Microbacterium memoriense sp. nov., a member of the Actinomycetota from marine beach sediment of the north coast of Portugal.

The oceans harbour a myriad of unknown micro-organisms that remain unstudied because of a failure to establish the right growth conditions under laboratory conditions. To overcome this limitation, an isolation effort inspired by the iChip was performed using marine sediments from Memória beach, Portugal. A novel strain, PMIC_1C1BT, was obtained and subjected to a polyphasic study. Cells of strain PMIC_1C1BT were Gram-positive, rod-shaped, divided by binary fission and formed colonies that were shiny light-yellow. Based on its full 16S rRNA gene sequence, strain PMIC_1C1BT was phylogenetically associated to the genus Microbacterium and its closest relatives were Microbacterium aurum KACC 15219T (98.55 %), Microbacterium diaminobutyricum RZ63T (98.48 %) and Microbacterium hatanonis JCM 14558T (98.13 %). Strain PMIC_1C1BT had a genome size of 2 761 607 bp with 67.71 mol% of G+C content and 2582 coding sequences, which is lower than the genus average. Strain PMIC_1C1BT grew from 15 to 30 °C, optimally at 25 °C, at pH 6.0 to 11.0, optimally between pH 6.0 and 8.0, and from 0 to 5 % (w/v) NaCl, optimally between 2.0 and 3.0 %. It grew with casamino acids, glutamine, methionine, N-acetylglucosamine, sodium nitrate, tryptophan, urea and valine as sole nitrogen sources, and arabinose and cellobiose as sole carbon sources. The major cellular fatty acids were anteiso-C15 : 0, iso-C16 : 0 and iso-C17 : 0. Genome mining revealed the presence of four biosynthetic gene clusters (BGCs) with low similarities to other known BCGs. Based on the polyphasic data, strain PMIC_1C1BT is proposed to represent a novel species, for which the name Microbacterium memoriense sp. nov. (=CECT 30366T=LMG 32350T) is proposed.

Nanostructured Lipid Carriers Enriched Hydrogels for Skin Topical Administration of Quercetin and Omega-3 Fatty Acid.

Chronic skin exposure to external hostile agents (e.g., UV radiation, microorganisms, and oxidizing chemicals) may increase oxidative stress, causing skin damage and aging. Because of their well-known skincare and protective benefits, quercetin (Q) and omega-3 fatty acids (ω3) have attracted the attention of the dermocosmetic and pharmaceutical sectors. However, both bioactives have inherent properties that limit their efficient skin delivery. Therefore, nanostructured lipid carriers (NLCs) and enriched PFC® hydrogels (HGs) have been developed as a dual-approach vehicle for Q and/or ω3 skin topical administration to improve bioactives' stability and skin permeation. Two NLC formulations were prepared with the same lipid composition but differing in surfactant composition (NLC1-soy lecithin and poloxamer 407; NLC2-Tween® 80 and dioctyl sodium sulfosuccinate (DOSS)), which have an impact on physicochemical properties and pharmaceutical and therapeutic performance. Despite both NLCs presenting high Q loading capacity, NLC2's physicochemical properties make them more suitable for topical skin administration and ensure longer colloidal stability. Additionally, NLC2 demonstrated a more sustained Q release, indicating higher bioactive storage while improving permeability. The occlusive effect of NLCs-enriched HGs also has a positive impact on skin permeability. Q-loaded NLC2, with or without ω3, -enriched HGs demonstrated efficacy as antioxidant and photoprotective formulations as well as effective reduction in S. aureus growth, indicating that they constitute a promising approach for topical skin administration to prevent skin aging and other damaging cutaneous processes.

Non-infectious uveitis referred for pediatric rheumatologic assessment and management: a Portuguese retrospective study.

BACKGROUND: Pediatric uveitis poses challenges in diagnosis and treatment due to asymptomatic or oligosymptomatic presentations and high rates of intraocular complications. OBJECTIVES: This study aimed to characterize clinical manifestations and treatment approaches of pediatric uveitis patients in a northern Portuguese tertiary hospital. METHODOLOGY: A retrospective study was conducted involving forty-one patients diagnosed with uveitis between 2006 and 2021. All individuals identified by the Opthalmology department were referred to Pediatric Rheumatology outpatient clinic. Demographic, clinical, treatment, and intraocular complications data were collected. RESULTS: Of the patients, 78% had anterior uveitis, 17% had panuveitis, and 5% had intermediate uveitis. Uveitis associated with juvenile idiopathic arthritis was the most common cause (43.9%), predominantly in the oligoarticular, anti-nuclear antibody-positive subgroup. Complications were identified in 80.5% of the patients. Uveitis associated with JIA was diagnosed earlier (5,0 years (3,0-10,5) vs. 9,0 years (5,5-14,0), p=0,036), more frequently in asymptomatic patients (71% vs. 23%, p=0,010), had a more insidious installation (71% vs. 17%, p=0,004), and required more TNF inhibitor treatment (70% vs. 39%, p=0,027). CONCLUSION: The high rates of intraocular complications and systemic pathology association highlight the need for a combined approach of ophthalmology and pediatric rheumatology in the diagnosis and treatment of pediatric uveitis.

Streptomyces meridianus sp. nov. isolated from brackish water of the Tagus estuary in Alcochete, Portugal.

An isolation effort focused on sporogenous Actinomycetota from the Tagus estuary in Alcochete, Portugal, yielded a novel actinomycetal strain, designated MTZ3.1T, which was subjected to a polyphasic taxonomic study. MTZ3.1T is characterised by morphology typical of members of the genus Streptomyces, with light beige coloured substrate mycelium, which does not release pigments to the culture medium and with helicoidal aerial hyphae that differentiate into spores with a light-grey colour. The phylogeny of MTZ3.1T, based on the full 16S rRNA gene sequence, indicated that its closest relatives were Streptomyces alkaliterrae OF1T (98.48 %), Streptomyces chumphonensis KK1-2T (98.41 %), Streptomyces albofaciens JCM 4342T (98.34 %), Streoptomyces paromomycinus NBRC 15454T (98.34 %) and Streptomyces chrestomyceticus NRBC 13444T (98.34 %). Moreover, average nucleotide identity (ANI), average amino acid identity (AAI) and digital DNA-DNA hybridisation (dDDH) are below the species cutoff values (ANI 67.70 and 68.35 %, AAI 77.06 and 76.71 % and dDDH 22.10 and 21.50 % for S. alkaliterrae OF1T and S. chumphonensis KK1-2T, respectively). Whole genome sequencing revealed that MTZ3.1T has a genome of 5 644 485 bp with a DNA G+C content of 71.29 mol% and 5044 coding sequences. Physiologically, MTZ3.1T is strictly aerobic, able to grow at 15-37 °C, optimally at 25 °C and between pH5 and 8 and showed high salinity tolerance, growing with 0-10 %(w/v) NaCl. Major cellular fatty acids are C15 : 0, iso-C15 : 0, anteiso-C15 : 0 and iso-C16 : 0. Furthermore, it was able to utilise a variety of nitrogen and carbon sources. Antimicrobial screening indicated that MTZ3.1T has potent anti-Staphylococcus aureus activity. On the basis of the polyphasic data, MTZ3.1T is proposed to represent a novel species, Streptomyces meridianus sp. nov. (= CECT 30416T = DSM 114037T=LMG 32463T).

Streptomyces marispadix sp. nov., isolated from marine beach sediment.

A novel actinomycetal strain, designated M600PL45_2T, was isolated from marine sediments obtained from Ingleses beach, Porto, on the Northern Coast of Portugal and was subjected to a polyphasic taxonomic characterisation study. The here described Gram-reaction-positive strain is characterised by the production of a brown pigment in both solid and liquid medium and forms typical helical hyphae that differentiate into smooth spores. The results of a phylogenetic analysis based on the 16S rRNA gene sequence indicated that M600PL45_2T has a high similarity to two members of the genus Streptomyces, Streptomyces bathyalis ASO4wetT (98.51 %) and Streptomyces daqingensis NEAU ZJC8T (98.44 %). The genome of M600PL45_2T has a size of 6 695 159 bp, a DNA G+C content of 70.71 mol% and 5538 coding sequences. M600PL45_2T grows at 15-37 °C and with a maximal growth rate between 25 °C and 30 °C. Growth at pH 6.0 to 9.0 with the optimal range between 6.0 and 7.5 was observed. M600PL45_2T showed a high salinity tolerance, growing with 0-10 % (w/v) NaCl, with best growth with 1-3% (w/v) NaCl. Major cellular fatty acids are iso-C15:0 (25.03 %), anteiso-C15:0 (17.70) and iso-C16:0 (26.90 %). The novel isolate was able to grow in media containing a variety of nitrogen and carbon sources. An antimicrobial activity screening indicated that an extract of M600PL45_2T has inhibitory activity against Staphylococcus aureus. On the basis of the polyphasic data, M600PL45_2T (= CECT 30365T = DSM 114036T) is introduced as the type strain of a novel species, that we named Streptomyces marispadix sp. nov.

On the economic impacts of COVID-19: A text mining literature analysis.

The COVID-19 outbreak has affected everyday lives worldwide. As governments started to implement confinement and business closure measures, the economic impact was felt by entire societies immediately. The urgency of such a theme has led researchers to study the phenomenon. Accordingly, the purpose of this research is to provide the state of the art on relevant dimensions and hot topics of research to understand the economic impacts of COVID-19. In this survey, we conduct a text mining analysis of 301 articles published during 2020 which analyzed such economic impacts. By defining a set of relevant dimensions grounded on existing literature, we were able to extract a set of coherent topics that aggregate the collected articles, characterized by the predominance of a few sets of dimensions. We found that the impact on "financial markets" was widely studied, especially in relation to Asia. Next, we found a more diverse range of themes analyzed in Europe, from "government measures" to "macroeconomic variables." We also discovered that America has not received the same degree of attention, and "institutions," "Africa," or "other pandemics" were studied less. We anticipate that future research will proliferate focusing on several themes, from environmental issues to the effectiveness of government measures.

Formulation, Characterization, and Cytotoxicity Evaluation of Lactoferrin Functionalized Lipid Nanoparticles for Riluzole Delivery to the Brain.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a very poor prognosis. Its treatment is hindered by a lack of new therapeutic alternatives and the existence of the blood-brain barrier (BBB), which restricts the access of drugs commonly used in ALS, such as riluzole, to the brain. To overcome these limitations and increase brain targeting, riluzole-loaded nanostructured lipid carriers (NLC) were prepared and functionalized with lactoferrin (Lf), facilitating transport across the BBB by interacting with Lf receptors expressed in the brain endothelium. NLC were characterized with respect to their physicochemical properties (size, zeta potential, polydispersity index) as well as their stability, encapsulation efficiency, morphology, in vitro release profile, and biocompatibility. Moreover, crystallinity and melting behavior were assessed by DSC and PXRD. Nanoparticles exhibited initial mean diameters between 180 and 220 nm and a polydispersity index below 0.3, indicating a narrow size distribution. NLC remained stable over at least 3 months. Riluzole encapsulation efficiency was very high, around 94-98%. FTIR and protein quantification studies confirmed the conjugation of Lf on the surface of the nanocarriers, with TEM images showing that the functionalized NLC presented a smooth surface and uniform spherical shape. An MTT assay revealed that the nanocarriers developed in this study did not cause a substantial reduction in the viability of NSC-34 and hCMEC/D3 cells at a riluzole concentration up to 10 µM, being therefore biocompatible. The results suggest that Lf-functionalized NLC are a suitable and promising delivery system to target riluzole to the brain.

Singularidade e falibilismo: um diálogo inicial entre Milton Erickson e Charles Peirce / Singularity and fallibilism: Milton Erickson and Charles Peirce in dialogue / Singularité et faillibilisme: Milton Erickson et Charles Peirce en dialogue / Singularidad y falibilismo: un diálogo entre Milton Erickson y Charles Peirce

Resumo Este trabalho busca desenvolver uma aproximação entre o pensamento de Milton Erickson (1901-1980) e Charles Peirce (1839-1914), focalizando as noções de singularidade e falibilismo, com o objetivo de demonstrar as semelhanças existentes, o papel que desempenham em suas obras, como se relacionam e as implicações teóricas que geram para a hipnose. Descreve-se brevemente como o contexto histórico de cada um influenciou suas concepções iniciais. Em seguida, discute-se o modo como o falibilismo presente na concepção de semiose considera a singularidade dos fenômenos existentes e viabiliza o sinequismo, bem como os processos de evolução constante por meio de mudança de hábitos. Este estudo desenvolve a observação de Erickson sobre o sujeito enquanto signo representante de experiências de vida e relaciona as implicações teóricas do conceito de mente como semiose em torno do processo constitutivo de fenômenos acessíveis em experiência de transe.

Abstract This paper attempts a theoretical rapprochement between Milton Erickson's (1901-1980) and Charles Peirce's (1839-1914) thought, focusing on the concepts of singularity and fallibilism to point out their similarities, the role they play on their works, how they relate to each other, and their theoretical implications regarding hypnosis. First, the text briefly describes both authors' historical background and its influence over their early conceptions. Then, it discusses how fallibilism, present in the concept of semiosis, considers the singularity of existing phenomena and enables synechism, as well as the processes of constant evolution through change of habits. This study develops Erickson's observation about the subject as a representative sign of life experiences and relates, initially, the theoretical implications of mind-as-semiosis concerning the constitutive process of phenomena accessible in trance experience.

Résumé Cet article tente un rapprochement entre la pensée de Milton Erickson (1901-1980) et celle de Charles Peirce (1839-1914), en se concentrant sur les concepts de singularité et de faillibilisme afin de mettre en évidence leurs similitudes, le rôle qu'ils jouent dans leurs œuvres, la façon dont ils se rapportent l'un à l'autre, et leurs implications théoriques concernant l'hypnose. Tout d'abord, le texte décrit brièvement le contexte historique des deux auteurs et son influence sur leurs premières conceptions. Ensuite, il aborde la manière dont le faillibilisme, présent dans le concept de sémiose, considère la singularité des phénomènes existants et permet le sinéquisme, ainsi que les processus d'évolution constante par le changement d'habitudes. Cette étude développe l'observation d'Erickson sur le sujet comme signe représentatif des expériences de vie et relate, dans un premier temps, les implications théoriques de l'esprit comme sémiose concernant le processus constitutif des phénomènes accessibles dans l'expérience de transe.

Resumen Este trabajo busca desarrollar una aproximación entre el pensamiento de Milton Erickson (1901-1980) y el de Charles Peirce (1839-1914) enfocándose en las nociones de singularidad y falibilismo para demostrar las similitudes existentes, el papel que juegan en sus trabajos, cómo se relacionan y las implicaciones teóricas que generan para la hipnosis. El artículo describe brevemente el contexto histórico de ambos autores y cómo esto influyó en sus concepciones iniciales. A seguir, se discute cómo el falibilismo presente en la concepción de la semiosis considera la singularidad de los fenómenos existentes y viabiliza el sinequismo, así como los procesos de evolución constante a través del cambio de hábitos. Este estudio desarrolla la observación de Erickson sobre el sujeto como signo representativo de las experiencias vitales y relaciona, inicialmente, las implicaciones teóricas del concepto de mente como semiosis en torno al proceso constitutivo de los fenómenos accesibles en la experiencia de trance.

Poly(Lactic Acid)/Graphite Nanoplatelet Nanocomposite Filaments for Ligament Scaffolds.

The anterior cruciate ligament (ACL) is one of the most prone to injury in the human body. Due to its insufficient vascularization and low regenerative capacity, surgery is often required when it is ruptured. Most of the current tissue engineering (TE) strategies are based on scaffolds produced with fibers due to the natural ligament's fibrous structure. In the present work, composite filaments based on poly(L-lactic acid) (PLA) reinforced with graphite nanoplatelets (PLA+EG) as received, chemically functionalized (PLA+f-EG), or functionalized and decorated with silver nanoparticles [PLA+((f-EG)+Ag)] were produced by melt mixing, ensuring good filler dispersion. These filaments were produced with diameters of 0.25 mm and 1.75 mm for textile-engineered and 3D-printed ligament scaffolds, respectively. The resulting composite filaments are thermally stable, and the incorporation of graphite increases the stiffness of the composites and decreases the electrical resistivity, as compared to PLA. None of the filaments suffered significant degradation after 27 days. The composite filaments were processed into 3D scaffolds with finely controlled dimensions and porosity by textile-engineered and additive fabrication techniques, demonstrating their potential for ligament TE applications.

Electrospun fibers for vaginal administration of tenofovir disoproxil fumarate and emtricitabine in the context of topical pre-exposure prophylaxis.

Women are particularly vulnerable to sexual HIV-1 transmission. Oral pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) is highly effective in avoiding new infections in men, but protection has only been shown to be moderate in women. Such differences have been associated, at least partially, to poor drug penetration of the lower female genital tract and the need for strict adherence to continuous daily oral intake of TDF/FTC. On-demand topical microbicide products could help circumvent these limitations. We developed electrospun fibers based on polycaprolactone (PCL fibers) or liposomes associated to poly(vinyl alcohol) (liposomes-in-PVA fibers) for the vaginal co-delivery of TDF and FTC, and assessed their pharmacokinetics in mice. PCL fibers and liposomes-in-PVA fibers were tested for morphological and physicochemical properties using scanning electron microscopy, differential scanning calorimetry and X-ray diffractometry. Fibers featured organoleptic and mechanical properties compatible with their suitable handling and vaginal administration. Fluorescent quenching of mucin in vitro - used as a proxy for mucoadhesion - was intense for PCL fibers, but mild for liposomes-in-PVA fibers. Both fibers were shown safe in vitro and able to rapidly release drug content (15-30 min) under sink conditions. Liposomes-in-PVA fibers allowed increasing genital drug concentrations after a single intravaginal administration when compared to continuous daily treatment for five days with 25-times higher oral doses. For instance, the levels of tenofovir and FTC in vaginal lavage were around 4- and 29-fold higher, respectively. PCL fibers were also superior to oral treatment, although to a minor extent (approximately 2-fold higher drug concentrations in lavage). Vaginal tissue drug levels were generally low for all treatments, while systemic drug exposure was negligible in the case of fibers. These data suggest that proposed fibers may provide an interesting alternative or an ancillary option to oral PrEP in women.

Lipid Nanosystems and Serum Protein as Biomimetic Interfaces: Predicting the Biodistribution of a Caffeic Acid-Based Antioxidant.

PURPOSE: AntiOxCIN3 is a novel mitochondriotropic antioxidant developed to minimize the effects of oxidative stress on neurodegenerative diseases. Prior to an investment in pre-clinical in vivo studies, it is important to apply in silico and biophysical cell-free in vitro studies to predict AntiOxCIN3 biodistribution profile, respecting the need to preserve animal health in accordance with the EU principles (Directive 2010/63/EU). Accordingly, we propose an innovative toolbox of biophysical studies and mimetic models of biological interfaces, such as nanosystems with different compositions mimicking distinct membrane barriers and human serum albumin (HSA). METHODS: Intestinal and cell membrane permeation of AntiOxCIN3 was predicted using derivative spectrophotometry. AntiOxCIN3 -HSA binding was evaluated by intrinsic fluorescence quenching, synchronous fluorescence, and dynamic/electrophoretic light scattering. Steady-state and time-resolved fluorescence quenching was used to predict AntiOxCIN3-membrane orientation. Fluorescence anisotropy, synchrotron small- and wide-angle X-ray scattering were used to predict lipid membrane biophysical impairment caused by AntiOxCIN3 distribution. RESULTS AND DISCUSSION: We found that AntiOxCIN3 has the potential to permeate the gastrointestinal tract. However, its biodistribution and elimination from the body might be affected by its affinity to HSA (>90%) and by its steady-state volume of distribution (VDSS =1.89± 0.48 L∙Kg-1). AntiOxCIN3 is expected to locate parallel to the membrane phospholipids, causing a bilayer stiffness effect. AntiOxCIN3 is also predicted to permeate through blood-brain barrier and reach its therapeutic target - the brain. CONCLUSION: Drug interactions with biological interfaces may be evaluated using membrane model systems and serum proteins. This knowledge is important for the characterization of drug partitioning, positioning and orientation of drugs in membranes, their effect on membrane biophysical properties and the study of serum protein binding. The analysis of these interactions makes it possible to collect valuable knowledge on the transport, distribution, accumulation and, eventually, therapeutic impact of drugs which may aid the drug development process.

Novel amphiphilic chitosan micelles as carriers for hydrophobic anticancer drugs.

Chitosan was grafted with O-methyl-O'-succinylpolyethylene glycol and oleic acid after a two-step carbodiimide coupling. The structural and physicochemical characterization of the compounds confirmed the successful conjugation of the hydrophilic and hydrophobic moieties to the chitosan backbone. The amphiphilic chitosan derivative obtained allowed the formation of polymeric micelles with an average size of 140 nm, a polydispersity index <0.234, and a positive superficial charge. Camptothecin, used as a model hydrophobic drug, was successfully carried into the polymeric micelles with an encapsulation efficiency of 78%. The in vitro drug release was evaluated in simulated gastrointestinal fluids, exhibiting a low release of camptothecin in gastric media and a controlled release in intestinal fluids. Furthermore, it was demonstrated that chitosan micelles were able to stabilize camptothecin, protecting up to 75% of the drug from hydrolysis, preserving its active lactone form. This new chitosan amphiphilic system exhibits great potential to load hydrophobic drugs, acting as a promising delivery system.

Prediction of paclitaxel pharmacokinetic based on in vitro studies: Interaction with membrane models and human serum albumin.

Interactions of paclitaxel (PTX) with models mimicking biological interfaces (lipid membranes and serum albumin, HSA) were investigated to test the hypothesis that the set of in vitro assays proposed can be used to predict some aspects of drug pharmacokinetics (PK). PTX membrane partitioning was studied by derivative spectrophotometry; PTX effect on membrane biophysics was evaluated by dynamic light scattering, fluorescence anisotropy, atomic force microscopy and synchrotron small/wide-angle X-ray scattering; PTX distribution/molecular orientation in membranes was assessed by steady-state/time-resolved fluorescence and computer simulations. PTX binding to HSA was studied by fluorescence quenching, derivative spectrophotometry and dynamic/electrophoretic light scattering. PTX high membrane partitioning is consistent with its efficacy crossing cellular membranes and its off-target distribution. PTX is closely located in the membrane phospholipids headgroups, also interacting with the hydrophobic chains, and causes a major distortion of the alignment of the membrane phospholipids, which, together with its fluidizing effect, justifies some of its cellular toxic effects. PTX binds strongly to HSA, which is consistent with its reduced distribution in target tissues and toxicity by bioaccumulation. In conclusion, the described set of biomimetic models and techniques has the potential for early prediction of PK issues, alerting for the required drug optimizations, potentially minimizing the number of animal tests used in the drug development process.

Rational Development of Liposomal Hydrogels: A Strategy for Topical Vaginal Antiretroviral Drug Delivery in the Context of HIV Prevention.

HIV/AIDS stands as a global burden, and vaginal microbicides constitute a promising strategy for topical pre-exposure prophylaxis. Preceding the development of a microbicide containing tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC), in silico and in vitro studies were performed to evaluate the physicochemical characteristics of both drugs, and to study their biophysical impact in lipid model systems. Results from these pre-formulation studies defined hydrogels as adequate vehicles to incorporate TDF-loaded liposomes and FTC. After studying interactions with mucin, zwitterionic liposomes with a mean diameter of 134 ± 13 nm, an encapsulation TDF efficiency of approximately 84%, and a transition temperature of 41 °C were selected. The chosen liposomal formulation was non-cytotoxic to HEC-1-A and CaSki cells, and was able to favor TDF permeation across polysulfone membranes (Jss = 9.9 µg·cm-2·h-1). After the incorporation of TDF-loaded liposomes and FTC in carbomer hydrogels, the drug release profile was sustained over time, reaching around 60% for both drugs within 3-6 h, and best fitting the Weibull model. Moreover, liposomal hydrogels featured pseudoplastic profiles that were deemed suitable for topical application. Overall, the proposed liposomal hydrogels may constitute a promising formulation for the vaginal co-delivery of TDF/FTC.

Iconicidade como alternativa de explicação para a hipnose de Milton Erickson / Iconicity as an alternative explanation of Milton Erickson's hypnosis / Iconicidad como alternativa de explicación para la hipnosis de Milton Erickson

O presente trabalho busca propor uma alternativa de explicação para a hipnose de Milton Erickson (1901-1980) a partir da noção semiótica de iconicidade, que consiste na capacidade dos signos em transmitir qualidades de seus objetos. Neste trabalho, a possibilidade de explicação será desenvolvida, a partir de uma ilustração clínica de Erickson, em torno da discussão sobre três questões principais: a heterogeneidade da experiência hipnótica, a temporalidade e o papel do eu face às influências do inconsciente. Ao apontar as diferentes potencialidades lógicas dos signos, a iconicidade oferece subsídios de grande pertinência para compreender a diversidade do tecido vivido que compõe a experiência hipnótica, a presentificação da experiência de tempo e as diferentes formas de inserção e relação do eu quanto ao universo inconsciente que o precede. Nesse sentido, as contribuições daí consequentes são de grande pertinência para favorecer o afastamento de uma lógica puramente tecnicista da obra de Erickson, como também debates e apropriações coletivas em torno da mesma, condições necessárias para seu progresso como proposta de pensamento e terapia.

This study's intent is to propose an alternative explanation for Milton Erickson's (1901-1980) hypnosis from the semiotics notion of iconicity, which consists on the capacity of signs to transmit qualities of its objects. In this study, the possible explanation unfolds from a clinical illustration of Erickson into a discussion addressing three main subjects: the heterogeneity of the hypnotic experience, the temporality, and the roles of the ego acing the unconscious influences. By pointing the different logical potentialities of signs, iconicity offers subsidies of great pertinence to comprehend the diversity of the living fabric which composes the hypnotic experience, the presentification of time experience, and the different forms of insertion and relation between the ego and the unconscious universe that precedes him. In that sense, the consequent contributions are of great pertinence, favoring a purely technical logic with its debates and surrounding collective appropriations to move away from Erickson's work, necessary conditions for its progress as proposal of thought a therapy.

El presente trabajo propone una alternativa de explicación para la hipnosis de Milton Erickson (19011980) a partir de la noción semiótica de iconicidad, que consiste en la capacidad de los signos para transmitir cualidades de sus objetos. En este trabajo, la posibilidad de explicación será desarrollada, a partir de una ilustración clínica de Erickson, en torno a la discusión sobre tres cuestiones principales: la heterogeneidad de la experiencia hipnótica, la temporalidad y el papel del yo frente a las influencias del inconsciente. De este modo, al senalar las diferentes potencialidades lógicas de los signos, la iconicidad ofrece subsidios de gran importancia para comprender la diversidad del tejido vivido que compone la experiencia hipnótica, la presentificación de la experiencia del tiempo y las diferentes formas de inserción y relación del yo en cuanto al universo inconsciente que lo precede. En ese sentido, las contribuciones consecuentes son de gran importancia para favorecer el alejamiento de una lógica puramente tecnicista de la obra de Erickson, así como debates e apropiaciones colectivas en torno a la misma, condiciones necesarias para su progreso como propuesta de pensamiento y terapia.

A Molecular Biophysical Approach to Diclofenac Topical Gastrointestinal Damage.

Diclofenac (DCF), the most widely consumed non-steroidal anti-inflammatory drug (NSAID) worldwide, is associated with adverse typical effects, including gastrointestinal (GI) complications. The present study aims to better understand the topical toxicity induced by DCF using membrane models that mimic the physiological, biophysical, and chemical environments of GI mucosa segments. For this purpose, phospholipidic model systems that mimic the GI protective lining and lipid models of the inner mitochondrial membrane were used together with a wide set of techniques: derivative spectrophotometry to evaluate drug distribution at the membrane; steady-state and time-resolved fluorescence to predict drug location at the membrane; fluorescence anisotropy, differential scanning calorimetry (DSC), dynamic light scattering (DLS), and calcein leakage studies to evaluate the drug-induced disturbance on membrane microviscosity and permeability; and small- and wide-angle X-ray scattering studies (SAXS and WAXS, respectively), to evaluate the effects of DCF at the membrane structure. Results demonstrated that DCF interacts chemically with the phospholipids of the GI protective barrier in a pH-dependent manner and confirmed the DCF location at the lipid headgroup region, as well as DCF's higher distribution at mitochondrial membrane contact points where the impairment of biophysical properties is consistent with the uncoupling effects reported for this drug.

Spectroscopic Studies as a Toolbox for Biophysical and Chemical Characterization of Lipid-Based Nanotherapeutics.

The goal of this study is to provide tools to minimize trial-and-error in the development of novel lipid-based nanotherapeutics, in favor of a rational design process. For this purpose, we present case-study examples of biophysical assays that help addressing issues of lipid-based nanotherapeutics' profiling and assist in the design of lipid nanocarriers for therapeutic usage. The assays presented are rooted in spectroscopic methods (steady-state and time-resolved fluorescence; UV-Vis derivative spectroscopy; fluorescence anisotropy and fluorescence lifetime image microscopy) and allow accessing physical-chemical interactions between drugs and lipid nanocarriers, as well as studying interactions between lipid-based nanotherapeutics and membranes and/or proteins, as this is a key factor in predicting their therapeutic and off target effects. Derivative spectroscopy revealed Naproxen's high distribution (LogD ≈ 3) in different lipid-based nanocarriers (micelles and unilamellar or multilamellar vesicles) confirming the adequacy of such systems for encapsulating this anti-inflammatory drug. Fluorescence quenching studies revealed that the anti-inflammatory drugs Acemetacin and Indomethacin can reach an inner location at the lipid nanocarrier while being anchored with its carboxylic moiety at the polar headgroup. The least observed quenching effect suggested that Tolmetin is probably located at the polar headgroup region of the lipid nanocarriers and this superficial location may translate in a fast drug release from the nanocarriers. Fluorescent anisotropy measurements indicated that the drugs deeply buried within the lipid nanocarrier where the ones that had a greater fluidizing effect which can also translate in a faster drug release. The drug binding strength to serum albumin was also compared for a free drug (Clonixin) or for the same drug after encapsulation in a lipid nanocarrier DSPC:DODAP (2:1). Under both conditions there is a strong binding to serum albumin, at one binding site, suggesting the need to produce a stealth nanosystem. Finally the cellular uptake of lipid nanocarriers loaded with Daunorubicin was investigated in cancer cells using fluorescence lifetime imaging microscopy. From the images obtained it was possible to conclude that even at short incubation times (15 min) there was a distribution of the drug in the cytoplasm, whereas for longer incubation periods (4 h) the drug has reached the nucleus.

Enhancement of graphene visibility on transparent substrates by refractive index optimization.

Optical reflection microscopy is one of the main imaging tools to visualize graphene microstructures. Here is reported a novel method that employs refractive index optimization in an optical reflection microscope, which greatly improves the visibility of graphene flakes. To this end, an immersion liquid with a refractive index that is close to that of the glass support is used in-between the microscope lens and the support improving the contrast and resolution of the sample image. Results show that the contrast of single and few layer graphene crystals and structures can be enhanced by a factor of 4 compared to values commonly achieved with transparent substrates using optical reflection microscopy lacking refractive index optimization.