Identification and reciprocal introgression of a QTL affecting body mass in mice

The aim of this study was to examine the effects of a QTL in different genetic backgrounds. A QTL affecting body mass on chromosome 6 was identified in an F2 cross between two lines of mice that have been divergently selected for this trait. The effect of the QTL on mass increased between 6 and 10 weeks of age and was not sex-specific. Body composition analysis showed effects on fat-free dry body mass and fat mass. To examine the effect of this QTL in different genetic backgrounds, the high body mass sixth chromosome was introgressed into the low body mass genetic background and vice versa by repeated marker-assisted backcrossing. After three generations of backcrossing, new F2 populations were established within each of the introgression lines by crossing individuals that were heterozygous across the sixth chromosome. The estimated additive effect of the QTL on 10-week body mass was similar in both genetic backgrounds and in the original F2 population (i.e., ~0.4 phenotypic standard deviations); no evidence of epistatic interaction with the genetic background was found. The 95% confidence interval for the location of the QTL was refined to a region of approximately 7 cM between D6Mit268 and D6Mit123

Water-Based 3D Inkjet Printing of an Oral Pharmaceutical Dosage Form

Inkjet printing is a form of additive manufacturing where liquid droplets are selectively deposited onto a substrate followed by solidification. The process provides significant potential advantages for producing solid oral dosage forms or tablets, including a reduction in the number of manufacturing steps as well as the ability to tailor a unique dosage regime to an individual patient. This study utilises solvent inkjet printing to print tablets through the use of a Fujifilm Dimatix printer. Using polyvinylpyrrolidone and thiamine hydrochloride (a model excipient and drug, respectively), a water-based ink formulation was developed to exhibit reliable and effective jetting properties. Tablets were printed on polyethylene terephthalate films where solvent evaporation in the ambient environment was the solidification mechanism. The tablets were shown to contain a drug loading commensurate with the composition of the ink, in its preferred polymorphic phase of a non-stoichiometric hydrate distributed homogenously. The printed tablets displayed rapid drug release. This paper illustrates solvent inkjet printing’s ability to print entire free-standing tablets without an edible substrate being part of the tablet and the use of additional printing methods. Common problems with solvent-based inkjet printing, such as the use toxic solvents, are avoided. The strategy developed here for tablet manufacturing from a suitable ink is general and provides a framework for the formulation for any drug that is soluble in water

Translocal imagination of Hong Kong connections: the shifting of Chow Yun-Fat's star image since 1997

Anyone who is interested in Hong Kong cinema must be familiar with one name: Chow Yun-fat (b. 1955). He rose to film stardom in the 1980s when Hong Kong cinema started to attract global attention beyond East Asia. During his early screen career, Chow established a star image as an urban citizen of modern Hong Kong through films such as A Better Tomorrow/Yingxiong bense (John Woo, 1986), City on Fire/Longhu fengyun (Ringo Lam, 1987), All About Ah-Long/A Lang de gushi (Johnnie To, 1989), God of Gamblers/Du shen (Wong Jing, 1989), and Hard Boiled/Lashou shentan (John Woo, 1992)

Carbon nanotubes as electrically active nanoreactors for multi-step inorganic synthesis: sequential transformations of molecules to nanoclusters, and nanoclusters to nanoribbons

In organic synthesis, the composition and structure of products are predetermined by the reaction conditions; however, the synthesis of well-defined inorganic nanostructures often presents a significant challenge yielding non-stoichiometric or polymorphic products. In this study, confinement in the nanoscale cavities of single-walled carbon nanotubes (SWNT) provides a new approach for multi-step inorganic synthesis where sequential chemical transformations take place within the same nanotube. In the first step, SWNT donate electrons to the reactant iodine molecules (I2) transforming them to iodide anions (I-). These then react with metal hexacarbonyls (M(CO)6, M = Mo or W) in the next step yielding anionic nanoclusters [M6I14]2-, the size and composition of which are strictly dictated by the nanotube cavity, as demonstrated by aberration corrected high resolution transmission electron microscopy (AC-HRTEM), scanning transmission electron microscopy (STEM) and energy dispersive X-ray (EDX) spectroscopy. Atoms in the nanoclusters [M6I14]2- are arranged in a perfect octahedral geometry and can engage in further chemical reactions within the nanotube, either reacting with each other leading to a new polymeric phase of molybdenum iodide [Mo6I12]n, or with hydrogen sulphide gas giving rise to nanoribbons of molybdenum/tungsten disulphide [MS2]n in the third step of the synthesis. Electron microscopy measurements demonstrate that the products of the multi-step inorganic transformations are precisely controlled by the SWNT nanoreactor, with complementary Raman spectroscopy revealing the remarkable property of SWNT to act as a reservoir of electrons during the chemical transformation. The electron transfer from the host-nanotube to the reacting guest-molecules is essential for stabilising the anionic metal iodide 2 nanoclusters and for their further transformation to metal disulphide nanoribbons synthesised in the nanotubes in high yield

Laboratorial approach in the diagnosis of food allergy

OBJCTIVE: Review the available laboratory tests used to assist in the diagnosis of IgE-mediated and non-IgE-mediated food allergy. DATA SOURCES: Papers in English and Portuguese published in PubMed and Embase, in the last ten years. Terms searched were food allergy, diagnose and laboratory, isolated and/or associated. DATA SYNTHESIS: The diagnostic approach to food allergy reactions includes a good medical history, laboratory studies, elimination diets and blinded food challenges. More recently, the use of a quantitative measurement of food-specific IgE antibodies has been shown to be more predictive of symptomatic IgE-mediated food allergy. Food-specific IgE serum levels exceeding the diagnostic values indicate that the patient is greater than 95% likely to experience an allergic reaction if he/she ingests the specific food. Such decision point values have been defined just for some foods and inconsistent results were obtained when allergy to the same food was studied in different centers. Food challenges, in particular the double-blind placebo-controlled food challenge (DBPCFC), represent the most reliable way to establish or rule out food hypersensitivity. CONCLUSIONS: A number of recent developments are improving the predictive value of some laboratory tests for the diagnosis of food allergies. However, to date, no in-vitro or in-vivo test shows full correlation with clinical food allergy and the DBPCFC remains the gold standard for the definitive diagnosis of specific food allergies. There is an urgent need for new and fundamentally improved diagnostic approaches, which must be validated in patients with food allergy confirmed by a positive DBPCFC.OBJETIVO: Revisar os exames laboratoriais disponíveis utilizados no diagnóstico da alergia alimentar mediada ou não por IgE. FONTES DE DADOS: Artigos publicados em base de dados PubMed e Embase (língua inglesa e portuguesa) nos últimos dez anos. As palavras-chave utilizadas como fonte de busca foram alergia alimentar, diagnóstico e laboratório, isolados e/ou associados. SÍNTESE DOS DADOS: A abordagem diagnóstica das reações alérgicas a alimentos inclui história clínica completa, estudos laboratoriais, dietas de eliminação e desencadeamentos cegos com alimentos. Recentemente, a medida quantitativa de anticorpos IgE específicos a alimentos tem mostrado ser mais preditiva de alergia alimentar sintomática mediada por IgE. Níveis séricos de IgE específica a alimento que excedam os valores diagnósticos indicam que o paciente tem chance maior que 95% de apresentar uma reação alérgica se ingerir o alimento em questão. Estes valores de decisão foram definidos para alguns alimentos e resultados inconsistentes são obtidos ao se estudar diferentes populações. Os desencadeamentos com alimento, especialmente o duplo-cego controlado por placebo (DADCCP), representa a maneira mais confiável de estabelecer ou descartar o diagnóstico de hipersensibilidade alimentar. CONCLUSÕES: Número crescente de aquisições tem melhorado o valor preditivo de alguns testes laboratoriais empregados no diagnóstico de alergias alimentares. Entretanto, até hoje, não há teste in vitro ou in vivo que mostre correlação completa com a clínica da alergia alimentar. O DADCCP continua sendo o padrão-ouro no diagnóstico definitivo de alergia alimentar específica. São necessárias, urgentemente, novas abordagens diagnósticas válidadas em pacientes com alergia alimentar confirmada por DADCCP positivo.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PediatriaUNIFESP-EPM Departamento de PediatriaUniversidade de São Paulo Faculdade de Medicina Departamento de PediatriaUniversidade Federal da Bahia Departamento de PediatriaUNIFESP-EPMUniversidade Federal do Paraná Departamento de PediatriaUNIFESP, EPM, Depto. de PediatriaUNIFESP, EPM Depto. de PediatriaUNIFESP, EPMSciEL

Perceptions of asthma and exercise in adolescents with and without asthma

Objective: To elicit the views of adolescents, with and without asthma, about exercise and asthma, and the perceived benefits of and barriers to participation. The adolescent views elicited would subsequently inform the design of a high-intensity exercise intervention to improve asthma control. Methods: Fifty-four adolescents (age 13.1±0.9years; 26 with asthma) participated in twelve semi-structured group interviews. Questions were structured around knowledge, attitudes and beliefs towards asthma and its impact on exercise participation and lifestyle. The interviews were transcribed verbatim, thematically analysed and presented via diagrams of emergent themes. Ethical approval was granted by the institutional research ethics committee. Results: Fear of an asthma attack emerged as the main barrier to exercise, with many adolescents with asthma withdrawing from exercise as a coping strategy; many healthy adolescents perceived this withdrawal as laziness or an excuse. Despite this, the majority (81%) of adolescents with asthma reported exercise to be their most enjoyable activity. Adolescents suggested incorporating mixed activities, such as team games (e.g., rounders, football, netball), for future interventions to ensure adherence. Conclusions: Whilst exercise is important in the management of asthma, the tendency of those with asthma to withdraw from exercise to avoid adverse events could be addressed through a games-based high-intensity exercise intervention. Furthermore, educating all adolescents on asthma could simultaneously reduce stigmatisation and enhance exercise engagement

Methylation levels of a novel genetic element, EgNB3 as a candidate biomarker associated with the embryogenic competency of oil palm

The association between DNA methylation status and embryogenic competency in oil palm tissue culture was examined through Representational Difference Analysis (RDA) approach, using methylation-sensitive restriction endonucleases. "Difference Products" (DPs) of RDA derived from palms of similar genetic backgrounds but exhibiting different embryogenesis rates during the regeneration process were isolated. The DPs were sequenced using a pyrosequencing platform. To our knowledge, this is the first study profiling partial HpaII methylation sites in oil palm young leaf tissues which are potentially associated with embryogenic amenability through a genomic subtractive approach. Quantitative real-time PCR analysis demonstrated that the methylation status of a novel fragment, EgNB3, was higher in highly embryogenic leaf explants compared to low embryogenesis rate materials. These differences are likely to be contributed by the 5′-mCCGG-3′ and/or 5′-mCmCGG-3′ methylation patterns. Our data suggest that the differentially methylated site in EgNB3 has potential as a molecular biomarker for the screening of oil palm leaf explants for their embryogenic potentials

Active children through incentive vouchers – evaluation (ACTIVE): a mixed-method feasibility study

BackgroundAdolescents face many barriers to physical activity, demonstrated by the decline in physical activity levels in teenage populations. This study aimed to assess the feasibility of overcoming such barriers via the implementation of an activity-promoting voucher scheme to teenagers in deprived areas.MethodsAll Year 9 pupils (n = 115; 13.3 ± 0.48 years; 51 % boys) from one secondary school in Wales (UK) participated. Participants received £25 of activity vouchers every month for six months for physical activity or sporting equipment. Focus groups (n = 7), with 43 pupils, and qualitative interviews with teachers (n = 2) were conducted to assess feasibility, in addition to a process evaluation utilising the RE-AIM framework. Quantitative outcomes at baseline, five months (during intervention) and twelve months (follow-up) included: physical activity (accelerometer), aerobic fitness (12 min Cooper run) and self-reported activity (PAQ-A). Motivation to exercise (BREQ-2) was measured three months post-baseline and at follow-up.ResultsQualitative findings showed that vouchers encouraged friends to socialise through activity, provided opportunities to access local activities that pupils normally could not afford, and engaged both those interested and disinterested in physical education. Improvements in weekend moderate-to-vigorous physical activity and reductions in sedentary behaviour were observed in both sexes. Boys’ fitness significantly improved during the voucher scheme. ‘Non-active’ pupils (those not meeting recommended guidelines of 60 mins∙day−1) and those with higher motivation to exercise had higher voucher use.ConclusionsAdolescents, teachers and activity providers supported the voucher scheme and felt the vouchers enabled deprived adolescents to access more physical activity opportunities. Voucher usage was associated with improved attitudes to physical activity, increased socialisation with friends and improved fitness and physical activity; presenting interesting avenues for further exploration in a larger intervention trial

Citrobacter rodentium is an unstable pathogen showing evidence of significant genomic flux.

Citrobacter rodentium is a natural mouse pathogen that causes attaching and effacing (A/E) lesions. It shares a common virulence strategy with the clinically significant human A/E pathogens enteropathogenic E. coli (EPEC) and enterohaemorrhagic E. coli (EHEC) and is widely used to model this route of pathogenesis. We previously reported the complete genome sequence of C. rodentium ICC168, where we found that the genome displayed many characteristics of a newly evolved pathogen. In this study, through PFGE, sequencing of isolates showing variation, whole genome transcriptome analysis and examination of the mobile genetic elements, we found that, consistent with our previous hypothesis, the genome of C. rodentium is unstable as a result of repeat-mediated, large-scale genome recombination and because of active transposition of mobile genetic elements such as the prophages. We sequenced an additional C. rodentium strain, EX-33, to reveal that the reference strain ICC168 is representative of the species and that most of the inactivating mutations were common to both isolates and likely to have occurred early on in the evolution of this pathogen. We draw parallels with the evolution of other bacterial pathogens and conclude that C. rodentium is a recently evolved pathogen that may have emerged alongside the development of inbred mice as a model for human disease