Highly diverse and highly successful: invasive Australian acacias have not experienced genetic bottlenecks globally.

BACKGROUND AND AIMS: Invasive species may undergo rapid evolution despite very limited standing genetic diversity. This so-called genetic paradox of biological invasions assumes that an invasive species has experienced (and survived) a genetic bottleneck and then underwent local adaptation in the new range. In this study, we test how often Australian acacias (genus Acacia), one of the world's most problematic invasive tree groups, have experienced genetic bottlenecks and inbreeding. METHODS: We collated genetic data from 51 different genetic studies on Acacia species to compare genetic diversity between native and invasive populations. These studies analysed 37 different Acacia species, with genetic data from the invasive ranges of 11 species, and data from the native range for 36 species (14 of these 36 species are known to be invasive somewhere in the world, and the other 22 are not known to be invasive). KEY RESULTS: Levels of genetic diversity are similar in native and invasive populations, and there is little evidence of invasive populations being extensively inbred. Levels of genetic diversity in native range populations also did not differ significantly between species that have and that do not have invasive populations. CONCLUSION: We attribute our findings to the impressive movement, introduction effort and human usage of Australian acacias around the world.

In vitro evaluation of the internalization and toxicological profile of silica nanoparticles and submicroparticles for the design of dermal drug delivery strategies.

The use of colloidal silica nanoparticles and sub-microparticles (SiPs) have been considered a very interesting strategy for drug delivery applications. In the present study, we have focused our attention on the suitability of these nanomaterials as potential carriers for dermal drug delivery, thus studying their toxicological profile in vitro, cellular uptake and intracellular localization in both human keratinocytes (K17) and human dermal fibroblasts (HDF) as a function of their particle size (SiPs of 20, 70, 200 and 500 nm). Full characterization of these aspects enabled us to observe a strong cell-type dependency in terms of cytotoxicity and cell internalization, whereas particle size was only relevant for ultra-small SiPs (20 nm), being the most toxic SiPs. For 70, 200 and 500 nm SiPs, the differences in uptake and intracellular trafficking determined the different toxicological profiles in K17 and HDF. In addition, these characteristics can further define different drug delivery strategies. Hence, phagocytosis has been identified as the main internalization mechanism for K17, and caveolae-mediated endocytosis for HDF. This relevant information led us to conclude that fibroblasts would be optimal targets for delivering delicate therapeutic molecules such as proteins or genetic material using SiPs while maintaining a low toxicity profile, whereas keratinocytes could enable accelerated drug release therapies based on SiPs.

mHealth for pre-exposure prophylaxis adherence by young adult men who have sex with men.

BACKGROUND: Young adult men who have sex with men (YMSM) are at increased risk for HIV, especially minority YMSM. Pre-exposure prophylaxis (PrEP) is a breakthrough daily pill to prevent HIV. Consistent adherence is key to PrEP effectiveness, which is why the CDC recommends adherence support be provided to all PrEP patients. Mobile health can overcome barriers to the delivery of adherence support, particularly for YMSM who may be most in need of it due, at least in part, to their young age. METHODS: We created a culturally- and developmentally-sensitive PrEP adherence mobile app (called "Dot") that was tailored for culturally-diverse young adult MSM. After formative research and usability testing, we conducted a 6-week pre-post study to evaluate the impact of Dot on self-reported PrEP adherence, PrEP treatment self-efficacy, PrEP knowledge, and intention to practice safe sex among culturally-diverse YMSM, age 20-29. RESULTS: At 6 weeks, there were significant improvements in PrEP adherence, PrEP self-efficacy, and intention to practice safe sex. PrEP knowledge scores did not significantly change. CONCLUSIONS: The Dot app proved feasible and effective at improving PrEP adherence among culturally-diverse YMSM. Moreover, the app had a high-degree of user appeal, which is foundational to success of an mhealth intervention.

Development and Feasibility of an App to Decrease Risk Factors for Type 2 Diabetes in Hispanic Women With Recent Gestational Diabetes (Hola Bebé, Adiós Diabetes): Pilot Pre-Post Study.

BACKGROUND: Hispanic women have increased risk of gestational diabetes mellitus (GDM), which carries an increased risk for future type 2 diabetes, compared to non-Hispanic women. In addition, Hispanic women are less likely to engage in healthy eating and physical activity, which are both risk factors for type 2 diabetes. Supporting patients to engage in healthy lifestyle behaviors through mobile health (mHealth) interventions is increasingly recognized as a viable, underused tool for disease prevention, as they reduce barriers to access frequently experienced in face-to-face interventions. Despite the high percentage of smartphone ownership among Hispanics, mHealth programs to reduce risk factors for type 2 diabetes in Hispanic women with prior GDM are lacking. OBJECTIVE: This study aimed to (1) develop a mobile app (¡Hola Bebé, Adiós Diabetes!) to pilot test a culturally tailored, bilingual (Spanish/English) lifestyle program to reduce risk factors for type 2 diabetes in Hispanic women with GDM in the prior 5 years; (2) examine the acceptability and usability of the app; and (3) assess the short-term effectiveness of the app in increasing self-efficacy for both healthy eating and physical activity, and in decreasing weight. METHODS: Social cognitive theory provided the framework for the study. A prototype app was developed based on prior research and cultural tailoring of content. Features included educational audiovisual modules on healthy eating and physical activity; personal action plans; motivational text messages; weight tracking; user-friendly, easy-to-follow recipes; directions on building a balanced plate; and tiered badges to reward achievements. Perceptions of the app's acceptability and usability were explored through four focus groups. Short-term effectiveness of the app was tested in an 8-week single group pilot study. RESULTS: In total, 11 Hispanic women, receiving care at a federally qualified community health center, aged 18-45 years, and with GDM in the last 5 years, participated in four focus groups to evaluate the app's acceptability and usability. Participants found the following sections most useful: audiovisual modules, badges for completion of activities, weight-tracking graphics, and recipes. Suggested modifications included adjustments in phrasing, graphics, and a tiering system of badges. After app modifications, we conducted usability testing with 4 Hispanic women, with the key result being the suggestion for a "how-to tutorial." To assess short-term effectiveness, 21 Hispanic women with prior GDM participated in the pilot. There was a statistically significant improvement in both self-efficacy for physical activity (P=.003) and self-efficacy for healthy eating (P=.007). Weight decreased but not significantly. Backend process data revealed a high level of user engagement. CONCLUSIONS: These data support the app's acceptability, usability, and short-term effectiveness, suggesting that this mHealth program has the potential to fill the gap in care experienced by Hispanic women with prior GDM following pregnancy. Future studies are needed to determine the effectiveness of an enhanced app in a randomized controlled trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT04149054; https://clinicaltrials.gov/ct2/show/NCT04149054.

A Web-Based HIV/STD Prevention Intervention for Divorced or Separated Older Women.

BACKGROUND AND OBJECTIVE: Sexually transmitted diseases (STDs) are increasing among older adults concomitant with a rise in divorce after the age of 50 years. The objective of this study was to examine the effectiveness of a web-based human immunodeficiency virus (HIV)/STD risk reduction intervention for divorced and separated women aged more than 50 years. RESEARCH DESIGN AND METHODS: Two hundred nineteen divorced or separated women, aged 50 years and older, participated in 60-day randomized pre-post control group study. Recruitment occurred via health agencies in Boston and Columbia, SC, and Craigslist advertisements placed in Boston, Columbia, Charleston, New York City, Washington DC, Baltimore, Chicago, Atlanta, Orlando, and Miami. RESULTS: Intervention group reported greater intention to practice safe sex compared to the control group (B = .55, p = .03). Intention to practice safe sex differed by perceived stress (B = .15, p = .005), with no difference between control and intervention groups for those with low levels of stress. For high levels of stress, intervention group reported greater intention to practice safe sex compared to controls. Sexual risk was reduced by 6.10 points (SD: 1.10), and self-efficacy for sexual discussion was increased by 2.65 points (SD: 0.56) in the intervention group. DISCUSSION AND IMPLICATIONS: A web-based intervention represents a promising tool to reduce HIV/STD risk among older women. Offering HIV/STD education in the context of other topics of interest to at-risk older women, such as divorce, may solve the problem of at-risk older women not seeking out prevention information due to lack of awareness of their heightened risk.

Biodistribution of radiolabeled polyglutamic acid and PEG-polyglutamic acid nanocapsules.

Recently we reported the development of 100nm polyglutamic acid (PGA)-based nanocapsules, which were intended to carry anticancer drugs to the lymphatic system (Abellan-Pose et al., 2016). In this work, the objective was to further assess the potential "lympho-targeting" properties of radiolabeled 111In-PGA and 111In-PGA-PEG, following intravenous or subcutaneous administration. The results indicate that, following intravenous administration, both types of nanocapsules exhibit a modest accumulation in the lymph nodes (⩽2.3% ID/g). On the contrary, following subcutaneous administration, and irrespective of the presence of PEG on their surface, the nanocapsules were found to form a reservoir at the injection site, from which they drained slowly into the popliteal and the iliac lymph nodes. The significant accumulation of the radiolabeled nanocapsules in the lymph nodes was attained at 24 and 48h post-injection, reaching values comprised between 70% and 187% ID/g in the popliteal lymph nodes. Altogether, the results led us to validate our hypothesis about the ability of the PGA and PGA-PEG nanocapsules to reach the lymphatic system, especially following subcutaneous administration.

Lifting Object Detection Datasets into 3D.

While data has certainly taken the center stage in computer vision in recent years, it can still be difficult to obtain in certain scenarios. In particular, acquiring ground truth 3D shapes of objects pictured in 2D images remains a challenging feat and this has hampered progress in recognition-based object reconstruction from a single image. Here we propose to bypass previous solutions such as 3D scanning or manual design, that scale poorly, and instead populate object category detection datasets semi-automatically with dense, per-object 3D reconstructions, bootstrapped from:(i) class labels, (ii) ground truth figure-ground segmentations and (iii) a small set of keypoint annotations. Our proposed algorithm first estimates camera viewpoint using rigid structure-from-motion and then reconstructs object shapes by optimizing over visual hull proposals guided by loose within-class shape similarity assumptions. The visual hull sampling process attempts to intersect an object's projection cone with the cones of minimal subsets of other similar objects among those pictured from certain vantage points. We show that our method is able to produce convincing per-object 3D reconstructions and to accurately estimate cameras viewpoints on one of the most challenging existing object-category detection datasets, PASCAL VOC. We hope that our results will re-stimulate interest on joint object recognition and 3D reconstruction from a single image.

Biodistribution and lymph node retention of polysaccharide-based immunostimulating nanocapsules.

The adjuvant properties of polyglucosamine/squalene-based nanocapsules (PG-nanocapsules) associated with different subunit antigens has been previously reported. Thus, the aim of the present study was to monitor the biodistribution of PG-nanocapsules and their affinity for the draining lymph nodes after subcutaneous (s.c.) injection. The nanocapsules were efficiently radiolabeled with indium-111 ((111)In) (labeling efficiency of 98%). The diameter and zeta potential values of the unlabeled nanocapsules was preserved after the radiolabeling process and only 20% of the (111)In dissociated from the nanocapsules after 48h of incubation in serum. The radiolabeled nanocapsules and the control (111)InCl3 in saline solution (18.5MBq (500µCi) in 100µL) were injected s.c. in New Zealand White rabbits. The γ-scintigraphy imaging analysis revealed a slow clearance of the nanocapsules from the injection site and their progressive accumulation in the popliteal lymph node over time (3.8%±1.2 of the injected dose at 48h). Indeed, the clearance rate of the nanocapsules from the injection site was significantly slower than that of the control (free (111)InCl3), which rapidly drained into systemic circulation and accumulated mainly in excretion organs (i.e. kidneys and liver). In contrast, the biodistribution of nanocapsules was preferably limited to the lymphatic circulation. These results suggest that the immune potentiating effect previously observed for PG-nanocapsules is mainly due to the formation of a depot at the injection site, which was followed by a slow drainage into the lymphatic system and a prolonged retention in the lymph nodes.

Highly versatile immunostimulating nanocapsules for specific immune potentiation.

AIM: To develop a new core-shell type (nanocapsules) adjuvant system composed of squalene and polyglucosamine (PG) and to evaluate its immunostimulant capacity. RESULTS: The defined PG nanocapsules exhibited the capacity to efficiently associate the selected antigens (recombinant hepatitis B surface antigen and hemagglutinin of influenza virus) onto their polymeric surface (70-75%), and the immunostimulant imiquimod within the oily core. The resulting nanovaccines, with a particle size of 200-250 nm and a positive zeta-potential (∼+60 mV), were able to significantly potentiate and modulate the immune response to the selected antigens upon intramuscular administration to mice. Their efficacy as novel adjuvants was attributed to their enhanced cell internalization and effective intracellular imiquimod/antigen delivery, together with their prolonged residence time at the injection site. CONCLUSION: The nanocapsules described herein have the capacity to enhance, prolong and modulate the immune response of subunit antigens and, therefore, they could be proposed as a platform for the codelivery of different antigens and immunostimulators.

Co-delivery of viral proteins and a TLR7 agonist from polysaccharide nanocapsules: a needle-free vaccination strategy.

Here we report a new nanotechnology-based nasal vaccination concept intended to elicit both, specific humoral and cellular immune responses. The concept relies on the use of a multifunctional antigen nanocarrier consisting of a hydrophobic nanocore, which can allocate lipophilic immunostimulants, and a polymeric corona made of chitosan (CS), intended to associate antigens and facilitate their transport across the nasal mucosa. The Toll-like receptor 7 (TLR7) agonist, imiquimod, and the recombinant hepatitis B surface antigen (HB), were selected as model molecules for the validation of the concept. The multifunctional nanocarriers had a nanometric size (around 200 nm), a high positive zeta potential (+45 mV) and a high antigen association efficiency (70%). They also exhibited the ability to enter macrophages in vitro and to effectively deliver the associated imiquimod intracellularly, as noted by the secretion of pro-inflammatory cytokines (i.e. IL-6 and TNF-α). However, the nanocarriers did not induce the in vitro activation of the complement cascade. Finally, the positive effect of the co-delivery of HB and imiquimod from the nanocapsules was evidenced upon intranasal administration to mice. The nanocapsules containing imiquimod elicited a protective immune response characterized by increasing IgG levels over time and specific immunological memory. Additionally, the levels of serum IgG subclasses (IgG1 and IgG2a) indicated a balanced cellular/humoral response, thus suggesting the capacity of the nanocapsules to modulate the systemic immune response upon nasal vaccination.

A polymer/oil based nanovaccine as a single-dose immunization approach.

The recognized necessity for new antigen delivery carriers with the capacity to boost, modulate and prolong neutralizing immune responses prompted our approach, in which we describe a multifunctional nanocarrier consisting of an oily nanocontainer protected by a polymeric shell made of chitosan (CS), named CS nanocapsules (CSNC). The CS shell can associate the antigen on its surface, whereas the oily core might provide additional immunostimulating properties. In this first characterization of the system, we intended to study the influence of different antigen organizations on the nanocarrier's surface (using the recombinant hepatitis B surface antigen -rHBsAg- as a model antigen) on their long-term immunopotentiating effect, without any additional immunostimulant. Thus, two prototypes of antigen-loaded CSNC (CSNC+ and CSNC-), exhibiting similar particle size (200 nm) and high antigen association efficiency (>80%), were developed with different surface composition (polymer/antigen ratios) and surface charge (positive/negative, respectively). The biological evaluation of these nanovaccines evidenced the superiority of the CSNC+ as compared to CSNC- and alum-rHBsAg in terms of neutralizing antibody responses, following intramuscular vaccination. Moreover, a single dose of CSNC+ led to similar IgG levels to the positive control. The IgG1/IgG2a ratio suggested a mixed Th1/Th2 response elicited by CSNC+, in contrast to the typical Th2-biased response of alum. Finally, CSNC+ could be freeze-dried without altering its physicochemical properties and adjuvant effect in vivo. In conclusion, the evaluation of CSNC+ confirms its interesting features for enhancing, prolonging and modulating the type of immune response against subunit antigens, such as rHBsAg.

Chitosan-based nanoparticles for improving immunization against hepatitis B infection.

The design of effective vaccine delivery vehicles is opening up new possibilities for making immunization more equitable, safe and efficient. In this work, we purpose polysaccharidic-based nanoparticles as delivery structures for virus-like particle antigens, using recombinant hepatitis B surface antigen (rHBsAg) as a model. Polysaccharidic-based nanoparticles were prepared using a very mild ionic gelation technique, by cross-linking the polysaccharide chitosan (CS) with a counter ion. The resulting nanoparticles could be easily isolated with a size in the nanometric range (160-200 nm) and positive surface charge (+6 to +10 mV). More importantly, CS-based nanoparticles allowed the efficient association of the antigen (>60%) while maintaining the antigenic epitope intact, as determined by ELISA and Western blot. The entrapped antigen was further released in vitro from the nanoparticles in a sustained manner without compromising its antigenicity. In addition, loaded CS-based nanoparticles were stable, and protected the associated antigen during storage, either as an aqueous suspension under different temperature conditions (+4 degrees C and -20 degrees C), or as a dried form after freeze-drying the nanoparticles. Finally, immunization studies showed the induction of important seroprotection rates after intramuscular administration of the nanoparticles, indicating their adjuvant capacity. In fact, CS-based nanoparticles were able to induce anti-HBsAg IgG levels up to 5500 mIU/ml, values 9-fold the conventional alum-adsorbed vaccine. In conclusion, we report here a polysaccharidic nanocarrier which exhibits a number of in vitro and in vivo features that make it a promising adjuvant for vaccine delivery of subunit antigens.

Contributos para a construção de um texto foneticamente equilibrado para o Português-Europeu / Contributions to the elaboration of a phonetically balanced text for the European-Portuguese

OBJECTIVO: o objectivo deste estudo consiste na criação de um Texto Foneticamente Equilibrado para o Português-Europeu (PE) designado "O Sol". MÉTODO: quatro sujeitos da região de Setúbal, entre [21-49] anos (dois do sexo feminino e dois do masculino) leram em voz alta o texto "O Sol". As gravações realizadas com Olympus (VN- 240PC e VN- 2100PC com microfones integrados) serviram para a contabilização dos fonemas produzidos. Os procedimentos foram: 1) a comparação entre as frequências relativas dos fonemas do "O Sol" e as frequências relativas descritas no PF_fone, através do coeficiente de correlação de Pearson e do teste de Mann-Whitney; 2) a comparação entre a transcrição larga e a estreita, verificando-se os fenómenos de coarticulação; e 3) a análise dos formatos silábicos. RESULTADOS: a análise estatística demonstrou que as frequências relativas de ocorrência dos fonemas do texto "O Sol" têm uma correlação forte com as do PF_fone (r = 0,924). As medianas das frequências relativas de ocorrência dos fonemas do texto foram significativamente iguais das do PF_fone (p<.05). CONCLUSÃO: o texto "O Sol" está próximo de um texto foneticamente equilibrado ideal, uma vez que se verificaram os pressupostos pré-definidos. Fonologicamente, apresenta os formatos silábicos mais frequentes no PE, verificou-se ainda uma diminuição na frequência relativa de fonemas na transcrição estreita, devido a fenómenos de coarticulação. Futuros trabalhos incidirão no aumento da amostra.

PURPOSE: the aim of this study is to elaborate a Phonetically Balanced Text for the European-Portuguese (EP) called "O Sol" (The Sun). METHOD: four subjects (two females and two males) with [21-49] year-old read aloud the text. Recordings were obtained with Olympus (VN-240PC and VN-2100PC) and were used to account the produced phonemes. The procedures were: 1) the comparison between the relative frequency of the phonemes of "O Sol" and the relative frequency described in PF_fone through the correlation coefficient of Pearson and the Mann-Whitney, 2) the comparison between the large and short transcriptions in order to analyze the co-articulation phenomenon 3) the analysis of the syllabic formats. RESULTS: statistical analysis showed that relative frequency occurrence of phonemes of the text "O Sol" have a strong correlation with those of PF_fone (r = 0,924). The median values of the relative frequency occurrence of phonemes of "O Sol" were significantly equal to the PF_fone (p<.05). CONCLUSION: the text "O Sol (The Sun)" is close to an ideal phonetically balanced text, since it achieved the predefined assumptions. Phonologically, it shows the most common formats syllable in the EP. We verified a decrease in relative frequency of phonemes in the close transcription, due to co-articulation phenomenon. Future work will focus on increasing said sample.

Efeito dos comportamentos de mobilização dos enfermeiros nos resultados organizacionais: Um estudo empírico realizado em contexto hospitalar / Effect of nurses' mobilization behaviors nurses on organizational outcomes: An empirical study conducted in a hospital setting

As organizações de saúde caracterizam-se por um ambiente profissional altamente especializado, complexo e de difícil mensuração, onde a estratégia de gestão organizacional assume um papel fulcral e a gestão de recursos humanos constitui um grande desafio. O enfermeiro como membro destas organizações deve assumir um papel ativo relativamente às suas práticas de organização do trabalho, concretamente em relação aos seus próprios comportamentos de mobilização, tornando-se fundamental compreender a relação entre as referidas práticas e os resultados organizacionais. Conduzimos o presente estudo com o objetivo de compreender em que medida os comportamentos no trabalho dos enfermeiros intervêm nos resultados organizacionais, nomeadamente na satisfação geral no trabalho e na intenção de abandonar a profissão e/ou a organização (turnover). Para tal, realizou-se um estudo quantitativo, segundo uma lógica descritiva e correlacional, onde 338 enfermeiros (79.2% do género feminino e média de idade de 38.63 anos) responderam a um questionário sobre comportamentos no trabalho (escala de Tremblay, Rondeau e Lemelin,1998 e adaptada por Tremblay, Wils e Guay, 2000), sobre a satisfação geral no trabalho (escala de Brayfield e Rothe, 1951), sobre o turnover (escala de Meyer et al., 1993) e um questionário sociodemográfico. Os resultados obtidos permitem-nos concluir que o modelo ajustado dos comportamentos no trabalho explica 20% da variabilidade da satisfação geral e apenas 3% da variabilidade do turnover. A satisfação geral no trabalho mostrou ser prevista pela lealdade organizacional e pela participação na vida cívica, não se mostrando a colaboração um preditor significativo. Já o turnover, apenas se mostrou previsto negativamente pela lealdade organizacional, embora com baixa magnitude. Os resultados foram discutidos atendendo às suas implicações e contributos para as boas práticas e melhoria da qualidade dos cuidados de enfermagem prestados.