Publications by authors named "David La"

Background: Towards improving outcomes for adolescents with obesity, we aimed to define metabolic and microbiome phenotypes at baseline and post-weight loss intervention.

Methods: The Pediatric Obesity Microbiome and Metabolism Study enrolled 220 adolescents aged 10-18 with severe obesity (OB) and 67 healthy weight controls (HWC). Blood, stool, and clinical measures were collected at baseline and after a 6-month intervention for the OB group.

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Objective: We assessed the impact of a food-provisioning intervention on diet quality in children with obesity.

Methods: Participants (n = 33, aged 6-11 years) were randomly assigned to either usual care (intensive health behavior and lifestyle treatment) or intervention (usual care + food provisioning; high-fiber, low-dairy diet) for 4 weeks. The primary outcome was a change in child diet quality at Week 4.

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This article shows the most recent data on the evolution of the number of resident physicians and vacancies from R1 to R5, as well as the number of programs and institutions accredited by the National Commission for Medical Residency (CNRM). It also discusses the types and modalities of evaluation of medical residency, with a focus on the assessment of competencies throughout in-service training, which were incorporated into the most recent CNRM resolution, at the end of 2023, which amended and updated the 2006 directives. Finally, it shows the experience of six Medical Societies that conduct periodic evaluation of resident physicians, presented at a Brazilian Medical Association event.

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Metabolites derived from the intestinal microbiota, including bile acids (BA), extensively modulate vertebrate physiology, including development, metabolism, immune responses and cognitive function. However, to what extent host responses balance the physiological effects of microbiota-derived metabolites remains unclear. Here, using untargeted metabolomics of mouse tissues, we identified a family of BA-methylcysteamine (BA-MCY) conjugates that are abundant in the intestine and dependent on vanin 1 (VNN1), a pantetheinase highly expressed in intestinal tissues.

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Objective biomarkers of food intake are a sought-after goal in nutrition research. Most biomarker development to date has focused on metabolites detected in blood, urine, skin, or hair, but detection of consumed foods in stool has also been shown to be possible DNA sequencing. An additional food macromolecule in stool that harbors sequence information is protein.

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Article Synopsis
  • Physical particles, specifically fecal particle size (FPS), are influenced by gut microbiomes in humans, highlighting their role as abiotic factors in microbial ecology.
  • A study involving 76 individuals revealed that FPS is highly individualized and not significantly impacted by chewing efficiency or diet, contrary to initial assumptions.
  • Findings indicate that gut microbiota diversity and composition, as well as factors like transit time, are critical in determining FPS, suggesting that the microbiome is essential for efficient digestion and energy extraction in the gastrointestinal tract.
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Fructans are commonly used as dietary fibre supplements for their ability to promote the growth of beneficial gut microbes. However, fructan consumption has been associated with various dosage-dependent side effects. We characterised side effects in an exploratory analysis of a randomised trial in healthy adults ( = 40) who consumed 18 g/day inulin or placebo.

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Article Synopsis
  • Physical particles, specifically fecal particle size (FPS), play an important role in shaping the ecology of microbial communities in the gut.
  • While chewing efficiency and diet influence FPS in non-human vertebrates, a study on humans showed that FPS variability is primarily linked to gut microbiome composition rather than behavior or diet.
  • Findings indicate that gut microbiomes can significantly alter FPS, suggesting that human digestion and microbial interaction have unique processes compared to other mammals.
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Objective biomarkers of food intake are a sought-after goal in nutrition research. Most biomarker development to date has focused on metabolites detected in blood, urine, skin or hair, but detection of consumed foods in stool has also been shown to be possible via DNA sequencing. An additional food macromolecule in stool that harbors sequence information is protein.

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The retina is exquisitely patterned, with neuronal somata positioned at regular intervals to completely sample the visual field. Here, we show that phosphatase and tensin homolog (Pten) controls starburst amacrine cell spacing by modulating vesicular trafficking of cell adhesion molecules and Wnt proteins. Single-cell transcriptomics and double-mutant analyses revealed that Pten and Down syndrome cell adhesion molecule Dscam) are co-expressed and function additively to pattern starburst amacrine cell mosaics.

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Antibodies to DNA are a diverse set of antibodies that bind sites on DNA, a polymeric macromolecule that displays various conformations. In a previous study, we showed that sera of normal healthy subjects (NHS) contain IgG antibodies to Z-DNA, a left-handed helix with a zig-zig backbone. Recent studies have demonstrated the presence of Z-DNA in bacterial biofilms, suggesting a source of this conformation to induce responses.

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The infant gut microbiome is a crucial factor in health and development. In preterm infants, altered gut microbiome composition and function have been linked to serious neonatal complications such as necrotizing enterocolitis and sepsis, which can lead to long-term disability. Although many studies have described links between microbiome composition and disease risk, there is a need for biomarkers to identify infants at risk of these complications in practice.

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Background: Aging is associated with gut dysbiosis, low-grade inflammation, and increased risk of type 2 diabetes (T2D). Prediabetes, which increases T2D and cardiovascular disease risk, is present in 45-50% of mid-life adults. The gut microbiota may link ultra-processed food (UPF) with inflammation and T2D risk.

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The infant gut microbiome is a crucial factor in health and development. In preterm infants, altered gut microbiome composition and function have been linked to serious neonatal complications such as necrotizing enterocolitis and sepsis, which can lead to long-term disability. Although many studies have described links between microbiome composition and disease risk, there is a need for biomarkers to identify infants at risk of these complications in practice.

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Eating a varied diet is a central tenet of good nutrition. Here, we develop a molecular tool to quantify human dietary plant diversity by applying DNA metabarcoding with the chloroplast -P6 marker to 1,029 fecal samples from 324 participants across two interventional feeding studies and three observational cohorts. The number of plant taxa per sample (plant metabarcoding richness or pMR) correlated with recorded intakes in interventional diets and with indices calculated from a food frequency questionnaire in typical diets (ρ = 0.

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Akkermansia muciniphila, a mucophilic member of the gut microbiota, protects its host against metabolic disorders. Because it is genetically intractable, the mechanisms underlying mucin metabolism, gut colonization and its impact on host physiology are not well understood. Here we developed and applied transposon mutagenesis to identify genes important for intestinal colonization and for the use of mucin.

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Temporal identity factors are sufficient to reprogram developmental competence of neural progenitors and shift cell fate output, but whether they can also reprogram the identity of terminally differentiated cells is unknown. To address this question, we designed a conditional gene expression system that allows rapid screening of potential reprogramming factors in mouse retinal glial cells combined with genetic lineage tracing. Using this assay, we found that coexpression of the early temporal identity transcription factors Ikzf1 and Ikzf4 is sufficient to directly convert Müller glial (MG) cells into cells that translocate to the outer nuclear layer (ONL), where photoreceptor cells normally reside.

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Cross feeding between microbes is ubiquitous, but its impact on the diversity and productivity of microbial communities is incompletely understood. A reductionist approach using simple microbial communities has the potential to detect cross feeding interactions and their impact on ecosystem properties. However, quantifying abundance of more than two microbes in a community in a high throughput fashion requires rapid, inexpensive assays.

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The functions of many microbial communities exhibit remarkable stability despite fluctuations in the compositions of these communities. To date, a mechanistic understanding of this function-composition decoupling is lacking. Statistical mechanisms have been commonly hypothesized to explain such decoupling.

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Article Synopsis
  • Previous research indicates that disruptions in gut microbiome due to chemotherapy, diet, or antibiotics may lead to higher rates of acute graft-versus-host disease (aGVHD) after hematopoietic stem cell transplantation (HSCT).
  • A study by Holmes et al. used a mouse model to show that giving galactooligosaccharides (GOS) as a prebiotic can reduce the severity of lethal aGVHD associated with gut microbiome disruption.
  • The findings suggest a need for clinical trials to test the effects of GOS prebiotic diets on patients undergoing HSCT.
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Background: Short-chain fatty acids (SCFAs) derived from gut bacteria are associated with protective roles in diseases ranging from obesity to colorectal cancers. Intake of microbially accessible dietary fibers (prebiotics) lead to varying effects on SCFA production in human studies, and gut microbial responses to nutritional interventions vary by individual. It is therefore possible that prebiotic therapies will require customizing to individuals.

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Many ecosystems have been shown to retain a memory of past conditions, which in turn affects how they respond to future stimuli. In microbial ecosystems, community disturbance has been associated with lasting impacts on microbiome structure. However, whether microbial communities alter their response to repeated stimulus remains incompletely understood.

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Understanding how retinal progenitor cells (RPCs) give rise to the variety of neural cell types of the retina has been a question of major interest over the last few decades. While environmental cues and transcription factor networks have been shown to control specific cell fate decisions, how RPCs alter fate output over time to control proper histogenesis remains poorly understood. In recent years, the identification of "temporal identity factors (TIFs)", which control RPC competence states to ensure that the right cell types are produced at the right time, has contributed to increasing our understanding of temporal patterning in the retina.

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Vision commences in the retina with rod and cone photoreceptors that detect and convert light to electrical signals. The irreversible loss of photoreceptors due to neurodegenerative disease leads to visual impairment and blindness. Interventions now in development include transplanting photoreceptors, committed photoreceptor precursors, or retinal pigment epithelial (RPE) cells, with the latter protecting photoreceptors from dying.

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Microbial communities inhabit spatial architectures that divide a global environment into isolated or semi-isolated local environments, which leads to the partitioning of a microbial community into a collection of local communities. Despite its ubiquity and great interest in related processes, how and to what extent spatial partitioning affects the structures and dynamics of microbial communities are poorly understood. Using modeling and quantitative experiments with simple and complex microbial communities, we demonstrate that spatial partitioning modulates the community dynamics by altering the local interaction types and global interaction strength.

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