenic Kras(G12D) allele on aggressiveness and metastatic potential of PC cells. We silenced the oncogenic Kras(G12D) allele expression in CD18/HPAF and ASPC1 cell lines by stable expression of shRNA specific to the Kras(G12D)allele. RESULTS: The Kras(G12D) knockdown cells exhibited a significant decrease in motility (P<0.0001), invasion (P<0.0001), anchorage-dependent (P<0.0001) and anchorage-independent growth (P<0.0001), proliferation (P<0.005) and an increase in cell doubling time (P<0.005) in vitro and a decrease in the incidence of metastases upon orthotopic implantation into nude mice. The knockdown of the Kras(G12D) allele led to a significant increase in the expression of E-cadherin (mRNA and protein) both in vitro and in vivo. This was associated with a decrease in the expression of phoshpo-ERK-1/2, NF-κB and MMP-9, and transcription factors such as δEF1, Snail and ETV4. Furthermore, the expression of several proteins involved in cell survival, invasion and metastasis was decreased in the Kras(G12D) knockdown cells. CONCLUSIONS: The results of this study suggest that the Kras(G12D) allele promotes metastasis in PC cells partly through the downregulation of E-cadherin.


Asunto(s)
Adenocarcinoma/genética , Adenocarcinoma/patología , Cadherinas/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Proteínas Proto-Oncogénicas/genética , Proteínas ras/genética , Sustitución de Aminoácidos/genética , Sustitución de Aminoácidos/fisiología , Animales , Ácido Aspártico/genética , Cadherinas/fisiología , Regulación hacia Abajo/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glicina/genética , Humanos , Ratones , Ratones Desnudos , Invasividad Neoplásica , Metástasis de la Neoplasia , Mutación Puntual , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas p21(ras) , ARN Interferente Pequeño/farmacología , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto , Proteínas ras/metabolismo
16.
Nanotechnology ; 22(27): 275607, 2011 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-21597144

RESUMEN

We examine the growth and evolution with time of bipyramidal gold nanoparticles grown by a seed-mediated process. The nanoparticles are characterized both by their physical dimensions determined by transmission electron microscopy and by the wavelength position of their localized surface plasmon resonance. Each growth's physical dimensions correspond to particular initial conditions, and we observe two distinct modes of temporal evolution during growth. The effects of varying silver nitrate concentration and growth time are also explored. We observe a linear relationship between the tip radius of curvature and the wavelength of the longitudinal localized surface plasmon resonance (LSPR) peak. Critical parameters for synthesizing bipyramidal nanoparticles with sharp tips and correct length to width ratio are determined.

17.
Child Care Health Dev ; 37(1): 143-9, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20854448

RESUMEN

BACKGROUND: The study aimed to determine if child obesity rates have risen in the Caribbean nation of Saint Lucia, as found globally, and whether under-nutrition coexists, as in other developing nations. The average adult in Saint Lucia is overweight, thus considerable child obesity might be expected, but there are no current data. METHODS: Heights and weights were obtained from a sample (n= 425) of the 2001 birth cohort of Saint Lucian children measured during the nation-wide 2006/2007 Prior to School Entry Five-Year Assessment. Prevalence of overweight, obesity and underweight were estimated by Centers for Disease Control (CDC), Cole et al. and new World Health Organization (WHO) methods. Previously reported 1976 estimates, including children ≤60 months of age only, based on National Centre for Health Statistics curves, were adjusted to new WHO equivalents using an algorithm developed by Yang and de Onis, and compared with rates in our subsample of children ≤60 months of age (n= 99). RESULTS: Regardless of classification method, overweight and obesity rates were high: 14.4% and 9.2% (WHO); 11.3% and 12.0% (CDC); and 9.9% and 7.1% (Cole et al.), respectively. Underweight estimates also varied: 4.7% (WHO); 11.3% (CDC) and 6.6% (Cole et al.). Obesity in our young subsample (15.2%; WHO) was more than 3 times the adjusted 1976 rate (4.3%). CONCLUSIONS: Obesity among Saint Lucian pre-schoolers has tripled in 30 years. Our findings also suggest that this country, like many undergoing a 'nutrition transition', faces the dual challenge of over-nutrition and under-nutrition. Routine monitoring of overweight and underweight is needed in Saint Lucia, as is the implementation and evaluation of programmes to address these problems.


Asunto(s)
Índice de Masa Corporal , Sobrepeso/diagnóstico , Delgadez/diagnóstico , Preescolar , Estudios de Cohortes , Humanos , Estado Nutricional , Sobrepeso/epidemiología , Prevalencia , Santa Lucia/epidemiología , Factores Sexuales , Delgadez/epidemiología , Factores de Tiempo
18.
Br J Cancer ; 103(5): 676-84, 2010 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-20664585

RESUMEN

BACKGROUND: CD70 is an ideal target for antibody-based therapies because of its aberrant high expression in renal carcinomas and non-Hodgkin lymphomas and its highly restricted expression in normal tissues. The expression profiling of CD70 in carcinomas has been limited because of the lack of a CD70-specific reagent that works in formalin-fixed paraffin-embedded (FFPE) tissues. METHODS: We generated murine monoclonal antibodies (mAbs) specific for CD70 and validated their specificity by western blot analysis and developed a protocol for immunohistochemistry on FFPE tissues. CD70+ tumour cell lines were used for testing the anti-tumour activity of the anti-CD70 antibody-drug conjugate, SGN-75. RESULTS: We report novel detection of CD70 expression in multiple cancers including pancreatic (25%), larynx/pharynx (22%), melanoma (16%), ovarian (15%), lung (10%), and colon (9%). Our results show that pancreatic and ovarian tumour cell lines, which express high levels of endogenous or transfected CD70, are sensitive to the anti-tumour activity of SGN-75 in vitro and in vivo. CONCLUSION: Development of murine mAbs for robust and extensive screening of FFPE samples coupled with the detection of anti-tumour activity in novel indications provide rationale for expanding the application of SGN-75 for the treatment of multiple CD70 expressing cancers.


Asunto(s)
Aminobenzoatos/administración & dosificación , Ligando CD27/inmunología , Inmunoconjugados/uso terapéutico , Oligopéptidos/administración & dosificación , Neoplasias Ováricas/terapia , Neoplasias Pancreáticas/terapia , Animales , Anticuerpos Monoclonales/uso terapéutico , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Ratones , Ratones Desnudos
19.
Nanotechnology ; 21(3): 035604, 2010 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-19966397

RESUMEN

Straight, vertically aligned GaAs nanowires were grown on Si(111) substrates coated with thin GaAs buffer layers. We find that the V/III precursor ratio and growth temperature are crucial factors influencing the morphology and quality of buffer layers. A double layer structure, consisting of a thin initial layer grown at low V/III ratio and low temperature followed by a layer grown at high V/III ratio and high temperature, is crucial for achieving straight, vertically aligned GaAs nanowires on Si(111) substrates. An in situ annealing step at high temperature after buffer layer growth improves the surface and structural properties of the buffer layer, which further improves the morphology of the GaAs nanowire growth. Through such optimizations we show that vertically aligned GaAs nanowires can be fabricated on Si(111) substrates and achieve the same structural and optical properties as GaAs nanowires grown directly on GaAs(111)B substrates.

20.
J Musculoskelet Neuronal Interact ; 10(2): 142-50, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20516631

RESUMEN

OBJECTIVES: To ascertain the risk factors for falls, stumbles and recurrent falls in a cohort of elderly people with mean age of 76.7-/+6.1 years. METHODS: 137 community dwelling elderly living independently or in assisted living institutions participated in the study. Each subject was assessed by history, physical examination and physical performance tests at the beginning and end of study. Falls and stumbles were recorded in a falls dairy for 1 year. RESULTS: Significant predictors of being a faller were a history of falls at baseline (Odds Ratio (OR) = 3.85, 95% Confidence Interval (CI) = 1.56 - 9.50), depression (OR = 1.19, 95% CI = 1.02 - 1.38) and timed rise (Incident Rate Ratio (IRR) = 1.24, 95% CI = 1.03 - 1.50). For predicting recurrent fallers Receiver Operator Characteristic (ROC) curves were as follows: 0.71 (95%CI 0.61-0.81) for timed up and go, 0.67 (95%CI 0.56-0.78) for timed rise and 0.70 (95%CI 0.60-0.80) for timed walk fast pace. CONCLUSIONS: Timed rise was the single most important test that was able to predict both a first time faller and recurrent faller. Timed up and go was the most significant test to predict recurrent fallers.


Asunto(s)
Accidentes por Caídas , Evaluación Geriátrica , Medición de Riesgo , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Distribución de Chi-Cuadrado , Estudios Transversales , Depresión , Humanos , Oportunidad Relativa , Equilibrio Postural , Estudios Prospectivos , Curva ROC , Análisis de Regresión , Factores de Riesgo , Vitamina D/análogos & derivados , Vitamina D/sangre
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