Cytogenotoxic screening of the natural compound niga-ichigoside F1 from Rubus imperialis (Rosaceae).

Rubus imperialis Chum. Schl. (Rosaceae) have demonstrated some pharmacological activities, including gastroprotective action. However, genotoxic effects of R. imperialis extract was also reported. Since niga-ichigoside F1 (NIF1) is a major compound of this plant species, and which has proven pharmacological properties, it is essential to investigate whether this compound is responsible for the observed toxicity. Therefore, the objective of this study was to analyze the effects of NIF1 on HepG2/C3A cells for possible cytogenotoxicity, cell cycle and apoptosis influence, and expression of genes linked to the DNA damage, cell cycle, cell death, and xenobiotic metabolism. The results showed no cytogenotoxic effects of NIF1 at concentrations between 0.1 and 20 µg/ml. Flow cytometry also showed no cell cycle or apoptosis disturbance. In the gene expression analysis, none of the seven genes investigated showed altered expression. The data indicate that NIF1 has no cytogenotoxic effects, and no interruption of the cell cycle, or induction of apoptosis, apparently not being responsible for the cytotoxic effects observed in the crude extract of R. imperialis.

Disruption of caspase-independent cell proliferation pathway on spheroids (HeLa cells) treated with curcumin.

Curcumin is an antiproliferative phytochemical extracted from Curcuma longa L and which has been studied in preclinical drug screening using cell monolayers and animal models. However, several limitations of these culture systems may be overcome by performing screening with three-dimensional (3-D) cell culture. The aim of this study was to investigate the effects of curcumin on cytotoxicity and genotoxicity as well as spheroid growth using cervical adenocarcinoma HeLa cell spheroids by performing RT-PCR mRNA expression of genes involved in cell death (CASP3, CASP8, CASP9, PARP1, BBC3, BIRC5, BCL2, TNF), autophagy (BECN1, SQSTM1), cell cycle regulation (TP53, C-MYC, NF-kB, CDKN1A, m-TOR, TRAF-2), DNA damage repair (H2AFX, GADD45A, GADD45G), oxidative stress (GPX1), reticulum stress (EIF2AK3, ERN1), and invasion (MMP1, MMP9) was investigated. Curcumin was cytotoxic in a concentration-dependent manner. Curcumin-treated spheroids exhibited lower proliferative recovery and cell proliferation attenuation, as observed in the clonogenic assay. Further, no marked genotoxicity was detected. Curcumin-treated spheroids displayed reduced expression of BECN1 (2.9×), CASP9 (2.1×), and PARP1 (2.1×) mRNA. PARP1 inhibition suggested disruption of essential pathways of proliferation maintenance. Downregulated expression of CASP9 mRNA and unchanged expression of CASP3/8 mRNA suggested caspase-independent cell death, whereas downregulated expression of BECN1 mRNA indicated autophagic disruption. Therefore, curcumin exhibits the potential for drug development with antiproliferative activity to be considered for use in cancers.

Region 1p13.2 including the RSBN1, PTPN22, AP4B1 and long non-coding RNA genes does not bear risk factors for endemic pemphigus foliaceus (fogo selvagem).

Pemphigus foliaceus (PF) is an autoimmune skin disease characterized by autoantibodies directed mainly against desmoglein-1. The purpose of this study was to determine whether differential susceptibility to endemic PF in Brazil (fogo selvagem) is associated with polymorphisms at the cytogenetic location 1p13.2. Four single nucleotide polymorphisms that together tag 28 SNPs on a segment of approximately 312,000 bp encompassing the protein-coding genes MAGI3, PHTF1, RSBN1, PTPN22, BCL2L15, AP4B1, DCLRE1B, the pseudogenes MTND5P20, RPS2P14 (AL133517.1) and the long non-coding RNA genes AL137856.1, and AP4B1-AS1 were used as markers for association analysis in a case-control study. Allele, genotype and haplotype frequencies of rs33996649, rs2476601, rs3789604 and rs3195954 were compared between patient and control samples. No significant association was found. Lack of association with rs2476601 of the PTPN22 gene agrees with previous results for pemphigus vulgaris and the Tunisian form of endemic pemphigus foliaceus. The other three SNPs had never been analysed before in any form of pemphigus. We conclude that variants in structural and regulatory sites of region 1p13.2 are not susceptibility factors for fogo selvagem. We suggest careful investigation of this genomic region in diseases that had been previously associated with PTPN22, since there are several other genes relevant for immune-mediated diseases located in 1p13.2.

A 3'UTR polymorphism marks differential KLRG1 mRNA levels through disruption of a miR-584-5p binding site and associates with pemphigus foliaceus susceptibility.

Genetic variations mapping to 3' untranslated regions (3'UTRs) may overlap with microRNA (miRNA) binding sites, therefore potentially interfering with translation inhibition or messenger RNA (mRNA) degradation. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) located within the 3'UTRs of six candidate genes and predicted to interfere with miRNA ligation could account for disease-relevant differential mRNA levels. Focusing on pemphigus foliaceus (PF) - an autoimmune blistering skin condition with unique endemic patterns - we investigated whether nine 3'UTR SNPs from the CD1D, CTLA4, KLRD1, KLRG1, NKG7, and TNFSF13B genes differentially expressed in PF were disease-associated. The heterozygous genotype of the KLRG1 rs1805672 polymorphism was associated with increased predisposition to PF (A/G vs. A/A: P=0.038; OR=1.60), and a trend for augmented susceptibility was observed for carriers of the G allele (P=0.094; OR=1.44). In silico analyses suggested that rs1805672 G allele could disrupt binding of miR-584-5p, and indicated rs1805672 as an expression Quantitative Trait Locus (eQTL), with an effect on KLRG1 gene expression. Dual-luciferase assay showed that miR-584-5p mediated approximately 50% downregulation of the reporter gene's activity through the 3'UTR of KLRG1 harboring rs1805672 A allele (vs. miRNA-negative condition, P=0.006). This silencing relationship was lost after site-directed mutation to G allele (vs. miRNA-negative condition, P=0.391; vs. rs1805672 A allele, P=0.005). Collectively, these results suggest that a disease-associated SNP located within the 3'UTR of KLRG1 directly interferes with miR-584-5p binding, allowing for KLRG1 mRNA differential accumulation, which in turn may contribute to pathogenesis of autoimmune diseases, such as pemphigus.

The conservation of native priority medicinal plants in a Caatinga area in Ceará, northeastern Brazil.

Much of the Brazilian semiarid region faces a considerable process of degradation of natural resources, and ethnobotanical studies have collaborated with important information about the use and traditional knowledge, serving as a tool to design conservation strategies of native plant species. Thus, this study aimed to determine medicinal species meriting conservation priorities in a "Caatinga" area in the northeastern of Brazilian territory. The ethnobotanical data were collected through semi-structured interviews with key subjects selected through the "snowball" technique. The availability and species conservation priority was verified by relative density, risk of collection, local use and use of diversity in the forest fragment sampled. It was recorded 42 native medicinal plants and conservation priority score was calculated for seven species, including Mimosa tenuiflora, Hymenaea courbaril, Ximenia americana and Amburana cearensis need immediate conservation and attention, since their collection does not occur in a sustainable way. In order to ensure the perpetuation of the species and the sustainability of traditional therapeutic practice there needs to be a development of conservation practices of caatinga remaining to better conserve the species of the biome.

Anti-Desmoglein 1 and 3 Autoantibody Levels in Endemic Pemphigus Foliaceus and Pemphigus Vulgaris from Brazil.

BACKGROUND: Pemphigus is a group of autoimmune blistering diseases of which the major forms are pemphigus foliaceus (PF) and vulgaris (PV). In Brazil, PF occurs in an endemic form also known as fogo selvagem. The main autoantibody in PF is against desmoglein 1 (DSG1), while in PV the main antibody is anti-desmoglein 3 (DSG3), but often anti-DSG1 is also present. The aim of the present study was to analyze the levels of anti-DSG1 and antiDSG3 autoantibodies in Brazilian PF and PV patients, considering different stages of the disease for PF patients and comparing these levels to those of healthy individuals living in and outside the endemic regions. METHODS: Levels of anti-DSG1 and anti-DSG3 were measured in the sera of Brazilian PF (n = 68) and PV (n = 20) patients as well as in clinically healthy (control) individuals (n = 48) by Enzyme Linked Immunosorbent Assay (ELISA). Comparisons were made using Kruskal-Wallis and Mann-Whitney tests. RESULTS: As expected, anti-DSG1 was more prevalent among PF patients (84% against 43% in PV), while antiDSG3 was more prevalent in PV patients (50% against 4% in PF). Levels of anti-DSG1 in PF patients in remission differed from those in patients undergoing active disease (p = 0.003), and patients in long-term remission (more than two years without presenting new lesions) were similar to control individuals living in the endemic region and surrounding area (p = 0.09). Moreover, patients with a more severe form of the disease had higher levels of anti-DSG1 (at least 134 U/mL, mean of 233 U/mL) than patients with a less severe form (fewer lesions) (mean of 193 U/mL, including two negative individuals). CONCLUSIONS: Despite the importance of these antibodies for diagnosis and management purposes, their presence in a healthy individual and in patients under remission indicates that caution should be taken when using anti-DSG for diagnosis, especially in endemic areas.

Long noncoding RNA expression in acute lymphoblastic leukemia: A systematic review.

Long noncoding RNAs (lncRNAs), as gene expression modulators, are potential players in Acute Lymphoblastic Leukemia (ALL) pathogenesis. We systematically explored current literature on lncRNA expression in ALL to identify lncRNAs consistently reported as differentially expressed (DE) either in ALL versus controls or between ALL subtypes. By comparing articles that provided global expression data for DE lncRNAs in the ETV6::RUNX1-positive ALL subtype, we identified four DE lncRNAs in three independent studies (two versus other subtypes and one versus controls), showing concordant expression of LINC01013, CRNDE and lnc-KLF7-1. Additionally, LINC01503 was consistently downregulated on ALL versus controls. Within RT-qPCR studies, twelve lncRNA were DE in more than one source. Thus, several lncRNAs were supported as DE in ALL by multiple sources, highlighting their potential role as candidate biomarkers or therapeutic targets. Finally, as lncRNA annotation is rapidly expanding, standardization of reporting and nomenclature is urgently needed to improve data verifiability and compilation.

Cellular and molecular antiproliferative effects in 2D monolayer and 3D-cultivated HT-29 cells treated with zerumbone.

Zerumbone (ZER) is a phytochemical isolated from plants of the Zingiberaceae family. Numerous studies have demonstrated its diverse pharmacological properties, particularly its potent antitumorigenic activity. This study aimed to assess the antiproliferative effects of ZER on HT-29 cells cultivated in both two-dimensional (2D) monolayer and three-dimensional (3D) spheroid culture systems. The evaluation of growth (size), cell death, and cell cycle arrest in 3D spheroid HT-29 cells was correlated with mRNA expression data. Treatment of 2D cells revealed that ZER exhibited cytotoxicity at concentrations above 30 µM, and an IC50 of 83.54 µM (24-h post-ZER treatment) effectively suppressed cell migration. In the 3D model, ZER induced an increase in spheroid volume over a 72-h period attributed to disaggregation and reconfiguration of characteristic zones. Analysis of cell death demonstrated a significant rise in apoptotic cells after 24 h of ZER treatment, along with cell cycle arrest in the G1 phase. Furthermore, ZER treatment resulted in alterations in mRNA expression, affecting key signaling pathways involved in cell death (BCL2 and BBC3), endoplasmic reticulum stress (ERN1), DNA damage (GADD45A), cell cycle regulation (CDKN1A, NFKB1, MYC, and TP53), and autophagy (BECN1 and SQSTM1). These findings suggested that ZER holds promise as a potential candidate for the development of novel anticancer agents that can modulate crucial cell signaling pathways. Additionally, the use of the 3D culture system proved to be a valuable tool in our investigation.

ORTHOSTATIC SUPPORT IN PARAPLEGIC AND AMPUTEE PATIENTS: A CONTROLLED TRIAL.

Introduction: Functional incapacity caused by physical alterations leads to significant limitations in daily activities and has a major impact on the return of people with disabilities to the social space and the workplace. This calls for an evaluation of the long-term influence of the use of a device specially developed for orthostatic posture on the physiological, biomechanical and functional parameters of amputees and spinal cord patients. Objective: The objective was evaluate the effect of postural support device use on function, pain, and biomechanical and cardiologic parameters in spinal cord injury and amputees patients compared to a control group. Methods: The orthostatic device was used by the participants for a period of ten consecutive days, for three cycles of 50 minutes each day, and a 15-day follow-up. Participants were positioned and stabilized using adjustable straps on the shoulders, trunk, and hips. The primary outcome was brief pain inventory. Fifteen participants were included the control group, 15 in the amputee group, and 15 in the spinal cord group. Results: Our results demonstrate that the use of the device allows the orthostatic position of amputees and spinal cord patients evaluated for ten days, leading to improved functionality and pain in the spinal cord and amputee groups compared to the control group. In addition, no changes were observed for secondary outcomes, indicating that the use of the device did not cause harm interference to patients. Conclusion: The long-term use of the orthostatic device is beneficial for improving functionality, reduce pain in amputees and spinal cord injury patients. Level of evidence II; Therapeutic Studies - Investigating the results of treatment.

Introdução: A incapacidade funcional causada por alterações físicas leva a limitações significativas nas atividades diárias e gera um grande impacto no retorno das pessoas com deficiência ao espaço social e ao local de trabalho, demandando a avaliação da influência em longo prazo do uso de um dispositivo especialmente desenvolvido para a postura ortostática nos parâmetros fisiológicos, biomecânicos e funcionais de pacientes amputados e com medula espinhal. Objetivo: O objetivo foi avaliar o efeito do uso do dispositivo de suporte postural na função, dor e parâmetros biomecânicos e cardiológicos em pacientes com lesão medular e amputados em comparação com um grupo controle. Métodos: O aparelho ortostático foi utilizado pelos participantes por um período de dez dias consecutivos, em três ciclos de 50 minutos diários, com acompanhamento de 15 dias. Os participantes foram posicionados e estabilizados por meio de alças ajustáveis nos ombros, tronco e quadris. O desfecho primário foi o questionário Breve Inventário de Dor. Quinze participantes foram incluídos no grupo controle, 15 no grupo amputado e 15 no grupo medular. Resultados: Nossos resultados demonstram que o uso do dispositivo permite a posição ortostática de amputados e pacientes com lesão medular avaliados por dez dias, levando a melhora da funcionalidade e dor nos grupos de amputados e medula espinhal em relação ao grupo controle. Além disso, não foram observadas alterações nos resultados secundários, indicando que o uso do dispositivo não causou interferência prejudicial aos pacientes. Conclusão: O uso prolongado do dispositivo ortostático é benéfico para melhorar a funcionalidade, reduzir a dor em amputados e pacientes com lesão medular. Nível de Evidência II; Estudos Terapêuticos - Investigação dos resultados de tratamento.

Real-World Evidence to Reinforce Clinical Trial Evidence in Health Technology Assessment: A Critical Review of Real-World Evidence Requirements from Seven Countries and Recommendations to Improve Acceptance.

BACKGROUND: Real-world evidence (RWE) can reinforce clinical trial evidence in health technology assessment (HTA). OBJECTIVES: Review HTA bodies' (HTAbs) requirements for RWE, real uses, and acceptance across seven countries (Brazil, Canada, France, Germany, Italy, Spain, and the United Kingdom) and outline recommendations that may improve acceptance of RWE in efficacy/effectiveness assessments and appraisals processes. METHODS: RWE requirements were summarized based on HTAbs' guidelines. Acceptance by HTAbs was evaluated based on industry experience and case studies. RESULTS: As of June 2022, RWE methodological guidelines were in place in three of the seven countries. HTAbs typically requested analyses based on local data sources, but the preferred study design and data sources differed. HTAbs had individual submission, assessment, and appraisal processes; some allowed early meetings for the protocol and/or results validation, though few involved external experts or medical societies to provide input to assessment and appraisal. The extent of submission, assessment, and appraisal requirements did not necessarily reflect the degree of acceptance. CONCLUSION: All the countries reviewed face common challenges regarding the use of RWE. Our proposals address the need to facilitate collaboration and communication with industry and regulatory agencies and the need for specific guidelines describing RWE design and criteria of acceptance throughout the assessment and appraisal processes.

Regulation of cytokinesis and necroptosis pathways by diosgenin inhibits the proliferation of NCI-H460 lung cancer cells.

Aim Overcoming resistance to apoptosis and antimitotic chemotherapy is crucial for effective treatment of lung cancer. Diosgenin (DG), a promising phytochemical, can regulate various molecular pathways implicated in tumor formation and progression. However, the precise biological activity of DG in lung cancer remains unclear. This study aimed to investigate the antiproliferative activity of DG in NCI-H460 lung carcinoma cells to explore the underlying antimitotic mechanisms and alternative cell death pathways. MATERIALS AND METHODS: In a 2D culture system, we analyzed cell viability, multinucleated cell frequency, cell concentration, cell cycle changes, cell death induction, intracellular reactive oxygen species (ROS) production, and nuclear DNA damage, particularly in relation to target gene expression. We also evaluated the antiproliferative activity of DG in a 3D culture system of spheroids, assessing volume changes, cell death induction, and inhibition of proliferation recovery and clonogenic growth. KEY FINDINGS: DG reduced cell viability and concentration while increasing the frequency of cells with multiple nuclei, particularly binucleated cells resulting from daughter cell fusion. This effect was associated with genes involved in cytokinesis regulation (RAB35, OCRL, BIRC5, and AURKB). Additionally, DG-induced cell death was linked to necroptosis, as evidenced by increased intracellular ROS production and RIPK3, MLKL, TRAF2, and HSPA5 gene expression. In tumor spheroids, DG increased spheroid volume, induced cell death, and inhibited proliferation recovery and clonogenic growth. SIGNIFICANCE: Our study provides new insights into the biological activities of DG in lung cancer cells, contributing to the development of novel oncological therapies.

The Use of Orthostatic Device for 90 Minutes Does Not Change Cardiovascular and Biomechanical Parameters of Patients with Spinal Cord Injury.

Background: Changes in autonomic function are often caused by spinal cord injuries, which lead to limited orthostatic positioning in these patients. Objective: To investigate the cardiovascular and biomechanical parameters during 90 min of postural elevation equipment usage comparing spinal cord injury and healthy subjects. Methods: A device was used that allowed patients with spinal cord injuries to remain in an orthostatic posture for 90 min. During this period, the physiological parameters were measured every 15 min. Cardiovascular parameters (heart rate, oxygen saturation, blood pressure, and autonomic nervous system) and biomechanical parameters of the plantar pressure distribution were evaluated. For blood pressure, heart rate, oxygen saturation, and autonomic nervous system, a two-way analysis of variance was applied. The mixed-effect model was applied to plantar pressure. The significance level was set at p < 0.05 for all statistical analyses. Results: No differences were observed between the groups in systolic blood pressure (F = 0.07), diastolic blood pressure (F = 0.14), heart rate (F = 0.56), and oxygen saturation (F = 0.23) at any of the time intervals throughout the experiment (p > 0.05). No statistical difference was observed in the mean plantar pressure values between the groups (p = 0.35) during the period in which they remained in the orthostatic position. Conclusion: The present study showed the absence of differences between spinal cord injury patients and control participants using the orthostatic device in terms of cardiovascular and biomechanical parameters over 90 min.

Estimations of body fat by anthropometry or bioelectrical impedance differ from those by dual-energy X-ray absorptiometry in prefrail community-dwelling older women.

This study aimed to compare different methods to assess body fat (BF). We hypothesized that bioelectrical impedance analysis (BIA) or anthropometry may be used to estimate BF in prefrail older women, equivalently to dual-energy X-ray absorptiometry (DXA). The cross-sectional study included 72 prefrail community-dwelling older women (71.13 ± 4.65 years old; body mass index [BMI] 28.89 ± 4.23 kg/m2). The BF percentage (%BF) was estimated using anthropometry with the Durnin & Womersley (D&W) and Petroski's predictive equations, BIA with 2 Baumgartner predictive equations (BIA 1 and BIA 2), and DXA. All methods differed significantly from DXA according to assessments using repeated measures ANOVA and pairwise comparisons. The mean %BF varied between 39.99 ± 3.42% (D&W) and 43.93 ±â€¯5.06% (DXA). Multiple regression analysis with age and BMI as covariates showed positive correlations (R2 = 0.91) in models with D&W equation and BMI, and with BIA 2 and BMI; however, BMI explained more of the model (71%) than the equations. Furthermore, Bland-Altman test revealed a proportional bias for D&W and for BIA 2, with underestimation of BF varying across different %BF values. Petroski's skinfold equation showed a positive correlation on linear regression (R2 = 0.74) and no proportional bias; however, Bland-Altman analysis revealed high limits of agreement (-13.6 to -0.05), thus compromising clinical application. To conclude, compared with DXA, all the equations tested showed a high disagreement and wide limits of agreement, restricting their use in clinical practice to estimate the BF in prefrail older women.

Orthostatic support in paraplegic and amputee patients: a controlled trial / Suporte ortostático em paraplégicos e amputados: um ensaio controlado

ABSTRACT Introduction: Functional incapacity caused by physical alterations leads to significant limitations in daily activities and has a major impact on the return of people with disabilities to the social space and the workplace. This calls for an evaluation of the long-term influence of the use of a device specially developed for orthostatic posture on the physiological, biomechanical and functional parameters of amputees and spinal cord patients. Objective: The objective was evaluate the effect of postural support device use on function, pain, and biomechanical and cardiologic parameters in spinal cord injury and amputees patients compared to a control group. Methods: The orthostatic device was used by the participants for a period of ten consecutive days, for three cycles of 50 minutes each day, and a 15-day follow-up. Participants were positioned and stabilized using adjustable straps on the shoulders, trunk, and hips. The primary outcome was brief pain inventory. Fifteen participants were included the control group, 15 in the amputee group, and 15 in the spinal cord group. Results: Our results demonstrate that the use of the device allows the orthostatic position of amputees and spinal cord patients evaluated for ten days, leading to improved functionality and pain in the spinal cord and amputee groups compared to the control group. In addition, no changes were observed for secondary outcomes, indicating that the use of the device did not cause harm interference to patients. Conclusion: The long-term use of the orthostatic device is beneficial for improving functionality, reduce pain in amputees and spinal cord injury patients. Level of evidence II; Therapeutic Studies - Investigating the results of treatment.

RESUMO Introdução: A incapacidade funcional causada por alterações físicas leva a limitações significativas nas atividades diárias e gera um grande impacto no retorno das pessoas com deficiência ao espaço social e ao local de trabalho, demandando a avaliação da influência em longo prazo do uso de um dispositivo especialmente desenvolvido para a postura ortostática nos parâmetros fisiológicos, biomecânicos e funcionais de pacientes amputados e com medula espinhal. Objetivo: O objetivo foi avaliar o efeito do uso do dispositivo de suporte postural na função, dor e parâmetros biomecânicos e cardiológicos em pacientes com lesão medular e amputados em comparação com um grupo controle. Métodos: O aparelho ortostático foi utilizado pelos participantes por um período de dez dias consecutivos, em três ciclos de 50 minutos diários, com acompanhamento de 15 dias. Os participantes foram posicionados e estabilizados por meio de alças ajustáveis nos ombros, tronco e quadris. O desfecho primário foi o questionário Breve Inventário de Dor. Quinze participantes foram incluídos no grupo controle, 15 no grupo amputado e 15 no grupo medular. Resultados: Nossos resultados demonstram que o uso do dispositivo permite a posição ortostática de amputados e pacientes com lesão medular avaliados por dez dias, levando a melhora da funcionalidade e dor nos grupos de amputados e medula espinhal em relação ao grupo controle. Além disso, não foram observadas alterações nos resultados secundários, indicando que o uso do dispositivo não causou interferência prejudicial aos pacientes. Conclusão: O uso prolongado do dispositivo ortostático é benéfico para melhorar a funcionalidade, reduzir a dor em amputados e pacientes com lesão medular. Nível de Evidência II; Estudos Terapêuticos - Investigação dos resultados de tratamento.

Pressure pain threshold in people with amputation submitted to the use of postural lifting equipment: crossover experimental study / Limiar de dor por pressão em pessoas com amputação submetidas ao uso de equipamento de elevação postural: um estudo experimental cruzado

ABSTRACT BACKGROUND AND OBJECTIVES: Amputation is an event that has consequences that can affect daily life, including pain, enhancing changes, whether in sleep or in quality of life. The objective of this study was to evaluate the pressure pain threshold (PPT) in people with amputations submitted to the use of different postural elevation equipment. METHODS: Experimental crossover study, carried out from September to October 2022, with people with lower limb amputation (n=15) and people without amputation (n=15). PPT in four regions (T12-L1, L5-S1, anterior tuberosity of the tibia and calcaneus) were evaluated before and after the use of different versions (A and B) of an equipment for postural elevation, gravity and pain interference. Presence of signs and symptoms of central sensitization (CS) and sleep quality. RESULTS: The groups did not present PPT alterations when compared between the different versions of the equipment (p<0.05) in the four locations analyzed. Furthermore, the groups did not show differences in relation to the evaluation days or among themselves regarding the severity and interference of pain and the presence of signs and symptoms of CS. The control group indicated poor sleep quality (p=0.0173) and remained worse than people with amputation. CONCLUSION: The versions of the equipment did not change PPT in the analyzed areas. The groups did not differ between themselves, suggesting that the equipment promoted similar responses, that is, no change in sensitivity was evidenced in the analyzed regions which have greater contact with stabilization elements and weight discharge of the equipment.

RESUMO JUSTIFICATIVA E OBJETIVOS: A amputação é um evento que acarreta consequências que podem afetar o cotidiano, entre elas a dor, potencializando alterações, seja no sono ou na qualidade de vida. O objetivo deste estudo foi avaliar o limiar de dor por pressão (LDP) em pessoas com amputação submetidas ao uso de diferentes equipamentos de elevação postural. MÉTODOS: Estudo experimental cruzado, realizado de setembro a outubro de 2022, com pessoas com amputação no membro inferior (n=15) e pessoas sem amputação (n=15). Foram avaliados o LDP em quatro regiões (T12-L1, L5-S1, tuberosidade anterior da tíbia e calcâneo) pré e pós uso de distintas versões (A e B) de um equipamento de elevação postural, gravidade e interferência da dor. Presença de sinais e sintomas de sensibilização central (SC) e qualidade do sono. RESULTADOS: Os grupos não apresentaram alterações no LDP quando comparados em relação às diferentes versões do equipamento (p<0,05) nos quatro locais analisados. Além disso, os grupos não mostraram diferenças em relação aos dias de avaliação ou entre si quanto a severidade e interferência de dor e presença de sinais e sintomas de SC. O grupo controle indicou uma qualidade de sono ruim (p=0,0173) e manteve-se pior que as pessoas com amputação. CONCLUSÃO: As versões do equipamento não alteraram o LDP nas áreas analisadas. Os grupos não apresentaram diferença entre si, sugerindo que o equipamento promoveu respostas semelhantes, ou seja, não foi evidenciada uma alteração de sensibilidade nas regiões que possuem maior contato com elementos de estabilização e descarga de peso dos equipamentos.

Modulation of brain waves in spinal cord injury patients with pain: cross-sectional analysis / Modulação de ondas cerebrais em pacientes com lesão medular e dor: uma análise transversal / Modulación de ondas cerebrales en pacientes con lesión de médula espinal y dolor: un análisis transversal

ABSTRACT: Objective: This study aimed to describe the encephalographic electrical rhythm pattern of the Alpha wave in patients with traumatic spinal cord injury in the thoracic spine. Methodology: This is a cross-sectional observational study conducted from January to March 2022. A total of 20 patients with traumatic spinal cord injury were included in the study and divided into two groups, with pain symptoms and without pain symptoms. Both groups were submitted for evaluation for population characterization, identification of the presence of pain and the possible presence of signs and symptoms of central sensitization and quantitative electroencephalographic examination. Results: Comparing them, it was possible to observe a reduction of 38.7% (2.69µV; 95%CI 1.28 to 4.09) in the Alpha 2 wave (10-12 Hz) in the group with pain symptoms. This alteration was identified in the parietal lobe, mainly in PZ. Conclusion: We observed a selective reduction of Alpha 2 waves, mainly in the parietal region (PZ), in spinal cord injury patients with pain compared to spinal cord injury patients without pain. Level of Evidence III; Diagnostic Studies.

RESUMO: Objetivo: O objetivo deste estudo foi descrever o padrão do ritmo eletroencefalográfico da onda Alfa em pacientes com lesão medular traumática na coluna torácica. Metodologia: Trata-se de um estudo observacional transversal, realizado no período de janeiro a março de 2022. No total 20 pacientes com lesão medular traumática foram incluídos no estudo e divididos em dois grupos, com sintomas de dor e sem sintomas de dor. Ambos os grupos foram submetidos a avaliação para caracterização populacional, identificação de presença de dor e possível presença de sinais e sintomas de sensibilização central e ao exame Eletroencefalográfico quantitativo. Resultados: Ao compará-los foi possível constatar uma redução de 38,7% (2.69µV; 95%IC 1,28 to 4.09) da onda Alfa 2 (10-12 Hz) do grupo com sintomas de dor. Essa alteração foi identificada no lobo parietal, principalmente em PZ. Conclusão: Observamos uma redução seletiva de ondas Alfa 2, principalmente na região parietal (PZ), em pacientes com lesão medular com dor em relação aos pacientes lesão medular sem dor. Nível de Evidência III; Estudo diagnóstico.

RESUMEN: Objetivo: El objetivo de este estudio fue describir el patrón del ritmo electroencefalográfico de la onda Alfa en pacientes con lesión medular traumática en la columna torácica. Metodología: Se trata de un estudio observacional transversal realizado entre enero y marzo de 2022. En total, se incluyeron 20 pacientes con lesión medular traumática en el estudio, divididos en dos grupos, uno con síntomas de dolor y otro sin síntomas de dolor. Ambos grupos fueron sometidos a evaluación para caracterización poblacional, identificación de presencia de dolor y posible presencia de signos y síntomas de sensibilización central, así como al examen electroencefalográfico cuantitativo. Resultados: Al compararlos, se pudo constatar una reducción del 38,7% (2,69 µV; IC del 95%: 1,28 a 4,09) en la onda Alfa 2 (10-12 Hz) del grupo con síntomas de dolor. Esta alteración se identificó en el lóbulo parietal, principalmente en PZ. Conclusión: Observamos una reducción selectiva de las ondas Alfa 2, principalmente en la región parietal (PZ), en pacientes con lesión medular y dolor en comparación con pacientes con lesión medular sin dolor. Nivel de Evidencia III; Estudios de diagnósticos.

Immediate effect of an orthostatic device in amputees who practice physical activity / Efecto inmediato de un dispositivo ortostático en amputados que practican actividad física / Efeito imediato de um dispositivo ortostático em amputados praticantes de atividade física

ABSTRACT Introduction: Lower limb amputation affects mainly economically active young adults, causing great socio-economic impact due to impaired work capacity, socialization, and quality of life. Thus, the use of orthostatic devices could make reintegration of the individual back into the work environment possible. Objective: To evaluate the immediate effect of using a postural elevation device on physiological parameters and plantar pressure levels in amputees who practice physical activity. Methods: Sociodemographic and perceived sleep quality data were collected from 14 adults of both sexes with lower limb amputations, who practice physical activity. The participants were placed in postural elevation equipment for a period of 90 minutes with monitoring of physiological parameters such as blood pressure, heart rate, and oxygen saturation. Parameters related to the autonomic nervous system and plantar pressure levels were also evaluated. Data were also collected during recovery at 15- and 30-minute intervals after using the device. Data analysis was performed using two-way ANOVA or a mixed-effects model with Sidak's multiple comparisons test. Results: For all cardiovascular parameters (p>0.05) analyzed, the activation level of the autonomic nervous system (p>0.05), and plantar pressure (p>0.05), no evidence of differences was observed during use of the orthostatic device in all evaluated periods. Conclusion: The use of postural elevation equipment for 90 minutes does not generate, as an immediate effect, changes in physiological parameters and postural control in amputees who practice physical activity. Level of evidence II; Therapeutic studies - investigation of treatment results. Clinical relevance statement .

RESUMEN Introducción: La amputación de miembros inferiores afecta mayoritariamente a jóvenes adultos económicamente activos, lo que provoca un gran impacto socioeconómico debido al compromiso de la capacidad laboral, la socialización y la calidad de vida. Así, el uso de dispositivos ortostáticos permitiría la reinserción del individuo en el entorno laboral. Objetivo: Evaluar el efecto inmediato del uso de un dispositivo de elevación postural en los parámetros fisiológicos y en los niveles de presión plantar de amputados que practican actividad física. Métodos: Se recogieron datos sociodemográficos y la percepción de la calidad del sueño de 14 adultos de ambos sexos con amputaciones de miembros inferiores, practicantes de actividad física. Los participantes fueron colocados en equipos de elevación postural durante 90 minutos con monitoreo de parámetros fisiológicos como presión arterial, frecuencia cardíaca, saturación y sistema nervioso autónomo, además de los niveles de presión plantar. También se recopilaron datos durante la recuperación a intervalos de 15 y 30 minutos después de usar el dispositivo. El análisis de datos se realizó mediante ANOVA two-way o un modelo de efectos mixtos con la prueba de comparaciones múltiples de Sidak, p < 0,05. Resultados: Para todos los parámetros cardiovasculares (p> 0,05) analizados, el nivel de activación del sistema nervioso autónomo (p> 0,05) y la presión plantar (p> 0,05), no se observaron diferencias a lo largo del uso del dispositivo ortostático en todos los períodos evaluados. Conclusión: El uso del equipo de elevación postural durante 90 minutos no genera, como efecto inmediato, cambios en los parámetros fisiológicos y en el control postural de los amputados que practican actividades físicas. Nivel de evidencia II; Estudios terapéuticos: investigación de los resultados de los tratamientos. Declaración de relevancia clínica .

RESUMO Introdução: A amputação de membros inferiores afeta em sua maioria adultos jovens economicamente ativos, o que ocasiona grande impacto socioeconômico devido ao comprometimento da capacidade laboral, socialização e qualidade de vida. Desta forma, as utilizações de dispositivos ortostáticos possibilitariam a reinserção do indivíduo no ambiente de trabalho. Objetivo: Avaliar o efeito imediato da utilização de um dispositivo de elevação postural nos parâmetros fisiológicos e nos níveis da pressão plantar de amputados praticantes de atividade física. Métodos: Foram coletados os dados sociodemográficos e a percepção da qualidade do sono de 14 adultos de ambos os sexos com amputações de membro inferior que praticam atividade física. Os participantes foram colocados em um equipamento de elevação postural durante 90 minutos com monitorização dos parâmetros fisiológicos como pressão arterial, frequência cardíaca, saturação e sistema nervoso autônomo, além dos níveis da pressão plantar. Os dados também foram coletados durante a recuperação (15 e 30 minutos depois do uso do dispositivo). A análise dos dados foi realizada pela ANOVA two-way ou modelo de efeitos mistos com teste de comparações múltiplas de Sidak, p < 0,05. Resultados: Para todos os parâmetros cardiovasculares (p > 0,05) analisados, nível de ativação sistema nervoso autônomo (p > 0,05) e pressão plantar (p > 0,05) não foram observadas diferenças ao longo do uso do dispositivo ortostático em todos os períodos avaliados. Conclusão: A utilização do equipamento de elevação postural por 90 minutos não gera como efeito imediato, alterações nos parâmetros fisiológicos e no controle postural de amputados praticantes de atividade física. Nível de evidência II; Estudos terapêuticos: investigação dos resultados dos tratamentos Declaração de relevância clínica.

Analysis of the Variability of Therapeutic Indications of Medicinal Species in the Northeast of Brazil: Comparative Study.

ETHNOPHARMACOLOGICAL RELEVANCE: This study aims to evaluate the versatility of these species and their agreement of use and/or the informants' knowledge and verify the variability of the information on the indicated medicinal species in comparison to other species from northeastern Brazilian areas. MATERIALS AND METHODS: Ethnobotanical information was acquired through interviews with 23 residents of the Quincuncá community, northeastern Brazil. From the obtained data, a comparative analysis of the therapeutic indications with other 40 areas in different biomes was conducted. For that, the relative importance index and informant consensus factor were calculated and compared to other indices evaluated in the literature. RESULTS: A total of 39 medicinal species were cited and twenty-six species showed similarities among their therapeutic indications; however, species as Geoffroea spinosa, Lantana camara, and others can be highlighted, present in community disease indications that were not verified for other areas. Myracrodruon urundeuva, Mimosa tenuiflora, Stryphnodendron rotundifolium, and Amburana cearensis had the greatest versatility. In the Quincuncá community, medicinal species were indicated for 49 diseases, which were grouped into 15 categories of body systems. CONCLUSION: This study shows the presented divergence in relation to their therapeutic use; in this point, these divergences reinforce the importance of pharmacological research.

Vacinas COVID-19 e suas implicações imunológicas: uma revisão de literatura / COVID-19 vaccines and immunological implications: A literature review

A COVID-19 e seus mecanismos imunológicos são, atualmente, temas de grande relevância mundial. Suas manifestações clínicas e as perigosas complicações decorrentes da tempestade de citocinas motivaram a criação de vacinas contra o SARS-CoV-2 em um ritmo acelerado, gerando desconfianças e diferentes níveis de eficácia e segurança. Este estudo trata-se de um artigo de revisão que abordou pesquisas publicadas no período de 2020 e 2021, utilizando as bibliotecas eletrônicas SciELO (Scientific Electronic Library Online), PubMed, LILACS (Literatura Latino-Americana e do Caribe em Ciências da Saúde) e MEDLINE com o rastreamento específico por meio dos seguintes descritores: vacinas COVID-19, SARS-CoV-2, imunologia do COVID-19. Questões como o mecanismo imunológico, eficácia e efeitos adversos das vacinas disponíveis no mercado mundial atual foram amplamente discutidas.

COVID-19 and immunological mechanisms currently are topics of great worldwide relevance. Clinical manifestations and the dangerous complications resulting from a cytokine storm motivated the creation of vaccines against SARS-CoV-2 at an accelerated pace, generating suspicions and different levels of efficacy and safety. This is a review article addressing research published in 2020 and 2021. The electronic libraries SciELO (Scientific Electronic Library Online), PubMed, LILACS (Latin American and Caribbean Literature in Health Sciences), and MEDLINE were used for specific screening with the following descriptors: COVID- 19 vaccines, SARS-CoV-2, immunology of COVID-19. Issues such as the immunological mechanism, efficacy, and adverse effects of vaccines currently available on the world market are widely discussed.

Plant species as a therapeutic resource in areas of the savanna in the state of Pernambuco, Northeast Brazil.

ETHNOPHARMACOLOGICAL RELEVANCE: Ethnobotanical studies have contributed significantly in research of plants with therapeutic potential. The aim of the present study was to learn about the use of native medicinal plants cited by the traditional population in "cerradão" (savanna woodland) areas in Northeast Brazil, providing data on therapeutic indications of the species used and their versatility. MATERIALS AND METHODS: Semi-structured interviews were conducted on the basis of a standardized questionnaire designed for key informants selected using the "snowball" technique. The selection of plants species with therapeutic potential was performed on the basis of the relative importance (RI) and informant consensus fator (ICF). RESULTS: A total of 78 species were indicated for 87 therapeutic purposes. Of these, 11 species presented great versatility of use (RI>1), as e.g.including Copaifera langsdorffii Desf., Hybanthus calceolaria (Mart.) Plumel., Heliotropium cf. indicum L., Croton zehntneri, Croton heliotropiifolius, Myracrodruon urundeuva, Stryphnodendro rotundifolium. Medicinal uses could be generalized Pax & K. Hoffm and Hymenaea courbaril L. The therapeutic indications were grouped into 14 use 15 categories with 594 species-category combinations. The largest number of medicinal species was indicated for illnesses or undefined pain, followed by diseases associated with respiratory, digestive and genitourinaryof body systems. The factor informant consensus highlighted the agreement in the use of plants and showed that the, of which Diseases of the Nervous System and, Diseases of the Circulatory System had the greatest agreement 1.0 and 0.87 repectively, Disorders of the Visual Sensory System - Eyes and Respiratory System Disorder showed the highest agreement of use. CONCLUSIONS: Most of the species cited by the key informants are well known scientifically, but it is interesting that some have been studied little or not all with regard to confirming their purported medicinal properties and can contribute substantially to pharmacological and phytochemical investigations in the search for new drugs.