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1.
Neuroimage ; 135: 311-23, 2016 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-27138209

RESUMEN

We propose a novel method to harmonize diffusion MRI data acquired from multiple sites and scanners, which is imperative for joint analysis of the data to significantly increase sample size and statistical power of neuroimaging studies. Our method incorporates the following main novelties: i) we take into account the scanner-dependent spatial variability of the diffusion signal in different parts of the brain; ii) our method is independent of compartmental modeling of diffusion (e.g., tensor, and intra/extra cellular compartments) and the acquired signal itself is corrected for scanner related differences; and iii) inter-subject variability as measured by the coefficient of variation is maintained at each site. We represent the signal in a basis of spherical harmonics and compute several rotation invariant spherical harmonic features to estimate a region and tissue specific linear mapping between the signal from different sites (and scanners). We validate our method on diffusion data acquired from seven different sites (including two GE, three Philips, and two Siemens scanners) on a group of age-matched healthy subjects. Since the extracted rotation invariant spherical harmonic features depend on the accuracy of the brain parcellation provided by Freesurfer, we propose a feature based refinement of the original parcellation such that it better characterizes the anatomy and provides robust linear mappings to harmonize the dMRI data. We demonstrate the efficacy of our method by statistically comparing diffusion measures such as fractional anisotropy, mean diffusivity and generalized fractional anisotropy across multiple sites before and after data harmonization. We also show results using tract-based spatial statistics before and after harmonization for independent validation of the proposed methodology. Our experimental results demonstrate that, for nearly identical acquisition protocol across sites, scanner-specific differences can be accurately removed using the proposed method.


Asunto(s)
Algoritmos , Imagen de Difusión por Resonancia Magnética/instrumentación , Imagen de Difusión por Resonancia Magnética/métodos , Interpretación de Imagen Asistida por Computador/instrumentación , Interpretación de Imagen Asistida por Computador/métodos , Técnica de Sustracción/instrumentación , Adulto , Diseño de Equipo , Análisis de Falla de Equipo , Femenino , Humanos , Aumento de la Imagen/métodos , Almacenamiento y Recuperación de la Información/métodos , Masculino , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
2.
Br J Cancer ; 110(3): 656-67, 2014 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-24281001

RESUMEN

BACKGROUND: Histone deacetylase inhibitors (HDACi) are promising antineoplastic agents, but their precise mechanisms of actions are not well understood. In particular, the relevance of p53 for HDACi-induced effects has not been fully elucidated. We investigated the anticancer effects of four structurally distinct HDACi, vorinostat, entinostat, apicidin and valproic acid, using isogenic HCT-116 colon cancer cell lines differing in p53 status. METHODS: Effects were assessed by MTT assay, flow-cytometric analyses of propidium iodide uptake, mitochondrial depolarisation and cell-cycle distribution, as well as by gene expression profiling. RESULTS: Vorinostat was equally effective in p53 wild-type and null cells, whereas entinostat was less effective in p53 null cells. Histone deacetylase inhibitors treatment suppressed the expression of MDM2 and increased the abundance of p53. Combination treatments showed that vorinostat enhanced the cytotoxic activity of TRAIL and bortezomib, independent of the cellular p53 status. Investigations into the effects of an inhibitor of the sirtuin class of HDAC, tenovin-1, revealed that tenovin-1-mediated cell death hinged on p53. CONCLUSION: These results demonstrate that vorinostat activates p53, but does not require p53 for inducing its anticancer action. Yet they also demonstrate that entinostat-induced cytotoxic effects partially depend on p53, indicating that different HDACi have a different requirement for p53.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Neoplasias del Colon/tratamiento farmacológico , Inhibidores de Histona Desacetilasas/administración & dosificación , Proteína p53 Supresora de Tumor/metabolismo , Benzamidas/administración & dosificación , Neoplasias del Colon/patología , Citometría de Flujo , Regulación Neoplásica de la Expresión Génica , Células HCT116 , Humanos , Ácidos Hidroxámicos/administración & dosificación , Péptidos Cíclicos/administración & dosificación , Proteínas Proto-Oncogénicas c-mdm2 , Piridinas/administración & dosificación , Proteína p53 Supresora de Tumor/genética , Ácido Valproico/administración & dosificación , Vorinostat
3.
Eur J Nucl Med Mol Imaging ; 41(1): 59-67, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23974666

RESUMEN

PURPOSE: This study was designed to assess the additional value of SPECT/CT of the trunk used in conjunction with conventional nuclear imaging and its effects on patient management in a large patient series. METHODS: In 353 patients, whole-body scintigraphy (WBS), SPECT, and SPECT/CT were prospectively performed for staging and restaging. SPECT/CT of the trunk was performed in all patients. In the 308 evaluable patients (211 with breast cancer, 97 with prostate cancer), clinical follow-up was used as the gold standard. Bone metastases were confirmed in 72 patients and excluded in 236. Multistep analyses per lesion and per patient were performed. Clinical relevance was expressed in terms of downstaging and upstaging rates on a per-patient basis. RESULTS: In the total patient group, sensitivities, specificities, and negative and positive predictive values on a per-patient basis were 93 %, 78 %, 95 % and 59 % for WBS, 94 %, 71 %, 97 % and 53 % for SPECT, and 97 %, 94 %, 97 % and 88 % for SPECT/CT, respectively. In all subgroups, specificity and positive predictive value were significantly (p<0.01) better with SPECT/CT. Downstaging of metastatic disease in the total, breast cancer and prostate cancer groups using SPECT/CT was possible in 32.1 %, 33.8 % and 29.5 % of patients, respectively. Upstaging in previously negative patients by additional SPECT/CT was observed in three breast cancer patients (2.1 %). Further diagnostic imaging procedures for unclear scintigraphic findings were necessary in only 2.5 % of patients. SPECT/CT improved diagnostic accuracy for defining the extent of multifocal metastatic disease in 34.6 % of these patients. CONCLUSIONS: SPECT/CT significantly improved the specificity and positive predictive value of bone scintigraphy in cancer patients. In breast cancer patients, we found a slight increase in sensitivity. SPECT/CT had a significant effect on clinical management because of correct downstaging and upstaging, better definition of the extent of metastases, and a reduction in further diagnostic procedures.


Asunto(s)
Neoplasias Óseas/secundario , Huesos/diagnóstico por imagen , Imagen Multimodal , Tomografía Computarizada de Emisión de Fotón Único , Tomografía Computarizada por Rayos X , Imagen de Cuerpo Entero , Neoplasias Óseas/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC
4.
Int J Clin Pract ; 68(11): 1309-17, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25113816

RESUMEN

AIMS: Examine the association between weight loss and adherence with glycaemic goal attainment in patients with inadequately controlled T2DM. MATERIALS AND METHODS: Patients ≥ 18 years with T2DM from a US integrated health system starting a new class of diabetes medication between 11/1/10 and 4/30/11 (index date) with baseline HbA1c ≥ 7.0% were included in this cohort study. Target HbA1c and weight change were defined at 6-months as HbA1c < 7.0% and ≥ 3% loss in body weight. Patient-reported medication adherence was assessed per the Medication Adherence Reporting Scale. Structural equation modelling was used to describe simultaneous associations between adherence, weight loss and HbA1c goal attainment. RESULTS: Inclusion criteria were met by 477 patients; mean (SD) age 59.1 (11.6) years; 50.9% were female; 30.4% were treatment naïve; baseline HbA1c 8.6% (1.6); weight 102.0 kg (23.0). Most patients (67.9%) reported being adherent to the index diabetes medication. At 6 months mean weight change was -1.3 (5.1) kg (p = 0.39); 28.1% had weight loss of ≥ 3%. Mean HbA1c change was -1.2% (1.8) (p< 0.001); 42.8% attained HbA1c goal. Adherent patients (OR 1.70; p = 0.02) and diabetes therapies that lead to weight loss (metformin, GLP-1) were associated with weight loss ≥ 3% (OR 2.96; p< 0.001). Weight loss (OR 3.60; p < 0.001) and adherence (OR 1.59; p < 0.001) were associated with HbA1c goal attainment. CONCLUSIONS: Weight loss ≥ 3% and medication adherence were associated with HbA1c goal attainment in T2DM; weight loss was a stronger predictor of goal attainment than medication adherence in this study population. It is important to consider weight-effect properties, in addition to patient-centric adherence counselling, when prescribing diabetes therapy.


Asunto(s)
Diabetes Mellitus Tipo 2/dietoterapia , Índice Glucémico , Pérdida de Peso , Adulto , Anciano , Peso Corporal , Estudios de Cohortes , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/rehabilitación , Femenino , Péptido 1 Similar al Glucagón/uso terapéutico , Humanos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Compuestos de Sulfonilurea/uso terapéutico
5.
Sci Total Environ ; 900: 165764, 2023 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-37516173

RESUMEN

Long-term records of combined stream flow and water chemistry can be an invaluable source of information on changes in the quantity and quality of water resources. To understand the effect of hydroclimate and water management on the heavily urbanized Panke catchment in Berlin, Germany, an extensive search, collation and digitization of historic data from various sources was undertaken. This integrated a unique 66-year spatially distributed record of stream water quality, a 21-year record of groundwater quality and a 31-year stream flow record. These data were analysed in the context of hydroclimatic variability, as well as the history and technological evolution of water resource management in the catchment. To contextualize the effect of droughts, "average" and wet years the Standard Precipitation Index (SPI) was applied. As upstream sites have been less regulated by human impacts, the flow regime is most sensitive to changes in hydroclimatic conditions, while downstream sites are more influenced by wastewater effluents, urban storm drains and inter-basin transfers for flood alleviation. However, at all sites, a general increase in maximum event discharge was observed until a recent drought, starting in 2018. In general, water quality in the catchment has gradually improved as a result of management change and increasingly effective wastewater treatment, though in some places legacy and/or contemporary urban and rural groundwater contamination may be affecting the stream. Hydroclimatic changes, particularly drought years can affect water quality classes, and alter the chemostatic/dynamic behaviour of catchment export patterns. These insights from the Panke catchment underline the importance of strategic adaptation and improvement of water treatment and water resource management in order to enhance the quality of urban water courses. It also demonstrates the importance of long-term integrated data sets.

6.
Abdom Radiol (NY) ; 46(5): 1912-1921, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33156949

RESUMEN

BACKGROUND: The aim of this proof-of-concept study was to show that the liver segmental volume and attenuation ratio (LSVAR) improves the detection of significant liver fibrosis on portal venous CT scans by adding the liver vein to cava attenuation (LVCA) to the liver segmental volume ratio (LSVR). MATERIAL AND METHODS: Patients who underwent portal venous phase abdominal CT scans and MR elastography (reference standard) within 3 months between 02/2016 and 05/2017 were included. The LSVAR was calculated on portal venous CT scans as LSVR*LVCA, while the LSVR represented the volume ratio between Couinaud segments I-III and IV-VIII, and the LVCA represented the density of the liver veins compared to the density in the vena cava. The LSVAR and LSVR were compared between patients with and without significantly elevated liver stiffness (based on a cutoff value of 3.5 kPa) using the Mann-Whitney U test and ROC curve analysis. RESULTS: The LSVR and LSVAR allowed significant differentiation between patients with (n = 19) and without (n = 122) significantly elevated liver stiffness (p < 0.001). However, the LSVAR showed a higher area under the curve (AUC = 0.96) than the LSVR (AUC = 0.74). The optimal cutoff value was 0.34 for the LSVR, which detected clinically increased liver stiffness with a sensitivity of 53% and a specificity of 88%. With a cutoff value of 0.67 for the LSVAR, the sensitivity increased to 95% while maintaining a specificity of 89%. CONCLUSION: The LSVAR improves the detection of significant liver fibrosis on portal venous CT scans compared to the LSVR.


Asunto(s)
Diagnóstico por Imagen de Elasticidad , Cirrosis Hepática , Humanos , Hígado/diagnóstico por imagen , Hígado/patología , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/patología , Vena Porta/diagnóstico por imagen , Tomografía Computarizada por Rayos X
7.
Osteoporos Int ; 21(8): 1427-36, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19798459

RESUMEN

SUMMARY: We identified factors associated with oral bisphosphonate treatment in 50+-year-old female patients with a first fracture, osteoporosis diagnosis, or BMD < or =-2.5 in the Geisinger Health System electronic health record database. Treatment was positively associated with age, oral corticosteroids, and smoking, and negatively associated with body mass index and bone mineral density scores. INTRODUCTION: To identify factors associated with oral bisphosphonate treatment in patients with an indicator for post-menopausal osteoporosis. METHODS: Females age 50+ years with a first fracture, osteoporosis diagnosis, or bone mineral density (BMD) < or =-2.5 (index date) were identified in the Geisinger Health System electronic health record database. Treatment was defined as an oral bisphosphonate prescription order (risedronate sodium, ibandronate sodium, or alendronate) < or =90 days post-index date. Treatment rates were assessed and a multivariate logistic model was used to identify predictors of treatment separately for patients with fracture (FRAC) and with diagnosis or low BMD (ICD-9-BMD). RESULTS: The FRAC group had 2,003 female patients with a mean (SD) age of 69.0 (+/-11.3) years and the ICD-9-BMD group had 12,976 female patients with a mean (SD) age of 66.9 (+/-10.0) years. Within 90 days of the index date of fracture, diagnosis, or low BMD score, 188 (9.4%) patients in the FRAC group and 5,395 (41.6%) in the ICD-9-BMD group received treatment. Treatment was positively associated with age and oral corticosteroids and negatively associated with body mass index and subsequent BMD in both groups. Smoking currently was positively associated with treatment in the ICD-9-BMD group. CONCLUSION: Certain patient characteristics are predictors of physicians prescribing oral bisphosphonates. However, many patients remain untreated.


Asunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Difosfonatos/uso terapéutico , Osteoporosis Posmenopáusica/tratamiento farmacológico , Administración Oral , Factores de Edad , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Densidad Ósea/efectos de los fármacos , Conservadores de la Densidad Ósea/administración & dosificación , Difosfonatos/administración & dosificación , Prescripciones de Medicamentos/estadística & datos numéricos , Utilización de Medicamentos/estadística & datos numéricos , Métodos Epidemiológicos , Femenino , Glucocorticoides/uso terapéutico , Humanos , Persona de Mediana Edad , Osteoporosis Posmenopáusica/fisiopatología , Fracturas Osteoporóticas/fisiopatología , Fracturas Osteoporóticas/prevención & control
8.
Diabetes Obes Metab ; 12(1): 54-64, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19758356

RESUMEN

BACKGROUND: Insulin is a mainstay in the treatment of type 1 diabetes and is a recommended option in patients with type 2 diabetes who fail to maintain glycaemic control on other non-insulin therapies. The purpose of this study was to describe patient characteristics and evaluate changes in glycaemic control and weight in patients treated with insulin in an ambulatory care setting. METHODS: Patients with diabetes were identified from the General Electric electronic medical record (EMR) database (1 September 2004 to 30 April 2008). Patients were > or =18 years, insulin naive, newly treated with monoinsulin therapy (index date). Baseline characteristics were identified overall and stratified by insulin type (basal, mixed, and rapid). Basal insulins were described by human versus analog and for insulin detemir and insulin glargine. Change in haemoglobin A1C (HbA1C) and weight from baseline (45 days pre- to 15 days postindex date) to 6 months (+/-90 days) were compared. Regression analyses were used to evaluate HbA1C outcomes across insulins and for the likelihood of gaining 0.9 kg (2 lbs) for detemir versus glargine controlling for baseline characteristics. RESULTS: A total of 12 136 patients were included. A majority were initiated on a basal insulin (64.7%) followed by mixed (20.8%) and rapid (14.4%). Basal users had significantly higher mean body weight and lower mean baseline HbA1C than mixed users (p < 0.001 for all), and were significantly older, had higher baseline HbA1C and higher baseline body mass index (BMI) than rapid insulin users (p < 0.001 for all). Glargine patients had a significantly higher mean baseline HbA1C (p = 0.003) than detemir patients. The adjusted reduction in HbA1C was greater for rapid insulin than for mixed or basal insulin (p < or = 0.05). The adjusted differences in HbA1C between basal human and basal analog insulins and between detemir and glargine were not statistically significant (p > 0.05). Patients using detemir were 30% less likely to gain 0.9 kg or more than glargine users (p < 0.05). CONCLUSIONS: HbA1C outcomes in the ambulatory care setting were generally not different between insulin classes. The likelihood of weight gain was less with insulin detemir than with insulin glargine. Thus, real-world weight outcomes for basal analog insulin may differ by specific product.


Asunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Aumento de Peso/efectos de los fármacos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Atención Ambulatoria , Índice de Masa Corporal , Peso Corporal/fisiología , Diabetes Mellitus Tipo 1/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Esquema de Medicación , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/efectos adversos , Insulina/efectos adversos , Insulina/análogos & derivados , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
9.
Clin Anat ; 23(6): 693-701, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20821404

RESUMEN

Changes in the intraneural anatomy with age can cause poor prognosis of nerve repair in patients after nerve injury. The occurrence of Complex Regional Pain Syndrome-Type II, secondary to peripheral nerve injury, is common. The purpose of this study is to asses changes in cross-sectional anatomy of the lateral antebrachial cutaneous nerve of forearm (LCNF) at the antecubital fossa in the fascicular, nonfascicular components (adipose and nonadipose tissue), and sympathetic fibers area with respect to age. For the purpose of the study, 32 human (37-88 years) fresh cadaveric LCNF were collected from left-antecubital fossae and processed for histological, morphometric analysis [total cross-sectional (Asc), fascicular (Af), and nonfascicular area (Anonf)], and immunohistochemical method (tyrosine hydroxylase) for sympathetic fibers. The LCNF's average total cross-sectional area was 3.024 mm(2), and fascicular area was 0.582 mm(2). The average number of fascicles per mm(2) was 3.09. The cross-sectional area in the nerve was mainly occupied by nonfascicular connective tissue (80.75%). There was increased adipose tissue deposition (48.48% of Asc) and decreased collagen fibers (32.24% of Asc) in interfascicular domains without any definite relationship with age. The average sympathetic fiber area was 0.026 mm(2) within the nerve fascicular area without any correlation with age. In LCNF, there was more adipose tissue and less collagen fibers deposition in the interfascicular domains of all age cases, and this may act as an obstacle for nerve fiber regeneration on using LCNF as an interpositional nerve graft.


Asunto(s)
Anatomía Transversal , Antebrazo/inervación , Nervio Musculocutáneo/anatomía & histología , Piel/inervación , Tejido Adiposo/anatomía & histología , Adulto , Anciano , Anciano de 80 o más Años , Animales , Biomarcadores/metabolismo , Colágeno , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Nervio Musculocutáneo/enzimología , Fibras Nerviosas/clasificación , Fibras Nerviosas/enzimología , Ratas , Ratas Wistar , Tirosina 3-Monooxigenasa/metabolismo
10.
Surg Radiol Anat ; 32(9): 865-71, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20229241

RESUMEN

PURPOSE: Secondary to peripheral nerve injuries, involvement of sympathetic fibers complications such as complex regional pain syndrome (CRPS) have been reported. There are limited studies on the sympathetic fibers and their distribution in the upper limb nerves. There are no reports available in the distribution of the sympathetic fibers/areas of radial nerve in the forearm. The aim of the present study was an attempt to find the distribution of sympathetic fibers in the radial nerve just above cubital fossa (RN), superficial branch of radial nerve at cubital fossa (SBRN-1) and above wrist (SBRN-2). METHODS: We have studied on 19 fresh human cadaveric RN, SBRN-1, and SBRN-2 samples. Frozen sections of these nerves were processed by immunohistochemical (tyrosine hydroxylase) method for sympathetic fibers. RESULTS: The sympathetic fibers area (Asym) was found to be more in RN when compared to SBRN-1 and SBRN-2. The comparison of the sympathetic index (SI = sympathetic fibers area/total fascicular area of the nerve) between RN and SBRN-1 (p < 0.001), RN and SBRN-2 (p < 0.001), and SBRN-1 and SBRN-2 (p = 0.016) were statistically significant. The sympathetic index (SI) for SBRN-1 was more when compared to RN and SBRN-2. CONCLUSIONS: Sympathetic fibers area (Asym) was found to be more in RN when compared to SBRN-1 and SBRN-2. The sympathetic ratio (SI) and percentage of sympathetic fibers area (Asym %) was more in SBRN-1 when compared to RN and SBRN-2. These results of the study might help to explain sympathetic system-related diseases in the area of distribution of RN and SBRN.


Asunto(s)
Fibras Adrenérgicas , Antebrazo/inervación , Nervio Radial/anatomía & histología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad
11.
Rom J Morphol Embryol ; 51(4): 751-8, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-21103637

RESUMEN

PURPOSE: Age as poor prognostic factor following nerve repair may be due to change in intraneural anatomy with age. The purpose of this study is to find out the cross sectional microanatomy of the superficial branch of radial nerve (SBRN) at distal part of forearm for changes in the fascicular, non-fascicular components with respect to age and also to find cross section area of SBRN in healthy volunteers. MATERIAL AND METHODS: Sixty fresh human (37-88-year-old) cadaveric SBRN were collected from the distal part of forearm and studied at different magnifications after histological processing for morphometric analysis - total cross-sectional (Asc), fascicular (Af) and non-fascicular area (Anonf). Fifteen volunteers SBRN cross sectional area was measured by ultrasonography (US). RESULTS: The SBRN was found to have 6-12 fascicles. Morphometric and correlation analysis confirmed that there was a significant increase of total cross section area, with significant increase of interfascicular adipose tissue in relation to advancing age. Ultrasonographic cross-sectional area ranged from 2 to 3.3 mm². CONCLUSIONS: Our study revealed comparatively more adipose tissue in human SBRN with advancing age. These findings may help to explain poor prognosis with advancing age following repair. SBRN ultrasonographical Asc was comparable to histological Asc. Further, it is possible to find Asc of SBRN by non-invasive US study and calculate the fascicular and non-fascicular area using our histological findings.


Asunto(s)
Nervio Radial/anatomía & histología , Nervio Radial/diagnóstico por imagen , Tejido Adiposo/anatomía & histología , Tejido Adiposo/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento/patología , Cadáver , Disección , Femenino , Antebrazo/inervación , Humanos , Masculino , Persona de Mediana Edad , Nervio Radial/lesiones , Nervio Radial/cirugía , Coloración y Etiquetado , Ultrasonografía
12.
PLoS One ; 15(6): e0234638, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32569325

RESUMEN

Hematopoietic stem cell transplantation is successfully applied since the late 1950s; however, its efficacy still needs to be increased. A promising strategy is to transplant high numbers of pluripotent hematopoietic stem cells (HSCs). Therefore, an improved ex vivo culture system that supports proliferation and maintains HSC pluripotency would override possible limitations in cell numbers gained from donors. To model the natural HSC niche in vitro, we optimized the HSC medium composition with a panel of cytokines and valproic acid and used an artificial 3D bone marrow-like scaffold made of polydimethylsiloxane (PDMS). This 3D scaffold offered a suitable platform to amplify human HSCs in vitro and, simultaneously, to support their viability, multipotency and ability for self-renewal. Silicon oxide-covering of PDMS structures further improved amplification of CD34+ cells, although the conservation of naïve HSCs was better on non-covered 3D PDMS. Finally, we found that HSC cultivated on non-covered 3D PDMS generated most pluripotent colonies within colony forming unit assays. In conclusion, by combining biological and biotechnological approaches, we optimized in vitro HSCs culture conditions, resulting in improved amplification, multipotency maintenance and vitality of HSCs.


Asunto(s)
Materiales Biomiméticos/farmacología , Células Madre Hematopoyéticas/citología , Nicho de Células Madre , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Colágeno/farmacología , Dimetilpolisiloxanos/farmacología , Femenino , Fibronectinas/farmacología , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Masculino , Purinas/farmacología , Nicho de Células Madre/efectos de los fármacos , Ácido Valproico/farmacología
13.
Diabetes Obes Metab ; 11(12): 1122-30, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19930004

RESUMEN

AIM: This study evaluated changes in clinical effectiveness measures of patients with type 2 diabetes initiating exenatide therapy in a real-world setting. METHODS: Eligible patients identified in the General Electric (GE) electronic medical record (EMR) research database from 1 January 2000 through 31 December 2007 were > or =18 years old with type 2 diabetes. Patients had prescription orders in the previous 395 days for metformin, a sulfonylurea, or a thiazolidinedione as monotherapy or in combination, and had at least 6 months of follow-up activity. Baseline clinical measures were documented from 45 days prior up to 15 days after exenatide initiation and follow-up measures documented at 6 months +/- 45 days. RESULTS: A total of 1709 patients were identified for study inclusion. The overall mean A1C reduction (s.e.m.) at 6 months was -0.8% (0.05) (p<0.001), weight loss was -3.2 kg (0.14) (p<0.001), blood pressure (BP) lowering was -1.9 mmHg (0.46) systolic blood pressure (SBP) (p<0.001) and -0.5 mmHg (0.27) diastolic blood pressure (DBP) (p = 0.078). Changes in low-density lipoprotein (LDL), triglycerides and HDL were -7.4 mg/dl (1.7) (p<0.001), -23.2 mg/dl (6.7) (p = 0.001) and -0.8 mg/dl (0.33) (p = 0.012) respectively. In a quartile analysis by weight loss, mean A1C reduction ranged from -1.1 to -0.65% in the highest to lowest weight loss quartiles respectively. CONCLUSIONS: In a real-world setting, exenatide initiation is associated with significant improvements in the measures of clinical effectiveness for type 2 diabetes. These reductions were comparable to those reported in randomized, controlled registration trials after 6 months of therapy.


Asunto(s)
Peso Corporal/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Angiopatías Diabéticas/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Péptidos/uso terapéutico , Ponzoñas/uso terapéutico , Adulto , Anciano , Atención Ambulatoria , Diabetes Mellitus Tipo 2/sangre , Angiopatías Diabéticas/sangre , Angiopatías Diabéticas/prevención & control , Exenatida , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
14.
Surgeon ; 7(4): 243-9, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19736893

RESUMEN

The eLogbook is used to collect and collate the operative experience of every orthopaedic trainee in the UK and Ireland. We describe the project and discuss the national data now emerging on elective and trauma training.


Asunto(s)
Educación Médica/organización & administración , Sistemas en Línea , Procedimientos Ortopédicos/educación , Procedimientos Ortopédicos/estadística & datos numéricos , Ortopedia/educación , Traumatología/educación , Competencia Clínica/estadística & datos numéricos , Humanos , Irlanda , Reino Unido
15.
Sci Rep ; 9(1): 8106, 2019 05 30.
Artículo en Inglés | MEDLINE | ID: mdl-31147588

RESUMEN

Magnetic resonance (MR) T1 and T2* mapping allows quantification of liver relaxation times for non-invasive characterization of diffuse liver disease. We hypothesized that liver relaxation times are not only influenced by liver fibrosis, inflammation and fat, but also by air in liver segments adjacent to the lung - especially in MR imaging at 3T. A total of 161 study participants were recruited, while 6 patients had to be excluded due to claustrophobia or technically uninterpretable MR elastography. Resulting study population consisted of 12 healthy volunteers and 143 patients who prospectively underwent multiparametric MR imaging at 3T. Of those 143 patients, 79 had normal liver stiffness in MR elastography (shear modulus <2.8 kPa, indicating absence of fibrosis) and normal proton density fat fraction (PDFF < 10%, indicating absence of steatosis), defined as reference population. T1 relaxation times in these patients were significantly shorter in liver segments adjacent to the lung than in those not adjacent to the lung (p < 0.001, mean of differences 33 ms). In liver segments not adjacent to the lung, T1 allowed to differentiate significantly between the reference population and patients with steatosis and/or fibrosis (p ≤ 0.011), while there was no significant difference of T1 between the reference population and healthy volunteers. In conclusion, we propose to measure T1 relaxation times in liver segments not adjacent to the lung. Otherwise, we recommend taking into account slightly shorter T1 values in liver segments adjacent to the lung.


Asunto(s)
Hígado Graso/patología , Hepatopatías/patología , Hígado/patología , Imagen por Resonancia Magnética , Anciano , Hígado Graso/diagnóstico por imagen , Hígado Graso/metabolismo , Femenino , Humanos , Hígado/diagnóstico por imagen , Hepatopatías/diagnóstico por imagen , Hepatopatías/metabolismo , Pulmón/diagnóstico por imagen , Pulmón/metabolismo , Pulmón/patología , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Protones , Relajación/fisiología , Factores de Riesgo
16.
Diabetes Obes Metab ; 10(8): 638-45, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17645555

RESUMEN

OBJECTIVE: To quantify adverse events (AEs) associated with the use of metformin (MET), sulphonylureas (SUs) and thiazolidinediones (TZDs) in a usual care setting, and to assess the relationship of AEs to treatment patterns and glycaemic response in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: An electronic medical record database was used to identify patients with type 2 diabetes age >or=18 years from 1996 to 2005. Patients naïve to oral antidiabetic therapy were followed for 395 days postinitiation of MET, SU or TZD treatment. AEs related to study drugs were evaluated during the follow-up period. Baseline and follow-up A1C levels were compared by drug regimen. Associations between the change in A1C, drug regimen changes and AEs were evaluated. RESULTS: A total of 14,512 patients (mean age 60.8 years, 52.9% female) were identified. During the follow-up period, 12.7% of patients experienced an AE (8.6% MET, 15.9% SU and 19.8% TZD patients). SU and TZD patients were more likely to experience an AE than MET (p < 0.001) patients. AEs did not significantly influence A1C outcomes, although MET and SU patients experiencing an AE were more likely to add-on therapy (odds ratio (OR) = 1.34 and OR = 1.37, respectively; p < 0.05) than those without an AE. MET patients with AEs were more likely to switch therapy (OR = 1.91; p < 0.05) than those without an AE. CONCLUSIONS: The occurrence of AEs did not significantly impact glycaemic response to therapy. However, AEs may lead to greater treatment switches for patients receiving MET and add-on therapy for MET-treated and SU-treated patients.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hemoglobina Glucada/metabolismo , Hipoglucemiantes/administración & dosificación , Metformina/administración & dosificación , Compuestos de Sulfonilurea/administración & dosificación , Tiazolidinedionas/administración & dosificación , Administración Oral , Adolescente , Adulto , Femenino , Hemoglobina Glucada/efectos de los fármacos , Humanos , Hipoglucemiantes/efectos adversos , Masculino , Metformina/efectos adversos , Persona de Mediana Edad , Compuestos de Sulfonilurea/efectos adversos , Tiazolidinedionas/efectos adversos , Resultado del Tratamiento , Adulto Joven
17.
BJS Open ; 1(3): 67-74, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29951608

RESUMEN

BACKGROUND: The Intercollegiate Membership of the Royal College of Surgeons (MRCS) examination is undertaken by large numbers of trainees in the UK and internationally as a mandatory step within surgical training. Unlike some high-stakes medical examinations, the MRCS is yet to be validated. A quantitative study was undertaken to assess its predictive validity by investigating the relationship between MRCS (Parts A and B) and national selection interview scores for general and vascular surgery in the UK. METHODS: Pearson correlation coefficients were used to examine the linear relationship between each assessment, and linear regression analyses were employed to identify potential independent predictors of the national selection score. All UK medical graduates who attempted the interview in 2011-2015 were included. RESULTS: Some 84·4 per cent of the candidates (1231 of 1458) were matched with MRCS data. There was a significant positive correlation between the first attempt score at Part B of the MRCS examination and the national selection score (r = 0·38, P < 0·001). In multivariable analysis, 17 per cent of variance in the national selection first attempt score was explained by the Part B MRCS score and number of attempts (change in R 2 value of 0·10 and 0·07 respectively; P < 0·001). Candidates who required more than two attempts at Part B were predicted to score 8·1 per cent less than equally matched candidates who passed at their first attempt. CONCLUSION: This study supports validity of the MRCS examination, and indicates its predictive value regarding entry into specialist training.

18.
Schizophr Res ; 84(1): 165-9, 2006 May.
Artículo en Inglés | MEDLINE | ID: mdl-16567080

RESUMEN

The purpose of this study was to determine if patients with schizophrenia or schizoaffective disorders and comorbid posttraumatic stress disorder (PTSD) are at higher risk for suicidality than patients without comorbid PTSD. Participants were 165 male veterans with primary diagnoses of schizophrenia or schizoaffective disorder. Those with comorbid PTSD reported higher rates of suicidal ideation and suicidal behaviors compared to those without comorbid PTSD. These findings suggest that patients with comorbid PTSD are at higher risk for suicidality. Enhanced screening and targeted interventions may be warranted to address comorbid PTSD and increased suicide risk in this population.


Asunto(s)
Trastornos Psicóticos/epidemiología , Trastornos por Estrés Postraumático/epidemiología , Intento de Suicidio/estadística & datos numéricos , Veteranos/estadística & datos numéricos , Adulto , Comorbilidad , Demografía , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Humanos , Masculino , Trastornos Psicóticos/diagnóstico , Índice de Severidad de la Enfermedad , Trastornos por Estrés Postraumático/diagnóstico , Trastornos Relacionados con Sustancias/epidemiología
19.
Obes Sci Pract ; 2(2): 144-153, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-29071097

RESUMEN

OBJECTIVE: This study examined the link between worksite environmental supports for nutrition behaviours and sugar-sweetened beverage (SSB) consumption and offers insight into potential intervention points for reducing SSB consumption and combatting overweight and obesity. METHODS: Perceived worksite supports for healthy nutrition and self-reported SSB consumption were analysed for 2,015 working adults in the state of Missouri using a subset of questions from the Supports at Home and Work for Maintaining Energy Balance (SHOW-ME) study. RESULTS: Employees' use of vending facilities and the availability of water coolers/water bottles was significantly associated with increased SSB consumption, while use of cafeterias was significantly associated with decreased SSB consumption. Symbols or signs to identify healthy alternatives were significantly associated with sports drink consumption. CONCLUSIONS: This study supports previous work indicating the worksite as a necessary environment for nutrition interventions. When choices (vending and cafeteria) are provided, employees report making healthier decisions. For worksites without cafeterias, alternatives should be explored including mobile food trucks and farmer's markets.

20.
Rofo ; 188(9): 853-8, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27579680

RESUMEN

PURPOSE: To determine epicardial fat volume (EFV) and aortic stiffness (assessed by aortic pulse wave velocity (PWV)) in healthy individuals, and to investigate the relationship of these parameters, and their association with body mass index (BMI) and age. MATERIALS AND METHODS: 58 subjects (29 men, mean age 44.7 ± 13.9 years[y]) underwent a CMR exam at 1.5 Tesla. A 2 D velocity-encoded CMR scan was acquired to determine PWV. The EFV was measured based on a 3 D-mDixon sequence. Group comparisons were made between younger (age < 45y; n = 30; mean age 33.4 ±â€Š6.6y) and older (> 45y; n = 28; 56.7 ± 8.4y) subjects and between subjects with a BMI < 25 kg/m(2) (n = 28; BMI 21.9 ±â€Š2.5 kg/m(2)) and a BMI > 25 kg/m(2) (n = 30; 28.7 ±â€Š4.0 kg/m(2)). Associations between the determined parameters were assessed by analyses of covariance (ANCOVAs). RESULTS: The mean values of PWV and EFV (normalized to body surface area) were 6.9 ±â€Š1.9 m/s and 44.2 ±â€Š25.0 ml/m(2), respectively. The PWV and EFV were significantly higher in the older group (PWV = 7.9 ±â€Š2.0 m/s vs. 6.0 ±â€Š1.2 m/s; EFV = 54.7 ml/m² vs. 34.5 ml/m²; p < 0.01, each), with no significant differences in BMI or sex. In the overweighted group the EFV was significantly higher than in subjects with a BMI < 25 kg/m² (EFV = 56.1 ±â€Š27.1 ml/m(2) vs. 31.5 ±â€Š14.6 ml/m(2); p < 0.01) but without a significant difference in PWV. ANCOVA revealed a significant correlation between EFV and PWV, also after adjustment for age (p = 0.025). CONCLUSION: An association was found between age and EFV as well as PWV. EFV and PWV were related to each other also after adjustment for age. The metabolic and pro-inflammatory activity found with increased epicardial fat volume may promote the development of atherosclerosis and aortic stiffness. CMR may be valuable for future studies investigating the relationship between EFV and PWV in patients with increased cardiovascular risk. KEY POINTS: • EFV and PWV can be assessed in a single CMR exam.• EFV and aortic stiffness are both associated with cardiovascular risk.• EFV correlates with aortic stiffness, possibly due to similar pro-inflammatory mechanisms. Citation Format: • Homsi R, Thomas D, Gieseke J et al. Epicardial Fat Volume and Aortic Stiffness in Healthy Individuals: A Quantitative Cardiac Magnetic Resonance Study. Fortschr Röntgenstr 2016; 188: 853 - 858.


Asunto(s)
Tejido Adiposo/fisiología , Envejecimiento/fisiología , Aorta/fisiología , Imagen por Resonancia Magnética/métodos , Pericardio/fisiología , Rigidez Vascular/fisiología , Tejido Adiposo/diagnóstico por imagen , Adiposidad/fisiología , Adulto , Aorta/diagnóstico por imagen , Índice de Masa Corporal , Simulación por Computador , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Masculino , Modelos Cardiovasculares , Pericardio/diagnóstico por imagen , Valores de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
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