Análisis de la discapacidad por trastornos musculoesqueléticos en México de 1990 a 2021 / Analysis of musculoskeletal disorders-associated disability in Mexico from 1990 to 2021

Resumen Antecedentes: Los trastornos musculoesqueléticos (TME) afectan a 1710 millones de personas en todo el mundo y es la principal causa de discapacidad. Objetivo: Analizar los años vividos con discapacidad (AVD) por TME en México entre 1990 y 2021. Material y métodos: Con las estimaciones del estudio de la Carga Global de la Enfermedad 2021 se analizaron los AVD por TME y sus seis categorías: osteoartritis, artritis reumatoide, gota, dolor cervical, lumbalgia y otros TME. Se evaluaron patrones y tendencias del número, tasa cruda y tasa estandarizada por edad de los AVD a nivel nacional, estatal, por grupos de edad y sexo. Resultados: Los TME constituyeron la principal causa de AVD en México entre 1990 y 2021, con un incremento de 57.3 %; pasaron de 1458.4 a 2293.7 por 100 000 habitantes. La lumbalgia (840.6 AVD) destacó con la mayor tasa en 2021 y la osteoartritis, con el mayor incremento. Los TME se incrementaron con la edad y, con excepción de la gota, afectaron más a las mujeres. Conclusiones: De 1990 a 2021, los TME constituyeron la principal causa de AVD en México, con mayor impacto en adultos y mujeres. Los TME se evidencian desde edades tempranas, de ahí la necesidad de intervenciones continuas para preservar la calidad de vida.

Abstract Background: Musculoskeletal disorders (MSD) affect 1.71 billion people worldwide and are the leading cause of disability. Objective: To analyze the years lived with disability (YLD) attributed to MSD in Mexico between 1990 and 2021. Material and methods: With estimates from the Global Burden of Disease 2021 study, the YLDs due to MSD and their six categories were analyzed, including osteoarthritis, rheumatoid arthritis, gout, neck pain, low back pain, as well as other MSDs. Patterns and trends in the number, crude rate, and YLD age-standardized rate were evaluated at the national and state levels, as well as by age group and gender. Results: MSDs were the main cause of YLDs in Mexico between 1990 and 2021, with an increase of 57.3%, going from 1,458.4 to 2,293.7 per 100,000 population. Low back pain (840.6 YLD) showed the highest rate in 2021, while osteoarthritis had the largest increase. MSDs increased with age and, and except for gout, affected women more often. Conclusions: From 1990 to 2021, MSDs were the main cause of YLDs in Mexico, with a higher impact on adults and women. MSDs can appear early in life, hence the need for continuous interventions in order to preserve quality of life.

Burden of disease due to amphetamines, cannabis, cocaine, and opioid use disorders in South America, 1990-2019: a systematic analysis of the Global Burden of Disease Study 2019.

BACKGROUND: South America's substance use profile, poverty, income inequality, and cocaine-supplier role make it a unique place for substance use research. This study investigated the burden of disease attributable to amphetamine use disorder, cannabis use disorder (CAD), cocaine use disorder, and opioid use disorder (OUD) in South America from 1990 to 2019, on the basis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. METHODS: GBD 2019 estimated the incidence, prevalence, mortality, years of life lost (YLL), years of life lived with disability (YLD), and disability-adjusted life-years (DALYs) due to substance use disorders in each of the 12 South American countries (Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Guyana, Paraguay, Peru, Suriname, Uruguay, and Venezuela). Data were modelled using standardised tools (ie, the Cause of Death Ensemble model, spatio-temporal Gaussian process regression, and disease modelling meta-regression) to generate estimates of each quantity of interest by sex, location, and year. The analysis included comparisons by sex and country, and against regional and global estimates. FINDINGS: In 2019, the highest amphetamine use disorder burden per 100 000 population in South America was in Peru (66 DALYs). CAD DALY rates per 100 000 in South America were stable between 1990 and 2019, except in Chile and Colombia, which had the highest rates in 2019 (19 DALYs for Chile and 18 DALYs for Colombia). OUD DALYs per 100 000 increased during the period in Brazil and Peru, which in 2019 had the highest rates in South America (82 DALYs for Brazil and 70 DALYs for Peru). In 2019, Brazil had the highest cocaine use disorder DALYs per 100 000 (45 DALYs), nearly double its rate in 1990. DALY rates were higher in males than females for each substance use disorder, except in Paraguay. The overall burden of substance use disorders was higher in males than in females, mainly because of cocaine use disorder and CAD, whereas for amphetamine use disorder, the difference between sexes was minimal, and for OUD there was no difference. For males and females, the highest rate of substance use disorders DALYs per 100 000 was for OUD except in Argentina (in males, 58 DALYs for cocaine use disorder vs 52 DALYs for OUD) and in Paraguay (in females, 77 for amphetamine use disorder vs 50 for OUD). CAD DALY rates were generally the lowest among the substance use disorders for males and females. Amphetamine use disorder YLD rates were reasonably stable throughout the period and were highest in Peru, Paraguay, and Uruguay (>40 YLD per 100 000). For CAD, YLD rates were stable in all countries except Chile and Colombia. Cocaine use disorder YLD rates per 100 000 for the top four countries (Argentina, Uruguay, Chile, and Brazil) increased from 1990 to 2010 (eg, from 19 to 33 in Brazil), but decreased between 2010 and 2019 (eg, from 36 to 31 in Chile). For OUD, YLD rates showed a slight increase in most countries apart from Brazil, which increased from 52 in 1990 to 80 in 2019 and was top among the countries. Amphetamine use disorder YLL rates per 100 000 were highest in Suriname and Peru during the period, although in Suriname it increased from 2·7 in 2010 to 3·2 in 2019, whereas in Peru it decreased from 2·1 to 1·7. The highest YLL rate for cocaine use disorder was in Brazil, which increased from 3·7 in 1990 to 18·1 in 2019. Between 2000 and 2019, Chile and Uruguay showed the highest OUD YLL rates (11·6 for Chile and 10·9 for Uruguay). A high incidence of CAD was found in Chile, Colombia, Guyana, and Suriname. There were high incidences of amphetamine use disorder in Paraguay, cocaine use disorder in Argentina, and OUD in Ecuador. A decrease in annual prevalence for substance use disorders during the period was observed in Venezuela (amphetamine use disorder, CAD, and OUD), Brazil (CAD and amphetamine use disorder), Colombia (amphetamine use disorder and cocaine use disorder), Peru (amphetamine use disorder and cocaine use disorder), Chile and Suriname (amphetamine use disorder), Uruguay (CAD), and Bolivia (OUD). Overall, the cocaine use disorder burden stabilised then decreased. OUD was less prevalent than other substance use disorders but its burden was the highest. INTERPRETATION: The decrease in the burden of cocaine use disorder probably reflects the success of national standardised treatment programmes. Programmes for amphetamine use disorder, CAD, and OUD management should be improved. We did not find an increase in CAD burden in Uruguay, the country with the highest degree of cannabis decriminalisation in the region. Countries in South America should improve monitoring of substance use disorders, including regular surveys to provide more accurate data on which to base policy decisions. FUNDING: The Bill & Melinda Gates Foundation.

Analysis of musculoskeletal disorders-associated disability in Mexico from 1990 to 2021.

BACKGROUND: Musculoskeletal disorders (MSD) affect 1.71 billion people worldwide and are the leading cause of disability. OBJECTIVE: To analyze the years lived with disability (YLD) attributed to MSD in Mexico between 1990 and 2021. MATERIAL AND METHODS: With estimates from the Global Burden of Disease 2021 study, the YLDs due to MSD and their six categories were analyzed, including osteoarthritis, rheumatoid arthritis, gout, neck pain, low back pain, as well as other MSDs. Patterns and trends in the number, crude rate, and YLD age-standardized rate were evaluated at the national and state levels, as well as by age group and gender. RESULTS: MSDs were the main cause of YLDs in Mexico between 1990 and 2021, with an increase of 57.3%, going from 1,458.4 to 2,293.7 per 100,000 population. Low back pain (840.6 YLD) showed the highest rate in 2021, while osteoarthritis had the largest increase. MSDs increased with age and, and except for gout, affected women more often. CONCLUSIONS: From 1990 to 2021, MSDs were the main cause of YLDs in Mexico, with a higher impact on adults and women. MSDs can appear early in life, hence the need for continuous interventions in order to preserve quality of life.

ANTECEDENTES: Los trastornos musculoesqueléticos (TME) afectan a 1710 millones de personas en todo el mundo y es la principal causa de discapacidad. OBJETIVO: Analizar los años vividos con discapacidad (AVD) por TME en México entre 1990 y 2021. MATERIAL Y MÉTODOS: Con las estimaciones del estudio de la Carga Global de la Enfermedad 2021 se analizaron los AVD por TME y sus seis categorías: osteoartritis, artritis reumatoide, gota, dolor cervical, lumbalgia y otros TME. Se evaluaron patrones y tendencias del número, tasa cruda y tasa estandarizada por edad de los AVD a nivel nacional, estatal, por grupos de edad y sexo. RESULTADOS: Los TME constituyeron la principal causa de AVD en México entre 1990 y 2021, con un incremento de 57.3 %; pasaron de 1458.4 a 2293.7 por 100 000 habitantes. La lumbalgia (840.6 AVD) destacó con la mayor tasa en 2021 y la osteoartritis, con el mayor incremento. Los TME se incrementaron con la edad y, con excepción de la gota, afectaron más a las mujeres. CONCLUSIONES: De 1990 a 2021, los TME constituyeron la principal causa de AVD en México, con mayor impacto en adultos y mujeres. Los TME se evidencian desde edades tempranas, de ahí la necesidad de intervenciones continuas para preservar la calidad de vida.

What's new in atopic eczema? An analysis of systematic reviews published in 2018. Part 2: systemic therapies.

This review forms part of an annual update series on atopic eczema (AE), where systematic reviews (SRs) are gathered and appraised to provide a summary of key recent research findings. The focus of this article is systemic therapies used in AE, while a review on prevention and topical therapies is provided in Part 1. In total, 17 SRs on various systemic treatments used in AE were first published or indexed in 2018. There is a lack of evidence to support vitamin D supplementation, montelukast and naltrexone in AE treatment. The adverse effects of systemic corticosteroids are the main barrier to their use, and there is also a lack of data to determine the optimal delivery and duration of treatment with them. Of other immunosuppressants, ciclosporin has the most robust evidence of efficacy. Biologic therapies in AE treatment are being increasingly investigated, and to date, the greatest quantity of data and evidence of efficacy relates to dupilumab. The most commonly reported adverse effects are injection-site reactions and conjunctivitis. Other biologics showing some evidence of efficacy include nemolizumab, lebrikizumab and tralokinumab, although further data are needed. There are currently insufficient data on oral small molecules, including Janus kinase inhibitors, in the treatment of AE. A Cochrane review on probiotics showed no significant benefit, and SRs and meta-analyses on complementary and alternative medicines, including probiotics, in paediatric AE demonstrated significant heterogeneity, thereby limiting their interpretation. This summary of recent SRs provides up-to-date evidence for clinicians on systemic therapies in AE.

Locomotor activity, growth hormones, and systemic robusticity: An investigation of cranial vault thickness in mouse lines bred for high endurance running.

OBJECTIVES: To use a mouse model to investigate the relationships among the components of the systemic robusticity hypothesis (SRH): voluntary exercise on wheels, spontaneous physical activity (SPA) in cages, growth hormones, and skeletal robusticity, especially cranial vault thickness (CVT). MATERIALS AND METHODS: Fifty female mice from lines artificially selected for high running (HR) and 50 from nonselected control (C) lines were housed in cages with (Active) or without wheels (Sedentary). Wheel running and SPA were monitored daily. The experiment began at 24-27 days of age and lasted 12 weeks. Food consumption was measured weekly. Mice were skeletonized and their interparietal, parietal, humerus, and femur were µCT scanned. Mean total thickness of the parietal and interparietal bones was determined, along with thickness of the cortical and diploe layers individually. Geometric cross-sectional indicators of strength were calculated for the long bones. Blood samples were assayed for IGF-1 and IGFBP-3. RESULTS: Physical activity differed significantly among groups, based both on linetype (C vs. HR) and activity (A vs. S). However, contrary to our predictions, the ratio of IGF-1 to IGFBP-3 was higher in C mice than in HR mice. Neither CVT nor postcranial robusticity was affected by linetype or activity, nor were most measures of CVT and postcranial robusticity significantly associated with one another. DISCUSSION: Our results fail to provide support for the systemic robusticity hypothesis, suggesting it is important to rethink the long-standing theory that increased CVT in Homo erectus reflects increased physical activity compared other hominin species.

An Assessment of Phylogenetic Tools for Analyzing the Interplay Between Interspecific Interactions and Phenotypic Evolution.

Much ecological and evolutionary theory predicts that interspecific interactions often drive phenotypic diversification and that species phenotypes in turn influence species interactions. Several phylogenetic comparative methods have been developed to assess the importance of such processes in nature; however, the statistical properties of these methods have gone largely untested. Focusing mainly on scenarios of competition between closely-related species, we assess the performance of available comparative approaches for analyzing the interplay between interspecific interactions and species phenotypes. We find that many currently used statistical methods often fail to detect the impact of interspecific interactions on trait evolution, that sister-taxa analyses are particularly unreliable in general, and that recently developed process-based models have more satisfactory statistical properties. Methods for detecting predictors of species interactions are generally more reliable than methods for detecting character displacement. In weighing the strengths and weaknesses of different approaches, we hope to provide a clear guide for empiricists testing hypotheses about the reciprocal effect of interspecific interactions and species phenotypes and to inspire further development of process-based models.

Ecological and phylogenetic variability in the spinalis muscle of snakes.

Understanding the origin and maintenance of functionally important subordinate traits is a major goal of evolutionary physiologists and ecomorphologists. Within the confines of a limbless body plan, snakes are diverse in terms of body size and ecology, but we know little about the functional traits that underlie this diversity. We used a phylogenetically diverse group of 131 snake species to examine associations between habitat use, sidewinding locomotion and constriction behaviour with the number of body vertebrae spanned by a single segment of the spinalis muscle, with total numbers of body vertebrae used as a covariate in statistical analyses. We compared models with combinations of these predictors to determine which best fit the data among all species and for the advanced snakes only (N = 114). We used both ordinary least-squares models and phylogenetic models in which the residuals were modelled as evolving by the Ornstein-Uhlenbeck process. Snakes with greater numbers of vertebrae tended to have spinalis muscles that spanned more vertebrae. Habitat effects dominated models for analyses of all species and advanced snakes only, with the spinalis length spanning more vertebrae in arboreal species and fewer vertebrae in aquatic and burrowing species. Sidewinding specialists had shorter muscle lengths than nonspecialists. The relationship between prey constriction and spinalis length was less clear. Differences among clades were also strong when considering all species, but not for advanced snakes alone. Overall, these results suggest that muscle morphology may have played a key role in the adaptive radiation of snakes.

High motivation for exercise is associated with altered chromatin regulators of monoamine receptor gene expression in the striatum of selectively bred mice.

Although exercise is critical for health, many lack the motivation to exercise, and it is unclear how motivation might be increased. To uncover the molecular underpinnings of increased motivation for exercise, we analyzed the transcriptome of the striatum in four mouse lines selectively bred for high voluntary wheel running and four non-selected control lines. The striatum was dissected and RNA was extracted and sequenced from four individuals of each line. We found multiple genes and gene systems with strong relationships to both selection and running history over the previous 6 days. Among these genes were Htr1b, a serotonin receptor subunit and Slc38a2, a marker for both glutamatergic and γ-aminobutyric acid (GABA)-ergic signaling. System analysis of the raw results found enrichment of transcriptional regulation and kinase genes. Further, we identified a splice variant affecting the Wnt-related Golgi signaling gene Tmed5. Using coexpression network analysis, we found a cluster of interrelated coexpression modules with relationships to running behavior. From these modules, we built a network correlated with running that predicts a mechanistic relationship between transcriptional regulation by nucleosome structure and Htr1b expression. The Library of Integrated Network-Based Cellular Signatures identified the protein kinase C δ inhibitor, rottlerin, the tyrosine kinase inhibitor, Linifanib and the delta-opioid receptor antagonist 7-benzylidenenaltrexone as potential compounds for increasing the motivation to run. Taken together, our findings support a neurobiological framework of exercise motivation where chromatin state leads to differences in dopamine signaling through modulation of both the primary neurotransmitters glutamate and GABA, and by neuromodulators such as serotonin.

The evolution of the placenta drives a shift in sexual selection in livebearing fish.

The evolution of the placenta from a non-placental ancestor causes a shift of maternal investment from pre- to post-fertilization, creating a venue for parent-offspring conflicts during pregnancy. Theory predicts that the rise of these conflicts should drive a shift from a reliance on pre-copulatory female mate choice to polyandry in conjunction with post-zygotic mechanisms of sexual selection. This hypothesis has not yet been empirically tested. Here we apply comparative methods to test a key prediction of this hypothesis, which is that the evolution of placentation is associated with reduced pre-copulatory female mate choice. We exploit a unique quality of the livebearing fish family Poeciliidae: placentas have repeatedly evolved or been lost, creating diversity among closely related lineages in the presence or absence of placentation. We show that post-zygotic maternal provisioning by means of a placenta is associated with the absence of bright coloration, courtship behaviour and exaggerated ornamental display traits in males. Furthermore, we found that males of placental species have smaller bodies and longer genitalia, which facilitate sneak or coercive mating and, hence, circumvents female choice. Moreover, we demonstrate that post-zygotic maternal provisioning correlates with superfetation, a female reproductive adaptation that may result in polyandry through the formation of temporally overlapping, mixed-paternity litters. Our results suggest that the emergence of prenatal conflict during the evolution of the placenta correlates with a suite of phenotypic and behavioural male traits that is associated with a reduced reliance on pre-copulatory female mate choice.

Effects of early-life exposure to Western diet and wheel access on metabolic syndrome profiles in mice bred for high voluntary exercise.

Experimental studies manipulating diet and exercise have shown varying effects on metabolic syndrome components in both humans and rodents. To examine the potential interactive effects of diet, exercise and genetic background, we studied mice from four replicate lines bred (52 generations) for high voluntary wheel running (HR lines) and four unselected control lines (C). At weaning, animals were housed for 60 days with or without wheels and fed either a standard chow or Western diet (WD, 42% kcal from fat). Four serial (three juvenile and one adult) blood samples were taken to measure fasting total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides and glucose. Western diet was obesogenic for all mice, even after accounting for the amount of wheel running and kilojoules consumed. Western diet significantly raised glucose as well as TC and HDL-C concentrations. At the level of individual variation (repeatability), there was a modest correlation (r = 0.3-0.5) of blood lipids over time, which was reduced with wheel access and/or WD. Neither genetic selection history nor wheel access had a statistically significant effect on blood lipids. However, HR and C mice had divergent ontogenetic trajectories for body mass and caloric intake. HR mice also had lower adiposity, an effect that was dependent on wheel access. The environmental factors of diet and wheel access had pronounced effects on body mass, food consumption and fasting glucose concentrations, interacting with each other and/or with genetic strain. These data underscore the importance (and often unpredictable nature) of genotype-by-environment and environment-by-environment interactions when studying body weight regulation.

Neurological disease in lambs associated with exposure to high environmental temperature and humidity.

BACKGROUND: We detected a pattern of lambs presenting with hyperthermia and neurological signs during the summer. OBJECTIVES: The main objectives of this study were to compare clinical findings and results of diagnostic testing and to identify a potential etiology. ANIMALS: Fifteen clinical cases of lambs less than 12 months of age presenting with neurological signs, tachypnea, and hyperthermia over 4 summers. METHODS: Retrospective case series. Medical records were searched for lambs less than 12 months of age that presented with neurological signs including the following: kyphosis, pelvic limb hyperextension, treading of feet, muscle tremors and recumbency, and hyperthermia of greater than 104°F. A grading system was established to describe severity of presenting neurological signs. Weather data were collected from weather stations near the farm of origin for 3 days prior to presentation. RESULTS: The lambs were from 7 flocks in central Texas. All cases occurred between July and September, with a median heat index of 90.5 for the 3 days before presentation. Complete blood count, serum chemistry, necropsy examination, rumen content, virology, brain MRI, liver copper, selenium, and vitamin E failed to identify a consistent etiology for the signs presented. The only common factor was high heat and humidity. Histopathological examination identified axonal degeneration and skeletal muscle necrosis in some lambs. CONCLUSIONS AND CLINICAL IMPORTANCE: These clinical cases appeared similar to the Australian disease humpyback and indicate that lambs exposed to high environmental temperatures and humidity might be at risk of developing the described clinical presentation.

Selection for increased voluntary wheel-running affects behavior and brain monoamines in mice.

Selective-breeding of house mice for increased voluntary wheel-running has resulted in multiple physiological and behavioral changes. Characterizing these differences may lead to experimental models that can elucidate factors involved in human diseases and disorders associated with physical inactivity, or potentially treated by physical activity, such as diabetes, obesity, and depression. Herein, we present ethological data for adult males from a line of mice that has been selectively bred for high levels of voluntary wheel-running and from a non-selected control line, housed with or without wheels. Additionally, we present concentrations of central monoamines in limbic, striatal, and midbrain regions. We monitored wheel-running for 8 weeks, and observed home-cage behavior during the last 5 weeks of the study. Mice from the selected line accumulated more revolutions per day than controls due to increased speed and duration of running. Selected mice exhibited more active behaviors than controls, regardless of wheel access, and exhibited less inactivity and grooming than controls. Selective-breeding also influenced the longitudinal patterns of behavior. We found statistically significant differences in monoamine concentrations and associated metabolites in brain regions that influence exercise and motivational state. These results suggest underlying neurochemical differences between selected and control lines that may influence the observed differences in behavior. Our results bolster the argument that selected mice can provide a useful model of human psychological and physiological diseases and disorders.

Mice selectively bred for high voluntary wheel running have larger midbrains: support for the mosaic model of brain evolution.

Increased brain size, relative to body mass, is a primary characteristic distinguishing the mammalian lineage. This greater encephalization has come with increased behavioral complexity and, accordingly, it has been suggested that selection on behavioral traits has been a significant factor leading to the evolution of larger whole-brain mass. In addition, brains may evolve in a mosaic fashion, with functional components having some freedom to evolve independently from other components, irrespective of, or in addition to, changes in size of the whole brain. We tested whether long-term selective breeding for high voluntary wheel running in laboratory house mice results in changes in brain size, and whether those changes have occurred in a concerted or mosaic fashion. We measured wet and dry brain mass via dissections and brain volume with ex vivo magnetic resonance imaging of brains that distinguished the caudate-putamen, hippocampus, midbrain, cerebellum and forebrain. Adjusting for body mass as a covariate, mice from the four replicate high-runner (HR) lines had statistically larger non-cerebellar wet and dry brain masses than those from four non-selected control lines, with no differences in cerebellum wet or dry mass or volume. Moreover, the midbrain volume in HR mice was ~13% larger (P<0.05), while volumes of the caudate-putamen, hippocampus, cerebellum and forebrain did not differ statistically between HR and control lines. We hypothesize that the enlarged midbrain of HR mice is related to altered neurophysiological function in their dopaminergic system. To our knowledge, this is the first example in which selection for a particular mammalian behavior has been shown to result in a change in size of a specific brain region.

The comparative biology of diving in two genera of European Dytiscidae (Coleoptera).

Surfacing behaviour is fundamental in the ecology of aquatic air-breathing organisms; however, it is only in vertebrates that the evolutionary ecology of diving has been well characterized. Here, we explore the diving behaviour of dytiscid beetles, a key group of surface-exchanging freshwater invertebrates, by comparing the dive responses of 25 taxa (Deronectes and Ilybius spp.) acclimated at two temperatures. The allometric slopes of dive responses in these dytiscids appear similar to those of vertebrate ectotherms, supporting the notion that metabolic mode shapes the evolution of diving performance. In both genera, beetles spend more time submerged than on the surface, and surface time does not vary with the temperature of acclimation. However, presumably in order to meet increased oxygen demand at higher temperatures, Deronectes species increase surfacing frequency, whereas Ilybius species decrease dive time, an example of 'multiple solutions.' Finally, widespread northern species appear to possess higher diving performances than their geographically restricted southern relatives, something which may have contributed to their range expansion ability.

Variation in within-bone stiffness measured by nanoindentation in mice bred for high levels of voluntary wheel running.

The hierarchical structure of bone, involving micro-scale organization and interaction of material components, is a critical determinant of macro-scale mechanics. Changes in whole-bone morphology in response to the actions of individual genes, physiological loading during life, or evolutionary processes, may be accompanied by alterations in underlying mineralization or architecture. Here, we used nanoindentation to precisely measure compressive stiffness in the femoral mid-diaphysis of mice that had experienced 37 generations of selective breeding for high levels of voluntary wheel running (HR). Mice (n = 48 total), half from HR lines and half from non-selected control (C) lines, were divided into two experimental groups, one with 13-14 weeks of access to a running wheel and one housed without wheels (n = 12 in each group). At the end of the experiment, gross and micro-computed tomography (microCT)-based morphometric traits were measured, and reduced elastic modulus (E(r)) was estimated separately for four anatomical quadrants of the femoral cortex: anterior, posterior, lateral, and medial. Two-way, mixed-model analysis of covariance (ancova) showed that body mass was a highly significant predictor of all morphometric traits and that structural change is more apparent at the microCT level than in conventional morphometrics of whole bones. Both line type (HR vs. C) and presence of the mini-muscle phenotype (caused by a Mendelian recessive allele and characterized by a approximately 50% reduction in mass of the gastrocnemius muscle complex) were significant predictors of femoral cortical cross-sectional anatomy. Measurement of reduced modulus obtained by nanoindentation was repeatable within a single quadrant and sensitive enough to detect inter-individual differences. Although we found no significant effects of line type (HR vs. C) or physical activity (wheel vs. no wheel) on mean stiffness, anterior and posterior quadrants were significantly stiffer (P < 0.0001) than medial and lateral quadrants (32.67 and 33.09 GPa vs. 29.78 and 30.46 GPa, respectively). Our findings of no significant difference in compressive stiffness in the anterior and posterior quadrants agree with previous results for mice, but differ from those for large mammals. Integrating these results with others from ongoing research on these mice, we hypothesize that the skeletons of female HR mice may be less sensitive to the effects of chronic exercise, due to decreased circulating leptin levels and potentially altered endocannabinoid signaling.

Behavioral traits are affected by selective breeding for increased wheel-running behavior in mice.

Voluntary physical activity may be related to personality traits. Here, we investigated these relations in two mouse lines selectively bred for high voluntary wheel-running behavior and in one non-selected control line. Selection lines were more explorative and "information gathering" in the open-field test, either with increased upright positions or horizontal locomotion toward the middle ring. Furthermore, one of the selection lines had an increased risk-taking behavior relative to the control line in approaching a novel object placed in the center of the open field. However, anxiety behavior was increased in selection lines during the plus-maze test. Maze learning was not statistically different among lines, but routine behavior was increased in both selection lines when the maze exit after 2 days of testing was displaced. Specifically, in the displaced maze, selected mice traveled more frequently to the old, habituated exit, bypassing the new exit attached to their home cage. Although the generality of the results would need to be confirmed in future studies including all eight lines in the selection experiment, the increased routine and exploratory behavior (at least in the lines used in the present study) may be adaptive to sustain high activity levels.

Western diet increases wheel running in mice selectively bred for high voluntary wheel running.

OBJECTIVE: Mice from a long-term selective breeding experiment for high voluntary wheel running offer a unique model to examine the contributions of genetic and environmental factors in determining the aspects of behavior and metabolism relevant to body-weight regulation and obesity. Starting with generation 16 and continuing through to generation 52, mice from the four replicate high runner (HR) lines have run 2.5-3-fold more revolutions per day as compared with four non-selected control (C) lines, but the nature of this apparent selection limit is not understood. We hypothesized that it might involve the availability of dietary lipids. METHODS: Wheel running, food consumption (Teklad Rodent Diet (W) 8604, 14% kJ from fat; or Harlan Teklad TD.88137 Western Diet (WD), 42% kJ from fat) and body mass were measured over 1-2-week intervals in 100 males for 2 months starting 3 days after weaning. RESULTS: WD was obesogenic for both HR and C, significantly increasing both body mass and retroperitoneal fat pad mass, the latter even when controlling statistically for wheel-running distance and caloric intake. The HR mice had significantly less fat than C mice, explainable statistically by their greater running distance. On adjusting for body mass, HR mice showed higher caloric intake than C mice, also explainable by their higher running. Accounting for body mass and running, WD initially caused increased caloric intake in both HR and C, but this effect was reversed during the last four weeks of the study. Western diet had little or no effect on wheel running in C mice, but increased revolutions per day by as much as 75% in HR mice, mainly through increased time spent running. CONCLUSION: The remarkable stimulation of wheel running by WD in HR mice may involve fuel usage during prolonged endurance exercise and/or direct behavioral effects on motivation. Their unique behavioral responses to WD may render HR mice an important model for understanding the control of voluntary activity levels.

Erythropoietin elevates VO2,max but not voluntary wheel running in mice.

Voluntary activity is a complex trait, comprising both behavioral (motivation, reward) and anatomical/physiological (ability) elements. In the present study, oxygen transport was investigated as a possible limitation to further increases in running by four replicate lines of mice that have been selectively bred for high voluntary wheel running and have reached an apparent selection limit. To increase oxygen transport capacity, erythrocyte density was elevated by the administration of an erythropoietin (EPO) analogue. Mice were given two EPO injections, two days apart, at one of two dose levels (100 or 300 microg kg(-1)). Hemoglobin concentration ([Hb]), maximal aerobic capacity during forced treadmill exercise (VO2,max) and voluntary wheel running were measured. [Hb] did not differ between high runner (HR) and non-selected control (C) lines without EPO treatment. Both doses of EPO significantly (P<0.0001) increased [Hb] as compared with sham-injected animals, with no difference in [Hb] between the 100 microg kg(-1) and 300 microg kg(-1) dose levels (overall mean of 4.5 g dl(-1) increase). EPO treatment significantly increased VO2,max by approximately 5% in both the HR and C lines, with no dosexline type interaction. However, wheel running (revolutions per day) did not increase with EPO treatment in either the HR or C lines, and in fact significantly decreased at the higher dose in both line types. These results suggest that neither [Hb] per se nor VO2,max is limiting voluntary wheel running in the HR lines. Moreover, we hypothesize that the decrease in wheel running at the higher dose of EPO may reflect direct action on the reward pathway of the brain.

Effects of selective breeding for increased wheel-running behavior on circadian timing of substrate oxidation and ingestive behavior.

Fluctuations in substrate preference and utilization across the circadian cycle may be influenced by the degree of physical activity and nutritional status. In the present study, we assessed these relationships in control mice and in mice from a line selectively bred for high voluntary wheel-running behavior, either when feeding a carbohydrate-rich/low-fat (LF) or a high-fat (HF) diet. Housed without wheels, selected mice, and in particular the females, exhibited higher cage activity than their non-selected controls during the dark phase and at the onset of the light phase, irrespective of diet. This was associated with increases in energy expenditure in both sexes of the selection line. In selected males, carbohydrate oxidation appeared to be increased compared to controls. In contrast, selected females had profound increases in fat oxidation above the levels in control females to cover the increased energy expenditure during the dark phase. This is remarkable in light of the finding that the selected mice, and in particular the females showed higher preference for the LF diet relative to controls. It is likely that hormonal and/or metabolic signals increase carbohydrate preference in the selected females, which may serve optimal maintenance of cellular metabolism in the presence of augmented fat oxidation.

Morphological evolution in Tropidurinae squamates: an integrated view along a continuum of ecological settings.

Variation in squamate foot morphology is likely relevant during evolutionary processes of habitat colonization because distinct surfaces differ in energetic and functional demands for locomotion. We combined new foot morphological data with published information of limb and tail lengths to investigate evolutionary changes possibly associated with the differential usage of ecological settings by Tropidurinae species. Several traits exhibited significant phylogenetic signal, and we performed conventional and phylogenetic regressions of PC scores (retained from Principal Components Analyses of morphometric traits) on continuous ecological indices. Tropidurines from sandy habitats exhibit larger foot soles, opposite to the evolution of narrow feet in species that use branches and rocks. Also, species that usually move along trunks present longer femora. This study provides evidence for morphological adaptations associated with substrate usage in Tropidurinae, and suggests that opposite morphological profiles might evolve associated with the use of surfaces energetically and functionally contrasting, possibly leading to trade-offs.