Immobilized photosensitizers for antimicrobial applications

Photodynamic antimicrobial chemotherapy (PACT) is a very promising alternative to conventional antibiotics for the efficient inactivation of pathogenic microorganisms; this is due to the fact that it is virtually impossible for resistant strains to develop due to the mode of action employed. PACT employs a photosensitizer, which preferentially associates with the microorganism, and is then activated with non-thermal visible light of appropriate wavelength(s) to generate high localized concentrations of reactive oxygen species (ROS), inactivating the microorganism. The concept of using photosensitizers immobilized on a surface for this purpose is intended to address a range of economic, ecological and public health issues. Photosensitising molecules that have been immobilized on solid support for PACT applications are described herein. Different supports have been analyzed as well as the target microorganism and the effectiveness of particular combinations of support and photosensitiser

Plasma membrane localization and fusion inhibitory activity of the cowpox virus serpin SPI-3 require a functional signal sequence and the virus encoded hemagglutinin

AbstractThe cowpox virus (CPV) glycoprotein serpin SPI-3, a functional protease inhibitor, and the viral hemagglutinin (HA) are required to prevent fusion of wt CPV infected cells. SPI-3 and HA from CPV infected cells co-localize to the plasma membrane and are found in extracellular enveloped virus (EEV). We also show that an N-terminal SPI-3 signal sequence, but not glycosylation, is required for membrane localization and fusion inhibition. In the absence of HA (CPVΔHA), no SPI-3 is found on the membrane and infected cells fuse. Conversely, HA from both wt CPV and CPVΔSPI-3 infections is on the membrane, indicating a requirement of HA for SPI-3 plasma membrane localization. In the absence of HA, secretion of SPI-3 or SPI-3 N-glyc(−) was markedly enhanced, suggesting HA serves to retain SPI-3 on the plasma membrane,thereby preventing cell fusion

Student Influences in Choosing Pharmacy

To determine the race, cultural background, gender, and regional factors on students’ perceptions and influences in choosing pharmacy as a profession on a national scale

Ad hoc Joint FAO/WHO Expert Consultation on Risk Assessment of Food Allergens Part 2: Review and establish threshold levels in foods of the priority allergens

The main purpose of this second meeting was to establish threshold levels in foods of the priority allergens. Based on the defined approach, the Expert Committee discussed and agreed on the safety objective, which could be described as “to minimise, to a point where further refinement does not meaningfully reduce health impact, the probability of any clinically relevant objective allergic response, as defined by dose distribution modelling of minimum eliciting doses (MEDs) and supported by data regarding severity of symptoms in the likely range of envisioned Reference Doses (RfD)”. The Committee further identified several important considerations to guide decision-making. These included a clear definition of criteria to be met by quantitative data on which reference doses (RfD) are based, supporting data on health manifestations (severity) at the proposed RfD, quality, quantity, availability and accessibility of data (for priority allergens), as well as how to deal with priority allergens for which information supporting one or more of those considerations was lacking.El objetivo principal de esta segunda reunión fue establecer niveles umbral en los alimentos de los alérgenos prioritarios. Sobre la base del enfoque definido, el Comité de Expertos discutió y acordó el objetivo de seguridad, que podría describirse como “minimizar, hasta un punto en el que un mayor refinamiento no reduzca significativamente el impacto en la salud, la probabilidad de cualquier respuesta alérgica objetiva clínicamente relevante, como definido por el modelo de distribución de dosis de dosis mínimas provocadoras (MED) y respaldado por datos sobre la gravedad de los síntomas en el rango probable de dosis de referencia previstas (RfD) ”. El Comité identificó además varias consideraciones importantes para orientar la toma de decisiones. Estos incluyeron una definición clara de los criterios que deben cumplir los datos cuantitativos en los que se basan las dosis de referencia (RfD), datos de apoyo sobre manifestaciones de salud (gravedad) en la RfD propuesta, calidad, cantidad, disponibilidad y accesibilidad de los datos (para alérgenos prioritarios). , así como cómo tratar los alérgenos prioritarios para los que faltaba información que respaldara una o más de esas consideraciones.Instituto de Investigación de Tecnología de AlimentosFil: Baumert, Joseph. Universidad de Nebraska-Lincoln. Departamento de Ciencia y Tecnología de Alimentos; Estados UnidosFil: Brooke-Taylor, Simon. Brooke-Taylor & Co. Consultor australiano de regulación alimentaria y análisis de riesgos (Pty Ltd); Australia.Fil: Crevel, René W.R. René Crevel Consulting Limited; Reino Unido.Fil: Houben, Geert F. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Jackson, Lauren. Administración de Alimentos y Medicamentos de los Estados Unidos. División de Ciencia y Tecnología del Procesamiento de Alimentos. Ingeniería de Procesos; Estados UnidosFil: Kyriakidis, Symeon. Laboratorio Estatal de Química General (GCSL).Autoridad Independiente de Ingresos Públicos (IAPR); Grecia.Fil: La Vieille, Sébastien. Universidad Laval. Departamento de Ciencias de los Alimentos; Canadá.Fil: Lee, N Alice. Universidad de Nueva Gales del Sur. Escuela de Química e Ingeniería. Ciencia e ingeniería de los alimentos; Australia.Fil: López, María Cristina. Universidad Nacional de San Martín. Ingeniería de Alimentos; Argentina.Fil: Luccioli, Stefano. Administración de Alimentos y Medicamentos de los Estados Unidos. Centro de Seguridad Alimentaria y Nutrición Aplicada; Estados UnidosFil: O’Mahony, Patrick. Autoridad de Seguridad Alimentaria de Irlanda; Irlanda.Fil: O’Mahony, Patrick. Universidad College Dublin; Irlanda.Fil: Polenta, Gustavo Alberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Investigación Tecnología de Alimentos; Argentina.Fil: Polenta, Gustavo Alberto. Instituto de Ciencia y Tecnología de los Sistemas Alimentarios Sustentables (ICyTeSAS) UEDD INTA-CONICET; Argentina.Fil: Pöpping, Bert. Food Consulting Strategically (FOCO); Alemania.Fil: Pöpping, Bert. Comités de Normalización ISO - CEN. Grupo de trabajo CEN Alérgenos Alimentarios (CEN TC 275 WG 12).); Alemania.Fil: Remington, Benjamin C. Remington Consulting Group B.V.; Holanda.Fil: Remington, Benjamin C. Universidad de Nebraska–Lincoln. Programa de Recursos e Investigación de Alergias Alimentarias. Estados UnidosFil: Srikulnath, Sirinrat. Universidad de Kasetsart (UKaset). Instituto de Investigación y Desarrollo de Productos Alimentarios. Centro de Servicio de Aseguramiento de la Calidad de los Alimentos. Unidad de Alérgenos Alimentarios; Tailandia.Fil: Taylor, Stephen L. Universidad de Nebraska-Lincoln. Departamento de Ciencia y Tecnología de Alimentos; Estados UnidosFil: Turner, Paul J. Colegio Imperial de Ciencia, Tecnología y Medicina. Alergia e Inmunología Pediátricas; Inglaterra

Neural mechanisms of negative reinforcement in children and adolescents with autism spectrum disorders

Abstract Background Previous research has found accumulating evidence for atypical reward processing in autism spectrum disorders (ASD), particularly in the context of social rewards. Yet, this line of research has focused largely on positive social reinforcement, while little is known about the processing of negative reinforcement in individuals with ASD. Methods The present study examined neural responses to social negative reinforcement (a face displaying negative affect) and non-social negative reinforcement (monetary loss) in children with ASD relative to typically developing children, using functional magnetic resonance imaging (fMRI). Results We found that children with ASD demonstrated hypoactivation of the right caudate nucleus while anticipating non-social negative reinforcement and hypoactivation of a network of frontostriatal regions (including the nucleus accumbens, caudate nucleus, and putamen) while anticipating social negative reinforcement. In addition, activation of the right caudate nucleus during non-social negative reinforcement was associated with individual differences in social motivation. Conclusions These results suggest that atypical responding to negative reinforcement in children with ASD may contribute to social motivational deficits in this population

Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings: 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p<0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p<0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0·0001 for each) than those observed in the standard frequency groups. Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency. Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

FGFR2 amplification has prognostic significance in gastric cancer: results from a large international multicentre study

Background: In preclinical gastric cancer (GC) models, FGFR2 amplification was associated with increased tumour cell proliferation and survival, and drugs targeting this pathway are now in clinical trials. Methods: FGFR2 FISH was performed on 961 GCs from the United Kingdom, China and Korea, and the relationship with clinicopathological data and overlap with HER2 amplification were analysed. Results: The prevalence of FGFR2 amplification was similar between the three cohorts (UK 7.4%, China 4.6% and Korea 4.2%), and intratumoral heterogeneity was observed in 24% of FGFR2 amplified cases. FGFR2 amplification was associated with lymph node metastases (Po0.0001). FGFR2 amplification and polysomy were associated with poor overall survival (OS) in the Korean (OS: 1.83 vs 6.17 years, P ¼ 0.0073) and UK (OS: 0.45 vs 1.9 years, Po0.0001) cohorts, and FGFR2 amplification was an independent marker of poor survival in the UK cohort (P ¼ 0.0002). Co-amplification of FGFR2 and HER2 was rare, and when high-level amplifications did co-occur these were detected in distinct areas of the tumour. Conclusion: A similar incidence of FGFR2 amplification was found in Asian and UK GCs and was associated with lymphatic invasion and poor prognosis. This study also shows that HER2 and FGFR2 amplifications are mostly exclusive

Genetic modifiers in rare disorders: the case of fragile X syndrome.

Methods employed in genome-wide association studies are not feasible ways to explore genotype-phenotype associations in rare disorders due to limited statistical power. An alternative approach is to examine relationships among specific single nucleotide polymorphisms (SNPs), selected a priori, and behavioural characteristics. Here, we adopt this strategy to examine relationships between three SNPs (5-HTTLPR, MAOA, COMT) and specific clinically-relevant behaviours that are phenotypic of fragile X syndrome (FXS) but vary in severity and frequency across individuals. Sixty-four males with FXS participated in the current study. Data from standardised informant measures of challenging behaviour (defined as physical aggression, property destruction, stereotyped behaviour, and self-injury), autism symptomatology, attention-deficit-hyperactivity-disorder characteristics, repetitive behaviour and mood/interest and pleasure were compared between each SNP genotype. No association was observed between behavioural characteristics and either 5-HTTLPR (serotonin) or MAOA (monoamine oxidase) genotypes. However, compared to the COMT (dopamine) AG and GG genotypes, the AA genotype was associated with greater interest and pleasure in the environment, and with reduced risk for property destruction, stereotyped behaviour and compulsive behaviour. The results suggest that common genetic variation in the COMT genotype affecting dopamine levels in the brain may contribute to the variability of challenging and repetitive behaviours and interest and pleasure in this population. This study identifies a role for additional genetic risk in understanding the neural and genetic mechanisms contributing to phenotypic variability in neurodevelopmental disorders, and highlights the merit of investigating SNPs that are selected a priori on a theoretical basis in rare populations