RESUMEN
Congenital disorders of glycosylation (CDG) and Niemann-Pick type C (NPC) disease are inborn errors of metabolism that can both present with infantile-onset severe liver disease and other multisystemic manifestations. Plasma bile acid and N-palmitoyl-O-phosphocholineserine (PPCS) are screening biomarkers with proposed improved sensitivity and specificity for NPC. We report an infant with ATP6AP1-CDG who presented with cholestatic liver failure and elevated plasma oxysterols and bile acid, mimicking NPC clinically and biochemically. On further investigation, PPCS, but not the bile acid derivative N-(3ß,5α,6ß-trihydroxy-cholan-24-oyl) glycine (TCG), were elevated in plasma samples from individuals with ATP6AP1-, ALG1-, ALG8-, and PMM2-CDG. These findings highlight the importance of keeping CDG within the diagnostic differential when evaluating children with early onset severe liver disease and elevated bile acid or PPCS to prevent delayed diagnosis and treatment.
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Trastornos Congénitos de Glicosilación , Enfermedad de Niemann-Pick Tipo C , Oxiesteroles , ATPasas de Translocación de Protón Vacuolares , Lactante , Niño , Humanos , Glicosilación , Ácidos y Sales Biliares , HidrolasasRESUMEN
INTRODUCTION: The legalization of nonmedical cannabis in 2018 may have important implications for tobacco use in Canada. There is a risk of renormalizing tobacco use with co-use of tobacco and cannabis introducing nontobacco users to tobacco. Co-use is the use of both substances by the same individual at the same time or on different occasions, as well as mixed together. This study assessed the prevalence of co-use and mixing of tobacco and cannabis among Ontario adults and the characteristics of the users. AIMS AND METHODS: Data from the 1996 to 2017 cycles of the Centre for Addiction and Mental Health Monitor (nâ =â 4481) were used to examine trends in prevalence and the proportion of Ontario adults co-using and mixing tobacco and cannabis. Logistic regression was used to study associations between user characteristics and co-use and mixing. RESULTS: Co-use of cigarettes and cannabis among cannabis users declined from 59.8% in 1996 to 41.7% in 2017. Past-year e-cigarette use was the only predictor of co-use. From 2015 to 2017, 31.1% (95% confidence interval 27.0, 35.9) of Ontario adults who used cannabis reported mixing it with tobacco in the past year. Being white, past-year e-cigarette use, having moderate or high nicotine dependence, and having moderate or high risk for cannabis problems were significant predictors of mixing among cannabis users. CONCLUSION: Given the well-established negative health effects associated with tobacco use, alongside a growing evidence base for negative health effects of cannabis smoking, co-use and mixing could pose a considerable public health concern in the context of legalization. IMPLICATIONS: Considerable effort has been expended to reduce tobacco smoking. However, current efforts to reduce tobacco smoking may be diminished since this study found the prevalence of mixing tobacco and cannabis among cannabis users in Ontario to be higher than expected. Mixing tobacco and cannabis may introduce nontobacco smokers to tobacco, exposing them to health risks associated with both cannabis and tobacco smoke. Therefore, there is a need to monitor changes in tobacco use and understanding implications for tobacco control and cessation programs within the changing environment of cannabis legalization in Canada and other jurisdictions.
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Sistemas Electrónicos de Liberación de Nicotina/estadística & datos numéricos , Fumar Marihuana/epidemiología , Fumadores/psicología , Uso de Tabaco/epidemiología , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ontario/epidemiología , Prevalencia , Tabaquismo/epidemiología , Adulto JovenRESUMEN
BACKGROUND: The prevalence of e-cigarette use among youth and young adults has increased markedly in recent years; however, little is known about young people's perceptions of e-cigarette addiction. This study examines factors associated with self-reported addiction to e-cigarette use among this population. METHODS: In 2018, 1048 Canadians aged 16-25 years were recruited through online social media platforms to complete a survey. Quota sampling was used to oversample regular e-cigarette users (vaping at least weekly); these 578 regular users were included in this analysis. Self-perceived addiction was assessed by asking participants if they felt they were 'very', 'somewhat' or 'not at all' addicted to e-cigarettes. A proportional odds model was employed to identify factors associated with the ordinal outcome. RESULTS: Almost half of regular users perceived themselves to be 'not at all addicted', 41% felt they were 'somewhat addicted' and 13% felt they were very addicted to e-cigarettes. Women, former cigarette smokers, daily vapers and those vaping for more than a year were more likely to report higher levels of perceived addiction. Similarly, high sensation-seeking youth, those reading blogs and websites about vaping, those frequently dripping and those using higher nicotine strengths had a greater likelihood of higher perceived addiction than their respective counterparts. CONCLUSION: More than half of youth and young adult regular e-cigarette users felt they had some level of addiction. The findings identify possible opportunities for targeted programming for education and treatment, as well as potential opportunities for policy change such as maximum allowable nicotine strengths.
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Sistemas Electrónicos de Liberación de Nicotina , Productos de Tabaco , Vapeo , Adolescente , Canadá/epidemiología , Femenino , Humanos , Fumadores , Encuestas y Cuestionarios , Adulto JovenRESUMEN
INTRODUCTION: Phillip Morris International (PMI) is pushing hard to promote IQOS heat-not-burn cigarettes in Ontario, Canada. Canada regulates IQOS as a tobacco product so that the robust tobacco marketing ban creates challenges to its promotion. METHODS: We collected data on IQOS promotion in 49 retail outlets, and through interviews with clerks and observations outside an IQOS store. RESULTS: The dominant marketing channel is the visible availability of IQOS in a large number of tobacco retail outlets-1029 across Ontario. Several stores display the price of 'heated tobacco' on one of three price signs which are permitted despite Ontario's total display ban. IQOS boutique stores are the locus of aggressive promotion including exchanging a pack of cigarettes or lighter for an IQOS device, launch parties, 'meet and greet' lunches and after-hour events. Outside the store, promotion includes a prominent IQOS sign, a sandwich board sign reading 'Building a Smoke-Free Future' and sales representatives regularly smoking IQOS. Membership services: Upon acquiring an IQOS device one can register to access the IQOS website store5 and receive customer support services, a map of retail locations and a product catalogue. Members receive regular email invitations to complete surveys with opportunities to win prizes. CONCLUSIONS: These promotion activities have undoubtedly made substantial numbers of Ontarians aware of IQOS. Yet, the government has not provided guidance as to absolute and relative potential harms. Our observations of tactics to promote a new tobacco product in a dark market may inform government regulatory policy and non-governmental organisation efforts wherever heat-not-burn products are introduced.
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Mercadotecnía/métodos , Industria del Tabaco/métodos , Productos de Tabaco/estadística & datos numéricos , Humanos , Mercadotecnía/estadística & datos numéricos , OntarioRESUMEN
BACKGROUND: As of 1 January 2017, the Canadian province of Ontario banned the distribution and sale of menthol tobacco products. There is limited knowledge about how tobacco companies will adapt their packaging in response to a menthol ban. METHODS: We conducted a content analysis of preban traditional menthol (no capsule) and menthol capsule cigarette packs and their postban replacements. Preban and postban packs were matched using tobacco company descriptions of replacement brands in business-to-business marketing materials, advertising on cigarette pack cellophane and a tobacco company website. RESULTS: A total of 63 menthol (n=30) and 'non-menthol alternative' (n=33) cigarette packs were included in the analysis. Approximately half of the preban packs were menthol capsule cigarettes and half traditional menthol cigarettes. While some postban brands continued to convey menthol-like qualities via the colour and/or brand descriptor 'green', 'blue' was the most common colour and brand descriptor postban. Packs shifted from using 'menthol' and/or 'fresh' as taste descriptor preban to using 'smooth' postban; some postban packs had 'non-menthol alternative' or 'without menthol/capsules' written on their cellophane. The presence of innovative filter technologies continued in the postban samples. CONCLUSION: Results suggest that tobacco companies attempted to maintain menthol smokers in Ontario by aggressive preban promotion of menthol capsule cigarettes, continued promotion of innovative filter technologies and by directing smokers to non-menthol alternatives whose packaging both in text and in colour connoted menthol-like qualities (eg, green) and reduced harshness or harm (eg, blue, white, silver, smooth taste).
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Mercadotecnía/métodos , Embalaje de Productos/métodos , Productos de Tabaco/legislación & jurisprudencia , Color , Aromatizantes , Humanos , Mentol , Ontario , Industria del TabacoRESUMEN
BACKGROUND: Maternal birth trauma to the pelvic floor muscles is thought to be consequent to mechanical demands placed on these muscles during fetal delivery that exceed muscle physiological limits. The above is consistent with studies of striated limb muscles that identify hyperelongation of sarcomeres, the functional muscle units, as the primary cause of mechanical muscle injury and resultant muscle dysfunction. However, pelvic floor muscles' mechanical response to strains have not been examined at a tissue level. Furthermore, we have previously demonstrated that during pregnancy, rat pelvic floor muscles acquire structural and functional adaptations in preparation for delivery, which likely protect against mechanical muscle injury by attenuating the strain effect. OBJECTIVE: We sought to determine the mechanical impact of parturition-related strains on pelvic floor muscles' microstructure, and test the hypothesis that pregnancy-induced adaptations modulate muscle response to strains associated with vaginal delivery. STUDY DESIGN: Three-month-old Sprague-Dawley late-pregnant (N = 20) and nonpregnant (N = 22) rats underwent vaginal distention, replicating fetal crowning, with variable distention volumes. Age-matched uninjured pregnant and nonpregnant rats served as respective controls. After sacrifice, pelvic floor muscles, which include coccygeus, iliocaudalis, and pubocaudalis, were fixed in situ and harvested for fiber and sarcomere length measurements. To ascertain the extent of physiological strains during spontaneous vaginal delivery, analogous measurements were obtained in intrapartum rats (N = 4) sacrificed during fetal delivery. Data were compared with repeated measures and 2-way analysis of variance, followed by pairwise comparisons, with significance set at P < .05. RESULTS: Gross anatomic changes were observed in the pelvic floor muscles following vaginal distention, particularly in the entheseal region of pubocaudalis, which appeared translucent. The above appearance resulted from dramatic stretch of the myofibers, as indicated by significantly longer fiber length compared to controls. Stretch ratios, calculated as fiber length after vaginal distention divided by baseline fiber length, increased gradually with increasing distention volume. Paralleling these macroscopic changes, vaginal distention resulted in acute and progressive increase in sarcomere length with rising distention volume. The magnitude of strain effect varied by muscle, with the greatest sarcomere elongation observed in coccygeus, followed by pubocaudalis, and a smaller increase in iliocaudalis, observed only at higher distention volumes. The average fetal rat volume approximated 3 mL. Pelvic floor muscle sarcomere lengths in pregnant animals undergoing vaginal distention with 3 mL were similar to intrapartum sarcomere lengths in all muscles (P > .4), supporting the validity of our experimental approach. Vaginal distention resulted in dramatically longer sarcomere lengths in nonpregnant compared to pregnant animals, especially in coccygeus and pubocaudalis (P < .0001), indicating significant attenuation of sarcomere elongation in the presence of pregnancy-induced adaptations in pelvic floor muscles. CONCLUSION: Delivery-related strains lead to acute sarcomere elongation, a well-established cause of mechanical injury in skeletal muscles. Sarcomere hyperelongation resultant from mechanical strains is attenuated by pregnancy-induced adaptations acquired by the pelvic floor muscles prior to parturition.
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Adaptación Fisiológica/fisiología , Músculo Esquelético/fisiología , Parto/fisiología , Diafragma Pélvico/fisiología , Animales , Femenino , Músculo Esquelético/ultraestructura , Embarazo , Ratas , Ratas Sprague-Dawley , Sarcómeros/ultraestructuraRESUMEN
Muscle force is dictated by micrometer-scale contractile machines called sarcomeres. Whole-muscle force drops from peak force production to zero with just a few micrometers of sarcomere length change. No current technology is able to capture adequate dynamic sarcomere data in vivo, and thus we lack fundamental data needed to understand human movement and movement disorders. Methods such as diffraction, endoscopy, and optical coherence tomography have been applied to muscle but are prohibitively invasive, sensitive to motion artifact, and/or imprecise. Here, we report dynamic sarcomere length measurement in vivo using a combination of our recently validated resonant reflection spectroscopy method combined with optical frequency domain interferometry. Using a 250-µm-wide fiber optic probe, we captured nanometer sarcomere length changes from thousands of sarcomeres on the sub-millisecond timescale during whole-muscle stretch and twitch contraction. We believe that this demonstrates the first large-scale sensing of sarcomere dynamics in vivo, which is a necessary first step to understand movement disorders and to create patient-specific surgical interventions and rehabilitation.
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Contracción Muscular , Sarcómeros/fisiología , Animales , Modelos Biológicos , ConejosRESUMEN
As we walk, we must accurately place our feet to stabilize our motion and to navigate our environment. We must also achieve this accuracy despite imperfect sensory feedback and unexpected disturbances. In this study we tested whether the nervous system uses state estimation to beneficially combine sensory feedback with forward model predictions to compensate for these challenges. Specifically, subjects wore prism lenses during a visually guided walking task, and we used trial-by-trial variation in prism lenses to add uncertainty to visual feedback and induce a reweighting of this input. To expose altered weighting, we added a consistent prism shift that required subjects to adapt their estimate of the visuomotor mapping relationship between a perceived target location and the motor command necessary to step to that position. With added prism noise, subjects responded to the consistent prism shift with smaller initial foot placement error but took longer to adapt, compatible with our mathematical model of the walking task that leverages state estimation to compensate for noise. Much like when we perform voluntary and discrete movements with our arms, it appears our nervous systems uses state estimation during walking to accurately reach our foot to the ground. NEW & NOTEWORTHY: Accurate foot placement is essential for safe walking. We used computational models and human walking experiments to test how our nervous system achieves this accuracy. We find that our control of foot placement beneficially combines sensory feedback with internal forward model predictions to accurately estimate the body's state. Our results match recent computational neuroscience findings for reaching movements, suggesting that state estimation is a general mechanism of human motor control.
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Adaptación Fisiológica/fisiología , Retroalimentación Sensorial/fisiología , Pie , Postura/fisiología , Percepción Visual/fisiología , Caminata/fisiología , Simulación por Computador , Femenino , Humanos , Masculino , Modelos Biológicos , Movimiento , Desempeño Psicomotor , Adulto JovenRESUMEN
People can adapt their gait to minimize energetic cost, indicating that walking's neural control has access to ongoing measurements of the body's energy use. In this study we tested the hypothesis that an important source of energetic cost measurements arises from blood gas receptors that are sensitive to O2 and CO2 concentrations. These receptors are known to play a role in regulating other physiological processes related to energy consumption, such as ventilation rate. Given the role of O2 and CO2 in oxidative metabolism, sensing their levels can provide an accurate estimate of the body's total energy use. To test our hypothesis, we simulated an added energetic cost for blood gas receptors that depended on a subject's step frequency and determined if subjects changed their behavior in response to this simulated cost. These energetic costs were simulated by controlling inspired gas concentrations to decrease the circulating levels of O2 and increase CO2 We found this blood gas control to be effective at shifting the step frequency that minimized the ventilation rate and perceived exertion away from the normally preferred frequency, indicating that these receptors provide the nervous system with strong physiological and psychological signals. However, rather than adapt their preferred step frequency toward these lower simulated costs, subjects persevered at their normally preferred frequency even after extensive experience with the new simulated costs. These results suggest that blood gas receptors play a negligible role in sensing energetic cost for the purpose of optimizing gait.NEW & NOTEWORTHY Human gait adaptation implies that the nervous system senses energetic cost, yet this signal is unknown. We tested the hypothesis that the blood gas receptors sense cost for gait optimization by controlling blood O2 and CO2 with step frequency as people walked. At the simulated energetic minimum, ventilation and perceived exertion were lowest, yet subjects preferred walking at their original frequency. This suggests that blood gas receptors are not critical for sensing cost during gait.
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Dióxido de Carbono/sangre , Metabolismo Energético , Oxígeno/sangre , Caminata , Adaptación Fisiológica , Adolescente , Humanos , Adulto JovenRESUMEN
Congenital disorders of glycosylation (CDG) arise from pathogenic mutations in over 100 genes leading to impaired protein or lipid glycosylation. ALG1 encodes a ß1,4 mannosyltransferase that catalyzes the addition of the first of nine mannose moieties to form a dolichol-lipid linked oligosaccharide intermediate required for proper N-linked glycosylation. ALG1 mutations cause a rare autosomal recessive disorder termed ALG1-CDG. To date 13 mutations in 18 patients from 14 families have been described with varying degrees of clinical severity. We identified and characterized 39 previously unreported cases of ALG1-CDG from 32 families and add 26 new mutations. Pathogenicity of each mutation was confirmed based on its inability to rescue impaired growth or hypoglycosylation of a standard biomarker in an alg1-deficient yeast strain. Using this approach we could not establish a rank order comparison of biomarker glycosylation and patient phenotype, but we identified mutations with a lethal outcome in the first two years of life. The recently identified protein-linked xeno-tetrasaccharide biomarker, NeuAc-Gal-GlcNAc2 , was seen in all 27 patients tested. Our study triples the number of known patients and expands the molecular and clinical correlates of this disorder.
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Trastornos Congénitos de Glicosilación/genética , Manosiltransferasas/genética , Mutación , Polisacáridos/metabolismo , Biomarcadores/metabolismo , Trastornos Congénitos de Glicosilación/metabolismo , Femenino , Genes Letales , Glicosilación , Humanos , Masculino , Análisis de Secuencia de ADN , Análisis de SupervivenciaRESUMEN
Laser diffraction (LD) is a valuable tool for measuring sarcomere length (Ls), a major determinant of muscle function. However, this method relies on few measurements per sample that are often extrapolated to whole muscle properties. Currently it is not possible to measure Ls throughout an entire muscle and determine how Ls varies at this scale. To address this issue, we developed an actuated LD scanner for sampling large numbers of sarcomeres in thick whole muscle longitudinal sections. Sections of high optical quality and fixation were produced from tibialis anterior and extensor digitorum longus muscles of Sprague-Dawley rats (N=6). Scans produced two-dimensional Ls maps, capturing >85% of the muscle area per section. Individual Ls measures generated by automatic LD and bright-field microscopy showed excellent agreement over a large Ls range (ICC>0.93). Two-dimensional maps also revealed prominent regional Ls variations across muscles.
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Secciones por Congelación , Músculo Esquelético/fisiología , Sarcómeros/fisiología , Animales , Rayos Láser , Masculino , Ratas Sprague-Dawley , Descanso/fisiologíaRESUMEN
OBJECTIVE: This report describes how staff-designed behavior changes among senior leaders can have a positive impact on clinical nursing staff and enhance the culture of safety in a community hospital. BACKGROUND: A positive culture of safety in a hospital improves outcomes for patients and staff. Senior leaders are accountable for developing an environment that supports a culture of safety. At 1 community hospital, surveys demonstrated that staff members did not view senior leaders as supportive of or competent in creating a culture of safety. METHODS: After approval from the hospital's institutional review board was obtained, clinical nurses generated and selected ideas for senior leader behavior change. The new behaviors were assessed by a convenience sample survey of clinical nurses. In addition, culture of safety survey results were compared. Risk reports and harm events were also measured before and after behavior changes. RESULTS: The volume of risk and near-miss reports increased, showing that clinical staff were more inclined to report events after senior leader communication, access, and visibility increased. Harm events went down. The culture of safety survey demonstrated an improvement in the senior leadership domain in 4 of 6 units. The anonymous convenience survey demonstrated that staff members recognized changes that senior leaders had made and felt that these changes positively impacted the culture of safety. CONCLUSIONS: By developing skills in communication, advocacy, visibility, and access, senior leaders can enhance a hospital's culture of safety and create stronger ties with clinical staff.
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Liderazgo , Enfermeras Administradoras , Personal de Enfermería en Hospital , Cultura Organizacional , Seguridad del Paciente , Administración de la Seguridad/organización & administración , Hospitales Comunitarios , HumanosRESUMEN
Genomic disruptions, altered epigenetic mechanisms, and environmental factors contribute to the heterogeneity of congenital heart defects (CHD). In recent years, chromosomal microarray analysis (CMA) has led to the identification of numerous copy number variations (CNV) in patients with CHD. Genes disrupted by and within these CNVs thus represent excellent candidate genes for CHD. Microduplications of 9q (9q+) have been described in patients with CHD, however, the critical gene locus remains undetermined. Here we discuss an infant with tetralogy of Fallot with absent pulmonary valve, fetal hydrops, and a 3.76 Mb de novo contiguous gain of 9q34.2-q34.3 detected by CMA, and confirmed by karyotype and FISH studies. This duplicated interval disrupted RXRA (retinoid X receptor alpha; OMIM #180245) at intron 1. We also review CHD findings among previously reported patients with 9q (9q+) duplication syndrome. This is the first report implicating RXRA in CHD with 9q duplication, providing additional data in understanding the genetic etiology of tetralogy of Fallot, CHD, and disorders linked to 9q microduplication syndrome. This report also highlights the significance of CMA in the clinical diagnosis and genetic counseling of patients and families with complex CHD.
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Cardiopatías Congénitas/genética , Válvula Pulmonar/anomalías , Tetralogía de Fallot/genética , Trisomía , Cromosomas Humanos Par 9 , Femenino , Humanos , Recién Nacido , Receptor alfa X Retinoide/genética , Tetralogía de Fallot/etiologíaRESUMEN
INTRODUCTION: There are limited data on the use of electronic cigarettes (e-cigarettes) among youth, particularly with regard to the use of nicotine versus nonnicotine products. This study investigates ever use of nicotine and nonnicotine e-cigarettes and examines the demographic and behavioral correlates of e-cigarette use in Ontario, Canada. METHODS: Data for 2,892 high school students were derived from the 2013 Ontario Student Drug Use and Health Survey. This province-wide school-based survey is based on a 2-stage cluster design. Bivariate and multivariate analyses were used to investigate the factors associated with ever use of e-cigarettes. Ever use of e-cigarettes was derived from the question, "Have you ever smoked at least one puff from an electronic cigarette?" All analyses included appropriate adjustments for the complex study design. RESULTS: Fifteen percent of high school students reported using e-cigarettes in their lifetime. Most students who ever used e-cigarettes reported using e-cigarettes without nicotine (72%), but 28% had used e-cigarettes with nicotine. Male, White/Caucasian, and rural students, as well as those with a history of using tobacco cigarettes, were at greater odds of e-cigarette use. Seven percent of students who had never smoked a tobacco cigarette in their lifetime reported using an e-cigarette. Five percent of those who had ever used an e-cigarette had never smoked a tobacco cigarette. CONCLUSION: More students reported ever using e-cigarettes without nicotine than with nicotine in Ontario, Canada. This underscores the need for greater knowledge of the contents of both nicotine and nonnicotine e-cigarettes to better guide public health policies.
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Conducta del Adolescente , Sistemas Electrónicos de Liberación de Nicotina/estadística & datos numéricos , Nicotina/administración & dosificación , Estudiantes/estadística & datos numéricos , Adolescente , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Ontario/epidemiología , Instituciones Académicas , Fumar/epidemiología , Prevención del Hábito de Fumar , Estudiantes/psicologíaRESUMEN
OBJECTIVE: To examine the effect of varying levels of comprehensive tobacco control on smoking in a global context. METHODS: Using data from WHO's Reports on the Global Tobacco Epidemic, scatter plots were produced to visualise the relationship between comprehensive tobacco control policy (2008 MPOWER composite score) and change in current tobacco smoking between 2006 and 2009. Fixed-effect regression models assessed the effect of changes in each MPOWER measure on changes in current tobacco smoking between 2006 and 2009. All analyses were stratified by sex. RESULTS: Overall, countries with higher MPOWER composite scores experienced greater decreases in current tobacco smoking between the years 2006 and 2009. Regression analyses revealed that the M and R measures showed a negative association with current tobacco smoking over time. Current tobacco smoking decreased (1.07 percentage points for males, 1.04 percentage points for females) with each increase in score value for monitoring tobacco use (M). Also, current tobacco smoking decreased (0.95 percentage points for males, 0.41 percentage points for females) with each increase in score value for raising taxes on tobacco (R). The effect of the MPOWER measures on current tobacco smoking varied by country income status (P measure in the female analysis; p<0.05) and/or by WHO region (M, P and O measures in the male analysis; p<0.05). CONCLUSIONS: Higher levels of MPOWER combined, as well as continued and frequent monitoring of tobacco use (M) and increasing taxation (R), were associated with a decrease in current tobacco smoking over time.
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Salud Global , Política de Salud , Fumar/epidemiología , Impuestos/economía , Femenino , Humanos , Masculino , Prevalencia , Análisis de Regresión , Factores Sexuales , Fumar/economía , Prevención del Hábito de Fumar , Organización Mundial de la SaludRESUMEN
Sarcomeres, the functional units of contraction in striated muscle, are composed of an array of interdigitating protein filaments. Direct interaction between overlapping filaments generates muscular force, which produces animal movement. When filament length is known, sarcomere length successfully predicts potential force, even in whole muscles that contain billions of sarcomere units. Inability to perform in vivo sarcomere measurements with submicrometer resolution is a long-standing challenge in the muscle physiology field and has hampered studies of normal muscle function, adaptation, injury, aging, and disease, particularly in humans. Here, we develop theory and demonstrate the feasibility of to our knowledge a new technique that measures sarcomere length with submicrometer resolution. In this believed novel approach, we examine sarcomere structure by measuring the multiple resonant reflections that are uniquely defined by Fourier decomposition of the sarcomere protein spatial framework. Using a new supercontinuum spectroscopic system, we show close agreement between sarcomere lengths measured by resonant reflection spectroscopy and laser diffraction in an ensemble of 10 distinct muscles.
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Sarcómeros/metabolismo , Análisis Espectral , Animales , Estudios de Factibilidad , Ratones , Modelos Biológicos , Proteínas Musculares/metabolismo , Fenómenos Ópticos , ConejosRESUMEN
When moving slowly, kangaroos plant their tail on the ground in sequence with their front and hind legs. To determine the tail's role in this 'pentapedal' gait, we measured the forces the tail exerts on the ground and calculated the mechanical power it generates. We found that the tail is responsible for as much propulsive force as the front and hind legs combined. It also generates almost exclusively positive mechanical power, performing as much mass-specific mechanical work as does a human leg during walking at the same speed. Kangaroos use their muscular tail to support, propel and power their pentapedal gait just like a leg.
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Locomoción/fisiología , Macropodidae/fisiología , Cola (estructura animal)/fisiología , Animales , Fenómenos Biomecánicos , Extremidades/fisiología , Femenino , Marcha , Masculino , Músculo Esquelético/fisiología , Esfuerzo Físico/fisiologíaRESUMEN
The ability of an animal to detect and respond to changes in the environment is crucial to its survival. However, two elements of sensorimotor control - the time required to respond to a stimulus (responsiveness) and the precision of stimulus detection and response production (resolution) - are inherently limited by a competition for space in peripheral nerves and muscles. These limitations only become more acute as animal size increases. In this paper, we investigated whether the physiology of giraffes has found unique solutions for maintaining sensorimotor performance in order to compensate for their extreme size. To examine responsiveness, we quantified three major sources of delay: nerve conduction delay, muscle electromechanical delay and force generation delay. To examine resolution, we quantified the number and size distribution of nerve fibers in the sciatic nerve. Rather than possessing a particularly unique sensorimotor system, we found that our measurements in giraffes were broadly comparable to size-dependent trends seen across other terrestrial mammals. Consequently, both giraffes and other large animals must contend with greater sensorimotor delays and lower innervation density in comparison to smaller animals. Because of their unconventional leg length, giraffes may experience even longer delays compared with other animals of the same mass when sensing distal stimuli. While there are certainly advantages to being tall, there appear to be challenges as well - our results suggest that giraffes are less able to precisely and accurately sense and respond to stimuli using feedback alone, particularly when moving quickly.
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Tamaño Corporal/fisiología , Contracción Muscular/fisiología , Conducción Nerviosa/fisiología , Rumiantes/fisiología , Nervio Ciático/fisiología , Animales , Fenómenos Biomecánicos , Masculino , Neuronas Motoras/fisiología , Especificidad de la Especie , Factores de TiempoRESUMEN
BACKGROUND: Sleep plays a critical role in maintaining health and well-being; however, patients who are hospitalized are frequently exposed to noise that can disrupt sleep. Efforts to attenuate hospital noise have been limited by incomplete information on the interaction between sounds and sleep physiology. OBJECTIVE: To determine profiles of acoustic disruption of sleep by examining the cortical (encephalographic) arousal responses during sleep to typical hospital noises by sound level and type and sleep stage. DESIGN: 3-day polysomnographic study. SETTING: Sound-attenuated sleep laboratory. PARTICIPANTS: Volunteer sample of 12 healthy participants. INTERVENTION: Baseline (sham) night followed by 2 intervention nights with controlled presentation of 14 sounds that are common in hospitals (for example, voice, intravenous alarm, phone, ice machine, outside traffic, and helicopter). The sounds were administered at calibrated, increasing decibel levels (40 to 70 dBA [decibels, adjusted for the range of normal hearing]) during specific sleep stages. MEASUREMENTS: Encephalographic arousals, by using established criteria, during rapid eye movement (REM) sleep and non-REM (NREM) sleep stages 2 and 3. RESULTS: Sound presentations yielded arousal response curves that varied because of sound level and type and sleep stage. Electronic sounds were more arousing than other sounds, including human voices, and there were large differences in responses by sound type. As expected, sounds in NREM stage 3 were less likely to cause arousals than sounds in NREM stage 2; unexpectedly, the probability of arousal to sounds presented in REM sleep varied less by sound type than when presented in NREM sleep and caused a greater and more sustained elevation of instantaneous heart rate. LIMITATIONS: The study included only 12 participants. Results for these healthy persons may underestimate the effects of noise on sleep in patients who are hospitalized. CONCLUSION: Sounds during sleep influence both cortical brain activity and cardiovascular function. This study systematically quantifies the disruptive capacity of a range of hospital sounds on sleep, providing evidence that is essential to improving the acoustic environments of new and existing health care facilities to enable the highest quality of care. PRIMARY FUNDING SOURCE: Academy of Architecture for Health, Facilities Guidelines Institute, and The Center for Health Design.
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Hospitalización , Ruido/efectos adversos , Fases del Sueño/fisiología , Estimulación Acústica , Electroencefalografía , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Polisomnografía , Estudios Prospectivos , Vigilia/fisiología , Adulto JovenRESUMEN
Newborn male circumcision has potential benefits and advantages as well as disadvantages and risks. Families will at times have medical questions regarding newborn male circumcision that clinicians must be prepared to answer.