Self-modulation of the sense of agency via neurofeedback enhances sensory-guided behavioral control.

The sense of agency is a fundamental aspect of human self-consciousness, whose neural correlates encompass widespread brain networks. Research has explored the neuromodulatory properties of the sense of agency with noninvasive brain stimulation, which induces exogenous manipulations of brain activity; however, it is unknown whether endogenous modulation of the sense of agency is also achievable. We investigated whether the sense of agency can be self-regulated with electroencephalography-based neurofeedback. We conducted 2 experiments in which healthy humans performed a motor task while their motor control was artificially disrupted, and gave agency statements on their perceived control. We first identified the electrophysiological response to agency processing, and then applied neurofeedback in a parallel, sham-controlled design, where participants learnt to self-modulate their sense of agency. We found that behavioral measures of agency and performance on the task decreased with the increasing disruption of control. This was negatively correlated with power spectral density in the theta band, and positively correlated in the alpha and beta bands, at central and parietal electrodes. After neurofeedback training of central theta rhythms, participants improved their actual control over the task, and this was associated with a significant decrease in the frequency band trained via neurofeedback. Thus, self-regulation of theta rhythms can improve sensory-guided behavior.

Derotational distal femoral osteotomy corrects excessive femoral anteversion in patients with patellofemoral instability: A systematic review.

PURPOSE: Patellofemoral instability (PFI) is a common condition that can be caused from multiple factors, including lower limb rotational malalignments. Determining precise criteria for performing corrective torsional osteotomy can be a daunting task due to the lack of consensus on normal and excessive values and the limited evidence-based data in the postoperative results. The purpose was to assess the clinical, functional and imaging outcomes following derotational distal femoral osteotomy (DDFO) in patients with PFI and/or anterior knee pain (AKP) associated with lower limb rotational malalignments. METHODS: Searches were conducted on PubMed, EMBASE and Web of Science databases up to October 2023. Studies reporting outcomes after DDFO in patients with PFI and/or AKP were eligible for the systematic review. The primary outcome was imaging metrics, especially femoral anteversion. Secondary outcomes included the patient-reported outcome measures (PROMs) (clinical and functional). Quantitative synthesis involved the use of weighted averages to calculate pre- to postoperative mean differences (MD) and compare them against the minimal clinically important difference (MCID). RESULTS: Ten studies (309 knees) were included with a mean follow-up of 36.1 ± 11.7 months. Imaging outcomes consistently indicated the correction of femoral anteversion (MD = -19.4 degrees, 95% confidence interval: -20.1 to -18.7) following DDFO. PROMs showed significant improvements in most studies, exceeding the MCID. Patient satisfaction with the DDFO was high (93.3%). CONCLUSIONS: The DDFO was an effective treatment option for correcting excessive femoral anteversion in patients with PFI associated with clinically relevant functional and clinical improvement and a high satisfaction rate. LEVEL OF EVIDENCE: Level IV, systematic review of level II-IV studies.

Effect of toothbrushing with conventional and whitening dentifrices on monolithic zirconia after finishing procedures.

PURPOSE: To evaluate the effect of toothbrushing with conventional and whitening dentifrices on the color difference (ΔE00), gloss (Δgloss), and surface roughness (SR) of stained stabilized zirconia with 5 mol% of yttrium oxide (5Y-TZP) after polishing or glazing. METHODS: Specimens were divided into four groups (n=20): C (control), S (staining), SG (staining and glazing) and SP (staining and polishing). 50,000 toothbrushing cycles were performed with conventional (n=10) and whitening (n= 10) dentifrice slurries. The ΔE00 and Δgloss were measured using a spectrophotometer and CIEDE2000 system while SR was measured by laser confocal microscope. The ΔE00 and Δgloss data were analyzed using 2-way ANOVA, and SR data were analyzed using the linear repeated measures model, with Bonferroni's complementary test (α= 0.05). RESULTS: The ΔE00 values were beyond the acceptability threshold and no differences were found among the groups. There was no difference among groups to Δgloss after toothbrushing with conventional dentifrice while SP presented the highest values of Δgloss after toothbrushing with whitening dentifrice. Conventional dentifrice decreased the SR of stained groups and whitening dentifrice decreased SR of S and SG. The toothbrushing with conventional and whitening dentifrices promoted color difference, but did not impair gloss and surface roughness of stained 5Y-TZP. CLINICAL SIGNIFICANCE: Monolithic zirconia has been routinely used for esthetic restorations, however the type of finishing procedures that is carried out on it must be taken into consideration, in addition to the fact that brushing can influence the color difference of the material as well as interfere with surface roughness and gloss.

Effect of Staining, Glazing and Polishing on the Survival Probability of Monolithic Zirconia Crowns.

OBJECTIVE: The purpose of this in vitro study was to evaluate the effect of staining, glazing, and polishing on the survival probability of monolithic crowns manufactured with preshaded stabilized zirconia with 5 mol% of yttrium oxide (5Y-TZP). MATERIALS AND METHODS: Monolithic crowns in the shape of an upper canine (1.5 mm of thickness) were manufactured by CAD/CAM, adhesively cemented on metallic foundation, and divided into 6 groups (n = 21): C (control), S (staining), G (glazing), P (polishing), SG (staining and glazing), and SP (staining and polishing). The survival probability was determined by step-stress accelerated life testing with a load applied to the palatine concavity of the crown. First, the specimens were subjected to a single-load to fracture test (SLF) and next to the fatigue test (5 Hz, thermocycling immersed in water varying 5-55°C), including the light (n = 9), moderate (n = 6), and aggressive (n = 3) loading profiles (load ranged between 20% and 60% of SLF). The survival probability was calculated considering the cycles for failure (CFF) and fatigue failure load (FFL) and illustrated using a Kaplan-Meier graph. The comparison among groups was performed using a Log-Rank test (α = 0.05). RESULTS: The mean value of SLF was 586.7 N. There was no difference among groups in survival probability, considering CFF and FFL. CONCLUSION: Staining, glazing, and polishing can be performed safely without damaging the mechanical behavior of 5Y-TZP monolithic crowns. CLINICAL SIGNIFICANCE: Staining is used to characterize and improve the esthetic of zirconia monolithic crowns. It can be used to reproduce the color gradient in the cervical region of the crown and pigmented grooves. This study showed that staining, glazing, and polishing did not affect the survival probability and the use of finishing procedures (glazing or polishing) after staining did not improve the survival probability of zirconia monolithic crowns.

Evaluation of Vertical Misfit and Torque Loss of Different Abutments for Tri-Channel Type Internal Connection Dental Implants After Mechanical Cycling.

The aim of this study was to evaluate the mechanical behavior of UCLA and Mini-conical abutments for implants with Tri-channel connections regarding torque loss and vertical misfit. Twenty 3-element metal-ceramic fixed partial dentures (FPD) supported by 2 implants were manufactured and divided into 2 groups (n = 10): UCLA (group 1) and Mini-conical Abutments (group 2). The evaluation of torque loss was carried out before and after mechanical cycling, while the vertical fit was evaluated throughout the different stages of manufacturing the prostheses, as well pre- and postcycling (300,000 cycles, 30 N). Statistical analyses of torque loss and vertical misfit were performed using the linear mixed effects model. Both groups showed torque loss after mechanical cycling (P < .05); however, there was no significant percentage differences between them (P = .795). Before cycling, the groups showed a significant difference in terms of vertical misfit values (P < .05); however, this difference was no long observed after cycling (P = .894). Both groups showed torque loss after the cycling test, with no significant difference (P > .05). There was no significant difference in vertical misfit after mechanical cycling; however, in group 1 (UCLA) there was accommodation of the implant-UCLA abutment interface, while group 2 (Mini-conical abutment) did not show changes in the interface with the implant after the test. Both groups behaved similarly regarding the torque loss of the prosthesis retention screws pre- and postmechanical cycling, with greater loss after the test.

Therapeutic Potential of Marine-Derived Cyclic Peptides as Antiparasitic Agents.

Parasitic diseases still compromise human health. Some of the currently available therapeutic drugs have limitations considering their adverse effects, questionable efficacy, and long treatment, which have encouraged drug resistance. There is an urgent need to find new, safe, effective, and affordable antiparasitic drugs. Marine-derived cyclic peptides have been increasingly screened as candidates for developing new drugs. Therefore, in this review, a systematic analysis of the scientific literature was performed and 25 marine-derived cyclic peptides with antiparasitic activity (1-25) were found. Antimalarial activity is the most reported (51%), followed by antileishmanial (27%) and antitrypanosomal (20%) activities. Some compounds showed promising antiparasitic activity at the nM scale, being active against various parasites. The mechanisms of action and targets for some of the compounds have been investigated, revealing different strategies against parasites.

Epigenome-wide DNA methylation and transcriptome profiling of localized and locally advanced prostate cancer: Uncovering new molecular markers.

BACKGROUND: It has become increasingly important to identify molecular markers for accurately diagnosing prostate cancer (PCa) stages between localized PCa (LPC) and locally advanced PCa (LAPC). However, there is a lack of profiling both epigenome-wide DNA methylation and transcriptome for the same patients with PCa at different stages. This study aims to identify epitranscriptomic biomarkers screened in the peri-prostatic (PP) adipose tissue for predicting LPC and LAPC. METHODS: We profiled gene expression and DNA methylation of 10 PCa patients' PP adipose tissue (4 LPC and 6 LAPC). Differential analysis was used to identify differentially methylated CpG sites and expressed genes. An integrative analysis of the microarray gene expression profiles and DNA methylation profiles was conducted using LASSO (least absolute shrinkage and selection operator) between each studied gene and the CpG sites in their promoter region. This epitranscriptomic signature was constructed by combining the association and differential analyses. The signature was then refined using the genetic mutation data of >1500 primary PCa and metastasis PCa samples from 4 different studies. We determined genes that were the most significantly affected by mutations. Machine learning models were built to evaluate the classification ability of the identified signature using the gene expression profiles from three external cohorts. RESULTS: From the LASSO-based association analysis, we identified 56 genes presenting significant anti-correlation between the expression level and the methylation level of at least one CpG site in the promoter region (p-value<5 × 10-8). From the differential analysis, we detected 16,405 downregulated genes and 9485 genes containing at least one hypermethylated CpG site. We identified 30 genes that showed anti-correlation, down-regulation and hyper-methylation simultaneously. Using genetic mutation data, we determined that 6 of the 30 genes showed significant differences (adjusted p-value<0.05) in mutation frequencies between the primary PCa and metastasis PCa samples. The identified 30 genes performed well in distinguishing PCa patients with metastasis from PCa patient without metastasis (area under the receiver operating characteristic curve (AUC) = 0.81). The gene signature also performed well in distinguishing PCa patients with high risk of progression from PCa patients with low risk of progression (AUC = 0.88). CONCLUSIONS: We established an integrative framework to identify differentially expressed genes with an aberrant methylation pattern on PP adipose tissue that may represent novel candidate molecular markers for distinguishing between LPC and LAPC.

Teaching and learning pharmacology in Brazil before COVID-19 pandemic: a case study in Rio de Janeiro.

BACKGROUND: Knowledge of pharmacology is crucial for physicians to perform rational and safe medicine. Medical professionals are responsible for prescribing drugs and a weak performace of those can result in medication errors leading to disability, hospitalization, and death, among other situations. It occurs worldwide, including in Brazil, so that learning pharmacology impacts on public health service. We aim to investigate the current pharmacology educational practices in medical schools in the state of Rio de Janeiro, Brazil. METHODS: We surveyed 14 of 22 medical schools in Rio de Janeiro. Pharmacology teachers (n=16) and medical students (n=89) answered a semi-structured questionnaire that included questions about the staff characteristics, pharmacology content, teacher's concepts, and common practices and resources that were used in pharmacology classes. RESULTS: Our results revealed that the medical schools had similar overall curriculums. Pharmacology teachers work more than 30hs a week (75%) and conducted both research and teaching (62.5%). We also found that the multimedia projector was the most common resource (71.9%), and passive pedagogical methodologies (e.g., expository classes) remain a current strategy in pharmacology classes (89.9%). In general, medical students are poorly motivated (55%), which may be related to their performance in assessments. In addition, students believe that pharmacology is a complex (52%) or very complex subject (46%) since for its full understanding the student needs concepts from other disciplines, which can have an impact on the performance and motivation of students. As a result, these medical students do not fully understand the integration between pharmacology's basic concepts and their clinical applications. CONCLUSION: These data seem to demonstrate that the adopted teaching and learning pharmacology strategies and methodologies can be improved in Rio de Janeiro.

Absolute Stereochemistry Determination of Bioactive Marine-Derived Cyclopeptides by Liquid Chromatography Methods: An Update Review (2018-2022).

Cyclopeptides are considered as one of the most important classes of compounds derived from marine sources, due to their structural diversity and a myriad of their biological and pharmacological activities. Since marine-derived cyclopeptides consist of different amino acids, many of which are non-proteinogenic, they possess various stereogenic centers. In this respect, the structure elucidation of new molecular scaffolds obtained from natural sources, including marine-derived cyclopeptides, can become a very challenging task. The determination of the absolute configurations of the amino acid residues is accomplished, in most cases, by performing acidic hydrolysis, followed by analyses by liquid chromatography (LC). In a continuation with the authors' previous publication, and to analyze the current trends, the present review covers recently published works (from January 2018 to November 2022) regarding new cyclopeptides from marine organisms, with a special focus on their biological/pharmacological activities and the absolute stereochemical assignment of the amino acid residues. Ninety-one unreported marine-derived cyclopeptides were identified during this period, most of which displayed anticancer or antimicrobial activities. Marfey's method, which involves LC, was found to be the most frequently used for this purpose.