Prognostic impact of hyperreflective foci in nonsyndromic retinitis pigmentosa.

PURPOSE: To evaluate the prognostic impact of hyperreflective foci (HRF) on spectral-domain optical coherence tomography (SD-OCT) in nonsyndromic retinitis pigmentosa (RP). METHODS: Retrospective, single-center cohort study including genetically-tested RP patients with a minimum follow-up of 24 months. Clinical data including demographics, genetic results and best-corrected visual acuity (BCVA) at baseline and follow-up were collected. Horizontal and vertical SD-OCT scans were analyzed by 2 independent graders. Outer nuclear layer (ONL) thickness and ellipsoid zone (EZ) width were manually measured in horizontal and vertical scans. HRF were classified according to location: outer retinal layers within the central 3mm (central-HRF), outer retinal layers beyond the central 3mm (perifoveal-HRF), and choroid (choroidal-HRF). Central macular thickness (CMT), central point thickness (CPT) and choroidal thickness (CT) at baseline and follow-up were also recorded. RESULTS: A total of 175 eyes from 94 RP patients (47.9% female, mean age 50.7±15.5 years) were included, with a mean follow-up of 29.24±7.17 months. Mean ETDRS (early treatment diabetic retinopathy study) BCVA decreased from 61.09±23.54 to 56.09±26.65 (p=0.082). At baseline, 72 eyes (41.1%) showed central-HRF, 110 eyes (62.9%) had perifoveal-HRF and 149 eyes (85.1%) exhibited choroidal-HRF. Central-HRF and perifoveal-HRF were associated with worse final BCVA, as well as greater BCVA deterioration (all p<0.0029). Only central-HRF were associated with a worse final CMT (p<0.001). Shorter EZ widths were associated with all types of HRF (p<0.05). Perifoveal and choroidal-HRF predicted smaller final EZ areas (p<0.01). CONCLUSION: HRF are highly prevalent in RP patients and appear to have a negative prognostic impact in visual function and EZ area.

Mutational spectrum and deep phenotyping in Pseudoxanthoma Elasticum: Findings from a Portuguese cohort.

INTRODUCTION: Pseudoxanthoma Elasticum (PXE) is a rare autosomal recessive disorder originated by disease-causing variants in ABCC6 gene. The purpose of this study was to characterize the genetic landscape, phenotypic spectrum and genotype-phenotype correlations in a Portuguese cohort of PXE patients. METHODS: Multicentric cross-sectional study conducted in patients with a clinical and genetic diagnosis of PXE. Patients were identified using the IRD-PT registry (www.retina.com.pt). Genotypes were classified into 3 groups: (1) two truncating variants, (2) two non-truncating variants, or (3) mixed variants. Deep phenotyping comprised a comprehensive ophthalmologic and systemic evaluation using the updated Phenodex Score (PS). RESULTS: Twenty-seven patients (23 families) were included. Sixteen different ABCC6 variants were identified, 7 of which are novel. The most prevalent variant was the nonsense variant c.3421C > T p.(Arg1141*) with an allele frequency of 18.5%. All patients exhibited ocular manifestations. Cutaneous manifestations were present in most patients (88.9%, n = 24/27). A PS score > E2 was strongly associated with worse visual acuity (B = -29.02; p = 0.001). No association was found between genotypic groups and cutaneous, vascular or cardiac manifestations. CONCLUSIONS: This study describes the genetic spectrum of patients with PXE for the first time in a Portuguese cohort. A total of 16 different variants in ABCC6 were found (7 of which are novel), thus highlighting the genotypic heterogeneity associated with this condition and expanding its mutational spectrum. Still, no major genotype-phenotype associations could be established.

The socioeconomic epidemiology of inherited retinal diseases in Portugal.

BACKGROUND: Inherited retinal diseases (IRDs) are a group of rare degenerative disorders of the retina that can lead to blindness from birth to late middle age. Knowing the target population and its resources is essential to better plan support measures. The aim of this study was to evaluate the socioeconomic characteristics of regions in Portugal where IRD patients reside to inform the planning of vision aid and rehabilitation intervention measures. RESULTS: This study included 1082 patients from 973 families, aged 3 to 92 years, with a mean age of 44.8 ± 18.1 years. Patients living with an IRD were identified in 190 of the 308 municipalities. According to this study, the estimated IRD prevalence in Portugal was 10.4 per 100,000 inhabitants, and by municipalities, it ranged from 0 to 131.2 per 100,000 inhabitants. Overall, regions with a higher prevalence of IRD have a lower population density (r=-0.371, p < 0.001), a higher illiteracy rate (r = 0.404, p < 0.001) and an overall older population (r = 0.475, p < 0.001). Additionally, there is a lower proportion of doctor per capita (r = 0.350, p < 0.001), higher social security pensions beneficiaries (r = 0.439, p < 0.001), worse water quality for human consumption (r=-0.194, p = 0.008), fewer audiences at the cinema (r=-0.315, p < 0.001) and lower proportion of foreign guests in tourist accommodations (r=-0.287, p < 0.001). CONCLUSION: The number of identified patients with IRD varied between regions. Using data from national statistics (PORDATA), we observed differences in socioeconomic characteristics between regions. Multiple targeted aid strategies can be developed to ensure that all IRD patients are granted full clinical and socioeconomic support.

The adaptor protein 2 (AP2) complex modulates habituation and behavioral selection across multiple pathways and time windows.

Animals constantly integrate sensory information with prior experience to select behavioral responses appropriate to the current situation. Genetic factors supporting this behavioral flexibility are often disrupted in neuropsychiatric conditions, such as the autism-linked ap2s1 gene which supports acoustically evoked habituation learning. ap2s1 encodes an AP2 endocytosis adaptor complex subunit, although its behavioral mechanisms and importance have been unclear. Here, we show that multiple AP2 subunits regulate acoustically evoked behavior selection and habituation learning in zebrafish. Furthermore, ap2s1 biases escape behavior choice in sensory modality-specific manners, and broadly regulates action selection across sensory contexts. We demonstrate that the AP2 complex functions acutely in the nervous system to modulate acoustically evoked habituation, suggesting several spatially and/or temporally distinct mechanisms through which AP2 regulates escape behavior selection and performance. Altogether, we show the AP2 complex coordinates action selection across diverse contexts, providing a vertebrate model for ap2s1's role in human conditions including autism spectrum disorder.

Impact of symbiotic insect-specific viruses on mosquito vector competence for arboviruses.

Mosquitoes are vectors for arboviruses, such as dengue, Zika, and Chikungunya. Symbiotic interactions can affect the intrinsic ability of mosquitoes to acquire and transmit arboviruses, referred to as vector competence. Insect-specific viruses (ISVs) are commonly found in symbiotic associations with mosquitoes in the wild and can affect many aspects of mosquito biology. Here, we review current knowledge on the effects of symbiotic ISV-mosquito interactions on vector competence. We discuss potential mechanisms underlying these interactions and their implications for shaping new biological control strategies. Finally, we highlight the need for field data analyzing the circulation of ISVs in mosquitoes associated with mechanistic studies in the laboratory.

First investigation into the genetic control of meiosis in sugarcane.

The sugarcane (Saccharum spp.) genome is one of the most complex of all. Modern varieties are highly polyploid and aneuploid as a result of hybridization between Saccharum officinarum and S. spontaneum. Little research has been done on meiotic control in polyploid species, with the exception of the wheat Ph1 locus harboring the ZIP4 gene (TaZIP4-B2) which promotes pairing between homologous chromosomes while suppressing crossover between homeologs. In sugarcane, despite its interspecific origin, bivalent association is favored, and multivalents, if any, are resolved at the end of prophase I. Thus, our aim herein was to investigate the purported genetic control of meiosis in the parental species and in sugarcane itself. We investigated the ZIP4 gene and immunolocalized meiotic proteins, namely synaptonemal complex proteins Zyp1 and Asy1. The sugarcane ZIP4 gene is located on chromosome 2 and expressed more abundantly in flowers, a similar profile to that found for TaZIP4-B2. ZIP4 expression is higher in S. spontaneum a neoautopolyploid, with lower expression in S. officinarum, a stable octoploid species. The sugarcane Zip4 protein contains a TPR domain, essential for scaffolding. Its 3D structure was also predicted, and it was found to be very similar to that of TaZIP4-B2, reflecting their functional relatedness. Immunolocalization of the Asy1 and Zyp1 proteins revealed that S. officinarum completes synapsis. However, in S. spontaneum and SP80-3280 (a modern variety), no nuclei with complete synapsis were observed. Importantly, our results have implications for sugarcane cytogenetics, genetic mapping, and genomics.

Evolutionary and functional characterization of lagomorph guanylate-binding proteins: a story of gain and loss and shedding light on expression, localization and innate immunity-related functions.

Guanylate binding proteins (GBPs) are an evolutionarily ancient family of proteins that are widely distributed among eukaryotes. They belong to the dynamin superfamily of GTPases, and their expression can be partially induced by interferons (IFNs). GBPs are involved in the cell-autonomous innate immune response against bacterial, parasitic and viral infections. Evolutionary studies have shown that GBPs exhibit a pattern of gene gain and loss events, indicative for the birth-and-death model of evolution. Most species harbor large GBP gene clusters that encode multiple paralogs. Previous functional and in-depth evolutionary studies have mainly focused on murine and human GBPs. Since rabbits are another important model system for studying human diseases, we focus here on lagomorphs to broaden our understanding of the multifunctional GBP protein family by conducting evolutionary analyses and performing a molecular and functional characterization of rabbit GBPs. We observed that lagomorphs lack GBP3, 6 and 7. Furthermore, Leporidae experienced a loss of GBP2, a unique duplication of GBP5 and a massive expansion of GBP4. Gene expression analysis by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and transcriptome data revealed that leporid GBP expression varied across tissues. Overexpressed rabbit GBPs localized either uniformly and/or discretely to the cytoplasm and/or to the nucleus. Oryctolagus cuniculus (oc)GBP5L1 and rarely ocGBP5L2 were an exception, colocalizing with the trans-Golgi network (TGN). In addition, four ocGBPs were IFN-inducible and only ocGBP5L2 inhibited furin activity. In conclusion, from an evolutionary perspective, lagomorph GBPs experienced multiple gain and loss events, and the molecular and functional characteristics of ocGBP suggest a role in innate immunity.

Spatial distribution of Pb and Zn in soils under native vegetation in Southeast Brazil.

Heavy metals can play an important biological role as micronutrients but also as potentially toxic elements (PTEs). Understanding the natural concentrations of PTEs-Pb and Zn included-in soils allows for the identification and monitoring of contaminated areas and their role in environmental risk assessment. In this study, we aim to determine semi-total or natural and available concentrations of Pb and Zn in topsoils (0-20 cm depth) from 337 samples under native vegetation in the State of Minas Gerais, Brazil. Additionally, we sought to interpret the spatial geochemical variability using geostatistical techniques and quality reference values for these elements in soils were established. The semi-total concentrations were determined by flame and graphite furnace atomic absorption after microwave-assisted nitric acid digestion method. The available concentrations were extracted using the Mehlich-I extractor and determined by atomic absorption spectrometer. Spatial variability was modeled using semivariance estimators: Matheron's classic, Cressie and Hawkins' robust, and Cressie median estimators, the last two being less sensitive to extreme values. This allowed the construction of digital maps through kriging of semi-total Pb and Zn contents using the median estimator, as well as other soil properties by the robust estimator. The dominance of acidic pH and low CEC values reflects highly weathered low-fertility soils. Semi-total Pb contents ranged from 2.1 to 278 mg kg-1 (median: 9.35 mg kg-1) whereas semi-total Zn contents ranged from 2.7 to 495 mg kg-1 (median: 7.7 mg kg-1). The available Pb contents ranged from 0.1 to 6.92 mg kg-1 (median: 0.54 mg kg-1) whereas available Zn contents ranged from 0.1 to 78.2 mg kg-1 (median: 0.32 mg kg-1). The highest Pb and Zn concentrations were observed near Januária, in the northern part of the territory, probably on limestone rocks from the Bambuí group. Finally, the QRVs for Pb and Zn in natural soils were lower than their background values from other Brazilian region and below the prevention values suggested by Brazilian environmental regulations.

Wearables for Monitoring and Postural Feedback in the Work Context: A Scoping Review.

Wearables offer a promising solution for simultaneous posture monitoring and/or corrective feedback. The main objective was to identify, synthesise, and characterise the wearables used in the workplace to monitor and postural feedback to workers. The PRISMA-ScR guidelines were followed. Studies were included between 1 January 2000 and 22 March 2023 in Spanish, French, English, and Portuguese without geographical restriction. The databases selected for the research were PubMed®, Web of Science®, Scopus®, and Google Scholar®. Qualitative studies, theses, reviews, and meta-analyses were excluded. Twelve studies were included, involving a total of 304 workers, mostly health professionals (n = 8). The remaining studies covered workers in the industry (n = 2), in the construction (n = 1), and welders (n = 1). For assessment purposes, most studies used one (n = 5) or two sensors (n = 5) characterised as accelerometers (n = 7), sixaxial (n = 2) or nonaxialinertial measurement units (n = 3). The most common source of feedback was the sensor itself (n = 6) or smartphones (n = 4). Haptic feedback was the most prevalent (n = 6), followed by auditory (n = 5) and visual (n = 3). Most studies employed prototype wearables emphasising kinematic variables of human movement. Healthcare professionals were the primary focus of the study along with haptic feedback that proved to be the most common and effective method for correcting posture during work activities.

Ray resection in pediatric population after trauma injuries.

The aim of this study is to assess the functional, emotional, and social adaptation of pediatric patients submitted to a hand ray resection to treat a traumatic hand injury. Retrospective study of pediatric patients undergoing hand ray resection, in the period 2013-2022, performed in two hospital institutions. Inclusion criteria: age less than 18 years, primary/secondary resection due to traumatic etiology and follow-up time of more than 1 year. Data concerning demographic information, lesion location, traumatic mechanism and surgical description were collected. Functional outcomes (QuickDASH Score), social and emotional integration (PEDSQL) and satisfaction were evaluated. Seven patients were included, with male predominance (n = 4) and the right side was the most affected (n = 5). Median age at the time of surgery was 10 years (2-15). Primary ray resection, without previous revascularization, was performed in three patients. Secondary ray resection was performed in four patients. Three patients with an unsuccessful revascularization procedure attempt another patient with a sequela with severe deformity. All patients presented a good adaptation to daily living activities, with good pinch and grip function. The median follow-up was 4 years (min:1; max:9). The scores were collected on six out of seven patients. Median QuickDASH score of 14 (min:11; max:22), and PEDSQL[physical] of 95.31 (min:78.13; max:100) and PEDSQL[social] of 93.47 (min:66.3; max:100). Hand ray resection is a rare procedure in pediatric age and usually difficult for patients and parents to accept. However, it is a useful and safe technique that allows for an improvement in overall hand function and psychosocial readaptation in specific and selected cases. Level of evidence: Level of evidence IV - case series.

Three-dimensional simulation for interventional cardiology procedures: Face and content validity.

INTRODUCTION AND OBJECTIVES: Three-dimensional (3D) model simulation provides the opportunity to manipulate real devices and learn intervention skills in a realistic, controlled, and safe environment. To ensure that simulators provide a realistic surrogate to real procedures they must undergo scientific validation. We aimed to evaluate the 3D-printed simulator SimulHeart® for face and content validity to demonstrate its value as a training tool in interventional cardiology (IC). METHODS: Health professionals were recruited from sixteen Portuguese IC units. All participants received a 30-minute theoretical introduction, 10-minute demonstration of each task and then performed the intervention on a 3D-printed simulator (SimulHeart®). Finally, a post-training questionnaire focusing on the appearance of the simulation, simulation content, and satisfaction/self-efficacy was administered. RESULTS: We included 56 participants: 16 "experts" (general and interventional cardiologists), 26 "novices" (cardiology residents), and 14 nurses and allied professionals. On a five-point Likert scale, the overall mean score of face validity was 4.38±0.35 and the overall mean score of content validity was 4.69±0.32. There was no statistically significant difference in the scores provided by "experts" and "novices". Participants reported a high level of satisfaction/self-efficacy with 60.7% considering it strongly improved their skills. The majority (82.1%) "agreed" or "strongly agreed" that after the simulation they felt confident to perform the procedure on a patient. CONCLUSION: The 3D-printed simulator (SimulHeart®) showed excellent face and content validity. 3D simulation may play an important role in future IC training programs. Further research is required to correlate simulator performance with clinical performance in real patients.

Ribogenesis boosts controlled by HEATR1-MYC interplay promote transition into brain tumour growth.

Cell commitment to tumourigenesis and the onset of uncontrolled growth are critical determinants in cancer development but the early events directing tumour initiating cell (TIC) fate remain unclear. We reveal a single-cell transcriptome profile of brain TICs transitioning into tumour growth using the brain tumour (brat) neural stem cell-based Drosophila model. Prominent changes in metabolic and proteostasis-associated processes including ribogenesis are identified. Increased ribogenesis is a known cell adaptation in established tumours. Here we propose that brain TICs boost ribogenesis prior to tumour growth. In brat-deficient TICs, we show that this dramatic change is mediated by upregulated HEAT-Repeat Containing 1 (HEATR1) to promote ribosomal RNA generation, TIC enlargement and onset of overgrowth. High HEATR1 expression correlates with poor glioma patient survival and patient-derived glioblastoma stem cells rely on HEATR1 for enhanced ribogenesis and tumourigenic potential. Finally, we show that HEATR1 binds the master growth regulator MYC, promotes its nucleolar localisation and appears required for MYC-driven ribogenesis, suggesting a mechanism co-opted in ribogenesis reprogramming during early brain TIC development.

Sistema de Análise de Informação do Treinador de Futebol em Competição (SAITFC) -Validação e Aplicação de Instrumento de Observação num Estudo Piloto / istema de Análisis de Información del Entrenador de Fútbol en Competición (SAITFC) -Validación y Aplicación de un Instrumento de Observación en un Estudio Piloto / The Information Analysis System for Football Coaches in Competition (SAITFC) -Validationand Application of an Observation Instrument in a Pilot Study

La observación sistemática es un método que permite obtener numerosas informaciones sobre el comportamiento del entrenador, incluida la comunicación, que es parte integral del proceso de eficacia pedagógica. Tras revisar varios sistemas de observación y comprobar su potencial, pero principalmente sus debilidades, surge el Sistema de Análisis de Información del Entrenador de Fútbol en Competición (SAITFC) desde una perspectiva de evolución y aportación científica. Un sistema flexible que incluye dimensiones, categorías y subcategorías, que hacen referencia a la información en un intento de hacer inclusivos todos los comportamientos relacionados con la información emitida por el entrenador, ayudando a elaborar un perfil de comportamiento en competición. El cálculo de los porcentajes de concordancia, complementando con las estadísticas Kappa de Cohen, mostró altos niveles de fidelidad de las observaciones para ser utilizadas como herramienta científica. Con este estudio piloto, los resultados obtenidos en esta investigación sugieren que los entrenadores emiten cada vez más información, no solo a los atletas, en forma de instrucción y feedback, sino a todos los agentes deportivos involucrados en la competencia, es decir, el arbitraje, el oponente y el equipo técnico en forma de conversaciones. El feedback tiende a ser prescriptive, auditive, dirigido al atleta, táctico y afectivamente neutral. Es importante destacar la expresividad de los feedbacks relacionados con esquemas tácticos y velocidad de reacción. El SAITFC, como herramienta para ayudar a sistematizar el comportamiento del entrenador, demostró ser un método eficaz, contribuyendo así a la formación de los entrenadores, pero también a nivel científico, ayudándolos en el campo.(AU)

Systematic observation is a method that allows obtaining numerous information about the coach ́s behavior, including communication, whichis an integral part of the process of pedagogical effectiveness. After reviewing several observation systems and verifying their potential, mainly their weaknesses, the Information Analysis System for Football Coaches in Competition (SAITFC) emerges from a perspective of evolution andscientific contribution. A flexible system that includes dimensions, categories, and subcategories, which refer to the information in an attempt to make all behaviors related to the information issued by the coach inclusive, helping to elaborate a behavioral profile in the competition. The calculation of agreement percentages, complemented by Cohen ́s Kappa statistics, showed substantial levels of reliability for the observations to be used as a scientific tool. With this pilotstudy, the results obtainedin this investigation suggest that coaches issue more and more information, not only to athletes, in the form of instruction and feedback but to all sports agents involved in the competition, namely arbitration, opponent, and technical team in the form of conversations. Feedback tends to be prescriptive, auditory, addressed to the athlete, tactical, and effectively neutral. It is essential to emphasize the expressiveness of the feedback related to tactical schemes and reaction speed. The SAITFC, as a tool tohelp systematize the coach ́s behavior, proved to be an effective method, thus contributing tothe training of coaches, but also at a scientific level, helping them in the field.(AU)

A observação sistemática é um método que permite obter inúmeras informações sobre o comportamento do treinador, entre elas a comunicação, a qual é parte integrante do processo de eficácia pedagógica.Após revisão de vários sistemas de observação e constatação das suas potencialidades, mas principalmente das suas fragilidades, surge assim numa perspetiva de evolução e de contributo científico, o Sistema de Análise da Informação do Treinador de Futebol em Competição (SAITFC). Um sistema flexível que inclui dimensões, categorias e subcategorias, as quais remetem para a informação numa tentativa de tornar inclusivo todos os comportamentos relacionadoscom a informação emitida pelo treinador, ajudando a umaelaboração de um perfil comportamental emcompetição. O cálculo de percentagens de acordos, complementada pela estatística de Kappa de Cohen, mostrou níveis fortes de fidelidade para as observações serem utilizadas como ferramenta científica. Com este estudo piloto, os resultados obtidos nesta investigação sugerem que os treinadores emitam cada vez mais informação, não só para os atletas, em forma de instrução e feedback, mas para todos os agentes desportivos envolvidos na competição, nomeadamente equipas de arbitragem, adversária e técnica em forma de conversas. O feedback tende a ser prescritivo, auditivo, dirigido ao atleta, tático e de afetividade neutra. De realçar a expressividade dos feedbacks relacionados com esquemas táticos e de velocidade de reação. O SAITFC enquanto ferramenta de auxílio à sistematização do comportamento do treinador, mostrou ser um método eficaz, contribuindo assim para a formação de treinadores, mas também a nível científico, auxiliando-os no terreno.(AU)

Genetic profile of syndromic retinitis pigmentosa in Portugal.

PURPOSE: Retinitis pigmentosa (RP) comprises a genetically and clinically heterogeneous group of inherited retinal degenerations, where 20-30% of patients exhibit extra-ocular manifestations (syndromic RP). Understanding the genetic profile of RP has important implications for disease prognosis and genetic counseling. This study aimed to characterize the genetic profile of syndromic RP in Portugal. METHODS: Multicenter, retrospective cohort study. Six Portuguese healthcare providers identified patients with a clinical diagnosis of syndromic RP and available genetic testing results. All patients had been previously subjected to a detailed ophthalmologic examination and clinically oriented genetic testing. Genetic variants were classified according to the American College of Medical Genetics and Genomics; only likely pathogenic or pathogenic variants were considered relevant for disease etiology. RESULTS: One hundred and twenty-two patients (53.3% males) from 100 families were included. Usher syndrome was the most frequent diagnosis (62.0%), followed by Bardet-Biedl (19.0%) and Senior-Løken syndromes (7.0%). Deleterious variants were identified in 86/100 families for a diagnostic yield of 86.0% (87.1% for Usher and 94.7% for Bardet-Biedl). A total of 81 genetic variants were identified in 25 different genes, 22 of which are novel. USH2A and MYO7A were responsible for most type II and type I Usher syndrome cases, respectively. BBS1 variants were the cause of Bardet-Biedl syndrome in 52.6% of families. Best-corrected visual acuity (BCVA) records were available at baseline and last visit for 99 patients (198 eyes), with a median follow-up of 62.0 months. The mean BCVA was 56.5 ETDRS letters at baseline (Snellen equivalent ~ 20/80), declining to 44.9 ETDRS letters (Snellen equivalent ~ 20/125) at the last available follow-up (p < 0.001). CONCLUSION: This is the first multicenter study depicting the genetic profile of syndromic RP in Portugal, thus contributing toward a better understanding of this heterogeneous disease group. Usher and Bardet-Biedl syndromes were found to be the most common types of syndromic RP in this large Portuguese cohort. A high diagnostic yield was obtained, highlighting current genetic testing capabilities in providing a molecular diagnosis to most affected individuals. This has major implications in determining disease-related prognosis and providing targeted genetic counseling for syndromic RP patients in Portugal.

ECG Forecasting System Based on Long Short-Term Memory.

Worldwide, cardiovascular diseases are some of the primary causes of death; yet the early detection and diagnosis of such diseases have the potential to save many lives. Technological means of detection are becoming increasingly essential and numerous techniques have been created for this purpose, such as forecasting. Of these techniques, the time series forecasting technique seeks to predict future events. The long-term time series forecasting of physiological data could assist medical professionals in predicting and treating patients based on very early diagnosis. This article presents a model that utilizes a deep learning technique to predict long-term ECG signals. The forecasting model can learn signals' nonlinearity, nonstationarity, and complexity based on a long short-term memory architecture. However, this is not a trivial task as the correct forecasting of a signal that closely resembles the original complex signal's structure and behavior while minimizing any differences in amplitude continues to pose challenges. To achieve this goal, we used a dataset available on the Physio net database, called MIT-BIH, with 48 ECG recordings of 30 min each. The developed model starts with pre-processing to reduce interference in the original signals, then applies a deep learning algorithm, based on a long short-term memory (LTSM) neural network with two hidden layers. Next, we applied the root mean square error (RMSE) and mean absolute error (MAE) metrics to evaluate the performance of the model and obtained an average RMSE of 0.0070±0.0028 and an average MAE of 0.0522±0.0098 across all simulations. The results indicate that the proposed LSTM model is a promising technique for ECG forecasting, considering the trends of the changes in the original data series, most notably in R-peak amplitude. Given the model's accuracy and the features of the physiological signals, the system could be used to improve existing predictive healthcare systems for cardiovascular monitoring.

Neofunctionalization driven by positive selection led to the retention of the loqs2 gene encoding an Aedes specific dsRNA binding protein.

BACKGROUND: Mosquito borne viruses, such as dengue, Zika, yellow fever and Chikungunya, cause millions of infections every year. These viruses are mostly transmitted by two urban-adapted mosquito species, Aedes aegypti and Aedes albopictus. Although mechanistic understanding remains largely unknown, Aedes mosquitoes may have unique adaptations that lower the impact of viral infection. Recently, we reported the identification of an Aedes specific double-stranded RNA binding protein (dsRBP), named Loqs2, that is involved in the control of infection by dengue and Zika viruses in mosquitoes. Preliminary analyses suggested that the loqs2 gene is a paralog of loquacious (loqs) and r2d2, two co-factors of the RNA interference (RNAi) pathway, a major antiviral mechanism in insects. RESULTS: Here we analyzed the origin and evolution of loqs2. Our data suggest that loqs2 originated from two independent duplications of the first double-stranded RNA binding domain of loqs that occurred before the origin of the Aedes Stegomyia subgenus, around 31 million years ago. We show that the loqs2 gene is evolving under relaxed purifying selection at a faster pace than loqs, with evidence of neofunctionalization driven by positive selection. Accordingly, we observed that Loqs2 is localized mainly in the nucleus, different from R2D2 and both isoforms of Loqs that are cytoplasmic. In contrast to r2d2 and loqs, loqs2 expression is stage- and tissue-specific, restricted mostly to reproductive tissues in adult Ae. aegypti and Ae. albopictus. Transgenic mosquitoes engineered to express loqs2 ubiquitously undergo developmental arrest at larval stages that correlates with massive dysregulation of gene expression without major effects on microRNAs or other endogenous small RNAs, classically associated with RNA interference. CONCLUSIONS: Our results uncover the peculiar origin and neofunctionalization of loqs2 driven by positive selection. This study shows an example of unique adaptations in Aedes mosquitoes that could ultimately help explain their effectiveness as virus vectors.

[Evaluation of the Scientific Production in the Field of General Practice and Family Medicine in Portugal]. / Avaliação da Produção Científica na Área da Medicina Geral e Familiar em Portugal.

INTRODUCTION: The Portuguese publications in the field of General Practice and Family Medicine have not yet been assessed in bibliometric studies. The aim of this study was to analyze that production between 2012 and 2022. METHODS: The Web of Science Core Collection was used to gather the number of articles, journals and citations obtained; the Journal Citation Reports to obtain the Impact Factor and quartile of journals; and Scimago Journal & Country Rank, for the comparison of data with other European countries. The search was based on the following query: "usf OR unidade de Saude Familiar OR centro de Saude OR ACeS OR medicina geral familiar OR Gen Practice Family SAME Portugal", and a time window between 2012 and 2022 was defined. The study considered the following quantitative indicators: total number of publications, typology, language, affiliation, co-authors, geographical distribution, thematic areas, and the number of publications/inhabitant and publications/physician from European countries; the qualitative indicators selected were the Impact Factor (IF), the quartile and the number of citations. RESULTS: Between 2012 and 2022, the national scientific production had an average annual growth rate of 36.6%. Of 389 publications, 73.8% were 'Articles' and 11.8% were 'Review Articles', predominantly in English (88.4%). The fields of 'General Internal Medicine' (24.7%) and 'Public Environmental Health' (14.9%) had the highest publication rates among the journals. The 389 publications received 5354 citations, for an average of 13.76 citations per article, and the average yearly citation growth was 115%. According to IF, 22.5% of the 222 journals belonged to Q4, 27.5% to Q3, 29.7% to Q2 and 20.3% to Q1, and therefore no significant bias regarding the journals where Portuguese doctors publish was observed. CONCLUSION: The bibliometric analysis allowed us to examine the evolution of the scientific production in the field of Portuguese General Practice and Family Medicine by observing an increasing publication trend and with a high potential for publication growth.

Introdução: As publicações portuguesas da área de Medicina Geral e Familiar ainda não foram alvo de estudos bibliométricos. Pretendeu-se analisar tal produção no período entre 2012 e 2022. Métodos: Usou-se a Web of Science Core Collection para obter o número de artigos, as revistas de publicação e as respetivas citações; o Journal Citation Reports para obter o Fator de Impacto e o quartil das revistas; e o Scimago Journal & Country Rank para a comparação de dados com outros países europeus. Utilizou-se a equação de pesquisa "usf OR unidade de Saude Familiar OR centro de Saude OR ACeS OR medicina geral familiar OR Gen Practice Family SAME Portugal", e selecionaram-se os resultados obtidos no período entre 2012 e 2022. Os indicadores quantitativos selecionados foram o total de publicações, tipologia, idioma, afiliação, coautorias, distribuição geográfica, áreas temáticas e o número de publicações/habitante e de publicações/médico em países europeus. Como indicadores qualitativos escolheu-se o Fator de Impacto (FI), o quartil das revistas e o número de citações. Resultados: Entre 2012 e 2022, a produção científica nacional teve uma taxa de crescimento médio anual de 36,6%. Em 389 publicações, 73,8% foram de 'Article' e 11,8% de 'Review Article', predominando a publicação em língua inglesa (88,4%). As revistas com maior publicação pertencem às áreas 'General Internal Medicine' (24,7%) e 'Public Environmental Health' (14,9%). As 389 publicações tiveram 5354 citações, com uma média de 13,76 citações por artigo e a taxa de crescimento médio anual de citações foi de 115%. Em função do FI, das 222 revistas, 22,5% pertenciam ao Q4, 27,5% ao Q3, 29,7% ao Q2 e 20,3% ao Q1, não se observando por isso nenhum viés assinalável relativamente às revistas onde os médicos portugueses publicam. Conclusão: A análise bibliométrica permitiu avaliar a evolução e o estado da produção científica da área da Medicina Geral e Familiar por investigadores portugueses, observando-se uma tendência de publicação crescente, e com forte potencial de crescimento.

Homeless Outreach Psychiatric Engagement for Lisboa (HOPE 4 Lisboa): One year of marontology, and one John Doe living with Diogenes syndrome.

BACKGROUND: In Europe, psychiatric disorders seem to affect up to 50% of the homeless. In Portugal there were, at a certain time, circa 3,396 homeless people, half living in the capital city, Lisboa. AIMS: The Homeless Outreach Psychiatric Engagement for Lisboa (HOPE 4 Lisboa) was created, in January 1st 2022, as a collaboration including staff from the local state asylum, medical school and town hall in Lisboa, Portugal, in order to provide better treatment for the super difficult cases of psychiatric patients living homeless in Lisboa. METHOD: During 2022, the HOPE 4 team made night rounds, every 15 days on Tuesday's night (20:30 to 23:30) trying to reach, at least, one dozen of homeless psychiatric patients, previously identified. RESULTS: The HOPE 4 Lisboa interviewed 101 patients (53.4%) out of the 189 programed visits. From this group, 72 (72%) had already a previous psychiatric diagnosis. From those 101 patients, reports for 47 (47%) were sent for an eventual compulsory psychiatric assessment. From those 47 only 21 patients (21%) were admitted in the psychiatry ward. Finally we discuss the most super difficult patient we found, as a small case report: a John Doe living in complete Diogenes syndrome. CONCLUSIONS: there are still a few psychiatrists interested in treating homeless people completely or partially out of the classic mental health care systems. Some claim to be doing interstitial psychiatry, others street psychiatry, but we could also call it marontology.

The European Portuguese Version of the Brief Negative Symptom Scale.

Negative symptoms reflect a currently much-untreated loss of normal functioning and are frequently found in psychotic disorders. We present the first translation of the Brief Negative Symptom Scale (BNSS) to European Portuguese and evaluate its validity in a sample of Portuguese male patients with a psychotic spectrum disorder. The Portuguese BNSS showed excellent internal consistency, high convergent validity (i.e., strong correlation with the PANSS negative factor), and high discriminant validity (i.e., a lack of association with the PANSS positive factor). In sum, the present European Portuguese BNSS has shown to be reliable, thus extending this instrument's clinical availability worldwide.

Intraocular lens power calculation: the contribute of angle kappa and ocular biomechanics.

PURPOSE: The effective lens position depends not only in static biometry but also on the dynamic interaction of the lens bag with the remaining ocular structures during the postoperative period. Our purpose was to study the effect of ocular biomechanics on the prediction error of IOL power calculation. SETTING: Ophthalmology Department, Centro Hospitalar Universitário do Porto, Portugal. DESIGN: Prospective longitudinal study. MATERIALS: Before cataract surgery subjects underwent biometry with IOL Master® 700 (Zeiss, Germany) and biomechanical analysis with Corvis Scheimpflug Technology® (Oculus, Germany). The targeted spherical equivalent was calculated with SRK-T and Barrett Universal II. Associations between prediction error (PE), absolute prediction error (AE) and biometric and biomechanical parameters were performed with stepwise multivariable linear correlation analysis. RESULTS: This study included 67 subjects. Using the SRKT formula, there was association between PE and Corvis Biomechanical Index (CBI, B=-0.531, p=0.011) and between AE and the horizontal offset between the center of the pupil and the visual axis (angle kappa, B=-0.274, p=0.007). Considering the Barret Universal II formula, PE was independently associated with anterior chamber depth (B=-0.279, p=0.021) and CBI (B=-0.520, p=0.013) and AE was associated with angle kappa (B=-0.370, p=0.007). CONCLUSION: A large angle kappa may reduce the predictability of IOL power calculation. Ocular biomechanics likely influence the refractive outcomes after IOL implantation. This study shows that eyes with softer corneal biomechanics have more myopic prediction error. This may relate to anteriorization of the effective lens position. Dynamic measurements may be the way to progress into future formulas.