8 research outputs found
Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults
Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We
estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from
1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories.
Methods We used data from 3663 population-based studies with 222 million participants that measured height and
weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate
trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children
and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the
individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For schoolaged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference)
and obesity (BMI >2 SD above the median).
Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in
11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed
changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and
140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of
underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and
countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior
probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse
was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of
thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a
posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%)
with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and
obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for
both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such
as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged
children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls
in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and
42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents,
the increases in double burden were driven by increases in obesity, and decreases in double burden by declining
underweight or thinness.
Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an
increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy
nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of
underweight while curbing and reversing the increase in obesit
Optimization by Molecular Fine Tuning of Dihydro-β-agarofuran Sesquiterpenoids as Reversers of P‑Glycoprotein-Mediated Multidrug Resistance
P-glycoprotein
(P-gp) plays a crucial role in the development of multidrug resistance
(MDR), a major obstacle for successful chemotherapy in cancer. Herein,
we report on the development of a natural-product-based library of
81 dihydro-β-agarofuran sesquiterpenes (<b>2</b>–<b>82</b>) by optimization of the lead compound <b>1</b>. The
compound library was evaluated for its ability to inhibit P-gp-mediated
daunomycin efflux in MDR cells. Selected analogues were further analyzed
for their P-gp inhibition constant, intrinsic toxicity, and potency
to reverse daunomycin and vinblastine resistances. Analogues <b>6</b>, <b>24</b>, <b>28</b>, <b>59</b>, and <b>66</b> were identified as having higher potency than compound <b>1</b> and verapamil, a first-generation P-gp modulator. SAR analysis
revealed the size of the aliphatic chains and presence of nitrogen
atoms are important structural characteristics to modulate reversal
activity. The present study highlights the potential of these analogues
as modulators of P-gp mediated MDR in cancer cells
Restoration of Chemosensitivity in P‑Glycoprotein-Dependent Multidrug-Resistant Cells by Dihydro-β-agarofuran Sesquiterpenes from <i>Celastrus vulcanicola</i>
Multidrug resistance (MDR) caused
by the overexpression of ABC
drug transporters is a major obstacle in clinical cancer chemotherapy
and underlines the urgent need for the development of new, potent,
and safe reversal agents. Toward this goal, reported herein are the
structure elucidation and biological activity of nine new (<b>1</b>–<b>9</b>) and four known (<b>10</b>–<b>13</b>) dihydro-β-agarofuran sesquiterpenes, isolated from
the leaves of <i>Celastrus vulcanicola,</i> as reversers
of MDR mediated by human P-glycoprotein expression. The structures
of these compounds were elucidated by extensive NMR spectroscopic
and mass spectrometric analysis, and their absolute configurations
were determined by circular dichroism studies, chemical correlations
(<b>1a</b>, <b>8a</b>, and <b>8b</b>), and biogenetic
means. Four compounds from this series were discovered as potent chemosensitizers
for MDR1-G185 NIH-3T3 murine cells (<b>3</b>, <b>4</b>, <b>6</b>, and <b>7</b>), showing higher efficacies
than the classical P-glycoprotein inhibitor verapamil, a first-generation
chemosensitizer, when reversing resistance to daunomycin and vinblastine
at the lowest concentration tested of 1 μM
Neurobehavioral and neurodevelopmental profiles of a heuristic genetic model of differential schizophrenia- and addiction-relevant features: The RHA vs. RLA rats
The Roman High-(RHA) and Low-(RLA) avoidance rat lines/strains were generated through bidirectional selective breeding for rapid (RHA) vs. extremely poor (RLA) two-way active avoidance acquisition. Compared with RLAs and other rat strains/stocks, RHAs are characterized by increased impulsivity, deficits in social behavior, novelty-induced hyper-locomotion, impaired attentional/cognitive abilities, vulnerability to psychostimulant sensitization and drug addiction. RHA rats also exhibit decreased function of the prefrontal cortex (PFC) and hippocampus, increased functional activity of the mesolimbic dopamine system and a dramatic deficit of central metabotropic glutamate-2 (mGlu2) receptors (due to a stop codon mutation at cysteine 407 in Grm2-cys407*-), along with increased density of 5-HT2A receptors in the PFC, alterations of several synaptic markers and increased density of pyramidal "thin" (immature) dendntic spines in the PFC. These characteristics suggest an immature brain of RHA rats, and are reminiscent of schizophrenia features like hypofrontality and disruption of the excitation/inhibition cortical balance. RHA rats represent a promising heuristic model of neurodevelopmental schizophrenia-relevant features and comorbidity with drug addiction vulnerability
Adjustment of annual NEE and ET for the open-path IRGA self-heating correction : magnitude and approximation over a range of climate
The self-heating correction is known to modify open-path eddy covariance estimates of net ecosystem CO2 exchange, typically towards reduced uptake or enhanced emissions, but with a magnitude heretofore not generally documented. We assess the magnitude of this correction to be of order 1 μmol m−2 s−1 (daytime) for half-hourly fluxes and consistently over 100 g C m−2 for annual integrations, across a tower network (CARBORED-ES) spanning climate zones from Mediterranean temperate to cool alpine. We furthermore examine the sensitivity of the correction to its determining factors. Due to significant diurnal variation, the means of discriminating day versus night can lead to differences of up to several tens of g C m−2 year−1. Since its principal determinants – temperature and wind speed – do not include gas flux data, the annual correction can be estimated using only meteorological data so as to avoid uncertainties introduced when filling gaps in flux data. For fast retro-correction of annual integrations published prior to the recognition of this instrument surface heating effect, the annual impact can be roughly approximated to within 12 g C m−2 year−1 by a linear function of mean annual temperature. These determinations highlight the need for the flux community to reach a consensus regarding the need for and the specific form of this correction
Safety of hospital discharge before return of bowel function after elective colorectal surgery
Background Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function. Methods A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien-Dindo classification system. Results A total of 3288 patients were included in the analysis, of whom 301 (9 center dot 2 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4-7) and 7 (6-8) days respectively (P < 0 center dot 001). There were no significant differences in rates of readmission between these groups (6 center dot 6 versus 8 center dot 0 per cent; P = 0 center dot 499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0 center dot 90, 95 per cent c.i. 0 center dot 55 to 1 center dot 46; P = 0 center dot 659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34 center dot 7 versus 39 center dot 5 per cent; major 3 center dot 3 versus 3 center dot 4 per cent; P = 0 center dot 110). Conclusion Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients
Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults
Background: Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods: We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5-19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For school-aged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median). Findings: From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation: The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesity. Funding: UK Medical Research Council, UK Research and Innovation (Research England), UK Research and Innovation (Innovate UK), and European Union