New adsorbers for the removal of genotoxic impurities from active pharmaceutical ingredients

Active pharmaceutical ingredients (APIs) available in the market are mostly synthesized, in organic solvent media, using highly reactive molecules that may be present in the final product as genotoxic impurities (GTIs). These compounds have the ability to react with DNA, preventing its normal replication, resulting in an associated carcinogenic risk, becoming an increasing concern from pharmaceutical companies and regulatory authorities [1]. Although it is desirable to avoid the use of GTIs in the manufacture of APIs, this is not always possible. Therefore, there is a call to develop simple, robust and economical routes to remove GTIs to limits below the Threshold of Toxicological Concern (1.5 µg/day) [2]. Such adsorbents should be highly selective to reach ultra-low GTI levels with minimal API losses and compatible with organic solvents where the API synthesis takes place [3]. Herein we report two different strategies for the development of new adsorbing materials designed for selective removal of GTIs from API organic solvent solutions. These new materials are: i) molecular imprinted polymers (MIPs), in the particular case designed for removal of an aromatic amine GTI, 4-dymethylaminopyridine) [4]; and ii) a novel functionalized polymer consisting on polybenzimidazole (PBI) modified with a DNA base (PBI-adenine). PBI-Adenine is designed to have a high affinity for a broad range of DNA alkylating agents mimicking the DNA-GTI adduct formation that takes place in vivo [5,6]. These platforms proved to be robust materials being able to remove, in a single stage, more than 95% of the GTIs from organic solvent API mixtures. Both approaches, meet the pharmaceutical industry challenges, by opening new horizons for the use of these adsorbers as a complement to the existing operation units as MIPs, as well as their assembling as membranes for organic solvent nanofiltration (OSN) derived from PBI. References [1] Teasdale A. et al., Org. Process Res. Dev. 17, 2013, 221-230. [2] EMEA Guidelines on the “Limits on Genotoxic Impurities”, EMEA/CHMP/QWP/251344/2006, 2006. [3] Székely G. et al., Green Chem. 15, 2013, 210-225. [4] Esteves T. et al., Sep. Purif. Technol. 163, 2016, 206-214. [5] Ferreira F. C.; Esteves T.; Vicente A. I.; Afonso C. A. M., “Polímeros polibenzimidazolo com cadeia espaçadora funcionalizada e seu método de obtenção para remoção de impurezas genotóxicas.” Patent request Nº 109480, with priority date of 22 June 2016. [6] Vicente A. I. et al., Chem. Mat., 2016, under preparation. Acknowledgements: We thank financial support from Fundação para a Ciência e Tecnologia (FCT) through the Project SelectHost (PTDC/QEQ-PRS/4157/2014) and iBB-Institute for Bioengineering and Biosciences (UID/BIO/04565/2013), from Programa Operacional Regional de Lisboa 2020 (Lisboa-01-0145-FEDER-007317). We thank to Hovione PharmaScience Ltd for supplying the API and technical know-how

Traumatic brain injury patients: does frontal brain lesion influence basic emotion recognition?

Adequate emotion recognition is relevant to individuals’ interpersonal communication. Patients with frontal traumatic brain injury (TBI) exhibit a lower response to facial emotional stimuli, influencing social interactions. In this sense, the main goal of the current study was to assess the ability of TBI patients in recognizing basic emotions. Photographs of facial expressions of five basic emotions (happiness, sadness, fear, anger, and surprise) were presented to 32 TBI patients and 41 healthy controls. Emotion recognition was measured by accuracy and reaction time. Overall performance of the TBI group was poorer than control group for emotion recognition, both in terms of accuracy and reaction time. It is suggested that TBI patients show impairment on emotion recognition, and this relation seems to be moderated by the lesion localization. Keywords: emotion recognition, basic emotions, TBI patients

Projecto de educação pelos pares em escolas do Porto durante o ano lectivo 2009/2010

O Projecto Nacional de Educação pelos Pares, criado pela Fundação Portuguesa “A Comunidade Contra a Sida” visa a prevenção do VIH/SIDA e outros comportamentos de risco, através do desenvolvimento de projectos educativos implementados por voluntários universitários nos 7º e 8º anos de escolaridade. Estes estudantes universitários foram formados científica e pedagogicamente pela Fundação, e implementaram o projecto nacional de educação pelos pares com a supervisão de professores destacados para a FPCCS. Quando os alunos que iniciaram este projecto no 7º ano de escolaridade (12-13 anos) chegam ao 9º ano (14-15 anos), educam os seus pares dos 1º e 2º ciclos (6-11 anos) do ensino básico. A presente comunicação pretende discutir alguns dados recolhidos em seis escolas do porto envolvidas no Projecto Nacional de Educação pelos Pares, através de dois questionários de auto-resposta, designados "Sexualidade e SIDA", implementados no início do 1º e 2º anos de intervenção, que visam avaliar as necessidades de formação dos alunos nesta área. Os resultados obtidos mostraram que alguns alunos das escolas ignoram como prevenir a infecção pelo VIH e quais são os seus meios de transmissão. Por outro lado, têm a noção de que a infecção pelo VIH está associada a 'comportamentos de risco' não a 'grupos de risco'. A análise dos questionários do 8º ano evidenciou que os alunos gostaram mais de realizar dinâmicas de grupo, pelo impacto que tiveram na sua assertividade e na capacidade para reflectir sobre as consequências das suas escolhas e das decisões que tomam em relação ao seu comportamento sexual

DRESS syndrome and juvenile systemic lupus erythematosus in a two year old girl

DRESS syndrome (drug rash with eosinophilia and systemic symptoms) consists in an adverse reaction to some drugs characterized by systemic features such as severe cutaneous eruption, fever, lymphadenopathy, hepatitis and hematological abnormalities (hypereosinophilia and atypical lymphocytosis). Mortality rate accounts to 10%. The low prevalence in children and small number of published cases, increase the difficulty and importance of a prompt diagnosis of this syndrome in pediatric patients. This is a report of one case of DRESS in association with juvenile systemic lupus erithematosus in a two year old girl.A síndrome DRESS (drug rash with eosinophilia andsystemic symptoms - erupção à droga com eosinofilia e sintomas sistêmicos) é uma reação adversa a medicamentos com características sistêmicas, que inclui, principalmente, erupção cutânea grave, febre, linfadenopatia, hepatite e anormalidades hematológicas (hipereosinofilia e linfocitose atípica). A taxa de mortalidade é de aproximadamente 10%. É rara na faixa etária pediátrica, com poucos casos descritos. Por causa da raridade desta reação e da dificuldade e importância de seu reconhecimento, relata-se o caso de uma menina de dois anos de idade com DRESS associado a lúpus eritematoso sistêmico juvenil (LESj).Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PediatriaUNIFESP-EPM Setor de ReumatologiaUNIFESP, EPM, Depto. de PediatriaUNIFESP, EPM Setor de ReumatologiaSciEL

Luminescence studies on green emitting InGaN/GaN MQWs implanted with nitrogen

We studied the optical properties of metalorganic chemical vapour deposited (MOCVD) InGaN/GaN multiple quantum wells (MQW) subjected to nitrogen (N) implantation and post-growth annealing treatments. The optical characterization was carried out by means of temperature and excitation density-dependent steady state photoluminescence (PL) spectroscopy, supplemented by room temperatura PL excitation (PLE) and PL lifetime (PLL) measurements. The as-grown and as-implanted samples were found to exhibit a single green emission band attributed to localized excitons in the QW, although the N implantation leads to a strong reduction of the PL intensity. The green band was found to be surprisingly stable on annealing up to 14006C. A broad blue band dominates the low temperature PL after termal annealing in both samples. This band is more intense for the implanted sample, suggesting that defects generated by N implantation, likely related to the diffusion/segregation of indium (In), have been optically activated by the thermal treatmentThe authors acknowledge FCT for the final funding from PEst-C/CTM/LA0025/2013-14, PTDC/CTM-NAN/2156/2012, PTDC/FIS-NAN/0973/2012 and RECI/FIS-NAN/0183/ 2012 (FCOMP-01-0124-FEDER-027494) projects. J. Rodrigues thanks FCT for her PhD grant, SFRH/BD/76300/2011. ARC acknowledges financial support under the ‘Juan de la Cierva’ program (MECO, Spain) through grant JCI-2012-14509

Functional Hemispheric (A)symmetries in the Aged Brain-Relevance for Working Memory

Functional hemispheric asymmetries have been described in different cognitive processes, such as decision-making and motivation. Variations in the pattern of left/right activity have been associated with normal brain functioning, and with neuropsychiatric diseases. Such asymmetries in brain activity evolve throughout life and are thought to decrease with aging, but clear associations with cognitive function have never been established. Herein, we assessed functional laterality during a working memory task (N-Back) in a healthy aging cohort (over 50 years old) and associated these asymmetries with performance in the test. Activity of lobule VI of the cerebellar hemisphere and angular gyrus was found to be lateralized to the right hemisphere, while the precentral gyrus presented left > right activation during this task. Interestingly, 1-Back accuracy was positively correlated with left > right superior parietal lobule activation, which was mostly due to the influence of the left hemisphere. In conclusion, although regions were mostly symmetrically activated during the N-Back task, performance in working memory in aged individuals seems to benefit from lateralized involvement of the superior parietal lobule.NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER), and was funded by the European Commission (FP7) “SwitchBox—Maintaining health in old age through homeostasis” (Seventh Framework Programme; Contract HEALTH-F2-2010-259772), by FEDER through the Competitiveness Factors Operational Programme (COMPETE) and by National Funds, through the Foundation for Science and Technology (FCT) under the scope of the project POCI-01-0145-FEDER-007038, by the Fundação Calouste Gulbenkian (Portugal; Contract Grant No: P-139977; project “TEMPO—Better mental health during ageing based on temporal prediction of individual brain ageing trajectories”) and by “PANINI—Physical Activity and Nutrition Influences In Ageing” (European Commission (Horizon 2020), Contract GA 675003); Fundação para a Ciência e a Tecnologia (FCT) (Grant Nos. SFRH/BD/52291/2013 to ME and PD/BD/106050/2015 to CP-N via Inter-University Doctoral Programme in Ageing and Chronic Disease (PhDOC), SFRH/BPD/80118/2011 to HL-A and SFRH/BD/90078/2012 to TCC); and FCT/MEC and ON.2–ONOVONORTE—North Portugal Regional Operational Programme 2007/2013, of the National Strategic Reference Framework (NSRF) 2007/2013, through FEDER (project FCTANR/NEU-OSD/0258/2012 to RM)info:eu-repo/semantics/publishedVersio