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Background: Glycemic markers, including postprandial glucose, insulin, and insulin resistance, are strong predictors of morbidity and mortality in individuals with and without diabetes. Stair-climbing and -descending (SCD) at a comfortable pace for 3 minutes after a sugary beverage (300 kilocalories; 100% carbohydrate) lowers insulin, with insulin sensitivity improving in 10 minutes. If similar benefits are seen following consumption of a mixed meal is unknown. We hypothesize SCD will improve these markers in a dose-response manner following a mixed meal. Methods: In a randomized, controlled, crossover trial, young adults (N = 31) performed SCD for 0 (seated control), 1, 3, and 10 minutes after a mixed meal (650 kilocalories; 53% carbohydrates, 33% fat, and 14% protein). Differences in glucose, insulin, and insulin sensitivity (ISI) from baseline to 30 min were analyzed using a mixed-effects ANOVA. Results: A significant fixed-effect was found for change in glucose [F(2.551,67.17) = 4.724,p = 0.007)], insulin [F(2.692,74.49) = 11.28,p < 0.001)], and ISI [F(2.127,56.00) = 5.848,p = 0.004)]. Compared to the seated control (0 minutes), changes in glucose were lower after 1 minute (-14.0 (-7.2)mg/dL,p < 0.001), 3 minutes (-18.4 (-7.0)mg/dL,p = 0.0007), and 10 minutes (-10.0 (-8.1)mg/dL,p = 0.039); changes in insulin were lower after 1 minute (-1.8 (-0.9)µIU/mL,p = 0.0011), 3 minutes (-2.8 (-0.9)µIU/mL,p < 0.001), and 10 minutes (-1.1 (-0.9)µIU/mL,p = 0.033); and changes in ISI were significantly higher after 3 minutes (2.4 (1.5),p < 0.001) and 10 minutes (1.3 (1.6),p = 0.014) but not 1 minute (1.2 (1.5),p = 0.059). Conclusion: Postprandial glucose and insulin improved with 1 minute, and insulin resistance improved with 3 minutes, of SCD at a self-selected, comfortable pace, after consumption of a mixed meal in apparently healthy young adults. Protocol: Trial registration: ClinicalTrials.gov Identifier: NCT04232475.
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Fluctuations in prey abundance, composition, and distribution can impact predators, and when predators and fisheries target the same species, predators become essential to ecosystem-based management. Because of the difficulty in collecting concomitant predator-prey data at appropriate scales in patchy environments, few studies have identified strong linkages between cetaceans and prey, especially across large geographic areas. During summer 2018, a line-transect survey for cetaceans and coastal pelagic species was conducted over the continental shelf and slope of British Columbia, Canada, and the US West Coast, allowing for a large-scale investigation of predator-prey spatial relationships. We report on a case study of humpback whales (Megaptera novaeangliae) and their primary prey-Pacific herring (Clupea pallasii), northern anchovy (Engraulis mordax), and krill-using generalized additive models to explore the relationships between whale abundance on 10-km transect segments and prey metrics. Prey metrics included direct measures of biomass densities on segments and an original hotspot metric. For each prey species, segments in the upper fifth percentile for biomass density (across all segments) were designated hotspots, and whale counts on a segment were evaluated for their relationship to number of hotspot segments (species-specific and multispecies) within 25, 50, or 100 km. Whale abundance was not strongly related to direct measures of biomass densities, whereas models using hotspot metrics were more effective at describing variation in whale abundance, underscoring that evaluating prey at relevant and measurable scales is critical in patchy, dynamic marine environments. Our analysis highlighted differences in the distribution and prey availability for three humpback whale distinct population segments (DPSs) as defined under the US Endangered Species Act, including threatened and endangered DPSs that forage within the California Current Large Marine Ecosystem. These linkages provide insights into which prey species whales may be targeting in different regions and across multiple scales and, consequently, how climatic variability and anthropogenic risks may differentially impact these distinct predator-prey assemblages. By identifying scale-appropriate prey hotspots that co-occur with humpback whale aggregations, and with targeted, consistent prey sampling and estimations of potential consumption rates by whales, these findings can help inform the conservation and management of humpback whales within an ecosystem-based management framework.
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Ecosistema , Yubarta , Animales , Estaciones del Año , Biomasa , Colombia Británica , PecesRESUMEN
BACKGROUND: Direct oral anticoagulants (DOACs) have been associated with less calcification and coronary plaque progression than warfarin. Whether different DOACs have different effects on coronary plaque burden and progression is not known. We compared the 12-month effects of apixaban and rivaroxaban on plaque characteristics and vascular morphology in patients with atrial fibrillation through quantitative cardiac computed tomographic angiography. STUDY QUESTION: In patients with nonvalvular atrial fibrillation using apixaban or rivaroxaban, are there differences in plaque quantification and progression measured with cardiac computed tomography? STUDY DESIGN: This is a post hoc analysis of 2 paired prospective, single-centered, randomized, open-label trials with blinded adjudication of results. In total, 74 patients were prospectively randomized in parallel trials: 29 to apixaban (2.5-5 mg BID) and 45 to rivaroxaban (20 mg QD). Serial cardiac computed tomographic angiography was performed at baseline and 52 weeks. MEASURES AND OUTCOMES: Comprehensive whole-heart analysis was performed for differences in the progression of percent atheroma volume (PAV), calcified plaque (CP) PAV, noncalcified plaque (NCP) PAV, positive arterial remodeling (PR) ≥1.10, and high-risk plaque (Cleerly Labs, New York, NY). RESULTS: Both groups had progression of all 3 plaque types (apixaban: CP 8.7 mm 3 , NCP 69.7 mm 3 , and LD-NCP 27.2 mm 3 ; rivaroxaban: CP 22.9 mm 3 , NCP 66.3 mm 3 , and LD-NCP 11.0 mm 3 ) and a total annual plaque PAV change (apixaban: PAV 1.5%, PAV-CP 0.12%, and PAV-NCP 0.92%; rivaroxaban: PAV 2.1%, PAV-CP 0.46%, and PAV-NCP 1.40%). There was significantly lower PAV-CP progression in the apixaban group compared with the rivaroxaban group (0.12% vs. 0.46% P = 0.02). High-risk plaque characteristics showed a significant change in PR of apixaban versus rivaroxaban ( P = 0.01). When the propensity score weighting model is applied, only PR changes are statistically significant ( P = 0.04). CONCLUSIONS: In both groups, there is progression of all types of plaque. There was a significant difference between apixaban and rivaroxaban on coronary calcification, with significantly lower calcific plaque progression in the apixaban group, and change in positive remodeling. With weighted modeling, only PR changes are statistically significant between the 2 DOACs.
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Fibrilación Atrial , Placa Aterosclerótica , Accidente Cerebrovascular , Humanos , Rivaroxabán/efectos adversos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Anticoagulantes/efectos adversos , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/tratamiento farmacológico , Placa Aterosclerótica/complicaciones , Estudios Prospectivos , Piridonas/efectos adversos , Tomografía Computarizada por Rayos X/métodos , Dabigatrán , Accidente Cerebrovascular/complicacionesRESUMEN
BACKGROUND AND AIMS: This study examined the effect of moderate intensity stair stepping exercise on the glycemic response, and antioxidant capacity (TAC) during an oral glucose tolerance test (OGTT). METHODS AND RESULTS: Thirty participants (women = 12) completed 4 OGTTs during rest or stair walking bouts of 1, 3, and 10 min in a randomized order. Blood was collected at baseline and 30 min during the OGTTs and analyzed for glucose, insulin, TAC, and lactate. Glucose concentrations were decreased following the 10 min (-22.69 (-34.66 to -10.72) mg/dL, p < 0.002) and 3 min (-15.37 (-25.05 to -5.69) mg/dL, p < 0.004) bouts but not the 1 min bout (-6.18 (-19.54 to 7.18) mg/dL, p = 0.352). Insulin concentrations were decreased following the 10 min (-6.11 (-8.86 to -3.36 µIU/dL), p < 0.001) and 3 min (-2.589 (-4.54 to -0.63) µIU/dL, p < 0.012) bouts but not the 1 min bout (-0.37 (-1.87 to 1.13) µIU/dL, p = 0.616). Insulin sensitivity index values showed a significant increase in the 10-min trial (1.81 (0.03-3.58), p < 0.048), but not during the 3 min (0.65 (-0.66 to 1.96) p = 0.317) or 1 min trial (0.13 (-1.58 to 1.84) p = 0.878). There was no omnibus effect for trial in TAC (p = 0.132, η2 = 0.07). There was no interaction between trial and time for blood lactate (p = 0.621, η2 = 0.02). CONCLUSION: This study provides evidence bouts as short as 3 min decrease postprandial blood glucose and insulin levels but longer bouts are needed to affect insulin sensitivity.
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Antioxidantes , Resistencia a la Insulina , Glucemia , Femenino , Glucosa , Humanos , Insulina , Periodo Posprandial/fisiología , Caminata/fisiologíaRESUMEN
BACKGROUND AND AIMS: Postprandial blood glucose (PBG) is an independent predictor of disease and mortality risk. To date, the shortest, single, moderate-intensity exercise intervention to reduce PBG is a 1 min bout of stair stepping during an oral glucose tolerance test. Whether this effect translates to real meal consumption is unknown. METHODS AND RESULTS: Subjects (N = 30) participated in a randomized controlled crossover trial performing 0 min (seated control), 1 min, 3 min or 10 min of stair climbing and descending bouts (SCD) at a self-selected pace after consumption of a mixed meal on four separate visits. Compared to control, all SCD reduced PBG at least one timepoint: at 30-min the 3 min (-10.8 (-18.7 to -2.8) mg/dL, p = 0.010) and 10 min (-36.3 (-46.4 to -26.3) mg/dL), p < .001), and at 45-min the 1 min (-7.3 (-13.9 to -0.7) mg/dL, p = 0.030, 3 min (-8.7 (-13.9 to -3.6) mg/dL, p = 0.002 and 10 min SCD (-12.2 (-18.2 to -6.1)mg/dL, p < 0.000) reduced PBG. The area under the curve (AUC) for PBG was lower following the 3 min (-4.4% (-7.5 to -1.4%), p = 0.006) and 10 min (-8.9% (-12.4 to -5.3%), p < 0.001), while the incremental AUC (iAUC) was reduced only following the 10 min (-38.0% (-63.7 to -12.3%), p = 0.005) SCD. All SCD were rated by subjects as very light to light intensity. CONCLUSIONS: Single, subjectively "light" intensity stair climbing and descending bouts as short as 1 min in duration attenuate the postprandial glucose response in normal weight individuals following consumption of a mixed meal. More pronounced effects require longer bouts in a dose-dependent manner.
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Glucemia/metabolismo , Terapia por Ejercicio , Control Glucémico/métodos , Hiperglucemia/prevención & control , Subida de Escaleras , Adulto , Biomarcadores/sangre , California , Estudios Cruzados , Regulación hacia Abajo , Femenino , Humanos , Hiperglucemia/sangre , Hiperglucemia/diagnóstico , Hiperglucemia/etiología , Masculino , Periodo Posprandial , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Vitamin D is widely known to regulate bone health, but there is increasing evidence that it may also ameliorate colitis through inflammation, cell proliferation and apoptosis, and the microbiota. The purpose of this review is to systematically examine the mechanisms by which vitamin D reduces colitis. PubMed and Web of Science were searched for articles published between 2008 and 2019 using key words such as "vitamin D," "colitis," "inflammatory bowel disease," "inflammation," "apoptosis," "cell proliferation," and "gut bacteria". Retrieved articles were further narrowed and it was determined whether their title and abstracts contained terminology pertaining to vitamin D in relation to colitis in human clinical trials, animal studies, and cell culture/biopsy studies, as well as selecting the best match sorting option in relation to the research question. In total, 30 studies met the established criteria. Studies consistently reported results showing that vitamin D supplementation can downregulate inflammatory pathways of COX-2, TNF-α, NF-κB, and MAPK, modify cell kinetics, and alter gut microbiome, all of which contribute to an improved state of colitis. Although vitamin D and vitamin D analogs have demonstrated positive effects against colitis, more randomized, controlled human clinical trials are needed to determine the value of vitamin D as a therapeutic agent in the treatment of colitis.
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Colitis/dietoterapia , Suplementos Dietéticos , Regulación de la Expresión Génica/efectos de los fármacos , Enfermedades Inflamatorias del Intestino/dietoterapia , Vitamina D/administración & dosificación , Animales , Ensayos Clínicos como Asunto , Colitis/genética , Colitis/microbiología , Colitis/patología , Colon/efectos de los fármacos , Colon/microbiología , Colon/patología , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/microbiología , Células Epiteliales/patología , Microbioma Gastrointestinal/efectos de los fármacos , Microbioma Gastrointestinal/fisiología , Humanos , Inflamación , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/microbiología , Enfermedades Inflamatorias del Intestino/patología , Ratones , Proteínas Quinasas Activadas por Mitógenos/genética , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Transducción de Señal , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVES: To assess neurodevelopmental outcomes among participants with biliary atresia with their native liver at ages 12 months (group 1) and 24 months (group 2), and to evaluate variables predictive of neurodevelopmental impairment. STUDY DESIGN: Participants enrolled in a prospective, longitudinal, multicenter study underwent neurodevelopmental testing with either the Bayley Scales of Infant Development, 2nd edition, or Bayley Scales of Infant and Toddler Development, 3rd edition. Scores (normative mean = 100 ± 15) were categorized as ≥100, 85-99, and <85 for χ2 analysis. Risk for neurodevelopmental impairment (defined as ≥1 score of <85 on the Bayley Scales of Infant Development, 2nd edition, or Bayley Scales of Infant and Toddler Development, 3rd edition, scales) was analyzed using logistic regression. RESULTS: There were 148 children who completed 217 Bayley Scales of Infant and Toddler Development, 3rd edition, examinations (group 1, n = 132; group 2, n = 85). Neurodevelopmental score distributions significantly shifted downward compared with test norms at 1 and 2 years of age. Multivariate analysis identified ascites (OR, 3.17; P = .01) and low length z-scores at time of testing (OR, 0.70; P < .04) as risk factors for physical/motor impairment; low weight z-score (OR, 0.57; P = .001) and ascites (OR, 2.89; P = .01) for mental/cognitive/language impairment at 1 year of age. An unsuccessful hepatoportoenterostomy was predictive of both physical/motor (OR, 4.88; P < .02) and mental/cognitive/language impairment (OR, 4.76; P = .02) at 2 years of age. CONCLUSION: Participants with biliary atresia surviving with native livers after hepatoportoenterostomy are at increased risk for neurodevelopmental delays at 12 and 24 months of age. Those with unsuccessful hepatoportoenterostomy are >4 times more likely to have neurodevelopmental impairment compared with those with successful hepatoportoenterostomy. Growth delays and/or complications indicating advanced liver disease should alert clinicians to the risk for neurodevelopmental delays, and expedite appropriate interventions. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00061828 and NCT00294684.
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Atresia Biliar/terapia , Discapacidades del Desarrollo/etiología , Hígado/fisiología , Pruebas Neuropsicológicas , Atresia Biliar/complicaciones , Preescolar , Cognición , Discapacidades del Desarrollo/diagnóstico , Femenino , Humanos , Lactante , Estudios Longitudinales , Masculino , Destreza Motora , Análisis Multivariante , Estudios Observacionales como Asunto , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Análisis de Regresión , Riesgo , Resultado del Tratamiento , Poblaciones VulnerablesRESUMEN
BACKGROUND: Choline depletion is seen in cystic fibrosis (CF) and pancreatic insufficiency in spite of enzyme treatment and may result in liver, fatty acid, and muscle abnormalities. This study evaluated the efficacy and safety of an easily absorbed choline-rich structured lipid (LYM-X-SORB™ [LXS]) to improve choline status. METHODS: Children with CF and pancreatic insufficiency were randomized to LXS or placebo in a 12-month double blind trial. Dietary choline intake, plasma cholines, plasma and fecal phospholipids, coefficient of fat absorption, pulmonary function, growth status, body composition, and safety measures were assessed. Magnetic resonance spectroscopy for calf muscle choline and liver fat were assessed in a subgroup and compared with a healthy comparison group matched for age, sex, and body size. RESULTS: A total of 110 subjects were enrolled (age 10.4â±â3.0 years). Baseline dietary choline, 88% recommended, increased 3-fold in the LXS group. Plasma choline, betaine, and dimethylglycine increased in the LXS but not placebo (Pâ=â0.007). Plasma lysophosphatidylcholine and phosphatidylcholine increased, and fecal phosphatidylcholine/phosphatidylethanolamine ratio decreased (Pâ≤â0.05) in LXS only, accompanied by a 6% coefficient of fat absorption increase (Pâ=â0.001). Children with CF had higher liver fat than healthy children and depleted calf muscle choline at baseline. Muscle choline concentration increased in LXS and was associated with improvement in plasma choline status. No relevant changes in safety measures were evident. CONCLUSIONS: LXS had improved choline intake, plasma choline status, and muscle choline stores compared with placebo group. The choline-rich supplement was safe, accepted by participants, and improved choline status in children with CF.
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Fenómenos Fisiológicos Nutricionales de los Adolescentes , Fenómenos Fisiológicos Nutricionales Infantiles , Colina/uso terapéutico , Fibrosis Quística/dietoterapia , Grasas de la Dieta , Suplementos Dietéticos , Lisofosfatidilcolinas/uso terapéutico , Estado Nutricional , Adolescente , Niño , Preescolar , Colina/efectos adversos , Colina/análisis , Colina/sangre , Deficiencia de Colina/etiología , Deficiencia de Colina/prevención & control , Fibrosis Quística/sangre , Fibrosis Quística/metabolismo , Grasas de la Dieta/efectos adversos , Grasas de la Dieta/análisis , Grasas de la Dieta/metabolismo , Suplementos Dietéticos/efectos adversos , Suplementos Dietéticos/análisis , Método Doble Ciego , Femenino , Humanos , Absorción Intestinal , Pierna , Metabolismo de los Lípidos , Hígado/metabolismo , Lisofosfatidilcolinas/efectos adversos , Lisofosfatidilcolinas/análisis , Lisofosfatidilcolinas/metabolismo , Masculino , Músculo Esquelético/metabolismo , Aceptación de la Atención de SaludRESUMEN
Colchicine is an anti-inflammatory medication, classically used to treat a wide spectrum of autoimmune diseases. More recently, colchicine has proven itself a key pharmacotherapy in cardiovascular disease (CVD) management, atherosclerotic plaque modification, and coronary artery disease (CAD) treatment. Colchicine acts on many anti-inflammatory pathways, which translates to cardiovascular event reduction, plaque transformation, and plaque reduction. With the FDA's 2023 approval of colchicine for reducing cardiovascular events, a novel clinical pathway opens. This advancement paves the route for CVD management that synergistically merges lipid lowering approaches with inflammation inhibition modalities. This pioneering moment spurs the need for this manuscript's comprehensive review. Hence, this paper synthesizes and surveys colchicine's new role as an atherosclerotic plaque modifier, to provide a framework for physicians in the clinical setting. We aim to improve understanding (and thereby application) of colchicine alongside existing mechanisms for CVD event reduction. This paper examines colchicine's anti-inflammatory mechanism, and reviews large cohort studies that evidence colchicine's blossoming role within CAD management. This paper also outlines imaging modalities for atherosclerotic analysis, reviews colchicine's mechanistic effect upon plaque transformation itself, and synthesizes trials which assess colchicine's nuanced effect upon atherosclerotic transformation.
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Antiinflamatorios , Colchicina , Placa Aterosclerótica , Colchicina/uso terapéutico , Humanos , Placa Aterosclerótica/tratamiento farmacológico , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/diagnóstico , Valor Predictivo de las Pruebas , Animales , Resultado del Tratamiento , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/diagnósticoRESUMEN
Mammalian cell line stability is an important consideration when establishing a biologics manufacturing process in the biopharmaceutical and in vitro diagnostics (IVD) industries. Traditional Chinese hamster ovary (CHO) cell line development methods use a random integration approach that requires transfection, selection, optional amplification, screenings, and single-cell cloning to select clones with acceptable productivity, product quality, and genetic stability. Site-specific integration reduces these disadvantages, and new technologies have been developed to mitigate risks associated with genetic instability. In this study, we applied the Leap-In® transposase-mediated expression system from ATUM to generate stable CHOK1 pools for the production of four recombinant antibody reagents for IVD immunoassays. CHO cell line stability is defined by consistent antibody production over time. Three of the CHOK1 pools maintained productivity suitable for manufacturing, with high antibody yields. The productivity of the remaining CHOK1 pool decreased over time; however, derivative clones showed acceptable stability. l-glutamine had variable effects on CHOK1 cell line or stable pool stability and significantly affected antibody product titer. Compared with traditional random integration methods, the ATUM Leap-In system can reduce the time needed to develop new immunoassays by using semi site-specific integration to generate high-yield stable pools that meet manufacturing stability requirements.
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Cricetulus , Proteínas Recombinantes , Células CHO , Animales , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/biosíntesis , Anticuerpos Monoclonales/biosíntesis , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/genética , Cricetinae , Humanos , Transposasas/genética , Transposasas/metabolismoRESUMEN
For the 40 years after the end of commercial whaling in 1976, humpback whale populations in the North Pacific Ocean exhibited a prolonged period of recovery. Using mark-recapture methods on the largest individual photo-identification dataset ever assembled for a cetacean, we estimated annual ocean-basin-wide abundance for the species from 2002 through 2021. Trends in annual estimates describe strong post-whaling era population recovery from 16 875 (± 5955) in 2002 to a peak abundance estimate of 33 488 (± 4455) in 2012. An apparent 20% decline from 2012 to 2021, 33 488 (± 4455) to 26 662 (± 4192), suggests the population abruptly reached carrying capacity due to loss of prey resources. This was particularly evident for humpback whales wintering in Hawai'i, where, by 2021, estimated abundance had declined by 34% from a peak in 2013, down to abundance levels previously seen in 2006, and contrasted to an absence of decline in Mainland Mexico breeding humpbacks. The strongest marine heatwave recorded globally to date during the 2014-2016 period appeared to have altered the course of species recovery, with enduring effects. Extending this time series will allow humpback whales to serve as an indicator species for the ecosystem in the face of a changing climate.
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Daptomycin (DAP) is a cyclic lipopeptide antibiotic used for the treatment of certain Staphylococcus aureus infections. Although rare, strains have been isolated that are DAP resistant. These strains usually have mutations in mprF, a gene encoding a membrane protein with both lysylphosphatidylglycerol (LPG) synthase and flippase activities. Because ΔmprF strains have increased DAP susceptibility, the mechanism of resistance is not likely due to a loss of mprF function. In this study, we developed an LC-MS assay to examine the effect of different mprF mutations on the ratio of phosphatidylglycerol (PG) to LPG in the membrane. Our assay demonstrated that some, but not all, mutations in the flippase and synthase domains result in small but reproducible increases in the proportion of LPG relative to PG. Techniques described herein represent a higher throughput and more sensitive method for measuring relative phospholipids levels. These results offer guidance in the understanding of how mprF confers DAP resistance; namely, mprF-mediated resistance may be through more than one mechanism, including increased overall LPG synthesis and increased LPG present on the outer leaflet of the cytoplasmic membrane.
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Aminoaciltransferasas/genética , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Daptomicina/farmacología , Mutación , Fosfolípidos/química , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/genética , Cromatografía Liquida , Iones/química , Lisina/análisis , Lisina/química , Pruebas de Sensibilidad Microbiana , Fosfatidilgliceroles/análisis , Fosfatidilgliceroles/química , Fosfolípidos/análisis , Staphylococcus aureus/química , Espectrometría de Masas en TándemRESUMEN
BACKGROUND: Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are associated with a high incidence of cardiovascular disease. Coronary atherosclerosis, particularly total plaque and noncalcified plaque on coronary computed tomography angiography (CCTA) has been correlated with cardiovascular events. We compared baseline coronary plaque burden and progression by serial CCTA in SLE and RA patients. METHODS: We prospectively evaluated 44 patients who underwent serial CCTA examinations to quantify coronary plaque progression, 22 SLE patients, and 22 age- and sex-matched RA patients. Semiautomated plaque software was used for quantitative plaque assessment. Linear regression examined the effect of SLE diagnosis (versus RA) on annualized change in natural log-transformed total normalized atheroma volume (ln-TAV norm ) for low-attenuation, fibrofatty, fibrous, total noncalcified, densely calcified, and total plaque. RESULTS: No quantitative differences for any plaque types were observed at baseline between SLE and RA patients ( P = 0.330-0.990). After adjustment for baseline plaque and cardiovascular risk factors, the increase in ln-TAV norm was higher in SLE than RA patients for fibrous [Exp-ß: 0.202 (0.398), P = 0.0003], total noncalcified [Exp-ß: 0.179 (0.393), P = 0.0001], and total plaque volume [Exp-ß: 0.154 (0.501), P = 0.0007], but not for low-attenuation, fibrofatty, or densely calcified plaque ( P = 0.103-0.489). Patients with SLE had 80% more fibrous, 82% more noncalcified, and 85% more total plaque increase than those with RA. CONCLUSION: Coronary plaque volume was similar in RA and SLE at baseline. Progression was greater in SLE, which may explain the greater cardiovascular risk in this disease. Further research to evaluate screening and management strategies for cardiovascular disease in these high-risk patients is warranted.
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Artritis Reumatoide , Enfermedades Cardiovasculares , Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/epidemiología , Artritis Reumatoide/complicaciones , Artritis Reumatoide/epidemiologíaRESUMEN
The quantification of protein biomarkers in blood at picomolar-level sensitivity requires labour-intensive incubation and washing steps. Sensing proteins in sweat, which would allow for point-of-care monitoring, is hindered by the typically large interpersonal and intrapersonal variations in its composition. Here we report the design and performance of a wearable and wireless patch for the real-time electrochemical detection of the inflammatory biomarker C-reactive (CRP) protein in sweat. The device integrates iontophoretic sweat extraction, microfluidic channels for sweat sampling and for reagent routing and replacement, and a graphene-based sensor array for quantifying CRP (via an electrode functionalized with anti-CRP capture antibodies-conjugated gold nanoparticles), ionic strength, pH and temperature for the real-time calibration of the CRP sensor. In patients with chronic obstructive pulmonary disease, with active or past infections or who had heart failure, the elevated concentrations of CRP measured via the patch correlated well with the protein's levels in serum. Wearable biosensors for the real-time sensitive analysis of inflammatory proteins in sweat may facilitate the management of chronic diseases.
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Nanopartículas del Metal , Dispositivos Electrónicos Vestibles , Humanos , Sudor/química , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Oro , Monitoreo Fisiológico , Biomarcadores/metabolismoRESUMEN
We present an ocean-basin-scale dataset that includes tail fluke photographic identification (photo-ID) and encounter data for most living individual humpback whales (Megaptera novaeangliae) in the North Pacific Ocean. The dataset was built through a broad collaboration combining 39 separate curated photo-ID catalogs, supplemented with community science data. Data from throughout the North Pacific were aggregated into 13 regions, including six breeding regions, six feeding regions, and one migratory corridor. All images were compared with minimal pre-processing using a recently developed image recognition algorithm based on machine learning through artificial intelligence; this system is capable of rapidly detecting matches between individuals with an estimated 97-99% accuracy. For the 2001-2021 study period, a total of 27,956 unique individuals were documented in 157,350 encounters. Each individual was encountered, on average, in 5.6 sampling periods (i.e., breeding and feeding seasons), with an annual average of 87% of whales encountered in more than one season. The combined dataset and image recognition tool represents a living and accessible resource for collaborative, basin-wide studies of a keystone marine mammal in a time of rapid ecological change.
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Yubarta , Animales , Inteligencia Artificial , Océano Pacífico , Estaciones del AñoRESUMEN
Despite long established comparatively poor health outcomes there has been limited research into the healthcare access of Irish migrants in the UK. This study examines the relationship between demography, self-reported health (SRH) and social support and healthcare access and the influence of gender on these associations. Data was collected as part of a community-based action research project with Irish migrants in London (n = 790). Hierarchical logistic regression was used to predict self-reported access to a GP (compared with no reported access). The effect of gender was measured via interactions entered in the second step of the model. Older participants and males were less likely to report GP access. SRH was a significant predictor. Gender moderated the relationship between SRH, social support, employment and GP access. Findings highlight the help-seeking vulnerability of male and older Irish migrants and the potential of social support in promoting healthcare access for males.
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Migrantes , Estudios Transversales , Accesibilidad a los Servicios de Salud , Humanos , Masculino , Atención Primaria de Salud , Apoyo SocialRESUMEN
BACKGROUND/AIM: Nut consumption is associated with lower risk of colorectal cancer (CRC). Previously, single nut varieties have been investigated but there is limited research on the consumption of a nut mixture and the underlying mechanisms. This study examined mixed nut consumption's effect on colonic cell proliferation, apoptosis, and gene expression involved in CRC. MATERIALS AND METHODS: Thirty 21-day old Sprague Dawley rats were divided into three groups: control (no nuts), pistachio or mixed nut for 8 weeks. Ki-67 quantitative immunostaining was used to mark proliferative cells and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay for apoptotic cells. Real-time quantitative polymerase chain reaction analysis was used to determine colonic gene expression of prostaglandin endoperoxide synthase 2 (Ptgs2), nuclear factor kappa-B p65 subunit (Rela), cyclin D1 (Ccnd1), peroxisome proliferator-activated receptor gamma (Pparg), O6-methylguanine-DNA-methyltransferase (Mgmt), 8-oxoguanine glycosylase (Ogg1), superoxide dismutase (Sod), and catalase (Cat). RESULTS: DNA damage, determined using 8-oxo-deoxyguanosin, was found to be lower in the mixed nut group only (p<0.05). Differences in proliferation and apoptosis among all three groups were not significant. Lower levels of the inflammatory marker, Ptgs2, were observed between the pistachio group and the control (p=0.035). The pistachio and mixed nut groups had lower levels of Rela compared to the control (p=0.029). Differences among diets for Ccnd1, Pparg, Mgmt, Ogg1, Sod, and Cat were not significant. CONCLUSION: Mixed nut consumption reduced DNA damage possibly via down-regulation of Rela inflammation gene expression without changes to colonic cell proliferation and apoptosis.
Asunto(s)
Nueces , PPAR gamma , Pistacia , Animales , Proliferación Celular , Colon , Ciclooxigenasa 2/genética , Expresión Génica , Pistacia/metabolismo , Ratas , Ratas Sprague-Dawley , Superóxido Dismutasa/metabolismo , Factor de Transcripción ReIA/metabolismoRESUMEN
Herein, a case study of an individual with fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), and postprandial blood glucose (PBG) measures from the 3 years preceding their type 1 diabetes mellitus diagnosis is used to highlight discordance among these common diagnostic tests. Data from the patient's own records, participation in clinical research, and healthcare provider were collated. Measures of FBG (90-160 mg/dL) and PBG (195-247 mg/dL) were elevated for 3 years with a normal HbA1c (5.0-5.4%) and without any symptoms. Overt symptoms, including polyuria, polydipsia, and unexplained weight loss, manifested 3 years later prompting the patient to contact their physician. Testing revealed an elevated HbA1c (9.8%) and presence of glutamic acid decarboxylase autoantibodies (GAD) (9 IU/mL). Daily body composition measures and weighed food logs from the 3 months preceding and 4 months after diagnosis illustrate the effects of glucose spilling and inadequate insulin levels. Both FBG and PBG indicated diabetes 3 years prior to HbA1c. While FBG, PBG, and HbA1c are considered equally appropriate for screening and diagnosing diabetes, this case study highlights the need to revisit important distinctions between these tests that explain their frequent discordance.
Asunto(s)
Diabetes Mellitus Tipo 1 , Insulinas , Adulto Joven , Humanos , Hemoglobina Glucada/análisis , Ayuno , Glucemia , Diabetes Mellitus Tipo 1/diagnóstico , Glucosa , Glutamato Descarboxilasa , AutoanticuerposRESUMEN
Single, short stair climbing and descending (SCD) bouts of low to moderate intensity effectively lower postprandial blood glucose but previous reports have found conflicting results on interactions by sex during exercise. We hypothesize that SCD at a self-selected intensity will be equally effective at lowering postprandial blood glucose in males and females. Methods and Results: Thirty subjects (age: 23.8 (3.0) years) performed 0, 1, 3, and 10 min of SCD following consumption of a mixed meal. SCD was performed at a self-selected comfortable pace and all bouts ended at minute 28. Postprandial blood glucose was measured every 15 min for 1 h and analyzed as glucose over time, area under the curve (AUC), and incremental AUC (iAUC) using mixed-design ANOVAs with repeated measures. Although there was no interaction between sex and condition or time (p = .129 to .541) for glucose over time, AUC, or iAUC, there was a main effect for sex for glucose over time (p = .004) and AUC (p = .006), but not iAUC (p = .125). Females had higher blood glucose throughout each trial (22% (13 to 31%), p = .004) but both males' and females' postprandial blood glucose was lowered following 10 min of SCD relative to the seated control condition. Conclusions: Males and females benefited equally from single, short SCD bouts of low to moderate intensity despite females having higher blood glucose at all time points. Previous findings of sex differences in the attenuating effect of exercise on postprandial blood glucose are likely due to the use of absolute workloads leading to varying relative intensities.