A simple rodent subcutaneous assay for identification of new osteoinductive molecules: The key method for screening of novel bone regeneration implants

Treatment of large bone defects and degenerative diseases of the spine is among the most challeng- ing and still unresolved issues in clinical medicine. Therefore, substantial effort has been devoted to the development of novel bone regenerative therapies. Due to their potent osteoinductive properties, Bone Morphogenetic Proteins (BMPs) have been the basis for the development of novel strategies for bone regeneration. The use of animal models is an indispensable part of the preclinical testing of novel therapeutic solutions. The rat subcutaneous assay became the initial screening procedure for the evalu- ation of promising BMP-based osteoinductive devices for bone regeneration because only osteogenic BMPs can induce new bone at any ectopic rodent site. Moreover, this model is used for research on the mechanisms of ectopic bone formation as well as for the evaluation of the inflammatory response to different materials. In this review, we provided an overview of the assay development and previously conducted studies with different methods (flow cytometry, histological and microCT analyses) for the study outcome evaluation. Moreover, we addressed essential issues in the experimental design such as the follow-up period and the sample size. The rat subcutaneous bone induction assay layed the founda- tion for isolation and identification of BMPs followed by testing of new osteogenic devices in higher animal species and humans

Direct momentum imaging of charge transfer following site-selective ionization

We study ultrafast charge rearrangement in dissociating 2-iodopropane (2−C3H7I) using site-selective core ionization at the iodine atom. Clear signatures of electron transfer between the neutral propyl fragment and multiply charged iodine ions are observed in the recorded delay-dependent ion momentum distributions. The detected charge-transfer pathway is only favorable within a small (few angstroms), charge-state-dependent spatial window located at C-I distances longer than that of the neutral ground-state molecule. These results offer insights into the physics underpinning charge transfer in isolated molecules and pave the way for a different class of time-resolved studies

Disentangling sequential and concerted fragmentations of molecular polycations with covariant native frame analysis

Using covariance analysis methods, we study the fragmentation dynamics of multiply ionized 1- and 2-iodopropane. Signatures of isomer-specific nuclear motion occurring during sequential fragmentation pathways are identified.</jats:p

Diet and Physical Activity for the Prevention of Noncommunicable Diseases in Low- and Middle-Income Countries: A Systematic Policy Review

Background: Diet-related noncommunicable diseases (NCDs) are increasing rapidly in low-and middle-income countries (LMICs) and constitute a leading cause of mortality. Although a call for global action has been resonating for years, the progress in national policy development in LMICs has not been assessed. This review of strategies to prevent NCDs in LMICs provides a benchmark against which policy response can be tracked over time. Methods and Findings: We reviewed how government policies in LMICs outline actions that address salt consumption, fat consumption, fruit and vegetable intake, or physical activity. A structured content analysis of national nutrition, NCDs, and health policies published between 1 January 2004 and 1 January 2013 by 140 LMIC members of the World Health Organization (WHO) was carried out. We assessed availability of policies in 83% (116/140) of the countries. NCD strategies were found in 47% (54/116) of LMICs reviewed, but only a minority proposed actions to promote healthier diets and physical activity. The coverage of policies that specifically targeted at least one of the risk factors reviewed was lower in Africa, Europe, the Americas, and the Eastern Mediterranean compared to the other two World Health Organization regions, South-East Asia and Western Pacific. Of the countries reviewed, only 12% (14/116) proposed a policy that addressed all four risk factors, and 25% (29/116) addressed only one of the risk factors reviewed. Strategies targeting the private sector were less frequently encountered than strategies targeting the general public or policy makers. Conclusions: This review indicates the disconnection between the burden of NCDs and national policy responses in LMICs. Policy makers urgently need to develop comprehensive and multi-stakeholder policies to improve dietary quality and physical activity

Assessment of vitamin D intake among Libyan women - adaptation and validation of specific food frequency questionnaire

Vitamin D deficiency (VDD) has pandemic proportions worldwide. Numerous studies report on high prevalence of VDD in sunny regions like Near East and North Africa (NENA). Previous studies indicated that Libyan population was at risk of VDD. To contribute to the body of evidence, measurement of vitamin D status on children, adults, in Misurata region was conducted, and confirmed with validated dietary intake study. Serum 25(OH)D was analysed using electrochemiluminescence protein binding assay. Existing Food Frequency Questionnaires (FFQ) were adapted to Libyan Women Food Frequency Questionnaire (LW-FFQ). Repeated 24h dietary recalls and LW-FFQ were employed in vitamin D intake evaluation. LW-FFQ was validated using 24h dietary recall and vitamin D status as referent methods. The questionnaires included anthropometry and lifestyle information. Vitamin D status assessment revealed inadequate levels (25(OH)D lt 50nmol/l) in almost 80% of participants. Women (25-64y) were identified as the most vulnerable group with vitamin D inadequacy present in 82% (61.6% had 25(OH)D lt 25nmol/l, and 20.2% had 25-50nmol/l 25(OH)D). Average Vitamin D intake within the study sample (n=316) was 3.9 +/- 7.9 mu g/d, with 92% participants below both Institute of Medicine (IOM) (10 mu g/d) and European Food Safety Authority (15 mu g/d) recommendations. Measured vitamin D status, in 13% of this group, correlated significantly (p=0.015) with intake estimates. Based on self-report, consumption of vitamin D supplements does not exist among study participants. Additional lifestyle factors influencing vitamin D status were analysed. Only 2% of study participants spend approximately 11 min on the sun daily, 60.4% were obese, 23.1% were overweight and 71.2% reported low physical activity. These findings confirm previous reports on high prevalence of VDD in women across NENA, and in Libya. The situation calls for multi-sectoral actions and public health initiatives to address dietary and lifestyle habits

Update of the tolerable upper intake level for vitamin D for infants

Following a request from the European Commission, the Panel&nbsp;on Dietetic Products, Nutrition and Allergies (NDA) was asked to revise the tolerable upper intake level (UL) for vitamin D for infants ( 64&nbsp;1&nbsp;year) set in 2012. From its literature review, the Panel&nbsp;concluded that the available evidence on daily vitamin D intake and the risk of adverse health outcomes (hypercalciuria, hypercalcaemia, nephrocalcinosis and abnormal growth patterns) cannot be used alone for deriving the UL for infants. The Panel&nbsp;conducted a meta-regression analysis of collected data, to derive a dose\u2013response relationship between daily supplemental intake of vitamin D and mean achieved serum 25(OH)D concentrations. Considering that a serum 25(OH)D concentration of 200&nbsp;nmol/L or below is unlikely to pose a risk of adverse health outcomes in infants, the Panel&nbsp;estimated the percentage of infants reaching a concentration above this value at different intakes of vitamin D. Based on the overall evidence, the Panel&nbsp;kept the UL of 25&nbsp;\u3bcg/day for infants aged up to 6 months and set a UL of 35&nbsp;\u3bcg/day for infants 6\u201312&nbsp;months. The Panel&nbsp;was also asked to advise on the safety of the consumption of infant formulae with an increased maximum vitamin D content of 3&nbsp;\u3bcg/100&nbsp;kcal (Commission Delegated Regulation (EU) 2016/127 repealing Directive 2006/141/EC in 2020). For infants aged up to 4&nbsp;months, the intake assessment showed that the use of infant formulae containing vitamin D at 3&nbsp;\u3bcg/100&nbsp;kcal may lead some infants to receive an intake above the UL of 25&nbsp;\u3bcg/day from formulae alone without considering vitamin D supplemental intake. For infants aged 4\u201312&nbsp;months, the 95th percentile of vitamin D intake (high consumers) estimated from formulae and foods fortified or not with vitamin&nbsp;D does not exceed the ULs, without considering vitamin D supplemental intake

Disentangling sequential and concerted fragmentations of molecular polycations with covariant native frame analysis

We present results from an experimental ion imaging study into the fragmentation dynamics of 1-iodopropane and 2-iodopropane following interaction with extreme ultraviolet intense femtosecond laser pulses with a photon energy of 95 eV. Using covariance imaging analysis, a range of observed fragmentation pathways of the resulting polycations can be isolated and interrogated in detail at relatively high ion count rates (∼12 ions shot−1). By incorporating the recently developed native frames analysis approach into the three-dimensional covariance imaging procedure, contributions from three-body concerted and sequential fragmentation mechanisms can be isolated. The angular distribution of the fragment ions is much more complex than in previously reported studies for triatomic polycations, and differs substantially between the two isomeric species. With support of simple simulations of the dissociation channels of interest, detailed physical insights into the fragmentation dynamics are obtained, including how the initial dissociation step in a sequential mechanism influences rovibrational dynamics in the metastable intermediate ion and how signatures of this nuclear motion manifest in the measured signals.</p

Photoinduced chemistry of biomolecular building blocks and molecules in space

The interactions between light and matter are ubiquitous in the universe and initiate many fundamental chemical processes, such as photosynthesis and vitamin D production. Therefore, gaining a better understanding of how light interacts with molecules and how light-induced reaction mechanisms develop from reactants to products is of great interest. This work uses a velocity-map imaging time-of-flight spectrometer to study the unimolecular photodissociation dynamics of molecules in the gas phase. The observables of the experiment are the product scattering distributions, which are a fingerprint of the chemical reaction, and the product time-of-flight, which reveals the fragment identities. The experiments aim to understand which chemical bonds break, how the system evolves on the potential energy surfaces involved in the reaction, and how the available energy is distributed over the product degrees of freedom. The first part of this thesis studies the photodissociation of tetrahydrofuran at 193 nm, N,N-dimethylformamide at 225 nm and 245 nm, and the N,N-dimethylformamide cation at 225nm, 245nm, and 280nm. Tetrahydrofuran is a model for the DNA backbone molecule ribose, and N,N-dimethylformamide is a model for the peptide bond, which forms the backbone of proteins. Both molecules reveal complex dissociation dynamics, in which population transfer to lower electronic states is possible after the initial excitation. This population transfer probably plays an important role in the photoprotection of molecules in biological species. The great majority of the available energy is distributed into the internal product modes rather than product kinetic energy. This observation is pronounced in the N,N-dimethylformamide cation study, in which a change in photon energy of more than 0.5 eV leads to the same product kinetic energy release. The second part of the thesis describes the design and characterization of a novel femtosecond laser beamline to the experiment which allows us to conduct Coulomb explosion imaging experiments, and a fibre-coupled laser-induced thermal desorption source capable of introducing non-volatile samples into the spectrometer. In a study combining both techniques, we investigate the fragmentation pattern of three singly and doubly charged polycyclic aromatic hydrocarbons: triphenylene, perylene, and benzo[a]pyrene. All three molecules display a common fragmentation pattern in which the summed number of carbon atoms in the fragment ions deviates from the carbon number of the parent molecule by a multiple of two, which we interpret in terms of a fragmentation mechanism involving sequential loss of neutral acetylene (C2H2) units. We also show that loss of the neutral acetylene units occurs preferably from the heavier fragment ion after an initial charge separation step

Inductive influence of 25 kV, 50 Hz electrified single rail traction system

The paper presents the methodology for calculation and measurement of induced voltage caused by railway system operation on the sensitive metallic structures. The arrangement and characteristics of railway system 25 kV, 50 Hz are provided. The procedures of short-circuit current calculation and supply current measurement in the railway system are described. The basic theoretic background of inductive interference is explained. The reduction factors of the communication cable, railway system and environment are mentioned and clarified. On a case study, the results of the induced voltage calculation and measurement is compared. It is proved that induced voltage directly depends of supply current or shortcircuit value