Percutaneous kidney biopsies in children: a 24-year review in a tertiary center in northern Portugal.

INTRODUCTION: Percutaneous kidney biopsy (KB) is crucial to the diagnosis and management of several renal pathologies. National data on native KB in pediatric patients are scarce. We aimed to review the demographic and clinical characteristics and histopathological patterns in children who underwent native percutaneous KB over 24 years. METHODS: Retrospective observational study of patients undergoing native percutaneous KB in a pediatric nephrology unit between 1998 and 2021, comparing 3 periods: period 1 (1998-2005), period 2 (2006-2013), and period 3 (2014-2021). RESULTS: We found that 228 KB were performed, 78 (34.2%) in period 1, 91 (39.9%) in period 2, and 59 (25.9%) in period 3. The median age at KB was 11 (7-14) years. The main indications for KB were nephrotic syndrome (NS) (42.9%), hematuria and/or non-nephrotic proteinuria (35.5%), and acute kidney injury (13.2%). Primary glomerulopathies were more frequent (67.1%), particularly minimal change disease (MCD) (25.4%), IgA nephropathy (12.7%), and mesangioproliferative glomerulonephritis (GN) (8.8%). Of the secondary glomerulopathies, lupus nephritis (LN) was the most prevalent (11.8%). In group 1, hematuria and/or non-nephrotic proteinuria were the main reasons for KB, as opposed to NS in groups 2 and 3 (p < 0.01). LN showed an increasing trend (period 1-3: 2.6%-5.3%) and focal segmental glomerular sclerosis (FSGS) showed a slight decreasing trend (period 1-3: 3.1%-1.8%), without statistical significance. CONCLUSIONS: The main indication for KB was NS, which increased over time, justifying the finding of MCD as main histological diagnosis. LN showed an increase in incidence over time, while FSGS cases did not increase.

Pharmacokinetic/pharmacodynamic modeling of cortical dopamine concentrations after quetiapine lipid core nanocapsules administration to schizophrenia phenotyped rats.

Schizophrenia (SCZ) response to pharmacological treatment is highly variable. Quetiapine (QTP) administered as QTP lipid core nanocapsules (QLNC) has been shown to modulate drug delivery to the brain of SCZ phenotyped rats (SPR). In the present study, we describe the brain concentration-effect relationship after administrations of QTP as a solution or QLNC to SPR and naïve animals. A semimechanistic pharmacokinetic (PK) model describing free QTP concentrations in the brain was linked to a pharmacodynamic (PD) model to correlate the drug kinetics to changes in dopamine (DA) medial prefrontal cortex extracellular concentrations determined by intracerebral microdialysis. Different structural models were investigated to fit DA concentrations after QTP dosing, and the final model describes the synthesis, release, and elimination of DA using a pool compartment. The results show that nanoparticles increase QTP brain concentrations and DA peak after drug dosing to SPR. To the best of our knowledge, this is the first study that combines microdialysis and PK/PD modeling in a neurodevelopmental model of SCZ to investigate how a nanocarrier can modulate drug PK and PD, contributing to the development of new treatment strategies for SCZ.

Deep (aggressive) angiomyxoma of the vulva in a pregnant woman.

Aggressive angiomyxoma is a rare mesenchymal tumour, which usually appears in the pelvic region of women in their reproductive age. Although benign, it is a locally infiltrative tumour with frequent recurrence. We report a case of a pregnant woman in her 30s with a vulvar aggressive angiomyxoma which was initially misdiagnosed. Features of this case are discussed, highlighting the difficulty in its diagnosis and the challenge of the follow-up and treatment of recurrences.

Effects of a supervised exercise training on body composition after bariatric surgery: a randomized controlled trial.

OBJECTIVE: This study aimed to determine the effects of a multicomponent exercise intervention during the first year post-bariatric surgery (BS) on body composition, weight loss (WL), energy expenditure, and nutrient intake. METHODS: A total of 84 patients were included in this study and were randomly assigned to either an exercise group (n = 41) or a control group (n = 20). The exercise group participated in a multicomponent exercise program that began 1-month post-BS, whereas the control group received only standard medical care post-BS. Body composition was assessed by dual-energy x-ray absorptiometry, and physical activity energy expenditure was assessed by accelerometers. Nutritional intake was assessed through a 4-day food diary. RESULTS: A total of 6-months post-BS, exercise was found to be effective in mitigating the loss of lower-limb and appendicular lean mass (LM), as well as favoring trunk fat mass (FM) loss. Moreover, it further decreased percent FM and promoted additional excess WL. After 12 months, exercise not only reduced waist circumference but also helped to lessen the loss of total, trunk, and appendicular LM. CONCLUSIONS: Exercise further induced trunk fat mass, percent FM, excess WL, and waist circumference reductions. Moreover, exercise attenuated the loss of total and regional LM.

Lifestyle Patterns in the Late Postoperative Period of Bariatric Surgery: a Descriptive Analysis of the CINTO Study.

BACKGROUND: The behavior of patients undergoing metabolic bariatric surgery (MBS) has been widely investigated to better understand their attitudes and to formulate effective advisory strategies. Although these elements have been studied separately, the magnitude of these behaviors still needs to be determined from a combined factors approach. This study aimed to identify the lifestyle patterns of patients who underwent MBS 5 or more years ago. METHODS: In this observational study, 123 patients who underwent MBS at least 5 years ago were included. Anthropometric data, sociodemographic profile, dietary intake, physical activity level, sleeping, smoking, and alcohol consumption were collected for all participants. Lifestyle pattern was evaluated using principal component analysis (PCA) and the Kaiser-Meyer-Olkin (KMO) index was applied to evaluate data factorability. RESULTS: PCA identified two patterns of behavior adopted by the participants in the late postoperative (PO) period (more than 5 years PO) of MBS. In the first pattern, a positive correlation was found between consumption of ultra-processed foods (r = 0.459), risky consumption of alcoholic beverages (r = 0.630), and tobacco use (r = 0.584). In the second, a positive correlation was observed between the consumption of unprocessed or minimally processed foods (r = 0.692) and more sleep time per day (r = 0.654). CONCLUSION: After 5 years of PO, combined behavior analysis revealed healthy and unhealthy lifestyle patterns, which points to the relevance of permanent clinical follow-up of these patients to ensure the best health status.

Methods for the Clinical Validation of Digital Endpoints: Protocol for a Scoping Review Abstract.

BACKGROUND: Clinical trials often use digital technologies to collect data continuously outside the clinic and use the derived digital endpoints as trial endpoints. Digital endpoints are also being developed to support diagnosis, monitoring, or therapeutic interventions in clinical care. However, clinical validation stands as a significant challenge, as there are no specific guidelines orienting the validation of digital endpoints. OBJECTIVE: This paper presents the protocol for a scoping review that aims to map the existing methods for the clinical validation of digital endpoints. METHODS: The scoping review will comprise searches from the electronic literature databases MEDLINE (PubMed), Scopus (including conference proceedings), Embase, IEEE (Institute of Electrical and Electronics Engineers) Xplore, ACM (Association for Computing Machinery) Digital Library, CENTRAL (Cochrane Central Register of Controlled Trials), Web of Science Core Collection (including conference proceedings), and Joanna Briggs Institute Database of Systematic Reviews and Implementation Reports. We will also include various sources of gray literature with search terms related to digital endpoints. The methodology will adhere to the Joanna Briggs Institute Scoping Review and the Guidance for Conducting Systematic Scoping Reviews. RESULTS: A search for reviews on the existing evidence related to this topic was conducted and has shown that no such review was previously undertaken. This review will provide a systematic assessment of the literature on methods for the clinical validation of digital endpoints and highlight any potential need for harmonization or reporting of methods. The results will include the methods for the clinical validation of digital endpoints according to device, digital endpoint, and clinical application goal of digital endpoints. The study started in January 2023 and is expected to end by December 2023, with results to be published in a peer-reviewed journal. CONCLUSIONS: A scoping review of methodologies that validate digital endpoints is necessary. This review will be unique in its breadth since it will comprise digital endpoints collected from several devices and not focus on a specific disease area. The results of our work should help guide researchers in choosing validation methods, identify potential gaps in the literature, or inform the development of novel methods to optimize the clinical validation of digital endpoints. Resolving these gaps is the key to presenting evidence in a consistent way to regulators and other parties and obtaining regulatory acceptance of digital endpoints for patient benefit. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/47119.

Rituximab therapy for childhood onset idiopathic nephrotic syndrome: experience of a Portuguese tertiary center / Terapia com Rituximabe para síndrome nefrótica idiopática de início na infância: experiência de um centro terciário português

ABSTRACT Introduction: Rituximab (RTX) is a therapeutic option in pediatric difficult-to-treat idiopathic nephrotic syndrome (NS). We aimed to assess the efficacy and safety of RTX use in these patients. Method: A retrospective study of all patients with idiopathic NS treated with RTX was conducted in a pediatric nephrology division of a tertiary hospital. Demographic, anthropometric, clinical and analytical data were collected prior to treatment and at 6, 12, and 24 months. Results: Sixteen patients were included (11 males), with a median (25th-75th percentile, P25-P75) age at diagnosis of 2 (2.0-2.8) years. Fifteen were steroid-sensitive and 1 was steroid-resistant and sensitive to cyclosporine. The median age at administration of RTX was 10 (6.3-14.0) years. Throughout a median follow-up time of 2.5 (1.0-3.0) years, 6 (37.5%) patients achieved partial remission and 7 (43.8%) had no relapses and were not taking any immunosuppressants at the 24-month follow-up visit. Regarding complications, 1 patient presented persistent hypogammaglobulinemia. Compared with the 12-month period before RTX, there was a decrease in the median number of relapses at 6 and 12 months [3 (3.0-4.0) vs 0 (0-0.8) and 0.50 (0-1.0), respectively; p = 0.001] and in the daily steroids dose (mg/kg/day) at 6, 12, and 24 months [0.29 (0.15-0.67)vs [0.10 (0.07-0.13); p = 0.001], [0.12 (0.05-0.22); p = 0.005] and [0.07(0.04-0.18); p = 0.021]], respectively. There was also a reduction in the median BMI z score at 24 months [2.11 (0.45-3.70) vs. 2.93 (2.01-3.98); p = 0.049]. Conclusion: Our results confirm the efficacy and safety of RTX use in pediatric idiopathic NS and highlight its' potential cardiometabolic benefits.

Resumo Introdução: Rituximabe (RTX) é uma opção terapêutica na síndrome nefrótica (SN) idiopática pediátrica de difícil tratamento. Visamos avaliar eficácia e segurança do uso de RTX nestes pacientes. Método: Realizou-se estudo retrospectivo de todos os pacientes com SN idiopática tratados com RTX, em uma unidade de nefrologia pediátrica de um hospital terciário. Dados demográficos, antropométricos, clínicos e analíticos foram coletados antes do tratamento e aos 6, 12 e 24 meses. Resultados: Incluímos 16 pacientes (11 do sexo masculino), com idade mediana (percentil 25-75, P25-P75) de 2 (2,0-2,8) anos ao diagnóstico. Quinze eram sensíveis a esteroides, e 1 resistente a esteroides e sensível à ciclosporina.A idade mediana na administração do RTX foi 10 (6,3-14,0) anos. Durante um tempo mediano de acompanhamento de 2,5(1,0-3,0) anos, 6 (37,5%) pacientes alcançaram remissão parcial e 7 (43,8%) não tiveram recidivas e não estavam tomando imunossupressor no acompanhamento aos 24 meses. Quanto às complicações,1 paciente apresentou hipogamaglobulinemia persistente. Comparado ao período de12 meses anterior ao RTX, houve diminuição no número mediano de recidivas em 6 e 12 meses [3 (3,0-4,0) vs 0 (0-0,8) e 0,50 (0-1,0), respectivamente; p = 0,001] e na dose diária de esteroides (mg/kg/dia) aos 6, 12 e 24 meses [0,29 (0,15-0,67) >vs [0,10 (0,07-0,13); p = 0,001], [0,12 (0,05-0,22); p = 0,005] e [0,07 (0,04-0,18); p = 0,021], respectivamente. Houve também redução na mediana do escore z do IMC aos 24 meses [2,11 (0,45-3,70) vs 2,93 (2,01-3,98);p = 0,049]. Conclusões: Nossos resultados confirmam a eficácia e segurança do uso de RTX em SN idiopática pediátrica, destacando seus potenciais benefícios cardiometabólicos.

Estimating the Glomerular Filtration Rate in Pediatric Patients With Neurogenic Bladder: A Comparison Between Creatinine- and Cystatin C-Equations.

Background and objective Patients with neurogenic bladder (NB) are at a higher risk of developing chronic kidney disease (CKD). Due to their lower muscle mass, the estimated glomerular filtration rate (eGFR) based on creatinine (Cr) may be overestimated and delay the diagnosis of renal failure. This study compared eGFR calculated with different equations based on Cr and/or cystatin C (CysC) in children with NB, and the differences between patients with lower muscle mass (underdeveloped lower limbs) and those with independent gait (less muscle depletion). Methods We calculated the eGFR in pediatric patients with NB and CKD stages 1 and 2 by using the following equations: Chronic Kidney Disease in Children equation for serum creatinine (CKiD-Cr), CKiD-CysC, CKiD combined-Cr/CysC, Zappitelli-CysC, and Zappitelli combined-Cr/CysC. Results We evaluated a total of 47 patients, 74.5% with CKD stage 1, with a median age of 14.1 years. Of these participants, 59.6% had lipo/myelomeningocele. The CKiD-Cr and CysC-based equations led to significantly lower calculated eGFR ​​(p<0.05), specifically CKiD-CysC (p<0.001), Zappitelli-CysC (p<0.001), CKiD-Cr/CysC (p<0.001), and Zappitelli combined-Cr/CysC (p<0.05). When CKiD-CysC was used, 68% of the patients moved to a more advanced CKD stage. In patients without independent gait, with lower muscle mass (55.3%), the median eGFR calculated using the CKiD-Cr and CKiD combined-Cr/CysC equations was significantly higher (p<0.05). However, there were no differences between the two groups when using the other CysC-based equations. Conclusion In patients with NB and poor muscle mass, the CKiD-Cr equation may overestimate renal function. CysC-based equations seem more reliable in these patients, especially in those with greater muscular atrophy.

Population pharmacokinetic modeling of the influence of chronic and acute biofilm-forming Pseudomonas aeruginosa lung infection on ciprofloxacin free pulmonary and epithelial lining fluid concentrations.

We previously reported that ciprofloxacin (CIP) free lung interstitial concentrations are decreased by biofilm-forming Pseudomonas aeruginosa pulmonary chronic (14 d) infection. To get a better understanding on the influence of infection on CIP lung distribution, in the present study free lung interstitial fluid and epithelial lining fluid (ELF) concentrations were determined by microdialysis in biofilm-forming P. aeruginosa acutely (2 d) and chronically infected (14 d) Wistar rats following CIP 20 mg/kg i.v. bolus dosing. A popPK model was developed, using NONMEM® (version 7.4.3) with FOCE+I, with plasma data described as a three-compartment model with first-order elimination. For lung data inclusion, the model was expanded to four compartments and ELF concentrations were described as a fraction of lung levels estimated as a distribution factor (ƒD). Acute infection had a minor impact on plasma and lung CIP distribution and both infection stages did not alter ELF drug penetration. Probability of target attainment of ƒAUC0-24/MIC ≥ 90 using 20 mg q8h, equivalent to 400 mg q8h in humans, showed that CIP free concentrations in plasma are adequate to successfully treat lung infections. However, lung and ELF free interstitial concentrations might be insufficient to result in efficacious treatment of biofilm-forming P. aeruginosa chronic infection. However, lung and ELF free interstitial concentrations might be insufficient to result in efficacious treatment of biofilm-forming P. aeruginosa chronic infection.

Intermediate-Level Diet Quality of Brazilian Paralympic Athletes Based on National and International Indexes.

Diet quality indexes are used to characterize the dietary patterns of individuals and populations. The objective of this study was to compare two specific diet quality indexes, namely the Brazilian Healthy Eating Index Revised (BHEI-R) and the Global Diet Quality Score (GDQS), among Brazilian parathletes. This comparison was performed using either the initial 24 h recall (Rec1) or an assessment of usual dietary intake. Additionally, our study aimed to explore the association of these indexes with sociodemographic and behavioral sport variables. This cross-sectional, observational study evaluated 101 disabled athletes, including 23 international-level and 78 regional-/national-level participants, with a distribution of 82 males and 19 females across 13 Paralympic modalities. The Multiple Source Method (MSM) was employed, utilizing data from two or four non-consecutive 24 h food recalls. The comparison between the Rec1 and the assessment of usual dietary intake revealed the following median (IQR) values: for the BHEI-R, they were 60.3 ± 11.1 and 80.7 ± 6.2, respectively; for the GDQS, they were 19.5 ± 6.5 and 18.3 ± 2.6, respectively. Most athletes had diets classified as either "in need of modification" (according to BHEI-R) or of "moderate risk" (according to GDQS). The comparison between type of sport (team/individual), age, sex, income, education, sport scholarship, and nutritional support between the diet quality indexes is presented. Athletes involved in individual sports exhibited higher scores than team sports for BHEI-R (p < 0.02), and athletes receiving nutritional support achieved higher scores on both indexes (p < 0.03). The analysis of diet quality using the initial Rec1 with the BHEI-R was deemed sufficient to evaluate the diet quality of these athletes. However, when evaluating sporadically consumed food groups, the adoption of GDQS is necessary to assess usual dietary intake. We found that both BHEI-R and GDQS can be utilized to evaluate the diet quality of athletes with disabilities, and the diet quality of parathletes reached an intermediate score level.

Population Pharmacokinetic Modeling of Free Plasma and Free Brain Concentrations of Ceftaroline in Healthy and Methicillin-Resistant Staphylococcus aureus-Infected Wistar Rats.

A population pharmacokinetic model was developed to describe alterations in ceftaroline brain disposition caused by meningitis in healthy and methicillin-resistant Staphylococcus aureus (MRSA)-infected rats. Blood and brain microdialysate samples were obtained after a single bolus dose of ceftaroline fosamil (20 mg/kg) administered intravenously. Plasma data were modeled as one compartment, and brain data were added to the model as a second compartment, with bidirectional drug transport between plasma and brain (Qin and Qout). The cardiac output (CO) of the animals showed a significant correlation with the relative recovery (RR) of plasma microdialysis probes, with animals with greater CO presenting lower RR values. The Qin was approximately 60% higher in infected animals, leading to greater brain exposure to ceftaroline. Ceftaroline brain penetration was influenced by MRSA infection, increasing from 17% (Qin/Qout) in healthy animals to 27% in infected animals. Simulations of a 2-h intravenous infusion of 50 mg/kg every 8 h achieved >90% probability of target attainment (PTA) in plasma and brain for the modal MRSA MIC (0.25 mg/L), suggesting that the drug should be considered an option for treating central nervous system infections.

Population Pharmacokinetic Model of Methotrexate in Brazilian Pediatric Patients with Acute Lymphoblastic Leukemia.

OBJECTIVES: Methotrexate (MTX) is subject to therapeutic drug monitoring because of its high pharmacokinetic variability and safety risk outside the therapeutic window. This study aimed to develop a population pharmacokinetic model (popPK) of MTX for Brazilian pediatric acute lymphoblastic leukemia (ALL) patients who attended the Hospital de Clínicas de Porto Alegre, Brazil. METHODS: The model was developed using NONMEM 7.4 (Icon®), ADVAN3 TRANS4, and FOCE-I. To explain inter-individual variability, we evaluated covariates from demographic, biochemical, and genetic data (single nucleotide polymorphisms [SNPs] related to the transport and metabolism of drugs). RESULTS: A two-compartment model was built using 483 data points from 45 patients (0.33-17.83 years of age) treated with MTX (0.25-5 g/m2) in different cycles. Serum creatinine (SCR), height (HT), blood urea nitrogen (BUN) and a low BMI stratification (according to the z-score defined by the World Health Organization [LowBMI]) were added as clearance covariates. The final model described MTX clearance as [Formula: see text]. In the two-compartment structural model, the central and peripheral compartment volumes were 26.8 L and 8.47 L, respectively, and the inter-compartmental clearance was 0.218 L/h. External validation of the model was performed through a visual predictive test and metrics using data from 15 other pediatric ALL patients. CONCLUSION: The first popPK model of MTX was developed for Brazilian pediatric ALL patients, which showed that inter-individual variability was explained by renal function and factors related to body size.

Dietary assessment of 101 para-athletes from team and individual sports.

Assessing the usual food intake of para-athletes enables knowledge and description of nutrient intakes, providing insight into the potential nutritional status of para-athletes and may help tailor dietary intake to their specific training needs. This study aimed to evaluate the usual intake of macronutrients and food groups and meal food patterns of athletes with a disability. We also compared dietary intake data between team and individual sport para-athletes. One hundred and one athletes with a disability from 13 Paralympic disciplines living in Brasília, Federal District, Brazil were included. Food intake was estimated from two or four non-consecutive 24-h food recalls in which para-athletes reported all food, beverages, and supplements consumed in the previous 24-h. Dietary intake analysis was performed by implementing the National Cancer Institute (NCI) method to calculate the macronutrient and food group usual intake. Macronutrient intakes were compared to Acceptable Macronutrient Distribution Ranges for the general population and food group intakes were compared to the 2008 Brazilian National Dietary Guidelines. Para-athletes consumed a low-carbohydrate, adequate protein, high-fat diet. There was no significant difference in macronutrient intake distribution between team sport and individual sport para-athletes. Most para-athletes had three main meals during the day. The prevalence of inadequate fruit servings in the middle and highest energy intake tertiles was significantly higher in team sport para-athletes (92.5% and 98.4%) than in individual sport para-athletes (90.8% and 65.5%), respectively. The prevalence of inadequate vegetable servings was significantly higher between team and individual para-athletes for the middle energy intake tertiles. Para-athletes generally consumed an imbalanced diet, which is a cause for concern given their additional physiological demands and specific training needs.

Development and validation of an LC-MS/MS method to quantify ceftaroline in microdialysate samples from plasma and brain: Application to a preclinical pharmacokinetic investigation.

A bioanalytical LC-MS/MS method was developed and validated to determine ceftaroline in microdialysate samples from plasma and brain. Ceftaroline was separated using a C18 column and a mobile phase consisting of water and acetonitrile, both with 5 mM of ammonium formate and acid formic 0.1%, eluted as gradient. Ceftaroline was monitored using electrospray ionization operating on positive mode (ESI+) monitoring the transition 604.89 > 209.3 m/z. The method showed linearity in the concentration range of 0.5-500 ng/mL for brain microdialysate and 0.5-2500 ng/mL for plasma microdialysate with coefficients of determination ≥0.997. The inter-and intra-day precision, the accuracy, and the stability of the drug in different conditions were in accordance with the acceptable limits determined by international guidelines. Plasma pharmacokinetics and brain distribution of the drug were carried out after intravenous administration of 20 mg/kg of ceftaroline to male Wistar rats. The estimated geometric mean (geometric coefficient of variation) area under the curve (AUC0-∞) was 4.68 (45.8%) mg·h/L and 1.20 (54.2%) mg·h/L for plasma and brain, respectively, resulting in a brain exposure of about 33% (AUCfree brain/AUCfree plasma). The results indicate that ceftaroline presents good penetration in the brain when considering free plasma and free brain concentrations.

Histological tumor response predicts clinical outcome in patients with colorectal peritoneal metastasis treated with preoperative chemotherapy followed by cytoreduction and HIPEC.

Objectives: Up to one quarter of the patients with colorectal cancer (CRC) develop peritoneal carcinomatosis (PM). The aims of this retrospective study were to characterize the histological response of the PM of CRC to preoperative chemotherapy and evaluate the potential prognostic value, in terms of survival. Methods: This retrospective unicentric study evaluated a group of 30 patients treated between 2010 and 2020 at the São João University Hospital Center with preoperative chemotherapy, followed by cytoreduction surgery plus hyperthermic intraperitoneal chemotherapy. The evaluation of the histological response was done using two scores: the tumor regression grading (TRG) and the peritoneal regression grading score (PRGS). Results: Mean post-procedure survival is higher in the PRGS 1-2 group (74.19 months) vs. the PRGS 3-4 group (25.27 months) (p=0.045), as well as in the TRG 1-2 group (74.58 months) vs. TRG 4-5 (25.27 months) (p=0.032). As for progression-free survival (PFS), the PRGS 1-2 group had a mean value of 58.03 months vs. PRGS 3-4 which had 11.67 months (p=0.002). Similar was observed with the TRG 1-2 group, which had a mean PFS of 61.68 months vs. TRG 4-5 with 11.67 months (p=0.003). Conclusions: A better histological response to preoperative chemotherapy, represented as a lower PRGS and TRG value, is associated with longer post-procedure survival and progression-free survival in this group of patients. That is, these two scores have prognostic value.

Patients' physiological reactions to competitive rehabilitation therapies assisted by robotic devices.

BACKGROUND: The aging of the population and the progressive increase in life expectancy in developed countries is leading to a high incidence of cerebrovascular diseases. Several studies have demonstrated that robot-assisted rehabilitation therapies combined with serious games can improve rehabilitation outcomes. Social interaction in the form of multiplayer games has been highlighted as a potential element to increase patient's motivation and exercise intensity, which professionals have described as one of the determining factors in maximizing rehabilitation outcomes. Despite this, it has not been widely studied. Physiological measures have been proven as an objective tool to evaluate patients' experience in robot-assisted rehabilitation environments. However, they have not been used to evaluate patients' experience in multiplayer robot-assisted rehabilitation therapies. The main objective of this study is to analyze whether the interpersonal interaction inherent in a competitive game mode affects the patients' physiological responses in robot-assisted rehabilitation environments. METHODS: A total of 14 patients participated in this study. The results of a competitive game mode were compared with a single-player game mode with different difficulty levels. Exercise intensity and performance were measured through parameters extracted from the game and the information provided by the robotic rehabilitation platforms. The physiological response of patients in each game mode was measured by the heart rate (HR) and the galvanic skin response (GSR). Patients were asked to fill out the IMI and the overall experience questionnaire. RESULTS: The exercise intensity results show that high-difficulty single-player game mode is similar in terms of intensity level to a competitive game mode, based on velocity values, reaction time and questionnaire results. However, the results of the physiological responses of the patients measured by GSR and HR are lower in the case of the competitive mode compared to the high-difficulty single-player game mode, obtaining results similar to those obtained in the low-difficulty single-player game mode. CONCLUSIONS: Patients find the competitive game mode the most fun, which is also the mode they report experiencing the most effort and stress level. However, this subjective evaluation is not in line with the results of physiological responses. This study concludes that interpersonal interaction inherent to a competitive game mode influences patients' physiological responses. This could mean that social interaction is an important factor to consider when interpreting the results obtained from physiological measurements.

Improved Local Anesthesia at Inflamed Tissue Using the Association of Articaine and Copaiba Oil in Avocado Butter Nanostructured Lipid Carriers.

Unsuccessful anesthesia often occurs under an inflammatory tissue environment, making dentistry treatment extremely painful and challenging. Articaine (ATC) is a local anesthetic used at high (4%) concentrations. Since nanopharmaceutical formulations may improve the pharmacokinetics and pharmacodynamics of drugs, we encapsulated ATC in nanostructured lipid carriers (NLCs) aiming to increase the anesthetic effect on the inflamed tissue. Moreover, the lipid nanoparticles were prepared with natural lipids (copaiba (Copaifera langsdorffii) oil and avocado (Persia gratissima) butter) that added functional activity to the nanosystem. NLC-CO-A particles (~217 nm) showed an amorphous lipid core structure according to DSC and XDR. In an inflammatory pain model induced by λ-carrageenan in rats, NLC-CO-A improved (30%) the anesthetic efficacy and prolonged anesthesia (3 h) in relation to free ATC. In a PGE2-induced pain model, the natural lipid formulation significantly reduced (~20%) the mechanical pain when compared to synthetic lipid NLC. Opioid receptors were involved in the detected analgesia effect since their blockage resulted in pain restoration. The pharmacokinetic evaluation of the inflamed tissue showed that NLC-CO-A decreased tissue ATC elimination rate (ke) by half and doubled ATC's half-life. These results present NLC-CO-A as an innovative system to break the impasse of anesthesia failure in inflamed tissue by preventing ATC accelerated systemic removal by the inflammatory process and improving anesthesia by its association with copaiba oil.