Very low-carbohydrate, high-fat ketogenic diets (KDs) induce a pronounced shift in metabolic fuel utilization that elevates circulating ketone bodies; however, the consequences of these compounds for ...host-microbiome interactions remain unknown. Here, we show that KDs alter the human and mouse gut microbiota in a manner distinct from high-fat diets (HFDs). Metagenomic and metabolomic analyses of stool samples from an 8-week inpatient study revealed marked shifts in gut microbial community structure and function during the KD. Gradient diet experiments in mice confirmed the unique impact of KDs relative to HFDs with a reproducible depletion of bifidobacteria. In vitro and in vivo experiments showed that ketone bodies selectively inhibited bifidobacterial growth. Finally, mono-colonizations and human microbiome transplantations into germ-free mice revealed that the KD-associated gut microbiota reduces the levels of intestinal pro-inflammatory Th17 cells. Together, these results highlight the importance of trans-kingdom chemical dialogs for mediating the host response to dietary interventions.
Display omitted
•Ketogenic diets (KDs) alter the gut microbiota in a manner distinct from high-fat diets•Gut microbial shifts on KDs are driven in part through host production of ketone bodies•β-hydroxybutyrate selectively inhibits bifidobacterial growth•The KD-associated gut microbiota reduces levels of intestinal Th17 cells
Ketogenic diets differ from high fat diets in that they alter the gut microbiome to affect the level of gut Th17 cells.
Objectives
Dizziness and vertigo account for roughly 4% of chief symptoms in the emergency department (ED). Little is known about the aggregate costs of ED evaluations for these patients. The authors ...sought to estimate the annual national costs associated with ED visits for dizziness.
Methods
This cost study of adult U.S. ED visits presenting with dizziness or vertigo combined public‐use ED visit data (1995 to 2009) from the National Hospital Ambulatory Medical Care Survey (NHAMCS) and cost data (2003 to 2008) from the Medical Expenditure Panel Survey (MEPS). We calculated total visits, test utilization, and ED diagnoses from NHAMCS. Diagnosis groups were defined using the Healthcare Cost and Utilization Project's Clinical Classifications Software (HCUP‐CCS). Total visits and the proportion undergoing neuroimaging for future years were extrapolated using an autoregressive forecasting model. The average ED visit cost‐per‐diagnosis‐group from MEPS were calculated, adjusting to 2011 dollars using the Hospital Personal Health Care Expenditures price index. An overall weighted mean across the diagnostic groups was used to estimate total national costs. Year 2011 data are reported in 2011 dollars.
Results
The estimated number of 2011 US ED visits for dizziness or vertigo was 3.9 million (95% confidence interval CI = 3.6 to 4.2 million). The proportion undergoing diagnostic imaging by computed tomography (CT), magnetic resonance imaging (MRI), or both in 2011 was estimated to be 39.9% (39.4% CT, 2.3% MRI). The mean per‐ED‐dizziness‐visit cost was $1,004 in 2011 dollars. The total extrapolated 2011 national costs were $3.9 billion. HCUP‐CCS key diagnostic groups for those presenting with dizziness and vertigo included the following (fraction of dizziness visits, cost‐per‐ED‐visit, attributable annual national costs): otologic/vestibular (25.7%; $768; $757 million), cardiovascular (16.5%, $1,489; $941 million), and cerebrovascular (3.1%; $1059; $127 million). Neuroimaging was estimated to account for about 12% of the total costs for dizziness visits in 2011 (CT scans $360 million, MRI scans $110 million).
Conclusions
Total U.S. national costs for patients presenting with dizziness to the ED are substantial and are estimated to now exceed $4 billion per year (about 4% of total ED costs). Rising costs over time appear to reflect the rising prevalence of ED visits for dizziness and increased rates of imaging use. Future economic studies should focus on the specific breakdown of total costs, emphasizing areas of high cost and use that might be safely reduced.
Resumen
Incremento Anual de los Costes de las Atenciones por Mareo en los Servicios de Urgencias de Estados Unidos
Objectivos
El mareo y el vértigo suman aproximadamente el 4% de los motivos de consulta en el servicio de urgencias (SU). Se conoce poco sobre los costes globales de las evaluaciones del SU en estos pacientes. Se buscó estimar los costes anuales nacionales asociados con las visitas al SU por mareo.
Metodología
Este estudio de costes de visitas al SU de adultos norteamericanos que acudieron con mareo o vértigo combinó los datos públicos de las visitas a los SU (1995 a 2009) recogidos por el National Hospital Ambulatory Medical Care Survey (NHAMCS) y los costes (2003 a 2008) recogidos por el Medical Expenditure Panel Survey (MEPS). Se calcularon el total de visitas, el uso de pruebas diagnósticas y los diagnósticos del SU del NHAMCS. Los grupos diagnósticos se definieron según el Healthcare Cost and Utilization Project's Clinical Classifications Software (HCUP‐CCS). Los datos del año 2011 se documentaron en dólares de 2011. El total de visitas y la proporción de neuroimagen llevada a cabo en los futuros años se extrapoló usando un modelo predictivo autorregresivo. La media del coste por visita al SU por grupo diagnóstico del MEPS se calculó, ajustándose a dólares de 2011, mediante el índice de precios de los Hospital Personal Health Care Expenditures. Se utilizó una media ponderada global entre los grupos diagnósticos para estimar los costes totales nacionales.
Resultados
El número de visitas al SU en Estados Unidos en 2011 por mareo o vértigo fue de 3,9 millones (IC 95% = 3,6 a 4,2 millones). El porcentaje de pruebas diagnósticas de imagen llevadas a cabo por tomografía computarizada (TC), resonancia magnética (RM) o ambas en 2011 se estimó en un 39,9% (39,4% TC, 2,3% RM). La media de coste por visita al SU por mareo fue de 1.004 dólares de 2011. Los costes totales, extrapolados para todo el país, fueron de 3.900 millones de dólares. Los grupos diagnósticos HCUP‐CCS para aquéllos que presentaron mareo o vértigo incluyeron los siguientes (proporción de visitas por mareo; coste por visita al SU; costes anuales nacionales atribuibles): otológico/vestibular (25,7%; 768 dólares; 757 millones de dólares), cardiovascular (16,5%, 1.489 dólares; 941 millones de dólares) y cerebrovascular (3,1%; 1.059 dólares; 127 millones de dólares). Se estimó una suma en la neuroimagen del 12% del total de costes para las visitas por mareo en 2011 (360 millones de dólares para la TC y 110 millones de dólares para la RM).
Conclusiones
Los costes totales en Estados Unidos para los pacientes que acuden por mareo al SU son sustanciales, y se estima que sobrepasan en estos momentos los 4.000 millones de dólares por año (aproximadamente un 4% de los costes totales del SU). El incremento de los costes con el paso del tiempo parece reflejar el crecimiento de la prevalencia de las visitas al SU por mareo y el aumento de porcentajes de utilización de la neuroimagen. Futuros estudios económicos deberían centrarse en el desglose de los costes totales, y hacer énfasis en las áreas de alto uso y coste que pueden ser reducidas sin riesgo.
Avian nests are fundamental structures in avian reproduction and face strong selective forces. Climatic conditions are likely to have shaped the evolution of specific nest traits, but evidence is ...scarce at a macroevolutionary level. The Thraupidae family (commonly known as tanagers) is an ideal clade to understand the link between nest architecture and climate because it presents wide variation in nest traits. To understand whether climatic variables have played a role in the diversification of nest traits among species in this family, we measured nests from 49 species using museum collections. We observed that dome‐nesting species are present in dryer and hotter environments, in line with previous findings suggesting that domed nests are a specialisation for arid conditions. We also found evidence that nests with thicker walls are present in locations with lower precipitation and that solar radiation can influence the shape of domed nests; birds tend to build shorter and narrower domes in areas with high levels of solar radiation. Open nest architecture is also potentially influenced by wind speed, with longer and deeper nests in areas characterised by strong winds. Our results support the hypothesis that different climatic variables can drive the evolution of specific aspects of nest architecture and contribute to the diversity of nest shapes we currently observe. However, climatic variables account only for a small fraction of the observed structural variation, leaving a significant portion still unexplained.
Bird nests play a crucial role in the survival and fitness of eggs, nestlings, and incubating parents, but the role of climate variables on the evolution and diversity of avian nest traits is still largely unknown. Previous studies have focused on (i) single species and few environmental variables or (ii) multiple species and general nest morphology. In our study, we explore the relationship between several climatic variables and specific nest traits in a family of birds, Thraupidae (commonly known as tanagers). Thraupidae represents an ideal clade for our study as species belonging to this family vary considerably in their nest architecture. We found evidence that nests with thicker walls are present in locations with lower precipitation and that solar radiation can influence the shape of domed nests; birds tend to build shorter and narrower nests in areas with high levels of solar radiation. Open nest architecture is also potentially influenced by wind speed, with longer and deeper nests in areas characterized by strong winds.
High salt intake is a well‐recognized risk factor for osteoporosis because it induces calciuria, but the effects of salt on calcium metabolism and the potential impact on bone health in ...postmenopausal women have not been fully characterized. This study investigated adaptive mechanisms in response to changes in salt and calcium intake in postmenopausal women. Eleven women completed a randomized cross‐over trial consisting of four successive 5‐wk periods of controlled dietary intervention, each separated by a minimum 4‐wk washout. Moderately low and high calcium (518 versus 1284 mg) and salt (3.9 versus 11.2 g) diets, reflecting lower and upper intakes in postmenopausal women consuming a Western‐style diet, were provided. Stable isotope labeling techniques were used to measure calcium absorption and excretion, compartmental modeling was undertaken to estimate bone calcium balance, and biomarkers of bone formation and resorption were measured in blood and urine. Moderately high salt intake (11.2 g/d) elicited a significant increase in urinary calcium excretion (p = 0.0008) and significantly affected bone calcium balance with the high calcium diet (p = 0.024). Efficiency of calcium absorption was higher after a period of moderately low calcium intake (p < 0.05) but was unaffected by salt intake. Salt was responsible for a significant change in bone calcium balance, from positive to negative, when consumed as part of a high calcium diet, but with a low calcium intake, the bone calcium balance was negative on both high and low salt diets.
The 2010 Dietary Guidelines for Americans (DGA) recommend nutrient needs be met by increasing fruit, vegetable, and whole-grain intake with the use of low-fat or fat-free dairy products and by ...reducing sodium, solid fats, and added sugars. However, the DGA, as a dietary pattern, have not been tested in an intervention trial.
The aim of this study was to evaluate the impact of a DGA-based diet compared with a representative typical American diet (TAD) on glucose homeostasis and fasting lipids in individuals at risk of cardiometabolic disease.
A randomized, double-blind, controlled 8-wk intervention was conducted in overweight and obese women selected according to indexes of insulin resistance or dyslipidemia. Women were randomly assigned to the DGA or TAD group (n = 28 DGA and 24 TAD). The TAD diet was based on average adult intake from the NHANES 2009–2010. The DGA and TAD diets had respective Healthy Eating Index scores of 98 and 62. All foods and beverages were provided during the intervention. Oral-glucose tolerance and fasting lipids were evaluated at 0, 2, and 8 wk of the intervention. Insulin resistance and sensitivity were estimated with the use of surrogates (e.g., homeostasis model assessment of insulin resistance).
By design, volunteers maintained their weight during the intervention. Fasting insulin, glucose, triglycerides, oral-glucose tolerance, and indexes of insulin resistance were not affected by either of the diets. Systolic blood pressure decreased in the DGA group (∼−9 mm Hg; P < 0.05). Total and HDL cholesterol also decreased in both groups (P < 0.05). Exploratory analysis comparing volunteers entering the study with insulin resistance and dyslipidemia with those with only dyslipidemia did not show an effect of pre-existing conditions on glucose tolerance or fasting lipid outcomes.
The consumption of a DGA dietary pattern for 8 wk without weight loss reduced systolic blood pressure. There were no differences between the DGA and TAD diets in fasting insulin, glucose, indexes of insulin resistance, or fasting lipids. This trial was registered at www.clinicaltrials.gov as NCT02298725.
Myocardin (MYOCD) is the founding member of a class of transcriptional coactivators that bind the serum-response factor to activate gene expression programs critical in smooth muscle (SM) and cardiac ...muscle development. Insights into the molecular functions of MYOCD have been obtained from cell culture studies, and to date, knowledge about in vivo roles of MYOCD comes exclusively from experimental animals. Here, we defined an often lethal congenital human disease associated with inheritance of pathogenic MYOCD variants. This disease manifested as a massively dilated urinary bladder, or megabladder, with disrupted SM in its wall. We provided evidence that monoallelic loss-of-function variants in MYOCD caused congenital megabladder in males only, whereas biallelic variants were associated with disease in both sexes, with a phenotype additionally involving the cardiovascular system. These results were supported by cosegregation of MYOCD variants with the phenotype in 4 unrelated families by in vitro transactivation studies in which pathogenic variants resulted in abrogated SM gene expression and by the finding of megabladder in 2 distinct mouse models with reduced Myocd activity. In conclusion, we have demonstrated that variants in MYOCD result in human disease, and the collective findings highlight a vital role for MYOCD in mammalian organogenesis.
Objective To determine the incidence and clinical consequences of postoperative hyponatremia in children. Study design We performed a retrospective analysis of postoperative admissions to the ...pediatric intensive care unit (excluding cardiac, neurosurgical, and renal). The incidence of severe (serum sodium < 125 mmol/L or symptoms) and moderate (serum sodium < 130 mmol/L) hyponatremia in children receiving hypotonic (HT) and normotonic (NT) fluids was calculated. Results Out of a total of 145 children (568 sodium measurements; 116 HT and 29 NT), we identified 16 with hyponatremia (11%). The incidences of moderate (10.3% vs 3.4%, P = .258) and severe (2.6% vs 0%; P = .881) hyponatremia were not significantly different in the HT and NT groups. There were no neurologic sequelae or deaths related to hyponatremia. Conclusions In our study group, hyponatremia was common, but morbidity and death were not observed. Careful monitoring of serum sodium level may be responsible for this lack of adverse outcomes. Larger, prospective studies are needed to determine whether the incidence of hyponatremia differs between the HT and NT groups.
Pulmonary arterial hypertension (PAH) is a deadly disease of the small pulmonary vasculature with an increased prevalence of insulin resistance (IR). Insulin regulates both glucose and lipid ...homeostasis. We sought to quantify glucose- and lipid-related IR in human PAH, testing the hypothesis that lipoprotein indices are more sensitive indices of IR in PAH.
Oral glucose tolerance testing in PAH patients and triglyceride-matched (TG-matched) controls and proteomic, metabolomics, and lipoprotein analyses were performed in PAH and controls. Results were validated in an external cohort and in explanted human PAH lungs.
PAH patients were similarly glucose intolerant or IR by glucose homeostasis metrics compared with control patients when matched for the metabolic syndrome. Using the insulin-sensitive lipoprotein index, TG/HDL ratio, PAH patients were more commonly IR than controls. Proteomic and metabolomic analysis demonstrated separation between PAH and controls, driven by differences in lipid species. We observed a significant increase in long-chain acylcarnitines, phosphatidylcholines, insulin metabolism-related proteins, and in oxidized LDL receptor 1 (OLR1) in PAH plasma in both a discovery and validation cohort. PAH patients had higher lipoprotein axis-related IR and lipoprotein-based inflammation scores compared with controls. PAH patient lung tissue showed enhanced OLR1 immunostaining within plexiform lesions and oxidized LDL accumulation within macrophages.
IR in PAH is characterized by alterations in lipid and lipoprotein homeostasis axes, manifest by elevated TG/HDL ratio, and elevated circulating medium- and long-chain acylcarnitines and lipoproteins. Oxidized LDL and its receptor OLR1 may play a role in a proinflammatory phenotype in PAH.
NIH DK096994, HL060906, UL1 RR024975-01, UL1 TR000445-06, DK020593, P01 HL108800-01A1, and UL1 TR002243; American Heart Association 13FTF16070002.
Wetlands cover a small portion of the world, but have disproportionate influence on global carbon (C) sequestration, carbon dioxide and methane emissions, and aquatic C fluxes. However, the ...underlying biogeochemical processes that affect wetland C pools and fluxes are complex and dynamic, making measurements of wetland C challenging. Over decades of research, many observational, experimental, and analytical approaches have been developed to understand and quantify pools and fluxes of wetland C. Sampling approaches range in their representation of wetland C from short to long timeframes and local to landscape spatial scales. This review summarizes common and cutting-edge methodological approaches for quantifying wetland C pools and fluxes. We first
define
each of the major C pools and fluxes and provide
rationale
for their importance to wetland C dynamics. For each approach, we clarify
what
component of wetland C is measured and its spatial and temporal representativeness and constraints. We describe practical considerations for each approach, such as
where
and
when
an approach is typically used,
who
can conduct the measurements (expertise, training requirements), and
how
approaches are conducted, including considerations on equipment complexity and costs. Finally, we review
key covariates
and
ancillary measurements
that enhance the interpretation of findings and facilitate model development. The protocols that we describe to measure soil, water, vegetation, and gases are also relevant for related disciplines such as ecology. Improved quality and consistency of data collection and reporting across studies will help reduce global uncertainties and develop management strategies to use wetlands as nature-based climate solutions.
Metabolic imbalance is a key determinant of risk of chronic diseases. Metabolic health cannot be assessed solely by body mass calculations or by static, fasted state biochemical readouts. Although ...previous studies have described temporal responses to dietary challenges, these studies fail to assess the environmental factors associated with certain metabolic phenotypes and therefore, provide little scientific rationale for potentially effective intervention strategies.
In this phenotyping study of healthy US adults, we are evaluating lifestyle, biological and environmental factors in addition to metabolic parameters to determine the factors associated with variations in metabolic health. A series of practical fitness, dietary, and emotional challenges are introduced and temporal responses in various areas of specialization, including immunology, metabolomics, and endocrinology, are monitored. We expect that this study will identify key factors related to healthy or unhealthy metabolic phenotypes (metabotypes) that may be modifiable targets for the prevention of chronic diseases in an individual.
This study will provide novel insights into metabolic variability among healthy adults in balanced strata defined by sex, age and body mass index. Usual dietary intake and physical activity will be evaluated across these strata to determine how diet is associated with health status defined using many indicators including immune function, metabolism, body composition, physiology, response to exercise andmeal challenges and neuroendocrine assessment. A principal study goal is to identify dietary and other personal factors that will differentiate different levels of "health" among study participants.
ClinicalTrials.gov NCT02367287.
PDF
