Expression of amphetamine sensitization is associated with recruitment of a reactive neuronal population in the nucleus accumbens core

Rationale: Repeated exposure to psychostimulant drugs causes a long-lasting increase in the psychomotor and reinforcing effects of these drugs and an array of neuroadaptations. One such alteration is a hypersensitivity of striatal activity such that a low dose of amphetamine in sensitized animals produces dorsal striatal activation patterns similar to acute treatment with a high dose of amphetamine. Objectives: To extend previous findings of striatal hypersensitivity with behavioral observations and with cellular activity in the nucleus accumbens and prefrontal cortex in sensitized animals. Materials and methods: Rats treated acutely with 0, 1, 2.5, or 5 mg/kg i.p. amphetamine and sensitized rats challenged with 1 mg/kg i.p. amphetamine were scored for stereotypy, rearing, and grooming, and locomotor activity recorded. c-fos positive nuclei were quantified in the nucleus accumbens and prefrontal cortex after expression of sensitization with 1 mg/kg i.p. amphetamine. Results: Intense stereotypy was seen in animals treated acutely with 5 mg/kg amphetamine, but not in the sensitized group treated with 1 mg/kg amphetamine. The c-fos response to amphetamine in the accumbens core was augmented in amphetamine-pretreated animals with a shift in the distribution of optical density, while no effect of sensitization was seen in the nucleus accumbens shell or prefrontal cortex. Conclusions A lack of stereotypy in the sensitized group indicates a dissociation of behavioral responses to amphetamine and striatal immediate-early gene activation patterns. The increase in c-fos positive nuclei and shift in the distribution of optical density observed in the nucleus accumbens core suggests recruitment of a new population of neurons during expression of sensitization

A novel c.-22T>C mutation in GALK1 promoter is associated with elevated galactokinase phenotype

<p>Abstract</p> <p>Background</p> <p>Many genetic variations of <it>GALK1 </it>have been identified in the patients with galactokinase (GALK1) deficiency. However, the molecular characteristics of <it>GALK1 </it>in individuals with elevated GALK1 activity are relatively unknown.</p> <p>Methods</p> <p>We investigated the relationship between elevated GALK1 activity and the molecular <it>GALK1 </it>gene variations, and the molecular mechanism underlying elevated GALK1 activity. PCR products from 63 subjects, without any attenuation of galactose degradation enzymes, were sequenced to screen for nucleotide alterations in the <it>GALK1 </it>promoter.</p> <p>Results</p> <p>Three nucleotide substitutions were identified: c.-179A>G, c.-27A>C, and c.-22T>C. With respect to the c.-22T>C mutation, GALK1 activity in 13 subjects with the T/C or C/C genotype was significantly higher than those in 50 subjects with the T/T genotype (p < 0.001). The dual luciferase reporter assay in Hep3B cells showed that the luciferase activity with the <it>GALK1 </it>promoter with the c.-22C mutant allele increased approximately 2.5-fold, compared to that with the c.-22T. A specific DNA-protein complex was observed in an electrophoretic mobility shift assay, with slightly higher affinity to c.-22C than to c.-22T.</p> <p>Conclusion</p> <p>The c.-22T>C mutation, which was observed frequently in individuals with elevated GALK1 activity, increased the expression of a reporter gene through enhanced binding of a currently unidentified nuclear protein. These results suggest that the elevated GALK1 activity resulted from enhanced gene expression, due to nucleotide variation within <it>GALK1 </it>promoter.</p

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Dynamic thoracohumeral kinematics are dependent upon the etiology of the shoulder injury

[EN] Obtaining kinematic patterns that depend on the shoulder injury may be important when planning rehabilitation. The main goal of this study is to explore whether the kinematic patterns of continuous and repetitive shoulder elevation motions are different according to the type of shoulder injury in question, specifically tendinopathy or rotator cuff tear, and to analyze the influence of the load handled during its assessment. For this purpose, 19 individuals with tendinopathy and 9 with rotator cuff tear performed a repetitive scaption movement that was assessed with stereophotogrammetry. Furthermore, static range of motion (ROM) and isometric strength were evaluated with a goniometer and a dynamometer, respectively. Dynamic measurements of maximum elevation (Emax), variablility of the maximum angle (VMA), maximum angular velocity (Velmax), and time to maximum velocity (tmaxvel) were found to be significantly different between the tendinopathy group (TG) and the rotator cuff tear group (RTCG). No differences were found in the ROM assessed with goniometry and the isometric strength. The effect of increasing the load placed in the hand during the scaption movement led to significant differences in Emax, VMA, tmaxvel and repeatability. Therefore, only the dynamic variables showed sufficient capability of detecting differences in functional performance associated with structural shoulder injury. The differences observed in the kinematic variables between patients with tendinopathy and rotator cuff tear seem to be related to alterations in thoracohumeral rhythm and neuromuscular control. Kinematic analysis may contribute to a better understanding of the functional impact of shoulder injuries, which would help in the assessment and treatment of shoulder pain.This work was funded by the Spanish Government, Secretaria de Estado de Investigacion, Desarrollo e Innovacion, and co-financed by EU FEDER funds (Grant DPI2013-44227-R). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Lopez Pascual, J.; Page Del Pozo, AF.; Serra Añó, P. (2017). Dynamic thoracohumeral kinematics are dependent upon the etiology of the shoulder injury. PLoS ONE. 12(8). https://doi.org/10.1371/journal.pone.0183954S12

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand

Objective: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. Design: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. Methods: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. Results: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. Conclusion: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

The Design of a Holistic mHealth Community Library Model and Its Impact on Empowering Rural America

Healthcare delivery in rural America poses additional challenges than its urban counterpart. Rural locations more commonly face shortage of physicians, a lack of high-paying jobs with adequate insurance benefits, transportation, health literacy, a stigma with health conditions due to lack of anonymity and difficulties accessing specialty care. Rural communities see higher rates of suicide, heart diseases, respiratory disease, stroke, social isolation, and public health crisis such as the opioid epidemic. More than 46 million Americans, or 15% of the population, live in rural areas within the United States. Communities play an important role in the health of their residents, as social and economic factors, physical environment, and healthy behaviors make up 80% of an individual’s overall health, while clinical care accounts for only 20%. Chronic disease doesn’t occur in isolation. Conditions such as diabetes, asthma, heart disease, and obesity are all tied very closely to the environments, culture, and behaviors that surround individuals. Therefore, a significant amount of human health is determined beyond clinical care. For many individuals who are at an elevated risk of developing chronic disease, episodic care that begins and ends inside a hospital or clinic is not adequate to accurately treat the patient. We propose a holistic mHealth community model for residents to overcome significant barriers of care in rural America by providing an application capable of integrating multiple health and safety data sources through a mobile digital personal health library application. Users are able to securely share their health data with others (e.g. primary care physician, caregiver). Artificial Intelligence (AI) algorithms can strategically connect residents to community resources and provide customized health education aimed at increasing the health literacy, empowerment, and self-management of the user. Communities can use de-identified population health data from this model to improve decision-making and allocation of community resources

Health literacy and substance use in young Swiss men.

OBJECTIVES: The purpose of the present study was to describe health literacy and its association with substance use among young men. METHODS: The present study was part of the Cohort Study on Substance Use Risk Factors that included 11,930 Swiss males participating in initial screening from August 2010 to July 2011. Self-completed questionnaires covered use of three substances and three components of health literacy. RESULTS: Roughly 22 % reported having searched the Internet for health information and 16 % for information on substances over the past 12 months. At-risk and not at-risk users of alcohol (adjusted odds ratio (AOR) = 2.50 and 1.46), tobacco (AOR = 2.51 and 1.79) and cannabis (AOR = 4.86 and 3.53) searched for information about substances significantly more often via the Internet than abstainers. Furthermore, at-risk users reported better knowledge of risks associated with substance use and a marginally better ability to understand health information than abstainers. CONCLUSIONS: Substance users appear to be more informed and knowledgeable about the risks of substance use than non-users. Consequently, interventions that focus only on information provision may be of limited benefit for preventing substance use