Descriptive study of perineuronal net in enteric nervous system of humans and mice.

Perineuronal nets (PNN) are highly specialized structures of the extracellular matrix around specific groups of neurons in the central nervous system (CNS). They play functions related to optimizing physiological processes and protection neurons against harmful stimuli. Traditionally, their existence was only described in the CNS. However, there was no description of the presence and composition of PNN in the enteric nervous system (ENS) until now. Thus, our aim was to demonstrate the presence and characterize the components of the PNN in the enteric nervous system. Samples of intestinal tissue from mice and humans were analyzed by RT-PCR and immunofluorescence assays. We used a marker (Wisteria floribunda agglutinin) considered as standard for detecting the presence of PNN in the CNS and antibodies for labeling members of the four main PNN-related protein families in the CNS. Our results demonstrated the presence of components of PNN in the ENS of both species; however its molecular composition is species-specific.

Somatosensory alterations after single-unit dental implant immediate loading: A 1-year follow-up study.

OBJECTIVE: This cohort study aimed to assess the incidence of somatosensory alterations after implant surgery using standardized quantitative and qualitative sensory testing. METHODS: 33 participants with single-tooth loss, undergoing immediate implant loading were included. Quantitative Sensory Testing (QST) and Qualitative Sensory Testing (QualST) were conducted at eight time points over a year (baseline to 1 year). Two-Way Repeated Measures ANOVA and post hoc Tukey test were used on QST values and Cochran Q test on QualST. RESULTS: The study revealed significant increase in thermal thresholds overtime. At the operated side, overall Cold Pain Threshold (extraoral: p = 0.030; intraoral: p < 0.001), and Cold Detection Threshold (intraoral: p < 0.001) increased overtime. In contralateral region, maxilla Cold Detection Threshold (extraoral: p = 0.024; intraoral: p = 0.031), Warm Detection Threshold (extraoral: p = 0.026; intraoral: p = 0.047) and overall Cold Pain Threshold (extraoral and intraoral: p < 0.001) also increased. QualST showed extraoral pinprick (p = 0.032) and intraoral pinprick (p = 0.000), cold (p = 0.000) and touch (p = 0.002) stimuli abnormalities overtime. CONCLUSIONS: Somatosensory alterations after implant surgery were detected in both quantitative and qualitative sensory assessments, but rapidly decreased during the first follow-ups, and then continuously until 1-year. CLINICAL SIGNIFICANCE: This study provides clinical and controlled evidence on the real effect of the somatosensory alterations overtime, leading to a better understanding of neurosensory behaviour after single-tooth dental implant rehabilitation.

Acute toxicity and genotoxicity of Schinus molle L. aqueous extract/ethanol-soluble fraction in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Schinus molle L. is a medicinal species belonging to the Anacardiaceae family. It is commonly referred to as "aroeira" and its leaves and roots are utilized for treating different pathological conditions. However, despite its widespread use in traditional medicine, there is a lack of in-depth toxicological studies. AIM: To evaluate the acute toxicity and genotoxicity of S. molle aqueous extract/ethanol-soluble fraction in rats. MATERIAL AND METHODS: First, a purified aqueous extract was obtained from the leaves of S. mole through infusion (referred to as EESM) and its compounds were identified using LC-DAD-MS data. Female rats were then subjected to acute oral toxicity tests using doses of 5, 50, 300, and 2000 mg/kg of ESSM. Studies on genetic material, including the micronucleus test and comet assay, were conducted on male and female Wistar rats using the same doses as in the acute toxicity test. For both assays, ESSM was administered orally. RESULTS: The main metabolites annotated from ESSM were dimeric proanthocyanidins, phenylpropanoids acids, flavan-3-ols, simple organic acids (C6-C1), a flavonol di-O-glycosylated (rutin), and O-glycosylated megastigmane. The ESSM did not exhibit any acute toxic effects, such as changes in biochemical, hematologic, or histopathological analysis. Furthermore, no changes were observed in comet assay or micronucleus tests when rats were given doses of 5, 50, 300, or 2000 mg/kg of ESSM. CONCLUSION: The results showed that the ESSM does not induce acute toxicity or exhibit genotoxicity up to a dose of 2000 mg/kg.

Effect of transcranial direct current stimulation and transcranial magnetic stimulation on the cognitive function of individuals with Alzheimer's disease: a systematic review with meta-analysis and meta-regression.

OBJECTIVE: To analyze the effects of transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) on the cognitive function of individuals with Alzheimer's disease (AD). METHODS: This systematic review with meta-analysis and meta-regression included randomized clinical trials published until 05/2022. We included studies conducted with individuals with AD of both sexes, aged between 55 and 85 years, treated with tDCS, TMS, or both. RESULTS: Twenty-one studies were included in the systematic review and sixteen in the meta-analysis. Meta-regression suggested a significant influence of anodic tDCS with current intensity of 1.5 mA on cognitive function. Significant results were found with treatment frequencies of three and five days a week for two weeks. Subgroup analysis found that anodic tDCS influences cognitive function, regardless of AD stage. Similar was observed for TMS using a frequency of 20 Hz and current intensity of 90% of the resting motor threshold. DISCUSSION: Anodal tDCS and 20 Hz TMS have demonstrated the ability to improve cognitive function in AD by modulating neural activity. These therapies are safe and well-tolerated, offering promise as adjuncts to available pharmacological treatments. Studies with greater methodological rigor and parameter standardization are warranted. Comprehensive investigations involving neuroimaging techniques may provide a better understanding of the interaction between induced electrical fields and the complex neural networks affected in AD, paving the way for more personalized and effective neurostimulation approaches.

Perineuronal net in the extrinsic innervation of the distal colon of mice and its remodeling in ulcerative colitis.

The perineuronal net (PNN) is a well-described highly specialized extracellular matrix structure found in the central nervous system. Thus far, no reports of its presence or connection to pathological processes have been described in the peripheral nervous system. Our study demonstrates the presence of a PNN in the spinal afferent innervation of the distal colon of mice and characterizes structural and morphological alterations induced in an ulcerative colitis (UC) model. C57Bl/6 mice were given 3% dextran sulfate sodium (DSS) to induce acute or chronic UC. L6/S1 dorsal root ganglia (DRG) were collected. PNNs were labeled using fluorescein-conjugated Wisteria Floribunda (WFA) l lectin, and calcitonin gene-related peptide (CGRP) immunofluorescence was used to detect DRG neurons. Most DRG cell bodies and their extensions toward peripheral nerves were found surrounded by the PNN-like structure (WFA+), labeling neurons' cytoplasm and the pericellular surfaces. The amount of WFA+ neuronal cell bodies was increased in both acute and chronic UC, and the PNN-like structure around cell bodies was thicker in UC groups. In conclusion, a PNN-like structure around DRG neuronal cell bodies was described and found modulated by UC, as changes in quantity, morphology, and expression profile of the PNN were detected, suggesting a potential role in sensory neuron peripheral sensitization, possibly modulating the pain profile of ulcerative colitis.

Investigations on the morpho-anatomy and histochemistry of Aconitum napellus L.

Aconitum napellus L. is a popular medicinal plant extensively used in homeopathy. This article provides detailed morphology and microscopy, including the anatomical and histochemical features of the herb, to aid authentication and quality control. In cross-section, the root in secondary growth shows the phloem surrounded by pericyclic fibers and a well-developed xylem. The stem is irregular in outline, displaying unicellular trichomes and many free collateral vascular bundles encircling the pith. The leaf is dorsiventral, hypostomatic with anomocytic and anisocytic stomata, and shows non-glandular trichomes. The floral parts are characterized by uniseriate epidermises, homogeneous mesophyll, anomocytic stomata on the abaxial surface, trichomes, and oval pollen grains. The tissue fragments in powdered herbs show these characteristics and have numerous starch grains with thimble-shaped, linear or star-shaped hilum. The detailed macroscopic and microscopic analysis provided in this study can help in the authentication and quality control of A. napellus raw materials. RESEARCH HIGHLIGHTS: Key anatomical, micromorphological, and microchemical features of Aconitum napellus are described. The results of the study can support the taxonomy of the genus Aconitum. Morphological standardization of the species reported here is helpful in the quality control of this herb.

Membrane-derived particles shed by PSMA-positive cells function as pro-angiogenic stimuli in tumors.

Cell membrane-derived particles (Mp) are rounded membrane-enclosed particles that are shed from tumor cells. Mp are formed from tumor membranes and are capable of tumor targeting and immunotherapeutic agents because they share membrane homology with parental cells; thus, they are under consideration as a drug delivery vehicle. Prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein with enzymatic functionality, is highly expressed in Mp and extracellular vesicles (EV) from prostate cancer (PCa) with poor clinical prognosis. Although PSMA expression was previously shown in EV and Mp isolated from cell lines and from the blood of patients with high-grade PCa, no pathophysiological effects have been linked to PCa-derived Mp. Here, we compared Mp from PSMA-expressing (PSMA-Mp) and PSMA-non-expressing (WT-Mp) cells side by side in vitro and in vivo. PSMA-Mp can transfer PSMA and new phenotypic characteristics to the tumor microenvironment. The consequence of PSMA transfer to cells and increased secretion of vascular endothelial growth factor-A (VEGF-A), pro-angiogenic and pro-lymphangiogenic mediators, with increased 4E binding protein 1 (4EBP-1) phosphorylation.

Vascularized tumor on a microfluidic chip to study mechanisms promoting tumor neovascularization and vascular targeted therapies.

The cascade of events leading to tumor formation includes induction of a tumor supporting neovasculature as a primary hallmark of cancer. Developing vasculature is difficult to evaluate in vivo but can be captured using microfluidic chip technology and patient derived cells. Herein, we established an on chip approach to investigate the mechanisms promoting tumor vascularization and vascular targeted therapies via co-culture of metastatic renal cell carcinoma spheroids and endothelial cells in a 3D environment. Our model permitted real-time, high-resolution observation and assessment of tumor-induced angiogenesis, where endothelial cells sprout towards the tumor and mimic a vascular network. Bevacizumab, an angiogenic inhibitor, disrupted interactions between vessels and tumors, destroying the vascular network. The on chip approach enabled assessment of endothelial cell biology, vessel's functionality, drug delivery, and molecular expression of PSMA. Finally, observations in the vascularized tumor on chip permitted direct and conclusive quantification of this therapy in weeks as opposed to months in a comparable animal model. Teaser: Vascularized tumor on microfluidic chip provides opportunity to study targeted therapies and improves preclinical drug discovery.

99mTc-HYNIC/Cy7-Fab(Bevacizumab): su empleo como agente de imagen en mieloma múltiple / 99mTc-HYNIC/Cy7-Fab(Bevacizumab): its use as an imaging agent in Multiple Myeloma / 99mTc-HYNIC/Cy7-Fab (Bevacizumab): seu uso como agente de imagem em mieloma múltiplo

Introducción: el mieloma múltiple es un trastorno hematológico maligno y el segundo cáncer de la sangre más frecuente. El proceso de la angiogénesis tumoral es fundamental para el crecimiento y metástasis de muchos tipos de tumores, incluido en mieloma múltiple. Se sabe que la sobreexpresión del factor de crecimiento endothelial vascular se encuentra asociado a un mal pronóstico en esta patología, representando un blanco clave para la terapia anti-angiogénica en mieloma múltiple. El anticuerpo monoclonal Bevacizumab es capaz de unirse con gran afinidad al factor de crecimiento endothelial vascular bloqueando su acción. Objetivo: evaluar el Fab(Bevacizumab) marcado con 99mTc o Cy7 como potenciales agentes de imagen moleculares de la expresión de factor de crecimiento endothelial vascular en mieloma múltiple. Material y métodos: la expresión de factor de crecimiento endothelial vascular fue analizada mediante citometría de flujo en la línea celular huaman de mieloma múltiple, la MM1S. Fab(Bevacizumab) fue producido mediante digestión de Bevacizumab con papaína, conjugado a NHS-HYNIC-Tfa y radiomarcado con 99mTc. Se realizaron estudios de biodistribución y de tomografía computarizada por emisión del fotón simple. A su vez, Fab(Bevacizumab) fue marcado con Cy7 para obtener imágenes de fluorescencia in vivo hasta 96 horas. Resultados: el análisis por citometría de flujo en la línea celular MM1S reveló que la expresión de factor de crecimiento endothelial vascular es predominantemente intracelular. Los estudios de biodistribución y SPECT/CT del complejo 99mTc-HYNIC-Fab(Bevacizumab) mostraron una rápida eliminación sanguínea y una significativa captación a nivel renal y tumoral. Las imágenes por fluorescencia empleando Cy7-Fab(Bevacizumab) permitieron la visualización tumoral hasta 96 h p.i. Conclusiones: logramos visualizar la expresión de factor de crecimiento endothelial vascular in vivo en mieloma múltiple mediante el empleo del fragmento Fab del anticuerpo anti-VEGF (Bevacizumab) marcado con 99mTc y Cy7. Estos nuevos agentes de imagen molecular podrían ser empleados potencialmente en el ámbito clínico para la estadificación y el seguimiento de pacientes con mieloma múltiple, mediante la visualización radioactiva in vivo de la expresión de factor de crecimiento endothelial vascular en todo el cuerpo. La imagen óptica de estos trazadores mejoraría el muestreo tumoral y podría guiar la extirpación quirúrgica.

Introduction: Multiple myeloma is a hematologic malignancy and the second most common blood cancer. The process of tumor angiogenesis is central to the growth and metastasis of many types of tumors, including multiple myeloma. Overexpression of vascular endothelial growth factor is known to be associated with poor prognosis in this pathology, representing a key target for anti-angiogenic therapy in multiple myeloma. The monoclonal antibody Bevacizumab is able to bind with high affinity to vascular endothelial growth factor blocking its action. Objective: to evaluate 99mTc- or Cy7-labeled Fab(Bevacizumab) as potential molecular imaging agents of vascular endothelial growth factor expression in multiple myeloma. Methods: Vascular endothelial growth factor expression was analyzed by flow cytometry in the multiple myeloma huaman cell line, MM1S. Fab(Bevacizumab) was produced by digestion of Bevacizumab with papain, conjugated to NHS-HYNIC-Tfa and radiolabeled with 99mTc. Biodistribution and single photon emission computed tomography studies were performed. In turn, Fab(Bevacizumab) was labeled with Cy7 to obtain in vivo fluorescence images up to 96 hours. Results: Flow cytometry analysis in the MM1S cell line revealed that vascular endothelial growth factor expression is predominantly intracellular. Biodistribution and SPECT/CT studies of the 99mTc-HYNIC-Fab(Bevacizumab) complex showed rapid blood clearance and significant renal and tumor uptake. Fluorescence imaging using Cy7-Fab(Bevacizumab) allowed tumor visualization up to 96 h p.i. Conclusions: we were able to visualize vascular endothelial growth factor expression in vivo in multiple myeloma using the Fab fragment of the anti-VEGF antibody (Bevacizumab) labeled with 99mTc and Cy7. These new molecular imaging agents could potentially be employed in the clinical setting for staging and monitoring of patients with multiple myeloma by in vivo radioactive visualization of vascular endothelial growth factor expression throughout the body. Optical imaging of these tracers would improve tumor sampling and could guide surgical excision.

Introdução: O mieloma múltiplo é uma malignidade hematológica e o segundo câncer de sangue mais comum. O processo de angiogênese tumoral é fundamental para o crescimento e a metástase de muitos tipos de tumores, incluindo o mieloma múltiplo. Sabe-se que a superexpressão do fator de crescimento endotelial vascular está associada a um prognóstico ruim no mieloma múltiplo, representando um alvo importante para a terapia antiangiogênica no mieloma múltiplo. O anticorpo monoclonal Bevacizumab é capaz de se ligar com alta afinidade ao fator de crescimento endotelial vascular e bloquear sua ação. Objetivo: avaliar o Fab(Bevacizumab) marcado com 99mTc ou Cy7 como possíveis agentes de imagem molecular da expressão do fator de crescimento endotelial vascular no mieloma múltiplo. Métodos: A expressão do fator de crescimento endotelial vascular foi analisada por citometria de fluxo na linha celular de mieloma múltiplo MM1S. O Fab(Bevacizumab) foi produzido pela digestão do Bevacizumab com papaína, conjugado com NHS-HYNIC-Tfa e radiomarcado com 99mTc. Foram realizados estudos de biodistribuição e tomografia computadorizada por emissão de fóton único. Por sua vez, o Fab(Bevacizumab) foi marcado com Cy7 para geração de imagens de fluorescência in vivo por até 96 horas. Resultados: A análise de citometria de fluxo na linha celular MM1S revelou que a expressão do fator de crescimento endotelial vascular é predominantemente intracelular. Os estudos de biodistribuição e SPECT/CT do complexo 99mTc-HYNIC-Fab(Bevacizumab) mostraram uma rápida depuração sanguínea e uma captação renal e tumoral significativa. A imagem de fluorescência usando Cy7-Fab(Bevacizumab) permitiu a visualização do tumor até 96 horas p.i. Conclusões: Conseguimos visualizar a expressão do fator de crescimento endotelial vascular in vivo no mieloma múltiplo usando o fragmento Fab do anticorpo anti-VEGF (Bevacizumab) marcado com 99mTc e Cy7. Esses novos agentes de imagem molecular poderiam ser usados no cenário clínico para o estadiamento e o monitoramento de pacientes com mieloma múltiplo, visualizando radioativamente a expressão do fator de crescimento endotelial vascular in vivo em todo o corpo. A geração de imagens ópticas desses traçadores melhoraria a amostragem do tumor e poderia orientar a excisão cirúrgica.

Poison cassette exon splicing of SRSF6 regulates nuclear speckle dispersal and the response to hypoxia.

Hypoxia induces massive changes in alternative splicing (AS) to adapt cells to the lack of oxygen. Here, we identify the splicing factor SRSF6 as a key factor in the AS response to hypoxia. The SRSF6 level is strongly reduced in acute hypoxia, which serves a dual purpose: it allows for exon skipping and triggers the dispersal of nuclear speckles. Our data suggest that cells use dispersal of nuclear speckles to reprogram their gene expression during hypoxic adaptation and that SRSF6 plays an important role in cohesion of nuclear speckles. Down-regulation of SRSF6 is achieved through inclusion of a poison cassette exon (PCE) promoted by SRSF4. Removing the PCE 3' splice site using CRISPR/Cas9 abolishes SRSF6 reduction in hypoxia. Aberrantly high SRSF6 levels in hypoxia attenuate hypoxia-mediated AS and impair dispersal of nuclear speckles. As a consequence, proliferation and genomic instability are increased, while the stress response is suppressed. The SRSF4-PCE-SRSF6 hypoxia axis is active in different cancer types, and high SRSF6 expression in hypoxic tumors correlates with a poor prognosis. We propose that the ultra-conserved PCE of SRSF6 acts as a tumor suppressor and that its inclusion in hypoxia is crucial to reduce SRSF6 levels. This may prevent tumor cells from entering the metastatic route of hypoxia adaptation.

Are the EEG microstates correlated with motor and non-motor parameters in patients with Parkinson's disease?

OBJECTIVES: This study compared electroencephalography microstates (EEG-MS) of patients with Parkinson's disease (PD) to healthy controls and correlated EEG-MS with motor and non-motor aspects of PD. METHODS: This cross-sectional exploratory study was conducted with patients with PD (n = 10) and healthy controls (n = 10) matched by sex and age. We recorded EEG-MS using 32 channels during eyes-closed and eyes-open conditions and analyzed the four classic EEG-MS maps (A, B, C, D). Clinical information (e.g., disease duration, medications, levodopa equivalent daily dose), motor (Movement Disorder Society - Unified Parkinson Disease Rating Scale II and III, Timed Up and Go simple and dual-task, and Mini-Balance Evaluation Systems Test) and non-motor aspects (Mini-Mental State Exam [MMSE], verbal fluency, Hospital Anxiety and Depression Scale, and Parkinson's Disease Questionnaire-39 [PDQ-39]) were assessed in the PD group. Mann-Whitney U test was used to compare groups, and Spearman's correlation coefficient to analyze the correlations between coverage of EEG-MS and clinical aspects of PD. RESULTS: The PD group showed a shorter duration of EEG-MS C in the eyes-closed condition than the control group. We observed correlations (rho = 0.64 to 0.82) between EEG-MS B, C, and D and non-motor aspects of PD (MMSE, verbal fluency, PDQ-39, and levodopa equivalent daily dose). CONCLUSION: Alterations in EEG-MS and correlations between topographies and cognitive aspects, quality of life, and medication dose indicate that EEG could be used as a PD biomarker. Future studies should investigate these associations using a longitudinal design.

Geographical variation in the chemical composition, anti-inflammatory activity of the essential oil, micromorphology and histochemistry of Schinus terebinthifolia Raddi.

ETHNOPHARMACOLOGICAL RELEVANCE: Schinus terebinthifolia Raddi (Anacardiaceae) is rich in essential oil, distinguished by a predominance of monoterpenes and sesquiterpenes, it being widely used in traditional medicine for the treatment of inflammations. AIM OF STUDY: This study's objective was to investigate the chemical composition of the essential oil of S. terebinthifolia (EOST) collected in six states of Brazil, evaluate its anti-inflammatory effects in mice, and analyze the histochemistry and micromorphology of leaves and stems. MATERIALS AND METHODS: Aerial parts of S. terebinthifolia were collected in six states of Brazil, and the essential oil was extracted by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS). The histochemistry and micromorphology of leaves and stems were performed using standard reagents, light and field emission scanning electron microscopy, beyond energy-dispersive X-ray spectroscopy. The EOST were evaluated for anti-inflammatory activity and hyperalgesia using the carrageenan-induced paw edema methodology. RESULTS: The EOST showed variation across the six states in its yield (0.40%-0.86%) and chemical composition: hydrocarbon monoterpenes (28.76%-47.73%), sesquiterpenes, (31.43%-41.76%), oxygenated monoterpenes (14.31%-19.57%), and oxygenated sesquiterpenes (4.87%-14.38%). Both α-pinene and limonene were predominant constituents of essential in five regions, except for one state where α-phellandrene and limonene were the dominant components. A comprehensive description of the leaf and stem micromorphology and histochemistry was performed. In the in vivo testing, all EOST samples exerted antiedematogenic and anti-hyperalgesic effects, when tested in a carrageenan-induced paw inflammation (mechanical and thermal hyperalgesia) model with oral doses of 30 mg/kg. CONCLUSION: Our results indicate that the EOST samples collected in six Brazilian states differed in their chemical composition but not their anti-inflammatory and antihyperalgesic effects, which was correlated with the synergistic effect of its components, collaborating the etnhopharmacologycal use of this plant due to its an anti-inflammatory effect. Also, micromorphology and histochemistry of leaves and stems presented in this study provide anatomical and microchemical information, which aids species identification.

Gravidade do pé diabético: fatores socioeconômicos em estudo envolvendo 5300 operados / Diabect foot severety: socieconomic factors in a study with 5300 patients / Gravedad del pie diabético: factores socioeconómicos en un estudio con 5300 operados

As amputações decorrentes de pé diabético são graves e geram impacto social e econômico, porém são passíveis de prevenção. O objetivo deste estudo foi testar a hipótese de que há associação entre fatores socioeconômicos e a gravidade do pé diabético. Em estudo observacional restrospectivo, foram avaliados 5.300 prontuários de pacientes portadores de pé diabético operados pelo Serviço de Cirurgia Vascular do Hospital Geral Roberto Santos (HGRS), no período de fevereiro de 2005 a dezembro de 2015. Foram coletadas as condições socioeconômicas para verificar correlação com a gravidade do pé diabético. Os dados foram tabulados no Excel e a distribuição foi analisada no GraphPad Prism 8.0, por meio do teste qui-quadrado e da técnica de regressão logística. Foram considerados valores de p < 0,05 como estatisticamente significantes. A maioria dos pacientes era de meia-idade (entre 53 e 58 anos), do sexo masculino (57,58%), com o ensino fundamental completo (50,38%) e ganhava menos de um salário mínimo (56,81%). A principal doença associada foi a hipertensão arterial sistêmica (HAS) (55,64%). Com relação à distância, foi observado que 48,15% residiam a menos de 100 km da unidade hospitalar. Observou-se prevalência de amputação menor (37,36%) e taxa de letalidade de 6,32%. Também foi possível correlacionar, quanto à amputação maior, maiores frequências nos pacientes acima de 70 anos (p = 0,045), naqueles com renda familiar abaixo de um salário mínimo (p = 0,05), nos portadores de doença arterial coronariana (Daop) (p = 0,035) e nos indivíduos que residiam a uma distância acima de 400 km do HGRS. Registrou-se maior taxa de óbito nos portadores de coronariopatia, com idade superior a 70 anos e nos submetidos à amputação maior. Diante disso, faz-se necessário treinamento de profissionais e adoção de medidas de saúde pública, visando identificar precocemente a população de maior gravidade, a fim de evitar desfechos desfavoráveis.

Amputations due to diabetic foot are serious and generate social and economic impact, but are preventable. This research sought to verify whether socioeconomic factors are associated with diabetic foot severity. A retrospective observational study evaluated 5,300 medical records from patients with diabetic foot, operated by the Vascular Surgery Service at Roberto Santos General Hospital (HGRS), between February 2005 and December 2015. Socioeconomic data were collected to verify correlation with diabetic foot severity. After tabulation in Excel, data distribution was analyzed by GraphPad Prism 8.0 using the Chi-square test and logistic regression. P-values of < 0.05 were considered statistically significant. Most patients were middle-aged (between 53 and 58 years old) men (57.58%), with basic education (50.38%) and earning less than one minimum wage (56.81%). Hypertension was the main associated disease (55.64%). Regarding distance, 48.15% of the patients lived less than 100 km from the hospital unit. Results showed prevalence of minor amputation (37.36%) and a fatality rate of 6.32%. Major amputation was associated with patients over 70 years of age (p = 0.045), family income below 1 MW (p = 0.05), patients with coronary artery disease (CAD) (p = 0.035), and individuals who lived 400 km away from the HGRS. Patients with CAD aged over 70 years and those who underwent major amputation showed a higher death rate. As such, training professionals and adopting public health measures aimed at early identification of at risk population are necessary to avoid unfavorable outcomes.

Las amputaciones por pie diabético son graves y generan impacto social y económico, pero son prevenibles. El objetivo de este estudio fue probar el hipótesis de que existe una asociación entre los factores socioeconómicos y la gravedad de pie diabético. En un estudio observacional retrospectivo, se evaluaron 5.300 historias clínicas de pacientes con pie diabético operados por el Servicio de Cirugía Vascular del Hospital General Roberto Santos (HGRS), en el período comprendido entre febrero 2005 a diciembre 2015. Se recogieron condiciones socioeconómicas para verificar una correlación con la gravedad del pie diabético. Los datos se tabularon en Excel y la distribución se analizó en GraphPad Prism 8.0 mediante la prueba de chi-cuadrado y la técnica de regresión logística. Los valores de p < 0,05 se consideraron estadísticamente significativos. La mayoría de los pacientes eran de mediana edad (entre 53 y 58 años), del sexo masculino (57,58%), con el nivel de estudios de la primaria (50,38%) y que ganaban menos de 1 salario mínimo (56,81%). La principal enfermedad asociada fue la hipertensión arterial sistémica ­HAS­ (55,64%). En cuanto a la distancia, se observó que el 48,15% vive a menos de 100 km de la unidad hospitalaria. Hubo mayor frecuencia de amputaciones menores (37,36%) y una tasa de mortalidad del 6,32%. También fue posible correlacionar la amputación mayor, mayor frecuencia en pacientes mayores de 70 años (p = 0,045), en aquellos con renta familiar inferior a 1 salario mínimo (p = 0,05), en aquellos con enfermedad arterial coronaria ­Daop­ (p = 0,035) y en personas que residen a una distancia superior a 400 km del HGRS. Hubo una mayor tasa de muerte en pacientes con enfermedad de las arterias coronarias, mayores de 70 años y sometidos a una amputación importante. Ante esto, es necesario una formación de profesionales y adopción de medidas de salud pública, con el objetivo de identificar tempranamente la población más grave y así evitar resultados desfavorables.

Níveis de ruído em Unidade Terapia Intensiva Neonatal antes e após intervenção educativa / Noise levels in a Neonatal Intensive Care Unit before and after an educational intervention / Niveles de ruido en una Unidad de Cuidados Intensivos Neonatales antes y después de una intervención educativa

Objetivo: comparar os níveis de ruído dentro de uma Unidade de Terapia Intensiva Neonatal antes e após uma intervenção educativa. Métodos: estudo quase-experimental, tipo antes-depois, com único grupo, realizado no período de dezembro de 2020 a fevereiro de 2021 em uma Unidade de Terapia Intensiva Neonatal de Minas Gerais. Amostra composta por 94 profissionais da equipe multiprofissional. A coleta de dados ocorreu em três etapas: medição do ruído pré-intervenção, realização de intervenção educativa e medição do ruído pós-intervenção. Realizou-se análise descritiva e o estudo foi aprovado pelo Comitê de Ética em Pesquisa. Resultados: na primeira aferição a média do nível de ruído de todos os horários por área foi de 58,5dB(Área A), 61,5dB (Área B) e 61,9dB (Área C), após a intervenção a média reduziu para 56,1dB (Área A), 57,4dB (Área B) e 57,3dB (Área C).Conclusão: o nível de ruído após a intervenção foi menor, embora ainda acima do recomendado.

Objective: to compare noise levels in a Neonatal Intensive Care Unit before and after an educational intervention. Methods: Quasi-experimental, before-after type study of a single group was conducted from December 2020 to February 2021 in a Neonatal Intensive Care Unit in Minas Gerais with a sample of 94 personnel of the multidisciplinary team. Data were collected in three stages ­ pre-intervention noise measurement, educational intervention, and post-intervention noise measurement ­ and were examined by descriptive analysis. The study was approved by the research ethics committee. Results: at the first measurement, mean noise level at all times, by area, was 58.5dB (Area A), 61.5dB (Area B), and 61.9dB (Area C). After the intervention, the means decreased to 56.1dB (Area A), 57.4dB (Area B), and 57.3dB (Area C). Conclusion: noise levels after the intervention were lower, although still above recommended levels.

Objetivo: Comparar los niveles de ruido dentro de una Unidad de Cuidados Intensivos Neonatales antes y después de una intervención educativa. Métodos: Estudio casi experimental, de tipo antes-después, con un solo grupo, realizado de diciembre de 2020 a febrero de 2021 en una Unidad de Cuidados Intensivos Neonatales de Minas Gerais. La muestra abarcó 94 profesionales del equipo multidisciplinario. La recolección de datos se llevó a cabo en tres etapas: medición de ruido antes de la intervención, realización de la intervención educativa y medición de ruido después de la intervención. Se realizó un análisis descriptivo y el Comité de Ética en Investigación aprobó el estudio. Resultados: En la primera medición, el nivel de ruido promedio en todos los horarios, por área, fue de 58.5dB (Área A), 61.5dB (Área B) y 61.9dB (Área C); tras la intervención, el promedio se redujo a 56.1dB (Área A), 57,4 dB (Área B) y 57,3 dB (Área C). Conclusión: el nivel de ruido tras la intervención fue inferior, aunque todavía por encima de lo recomendado.

As artimanhas da titularidade feminina: análise a partir das histórias de vida das mulheres do Bolsa Família / The tricks of female ownership: analysis from the life stories of "Bolsa Família" women (Brazilian Family Assistance Program women) / Las artimañas de la titularidad femenina: análisis a partir de las historias de vida de las mujeres de "Bolsa Família" (Programa de Asistencia Económica Familiar)

Este artigo objetivou evidenciar as concepções das mulheres do Bolsa Família acerca da titularidade feminina. Para tanto, quatro entrevistas semiestruturadas, baseadas no método da história de vida foram realizadas, cuja técnica de análise dos dados empregada foi do tipo temática. Dentre os resultados, identificamos que para as mulheres, a titularidade é compreendida como um avanço político importante por contribuir nas tomadas de decisão no espaço doméstico. Elas também não identificaram problemas no tocante ao cumprimento das condicionalidades, o que tencionamos tratar de ações compreendidas como da ordem "materna". Ademais, elas pouco se compreenderam enquanto sujeitos ativos do processo de transformação da realidade, o que nos exige repensar a nossa prática profissional. Por fim, conclui-se que as artimanhas da titularidade feminina tendem a retroalimentar a fusão entre a ideologia patriarcal e o neoliberalismo, na medida em que o Estado se ausenta e transfere para as titulares-mães responsabilidades na erradicação da pobreza.

This article aimed to highlight the conceptions of Bolsa Família women (Family Assistance Program women) about female ownership. Therefore, four semi-structured interviews were carried out, based on the life history method, which data analysis technique was of the thematic type. Among the results, we identified that for women, ownership is understood as an important political advance for contributing to decision-making in the domestic space. They also did not identify problems regarding the fulfillment of conditionalities, which we intend to deal with actions understood as of the "maternal" order. Furthermore, they were poorly comprehended as active subjects in the process of transforming reality, which requires us to rethink our professional practice. Finally, it is concluded that the tricks of female ownership tend to feed back the fusion between patriarchal ideology and neoliberalism, insofar as the State is absent and transfers responsibilities in the eradication of poverty to the owner-mothers.

Este artículo tuvo como objetivo resaltar las concepciones de las mujeres de Bolsa Família (Programa de Asistencia Económica Familiar) sobre la titularidad femenina. Para ello, se realizaron cuatro entrevistas semiestructuradas, basadas en el método de historia de vida, cuya técnica de análisis de datos fue de tipo temático. Entre los resultados, identificamos que para las mujeres la titularidad es entendida como un avance político importante para contribuir a la toma de decisiones en el espacio doméstico. Tampoco identificaron problemas en cuanto al cumplimiento de condicionalidades, que pretendemos atender con acciones entendidas como de orden "materno". Además, fueron poco comprendidas como sujetos activos en el proceso de transformación de la realidad, lo que nos obliga a repensar nuestra práctica profesional. Finalmente, se concluye que las artimañas de la titularidad femenina tienden a retroalimentar la fusión entre la ideología patriarcal y el neoliberalismo, en la medida en que el Estado está ausente y transfiere las responsabilidades de la erradicación de pobreza a las madres-titulares.

CRISPR/Cas- and Topical RNAi-Based Technologies for Crop Management and Improvement: Reviewing the Risk Assessment and Challenges Towards a More Sustainable Agriculture.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated gene (Cas) system and RNA interference (RNAi)-based non-transgenic approaches are powerful technologies capable of revolutionizing plant research and breeding. In recent years, the use of these modern technologies has been explored in various sectors of agriculture, introducing or improving important agronomic traits in plant crops, such as increased yield, nutritional quality, abiotic- and, mostly, biotic-stress resistance. However, the limitations of each technique, public perception, and regulatory aspects are hindering its wide adoption for the development of new crop varieties or products. In an attempt to reverse these mishaps, scientists have been researching alternatives to increase the specificity, uptake, and stability of the CRISPR and RNAi system components in the target organism, as well as to reduce the chance of toxicity in nontarget organisms to minimize environmental risk, health problems, and regulatory issues. In this review, we discuss several aspects related to risk assessment, toxicity, and advances in the use of CRISPR/Cas and topical RNAi-based technologies in crop management and breeding. The present study also highlights the advantages and possible drawbacks of each technology, provides a brief overview of how to circumvent the off-target occurrence, the strategies to increase on-target specificity, the harm/benefits of association with nanotechnology, the public perception of the available techniques, worldwide regulatory frameworks regarding topical RNAi and CRISPR technologies, and, lastly, presents successful case studies of biotechnological solutions derived from both technologies, raising potential challenges to reach the market and being social and environmentally safe.

Copper in tumors and the use of copper-based compounds in cancer treatment.

Copper homeostasis is strictly regulated by protein transporters and chaperones, to allow its correct distribution and avoid uncontrolled redox reactions. Several studies address copper as involved in cancer development and spreading (epithelial to mesenchymal transition, angiogenesis). However, being endogenous and displaying a tremendous potential to generate free radicals, copper is a perfect candidate, once opportunely complexed, to be used as a drug in cancer therapy with low adverse effects. Copper ions can be modulated by the organic counterpart, after complexed to their metalcore, either in redox potential or geometry and consequently reactivity. During the last four decades, many copper complexes were studied regarding their reactivity toward cancer cells, and many of them could be a drug choice for phase II and III in cancer therapy. Also, there is promising evidence of using 64Cu in nanoparticles as radiopharmaceuticals for both positron emission tomography (PET) imaging and treatment of hypoxic tumors. However, few compounds have gone beyond testing in animal models, and none of them got the status of a drug for cancer chemotherapy. The main challenge is their solubility in physiological buffers and their different and non-predictable mechanism of action. Moreover, it is difficult to rationalize a structure-based activity for drug design and delivery. In this review, we describe the role of copper in cancer, the effects of copper-complexes on tumor cell death mechanisms, and point to the new copper complexes applicable as drugs, suggesting that they may represent at least one component of a multi-action combination in cancer therapy.

Validação de aparência do bundle para manuseio do cateter central de inserção periférica em neonatos / Bundle appearance validation for peripherally inserted central catheter handling in neonates / Validación de la apariencia del paquete para el manejo del catéter central insertado periféricamente en neonatos

Objetivo: validar a aparência do bundle para manuseio do cateter central de inserção periférica em neonatos pela equipe de enfermagem. Método: estudo metodológico, desenvolvido durante os meses de novembro de 2020 e fevereiro de 2021, em unidades neonatais de um hospital de ensino. A amostra foi composta por 43 membros da equipe de enfermagem e os dados analisados pelo índice de validade de conteúdo acima de 80%. Aplicou-se um instrumento contendo dados de identificação, o bundle e a relevância para prática clínica no Google Formulários. Resultados: todos os itens do bundle apresentaram índice de validade de conteúdo acima de 80% e foram considerados relevantes para prática clínica. Conclusão: este estudo permitiu validar a aparência do bundle junto a equipe de enfermagem e incluiu cuidados relacionados a manutenção do cateter central de inserção periférica em neonatos.

Objective: to validate the appearance of the bundle and ematos of the central insertion catheter by the nursing team. Method:methodological study, developed during the months of November 2020 and February 2021, in neonatal units of a teaching hospital. The sample consisted of 43 members of the nursing team and the data analyzed by the content validity index above 80%. An instrument containing identification data, the bundle and relevance to clinical practice on Google Forms was applied. Results:all bundle items had a content validity index above 80% and were considered relevant for clinical practice. Conclusion: this study allowed us to validate the appearance of the bundle with the nursing team and included care related to the maintenance of peripherally inserted central catheter in neonates.

Objetivo: validar el aspecto del fascículo para manipulación del catéter central de inserción periférica en neonatos por el equipo de enfermería. Método: estudio metodológico, desarrollado durante los meses de noviembre de 2020 y febrero de 2021, en unidades neonatales de un hospital de enseñanza. La muestra estuvo compuesta por 43 miembros del equipo de enfermería y los datos analizados por el índice de validez de contenido superior al 80%. Se aplicó un instrumento que contiene los datos de identificación, el paquete y la relevancia para la práctica clínica en Google Forms. Resultados: todos los ítems del paquete tuvieron un índice de validez de contenido superior al 80% y se consideraron relevantes para la práctica clínica. Conclusión: este estudio permitió validar la apariencia del paquete con el equipo de enfermería e incluyó cuidados relacionados con el mantenimiento del catéter central de inserción periférica en los recién nacidos.

Multisite non-invasive brain stimulation in Parkinson's disease: A scoping review.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder, characterized by cardinal motor symptoms in addition to cognitive impairment. New insights concerning multisite non-invasive brain stimulation effects have been gained, which can now be used to develop innovative treatment approaches. OBJECTIVE: Map the researchs involving multisite non-invasive brain stimulation in PD, synthesize the available evidence and discuss future directions. METHODS: The databases PubMed, PsycINFO, CINAHL, LILACS and The Cochrane Library were searched from inception until April 2020, without restrictions on the date of publication or the language in which it was published. The reviewers worked in pairs and sequentially evaluated the titles, abstracts and then the full text of all publications identified as potentially relevant. RESULTS: Twelve articles met the inclusion criteria. The target brain regions included mainly the combination of a motor and a frontal area, such as stimulation of the primary motor córtex associated with the dorsolateral prefrontal cortex. Most of the trials showed that this modality was only more effective for the motor component, or for the cognitive and/or non-motor, separately. CONCLUSIONS: Despite the results being encouraging for the use of the multisite aproach, the indication for PD management should be carried out with caution and deserves scientific deepening.

Smartphone use as an aid in evaluating conventional radiographs.

This study aimed to evaluate the accuracy of smartphones for digitizing, sharing, and viewing conventional radiographic images. Eighty conventional radiographs of 40 teeth with metallic mesio-occlusodistal restorations (40 radiographs showing perfectly adapted restorations and 40 showing restorations with a 0.4-mm proximal gap) were digitized using a smartphone and then evaluated using 2 viewing methods: a light box (LB) and a smartphone screen (SS). Three examiners assessed all radiographs for the presence of marginal gaps using a dichotomous yes/no scale. To analyze examiner reproducibility, 10% of the samples was reassessed. The sensitivity, specificity, and overall accuracy were calculated for each examiner and viewing method. The McNemar test was used to compare examiners' diagnoses based on the 2 viewing methods. The level of statistical significance was set at P < 0.05. The level of agreement was κ > 0.8 for all examiners and both viewing methods. The LB group presented greater sensitivity, specificity, and overall accuracy than the SS group, but no statistically significant differences were found between the methods (P > 0.05). The results achieved were promising, suggesting that the smartphone can be presented as a new aid for radiographic evaluation (LB accuracy, 0.899 to 0.911; SS accuracy, 0.823 to 0.873). Smartphones offer similar accuracy to the traditional viewing method for evaluation of metallic restorations on conventional radiographs.