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1.
Artículo en Inglés | MEDLINE | ID: mdl-39038562

RESUMEN

INTRODUCTION: Early substitution of calcineurin inhibitor (CNI) with mammalian target of rapamycin inhibitors has been shown to improve kidney function and reduce intimal hyperplasia in heart transplant (HTx) recipients but data on long-term outcome of such a regime are still sparse. METHODS: In the SCHEDULE trial, 115 de novo HTx recipients were randomized to a) everolimus with reduced exposure of CNI followed by CNI withdrawal at week 7-11 post-transplant or b) standard-exposure with CNI. Both groups received mycophenolate mofetil and corticosteroids. Herein we report on the 10-12 year long-term follow-up of the study. RESULTS: A total of 78 patients attended the follow-up visit at a median time of 11 years post-transplant. In the everolimus intention to treat (ITT) group 87.5% (35/40 patients) still received everolimus and in the CNI ITT group 86.8 % (33/38) still received CNI. Estimated glomerular filtration rate (eGFR) (least square mean (95% CI)) at the 10-12 years visit was 82.7 (74.2-91.1) ml/min/1.73m2 and 61.0 (52.3-69.7) ml/min/1.73m2 in the everolimus and CNI group, respectively (p<0.001). Graft function measured by ejection fraction, ECG, NT-proBNP and drug safety were comparable between groups. During the study period there was a total of 28 deaths, but there was no difference in survival between the everolimus and the CNI group (aHR 0.61 (95% CI 0.29-1.30) p=0.20). For the composite endpoint of death, re-transplantation, myocardial infarction, PCI, dialysis, kidney transplantation or cancer no between group differences were found (aHR 1.0 (95% CI 0.57-1.77) p=0.99). CONCLUSIONS: De novo HTx patients randomized to everolimus and low dose CNI followed by CNI free therapy sustained significantly better long-term kidney function than patients randomized to standard therapy. The graft function at 10-12 years was similar in both groups and there was no difference in survival.

2.
Sci Rep ; 14(1): 10807, 2024 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-38734730

RESUMEN

This study assessed the association between arthritis, functional impairment, and nutritional risk (NR). Cross-sectional data were from the Canadian Longitudinal Study on Aging, a nationally representative sample of 45-85-year-old community-dwelling Canadians (n = 41,153). The abbreviated Seniors in the Community: Risk Evaluating for Eating and Nutrition II (SCREEN II-AB) Questionnaire determined NR scores (continuous), and high NR (score < 38); the Older American Resources and Services scale measured functional impairment. NR scores and status (low/high) were modelled using multiple linear and logistic regressions, respectively. Analyses adjusted for demographic characteristics, functional impairment, and health (body mass index, self-rated general and mental health). Additional analyses stratified the models by functional impairment. People with arthritis had poorer NR scores (B: - 0.35, CI - 0.48, - 0.22; p < 0.05) and increased risks of high NR (OR 1.11, 95% CI 1.06, 1.17). Among those with functional impairment, the likelihood of high NR was 31% higher in people with arthritis compared to those without arthritis (95% CI 1.12, 1.53). Among those with no functional impairment, the likelihood of high NR was 10% higher in people with arthritis compared to those without (95% CI 1.04, 1.16). These relationships differed based on the type of arthritis. Arthritis is associated with high NR in community-dwelling older adults, both with and without functional impairment. Findings highlight the need for further research on these relationships to inform interventions and improve clinical practices.


Asunto(s)
Artritis , Estado Nutricional , Humanos , Canadá/epidemiología , Anciano , Femenino , Masculino , Estudios Longitudinales , Artritis/epidemiología , Anciano de 80 o más Años , Persona de Mediana Edad , Envejecimiento , Estudios Transversales , Factores de Riesgo , Encuestas y Cuestionarios
3.
PeerJ ; 11: e16146, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38025759

RESUMEN

The Minnesota Bee Atlas project contributed new information about bee distributions, phenologies, and community structure by mobilizing participatory science volunteers to document bees statewide. Volunteers submitted iNaturalist (©2016 California Academy of Sciences) photograph observations, monitored nest-traps for tunnel-nesting bees, and conducted roadside observational bumble bee surveys. By pairing research scientists and participatory science volunteers, we overcame geographic and temporal challenges to document the presence, phenologies, and abundances of species. Minnesota Bee Atlas project observations included new state records for Megachile inimica, Megachile frugalis, Megachile sculpturalis, Osmia georgica, Stelis permaculata, and Bombus nevadensis, nesting phenology for 17 species, a new documentation of bivoltinism for Megachile relativa in Minnesota, and over 500 observations of the endangered species Bombus affinis. We also expanded known ranges for 16 bee species compared with specimens available from the University of Minnesota (UMN) Insect Collection. Surveys with standardized effort across the state found ecological province associations for six tunnel-nesting species and lower bumble bee abundance in the Prairie Parkland ecological province than the Laurentian Mixed Forest or Eastern Broadleaf Forest ecological provinces, indicating potential benefit of a focus on bumble bee habitat management in the Prairie Parkland. Landcover analysis found associations for four tunnel-nesting species, as well as a possible association of B. affinis with developed areas. These data can inform management decisions affecting pollinator conservation and recovery of endangered species. By engaging over 2,500 project volunteers and other iNaturalist users, we also promoted conservation action for pollinators through our educational programs and interactions.


Asunto(s)
Ecosistema , Bosques , Humanos , Abejas , Animales , Minnesota , Especies en Peligro de Extinción
4.
BMC Nephrol ; 24(1): 254, 2023 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-37626301

RESUMEN

BACKGROUND: Diabetes mellitus (DM), either preexisting or developing after transplantation, remains a crucial clinical problem in kidney transplantation. To obtain insights into the molecular mechanisms underlying PTDM development and early glomerular damage before the development of histologically visible diabetic kidney disease, we comparatively analysed the proteome of histologically normal glomeruli from patients with PTDM and normoglycaemic (NG) transplant recipients. Moreover, to assess specificities inherent in PTDM, we also comparatively evaluated glomerular proteomes from transplant recipients with preexisting type 2 DM (T2DM). METHODS: Protocol biopsies were obtained from adult NG, PTDM and T2DM patients one year after kidney transplantation. Biopsies were formalin-fixed and embedded in paraffin, and glomerular cross-sections were microdissected. A total of 4 NG, 7 PTDM and 6 T2DM kidney biopsies were used for the analysis. The proteome was determined by liquid chromatography-tandem mass spectrometry. Relative differences in protein abundance and significantly dysregulated pathways were analysed. RESULTS: Proteins involved in cell adhesion, immune response, leukocyte transendothelial filtration, and cell localization and organization were less abundant in glomeruli from PTDM patients than in those from NG patients, and proteins associated with supramolecular fibre organization and protein-containing complex binding were more abundant in PTDM patients. Overall, proteins related to adherens and tight junctions and those related to the immune system, including leukocyte transendothelial migration, were more abundant in NG patients than in transplanted patients with DM, irrespective of the timing of its development. However, proteins included in cell‒cell junctions and adhesion, insulin resistance, and vesicle-mediated transport were all less abundant in PTDM patients than in T2DM patients. CONCLUSIONS: The glomerular proteome profile differentiates PTDM from NG and T2DM, suggesting specific pathogenetic mechanisms. Further studies are warranted to validate these results, potentially leading to an improved understanding of PTDM kidney transplant pathophysiology and to the identification of novel biomarkers.


Asunto(s)
Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Trasplante de Riñón , Adulto , Humanos , Proteoma , Proteómica , Riñón , Aloinjertos
5.
Anal Chem ; 95(35): 13046-13054, 2023 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-37612789

RESUMEN

Polymer nanoparticles are widely used in drug delivery and are also a potential concern due to the increased burden of nano- or microplastics in the environment. In order to use polymer nanoparticles safely and understand their mechanism of action, it is useful to know where within cells and tissues they end up. To this end, we labeled polymer nanoparticles with nanodiamond particles. More specifically, we have embedded nanodiamond particles in the polymer particles and characterized the composites. Compared to conventional fluorescent dyes, these labels have the advantage that nanodiamonds do not bleach or blink, thus allowing long-term imaging and tracking of polymer particles. We have demonstrated this principle both in cells and entire liver tissues.


Asunto(s)
Nanodiamantes , Plásticos , Colorantes Fluorescentes , Sistemas de Liberación de Medicamentos , Polímeros
6.
Infancy ; 28(4): 836-860, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37194939

RESUMEN

Infants vary in their ability to follow others' gazes, but it is unclear how these individual differences emerge. We tested whether social motivation levels in early infancy predict later gaze following skills. We longitudinally tracked infants' (N = 82) gazes and pupil dilation while they observed videos of a woman looking into the camera simulating eye contact (i.e., mutual gaze) and then gazing toward one of two objects, at 2, 4, 6, 8, and 14 months of age. To improve measurement validity, we used confirmatory factor analysis to combine multiple observed measures to index the underlying constructs of social motivation and gaze following. Infants' social motivation-indexed by their speed of social orienting, duration of mutual gaze, and degree of pupil dilation during mutual gaze-was developmentally stable and positively predicted the development of gaze following-indexed by their proportion of time looking to the target object, first object look difference scores, and first face-to-object saccade difference scores-from 6 to 14 months of age. These findings suggest that infants' social motivation likely plays a role in the development of gaze following and highlight the use of a multi-measure approach to improve measurement sensitivity and validity in infancy research.


Asunto(s)
Fijación Ocular , Motivación , Femenino , Humanos , Lactante
7.
Molecules ; 28(8)2023 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-37110781

RESUMEN

Crescentia cujete is widely known as a medical plant with broad indigenous ethnomedicinal uses, including anti-inflammatory, and antioxidant. Despite being used for remedies and ethnomedicinal purposes, the benefits obtained from C. cujete still need to be fully utilized. The underwhelming studies on its pharmacological potential, bioactive compounds, and mechanism of action keep the pharmacological and new drug discovery progress of this plant slow. This study focuses on the incorporation of in silico analyses such as ADME prediction and molecular docking simulations on the bioactive compounds identified in the plant to assess their potential for antioxidant and anti-inflammatory applications. A comparison of the ADME properties and molecular docking scores showed that naringenin, pinocembrin, and eriodictyol had the most potential to act as inhibitors of the target proteins involved in inflammation and oxidation pathways against the positive controls.


Asunto(s)
Antiinflamatorios , Antioxidantes , Humanos , Antioxidantes/farmacología , Simulación del Acoplamiento Molecular , Oxidación-Reducción , Antiinflamatorios/farmacología , Inflamación/tratamiento farmacológico , Extractos Vegetales/farmacología
8.
Proc Natl Acad Sci U S A ; 119(40): e2209471119, 2022 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-36161922

RESUMEN

The transmission of chromatin states from parent cells to daughter cells preserves cell-specific transcriptional states and thus cell identity through cell division. The mechanism that underpins this process is not fully understood. The role that chromatin states serve in transmitting gene expression information across generations via sperm and oocytes is even less understood. Here, we utilized a model in which Caenorhabditis elegans sperm and oocyte alleles were inherited in different states of the repressive mark H3K27me3. This resulted in the alleles achieving different transcriptional states within the nuclei of offspring. Using this model, we showed that sperm alleles inherited without H3K27me3 were sensitive to up-regulation in offspring somatic and germline tissues, and tissue context determined which genes were up-regulated. We found that the subset of sperm alleles that were up-regulated in offspring germlines retained the H3K27me3(-) state and were transmitted to grandoffspring as H3K27me3(-) and up-regulated epialleles, demonstrating that H3K27me3 can serve as a transgenerational epigenetic carrier in C. elegans.


Asunto(s)
Alelos , Caenorhabditis elegans , Epigénesis Genética , Histonas , Espermatozoides , Animales , Caenorhabditis elegans/genética , Cromatina/metabolismo , Histonas/genética , Masculino , Oocitos/metabolismo , Semen/metabolismo , Espermatozoides/metabolismo
9.
Redox Biol ; 52: 102279, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35349928

RESUMEN

Although viruses are known to modify the free radical concentration in infected cells, the exact location and concentrations of such changes remain unknown. Although this information is important to understand the virus pathogenesis and design better anti-viral drugs or vaccines, obtaining it with the conventional free radical/ROS detection techniques is impossible. Here, we elucidate the utility of diamond magnetometry for studying the free radical response of baby hamster kidney-21 cells upon Semliki Forest virus infection. Specifically, we optically probe the alterations in free radical concentration near infectious viruses via measuring the spin-lattice relaxation (T1) of NV defect ensembles embedded in intracellular nanodiamonds. We performed measurements both at random locations as well as close to the virus entry by conjugating viruses to nanodiamond sensors. We observed alterations of T1, which represent the intracellular free radical concentration during the viral replication process. Moreover, relaxometry is also used to monitor real-time free radical variation during the early infectious process.


Asunto(s)
Nanodiamantes , Virosis , Diamante , Radicales Libres , Humanos
10.
Cell Rep ; 30(13): 4321-4331.e4, 2020 03 31.
Artículo en Inglés | MEDLINE | ID: mdl-32234470

RESUMEN

Cellular translation surveillance rescues ribosomes that stall on problematic mRNAs. During translation surveillance, endonucleolytic cleavage of the problematic mRNA is a critical step in rescuing stalled ribosomes. Here we identify NONU-1 as a factor required for translation surveillance pathways including no-go and nonstop mRNA decay. We show that (1) NONU-1 reduces nonstop and no-go mRNA levels; (2) NONU-1 contains an Smr RNase domain required for mRNA decay; (3) the domain architecture and catalytic residues of NONU-1 are conserved throughout metazoans and eukaryotes, respectively; and (4) NONU-1 is required for the formation of mRNA cleavage fragments in the vicinity of stalled ribosomes. We extend our results in C. elegans to homologous factors in S. cerevisiae, showing the evolutionarily conserved function of NONU-1. Our work establishes the identity of a factor critical to translation surveillance and will inform mechanistic studies at the intersection of translation and mRNA decay.


Asunto(s)
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Secuencia Conservada , Endonucleasas/metabolismo , Biosíntesis de Proteínas , Secuencia de Aminoácidos , Animales , Biocatálisis , Evolución Molecular , Dominios Proteicos , Estabilidad del ARN , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ribosomas/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo
11.
Sci Rep ; 9(1): 12483, 2019 08 28.
Artículo en Inglés | MEDLINE | ID: mdl-31462719

RESUMEN

The response of the major salivary glands, the parotid glands, to radiation dose is patient-specific. This study was designed to investigate whether parotid gland changes seen in weekly CT during treatment, quantified by delta-radiomics features (Δfeatures), could improve the prediction of moderate-to-severe xerostomia at 12 months after radiotherapy (Xer12m). Parotid gland Δfeatures were extracted from in total 68 planning and 340 weekly CTs, representing geometric, intensity and texture characteristics. Bootstrapped forward variable selection was performed to identify the best predictors of Xer12m. The predictive contribution of the resulting Δfeatures to a pre-treatment reference model, based on contralateral parotid gland mean dose and baseline xerostomia scores (Xerbaseline) only, was evaluated. Xer12m was reported by 26 (38%) of the 68 patients included. The most predictive Δfeature was the contralateral parotid gland surface change, which was significantly associated with Xer12m for all weeks (p < 0.04), but performed best for week 3 (ΔPG-surfacew3; p < 0.001). Moreover, ∆PG-surfacew3 showed a significant predictive contribution in addition to the pre-treatment reference model (likelihood-ratio test; p = 0.003), resulting in a significantly better model performance (AUCtrain = 0.92; AUCtest = 0.93) compared to that of the pre-treatment model (AUCtrain = 0.82; AUCtest = 0.82). These results suggest that mid-treatment parotid gland changes substantially improve the prediction of late radiation-induced xerostomia.


Asunto(s)
Neoplasias de Cabeza y Cuello , Glándula Parótida/diagnóstico por imagen , Traumatismos por Radiación/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Xerostomía , Adolescente , Adulto , Anciano , Femenino , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Dosificación Radioterapéutica , Xerostomía/diagnóstico por imagen , Xerostomía/etiología
12.
J Nutr Educ Behav ; 51(9): 1058-1066, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31399331

RESUMEN

OBJECTIVE: To describe the impact of arthritis-related disability on aspects of food insecurity and to gain insight into the incentives and barriers to participating in a nutrition intervention. DESIGN: Four focus groups were held in April to May, 2018. Participants completed questionnaires about socioeconomic status, diet, and health. SETTING: The Perform Centre, Concordia University, Montreal, Canada. PARTICIPANTS: A convenience sample of 27 adults diagnosed with arthritis. PHENOMENON OF INTEREST: Perceived impact of arthritis-related disability on food behaviors as well as incentives and deterrents to participating in a nutrition intervention. ANALYSIS: Transcriptions of the focus group discussions were coded using the constant comparative method. Basic descriptive statistics were used to analyze the questionnaire data. RESULTS: The themes of pain, fatigue, knowledge, and social support emerged in discussions on food choices, procurement, preparation, consumption, and other lifestyle behaviors. Participants reported common barriers, although the extent to which they were affected varied. Questionnaire results revealed low disability. Timing, cost, and information quality were important incentives to participate in a nutrition intervention. CONCLUSIONS AND IMPLICATIONS: Results highlight the need for further research among people with greater limitations related to arthritis and adapted nutrition interventions that provide both knowledge and experience to help individuals overcome the challenges of arthritis.


Asunto(s)
Artritis , Personas con Discapacidad/psicología , Conducta Alimentaria/fisiología , Abastecimiento de Alimentos , Promoción de la Salud/métodos , Adulto , Anciano , Artritis/fisiopatología , Artritis/psicología , Dieta Saludable , Femenino , Grupos Focales , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Motivación , Quebec
13.
Inflamm Bowel Dis ; 25(12): 1945-1956, 2019 11 14.
Artículo en Inglés | MEDLINE | ID: mdl-31050763

RESUMEN

BACKGROUND: Anxiety and depressive symptoms are prevalent in patients with inflammatory bowel disease (IBD) and may negatively influence disease course. Disease activity could be affected positively by treatment of psychological symptoms. We investigated the effect of cognitive behavioral therapy (CBT) on clinical disease course in 10-25-year-old IBD patients experiencing subclinical anxiety and/or depression. METHODS: In this multicenter parallel group randomized controlled trial, IBD patients were randomized to disease-specific CBT in addition to standard medical care (CBT + care us usual [CAU]) or CAU only. The primary outcome was time to first relapse in the first 12 months. Secondary outcomes were clinical disease activity, fecal calprotectin, and C-reactive protein (CRP). Survival analyses and linear mixed models were performed to compare groups. RESULTS: Seventy patients were randomized (CBT+CAU = 37, CAU = 33), with a mean age of 18.3 years (±50% < 18 y, 31.4% male, 51.4% Crohn's disease, 93% in remission). Time to first relapse did not differ between patients in the CBT+CAU group vs the CAU group (n = 65, P = 0.915). Furthermore, clinical disease activity, fecal calprotectin, and CRP did not significantly change over time between/within both groups. Exploratory analyses in 10-18-year-old patients showed a 9% increase per month of fecal calprotectin and a 7% increase per month of serum CRP in the CAU group, which was not seen in the CAU+CBT group. CONCLUSIONS: CBT did not influence time to relapse in young IBD patients with subclinical anxiety and/or depression. However, exploratory analyses may suggest a beneficial effect of CBT on inflammatory markers in children.


Asunto(s)
Ansiedad/terapia , Terapia Cognitivo-Conductual , Depresión/terapia , Enfermedades Inflamatorias del Intestino/psicología , Calidad de Vida/psicología , Adolescente , Ansiedad/complicaciones , Proteína C-Reactiva/metabolismo , Depresión/complicaciones , Progresión de la Enfermedad , Heces/química , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Complejo de Antígeno L1 de Leucocito/análisis , Modelos Lineales , Masculino , Países Bajos , Escalas de Valoración Psiquiátrica , Recurrencia , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto Joven
14.
Genetics ; 212(1): 125-140, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30910798

RESUMEN

Repression of germline-promoting genes in somatic cells is critical for somatic development and function. To study how germline genes are repressed in somatic tissues, we analyzed key histone modifications in three Caenorhabditis elegans synMuv B mutants, lin-15B, lin-35, and lin-37-all of which display ectopic expression of germline genes in the soma. LIN-35 and LIN-37 are members of the conserved DREAM complex. LIN-15B has been proposed to work with the DREAM complex but has not been shown biochemically to be a member of the complex. We found that, in wild-type worms, synMuv B target genes and germline genes are enriched for the repressive histone modification dimethylation of histone H3 on lysine 9 (H3K9me2) at their promoters. Genes with H3K9me2 promoter localization are evenly distributed across the autosomes, not biased toward autosomal arms, as are the broad H3K9me2 domains. Both synMuv B targets and germline genes display a dramatic reduction of H3K9me2 promoter localization in lin-15B mutants, but much weaker reduction in lin-35 and lin-37 mutants. This difference between lin-15B and DREAM complex mutants likely represents a difference in molecular function for these synMuv B proteins. In support of the pivotal role of H3K9me2 in regulation of germline genes by LIN-15B, global loss of H3K9me2 but not H3K9me3 results in phenotypes similar to synMuv B mutants, high-temperature larval arrest, and ectopic expression of germline genes in the soma. We propose that LIN-15B-driven enrichment of H3K9me2 at promoters of germline genes contributes to repression of those genes in somatic tissues.


Asunto(s)
Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/genética , Regulación del Desarrollo de la Expresión Génica , Histonas/metabolismo , Regiones Promotoras Genéticas , Procesamiento Proteico-Postraduccional , Animales , Caenorhabditis elegans/metabolismo , Células Germinativas , Metilación
15.
Nat Commun ; 9(1): 4310, 2018 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-30333496

RESUMEN

Paternal contributions to epigenetic inheritance are not well understood. Paternal contributions via marked nucleosomes are particularly understudied, in part because sperm in some organisms replace the majority of nucleosome packaging with protamine packaging. Here we report that in Caenorhabditis elegans sperm, the genome is packaged in nucleosomes and carries a histone-based epigenetic memory of genes expressed during spermatogenesis, which unexpectedly include genes well known for their expression during oogenesis. In sperm, genes with spermatogenesis-restricted expression are uniquely marked with both active and repressive marks, which may reflect a sperm-specific chromatin signature. We further demonstrate that epigenetic information provided by sperm is important and in fact sufficient to guide proper germ cell development in offspring. This study establishes one mode of paternal epigenetic inheritance and offers a potential mechanism for how the life experiences of fathers may impact the development and health of their descendants.


Asunto(s)
Caenorhabditis elegans/metabolismo , Epigénesis Genética , Histonas/metabolismo , Nucleosomas/metabolismo , Espermatozoides/metabolismo , Animales , Caenorhabditis elegans/crecimiento & desarrollo , Fertilidad , Masculino , Oogénesis , Espermatogénesis
16.
J Pediatr Psychol ; 43(9): 967-980, 2018 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-29850915

RESUMEN

Objective: To evaluate the effectiveness of a disease-specific cognitive behavioral therapy (CBT) protocol on anxiety and depressive symptoms and health-related quality of life (HRQOL) in adolescents and young adults with inflammatory bowel disease (IBD). Method: A parallel group randomized controlled trial was conducted in 6 centers of (pediatric) gastroenterology. Included were 70 patients and young adults (10-25 years) with IBD and subclinical anxiety and/or depressive symptoms. Patients were randomized into 2 groups, stratified by center: (a) standard medical care (care-as-usual [CAU]) plus disease-specific manualized CBT (Primary and Secondary Control Enhancement Training for Physical Illness; PASCET-PI), with 10 weekly sessions, 3 parent sessions, and 3 booster sessions (n = 37), or (b) CAU only (n = 33). Primary analysis concerned the reliable change in anxiety and depressive symptoms after 3 months (immediate posttreatment assessment). Exploratory analyses concerned (1) the course of anxiety and depressive symptoms and HRQOL in subgroups based on age, and (2) the influence of age, gender, and disease type on the effect of the PASCET-PI. Results: Overall, all participants improved significantly in their anxiety and depressive symptoms and HRQOL, regardless of group, age, gender, and disease type. Primary chi-square tests and exploratory linear mixed models showed no difference in outcomes between the PASCET-PI (n = 35) and the CAU group (n = 33). Conclusions: In youth with IBD and subclinical anxiety and/or depressive symptoms, preliminary results of immediate post-treatment assessment indicated that a disease-specific CBT added to standard medical care did not perform better than standard medical care in improving psychological symptoms or HRQOL. ClinicalTrials.gov: NCT02265588.


Asunto(s)
Trastornos de Ansiedad/terapia , Terapia Cognitivo-Conductual/métodos , Trastorno Depresivo/terapia , Enfermedades Inflamatorias del Intestino/psicología , Calidad de Vida/psicología , Adolescente , Adulto , Trastornos de Ansiedad/complicaciones , Niño , Trastorno Depresivo/complicaciones , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Masculino , Resultado del Tratamiento , Adulto Joven
17.
Diabetes Care ; 39(4): 617-24, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26908914

RESUMEN

OBJECTIVE: Development of posttransplantation diabetes (PTDM) is characterized by reduced insulin secretion and sensitivity. We aimed to investigate whether hyperglucagonemia could play a role in PTDM and to examine the insulinotropic and glucagonostatic effects of the incretin hormone glucagon-like peptide 1 (GLP-1) during fasting and hyperglycemic conditions, respectively. RESEARCH DESIGN AND METHODS: Renal transplant recipients with (n = 12) and without (n = 12) PTDM underwent two separate experimental days with 3-h intravenous infusions of GLP-1 (0.8 pmol/kg/min) and saline, respectively. After 1 h of infusion, a 2-h hyperglycemic clamp (fasting plasma glucose + 5 mmol/L) was established. Five grams of arginine was given as an intravenous bolus 10 min before termination of the clamp. RESULTS: Fasting concentrations of glucagon (P = 0.92) and insulin (P = 0.23) were similar between the groups. In PTDM patients, glucose-induced glucagon suppression was significantly less pronounced (maximal suppression from baseline: 43 ± 12 vs. 65 ± 12%, P < 0.001), while first- and second-phase insulin secretion were significantly lower. The PTDM group also exhibited a significantly lower insulin response to arginine (P = 0.01) but similar glucagon and proinsulin responses compared with control subjects. In the preclamp phase, GLP-1 lowered fasting plasma glucose to the same extent in both groups but reduced glucagon only in PTDM patients. During hyperglycemic clamp, GLP-1 reduced glucagon concentrations and increased first- and second-phase insulin secretion in both groups. CONCLUSIONS: PTDM is characterized by reduced glucose-induced insulin secretion and attenuated glucagon suppression during a hyperglycemic clamp. Similar to the case in type 2 diabetes, GLP-1 infusion seems to improve (insulin) or even normalize (glucagon) these pathophysiological defects.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptido 1 Similar al Glucagón/administración & dosificación , Glucagón/metabolismo , Insulina/metabolismo , Trasplante de Riñón , Adulto , Anciano , Glucemia/metabolismo , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/sangre , Femenino , Glucagón/sangre , Péptido 1 Similar al Glucagón/sangre , Hemoglobina Glucada/metabolismo , Humanos , Incretinas/sangre , Infusiones Intravenosas , Insulina/sangre , Secreción de Insulina , Masculino , Persona de Mediana Edad , Proinsulina/sangre
18.
Mol Genet Genomics ; 290(3): 1169-80, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25663138

RESUMEN

Single-nucleotide polymorphisms, which can be identified in the thousands or millions from comparisons of transcriptome or genome sequences, are ideally suited for making high-resolution genetic maps, investigating population evolutionary history, and discovering marker-trait linkages. Despite significant results from their use in human genetics, progress in identification and use in plants, and particularly polyploid plants, has lagged. As part of a long-term project to identify and use SNPs suitable for these purposes in cultivated peanut, which is tetraploid, we generated transcriptome sequences of four peanut cultivars, namely OLin, New Mexico Valencia C, Tamrun OL07 and Jupiter, which represent the four major market classes of peanut grown in the world, and which are important economically to the US southwest peanut growing region. CopyDNA libraries of each genotype were used to generate 2 × 54 paired-end reads using an Illumina GAIIx sequencer. Raw reads were mapped to a custom reference consisting of Tifrunner 454 sequences plus peanut ESTs in GenBank, compromising 43,108 contigs; 263,840 SNP and indel variants were identified among four genotypes compared to the reference. A subset of 6 variants was assayed across 24 genotypes representing four market types using KASP chemistry to assess the criteria for SNP selection. Results demonstrated that transcriptome sequencing can identify SNPs usable as selectable DNA-based markers in complex polyploid species such as peanut. Criteria for effective use of SNPs as markers are discussed in this context.


Asunto(s)
Arachis/genética , Genoma de Planta/genética , Polimorfismo de Nucleótido Simple/genética , Transcriptoma , Arachis/clasificación , Secuencia de Bases , Ligamiento Genético , Marcadores Genéticos/genética , Genotipo , Secuenciación de Nucleótidos de Alto Rendimiento , Mutación INDEL , ARN de Planta/química , ARN de Planta/aislamiento & purificación , Análisis de Secuencia de ADN , Sudoeste de Estados Unidos , Tetraploidía
19.
BMC Med Educ ; 14: 211, 2014 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-25280918

RESUMEN

BACKGROUND: In a professional learner-centered(ness) educational environment, communication and alignment of expectations about teaching are indispensable. Professional education of residents could benefit from an analysis and comparison of teachers' and residents' educational expectations and beliefs. Our purpose is to identify success factors and barriers related to aligning expectations and beliefs and building a supportive professional learner-centered educational environment. METHODS: We conducted semi-structured individual interviews with teachers and semi-structured focus groups with residents. A single interview format was used to make it possible to compare the results. Data were analysed using a qualitative software package (AtlasTi). Data analysis steps were followed by the author team, which identified four domains of good teaching: personal traits, knowledge, relationships and teaching qualities. RESULTS: Teachers and residents agreed about the importance of personal professional characteristics like being a role model and having an open and enthusiastic attitude. They all thought that having a specific knowledge base was essential for teaching. Approaching residents as adult learners was found to be an important element of the learner-centred environment and it was agreed that teachers should take practical experiences to a higher level. However, teachers and residents had different expectations about the practical consequences of being a role model, adult learning, coaching and openness, and the type of knowledge that was needed in the professional development program. Communication about different expectations appeared to be difficult. CONCLUSIONS: Teachers and residents agreed on a conceptual level about expectations and beliefs regarding good teaching, but disagreed on an executive level. According to the residents, the disagreement about good teaching was not the biggest barrier to creating alignment and a supportive professional relationship; instead, it was the absence of a proper dialogue regarding issues about expectations and beliefs.


Asunto(s)
Actitud del Personal de Salud , Comunicación , Cultura , Educación de Postgrado en Medicina , Medicina General/educación , Internado y Residencia , Adulto , Docentes Médicos , Femenino , Humanos , Capacitación en Servicio , Masculino , Países Bajos , Investigación Cualitativa , Enseñanza/normas
20.
Clin Transplant ; 28(10): 1167-76, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25124959

RESUMEN

UNLABELLED: Uric acid is associated with increased mortality in kidney transplant recipients (KTRs), but it is uncertain if this involves endothelial dysfunction. We hypothesized, first, that there was an association between uric acid and endothelial function, and second, that there were associations between endothelial function and cardiac and mortality risk scores. METHODS: One hundred and fifty-two patients were examined 10 wk after kidney transplantation by two measures of endothelial function, the brachial artery flow-mediated dilatation (FMD) expressed as percent dilatation (FMD%), and fingertip peripheral arterial tone (PAT) expressed as log-reactive hyperemia index (LnRHI). Risk scores were calculated from a recently validated formula. Other clinical correlates of endothelial function were described in stepwise linear regression models. RESULTS: Uric acid was associated negatively with FMD% in an age- and gender-adjusted model, while not in the multivariable model. No association was shown between uric acid and LnRHI. FMD% was associated negatively with risk scores in both crude and age- and gender-adjusted models (p < 0.01). LnRHI was associated negatively with risk scores in the latter model only (p < 0.05). CONCLUSIONS: Uric acid was neither associated with FMD% nor LnRHI in KTRs. There were significant associations between endothelial function indices and cardiac and mortality risk scores.


Asunto(s)
Endotelio Vascular/patología , Rechazo de Injerto/diagnóstico , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Ácido Úrico/sangre , Enfermedades Vasculares/diagnóstico , Estudios Transversales , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/sangre , Rechazo de Injerto/etiología , Supervivencia de Injerto , Humanos , Fallo Renal Crónico/sangre , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Pronóstico , Factores de Riesgo , Enfermedades Vasculares/sangre , Enfermedades Vasculares/etiología
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