A randomized, controlled trial comparing ganciclovir to ganciclovir plus foscarnet (each at half dose) for preemptive therapy of cytomegalovirus infection in transplant recipients

Forty-eight patients who provided 2 consecutive blood samples that tested positive for cytomegalovirus DNA by polymerase chain reaction (PCR) were randomized to receive either full-dose ganciclovir ( 5 mg/kg intravenously [iv] twice daily) or half-dose ganciclovir (5 mg/kg iv once daily) plus half-dose foscarnet (90 mg/kg iv once daily) for 14 days. In the ganciclovir arm, 17 (71%) of 24 patients reached the primary end point of being CMV negative by PCR within 14 days of initiation of therapy, compared with 12 (50%) of 24 patients in the ganciclovir-plus-foscarnet arm (P = .12). Toxicity was greater in the combination-therapy arm. In patients who failed to reach the primary end point, baseline virus load was 0.77 log(10) higher, the replication rate before therapy was faster (1.5 vs. 2.7 days), and the viral decay rate was slower (2.9 vs. 1.1 days) after therapy. Bivariable logistic regression models identified baseline virus load, bone-marrow transplantation, and doubling time and half-life of decay as the major factors affecting response to therapy within 14 days. This study did not support a synergistic effect of ganciclovir plus foscarnet in vivo

The potential impact of climate change on Australia's soil organic carbon resources

BACKGROUND: Soil organic carbon (SOC) represents a significant pool of carbon within the biosphere. Climatic shifts in temperature and precipitation have a major influence on the decomposition and amount of SOC stored within an ecosystem and that released into the atmosphere. We have linked net primary production (NPP) algorithms, which include the impact of enhanced atmospheric CO(2 )on plant growth, to the SOCRATES terrestrial carbon model to estimate changes in SOC for the Australia continent between the years 1990 and 2100 in response to climate changes generated by the CSIRO Mark 2 Global Circulation Model (GCM). RESULTS: We estimate organic carbon storage in the topsoil (0–10 cm) of the Australian continent in 1990 to be 8.1 Gt. This equates to 19 and 34 Gt in the top 30 and 100 cm of soil, respectively. By the year 2100, under a low emissions scenario, topsoil organic carbon stores of the continent will have increased by 0.6% (49 Mt C). Under a high emissions scenario, the Australian continent becomes a source of CO(2 )with a net reduction of 6.4% (518 Mt) in topsoil carbon, when compared to no climate change. This is partially offset by the predicted increase in NPP of 20.3% CONCLUSION: Climate change impacts must be studied holistically, requiring integration of climate, plant, ecosystem and soil sciences. The SOCRATES terrestrial carbon cycling model provides realistic estimates of changes in SOC storage in response to climate change over the next century, and confirms the need for greater consideration of soils in assessing the full impact of climate change and the development of quantifiable mitigation strategies

Brucellosis remains a neglected disease inthe developing world: a call forinterdisciplinary action

Brucellosis places significant burdens on the human healthcare system and limits the economic growth of individuals, communities, and nations where such development is especially important to diminish the prevalence of poverty. The implementation of public policy focused on mitigating the socioeconomic effects of brucellosis in human and animal populations is desperately needed. When developing a plan to mitigate the associated consequences, it is vital to consider both the abstract and quantifiable effects. This requires an interdisciplinary and collaborative, or One Health, approach that consists of public education, the development of an infrastructure for disease surveillance and reporting in both veterinary and medical fields, and campaigns for control in livestock and wildlife species

Role of the mesoamygdaloid dopamine projection in emotional learning

Amygdala dopamine is crucially involved in the acquisition of Pavlovian associations, as measured via conditioned approach to the location of the unconditioned stimulus (US). However, learning begins before skeletomotor output, so this study assessed whether amygdala dopamine is also involved in earlier 'emotional' learning. A variant of the conditioned reinforcement (CR) procedure was validated where training was restricted to curtail the development of selective conditioned approach to the US location, and effects of amygdala dopamine manipulations before training or later CR testing assessed. Experiment 1a presented a light paired (CS+ group) or unpaired (CS- group) with a US. There were 1, 2 or 10 sessions, 4 trials per session. Then, the US was removed, and two novel levers presented. One lever (CR+) presented the light, and lever pressing was recorded. Experiment 1b also included a tone stimulus. Experiment 2 applied intra-amygdala R(+) 7-OH-DPAT (10 nmol/1.0 A mu l/side) before two training sessions (Experiment 2a) or a CR session (Experiment 2b). For Experiments 1a and 1b, the CS+ group preferred the CR+ lever across all sessions. Conditioned alcove approach during 1 or 2 training sessions or associated CR tests was low and nonspecific. In Experiment 2a, R(+) 7-OH-DPAT before training greatly diminished lever pressing during a subsequent CR test, preferentially on the CR+ lever. For Experiment 2b, R(+) 7-OH-DPAT infusions before the CR test also reduced lever pressing. Manipulations of amygdala dopamine impact the earliest stage of learning in which emotional reactions may be most prevalent

Using visual methods to understand physical activity maintenance following cardiac rehabilitation

© 2015 Hardcastle et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Few studies have explored the factors associated with long-term maintenance of exercise following cardiac rehabilitation. The present study used auto-photography and interviews to explore the factors that influence motivation and continued participation in physical activity among post cardiac rehabilitation patients. Twenty-three semi-structured interviews were conducted alongside participant-selected photographs or drawings with participants that had continued participation in physical activity for at least two years following the cardiac rehabilitation programme. Participants were recruited from circuit training classes in East Sussex in the UK. Thematic content analysis revealed seven main themes: fear of death and ill health avoidance, critical incidents, overcoming aging, social influences, being able to enjoy life, provision of routine and structure, enjoyment and psychological well-being. Fear of death, illness avoidance, overcoming aging, and being able to enjoy life were powerful motives for continued participation in exercise. The social nature of the exercise class was also identified as a key facilitator of continued participation. Group-based exercise suited those that continued exercise participation post cardiac rehabilitation and fostered adherence

Anti-Allergic Cromones Inhibit Histamine and Eicosanoid Release from Activated Human and Murine Mast Cells by Releasing Annexin A1

PMCID: PMC3601088This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Genetic determinants of co-accessible chromatin regions in activated T cells across humans.

Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression

Prevalence of obesity and associated risk factors among adults in Kinondoni municipal district, Dar es Salaam Tanzania

Obesity is on the rise worldwide, not sparing developing countries. Both demographic and socio-economic factors play parts in obesity causation. Few surveys have been conducted in Tanzania to determine the magnitude of obesity and its association with these risk factors. This study aimed at determining the prevalence of obesity and its associated risk factors among adults aged 18 - 65 years in Kinondoni municipality, Dar es Salaam, Tanzania from April 2007 to April 2008. Random sampling of households was performed. Interviews and anthropometric measurement were carried out to eligible and consenting members of the selected households. Obesity was defined using Body Mass Index (BMI).\ud Out of 1249 subjects recruited, 814 (65.2%) were females. The overall prevalence of obesity was 19.2% (240/1249). However, obesity was significantly more prevalent in women (24.7%) than men (9%), p < 0.001, among respondents with high socio-economic status (29.2%) as compared to those with medium (14.3%) and low socio-economic status (11.3%), p value for trend < 0.001, and among respondents with light intensity activities (26.0%), p value for trend < 0.001.\ud This study revealed a higher prevalence of obesity among Kinondoni residents than previously reported in other parts of the country. Independent predictors of obesity in the population studied were increasing age, marriage and cohabitation, high SES, female sex and less vigorous physical activities