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1.
Eur J Pharm Biopharm ; 198: 114235, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38401742

RESUMEN

Nanotechnology-assisted RNA delivery has gotten a tremendous boost over the last decade and made a significant impact in the development of life-changing vaccines and therapeutics. With increasing numbers of emerging lipid- and polymer-based RNA nanoparticles progressing towards the clinic, it has become apparent that the safety and efficacy of these medications depend on the comprehensive understanding of their critical quality attributes (CQAs). However, despite the rapid advancements in the field, the identification and reliable quantification of CQAs remain a significant challenge. To support these efforts, this review aims to summarize the present knowledge on CQAs based on the regulatory guidelines and to provide insights into the available analytical characterization techniques for RNA-loaded nanoparticles. In this context, routine and emerging analytical techniques are categorized and discussed, focusing on the operation principle, strengths, and potential limitations. Furthermore, the importance of complementary and orthogonal techniques for the measurement of CQAs is discussed in order to ensure the quality and consistency of analytical methods used, and address potential technique-based differences.


Asunto(s)
Nanopartículas , Nanotecnología , ARN Mensajero , Nanotecnología/métodos
2.
Int J Psychol Res (Medellin) ; 16(2): 14-23, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38106955

RESUMEN

Introduction: The role of affective states on the creative process has been receiving the attention of researchers and has led to contradictory results. Most research in creativity has emphasized the role of affective states, mainly positive ones, on creativity levels, namely those resulting from divergent thinking tasks that reveal the unconventional way of thinking in the creative process. However, there are no studies to date that focus on the impact of affective states on conventional and unconventional thinking, during the same creative process, which consider a single creative assessment task. The aim of this experimental study was to analyze the effect of induced affective states on both conventional and unconventional thinking of creativity in adults by using the TCT-DP (Test for Creative Thinking-Drawing Production). Method: Seventy-five university students, mostly female, with a mean age of 26.95 years, were randomly assigned into three affect elicitation conditions (pleasant vs. unpleasant vs. neutral). Results: Results indicated that the negative affective state led to higher levels of conventional thinking when compared to positive and neutral affective states. However, no significant differences were found on unconventional thinking across the three conditions. Conclusions: Our results do not support the assumption that the negative affect has a hindering effect on creativity nor the positive affect increases creativity. Negative affect seems to promote conventional thinking, perhaps due to its cognitive correlates, which can be manifested in focusing attention and analytic thinking. Practical and theoretical implications for future research on the role of affective states on creativity are discussed.


Introducción: El papel de los estados afectivos en el proceso creativo ha sido objeto de atención por parte de los investigadores y ha dado lugar a resultados contradictorios. La mayor parte de la investigación en creatividad ha hecho hincapié en el papel de los estados afectivos, principalmente los positivos, sobre los niveles de creatividad. A saber, los resultantes de las tareas de pensamiento divergente que revelan la forma no convencional de pensar en el proceso creativo. Este estudio tuvo como objetivo analizar el efecto de los estados afectivos inducidos en dos dimensiones distintas del pensamiento creativo en adultos. Método: Setenta y cinco voluntarios, en su mayoría mujeres, con una edad media de 26.95 años, fueron asignados aleatoriamente a tres condiciones de elicitación de estados afectivos (agradable vs desagradable vs neutral), justo antes de realizar una tarea de creatividad figurativa. Resultados: Los resultados indicaron que el estado afectivo negativo condujo a niveles más altos de pensamiento convencional. Conclusiones: Nuestros resultados no apoyan ni la hipótesis de que el afecto negativo tiene un efecto perjudicial sobre la creatividad ni la de que el afecto positivo aumenta la creatividad. El afecto negativo parece promover el pensamiento convencional, quizá debido a sus correlatos cognitivos, que pueden manifestarse en la atención focalizada y el pensamiento analítico. Se discuten las implicaciones prácticas y teóricas para futuras investigaciones sobre el papel de los estados afectivos en la creatividad.

3.
Front Vet Sci ; 10: 1236136, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37711439

RESUMEN

Introduction: Cancer is a major public health problem with over 19 million cases reported in 2020. Similarly to humans, dogs are also largely affected by cancer, with non-Hodgkin's lymphoma (NHL) among the most common cancers in both species. Comparative medicine has the potential to accelerate the development of new therapeutic options in oncology by leveraging commonalities between diseases affecting both humans and animals. Within this context, in the present study, we investigated the potential of panobinostat (Pan)-loaded folate-targeted PEGylated liposomes (FA-PEG-Pan-Lip) for the treatment of canine B-cell lymphoma, while contributing to new perspectives in comparative oncology. Methods and results: Two formulations were developed, namely: PEG-Pan-Lip and FA-PEG-Pan-Lip. Firstly, folate receptor expression in the CLBL-1 canine B-cell lymphoma cell line was assessed. After confirming receptor expression, both Pan-loaded formulations (PEG-Pan-Lip, FA-PEG-Pan-Lip) demonstrated dose-dependent inhibitory effects on CLBL-1 cell proliferation. The FA-PEG-Pan-Lip formulation (IC50 = 10.9 ± 0.03 nM) showed higher cytotoxicity than the non-targeted PEG-Pan-Lip formulation (IC50 = 12.9 ± 0.03 nM) and the free panobinostat (Pan) compound (IC50 = 18.32±0.03 nM). Moreover, mechanistically, both Pan-containing formulations induced acetylation of H3 histone and apoptosis. Flow cytometry and immunofluorescence analysis of intracellular uptake of rhodamine-labeled liposome formulations in CLBL-1 cells confirmed cellular internalization of PEG-Lip and FA-PEG-Lip formulations and higher uptake profile for the latter. Biodistribution studies of both radiolabeled formulations in CD1 and SCID mice revealed a rapid clearance from the major organs and a 1.6-fold enhancement of tumor uptake at 24 h for 111In-FA-PEG-Pan-Lip (2.2 ± 0.1 %ID/g of tumor) compared to 111In-PEG-Pan-Lip formulation (1.2±0.2 %ID/g of tumor). Discussion: In summary, our results provide new data validating Pan-loaded folate liposomes as a promising targeted drug delivery system for the treatment of canine B-cell lymphoma and open innovative perspectives for comparative oncology.

4.
Sci Rep ; 13(1): 4837, 2023 03 24.
Artículo en Inglés | MEDLINE | ID: mdl-36964198

RESUMEN

Antibody-drug conjugates (ADCs) are among the fastest-growing classes of therapeutics in oncology. Although ADCs are in the spotlight, they still present significant engineering challenges. Therefore, there is an urgent need to develop more stable and effective ADCs. Most rabbit light chains have an extra disulfide bridge, that links the variable and constant domains, between Cys80 and Cys171, which is not found in the human or mouse. Thus, to develop a new generation of ADCs, we explored the potential of rabbit-derived VL-single-domain antibody scaffolds (sdAbs) to selectively conjugate a payload to Cys80. Hence, a rabbit sdAb library directed towards canine non-Hodgkin lymphoma (cNHL) was subjected to in vitro and in vivo phage display. This allowed the identification of several highly specific VL-sdAbs, including C5, which specifically target cNHL cells in vitro and present promising in vivo tumor uptake. C5 was selected for SN-38 site-selective payload conjugation through its exposed free Cys80 to generate a stable and homogenous C5-DAB-SN-38. C5-DAB-SN-38 exhibited potent cytotoxicity activity against cNHL cells while inhibiting DNA-TopoI activity. Overall, our strategy validates a platform to develop a novel class of ADCs that combines the benefits of rabbit VL-sdAb scaffolds and the canine lymphoma model as a powerful framework for clinically translation of novel therapeutics for cancer.


Asunto(s)
Antineoplásicos , Inmunoconjugados , Neoplasias , Animales , Perros , Conejos , Ratones , Humanos , Inmunoconjugados/farmacología , Anticuerpos Monoclonales/farmacología , Irinotecán , Neoplasias/terapia , Antígenos , Antineoplásicos/farmacología
5.
Mol Ther ; 31(2): 374-386, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36303436

RESUMEN

Emerging and re-emerging viruses, such as Zaire Ebola virus (EBOV), pose a global threat and require immediate countermeasures, including the rapid development of effective vaccines that are easy to manufacture. Synthetic self-amplifying RNAs (saRNAs) attend to these needs, being safe and strong immune stimulators that can be inexpensively produced in large quantities, using cell-free systems and good manufacturing practice. Here, the first goal was to develop and optimize an anti-EBOV saRNA-based vaccine in terms of its antigen composition and route of administration. Vaccinating mice with saRNAs expressing the EBOV glycoprotein (GP) alone or in combination with the nucleoprotein (NP) elicited antigen-specific immune responses. GP-specific antibodies showed neutralizing activity against EBOV. Strong CD4+ T cell response against NP and GP and CD8+ T cell response against NP were detected by ELISpot assays. Intramuscular vaccination with saRNAs conferred better immune response than intradermal. Finally, mice vaccinated in a prime-boost regimen with saRNAs encoding both GP and NP or with GP alone survived an EBOV infection. In addition, a single dose of GP and NP saRNAs was also protective against fatal EBOV infection. Overall, saRNAs expressing viral antigens represent a promising vaccine platform.


Asunto(s)
Vacunas contra el Virus del Ébola , Ebolavirus , Fiebre Hemorrágica Ebola , Animales , Ratones , Fiebre Hemorrágica Ebola/prevención & control , Anticuerpos Antivirales , Anticuerpos Neutralizantes , Ebolavirus/genética , Glicoproteínas/genética , Vacunas contra el Virus del Ébola/genética
6.
Cureus ; 14(10): e30763, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36447732

RESUMEN

The optimal alternative anticoagulation regimen for patients with heparin-induced thrombocytopenia (HIT) who need surgical procedures that involve higher levels of anticoagulation, usually performed under heparin, is not yet established. Argatroban has been reported as a safe alternative. Plasma levels and their anticoagulant effects follow a predictable profile. Also, it is easily monitored and its pharmacokinetic profile makes it suitable for patients with renal failure, as it undergoes hepatic elimination. However, its use as a substitute for heparin in HIT patients is not well-documented, especially in vascular surgery. We present a case of a successfully managed patient with acute HIT undergoing limb vascular surgery using anticoagulation with argatroban.

7.
Cureus ; 14(3): e23697, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35505719

RESUMEN

Urachal carcinoma is a rare and aggressive tumor, involving the urachus and the bladder. Symptoms of urachal carcinoma usually appear at later stages of the disease; therefore, these tumors are diagnosed in advanced stages, providing limited options for curative treatment. We report the clinical case of a 60-year-old man with a urachal carcinoma which presented as a mass of the abdominal wall invading the transverse colon, creating an enterocutaneous fistula. The patient underwent an en-bloc resection of the mass, segmentary resection of the transverse colon, and partial cystectomy.

8.
Drug Deliv Transl Res ; 12(11): 2581-2588, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35290656

RESUMEN

The triumphant success of mRNA vaccines is a testimony to the important role drug delivery technologies have played in protecting billions of people against SARS-CoV-2 (or the Corona Virus Disease 2019; COVID-19). Several lipid nanoparticle (LNP) mRNA vaccines were developed and have been instrumental in preventing the disease by boosting the immune system against the pathogen, SARS-CoV-2. These vaccines have been built on decades of scientific research in drug delivery of mRNA, vaccines, and other biologicals. In this manuscript, several leading and emerging scientists in the field of drug delivery share their perspective on the role of drug delivery technologies in developing safe and efficacious vaccines, in a roundtable discussion. The authors also discussed their viewpoint on the current challenges, and the key research questions that should drive this important area of research.


Asunto(s)
COVID-19 , Nanopartículas , Vacunas Virales , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Liposomas , ARN Mensajero , SARS-CoV-2
9.
Sci Rep ; 12(1): 2678, 2022 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-35177658

RESUMEN

Anti-CD20 therapies have revolutionized the treatment of B-cell malignancies. Despite these advances, relapsed and refractory disease remains a major treatment challenge. The optimization of CD20-targeted immunotherapies is considered a promising strategy to improve current therapies. However, research has been limited by the scarcity of preclinical models that recapitulate the complex interaction between the immune system and cancers. The addition of the canine lymphoma (cNHL) model in the development of anti-CD20 therapies may provide a clinically relevant approach for the translation of improved immunotherapies. Still, an anti-CD20 therapy for cNHL has not been established stressing the need of a comprehensive target characterization. Herein, we performed an in-depth characterization on canine CD20 mRNA transcript and protein expression in a cNHL biobank and demonstrated a canine CD20 overexpression in B-cell lymphoma samples. Moreover, CD20 gene sequencing analysis identified six amino acid differences in patient samples (C77Y, L147F, I159M, L198V, A201T and G273E). Finally, we reported the use of a novel strategy for the generation of anti-CD20 mAbs, with human and canine cross-reactivity, by exploring our rabbit derived single-domain antibody platform. Overall, these results support the rationale of using CD20 as a target for veterinary settings and the development of novel therapeutics and immunodiagnostics.


Asunto(s)
Antígenos CD20/inmunología , Antígenos de Neoplasias/inmunología , Enfermedades de los Perros , Inmunización Pasiva , Linfoma de Células B , Animales , Línea Celular Tumoral , Enfermedades de los Perros/inmunología , Enfermedades de los Perros/terapia , Perros , Células HEK293 , Humanos , Linfoma de Células B/inmunología , Linfoma de Células B/terapia , Linfoma de Células B/veterinaria
10.
Folia Parasitol (Praha) ; 682021 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-33576748

RESUMEN

Myxozoan parasites of the genus Kudoa Meglitsch, 1947 are associated with post-mortem tissue degradation that causes great financial losses to commercial fisheries. Kudoa thyrsites (Gilchrist, 1924) is a species with a very wide host range including commercial tunas, mackerels, salmonids and flatfishes. A sample of 190 fishes of 18 species from the Madeira Archipelago and 30 Atlantic chub mackerel, Scomber colias Gmelin, and 30 blue whiting, Micromesistius poutassou (Risso), from the Portuguese mainland coast were examined for the presence of species of Kudoa. The prevalence of Kudoa spp. was 80% in M. poutassou and 60% in S. colias. No spore was detected in S. colias from Madeira, which was confirmed by specific PCR screening of the muscle from all individuals of S. colias. SSU rDNA analysis revealed that M. poutassou and S. colias from the Portuguese mainland coast were infected with K. thyrsites, an economically important myxozoan parasite. Both sequences were identical with sequences of the eastern Atlantic K. thyrsites genotype, including that from the type host of this parasite. This is the first report of K. thyrsites from M. poutassou and S. colias. The fact that spores of species of Kudoa were not detected in fishes screened in the Madeira Archipelago may be explained by various ecological factors, such as the absence of a continental shelf, a short insular shelf, and oceanic waters with low productivity, all resulting in reduced abundance of benthic organisms. Consequently, it is possible that as yet unknown annelid definitive hosts of Kudoa spp. are absent or very rare near Madeiran coasts.


Asunto(s)
Enfermedades de los Peces/parasitología , Peces/parasitología , Myxozoa , Animales , ADN Ribosómico/genética , Gadiformes/parasitología , Genes Protozoarios , Myxozoa/clasificación , Myxozoa/genética , Myxozoa/aislamiento & purificación , Perciformes/parasitología , Filogenia , Portugal/epidemiología , Prevalencia , Esporas/citología
11.
Surg Endosc ; 35(12): 7191-7199, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-33398553

RESUMEN

BACKGROUND: For mid and low rectal cancer, transanal total mesorectal excision (TaTME) has been established as an alternative approach to laparoscopic surgery. However, there are concerns about an unexpected pattern of local recurrence. This study aimed to analyze the pattern of local recurrence for patients treated with TaTME in a tertiary referral center. METHODS: A retrospective single-center analysis was performed. Since 2011, all patients with rectal cancer undergoing TaTME with curative intent were prospectively included in a standardized database. Patients with tumors within 12 cm, clinical stage II or III were included. The primary endpoint of the study was the overall local recurrence rate, together with a critical analysis of the patterns of local failures. RESULTS: Two hundred and five patients were included in this analysis. At the time of surgery, patients had a mean age of 67.1 years (SD 12.3), and 66.8% were male. Neoadjuvant therapy was administered in 73.7%. Mesorectal specimen quality was complete or near-complete in 98.5%, while circumferential resection margin was ≤ 1 mm (including T4 tumors) in 11.8%. After a median follow-up of 34.3 months (95% CI 30.1-38.5), 3.4% (n = 7) presented with local recurrent disease. Six out of the seven patients were also diagnosed with hematogenous metastases. Of the seven patients, three presented with at least one of the following risk factors: T4 tumor, N2 disease, incomplete mesorectal specimen, or positive CRM. Local failure was noted posteriorly (n = 3), laterally (n = 2), anteriorly (n = 1), and in the axial compartment (n = 1). Median time to relapse was 31.5 months (10.3-40.9). The median follow-up after local recurrence was 7.9 (95% CI 6.7-9.1) months, with an overall survival of 85.7%. CONCLUSIONS: TaTME provided satisfactory local recurrence outcomes, and the most common patterns of failure were in the central pelvis.


Asunto(s)
Laparoscopía , Neoplasias del Recto , Cirugía Endoscópica Transanal , Anciano , Humanos , Masculino , Recurrencia Local de Neoplasia/epidemiología , Complicaciones Posoperatorias , Neoplasias del Recto/cirugía , Recto , Estudios Retrospectivos , Centros de Atención Terciaria , Resultado del Tratamiento
13.
Cells ; 9(9)2020 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-32899484

RESUMEN

Hybrid nanoparticles from lipidic and polymeric components were assembled to serve as vehicles for the transfection of messenger RNA (mRNA) using different portions of the cationic lipid DOTAP (1,2-Dioleoyl-3-trimethylammonium-propane) and the cationic biopolymer protamine as model systems. Two different sequential assembly approaches in comparison with a direct single-step protocol were applied, and molecular organization in correlation with biological activity of the resulting nanoparticle systems was investigated. Differences in the structure of the nanoparticles were revealed by thorough physicochemical characterization including small angle neutron scattering (SANS), small angle X-ray scattering (SAXS), and cryogenic transmission electron microscopy (cryo-TEM). All hybrid systems, combining lipid and polymer, displayed significantly increased transfection in comparison to lipid/mRNA and polymer/mRNA particles alone. For the hybrid nanoparticles, characteristic differences regarding the internal organization, release characteristics, and activity were determined depending on the assembly route. The systems with the highest transfection efficacy were characterized by a heterogenous internal organization, accompanied by facilitated release. Such a system could be best obtained by the single step protocol, starting with a lipid and polymer mixture for nanoparticle formation.


Asunto(s)
Biopolímeros/química , Lípidos/química , Nanopartículas/química , ARN Mensajero/metabolismo , Transfección/métodos , Animales , Línea Celular , Ácidos Grasos Monoinsaturados/química , Femenino , Heparina/química , Humanos , Ratones , Ratones Endogámicos BALB C , Imagen Óptica , Tamaño de la Partícula , Compuestos de Amonio Cuaternario/química , ARN Mensajero/química
14.
Parasitol Res ; 119(7): 2139-2147, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32476061

RESUMEN

Coccidian parasites of fish have received considerably less attention than their terrestrial counterparts, and within piscine hosts, most studies have focused on freshwater fish. The present study aimed to describe oocyst morphology, phylogenetic affinities, and the impacts of coccidian parasites infecting the internal organs of a commercially valuable marine fish, the blue whiting (Micromesistius poutassou), captured off the Portuguese coast. As part of the phylogenetic analysis, sequences from coccidians infecting the pout (Trisopterus luscus) and the Atlantic chub mackerel (Scomber colias) were included, and the oocyst morphology of the coccidians infecting the former was also reported. Results showed that the prevalence of coccidiosis in the blue whiting was very high (> 82%), occurring in all analyzed organs, despite being more abundant in the liver. A significant negative correlation was found between the abundance of the parasites in the liver and host condition index (p < 0.05), which indicates a negative effect on the fitness of this host. Phylogenetic analyses of the parasites found in all three species examined identified three different species of Goussia, closely related to Goussia clupearum. Adding to previous research, we propose the existence of a fourth group of Goussia, the clupearum type, able to infect multiple organs and phylogenetic related with G. clupearum.


Asunto(s)
Coccidiosis/veterinaria , Eimeriidae/clasificación , Eimeriidae/patogenicidad , Enfermedades de los Peces/parasitología , Gadiformes/parasitología , Animales , Coccidiosis/parasitología , Eimeriidae/citología , Eimeriidae/genética , Hígado/parasitología , Oocistos/clasificación , Oocistos/citología , Oocistos/genética , Perciformes/parasitología , Filogenia , Portugal , Alimentos Marinos/parasitología
15.
Int J Surg Case Rep ; 44: 4-7, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29454229

RESUMEN

INTRODUCTION: Pancreatic cancer is the fourth major cause of cancer-related deaths. About 50% of the patients are diagnosed with advanced disease. Metastatic disease to the colon is a very rare entity with only 5 cases described in english literature. CASE PRESENTATION: Male, 60 years-old, presents to a surgical consult with the diagnosis of an adenocarcinoma of the sigmoid colon. The physical exam revealed a periumbilical nodule with suspicious features. The staging CT-scan showed a mass in the tail of the pancreas involving the spleen and left kidney, thickening of the sigmoid colon, multiple mesenteric masses and trabecular changes in the ischium, suggesting metastatic disease. The case was discussed by a multidisciplinary team and it was decided to do a biopsy of the umbilical nodule and review the specimen obtained in colonoscopy. Pathological analysis revealed a metastasis from pancreatic adenocarcinoma. The patient was proposed to start palliative chemotherapy for metastatic pancreatic cancer. After 2 cycles of FOLFOX the patient was admitted in the OR with a perforation of the sigmoid mass. He was submitted to a sigmoidectomy with end colostomy, with discharge at the 5th postoperative day. Pathological analysis of the specimen confirmed the pancreatic origin of the tumor. Patient proceeded with palliative treatment, with death 9 months after the diagnosis. DISCUSSION: Pancreatic metastasis to the colon is a very rare entity. Care should be taken when addressing these patients. CONCLUSION: Although rare, a sigmoid tumor in a patient with known pancreatic adenocarcinoma must raise the suspicion of metastasis.

16.
JBRA Assist Reprod ; 22(1): 52-55, 2018 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-29303236

RESUMEN

OBJECTIVE: This study aimed to assess a novel protocol designed to improve poor ovarian response through intra-ovarian androgenization. The endpoints were: number of oocytes and mature oocytes retrieved, fertilization, cancellation and pregnancy rates. METHODS: This prospective crossover study enrolled poor responders from previous ovarian stimulation cycles submitted to a novel protocol called ANDRO-IVF. The protocol included pretreatment with transdermal AndroGel(r) (Besins) 25 mg, oral letrozole 2.5 mg and subcutaneous hCG 2500 IU; cycle control was performed with estradiol valerate and micronized progesterone; ovarian stimulation was attained with gonadotropins FSH/LH 450 IU, GnRH antagonist and hCG 5000 IU. RESULTS: Fourteen poor responders were enrolled. One patient did not meet the inclusion criteria. Thirteen patients previously summited to the standard protocol were offered the ANDRO-IVF Protocol.-Standard Protocol: Mean age: 35.30 years; cancellation rate: 61.53%; mean number of MII oocytes retrieved per patient: 1.8; fertilization rate: 33.33%. Only two patients had embryo transfers, and none got pregnant.-ANDRO-IVF Protocol: Mean age: 35.83 years; cancellation rate: 7.69%; mean number of oocytes retrieved per patient: 5.58, MII oocytes: 3.91. ICSI was performed in 84.61% of the patients and a mean of 1.5 embryos were transferred per patient. Fertilization rate: 62.5%; cumulative pregnancy rate: 16.66%; mean duration of stimulation: 9.77 days. CONCLUSION: ANDRO-IVF allows intra-ovarian androgenization by increasing serum and intra-follicular androgen levels and preventing androgen aromatization. This protocol apparently improved clinical outcomes of poor responders in parameters such as number of oocytes retrieved and clinical pregnancy rates. Further randomized controlled trials are needed to confirm these findings.


Asunto(s)
Resistencia a Medicamentos , Fertilización In Vitro/métodos , Infertilidad Femenina/terapia , Inducción de la Ovulación/métodos , Adulto , Estudios Cruzados , Transferencia de Embrión/métodos , Femenino , Humanos , Recién Nacido , Masculino , Embarazo , Índice de Embarazo , Inyecciones de Esperma Intracitoplasmáticas , Insuficiencia del Tratamiento , Resultado del Tratamiento
17.
Mol Pharm ; 15(2): 642-651, 2018 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-29232147

RESUMEN

Insertion of high molecular weight messenger RNA (mRNA) into lyotropic lipid phases as model systems for controlled release formulations for the mRNA was investigated. Low fractions of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) were used as an anchor to load the mRNA into a lamellar lipid matrix. Dispersions of zwitterionic lipid in the aqueous phase in the presence of increasing fractions of mRNA and cationic lipid were prepared, and the molecular organization was investigated as a function of mRNA and cationic lipid fraction. Insertion of both cationic lipid and mRNA was clearly proven from the physicochemical characteristics. The d-spacing of the lipid bilayers, as determined by small-angle X-ray scattering (SAXS) measurements, responded sensitively to the amount of inserted DOTAP and mRNA. A concise model of the insertion of the mRNA in the lipid matrices was derived, indicating that the mRNA was accommodated in the aqueous slab between lipid bilayers. Depending on the DOTAP and mRNA fraction, a different excess of water was present in this slab. Results from further physicochemical characterization, including determination of free and bound mRNA, zeta potential, and calorimetry data, were in line with this assumption. The structure of these concentrated lipid/mRNA preparations was maintained upon dilution. The functionality of the inserted mRNA was proven by cell culture experiments using C2C12 murine myoblast cells with the luciferase-encoding mRNA. The described lipid phases as carriers for the mRNA may be applicable for different routes of local administration, where control of the release kinetics and the form of the released mRNA (bound or free) is required.


Asunto(s)
Portadores de Fármacos/química , Composición de Medicamentos/métodos , ARN Mensajero/administración & dosificación , Animales , Cationes/química , Línea Celular , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/química , Membrana Dobles de Lípidos/química , Liposomas , Luciferasas/genética , Ratones , Modelos Moleculares , Mioblastos , ARN Mensajero/síntesis química , Dispersión del Ángulo Pequeño , Transfección/métodos , Difracción de Rayos X
18.
Estud. psicol. (Campinas) ; 33(3): 477-488, tab
Artículo en Portugués | LILACS | ID: lil-787462

RESUMEN

Pretende-se caracterizar e comparar os níveis de criatividade e os estilos de pensar e criar de uma amostra de 210 estudantes universitários dos cursos de Gestão, Arquitetura e Música, atendendo ao seu gênero e idade, bem como, analisar a possível correlação entre ambos. O Test for Creative Thinking - Drawing Production e a versão Portuguesa da Escala de Estilos de Pensar e Criar operacionalizaram as variáveis em estudo. A análise das diferenças entre médias mostrou que os estudantes de Arquitetura apresentam níveis de criatividade superiores comparativamente aos estudantes de Gestão. No que se refere aos estilos de pensar e criar, apenas o grupo etário entre 18 e 24 anos se revelou como mais Cauteloso/Reflexivo. O estudo das correlações aponta para uma correlação negativa significativa entre os níveis de criatividade e o estilo Cauteloso/Reflexivo para a totalidade da amostra e uma correlação positiva significativa entre os níveis de criatividade e o estilo Inconformista/Transformador, nos estudantes de Gestão.


The objective of this study is to characterize and compare the levels of creativity and the thinking and creating styles on a sample of 210 Management, Architecture, and Music university students considering their gender and age. The present study also aims to analyze the possible correlation between the levels of creativity and thinking and creating styles. The Test for Creative Thinking-Drawing Production and the Portuguese version of Thinking and Creating Styles Scale were used. The difference between means showed that Architecture students had higher levels of creativity than Management students. The analysis of the thinking and creating styles showed that only the students aged 18-24 years were more Cautious/Reflective. A strong negative correlation between the levels of creativity and the Cautious/Reflective style was found for the entire sample; a strong positive correlation between the levels of creativity and the Non-Conforming/Transformer style was found for the management students. We suggest critical reflection on the figurative nature and the social desirability of the tests used, as well as on the possible importance of special training in a certain area (e.g. Architecture) to explain the variance in creativity and in thinking and creating styles.


Asunto(s)
Humanos , Adolescente , Adulto , Creatividad , Organización y Administración , Pensamiento
19.
Estud. psicol. (Campinas) ; 33(3): 477-488, jul.-set. 2016. tab
Artículo en Portugués | Index Psicología - Revistas | ID: psi-68292

RESUMEN

Pretende-se caracterizar e comparar os níveis de criatividade e os estilos de pensar e criar de uma amostra de 210 estudantes universitários dos cursos de Gestão, Arquitetura e Música, atendendo ao seu gênero e idade, bem como, analisar a possível correlação entre ambos. O Test for Creative Thinking - Drawing Production e a versão Portuguesa da Escala de Estilos de Pensar e Criar operacionalizaram as variáveis em estudo. A análise das diferenças entre médias mostrou que os estudantes de Arquitetura apresentam níveis de criatividade superiores comparativamente aos estudantes de Gestão. No que se refere aos estilos de pensar e criar, apenas o grupo etário entre 18 e 24 anos se revelou como mais Cauteloso/Reflexivo. O estudo das correlações aponta para uma correlação negativa significativa entre os níveis de criatividade e o estilo Cauteloso/Reflexivo para a totalidade da amostra e uma correlação positiva significativa entre os níveis de criatividade e o estilo Inconformista/Transformador, nos estudantes de Gestão.(AU)


The objective of this study is to characterize and compare the levels of creativity and the thinking and creating styles on a sample of 210 Management, Architecture, and Music university students considering their gender and age. The present study also aims to analyze the possible correlation between the levels of creativity and thinking and creating styles. The Test for Creative Thinking-Drawing Production and the Portuguese version of Thinking and Creating Styles Scale were used. The difference between means showed that Architecture students had higher levels of creativity than Management students. The analysis of the thinking and creating styles showed that only the students aged 18-24 years were more Cautious/Reflective. A strong negative correlation between the levels of creativity and the Cautious/Reflective style was found for the entire sample; a strong positive correlation between the levels of creativity and the Non-Conforming/Transformer style was found for the management students. We suggest critical reflection on the figurative nature and the social desirability of the tests used, as well as on the possible importance of special training in a certain area (e.g. Architecture) to explain the variance in creativity and in thinking and creating styles.(AU)


Asunto(s)
Humanos , Adolescente , Adulto , Creatividad , Organización y Administración , Pensamiento
20.
Fisioter. Bras ; 17(3): f: 221-I: 226, maio.-jun. 2016.
Artículo en Portugués | LILACS | ID: biblio-879068

RESUMEN

Introdução: Pacientes submetidos à cirurgia de revascularização do miocárdio apresentam redução da função pulmonar que, associado à imobilidade, favorece ao colapso alveolar e ao aumento da carga elástica pulmonar, provocando distúrbio ventilação-perfusão com alterações na oxigenação sanguínea e aumento no tempo de internação hospitalar. Objetivo: Avaliar o impacto na funcionalidade e no equilíbrio de pacientes submetidos à cirurgia cardíaca. Material e métodos: Foi realizado um estudo prospectivo e analítico com pacientes submetidos à cirurgia de revascularização do miocárdio. A funcionalidade foi avaliada através da medida de independência funcional no primeiro, terceiro e sexto dia do pós-operatório e o equilíbrio através da escala de equilíbrio de Berg. Foi realizada análise estatística descritiva e inferencial com análise do coeficiente de correlação de Spearman e nível de significância de 5%. Os dados obtidos da medida de independência funcional em diferentes dias de pós-operatório foram comparados utilizando o teste de Kruskal-Wallis. Resultados: Foram analisados 22 pacientes submetidos à cirurgia cardíaca. Observou-se aumento estatisticamente significativo (p < 0,05) nos escores do 1º, 3º e 6º dia do pós-operatórioda medida de independência funcional. Associação moderada entre a funcionalidade e o equilíbrio foi identificada. Em adição, houve associação fraca entre tempo de circulação extracorpórea, funcionalidade e equilíbrio. Conclusão: Cirurgia de revascularização do miocárdio apresenta impacto negativo na funcionalidade e no equilíbrio. (AU)


Introduction: Patients undergoing coronary artery bypass surgery have reduced lung function, which associated with immobility increases alveolar collapse and lung elastic load, causing disorder with ventilation-perfusion changes in blood oxygenation and increasing hospital stay. Objective: To evaluate the impact of cardiac surgery on the functionality and balance of patients. Methods: We conducted a prospective, analytical study of patients after coronary artery bypass surgery. The functionality was assessed by functional independence measure in the first, third and sixth day after surgery and the balance by the Berg Balance Scale. A descriptive and inferential statistical analysis with the Spearman correlation coefficient and 5% significance level was performed. The data obtained from functional independence measured on different days after surgery were compared using the Kruskal-Wallis test. Results: 22 patients were analyzed. Statistically significant increase was observed (p < 0.05) in scores of 1, 3 and 6 day in postoperative functional independence measure. Moderate association between the functionality and the balance has been identified. In addition, there was a weak association between the extracorporeal circulation time, functionality and balance. Conclusion: Coronary artery bypass surgery has a negative impact on the functionality and balance. (AU)


Asunto(s)
Humanos , Clasificación Internacional del Funcionamiento, de la Discapacidad y de la Salud , Revascularización Miocárdica , Especialidad de Fisioterapia , Cirugía Torácica
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