Sourdough fermentation of wheat flour does not prevent the interaction of transglutaminase 2 with α2-gliadin or gluten.

The enzyme transglutaminase 2 (TG2) plays a crucial role in the initiation of celiac disease by catalyzing the deamidation of gluten peptides. In susceptible individuals, the deamidated peptides initiate an immune response leading to celiac disease. Several studies have addressed lactic fermentation plus addition of enzymes as a means to degrade gluten in order to prevent adverse response in celiacs. Processing for complete gluten degradation is often harsh and is not likely to yield products that are of comparable characteristics as their gluten-containing counterparts. We are concerned that incomplete degradation of gluten may have adverse effects because it leads to more available TG2-binding sites on gluten peptides. Therefore, we have investigated how lactic acid fermentation affects the potential binding of TG2 to gluten protein in wheat flour by means of estimating TG2-mediated transamidation in addition to measuring the available TG2-binding motif QLP, in α2-gliadin. We show that lactic fermentation of wheat flour, as slurry or as part of sourdough bread, did not decrease the TG2-mediated transamidation, in the presence of a primary amine, to an efficient level (73%–102% of unfermented flour). Nor did the lactic fermentation decrease the available TG2 binding motif QLP in α2-gliadin to a sufficient extent in sourdough bread (73%–122% of unfermented control) to be useful for celiac safe food

Low-level exposure to lead, blood pressure, and hypertension in a population-based cohort.

Abstract Background Environmental lead exposure is a possible causative factor for increased blood pressure and hypertension, but large studies at low-level exposure are scarce, and results inconsistent. Objective We aimed to examine the effects of environmental exposure to lead in a large population-based sample. Methods We assessed associations between blood lead and systolic/diastolic blood pressure and hypertension in 4452 individuals (46–67 years) living in Malmo, Sweden, in 1991–1994. Blood pressure was measured using a mercury sphygmomanometer after 10 min supine rest. Hypertension was defined as high systolic (≥140 mmHg) or diastolic (≥90 mmHg) blood pressure and/or current use of antihypertensive medication. Blood lead was calculated from lead in erythrocytes and haematocrit. Multivariable associations between blood lead and blood pressure or hypertension were assessed by linear and logistic regression. Two-thirds of the cohort was re-examined 16 years later. Results At baseline, mean blood pressure was 141/87 mmHg, 16% used antihypertensive medication, 63% had hypertension, and mean blood lead was 28 µg/L. Blood lead in the fourth quartile was associated with significantly higher systolic and diastolic blood pressure (point estimates: 1–2 mmHg) and increased prevalence of hypertension (odds ratio: 1.3, 95% confidence interval: 1.1–1.5) versus the other quartiles after adjustment for sex, age, smoking, alcohol, waist circumference, and education. Associations were also significant with blood lead as a continuous variable. Blood lead at baseline, having a half-life of about one month, was not associated with antihypertensive treatment at the 16-year follow-up. Conclusions Low-level lead exposure increases blood pressure and may increase the risk of hypertension

Carbon-Based Nanoelectromechanical Devices

Carbon-based nanoelectromechanical devices are approaching applications in electronics. Switches based on individual carbon nanotubes deliver record low off-state leakage currents. Arrays of vertically aligned carbon nanotubes or nanofibers can be fabricated to constitute varactors. Very porous, low density arrays of quasi-vertically aligned arrays of carbon nanotubes behave mechanically as a single unit with very unusual material properties

Unexpected Fat Distribution in Adolescents With Narcolepsy

Narcolepsy type 1 is a chronic sleep disorder with significantly higher BMI reported in more than 50% of adolescent patients, putting them at a higher risk for metabolic syndrome in adulthood. Although well-documented, the body fat distribution and mechanisms behind weight gain in narcolepsy are still not fully understood but may be related to the loss of orexin associated with the disease. Orexin has been linked to the regulation of brown adipose tissue (BAT), a metabolically active fat involved in energy homeostasis. Previous studies have used BMI and waist circumference to characterize adipose tissue increases in narcolepsy but none have investigated its specific distribution. Here, we examine adipose tissue distribution in 19 adolescent patients with narcolepsy type 1 and compare them to 17 of their healthy peers using full body magnetic resonance imaging (MRI). In line with previous findings we saw that the narcolepsy patients had more overall fat than the healthy controls, but contrary to our expectations there were no group differences in supraclavicular BAT, suggesting that orexin may have no effect at all on BAT, at least under thermoneutral conditions. Also, in line with previous reports, we observed that patients had more total abdominal adipose tissue (TAAT), however, we found that they had a lower ratio between visceral adipose tissue (VAT) and TAAT indicating a relative increase of subcutaneous abdominal adipose tissue (ASAT). This relationship between VAT and ASAT has been associated with a lower risk for metabolic disease. We conclude that while weight gain in adolescents with narcolepsy matches that of central obesity, the lower VAT ratio may suggest a lower risk of developing metabolic disease

Consensus statement from the 2014 International Microdialysis Forum.

Microdialysis enables the chemistry of the extracellular interstitial space to be monitored. Use of this technique in patients with acute brain injury has increased our understanding of the pathophysiology of several acute neurological disorders. In 2004, a consensus document on the clinical application of cerebral microdialysis was published. Since then, there have been significant advances in the clinical use of microdialysis in neurocritical care. The objective of this review is to report on the International Microdialysis Forum held in Cambridge, UK, in April 2014 and to produce a revised and updated consensus statement about its clinical use including technique, data interpretation, relationship with outcome, role in guiding therapy in neurocritical care and research applications.We gratefully acknowledge financial support for participants as follows: P.J.H. - National Institute for Health Research (NIHR) Professorship and the NIHR Biomedical Research Centre, Cambridge; I.J. – Medical Research Council (G1002277 ID 98489); A. H. - Medical Research Council, Royal College of Surgeons of England; K.L.H.C. - NIHR Biomedical Research Centre, Cambridge (Neuroscience Theme; Brain Injury and Repair Theme); M.G.B. - Wellcome Trust Dept Health Healthcare Innovation Challenge Fund (HICF-0510-080); L. H. - The Swedish Research Council, VINNOVA and Uppsala Berzelii Technology Centre for Neurodiagnostics; S. M. - Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico; D.K.M. - NIHR Senior Investigator Award to D.K.M., NIHR Cambridge Biomedical Research Centre (Neuroscience Theme), FP7 Program of the European Union; M. O. - Swiss National Science Foundation and the Novartis Foundation for Biomedical Research; J.S. - Fondo de Investigación Sanitaria (Instituto de Salud Carlos III) (PI11/00700) co-financed by the European Regional Development; M.S. – NIHR University College London Hospitals Biomedical Research Centre; N. S. - Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00134-015-3930-

Drug-resilient cancer cell phenotype is acquired via polyploidization associated with early stress response coupled to HIF-2α transcriptional regulation

Therapeutic resistance and recurrence remain core challenges in cancer therapy. How therapy resistance arises is currently not fully understood with tumors surviving via multiple alternative routes. Here, we demonstrate that a subset of cancer cells survives therapeutic stress by entering a transient state characterized by whole genome doubling. At the onset of the polyploidization program, we identified an upregulation of key transcriptional regulators, including the early stress-response protein AP-1 and normoxic stabilization of HIF-2α. We found altered chromatin accessibility, ablated expression of RB1, and enrichment of AP-1 motif accessibility. We demonstrate that AP-1 and HIF-2α regulate a therapy resilient and survivor phenotype in cancer cells. Consistent with this, genetic or pharmacologic targeting of AP-1 and HIF-2α reduced the number of surviving cells following chemotherapy treatment. The role of AP-1 and HIF-2α in stress-response by polyploidy suggest a novel avenue for tackling chemotherapy-induced resistance in cancer

Consensus statement from the 2014 International Microdialysis Forum

This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00134-015-3930-yMicrodialysis enables the chemistry of the extracellular interstitial space to be measured. Use of this technique in patients with acute brain injury has increased our understanding of the pathophysiology of several acute neurological disorders. In 2004 a consensus document on the clinical application of cerebral microdialysis was published. Since then there have been significant advances in the clinical use of microdialysis in neurocritical care. The objective of this review is to report on the International Microdialysis Forum held in Cambridge, UK, in April 2014 and to produce a revised and updated consensus statement about its clinical use including technique, data interpretation, relationship with outcome, role in guiding therapy in neurocritical care and research applications.We gratefully acknowledge financial support for participants as follows: P.J.H. - National Institute for Health Research (NIHR) Professorship and the NIHR Biomedical Research Centre, Cambridge; I.J. ? Medical Research Council (G1002277 ID 98489); A. H. - Medical Research Council, Royal College of Surgeons of England; K.L.H.C. - NIHR Biomedical Research Centre, Cambridge (Neuroscience Theme; Brain Injury and Repair Theme); M.G.B. - Wellcome Trust Dept Health Healthcare Innovation Challenge Fund (HICF-0510-080); L. H. - The Swedish Research Council, VINNOVA and Uppsala Berzelii Technology Centre for Neurodiagnostics; S. M. - Fondazione IRCCS C? Granda Ospedale Maggiore Policlinico; D.K.M. - NIHR Senior Investigator Award to D.K.M., NIHR Cambridge Biomedical Research Centre (Neuroscience Theme), FP7 Program of the European Union; M. O. - Swiss National Science Foundation and the Novartis Foundation for Biomedical Research; J.S. - Fondo de Investigaci?n Sanitaria (Instituto de Salud Carlos III) (PI11/00700) co-financed by the European Regional Development; M.S. ? NIHR University College London Hospitals Biomedical Research Centre; N. S. - Fondazione IRCCS C? Granda Ospedale Maggiore Policlinico

Professional warranty management - an issue in the construction business

A business is always dependent on its customers. It is therefore important to ensurethat customers are satisfied with the product and the warranty included.The study was conducted in cooperation with the building contacting companySkanska Sweden. The aim is to use interviews to collect and process experiences in order to answer the question: How should the recovery process in the construction industry be performed to ensure a professional handling of warranty? The results have shaped my conclusions and I have turned them into a proposal that companies in the industry can benefit from. The study indicates that the industry is not geared for a five year warranty, which was introduced in 2004 and 2006. This is manifested by difficulties to prioritize the management of guarantees, with long lead times and customer-, and employee dissatisfaction as a result. Achieving a professional management means to adapt the company to a longer warranty. It means taking responsibility, prioritizing and investing in the organization and effective computer systems. The investment will help to create a stronger brand and increase the profitability for the company. The results suggest that companies should set aside time for staff and implement an aftermarket organization that supports and relieves the staff. An important aspect is that a financial liability for the guarantees should be anchored in the production staff. Otherwise it can result in a reduced quality due to lack of responsibility during the construction process, leading to increased warranty costs. The industry is also in great need of accessible craftsmen that quickly can fix errors. The problem is that most craftsmen today are occupied in the new construction projects, it creates longer lead times for the process. The craftsmen must also be suitable for a job in the aftermarket. The way of handling the issues in the industry are not uniform and are often outdated. Therefore a need exists for a modern and computerized case management system, it would improve the situation for both staff and customers. Companies can also use an evaluation system to rate their partners on how they acted during the warranty period. The information can be valuable for future collaborations. Knowing that a classification is performed can also increase the corporate accountability. Contracts in the future can be added a clause to encourage responsibility for the work during the warranty period. The clause requires a meeting where the contractors, among other things, can agree on a case management system to use. But most important is to pay attention to the work during the warranty period, which must be improved

Professional warranty management - an issue in the construction business

A business is always dependent on its customers. It is therefore important to ensurethat customers are satisfied with the product and the warranty included.The study was conducted in cooperation with the building contacting companySkanska Sweden. The aim is to use interviews to collect and process experiences in order to answer the question: How should the recovery process in the construction industry be performed to ensure a professional handling of warranty? The results have shaped my conclusions and I have turned them into a proposal that companies in the industry can benefit from. The study indicates that the industry is not geared for a five year warranty, which was introduced in 2004 and 2006. This is manifested by difficulties to prioritize the management of guarantees, with long lead times and customer-, and employee dissatisfaction as a result. Achieving a professional management means to adapt the company to a longer warranty. It means taking responsibility, prioritizing and investing in the organization and effective computer systems. The investment will help to create a stronger brand and increase the profitability for the company. The results suggest that companies should set aside time for staff and implement an aftermarket organization that supports and relieves the staff. An important aspect is that a financial liability for the guarantees should be anchored in the production staff. Otherwise it can result in a reduced quality due to lack of responsibility during the construction process, leading to increased warranty costs. The industry is also in great need of accessible craftsmen that quickly can fix errors. The problem is that most craftsmen today are occupied in the new construction projects, it creates longer lead times for the process. The craftsmen must also be suitable for a job in the aftermarket. The way of handling the issues in the industry are not uniform and are often outdated. Therefore a need exists for a modern and computerized case management system, it would improve the situation for both staff and customers. Companies can also use an evaluation system to rate their partners on how they acted during the warranty period. The information can be valuable for future collaborations. Knowing that a classification is performed can also increase the corporate accountability. Contracts in the future can be added a clause to encourage responsibility for the work during the warranty period. The clause requires a meeting where the contractors, among other things, can agree on a case management system to use. But most important is to pay attention to the work during the warranty period, which must be improved