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Fanny Helena Martins Salles,1 Pedro San Martin Soares,1 Carolina David Wiener,1 Thaise Campos Mondin,1 Paula Moraes da Silva,1 Karen Jansen,1–3 Luciano Dias de Mattos Souza,1 Ricardo Azevedo da Silva,1 Jean Pierre Oses1–3 1Translational Science on Brain Disorders, Department of Health and Behavior, Catholic University of Pelotas, Pelotas, Rio Grande do Sul, Brazil; 2Translational Psychiatry Program, 3Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston (UTHealth) Medical School, Houston, TX, USA Abstract: Nerve growth factor (NGF) is an important member of the neurotrophin family and its alteration has been associated with psychiatric disorders. Functionality consists of the activities that an individual can perform, as well as their social participation, which is an important factor in analyzing the carrier living conditions of subjects with psychiatric suffering. Several studies have evaluated functionality in bipolar disorder; however, no studies have evaluated the functionality in other mental disorders. There are also few studies investigating the association between functionality and the biological bases of mental disorders. This study aimed to evaluate the serum NGF levels in psychiatric patients and to verify a possible association between the serum neurotrophic levels and functionality. This was a cross-sectional study with a convenient sample obtained from the Public Mental Health Service from the south of Brazil. The final sample was composed of 286 patients enrolled from July 2013 to October 2014. Data was collected using a sociodemographic questionnaire, and the diagnosis was confirmed using the Mini International Neuropsychiatric Interview (M.I.N.I) and a Functioning Assessment Short Test. The serum NGF levels were determined using the enzyme-linked immunosorbent assay method. Statistical analyses were performed using IBM SPSS Statistic 21.0 software. NGF serum levels were increased significantly in patients with obsessive–compulsive disorder compared with patients with no obsessive–compulsive disorder (P=0.015). An increase in serum NGF levels in generalized anxiety disorder patients was observed compared with patients with no generalized anxiety disorder (P=0.047). NGF was negatively associated with autonomy (P=0.024, r=–0.136), work (P=0.040, r=–0.124), and cognition (P=0.024, r=–0.137), thereby showing that changes in serum levels of NGF are associated with functionality in mental disorders. Keywords: NGF, mental disorders, functional impairment

Augusto Duarte Faria,1 Luciano Dias de Mattos Souza,2 Taiane de Azevedo Cardoso,2 Karen Amaral Tavares Pinheiro,2 Ricardo Tavares Pinheiro,2 Ricardo Azevedo da Silva,2 Karen Jansen21Department of Clinical and Health Psychology, Universidade Federal do Rio Grande – FURG, Rio Grande, RS, Brazil; 2Health and Behavior Postgraduate Program, Universidade Católica de Pelotas – UCPEL, Pelotas, RS, BrazilIntroduction: Changes in biological rhythm are among the various characteristics of bipolar disorder, and have long been associated with the functional impairment of the disease. There are only a few viable options of psychosocial interventions that deal with this specific topic; one of them is psychoeducation, a model that, although it has been used by practitioners for some time, only recently have studies shown its efficacy in clinical practice.Aim: To assess if patients undergoing psychosocial intervention in addition to a pharmacological treatment have better regulation of their biological rhythm than those only using medication.Method: This study is a randomized clinical trial that compares a standard medication intervention to an intervention combined with drugs and psychoeducation. The evaluation of the biological rhythm was made using the Biological Rhythm Interview of Assessment in Neuropsychiatry, an 18-item scale divided in four areas (sleep, activity, social rhythm, and eating pattern). The combined intervention consisted of medication and a short-term psychoeducation model summarized in a protocol of six individual sessions of 1 hour each.Results: The sample consisted of 61 patients with bipolar II disorder, but during the study, there were 14 losses to follow-up. Therefore, the final sample consisted of 45 individuals (26 for standard intervention and 19 for combined). The results showed that, in this sample and time period evaluated, the combined treatment of medication and psychoeducation had no statistically significant impact on the regulation of biological rhythm when compared to standard pharmacological treatment.Conclusion: Although the changes in biological rhythm were not statistically significant during the time period evaluated in this study, it is noteworthy that the trajectory of the score showed a trend towards improvement, which may indicate a positive impact on treatment, though it may take a longer time than expected.Keywords: neuropsychiatry, melatonin, depression, mania, lithium

Objective. While there is a recommendation to screen for postpartum depression (PPD), there are worries about the validity of instruments other than the Edinburgh Postnatal Depression Scale; little is known about the construct validity of one of the most used screening instruments, the Beck Depression Inventory, in this period. Methods. This study evaluated the validity and reliability of the BDI in a population-based sample of women and their spouses (n=772) in the postpartum. Additionally, we compared factor scores within the couple. Results. Exploratory factor analysis demonstrated a two-factor solution (depressive symptoms and somatic symptoms), accounting for 44.01% of the total variance. Internal consistency was good (Cronbach's α=0.90). Women had higher scores than their partners in both factors (P<0.001), but not a higher proportion of the total score attributable to somatic symptoms. Conclusion. With little factor variance between women and men, and a similar proportion of somatic symptoms, these results should be taken to reinforce the validity of the BDI in the postpartum. [ABSTRACT FROM AUTHOR]

Portland cement (PC) is a hydraulic binding material widely used in the building industry. The main interest in its use in dentistry is focused on a possible alternative to mineral trioxide aggregate (MTA) because PC is less expensive and is widely available. In dentistry, PC has been used in dental procedures such as pulpotomy, pulp capping, repair of root perforation and root-end filling. The purpose of this article is review the dental literature about the PC, its composition with special attention to arsenic content, properties, and application in dentistry. A bibliographic research was performed in Bireme, PubMed, LILACS and Scopus data bases looking for national and international studies about the PC composition, properties and clinical use. It was observed that PC has favorable biological properties very similar to those of MTA. The PC has shown good cell proliferation induction with formation of a monolayer cell, satisfactory inflammatory response, inhibitory effect of prostaglandin and antimicrobial effect. Studies have shown that PC is not cytotoxic, stimulates the apposition of reparative dentin and permits cellular attachment and growth. Regarding arsenic presence, its levels and release are low. PC has physical, chemical and biological properties similar to MTA. Arsenic levels and release are low, therefore, unable to cause toxic effects.

Abstract Background The lack of information on the care for sexually transmitted infections (STI) associated syndromes may contribute for its non-inclusion as prevention and control strategy for STI in Brazil. This study aims to analyze the cases of STI – Associated Syndromes assisted in primary health care center in a city in Northeast Brazil associating them with socio-demographic and behavioral variables. Methods This is a retrospective study that analyzed 5148 consultation forms and medical records of patients assisted in a primary health care center who presented at least one genital syndrome from 1999 to 2008. Was considered as dependent variables the genital syndromes and serologies for syphilis and HIV and as independent variables the socio-demographic and behavioral aspects. It was used Pearson’s chi-square test to analyze the differences between the categorical variables, with a significance level of 5%. It was performed a multivariate analysis through the multivariate logistic regression model with the variables with p Results The most frequent syndromes were vaginal discharge and/or cervicitis (44%) and genital wart (42.2%). Most people were between 20 and 39 years old (70%) and women (74.2%). Genital ulcer was most prevalent among men (OR = 2.67; CI 95% 1.99-3.58) and people who studied more than eight years (OR = 1.33; CI 95% 1.00-1.75) and wart prevailed among men (OR = 3.92; IC 95% 3.36-4.57), people under 29 years old (OR = 1.81; CI 95% 1.59-2.07) and who studied more than eight years (OR = 1.75; CI 95% 1.54-1.99). The Venereal Disease Research Laboratory (VDRL) was positive in 7.3% of men and in 7.1% of women and the Anti-HIV in 3.1% of men and 0.7% of women. Conclusion Vaginal discharge was the most frequent syndrome assisted in primary health care, followed by genital wart. The high prevalence of genital wart justifies the greater effort for the proper follow-up of these cases. Men presented more genital wart and ulcer and reported having more sexual partners, showing their need for a greater access and inclusion in health activities developed in primary health care in Brazil.

Abstract Aging and atherosclerosis are well-recognized risk factors for cardiac and neurovascular diseases. The Apolipoprotein E deficient (ApoE−/−) mouse on a high-fat diet is a classical model of atherosclerosis, characterized by the presence of atherosclerotic plaques in extracranial vessels but not in cerebral arteries. Increase in arginase activity was shown to participate in vascular dysfunction in the peripheral arteries of atherosclerotic mice by changing the level of nitric oxide (NO). NO plays a key role in the physiological functions of the neurovascular unit (NVU). However, the regulation of arginase expression and activity in the brain was never investigated in association with changes in the NVU, ApoE deficiency and high fat diet. Fourteen-month-old ApoE−/− mice on high-fat diet exhibited deposition of lipids in the NVU, impairment of blood–brain barrier properties, astrogliosis and an increase of aquaporin 4 staining. In association with these changes, brain arginase activity was significantly increased in the old ApoE−/− mice as compared to old wild type mice, with an increase in the level of arginase type I in the blood vessels. In conclusion, aging in this classical mouse model of atherosclerosis induces an increase in the level and activity of arginase I that may impair NO synthesis and contribute to changes in the NVU leading to blood–brain barrier leakage and inflammation.

Background: Here, we evaluated whether the histone lysine demethylase 5B (JARID1B), is involved in osteogenic phenotype commitment of periodontal ligament cells (PDLCs), by considering their heterogeneity for osteoblast differentiation., Materials and Methods: Epigenetic, transcriptional, and protein levels of a gene set, involved in the osteogenesis, were investigated by performing genome-wide DNA (hydroxy)methylation, mRNA expression, and western blotting analysis at basal (without osteogenic induction), and at the 3rd and 10th days of osteogenic stimulus, in vitro, using PDLCs with low (l) and high (h) osteogenic potential as biological models., Results: h-PDLCs showed reduced levels of JARID1B, compared to l-PDLCs, with significant inversely proportional correlations between RUNX2 and RUNX2/p57. Epigenetically, a significant reduction in the global H3K4me3 content was observed only in h-PDLCs. Immunoblotting data reveal a significant reduction in the global H3K4me3 content, at 3 days of induction only in h-PDLCs, while an increase in the global H3K4me3 content was observed at 10 days for both PDLCs. Additionally, positive correlations were found between global H3K4me3 levels and JARID1B gene expression., Conclusions: Altogether, our results show the crucial role of JARID1B in repressing PDLCs osteogenic phenotype and this claims to pre-clinical protocols proposing JARID1B as a potential therapeutic target., (© 2023 Wiley Periodicals LLC.)

Objective: To investigate the effects of combining a Pilates program with photobiomodulation therapy (PBMT) in patients with chronic nonspecific low back pain (CNLBP)., Methods: Thirty-eight adults with CNLBP were randomly assigned to two groups: Pilates exercise + active PBMT (PIL + PBMT) or Pilates exercise + sham PBMT (PIL + SHAM). Both groups performed an 8-week mat Pilates program and received PBMT on their lumbar muscles 10 min before and after each session. The following variables were assessed before and after intervention: peak pain intensity, postural balance (i.e., center of the pressure [A-COP], velocity anteroposterior [Vel AP], and velocity mediolateral [Vel ML]), perceived disability (i.e., Oswestry Disability Index [ODI] and Roland Morris Disability Questionnaire [RMDQ]), and pain-related fear of movement (i.e., Tampa Scale of Kinesiophobia [TSK], Fear Avoidance Beliefs Questionnaire [FABQ], and Pain Catastrophizing Scale [PCS])., Results: Postural balance variables showed no statistically significant differences ( p > 0.05) across time or between groups. The groups showed similar ( p < 0.05) reductions in peak pain intensity, ODI, RMDQ, and PCS scores, but no statistically significant difference ( p > 0.05) in TSK and FABQ scores., Conclusion: The mat Pilates program reduced peak pain intensity, perceived disability, and pain catastrophizing in adults with CNLBP, but PBMT had no additional effect on these variables. Mat Pilates alone or combined with PBMT was not able to improve postural balance.

Genome-wide association studies (GWASs) allow for inferences about the relationships between genomic variants and phenotypic traits in natural or breeding populations. However, few have used this methodology in Coffea arabica . We aimed to identify chromosomal regions with significant associations between SNP markers and agronomic traits in C. arabica . We used a coffee panel consisting of 195 plants derived from 13 families in F2 generations and backcrosses of crosses between leaf rust-susceptible and -resistant genotypes. The plants were phenotyped for 18 agronomic markers and genotyped for 21,211 SNP markers. A GWAS enabled the identification of 110 SNPs with significant associations ( p < 0.05) for several agronomic traits in C. arabica : plant height, plagiotropic branch length, number of vegetative nodes, canopy diameter, fruit size, cercosporiosis incidence, and rust incidence. The effects of each SNP marker associated with the traits were analyzed, such that they can be used for molecular marker-assisted selection. For the first time, a GWAS was used for these important agronomic traits in C. arabica , enabling applications in accelerated coffee breeding through marker-assisted selection and ensuring greater efficiency and time reduction. Furthermore, our findings provide preliminary knowledge to further confirm the genomic loci and potential candidate genes contributing to various structural and disease-related traits of C. arabica .

Background: Poor postural control has been reported in people with Parkinson's disease, which could be explained by the changes in muscular activation patterns related to antigravitational muscles. This study aims to measure the muscle activation of antigravitational muscles during balance tasks in individuals, with and without Parkinson's., Methods: Sixteen (16) participants (9 with Parkinson's), aged ≥65 yrs., performed 2 × 30-s trials of 4 balance tasks (bipodal and semi-tandem opened eyes and closed eyes) on a force platform (center of pressure measurement); while surface electromyography measurements were obtained bilaterally on the multifidus at L5, biceps femoris and medialis gastrocnemius. Electromyography amplitude analysis was processed by the Root Mean Square (250 ms window epochs) and normalized by the peak of activation during the balance task, to determine each muscle's activity level., Findings: The Parkinson's group reported lower muscle activation than control across tasks (in mean for multifidus = 8%, biceps femoris = 16%, gastrocnemius = 7%), although not statistically significant. Parkinson's reported significantly poorer postural control than control, mainly for the center of pressure sway ellipse area (p = 0.016) from challenge balance tasks such as semi-tandem., Interpretation: Poor postural control was confirmed in the Parkinson's group, but not significantly associated by the changes from muscle activation of trunk and lower limbs, during balance performance., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Caffeine has been extensively studied in the context of CNS pathologies as many researchers have shown that consuming it reduces pro-inflammatory biomarkers, potentially delaying the progression of neurodegenerative pathologies. Several lines of evidence suggest that adenosine receptors, especially A 1 and A 2 A receptors, are the main targets of its neuroprotective action. We found that caffeine pretreatment 15 min before LPS administration reduced the expression of Il1b in the hippocampus and striatum. The harmful modulation of caffeine-induced inflammatory response involved the downregulation of the expression of A 2 A receptors, especially in the hippocampus. Caffeine treatment alone promoted the downregulation of the adenosinergic receptor Adora2A; however, this promotion effect was reversed by LPS. Although administering caffeine increased the expression of the enzymes DNA methyltransferases 1 and 3A and decreased the expression of the demethylase enzyme Tet1, this effect was reversed by LPS in the hippocampus of mice that were administered Caffeine + LPS, relative to the basal condition; no significant differences were observed in the methylation status of the promoter regions of adenosine receptors. Finally, the bioinformatics analysis of the expanded network demonstrated the following results: the Adora2B gene connects the extended networks of the adenosine receptors Adora1 and Adora2A; the Mapk3 and Esr1 genes connect the extended Adora1 network; the Mapk4 and Arrb2 genes connect the extended Adora2A network with the extended network of the proinflammatory cytokine Il1β. These results indicated that the anti-inflammatory effects of acute caffeine administration in the hippocampus may be mediated by a complex network of interdependencies between the Adora2B and Adora2A genes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Objective: The present pilot study aimed to propose an innovative scale-independent measure based on electroencephalographic (EEG) signals for the identification and quantification of the magnitude of chronic pain., Methods: EEG data were collected from three groups of participants at rest: seven healthy participants with pain, 15 healthy participants submitted to thermal pain, and 66 participants living with chronic pain. Every 30 s, the pain intensity score felt by the participant was also recorded. Electrodes positioned in the contralateral motor region were of interest. After EEG preprocessing, a complex analytical signal was obtained using Hilbert transform, and the upper envelope of the EEG signal was extracted. The average coefficient of variation of the upper envelope of the signal was then calculated for the beta (13-30 Hz) band and proposed as a new EEG-based indicator, namely Piq β , to identify and quantify pain., Main Results: The main results are as follows: (1) A Piq β threshold at 10%, that is, Piq β ≥ 10%, indicates the presence of pain, and (2) the higher the Piq β (%), the higher the extent of pain., Conclusions: This finding indicates that Piq β can objectively identify and quantify pain in a population living with chronic pain. This new EEG-based indicator can be used for objective pain assessment based on the neurophysiological body response to pain., Significance: Objective pain assessment is a valuable decision-making aid and an important contribution to pain management and monitoring.

Annexin A1 (AnxA1) is a glucocorticoid-inducible protein and an important endogenous modulator of inflammation. However, its effect in the endometrial microenvironment is poorly explained. This study aimed to evaluate the role of endogenous AnxA1 in an endometritis mouse model induced by lipopolysaccharide (LPS). Female C57BL/6 wild-type (WT) and AnxA1 -/- mice were divided into two groups: SHAM and LPS. To induce endometritis, mice received a vaginal infusion of 50 μL of LPS (1 mg/mL) dissolved in phosphate-buffered saline. After 24 h, the mice were euthanized, and blood and uteri samples were collected. The endometrium inflammatory scores were significantly increased in the LPS-treated group. AnxA1 -/- mice from the LPS group demonstrated a significant increase in the number of degranulated mast cell levels compared to AnxA1 -/- SHAM mice. The Western blotting analysis revealed that a lack of AnxA1 promoted the upregulation of NLRP3 and pro-IL-1β in the acute endometritis animal model compared to WT LPS animals. LPS-induced endometritis increased the number of blood peripheral leukocytes in both WT and AnxA1 -/- mice compared with SHAM group mice (p < 0.001). AnxA1 -/- mice also showed increased plasma levels of IL-1β (p < 0.01), IL-6, IL-10, IL-17, and TNF-α (p < 0.05) following LPS-induced endometritis. In conclusion, a lack of endogenous AnxA1 exacerbated the inflammatory response in an endometritis model via NLRP3 dysregulation, increased uterine mast cell activation, and plasma pro-inflammatory cytokine release., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This work presents a magnetic purification method of human erythrocyte Acetylcholinesterase (EC 3.1.1.7; AChE) based on affinity binding to procainamide (Proca) as ligand. Acetylcholinesterase is an acetylcholine-regulating enzyme found in different areas of the body and associated with various neurological disorders, such as Parkinson, Alzheymer and Amyotrophic Lateral Sclerosis. AChE from human erythrocyte purification has been attempted in recent years with low degree of purity. Here, magnetic nanoparticles (MNP) were synthesized and coated with polyaniline (PANI) and procainamide (PROCA) was covalently linked to the PANI. The extracted human erythrocyte AChE formed a complex with the MNP@PANI-PROCA and an external magnet separated it from the undesired proteins. Finally, the enzyme was collected by increasing the ionic strength. Experimental Box-Behnken design was developed to optimize this process of human erythrocyte AChE purification protocol. The enzyme was purified in all fifteen experiments. However, the best AChE purification result was achieved, about 2000 times purified, when 100 mg of MNP@PANI-PROCA was incubated for one hour with 4 ml hemolysate extract. The SDS-PAGE of this preparation presented a molecular weight of approximately 70 kDa, corroborating with few previous studies of AChE from erythrocyte purification., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Epigenetic changes, particularly histone compaction modifications, have emerged as critical regulators in the epigenetic pathway driving endothelial cell phenotype under constant exposure to laminar forces induced by blood flow. However, the underlying epigenetic mechanisms governing endothelial cell behavior in this context remain poorly understood. To address this knowledge gap, we conducted in vitro experiments using human umbilical vein endothelial cells subjected to various tensional forces simulating pathophysiological blood flow shear stress conditions, ranging from normotensive to hypertensive forces. Our study uncovers a noteworthy observation wherein endothelial cells exposed to high shear stress demonstrate a decrease in the epigenetic marks H3K4ac and H3K27ac, accompanied by significant alterations in the levels of HDAC (histone deacetylase) proteins. Moreover, we demonstrate a negative regulatory effect of increased shear stress on HOXA13 gene expression and a concomitant increase in the expression of the long noncoding RNA, HOTTIP, suggesting a direct association with the suppression of HOXA13. Collectively, these findings represent the first evidence of the role of histone-related epigenetic modifications in modulating chromatin compaction during mechanosignaling of endothelial cells in response to elevated shear stress forces. Additionally, our results highlight the importance of understanding the physiological role of HOXA13 in vascular biology and hypertensive patients, emphasizing the potential for developing small molecules to modulate its activity. These findings warrant further preclinical investigations and open new avenues for therapeutic interventions targeting epigenetic mechanisms in hypertensive conditions., (© 2024 International Federation for Cell Biology.)

Oropouche virus (OROV) is a member of the Peribunyaviridae family and the causative agent of a dengue-like febrile illness transmitted by mosquitoes. Although mild symptoms generally occur, complications such as encephalitis and meningitis may develop. A lack of proper diagnosis, makes it a potential candidate for new epidemics and outbreaks like other known arboviruses such as Dengue, Yellow Fever and Zika virus. The study of natural molecules as potential antiviral compounds is a promising alternative for antiviral therapies. Wedelolactone (WDL) has been demonstrated to inhibit some viral proteins and virus replication, making it useful to target a wide range of viruses. In this study, we report the in silico effects of WDL on the OROV N-terminal polymerase and its potential inhibitory effects on several steps of viral infection in mammalian cells in vitro , which revealed that WDL indeed acts as a potential inhibitor molecule against OROV infection., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Holding and restraining children during non-urgent clinical procedures continues to be surrounded by uncertainty and mired in controversy. This review aimed to locate, appraise and map the evidence related to health professionals reported and observed practice of holding and restraining children, from birth to 16 years, for clinical procedures. This scoping review, conducted in April 2022, was based on the Joanna Briggs Institute protocol. Screening and full text review resulted in the inclusion of 30 papers. In total, 14 different terms were used to refer to the act of holding or restraining a child for a procedure, in many papers the action of holding was not defined. Professionals report the main factors influencing their decisions to use restraint and/or holding were the age of a child, with younger children being restrained or held most frequently; a child's behaviour; and concerns around a child's safety. Professionals also report that they can perceive pressure from parent/carers to hold or restrain their child and describe how holding practices can be influenced by service and organisational pressures. Health professionals, mainly nurses, continue to report ethical and moral tensions linked to their involvement in the restraint or holding of a child against their will for a clinical procedure. Evidence indicates a need to move practice forward as the issues identified in paediatric practice are long-standing and historical., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Major depressive disorder (MDD) is a global concern due to its widespread prevalence and morbidity. Identifying protective factors in high-risk individuals, including those with a familial predisposition, maltreatment history, and socio-economic vulnerabilities, is crucial., Methods: We assessed a high-risk subsample within a young adult population cohort (n = 791; mean age = 31.94 [SD = 2.18]) across three waves. Using multiple regression models to analyse higher education, feeling supported, spirituality, psychotherapy access, higher socioeconomic status, involvement in activities, cohabitation, and family unity in Waves 1 and 2, and their association with MDD resilience at Wave 3., Results: In the high-risk group, MDD incidence was 13.7% (n=24). Paternal support had a protective effect on MDD incidence (OR = 0.366; 95% CI [0.137 to 0.955], p = 0.040) and suicidal attempt risk (OR = 0.380; 95% CI [0.150 to 0.956], p = 0.038). Higher resilience scores were also protective (OR = 0.975; 95% CI [0.953 to 0.997], p = 0.030), correlating with reduced BDI (r = 0.0484; B = -0.2202; 95% CI [-0.3572 to -0.0738]; p = 0.003) and MADRS scores (r = 0.0485; B = -0.2204; 95% CI [-0.3574 to -0.0741]; p = 0.003)., Conclusions: Our paper emphasizes reorienting the MDD approach, focusing on positive prevention strategies. It highlights fathers' crucial role in family-based interventions and promoting resilience in high-risk populations., Competing Interests: No conflicts of interest declared concerning the publication of this article.

Anti-VEGF (vascular endothelial growth factor) drugs such as aflibercept (AFL) and bevacizumab (BVZ) inhibit pathological neo-angiogenesis and vascular permeability in retinal vascular diseases. As cytokines and growth factors are produced by Müller glial cells under stressful and pathological conditions, we evaluated the in vitro effect of AFL (Eylea®, 0.5 mg/mL) and BVZ (Avastin®, 0.5 mg/mL) on cell viability/metabolism, and cytokine/growth factor production by Müller cells (MIO-M1) under cobalt chloride (CoCl2)-induced hypoxia after 24h, 48h and 72h. Cell viability/metabolism were analyzed by Trypan Blue and MTT assays and cytokine/growth factors in supernatants by Luminex xMAP-based multiplex bead-based immunoassay. Cell viability increased with AFL at 48h and 72h and decreased with BVZ or hypoxia at 24h. BVZ-treated cells showed lower cell viability than AFL at all exposure times. Cell metabolism increased with AFL but decreased with BVZ (72h) and hypoxia (48h and72h). As expected, AFL and BVZ decreased VEGF levels. AFL increased PDGF-BB, IL-6 and TNF-α (24h) and BVZ increased PDGF-BB (72h). Hypoxia reduced IL-1β, -6, -8, TNF-α and PDGF-BB at 24h, and its suppressive effect was more prominent than AFL (EGF, PDGF-BB, IL-1β, IL-6, IL-8, and TNF-α) and BVZ (PDGF-BB and IL-6) effects. Hypoxia increased bFGF levels at 48h and 72h, even when combined with anti-VEGFs. However, the stimulatory effect of BVZ predominated over hypoxia for IL-8 and TNF-α (24h), as well as for IL-1β (72h). Thus, AFL and BVZ exhibit distinct exposure times effects on MIO-M1 cells viability, metabolism, and cytokines/growth factors. Hypoxia and BVZ decreased MIO-M1 cell viability/metabolism, whereas AFL likely induced gliosis. Hypoxia resulted in immunosuppression, and BVZ stimulated inflammation in hypoxic MIO-M1 cells. These findings highlight the complexity of the cellular response as well as the interplay between anti-VEGF treatments and the hypoxic microenvironment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Matsuda et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The effect of aerobic training on reliever medication consumption (short-acting β 2 -agonist (SABA)) and peak expiratory flow (PEF) in participants with asthma is poorly known. The comparison between constant-load exercise (CLE) and high-intensity interval training (HIIT) in these outcomes has never been tested. The purpose of the present study was to compare the effects of CLE or HIIT in SABA consumption and PEF improvement during an exercise programme in subjects with asthma., Methods: Clinically stable participants were randomised into CLE (n=27; 70-85% of the maximal load (W max )) or HIIT (n=28; 80-140% W max ). The programme lasted 12 weeks (two sessions per week, 40 min per session), and the intensity was based on cardiopulmonary exercise testing (CPET). PEF was assessed before and after each exercise session. SABA was used if PEF was <70%. Clinical control (Asthma Control Questionnaire (ACQ)-6), CPET and aerobic fitness were also assessed before and after the intervention., Results: Both groups were similar at baseline. CLE and HIIT reduced SABA consumption throughout the intervention (p<0.05). Before training, 14 patients required SABA before exercising, but only one needed it after the intervention. Changes in post-exercise PEF were lower in the CLE group than in the HIIT group (1.6±25.3 versus 10.3±13.7%). Both groups improved aerobic fitness (10.1±12.8% versus 5.7±15.6%) and clinical asthma control; however, only the HIIT group achieved a minimal clinically important difference in the ACQ-6 post-intervention (-0.23±1.06 versus -0.52±0.73 Δ score)., Conclusion: CLE and HIIT reduced SABA consumption; however, only HIIT increased PEF and asthma clinical control after the intervention. These results reinforce the importance of exercise training in moderate-to-severe asthma., Competing Interests: Conflict of interest: The authors declare no conflicts of interest related to the contents of the manuscript., (Copyright ©The authors 2024.)

Objectives: This cross-sectional school-based study explored the influence of malocclusion on temporomandibular disorders (TMD) pain complaints, and whether this association would be mediated by sleep bruxism in a representative sample of 7- to 8-year-old children., Methods: Path analysis estimated direct, indirect, and total effects of occlusal features on sleep bruxism and TMD pain in 7- to 8-year-old children. Occlusal features were assessed with Dental Aesthetic Index (DAI), orofacial pain complaints using the TMD pain screener, possible sleep bruxism based on self-reports, and probable sleep bruxism based on self-reports combined with clinical findings. Structural equation modeling analyzed data with confounding factors., Results: From 580 participants, possible sleep bruxism was observed in 136 children (31.5%), probable sleep bruxism in 30 children (6.7%), and TMD pain complaints in 78 children (13.8%). Malocclusion had no direct effect on either possible sleep bruxism [standardized coefficient (SC) 0.000; p = 0.992], or TMD pain complaints (SC - 0.01; p = 0.740). When probable sleep bruxism was set as the mediator of interest, malocclusion did not directly affect probable sleep bruxism (SC 0.01; p = 0.766), nor TMD pain complaints (SC - 0.02; p = 0.515). A direct effect of probable sleep bruxism on TMD pain complaints was observed with an SC of 0.60 (p < 0.001). However, in neither case, malocclusion indirectly affected TMD pain complaints via bruxism., Conclusion: Malocclusion in 7- to 8-year-old children did not directly influence possible or probable sleep bruxism or TMD pain complaints. Instead, probable sleep bruxism was strongly associated with TMD pain complaints., Clinical Significance: The impact of occlusal features on TMD pain complaints and bruxism has been a long-standing controversy in dentistry. However, the scientific literature linking this association may be inconsistent, mainly due to biased sample selection methods with inadequate consideration of confounders. Further research should try to identify additional risk factors for TMD pain in addition to probable sleep bruxism in children., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Women with premenstrual dysphoric disorder (PMDD) are more likely to report suicide ideation and behavior when compared to women without PMDD. However, there is a lack of studies investigating the risk factors for suicide risk in women with PMDD. Thus, the aim of this study is to assess the factors associated with suicide risk in young women with PMDD., Methods: This is a cross-sectional study including 128 young women with PMDD who were recruited from the community. PMDD and suicide risk were assessed by trained psychologists using the Mini International Neuropsychiatric Interview (MINI-PLUS). Suicide risk evaluation includes six questions that assess suicidal intention, planning and previous attempts. Subjects who answer yes to any of the six questions are classified as having current suicide risk., Results: The prevalence of current suicide risk in women with PMDD was 28.1%. The factors associated with suicide risk in this population were: presenting current panic disorder (OR: 18.71 [95% CI: 1.02 - 343.27], p=0.048), a non-white skin color (OR: 4.18 [CI 95%: 1.28 - 13.61], p=0.018), greater severity of depressive symptoms (OR: 1.22 [95% CI: 1.12 - 1.32], < 0.001), and history of childhood trauma (OR: 1.04 [95% CI: 1.01 - 1.08], 0.010)., Conclusion: Our findings indicate that there are key sociodemographic and clinical factors associated with suicide risk in young women with PMDD, enabling clinicians to identify at-risk individuals who could benefit from further screening and interventions., Competing Interests: No conflicts of interest declared concerning the publication of this article.

Background: Parkinson's Disease (PD), a neurodegenerative condition, affects normal aging and leads to reduced motor abilities. In addition, frailty syndrome can increase vulnerability and risks of undesirable effects such as disease progression, falls, disability, and premature death among individuals with PD., Aims: To assess the impact of frailty on balance and gait parameters in older with PD and to determine if sex mediates these measures., Methods: Twenty-seven (27) participants (n = 18 men; n = 10 frail) performed 4 balance tasks on a force platform (eyes opened/closed in bipodal/semi-tandem position) while linear center of pressure (COP) parameters were calculated. Participants also performed two different speed walks on a gait analysis system to assess gait parameters., Results: Significant differences between the frail and non-frail group were observed on postural control (mainly for area of COP p = 0.013/d = 0.47/70 %; sway velocity p = 0.048/d = 0.41/23 %) where frail reported poor balance. No significant sex differences were reported for postural control. Gait analysis was comparable between frail and non-frail, while significant differences between men and women were observed for step length (p = 0.002, d = 0.71), step width (p = 0.001, d = 0.75) and base of support (p = 0.012, d = 0.64) variables., Conclusion: Frail Parkinson's individuals present poorer postural control than non-frail individuals, but comparable gait parameters. Men and women are comparable on postural control but show different gait parameters. These results may have implications in clinical decision-making in rehabilitation for frailty in older adults, men and women with Parkinson's disease when balance and gait are of concern., Competing Interests: Declaration of competing interest No conflicts of interest are declared for any author., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Ebola virus disease (EVD) causes outbreaks and epidemics in West Africa that persist until today. The envelope glycoprotein of Ebola virus (GP) consists of two subunits, GP1 and GP2, and plays a key role in anchoring or fusing the virus to the host cell in its active form on the virion surface. Toremifene (TOR) is a ligand that mainly acts as an estrogen receptor antagonist; however, a recent study showed a strong and efficient interaction with GP. In this context, we aimed to evaluate the energetic affinity features involved in the interaction between GP and toremifene by computer simulation techniques using the Molecular Fractionation Method with Conjugate Caps (MFCC) scheme and quantum-mechanical (QM) calculations, as well as missense mutations to assess protein stability. We identified ASP522, GLU100, TYR517, THR519, LEU186, LEU515 as the most attractive residues in the EBOV glycoprotein structure that form the binding pocket. We divided toremifene into three regions and evaluated that region i was more important than region iii and region ii for the formation of the TOR-GP1/GP2 complex, which might control the molecular remodeling process of TOR. The mutations that caused more destabilization were ARG134, LEU515, TYR517 and ARG559, while those that caused stabilization were GLU523 and ASP522. TYR517 is a critical residue for the binding of TOR, and is highly conserved among EBOV species. Our results may help to elucidate the mechanism of drug action on the GP protein of the Ebola virus and subsequently develop new pharmacological approaches against EVD.Communicated by Ramaswamy H. Sarma.

The epiretinal membrane is a fibrocontractile tissue that forms on the inner surface of the retina, causing visual impairment ranging from mild to severe, and even retinal detachment. Müller glial cells actively participate in the formation of this membrane. Current research is constantly seeking for new therapeutic approaches that aim to prevent or treat cellular dysfunctions involved in the progression of this common fibrosis condition. The Rho GTPases signaling pathway regulates several processes associated with the epiretinal membrane, such as cell proliferation, migration, and contraction. Rho kinase (ROCK), an effector of the RhoA GTPase, is an interesting potential therapeutic target. This study aimed to evaluate the effects of a ROCK inhibitor (Y27632) on human Müller cells viability, growth, cytoskeletal organization, expression of extracellular matrix components, myofibroblast differentiation, migration, and contractility. Müller cells of the MIO-M1 lineage were cultured and treated for different periods with the inhibitor. Viability was evaluated by MTT assay and trypan blue exclusion method, and growth was evaluated by growth curve and BrdU incorporation assay. The actin cytoskeleton was stained with fluorescent phalloidin, intermediate filaments and microtubules were analyzed with immunofluorescence for vimentin and α-tubulin. Gene and protein expression of collagens I and V, laminin and fibronectin were evaluated by rt-PCR and immunofluorescence. Chemotactic and spontaneous cell migration were studied by transwell assay and time-lapse observation of live cells, respectively. Cell contractility was assessed by collagen gel contraction assay. The results showed that ROCK inhibition by Y27632 did not affect cell viability, but decreased cell growth and proliferation after 72 h. There was a change in cell morphology and organization of F-actin, with a reduction in the cell body, disappearance of stress fibers and formation of long, branched cell extensions. Microtubules and vimentin filaments were also affected, possibly because of F-actin alterations. The inhibitor also reduced gene expression and immunoreactivity of smooth muscle α-actin, a marker of myofibroblasts. The expression of extracellular matrix components was not affected by the inhibitor. Chemotactic cell migration showed no significant changes, while cell contractility was substantially reduced. No spontaneous migration of MIO-M1 cells was observed. In conclusion, pharmacological inhibition of ROCK in Müller cells could be a potentially promising approach to treat epiretinal membranes by preventing cell proliferation, contractility and transdifferentiation, without affecting cell viability., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Full-thickness cutaneous trauma, due to the lack of dermis, leads to difficulty in epithelialization by keratinocytes, developing a fibrotic scar, with less elasticity than the original skin, which may have disorders in predisposed individuals, resulting in hypertrophic scar and keloids. Biomedical materials have excellent characteristics, such as good biocompatibility and low immunogenicity, which can temporarily replace traditional materials used as primary dressings. In this work, we developed two dermal matrices based on Nile tilapia collagen, with (M&#95;GAG) and without (M) glycosaminoglycans, using a sugarcane polymer membrane as a matrix support. To assess the molecular mechanisms driving wound healing, we performed qualitative proteomic analysis on the wound bed in an in vivo study involving immunocompetent murine models at 14 and 21 days post-full-thickness skin injury. Gene Ontology and Pathway analysis revealed that both skins were markedly represented by modulation of the immune system, emphasizing controlling the acute inflammation response at 14 and 21 days post-injury. Furthermore, both groups showed significant enrichment of pathways related to RNA and protein metabolism, suggesting an increase in protein synthesis required for tissue repair and proper wound closure. Other pathways, such as keratinization and vitamin D3 metabolism, were also enriched in the groups treated with M matrix. Finally, both matrices improved wound healing in a full post-thick skin lesion. However, our preliminary molecular data reveals that the collagen-mediated healing matrix lacking glycosaminoglycan (M) exhibited a phenotype more favorable to tissue repair, making it more suitable for use before skin grafts., (© 2023 John Wiley & Sons, Ltd.)

Oropouche virus (OROV) is an emerging vector-borne arbovirus found in South America that causes Oropouche fever, a febrile infection similar to dengue fever. It has a high epidemic potential, causing illness in over 500,000 cases diagnosed since the virus was first discovered in 1955. Currently, the prevention of human viral infection depends on vaccination, but availability for many viruses is limited, and they are classified as neglected viruses. At present, there are no vaccines or antiviral treatments available. An alternative approach to limiting the spread of the virus is to selectively disrupt viral replication mechanisms. Here, we demonstrate the inhibitory effect of acridones, which efficiently inhibited viral replication by 99.9 % in vitro . To evaluate possible mechanisms of action, we conducted tests with dsRNA, an intermediate in virus replication, as well as MD simulations, docking, and binding free energy analysis. The results showed a strong interaction between FAC21 and the OROV endonuclease, which possibly limits the interaction of viral RNA with other proteins. Therefore, our results suggest a dual mechanism of antiviral action, possibly caused by ds-RNA intercalation. In summary, our findings demonstrate that a new generation of antiviral drugs could be developed based on the selective optimization of molecules., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mauricio Lacerda Nogueira reports financial support was provided by The Coordinating Research on Emerging Arboviral Threats Encompassing the Neotropics., (© 2023 The Author(s).)

The Oropouche virus (OROV) is a member of the family Peribunyaviridae (order Bunyavirales ) and the cause of a dengue-like febrile illness transmitted mainly by biting midges and mosquitoes. In this study, we aimed to explore acylphloroglucinols and xanthohumol from hops ( Humulus lupulus L.) as a promising alternative for antiviral therapies. The evaluation of the inhibitory potential of hops compounds on the viral cycle of OROV was performed through two complementary approaches. The first approach applies cell-based assay post-inoculation experiments to explore the inhibitory potential on the latest steps of the viral cycle, such as genome translation, replication, virion assembly, and virion release from the cells. The second part covers in silico methods evaluating the ability of those compounds to inhibit the activity of the endonuclease domain, which is essential for transcription, binding, and cleaving RNA. In conclusion, the beta acids showed strongest inhibitory potential in post-treatment assay (EC 50 = 26.7 µg/mL). Xanthohumol had the highest affinity for OROV endonuclease followed by colupulone and cohumulone. This result contrasts with that observed for docking and MM/PBSA analysis, where cohumulone was found to have a higher affinity. Finally, among the three tested ligands, Lys92 and Arg33 exhibited the highest affinity with the protein.

Anxiety disorders are among the most common psychiatric disorders in the general population. Our objective was to describe the cumulative incidence and risk factors of anxiety disorders, including obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD), in a follow-up of young adults over a five-year period. This is a prospective cohort conducted in two waves. The first took place from 2007 to 2009, in which 1,560 young adults aged between 18 and 24 years were evaluated using the Mini-International Neuropsychiatric Interview (MINI). Subjects were invited to participate in the second wave, which wave took place from 2012 to 2014, where 1,244 young adults were evaluated using the MINI-Plus. Our findings showed a cumulative incidence of 10.9% for any anxiety disorder, 6.5% for generalized anxiety disorder, 6.0% for agoraphobia, 2.0% for OCD, 1.6% for panic disorder, 1.1% for social anxiety and 0.7% for PTSD. Being female and having had a depressive episode were risk factors to develop any anxiety disorder. We observed a high cumulative incidence of anxiety disorders in a population-based sample of young adults. Our data highlights the importance of the early identification of these disorders as this could lead to early illness detection, early illness management and a reduced burden of disease., (Copyright © 2022 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)