Metabolomic biomarkers of pancreatic cancer - a meta-analysis study

Pancreatic cancer (PC) is an aggressive disease with high mortality rates, however, there is no blood test for early detection and diagnosis of this disease. Several research groups have reported on metabolomics based clinical investigations to identify biomarkers of PC, however there is a lack of a centralized metabolite biomarker repository that can be used for meta-analysis and biomarker validation. Furthermore, since the incidence of PC is associated with metabolic syndrome and Type 2 diabetes mellitus (T2DM), there is a need to uncouple these common metabolic dysregulations that may otherwise diminish the clinical utility of metabolomic biosignatures. Here, we attempted to externally replicate proposed metabolite biomarkers of PC reported by several other groups in an independent group of PC subjects. Our study design included a T2DM cohort that was used as a non-cancer control and a separate cohort diagnosed with colorectal cancer (CRC), as a cancer disease control to eliminate possible generic biomarkers of cancer. We used targeted mass spectrometry for quantitation of literature-curated metabolite markers and identified a biomarker panel that discriminates between normal controls (NC) and PC patients with high accuracy. Further evaluation of our model with CRC, however, showed a drop in specificity for the PC biomarker panel. Taken together, our study underscores the need for a more robust study design for cancer biomarker studies so as to maximize the translational value and clinical implementation.This work was supported by ACS IRG-92-152-17 pilot award number AWD4470404 to KU and AKC. The authors would like to acknowledge the Metabolomics Shared Resource in Georgetown University (Washington DC, USA) partially supported by NIH/NCI/CCSG grant P30-CA05100

Anxiety Sensitivity and Depression: Explaining Posttraumatic Stress Disorder Symptoms in Female Veterans With Chronic Pain

10.1080/21635781.2014.906293Military Behavioral Health22173-17

Planting seeds for the future of food

The health and wellbeing of future generations will depend onhumankind's ability to deliver sufficient nutritious food to a world population in excess of 9 billion. Feeding this many people by 2050 will require science-based solutions that address sustainable agricultural productivity and enable healthful dietary patterns in a more globally equitable way. This topic was the focus of a multi-disciplinary international conference hosted by Nestle in June 2015, and provides the inspiration for the present article. The conference brought together a diverse range of expertise and organisations from the developing and industrialised world, all with a common interest in safeguarding the future of food. This article provides a snapshot of three of the recurring topics that were discussed during this conference: soil health, plant science and the future of farming practice. Crop plants and their cultivation are the fundamental building blocks for a food secure world. Whether these are grown for food or feed for livestock, they are the foundation of food and nutrient security. Many of the challenges for the future of food will be faced where the crops are grown: on the farm. Farmers need to plant the right crops and create the right conditions to maximise productivity (yield) and quality (e.g. nutritional content), whilst maintaining the environment, and earning a living. New advances in science and technology can provide the tools and know-how that will, together with a more entrepreneurial approach, help farmers to meet the inexorable demand for the sustainable production of nutritious foods for future generations. (C) 2015 The Authors. Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry

Alterations in striatal dopamine catabolism precede loss of substantia nigra neurons in a mouse model of juvenile neuronal ceroid lipofuscinosis

Batten disease, or juvenile neuronal ceroid lipofuscinosis (JNCL), results from mutations in the CLN3 gene. This disorder presents clinically around the age of five years with visual deficits progressing to include seizures, cognitive impairment, motor deterioration, hallucinations, and premature death by the third to forth decade of life. The motor deficits include coordination and gait abnormalities, myoclonic jerks, inability to initiate movements, and spasticity. Previous work from our laboratory has identified an early reduction in catechol-O-methyltransferase (COMT), an enzyme responsible for the efficient degradation of dopamine. Alterations in the kinetics of dopamine metabolism could cause the accumulation of undegraded or unsequestered dopamine leading to the formation of toxic dopamine intermediates. We report an imbalance in the catabolism of dopamine in three month Cln3(-/-) mice persisting through nine months of age that may be causal to oxidative damage within the striatum at nine months of age. Combined with the previously reported inflammatory changes and loss of post-synaptic D1α receptors, this could facilitate cell loss in striatal projection regions and underlie a general locomotion deficit that becomes apparent at twelve months of age in Cln3(-/-) mice. This study provides evidence for early changes in the kinetics of COMT in the Cln3(-/-) mouse striatum, affecting the turnover of dopamine, likely leading to neuron loss and motor deficits. These data provide novel insights into the basis of motor deficits in JNCL and how alterations in dopamine catabolism may result in oxidative damage and localized neuronal loss in this disorder