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A four-year-old spayed female Shiba Inu dog weighing 6.1 kg presented with ascites. Cor triatriatum dexter (CTD) without any other concurrent cardiovascular anomalies was diagnosed using echocardiography. The ostium of the abnormal membrane dividing the right atrium into two abnormal chambers was surgically excised under cardiopulmonary bypass. All clinical abnormalities were resolved after surgery. However, seven months later, ascites and CTD recurred. A balloon-expandable stent was placed at the site of recurrence, which improved caudal venous return to the right ventricle. After the second procedure, ascites were resolved, and the dog remained asymptomatic for 18 months without complications. There are previous reports of successful surgical resection of the CTD and of stenting in recurrent CTD following balloon dilation in dogs. However, to the authors' knowledge, no previous reports have described recurrent CTD in dogs after surgical resection of the CTD. In this case, as with recurrent CTD following balloon dilation, stent placement at the site of the CTD can be a viable treatment option when the abnormal membrane recurs.
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OBJECTIVES: To compare the discriminative capabilities for the manifestation of sarcopenia or physical frailty between serum creatinine- and cystatin C-derived indices among community-dwelling older adults. DESIGN: Cross-sectional study. SETTING: Primary Care and Community. PARTICIPANTS: We utilized a subset of data from the Frail Elderly in the Sasayama-Tamba Area (FESTA) study, which was initiated in 2015 to gather comprehensive information on various health-related parameters among community-dwelling older individuals (age ≥65 years). MEASUREMENTS: Five serum creatinine-cystatin C based indices including the Sarcopenia Index, the serum creatinine/cystatin C ratio, the disparity between serum cystatin-C-based and creatinine-based estimated GFR, the total body muscle mass index (TBMM), and the prediction equation for skeletal muscle mass index (pSMI) were employed. Sarcopenia and physical frailty were identified based on the Asian Working Group for Sarcopenia criteria and the revised Japanese version of the Cardiovascular Health Study criteria, respectively. The receiver operating characteristic (ROC) and logistic regression analyses were performed to assess the discriminative abilities of these tools. RESULTS: In the analysis of 954 participants, 52 (5.5%) were identified with sarcopenia and 35 (3.7%) with physical frailty. Regarding sarcopenia discrimination, TBMM and pSMI both exhibited area under the curve (AUC) values exceeding 0.8 for both men and women. Concerning the identification of physical frailty, AUC values ranged from 0.61 to 0.77 for males and 0.50 to 0.69 for females. In the multivariate logistic regression analyses, only TBMM and pSMI consistently displayed associations with sarcopenia, irrespective of sex (P<0.001, respectively). On the other hand, no consistent associations were observed between the indices and physical frailty. CONCLUSIONS: This study provides a robust association of a serum creatinine- and cystatin C-derived indices, especially TBMM and pSMI, with sarcopenia among community-dwelling older adults. Conversely, the application of these indices for the screening of physical frailty has its constraints, necessitating further investigation.
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Fragilidad , Sarcopenia , Anciano , Masculino , Humanos , Femenino , Cistatina C , Creatinina , Estudios Transversales , Fragilidad/diagnóstico , Fragilidad/epidemiología , Vida Independiente , Sarcopenia/diagnóstico , Sarcopenia/epidemiologíaRESUMEN
In this work, a measurement setup to study the Seebeck and Nernst effect at high temperatures and high magnetic fields is introduced and discussed. The measurement system allows for simultaneous measurements of both thermoelectric effects up to 700 K and magnetic fields up to 12 T. Based on theoretical concepts, measurement equations are derived that counteract constant spurious offset voltages and, therefore, inhibit systematic errors in the measurement setup. The functionality is demonstrated on polycrystalline samples of elemental bismuth as well as various full-Heusler materials, exhibiting an anomalous Nernst effect. In all samples, the measured Seebeck and Nernst coefficients align excellently with the reported values. This allows future research to substantially extend the measured temperature and field intervals, commonly limited to temperatures below room temperature. For the first time, the thermoelectric and thermomagnetic properties of these materials are reported up to temperatures of 560 K.
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AIM: To compare the radiation dose, image quality, and conspicuity of pancreatic ductal adenocarcinoma (PDAC) in pancreatic protocol dual-energy computed tomography (CT) between two X-ray tubes mounted in the same CT machine. MATERIAL AND METHODS: This retrospective study comprised 80 patients (median age, 73 years; 45 men) who underwent pancreatic protocol dual-energy CT from January 2019 to March 2022 using either old (Group A, n=41) or new (Group B, n=39) X-ray tubes mounted in the same CT machine. The imaging parameters were completely matched between the two groups, and CT data were reconstructed at 70 and 40 keV. The CT dose-index volume (CTDIvol); CT attenuation of the abdominal aorta, pancreas, and PDAC; background noise; and qualitative scores for the image noise, overall image quality, and PDAC conspicuity were compared between the two groups. RESULTS: The CTDIvol was lower in Group B than Group A (7.9 versus 9.2 mGy; p<0.001). The CT attenuation of all anatomical structures at 70 and 40 keV was comparable between the two groups (p=0.06-0.78). The background noise was lower in Group B than Group A (12 versus 14 HU at 70 keV, p=0.046; and 26 versus 30 HU at 40 keV, p<0.001). Qualitative scores for image noise and overall image quality at 70 and 40 keV and PDAC conspicuity at 40 keV were higher in Group B than Group A (p<0.001-0.045). CONCLUSION: The latest X-ray tube could reduce the radiation dose and improve image quality in pancreatic protocol dual-energy CT.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Imagen Radiográfica por Emisión de Doble Fotón , Masculino , Humanos , Anciano , Intensificación de Imagen Radiográfica/métodos , Estudios Retrospectivos , Rayos X , Tomografía Computarizada por Rayos X/métodos , Neoplasias Pancreáticas/diagnóstico por imagen , Páncreas/diagnóstico por imagen , Carcinoma Ductal Pancreático/diagnóstico por imagen , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Dosis de Radiación , Imagen Radiográfica por Emisión de Doble Fotón/métodosRESUMEN
Dental plaque, a highly structured polymicrobial biofilm, persistently forms in the oral cavity and is a common problem affecting oral health. The role of oral defense factors in either collaborating or disrupting host-microbiome interactions remains insufficiently elucidated. This study aims to explore the role of LL-37, a critical antimicrobial peptide in the oral cavity, in dental plaque formation. Through immunostaining dental plaque specimens, we observed that LL-37 and DNA colocalized in the samples, appearing as condensed clusters. In vitro experiments revealed that LL-37 binds rapidly to oral bacterial DNA, forming high molecular weight, DNase-resistant complexes. This interaction results in LL-37 losing its inherent antibacterial activity. Further, upon the addition of LL-37, we observed a visible increase in the precipitation of bacterial DNA. We also discovered a significant correlation between the levels of the DNA-LL-37 complex and LL-37 within dental plaque specimens, demonstrating the ubiquity of the complex within the biofilm. By using immunostaining on dental plaque specimens, we could determine that the DNA-LL-37 complex was present as condensed clusters and small bacterial cell-like structures. This suggests that LL-37 immediately associates with the released bacterial DNA to form complexes that subsequently diffuse. We also demonstrated that the complexes exhibited similar Toll-like receptor 9-stimulating activities across different bacterial species, including Porphyromonas gingivalis, Fusobacterium nucleatum, Prevotella intermedia, and Streptococcus salivarius. However, these complexes prompted dissimilar activities, such as the production of IL-1ß in monocytic cells via both NLRP3 pathway-dependent and pathway-independent mechanisms. This study, therefore, reveals the adverse role of LL-37 in dental plaque, where it binds bacterial DNA to form complexes that may precipitate to behave like an extracellular matrix. Furthermore, the unveiled stimulating properties and species-dependent activities of the oral bacterial DNA-LL-37 complexes enrich our understanding of dental plaque pathogenicity and periodontal innate immune responses.
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Placa Dental , Humanos , ADN Bacteriano , Placa Dental/microbiología , Porphyromonas gingivalis/genética , Fusobacterium nucleatum , ADNRESUMEN
We report the first study of electrical resistivity, magnetization, and specific heat on YbCo2. The measurements on a single-phased sample of YbCo2bring no evidence of magnetic ordering down to 0.3 K in a zero magnetic field. The manifestations of low Kondo temperature are observed. The specific heat value divided by temperature,C/T, keeps increasing logarithmically beyond 7 J/mol K2with decreasing temperature down to 0.3 K without no sign of magnetic ordering, suggesting a very large electronic specific heat. Analysis of the magnetic specific heat indicates that the large portion of the low-temperature specific heat is not explained simply by the low Kondo temperature but is due to the strong intersite magnetic correlation in both the 3dand 4felectrons. Temperature-dependent measurements under static magnetic fields up to 7 T are carried out, which show the evolution of field-induced transition above 2 T. The transition temperature increases with increasing field, pointing to a ferromagnetic character. The extrapolation of the transition temperature to zero field suggests that YbCo2is in the very proximity of the quantum critical point. These results indicate that in the unique case of YbCo2, the itinerant electron magnetism of Co 3d-electrons and the Kondo effect within the vicinity of quantum criticality of Yb 4f-local moments can both play a role.
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BACKGROUND AND AIMS: Epigenetic modifications are associated with hepatic fat accumulation and non-alcoholic fatty liver disease (NAFLD). However, few epigenetic modifications directly implicated in such processes have been identified during adolescence, a critical developmental window where physiological changes could influence future disease trajectory. To investigate the association between DNA methylation and NAFLD in adolescence, we undertook discovery and validation of novel methylation marks, alongside replication of previously reported marks. APPROACH AND RESULTS: We performed a DNA methylation epigenome-wide association study (EWAS) on DNA from whole blood from 707 Raine Study adolescents phenotyped for steatosis score and NAFLD by ultrasound at age 17. Next, we performed pyrosequencing validation of loci within the most 100 strongly associated differentially methylated CpG sites (dmCpGs) for which ≥ 2 probes per gene remained significant across four statistical models with a nominal p value < 0.007. EWAS identified dmCpGs related to three genes (ANK1, MIR10a, PTPRN2) that met our criteria for pyrosequencing. Of the dmCpGs and surrounding loci that were pyrosequenced (ANK1 n = 6, MIR10a n = 7, PTPRN2 n = 3), three dmCpGs in ANK1 and two in MIR10a were significantly associated with NAFLD in adolescence. After adjustment for waist circumference only dmCpGs in ANK1 remained significant. These ANK1 CpGs were also associated with γ-glutamyl transferase and alanine aminotransferase concentrations. Three of twenty-two differentially methylated dmCpGs previously associated with adult NAFLD were associated with NAFLD in adolescence (all adjusted p < 2.3 × 10-3). CONCLUSIONS: We identified novel DNA methylation loci associated with NAFLD and serum liver biochemistry markers during adolescence, implicating putative dmCpG/gene regulatory pathways and providing insights for future mechanistic studies.
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Metilación de ADN , Enfermedad del Hígado Graso no Alcohólico , Adulto , Humanos , Adolescente , Enfermedad del Hígado Graso no Alcohólico/genética , Epigénesis Genética , ADN , BiomarcadoresRESUMEN
Bright, short-pulsed neutron beams from laser-driven neutron sources (LANSs) provide a new perspective on material screening via fast neutron activation analysis (FNAA). FNAA is a nondestructive technique for determining material elemental composition based on nuclear excitation by fast neutron bombardment and subsequent spectral analysis of prompt γ-rays emitted by the active nuclei. Our recent experiments and simulations have shown that activation analysis can be used in practice with modest neutron fluences on the order of 105 n/cm2, which is available with current laser technology. In addition, time-resolved γ-ray measurements combined with picosecond neutron probes from LANSs are effective in mitigating the issue of spectral interference between elements, enabling highly accurate screening of complex samples containing many elements. This paper describes the predictive capability of LANS-based activation analysis based on experimental demonstrations and spectral calculations with Monte Carlo simulations.
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STUDY QUESTION: Is the cardiometabolic health of adolescents conceived through ART worse than that of their counterparts conceived without ART? SUMMARY ANSWER: The majority of cardiometabolic and vascular health parameters of adolescents conceived through ART are similar or more favourable, than those of their counterparts of similar age and conceived without ART. WHAT IS KNOWN ALREADY: It has been proposed that the cardiometabolic health of offspring conceived with ART may be unfavourable compared to that of their counterparts conceived without ART. The literature pertaining to cardiometabolic health of offspring conceived after ART is contradictory, but generally suggests unfavourable cardiometabolic health parameters, such as an increase in blood pressure (BP), vascular dysfunction and adiposity, as well as unfavourable glucose and lipid profiles. With over 8 million children and adults born through ART worldwide, it is important to investigate whether these early signs of adverse cardiometabolic differences persist into adolescence and beyond. STUDY DESIGN, SIZE, DURATION: The Growing Up Healthy Study (GUHS) is a prospective cohort study that recruited 303 adolescents and young adults conceived after ART (aged 13-21 years) and born between 1991 and 2001 in Western Australia. Their health parameters, including cardiometabolic factors, were assessed and compared with counterparts from the Raine Study Generation 2 (Gen2). The 2868 Gen2 participants were born 1989-1992 and are representative of the Western Australian adolescent population. At â¼17 years of age (2013-2017), 163 GUHS participants replicated assessments previously completed by Gen2 at a similar age. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cardiometabolic parameters were compared between a total of 163 GUHS and 1457 Gen2 adolescents. Separate male (GUHS n = 81, Gen2 n = 735) and female (GUHS n = 82, Gen2 n = 722) analyses were conducted. Assessments consisted of a detailed questionnaire including health, lifestyle and demographic parameters, anthropometric assessments (height, weight, BMI, waist circumference and skinfold thickness), fasting serum biochemistry, arterial stiffness and BP (assessed using applanation tonometry). Abdominal ultrasonography was used to assess the presence and severity of hepatic steatosis, and thickness of abdominal fat compartments. Non-alcoholic fatty liver disease (NAFLD) was diagnosed if there was sonographic fatty liver in the absence of significant alcohol consumption. Chi2, Fisher's exact and Mann-Whitney U tests, performed in SPSS V25, examined cohort differences and generalized estimating equations adjusted for the following covariates: singleton vs non-singleton pregnancy, birthweight (z-score), gestational age, BMI, smoking, alcohol consumption in the past 6 months and parent cardiovascular status. Arterial stiffness measures and waist circumference were additionally adjusted for height, and female analyses were additionally adjusted for use of oral contraceptives in the preceding 6 months. MAIN RESULTS AND THE ROLE OF CHANCE: In adjusted analyses, GUHS females had a lower BMI (22.1 vs 23.3 kg/m2, P = 0.014), and thinner skinfolds (triceps, subscapular, mid-abdominal; 16.9 vs 18.7 mm, P = 0.021, 13.4 vs 15.0 mm, P = 0.027, 19.7 vs 23.2 mm, P < 0.001, respectively), whereas males were not significantly different. Waist circumference was lower in GUHS adolescents (males: 78.1 vs 81.3 cm, P = 0.008, females: 76.7 vs 83.3 cm, P = 0.007). There were no significant differences between the two groups in glucose, insulin, homeostatic model assessment for insulin resistance, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), alanine aminotransferase and high-sensitivity C-reactive protein in both sexes. In females, serum triglycerides were lower in GUHS adolescents (1.0 vs 1.2 mmol/l, P = 0.029). GUHS males had higher serum HDL-C (1.1 vs 1.0 mmol/l, P = 0.004) and a lower TC/HDL-C ratio (3.2 vs 3.6, P = 0.036). There were no significant differences in the prevalence of NAFLD or steatosis severity scores between the cohorts in males and females. GUHS females had less subcutaneous adipose tissue (9.4 vs 17.9 mm, P < 0.001), whereas GUHS males had greater visceral adipose thickness (44.7 vs 36.3 mm, P < 0.001). There was no significant difference in pre-peritoneal adipose thickness. Pulse wave velocity was lower in GUHS males (5.8 vs 6.3 m/s, P < 0.001) and heart rate corrected augmentation index was lower in GUHS females (-8.4 vs -2.7%, P = 0.048). There were no significant differences in BP or heart rate in males or females between the two groups. LIMITATIONS, REASONS FOR CAUTION: Despite the substantial study size and the unique study design of the ART cohort, we were unable to differentiate between different types of ART, due to the low number of ICSI cycles (e.g. IVF vs ICSI), draw definite conclusions, or relate the outcomes to the cause of infertility. Considering the differences in time points when both cohorts were studied, external factors could have changed, which could not be accounted for. Given the observational nature of this study, causation cannot be proven. WIDER IMPLICATIONS OF THE FINDINGS: Contrary to our hypothesis and previous findings focussing mainly on childhood, this study reports mostly similar or favourable cardiometabolic markers in adolescents conceived with ART compared to those conceived without ART. The greater visceral adipose thickness, particularly present in males, requires further investigation. While these findings are generally reassuring, future well-designed and appropriately powered studies are required to definitively address the issue of cardiometabolic health in ART adults. STUDY FUNDING/COMPETING INTEREST(S): This project was supported by NHMRC project grant number 1042269 and R.J.H. received education grant funding support from Ferring Pharmaceuticals. R.J.H. is the Medical Director of Fertility Specialists of Western Australia and a shareholder in Western IVF. He has received educational sponsorship from MSD, Merck-Serono and Ferring Pharmaceuticals. P.B. is the Scientific Director of Concept Fertility Centre, Subiaco, Western Australia. J.L.Y. is the Medical Director of PIVET Medical Centre, Perth, Western Australia. TRIAL REGISTRATION NUMBER: N/A.
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Enfermedades Cardiovasculares , Enfermedad del Hígado Graso no Alcohólico , Adolescente , Australia , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Niño , Estudios de Cohortes , Femenino , Fertilización In Vitro/métodos , Glucosa , Humanos , Masculino , Embarazo , Estudios Prospectivos , Análisis de la Onda del Pulso , Adulto JovenRESUMEN
OBJECTIVES: This study aimed to investigate whether inflammation affects the outcome of swallowing ability to improve treatment for sarcopenic dysphagia. DESIGN: A retrospective observational cohort study was performed using data from the Japanese sarcopenic dysphagia database. SETTING: The database was constructed using data from 19 hospitals and one home visiting rehabilitation team. PARTICIPANTS: Patients with sarcopenic dysphagia with measurements of C-reactive protein (CRP) and serum albumin (Alb) were included. MEASUREMENTS: Patients were assigned to two groups using CRP, Alb, and the Japanese modified Glasgow Prognostic Score (mGPS). The Food Intake LEVEL Scale (FILS) was measured at the times of admission and follow-up (FILS follow-up) to assess swallowing function. RESULTS: A total of 197 patients were included. Mean or median values of each parameter were as follows: age: 83.8±8.7, Alb: 3.2 ± 0.6 g/dL, CRP: 8.0 [3.0, 29.0] mg/L, mGPS: 1 [1-2], FILS: 7 [6-8], FILS follow-up: 8 [7-8], and duration of follow-up: 57.0 [27.0, 85.0] days. The FILS score at follow-up was significantly lower in the high CRP group (≥ 5.0 mg/L) than in the low CRP group (< 5.0 mg/L) (p = 0.01). Further, the FILS score at follow-up was significantly lower in the high mGPS group (class; 2) than in the low mGPS group (class; 0 and 1) (p = 0.03). In the multiple linear regression analyses without FILS at baseline, CRP and mGPS were independent risk factors for FILS follow-up. When FILS at baseline was entered, CRP and mGPS were not an independent risk factors for FILS follow-up. CONCLUSIONS: Inflammation could modify the outcome of the patients with sarcopenic dysphagia. Inflammation may be an important risk factor in evaluating patients with sarcopenic dysphagia.
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Trastornos de Deglución , Sarcopenia , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/análisis , Deglución , Trastornos de Deglución/complicaciones , Trastornos de Deglución/rehabilitación , Humanos , Inflamación/complicaciones , Pronóstico , Estudios Retrospectivos , Sarcopenia/complicacionesRESUMEN
OBJECTIVES: To investigate the prevalence of hoarseness and its association with the severity of dysphagia in patients with sarcopenic dysphagia. DESIGN: Cross-sectional study using the Japanese sarcopenic dysphagia database. SETTING: 19 hospitals including 9 acute care hospitals, 8 rehabilitation hospitals, 2 long-term care hospitals, and 1 home visit rehabilitation team. PARTICIPANTS: 287 patients with sarcopenic dysphagia, aged 20 years and older. MEASUREMENTS: Sarcopenic dysphagia was diagnosed using a reliable and validated diagnostic algorithm for the condition. The presence and characteristics of hoarseness classified as breathy, rough, asthenic, and strained were assessed. The prevalence of hoarseness and the relationship between hoarseness and Food Intake LEVEL Scale (FILS) were examined. Order logistic regression analysis adjusted for age, sex, naso-gastric tube, and handgrip strength was used to examine the relationship between hoarseness and FILS at baseline and at follow-up. RESULTS: The mean age was 83 ± 10 years. Seventy-four (26%) patients had hoarseness, while 32 (11%), 20 (7%), 22 (8%), and 0 (0%) patients had breathy, rough, asthenic, and strained hoarseness, respectively. Median FILS at the initial evaluation was 7 (interquartile range, 5-8). Hoarseness (ß=0.747, 95% confidence intervals= 0.229, 1.265, p=0.005), age, sex, naso-gastric tube, and handgrip strength were associated independently with baseline FILS, while hoarseness (ß=0.213, 95% confidence intervals= -0.324, 0.750, p=0.438) was not associated independently with the FILS at follow-up. CONCLUSIONS: Hoarseness was associated with the severity of dysphagia at baseline, however not a prognostic factor for sarcopenic dysphagia. Resistance training of swallowing and respiratory muscles and voice training as part of rehabilitation nutrition might be useful for treating sarcopenic dysphagia.
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Trastornos de Deglución , Sarcopenia , Anciano , Anciano de 80 o más Años , Astenia/complicaciones , Estudios Transversales , Trastornos de Deglución/complicaciones , Trastornos de Deglución/epidemiología , Fuerza de la Mano , Ronquera/complicaciones , Ronquera/epidemiología , Humanos , Prevalencia , Sarcopenia/complicaciones , Sarcopenia/diagnóstico , Sarcopenia/epidemiologíaRESUMEN
Molecular subtyping in gastrointestinal stromal tumours is a useful method for predicting the efficacy of treatment using tyrosine kinase inhibitors in humans. However, owing to the paucity of reports on mutational analyses, the association between genetic mutations and the therapeutic response to tyrosine kinase inhibitors remains unclear in feline gastrointestinal stromal tumours. In this report, we describe the case of a cat with a gastrointestinal stromal tumour which was unresponsive to tyrosine kinase inhibitors. A mutational analysis revealed that the cat lacked mutations in both the KIT and platelet-derived growth factor receptor-alpha (PDGFRA) genes. Our findings are consistent with the fact that KIT/PDGFRA wild-type gastrointestinal stromal tumours are less responsive to tyrosine kinase inhibitors in humans. This signifies the need for further evaluation and possibly individualised treatment for gastrointestinal stromal tumours in cats on the basis of mutational analyses.
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Enfermedades de los Gatos , Tumores del Estroma Gastrointestinal , Animales , Enfermedades de los Gatos/tratamiento farmacológico , Enfermedades de los Gatos/genética , Gatos , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/genética , Tumores del Estroma Gastrointestinal/veterinaria , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/metabolismo , Proteínas Proto-Oncogénicas c-kit/uso terapéutico , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genéticaRESUMEN
Epigenetics links perinatal influences with later obesity. We identifed differentially methylated CpG (dmCpG) loci measured at 17 years associated with concurrent adiposity measures and examined whether these were associated with hsCRP, adipokines, and early life environmental factors. Genome-wide DNA methylation from 1192 Raine Study participants at 17 years, identified 29 dmCpGs (Bonferroni corrected p < 1.06E-07) associated with body mass index (BMI), 10 with waist circumference (WC) and 9 with subcutaneous fat thickness. DmCpGs within Ras Association (RalGDS/AF-6), Pleckstrin Homology Domains 1 (RAPH1), Musashi RNA-Binding Protein 2 (MSI2), and solute carrier family 25 member 10 (SLC25A10) are associated with both BMI and WC. Validation by pyrosequencing confirmed these associations and showed that MSI2 , SLC25A10 , and RAPH1 methylation was positively associated with serum leptin. These were also associated with the early environment; MSI2 methylation (ß = 0.81, p = 0.0004) was associated with pregnancy maternal smoking, SLC25A10 (CpG2 ß = 0.12, p = 0.002) with pre- and early pregnancy BMI, and RAPH1 (ß = -1.49, p = 0.036) with gestational weight gain. Adjusting for perinatal factors, methylation of the dmCpGs within MSI2, RAPH1, and SLC25A10 independently predicted BMI, accounting for 24% of variance. MSI2 methylation was additionally associated with BMI over time (17 years old ß = 0.026, p = 0.0025; 20 years old ß = 0.027, p = 0.0029) and between generations (mother ß = 0.044, p = 7.5e-04). Overall findings suggest that DNA methylation in MSI2, RAPH1, and SLC25A10 in blood may be robust markers, mediating through early life factors.