Thioredoxin Interacting Protein Is Required for a Chronic Energy-Rich Diet to Promote Intestinal Fructose Absorption

Increased consumption of fats and added sugars has been associated with an increase in metabolic syndromes. Here we show that mice chronically fed an energy-rich diet (ERD) with high fat and moderate sucrose have enhanced the absorption of a gastrointestinal fructose load, and this required expression of the arrestin domain protein Txnip in the intestinal epithelial cells. ERD feeding induced gene and protein expression of Glut5, and this required the expression of Txnip. Furthermore, Txnip interacted with Rab11a, a small GTPase that facilitates the apical localization of Glut5. We also demonstrate that ERD promoted Txnip/Glut5 complexes in the apical intestinal epithelial cell. Our findings demonstrate that ERD facilitates fructose absorption through a Txnip-dependent mechanism in the intestinal epithelial cell, suggesting that increased fructose absorption could potentially provide a mechanism for worsening of metabolic syndromes in the setting of a chronic ERD

Solar Thermal Processing to Disinfect Human Waste

Almost half of the world&rsquo;s population is living without access to sanitation services that are safe, reliable, and minimize public health risk of human waste exposure. Modern flush-based sanitation networks are unsustainable: substantial resources, namely water and fuel, are required to bring human waste to centralized treatment facilities. Moving toward sustainable sanitation requires the implementation of innovative renewable energy technologies for stabilization and disinfection of waste, at the local or household scale, where minimal inputs of water, electricity or chemicals are required. A novel solar thermal disinfection toilet prototype has been constructed and is assessed for overall solar to receiver efficiency in treating waste without electrical, chemical, or water inputs from municipal supply. The measured solar to receiver efficiency is 28%, incorporating the capturing and concentration of sunlight and transmission of the energy to the receiver. For a typical sunny day, the current system can achieve thermal treatment of 0.8 kg human waste in roughly 100 min. The novel toilet is available for any location in the world with sufficient sunlight and irradiance data, and is scalable by adding solar collectors for sizes from single dwellings to communities. &nbsp;</p

Breeding progress and preparedness for mass‐scale deployment of perennial lignocellulosic biomass crops switchgrass, miscanthus, willow and poplar

UK: The UK‐led miscanthus research and breeding was mainly supported by the Biotechnology and Biological Sciences Research Council (BBSRC), Department for Environment, Food and Rural Affairs (Defra), the BBSRC CSP strategic funding grant BB/CSP1730/1, Innovate UK/BBSRC “MUST” BB/N016149/1, CERES Inc. and Terravesta Ltd. through the GIANT‐LINK project (LK0863). Genomic selection and genomewide association study activities were supported by BBSRC grant BB/K01711X/1, the BBSRC strategic programme grant on Energy Grasses & Bio‐refining BBS/E/W/10963A01. The UK‐led willow R&D work reported here was supported by BBSRC (BBS/E/C/00005199, BBS/E/C/00005201, BB/G016216/1, BB/E006833/1, BB/G00580X/1 and BBS/E/C/000I0410), Defra (NF0424) and the Department of Trade and Industry (DTI) (B/W6/00599/00/00). IT: The Brain Gain Program (Rientro dei cervelli) of the Italian Ministry of Education, University, and Research supports Antoine Harfouche. US: Contributions by Gerald Tuskan to this manuscript were supported by the Center for Bioenergy Innovation, a US Department of Energy Bioenergy Research Center supported by the Office of Biological and Environmental Research in the DOE Office of Science, under contract number DE‐AC05‐00OR22725. Willow breeding efforts at Cornell University have been supported by grants from the US Department of Agriculture National Institute of Food and Agriculture. Contributions by the University of Illinois were supported primarily by the DOE Office of Science; Office of Biological and Environmental Research (BER); grant nos. DE‐SC0006634, DE‐SC0012379 and DE‐SC0018420 (Center for Advanced Bioenergy and Bioproducts Innovation); and the Energy Biosciences Institute. EU: We would like to further acknowledge contributions from the EU projects “OPTIMISC” FP7‐289159 on miscanthus and “WATBIO” FP7‐311929 on poplar and miscanthus as well as “GRACE” H2020‐EU.3.2.6. Bio‐based Industries Joint Technology Initiative (BBI‐JTI) Project ID 745012 on miscanthus.Peer reviewedPostprintPublisher PD

The role of economic evaluation in the decision-making process of family physicians: design and methods of a qualitative embedded multiple-case study

<p>Abstract</p> <p>Background</p> <p>A considerable amount of resource allocation decisions take place daily at the point of the clinical encounter; especially in primary care, where 80 percent of health problems are managed. Ignoring economic evaluation evidence in individual clinical decision-making may have a broad impact on the efficiency of health services. To date, almost all studies on the use of economic evaluation in decision-making used a quantitative approach, and few investigated decision-making at the clinical level. An important question is whether economic evaluations affect clinical practice. The project is an intervention research study designed to understand the role of economic evaluation in the decision-making process of family physicians (FPs). The contributions of the project will be from the perspective of Pierre Bourdieu's sociological theory.</p> <p>Methods/design</p> <p>A qualitative research strategy is proposed. We will conduct an embedded multiple-case study design. Ten case studies will be performed. The FPs will be the unit of analysis. The sampling strategies will be directed towards theoretical generalization. The 10 selected cases will be intended to reflect a diversity of FPs. There will be two embedded units of analysis: FPs (micro-level of analysis) and field of family medicine (macro-level of analysis). The division of the determinants of practice/behaviour into two groups, corresponding to the macro-structural level and the micro-individual level, is the basis for Bourdieu's mode of analysis. The sources of data collection for the micro-level analysis will be 10 life history interviews with FPs, documents and observational evidence. The sources of data collection for the macro-level analysis will be documents and 9 open-ended, focused interviews with key informants from medical associations and academic institutions. The analytic induction approach to data analysis will be used. A list of codes will be generated based on both the original framework and new themes introduced by the participants. We will conduct within-case and cross-case analyses of the data.</p> <p>Discussion</p> <p>The question of the role of economic evaluation in FPs' decision-making is of great interest to scientists, health care practitioners, managers and policy-makers, as well as to consultants, industry, and society. It is believed that the proposed research approach will make an original contribution to the development of knowledge, both empirical and theoretical.</p

The Ischemic Stroke Genetics Study (ISGS) Protocol

BACKGROUND: The molecular basis for the genetic risk of ischemic stroke is likely to be multigenic and influenced by environmental factors. Several small case-control studies have suggested associations between ischemic stroke and polymorphisms of genes that code for coagulation cascade proteins and platelet receptors. Our aim is to investigate potential associations between hemostatic gene polymorphisms and ischemic stroke, with particular emphasis on detailed characterization of the phenotype. METHODS/DESIGN: The Ischemic Stroke Genetic Study is a prospective, multicenter genetic association study in adults with recent first-ever ischemic stroke confirmed with computed tomography or magnetic resonance imaging. Patients are evaluated at academic medical centers in the United States and compared with sex- and age-matched controls. Stroke subtypes are determined by central blinded adjudication using standardized, validated mechanistic and syndromic classification systems. The panel of genes to be tested for polymorphisms includes β-fibrinogen and platelet glycoprotein Ia, Iba, and IIb/IIIa. Immortalized cell lines are created to allow for time- and cost-efficient testing of additional candidate genes in the future. DISCUSSION: The study is designed to minimize survival bias and to allow for exploring associations between specific polymorphisms and individual subtypes of ischemic stroke. The data set will also permit the study of genetic determinants of stroke outcome. Having cell lines will permit testing of future candidate risk factor genes

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

Cardiac Stroke Volume Index Is Associated With Early Neurological Improvement in Acute Ischemic Stroke Patients

Early neurological improvement as assessed with the NIH stroke scale (NIHSS) at 24 h has been associated with improved long-term functional outcomes following acute ischemic stroke (AIS). Cardiac dysfunction is often present in AIS, but its association with outcomes is incompletely defined. We performed a pilot study to evaluate the association between non-invasively measured cardiac parameters and 24-h neurological improvement in prospectively enrolled patients with suspected AIS who presented within 12 h of symptom-onset and had an initial systolic blood pressure\u3e140 mm Hg. Patients receiving thrombolytic therapy or mechanical thrombectomy were excluded. Non-invasive pulse contour analysis was used to measure mean arterial blood pressure (MAP), cardiac stroke volume index (cSVI), cardiac output (CO) and cardiac index (CI). Transcranial Doppler recorded mean middle cerebral artery flow velocity (MFV). We defined a decrease of 4 NIHSS points or NIHSS ≤ 1 at 24-h as neurological improvement. Of 75 suspected, 38 had confirmed AIS and did not receive reperfusion therapy. Of these, 7/38 (18.4%) had neurological improvement over 24 h. MAP was greater in those without improvement (108, IQR 96-123 mm Hg) vs. those with (89, IQR 73-104 mm Hg). cSVI, CO, and MFV were similar between those without and with improvement: 37.4 (IQR 30.9-47.7) vs. 44.7 (IQR 42.3-55.3) ml/m(2); 5.2 (IQR 4.2-6.6) vs. 5.3 (IQR 4.7-6.7) mL/min; and 39.9 (IQR 32.1-45.7) vs. 34.4 (IQR 27.1-49.2) cm/s, respectively. Multivariate analysis found MAP and cSVI as predictors for improvement (OR 0.93, 95%CI 0.85-0.98 and 1.14, 95%CI 1.03-1.31). In this pilot study, cSVI and MAP were associated with 24-h neurological improvement in AIS

Solar Thermal Processing to Disinfect Human Waste

Almost half of the world’s population is living without access to sanitation services that are safe, reliable, and minimize public health risk of human waste exposure. Modern flush-based sanitation networks are unsustainable: substantial resources, namely water and fuel, are required to bring human waste to centralized treatment facilities. Moving toward sustainable sanitation requires the implementation of innovative renewable energy technologies for stabilization and disinfection of waste, at the local or household scale, where minimal inputs of water, electricity or chemicals are required. A novel solar thermal disinfection toilet prototype has been constructed and is assessed for overall solar to receiver efficiency in treating waste without electrical, chemical, or water inputs from municipal supply. The measured solar to receiver efficiency is 28%, incorporating the capturing and concentration of sunlight and transmission of the energy to the receiver. For a typical sunny day, the current system can achieve thermal treatment of 0.8 kg human waste in roughly 100 min. The novel toilet is available for any location in the world with sufficient sunlight and irradiance data, and is scalable by adding solar collectors for sizes from single dwellings to communities