[Correction to the Article "Hansen's Disease: An Unusual Manifestation of an Ancient Disease", Published on Acta Med Port 2024 Mar;37(3):215-219]. / Errata ao Artigo "Doença de Hansen: Apresentação Incomum de uma Doença Antiga", Publicado em Acta Med Port 2024 Mar;37(3):215-219.

On page 215, list of authors, where it reads (in red): Mário FERREIRA1, Carlos GRIJÓ2, Joana PAULO1, Marta FONSECA1, Zélia NEVES1 It should read (in bold): Mário FERREIRA1, Carlos GRIJÓ2, Joana PAULO1, Marta FONSECA1, Zélia NEVES1, Rita BOUCEIRO MENDES3, Pedro VASCONCELOS3 On the same page 215, footer (authors affiliation), where it reads (in red): 1. Medicina III. Hospital Fernando Fonseca. Amadora. Portugal. 2. Serviço de Medicina Interna. Centro Hospitalar Universitário de São João. Porto. Portugal. It should read (in bold): 1. Medicina III. Hospital Fernando Fonseca. Amadora. Portugal. 2. Serviço de Medicina Interna. Centro Hospitalar Universitário de São João. Porto. Portugal. 3. Serviço de Dermatologia. Hospital de Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisboa. Portugal. Article published with errors: https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/20599.

Na página 215, na linha de autoria onde se lê, (a vermelho): Mário FERREIRA1, Carlos GRIJÓ2, Joana PAULO1, Marta FONSECA1, Zélia NEVES1 Deverá ler-se (a negrito): Mário FERREIRA1, Carlos GRIJÓ2, Joana PAULO1, Marta FONSECA1, Zélia NEVES1, Rita BOUCEIRO MENDES3, Pedro VASCONCELOS3 Na mesma página 215, em rodapé (afiliação dos autores), onde se lê (a vermelho): 1. Medicina III. Hospital Fernando Fonseca. Amadora. Portugal. 2. Serviço de Medicina Interna. Centro Hospitalar Universitário de São João. Porto. Portugal. Deverá ler-se (a negrito): 1. Medicina III. Hospital Fernando Fonseca. Amadora. Portugal. 2. Serviço de Medicina Interna. Centro Hospitalar Universitário de São João. Porto. Portugal. 3. Serviço de Dermatologia. Hospital de Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisboa. Portugal. Artigo publicado com erros: https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/20599.

Tackling the tumor microenvironment - how can complex tumor models in vitro aid oncology drug development?

INTRODUCTION: Identifying effective cancer drugs remains an inefficient process. Drug efficacy in traditional preclinical cancer models translates poorly into therapy in the clinic. Implementation of preclinical models that incorporate the tumor microenvironment (TME) is needed to improve selection of active drugs prior to clinical trials. AREAS COVERED: Progression of cancer results from the behavior of cancer cells in concert with the host's histopathological background. Nonetheless, complex preclinical models with a relevant microenvironment have yet to become an integral part of drug development. This review discusses existing models and provides a synopsis of active areas of cancer drug development where implementation would be of value. Their contribution to finding therapeutics in immune oncology, angiogenesis, regulated cell death and targeting tumor fibroblasts as well as optimization of drug delivery, combination therapy, and biomarkers of efficacy is considered. EXPERT OPINION: Complex tumor models in vitro (CTMIVs) that mimic the organotypic architecture of neoplastic tumors have boosted research into TME influence on traditional cytoreductive chemotherapy as well as the detection of specific TME targets. Despite advances in technical prowess, CTMIVs can only address specific aspects of cancer pathophysiology.

Exploring Metabolic Signatures of Ex Vivo Tumor Tissue Cultures for Prediction of Chemosensitivity in Ovarian Cancer.

Predicting patient response to treatment and the onset of chemoresistance are still major challenges in oncology. Chemoresistance is deeply influenced by the complex cellular interactions occurring within the tumor microenvironment (TME), including metabolic crosstalk. We have previously shown that ex vivo tumor tissue cultures derived from ovarian carcinoma (OvC) resections retain the TME components for at least four weeks of culture and implemented assays for assessment of drug response. Here, we explored ex vivo patient-derived tumor tissue cultures to uncover metabolic signatures of chemosensitivity and/or resistance. Tissue cultures derived from nine OvC cases were challenged with carboplatin and paclitaxel, the standard-of-care chemotherapeutics, and the metabolic footprints were characterized by LC-MS. Partial least-squares discriminant analysis (PLS-DA) revealed metabolic signatures that discriminated high-responder from low-responder tissue cultures to ex vivo drug exposure. As a proof-of-concept, a set of potential metabolic biomarkers of drug response was identified based on the receiver operating characteristics (ROC) curve, comprising amino acids, fatty acids, pyrimidine, glutathione, and TCA cycle pathways. Overall, this work establishes an analytical and computational platform to explore metabolic features of the TME associated with response to treatment, which can leverage the discovery of biomarkers of drug response and resistance in OvC.

UVB phototherapy in the treatment of vitiligo: State of the art and clinical perspectives.

Vitiligo is a chronic pigmentary skin disorder that results in white, hypopigmented macules and patches. It causes a considerable psychological and emotional burden on the affected individuals and their families. Several therapeutic options have been employed in vitiligo including topical and oral drugs, surgical techniques, and phototherapy which is considered the cornerstone treatment. Different wavelengths and modalities are available, but narrowband UVB (NB-UVB) is considered the safest and the most effective phototherapy alternative. NB-UVB acts on multiple steps in vitiligo pathogenesis, and it is capable of inducing stabilization and repigmentation of vitiligo lesions. Technological advances have led to the development of both new phototherapy devices and new medical and surgical therapeutic options that can be combined with phototherapy to achieve optimal results. There is no standard treatment, and individual patient and disease characteristics should be considered. We review the current evidence in what concerns UVB phototherapy for vitiligo treatment, including novel combination treatments that may help to provide the best care for these patients.

Application of LDH assay for therapeutic efficacy evaluation of ex vivo tumor models.

The current standard preclinical oncology models are not able to fully recapitulate therapeutic targets and clinically relevant disease biology, evidenced by the 90% attrition rate of new therapies in clinical trials. Three-dimensional (3D) culture systems have the potential to enhance the relevance of preclinical models. However, the limitations of currently available cellular assays to accurately evaluate therapeutic efficacy in these models are hindering their widespread adoption. We assessed the compatibility of the lactate dehydrogenase (LDH) assay in 3D spheroid cultures against other commercially available readout methods. We developed a standardized protocol to apply the LDH assay to ex vivo cultures, considering the impact of culture growth dynamics. We show that accounting for growth rates and background release levels of LDH are sufficient to make the LDH assay a suitable methodology for longitudinal monitoring and endpoint assessment of therapeutic efficacy in both cell line-derived xenografts (xenospheres) and patient-derived explant cultures. This method has the added value of being non-destructive and not dependent on reagent penetration or manipulation of the parent material. The establishment of reliable readout methods for complex 3D culture systems will further the utility of these tumor models in preclinical and co-clinical drug development studies.

Fighting S. aureus catheter-related infections with sophorolipids: Electing an antiadhesive strategy or a release one?

Staphylococcus aureus medical devices related-infections, such as blood stream catheter are of major concern. Their prevention is compulsory and strategies, not prone to the development of resistance, to prevent S. aureus biofilms on catheter surfaces (e.g. silicone) are needed. In this work two different approaches using sophorolipids were studied to prevent S. aureus biofilm formation on medical grade silicone: i) an antiadhesive strategy through covalent bond of sophorolipids to the surface; ii) and a release strategy using isolated most active sophorolipids. Sophorolipids produced by Starmerella bombicola, were characterized by UHPLC-MS and RMN, purified by automatic flash chromatography and tested for their antimicrobial activity towards S. aureus. Highest antimicrobial activity was observed for C18:0 and C18:1 diacetylated lactonic sophorolipids showing a MIC of 50 µg mL-1. Surface modification with acidic or lactonic sophorolipids when evaluating the anti-adhesive or release strategy, respectively, was confirmed by contact angle, FTIR-ATR and AFM analysis. When using a mixture of acidic sophorolipids covalently bonded to silicone surface as antiadhesive strategy cytocompatible surfaces were obtained and a reduction of 90 % on biofilm formation was observed. Nevertheless, if a release strategy is adopted with purified lactonic sophorolipids a higher effect is achieved. Most promising compound was C18:1 diacateylated lactonic sophorolipid that showed no cellular viability reduction when a concentration of 1.5 mg mL-1 was selected and a reduction on biofilm around 5 log units. Results reinforce the applicability of these antimicrobial biosurfactants on preventing biofilms and disclose that their antimicrobial effect is imperative when comparing to their antiadhesive properties.

Seeking faster, alternative methods for glycolipid biosurfactant characterization and purification.

Biosurfactants have been investigated as potential alternatives for synthetic surfactants in several areas, for example, in environmental and pharmaceutical fields. In that regard, extensive research has been carried out with sophorolipids and rhamnolipids that also present various biological properties with therapeutic significance. These biosurfactants are obtained as complex mixtures of slightly different molecules, and thus when studying these microbial glycolipids, the ability to identify and purify the produced compounds is of extreme importance. This study aimed to develop improved methodologies for the identification, separation, and purification of sophorolipids and rhamnolipids. Therefore, an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was modified to ensure faster characterization of both sophorolipids and rhamnolipids, enabling the identification and fragmentation pattern description of 10 and 13 congeners, respectively. The separation and purification of these biosurfactants was achieved with novel reversed-phase solid-phase extraction methods guaranteeing the isolation of different glycolipids, including those considered for their significant biological activity (e.g. antimicrobial, anticancer). It was possible to isolate sophorolipids and rhamnolipids with purity of 94% and 99%, respectively. The methods presented herein can be easily implemented and are expected to make purification of these biosurfactants easier, facilitating the study of their individual properties in further works.

A redução da idade de responsabilidade criminal na perspectiva de adolescentes / Lowering the minimum age of criminal responsibility from the perspective of adolescents / La reducción de la edad de responsabilidad penal desde la perspectiva de adolescentes

A proposta de emenda à Constituição Federal (PEC) 171/1993 prevê a redução da maioridade penal no Brasil de 18 para 16 anos. Essa proposta foi votada pela Câmara dos Deputados e está, atualmente, no Senado Federal, contando com intenso apoio do atual presidente. Embora haja evidências de que a idade não se relaciona a indicadores de violência, a opinião pública se manifesta favorável à medida. Diante disso, considera-se primordial escutar a fala dos próprios adolescentes sobre essa questão. Este trabalho objetivou investigar a perspectiva de adolescentes sobre a redução da maioridade penal. Participaram 25 adolescentes provenientes de uma escola pública e cinco que estavam em cumprimento de medida socioeducativa, todos na faixa etária entre 12 e 17 anos. A coleta de dados ocorreu por meio de rodas de conversa com o primeiro grupo e entrevistas com o segundo. Foram escritos relatos em ambos os momentos da coleta. Para a análise, esses relatos foram lidos e discutidos em grupo pelos pesquisadores. Os resultados apontam alguns analisadores que emergiram a partir das rodas e entrevistas: adolescência, raiva, medo, questão social, lei e violência. Observou-se que os participantes foram além de um posicionamento opinativo, produzindo importantes elaborações sobre o tema que foram disparadores capazes de abordar problemáticas próprias da adolescência e da realidade social. Considera-se que é tarefa ímpar da psicologia trazer à luz opiniões como as dos adolescentes objeto desta pesquisa.(AU)

The proposed amendment to the Federal Constitution (PEC 171/1993) of Brazil provides for the lowering of the minimum age of criminal responsibility from 18 to 16 years. This proposal was voted by the House of Representatives and is currently in the Federal Senate, being strongly supported by the elected President. Despite evidence showing that age is unrelated to indicators of violence, public opinion supports the measure, indicating the urge for listening to the opinion of adolescents on this subject. This study aimed to investigate the perspective of adolescents regarding the lowering of the minimum age of criminal responsibility in Brazil. The study sample consisted of 25 adolescents from a public school and five who fulfilled socioeducational measures, all aged from 12 to 17 years. Data on the first group were collected by means of conversation circles, and on the second group by interviews. A written record was kept for both moments of data collection, which was later read and discussed among the researchers involved in the study. The results indicate some common themes emerging from circles and interviews, namely: adolescence, anger, fear, social issues, law, and violence. When sharing their perspectives on the subject, participants went beyond an opinionated position, producing important elaborations. This also triggered the possibility of addressing specific problems of adolescence and social reality. In this scenario, Psychology plays a key role in bringing opinions to light, such as those of adolescents participating in this study - who tend to stay on the sidelines.(AU)

La propuesta de enmienda a la Constitución Federal (PEC 171/1993) prevé la reducción de la edad mínima de responsabilidad penal en Brasil de 18 para 16 años. Esta propuesta fue votada por la Cámara de Diputados y está actualmente en el Senado Federal, contando con intenso apoyo del actual Presidente. Aunque hay evidencias de que la edad no se relaciona con los indicadores de violencia, la opinión pública se manifiesta favorable a la medida. Por lo tanto, se considera esencial escuchar el discurso de los adolescentes sobre este tema. Este estudio tuvo como objetivo investigar la perspectiva de algunos adolescentes sobre la reducción de la edad de responsabilidad penal. Participaron 25 adolescentes provenientes de una escuela pública y cinco que estaban en cumplimiento de medida socioeducativa, todos en el grupo de edad de entre 12 y 17 años. La recopilación de datos se realizó por medio de círculos de conversación con el primer grupo y de entrevistas con el segundo. Los informes fueron escritos en ambas ocasiones. Para el análisis, los investigadores leyeron y discutieron estos informes en grupos. Los resultados muestran algunos analizadores que surgieron de los círculos y las entrevistas: adolescencia, ira, miedo, problemas sociales, derecho y violencia. Se observó que los participantes fueron más allá de una posición de opinión, produciendo elaboraciones importantes sobre el tema; esto también desencadenó la posibilidad de abordar problemas específicos de la adolescencia y la realidad social. Se considera que es una tarea única de la psicología sacar a la luz opiniones, como las de estos adolescentes, que tienden a permanecer al margen.(AU)

Patient-derived ovarian cancer explants: preserved viability and histopathological features in long-term agitation-based cultures.

Ovarian carcinoma (OvC) remains a major therapeutic challenge due to its propensity to develop resistance after an initial response to chemotherapy. Interactions of tumour cells with the surrounding microenvironment play a role in tumour survival, invasion capacity and drug resistance. Cancer models that retain tissue architecture and tumour microenvironment components are therefore essential to understand drug response and resistance mechanisms. Herein, our goal was to develop a long-term OvC patient-derived explant (OvC-PDE) culture strategy in which architecture and cell type heterogeneity of the original tumour would be retained. Samples from 25 patients with distinct OvC types and one with a benign tumour, were cultured for 30 days in agitation-based culture systems with 100% success rate. OvC-PDE cultures retained the original tumour architecture and main cellular components: epithelial cells, fibroblasts and immune cells. Epithelial cells kept their original levels of proliferation and apoptosis. Moreover, the major extracellular components, such as collagen-I and -IV, were retained in explants. OvC-PDE cultures were exposed to standard-of-care chemotherapeutics agents for 2 weeks, attesting the ability of the platform for drug assays employing cyclic drug exposure regimens. We established an OvC-PDE dynamic culture in which tumour architecture and cell type heterogeneity were preserved for the different OvC types, replicating features of the original tumour and compatible with long-term drug exposure for drug efficacy and resistance studies.

One person, two bilateral symmetrical giant Becker nevi.

Becker nevus, first described by Samuel William Becker in 1949, is a focal epidermal hypermelanotic disorder. It commonly presents as a unilateral hyperpigmented patch that is predominantly distributed on the upper trunk and proximal extremities and frequently associated with hypertrichosis. There have been few reports in the literature of Becker nevus with bilateral involvement; multiple Becker nevi is also unusual. Herein, we report a young man with two bilateral symmetrical giant Becker nevi, one on the trunk with extension to both arms and the second on the abdomen.

Prenatal or Childhood Serum Levels of Vitamin D and Dental Caries in Paediatric Patients: A Systematic Review.

PURPOSE: To assess the association between low prenatal or childhood levels of 25-hydroxyvitamin D (25(OH) D) and dental caries experience in children. MATERIALS AND METHODS: PubMed, B-On, Web of Science, Scopus, and Cochrane Library databases were searched. The inclusion criteria were randomised controlled trials, cohort and cross-sectional studies published between 1998 and 2019; caries outcomes expressed as prevalence or based on the decayed missing and filled index for primary and permanent teeth/surfaces; and vitamin D levels assessed by laboratory analysis. Two authors independently selected studies, collected data, and assessed risk of bias. The quality of the studies was also assessed. A narrative synthesis of the studies was performed without quantitative pooling of data due to clinical and methodological heterogeneity. RESULTS: Out of 399 studies identified, 13 were included in the data synthesis. Even though many of the included studies had a cross-sectional design, 11 were considered high quality. The studies indicated that vitamin D has an important role in caries experience, but also revealed that vitamin D levels equal to or above 75 nmol/l seem to be more closely related to caries experience than the reference value of the Institute of Medicine. CONCLUSION: Evidence of an association exists between low 25(OH) D levels (<75 nmol/l) and caries experience in children. Hence, low vitamin D levels should be considered a potential factor associated with caries in children. Clinicians should be aware that good prenatal nutrition and early childhood diet might influence caries experience.

Psychoanalysis in research: the investigative method and some essentials tatements to two recurring criticisms / Psicanálise em pesquisas: o método investigativo e algumas afirmações essenciais a duas críticas recorrentes

RESUMO: Compreende-se a Psicanálise enquanto método, técnica e um conjunto de teorias aplicadas no estudo dos processos inconscientes. Entretanto, não é raro constatarmos, em alguns contextos como na Academia, ou mesmo na comunidade analítica, o destaque atribuído à Psicanálise, ora como um tratamento psicanalítico, restringindo-a a uma prática terapêutica, ora identificado à sua teoria. Desse modo, objetiva-se nesse artigo enfatizar o potencial investigativo da Psicanálise através de seu método. Este, diferente do que alguns analistas acreditam, pode ser desenvolvido para além da clínica padrão, como temos acompanhado através das pesquisas acadêmicas.

Abstract: Psychoanalysis is understood as method, technique and a set of applied theories in the study of the unconscious processes. However, it is not uncommon to note, in some contexts such as the Academy, or even in the analytical community, the emphasis attributed to Psychoanalysis, sometimes as a psychoanalytic treatment, restricting it to a therapeutic practice, or as identified to its theory. In this article it is emphasized the investigative potential of Psychoanalysis through its method. This, unlike some analysts believe, can be developed beyond the standard clinical, as we have followed through academic research.

Improving the Anti-inflammatory Response via Gold Nanoparticle Vectorization of CO-Releasing Molecules.

CO-releasing molecules (CORMs) have been widely studied for their anti-inflammatory, antiapoptotic, and antiproliferative effects. CORM-3 is a water-soluble Ru-based metal carbonyl complex, which metallates serum proteins and readily releases CO in biological media. In this work, we evaluated the anti-inflammatory and wound-healing effects of gold nanoparticles-CORM-3 conjugates, AuNPs@PEG@BSA·Ru(CO)x, exploring its use as an efficient CO carrier. Our results suggest that the nanoformulation was capable of inducing a more pronounced cell effect, at the anti-inflammatory level and a faster tissue repair, probably derived from a rapid cell uptake of the nanoformulation that results in the increase of CO inside the cell.