Effects of digital transformation on firm performance: The role of IT capabilities and digital orientation.

Organisations undertake profound changes to fit in a rapidly evolving digital setting. However, although the IT capabilities of the organisational members play a critical role in this, the mechanism driving IT capabilities towards enhanced firm performance is not fully understood. A theoretical model to analyse the role of digital orientation and digital transformation in this relationship is introduced and tested on a set of 246 firms through the Partial Least Squares-Structural Equation Modeling method (PLS-SEM). This research contributes to the literature by introducing the social aspect to the study of technology management, delving also into the antecedents of digital transformation. Results confirm a positive effect of IT capabilities on firm performance through the development of a digital orientation and the digital transformation of the organisation.

Recent innovations in long-term care coverage and financing: a rapid scoping review.

OBJECTIVES: To identify, chart and analyse the literature on recent initiatives to improve long-term care (LTC) coverage, financial protection and financial sustainability for persons aged 60 and older. DESIGN: Rapid scoping review. DATA SOURCES: Four databases and four sources of grey literature were searched for reports published between 2017 and 2022. After using a supervised machine learning tool to rank titles and abstracts, two reviewers independently screened sources against inclusion criteria. ELIGIBILITY CRITERIA: Studies published from 2017-2022 in any language that captured recent LTC initiatives for people aged 60 and older, involved evaluation and directly addressed financing were included. DATA EXTRACTION AND ANALYSIS: Data were extracted using a form designed to answer the review questions and analysed using descriptive qualitative content analysis, with data categorised according to a prespecified framework to capture the outcomes of interest. RESULTS: Of 24 reports, 22 were published in peer-reviewed journals, and two were grey literature sources. Study designs included quasi-experimental study, policy analysis or comparison, qualitative description, comparative case study, cross-sectional study, systematic literature review, economic evaluation and survey. Studies addressed coverage based on the level of disability, income, rural/urban residence, employment and citizenship. Studies also addressed financial protection, including out-of-pocket (OOP) expenditures, copayments and risk of poverty related to costs of care. The reports addressed challenges to financial sustainability such as lack of service coordination and system integration, insufficient economic development and inadequate funding models. CONCLUSIONS: Initiatives where LTC insurance is mandatory and accompanied by commensurate funding are situated to facilitate ageing in place. Efforts to expand population coverage are common across the initiatives, with the potential for wider economic benefits. Initiatives that enable older people to access the services needed while avoiding OOP-induced poverty contribute to improved health and well-being. Preserving health in older people longer may alleviate downstream costs and contribute to financial sustainability.

Validation of the SCORE2 risk prediction algorithm in a Portuguese population: A new model to estimate 10-year cardiovascular disease incidence in Europe.

INTRODUCTION AND OBJECTIVES: Subjects without cardiovascular (CV) disease (CVD) may suffer from subclinical atherosclerosis, and are at increased risk for atherosclerotic CV events (ASCVE). The ESC/EAS risk SCORE was updated by SCORE2, which estimates 10-year risk of fatal and non-fatal CVD in European populations aged 40-69 years without established CVD or diabetes. Our aim was to compare the two ESC/EAS risk scores and to validate SCORE2 in our population. METHODS: A total of 1071 individuals (age 57.2±6.1 years; 75.2% male) without CVD or diabetes, from GENEMACOR study controls, were analyzed over 5.4±3.9 years. The population was stratified into risk categories according to the two scores, and the area under the ROC curve (AUC) and Harrell's C-index assessed the scores' performance. Calibration was performed using the goodness-of-fit test, and occurrence of the first event assessed by Cox regression. Kaplan-Meier analysis estimated SCORE2 survival. RESULTS: SCORE stratified subjects into four risk categories: low (7.4%), moderate (46.5%), high (25.3%) and very high (20.8%), and SCORE2 into three: low-to-moderate (24.7%), high (59.0%) and very high (16.2%). SCORE presented good discrimination for CV mortality (AUC=0.838; C-index=0.834, 95% CI: 0.728-0.940), as did SCORE2 for total CV events (AUC=0.744; C-index=0.728, 95% CI: 0.648-0.808). Calibration did not show a disparity between observed and expected ASCVE. The probability of ASCVE was eight times higher in very-high-risk SCORE2 (p=0.001), and three times in the high-risk group (p=0.049). Event-free survival was 99%, 90% and 72% in the low-to-moderate, high and very-high-risk categories, respectively (p<0.0001). CONCLUSIONS: SCORE2 improved population stratification by identifying higher-risk patients, enabling early preventive measures. It showed good discriminative ability for all ASCVE.

Predictive improvement of adding coronary calcium score and a genetic risk score to a traditional risk model for cardiovascular event prediction.

AIMS: Coronary artery calcium score (CACS) and polygenic risk score have been used as novel markers to predict cardiovascular (CV) events of asymptomatic individuals compared with traditional scores. No previous studies have directly compared the additive capacity of these two markers relative to conventional scores. The aim of the study was to evaluate the change in CV risk prediction ability when CACS, genetic risk score (GRS), or both are added to Systematic Coronary Risk Evaluation 2 (SCORE2). METHODS AND RESULTS: In a prospective, observational population-based study, 1002 asymptomatic subjects (mean age 53.1 ± 6.8 years, 73.8% male), free of clinical coronary disease and diabetes, were selected from GENEMACOR-study controls. SCORE2, CACS, and GRS were estimated to evaluate CV events' predictive and discriminative ability through Harrell's C-statistics. Net reclassification improvement (NRI) and integrated discrimination index were used to reclassify the population. Multivariable Cox proportional hazard ratio (HR) analysis assessed the variables independently associated with CV events. C-statistic demonstrated that the discriminative value for CV event occurrence was 0.608 for SCORE2, increasing to 0.749 (P = 0.001) when CACS was added, and improved to 0.802 (P = 0.0008) with GRS, showing a better discriminative capacity for CV events. Continuous NRI reclassified >70% of the population. Cox proportional analysis showed that the highest categories of SCORE2, CACS, and GRS remained in the equation with an HR of 2.9 (P = 0.003), 5.0 (P < 0.0001), and 3.2 (P = 0.003), respectively, when compared with the lowest categories. CONCLUSION: In our population, CACS added to SCORE2 had better ability than GRS in CV event risk prediction, discrimination, and reclassification. However, adding the three scores can become clinically relevant, especially in intermediate-risk persons.

Our study highlights the impact of including coronary artery calcium score (CACS) and genetic risk score (GRS) alongside Systematic Coronary Risk Evaluation 2 (SCORE2) for enhancing cardiovascular (CV) risk assessment in primary prevention. In our population, adding CACS to SCORE2 exhibited a superior discriminative capacity for CV events compared with GRS alone in terms of risk prediction, discrimination, and reclassification. Our results emphasize the potential clinical relevance of using all three scores to identify high-risk individuals who would benefit from earlier and more stringent cardiovascular risk management strategies to prevent future cardiovascular events.

Convergence and divergence in science and practice of urban and rural forest restoration.

Forest restoration has never been higher on policymakers' agendas. Complex and multi-dimensional arrangements across the urban-rural continuum challenge restorationists and require integrative approaches to strengthen environmental protection and increase restoration outcomes. It remains unclear if urban and rural forest restoration are moving towards or away from each other in practice and research, and whether comparing research outcomes can help stakeholders to gain a clearer understanding of the interconnectedness between the two fields. This study aims to identify the challenges and opportunities for enhancing forest restoration in both urban and rural systems by reviewing the scientific evidence, engaging with key stakeholders and using an urban-rural forest restoration framework. Using the Society for Ecological Restoration's International Principles as discussion topics, we highlight aspects of convergence and divergence between the two fields to broaden our understanding of forest restoration and promote integrative management approaches to address future forest conditions. Our findings reveal that urban and rural forest restoration have convergent and divergent aspects. We emphasise the importance of tailoring goals and objectives to specific contexts and the need to design different institutions and incentives based on the social and ecological needs and goals of stakeholders in different regions. Additionally, we discuss the challenges of achieving high levels of ecological restoration and the need to go beyond traditional ecology to plan, implement, monitor, and adaptively manage restored forests. We suggest that rivers and watersheds could serve as a common ground linking rural and urban landscapes and that forest restoration could interact with other environmental protection measures. We note the potential for expanding the creative vision associated with increasing tree-containing environments in cities to generate more diverse and resilient forest restoration outcomes in rural settings. This study underscores the value of integrative management approaches in addressing future forest conditions across the urban-rural continuum. Our framework provides valuable insights for policymakers, researchers, and decision-makers to advance the field of forest restoration and address the challenges of restoration across the urban-rural continuum. The rural-urban interface serves as a convergence point for forest restoration, and both urban and rural fields can benefit from each other's expertise.

Systemic and local responses of cytokines and tissue histology following intramammary lipopolysaccharide challenge in dairy cows.

During bovine mastitis, immune responses include the release of cytokines and the recruitment of leukocytes, resulting in profound structural and functional changes in the mammary gland. Our aims were to delineate systemic and local cytokine responses and to quantify histological changes in the mammary tissue of lactating cows after acute intramammary lipopolysaccharide (LPS) challenge. Ten multiparous dairy cows were paired to either treatment (TRT) or control (CON) groups. For TRT cows, one side of the udder was randomly assigned to receive treatment with LPS (50 µg in 10 mL of saline, TL) into both the front and rear quarters; the contralateral quarters received saline (10 mL). Udder-halves of CON cows were similarly assigned randomly to receive either saline (10 mL, CS) or no infusion (untreated). Temporal changes in the concentrations of 15 cytokines in the blood (0, 3, 6, 12, and 24 h relative to the LPS infusion) and in mammary tissue (0, 3, and 12 h) were determined, as were concomitant changes in mammary histology. The cytokines IL-6, IL-10, MCP-1, and MIP-1ß showed a systemic response as their concentrations were significantly different in the plasma of TRT cows as compared with CON cows after LPS challenge. The cytokines IL-1α, IL-1ß, IL-6, IL-8, IL-17A, IL-36RA, IP-10, MCP-1, MIP-1α, MIP-1ß, TNF-α, and VEGF-A showed a local response in TL glands, and 8 cytokines, IL-1ß, IL-6, IL-10, IL-17A, IL-36RA, IP-10, MIP-1ß, and VEGF-A showed systemic changes in the nonchallenged mammary glands adjacent to LPS-infused glands. Endotoxin challenge evoked changes in the histology of mammary tissue that included a 5.2- and 7.2-fold increases in the number of neutrophils in alveolar lumens at 3 h and 12 h, respectively. In summary, LPS challenge induced specific local and systemic responses in cytokine induction and elicited neutrophil infiltration in bovine mammary tissue.

Acute Hepatitis E-Associated Guillain-Barré Syndrome.

Guillain-Barré syndrome (GBS) is a rare autoimmune disorder of the peripheral nervous system that causes progressive weakness and sensory disturbances, usually following an infection or immunization. It has been associated with multiple causes, including bacterial and viral infections. Hepatitis E virus (HEV) is a common cause of acute viral hepatitis that can rarely develop neurological complications. We report a case of a 72-year-old man who developed GBS secondary to an acute HEV infection. He presented with numbness and weakness of the lower limbs that rapidly evolved into respiratory failure requiring mechanical ventilation and intravenous immunoglobulin therapy (IVIg). This case adds to the literature on the association between HEV infection and GBS and the importance of early detection of this rapidly progressive condition.

Clinical and molecular characterisation of metastatic papillary thyroid cancer according to radioiodine therapy outcomes.

PURPOSE: Radioiodine (RAI) therapy remains the gold-standard approach for distant metastatic differentiated thyroid cancer (TC). The main objective of our work was to identify the clinical and molecular markers that may help to predict RAI avidity and RAI therapy response of metastatic lesions in a cohort of papillary thyroid cancer (PTC) patients. METHODS: We performed a retrospective analysis of 122 PTC patients submitted to RAI therapy due to distant metastatic disease. We also analysed, through next-generation sequencing, a custom panel of 78 genes and rearrangements, in a smaller cohort of 31 metastatic PTC, with complete follow-up, available RAI therapy data, and existing tumour sample at our centre. RESULTS: The most frequent outcome after RAI therapy was progression of disease in 59.0% of cases (n = 71), with median estimate progression-free survival of 30 months. RAI avidity was associated with PTC subtype, age and stimulated thyroglobulin at first RAI therapy for metastatic disease. The most frequently altered genes in the cohort of 31 PTC patients' primary tumours were RAS isoforms (54.8%) and TERT promoter (TERTp) (51.6%). The presence of BRAF p.V600E or RET/PTC alterations was associated with lower avidity (p = 0.012). TERTp mutations were not associated with avidity (p = 1.000) but portended a tendency for a higher rate of progression (p = 0.063); similar results were obtained when RAS and TERTp mutations coexisted (p = 1.000 and p = 0.073, respectively). CONCLUSIONS: Early identification of molecular markers in primary tumours may help to predict RAI therapy avidity, the response of metastatic lesions and to select the patients that may benefit the most from other systemic therapies.

Role of monocytes and dendritic cells in cardiac reverse remodelling after cardiac resynchronization therapy.

BACKGROUND AND AIMS: Monocytes and dendritic cells (DC) are both key inflammatory cells, with recognized effects on cardiac repair. However, there are distinct subsets of monocytes with potential for beneficial or detrimental effects on heart failure (HF) pathogenesis. The connection between reverse cardiac remodelling, the potential anti-inflammatory effect of cardiac resynchronization therapy (CRT) and monocytes and DC homeostasis in HF is far from being understood. We hypothesized that monocytes and DC play an important role in cardiac reverse remodelling and CRT response. Therefore, we aimed to assess the potential role of baseline peripheral levels of blood monocytes and DC subsets and their phenotypic and functional activity for CRT response, in HF patients. As a secondary objective, we aimed to evaluate the impact of CRT on peripheral blood monocytes and DC subsets, by comparing baseline and post CRT circulating levels and phenotypic and functional activity. METHODS: Forty-one patients with advanced HF scheduled for CRT were included in this study. The quantification and phenotypic determination of classical (cMo), intermediate (iMo) and non-classical monocytes (ncMo), as well as of myeloid (mDC) and plasmacytoid DC (pDC) were performed by flow cytometry in a FACSCanto™II (BD) flow cytometer. The functional characterization of total monocytes and mDC was performed by flow cytometry in a FACSCalibur flow cytometer, after in vitro stimulation with lipopolysaccharide from Escherichia coli plus interferon (IFN)-γ, in the presence of Brefeldina A. Comparisons between the control and the patient group, and between responders and non-responders to CRT were performed. RESULTS: Compared to the control group, HF population presented a significantly lower frequency of pDC at baseline and a higher proportion of monocytes and mDC producing IL-6 and IL-1ß, both before and 6-months after CRT (T6). There was a remarkable decrease of cMo and an increase of iMo after CRT, only in responders. The responder group also presented higher ncMo values at T6 compared to the non-responder group. Both responders and non-responders presented a decrease in the expression of CD86 in all monocyte and DC populations after CRT. Moreover, in non-responders, the increased frequency of IL-6-producing DC persisted after CRT. CONCLUSION: Our study provides new knowledge about the possible contribution of pDC and monocytes subsets to cardiac reverse remodelling and response to CRT. Additionally, CRT is associated with a reduction on CD86 expression by monocytes and DC subsets and in their potential to produce pro-inflammatory cytokines, contributing, at least in part, for the well described anti-inflammatory effects of CRT in HF patients.

In Silico Screening and Molecular Dynamics Simulations against Tyrosine-protein Kinase Fyn Reveal Potential Novel Therapeutic Candidates for Bovine Papillomatosis.

BACKGROUND: Decreased beef productivity due to papillomatosis has led to the development and identification of novel targets and molecules to treat the disease. Protein kinases are promising targets for the design of numerous chemotherapy drugs. OBJECTIVE: This study aimed to screen and design new inhibitors of bovine Fyn, a protein kinase, using structure-based computational methods, such as molecular docking and molecular dynamics simulation (MDS). METHODS: To carry out the molecular docking analysis, five ligands obtained through structural similarity between active compounds along with the cross-inhibition function between the ChEMBL and Drugbank databases were used. Molecular modeling was performed, and the generated models were validated using PROCHECK and Verify 3D. Molecular docking was performed using Autodock Vina. The complexes formed between Fyn and the three best ligands had their stability assessed by MDS. In these simulations, the complexes were stabilized for 100 ns in relation to a pressure of 1 atm, with an average temperature of 300 k and a potential energy of 1,145,336 kJ/m converged in 997 steps. RESULTS: Docking analyses showed that all selected ligands had a high binding affinity with Fyn and presented hydrogen bonds at important active sites. MDS results support the docking results, as the ligand showed similar and stable interactions with amino acids present at the binding site of the protein. In all simulations, sorafenib obtained the best results of interaction with the bovine Fyn. CONCLUSION: The results highlight the identification of possible bovine Fyn inhibitors; however, further studies are important to confirm these results experimentally.

Peak nasal inspiratory flow in children and adolescents with sickle cell disease: a case-control study.

OBJECTIVE: Sickle cell disease is the most frequent of the hereditary hemoglobinopathies and it presents multisystemic effects. A manifestation that is commonly found in sickle cell disease is upper airway obstruction, particularly adenotonsillar hypertrophy. This study aims to evaluate the peak nasal inspiratory flow measurements of children and adolescents with sickle cell disease. METHODS: This is a case-control study on children aged between 8 and 15 years who were diagnosed with sickle cell disease. Peak nasal inspiratory flow measurements were obtained from patients. RESULTS: A total of 279 patients were enrolled in this study, with 93 in the case group and 186 in the control group. The case group had an 82.83% chance of having lower peak nasal inspiratory flow values than the control group. In the case group, 75% of the peak nasal inspiratory flow values were in the lower standards, whereas in the control group, only 25% were in the lower standards. CONCLUSION: This study showed a high prevalence of reduced peak nasal inspiratory flow values in children with sickle cell disease and could certainly be incorporated into the day-to-day clinical evaluation of patients as a screening instrument.

Longitudinally Extensive Transverse Myelitis as a First Manifestation of Sarcoidosis.

Longitudinally extensive transverse myelitis (LETM) is a debilitating inflammatory spinal cord lesion involving several spinal segments. There are several possible etiologies, with spinal cord sarcoidosis being a rare cause of LETM. Spinal cord sarcoidosis is, in itself, a rare manifestation of sarcoidosis that can be difficult to diagnose, especially in patients with no prior history of systemic sarcoidosis, frequently leading to a delayed diagnosis. We report the case of a 53-year-old man who developed LETM as the first manifestation of sarcoidosis. The patient presented with progressive lower limb weakness, urinary retention, sensory disturbances, and muscle spasms. Imaging studies showed hyperintense lesions extending over multiple spinal segments. After the exclusion of other causes and a lymph node biopsy showing non-caseating granulomas, the diagnosis of LETM secondary to sarcoidosis was confirmed.

SPRY4 as a Potential Mediator of the Anti-Tumoral Role of Macrophages in Anaplastic Thyroid Cancer Cells.

Anaplastic thyroid carcinoma (ATC) is the most lethal subtype of thyroid cancer, with high invasive and metastatic potential, not responding to conventional treatments. Its aggressiveness may be influenced by macrophages, which are abundant cells in the tumor microenvironment. To investigate the role of macrophages in ATC aggressiveness, indirect co-cultures were established between ATC cell lines and THP-1-derived macrophages. Macrophages significantly increased both the migration and invasion of T235 cells (p < 0.01; p < 0.01), contrasting with a decrease in C3948 (p < 0.001; p < 0.05), with mild effects in T238 migration (p < 0.01) and C643 invasion (p < 0.05). Flow cytometry showed upregulation of CD80 (pro-inflammatory, anti-tumoral) and downregulation of CD163 (anti-inflammatory, pro-tumoral) in macrophages from co-culture with T235 (p < 0.05) and C3948 (p < 0.05), respectively. Accordingly, we found an upregulation of secreted pro-inflammatory mediators (e.g., GM-CSF, IL-1α; p < 0.05) in C3948-macrophage co-cultures. Proteomic analysis showed the upregulation of SPRY4, an inhibitor of the MAPK pathway, in C3948 cells from co-culture. SPRY4 silencing promoted cancer cell invasion, reverting the reduced invasion of C3948 caused by macrophages. Our findings support that macrophages play a role in ATC cell aggressiveness. SPRY4 is a possible modulator of macrophage-ATC cell communication, with a tumor suppressor role relevant for therapeutic purposes.

Modified Dunn Technique for Unstable Slipped Capital Femoral Epiphysis: A Midterm Single Center Experience.

Objective To evaluate the safety and reproducibility of the surgery for unstable slipped capital femoral epiphysis (SCFE) through the modified Dunn technique in a single center cohort from Brazil. Methods We retrospectively analyzed a cohort of patients submitted to this procedure by a single surgeon who was a hip preservation specialist. Demographic data and radiographic angles were evaluated for the relative risk (RR) of avascular necrosis (AVN) using a log-binomial regression model with simple and random effects. Results Among the 30 patients (30 hips) with a mean age of 11.79 years at the time of the operation, there were 17 boys and 18 left hips, which were operated on in a mean of 11.5 days after the slip. The mean follow-up was of 38 months. The preoperative Southwick angle averaged 60.69° against 4.52° postoperatively ( p < 0.001). A larger preoperative slip angle was associated with the development of AVN (RR: 1.05; 95% confidence interval [95%CI]: 1.02-1.07; p < 0.01). The overall AVN rate was of 26.7%. Function was good or excellent in 86% of uncomplicated hips, and poor in 87.5% of the partients who developed AVN, as graded by the Harris Hip Score. There was no statistical relationship between epiphyseal bleeding and AVN development ( p = 0.82). Conclusion The modified Dunn technique is associated with restoration of the femoral alignment and function after unstable SCFE, when uncomplicated. Moreover, it was shown to be reproducible in our population, with a rate of 26% of femoral head necrosis.

Synthesis, Docking Studies and Evaluation of Chalcones as Anti-Helicobacter pylori and antitumoral Agents.

Helicobacter pylori colonizes the gastric epithelium of 50 % of world population and it is the main etiological agent of human chronic gastritis, peptic ulcer, and gastric cancer. In this study, we synthesized and characterized a series of 14 chalcones and evaluated their anti-H. pylori, NO inhibition (in vitro and in silico), and AGS cells cytotoxic effects. Compounds 3b and 3h showed MIC of 8 µg/mL. We observed structure-activity relationships, mainly related to the influence of methoxy substituent at C-2 (3b) and the nitro group at C-4 (3h) in chalcone scaffold. The fourteen chalcones inhibited the NO production in LPS-stimulated macrophages and showed potential for interaction on the active site of the iNOS enzyme. Finally, 3b and 3h showed the highest selectivity to the AGS cell lines. Thus, ours results suggest 3b and 3h as potential candidates for design of new and effective agents against H. pylori and related diseases.

Modified Dunn Technique for Unstable Slipped Capital Femoral Epiphysis: A Midterm Single Center Experience / Técnica de Dunn modificada no escorregamento da epífise femoral proximal com instabilidade: Experiência unicêntrica de médio prazo

Abstract Objective To evaluate the safety and reproducibility of the surgery for unstable slipped capital femoral epiphysis (SCFE) through the modified Dunn technique in a single center cohort from Brazil. Methods We retrospectively analyzed a cohort of patients submitted to this procedure by a single surgeon who was a hip preservation specialist. Demographic data and radiographic angles were evaluated for the relative risk (RR) of avascular necrosis (AVN) using a log-binomial regression model with simple and random effects. Results Among the 30 patients (30 hips) with a mean age of 11.79 years at the time of the operation, there were 17 boys and 18 left hips, which were operated on in a mean of 11.5 days after the slip. The mean follow-up was of 38 months. The preoperative Southwick angle averaged 60.69° against 4.52° postoperatively (p< 0.001). A larger preoperative slip angle was associated with the development of AVN (RR: 1.05; 95% confidence interval [95%CI]: 1.02-1.07; p< 0.01). The overall AVN rate was of 26.7%. Function was good or excellent in 86% of uncomplicated hips, and poor in 87.5% of the partients who developed AVN, as graded by the Harris Hip Score. There was no statistical relationship between epiphyseal bleeding and AVN development (p= 0.82). Conclusion The modified Dunn technique is associated with restoration of the femoral alignment and function after unstable SCFE, when uncomplicated. Moreover, it was shown to be reproducible in our population, with a rate of 26% of femoral head necrosis.

Resumo Objetivo Avaliar a segurança e a reprodutibilidade da cirurgia para escorregamento da epífise femoral proximal (EEPF) com instabilidade por meio da técnica de Dunn modificada em uma coorte unicêntrica no Brasil. Métodos Analisamos de forma retrospectiva uma coorte de pacientes submetidos a esse procedimento por um único cirurgião especialista em preservação do quadril. Avaliamos os dados demográficos e os ângulos radiográficos quanto ao risco relativo (RR) de necrose avascular (NAV) por meio do modelo de regressão log-binomial com efeitos simples e aleatórios. Resultados Entre os 30 pacientes (30 quadris) com idade média de 11,79 anos no momento da cirurgia, havia 17 meninos e 18 quadris esquerdos. O procedimento ocorreu em média 11,5 dias após o escorregamento. O tempo médio de acompanhamento foi de 38 meses. O ângulo de Southwick pré-operatório foi, em média, de 60,69° contra 4,52° após o procedimento (p< 0,001). O maior ângulo de escorregamento pré-operatório foi associado ao desenvolvimento de NAV (RR: 1,05; intervalo de confiança de 95% [IC95%]: 1,02-1,07; p< 0,01). A frequência geral de NAV foi de 26,7%. De acordo com a Escala de Quadril de Harris (Harris Hip Score), a função foi boa ou excelente em 86% dos quadris sem complicações, e ruim em 87,5% dos casos com NAV. Não houve relação estatística entre sangramento epifisário e desenvolvimento de NAV (p= 0,82). Conclusão A técnica de Dunn modificada restaura o alinhamento femoral e a função articular após o EEPF com instabilidade na ausência de complicações. Além disso, mostrou-se passível de reprodução em nossa população, com frequência de necrose da cabeça femoral de 26%.

Acute flaccid paralysis due to multifactorial hyperkalaemia.

A male patient in his late 30s with a history of Lynch syndrome and colorectal cancer relapse, which recently started chemotherapy, was admitted to the emergency department with acute lower limb weakness that had progressed to all limbs and resulted in complete flaccid paresis with general areflexia. Blood tests showed severe hyperkalaemia, severe acute kidney injury and hyperuricaemia. Ultrasound showed bilateral hydronephrosis due to pelvic mass obstruction. Hyperkalaemia correction measurements were started as well as rasburicase with the assumption of tumour lysis syndrome and postrenal kidney injury. The patient showed a favourable clinical response with complete return of limb movement in the following hours and progressive recovery of renal function in the following days. This case highlights the need for prompt diagnosis and correction of severe hyperkalaemia, and its multiple possible causes, as it can lead to acute flaccid paralysis and a fatal outcome.

Extracellular vesicles improve GABAergic transmission in Huntington's disease iPSC-derived neurons.

Background: Extracellular vesicles (EVs) carry bioactive molecules associated with various biological processes, including miRNAs. In both Huntington's disease (HD) models and human samples, altered expression of miRNAs involved in synapse regulation was reported. Recently, the use of EV cargo to reverse phenotypic alterations in disease models with synaptopathy as the end result of the pathophysiological cascade has become an interesting possibility. Methods: Here, we assessed the contribution of EVs to GABAergic synaptic alterations using a human HD model and studied the miRNA content of isolated EVs. Results: After differentiating human induced pluripotent stem cells into electrophysiologically active striatal-like GABAergic neurons, we found that HD-derived neurons displayed reduced density of inhibitory synapse markers and GABA receptor-mediated ionotropic signaling. Treatment with EVs secreted by control (CTR) fibroblasts reversed the deficits in GABAergic synaptic transmission and increased the density of inhibitory synapses in HD-derived neuron cultures, while EVs from HD-derived fibroblasts had the opposite effects on CTR-derived neurons. Moreover, analysis of miRNAs from purified EVs identified a set of differentially expressed miRNAs between manifest HD, premanifest, and CTR lines with predicted synaptic targets. Conclusion: The EV-mediated reversal of the abnormal GABAergic phenotype in HD-derived neurons reinforces the potential role of EV-miRNAs on synapse regulation.

Testicular prostheses - impact on quality of life and sexual function.

Orchiectomy is the recommended treatment for many testicular conditions. However, testicular prosthesis placement is not always performed for different reasons. In this study, we aimed to evaluate patients' opinions and the impact on sexual function and quality of life. This retrospective observational single-center study included patients who underwent orchiectomy between January 2014 and December 2020 at the Department of Urology, Braga's Hospital (Braga, Portugal), where testicular implants were always available and the decision to undergo the procedure was made fully independent of cost. Patients completed four questionnaires that assessed demographic data, satisfaction, self-esteem, and sexual function. Of the 96 patients who underwent orchidectomy, 59 replied to the questionnaires, and of these patients, 86.4% decided to undergo silicone-based testicular prostheses implantation. The remaining 13.6% refused the implant based on concerns about complications (37.5%), because they felt that it was unnecessary (37.5%), or because it was not offered by the doctor (25.0%). Overall, 96.1% of these patients were satisfied with the implant; however, 25.5% classified it as "too firm". No statistically significant differences were found in sexual function (all P > 0.05). However, it can be observed that there are more patients with prostheses presenting normal sexual activity compared to patients without prostheses (74.0% vs 50.0%), and none of them reported severe erectile dysfunction (0 vs 16.7%). Regarding self-esteem, both patients with and without prostheses present very similar average scores with no statistically significant differences. The present study highlights the highest level of satisfaction among patients who received testicular prostheses. Testicular prostheses implantation is a safe procedure that does not hamper sexual function after orchiectomy.