Four ways blue foods can help achieve food system ambitions across nations.

Blue foods, sourced in aquatic environments, are important for the economies, livelihoods, nutritional security and cultures of people in many nations. They are often nutrient rich1, generate lower emissions and impacts on land and water than many terrestrial meats2, and contribute to the health3, wellbeing and livelihoods of many rural communities4. The Blue Food Assessment recently evaluated nutritional, environmental, economic and justice dimensions of blue foods globally. Here we integrate these findings and translate them into four policy objectives to help realize the contributions that blue foods can make to national food systems around the world: ensuring supplies of critical nutrients, providing healthy alternatives to terrestrial meat, reducing dietary environmental footprints and safeguarding blue food contributions to nutrition, just economies and livelihoods under a changing climate. To account for how context-specific environmental, socio-economic and cultural aspects affect this contribution, we assess the relevance of each policy objective for individual countries, and examine associated co-benefits and trade-offs at national and international scales. We find that in many African and South American nations, facilitating consumption of culturally relevant blue food, especially among nutritionally vulnerable population segments, could address vitamin B12 and omega-3 deficiencies. Meanwhile, in many global North nations, cardiovascular disease rates and large greenhouse gas footprints from ruminant meat intake could be lowered through moderate consumption of seafood with low environmental impact. The analytical framework we provide also identifies countries with high future risk, for whom climate adaptation of blue food systems will be particularly important. Overall the framework helps decision makers to assess the blue food policy objectives most relevant to their geographies, and to compare and contrast the benefits and trade-offs associated with pursuing these objectives.

Can human nutrition be improved through better fish feeding practices? a review paper.

Achieving Sustainable Development Goal 2 of zero hunger and malnutrition by 2030 will require dietary shifts that include increasing the consumption of nutrient dense foods by populations in low- and middle-income countries. Animal source foods are known to be rich in a number of highly bioavailable nutrients that otherwise are not often consumed in the staple-food based diets of poorer populations throughout the world. Fish is the dominant animal source food in many low- and middle-income countries in the global south and is available from both fisheries and aquaculture. Consumers often perceive that wild caught fish have higher nutritional value than fish produced through aquaculture, and this may be true for some nutrients, for example omega-3 fatty acid content. However, there is potential to modify the nutritional value of farmed fish through feeds and through production systems, illustrated by the common practice of supplementing omega-3 fatty acids in fish diets to optimize their fatty acid profile. This manuscript reviews the evidence related to fish feeds and the nutritional composition of fish with respect to a number of nutrients of interest to human health, including iron, zinc, vitamins A and D, selenium, calcium, and omega-3 fatty acids, with low- and middle-income country populations in mind. In general, we find that the research on fortification of fish diet particularly with vitamins and minerals has not been directed toward human health but rather toward improvement of fish growth and health performance. We were unable to identify any studies directly exploring the impact of fish feed modification on the health of human consumers of fish, but as nutrition and health rises in the development agenda and consumer attention, the topic requires more urgent attention in future feed formulations.

Implementation of a pediatric enhanced recovery pathway decreases opioid utilization and shortens time to full feeding.

BACKGROUND: We hypothesized that an enhanced recovery after surgery (ERAS) pathway for pediatric patients undergoing surgery for inflammatory bowel disease (IBD) would be beneficial. METHODS: This is a single institution retrospective comparative study comparing patients treated with an ERAS pathway to consecutive patients in a Preimplementation Cohort (PIC) with similar open and laparoscopic surgeries for IBD. The pathway emphasized minimal preoperative fasting, multimodal and regional analgesia, and early enteral nutrition after surgery. Primary endpoints were time to 120 mL of PO intake (POI), length of stay (LOS), opioid utilization, and 30-day surgical outcomes. Continuous and categorical variables were compared (p < 0.05). RESULTS: There were 23 PIC and 28 ERAS patients with similar demographic data and surgical and anesthetic approaches. ERAS patients experienced a significant increase in the use of regional anesthesia, faster time to POI, and a nonsignificant decrease in mean LOS. ERAS patients had decreased total and daily opioid use with similar complication rates. CONCLUSION: This study demonstrates the effectiveness of a pediatric ERAS pathway for IBD patients requiring laparoscopic and (unique to this study) open surgery. The study demonstrates that opioid utilization and time to feeding can be positively impacted using ERAS pathways without negatively impacting outcomes. TYPE OF STUDY: Retrospective comparative study. LEVEL OF EVIDENCE: Level III.

Medically Useful Plant Terpenoids: Biosynthesis, Occurrence, and Mechanism of Action.

Specialized plant terpenoids have found fortuitous uses in medicine due to their evolutionary and biochemical selection for biological activity in animals. However, these highly functionalized natural products are produced through complex biosynthetic pathways for which we have a complete understanding in only a few cases. Here we review some of the most effective and promising plant terpenoids that are currently used in medicine and medical research and provide updates on their biosynthesis, natural occurrence, and mechanism of action in the body. This includes pharmacologically useful plastidic terpenoids such as p-menthane monoterpenoids, cannabinoids, paclitaxel (taxol®), and ingenol mebutate which are derived from the 2-C-methyl-d-erythritol-4-phosphate (MEP) pathway, as well as cytosolic terpenoids such as thapsigargin and artemisinin produced through the mevalonate (MVA) pathway. We further provide a review of the MEP and MVA precursor pathways which supply the carbon skeletons for the downstream transformations yielding these medically significant natural products.

Yellow lupin (Lupinus luteus L.) polysaccharides: Antioxidant, immunomodulatory and prebiotic activities and their structural characterisation.

Yellow lupin polysaccharides (YLP-1, YLP-2 and YLP-3) were isolated from the whole seeds of Lupinus luteus L. Their antioxidant activities were evaluated by ABTS+ and hydroxyl radical scavenging, and Fe2+ chelating assays. Immunostimulatory activities were measured by their ability to activate macrophages to produce TNF-α and NO. Four strains of probiotic bacteria were used to measure their prebiotic activities. YLP-2 with largest galactose content displayed the best activity amongst the three isolated polysaccharides. NMR and FT-IR spectroscopic methods have revealed that YLPs contain galactans and galactomannans which are linked with ß-(1,4) glycosidic bond in the main chain. The side chain Galp unit of galactomannan is connected to the main chain Manp by α-(1,6) linkage. The results presented in this paper strongly suggest that YLPs display significant antioxidant, immunostimulatory and prebiotic activities and hence hold great potential as nutraceutical and functional agents.

Changes in Arsenic, Copper, Iron, Manganese, and Zinc Levels Resulting from the Application of Poultry Litter to Agricultural Soils.

Twelve applications of poultry litter were made to a 2.1-ha field located in the Shenandoah Valley of Virginia, United States (USA), between March 1999 and August 2014. The field was planted with bermudagrass (Cynodon dactylon) and used as a pasture on an active farm. Copper, iron, manganese, zinc, and arsenic concentrations in the poultry litter were measured, and the application rates of these metals were calculated. The median application rates were: Cu, 1.32 kg/ha, Fe, 5.57 kg/ha, Mn, 1.80 kg/ha, Zn, 1.39 kg/ha, and As, 0.011 kg/ha. Twelve surface and subsurface soil samples were taken from the treated field in February 2016. Twelve samples were also taken from a comparison site. The comparison site was directly adjacent to the study site, consisted of the same soil type, and had been maintained as an undisturbed forest. Extractable Cu, Fe, Mn, Zn, and As concentrations in the soil samples were determined by atomic absorption spectroscopy, and the results of the chemical analysis were analyzed by ANOVA. Fe and Mn were depleted from the soil in the treated field, while Cu and Zn levels increased over the 12 years of treatment and grazing, and arsenic levels were unchanged in both the surface and subsurface soils between the comparison and the study site. The changes observed for Cu, Fe, Mn, and Zn are within the critical deficiency level and critical toxicity level for these metals, and no arsenic remains in the soil from roxarsone feed supplements, which were added to the poultry feed when the litter was applied to the study site.

Hyperbaric oxygen therapy is not associated with oxidative stress assessed using plasma F2-isoprostanes and isofurans.

BACKGROUND AND AIMS: Hyperbaric oxygen (HBO) therapy is increasingly used in medical practice as a means of enhancing the formation of collagen matrix and angiogenesis, thus promoting healing in wounds and necrotic tissue. However, there are concerns that oxygen can also associate with increased production of oxygen free radicals and oxidative stress. F2-Isoprostanes (F2-IsoPs) formed by non-enzymatic oxidation of arachidonic acid (AA) are reliable measures for assessing oxidative stress in vivo. In addition, under conditions of high oxygen tension isofurans (IsoFs) are preferentially formed from AA and are considered to better reflect oxidative stress in the setting of high oxygen tension. This study aimed to measure plasma IsoFs and F2-IsoP in patients receiving HBO therapy to treat osteonecrosis secondary to radiation therapy. Our hypothesis was that IsoFs would continue to rise with increasing oxygen pressures in contrast to F2-IsoPs whose synthesis would be reduced. METHODS: Twelve patients receiving hyperbaric therapy to treat osteonecrosis secondary to radiation therapy were studied during hyperbaric treatment. Blood samples were collected prior to, during and after cessation of HBO therapy that lasted for 119min. Seven serial blood samples were collected for measurement of plasma F2-IsoPs and IsoFs, blood gases and haemoglobin. RESULTS: Oxygen saturation and venous oxygen partial pressure (PvO2) rose significantly during hyperbaric therapy. However, there were no significant changes in plasma IsoFs or F2-IsoPs during the hyperbaric therapy session. CONCLUSION: In this study of patients with osteonecrosis, HBO therapy at a maximum pressure of 2.4atm with up to 100% oxygen did not worsen oxidative stress assessed using plasma F2- IsoFs and IsoPs.

Specialised pro-resolving mediators of inflammation in inflammatory arthritis.

INTRODUCTION: Specialised pro-resolving mediators (SPM) are derived from n-3 long chain polyunsaturated fatty acids (n-3FA). They promote resolution of inflammation and may contribute to the beneficial effects of n-3FA in patients with arthritis. This study compared SPM in knee effusions and plasma of patients with arthritis taking n-3FA, and plasma of healthy volunteers taking n-3FA. METHODS: Thirty six patients taking n-3FA undergoing arthrocentesis for an inflammatory knee effusion and 36 healthy volunteers who had taken n-3FA (2.4g/day) for 4 weeks were studied. SPM in synovial fluid and plasma were measured by liquid chromatography-tandem mass spectrometry included 18-hydroxyeicosapentaenoic acid (18-HEPE), the precursor of the E-series SPM (RvE1, RvE2, RvE3, 18R-RvE3), and 17-hydroxydocosahexaenoic acid (17-HDHA), the precursor of the D-series SPM (RvD1, 17R-RvD1, RvD2). Other SPM included protectin D1 (PD1), 10S,17S-dihydroxydocosahexaenoic acid (10,17S-DHDHA), maresin-1 (MaR-1) and 14-hydroxydocosahexaenoic acid (14-HDHA) derived from docosahexaenoic acid (DHA). RESULTS: E- and D-series SPM and the precursors 18-HEPE and 17-HDHA were present in synovial fluid and plasma of the patients with inflammatory arthritis. Plasma SPM were negatively related to erythrocyte sedimentation rate in arthritis patients (P<0.01) and synovial fluid RvE2 was negatively associated with pain score (P=0.02). Conversion from 18-HEPE and 17-HDHA to E- and D-series SPM was greater in synovial fluid (P<0.01). Most plasma SPM in arthritis patients were elevated (P<0.05) compared with healthy volunteers, and conversion to E- and D-series SPM was greater (P<0.01). CONCLUSIONS: SPM are present in chronic knee effusions and although the levels are lower than in plasma, the association between synovial fluid RvE2 and reduced pain scores suggests that synthesis of SPM at the site of inflammation is a relevant mechanism by which n-3FA alleviate the symptoms of arthritis.

Exercise Therapy for Parkinson's Disease: Pedaling Rate Is Related to Changes in Motor Connectivity.

Forced-rate lower-extremity exercise has recently emerged as a potential safe and low-cost therapy for Parkinson's disease (PD). The efficacy is believed to be dependent on pedaling rate, with rates above the subjects' voluntary exercise rates being most beneficial. In this study, we use functional connectivity magnetic resonance imaging (MRI) to further elucidate the mechanism underlying this effect. Twenty-seven PD patients were randomized to complete 8 weeks of forced-rate exercise (FE) or voluntary-rate exercise (VE). Exercise was delivered using a specialized stationary bicycle, which can augment patients' voluntary exercise rates. The FE group received assistance from the cycle. Imaging was conducted at baseline, end of therapy, and after 4 weeks of follow-up. Functional connectivity (FC) was determined via seed-based correlation analysis, using activation-based seeds in the primary motor cortex (M1). The change in FC after exercise was compared using linear correlation with pedaling rate. Results of the correlation analysis showed a strong positive correlation between pedaling rate and change in FC from the most affected M1 to the ipsilateral thalamus. This effect persisted after 4 weeks of follow-up. These results indicate that a plausible mechanism for the therapeutic efficacy of high-rate exercise in PD is that it improves thalamo-cortical connectivity.

Specialized proresolving lipid mediators in humans with the metabolic syndrome after n-3 fatty acids and aspirin.

BACKGROUND: The metabolic syndrome (MetS) is associated with a chronic low-grade inflammatory state and may be affected by the ability to resolve inflammation, which is an active process that involves specialized proresolving lipid mediators (SPMs) derived from n-3 (ω-3) fatty acids. OBJECTIVE: We compared plasma concentrations of SPMs in men and women with features of the MetS and in healthy matched control subjects in response to intakes of n-3 fatty acids and aspirin. DESIGN: MetS volunteers (n = 22) and healthy, matched controls (n = 21) were studied in parallel for 4 wk. Both groups took n-3 fatty acids (2.4 g/d) for 4 wk with the addition of aspirin (300 mg/d) during the last 7 d. Blood was collected at baseline and at 3 and 4 wk. Plasma SPMs were measured with the use of liquid chromatography-tandem mass spectrometry and included 18-hydroxyeicosapentaenoic acid (18-HEPE), E-series resolvins, 17-hydroxydocosahexaenoic acid (17-HDHA), D-series resolvins, 14-hydroxydocosahexaenoic acid (14-HDHA), and maresin-1. RESULTS: Baseline SPMs did not differ between groups. There was an increase in the SPM precursors 18-HEPE, 17-HDHA, and 14-HDHA after n-3 fatty acid supplementation that was significantly attenuated in the MetS (P < 0.05). However, the E-series resolvins increased to a similar extent in the groups after n-3 fatty acid supplementation, and the D-series resolvins were not different from those at baseline. The addition of aspirin to n-3 fatty acids did not alter any SPMs in either group. CONCLUSIONS: Volunteers with MetS had reduced plasma concentrations of the precursors of the E- and D- series resolvins as well as of 14-HDHA in response to n-3 fatty acid supplementation. However, plasma E-series resolvins were increased to a similar extent after n-3 fatty acid supplementation in both groups, and the addition of aspirin to n-3 fatty acid supplementation did not alter any of the plasma SPMs in MetS and control subjects. Additional studies in the MetS are required to determine whether SPMs affect the ability to mount an appropriate response to infection. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12610000708055.

Robust passive and active efflux of cellular cholesterol to a designer functional mimic of high density lipoprotein.

The ability of HDL to support macrophage cholesterol efflux is an integral part of its atheroprotective action. Augmenting this ability, especially when HDL cholesterol efflux capacity from macrophages is poor, represents a promising therapeutic strategy. One approach to enhancing macrophage cholesterol efflux is infusing blood with HDL mimics. Previously, we reported the synthesis of a functional mimic of HDL (fmHDL) that consists of a gold nanoparticle template, a phospholipid bilayer, and apo A-I. In this work, we characterize the ability of fmHDL to support the well-established pathways of cellular cholesterol efflux from model cell lines and primary macrophages. fmHDL received cell cholesterol by unmediated (aqueous) and ABCG1- and scavenger receptor class B type I (SR-BI)-mediated diffusion. Furthermore, the fmHDL holoparticle accepted cholesterol and phospholipid by the ABCA1 pathway. These results demonstrate that fmHDL supports all the cholesterol efflux pathways available to native HDL and thus, represents a promising infusible therapeutic for enhancing macrophage cholesterol efflux. fmHDL accepts cholesterol from cells by all known pathways of cholesterol efflux: unmediated, ABCG1- and SR-BI-mediated diffusion, and through ABCA1.

Repeated head trauma is associated with smaller thalamic volumes and slower processing speed: the Professional Fighters' Brain Health Study.

OBJECTIVES: Cumulative head trauma may alter brain structure and function. We explored the relationship between exposure variables, cognition and MRI brain structural measures in a cohort of professional combatants. METHODS: 224 fighters (131 mixed martial arts fighters and 93 boxers) participating in the Professional Fighters Brain Health Study, a longitudinal cohort study of licensed professional combatants, were recruited, as were 22 controls. Each participant underwent computerised cognitive testing and volumetric brain MRI. Fighting history including years of fighting and fights per year was obtained from self-report and published records. Statistical analyses of the baseline evaluations were applied cross-sectionally to determine the relationship between fight exposure variables and volumes of the hippocampus, amygdala, thalamus, caudate, putamen. Moreover, the relationship between exposure and brain volumes with cognitive function was assessed. RESULTS: Increasing exposure to repetitive head trauma measured by number of professional fights, years of fighting, or a Fight Exposure Score (FES) was associated with lower brain volumes, particularly the thalamus and caudate. In addition, speed of processing decreased with decreased thalamic volumes and with increasing fight exposure. Higher scores on a FES used to reflect exposure to repetitive head trauma were associated with greater likelihood of having cognitive impairment. CONCLUSIONS: Greater exposure to repetitive head trauma is associated with lower brain volumes and lower processing speed in active professional fighters.

Measuring the activity of 1-deoxy-D-xylulose 5-phosphate synthase, the first enzyme in the MEP pathway, in plant extracts.

The first enzyme in the methylerythritol phosphate (MEP) pathway is 1-deoxy-D-xylulose 5-phosphate (DXP) synthase (DXS). As such this enzyme is considered to be important in the control of plastidial isoprenoid production. Measuring the activity of DXS in plant extracts is therefore crucial to understanding the regulation of the MEP pathway. Due to the relatively low amounts of DXS, the activity of this enzyme can only be measured using highly sensitive analytical equipment. Here, a method is described to determine the DXS enzyme activity in a crude plant extract, by measuring DXP production directly using high performance liquid chromatography linked to a tandem triple quadrupole mass spectrometry detector (LC-MS/MS).

The protective effect of education on cognition in professional fighters.

Education has a protective effect against cognitive deficits following various forms of brain insult. Professional fighting (boxing and mixed martial arts) provides a model for assessing the impact of cumulative brain injuries on cognition and brain health. In the current cross-sectional observational study, we explore whether education would be protective against cognitive loss in fighters. We tested 141 professional fighters using a computerized neurocognitive battery, in addition to structural MRI. We used automated segmentation software to compute the volumes of various brain structures. We found fighters with high school education or less to show more associations between fight exposure and cognitive test scores. The relationship between brain structure volume and exposure did not differ based on education. These results are interpreted as putatively showing a protective effect of education on functional integrity in fighters, although longitudinal data and a larger sample size are required to further understand this relationship.

Risk factors for treatment failure of polymyxin B monotherapy for carbapenem-resistant Klebsiella pneumoniae infections.

Polymyxins are reserved for salvage therapy of infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Though synergy has been demonstrated for the combination of polymyxins with carbapenems or tigecycline, in vitro synergy tests are nonstandardized, and the clinical effect of synergy remains unclear. This study describes outcomes for patients with CRKP infections who were treated with polymyxin B monotherapy. We retrospectively reviewed the medical records of patients with CRKP infections who received polymyxin B monotherapy from 2007 to 2011. Clinical, microbiology, and antimicrobial treatment data were collected. Risk factors for treatment failure were identified by logistic regression. Forty patients were included in the analysis. Twenty-nine of 40 (73%) patients achieved clinical cure as defined by clinician-documented improvement in signs and symptoms of infections, and 17/32 (53%) patients with follow-up culture data achieved microbiological cure. End-of-treatment mortality was 10%, and 30-day mortality was 28%. In a multivariate analysis, baseline renal insufficiency was associated with a 6.0-fold increase in clinical failure after adjusting for septic shock (odds ratio [OR] = 6.0; 95% confidence interval [CI] = 1.22 to 29.59). Breakthrough infections with organisms intrinsically resistant to polymyxins occurred in 3 patients during the treatment. Eighteen of 40 (45%) patients developed a new CRKP infection a median of 23 days after initial polymyxin B treatment, and 3 of these 18 infections were polymyxin resistant. The clinical cure rate achieved in this retrospective study was 73% of patients with CRKP infections treated with polymyxin B monotherapy. Baseline renal insufficiency was a risk factor for treatment failure after adjusting for septic shock. Breakthrough infections with organisms intrinsically resistant to polymyxin B and development of resistance to polymyxin B in subsequent CRKP isolates are of concern.

Detection of volatile biomarkers of therapeutic radiation in breath.

Breath testing could provide a rational tool for radiation biodosimetry because radiation causes distinct stress-producing molecular damage, notably an increased production of reactive oxygen species. The resulting oxidative stress accelerates lipid peroxidation of polyunsaturated fatty acids, liberating alkanes and alkane metabolites that are excreted in the breath as volatile organic compounds (VOCs). Breath tests were performed before and after radiation therapy over five days in 31 subjects receiving daily fractionated doses: 180-400 cGy d(-1) standard radiotherapy (n = 26), or 700-1200 cGy d(-1) high-dose stereotactic body radiotherapy (n = 5). Breath VOCs were assayed using comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry. Multiple Monte Carlo simulations identified approximately 50 VOCs as greater-than-chance biomarkers of radiation on all five days of the study. A consistent subset of 15 VOCs was observed at all time points. A radiation response function was built by combining these biomarkers and the resulting dose-effect curve was significantly elevated at all exposures ⩾1.8 Gy. Cross-validated binary algorithms identified radiation exposures ⩾1.8 Gy with 99% accuracy, and ⩾5 Gy with 78% accuracy. In this proof of principal study of breath VOCs, we built a preliminary radiation response function based on 15 VOCs that appears to identify exposure to localized doses of 1.8 Gy and higher. VOC breath testing could provide a new tool for rapid and non-invasive radiation biodosimetry.

Professional fighters brain health study: rationale and methods.

Repetitive head trauma is a risk factor for Alzheimer's disease and is the primary cause of chronic traumatic encephalopathy. However, little is known about the natural history of, and risk factors for, chronic traumatic encephalopathy or about means of early detection and intervention. The Professional Fighters Brain Health Study is a longitudinal study of active professional fighters (boxers and mixed martial artists), retired professional fighters, and controls matched for age and level of education. The main objective of the Professional Fighters Brain Health Study is to determine the relationships between measures of head trauma exposure and other potential modifiers and changes in brain imaging and neurological and behavioral function over time. The study is designed to extend over 5 years, and we anticipate enrollment of more than 400 boxers and mixed martial artists. Participants will undergo annual evaluations that include 3-tesla magnetic resonance imaging scanning, computerized cognitive assessments, speech analysis, surveys of mood and impulsivity, and blood sampling for genotyping and exploratory biomarker studies. Statistical models will be developed and validated to predict early and progressive changes in brain structure and function. A composite fight exposure index, developed as a summary measure of cumulative traumatic exposure, shows promise as a predictor of brain volumes and cognitive function.

Results of the NeuroBlate System first-in-humans Phase I clinical trial for recurrent glioblastoma: clinical article.

OBJECT: Laser interstitial thermal therapy has been used as an ablative treatment for glioma; however, its development was limited due to technical issues. The NeuroBlate System incorporates several technological advances to overcome these drawbacks. The authors report a Phase I, thermal dose-escalation trial assessing the safety and efficacy of NeuroBlate in recurrent glioblastoma multiforme (rGBM). METHODS: Adults with suspected supratentorial rGBM of 15- to 40-mm dimension and a Karnofsky Performance Status score of ≥ 60 were eligible. After confirmatory biopsy, treatment was delivered using a rigid, gas-cooled, side-firing laser probe. Treatment was monitored using real-time MRI thermometry, and proprietary software providing predictive thermal damage feedback was used by the surgeon, along with control of probe rotation and depth, to tailor tissue coagulation. An external data safety monitoring board determined if toxicity at lower levels justified dose escalation. RESULTS: Ten patients were treated at the Case Comprehensive Cancer Center (Cleveland Clinic and University Hospitals-Case Medical Center). Their average age was 55 years (range 34-69 years) and the median preoperative Karnofsky Performance Status score was 80 (range 70-90). The mean tumor volume was 6.8 ± 5 cm(3) (range 2.6-19 cm(3)), the percentage of tumor treated was 78% ± 12% (range 57%-90%), and the conformality index was 1.21 ± 0.33 (range 1.00-2.04). Treatment-related necrosis was evident on MRI studies at 24 and 48 hours. The median survival was 316 days (range 62-767 days). Three patients improved neurologically, 6 remained stable, and 1 worsened. Steroid-responsive treatment-related edema occurred in all patients but one. Three had Grade 3 adverse events at the highest dose. CONCLUSIONS: NeuroBlate represents new technology for delivering laser interstitial thermal therapy, allowing controlled thermal ablation of deep hemispheric rGBM. CLINICAL TRIAL REGISTRATION NO.: NCT00747253 ( ClinicalTrials.gov ).

Pleiotropic regulatory locus 1 (PRL1) integrates the regulation of sugar responses with isoprenoid metabolism in Arabidopsis.

The biosynthesis of isoprenoids in plant cells occurs from precursors produced in the cytosol by the mevalonate (MVA) pathway and in the plastid by the methylerythritol 4-phosphate (MEP) pathway, but little is known about the mechanisms coordinating both pathways. Evidence of the importance of sugar signaling for such coordination in Arabidopsis thaliana is provided here by the characterization of a mutant showing an increased accumulation of MEP-derived isoprenoid products (chlorophylls and carotenoids) without changes in the levels of relevant MEP pathway transcripts, proteins, or enzyme activities. This mutant was found to be a new loss-of-function allele of PRL1 (Pleiotropic Regulatory Locus 1), a gene encoding a conserved WD-protein that functions as a global regulator of sugar, stress, and hormone responses, in part by inhibition of SNF1-related protein kinases (SnRK1). Consistent with the reported role of SnRK1 kinases in the phosphorylation and inactivation of the main regulatory enzyme of the MVA pathway (hydroxymethylglutaryl coenzyme-A reductase), its activity but not transcript or protein levels was reduced in prl1 seedlings. However, the accumulation of MVA-derived end products (sterols) was unaltered in mutant seedlings. Sucrose supplementation to wild-type seedlings phenocopied the prl1 mutation in terms of isoprenoid metabolism, suggesting that the observed isoprenoid phenotypes result from the increased sugar accumulation in the prl1 mutant. In summary, PRL1 appears to coordinate isoprenoid metabolism with sugar, hormone, and stress responses.

Thiamine supplementation increases serum thiamine and reduces pyruvate and lactate levels in burn patients.

The importance of vitamins for optimal metabolism is well established. However, currently little is known about the optimal vitamin levels required for burn patients. As a consequence, current practice both for macronutrient supplementation and vitamin supplementation varies widely between burn units. A better understanding of the effects of vitamins on metabolism may lead to better nutrition and subsequently improved outcomes for burn patients. Thiamine is an important co-factor required for multiple enzymes involved in carbohydrate metabolism. We have examined the levels of thiamine (B1) in burn patients as well as the effects of thiamine supplementation on the levels of serum thiamine, pyruvate and lactate. Twenty patients had blood samples taken on the day of admission, then on days 1, 3, and 7 post-admission and weekly thereafter until discharge. Of these, nine received enteral feeding. Six patients received thiamine supplementation. Serum thiamine, pyruvate and lactate levels were measured at each time point. Serum thiamine levels increased significantly with thiamine supplementation (p<0.001). Serum thiamine levels also increased with time of supplementation (p<0.001). Serum thiamine level was closely associated with pyruvate and lactate levels, with a decrease in both pyruvate and lactate associated with increased serum thiamine. Lastly, pyruvate and lactate levels appear closely associated in a linear relationship. This study suggests thiamine supplementation increases serum thiamine and that this increase is associated with a decrease in pyruvate and lactate levels. Further study of changes in metabolic flux associated with thiamine supplementation and a randomised control trial of thiamine supplementation are required to establish whether thiamine supplementation is beneficial to burn patients' metabolism and recovery.