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Acute leukemias (ALs) are the most common cancers in pediatric population. There are two types of ALs: acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Some studies suggest that the Renin Angiotensin System (RAS) has a role in ALs. RAS signaling modulates, directly and indirectly, cellular activity in different cancers, affecting tumor cells and angiogenesis. Our review aimed to summarize the role of RAS in ALs and to explore future perspectives for the treatment of these hematological malignancies by modulating RAS molecules. The database including Pubmed, Scopus, Cochrane Library, and Scielo were searched to find articles about RAS molecules in ALL and in pediatric patients. The search terms were "RAS", "Acute Leukemia", "ALL", "Angiotensin-(1-7)", "Pediatric", "Cancer", "Angiotensin II", "AML". In the bone marrow, RAS has been found to play a key role in blood cell formation, affecting several processes including apoptosis, cell proliferation, mobilization, intracellular signaling, angiogenesis, fibrosis, and inflammation. Local tissue RAS modulates tumor growth and metastasis through autocrine and paracrine actions. RAS mainly acts via two molecules, Angiotensin II (Ang II) and Angiotensin (1-7) [Ang-(1-7)]. While Ang II promotes tumor cell growth and stimulates angiogenesis, Ang-(1-7) inhibits the proliferation of neoplastic cells and the angiogenesis, suggesting a potential therapeutic role of this molecule in ALL. The interaction between ALs and RAS reveals a complex network of molecules that can affect the hematopoiesis and the development of hematological cancers. Understanding these interactions could pave the way for innovative therapeutic approaches targeting RAS components.
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Angiotensina II , Leucemia-Linfoma Linfoblástico de Células Precursoras , Sistema Renina-Angiotensina , Humanos , Sistema Renina-Angiotensina/fisiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Angiotensina II/metabolismo , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Transdução de Sinais , Angiotensina I/metabolismo , Neovascularização Patológica/metabolismo , Animais , Fragmentos de Peptídeos/metabolismoRESUMO
BACKGROUND: Surgical treatments of refractory gastroparesis include pyloromyotomy and gastric electrical stimulator (GES). It is unclear if patients may benefit from a combined approach with concomitant GES and pyloromyotomy. METHODS: Retrospective cohort analysis of all patients with refractory gastroparesis treated with GES implantation with and without concomitant pyloromyotomy at Cleveland Clinic Florida from January 2003 to January 2023. Primary endpoint was efficacy (clinical response duration and success rate) and secondary endpoints included safety (postoperative morbidity) and length of stay. Success rate was defined as the absence of one of the following reinterventions during follow-up: Roux-en-Y gastric bypass (RYGB), pyloromyotomy, GES removal. RESULTS: During a period of 20 years, 134 patients were treated with GES implantation. Three patients with history of previous surgical pyloromyotomy or RYGB were excluded from the analysis. Median follow-up was 31 months (IQR 10, 72). Forty patients (30.5%) had GES with pyloromyotomy, whereas 91 (69.5%) did not have pyloromyotomy. Most of the patients had idiopathic (n = 68, 51.9%) or diabetic (n = 58, 43.3%) gastroparesis. Except for preoperative use of opioids (47.5 vs 14.3%; p < 0.001), patient's characteristics were similar in both groups. There were no significant differences between the two groups in terms of overall postoperative complications (17.5% vs 14.3%; p = 0.610), major postoperative complications (0% vs 2.2%; p = 1), and length of stay (2(IQR 1, 2) vs 2(IQR 1, 3) days; p = 0.068). At 5 years, success rate was higher in patients with than without pyloromyotomy however not statistically significant (82% versus 62%, p = 0.066). Especially patients with diabetic gastroparesis seemed to benefit from pyloromyotomy during GES (100% versus 67%, p = 0.053). In an adjusted Cox regression, GES implantation without pyloromyotomy was associated with a 2.66 times higher risk of treatment failure compared to GES implantation with pyloromyotomy (HR 2.66, 95% CI 1.03-6.94, p = 0.044). CONCLUSION: Pyloromyotomy during GES implantation for gastroparesis seems to be associated with a longer clinical response with similar postoperative morbidity and length of hospital stay than GES without pyloromyotomy. Patient with diabetic gastroparesis might benefit from a combination of GES implantation and pyloromyotomy.
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BACKGROUND: Music therapy is an emerging and useful methodology for improving patient environments within healthcare fields. However, although it has been shown that music therapy interventions with hospitalised children and adolescents have been used for decades with positive effects, there are currently very few studies that specifically describe the perspectives of healthcare professionals regarding the value of music therapy when applied in these patients. OBJECTIVES: To describe the insights of healthcare professionals regarding music therapy, both on a personal level and in terms of its usefulness in the care of hospitalised children and adolescents. DESIGN: This was a qualitative descriptive-exploratory study with focus groups. PARTICIPANTS: Eighteen healthcare professionals. METHODS: In January 2023, two focus groups, containing nine healthcare professionals each, were created to collect data regarding their experiences concerning the effect of music therapy on hospitalised children and adolescents. Before recording their opinions, all these professionals participated in an interactive music therapy session. The thematic analysis in this work was performed using MAXQDA® software. RESULTS: Two main categories emerged: (a) the effects of music therapy on healthcare professionals, and (b) the benefits of music therapy to patients (children and adolescents). CONCLUSIONS: Music therapy was valued positively by healthcare professionals who described the benefits its use has for hospitalised children and adolescents. They also expressed positive viewpoints regarding the use of music therapy to improve their own self-knowledge and self-care. IMPLICATIONS TO PRACTICE: Healthcare professionals may utilise music therapists to improve patient outcomes and reduce the negative effects of hospitalisation.
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Atitude do Pessoal de Saúde , Criança Hospitalizada , Grupos Focais , Musicoterapia , Pesquisa Qualitativa , Humanos , Adolescente , Criança , Masculino , Feminino , Criança Hospitalizada/psicologia , Pessoal de Saúde/psicologia , AdultoRESUMO
At the height of the COVID-19 pandemic, the Public Good Projects, Hispanic Communications Network and World Voices Media joined forces to launch a nationwide, multifaceted campaign which aimed to increase vaccine confidence and decrease misinformation on social media within Hispanic communities. We created a Spanish vaccine misinformation tracking system to detect and assess misinformation circulating in online Spanish conversations. We used our media monitoring findings to work with Hispanic social media (SM) influencers, volunteers, and celebrities to spread pro-vaccine messaging online. We created misinformation-responsive SM assets, newsletters, talking points and trainings for Hispanic-serving community-based organizations (CBOs) to help them respond to misinformation and increase vaccine uptake. We used our misinformation findings to inform the creation of mass media communications such as radio PSAs and op-eds. In Year 1, our new Spanish monitoring system captured and organized 35 M Spanish and 212.7 M English posts about COVID-19 misinformation. We recruited 496 paid influencers, 2 Hispanic celebrities and 1,034 digital volunteers. We sent 70 newsletters to an average of 1539 CBO subscribers, containing 206 talking points and 344 resources (SM assets, toolkits, videos) in English and Spanish to support their outreach. Our radio PSAs reached 26.9 M people and the op-eds reached 2.9 M people. This project shows the proliferation of misinformation circulating in online Spanish conversations. It also shows we were effective at reaching our target audience with fact-based COVID-19 misinformation prebunk and debunk messaging.
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COVID-19 , Mídias Sociais , Humanos , Pandemias/prevenção & controle , Comunicação , Hispânico ou Latino , Meios de Comunicação de MassaRESUMO
To better understand the impact of solar light exposure on human skin, the chemical characterization of native melanins and their structural photo-modifications is of central interest. As the methods used today are invasive, we investigated the possibility of using multiphoton fluorescence lifetime (FLIM) imaging, along with phasor and bi-exponential fitting analyses, as a non-invasive alternative method for the chemical analysis of native and UVA-exposed melanins. We demonstrated that multiphoton FLIM allows the discrimination between native DHI, DHICA, Dopa eumelanins, pheomelanin, and mixed eu-/pheo-melanin polymers. We exposed melanin samples to high UVA doses to maximize their structural modifications. The UVA-induced oxidative, photo-degradation, and crosslinking changes were evidenced via an increase in fluorescence lifetimes along with a decrease in their relative contributions. Moreover, we introduced a new phasor parameter of a relative fraction of a UVA-modified species and provided evidence for its sensitivity in assessing the UVA effects. Globally, the fluorescence lifetime properties were modulated in a melanin-dependent and UVA dose-dependent manner, with the strongest modifications being observed for DHICA eumelanin and the weakest for pheomelanin. Multiphoton FLIM phasor and bi-exponential analyses hold promising perspectives for in vivo human skin mixed melanins characterization under UVA or other sunlight exposure conditions.
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Melaninas , Humanos , Melaninas/metabolismo , Fluorescência , OxirreduçãoRESUMO
BACKGROUND: Digital contact tracing (DCT) apps have been implemented as a response to the COVID-19 pandemic. Research has focused on understanding acceptance and adoption of these apps, but more work is needed to understand the factors that may contribute to their sustained use. This is key to public health because DCT apps require a high uptake rate to decrease the transmission of the virus within the general population. OBJECTIVE: This study aimed to understand changes in the use of the National Health Service Test & Trace (T&T) COVID-19 DCT app and explore how public trust in the app evolved over a 1-year period. METHODS: We conducted a longitudinal mixed methods study consisting of a digital survey in December 2020 followed by another digital survey and interview in November 2021, in which responses from 9 participants were explored in detail. Thematic analysis was used to analyze the interview transcripts. This paper focuses on the thematic analysis to unpack the reasoning behind participants' answers. RESULTS: In this paper, 5 themes generated through thematic analysis are discussed: flaws in the T&T app, usefulness and functionality affecting trust in the app, low trust in the UK government, varying degrees of trust in other stakeholders, and public consciousness and compliance dropping over time. Mistrust evolved from participants experiencing sociotechnical flaws in the app and led to concerns about the app's usefulness. Similarly, mistrust in the government was linked to perceived poor pandemic handling and the creation and procurement of the app. However, more variability in trust in other stakeholders was highlighted depending on perceived competence and intentions. For example, Big Tech companies (ie, Apple and Google), large hospitality venues, and private contractors were seen as more capable, but participants mistrust their intentions, and small hospitality venues, local councils, and the National Health Service (ie, public health system) were seen as well-intentioned but there is mistrust in their ability to handle pandemic matters. Participants reported complying, or not, with T&T and pandemic guidance to different degrees but, overall, observed a drop in compliance over time. CONCLUSIONS: These findings contribute to the wider implications of changes in DCT app use over time for public health. Findings suggest that trust in the wider T&T app ecosystem could be linked to changes in the use of the app; however, further empirical and theoretical work needs to be done to generalize the results because of the small, homogeneous sample. Initial novelty effects occurred with the app, which lessened over time as public concern and media representation of the pandemic decreased and normalization occurred. Trust in the sociotechnical capabilities of the app, stakeholders involved, and salience maintenance of the T&T app in conjunction with other measures are needed for sustained use.
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COVID-19 , Aplicativos Móveis , COVID-19/prevenção & controle , Busca de Comunicante/métodos , Ecossistema , Humanos , Pandemias/prevenção & controle , Medicina Estatal , Confiança , Reino UnidoRESUMO
The aim of this research communication was to examine and report the current situation of dairy farms in the province of Lugo (Galicia, Spain) regarding facility problems. We assessed the facilities of 168 free-stall dairy farms, housing in total 9228 Holstein cows in milk. Housing factors related to the resting area, circulation area, feeding area, ventilation area and milking area, as well as animal-handling features, were evaluated. Distance measurements were performed using a laser metre or a roll metric tape. A survey was conducted to gather information about cleaning and preventive protocols. Our results showed that most farms do not comply with the objective for cubicle measurements, width of the crossovers, type of flooring and presence of a quarantine pen, which may have a negative impact on the health and productivity of the animals. Therefore, to maximise the profits of the farm, the recommendations given in this study may be useful as a guide when building a new farm or remodelling the existing ones.
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BACKGROUND: AURA study reported 61% objective response rate and progression-free survival of 9.6 months with osimertinib in patients with EGFR/T790M+ non-small cell lung cancer. Due to lack of real-world data, we proposed this study to describe the experience with osimertinib in Spain. METHODS: Post-authorization, non-interventional Special Use Medication Program, multicenter, retrospective study in advanced EGFR/T790M+ non-small cell lung cancer. One hundred-fifty five patients were enrolled (August 2016-December 2018) from 30 sites. PRIMARY OBJECTIVE: progression-free survival. Secondary objectives: toxicity profile, objective response rate, and use of health service resources. RESULTS: 70% women, median age 66. 63.9% were non-smokers and 99% had adenocarcinoma. Most patients had received at least one prior treatment (97%), 91.7% had received previous EGFR-tyrosine kinase inhibitors and 2.8% osimertinib as first-line treatment. At data cutoff, median follow-up was 11.8 months. One hundred-fifty five patients were evaluable for response, 1.3% complete response, 40.6% partial response, 31% stable disease and 11.6% disease progression. Objective response rate was 42%. Median progression-free survival was 9.4 months. Of the 155 patients who received treatment, 76 (49%) did not reported any adverse event, 51% presented some adverse event, most of which were grade 1 or 2. The resource cost study indicates early use is warranted. CONCLUSION: This study to assess the real-world clinical impact of osimertinib showed high drug activity in pretreated advanced EGFR/T790M+ non-small cell lung cancer, with manageable adverse events. TRIAL REGISTRATION: Clinical trial registration number: NCT03790397 .
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Acrilamidas/administração & dosagem , Compostos de Anilina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Acrilamidas/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Seguimentos , Humanos , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Estudos Retrospectivos , Espanha/epidemiologiaRESUMO
Preliminary data in Europe have suggested a reduction in prematurity rates during the COVID-19 pandemic, implying that contingency measures could have an impact on prematurity rates. We designed a population-based prevalence proportion study to explore the potential link between national lockdown measures and a change in preterm births and stillbirths. Adjusted multivariate analyses did not show any decrease in preterm proportions during the lockdown period with respect to the whole prelockdown period or to the prelockdown comparison periods (2015-2019): 6.5% (95%CI 5.6-7.4), 6.6% (95%CI 6.5-6.8), and 6.2% (95%CI 5.7-6.7), respectively. Proportions of preterm live births did not change during lockdown when different gestational age categories were analyzed, nor when birthweight categories were considered. No differences in stillbirth rates among the different study periods were found: 0.33% (95%CI 0.04-0.61) during the lockdown period vs. 0.34% (95%CI 0.22-0.46) during the prelockdown comparison period (2015-2019).Conclusion: We did not find any link between prematurity and lockdown, nor between stillbirths and lockdown. Collaborative efforts are desirable to gather more data and additional evidence on this global health issue. What is Known: ⢠Prematurity is associated with increased risk of morbidity and mortality. ⢠Contingency measures during the COVID-19 pandemic may have an impact on reducing prematurity rates. What is New: ⢠Prematurity and stillbirth rates remained stable in Castilla-y-León, a Spanish region, during COVID-19 lockdown. ⢠The role of behavioral patterns and sociocultural factors in the prevention of preterm birth as a result of lockdown measures remains a subject for debate.
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COVID-19 , Nascimento Prematuro , Controle de Doenças Transmissíveis , Europa (Continente)/epidemiologia , Feminino , Humanos , Recém-Nascido , Pandemias , Gravidez , Nascimento Prematuro/epidemiologia , SARS-CoV-2 , Natimorto/epidemiologiaRESUMO
This study aims to better understand how one particular personal capacity-psychological resilience-may help consumers adapt to the 'new normal' provoked by the COVID-19 pandemic in the hotel context, which is characterized by high uncertainty. We conducted a quantitative empirical study among consumers of hotel services, which showed that their psychological resilience has a negative effect on their perceived health risk and emotional risk. This negative effect on risk helps increase tourist intention to return to consuming hotel services despite the on-going pandemic. The findings are of value to the literature and the professional sector alike, as they demonstrate both relationships jointly for the first time. The work can help hotel firms to design more effective strategies for approaching customers in the 'new normal'.
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BACKGROUND: In vivo multiphoton imaging and automatic 3D image processing tools provide quantitative information on human skin constituents. These multiphoton-based tools allowed evidencing retinoids epidermal effects in the occlusive patch test protocol developed for antiaging products screening. This study aimed at investigating their relevance for non-invasive, time course assessment of retinoids cutaneous effects under real-life conditions for one year. MATERIALS AND METHODS: Thirty women, 55-65 y, applied either retinol (RO 0.3%) or retinoic acid (RA 0.025%) on one forearm dorsal side versus a control product on the other forearm once a day for 1 year. In vivo multiphoton imaging was performed every three months, and biopsies were taken after 1 year. Epidermal thickness and dermal-epidermal junction undulation were estimated in 3D with multiphoton and in 2D with histology, whereas global melanin density and its z-epidermal distribution were estimated using 3D multiphoton image processing tools. RESULTS: Main results after one year were as follows: a) epidermal thickening with RO (+30%); b) slight increase in dermal-epidermal junction undulation with RO; c) slight decrease in 3D melanin density with RA; d) limitation of the melanin ascent observed with seasonality and time within supra-basal layers with both retinoids, using multiphoton 3D-melanin z-epidermal profile. CONCLUSIONS: With a novel 3D descriptor of melanin z-epidermal distribution, in vivo multiphoton imaging allows demonstrating that daily usage of retinoids counteracts aging by acting not only on epidermal morphology, but also on melanin that is shown to accumulate in the supra-basal layers with time.
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Microscopia de Fluorescência por Excitação Multifotônica , Retinoides , Pele , Idoso , Feminino , Humanos , Imageamento Tridimensional , Melaninas , Pessoa de Meia-Idade , Retinoides/uso terapêutico , Pele/diagnóstico por imagem , Pele/efeitos dos fármacosRESUMO
Cashew (Anacardium occidentale L.) is a cash crop with a highly significant economic importance in West Africa, particularly in Guinea-Bissau (Monteiro et al. 2015, 2017). In October 2018, dieback-like symptoms such as wilt and necrosis of apical shoots were observed in 10 % of the cashew trees grown in a 100 plant-orchard in Bolama Island at Bijagós archipelago, Guinea-Bissau. Six symptomatic apical shoots from individual plants were collected for fungal isolation and identification. Tissue pieces (3 × 2 mm) from healthy to diseased margins were surface sterilized with 1 % sodium hypochlorite, washed twice with sterilized water, placed on potato dextrose agar (PDA, Difco® Laboratories) supplemented with potassium thiocyanate (50 µg/ml), and incubated at 24 ± 1 °C in the dark for 7 days. Four fungal colonies were isolated (67 %) and purified through hyphal tips removal, displaying rapid growth rate, and aerial mycelia that initially was white, turning later to dark greenish on PDA. Pycnidia produced on 1.5 % water agar and sterilized pine needles (± 25ºC; near-UV light) were solitary, covered by mycelium, obpyriform to ampulliform (152.5 ± 41.6 × 135.2 ± 30.8 µm, n = 30). Conidia were unicellular, hyaline, smooth, fusoid to ovoid, thin-walled, measuring 16.21 ± 1.52 × 5.84 ± 0.66 µm (n = 50, L/W 2.8). Such morphological features are characteristic of Neofusicoccum spp. (Phillips et al. 2013). For molecular identification, genomic DNA was extracted from a representative isolate GB160 and partial regions of ribosomal internal transcriber spacer (ITS) (ITS1/ITS4; White et al. 1990), translation elongation factor 1-α (EF1-α) (EF1-688F/EF1-1251R; Alves et al. 2008) and ß-tubulin (ß-tub) (Bt2a/Bt2b; Glass and Donaldson 1995) genes were amplified as previously described, respectively, with BSA (50 mg/ml). Amplicons were sequenced and deposited in GenBank (ITS, MN952993; EF1-α, MN952204; ß-tub, MN952208). BLAST analysis of ITS, EF1-α and ß-tub gene sequences showed 100 % identity with Neofusicoccum batangarum reference strain CBS124923 (FJ900608, FJ900654, FJ900635, respectively). Maximum-likelihood and Bayesian Inference analyses from the concatenated dataset placed GB160 isolate within the N. batangarum cluster (BS = 72 %; PP = 0.95). For pathogenicity assessment, 3-month-old cashew "Caju di Terra" plants (n = 8) grown in a greenhouse under controlled conditions were inoculated following a randomized block design as described by Lima et al. (2013). Briefly, 3 mm diam. stem tissue bark was removed and replaced with a 3 mm diameter PDA plug retrieved from the colony margin. Inoculation wound was covered with sterilized wet cotton and sealed with parafilm. Eight control plants were only treated with PDA plugs and the wound covered and sealed as described. After 15 days, all inoculated plants displayed similar symptoms to those observed in the field, and vascular lesions (10.8 ± 4.0 cm), whereas control plants remained symptomless. Koch's postulates were fulfilled by successful re-isolation of the pathogen from all inoculated stems and identification by morphology and gene sequencing. N. batangarum was identified associated with Anacardium spp. in Brazil (Netto et al. 2017) and recently reported as causing grapevine dieback in Brazil (Rêgo et al. 2020). To our knowledge, this is the first report of N. batangarum causing cashew dieback in Guinea-Bissau and West Africa. Occurrence of this disease may represent a significant impact for cashew production since this crop is the major agricultural commodity in Guinea-Bissau.
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Antibodies for therapeutic use are being continuously approved and their demand has been steadily growing. As known, the golden standard for monoclonal antibody (mAb) purification is Protein A affinity chromatography, a technology that has gained high interest because of its great performance and capabilities. The main concerns are the elevated resins costs and their limited lifetime compared to other resins (e.g. ion exchange chromatography). Great efforts have been carried out to improve purification conditions, such as resin characterization and designing alkali/acid stable resins with a longer lifetime. Modification of Protein A ligands and alternative formats such as monoliths membranes and microshperes have been tested to increase the purification performance. New technology has been proposed to improve the large-scale separation; in addition, alternative ligands have been suggested to capture mAbs instead of Protein A ligand; however, most of the information is locked by pharmaceutical companies. This mini review summarizes and describes the advances, results, and impact on the Protein A chromatography purification processing.
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Anticorpos Monoclonais/isolamento & purificação , Cromatografia Líquida/métodos , Animais , Anticorpos Monoclonais/química , Cromatografia Líquida/tendências , Humanos , Proteína Estafilocócica A/químicaRESUMO
Over the previous decades, numerous studies focused on how oceanic islands have contributed to determine the phylogenetic relationships and times of origin and diversification of different endemic lineages. The Macaronesian Islands (i.e., Azores, Madeira, Selvagens, Canaries, and Cabo Verde), harbour biotas with exceptionally high levels of endemism. Within the region, the vascular plants and reptiles constitute two of the most important radiations. In this study we compare relevant published phylogenetic data and diversification rates retrieved within Cabo Verde endemic lineages and discuss the importance of choosing appropriate phylogeny-based methods to investigate diversification dynamics on islands. From this selective literature-based review, we summarize the software packages used in Macaronesian studies and discuss their adequacy considering the published data to obtain well-supported phylogenies in the target groups. We further debate the importance of Next Generation Sequencing (NGS), to investigate the evolutionary processes of diversification in the Macaronesian Islands. Analysis of genomic data provides phylogenetic resolution for rapidly evolving species radiations, suggesting a great potential to improve the phylogenetic signal and divergence time estimates in insular lineages. The most important Macaronesian reptile radiations provide good case-studies to compare classical phylogenetic methods with new tools, such as phylogenomics, revealing a high value for research on this hotspot area.
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Biodiversidade , Genômica/métodos , Filogenia , Répteis/classificação , Animais , Cabo Verde , Especiação Genética , Genômica/normas , Metanálise como Assunto , Répteis/genéticaRESUMO
Cinnamic acids are compounds of natural origin that can be found in many different parts of a wide panoply of plants, where they play the most diverse biological roles, often in a conjugated form. For a long time, this has been driving Medicinal Chemists towards the investigation of the therapeutic potential of natural, semi-synthetic, or fully synthetic cinnamic acid conjugates. These efforts have been steadily disclosing promising drug leads, but a wide chemical space remains that deserves to be further explored. Amongst different reported approaches, the combination or conjugation of cinnamic acids with known drugs has been addressed in an attempt to produce either synergistic or multi-target action. In this connection, the present review will focus on efforts of the past decade regarding conjugation with cinnamic acids as a tool for the rescuing or the repurposing of classical antimalarial drugs, and also on future perspectives in this particular field of research.
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Antimaláricos/farmacologia , Cinamatos/farmacologia , Reposicionamento de Medicamentos , Antimaláricos/química , Cinamatos/química , Humanos , Líquidos Iônicos/químicaRESUMO
Purpose Ethanol as an excipient is used to enhance the solubility of gemcitabine, but, sometimes, the dose of ethanol a patient may be given is much higher than the dose considered to be toxic. We aimed to assess ethanol-related symptoms and signs in patients receiving two formulations of gemcitabine, with and without ethanol. Methods A randomized double blind cross-over study was conducted. All patients being treated with gemcitabine received two consecutive doses of the drug, one diluted from a concentrate for solution for infusion (CSI) containing ethanol and the other from a lyophilized powder, without ethanol, which was used as control group. After each administration, patients were surveyed in order to assess the appearance of any alcohol consumption symptoms (dizziness, difficulty speaking, unsteady walking, impaired balance, mood swings and slower reactions). Widmark formula and the amount of alcohol measured on the breath (breathalyzer) were used to estimate blood alcohol concentration. Results Twenty-four patients received both formulations and were included in the analysis. Mean administered ethanol dose when prepared from CSI was 15.81 ± 2.25 g (mean ± SD). When using CSI gemcitabine, estimated blood ethanol concentration was 0.033 g/dl according to Widmark formula and 0.02 g/dl according to breathalyzer results. Although overall incidence of symptoms was higher in the study group, the difference was not statistically significant (33% vs. 25%; p = 0.53). Conclusions These findings prove there is no difference in the onset of ethanol related symptoms when using CSI instead of lyophilized powder on the reconstitution of gemcitabine.
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Concentração Alcoólica no Sangue , Desoxicitidina/análogos & derivados , Etanol/administração & dosagem , Idoso , Testes Respiratórios , Estudos Cross-Over , Desoxicitidina/administração & dosagem , Método Duplo-Cego , Etanol/efeitos adversos , Etanol/sangue , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Soluções Farmacêuticas , GencitabinaRESUMO
Studies performed on ejaculates from several species have identified discrete subpopulations of motile sperm. In dogs, motile sperm subpopulations have also been described in fresh and frozen-thawed semen. The subpopulation of the most rapid and progressively motile sperm has been suggested to be the most likely source of fertilizing spermatozoa. However, the significance of subpopulation differences among dogs and ejaculates relative to fertility is not known. The aim of this study was to investigate the relationship between the relative proportion of motile sperm subpopulations in frozen-thawed dog semen samples and their ability to bind to the zona pellucida of canine oocytes. Multiple linear regression analysis indicated that the subpopulation of the most rapid and progressively motile sperm was significantly and positively correlated with zona pellucida-binding assays (ZBA) outcomes: each 10% increase in this subpopulation was associated with an increase of 1.5 sperm bound per oocyte. Subpopulations of hyperactivated-like or locally motile sperm were negatively correlated with the ZBA results. It was concluded that subpopulation differences among frozen-thawed dog semen samples determined differences in the number of sperm bound to the ZP of canine oocytes.
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Cães/fisiologia , Motilidade dos Espermatozoides/fisiologia , Interações Espermatozoide-Óvulo/fisiologia , Espermatozoides/fisiologia , Animais , Criopreservação/veterinária , Feminino , Fertilização in vitro/veterinária , Congelamento , Masculino , Oócitos , Espermatozoides/classificação , Zona Pelúcida/fisiologiaRESUMO
The focus of this article is the life and work of the French thinker Michel de Certeau, here presented as a philosopher of special interest for nursing. Although in some countries he is relatively unknown, international authors from scientific disciplines regard his texts as a fundamental source in the opening of new intellectual perspectives on current global problems. Some nurses have also considered his ideas as a useful aid for reflecting on their professional activities, and their most important research is cited. Over these pages, we also examine how Certeau's work can enrich nursing philosophy in regard to three specific issues: resistance practices in nursing in the face of pressure from health institutions; the social configuration of nursing knowledge; and the importance of the body in current nursing practice.
Assuntos
Filosofia em Enfermagem , Filosofia/história , França , História do Século XX , HumanosRESUMO
Chickpea (Cicer arietinum L.) genotypes, nine kabuli from Mexico and 9 desi from other countries, were investigated for their phenolic profiles and antioxidant activity (AA). Phenolics in methanol extracts (ME) were analyzed by ultra-performance liquid chromatography coupled to diode array detection and mass spectrometry (UPLC-DAD-MS), whereas the AA was measured as Trolox equivalents (TE) by ABTS, DPPH and FRAP methods. Twenty phenolic compounds were identified in the ME and their levels showed a great variability among the chickpea genotypes. Phenolic acids and flavonoids were the most abundant compounds in kabuli and desi genotypes, respectively. The AA values (µmol TE/ 100 g dw) by ABTS (278-2417), DPPH (52-1650), and FRAP (41-1181) were mainly associated with the content of sinapic acid hexoside, gallic acid, myricetin, quercetin, catechin, and isorhamnetin, suggesting they are the main compounds responsible for the AA. The sum of the AA obtained for standards of these compounds evaluated at the concentration found in the extracts accounted for 34.3, 69.8, and 47.0% of the AA in the extract by ABTS, DPPH, and FRAP, respectively. In the AA by DPPH, most of the mixtures of these compounds resulted in synergistic interactions. Three desi genotypes with black seeds (ICC 4418, ICC 6306, and ICC 3761) showed the highest AA and flavonoids content, whereas the most promising kabuli genotypes were Surutato 77, Bco. Sin. 92, and Blanoro that showed the highest values of phenolic acids. These genotypes represent good sources of antioxidants for the improvement of nutraceutical properties in chickpea.
Assuntos
Antioxidantes/análise , Cicer/química , Flavonoides/análise , Hidroxibenzoatos/análise , Catequina/análise , Cromanos/análise , Cromatografia Líquida , Ácido Gálico/análise , Genótipo , Espectrometria de Massas , Quercetina/análogos & derivados , Quercetina/análise , Sementes/químicaRESUMO
Quorum sensing systems are essential for bacterial communication. We report here the purification and characterization of the Pseudomonas aeruginosa LasR quorum sensing regulator purified from lysates of E. coli cultures grown in the absence of added acyl-homoserine lactones (AHL). We show by isothermal titration calorimetry that LasR recognizes different AHLs with an affinity of approximately 1 µM. The affinity of LasR for its cognate 3-Oxo-C12-AHL was similar to that of other AHLs, indicating that this regulator has not evolved to preferentially recognize its cognate AHL. The α-helical content as determined by CD spectroscopy was found to be in agreement with the corresponding value derived from the homology model. Analytical ultracentrifugation studies show that LasR is a mixture of monomers and dimers and that AHL binding does not alter its oligomeric state. Thermal unfolding studies indicate that LasR has a significant thermal stability and that AHL binding does not significantly alter the unfolding temperature. Two LasR-DNA complexes were observed in electrophoretic mobility shift assays using the hcnABC promoter that has two lux boxes. Taken together, data indicate that the presence of AHLs is not a requisite for correct LasR protein folding. The protein is able to bind AHL ligands in a reversible manner, revising initial concepts of this regulator. The availability of AHL-free protein will permit further studies to determine more precisely its mode of action.