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V1 en V2 rondom Ommen. Onderaan hoofdstuk 01 Ons Verwonderen Rondom Ommen staat een. Op zoek naar… op http: V1 en V2 rondom Ommen meer afbeeldingen volgen later. Iris Delwel — V1 — katapult. De V1-startglijbaan bij de gemeentegrens op de Haarlerberg en nabij kamp Twilhaar. Inmiddels is er zoveel informatie over verzameld dat we deze hebben samengevoegd op deze aparte wegblog onder bovenstaande titel. Opvallend is dat er over de V2 bijzonder veel en daarbij vergeleken over de V1 bijzonder weinig op het internet aan afvuurlijsten staat.
Aan het eind van de oorlog werden vanaf meer dan 20 lanceerbanen in Overijssel en Gelderland vliegende VI-bommen, vuurkonten in het lokale dialect, gelanceerd richting Antwerpen dat destijds bevrijd was door de geallieerde legers. Zie de katapult op http: Ik had nog nooit van de Schleuder gehoord! Recent vrijgelegd en voorzien van bord waarop de historie van de lanceerbaan is te lezen.
De tekst op het bord luidt: Algemeen De V1 Vergeltungswaffe was destijds een zeer modern wapentuig, was ruim acht meter lang en had een totale breedte inclusief de vleugels van ruim vijf meter. Vanaf deze plek werden de vliegende bommen gelanceerd door middel van een soort katapultinstallatie.
Een pneumatisch kanon bracht de V1 langs een startbaan van ruim 46 meter met een helling van 6 graden in een vliegende baan. De snelheid van het vliegen was ongeveer twee honderd vijftig kilometer per uur bij de lancering. Vanaf 13 juni zetten de Duitsers hiermee vanaf de Kanaalkust in Noord-Frankrijk de aanval op Londen in. Vanaf deze plek gezien stonden aan de overkant van de Oerdijk, waar nu de Soestwetering stroomt, enige houten keten waarin en waarbij de onderdelen gemonteerd werden.
De tien gezinnen die op bevel van de Duitse bezetter op zondagmorgen 5 november , binnen 8 uur, hun boerderij of woonstee moesten verlaten konden hun min of meer gehavende eigendom weer betrekken.
Toen pas werd duidelijk wat er in de vluchtrichting van de V1 in de nabije bossen was gebeurd. Herdenking Te Lettele nabij de kruising Oerdijk — Bathmenseweg bevindt zich het monument ter herdenking aan de bezetting periode. Het monument is opgebouwd uit resten fundatie van de voormalige V1 baan. De gebruikte blokken zijn destijds tijdens bosbouw werkzaamheden vrijgekomen. Zwanenburg, schrijver van het boek: De laatste V-2 werd vanuit Den Haag gelanceerd op 27 maart De laatste V-1 in de richiting van London werd afgeschoten op 29 maart vanuit Vlaardingen.
Een dag later werd met het codewoord "Lutzow" het sein gegeven om alle V-activiteiten in Nederland te stoppen. Voor het staken van de lanceringen zijn een aantal mogelijke verklaringen. Eind maart was duidelijk geworden dat de Geallieerden niet meer van plan waren op de kust van West Europa te landen. Ook heeft een rol gespeeld dat de aanvoer van v-1 en v-2 vanuit Duitsland nar Nederland stagneerde.
Behalve de verklaringen van de ooggetuigen en de opgraving zijn er nog meer redenen om aan te nemen dat er geen V-2's maar V-1's zijn afgeschoten in Vogelenzang. De redenen volgen hierna:. Met zekerheid kan gesteld worden dat het om echte V-1's gaat en niet om de namaakvariant. Wist men in Bloemendaal het verschil tussen een V-1 en V-2?
Het is de vraag of mevrouw Nierhoff het verschil tussen een V-1 en V-2 wel wist. Waarschijnlijk heeft zij bij het samensetllen van haar Oorlogskroniek wat dat betreft vertrouwd op het rapport van opperwachtmeester Geertsema. Zij heeft diens aanduiding V-2 zonder nader onderzoek overgenomen. Het is ook moeilijk meer te achterhalen of de opperwachtmeester het verschil tussen een V-1 en V-2 kende.
Geertsema zag bij zijn inspectie op zaterdag 31 maart de nog aanwezige V-1 startbaan aan voor een V-2 installatie. De mogelijke verklaring daarvoor is dat hij voordien de V-1 startbaan, noch de V-2 installatie net eigen ogen had gezien.
Zelfs voor een politieman waren het geheime wapens. Bovendien wisten de Duitsers hun bedrijfsgeheim goed te bewaren. Dat blijkt uit het feit dat de Duitsers vrijwel direct na de valse landing de projectielen opbliezen. Die was langer, breder en sneller dan het eerdere type en had een groter bereik.
Het was niet onlogisch om deze nieuwe versie van de V-1 aan te duiden als V-2, ware het niet dat er al een totaal ander projectiel bestond met die naam.
Dat misverstand is ook recent weer bevestigd. Ook de opleiding Hbo Archeologie richt zich op deze zwarte bladzijde in de geschiedenis. Onder de studenten bestaat veel belangstelling voor deze periode en een aantal kiest dit thema als afstudeeronderwerp. Zij doet in Oost Nederland onderzoek naar resten van VI-lanceerbanen. Zo probeerde het Duitse leger de havens van Antwerpen te vernietigen. Deze havens vormden aan het eind van de oorlog een belangrijke logistieke schakel tijdens het Ardennen offensief.
Van de lanceerstellingen zijn op diverse locaties nog restanten aanwezig. Iris onderzoekt samen met andere studenten van de opleiding deze overgebleven resten. Het gaat vooral om betonnen onderdelen van de stellingen die worden getekend en gefotografeerd. Ook wordt bekeken in hoeverre de archeologische informatie een aanvulling vormen op de historische gegevens.
Hoewel er veel is geschreven over de V1's is er slechts een beperkte hoeveelheid historische bronnen beschikbaar. Het was de op de stellingen ingekwartierde soldaten namelijk ten strengste verboden om foto's te maken of over de werkzaamheden te praten. De schaarse informatie is vooral afkomstig van de inlichtingendienst van het Nederlandse verzet. Archeologisch onderzoek kan dus een belangrijke bijdrage leveren aan de kennis over dit oorlogserfgoed.
Naast het veldwerk bestaat het onderzoek uit het interviewen van ooggetuigen. Dit levert veel aanvullende informatie over de inrichting van de stellingen. Daarom is het belangrijk om, nu er nog ooggetuigen in leven zijn, zoveel mogelijk onderzoek te doen naar dergelijke resten en daarbij de ooggetuigenverslagen te betrekken.
Ook die kunnen belangrijke aanvullende informatie leveren. De aanwezigheid van de lanceerbanen had destijds trouwens veel impact op de omgeving. Mensen die in de buurt woonden waren erg bang voor de bommen omdat die nogal eens direct na de lancering in de omgeving neerstortten. Tijdens het onderzoek is gebleken dat, tegen de verwachtingen in, de stellingen niet allemaal hetzelfde waren.
Ze verschillen van elkaar in de wijze waarop ze zijn aangelegd en ingericht. Met het combineren van alle beschikbare informatie kan een completer beeld worden geschetst van deze episode uit de Tweede Wereldoorlog.
De V1 was een raket van 8 meter lang, die van metalen rails werd gelanceerd. Deze rails waren bevestigd op betonnen elementen. Rondom deze lanceerbaan waren werkplaatsen aanwezig waarin de raketten gereed werden gemaakt voor lancering en barakken waarin de manschappen werden ondergebracht.
De plaatsen waren verboden toegang en werden daarom als sperrgebiet ingesteld. Naast onderzoek naar de aanwezige resten en verstoringen wordt er archief -en historisch onderzoek uitgevoerd. Het doel van het onderzoek is om een volledig beeld te krijgen van de lanceerplaatsen. Op basis van het onderzoek zal de meest representatieve lanceerbaan voorgedragen worden voor behoud. Uiteindelijk verschijnt er een rapport waarin alle bevindingen zijn gebundeld.
Op het forum OudOmmen. We hebben al nadere informatie gevraagd en komen er hier dus nog wel op terug. De andere foto http: Kent iemand die locatie? Of is hier wellicht toch de plek bij het horizontale deel van de Toeristenweg bedoeld? De termen raket voor de V2 en vliegende bom voor de V1 worden hier en daar soms wat verhaspeld.
In de buurt van zijn berekende doel werd de motor stopgezet en stortte hij ter aarde; nauwkeurigheid was geen punt. De V2 was een echte raket die eerst recht omhoog ging en dan in een grote boog naar zijn doel viel. De moderne Scud-raket is er een late opvolger van. The roads needed to be hardened. Zie ook 53 Op zoek naar … wie was in Twilhaar? De katapult werkte op stoom van een chemische stoomgenerator. De katapult werd in grote delen aangevoerd en op een stevige betonnen fundering zwart op de tekening gemonteerd.
Zo'n fundering is nog te zien bij het Huis te Warmond. Zou die bijna 50 meter lange katapult werkelijk rechtop gestaan hebben? Of is toch de horizontale glijbaan bedoeld? Wie het weet mag het zeggen! Honderden foto's op het internet volgen als het lukt. In de loop van de Tweede Wereldoorlog werd de gemeente Rijssen-Holten door de Duitse Wehrmacht betrokken bij de luchtverdedigingslinie van Groot Duitsland en speelde op deze wijze bij de oorlogshandelingen ter bevrijding van Nederland een grote rol.
In de periode mei tot september zijn voortdurend luchtaanvallen van de geallieerden op het Ruhrgebied in Duitsland uitgevoerd evenals op het bestaande burgervliegveld ten noorden van het NS-station Rijssen dat als uitwijkvliegveld voor het militaire vliegveld Twente bij Enschede was omgebouwd.
Op onregelmatige tijdstippen tot aan de zomer van vielen geallieerde escorterende jachtvliegtuigen en terugkerende bommenwerpers in de gemeenten Rijssen en Holten de spoorlijn, het radarstation en de stellingen van de luchtafweer aan.
Het zuidelijk gedeelte van de Holterberg, een voormalig oefenterrein van het Nederlandse leger, werd door de Duitse Wehrmacht verder uitgebouwd voor zowel de opleiding van infanteristen als ook voor het beproeven van zwaar militair materieel.
Metabolome analysis was used in 70 healthy individuals. Multivariate analysis of plasma markers of fatty acid catabolism identified 2 distinct metabotype clusters A and B. Individuals from metabotype B showed slower glucose clearance, had increased intra-abdominal adipose tissue mass and higher hepatic lipid levels when compared with individuals from metabotype A. An NMR-based urine analysis revealed that these individuals also to have a less healthy dietary pattern.
Our study in healthy individuals demonstrates that more comprehensive phenotyping can reveal discrete metabotypes with different outcomes in a dietary intervention and that markers of lipid catabolism in plasma could allow early detection of the metabolic syndrome.
Plasma metabolome analysis identifies distinct human metabotypes in the postprandial state with different susceptibility to weight loss-mediated metabolic improvements. Insulin resistance IR and impaired beta-cell function are key determinants of type 2 diabetes mellitus T2DM. Intestinal absorption of bacterial components activates the toll-like receptors inducing inflammation, and this in turn IR.
We evaluated the role of endotoxemia in promoting inflammation-induced insulin resistance IR in the development of T2DM, and its usefulness as predictive biomarker. Our results suggest that a high postprandial endotoxemia precedes the development of T2DM. From a biological view, most of the processes involved in insulin resistance, which drives the pathobiology of type 2 diabetes, are reversible.
This theoretically makes the disease reversible and curable by changing dietary habits and physical activity, particularly when adopted early in the disease process. Yet, this is not fully implemented and exploited in health care due to numerous obstacles.
This article reviews the state of the art in all areas involved in a diabetes cure-focused therapy and discusses the scientific and technological advancements that need to be integrated into a systems approach sustainable lifestyle-based healthcare system and economy. The implementation of lifestyle as cure necessitates personalized and sustained lifestyle adaptations, which can only be established by a systems approach, including all relevant aspects personalized diagnosis and diet, physical activity and stress management, self-empowerment, motivation, participation and health literacy, all facilitated by blended care and ehealth.
Introduction of such a systems approach in type 2 diabetes therapy not only requires a concerted action of many stakeholders but also a change in healthcare economy, with new winners and losers. The solution provided for type 2 diabetes is translatable to other lifestyle-related disorders. The impact of micronutrient status on health: Correlation network analysis to understand the role of micronutrients in metabolic-inflammatory processes regulating homeostasis and phenotypic flexibility.
Background Vitamins and carotenoids are key micronutrients facilitating the maintenance of health, as evidenced by the increased risk of disease with low intake. Optimal phenotypic flexibility, i. Therefore, health can be measured by applying a challenge test and monitoring the response of relevant phenotypic processes. In this study, we assessed the correlation of three fat-soluble vitamins, i.
The phenotypic flexibility concept implies that health can be measured by the ability to adapt to a NCT, which may offer a more sensitive way to assess changes in health status of healthy subjects. ResultsCorrelation analyses of results after overnight fasting revealed a rather evenly distributed network in a number of relatively strong correlations per micronutrient, with minor overlap between correlation profiles of each compound.
Comparison of the networks revealed that there is merely overlap of two parameters inositol and oleic acid C Conclusions Our study shows that applying the challenge test concept is able to reveal previously unidentified correlations between specific micronutrients and health-related processes, with potential relevance for maintenance of health that were not observed by correlating homeostatic measurements. This approach will contribute to insights on the influence of micronutrients on health and help to create efficient micronutrient intervention programs.
Multi-parameter comparison of a standardized mixed meal tolerance test in healthy and type 2 diabetic subjects: A key feature of metabolic health is the ability to adapt upon dietary perturbations. Recently, it was shown that metabolic challenge tests in combination with the new generation biomarkers allow the simultaneous quantification of major metabolic health processes.
Currently, applied challenge tests are largely non-standardized. This study aimed to prove that PFT modulates all relevant processes governing metabolic health thereby allowing to distinguish subjects with different metabolic health status. During the 8-h response time course, parameters were quantified that report on 26 metabolic processes distributed over 7 organs gut, liver, adipose, pancreas, vasculature, muscle, kidney and systemic stress. In healthy subjects, of the parameters showed a time course response.
Patients with T2D showed 18 parameters to be significantly different after overnight fasting compared to healthy subjects, while 58 parameters were different in the post-challenge time course after the PFT.
This demonstrates the added value of PFT in distinguishing subjects with different health status. The OGTT and PFT response was highly comparable for glucose metabolism as identical amounts of glucose were present in both challenge tests. Yet the PFT reports on additional processes, including vasculature, systemic stress, and metabolic flexibility.
The PFT enables the quantification of all relevant metabolic processes involved in maintaining or regaining homeostasis of metabolic health. Studying both healthy subjects and subjects with impaired metabolic health showed that the PFT revealed new processes laying underneath health. This study provides the first evidence towards adopting the PFT as gold standard in nutrition research. HDL cholesterol efflux normalised to apoA-I is associated with future development of type 2 diabetes: This prospective study evaluated whether baseline cholesterol efflux is associated with future development of type 2 diabetes T2DM in cardiovascular patients.
Disposition index was estimated as beta-cell function indicator. During follow-up individuals progressed to T2DM. This association was independent of several T2DM risk factors, and may be related to a preserved beta-cell function. Ranges of phenotypic flexibility in healthy subjects. Background A key feature of metabolic health is the ability to adapt upon dietary perturbations.
Recently, it has been shown that the PFT enables the quantification of all relevant metabolic processes involved in maintaining or regaining homeostasis of metabolic health. Furthermore, it was demonstrated that quantification of PFT response was more sensitive as compared to fasting markers in demonstrating reduced phenotypic flexibility in metabolically impaired type 2 diabetes subjects.
Methods This study aims to demonstrate that quantification of PFT response can discriminate between different states of health within the healthy range of the population. Therefore, healthy subjects were enrolled 50 males, 50 females ranging in age young, middle, old and body fat percentage low, medium, high , assuming variation in phenotypic flexibility.
Biomarkers were selected to quantify main processes which characterize phenotypic flexibility in response to PFT: By quantifying and presenting the study subjects in this space, individual phenotypic flexibility was visualized. The health space showed a different adaptation to the metabolic PhenFlex test in the extremes of the recruited population; persons of young age with low to normal fat percentage had a markedly different position in the health space as compared to persons from old age with normal to high fat percentage.
Conclusion The results of the metabolic PhenFlex test in conjunction with the health space reliably assessed health on an individual basis. This quantification can be used in the future for personalized health quantification and advice. Electronic supplementary material The online version of this article Proposed guidelines to evaluate scientific validity and evidence for genotype-based dietary advice.
Nutrigenetic research examines the effects of inter-individual differences in genotype on responses to nutrients and other food components, in the context of health and of nutrient requirements. A practical application of nutrigenetics is the use of personal genetic information to guide recommendations for dietary choices that are more efficacious at the individual or genetic subgroup level relative to generic dietary advice. Nutrigenetics is unregulated, with no defined standards, beyond some commercially adopted codes of practice.
Only a few official nutrition-related professional bodies have embraced the subject, and, consequently, there is a lack of educational resources or guidance for implementation of the outcomes of nutrigenetic research. To avoid misuse and to protect the public, personalised nutrigenetic advice and information should be based on clear evidence of validity grounded in a careful and defensible interpretation of outcomes from nutrigenetic research studies. In addition, we propose that this framework be used as the basis for developing transparent and scientifically sound advice to the public based on nutrigenetic tests.
We feel that although this area is still in its infancy, minimal guidelines are required. Though these guidelines are based on semi-quantitative data, they should stimulate debate on their utility. This framework will be revised biennially, as knowledge on the subject increases. What we know and still need to know. Understanding health requires more than knowledge of the genome. Environmental factors regulate gene function through epigenetics.
Maternal dietary patterns, physical activity, degree of weight gain, and body composition while pregnant will influence not only fetal growth, but also the infant's metabolic response to nutrients and energy. Maternal over- or underweight, excess caloric intake, nutrient imbalances, glucose dysregulation, and presence of chronic inflammatory states have been shown to establish risk for many later chronic diseases. During the period from birth to age 3 y, when the infant's metabolic rate is high and synaptogenesis and myelination of the brain are occurring extremely rapidly, the infant is especially prone to damaging effects from nutrient imbalances.
During this period, the infant changes from a purely milk-based diet to one including a wide variety of foods. The process, timing, quality, and ultimate dietary pattern acquired are a direct outcome of the caregiver-infant feeding relationship, with potentially lifelong consequences.
More research on how meal time interactions shape food acceptance is needed to avoid eating patterns that augment existing disease risk. Traditional clinical trials in nutrition, meant to isolate single factors for study, are inadequate to study the highly interconnected realm of environment-gene interactions in early life.
Novel technologies are being used to gather broad exposure data on disparate populations, employing pioneering statistical approaches and correlations applied specifically to the individual, based on their genetic make-up and unique environmental experiences. Mediterranean Diet MedDiet adherence has been proven to produce numerous health benefits. In addition, nutrigenetic studies have explained some individual variations in the response to specific dietary patterns. The present research aimed to explore associations and potential interactions between MedDiet adherence and genetic background throughout the Food4Me web-based nutritional intervention.
Dietary, anthropometrical and biochemical data from volunteers of the Food4Me study were collected at baseline and after 6 months. Several genetic variants related to metabolic risk features were also analysed. Linear mixed model repeated measures analyses showed a significantly greater decrease in total cholesterol in participants with a low GRS after a 6-month period, compared to those with a high GRS.
These results suggest that a higher MedDiet adherence induces beneficial effects on metabolic outcomes, which can be affected by the genetic background in some specific markers. Systems biology of personalized nutrition. Personalized nutrition is fast becoming a reality due to a number of technological, scientific, and societal developments that complement and extend current public health nutrition recommendations.
Personalized nutrition tailors dietary recommendations to specific biological requirements on the basis of a person's health status and goals.
The biology underpinning these recommendations is complex, and thus any recommendations must account for multiple biological processes and subprocesses occurring in various tissues and must be formed with an appreciation for how these processes interact with dietary nutrients and environmental factors. Therefore, a systems biology-based approach that considers the most relevant interacting biological mechanisms is necessary to formulate the best recommendations to help people meet their wellness goals.
Here, the concept of "systems flexibility" is introduced to personalized nutrition biology. Systems flexibility allows the real-time evaluation of metabolism and other processes that maintain homeostasis following an environmental challenge, thereby enabling the formulation of personalized recommendations.
Examples in the area of macro- and micronutrients are reviewed. Genetic variations and performance goals are integrated into this systems approach to provide a strategy for a balanced evaluation and an introduction to personalized nutrition. Finally, modeling approaches that combine personalized diagnosis and nutritional intervention into practice are reviewed. Determinants of post-prandial plasma bile acid kinetics in human volunteers.
Bile acids BA are signaling molecules with a wide range of biological effects, also identified amongst the most responsive plasma metabolites in the post-prandial state. We here describe this response to different dietary challenges and report on key determinants linked to its inter-individual variability. Considering the average response of all 72 subjects, no effect of the successful weight loss intervention was found on plasma BA profiles.
Fasting and post-prandial BA profiles revealed high inter-individual variability and 3 main patterns in post-prandial BA response were identified using multivariate analysis.
Although the women enrolled were postmenopausal, gender effects in BA response were evident. Exome data revealed the contribution of preselected genes to the observed inter-individual variability. The analysis of plasma BA profiles in response to two different dietary challenges revealed a high inter-individual variability, which was mainly determined by genetics and gender of host with minimal effects of the microbiota.
Jun 30TH Bled eConference: Lifestyle recommendations for the prevention and management of metabolic syndrome: An international panel recommendation. The importance of metabolic syndrome MetS lies in its associated risk of cardiovascular disease and type 2 diabetes, as well as other harmful conditions such as nonalcoholic fatty liver disease. In this report, the available scientific evidence on the associations between lifestyle changes and MetS and its components is reviewed to derive recommendations for MetS prevention and management.
Weight loss through an energy-restricted diet together with increased energy expenditure. Online Supplementary Methods - Effect of personalized nutrition on health-related behaviour change: Optimal nutritional choices are linked with better health, but many current interventions to improve diet have limited effect.
Adults from seven European countries were recruited to an internet-delivered intervention Food4Me and randomized to: At baseline, mean age of participants was From the enrolled participants, completed the study. Following a 6-month intervention, participants randomized to PN consumed less red meat [ There was no evidence that including phenotypic and phenotypic plus genotypic information enhanced the effectiveness of the PN advice. Among European adults, PN advice via internet-delivered intervention produced larger and more appropriate changes in dietary behaviour than a conventional approach.
Associations of vitamin D status with dietary intakes and physical activity levels among adults from seven European countries: PurposeTo report the vitamin D status in adults from seven European countries and to identify behavioural correlates. The highest prevalence of vitamin D deficiency was found in the UK and the lowest in the Netherlands 8.
In addition, the prevalence of vitamin D insufficiency was higher in females compared with males Positive dose—response associations were also observed between OHD3 concentrations and dietary vitamin D intake from foods and supplements, as well as with physical activity PA levels.
Conclusions The prevalence of vitamin D deficiency varied considerably among European adults. Hepatic insulin resistance both in prediabetic and diabetic patients determines postprandial lipoprotein metabolism: However, the response in prediabetes population has not been established.
Methods patients were submitted to an oral fat load test meal OFTT with 0. Serial blood test analyzing lipid fractions were drawn at 0, 1, 2, 3 and 4 h during postprandial state. We explored the dynamic response in 57 non-diabetic, prediabetic and type 2 diabetic patients. Conclusions Our findings demonstrate that prediabetic patients show a lower phenotypic flexibility after external aggression, such as OFTT compared with nondiabetic patients. The postprandial response increases progressively according to non-diabetic, prediabetic and type 2 diabetic state and it is higher in patients with liver insulin-resistance.
To identify this subgroup of patients is important to treat more intensively in order to avoid future cardiometabolic complications. Effect of personalized nutrition on health-related behaviour change: Background Optimal nutritional choices are linked with better health, but many current interventions to improve diet have limited effect. Results At baseline, mean age of participants was Conclusions Among European adults, PN advice via internet-delivered intervention produced larger and more appropriate changes in dietary behaviour than a conventional approach.
Patients with coexisting coronary heart disease CHD and type 2 diabetes mellitus T2DM are at high risk of cardiovascular recurrence, however, it is not well established whether they exhibit an increased intima-media thickness of both common carotid arteries IMT-CC. Furthermore, whether this relationship is inherent to T2DM or depends on glycemic control has not been tested in large cohorts.
Our results highlight the importance of properly controlling glucose metabolism in CHD patients, in younger populations in particular, providing an easy way of categorizing patients with an increased IMT-CC. Moreover, glucose concentration at min could contribute to CVD risk and its determination could be used as a predictive tool to identify those CHD patients at the highest risk.
Metabolomic biomarkers for personalised glucose lowering drugs treatment in type 2 diabetes. Baseline glucose and 1,5 anhydro-glucitol were associated with HbA1c decrease in all medication groups. In patients on SU no other metabolite was associated with HbA1c decrease. These metabolites included metabolites related to liver metabolism, such as 2-hydroxybutanoic acid, 3-hydroxybutanoic acid, 2-hydroxypiperidine and 4-oxoproline. The associations between baseline metabolites and responsiveness to medication are in line with its mode of action.
If these results could be replicated in other populations, the most promising predictive candidates might be tested to assess whether they could enhance personalised treatment. Weight loss predictability by plasma metabolic signatures in adults with obesity and morbid obesity of the DiOGenes study. Aim is to predict successful weight loss by metabolic signatures at baseline and to identify which differences in metabolic status may underlie variations in weight loss success.
In DiOGenes, a randomized, controlled trial, weight loss was induced using a low-calorie diet kcal for 8 weeks. The relation between the metabolic status before weight loss and weight loss was assessed by stepwise regression on multiple data sets, including anthropometric parameters, NMR-based plasma metabolites, and LC-MS-based plasma lipid species. The most powerful predictive models were obtained in subjects with morbid obesity.
In these models, the metabolites most predictive for weight loss were acetoacetate, triacylglycerols, phosphatidylcholines, specific amino acids, and creatine and creatinine.
This metabolic profile suggests that high energy metabolism activity results in higher amounts of weight loss. Possible predictive pre-diet markers were found for amount of weight loss for specific subgroups. Next-Generation Biomarkers of Health. Current biomarkers used in health care and in nutrition and health research are based on quantifying disease onset and its progress.
Yet, both health care and nutrition should focus on maintaining optimal health, where the related biology is essentially differing from biomedical science. Health is characterized by the ability to continuously adapt in varying circumstances where multiple mechanisms of systems flexibility are involved. A new generation of biomarkers is needed that quantifies all aspects of systems flexibility, opening the door to real lifestyle-related health optimization, self-empowerment, and related products and services.
The insulin resistance phenotype muscle or liver interacts with the type of diet to determine changes in disposition index after 2 years of intervention: At baseline, the patients were classified into four phenotypes according to the type of IR: The hepatic insulin resistance index HIRI , muscular insulin sensitivity index MISI and disposition index were analysed at baseline and after 2 years of follow-up.
Quantifying phenotypic flexibility as the response to a high-fat challenge test in different states of metabolic health. Metabolism maintains homeostasis at chronic hypercaloric conditions, activating postprandial response mechanisms, which come at the cost of adaptation processes such as energy storage, eventually with negative health consequences.
This study quantified the metabolic adaptation capacity by studying challenge response curves. After a high-fat challenge, the 8 h response curves of 61 biomarkers related to adipose tissue mass and function, systemic stress, metabolic flexibility, vascular health, and glucose metabolism was compared between 3 metabolic health stages: The MetS subjects had increased fasting concentrations of biomarkers representing the 3 core processes, glucose, TG, and inflammation control, and the challenge response curves of most biomarkers were altered.
After the 4 wk hypercaloric dietary intervention, these 3 processes were not changed, as compared with the preintervention state in the healthy subjects, whereas the challenge response curves of almost all endocrine, metabolic, and inflammatory processes regulating these core processes were altered, demonstrating major molecular physiologic efforts to maintain homeostasis. This study thus demonstrates that change in challenge response is a more sensitive biomarker of metabolic resilience than are changes in fasting concentrations.
Phenotypic flexibility as a measure of health: Nutrition research is struggling to demonstrate beneficial health effects, since nutritional effects are often subtle and long term. Health has been redefined as the ability of our body to cope with daily-life challenges.
Physiology acts as a well-orchestrated machinery to adapt to the continuously changing environment. This may offer a more sensitive way to assess changes in health status of healthy subjects. Here, we performed a systematic review of 61 studies applying different nutritional stress tests to quantify health and nutritional health effects, with the objective to define an optimal nutritional stress test that has the potential to be adopted as the golden standard in nutrition research.
To acknowledge the multi-target role of nutrition, a relevant subset of 50 processes that govern optimal health, with high relevance to diet, was used to define phenotypic flexibility. Subsequently, we assessed the response of biomarkers related to this subset of processes to the different challenge tests.
Based on the obtained insights, we propose a nutritional stress test composed of a high-fat, high-caloric drink, containing 60 g palm olein, 75 g glucose and 20 g dairy protein in a total volume of ml. The use of such a standardized nutritional challenge test in intervention studies is expected to demonstrate subtle improvements of phenotypic flexibility, thereby enabling substantiation of nutritional health effects.
Electronic supplementary material The online version of this article doi: An increasing recognition has emerged of the complexities of the global health agenda-specifically, the collision of infections and noncommunicable diseases and the dual burden of over- and undernutrition. Of particular practical concern are both 1 the need for a better understanding of the bidirectional relations between nutritional status and the development and function of the immune and inflammatory response and 2 the specific impact of the inflammatory response on the selection, use, and interpretation of nutrient biomarkers.
Each WG was tasked with synthesizing a summary of the evidence for each of these topics and delineating the remaining gaps in our knowledge. White adipose tissue reference network: Optimal health is maintained by interaction of multiple intrinsic and environmental factors at different levels of complexity-from molecular, to physiological, to social.
Understanding and quantification of these interactions will aid design of successful health interventions. We introduce the reference network concept as a platform for multi-level exploration of biological relations relevant for metabolic health, by integration and mining of biological interactions derived from public resources and context-specific experimental data.
The WATRefNet 6, nodes and 32, edges is based on 1 experimental data obtained from 10 studies addressing different adiposity states, 2 seven public knowledge bases of molecular interactions, 3 expert's definitions of five physiologically relevant processes key to WAT health, namely WAT expandability, Oxidative capacity, Metabolic state, Oxidative stress and Tissue inflammation, and 4 a collection of relevant biomarkers of these processes identified by BIOCLAIMS http: The WATRefNet comprehends multiple layers of biological complexity as it contains various types of nodes and edges that represent different biological levels and interactions.
We have validated the reference network by showing overrepresentation with anti-obesity drug targets, pathology-associated genes and differentially expressed genes from an external disease model dataset. The resulting network has been used to extract subnetworks specific to the above-mentioned expert-defined physiological processes.
Each of these process-specific signatures represents a mechanistically supported composite biomarker for assessing and quantifying the effect of interventions on a physiological aspect that determines WAT health status. Following this principle, five anti-diabetic drug interventions and one diet intervention were scored for the match of their expression signature to the five biomarker signatures derived from the WATRefNet.
This confirmed previous observations of successful intervention by dietary lifestyle and revealed WAT-specific effects of drug interventions. The WATRefNet represents a sustainable knowledge resource for extraction of relevant relationships such as mechanisms of action, nutrient intervention targets and biomarkers and for assessment of health effects for support of health claims made on food products.
A knowledge resource for exploring health-relevant relations. Optimal health is maintained by interaction of multiple intrinsic and environmental factors at different levels of complexity—from molecular, to physiological, to social. Network signatures link hepatic effects of anti-diabetic interventions with systemic disease parameters. Background Multifactorial diseases such as type 2 diabetes mellitus T2DM , are driven by a complex network of interconnected mechanisms that translate to a diverse range of complications at the physiological level.
To optimally treat T2DM, pharmacological interventions should, ideally, target key nodes in this network that act as determinants of disease progression. By combining knowledge-based and data-driven networks with a random walks based algorithm, we extracted network signatures that link the DLI and two drug interventions to dyslipidemia-related disease parameters.
Conclusions This study identified specific and prioritized sets of key nodes in hepatic molecular networks underlying T2DM, uncovering pathways that are to be modulated by targeted T2DM drug interventions in order to modulate the complex disease phenotype. Phenotypic flexibility as key factor in the human nutrition and health relationship.
Metabolic adaptation to a disturbance of homeostasis is determined by a series of interconnected physiological processes and molecular mechanisms that can be followed in space i. The amplitudes of these responses of this "systems flexibility network" determine to what extent the individual can adequately react to external challenges of varying nature and thus determine the individual's health status and disease predisposition.
Connected pathways and regulatory networks act as "adaptive response systems" with metabolic and inflammatory processes as a core-but embedded into psycho-neuro-endocrine control mechanisms that in their totality define the phenotypic flexibility in an individual. Optimal metabolic health is thus the orchestration of all mechanisms and processes that maintain this flexibility in an organism as a phenotype.
Consequently, onset of many chronic metabolic diseases results from impairment or even loss of flexibility in parts of the system. This also means that metabolic diseases need to be diagnosed and treated from a systems perspective referring to a "systems medicine" approach.
This requires a far better understanding of the mechanisms involved in maintaining, optimizing and restoring phenotypic flexibility. Although a loss of flexibility in a specific part of the network may promote pathologies, this not necessarily takes place in the same part because the system compensates.
Diagnosis at systems level therefore needs the quantification of the response reactions of all relevant parts of the phenotypic flexibility system. This can be achieved by disturbing the homeostatic system by any challenge from extended fasting, to intensive exercise or a caloric overload.
Predicting individual responses to pravastatin using a physiologically based kinetic model for plasma cholesterol concentrations. We used a previously developed physiologically based kinetic PBK model to analyze the effect of individual variations in metabolism and transport of cholesterol on pravastatin response. A pravastatin pharmacokinetic model was constructed and the simulated hepatic pravastatin concentration was used to modulate the reaction rate constant of hepatic free cholesterol synthesis in the PBK model.
The integrated model was then used to predict plasma cholesterol concentrations as a function of pravastatin dose. Linear regression analysis of the pravastatin response in this virtual population showed that hepatic and peripheral cholesterol synthesis had the largest regression coefficients for the non-HDL-C response. However, the modeling also showed that these processes alone did not suffice to predict non-HDL-C response to pravastatin, contradicting the hypothesis that people with high cholesterol synthesis rates are good statin responders.
In conclusion, we have developed a PBK model that is able to accurately describe the effect of pravastatin treatment on plasma cholesterol concentrations and can be used to provide insight in the mechanisms behind individual variation in statin response.
A systems biology approach to understand the pathophysiological mechanisms of cardiac pathological hypertrophy associated with rosiglitazone. Background Cardiac pathological hypertrophy is associated with a significantly increased risk of coronary heart disease and has been observed in diabetic patients treated with rosiglitazone whereas most published studies do not suggest a similar increase in risk of cardiovascular events in pioglitazone-treated diabetic subjects.
This study sought to understand the pathophysiological and molecular mechanisms underlying the disparate cardiovascular effects of rosiglitazone and pioglitazone and yield knowledge as to the causative nature of rosiglitazone-associated cardiac hypertrophy. Methods We used a high-fat diet-induced pre-diabetic mouse model to allow bioinformatics analysis of the transcriptome of the heart of mice treated with rosiglitazone or pioglitazone.
Results Our data show that rosiglitazone and pioglitazone both markedly improved systemic markers for glucose homeostasis, fasting plasma glucose and insulin, and the urinary excretion of albumin. Only rosiglitazone, but not pioglitazone, tended to increase atherosclerosis and induced pathological cardiac hypertrophy, based on a significant increase in heart weight and increased expression of the validated markers, ANP and BNP.
This underlies the rosiglitazone-associated pathological hypertrophic cardiac phenotype in the current study. Conclusion Application of a systems biology approach uncovered a shift in energy metabolism by rosiglitazone that may impact cardiac pathological hypertrophy.
Jun Keystone Symposia -Pathogenesis of Diabetes: Emerging Insights into Molecular Mechanisms J8. We identified hepatic molecular mechanisms underlying these treatments using genome-wide transcriptome profiling and gas chromatography-mass spectrometry GCMS and oxylipid metabolomic platforms and determined processes and biomarkers associated with disease manifestation and their modulation by anti-diabetic treatments.
Dietary life style intervention largely reversed the patho physiological and hepatic effects of the high-fat diet. T and fenofibrate showed more pronounced effect than any other treatment, with certain processes even further deregulated than under untreated high fat condition.
T, fenofibrate and roziglitazone positively affect hepatic biomarkers that contribute to insulin sensitivity status and omental fat content, while T and fenofibrate aggravate hepatic processes related to atherosclerosis, plasma cholesterol and triglyceride levels and hepatic pathology. Analyzing metabolomics-based challenge tests. Challenge tests are used to assess the resilience of human beings to perturbations by analyzing responses to detect functional abnormalities.
Well known examples are allergy tests and glucose tolerance tests. Increasingly, metabolomics analysis of blood or serum samples is used to analyze the biological response of the individual to these challenges. The information content of such metabolomics challenge test data involves both the disturbance and restoration of homeostasis on a metabolic level and is thus inherently different from the analysis of steady state data. It opens doors to study the variation of resilience between individuals beyond the classical biomarkers; preferably in terms of underlying biological processes.
We review challenge tests in which metabolomics was used to analyze the biological response. Specifically, we describe strategies to perform statistical analyses on the responses and we will show some examples of these strategies applied to a postprandial challenge that was used to study a diet with anti-inflammatory properties.
Finally we discuss open issues and give recommendation for further research. Network Biology of Systems Flexibility: What does it take to take up a challenge?
To achieve such optimal function, flexibility should be established and maintained at all levels of systems complexity: Network biology is fundamentally suited to investigate flexibility of the system. We are developing solutions to address systems flexibility using network properties and implement these findings into healthcare, with focus on following critical aspects: Assessment of dynamic changes in network models e. Cardiovascular disease risk increases when lipoprotein metabolism is dysfunctional.
We have developed a computational model able to derive indicators of lipoprotein production, lipolysis, and uptake processes from a single lipoprotein profile measurement. This is the first study to investigate whether lipoprotein metabolism indicators can improve cardiovascular risk prediction and therapy management.
We calculated lipoprotein metabolism indicators for subjects cases, controls from the Framingham Heart Study offspring cohort in which NMR lipoprotein profiles were measured. We applied a statistical learning algorithm using a support vector machine to select conventional risk factors and lipoprotein metabolism indicators that contributed to predicting risk for general cardiovascular disease.
We added these indicators to a multivariate model with the best performing conventional risk markers. Our method significantly improved both CVD prediction and risk reclassification.
Two calculated VLDL metabolism indicators significantly improved cardiovascular risk prediction. These indicators may help to reduce prescription of unnecessary cholesterol-lowering medication, reducing costs and possible side-effects. For clinical application, further validation is required. Functional network signatures link anti-diabetic interventions with disease parameters. Our current methods to intervene with type 2 diabetes mellitus T2DM are insufficient, and novel interventions are being developed to improve treatment efficiency across the whole range of T2DM-related complications.
To understand and improve our ability to intervene with complex diseases such as T2DM, it is important to elucidate which and how underlying molecular mechanisms may contribute to development of pathology and its regression by different interventions.
The resulting network signatures explain molecular paths linking a dietary lifestyle intervention and two anti-diabetic drug interventions fenofibrate, T to the four dyslipidemia-related disease parameters atherosclerosis, plasma cholesterol levels, liver weight, and plasma triglyceride levels.
As these disease parameters were reverted to the healthy levels by a dietary lifestyle intervention and in turn were aggravated by the drugs, the resulting network signatures define putative signatures that should be mimicked or circumvented by the novel interventions to achieve optimal pathology outcome.
Together, the undertaken approach provides insight into the molecular pathways underlying both positive and negative effects of anti-diabetic interventions, holding promise for aiding an improved intervention design.
Exploring the benefits and challenges of establishing a DRI-like process for bioactives. Bioactives can be defined as: Although traditional nutrients, such as vitamins, minerals, protein, essential fatty acids and essential amino acids, have dietary reference intake DRI values, there is no such evaluative process for bioactives.
For certain classes of bioactives, substantial scientific evidence exists to validate a relationship between their intake and enhanced health conditions or reduced risk of disease. In addition, the study of bioactives and their relationship to disease risk is a growing area of research supported by government, academic institutions, and food and supplement manufacturers.
Importantly, consumers are purchasing foods containing bioactives, yet there is no evaluative process in place to let the public know how strong the science is behind the benefits or the quantitative amounts needed to achieve these beneficial health effects.
The role of low-grade inflammation and metabolic flexibility in aging and nutritional modulation thereof: A systems biology approach. Aging is a biological process characterized by the progressive functional decline of many interrelated physiological systems. In particular, aging is associated with the development of a systemic state of low-grade chronic inflammation inflammaging , and with progressive deterioration of metabolic function.
Systems biology has helped in identifying the mediators and pathways involved in these phenomena, mainly through the application of high-throughput screening methods, valued for their molecular comprehensiveness. Fortunately, they all paid off; and her life today is the reward for her years of hard work.
Rebecca displayed incredible tenacity and passion for creating art all through college. She also learned and drew inspiration from every artist she knew, regardless if he or she were in the theater, photography, or any creative industry.
By the end of it all, Rebecca had beefed up her creative skills; but not her portfolio, unfortunately. She was still intent on getting into an ad agency as an artist, but people in the industry finally set her straight. So, can I do commercials now? Handling an account for Gatorade inspired her to do commercial photography.
Gatorade loved her work. Upon learning the amount the company paid for them, something clicked: That was when she approached Francis Abraham for an apprenticeship. Somewhere in the middle of nowhere is a person showering. Hey, we just do the retouch! Send us a message at info paperboatcreative.
A post shared by Paper Boat Creative paperboatcreative on Apr 30, at Soon after, she moved to London to live with her sister. She was walking past the offices of Getty Images one day and remembered contacting the company while she was still in the Philippines. Could she send her photos for them to review? She never got a response. She gave her CV at the front desk, got a call a few days later, and went through a month-long interview and screening process. Getty Images hired her as a senior art director.
As awesome as her time was with Getty she had free rein to conceptualize creative photoshoots, and was one of only four senior art editors retained after the economic crash of , deep inside, Rebecca wanted to be her own boss.
After two years and three months with Getty Images, Rebecca started the path to entrepreneurship. She poured her life savings into paying the down payment for a commercial space. She got second-hand tables and chairs, painted the entire place white, and rented out spaces to London artists. That was the beginning of PaperBoat Creative. She held firm on this belief as a service provider, and later, as a mother and mentor.
Les brocanteurs ommen, Ommen, Netherlands. 47K likes. m2 woonwinkel in landelijke sfeer Slagenkampweg 5 TK OMMEN ricksteineralaska.com Welcome Chase Ommen, CNM to our Women's Health Team. May 25, As a certified nurse midwife, Chase can provide well-women care, including annual. Ommen is a municipality and a Hanseatic city in the Vecht valley of the Salland region, which is More locally, farming communities in the eastern Netherlands organised themselves into markes (autonomous areas) where Only the church and women's home de Heilige Geest (the Holy Spirit) survived the pillage and fire .