Triaza-based amphiphilic chelators : synthetic route, in vitro characterization and in vivo studies of their Ga(III) and Al(III) chelates

Radiogalium chelates are important for diagnostic imaging in nuclear medicine (PET and ƴ-scintigraphy). Micelles are adequate colloidal vehicles for the delivery of therapeutic and diagnostic agents to organs and tissues. In this paper we describe the synthesis and in vitro and in vivo studies of a series of micelles-forming Ga(III) chelates targeted for the liver. The amphiphilic ligands are based on NOTA (NOTA = 1,4,7-triazacyclonoane-N,N’N’’-triacetic acid) and bear a α-alkyl chain in one of the pendant acetate arms (the size of the chain changes from four to fourteen carbon atoms). A multinuclear NMR study (1H, 13C, 27Al and 71Ga) gave some insights into the structure and dynamics of the metal chelates in solution, consistent with their rigidity and octahedral or pseudo-octahedral geometry. The critical micellar concentration of the chelates was determined using a fluorescence method and 27Al NMR spectroscopy (Al(III) was used as a surrogate of Ga(III)), both showing similar results and suggesting that the chelates of NOTAC6 form pre-micellar aggregates. The logP (octanol-water) determination showed enhancement of the lipophilic character of the Ga(III) chelates with the increase of the number of carbons in the α-alkyl chain. Biodistribution and Ƴ-scintigraphic studies of the 67Ga(III) labeled chelates were performed on Wistar rats, showing higher liver uptake for [67Ga](NOTAC8) in comparison to [67Ga](NOTAC6), consistent with a longer α-alkyl chain and a higher lipophilicity. After 24 hours both chelates were completely cleared off from the tissues and organs with no deposition in the bones and liver/spleen. [67Ga](NOTAC8) showed high kinetic stability in blood serum.Fundação para a Ciência e a Tecnologia (FCT

Desenvolvimento sustentável, governação local algorítmica e cidades de proximidade: o futuro (da cidade inteligente) é hoje

[Excerto] Estamos certos de que as cidades e o seu consequente desenvolvimento representam, por muitas razões, um dos maiores desafios do século XXI. Por um lado, é o desenvolvimento desbragado e a urbanização crescente que traz consigo problemas de diversa natureza e preocupações de acolhimento de modelos de territórios do futuro com implementação de estratégias e políticas sustentáveis, onde até a cidade de proximidade, como seja a cidade 15 minutos, é apresentada como solução amiga do ambiente e de sociedade inclusiva e participativa; por outro, é a constante aceleração da aplicação das Tecnologias de Comunicação e Informação à Governação Pública que obriga a pensar como estas podem servir necessidades de acesso ao serviço e a bens que a pandemia Covid-19 acentuou, pondo a descoberto a falta de resiliência de tantas cidades, não planeadas, frágeis do ponto de vista da implementação das TIC e, em suma, pouco precavidas para a catástrofe, estando, por isso, aquém do standard europeu de resiliência e longe de alcançar os objetivos traçados pelas Nações Unidas para 2030. “Não deixar ninguém para trás” é o lema da Agenda 2030 para o Desenvolvimento Sustentável das Nações Unidas

Ga(III) chelates of amphiphilic DOTA-based ligands : synthetic route and in vitro and in vivo studies

In this work we report a synthetic strategy of amphiphilic DOTA-based chelators bearing a variable size α-alkyl chain at one of the pendant acetate arms (from six to fourteen carbon atoms), compatible with their covalent coupling to amine-bearing biomolecules. The amphiphilic behavior of the micelles-forming Ga(III) chelates (critical micelle concentration), their stability in blood serum and their lipophilicity (logP) were investigated. Biodistribution studies with the 67Ga-labeled chelates were performed in Wistar rats showing a predominant liver uptake with almost no traces of the radiochelates in the body after 24 hours.Fundação para a Ciência e a Tecnologia (FCT

Gallium labeled NOTA-based conjugates for peptide receptor-mediated medical imaging

We report a straightforward and efficient synthetic strategy for the synthesis of three model glycine-arginine-glycine-aspartic-glycine (GRGDG) conjugates based on derivatives of NOTA and of their Ga(III) complexes targeted to the integrin αѵβ₃receptor. 71Ga NMR spectroscopy showed that the Ga(III)-labeled conjugates are highly stable in aqueous solution. The 67Ga-labeled conjugates proved to have high kinetic stability and showed a weak but specific binding to the receptors in a U87MG-glioblastoma cell line.Fundação para a Ciência e a Tecnologia (FCT

Radiation tests on commercial instrumentation amplifiers, analog switches & DAC's

A study of several commercial instrumentation amplifiers (INA110, INA111, INA114, INA116, INA118 & INA121) under neutron and vestigial gamma radiation was done. Some parameters (Gain, input offset voltage, input bias currents) were measured on-line and bandwidth, and slew rate were determined before and after radiation. The results of the testing of some voltage references REF102 and ADR290GR and the DG412 analog switch are shown. Finally, different digital-to-analog converters were tested under radiation

CD4 recovery following antiretroviral treatment interruptions in children and adolescents with HIV infection in Europe and Thailand

Objectives: The aim of the study was to explore factors associated with CD4 percentage (CD4%) reconstitution following treatment interruptions (TIs) of antiretroviral therapy (ART). Methods: Data from paediatric HIV-infected cohorts across 17 countries in Europe and Thailand were pooled. Children on combination ART (cART; at least three drugs from at least two classes) for > 6 months before TI of ≥ 30 days while aged < 18 years were included. CD4% at restart of ART (r-ART) and in the long term (up to 24 months after r-ART) following the first TI was modelled using asymptotic regression. Results: In 779 children with at least one TI, the median age at first TI was 10.1 [interquartile range (IQR) 6.4, 13.6] years and the mean CD4% was 27.3% [standard deviation (SD) 11.0%]; the median TI duration was 9.0 (IQR 3.5, 22.5) months. In regression analysis, the mean CD4% was 19.2% [95% confidence interval (CI) 18.3, 20.1%] at r-ART, and 27.1% (26.2, 27.9%) in the long term, with half this increase in the first 6 months. r-ART and long-term CD4% values were highest in female patients and in children aged < 3 years at the start of TI. Long-term CD4% was highest in those with a TI lasting 1 to <3 months, those with r-ART after year 2000 and those with a CD4% nadir ≥ 25% (all P < 0.001). The effect of CD4% nadir during the TI differed significantly (P = 0.038) by viral suppression at the start of the TI; in children with CD4% nadir < 15% during TI, recovery was better in those virally suppressed prior to the TI; viral suppression was not associated with recovery in children with CD4% nadir ≥ 25%. Conclusions: After restart of ART following TI, most children reconstituted well immunologically. Nevertheless, several factors predicted better immunological reconstitution, including younger age and higher nadir CD4% during TI

Reconstructing the Indian Origin and Dispersal of the European Roma: A Maternal Genetic Perspective

Previous genetic, anthropological and linguistic studies have shown that Roma (Gypsies) constitute a founder population dispersed throughout Europe whose origins might be traced to the Indian subcontinent. Linguistic and anthropological evidence point to Indo-Aryan ethnic groups from North-western India as the ancestral parental population of Roma. Recently, a strong genetic hint supporting this theory came from a study of a private mutation causing primary congenital glaucoma. In the present study, complete mitochondrial control sequences of Iberian Roma and previously published maternal lineages of other European Roma were analyzed in order to establish the genetic affinities among Roma groups, determine the degree of admixture with neighbouring populations, infer the migration routes followed since the first arrival to Europe, and survey the origin of Roma within the Indian subcontinent. Our results show that the maternal lineage composition in the Roma groups follows a pattern of different migration routes, with several founder effects, and low effective population sizes along their dispersal. Our data allowed the confirmation of a North/West migration route shared by Polish, Lithuanian and Iberian Roma. Additionally, eleven Roma founder lineages were identified and degrees of admixture with host populations were estimated. Finally, the comparison with an extensive database of Indian sequences allowed us to identify the Punjab state, in North-western India, as the putative ancestral homeland of the European Roma, in agreement with previous linguistic and anthropological studies

“We have been working overnight without sleeping”: traditional birth attendants’ practices and perceptions of post-partum care services in rural Tanzania

Background: In many low-income countries, formal post-partum care utilization is much lower than that of skilled delivery and antenatal care. While Traditional Birth Attendants (TBAs) might play a role in post-partum care, research exploring their attitudes and practices during this period is scarce. Therefore, the aim of this study was to explore TBAs’ practices and perceptions in post-partum care in rural Tanzania. Methods: Qualitative in-depth interview data were collected from eight untrained and three trained TBAs. Additionally, five multiparous women who were clients of untrained TBAs were also interviewed. Interviews were conducted in February 2013. Data were digitally recorded and transcribed verbatim. Qualitative content analysis was used to analyze data. Results: Our study found that TBAs take care of women during post-partum with rituals appreciated by women. They report lacking formal post-partum care training, which makes them ill-equipped to detect and handle post-partum complications. Despite their lack of preparation, they try to provide care for some post-partum complications which could put the health of the woman at risk. TBAs perceive that utilization of hospital-based post-partum services among women was only important for the baby and for managing complications which they cannot handle. They are poorly linked with the health system. Conclusions: This study found that the TBAs conducted close follow-ups and some of their practices were appreciated by women. However, the fact that they were trying to manage certain post-partum complications can put women at risk. These findings point out the need to enhance the communication between TBAs and the formal health system and to increase the quality of the TBA services, especially in terms of prompt referral, through provision of training, mentoring, monitoring and supervision of the TBA servic