In vitro characterisation of a novel rubber contact allergen in protective gloves.

BACKGROUND: Allergic contact dermatitis (ACD) from protective gloves is often caused by rubber additives, such as accelerators. However, while accelerator-free rubber gloves are available, they still cause ACD in some individuals. OBJECTIVES: A new allergen, 2-cyаnоethyl dimethyldithiocarbamate, (CEDMC), has recently been identified in accelerator-free gloves, and we here provide a first in vitro characterisation of CEDMC in a dendritic cell (DC)-like cell model along with three reference sensitizer rubber chemicals, consisting of tetraethylthiuram disulfide (TETD) and two xanthogenates. METHODS: Cellular responses after the exposure to the rubber chemicals were assessed using a transcriptomic approach, multiplex cytokine secretion profiling, and flow cytometry to determine DC model activation marker expression and apoptosis induction. RESULTS: CEDMC and all other sensitizers were classified as strong skin sensitizers with the transcriptomic approach. They all significantly increased IL-8 secretion and exposure to all except one increased CD86 DC activation marker expression. When tested, CEDMC induced apoptosis, however, delayed compared to TETD. CONCLUSIONS: The in vitro data corroborate CEDMC, TETD, and investigated xanthogenates as skin sensitizers. Transcriptomic analyses further reveal unique cellular responses induced by CEDMC, which together with future study can contribute to better understanding of cellular mechanisms underlying the sensitising capacity of rubber chemicals.

Holistic in silico developability assessment of novel classes of small proteins using publicly available sequence-based predictors.

The development of novel therapeutic proteins is a lengthy and costly process, with an average attrition rate of 91% (Thomas et al. Clinical Development Success Rates and Contributing Factors 2011-2020, 2021). To increase the probability of success and ensure robust drug supply beyond approval, it is essential to assess the developability profile of new potential drug candidates as early and broadly as possible in development (Jain et al. MAbs, 2023. https://doi.org/10.1016/j.copbio.2011.06.002 ). Predicting these properties in silico is expected to be the next leap in innovation as it would enable significantly reduced development timelines combined with broader screens at lower costs. However, developing predictive algorithms typically requires substantial datasets generated under very defined conditions, a limiting factor especially for new classes of therapeutic proteins that hold immense clinical promise. Here we describe a strategy for assessing the developability of a novel class of small therapeutic Anticalin® proteins using machine learning in conjunction with a knowledge-driven approach. The knowledge-driven approach considers developability attributes such as aggregation propensity, charge variants, immunogenicity, specificity, thermal stability, hydrophobicity, and potential post-translational modifications, to calculate a holistic developability score. Based on sequence-derived descriptors as input parameters we established novel statistical models designed to predict the developability scores for Anticalin proteins. The best models yielded low root mean square errors across the entire dataset and were further validated by removing input data from individual screening campaigns and predicting developability scores for those drug candidates. The adoption of the described workflow will enable significantly streamlined preclinical development of Anticalin drug candidates and could potentially be applied to other therapeutic protein scaffolds.

Beyond the Classroom: Investigating the Relationship between Psychomotor Development and Academic Achievement in 4-12-Year-Olds.

BACKGROUND/OBJECTIVES: The relevance of psychomotor skills in children's growth is being increasingly recognized. The transversal role of psychomotor skills in learning performance is described through a link between cognitive and motor functioning, promoting socio-affective-expressive competencies, but there is a scarcity of evidence from the field. A two-fold goal was defined: to investigate the relationship between psychomotor functions and academic performance and to examine the factors affecting children's academic performance. METHODS: The Portuguese versions of the Neuropsychomotor Functions Assessment Battery for Children (NPmot.pt), Preschool Diagnostic Tasks (PRE), and School Learning Skills Battery (SLSB) were applied to 350 children (85.72 ± 24.23 months) with and without disabilities attending mainstream schools. RESULTS: Pearson correlations and regression analyses were used. NPmot.pt domains showed moderate to strong correlations with PRE domains (0.30 < r < 0.82) and weak ones with SLSB domains (r < 0.30). Psychomotor development is a stronger predictor (p < 0.001) of pre-academic performance outcomes: (ßTonus = 0.67, ßGross Motor Skills = 1.04, ßSpatial Orientation = -1.44, ßRhythm = -1.59 and ßAuditory Attention = 3.68) than of academic performance above 7 years old (p > 0.05). CONCLUSIONS: Results strengthen the importance of psychomotor skills development from an early age, also at school, with implications for an early psychomotor assessment and intervention for children with and without disabilities. Tailor-fit interventions, including strategies to improve psychomotor skills, should be promoted during the school process of all children for a successful learning process.

The Influence of the Diameter of Orthodontic Mini-Implants on Primary Stability: Bending Tests-An In Vitro Study.

Orthodontic Mini-Implants have a high success rate, but it is crucial to assess the load that they bear in order to maintain their primary stability. Increasing the diameter can improve this stability, but there are limitations due to the proximity of the tooth roots. To avoid damage, smaller diameters are used, which can decrease resistance and cause permanent deformations. OBJECTIVE: The objective of this study is to evaluate the influence of the diameter of Mini-Implants through bending force tests, taking into account primary stability after one and two insertions. METHODS: Here, 40 Ti6AI4V alloy Mini-Implants of two different brands and diameters were divided into eight groups, half of which received one insertion in the artificial bone, and the rest received two. All were subjected to a constant bending force using an INSTRON-Electropuls E10000LT (Norwood, MA, USA) until fracture. RESULTS: The smaller-diameter Mini-Implants were less resistant to fracture, but both were able to withstand the necessary loads produced by orthodontic movements. As for the inserts, there were no statistically significant differences. CONCLUSIONS: There is an advantage to using 1.6 mm Mini-Implants over 2.0 mm ones, as a smaller diameter does not lead to fracture due to the forces used in orthodontic treatment. Having one or two inserts did not have a statistically significant effect.

Comparison of postoperative chronic inguinal pain between the lichtenstein and laparoscopic techniques in the treatment of inguinal hernia: a systematic review and meta-analysis.

PURPOSE: Currently, inguinal hernias are highly prevalent in the Brazilian population, accounting for 75% of all abdominal wall hernias. The recommended treatment to correct them is inguinal herniorrhaphy, which can be performed through open surgery, mainly using the Lichtenstein technique, or laparoscopically, primarily through Transabdominal Preperitoneal Repair (TAPP) or Total Extraperitoneal Repair (TEP) approaches. Like any surgery, these procedures have post-operative complications, with pain being the most common and debilitating. Currently, in European and Brazilian guidelines, the open Lichtenstein and endoscopic inguinal hernia techniques are recommended as best evidence-based options for repair of a primary unilateral hernia providing the surgeon is sufficiently experienced in the specific procedure. In that matter, the surgeon should make a choice based on assessment of the benefits and risks of performing each of them, and practice shared making decision with it patient. Therefore, the objective of this review was to assess the incidence of chronic postoperative pain by comparing the aforementioned surgical approaches to evaluate which procedure causes less disability to the patient. METHODS: The search conducted until May 2024 was performed on Medline (PubMed), Cochrane (CENTRAL), and Lilacs databases. The selection was limited to randomized clinical trials, nonrandomized clinical trials and cohort studies comparing TAPP or TEP to LC, evaluating the incidence of chronic postoperative pain published between 2017 and 2023. Evidence certainty was assessed using the GRADE Pro tool, and bias risk was evaluated with the RoB 2.0 tool and ROBINS I tool. Thirteen studies were included.  RESULTS: The meta-analysis showed a significant difference between the groups in both techniques, favoring the laparoscopic approach, which had a lower occurrence of postoperative inguinodynia with a relative risk of 0.49 (95% CI = 0.32, 0.75; I2 = 66% (P = 0.001); Z = 3.28 (P = 0.001) with low certainty of evidence. CONCLUSION: The presence of chronic postoperative pain was lower in laparoscopic TEP/TAPP techniques when compared to the open Lichtenstein technique, meaning that the former can bring more benefits to patients who requires inguinal herniorrhaphy. Nevertheless, further randomized clinical trials are needed to optimize the analysis, minimizing the bias.

A SMARTR workflow for multi-ensemble atlas mapping and brain-wide network analysis.

In the last decade, activity-dependent strategies for labelling multiple immediate early gene (IEG) ensembles in mice have generated unprecedented insight into the mechanisms of memory encoding, storage, and retrieval. However, few strategies exist for brain-wide mapping of multiple ensembles, including their overlapping population, and none incorporate capabilities for downstream network analysis. Here, we introduce a scalable workflow to analyze traditionally coronally-sectioned datasets produced by activity-dependent tagging systems. Intrinsic to this pipeline is simple multi-ensemble atlas registration and statistical testing in R (SMARTR), an R package which wraps mapping capabilities with functions for statistical analysis and network visualization. We demonstrate the versatility of SMARTR by mapping the ensembles underlying the acquisition and expression of learned helplessness (LH), a robust stress model. Applying network analysis, we find that exposure to inescapable shock (IS), compared to context training (CT), results in decreased centrality of regions engaged in spatial and contextual processing and higher influence of regions involved in somatosensory and affective processing. During LH expression, the substantia nigra emerges as a highly influential region which shows a functional reversal following IS, indicating a possible regulatory function of motor activity during helplessness. We also report that IS results in a robust decrease in reactivation activity across a number of cortical, hippocampal, and amygdalar regions, indicating suppression of ensemble reactivation may be a neurobiological signature of LH. These results highlight the emergent insights uniquely garnered by applying our analysis approach to multiple ensemble datasets and demonstrate the strength of our workflow as a hypothesis-generating toolkit.

Clinical Characteristics of Ocular Mucous Membrane Pemphigoid: A Systematic Review and Meta-Analysis.

PURPOSE: To synthesize the evidence and generate a combined weighted measure on the frequency of ocular manifestations of mucous membrane pemphigoid (OMMP). METHODS: Systematic literature review and meta-analysis, searching PubMed, Embase, VHL, and Google Scholar. Articles reporting patients with mucous membrane pemphigoid and ocular involvement were included. At least, two reviewers independently and in parallel participated in all the following phases; preliminary screening, full-text review, risk of bias assessment by validated tools, and data extraction. Qualitative analysis and meta-analysis were conducted. This study was previously registered in PROSPERO (CRD42023451844). RESULTS: Thirty-five studies met the inclusion criteria, comprising 1,439 patients and 1,040 eyes summarized in qualitative analysis. Twenty-eight studies were included in the meta-analysis. Ages included ranged from 60.4 to 75 years. Women were reported with more frequency. The mean time for diagnosis was 55.1 months, usually with bilateral ocular disease in 90% (95% CI 78%; 96%). Trichiasis and entropion were the most frequent manifestations in up to 92%, followed by symblepharon and punctate keratitis. Ankyloblepharon, persistent epithelial defects, and visual impairment were less frequent complications. Direct immunofluorescence positivity in conjunctival biopsies was 54% (95% CI 43%; 64%). Extraocular involvement was highly frequent, being oral and skin involvement the most frequently reported. CONCLUSIONS: Our systematic review and meta-analysis evidenced that patients around 60 years of age are the most affected population with a female preponderance, usually with bilateral ocular involvement. Trichiasis and entropion were the most frequent findings; although visual impairment and persistent epithelial defects were less reported, they should not be overlooked in suspected OMMP.

Primary Gastric Tuberculosis in an Immunocompetent Patient: The Truth Lying beneath the Surface.

Gastrointestinal tuberculosis is an uncommon entity, in which clinical presentation can be widely variable, from mild and nonspecific symptoms to an acute abdomen and gastrointestinal bleeding. Gastric involvement by Mycobacterium tuberculosis is rare, especially when it occurs without other recognized infectious foci - primary gastric tuberculosis - with only a few reported cases. Endoscopic findings can be very heterogeneous, from areas of hyperemia to pseudotumor lesions. We present a case of primary gastric tuberculosis in an immunocompetent patient, in which the absence of an epidemiological context and nonspecific endoscopic findings led to a delay in the diagnosis. Bite-on-bite biopsies proved to be essential, allowing to obtain samples from deeper layers of the submucosa where M. tuberculosis was identified. This case aimed to increase awareness for this entity, especially in endemic countries or regions with a high prevalence of tuberculosis since the diagnosis is based mainly on a high index of suspicion.

A tuberculose gastrointestinal é uma entidade pouco comum, com uma apresentação clínica amplamente variável, desde sintomas ligeiros e inespecíficos até quadros de abdómen agudo e hemorragia digestiva. O envolvimento gástrico pelo Mycobacterium tuberculosis é raro, especialmente quando ocorre sem outros focos infeciosos reconhecidos ­ tuberculose gástrica primária ­, havendo apenas alguns casos descritos na literatura. Os achados endoscópicos podem ser muito heterogéneos, variando desde áreas de mucosa hiperemiada até lesões pseudo-tumorais. Apresentamos o caso de uma doente imunocompetente com diagnóstico de tuberculose gástrica primária, em que a ausência de um contexto epidemiológico e achados endoscópicos inespecíficos conduziram a um atraso no diagnóstico. As biópsias sobre biópsias mostraram ser essenciais para o diagnóstico, pois permitiram obter amostras de camadas mais profundas da submucosa do antro gástrico onde foi identificado o agente infecioso. Este caso pretende sensibilizar para existência desta entidade, especialmente em países endémicos ou regiões com alta prevalência de tuberculose, uma vez que o seu diagnóstico implica um elevado grau de suspeição.

The Pattern of GH Action in the Mouse Brain.

GH acts in numerous organs expressing the GH receptor (GHR), including the brain. However, the mechanisms behind the brain's permeability to GH and how this hormone accesses different brain regions remain unclear. It is well-known that an acute GH administration induces phosphorylation of the signal transducer and activator of transcription 5 (pSTAT5) in the mouse brain. Thus, the pattern of pSTAT5 immunoreactive cells was analyzed at different time points after IP or intracerebroventricular GH injections. After a systemic GH injection, the first cells expressing pSTAT5 were those near circumventricular organs, such as arcuate nucleus neurons adjacent to the median eminence. Both systemic and central GH injections induced a medial-to-lateral pattern of pSTAT5 immunoreactivity over time because GH-responsive cells were initially observed in periventricular areas and were progressively detected in lateral brain structures. Very few choroid plexus cells exhibited GH-induced pSTAT5. Additionally, Ghr mRNA was poorly expressed in the mouse choroid plexus. In contrast, some tanycytes lining the floor of the third ventricle expressed Ghr mRNA and exhibited GH-induced pSTAT5. The transport of radiolabeled GH into the hypothalamus did not differ between wild-type and dwarf Ghr knockout mice, indicating that GH transport into the mouse brain is GHR independent. Also, single-photon emission computed tomography confirmed that radiolabeled GH rapidly reaches the ventral part of the tuberal hypothalamus. In conclusion, our study provides novel and valuable information about the pattern and mechanisms behind GH transport into the mouse brain.

Biological Response Following the Systemic Injection of PEG-PAMAM-Rhodamine Conjugates in Zebrafish.

Numerous therapeutic and diagnostic approaches used within a clinical setting depend on the administration of compounds via systemic delivery. Biomaterials at the nanometer scale, as dendrimers, act as delivery systems by improving cargo bioavailability, circulation time, and the targeting of specific tissues. Although evaluating the efficacy of pharmacological agents based on nanobiomaterials is crucial, conducting toxicological assessments of biomaterials is essential for advancing clinical translation. Here, a zebrafish larvae model was explored to assess the biocompatibility of poly(amido amine) (PAMAM), one of the most exploited dendrimers for drug delivery. We report the impact of a systemic injection of polyethylene glycol (PEG)-modified G4 PAMAM conjugated with rhodamine (Rho) as a mimetic drug (PEG-PAMAM-Rho) on survival, animal development, inflammation, and neurotoxicity. A concentration- and time-dependent effect was observed on mortality, developmental morphology, and innate immune system activation (macrophages). Significant effects in toxicological indicators were reported in the highest tested concentration (50 mg/mL PEG-PAMAM-Rho) as early as 48 h post-injection. Additionally, a lower concentration of PEG-PAMAM-Rho (5 mg/mL) was found to be safe and subsequently tested for neurotoxicity through behavioral assays. In accordance, no significative signs of toxicity were detected. In conclusion, the dose response of the animal was assessed, and the safe dosage for future use in theragnostics was defined. Additionally, new methodologies were established that can be adapted to further studies in toxicology using other nanosystems for systemic delivery.

Systemic and Bilateral Severe Ocular Toxoplasmosis Resembling Autoimmune Phenomena: A Case Report.

PURPOSE: To present an atypical case of severe bilateral ocular toxoplasmosis with systemic involvement that initially mimicked an autoimmune etiology, posing challenges to its diagnosis and treatment. CASE REPORT: A 39-year-old immunocompetent male was admitted to the hospital due to a presumed pulmonary thromboembolism concomitant with an abrupt onset of vision loss. Initial differential diagnoses included antiphospholipid syndrome and systemic lupus erythematosus, prompting the administration of corticosteroid pulses and rituximab. Despite observing a partial systemic response, there was no improvement in visual acuity. Subsequent aqueous humor polymerase chain reaction confirmed Toxoplasma gondii infection, leading to the introduction of oral antibiotic therapy. The patient's condition showed a partially favorable response; however, the treatment could not reverse the permanent retinal damage. CONCLUSION AND IMPORTANCE: This case underscores the importance of ruling out an infectious etiology in all cases of uveitis. Additionally, it alerts clinicians to the possibility that elevated positive autoantibodies may result from a severe inflammatory reaction caused by pathogens rather than an autoimmune or autoinflammatory disease, particularly in instances of poor treatment response or atypical clinical presentation.

Enhancing Neuronal Cell Uptake of Therapeutic Nucleic Acids with Tetrahedral DNA Nanostructures.

The successful translation of therapeutic nucleic acids (NAs) for the treatment of neurological disorders depends on their safe and efficient delivery to neural cells, in particular neurons. DNA nanostructures can be a promising NAs delivery vehicle. Nonetheless, the potential of DNA nanostructures for neuronal cell delivery of therapeutic NAs is unexplored. Here, tetrahedral DNA nanostructures (TDN) as siRNA delivery scaffolds to neuronal cells, exploring the influence of functionalization with two different reported neuronal targeting ligands: C4-3 RNA aptamer and Tet1 peptide are investigated. Nanostructures are characterized in vitro, as well as in silico using molecular dynamic simulations to better understand the overall TDN structural stability. Enhancement of neuronal cell uptake of TDN functionalized with the C4-3 Aptamer (TDN-Apt), not only in neuronal cell lines but also in primary neuronal cell cultures is demonstrated. Additionally, TDN and TDN-Apt nanostructures carrying siRNA are shown to promote silencing in a process aided by chloroquine-induced endosomal disruption. This work presents a thorough workflow for the structural and functional characterization of the proposed TDN as a nano-scaffold for neuronal delivery of therapeutic NAs and for targeting ligands evaluation, contributing to the future development of new neuronal drug delivery systems based on DNA nanostructures.

Treatment of metastatic paraganglioma: experience of a single center.

PURPOSE: Data regarding treatment options and their efficacy for metastatic paragangliomas (mPPGL) is limited. This study aims to report a single center experience in treating mPPGL, comparing the efficacy and safety of various treatment approaches. METHODS: Retrospective analysis of patients with mPPGL treated at an Endocrinology Department of a cancer institute between January 2000 and October 2022. RESULTS: We analyzed 25 patients with mPPGL, 8 pheochromocytomas and 20 paragangliomas (12% multifocal), followed for a median of 9 [4; 14] years. Surgical approach, aimed at the primary tumor or at debulking of metastases, was the only treatment achieving complete response: 87% in primary tumor and 87.5% with debulking of metastases. These were long-lasting results with a duration of 69 (23.8; 136.8) months in primary tumor removal and 35.1 (15.3; 41) months in metastases debulking. As for other therapeutic approaches, such as radioactive isotopes, tyrosine kinase inhibitors, chemotherapy and external beam radiotherapy, the main outcome was stable disease, with few partial responses. At the last follow-up, 66% of the patients were alive, 15.4% were in remission and 84.6% had stable disease. Median overall survival was 14 years. The 5-year and 10-year survival rates from primary tumor diagnosis were 77.9% and 66.9% respectively, and from metastasis diagnosis were 67.4% and 55.6%, respectively. CONCLUSION: This is the only European single center analysis addressing outcomes of different therapies in mPGL. The results support surgery as a first-line treatment, being the only approach that may achieve complete response with satisfactory and long-lasting results.

Recognition of breast cancer subtypes using FTIR hyperspectral data.

Fourier-transform infrared spectroscopy (FTIR) is a powerful, non-destructive, highly sensitive and a promising analytical technique to provide spectrochemical signatures of biological samples, where markers like carbohydrates, proteins, and phosphate groups of DNA can be recognized in biological micro-environment. However, method of measurements of large cells need an excessive time to achieve high quality images, making its clinical use difficult due to speed of data-acquisition and lack of optimized computational procedures. To address such challenges, Machine Learning (ML) based technologies can assist to assess an accurate prognostication of breast cancer (BC) subtypes with high performance. Here, we applied FTIR spectroscopy to identify breast cancer subtypes in order to differentiate between luminal (BT474) and non-luminal (SKBR3) molecular subtypes. For this reason, we tested multivariate classification technique to extract feature information employing three-dimension (3D)-discriminant analysis approach based on 3D-principle component analysis-linear discriminant analysis (3D-PCA-LDA) and 3D-principal component analysis-quadratic discriminant analysis (3D-PCA-QDA), showing an improvement in sensitivity (98%), specificity (94%) and accuracy (98%) parameters compared to conventional unfolded methods. Our results evidence that 3D-PCA-LDA and 3D-PCA-QDA are potential tools for discriminant analysis of hyperspectral dataset to obtain superior classification assessment.

An MRI assessment of prostate cancer local recurrence using the PI-RR system: diagnostic accuracy, inter-observer reliability among readers with variable experience, and correlation with PSA values.

OBJECTIVES: The Prostate Imaging for Recurrence Reporting (PI-RR) system has been recently proposed to promote standardisation in the MR assessment of prostate cancer (PCa) local recurrence after radical prostatectomy (RP) and radiation therapy (RT). This study aims to evaluate PI-RR's diagnostic accuracy, assess the inter-observer reliability among readers with variable experience, and correlate imaging results with anatomopathological and laboratory parameters. METHODS: Patients who underwent a pelvic MRI for suspicion of PCa local recurrence after RP or RT were retrospectively enrolled (October 2017-February 2020). PI-RR scores were independently assessed for each patient by five readers with variable experience in prostate MRI (two senior and three junior radiologists). Biochemical data and histopathological features were collected. The reference standard was determined through biochemical, imaging, or histopathological follow-up data. Reader's diagnostic performance was assessed using contingency tables. Cohen's kappa coefficient (κ) and intraclass correlation coefficient (ICC) were calculated to measure inter-observer reliability. RESULTS: The final cohort included 120 patients (median age, 72 years [IQR, 62-82]). Recurrence was confirmed in 106 (88.3%) patients. Considering a PI-RR score ≥ 3 as positive for recurrence, minimum and maximum diagnostic values among the readers were as follows: sensitivity 79-86%; specificity 64-86%; positive predictive value 95-98%; negative predictive value 33-46%; accuracy 79-87%. Regardless of reader's level of experience, the inter-observer reliability resulted good or excellent (κ ranges across all readers: 0.52-0.77), and ICC was 0.8. Prostate-specific antigen (PSA) velocity, baseline-PSA, and trigger-PSA resulted predictive of local recurrence at imaging. CONCLUSIONS: The PI-RR system is an effective tool for MRI evaluation of PCa local recurrence and facilitates uniformity among radiologists. CLINICAL RELEVANCE STATEMENT: This study confirmed the PI-RR system's good diagnostic accuracy for the MRI evaluation of PCa local recurrences. It showed high reproducibility among readers with variable experience levels, validating it as a promising standardisation tool for assessing patients with biochemical recurrence. KEY POINTS: • In this retrospective study, the PI-RR system revealed promising diagnostic performances among five readers with different experience (sensitivity 79-86%; specificity 64-86%; accuracy 79-87%). • The inter-observer reliability among the five readers resulted good or excellent (κ ranges: 0.52-0.77) with an intraclass correlation coefficient of 0.8. • The PI-RR assessment score may facilitate standardisation and generalizability in the evaluation of prostate cancer local recurrence among radiologists.

Perfil de autodeterminação de adultos com e sem dificuldades intelectuais e desenvolvimentais: estudo comparativo / Self-determination profile of adults with and without intellectual and developmental difficulties: comparative study

RESUMO O reconhecimento da autodeterminação tem vindo a ser evidente também no campo da Dificuldade Intelectual e Desenvolvimental (DID), visto que a pessoa deve assumir-se como agente ativo e decisor na própria vida. A aprendizagem das competências autodeterminadas é fundamental dada a sua transversalidade contextual, não se devendo restringir apenas à adolescência. Em Portugal, as evidências são escassas e baseadas no anterior modelo. Assim sendo, o objetivo deste estudo foi identificar o perfil de autodeterminação, à luz da teoria do agente causal, de adultos com DID, no intuito de analisar as variáveis que o influenciam. A versão portuguesa do Inventário de Autodeterminação foi aplicada a 44 participantes entre os 21-73 anos (40.77±12.07), 20 do género feminino e 24 do masculino. Metade da amostra eram participantes com DID, todos institucionalizados. A consistência interna foi aceitável (α=.65). A análise comparativa pelo diagnóstico, género, idade, habilitações académicas, situação profissional e local de residência apontou a tendência para perfis semelhantes (p>.05). As diferenças encontradas estão associadas a perfis mais autodeterminados de adultos com DID, inferindo-se o maior peso das características envolvimentais do que individuais (diagnóstico). As pessoas com DID reconhecem a autodeterminação como relevante e apresentam as habilidades para a decisão. Recomendações para a investigação e para a prática serão avançadas.

ABSTRACT The recognition of self-determination has also become evident in the field of Intellectual and Developmental Disability (IDD), as the person must assume him/herself as an active agent and decision-maker in his/her own life. Learning self-determined skills is fundamental given their contextual transversality and should not be restricted to the period of adolescence. In Portugal, evidence is scarce and based on the previous model. Therefore, the aim of this study was to identify the self-determination profile, in the light of the causal agent theory, of adults with IDD, in order to analyze the variables that influence it. The Portuguese version of the Self-Determination Inventory was applied to 44 participants aged between 21-73 years old (40.77±12.07), 20 females and 24 males. Half of the sample were participants with IDD, all institutionalized. Internal consistency was acceptable (α=.65). The comparative analysis by diagnosis, gender, age, academic qualifications, professional status and place of residence showed a tendency towards similar profiles (p>.05). The differences found are associated with more self-determined profiles of adults with ID, inferring the greater weight of involvement characteristics than individual ones (diagnosis). People with IDD recognize self-determination as relevant and present decision-making skills. Recommendations for research and practice will be advanced.

Validação de um questionário sobre educação inclusiva: versão para professores e alunos / Validation of a questionnaire on inclusive education: teacher and student version

RESUMO Os atuais normativos no âmbito da educação inclusiva exigem metodologias de recolha de informação alinhadas com os mais recentes paradigmas. Assim, este estudo objetiva analisar as qualidades métricas (fiabilidade e validade) do Questionário sobre Educação Inclusiva, na dupla versão: professores e alunos. A partir da revisão de literatura e da consulta de instrumentos validados, estabeleceu-se uma versão inicial, avaliada por dez peritos, para a análise da validade de conteúdo (VC). Todos os itens foram considerados representativos, apresentando índices (IVC) superiores a .90 e acordos tendencialmente moderados (k>.30). No pré-teste, com dez participantes (n professores=5, n alunos=5), foi confirmada a fiabilidade ao nível da consistência interna total (α professores=.83; α alunos =.95) e estabilidade temporal (r professores=.92; r alunos=.80). A validade de constructo foi analisada com a aplicação da versão final a 305 professores, entre os 27 e os 68 anos (M=51.41; DP=7.73) e a 82 alunos, entre os 6 e os 20 anos (M=12.96; DP=3.32). As correlações entre secções são moderadas, mas contribuem significativamente (.74>r<.85) para o total. A análise fatorial exploratória aponta uma solução trifatorial e unifatorial explicando 41.88% e 48% da variância total, para professores e alunos, respetivamente. O questionário apresenta-se como um instrumento fiável para estudar perceções, práticas e culturas inclusivas vivenciadas na escola.

ABSTRACT Current legislative framework in the field of inclusive education requires collection methodologies aligned with the latest paradigms. Thus, this study aims to present the metric qualities (reliabillity and validity) of the Questionnaire on Inclusive Education, in its dual version: teachers and students. Based on the literature review and the consultation of validated instruments, an initial version, assessed by ten experts, was established for content validity (CV) analysis. All items were considered representative, presenting indices (IVC) higher than .90 and moderate agreement (k>.30). In the pre-test, with ten participants (n teachers=5, n students=5), reliability was confirmed at the level of total internal consistency (α teachers =.83; α students =.95) and temporal stability (r teachers=.92; r students=.80). The construct validity was analyzed by applying the final version to 305 teachers, aged 27 to 68 years (M=51.41; SD=7.73) and 82 students, aged 6 to 20 years (M=12.96; SD=3.32). The correlations between sections are moderate but contribute significantly (.74>r<.85) to the total. The exploratory factor analysis indicates a three-factor and a one-factor solution explaining 41.88% and 48% of the total variance, for teachers and students, respectively. The questionnaire is a reliable tool to study perceptions, practices and inclusive cultures experienced at school.

Enhanced expression of natural cytotoxicity receptors on cytokine-induced memory-like natural killer cells correlates with effector function.

Introduction: Natural killer (NK) cells are a key component of the innate immune system, involved in defending the host against virus-infected cells and tumor immunosurveillance. Under in vitro culture conditions, IL-12/15/18 can induce a memory-like phenotype in NK cells. These cytokine-induced memory-like (CIML) NK cells possess desirable characteristics for immunotherapies, including a longer lifespan and increased cytotoxicity. Methods: In this study, NK cells were isolated from peripheral blood of healthy donors and stimulated with IL-12/15/18 to induce a memory-like phenotype or with IL-15 alone as a control. After seven days of culture, multiparametric flow cytometry analysis was performed to evaluate the phenotypic and functional profiles of CIML and control NK cells. Results: Our results showed a significantly higher expression of CD25, CD69, NKG2D, NKp30, NKp44, NKp46, TACTILE, and Granzyme B in CIML NK cells compared to control NK cells. In contrast, KIR2D expression was significantly lower in CIML NK cells than in control NK cells. Moreover, functional experiments demonstrated that CIML NK cells displayed enhanced degranulation capacity and increased intracellular IFN-γ production against the target cell line K562. Interestingly, the degranulation capacity of CIML NK cells was positively correlated with the expression of the activating receptors NKp46 and NKp30, as well as with the inhibitory receptor TACTILE. Discussion: In conclusion, this study provides a deep phenotypic characterization of in vitro-expanded CIML NK cells. Moreover, the correlations found between NK cell receptors and degranulation capacity of CIML NK cells allowed the identification of several biomarkers that could be useful in clinical settings.

Gynaecological Causes of Acute Pelvic Pain: Common and Not-So-Common Imaging Findings.

In female patients, acute pelvic pain can be caused by gynaecological, gastrointestinal, and urinary tract pathologies. Due to the variety of diagnostic possibilities, the correct assessment of these patients may be challenging. The most frequent gynaecological causes of acute pelvic pain in non-pregnant women are pelvic inflammatory disease, ruptured ovarian cysts, ovarian torsion, and degeneration or torsion of uterine leiomyomas. On the other hand, spontaneous abortion, ectopic pregnancy, and placental disorders are the most frequent gynaecological entities to cause acute pelvic pain in pregnant patients. Ultrasound (US) is usually the first-line diagnostic technique because of its sensitivity across most common aetiologies and its lack of radiation exposure. Computed tomography (CT) may be performed if ultrasound findings are equivocal or if a gynaecologic disease is not initially suspected. Magnetic resonance imaging (MRI) is an extremely useful second-line technique for further characterisation after US or CT. This pictorial review aims to review the spectrum of gynaecological entities that may manifest as acute pelvic pain in the emergency department and to describe the imaging findings of these gynaecological conditions obtained with different imaging techniques.

Electrochemical miRNA-34a-based biosensor for the diagnosis of Alzheimer's disease.

Alzheimer's disease (AD) is the most common dementia type and a leading cause of death and disability in the elderly. Diagnosis is expensive and invasive, urging the development of new, affordable, and less invasive diagnostic tools. The identification of changes in the expression of non-coding RNAs prompts the development of diagnostic tools to detect disease-specific blood biomarkers. Building on this idea, this work reports a novel electrochemical microRNA (miRNA) biosensor for the diagnosis of AD, based on carbon screen-printed electrodes (C-SPEs) modified with two gold nanostructures and a complementary anti-miR-34a oligonucleotide probe. This biosensor showed good target affinity, reflected on a 100 pM to 1 µM linearity range and a limit of detection (LOD) of 39 pM in buffer and 94 aM in serum. Moreover, the biosensor's response was not affected by serum compounds, indicating selectivity for miR-34a. The biosensor also detected miR-34a in the cell culture medium of a common AD model, stimulated with a neurotoxin to increase miR-34a secretion. Overall, the proposed biosensor makes a solid case for the introduction of a novel, inexpensive, and minimally invasive tool for the early diagnosis of AD, based on the detection of a circulating miRNA overexpressed in this pathology.