Effects of prolonged endotoxemia on liver, skeletal muscle and kidney mitochondrial function

INTRODUCTION: Sepsis may impair mitochondrial utilization of oxygen. Since hepatic dysfunction is a hallmark of sepsis, we hypothesized that the liver is more susceptible to mitochondrial dysfunction than the peripheral tissues, such as the skeletal muscle. We studied the effect of prolonged endotoxin infusion on liver, muscle and kidney mitochondrial respiration and on hepatosplanchnic oxygen transport and microcirculation in pigs. METHODS: Twenty anesthetized pigs were randomized to receive either endotoxin or saline infusion for 24 hours. Muscle, liver and kidney mitochondrial respiration was assessed. The cardiac output (thermodilution) and the carotid, superior mesenteric and kidney arterial, portal venous (ultrasound Doppler) and microcirculatory blood flow (laser Doppler) were measured, and systemic and regional oxygen transport and lactate exchange were calculated. RESULTS: Endotoxin infusion induced hyperdynamic shock and impaired the glutamate-dependent and succinate-dependent mitochondrial respiratory control ratio in the liver (glutamate, median (range) endotoxemia 2.8 (2.3–3.8) vs controls 5.3 (3.8–7.0); P < 0.001; succinate, endotoxemia 2.9 (1.9–4.3) vs controls 3.9 (2.6–6.3), P = 0.003). While the ADP added/oxygen consumed ratio was reduced with both substrates, the maximal ATP production was impaired only in the succinate-dependent respiration. Hepatic oxygen consumption and extraction, and the liver surface laser Doppler blood flow remained unchanged. Glutamate-dependent respiration in the muscle and kidney was unaffected. CONCLUSION: Endotoxemia reduces the efficiency of hepatic mitochondrial respiration but neither skeletal muscle nor kidney mitochondrial respiration, independent of regional and microcirculatory blood flow changes

Producing valid statistics when legislation, culture, and medical practices differ for births at or before the threshold of survival: Report of a European workshop

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Small Nuclear RNAs Encoded by Herpesvirus saimiri Upregulate the Expression of Genes Linked to T Cell Activation in Virally Transformed T Cells

SummarySeven small nuclear RNAs of the Sm class are encoded by Herpesvirus saimiri (HVS), a γ Herpesvirus that causes aggressive T cell leukemias and lymphomas in New World primates and efficiently transforms T cells in vitro [1–4]. The Herpesvirus saimiri U RNAs (HSURs) are the most abundant viral transcripts in HVS-transformed, latently infected T cells but are not required for viral replication or transformation in vitro [5]. We have compared marmoset T cells transformed with wild-type or a mutant HVS lacking the most highly conserved HSURs, HSURs 1 and 2. Microarray and Northern analyses reveal that HSUR 1 and 2 expression correlates with significant increases in a small number of host mRNAs, including the T cell-receptor β and γ chains, the T cell and natural killer (NK) cell-surface receptors CD52 and DAP10, and intracellular proteins—SKAP55, granulysin, and NKG7—linked to T cell and NK cell activation. Upregulation of three of these transcripts was rescued after transduction of deletion-mutant-HVS-transformed cells with a lentiviral vector carrying HSURs 1 and 2. These changes indicate an unexpected role for the HSURs in regulating a remarkably defined and physiologically relevant set of host targets involved in the activation of virally transformed T cells during latency

The utility of the “Arable Weeds and Management in Europe” database: Challenges and opportunities of combining weed survey data at a European scale

Over the last 30 years many studies have surveyed weed vegetation on arable land. The “Arable Weeds and Management in Europe” (AWME) database is a collection of 36 of these surveys and the associated management data. Here we review the challenges associated with combining disparate datasets and explore some of the opportunities for future research that present themselves thanks to the advent of the AWME database. We present three case studies repeating previously published national scale analyses with data from a larger spatial extent. We demonstrate that i) the standardisation of abundance data to a common measure, prior to the analysis of the combined dataset, has little impact on the outcome of the analyses, ii) the increased length of environmental or management gradients allows for greater confidence in conclusions, iii) the main conclusions of analyses done at different spatial extents remain consistent. These case studies demonstrate the utility of a Europe-wide weed survey database, for clarifying or extending results obtained from studies at smaller scales. This Europe-wide data collection offers many more opportunities for analysis that could not be addressed in smaller datasets; including questions about the effects of climate change, macro-ecological and biogeographical issues related to weed diversity as well as the dominance or rarity of specific weeds in Europe

Students for global oncology: Building a movement for student education and engagement in an emerging field

Program/Project Purpose: Increased recognition of the global cancer burden and inequalities in care and outcomes have led to the growing field of global oncology, focused on strengthening health systems to improve cancer prevention and care. Motivated students and trainees are in need of pathways to approach these challenges. In 2012, Harvard Medical students formed Students for Global Oncology (S4GO), an adjunct to the larger inter-professional organization Global Oncology. The group had three aims: 1) connect students with mentors in the field, 2) develop novel approaches in global oncology, and 3) disseminate global oncology knowledge. Structure/Method/Design: S4GO has created content and organized events to increase awareness about the global cancer burden, while promoting trainee opportunities in research and practical hands-on projects. Engagement was enhanced by mentorship from more senior students and faculty, to interface with existing global oncology projects. Outcomes & Evaluation: Since 2012, S4GO has grown from two to 68 students. Currently, new chapters at seven other institutions in the US and Canada are being developed. As of October 2014, S4GO has developed a case-based cancer care delivery curriculum with six case-based seminars, along with numerous blog entries and interviews of leading researchers in the field of global oncology, all available on the S4GO website. Students have completed projects in over nine countries and are actively involved in technological and on-the-ground efforts to develop creative solutions and collaborations aimed at easing the global cancer burden. Held in February 2014, the inaugural student-led global oncology symposium involved 200 individuals from across the world, including leaders in global health, pharmaceutical industry, public policy and cancer care. This symposium has been viewed by hundreds online and has fostered novel collaborations and projects focused on enhancing cancer care delivery. Going Forward: In the coming years, S4GO will continue efforts to build awareness and catalyze creative solutions for cancer care in resource-limited settings. These efforts will increase exposure for novel and successful student efforts as well as intra-institutional and intra-professional activity

Simulation modeling for stratified breast cancer screening : a systematic review of cost and quality of life assumptions

BACKGROUND: The economic evaluation of stratified breast cancer screening gains momentum, but produces also very diverse results. Systematic reviews so far focused on modeling techniques and epidemiologic assumptions. However, cost and utility parameters received only little attention. This systematic review assesses simulation models for stratified breast cancer screening based on their cost and utility parameters in each phase of breast cancer screening and care. METHODS: A literature review was conducted to compare economic evaluations with simulation models of personalized breast cancer screening. Study quality was assessed using reporting guidelines. Cost and utility inputs were extracted, standardized and structured using a care delivery framework. Studies were then clustered according to their study aim and parameters were compared within the clusters. RESULTS: Eighteen studies were identified within three study clusters. Reporting quality was very diverse in all three clusters. Only two studies in cluster 1, four studies in cluster 2 and one study in cluster 3 scored high in the quality appraisal. In addition to the quality appraisal, this review assessed if the simulation models were consistent in integrating all relevant phases of care, if utility parameters were consistent and methodological sound and if cost were compatible and consistent in the actual parameters used for screening, diagnostic work up and treatment. Of 18 studies, only three studies did not show signs of potential bias. CONCLUSION: This systematic review shows that a closer look into the cost and utility parameter can help to identify potential bias. Future simulation models should focus on integrating all relevant phases of care, using methodologically sound utility parameters and avoiding inconsistent cost parameters

An investigation into the depth of penetration of low level laser therapy through the equine tendon in vivo

Low level laser therapy (LLLT) is frequently used in the treatment of wounds, soft tissue injury and in pain management. The exact penetration depth of LLLT in human tissue remains unspecified. Similar uncertainty regarding penetration depth arises in treating animals. This study was designed to test the hypothesis that transmission of LLLT in horses is increased by clipping the hair and/or by cleaning the area to be treated with alcohol, but is unaffected by coat colour. A LLLT probe (810 nm, 500 mW) was applied to the medial aspect of the superficial flexor tendon of seventeen equine forelimbs in vivo. A light sensor was applied to the lateral aspect, directly opposite the laser probe to measure the amount of light transmitted. Light transmission was not affected by individual horse, coat colour or leg. However, it was associated with leg condition (F = 4.42, p = 0.0032). Tendons clipped dry and clipped and cleaned with alcohol, were both associated with greater transmission of light than the unprepared state. Use of alcohol without clipping was not associated with an increase in light transmission. These results suggest that, when applying laser to a subcutaneous structure in the horse, the area should be clipped and cleaned beforehand