Ketogenic diets attenuate cyclooxygenase and lipoxygenase gene expression in multiple sclerosis

Background: Adapted ketogenic diet (AKD) and caloric restriction (CR) have been suggested as alternative therapeutic strategies for inflammatory, hyperproliferative and neurodegenerative diseases. Pro-inflammatory eicosanoids have been implicated in the pathogenesis of multiple sclerosis since they augment vascular permeability and induce leukocyte migration into the brain. We explored the impact of ketogenic diets on gene expression of biosynthetic enzymes for pro- (ALOX5, COX1, COX2) and anti-inflammatory (ALOX15) eicosanoids in patients with relapsing-remitting multiple sclerosis. Methods: 60 adults were prospectively recruited for this six months randomized controlled trial and the impact of dietary treatment on the Multiple Sclerosis Quality of Life-54 index (ClinicalTrials.gov (NCT01538355) has previously been published. Here we explored 24 patients (8 controls, 5 on CR and 11 on AKD). For statistical analysis we combined the two diet groups to a single pooled treatment group. Findings: Inter-group comparison indicated that expression of the pro-inflammatory ALOX5 in the pooled treatment group was significantly (p <0.05) reduced when compared with the control group. Moreover, intra-group comparison (same individuals before and after dietary treatment) suggested significantly impaired expression of other pro-inflammatory enzymes, such as COX1 (p < 0.001) and COX2 ( p < 0.05). Finally, pretreatment cross-group analysis revealed a significant positive correlation between expression of pro-inflammatory ALOX5 and COX2 and an inverse correlation of ALOX5 and COX1 expression with the MSQoL-54 index. Interpretation: Ketogenic diets can reduce the expression of enzymes involved in the biosynthesis of pro-inflammatory eicosanoids. Pharmacological interference with eicosanoid biosynthesis might constitute a strategy supplementing current therapeutic approaches for MS. (C) 2018 The Authors. Published by Elsevier B.V

Non-invasive removal of sandblasted and acid-etched titanium palatal implants, a retrospective study

BACKGROUND Short, rough-surfaced palatal implants are an established and reliable anchor for orthodontic treatment. Until recently, removal was only possible surgically using a hollow cylinder trephine. This standard method retrieves the implant combined with a larger bone volume and is therefore considered invasive and has known complications. Lately, an explantation tool which allows a sufficient force application to break the bone-implant-connection and unscrew the palatal implant was developed and, since its introduction, has been used as the method of choice in several orthodontic offices. OBJECTIVES The aim of this study was to assess the complications caused by removing rough-surfaced palatal implants simply by unscrewing them with an explantation tool in contrast to standard protocol by surgical removal with a trephine. MATERIAL AND METHODS The removal of 73 palatal implants using a customized explantation tool has been evaluated retrospectively and was compared to an existing sample of 44 conventional surgical explantations. RESULTS The new clinical procedure resulted in successful removal of 71 (97.3 per cent) palatal implants. In two cases, the new method failed but removal with the established surgical method was still possible with no further complications. The non-invasive palatal implant removal with a customized explantation tool had less medical complications compared to an existing sample of surgical explantations. CONCLUSIONS User's opinion was that the new method is more easily executed, less invasive, and also applicable without local anaesthesia. Therefore, it is considered to be beneficial for patients and the treatment approach of choice. However, further research is needed for verificatio

Schule macht Museum: Die Teilhabe von Jugendlichen bei der Neukonzeption einer Dauerausstellung im Jüdischen Museum in Rendsburg

Wie kann eine zeitgemäße und zielgruppenorientierte Ausstellung partizipativ erarbeitet werden? Diese Frage wird am Beispiel der Neukonzeption der historischen Dauerausstellung im Jüdischen Museum in Rendsburg beantwortet. Dabei wird besonders auf die spezifischen Rahmenbedingungen eines Jüdischen Museums in Deutschland eingegangen und ein exemplarisches Vorgehen beschrieben, wie Schüler*innen auf Augenhöhe einbezogen werden können.How can a contemporary and target group-oriented exhibition be developed in a participatory manner? This question is answered using the example of the redesign of the permanent historical exhibition at the Jewish Museum in Rendsburg. The specific framework conditions of a Jewish Museum in Germany will be addressed in particular and an exemplary procedure will be described on how pupils can be involved at eye level

A single vaccination with an inactivated bovine respiratory syncytial virus vaccine primes the cellular immune response in calves with maternal antibody

<p>Abstract</p> <p>Background</p> <p>The efficacy of a single dose of an inactivated bovine respiratory syncytial virus (BRSV) - Parainfluenaza type 3 (PI3) - <it>Mannheimia haemolytica </it>(<it>Mh</it>) combination vaccine, in calves positive for maternal antibodies, was established in a BRSV infection study.</p> <p>Results</p> <p>As expected the single vaccination did not have any effect on the decline of BRSV-specific neutralising or ELISA antibody. The cellular immune system was however primed by the vaccination. In the vaccinated group virus excretion with nasal discharge was reduced, less virus could be re-isolated from lung tissues and the lungs were less affected.</p> <p>Conclusions</p> <p>These results indicate that a single vaccination with an inactivated BRSV vaccine was able to break through the maternal immunity and induce partial protection in very young calves. It can be speculated that the level and duration of protection will improve after the second dose of vaccine is administered. A two-dose basic vaccination schedule is recommended under field conditions.</p

Protein Substitute Requirements of Patients with Phenylketonuria on BH4 Treatment: A Systematic Review and Meta-Analysis

The traditional treatment for phenylketonuria (PKU) is a phenylalanine (Phe)-restricted diet, supplemented with a Phe-free/low-Phe protein substitute. Pharmaceutical treatment with synthetic tetrahydrobiopterin (BH4), an enzyme cofactor, allows a patient subgroup to relax their diet. However, dietary protocols guiding the adjustments of protein equivalent intake from protein substitute with BH4 treatment are lacking. We systematically reviewed protein substitute usage with long-term BH4 therapy. Electronic databases were searched for articles published between January 2000 and March 2020. Eighteen studies (306 PKU patients) were eligible. Meta-analyses demonstrated a significant increase in Phe and natural protein intakes and a significant decrease in protein equivalent intake from protein substitute with cofactor therapy. Protein substitute could be discontinued in 51% of responsive patients, but was still required in 49%, despite improvement in Phe tolerance. Normal growth was maintained, but micronutrient deficiency was observed with BH4 treatment. A systematic protocol to increase natural protein intake while reducing protein substitute dose should be followed to ensure protein and micronutrient requirements are met and sustained. We propose recommendations to guide healthcare professionals when adjusting dietary prescriptions of PKU patients on BH4. Studies investigating new therapeutic options in PKU should systematically collect data on protein substitute and natural protein intakes, as well as other nutritional factors

Long-term dietary intervention with low Phe and/or a specific nutrient combination improve certain aspects of brain functioning in phenylketonuria (PKU)

Introduction In phenylketonuria (PKU), a gene mutation in the phenylalanine metabolic pathway causes accumulation of phenylalanine (Phe) in blood and brain. Although early introduction of a Phe-restricted diet can prevent severe symptoms from developing, patients who are diagnosed and treated early still experience deficits in cognitive functioning indicating shortcomings of current treatment. In the search for new and/or additional treatment strategies, a specific nutrient combination (SNC) was postulated to improve brain function in PKU. In this study, a long-term dietary intervention with a low-Phe diet, a specific combination of nutrients designed to improve brain function, or both concepts together was investigated in male and female BTBR PKU and WT mice. Material & methods 48 homozygous wild-types (WT, +/+) and 96 PKU BTBRPah2 (-/-) male and female mice received dietary interventions from postnatal day 31 till 10 months of age and were distributed in the following six groups: high Phe diet (WT C-HP, PKU C-HP), high Phe plus specific nutrient combination (WT SNC-HP, PKU SNC-HP), PKU low-Phe diet (PKU C-LP), and PKU low-Phe diet plus specific nutrient combination (PKU SNC- LP). Memory and motor function were tested at time points 3, 6, and 9 months after treatment initiation in the open field (OF), novel object recognition test (NOR), spatial object recognition test (SOR), and the balance beam (BB). At the end of the experiments, brain neurotransmitter concentrations were determined. Results In the NOR, we found that PKU mice, despite being subjected to high Phe conditions, could master the task on all three time points when supplemented with SNC. Under low Phe conditions, PKU mice on control diet could master the NOR at all three time points, while PKU mice on the SNC supplemented diet could master the task at time points 6 and 9 months. SNC supplementation did not consistently influence the performance in the OF, SOR or BB in PKU mice. The low Phe diet was able to normalize concentrations of norepinephrine and serotonin; however, these neurotransmitters were not influenced by SNC supplementation. Conclusion This study demonstrates that both a long-lasting low Phe diet, the diet enriched with SNC, as well as the combined diet was able to ameliorate some, but not all of these PKU-induced abnormalities. Specifically, this study is the first long-term intervention study in BTBR PKU mice that shows that SNC supplementation can specifically improve novel object recognition

A Selection of Benchmark Problems in Solid Mechanics and Applied Mathematics

In this contribution we provide benchmark problems in the field of computational solid mechanics. In detail, we address classical fields as elasticity, incompressibility, material interfaces, thin structures and plasticity at finite deformations. For this we describe explicit setups of the benchmarks and introduce the numerical schemes. For the computations the various participating groups use different (mixed) Galerkin finite element and isogeometric analysis formulations. Some programming codes are available open-source. The output is measured in terms of carefully designed quantities of interest that allow for a comparison of other models, discretizations, and implementations. Furthermore, computational robustness is shown in terms of mesh refinement studies. This paper presents benchmarks, which were developed within the Priority Programme of the German Research Foundation ‘SPP 1748 Reliable Simulation Techniques in Solid Mechanics—Development of Non-Standard Discretisation Methods, Mechanical and Mathematical Analysis’. © 2020, The Author(s)

Knowledge of pressure ulcer prevention: a cross-sectional and comparative study among nurses

BACKGROUND: Pressure ulcers are a common, painful and costly condition. Results of a 1991 study into the knowledge among Dutch hospital nurses on the usefulness of measures to prevent pressure ulcers showed moderate knowledge. Results were confirmed by subsequent studies. In recent years, Dutch guidelines have been updated and the attention given to pressure ulcer care has been increased. This was expected to improve pressure ulcer care and to increase nurses' knowledge. The aims of the current study were to investigate (1) how much nurses employed in Dutch hospitals know about the usefulness of 28 preventive measures considered in the most recent national pressure ulcer guideline; (2) whether differences in knowledge exist between nurses working in hospitals that audit pressure ulcers and those employed in hospitals that do not; and (3) to study whether knowledge among Dutch hospital nurses regarding the usefulness of preventive measures had changed between 1991 and 2003. METHODS: A cross-sectional study design among nurses employed in Dutch hospitals in 2003 was used to investigate their knowledge and differences in knowledge between nurses employed in different types of institution. A comparative design was used to assess whether knowledge differed between this population and that of Dutch hospital nurses in 1991. The nurses' knowledge was assessed by a written questionnaire. Data of 522 respondents meeting the inclusion criteria were analyzed and compared with the results of the 351 nurses included in the 1991 study. RESULTS: Knowledge in 2003 was slightly better than that in 1991. The nurses were moderately aware of the usefulness of preventive measures. Nurses employed in organizations that monitored pressure ulcers did not display greater knowledge than those employed in organizations that did not do so. CONCLUSION: Knowledge among Dutch hospital nurses about the usefulness of measures to prevent pressure ulcers seems to be moderate. Being employed in an institution that monitors pressure ulcer care hardly affects the knowledge level. Knowledge about prevention has improved little since 1991

Evaluation de l'efficacité et de la tolérance de trois mélanges conçus pour la nutrition entérale de longue durée (approches expérimentale et clinique)

Les mélanges standard de nutrition entérale ne permettent pas de couvrir les besoins nutritionnels spécifiques de différents types des patients. Trois nouveaux mélanges pour la nutrition entérale de longue durée ont été développés pour répondre respectivement aux besoins des patients en équilibre nutritionnel nécessitant une nutrition entérale de longue durée (Sondalis® Maintenance), à ceux des personnes âgées dénutries hospitalisées (Patriarch), et à ceux des patients atteints d un cancer cachectisant sous traitement actif (Formula One). Le but de ce travail était d évaluer expérimentalement et cliniquement l efficacité de ces mélanges. L efficacité de Sondalis® Maintenance à maintenir le poids corporel et la stabilité biochimique a été évaluée dans une étude clinique sur des patients en équilibre nutritionnel. Les résultats préliminaires sur neuf patients ont montré qu après six mois de nutrition, ce mélange permettait de maintenir la stabilité du poids et l équilibre biologique. Patriarch a été testé dans un premier temps chez le rat âgé sous nutrition entérale continue. Patriarch limitait la perte de poids induite par le stress chirurgical et améliorait le métabolisme protéique (augmentation du bilan d azote cumulé, du contenu protéique intestinal et de la biodisponibilité des acides aminés) et le transit (augmentation du poids des selles). Dans un deuxième temps, une étude clinique a été initiée chez la personne âgée dénutrie hospitalisée. Seulement quatre patients ont pu être recrutés, parmi lesquels seuls deux ont suivi le protocole jusqu à la fin, un dans le groupe Patriarch et un dans le groupe contrôle Sondalis Iso. L analyse de ces deux cas montre que le mélange Patriarch est bien toléré et qu il favorise une bonne homéostasie glucidique. Ces résultats encourageants devraient être confirmés dans une étude prospective. Enfin, Formula One associé à son module de GLN a été évalué dans un modèle d hypercatabolisme induit par injection sous-cutanée d essence de térébenthine chez le rat. Cette étude n a pas permis de démontrer un avantage en termes de statuts nutritionnel et inflammatoire du mélange Formula One + GLN par rapport à un mélange standard. De plus, l incidence importante de diarrhées dans le groupe Formula One suggérait une mauvaise tolérance digestive, probablement à cause d une osmolarité trop élevée du produit. Ce dernier devait faire également l objet d une évaluation clinique de sa tolérance et de son efficacité chez des patients atteints d un cancer des voies aérodigestives supérieures traités par radio-chimiothérapie concomitante. La mauvaise tolérance suggérée par l étude expérimentale et d importantes difficultés dans la mise en place de l étude clinique ont conduit à l arrêt de ce projet. En dehors de la difficulté inhérente à la validation expérimentale ou clinique de concepts en nutrition, ces travaux soulignent l intérêt de l adaptation de la nutrition entérale aux besoins spécifiques induits par différentes situations physio-pathologiques.Standard enteral nutrition formulas do not meet the specific requirements of various categories of patients. Three new formulas for long-term enteral feeding have been developed in order to cover the respective (specific) nutritional needs of clinically stable normally-fed patients requiring long-term enteral feeding (Sondalis® Maintenance), of hospitalized malnourished elderly subjects (Patriarch), and of cachectic cancer patients under active treatment (Formula One). Our aim was to evaluate the efficiency of this formulas experimentally and/or clinically. Sondalis® Maintenance's efficiency in maintaining body weight and blood chemistry was evaluated in a clinical study in well-nourished stable patients. The preliminary results on nine patients showed that this diet maintained the stability of their body weight and biological homeostasis after six months of nutrition. Patriarch was first evaluated in enterally-fed old rats. In this model Patriarch limited stress-induced weight loss, and improved protein metabolism (increased cumulative nitrogen balance, intestinal protein content and bioavailability of amino acids) and intestinal transit (increased stool weight). This formula was further evaluated in a clinical study in hospitalized malnourished elderly. However only four patients were enrolled and only two of them completed the study: one patient in the group Patriarch and one in the control group Sondalis® Iso. Analysis of these two cases indicated that Patriarch was well tolerated and improved glucose homeostasis. These encouraging results need to be confirmed in a prospective clinical trial. The efficiency of the third formula, Formula One + GLN was assessed in a model of turpentine-induced hypercatabolism in rats. This study did not allow us to demonstrate an advantage in terms of nutritional status and inflammatory state in favour of Formula One + GLN compared to a standard diet. In addition, the incidence of diarrhoea in the Formula One group suggested a poor digestive tolerance, probably due to the high osmolarity of Formula One + GLN. While a clinical trial was scheduled to assess the safety and efficacy of this formula in head and neck cancer patients treated with radiochemotherapy, the poor digestive tolerance observed in the experimental study and major difficulties in patient recruitment led to the project being postponed. Putting aside the difficulties encountered in the experimental and clinical demonstration of the efficiency of nutritional concept, this work demonstrates that the adaptation of enteral nutrition to the specific requirements of various clinical situations is feasible and potentially beneficial for the patient.PARIS-BIUP (751062107) / SudocSudocFranceF