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Sökning: WFRF:(Fischbach M.)

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  • Medema, M. H., et al. (författare)
  • Minimum Information about a Biosynthetic Gene cluster
  • 2015
  • Ingår i: Nature Chemical Biology. - : Springer Science and Business Media LLC. - 1552-4450 .- 1552-4469. ; 11:9, s. 625-631
  • Forskningsöversikt (refereegranskat)abstract
    • A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.
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  • Steinacker, J. M., et al. (författare)
  • Global Alliance for the Promotion of Physical Activity: the Hamburg Declaration
  • 2023
  • Ingår i: Bmj Open Sport & Exercise Medicine. ; 9:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Non-communicable diseases (NCDs), including coronary heart disease, stroke, hypertension, type 2 diabetes, dementia, depression and cancers, are on the rise worldwide and are often associated with a lack of physical activity (PA). Globally, the levels of PA among individuals are below WHO recommendations. A lack of PA can increase morbidity and mortality, worsen the quality of life and increase the economic burden on individuals and society. In response to this trend, numerous organisations came together under one umbrella in Hamburg, Germany, in April 2021 and signed the 'Hamburg Declaration'. This represented an international commitment to take all necessary actions to increase PA and improve the health of individuals to entire communities. Individuals and organisations are working together as the 'Global Alliance for the Promotion of Physical Activity' to drive long-term individual and population-wide behaviour change by collaborating with all stakeholders in the community: active hospitals, physical activity specialists, community services and healthcare providers, all achieving sustainable health goals for their patients/clients. The 'Hamburg Declaration' calls on national and international policymakers to take concrete action to promote daily PA and exercise at a population level and in healthcare settings.
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  • Haas, Brian J., et al. (författare)
  • Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans
  • 2009
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 461:7262, s. 393-398
  • Tidskriftsartikel (refereegranskat)abstract
    • Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement(1). To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population(1). Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion(2). Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars(3,4). Here we report the sequence of the P. infestans genome, which at similar to 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for similar to 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.
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  • Nemet, I., et al. (författare)
  • Atlas of gut microbe-derived products from aromatic amino acids and risk of cardiovascular morbidity and mortality
  • 2023
  • Ingår i: European Heart Journal. - 0195-668X. ; 44:32
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims Precision microbiome modulation as a novel treatment strategy is a rapidly evolving and sought goal. The aim of this study is to determine relationships among systemic gut microbial metabolite levels and incident cardiovascular disease risks to identify gut microbial pathways as possible targets for personalized therapeutic interventions.Methods and results Stable isotope dilution mass spectrometry methods to quantitatively measure aromatic amino acids and their metabolites were used to examine sequential subjects undergoing elective diagnostic cardiac evaluation in two independent cohorts with longitudinal outcome data [US (n = 4000) and EU (n = 833) cohorts]. It was also used in plasma from humans and mice before vs. after a cocktail of poorly absorbed antibiotics to suppress gut microbiota. Multiple aromatic amino acid-derived metabolites that originate, at least in part, from gut bacteria are associated with incident (3-year) major adverse cardiovascular event (MACE) risks (myocardial infarction, stroke, or death) and all-cause mortality independent of traditional risk factors. Key gut microbiota-derived metabolites associated with incident MACE and poorer survival risks include: (i) phenylacetyl glutamine and phenylacetyl glycine (from phenylalanine); (ii) p-cresol (from tyrosine) yielding p-cresol sulfate and p-cresol glucuronide; (iii) 4-OH-phenyllactic acid (from tyrosine) yielding 4-OH-benzoic acid and 4-OH-hippuric acid; (iv) indole (from tryptophan) yielding indole glucuronide and indoxyl sulfate; (v) indole-3-pyruvic acid (from tryptophan) yielding indole-3-lactic acid and indole-3-acetyl-glutamine, and (vi) 5-OH-indole-3-acetic acid (from tryptophan).Conclusion Key gut microbiota-generated metabolites derived from aromatic amino acids independently associated with incident adverse cardiovascular outcomes are identified, and thus will help focus future studies on gut-microbial metabolic outputs relevant to host cardiovascular health.
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  • Minoia, F, et al. (författare)
  • Development and initial validation of the MS score for diagnosis of macrophage activation syndrome in systemic juvenile idiopathic arthritis
  • 2019
  • Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:10, s. 1357-1362
  • Tidskriftsartikel (refereegranskat)abstract
    • To develop and validate a diagnostic score that aids in identifying macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (sJIA).MethodsThe clinical and laboratory features of 362 patients with sJIA-associated MAS and 404 patients with active sJIA without evidence of MAS were collected in a multinational collaborative project. Eighty percent of the study population was used to develop the score and the remaining 20% constituted the validation sample. A Bayesian Model Averaging approach was used to assess the role of each clinical and laboratory variables in the diagnosis of MAS and to obtain the coefficients of selected variables. The final score, named MAS/sJIA (MS) score, resulted from the linear combination of these coefficients multiplied by the values of each variable. The cut-off that best discriminated MAS from active sJIA was calculated by means of receiver operating characteristic (ROC) curve analysis. Score performance was evaluated in both developmental and validation samples.ResultsThe MS score ranges from −8.4 to 41.8 and comprises seven variables: central nervous system dysfunction, haemorrhagic manifestations, active arthritis, platelet count, fibrinogen, lactate dehydrogenase and ferritin. A cut-off value ≥−2.1 revealed the best performance in discriminating MAS from active sJIA, with a sensitivity of 0.85, a specificity of 0.95 and a kappa value of 0.80. The good performance of the MS score was confirmed in the validation sample.ConclusionThe MS score is a powerful and feasible tool that may assist practitioners in making a timely diagnosis of MAS in patients with sJIA.
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  • Drezner, Jonathan A, et al. (författare)
  • Abnormal electrocardiographic findings in athletes : recognising changes suggestive of primary electrical disease.
  • 2013
  • Ingår i: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 47:3, s. 153-67
  • Tidskriftsartikel (refereegranskat)abstract
    • Cardiac channelopathies are potentially lethal inherited arrhythmia syndromes and an important cause of sudden cardiac death (SCD) in young athletes. Other cardiac rhythm and conduction disturbances also may indicate the presence of an underlying cardiac disorder. The 12-lead ECG is utilised as both a screening and a diagnostic tool for detecting conditions associated with SCD. Fundamental to the appropriate evaluation of athletes undergoing ECG is an understanding of the ECG findings that may indicate the presence of a pathological cardiac disease. This article describes ECG findings present in primary electrical diseases afflicting young athletes and outlines appropriate steps for further evaluation of these ECG abnormalities. The ECG findings defined as abnormal in athletes were established by an international consensus panel of experts in sports cardiology and sports medicine.
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  • Drezner, Jonathan A, et al. (författare)
  • Abnormal electrocardiographic findings in athletes : recognising changes suggestive of cardiomyopathy.
  • 2013
  • Ingår i: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 47:3, s. 137-52
  • Tidskriftsartikel (refereegranskat)abstract
    • Cardiomyopathies are a heterogeneous group of heart muscle diseases and collectively are the leading cause of sudden cardiac death (SCD) in young athletes. The 12-lead ECG is utilised as both a screening and diagnostic tool for detecting conditions associated with SCD. Fundamental to the appropriate evaluation of athletes undergoing ECG is an understanding of the ECG findings that may indicate the presence of an underlying pathological cardiac disorder. This article describes ECG findings present in cardiomyopathies afflicting young athletes and outlines appropriate steps for further evaluation of these ECG abnormalities. The ECG findings defined as abnormal in athletes were established by an international consensus panel of experts in sports cardiology and sports medicine.
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  • Drezner, Jonathan A, et al. (författare)
  • Electrocardiographic interpretation in athletes : the 'Seattle criteria'.
  • 2013
  • Ingår i: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 47:3, s. 122-4
  • Tidskriftsartikel (refereegranskat)abstract
    • Sudden cardiac death (SCD) is the leading cause of death in athletes during sport. Whether obtained for screening or diagnostic purposes, an ECG increases the ability to detect underlying cardiovascular conditions that may increase the risk for SCD. In most countries, there is a shortage of physician expertise in the interpretation of an athlete's ECG. A critical need exists for physician education in modern ECG interpretation that distinguishes normal physiological adaptations in athletes from abnormal findings suggestive of pathology. On 13-14 February 2012, an international group of experts in sports cardiology and sports medicine convened in Seattle, Washington, to define contemporary standards for ECG interpretation in athletes. The objective of the meeting was to develop a comprehensive training resource to help physicians distinguish normal ECG alterations in athletes from abnormal ECG findings that require additional evaluation for conditions associated with SCD.
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  • Drezner, Jonathan A, et al. (författare)
  • Normal electrocardiographic findings : recognising physiological adaptations in athletes.
  • 2013
  • Ingår i: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 47:3, s. 125-36
  • Tidskriftsartikel (refereegranskat)abstract
    • Electrocardiographic changes in athletes are common and usually reflect benign structural and electrical remodelling of the heart as a physiological adaptation to regular and sustained physical training (athlete's heart). The ability to identify an abnormality on the 12-lead ECG, suggestive of underlying cardiac disease associated with sudden cardiac death (SCD), is based on a sound working knowledge of the normal ECG characteristics within the athletic population. This document will assist physicians in identifying normal ECG patterns commonly found in athletes. The ECG findings presented as normal in athletes were established by an international consensus panel of experts in sports cardiology and sports medicine.
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  • Fischbach, M., et al. (författare)
  • Measurement by magnetic resonance imaging of the peritoneal membrane in contact with dialysate in rats
  • 2005
  • Ingår i: Adv Perit Dial. - 1197-8554. ; 21, s. 17-20
  • Tidskriftsartikel (refereegranskat)abstract
    • To be optimal, a peritoneal dialysis prescription should consider the peritoneal surface area recruitment. In fact, as shown by computed tomography imaging, only a fraction of the available anatomic peritoneum is in contact with the dialysate (PDF). Various factors may dynamically affect the recruitment of the wetted membrane: posture, fill volume, PDF composition (biocompatibility), and pharmacologic agents (phospholipids). To precisely determine the peritoneal membrane recruitment capacity, we developed an animal model. In 5/6 bi-nephrectomized rats on peritoneal dialysis, between week 6 and week 8 post surgery, we used MRI to assess the contact area, with the dialysate acting as the contrast medium (fill volume: 10 mL per 100-g rat body weight). The MRI protocol consisted of axially oriented, turbo spin-echo, 3-mm slice, T2 weighted sequences. The contact area was measured using an adapted three-dimensional MRI reconstruction software based on DICOM (digital imaging and communications in medicine) images. The MRI studies (n=10) were successful. They showed that only a fraction of the presumed anatomic area (30% - 40%) was in contact with the PDF Peritoneal MRI in rats is a method that shows potential for assessing peritoneal contact area and its variation under experimental conditions.
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  • Fischbach, M., et al. (författare)
  • Effect of peritoneal dialysis fluid composition on peritoneal area available for exchange in children
  • 2004
  • Ingår i: Nephrol Dial Transplant. - : Oxford University Press (OUP). - 0931-0509. ; 19:4, s. 925-32
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Although conventional peritoneal dialysis fluids (PDFs), such as Dianeal, are non-physiological in composition, new PDFs including Physioneal have a more neutral pH, are at least partially buffered with bicarbonate and, most importantly, contain low concentrations of glucose degradation products (GDPs). METHODS: To evaluate the impact of new PDFs in childcare, we performed a comparative crossover study with Dianeal and Physioneal. We examined both intraperitoneal pressure (IPP), which partly reflects pain induction, and the total pore area available for exchange, which indicates the number of capillaries perfused in the peritoneal membrane at any given moment and therefore partly reflects peritoneal dialysis capacity. The IPP was determined after inflow of 1000 ml/m(2) body surface area (BSA) of dialysate (intraperitoneal volume; IPV). The steady-state unrestricted area over diffusion distance (A(0)/ triangle up x, in cm(2)/cm per 1.73 m(2) BSA) was calculated from the three-pore theory. Six children were enrolled in the study. On the first day, two consecutive peritoneal equilibration tests of 90 min each were performed using first Dianeal and then Physioneal. On the second study day, the procedure was repeated with the fluids given in the opposite order. RESULTS: The mean IPP normalized to IPV (ml/m(2)) was significantly higher for Dianeal (9.5 +/- 0.9 cm/1000 ml/m(2)) than for Physioneal (7.9 +/- 1.2 cm/1000 ml/m(2), P < 0.01). The mean A(0)/ triangle up x was 17 +/- 4% larger with Dianeal (36 095 +/- 2009 cm(2)/cm per 1.73 m(2)) than with Physioneal (31 780 +/- 2185 cm(2)/cm per 1.73 m(2), P < 0.001; based on 24 data pairs). CONCLUSIONS: These pilot study results suggest a higher biocompatibility for Physioneal than for Dianeal. Less inflow pain associated with Physioneal induced a lower IPP reflecting enhanced fill volume tolerance, and the lower A(0)/ triangle up x reflected less capillary recruitment. Taken together, these results suggest that the new more biocompatible PDFs will improve peritoneal dialysis therapy, although this conclusion will require verification in extended clinical trials.
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  • Fischbach, M., et al. (författare)
  • The influence of peritoneal surface area on dialysis adequacy
  • 2005
  • Ingår i: Perit Dial Int. - 0896-8608. ; 25 Suppl 3
  • Tidskriftsartikel (refereegranskat)abstract
    • In children, the prescription of peritoneal dialysis is based mainly on the choice of the peritoneal dialysis fluid, the intraperitoneal fill volume (mL/m2 body surface area (BSA)], and the contact time. The working mode of the peritoneal membrane as a dialysis membrane is more related to a dynamic complex structure than to a static hemodialyzer. Thus, the peritoneal surface area impacts on dialysis adequacy. In fact, the peritoneal surface area may be viewed as composed of three exchange entities: the anatomic area, the contact area, and the vascular area. First, in infants, the anatomic area appears to be two-fold larger than in adults when expressed per kilogram body weight. On the other hand, the anatomic area becomes independent of age when expressed per square meter BSA. Therefore, scaling of the intraperitoneal fill volume by BSA (m2) is necessary to prevent a too low ratio of fill volume to exchange area, which would result in a functional "hyperpermeable" peritoneal exchange. Second, the contact area, also called the wetted membrane, is only a portion of the anatomic area, representing 30% to 60% of this area in humans, as measured by computed tomography. Both posture and fill volume may affect the extent of recruitment of contact area. Finally, the vascular area is influenced by the availability of both the anatomic area and the recruited contact area. This surface is governed essentially by both peritonealvascular perfusion, represented by the mesenteric vascular flow and, hence, by the number of perfused capillaries available for exchange. This vascular area is dynamically affected by different factors, such as composition of the peritoneal fluid, the fill volume, and the production of inflammatory agents. Peritoneal dialysis fluids that will be developed in the future for children should allow an optimization of the fill volume owing to a better tolerance in terms of lower achieved intraperitoneal pressure for a given fill volume. Moreover, future peritoneal dialysis fluids should protect the peritoneal membrane from hyperperfusion (lower glucose degradation products).
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  • Fischbach, M., et al. (författare)
  • The peritoneal membrane: a dynamic dialysis membrane in children
  • 2003
  • Ingår i: Adv Perit Dial. ; 19, s. 265-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Peritoneal dialysis prescription in children should be individualized--based not only on numerical targets (Kt/Vurea, Kcreat), but also on consideration of the peritoneal membrane, a dynamic dialysis membrane. In fact, the effective peritoneal surface area is at least a triple entity: an anatomic area, a contact area, and an exchange area. The anatomic area appears to be twice as large in infants as in adults if expressed per kilogram of body weight (BW), although the area is independent of age if expressed per square meter of body surface area (BSA). Therefore, scaling of the intraperitoneal fill volume (IPV) by BSA in square meters is necessary to avoid a low IPV/area ratio, which results in a functionally "hyperpermeable" peritoneal exchange. The contact area (the wetted membrane) is only a fraction of the anatomic area--that is, 30%-60% in humans (by computed tomography). Contact area depends on a variety of factors, such as posture and fill volume, that affect the degree of recruitment of membrane contact area. The exchange area is influenced by both the anatomic are and the contact area. However, it is mainly governed by the specific vascular area as determined by the peritoneal vascular perfusion and the capillaries available for exchange. Vascular area is dynamically affected by a variety of factors, such as the composition of the peritoneal dialysis fluid, the fill volume, and possible inflammatory agents.
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