Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior

Midbrain dopamine neurons are crucial for many behavioral and cognitive functions. As the major excitatory input, glutamatergic afferents are important for control of the activity and plasticity of dopamine neurons. However, the role of glutamatergic input as a whole onto dopamine neurons remains unclear. Here we developed a mouse line in which glutamatergic inputs onto dopamine neurons are specifically impaired, and utilized this genetic model to directly test the role of glutamatergic inputs in dopamine-related functions. We found that while motor coordination and reward learning were largely unchanged, these animals showed prominent deficits in effort-related behavioral tasks. These results provide genetic evidence that glutamatergic transmission onto dopaminergic neurons underlies incentive motivation, a willingness to exert high levels of effort to obtain reinforcers, and have important implications for understanding the normal function of the midbrain dopamine system.Fil: Hutchison, M. A.. National Institutes of Health; Estados UnidosFil: Gu, X.. National Institutes of Health; Estados UnidosFil: Adrover, Martín Federico. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Lee, M. R.. National Institutes of Health; Estados UnidosFil: Hnasko, T. S.. University of California at San Diego; Estados UnidosFil: Alvarez, V. A.. National Institutes of Health; Estados UnidosFil: Lu, W.. National Institutes of Health; Estados Unido

Benefits and effectiveness of using a wrist heart rate monitor as a telerehabilitation device in cardiac patients A randomized controlled trial

Background: Telerehabilitation in cardiology has the potential to become the alternative to regular outpatient cardiac rehabilitation. Our study focuses on the wrist heart rate monitor as a telerehabilitation device, defines detected limitations, and compares results between home-based and regular outpatient rehabilitation methods, related to physical fitness, quality of life, and training adherence. The study design was a randomized controlled trial. Methods: Eligible 56 cardiac rehabilitation patients were randomized into a 12-week regular outpatient training group (ROT) and interventional home-based telerehabilitation group (ITG). For both groups, the intensity of the training was prescribed to be performed at 70% to 80% of heart rate reserve for 60 minutes, 3 times a week. The ITG patients started their training with a wrist heart rate monitor in their home environment. These patients received feedback once a week, reflecting data uploaded on the internet application. The ROT patients performed their exercise under the direct supervision of a physical specialist in a regular outpatient clinic. Physical fitness and health-related quality of life were assessed at baseline and after 12 weeks. Training adherence in both groups was determined and compared. Results: Fifty-one patients comleted the intervention (91%); no serious adverse events were recorded. Physical fitness expressed as peak oxygen uptake showed significant improvement (P < .001) in ROT group from 23.4 +/- 3.3 to 25.9 +/- 4.1 mL/kg/min and (P < .01) in ITG group from 23.7 +/- 4.1 to 26.5 +/- 5.7 mL/kg/min without significant between-group differences after 12 weeks of intervention. The training adherence between groups was similar. Conclusion: Our study shows that telerehabilitation via wrist heart rate monitor could become an alternative kind of cardiac rehabilitation which deserves attention and further analyzing

Risk factors for Brucella spp. and Coxiella burnetii infection among small ruminants in Eastern India

Small ruminants are the main reservoirs for brucellosis and coxiellosis, two zoonotic diseases affecting livestock production, and posing a public health threat in India. Understanding disease prevalence and risk factors associated with small ruminant infection can help mitigate disease transmission. We report a cross-sectional survey in the states of Assam and Odisha in Eastern India. We interviewed 244 farmers to assess knowledge, attitude and practices relevant to brucellosis and coxiellosis infection. Serum samples from 411 goats and 21 sheep were analysed using enzyme-linked immunosorbent assay and Rose-Bengal Brucella agglutination plate test. Higher Brucella and Coxiella burnetii seroprevalence were found in Odisha (22% and 11.5%, respectively) than Assam (9.8% and 1.6%, respectively), and certain districts in Odisha were at higher risk. No association was found between seropositive animals and clinical signs, a challenge when attempting to identify seropositive animals in the herd. None of the farmers interviewed were aware of brucellosis, its aetiology, clinical form, or zoonotic risk. This study acts as a first indication of the extent of these diseases among small ruminants in these Indian states, highlighting how farming practices are associated with increased risk of infection. More research is urgently needed to mitigate zoonoses transmission in this region

Patient advocacy: barriers and facilitators

BACKGROUND: During the two recent decades, advocacy has been a topic of much debate in the nursing profession. Although advocacy has embraced a crucial role for nurses, its extent is often limited in practice. While a variety of studies have been generated all over the world, barriers and facilitators in the patient advocacy have not been completely identified. This article presents the findings of a study exploring the barriers and facilitators influencing the role of advocacy among Iranian nurses. METHOD: This study was conducted by grounded theory method. Participants were 24 Iranian registered nurses working in a large university hospital in Tehran, Iran. Semi-structured interviews were used for data collection. All interviews were transcribed verbatim and simultaneously Constant comparative analysis was used according to the Strauss and Corbin method. RESULTS: Through data analysis, several main themes emerged to describe the factors that hindered or facilitated patient advocacy. Nurses in this study identified powerlessness, lack of support, law, code of ethics and motivation, limited communication, physicians leading, risk of advocacy, royalty to peers, and insufficient time to interact with patients and families as barriers to advocacy. As for factors that facilitated nurses to act as a patient advocate, it was found that the nature of nurse-patient relationship, recognizing patients' needs, nurses' responsibility, physician as a colleague, and nurses' knowledge and skills could be influential in adopting the advocacy role. CONCLUSION: Participants believed that in this context taking an advocacy role is difficult for nurses due to the barriers mentioned. Therefore, they make decisions and act as a patient's advocate in any situation concerning patient needs and status of barriers and facilitators. In most cases, they can not act at an optimal level; instead they accept only what they can do, which we called 'limited advocacy' in this study. It is concluded that advocacy is contextually complex, and is a controversial and risky component of the nursing practice. Further research is needed to determine the possibility of a correlation between identified barriers/ facilitators and the use of advocacy

The net effects of medical malpractice tort reform on health insurance losses: the Texas experience

In this paper, we examine the influence of medical malpractice tort reform on the level of private health insurance company losses incurred. We employ a natural experiment framework centered on a series of tort reform measures enacted in Texas in 2003 that drastically altered the medical malpractice environment in the state. The results of a difference-in-differences analysis using a variety of comparison states, as well as a difference-in-difference-in-differences analysis, indicate that ameliorating medical malpractice risk has little effect on health insurance losses incurred by private health insurers

A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect siz

Human H5N1 influenza infections in Cambodia 2005-2011: case series and cost-of-illness.

BACKGROUND: Southeast Asia has been identified as a potential epicentre of emerging diseases with pandemic capacity, including highly pathogenic influenza. Cambodia in particular has the potential for high rates of avoidable deaths from pandemic influenza due to large gaps in health system resources. This study seeks to better understand the course and cost-of-illness for cases of highly pathogenic avian influenza in Cambodia. METHODS: We studied the 18 laboratory-confirmed cases of avian influenza subtype H5N1 identified in Cambodia between January 2005 and August 2011. Medical records for all patients were reviewed to extract information on patient characteristics, travel to hospital, time to admission, diagnostic testing, treatment and disease outcomes. Further data related to costs was collected through interviews with key informants at district and provincial hospitals, the Ministry of Health and non-governmental organisations. An ingredient-based approach was used to estimate the total economic cost for each study patient. Costing was conducted from a societal perspective and included both financial and opportunity costs to the patient or carer. Sensitivity analysis was undertaken to evaluate potential change or variation in the cost-of-illness. RESULTS: Of the 18 patients studied, 11 (61%) were under the age of 18 years. The majority of patients (16, 89%) died, eight (44%) within 24 hours of hospital admission. There was an average delay of seven days between symptom onset and hospitalisation with patients travelling an average of 148 kilometres (8-476 km) to the admitting hospital. Five patients were treated with oseltamivir of whom two received the recommended dose. For the 16 patients who received all their treatment in Cambodia the average per patient cost of H5N1 influenza illness was US$300 of which 85.0$45 per patient (15.0%) of total economic cost. CONCLUSION: Cases of avian influenza in Cambodia were characterised by delays in hospitalisation, deficiencies in some aspects of treatment and a high fatality rate. The costs associated with medical care, particularly diagnostic testing and pharmaceutical therapy, were major contributors to the relatively high cost-of-illness

Effect of educational intervention on medication timing in Parkinson's disease: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Medicine usage in Parkinson's disease patients is often imperfect, in particular irregular timing of medication. The effect of informing Parkinson's disease patients about the continuous dopaminergic hypothesis (to encourage regular medicine intake) on medication adherence and motor control was tested.</p> <p>Methods</p> <p>Patients were randomised either to the active group (receiving the intervention) or control group (no extra information). Antiparkinson medicine usage was monitored for 3 months before and after the intervention using electronic pill bottles which record the date and time of opening (MEMS^®, Aardex, Switzerland) and data used to calculate the percentage of doses taken at correct time intervals.</p> <p>Results</p> <p>43 patients (52%) were randomised to active counselling, and 40 (48%) were controls (standard management). The intervention effect (difference in timing adherence pre- to post-intervention between the 2 groups) was 13.4% (CI 5.1 to 21.7), p = 0.002. Parkinson motor scores did not change significantly (active group 0.1, CI -3.4 to 3.7) versus controls (4.5, CI 1.6 to 7.1), p = 0.06.</p> <p>Conclusion</p> <p>Timing adherence, but not motor scores, improves by providing patients with extra information. Therapy timing is of potential importance in Parkinson's disease management.</p> <p>Trial registration number</p> <p>NCT00361205</p

Long-term and realistic global change manipulations had low impact on diversity of soil biota in temperate heathland

In a dry heathland ecosystem we manipulated temperature (warming), precipitation (drought) and atmospheric concentration of CO(2) in a full-factorial experiment in order to investigate changes in below-ground biodiversity as a result of future climate change. We investigated the responses in community diversity of nematodes, enchytraeids, collembolans and oribatid mites at two and eight years of manipulations. We used a structural equation modelling (SEM) approach analyzing the three manipulations, soil moisture and temperature, and seven soil biological and chemical variables. The analysis revealed a persistent and positive effect of elevated CO(2) on litter C:N ratio. After two years of treatment, the fungi to bacteria ratio was increased by warming, and the diversities within oribatid mites, collembolans and nematode groups were all affected by elevated CO(2) mediated through increased litter C:N ratio. After eight years of treatment, however, the CO(2)-increased litter C:N ratio did not influence the diversity in any of the four fauna groups. The number of significant correlations between treatments, food source quality, and soil biota diversities was reduced from six to three after two and eight years, respectively. These results suggest a remarkable resilience within the soil biota against global climate change treatments in the long term