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1.
Nature ; 626(7998): 335-340, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38233526

RESUMEN

Predators have a key role in structuring ecosystems1-4. However, predator loss is accelerating globally4-6, and predator mass-mortality events7 (MMEs)-rapid large-scale die-offs-are now emblematic of the Anthropocene epoch6. Owing to their rare and unpredictable nature7, we lack an understanding of how MMEs immediately impact ecosystems. Past predator-removal studies2,3 may be insufficient to understand the ecological consequences of MMEs because, in nature, dead predators decompose in situ and generate a resource pulse8, which could alter ensuing ecosystem dynamics by temporarily enhancing productivity. Here we experimentally induce MMEs in tritrophic, freshwater lake food webs and report ecological dynamics that are distinct from predator losses2,3 or resource pulses9 alone, but that can be predicted from theory8. MMEs led to the proliferation of diverse consumer and producer communities resulting from weakened top-down predator control1-3 and stronger bottom-up effects through predator decomposition8. In contrast to predator removals alone, enhanced primary production after MMEs dampened the consumer community response. As a consequence, MMEs generated biomass dynamics that were most similar to those of undisturbed systems, indicating that they may be cryptic disturbances in nature. These biomass dynamics led to trophic decoupling, whereby the indirect beneficial effects of predators on primary producers are lost and later materialize as direct bottom-up effects that stimulate primary production amid intensified herbivory. These results reveal ecological signatures of MMEs and demonstrate the feasibility of forecasting novel ecological dynamics arising with intensifying global change.


Asunto(s)
Biomasa , Ecología , Cadena Alimentaria , Conducta Predatoria , Animales , Herbivoria/fisiología , Lagos , Conducta Predatoria/fisiología , Densidad de Población , Predicción , Ecología/métodos , Cambio Climático
2.
Proc Natl Acad Sci U S A ; 121(33): e2310157121, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39102539

RESUMEN

The Amazon forest contains globally important carbon stocks, but in recent years, atmospheric measurements suggest that it has been releasing more carbon than it has absorbed because of deforestation and forest degradation. Accurately attributing the sources of carbon loss to forest degradation and natural disturbances remains a challenge because of the difficulty of classifying disturbances and simultaneously estimating carbon changes. We used a unique, randomized, repeated, very high-resolution airborne laser scanning survey to provide a direct, detailed, and high-resolution partitioning of aboveground carbon gains and losses in the Brazilian Arc of Deforestation. Our analysis revealed that disturbances directly attributed to human activity impacted 4.2% of the survey area while windthrows and other disturbances affected 2.7% and 14.7%, respectively. Extrapolating the lidar-based statistics to the study area (544,300 km2), we found that 24.1, 24.2, and 14.5 Tg C y-1 were lost through clearing, fires, and logging, respectively. The losses due to large windthrows (21.5 Tg C y-1) and other disturbances (50.3 Tg C y-1) were partially counterbalanced by forest growth (44.1 Tg C y-1). Our high-resolution estimates demonstrated a greater loss of carbon through forest degradation than through deforestation and a net loss of carbon of 90.5 ± 16.6 Tg C y-1 for the study region attributable to both anthropogenic and natural processes. This study highlights the role of forest degradation in the carbon balance for this critical region in the Earth system.


Asunto(s)
Carbono , Conservación de los Recursos Naturales , Bosques , Brasil/epidemiología , Carbono/metabolismo , Humanos , Árboles/crecimiento & desarrollo , Ciclo del Carbono
3.
Proc Natl Acad Sci U S A ; 120(33): e2302661120, 2023 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-37549288

RESUMEN

Polycystic Echinococcosis (PE), a neglected life-threatening zoonotic disease caused by the cestode Echinococcus vogeli, is endemic in the Amazon. Despite being treatable, PE reaches a case fatality rate of around 29% due to late or missed diagnosis. PE is sustained in Pan-Amazonia by a complex sylvatic cycle. The hunting of its infected intermediate hosts (especially the lowland paca Cuniculus paca) enables the disease to further transmit to humans, when their viscera are improperly handled. In this study, we compiled a unique dataset of host occurrences (~86000 records) and disease infections (~400 cases) covering the entire Pan-Amazonia and employed different modeling and statistical tools to unveil the spatial distribution of PE's key animal hosts. Subsequently, we derived a set of ecological, environmental, climatic, and hunting covariates that potentially act as transmission risk factors and used them as predictors of two independent Maximum Entropy models, one for animal infections and one for human infections. Our findings indicate that temperature stability promotes the sylvatic circulation of the disease. Additionally, we show how El Niño-Southern Oscillation (ENSO) extreme events disrupt hunting patterns throughout Pan-Amazonia, ultimately affecting the probability of spillover. In a scenario where climate extremes are projected to intensify, climate change at regional level appears to be indirectly driving the spillover of E. vogeli. These results hold substantial implications for a wide range of zoonoses acquired at the wildlife-human interface for which transmission is related to the manipulation and consumption of wild meat, underscoring the pressing need for enhanced awareness and intervention strategies.


Asunto(s)
Equinococosis , Echinococcus , Animales , Humanos , Punto Alto de Contagio de Enfermedades , Equinococosis/epidemiología , Zoonosis/epidemiología , Factores de Riesgo , El Niño Oscilación del Sur
4.
Hepatology ; 80(1): 152-162, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38446707

RESUMEN

BACKGROUND AND AIMS: High levels of serum matrix metalloproteinase-7 (MMP-7) have been linked to biliary atresia (BA), with wide variation in concentration cutoffs. We investigated the accuracy of serum MMP-7 as a diagnostic biomarker in a large North American cohort. APPROACH AND RESULTS: MMP-7 was measured in serum samples of 399 infants with cholestasis in the Prospective Database of Infants with Cholestasis study of the Childhood Liver Disease Research Network, 201 infants with BA and 198 with non-BA cholestasis (age median: 64 and 59 days, p = 0.94). MMP-7 was assayed on antibody-bead fluorescence (single-plex) and time resolved fluorescence energy transfer assays. The discriminative performance of MMP-7 was compared with other clinical markers. On the single-plex assay, MMP-7 generated an AUROC of 0.90 (CI: 0.87-0.94). At cutoff 52.8 ng/mL, it produced sensitivity = 94.03%, specificity = 77.78%, positive predictive value = 64.46%, and negative predictive value = 96.82% for BA. AUROC for gamma-glutamyl transferase = 0.81 (CI: 0.77-0.86), stool color = 0.68 (CI: 0.63-0.73), and pathology = 0.84 (CI: 0.76-0.91). Logistic regression models of MMP-7 with other clinical variables individually or combined showed an increase for MMP-7+gamma-glutamyl transferase AUROC to 0.91 (CI: 0.88-0.95). Serum concentrations produced by time resolved fluorescence energy transfer differed from single-plex, with an optimal cutoff of 18.2 ng/mL. Results were consistent within each assay technology and generated similar AUROCs. CONCLUSIONS: Serum MMP-7 has high discriminative properties to differentiate BA from other forms of neonatal cholestasis. MMP-7 cutoff values vary according to assay technology. Using MMP-7 in the evaluation of infants with cholestasis may simplify diagnostic algorithms and shorten the time to hepatoportoenterostomy.


Asunto(s)
Atresia Biliar , Biomarcadores , Metaloproteinasa 7 de la Matriz , Humanos , Metaloproteinasa 7 de la Matriz/sangre , Atresia Biliar/diagnóstico , Atresia Biliar/sangre , Biomarcadores/sangre , Lactante , Femenino , Masculino , Recién Nacido , Estudios de Cohortes , Colestasis/diagnóstico , Colestasis/sangre , Estudios Prospectivos
5.
Clin Gastroenterol Hepatol ; 22(5): 1024-1036.e2, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38145725

RESUMEN

BACKGROUND & AIMS: PNPLA3 G-allele is an important determinant of disease severity in nonalcoholic fatty liver disease (NAFLD). Here, we investigated the effect of age, body mass index (BMI), and type 2 diabetes mellitus (T2DM) on the relationship between PNPLA3 G-allele and advanced fibrosis in adults and children with histologically characterized NAFLD. METHODS: A total of 1047 children and 2057 adults were included. DNA was genotyped for rs738409 in duplicate. Primary outcome of interest was advanced fibrosis (fibrosis stage ≥3). Regression analyses were performed after controlling for relevant covariates. An additive model was used to assess the effect of PNPLA3 G-allele (CC vs CG vs GG). RESULTS: PNPLA3 G-allele was significantly associated with advanced fibrosis in children (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.16-2.09) and adults (OR, 1.55; 95% CI, 1.16-1.54). Across the cohort, older age significantly increased the risk for advanced fibrosis for PNPLA3 CC (OR, 1.019; 95% CI, 1.013-1.026), CG (OR, 1.024; 95% CI, 1.018-1.030), and GG (OR, 1.03; 95% CI, 1.023-1.037) genotypes. BMI significantly increased the relationship between PNPLA3 genotypes and advanced fibrosis in children and adults. A BMI of 30 kg/m2 was the cutoff beyond which PNPLA3 G-allele had exponential effect on the risk for advanced fibrosis in children and adults. T2DM significantly worsened the relationship between PNPLA3 G-allele and advanced fibrosis in children and adults (interaction P < .01 for both). CONCLUSIONS: Age, BMI, and T2DM modify the risk of advanced fibrosis associated with PNPLA3 G-allele. Preventing or reversing T2DM and obesity in persons carrying PNPLA3 G-allele may lower the risk for advanced fibrosis in NAFLD.


Asunto(s)
Aciltransferasas , Índice de Masa Corporal , Diabetes Mellitus Tipo 2 , Lipasa , Cirrosis Hepática , Proteínas de la Membrana , Enfermedad del Hígado Graso no Alcohólico , Fosfolipasas A2 Calcio-Independiente , Humanos , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/patología , Lipasa/genética , Proteínas de la Membrana/genética , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Masculino , Adulto , Niño , Persona de Mediana Edad , Adolescente , Factores de Edad , Cirrosis Hepática/genética , Adulto Joven , Anciano , Genotipo , Predisposición Genética a la Enfermedad
6.
Hepatology ; 2023 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-37870272

RESUMEN

BACKGROUND AND AIMS: Liver fibrosis is common in children with NAFLD and is an important determinant of outcomes. High-performing noninvasive models to assess fibrosis in children are needed. The objectives of this study were to evaluate the performance of existing pediatric and adult fibrosis prediction models and to develop a clinical prediction rule for identifying moderate-to-severe fibrosis in children with NAFLD. APPROACH AND RESULTS: We enrolled children with biopsy-proven NAFLD in the Nonalcoholic Steatohepatitis Clinical Research Network within 90 days of liver biopsy. We staged liver fibrosis in consensus using the Nonalcoholic Steatohepatitis Clinical Research Network scoring system. We evaluated existing pediatric and adult models for fibrosis and developed a new pediatric model using the least absolute shrinkage and selection operator with linear and spline terms for discriminating moderate-to-severe fibrosis from none or mild fibrosis. The model was internally validated with 10-fold cross-validation. We evaluated 1055 children with NAFLD, of whom 26% had moderate-to-severe fibrosis. Existing models performed poorly in classifying fibrosis in children, with area under the receiver operator curves (AUC) ranging from 0.57 to 0.64. In contrast, our new model, fibrosis in pediatric NAFLD was derived from fourteen common clinical variables and had an AUC of 0.79 (95% CI: 0.77-0.81) with 72% sensitivity and 76% specificity for identifying moderate-to-severe fibrosis. CONCLUSION: Existing fibrosis prediction models have limited clinical utility in children with NAFLD. Fibrosis in pediatric NAFLD offers improved performance characteristics for risk stratification by identifying moderate-to-severe fibrosis in children with NAFLD.

7.
Hepatology ; 77(1): 197-212, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-35560106

RESUMEN

BACKGROUND AND AIMS: NAFLD is the most common chronic liver disease in children. Large pediatric studies identifying single nucleotide polymorphisms (SNPs) associated with risk and histologic severity of NAFLD are limited. Study aims included investigating SNPs associated with risk for NAFLD using family trios and association of candidate alleles with histologic severity. APPROACH AND RESULTS: Children with biopsy-confirmed NAFLD were enrolled from the NASH Clinical Research Network. The Expert Pathology Committee reviewed liver histology. Genotyping was conducted with allele-specific primers for 60 candidate SNPs. Parents were enrolled for trio analysis. To assess risk for NAFLD, the transmission disequilibrium test was conducted in trios. Among cases, regression analysis assessed associations with histologic severity. A total of 822 children with NAFLD had mean age 13.2 years (SD 2.7) and mean ALT 101 U/L (SD 90). PNPLA3 (rs738409) demonstrated the strongest risk ( p = 2.24 × 10 -14 ) for NAFLD. Among children with NAFLD, stratifying by PNPLA3 s738409 genotype, the variant genotype associated with steatosis ( p = 0.005), lobular ( p = 0.03) and portal inflammation ( p = 0.002). Steatosis grade associated with TM6SF2 ( p = 0.0009), GCKR ( p = 0.0032), PNPLA3 rs738409 ( p = 0.0053), and MTTP ( p = 0.0051). Fibrosis stage associated with PARVB rs6006473 ( p = 0.0001), NR1I2 ( p = 0.0021), ADIPOR2 ( p = 0.0038), and OXTR ( p = 0.0065). PNPLA3 rs738409 ( p = 0.0002) associated with borderline zone 1 NASH. CONCLUSIONS: This study demonstrated disease-associated SNPs in children with NAFLD. In particular, rs6006473 was highly associated with severity of fibrosis. These hypothesis-generating results support future mechanistic studies of development of adverse outcomes such as fibrosis and generation of therapeutic targets for NAFLD in children.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Humanos , Niño , Adolescente , Enfermedad del Hígado Graso no Alcohólico/patología , Hígado/patología , Genotipo , Fibrosis , Polimorfismo de Nucleótido Simple , Predisposición Genética a la Enfermedad
8.
Hepatology ; 77(3): 862-873, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36131538

RESUMEN

BACKGROUND AND AIMS: In biliary atresia, serum bilirubin is commonly used to predict outcomes after Kasai portoenterostomy (KP). Infants with persistently high levels invariably need liver transplant, but those achieving normalized levels have a less certain disease course. We hypothesized that serum bile acid levels could help predict outcomes in the latter group. APPROACH AND RESULTS: Participants with biliary atresia from the Childhood Liver Disease Research Network were included if they had normalized bilirubin levels 6 months after KP and stored serum samples from the 6-month post-KP clinic visit ( n  = 137). Bile acids were measured from the stored serum samples and used to divide participants into ≤40 µmol/L ( n  = 43) or >40 µmol/L ( n  = 94) groups. At 2 years of age, the ≤40 µmol/L compared with >40 µmol/L group had significantly lower total bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, bile acids, and spleen size, as well as significantly higher albumin and platelet counts. Furthermore, during 734 person-years of follow-up, those in the ≤40 µmol/L group were significantly less likely to develop splenomegaly, ascites, gastrointestinal bleeding, or clinically evident portal hypertension. The ≤40 µmol/L group had a 10-year cumulative incidence of liver transplant/death of 8.5% (95% CI: 1.1%-26.1%), compared with 42.9% (95% CI: 28.6%-56.4%) for the >40 µmol/L group ( p  = 0.001). CONCLUSIONS: Serum bile acid levels may be a useful prognostic biomarker for infants achieving normalized bilirubin levels after KP.


Asunto(s)
Atresia Biliar , Lactante , Humanos , Niño , Atresia Biliar/cirugía , Portoenterostomía Hepática , Pronóstico , Bilirrubina , Ácidos y Sales Biliares , Biomarcadores , Resultado del Tratamiento , Estudios Retrospectivos
9.
Hepatology ; 77(2): 530-545, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36069569

RESUMEN

BACKGROUND AND AIMS: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis. APPROACH AND RESULTS: A targeted enzyme-linked immunosorbent assay-based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL-8, endoglin, periostin, Mac-2-binding protein, MMP-3, and MMP-7) was examined in children with biliary atresia (BA; n = 187), alpha-1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM were 9 years and 9.5 kPa. After adjusting for covariates, there were positive correlations among LSM and endoglin ( p = 0.04) and IL-8 ( p < 0.001) and MMP-7 ( p < 0.001) in participants with BA. The best prediction model for LSM in BA using clinical and lab measurements had an R2 = 0.437; adding IL-8 and MMP-7 improved R2 to 0.523 and 0.526 (both p < 0.0001). In participants with A1AT, CTGF and LSM were negatively correlated ( p = 0.004); adding CTGF to an LSM prediction model improved R2 from 0.524 to 0.577 ( p = 0.0033). Biomarkers did not correlate with LSM in ALGS. A significant number of biomarker/lab correlations were found in participants with BA but not those with A1AT or ALGS. CONCLUSIONS: Endoglin, IL-8, and MMP-7 significantly correlate with increased LSM in children with BA, whereas CTGF inversely correlates with LSM in participants with A1AT; these biomarkers appear to enhance prediction of LSM beyond clinical tests. Future disease-specific investigations of change in these biomarkers over time and as predictors of clinical outcomes will be important.


Asunto(s)
Síndrome de Alagille , Colestasis , Diagnóstico por Imagen de Elasticidad , Hepatopatías , Humanos , Niño , Hígado/patología , Metaloproteinasa 7 de la Matriz , Endoglina , Interleucina-8 , Colestasis/patología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/patología , Hepatopatías/patología , Biomarcadores , Síndrome de Alagille/patología
10.
Glob Chang Biol ; 30(3): e17203, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38433341

RESUMEN

Microbes affect the global carbon cycle that influences climate change and are in turn influenced by environmental change. Here, we use data from a long-term whole-ecosystem warming experiment at a boreal peatland to answer how temperature and CO2 jointly influence communities of abundant, diverse, yet poorly understood, non-fungi microbial Eukaryotes (protists). These microbes influence ecosystem function directly through photosynthesis and respiration, and indirectly, through predation on decomposers (bacteria and fungi). Using a combination of high-throughput fluid imaging and 18S amplicon sequencing, we report large climate-induced, community-wide shifts in the community functional composition of these microbes (size, shape, and metabolism) that could alter overall function in peatlands. Importantly, we demonstrate a taxonomic convergence but a functional divergence in response to warming and elevated CO2 with most environmental responses being contingent on organismal size: warming effects on functional composition are reversed by elevated CO2 and amplified in larger microbes but not smaller ones. These findings show how the interactive effects of warming and rising CO2 levels could alter the structure and function of peatland microbial food webs-a fragile ecosystem that stores upwards of 25% of all terrestrial carbon and is increasingly threatened by human exploitation.


Asunto(s)
Dióxido de Carbono , Ecosistema , Humanos , Temperatura , Eucariontes , Carbono
11.
Phys Rev Lett ; 132(18): 183802, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38759187

RESUMEN

The ability to tailor with a high accuracy the intersite connectivity in a lattice is a crucial tool for realizing novel topological phases of matter. Here, we report the experimental realization of photonic dimer chains with long-range hopping terms of arbitrary strength and phase, providing a rich generalization of the Su-Schrieffer-Heeger model which, in its conventional form, is limited to nearest-neighbor couplings only. Our experiment is based on a synthetic dimension scheme involving the frequency modes of an optical fiber loop platform. This setup provides direct access to both the band dispersion and the geometry of the Bloch wave functions throughout the entire Brillouin zone allowing us to extract the winding number for any possible configuration. Finally, we highlight a topological phase transition solely driven by a time-reversal-breaking synthetic gauge field associated with the phase of the long-range hopping, providing a route for engineering topological bands in photonic lattices belonging to the AIII symmetry class.

12.
Am J Public Health ; : e1-e4, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39208357

RESUMEN

Objectives. To document the prevalence of long COVID among a sample of survey respondents with long-term disabilities that existed before 2020 and to compare the prevalence among this group with that among the general population. Methods. We conducted a cross-sectional, descriptive study using data from the 2022 National Survey on Health and Disability (n = 2262) and comparative data for the general population from the federal Household Pulse Survey (HPS). Results. The prevalence of long COVID was higher among people with preexisting disabilities than in the general population (40.6% vs 18.9%). Conclusions. People with preexisting disabilities experienced and continue to experience increased exposure to COVID-19 and barriers to accessing health care, COVID-19 vaccines, and COVID-19 tests. These barriers, combined with long-standing health disparities in this population, may have contributed to the greater prevalence of long COVID among people with disabilities. Public Health Implications. The needs of people with disabilities must be centered in the response to the COVID-19 pandemic and future pandemics. (Am J Public Health. Published online ahead of print August 29, 2024:e1-e4. https://doi.org/10.2105/AJPH.2024.307794).

13.
Artículo en Inglés | MEDLINE | ID: mdl-39282813

RESUMEN

OBJECTIVES: Metabolic dysfunction-associated steatotic liver disease (MASLD) is common in children. We hypothesized environmental toxins could drive progression to metabolic dysfunction-associated steatohepatitis (MASH), and assayed serum toxins and metabolites in children with histologically characterized MASLD/MASH. METHODS: Environmental chemicals, common in household items, perfluoroalkyl substances (PFAS), brominated flame retardants (PBDEs), and metabolic profiles were assayed in children enrolled in the multicenter NASH Clinical Research Network Pediatric Database 2. Mixture models, using repeated holdout weighted quantile sum regression (WQSrh) were run in addition to single chemical/metabolite logistic regression. For metabolomic analyses, random subset version of WQSrh was used for the large number of predictors versus participants. Nominal and false discovery rate (FDR) p-values (two-sided) were computed. RESULTS: Four hundred and thirty-five children distributed across MASH (n = 293) and MASLD (n = 142), with 304 (69.9%) males. Mean (standard deviation) for Nonalcoholic Steatohepatitis Score (NAS) and alanine aminotransferase (ALT) for MASLD were 3.1 (1.0), 67.9 (43.4), and for MASH 4.2 (1.4), 144 (121). There was an inverse association between PFAS/PBDE mixture and MASH versus MASLD, lobular inflammation (p = 0.026), NAS (p = 0.009, FDR p = 0.04), and log-transformed ALT (p = 0.005, FDR p = 0.025) driven by perfluorohexane sulfonate (PFHxS). Metabolites from positive hydrophilic interaction liquid chromatography mode, biliverdin (p = 0.002) and 1-methylhistidine (associated with meat ingestion, p = 0.02) and reverse phase negative mode, hippuric acid (solvent exposure, p = 0.022) significantly associated with MASH. CONCLUSIONS: Significant negative PFAS/PBDE mixture effect and odds of MASH were dominated by PHFXS. Several metabolites are significantly associated with MASH which inform mechanistic pathways and could drive key therapeutic and diagnostic strategies in children.

14.
J Pediatr Gastroenterol Nutr ; 79(2): 238-249, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38828720

RESUMEN

OBJECTIVES: Renal impairment is prevalent in adults with nonalcoholic fatty liver disease (NAFLD/metabolic dysfunction associated steatotic liver disease [MASLD]) and is associated with increased mortality. Pediatric data are limited. Our objective was to determine the prevalence of hyperfiltration or chronic kidney disease (CKD) in children with NAFLD/MASLD and determine links with liver disease severity. METHODS: Data from children who had previously participated in prospective, multicenter, pediatric studies by the Nonalcoholic Steatohepatitis Clinical Research Network (NASH-CRN) were collected. Renal function was determined using the calculated glomerular filtration rate (cGFR). Hyperfiltration was defined as cGFR > 135 mL/min/1.73m2, while CKD stage 2 or higher as cGFR < 90 mL/min/1.73 m2. Renal dysfunction progression was defined as transition from normal to hyperfiltration or to CKD stage ≥ 2, or change in CKD by ≥1 stage. Multinomial logistic regression models were used to determine the prevalence of CKD and independent associations between CKD and liver disease severity. RESULTS: The study included 1164 children (age 13 ± 3 years, 72% male, 71% Hispanic). The median cGFR was 121 mL/min/1.73 m2; 12% had CKD stage 2-5, while 27% had hyperfiltration. Hyperfiltration was independently associated with significant liver fibrosis (odds ratio: 1.45). Baseline renal function was not associated with progression in liver disease over a 2-year period (n = 145). Renal dysfunction worsened in 19% independently of other clinical risk factors. Progression of renal impairment was not associated with change in liver disease severity. CONCLUSIONS: Renal impairment is prevalent in children with NAFLD/MASLD and hyperfiltration is independently associated with significant liver fibrosis. Almost 1/5 children have evidence of progression in renal dysfunction over 2 years, not associated with change in liver disease severity. Future assessments including additional renal impairment biomarkers are needed.


Asunto(s)
Tasa de Filtración Glomerular , Enfermedad del Hígado Graso no Alcohólico , Insuficiencia Renal Crónica , Índice de Severidad de la Enfermedad , Humanos , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Masculino , Femenino , Niño , Prevalencia , Adolescente , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/fisiopatología , Estudios Prospectivos , Progresión de la Enfermedad
15.
Nature ; 553(7688): 307-309, 2018 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-29291597

RESUMEN

Supermassive black holes, with masses more than a million times that of the Sun, seem to inhabit the centres of all massive galaxies. Cosmologically motivated theories of galaxy formation require feedback from these supermassive black holes to regulate star formation. In the absence of such feedback, state-of-the-art numerical simulations fail to reproduce the number density and properties of massive galaxies in the local Universe. There is, however, no observational evidence of this strongly coupled coevolution between supermassive black holes and star formation, impeding our understanding of baryonic processes within galaxies. Here we report that the star formation histories of nearby massive galaxies, as measured from their integrated optical spectra, depend on the mass of the central supermassive black hole. Our results indicate that the black-hole mass scales with the gas cooling rate in the early Universe. The subsequent quenching of star formation takes place earlier and more efficiently in galaxies that host higher-mass central black holes. The observed relation between black-hole mass and star formation efficiency applies to all generations of stars formed throughout the life of a galaxy, revealing a continuous interplay between black-hole activity and baryon cooling.

16.
Pediatr Dev Pathol ; 27(3): 218-227, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38221675

RESUMEN

BACKGROUND: Granulomas in pediatric liver biopsies (GPLB) are rare with the largest pediatric cohort reported over 25 years ago. METHODS: Single-center retrospective study of GPLB. RESULTS: Seventeen liver biopsies from 16 patients with granulomas were identified (9 boys, 56%) with a median age of 13 years (range: 1-18) for which the most common indication was the presence of a nodule/mass (47%). Significant comorbidities were seen in 13 patients (81%) and included: liver transplant (25%), history of a neoplasm (25%), autoimmune hepatitis (6%), Crohn disease (6%), bipolar disorder (6%), severe combined immunodeficiency (6%), and sickle cell disease (6%). Eleven patients were taking multiple medications at the time of biopsy. Granulomas were more commonly pan-acinar (11 cases) followed by subcapsular (4 cases), portal (1 case), and periportal (1 case). Necrosis was seen in 10 cases (59%). GMS stain was positive in 2 cases for Histoplasma-like yeast; microbiological cultures were negative in all cases (no: 4). A 18S and 16S rRNA gene sequencing performed in 15 cases revealed only 1 with a pathogenic microorganism, Mycobacterium angelicum. CONCLUSION: In our experience, GPLB are heterogenous with only 3 cases having an identifiable infectious etiology and many of the remaining cases being associated to multiple medications, suggesting drug-induced liver injury as possible etiology.


Asunto(s)
Granuloma , Hepatopatías , Humanos , Masculino , Niño , Femenino , Adolescente , Estudios Retrospectivos , Preescolar , Lactante , Biopsia , Granuloma/patología , Granuloma/diagnóstico , Hepatopatías/patología , Hepatopatías/diagnóstico , Hígado/patología
17.
Inj Prev ; 30(2): 138-144, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-37945329

RESUMEN

OBJECTIVES: Data on non-fatal injuries and visits to the emergency department (ED) for injuries are not readily available. The objective of this paper is to describe injury-related ED visits for people with intellectual and developmental disabilities who are covered by the Medicaid insurance programme. METHODS: We aggregated 2010-2016 Medicaid claims data from eight states. Using these data, we identified individuals with intellectual and developmental disabilities and then determined an all-cause ED visit rate, ED visit due to injury rate and admission from ED due to injury rate. Data were stratified by sex and age group. Results were compared with national rates. RESULTS: Medicaid members with intellectual and developmental disabilities visited EDs at approximately 1.8 times the rate of the general population. The ED visit rate due to injury was approximately 1.5 times that observed in the population overall. When ED visits due to injury data were stratified by age and sex, the largest discrepancy was observed in women ages 45-64, who visited EDs due to injury at a rate 2.1 times that of women of the same age in the general population. The admission rate from ED due to injury increased over the study period most notably in the older age groups. CONCLUSIONS: While rates and patterns of ED utilisation among Medicaid members with intellectual and developmental disabilities vary by age and gender, our findings suggest this group visits the ED due to injury at rates well above the general population.


Asunto(s)
Seguro , Medicaid , Niño , Estados Unidos/epidemiología , Humanos , Femenino , Anciano , Discapacidades del Desarrollo/epidemiología , Hospitalización , Servicio de Urgencia en Hospital
18.
Eur J Appl Physiol ; 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38849689

RESUMEN

PURPOSE: To evaluate the agreement between the two Gas Exchange Thresholds (GETs = GET1 and GET2), identified by the conventional V-Slope method, and two Respiratory Frequency Thresholds (fRTs = fRT1 and fRT2) obtained from a novel, low-cost, and simple method of breakpoint determination. METHODS: Fifty middle-aged males (age: 50-58 years; V ˙ o2peak: 37.5 ± 8.6 mL·Kg-1·min-1), either healthy or with chronic illnesses, underwent an incremental cycle exercise test to determine maximal oxygen uptake ( V ˙ o2max/ V ˙ o2peak), GETs and fRTs. RESULTS: There were no statistical differences [P > 0.05; ES: 0.17 to 0.32, small] between absolute and relative (56-60% V ˙ o2peak) oxygen uptake ( V ˙ o2) values at GET1 with those obtained at fRT1, nor between V ˙ o2 values at GET2 with those at fRT2 (76-78% V ˙ o2peak). Heart rate (HR) at fRT1, and V ˙ o2 and HR at fRT2 showed very large correlations (r = 0.75-0.82; P < 0.001) and acceptable precision (SEE < 7-9%) in determination of their corresponding values at GET1 and GET2. The precision in the estimation of V ˙ o2 at GET1 from fRT1 was moderate (SEE = 15%), while those of power output at GET1 (SEE = 23%) and GET2 (SEE = 12%) from their corresponding fRTs values were very poor to moderate. CONCLUSION: HR at fRT1 and V ˙ o2 and HR at fRT2, determined using a new objective and portable approach, may potentially serve as viable predictors of their respective GETs. This method may offer a simplified, cost-effective, and field-based approach for determining exercise threshold intensities during graded exercise.

19.
Health Educ Res ; 39(4): 339-350, 2024 07 18.
Artículo en Inglés | MEDLINE | ID: mdl-38517985

RESUMEN

Kids SIPsmartER is a 6-month behavioral and health literacy intervention effective at reducing sugar-sweetened beverage (SSB) intake among middle school students and their caregivers in the rural Appalachian region. This exploratory mixed methods study utilized a convergent parallel design to assess participant acceptability of a school-based curriculum for students and a text messaging program for caregivers. Acceptability was assessed using surveys (873 students and 453 caregivers), five focus groups (34 students) and telephone interviews (22 caregivers). Quantitative data were analyzed descriptively, and qualitative data were content coded. On a 5-point scale, average quantitative survey acceptability ratings ranged from 2.7 to 3.3 among three student-rated questions and 4.1 to 4.2 among four caregiver-rated questions. Qualitative focus group findings suggested that students preferred curricular activities that were hands-on and involved social interaction, while caregiver interview results showed high acceptability of the text messaging program's design, including usability, content messages and personalization. Students and caregivers reported similar program benefits: increased knowledge of SSBs and health risks, increased awareness of SSB behaviors and support to make beverage behavior changes. Results from this study can be used to understand Kids SIPsmartER's effectiveness data, communicate the intervention's acceptability with stakeholders and plan for future implementation studies.


Asunto(s)
Cuidadores , Grupos Focales , Estudiantes , Bebidas Azucaradas , Humanos , Femenino , Masculino , Cuidadores/educación , Cuidadores/psicología , Estudiantes/psicología , Adolescente , Envío de Mensajes de Texto , Niño , Servicios de Salud Escolar , Región de los Apalaches , Adulto , Promoción de la Salud/métodos , Conocimientos, Actitudes y Práctica en Salud , Persona de Mediana Edad
20.
Proc Natl Acad Sci U S A ; 118(42)2021 10 19.
Artículo en Inglés | MEDLINE | ID: mdl-34642248

RESUMEN

Microbial communities regulate ecosystem responses to climate change. However, predicting these responses is challenging because of complex interactions among processes at multiple levels of organization. Organismal traits that determine individual performance and ecological interactions are essential for scaling up environmental responses from individuals to ecosystems. We combine protist microcosm experiments and mathematical models to show that key traits-cell size, shape, and contents-each explain different aspects of species' demographic responses to changes in temperature. These differences in species' temperature responses have complex cascading effects across levels of organization-causing nonlinear shifts in total community respiration rates across temperatures via coordinated changes in community composition, equilibrium densities, and community-mean species mass in experimental protist communities that tightly match theoretical predictions. Our results suggest that traits explain variation in population growth, and together, these two factors scale up to influence community- and ecosystem-level processes across temperatures. Connecting the multilevel microbial processes that ultimately influence climate in this way will help refine predictions about complex ecosystem-climate feedbacks and the pace of climate change itself.


Asunto(s)
Microbiota , Temperatura , Cambio Climático , Ecosistema , Especificidad de la Especie
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