126 research outputs found

    Suplementación dietética con aguas residuales de una fábrica productora de caramelo y su efecto sobre el crecimiento de cerdos destetados y componentes del eje de factores de crecimiento semejantes a insulina

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    An experiment was conducted to evaluate the expression of insulin-like growth factor-I (IGF-I) and IGF-binding proteins (IGFBPs -II and -III) in response to a 10% inclusion of caramel plant wastewater (CPWW) in weaning pig diets; the objective was to assess associations between those growthrelated proteins to feed intake (Fl) and body weight gain (BWG). Sixteen purebred Landrace piglets were randomly distributed among eight pens (a gilt and boar per pen) and assigned to one of two treatments: 0% (control) and 10% inclusion of CPWW. During four consecutive weeks, live weight and Fl were recorded. Blood samples were drawn by jugular venipuncture during the first, second, and third weeks of the experiment and serum levels of IGF-I, IGFBP-II and IGFBP-III were determined. Feed intake, BWG and feed efficiency (FE) were not affected (P > 0.05) by the addition of 10% CPWW tothe diet, nor was animal health status visibly affected. Serum IGF-I levels were higher in control animals (P < 0.05) and increased from d 14 to d 28 of the experimental period (P < 0.05). Weekly increases were observed for IGFBP- III (P < 0.05) whereas IGFBP-II circulating levels decreased from d 14 to d 28 of the post-weaning test period. Simple correlation analysis revealed that there was a positive association between circulating levels of IGF-I and IGFBP-III (r = 0.88; P < 0.0001). However, the opposite was observed between these two and IGFBP-II (r = -0.84, P < 0.0001; r = -0.67, P < 0.0025, respectively). The changes observed in circulating levels of IGF-I, IGFBP-III and IGFBP-II were associated with weekly increases in Fl and BWG that occurred during the entire experimental period (P < 0.05). Se realizó un experimento para determinar si la inclusión de un 10% de aguas residuales de una fábrica de caramelo (CPWW, por sus siglas en inglés) en la dieta de cerdos post-destete resulta en cambios en los niveles del factor de crecimiento semejante a insulina-l (IGF-I, por sus siglas en inglés) y proteínas fijadoras de IGF (IGFBPs-ll y -III, por sus siglas en inglés) en la sangre, y si éstos se asocian a diferencias en consumo de alimento (CA), ganancia en peso (GP), y eficiencia de conversión (EC). Dieciséis cerdos de raza Landrace se distribuyeron al azar entre ocho jaulas (una cerda y un cerdo por jaula) y se asignaron a uno de dos tratamientos: 0% (control) y 10% de inclusión de CPWW. Durante cuatro semanas consecutivas se registró el peso vivo y el consumo de alimento de los animales. Se recolectaron muestras de sangre a través de sangrado yugular durante la primera, segunda y tercera semana del experimento y se determinaron los niveles de IGF-I, IGFBP-II y IGFBP-III en el suero. No hubo efecto significativo de la adición de 10% CPWW en la dieta sobre CA, GP y EC (P > 0.05). Mediante apreciación visual se determinó que la inclusión de CPWW no tuvo efectos adversos en la salud de los animales. Los niveles de IGF-I fueron más altos para los animales control (P < 0.05) y aumentaron del día 14 al día 28 del periodo post-destete (P < 0.05). Se observó un aumento semanal en los niveles de IGFBP-III (P < 0.05), mientras que los niveles de IGFBP-II disminuyeron a partir del día 14 al día 28 (P < 0.05). El análisis de correlación simple reveló que existe una asociación positiva entre los niveles de IGF-I y IGFBP-III circulando en la sangre (r = 0.88; P < 0.0001). Sin embargo, se observó un efecto opuesto entre éstos y IGFBP-II (r = -0.84, P < 0.0001; r = -0.67, P < 0.0025, respectivamente). Los cambios observados en los niveles sanguíneos de IGF-I, IGFBP-III y IGFBP-II se asociaron a aumentos semanales en CA y GP que ocurrieron durante todo el periodo experimental (P < 0.05)

    INtervention for Cognitive Reserve Enhancement in Delaying the Onset of Alzheimer\u27s Symptomatic Expression (INCREASE), a Randomized Controlled Trial: Rationale, Study Design, and Protocol

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    BACKGROUND: The course of Alzheimer\u27s disease (AD) includes a 10-20-year preclinical period with progressive accumulation of amyloid β (Aβ) plaques and neurofibrillary tangles in the absence of symptomatic cognitive or functional decline. The duration of this preclinical stage in part depends on the rate of pathologic progression, which is offset by compensatory mechanisms, referred to as cognitive reserve (CR). Comorbid medical conditions, psychosocial stressors, and inappropriate medication use may lower CR, hastening the onset of symptomatic AD. Here, we describe a randomized controlled trial (RCT) designed to test the efficacy of a medication therapy management (MTM) intervention to reduce inappropriate medication use, bolster cognitive reserve, and ultimately delay symptomatic AD. METHODS/DESIGN: Our study aims to enroll 90 non-demented community-dwelling adults ≥ 65 years of age. Participants will undergo positron emission tomography (PET) scans, measuring Aβ levels using standardized uptake value ratios (SUVr). Participants will be randomly assigned to MTM intervention or control, stratified by Aβ levels, and followed for 12 months via in-person and telephone visits. Outcomes of interest include: (1) medication appropriateness (measured with the Medication Appropriateness Index (MAI)); (2) scores from Trail Making Test B (TMTB), Montreal Cognitive Assessment (MoCA), and California Verbal Learning Test (CVLT); (3) perceived health status (measured with the SF-36). We will also evaluate pre- to post-intervention change in: (1) use of inappropriate medications as measured by MAI; 2) CR Change Score (CRCS), defined as the difference in scopolamine-challenged vs unchallenged cognitive scores at baseline and follow-up. Baseline Aβ SUVr will be used to examine the relative impact of preclinical AD (pAD) pathology on CRCS, as well as the interplay of amyloid burden with inappropriate medication use. DISCUSSION: This manuscript describes the protocol of INCREASE ( INtervention for Cognitive Reserve Enhancement in delaying the onset of Alzheimer\u27s Symptomatic Expression ): a randomized controlled trial that investigates the impact of deprescribing inappropriate medications and optimizing medication regimens on potentially delaying the onset of symptomatic AD and AD-related dementias. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02849639. Registered on 29 July 2016

    “...Our support is not enough”: a qualitative analysis of recommendations from informal caregivers of women with female genital fistula in Uganda

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    Informal caregivers remain critical across the care continuum for complex and stigmatized conditions including female genital fistula, particularly in lower-resource settings burdened by underfunded health systems and workforce shortages. These caregivers often provide significant nonmedical support in both community and facility settings, without pay. Despite their unique insight into the lived experiences of their patients, few studies center the perspectives of informal caregivers. We asked informal caregivers of women seeking surgical treatment of fistula in Kampala Uganda for their ideas about what would improve the recovery and reintegration experiences of their patients. Economic empowerment and community capacity building emerged as primary themes among their responses, and they perceived opportunities for clinical medicine and global health to strengthen strategies for fistula prevention through reintegration. Informal caregivers urged simultaneous investment in women's economic status and community capacity to build fistula-related awareness, knowledge, and skills to improve inclusion of both fistula patients and their informal caregivers

    Recognition and processing of a new repertoire of DNA substrates by human 3-methyladenine DNA glycosylase (AAG)

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    The human 3-methyladenine DNA glycosylase (AAG) recognizes and excises a broad range of purines damaged by alkylation and oxidative damage, including 3-methyladenine, 7-methylguanine, hypoxanthine (Hx), and 1,N[superscript 6]-ethenoadenine (εA). The crystal structures of AAG bound to εA have provided insights into the structural basis for substrate recognition, base excision, and exclusion of normal purines and pyrimidines from its substrate recognition pocket. In this study, we explore the substrate specificity of full-length and truncated Δ80AAG on a library of oligonucleotides containing structurally diverse base modifications. Substrate binding and base excision kinetics of AAG with 13 damaged oligonucleotides were examined. We found that AAG bound to a wide variety of purine and pyrimidine lesions but excised only a few of them. Single-turnover excision kinetics showed that in addition to the well-known εA and Hx substrates, 1-methylguanine (m1G) was also excised efficiently by AAG. Thus, along with εA and ethanoadenine (EA), m1G is another substrate that is shared between AAG and the direct repair protein AlkB. In addition, we found that both the full-length and truncated AAG excised 1,N[superscript 2]-ethenoguanine (1,N[superscript 2]-εG), albeit weakly, from duplex DNA. Uracil was excised from both single- and double-stranded DNA, but only by full-length AAG, indicating that the N-terminus of AAG may influence glycosylase activity for some substrates. Although AAG has been primarily shown to act on double-stranded DNA, AAG excised both εA and Hx from single-stranded DNA, suggesting the possible significance of repair of these frequent lesions in single-stranded DNA transiently generated during replication and transcription.United States. National Institutes of Health (grant ES05355)United States. National Institutes of Health (grant CA75576)United States. National Institutes of Health (grant CA55042)United States. National Institutes of Health (grant ES02109)United States. National Institutes of Health (grant T32-ES007020)United States. National Institutes of Health (grant CA80024)United States. National Institutes of Health (grant CA26731
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