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.

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.

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.

Targeting Tumor Microenvironment for Cancer Therapy.

Cancer development is highly associated to the physiological state of the tumor microenvironment (TME). Despite the existing heterogeneity of tumors from the same or from different anatomical locations, common features can be found in the TME maturation of epithelial-derived tumors. Genetic alterations in tumor cells result in hyperplasia, uncontrolled growth, resistance to apoptosis, and metabolic shift towards anaerobic glycolysis (Warburg effect). These events create hypoxia, oxidative stress and acidosis within the TME triggering an adjustment of the extracellular matrix (ECM), a response from neighbor stromal cells (e.g., fibroblasts) and immune cells (lymphocytes and macrophages), inducing angiogenesis and, ultimately, resulting in metastasis. Exosomes secreted by TME cells are central players in all these events. The TME profile is preponderant on prognosis and impacts efficacy of anti-cancer therapies. Hence, a big effort has been made to develop new therapeutic strategies towards a more efficient targeting of TME. These efforts focus on: (i) therapeutic strategies targeting TME components, extending from conventional therapeutics, to combined therapies and nanomedicines; and (ii) the development of models that accurately resemble the TME for bench investigations, including tumor-tissue explants, "tumor on a chip" or multicellular tumor-spheroids.

[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.

Quality indicators for in-hospital management of exacerbation of chronic obstructive pulmonary disease: results of an international Delphi study.

AIM: To report a Delphi study that was conducted to select process and outcome indicators that are relevant to study quality of care and impact of care pathways for patients hospitalized with exacerbation of chronic obstructive pulmonary disease. BACKGROUND: Management of patients hospitalized with exacerbation of chronic obstructive pulmonary disease is suboptimal and outcomes are poor. To evaluate the impact of care pathways properly, relevant indicators need to be selected. DESIGN: Delphi study. METHODS: The study was conducted over 4 months in 2008, with 35 experts out of 15 countries, including 19 medical doctors, 8 nurses and 8 physiotherapists. Participants were asked to rate, for 72 process and 21 outcome indicators, the relevance for follow-up in care pathways for in-hospital management of exacerbation of chronic obstructive pulmonary disease. Consensus (agreement by at least 75% of the participants) that an indicator is relevant for follow-up was sought in two rounds. RESULTS: Consensus was reached for 26 of 72 process indicators (36·1%) and 10 of 21 outcome indicators (47·6%). Highest consensus levels were found for the process indicators regarding oxygen therapy (100%), pulmonary rehabilitation (100%) and patient education (94·5-88·6%) and for the outcome indicators concerning understanding of therapy (91·4-85·7%) and self-management (88·6-88·2%). CONCLUSION: The selected indicators appear to be sensitive for improvement. Therefore, researchers and clinicians that want to study and improve the care for patients hospitalized with exacerbation of chronic obstructive pulmonary disease should primarily focus on these indicators.

The effect of care pathways for hip fractures: a systematic overview of secondary studies.

The aim of this paper was to perform a systematic overview of secondary literature studies on care pathways (CPs) for hip fracture (HF). The online databases MEDLINE-PubMed, Ovid-EMBASE, CINAHL-EBSCO-host, and The Cochrane Library were searched. A total of six papers, corresponding to six secondary studies, were included but only four secondary studies were HF-specific and thus assessed. Secondary studies were evaluated for patients' clinical outcomes. There were wide differences among the studies that assessed the effects of CPs on HF patients, with some contrasting clinical outcomes reported. Secondary studies that were non-specific for CPs and included other multidisciplinary care approaches as well showed, in some cases, a shorter hospital length of stay (LOS) compared to usual care; studies that focused on promoting early mobilization showed better outcomes of mortality, morbidity, function, or service utilization; CPs mainly based on intensive occupational therapy and/or physical therapy exercises improved functional recovery and reduced LOS, with patients also discharged to a more favorable discharge destination; CPs principally focused on early mobilization improved functional recovery. A secondary study specifically designed for CPs showed lower odds of experiencing common complications of hospitalization after HF. In conclusion, although our overview suggests that CPs can reduce significantly LOS and can have a positive impact on different outcomes, data are insufficient for formal recommendations. To properly understand the effects of CPs for HF, a systematic review is needed of primary studies that specifically examined CPs for HF.

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.

The effect of care pathways for hip fractures: a systematic review.

We performed a systematic review for primary studies on care pathways (CPs) for hip fracture (HF). The online databases MEDLINE-PubMed, Ovid-EMBASE, CINAHL-EBSCO host, and The Cochrane Library (Cochrane Central Register of Clinical Trials, Health Technology Assessment Database, NHS Economic Evaluation Database) were searched. Two researchers reviewed the literature independently. Primary studies that met predefined inclusion criteria were assessed for their methodological quality. A total of 15 publications were included: 15 primary studies corresponding with 12 main investigations. Primary studies were evaluated for clinical outcomes, process outcomes, and economic outcomes. The studies assessed a wide range of outcome measures. While a number of divergent clinical outcomes were reported, most studies showed positive results of process management and health-services utilization. In terms of mortality, the results provided evidence for a positive impact of CPs on in-hospital mortality. Most studies also showed a significantly reduced risk of complications, including medical complications, wound infections, and pressure sores. Moreover, time-span process measures showed that an improvement in the organization of care was achieved through the use of CPs. Conflicting results were observed with regard to functional recovery and mobility between patients treated with CPs compared to usual care. Although our review suggests that CPs can have positive effects in patients with HF, the available evidence is insufficient for formal recommendations. There is a need for more research on CPs with selected process and outcome indicators, for in-hospital and postdischarge management of HF, with an emphasis on well-designed randomized trials.

The Portuguese version of the Personal and Social Performance Scale (PSP): reliability, validity, and relationship with cognitive measures in hospitalized and community schizophrenia patients.

PURPOSE: Deficits in social functioning are a core feature of schizophrenia and are influenced by both symptomatic and neurocognitive variables. In the present study we aimed to determine the reliability and validity of the Portuguese version of the Personal and Social Performance (PSP) scale, and possible correlations with measures of cognitive functioning. METHODS: One-hundred and four community and inpatients with schizophrenia were assessed using measures of social functioning and symptom severity alongside measures of executive function, processing speed, and verbal memory. RESULTS: Convergent validity with the GAF in the four domains of the PSP varied from 0.357 to 0.899. Reliability was found to be satisfactory, with a Cronbach's alpha coefficient of 0.789. Inter-rater reliability in the four domains of the PSP varied from 0.430 to 0.954. Low-functioning patients (PSP < 70) were older, had longer duration of illness, were more symptomatic and had worse cognitive performances, as compared with high-functioning patients (PSP ≥ 70). In a regression model, deficits in social functioning were strongly predicted both by symptomatic and neurocognitive variables; these together accounted for up to 62% of the variance. CONCLUSIONS: The present study supports the reliability and validity of the Portuguese language version of the PSP and further supports the original measure. The co-administration of brief cognitive assessments with measures of functioning may lead to more focused interventions, possibly improving outcomes in this group.

The impact of care pathways for patients with proximal femur fracture: rationale and design of a cluster-randomized controlled trial.

BACKGROUND: Proximal femur fracture (PFF) is associated with considerable morbidity and mortality. The European Quality of Care Pathway (EQCP) study on PFF (NCT00962910) was designed to determine how care pathways (CP) for hospital treatment of PFF affect consistency of care, adherence to evidence-based key interventions, and clinical outcome. METHODS/DESIGN: An international cluster-randomized controlled trial (cRCT) will be performed in Belgium, Ireland, Italy and Portugal. Based on power analyses, a sample of 44 hospital teams and 437 patients per arm will be included in the study. In the control arm, usual care will be provided. Experimental teams will implement a care pathway which will include three active components: a formative evaluation of quality and organization of the care setting, a set of evidence-based key interventions, and support of the development and implementation of the CP. Main outcome will be the six-month mortality rate. DISCUSSION: The EQCP study constitutes the first international cRCT on care pathways. The EQCP project was designed as both a research and a quality improvement project and will provide a real-world framework for process evaluation to improve our understanding of why and when CP can really work. TRIAL REGISTRATION NUMBER: NCT00962910.

Cochlear implant in the treatment of incapacitating unilateral tinnitus: case report.

Several studies have shown that cochlear implants may reduce or even eliminate tinnitus in patients with bilateral profound hearing loss. However, there are not consistent references regarding ipsilateral tinnitus compared to unilateral profound hearing loss. The aim of this paper is to describe audiological results of a patient with asymmetrical hearing loss with incapacitating ipsilateral tinnitus in the ear subjected to cochlear implant surgery. Audiological exams and responses to perception protocols for tinnitus before and after surgery were analyzed. The tests showed improvements in the hearing threshold on the side with the implant, improvements in speech perception and a significant reduction in tinnitus perception, which consequently led to an improvement in the patient's quality of life.

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.

Immunostimulatory property of a synthetic peptide belonging to the soluble ATP diphosphohydrolase isoform (SmATPDase 2) and immunolocalisation of this protein in the Schistosoma mansoni egg.

A peptide (SmB2LJ; r175-194) that belongs to a conserved domain from Schistosoma mansoni SmATPDase 2 and is shared with potato apyrase, as predicted by in silico analysis as antigenic, was synthesised and its immunostimulatory property was analysed. When inoculated in BALB/c mice, this peptide induced high levels of SmB2LJ-specific IgG1 and IgG2a subtypes, as detected by enzyme linked immunosorbent assay. In addition, dot blots were found to be positive for immune sera against potato apyrase and SmB2LJ. These results suggest that the conserved domain r175-194 from the S. mansoni SmATPDase 2 is antigenic. Western blots were performed and the anti-SmB2LJ antibody recognised in adult worm (soluble worm antigen preparation) or soluble egg antigen antigenic preparations two bands of approximately 63 and 55 kDa, molecular masses similar to those predicted for adult worm SmATPDase 2. This finding strongly suggests the expression of this same isoform in S. mansoni eggs. To assess localisation of SmATPDase 2, confocal fluorescence microscopy was performed using cryostat sections of infected mouse liver and polyclonal antiserum against SmB2LJ. Positive reactions were identified on the external surface from the miracidium in von Lichtenberg's envelope and, in the outer side of the egg-shell, showing that this soluble isoform is secreted from the S. mansoni eggs.

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.

Detection of IgG1 and IgG4 subtypes reactive against potato apyrase in schistosomiasis patients.

In this paper, we showed for the first time that the conserved domains within Schistosoma mansoni ATP diphosphohydrolase isoforms, shared with potato apyrase, possess epitopes for the IgG1 and IgG4 subtypes, as 24 (80%) of the 30 schistosomiasis patients were seropositive for this vegetable protein. The analyses for each patient cured (n = 14) after treatment (AT) with praziquantel revealed variable IgG1 and IgG4 reactivity against potato apyrase. Different antigenic epitopes shared between the vegetable and parasite proteins could be involved in susceptibility or resistance to S. mansoni AT with praziquantel and these possibilities should be explored.

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.

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.