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Background: Diabetic foot ulcers (DFUs) are a serious complication of diabetes and are often difficult to treat. Hyperbaric oxygen therapy (HBOT) has been proposed as an adjunctive treatment to promote healing, but its long-term clinical and biological effects remain insufficiently characterized. This study aimed to evaluate the impact of HBOT on systemic biomarkers, local microvasculature, and clinical outcomes in patients with DFUs. Methods: In this non-randomized prospective study, 20 patients with ischemic DFUs were followed over a 36-month period. Fourteen received HBOT in addition to standard care, while six received standard care alone. Clinical outcomes—including DFU resolution, recurrence, lower extremity amputation (LEA), and mortality—were assessed alongside systemic inflammatory and angiogenic biomarkers and wound characteristics at baseline and at 3, 6, 12, and 36 months. CD31 immunostaining was performed on available tissue samples. Results: The two groups were comparable at baseline (mean age 62 ± 12 years; diabetes duration 18 ± 9 years). At 3 months, the HBOT group showed significant reductions in erythrocyte sedimentation rate and DFU size (p < 0.05), with downward trends observed in C-reactive protein (CRP), vascular endothelial growth factor (VEGF), and placental growth factor (PlGF), and an increase in stromal-derived factor-1 alpha (SDF1-α). No significant changes were observed in the control group. CD31+ microvessel density appeared to increase in HBOT-treated DFU tissue after one month, although the sample size was limited. Patients receiving HBOT had lower rates of LEA and mortality, improved wound healing, and sustained outcomes over three years. DFU recurrence rates were similar between groups. Conclusions: HBOT was associated with improved wound healing and favorable biomarker profiles in patients with treatment-resistant ischemic DFUs. While these findings are encouraging, the small sample size and non-randomized design limit their generalizability, highlighting the need for larger, controlled studies.

The activity of dopamine neurons in the substantia nigra pars compacta before movement initiation affects the probability and vigour of future movements. How dopamine neurons forge future movements Loss of dopamine neurons in a specific area of the brain, the substantia nigra pars compacta (SNc), causes failure to initiate and slowness of movement in patients with Parkinson's disease. Rui Costa and colleagues explore the role of these neurons in movement and reward. In mice, SNc dopamine neurons are transiently active before a self-initiated movement. The neurons affect movement initiation, but they are not selective for specific actions. Manipulation of dopamine neuron activity alters the probability of future movement initiation and the speed of movement, but does not affect ongoing movements. These findings suggest that dopamine signals serve as a general signal for gating and invigorating self-paced movements. Deciding when and whether to move is critical for survival. Loss of dopamine neurons (DANs) of the substantia nigra pars compacta (SNc) in patients with Parkinson’s disease causes deficits in movement initiation and slowness of movement 1 . The role of DANs in self-paced movement has mostly been attributed to their tonic activity, whereas phasic changes in DAN activity have been linked to reward prediction 2 , 3 . This model has recently been challenged by studies showing transient changes in DAN activity before or during self-paced movement initiation 4 , 5 , 6 , 7 . Nevertheless, the necessity of this activity for spontaneous movement initiation has not been demonstrated, nor has its relation to initiation versus ongoing movement been described. Here we show that a large proportion of SNc DANs, which did not overlap with reward-responsive DANs, transiently increased their activity before self-paced movement initiation in mice. This activity was not action-specific, and was related to the vigour of future movements. Inhibition of DANs when mice were immobile reduced the probability and vigour of future movements. Conversely, brief activation of DANs when mice were immobile increased the probability and vigour of future movements. Manipulations of dopamine activity after movement initiation did not affect ongoing movements. Similar findings were observed for the initiation and execution of learned action sequences. These findings causally implicate DAN activity before movement initiation in the probability and vigour of future movements.

The intracellular parasite Toxoplasma has an indirect life cycle, in which felids are the definitive host. It has been suggested that this parasite developed mechanisms for enhancing its transmission rate to felids by inducing behavioral modifications in the intermediate rodent host. For example, Toxoplasma-infected rodents display a reduction in the innate fear of predator odor. However, animals with Toxoplasma infection acquired in the wild are more often caught in traps, suggesting that there are manipulations of intermediate host behavior beyond those that increase predation by felids. We investigated the behavioral modifications of Toxoplasma-infected mice in environments with exposed versus non-exposed areas, and found that chronically infected mice with brain cysts display a plethora of behavioral alterations. Using principal component analysis, we discovered that most of the behavioral differences observed in cyst-containing animals reflected changes in the microstructure of exploratory behavior and risk/unconditioned fear. We next examined whether these behavioral changes were related to the presence and distribution of parasitic cysts in the brain of chronically infected mice. We found no strong cyst tropism for any particular brain area but found that the distribution of Toxoplasma cysts in the brain of infected animals was not random, and that particular combinations of cyst localizations changed risk/unconditioned fear in the host. These results suggest that brain cysts in animals chronically infected with Toxoplasma alter the fine structure of exploratory behavior and risk/unconditioned fear, which may result in greater capture probability of infected rodents. These data also raise the possibility that selective pressures acted on Toxoplasma to broaden its transmission between intermediate predator hosts, in addition to felid definitive hosts.

Os principais objetivos deste estudo são conhecer e comparar a infuência parental na iniciação e manutenção da prática desportiva de diferentes desportos (atletismo, karaté, basquetebol, voleibol, futebol), de acordo com a perceção de treinadores de crianças e jovens. A recolha de dados foi realizada através de entrevistas semiestruturadas. Os participantes deste estudo foram cinco treinadores (um do sexo feminino e quatro do sexo masculino) com idades entre 27 e 67 anos e com certifcação de treinador de nível 2 a 4. Os principais resultados estão divididos em quatro dimensões (social, económica, psicológica, pedagógica). A socialização está presente em todos os desportos abordados. O estatuto socioeconómico dos pais é infuenciador nos desportos individuais. Os pais infuenciam na iniciação e manutenção da prática desportiva, sendo os principais informadores de difculdades dos atletas, ou, os pais podem ser infuenciadores negativos quando procuram tornar os seus flhos atletas de rendimento, alterando assim o seu estado psicológico. Os desportos coletivos possuem intervenções pedagógicas com regras importantes, sendo os pais muitas vezes uma barreira na aplicação das mesmas. PALAVRAS-CHAVE: prática desportiva; infuência parental; jovens, iniciação desportiva; manutenção desportiva.

Toxoplasma gondii infects a broad range of hosts and can establish chronic infections with the formation of brain cysts. Infected animals show altered risk behaviour which has been suggested to increase capture probability of hosts, and thus enhance parasite transmission. It has been proposed that the ability of Toxoplasma cysts to secrete tyrosine hydroxylase could mediate these behavioural alterations. We tested the involvement of secreted tyrosine hydroxylase, coded by the parasite AaaH2 gene, in the development of alterations in mouse behaviour, by generating an AaaH2 deletion mutant parasite strain and testing its influence on behaviour. We found that both mice infected with wild type or AaaH2 mutant strains showed changes in risk behaviour. We confirmed these findings using factor analysis of the behaviour, which revealed that behavioural changes happened along a single dimension, and were observed in both infected groups. Furthermore, we developed a new behavioural paradigm in which animals are unpredictably trapped, and observed that both groups of infected animals perceive trapping but fail to adjust their behaviour to avoid further trapping. These results demonstrate that parasite-secreted AaaH2 TH is neither necessary for the generation of risky behaviour nor for the increased trappability observed during chronic Toxoplasma infection.

The motivation to accurately model the dynamics of flexible aircraft grew with the development of energy-efficient aircraft, consequently, great aspect ratio aircraft. The development of an accurate model that represents the flight dynamics of a flexible aircraft has been pursued by industry and aeronautical research organizations during the last decades. One of these approaches is to find a flexible aircraft model using systems identification methods. This research aims to apply an integrated model containing longitudinal and lateral directional rigid body dynamics, coupled to the first four flexible body modes, for identification and validation from flight test data. The Unmanned Aerial Vehicle (UAV) Eolo with the flexible wing is used during the experiments. Initially, a finite element structural model (FEM) based on beam elements, concentrated masses, and rigid bars was used. The quasi-stationary panel model based on the Vortex Lattice Method (VLM) was adopted for the aerodynamic model. Two diagonal matrices were used to correct the aerodynamic influence coefficients (AIC) matrix obtained via VLM before and post-multiplication for aircraft identification. The estimation of the main diagonal elements of each matrix was obtained through the Output Error Method in the time domain. A model validation analysis was carried out, which shows a good correlation between the model and measurement data. In conclusion, getting correction matrices instead of stability derivatives is beneficial because matrices can be used more directly during the aeronautical design and observe the behavior concerning loads.

This work proposes an analysis of the capability of three deep learning models—the feedforward neural network (FFNN), long short-term memory (LSTM) network, and physics-informed neural network (PINN)—to identify the parameters of a flexible fixed-wing aircraft using in-flight data. These neural networks, composed of multiple hidden layers, are evaluated for their ability to perform system identification and to capture the nonlinear and dynamic behavior of the aircraft. The FNN and LSTM models are compared to assess the impact of temporal dependency learning on parameter estimation, while the PINN integrates prior knowledge of the system’s governing of ordinary differential equations (ODEs) to enhance physical consistency in the identification process. The objective is to exploit the generalization capability of neural network-based models while preserving the accurate estimation of the physical parameters that characterize the analyzed system. The neural networks are evaluated for their ability to perform system identification and capture the nonlinear behavior of the aircraft. The results show that the FFNN achieved the best overall performance, with average Theil’s inequality coefficient (TIC) values of 0.162 during training and 0.386 during testing, efficiently modeling the input-output relationships but tending to fit high-frequency measurement noise. The LSTM network demonstrated superior noise robustness due to its temporal filtering capability, producing smoother predictions with average TIC values of 0.398 (training) and 0.408 (testing), albeit with some amplitude underestimation. The PINN, while successfully integrating physical constraints through pretraining with target aerodynamic derivatives, showed more complex convergence, with average TIC values of 0.243 (training) and 0.475 (testing), and its estimated aerodynamic coefficients differed significantly from the conventional values. All three architectures effectively captured the coupled rigid-body and flexible dynamics when trained with distributed wing sensor data, demonstrating that neural network-based approaches can model aeroelastic phenomena without requiring explicit high-fidelity flexible-body models. This study provides a comparative framework for selecting appropriate neural network architectures based on the specific requirements of aircraft system identification tasks.

Community-acquired acute kidney injury is a frequent diagnosis at hospital admission in developed countries. Due to the multiple comorbidities, patients admitted to internal medicine departments have a higher susceptibility to acute kidney injury. To determine the prevalence, risk factors, and impact of community-acquired acute kidney injury, we developed a retrospective observational case-control study in an internal medicine ward at a tertiary hospital comparing patients admitted with community-acquired acute kidney injury with patients without acute kidney injury at hospital admission. Patients who needed dialysis were excluded. Community-acquired acute kidney injury was present in 19.6% of patients, mostly prerenal acute kidney injury (68.8%) and Kidney Disease Improving Global Outcomes classification stage 1 (51.9%). Dementia (OR 3.3, [0.2–0.6]) and loop diuretics as outpatient medication (OR 2.2, [0.2–0.9]) were risk factors for community-acquired acute kidney injury. These patients presented higher mortality after hospital discharge (p=0.003), and 35.1% of deaths occurred in the first 90 days. At one-year follow-up, chronic kidney disease progression was more frequent in the community-acquired acute kidney injury group (24.6% versus 2.6%, p=0.002); otherwise, new-onset chronic kidney disease was similar between groups. The long-term consequences of community-acquired acute kidney injury can be severe, including renal disease progression and mortality after hospital discharge (mostly in the first 90 days); thus, it is important to implement programs to provide early evaluation for these patients. Patients taking diuretics are at increased risk of acute kidney injury. Also, patient and caregiver education on hydration of demented patients could prevent community-acquired acute kidney injury.

Explicit information obtained through instruction profoundly shapes human choice behaviour. However, this has been studied in computationally simple tasks, and it is unknown how model-based and model-free systems, respectively generating goal-directed and habitual actions, are affected by the absence or presence of instructions. We assessed behaviour in a variant of a computationally more complex decision-making task, before and after providing information about task structure, both in healthy volunteers and in individuals suffering from obsessive-compulsive or other disorders. Initial behaviour was model-free, with rewards directly reinforcing preceding actions. Model-based control, employing predictions of states resulting from each action, emerged with experience in a minority of participants, and less in those with obsessive-compulsive disorder. Providing task structure information strongly increased model-based control, similarly across all groups. Thus, in humans, explicit task structural knowledge is a primary determinant of model-based reinforcement learning and is most readily acquired from instruction rather than experience.Healthy volunteers and patients with obsessive-compulsive disorder learning a task from experience alone tend to repeat actions that lead to rewards. They are poor at learning predictive models, but their use of these models is strongly increased when explicit information is provided.

Animals exhibit a diverse behavioural repertoire when exploring new environments and can learn which actions or action sequences produce positive outcomes. Dopamine release after encountering a reward is critical for reinforcing reward-producing actions 1 – 3 . However, it has been challenging to understand how credit is assigned to the exact action that produced the dopamine release during continuous behaviour. Here we investigated this problem in mice using a self-stimulation paradigm in which specific spontaneous movements triggered optogenetic stimulation of dopaminergic neurons. Dopamine self-stimulation rapidly and dynamically changes the structure of the entire behavioural repertoire. Initial stimulations reinforced not only the stimulation-producing target action, but also actions similar to the target action and actions that occurred a few seconds before stimulation. Repeated pairings led to a gradual refinement of the behavioural repertoire to home in on the target action. Reinforcement of action sequences revealed further temporal dependencies of refinement. Action pairs spontaneously separated by long time intervals promoted a stepwise credit assignment, with early refinement of actions most proximal to stimulation and subsequent refinement of more distal actions. Thus, a retrospective reinforcement mechanism promotes not only reinforcement, but also gradual refinement of the entire behavioural repertoire to assign credit to specific actions and action sequences that lead to dopamine release. Initial dopamine self-stimulations reinforced not only the stimulation-producing target action, but also actions similar to the target action and actions that occurred a few seconds before stimulation, and repeated pairings led to a gradual refinement of the behavioural repertoire to home in on the target actions.