TrpM8‐mediated somatosensation in mouse neocortex Beukema, Patrick; Cecil, Katherine L.; Peterson, Elena ...
Journal of comparative neurology (1911),
June 15, 2018, Letnik:
526, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Somatosensation is a complex sense mediated by more than a dozen distinct neural subtypes in the periphery. Although pressure and touch sensation have been mapped to primary somatosensory cortex in ...rodents, it has been controversial whether pain and temperature inputs are also directed to this area. Here we use a well‐defined somatosensory modality, cool sensation mediated by peripheral TrpM8‐receptors, to investigate the neural substrate for cool perception in the mouse neocortex. Using activation of cutaneous TrpM8 receptor‐expressing neurons, we identify candidate neocortical areas responsive for cool sensation. Initially, we optimized TrpM8 stimulation and determined that menthol, a selective TrpM8 agonist, was more effective than cool stimulation at inducing expression of the immediate‐early gene c‐fos in the spinal cord. We developed a broad‐scale brain survey method for identification of activated brain areas, using automated methods to quantify c‐fos immunoreactivity (fos‐IR) across animals. Brain areas corresponding to the posterior insular cortex and secondary somatosensory (S2) show elevated fos‐IR after menthol stimulation, in contrast to weaker activation in primary somatosensory cortex (S1). In addition, menthol exposure triggered fos‐IR in piriform cortex, the amygdala, and the hypothalamus. Menthol‐mediated activation was absent in TrpM8‐knock‐out animals. Our results indicate that cool somatosensory input broadly drives neural activity across the mouse brain, with neocortical signal most elevated in the posterior insula, as well as S2 and S1. These findings are consistent with data from humans indicating that the posterior insula is specialized for somatosensory information encoding temperature, pain, and gentle touch.
Activation of cutaneous TrpM8 receptor‐expressing neurons was used to identify candidate neocortical areas responsive for cool sensation. Brain areas corresponding to the posterior insular cortex and secondary somatosensory (S2) show elevated fos‐IR after menthol stimulation, with weaker activation in primary somatosensory cortex (S1). Menthol‐mediated activation was absent in TrpM8‐knock‐out animals. Our results indicate that cool somatosensory input broadly drives neural activity across the mouse brain, with neocortical signal most elevated in the posterior insula, as well as S2 and S1.
Imaging of Overuse Injuries of the Hip Baal, Joe D; Cecil, Katherine L; Patel, Rina ...
The Radiologic clinics of North America
61, Številka:
2
Journal Article
Recenzirano
Overuse injuries of the hip are common, and clinical diagnosis may be difficult because of overlapping and nonspecific clinical symptoms. Imaging can play an essential role in guiding diagnosis and ...management. Femoroacetabular joint structural abnormalities result in various conditions that can predispose patients to early development of osteoarthritis. Repetitive stress on the skeletally immature hip can result in apophyseal injuries. Notable nonosseous overuse hip pathologies include athletic pubalgia, trochanteric bursitis, and injuries involving the iliopsoas myotendinous unit. Timely diagnosis of overuse injuries of the hip can facilitate improved response to conservative measures and prevent irreversible damage.
Huaca Prieta—one the world’s best-known, yet least understood, early maritime mound sites—and other Preceramic sites on the north coast of Peru bear witness to the beginnings of civilization in the ...Americas. Across more than fourteen millennia of human occupation, the coalescence of maritime, agricultural, and pastoral economies in the north coast settlements set in motion long-term biological and cultural transformations that led to increased social complexity and food production, and later the emergence of preindustrial states and urbanism. These developments make Huaca Prieta a site of global importance in world archaeology. This landmark volume presents the findings of a major archaeological investigation carried out at Huaca Prieta, the nearby mound Paredones, and several Preceramic domestic sites in the lower Chicama Valley between 2006 and 2013 by an interdisciplinary team of more than fifty international specialists. The book’s contributors report on and analyze the extensive material records from the sites, including data on the architecture and spatial patterns; floral, faunal, and lithic remains; textiles; basketry; and more. Using this rich data, they build new models of the social, economic, and ontological practices of these early peoples, who appear to have favored cooperation and living in harmony with the environment over the accumulation of power and the development of ruling elites. This discovery adds a crucial new dimension to our understanding of emergent social complexity, cosmology, and religion in the Neolithic period.
Active travel such as walking or cycling has been associated with more favorable health outcomes. However, evidence on patterns of transportation in Latin America is scarce. Therefore, the aim of ...this study was to quantify and characterise socio-demographic patterns of public, private and active travel in Latin American countries.
Data from the Latin American Study of Nutrition and Health, a population-based, cross-sectional survey conducted in eight Latin American countries including Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Peru and Venezuela (n = 9218; age range: 15–65 years). Transportation modes include public (bus, taxi, subway and train), private (car and motorcycle) and active (walking and/or cycling). Outcomes for this study include time spent in different modes of transportation. We performed overall and country-specific descriptive analyses to examine differences by sex, age, socioeconomic and education level.
For the overall cohort, public transport represent 34.9% of the total travel time, whereas private, walking and cycling represent 48.2%, 10.6% and 6.3% of the total travel time. Time spent using public travel was highest in Venezuela (48.4%); Peru had the highest proportions of private travel (52.5%); Time spent walking and cycling was highest in Costa Rica (14.8% and 12.2%, respectively). The average travel time spent in public and private transport were 299.5 min/week (95% CI: 292.4307.0) and 379.6 min/week (95% CI: 368.0, 391.5) respectively; figures for walking and cycling were 186.9 min/week (95% CI: 181.8, 191.9) and 201.1 min/week (95% CI: 187.8, 216.9).
Public and private transport were the most common forms of travel in Latin America. Active travel (walking or cycling) represent 17% of total physical activity, therefore, promoting and providing the right infrastructure for active commuting could translate in increasing the population overall levels of physical activity in Latin America.
Transporte activo como caminada o bicicleta ha sido asociado con una salud más favorable. Sin embrago, la evidencia en transporte activo en Latinoamérica es escasa. Por lo tanto, el objetivo de este estudio fue cuantificar y describir las características sociodemográficas del transporte público, privado y activo en países de Latino América.
Los datos provienen del “Estudio sobre Nutrición y Salud en Latinoamérica”, y fueron recogidos a través de encuestas nacionales en ocho países, incluyendo Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Peru y Venezuela (n = 9.218; edad: 15–65 años). Los modos de transportarse fueron, público (bus, taxi, metro y tren), privado (auto y motocicleta) y activo (caminar y/o bicicleta). Los resultados incluyeron el tiempo dedicado a los diferentes modos de transporte. Se realizó un análisis descriptivo de cada país para examinar las diferencias por sexo, edad, nivel socioeconómico y educativo.
En general, el tiempo utilizado para transporte público representó el 34,9%, mientras que para el transporte privado, caminar y desplazarse en bicicleta representaron un 48,2%, 10,6% y 6,3%. El tiempo utilizado en viajes públicos fue más alto en Venezuela (48,4%); Perú tuvo la mayor cantidad de viajes privados (52,5%); el tiempo dedicado a caminar y bicicleta fue más alto en Costa Rica (14,8% y 12,2%). El tiempo de viaje en transporte público y privado fue de 299,5 min/semana (IC95%: 292,4–307,0) y 379,6 min/semana (IC95%: 368,0–391,5); las cifras de caminar y bicicleta fueron 186,9 min/semana (IC95%: 181,8–191,9) y 201,1 min/semana (IC95%: 187,8–216,9).
El transporte público y privado fueron las formas de desplazamiento más comunes. Los viajes activos (caminada o bicicleta) representan el 17% de la actividad física total, por tanto, promover y proporcionar la infraestructura adecuada para los desplazamientos activos, podría traducirse en un aumento de los niveles generales de actividad física en América Latina.
O transporte ativo, como caminhada ou bicicleta, tem sido associado com uma saúde mais favorável. No entanto, as evidências do transporte ativo na América Latina são escassas. Portanto, o objetivo deste estudo foi quantificar e descrever as características sociodemográficas do transporte público, privado e ativo em países da América Latina.
Os dados são provenientes do “Estudo sobre Nutrição e Saúde na América Latina” e foram coletados por meio de pesquisas nacionais em oito países, incluindo Argentina, Brasil, Chile, Colômbia, Costa Rica, Equador, Perú e Venezuela (n = 9218; Idade: 15 a 65 anos). Os modos de transporte foram: público (ônibus, táxi, metrô e trem), privado (carro e moto) e ativo (caminhada e/ou bicicleta). Os resultados incluíram o tempo dedicado aos diferentes modos de transporte. Uma análise descritiva de cada país foi realizada para examinar as diferenças por sexo, idade, nível socioeconômico e educacional.
ados: Em geral, o tempo utilizado no transporte público representou 34,9%, enquanto no transporte privado, caminhada e ciclismo foram 48,2%, 10,6% e 6,3%. O tempo gasto em transporte público foi maior na Venezuela (48,4%); O Peru teve a maior quantidade de transporte privado (52,5%); o tempo gasto caminhando e andando de bicicleta foi maior na Costa Rica (14,8% e 12,2%). O tempo médio por transporte público e privado foi de 299,5 min/semana (IC95%: 292,4–307,0) e 379,6 min/semana (IC95%: 368,0–391,5); os números de caminhada e bicicleta foram 186,9 min/semana (IC 95%: 181,8–191,9) e 201,1 min/semana (IC 95%: 187,8–216,9).
O transporte público e privado foram as formas mais comuns de deslocamento. O transporte ativo (caminhada ou ciclismo) representam 17% da atividade física total, portanto, promover e fornecer infraestrutura adequada para o deslocamento ativo pode resultar em um aumento nos níveis gerais de atividade física da população em América Latina.
•Studies of active travel have historically under-represented Latin American countries due to the lack of surveillance data.•ELANS study collected data on transport and active travel which we have analyzed to quantify socio-demographic patterns.•Four-fifths of travel time was spent in transport; one-fifth was spent in active travel and differences between countries.•Mean levels of travel time spent walking and bicycling were lowest in Brazil and in Ecuador, respectively.•Our findings can help to develop and target policies to promote active travel in Latin America.
The number of words children produce (expressive vocabulary) and understand (receptive vocabulary) changes rapidly during early development, partially due to genetic factors. Here, we performed a ...meta–genome-wide association study of vocabulary acquisition and investigated polygenic overlap with literacy, cognition, developmental phenotypes, and neurodevelopmental conditions, including attention-deficit/hyperactivity disorder (ADHD).
We studied 37,913 parent-reported vocabulary size measures (English, Dutch, Danish) for 17,298 children of European descent. Meta-analyses were performed for early-phase expressive (infancy, 15–18 months), late-phase expressive (toddlerhood, 24–38 months), and late-phase receptive (toddlerhood, 24–38 months) vocabulary. Subsequently, we estimated single nucleotide polymorphism–based heritability (SNP-h2) and genetic correlations (rg) and modeled underlying factor structures with multivariate models.
Early-life vocabulary size was modestly heritable (SNP-h2 = 0.08–0.24). Genetic overlap between infant expressive and toddler receptive vocabulary was negligible (rg = 0.07), although each measure was moderately related to toddler expressive vocabulary (rg = 0.69 and rg = 0.67, respectively), suggesting a multifactorial genetic architecture. Both infant and toddler expressive vocabulary were genetically linked to literacy (e.g., spelling: rg = 0.58 and rg = 0.79, respectively), underlining genetic similarity. However, a genetic association of early-life vocabulary with educational attainment and intelligence emerged only during toddlerhood (e.g., receptive vocabulary and intelligence: rg = 0.36). Increased ADHD risk was genetically associated with larger infant expressive vocabulary (rg = 0.23). Multivariate genetic models in the ALSPAC (Avon Longitudinal Study of Parents and Children) cohort confirmed this finding for ADHD symptoms (e.g., at age 13; rg = 0.54) but showed that the association effect reversed for toddler receptive vocabulary (rg = −0.74), highlighting developmental heterogeneity.
The genetic architecture of early-life vocabulary changes during development, shaping polygenic association patterns with later-life ADHD, literacy, and cognition-related traits.
To determine the costs and hospital resource use from all PICU patients readmitted with a PICU stay within 12 months of hospital index discharge.
Cross-sectional, retrospective cohort study using ...Pediatric Health Information System.
Fifty-two tertiary children's hospitals.
Pediatric patients under 18 years old admitted to the PICU from January 1, 2016, to December 31, 2017.
None.
Patient characteristics and costs of care were compared between those with readmission requiring PICU care and those with only a single PICU admission per annum. In this 2-year cohort, there were 239,157 index PICU patients of which 36,970 (15.5%) were readmitted and required PICU care during the 12 months following index admission. The total hospital cost for all index admissions and readmissions was $17.3 billion, of which 21.5% ($3.71 billion) were incurred during a readmission stay involving care in the PICU; of the 3,459,079 hospital days, 20.3% (702,200) were readmission days including those where PICU care was required. Of the readmitted patients, 11,703 (30.0%) received only PICU care, accounting for $662 million in costs and 110,215 PICU days. Although 43.6% of all costs were associated with patients who required readmission, these patients only accounted for 15.5% of the index patients and 28% of index hospitalization expenditures. More patients in the readmitted group had chronic complex conditions at index discharge compared with those not readmitted (83.9% vs 54.9%;
< 0.001). Compared with those discharged directly to home without home healthcare, patients discharged to a skilled nursing facility had 18% lower odds of readmission (odds ratio 0.82 95% CI, 0.75-0.89;
< 0.001) and those discharged home with home healthcare had 43% higher odds of readmission (odds ratio, 1.43 95% CI, 1.36-1.51;
< 0.001).
Repeated admissions with PICU care resulted in significant direct medical costs and resource use for U.S. children's hospitals.
Liver fibrosis is common in children with NAFLD and is an important determinant of outcomes. High-performing noninvasive models to assess fibrosis in children are needed. The objectives of this study ...were to evaluate the performance of existing pediatric and adult fibrosis prediction models and to develop a clinical prediction rule for identifying moderate-to-severe fibrosis in children with NAFLD.
We enrolled children with biopsy-proven NAFLD in the Nonalcoholic Steatohepatitis Clinical Research Network within 90 days of liver biopsy. We staged liver fibrosis in consensus using the Nonalcoholic Steatohepatitis Clinical Research Network scoring system. We evaluated existing pediatric and adult models for fibrosis and developed a new pediatric model using the least absolute shrinkage and selection operator with linear and spline terms for discriminating moderate-to-severe fibrosis from none or mild fibrosis. The model was internally validated with 10-fold cross-validation. We evaluated 1055 children with NAFLD, of whom 26% had moderate-to-severe fibrosis. Existing models performed poorly in classifying fibrosis in children, with area under the receiver operator curves (AUC) ranging from 0.57 to 0.64. In contrast, our new model, fibrosis in pediatric NAFLD was derived from fourteen common clinical variables and had an AUC of 0.79 (95% CI: 0.77-0.81) with 72% sensitivity and 76% specificity for identifying moderate-to-severe fibrosis.
Existing fibrosis prediction models have limited clinical utility in children with NAFLD. Fibrosis in pediatric NAFLD offers improved performance characteristics for risk stratification by identifying moderate-to-severe fibrosis in children with NAFLD.
Seizures are an under-reported feature of the SATB2-associated syndrome phenotype. We describe the electroencephalographic findings and seizure semiology and treatment in a population of individuals ...with SATB2-associated syndrome.
We performed a retrospective review of 101 individuals with SATB2-associated syndrome who were reported to have had a previous electroencephalographic study to identify those who had at least one reported abnormal result. For completeness, a supplemental survey was distributed to the caregivers and input from the treating neurologist was obtained whenever possible.
Forty-one subjects were identified as having at least one prior abnormal electroencephalography. Thirty-eight individuals (93%) had epileptiform discharges, 28 (74%) with central localization. Sleep stages were included as part of the electroencephalographies performed in 31 individuals (76%), and epileptiform activity was recorded during sleep in all instances (100%). Definite clinical seizures were diagnosed in 17 individuals (42%) with a mean age of onset of 3.2 years (four months to six years), and focal seizures were the most common type of seizure observed (42%). Six subjects with definite clinical seizures needed polytherapy (35%). Delayed myelination and/or abnormal white matter hyperintensities were seen on neuroimaging in 19 individuals (61%).
Epileptiform abnormalities are commonly seen in individuals with SATB2-associated syndrome. A baseline electroencephalography that preferably includes sleep stages is recommended during the initial evaluation of all individuals with SATB2-associated syndrome, regardless of clinical suspicion of epilepsy.
Background
The number of words children produce (expressive vocabulary) and understand (receptive vocabulary) changes rapidly during early development, partially due to genetic factors. Here, we ...performed a meta–genome-wide association study of vocabulary acquisition and investigated polygenic overlap with literacy, cognition, developmental phenotypes, and neurodevelopmental conditions, including attention-deficit/hyperactivity disorder (ADHD).
Methods
We studied 37,913 parent-reported vocabulary size measures (English, Dutch, Danish) for 17,298 children of European descent. Meta-analyses were performed for early-phase expressive (infancy, 15–18 months), late-phase expressive (toddlerhood, 24–38 months), and late-phase receptive (toddlerhood, 24–38 months) vocabulary. Subsequently, we estimated single nucleotide polymorphism–based heritability (SNP-h2) and genetic correlations (rg) and modeled underlying factor structures with multivariate models.
Results
Early-life vocabulary size was modestly heritable (SNP-h2 = 0.08–0.24). Genetic overlap between infant expressive and toddler receptive vocabulary was negligible (rg = 0.07), although each measure was moderately related to toddler expressive vocabulary (rg = 0.69 and rg = 0.67, respectively), suggesting a multifactorial genetic architecture. Both infant and toddler expressive vocabulary were genetically linked to literacy (e.g., spelling: rg = 0.58 and rg = 0.79, respectively), underlining genetic similarity. However, a genetic association of early-life vocabulary with educational attainment and intelligence emerged only during toddlerhood (e.g., receptive vocabulary and intelligence: rg = 0.36). Increased ADHD risk was genetically associated with larger infant expressive vocabulary (rg = 0.23). Multivariate genetic models in the ALSPAC (Avon Longitudinal Study of Parents and Children) cohort confirmed this finding for ADHD symptoms (e.g., at age 13; rg = 0.54) but showed that the association effect reversed for toddler receptive vocabulary (rg = −0.74), highlighting developmental heterogeneity.
Conclusions
The genetic architecture of early-life vocabulary changes during development, shaping polygenic association patterns with later-life ADHD, literacy, and cognition-related traits.
Research analyzing behavioral activation (BA) teletherapy outcomes is limited. Among low-income real-world primary care patients receiving a brief BA teletherapy program for depression and anxiety, ...we analyzed descriptive statistics and changes in depression and anxiety scores throughout treatment.
One hundred thirty patients completed an intake assessment from June 2015 to August 2016; outcomes included the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7). Data from 74 low-income, primary care patients completing at least one therapy session were analyzed to characterize the demographics of therapy patients, to describe their depression and anxiety symptoms throughout treatment, and to examine whether patients who completed 4 or more sessions had statistically lower exit scores than those completing fewer than 4.
Patients were moderately depressed (PHQ-9 score: mean = 14.46) and anxious (GAD-7 score: mean = 11.91) at intake. Patients were predominantly Latino/Latina (68.9%), Spanish-speaking (54.0%), and female (79.7%). The majority of patients who received at least one therapy session achieved and sustained depression remission. Patients who completed ≥ 4 therapy sessions demonstrated lower final session depression (PHQ-9: mean = 5.13, SD = 4.75) and anxiety (GAD-7: mean = 4.77, SD = 4.21) scores compared to those completing < 4 sessions (PHQ-9: mean = 8.04, SD = 6.20, P = .029; GAD-7: mean = 8.00, SD = 6.02, P = .011).
Primary care patients demonstrated improvements in depressive and anxious symptoms throughout BA-based teletherapy. BA teletherapy is feasible and associated with improved outcomes as an adjunct or alternative intervention for primary care providers and in low-income, charity populations..
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