Representação social da Covid-19 para a população de uma cidade de pequeno porte / Social representation of Covid-19 for the population of a small-sized city / Representación social del Covid-19 para la población de un pequeño pueblo

Objetivo: analisar a representação social da Covid-19 para a população geral de uma cidade de pequeno porte do Estado do Rio de Janeiro. Método: estudo qualitativo, apoiado na abordagem estrutural das representações sociais. Participaram 100 usuários de serviços de saúde. Os dados foram coletados por questionário sociodemográfico de evocações livres de palavras e roteiro de entrevista semiestruturada. Os dados foram analisados com o auxílio dos softwares Excel, EVOC 2005 e análise de conteúdo temático-categorial para contextualização das evocações respectivamente. Resultados: os termos do possível núcleo central foram: morte, sofrimento, cuidados, ansiedade-angústia e vacina. Na primeira periferia: medo e prevenção. À segunda periferia: informação-desinformação; desgoverno; ter-fé e proteção. A zona de contrate: doença; isolamento-social; dificuldades; catástrofe-mundial; desemprego e pandemia. Considerações finais: marcaram essa representação os impactos psicossociais negativos resultantes da desestruturação da vida e das mortes ocasionadas pela nova doença, no entanto o grupo aderiu as medidas de cuidados de proteção.

Objective: to analyze the social representation of Covid-19 among the general population of a small-sized city in the State of Rio de Janeiro. Method: Qualitative study, based on the structural approach of social representations. One hundred healthcare service users participated. Data were collected through a sociodemographic questionnaire, free word evocation, and a semi-structured interview guide. The data were analyzed using Excel software, EVOC 2005, and thematic-categorical content analysis for contextualization of the evocations, respectively. Results: the terms of the possible central core were: death, suffering, care, anxiety-distress, and vaccine. In the first periphery: fear and prevention. In the second periphery: information-misinformation; mismanagement; having faith and protection. The contrast zone: disease; social isolation; difficulties; global catastrophe; unemployment; and pandemic. Final considerations: this representation was marked by the negative psychosocial impacts resulting from the disruption of life and the deaths caused by the new disease; however, the group adhered to protective care measures.

Objetivo: analizar la representación social del Covid-19 para la población general de una pequeña ciudad del Estado de Río de Janeiro. Método: estudio cualitativo, basado en el enfoque estructural de las representaciones sociales. Participaron 100 usuarios de servicios de salud. Los datos se recolectaron mediante un cuestionario sociodemográfico con evocación libre de palabras y una guía de entrevista semiestructurada. Los datos fueron analizados utilizando lo software Excel y EVOC 2005 y análisis de contenido temático-categórico para contextualizar las evocaciones respectivamente. Resultados: los términos del posible núcleo central eran: muerte, sufrimiento, cuidados, ansiedad-angustia y vacuna. En la primera periferia: miedo y prevención. En la segunda periferia: información-desinformación; desgobierno; tener fe y protección. La zona de contraste: enfermedad; aislamiento-social; dificultades; catástrofe-mundial; desempleo y pandemia. Consideraciones finales: esta representación se caracterizó por los impactos psicosociales negativos derivados de la desestructuración de la vida y de las muertes causada por la nueva enfermedad, sin embargo, el grupo adhirió a las medidas de protección.

Transplantation of autologous mesenchymal stromal cells in complete cervical spinal cord injury: a pilot study.

Objective: Spinal cord injury (SCI) is a serious condition that can lead to partial or complete paraplegia or tetraplegia. Currently, there are few therapeutic options for these conditions, which are mainly directed toward the acute phase, such as surgical intervention and high-dose steroid administration. Mesenchymal stromal cells (MSC) have been shown to improve neurological function following spinal cord injury. The aim of the study was to evaluate the safety, feasibility, and potential efficacy of MSC transplantation in patients with cervical traumatic SCI. Methods: We included seven subjects with chronic traumatic SCI (> 1 year) at the cervical level, classified as American Spinal Cord Injury Association impairment scale (AIS) grade A. Subjects received two doses of autologous bone marrow derived MSC, the first by direct injection into the lesion site after hemilaminectomy and the second three months later by intrathecal injection. Neurologic evaluation, spinal magnetic resonance imaging (MRI), urodynamics, and life quality questionnaires were assessed before and after treatment. Results: Cell transplantation was safe without severe or moderate adverse effects, and the procedures were well tolerated. Neurological evaluation revealed discrete improvements in sensitivity below the lesion level, following treatment. Five subjects showed some degree of bilateral sensory improvement for both superficial and deep mechanical stimuli compared to the pretreatment profile. No significant alterations in bladder function were observed during this study. Conclusion: Transplantation of autologous MSC in patients with chronic cervical SCI is a safe and feasible procedure. Further studies are required to confirm the efficacy of this therapeutic approach. Clinical trial registration: https://clinicaltrials.gov/study/NCT02574572, identifier NCT02574572.

Insight into the efficiency of microalgae' lipidic extracts as photosensitizers for Antimicrobial Photodynamic Therapy against Staphylococcus aureus.

Antibacterial resistance causes around 1.27 million deaths annually around the globe and has been recognized as a top 3 priority health threat. Antimicrobial photodynamic therapy (aPDT) is considered a promising alternative to conventional antibiotic treatments. Algal lipid extracts have shown antibacterial effects when used as photosensitizers (PSs) in aPDT. In this work we assessed the photodynamic efficiency of lipidic extracts of microalgae belonging to different phyla (Bacillariophyta, Chlorophyta, Cyanobacteria, Haptophyta, Ochrophyta and Rhodophyta). All the extracts (at 1 mg mL-1) demonstrated a reduction of Staphylococcus aureus >3 log10 (CFU mL-1), exhibiting bactericidal activity. Bacillariophyta and Haptophyta extracts were the top-performing phyla against S. aureus, achieving a reduction >6 log10 (CFU mL-1) with light doses of 60 J cm-2 (Bacillariophyta) and 90 J cm-2 (Haptophyta). The photodynamic properties of the Bacillariophyta Phaeodactylum tricornutum and the Haptophyta Tisochrysis lutea, the best effective microalgae lipid extracts, were also assessed at lower concentrations (75 µg mL-1, 7.5 µg mL-1, and 3.75 µg mL-1), reaching, in general, inactivation rates higher than those obtained with the widely used PSs, such as Methylene Blue and Chlorine e6, at lower concentration and light dose. The presence of chlorophyll c, which can absorb a greater amount of energy than chlorophylls a and b; rich content of polyunsaturated fatty acids (PUFAs) and fucoxanthin, which can also produce ROS, e.g. singlet oxygen (1O2), when photo-energized; a lack of photoprotective carotenoids such as ß-carotene, and low content of tocopherol, were associated with the algal extracts with higher antimicrobial activity against S. aureus. The bactericidal activity exhibited by the extracts seems to result from the photooxidation of microalgae PUFAs by the 1O2 and/or other ROS produced by irradiated chlorophylls/carotenoids, which eventually led to bacterial lipid peroxidation and cell death, but further studies are needed to confirm this hypothesis. These results revealed the potential of an unexplored source of natural photosensitizers (microalgae lipid extracts) that can be used as PSs in aPDT as an alternative to conventional antibiotic treatments, and even to conventional PSs, to combat antibacterial resistance.

Impact of Tricuspid Repair on Surgical Death in Patients Undergoing Mitral Valve Surgery Due to Rheumatic Disease.

Background: Tricuspid valve repair during mitral valve replacement surgery remains a controversial topic. The risk-benefit ratio in some populations remains uncertain, especially in rheumatic heart disease patients. Therefore, we aimed to evaluate the impact of concomitant tricuspid repair on surgical mortality in patients undergoing cardiac surgery due to rheumatic mitral valve disease who have moderate to severe functional tricuspid regurgitation. Methods: This is a prospective cohort study from January 1, 2017, to December 30, 2022. All patients over 18 years of age who underwent cardiac surgery to correct rheumatic mitral valve disease with concomitant moderate to severe tricuspid regurgitation were included. The primary outcome was a surgical death. In an exploratory analysis, clinical and echocardiographic data were obtained 2 years after the procedure. Results: Of the 144 patients included, 83 (57.6%) underwent tricuspid valve repair. The mean age was 46.2 (±12.3) years with 107 (74.3%) female individuals, the median left ventricular ejection fraction was 61.0% (55-67), and systolic pulmonary artery pressure (sPAP) was 55.0 mmHg (46-74), with 45 (31.3%) individuals with right ventricular dysfunction. The total in-hospital mortality was 15 (10.4%) individuals, and there was no difference between the groups submitted or not to tricuspid repair: 10 (12.0%) vs. 5 (7.5%); p = 0.46, respectively. There was an association with one variable independently: the sPAP value, relative risk 1.04 (1.01-1.07), p = 0.01. The estimated cut-off value of sPAP that indicates higher early mortality through the receiver operating characteristic curve (area 0.70, p = 0.012) was 73.5 mmHg. Conclusions: Performing tricuspid repair in individuals who were undergoing cardiac surgery to correct rheumatic mitral valve disease was not associated with increased surgical mortality. Our results suggest the safety of tricuspid repair even in this high-risk population, reinforcing the recommendations in current guidelines.

Platinum-based chemotherapy: trends in organic nanodelivery systems.

Despite the investment in platinum drugs research, cisplatin, carboplatin and oxaliplatin are still the only Pt-based compounds used as first line treatments for several cancers, with a few other compounds being approved for administration in some Asian countries. However, due to the severe and worldwide impact of oncological diseases, there is an urge for improved chemotherapeutic approaches. Furthermore, the pharmaceutical application of platinum complexes is hindered by their inherent toxicity and acquired resistance. Nanodelivery systems rose as a key strategy to overcome these challenges, with recognized versatility and ability towards improving the safety, bioavailability and efficacy of the available drugs. Among the known nanocarriers, organic systems have been widely applied, taking advantage of their potential as drug vehicles. Researchers have mainly focused on the development of lipidic and polymeric carriers, including supramolecular structures, with an overall improvement of encapsulated platinum complexes. Herein, an overview of recent trends and strategies is presented, with the main focus on the encapsulation of platinum compounds into organic nanocarriers, showcasing the evolution in the design and development of these promising systems. This comprehensive review highlights formulation methods as well as characterization procedures, providing insights that may be helpful for the development of novel platinum nanocarriers aiming at future pharmaceutical applications.

Tumor-Infiltrating T Cells in Skin Basal Cell Carcinomas and Squamous Cell Carcinomas: Global Th1 Preponderance with Th17 Enrichment-A Cross-Sectional Study.

Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) are high-incidence, non-melanoma skin cancers (NMSCs). The success of immune-targeted therapies in advanced NMSCs led us to anticipate that NMSCs harbored significant populations of tumor-infiltrating lymphocytes with potential anti-tumor activity. The main aim of this study was to characterize T cells infiltrating NMSCs. Flow cytometry and immunohistochemistry were used to assess, respectively, the proportions and densities of T cell subpopulations in BCCs (n = 118), SCCs (n = 33), and normal skin (NS, n = 30). CD8+ T cells, CD4+ T cell subsets, namely, Th1, Th2, Th17, Th9, and regulatory T cells (Tregs), CD8+ and CD4+ memory T cells, and γδ T cells were compared between NMSCs and NS samples. Remarkably, both BCCs and SCCs featured a significantly higher Th1/Th2 ratio (~four-fold) and an enrichment for Th17 cells. NMSCs also showed a significant enrichment for IFN-γ-producing CD8+T cells, and a depletion of γδ T cells. Using immunohistochemistry, NMSCs featured denser T cell infiltrates (CD4+, CD8+, and Tregs) than NS. Overall, these data favor a Th1-predominant response in BCCs and SCCs, providing support for immune-based treatments in NMSCs. Th17-mediated inflammation may play a role in the progression of NMSCs and thus become a potential therapeutic target in NMSCs.

Transport Properties in Multicomponent Systems Containing Cyclodextrins and Nickel Ions.

In this work, we propose a comprehensive experimental study of the diffusion of nickel ions in combination with different cyclodextrins as carrier molecules for enhanced solubility and facilitated transport. For this, ternary mutual diffusion coefficients measured by Taylor dispersion method are reported for aqueous solutions containing nickel salts and different cyclodextrins (that is, α-CD, ß-CD, and γ-CD) at 298.15 K. A combination of Taylor dispersion and other methods, such as UV-vis spectroscopy, will be used to obtain complementary information on these systems. The determination of the physicochemical properties of these salts with CDs in aqueous solution provides information that allows us to understand solute-solvent interactions, and gives a significant contribution to understanding the mechanisms underlying diffusional transport in aqueous solutions, and, consequently, to mitigating the potential toxicity associated with these metal ions. For example, using mutual diffusion data, it is possible to estimate the number of moles of each ion transported per mole of the cyclodextrin driven by its own concentration gradient.

Naturally occurring small molecules with dual effect upon inflammatory signaling pathways and endoplasmic reticulum stress response.

The endoplasmic reticulum (ER) is determinant to maintain cellular proteostasis. Upon unresolved ER stress, this organelle activates the unfolded protein response (UPR). Sustained UPR activates is known to occur in inflammatory processes, deeming the ER a potential molecular target for the treatment of inflammation. This work characterizes the inflammatory/UPR-related molecular machinery modulated by an in-house library of natural products, aiming to pave the way for the development of new selective drugs that act upon the ER to counter inflammation-related chronic diseases. Starting from a library of 134 compounds of natural occurrence, mostly occurring in medicinal plants, nontoxic molecules were screened for their inhibitory capacity against LPS-induced nuclear factor kappa B (NF-κB) activation in a luciferase-based reporter gene assay. Since several natural products inhibited NF-κB expression in THP-1 macrophages, their effect on reactive oxygen species (ROS) production and inflammasome activation was assessed, as well as their transcriptional outcome regarding ER stress. The bioactivities of several natural products are described herein for the first time. We report the anti-inflammatory potential of guaiazulene and describe 5-deoxykaempferol as a novel inhibitor of inflammasome activation. Furthermore, we describe the dual potential of 5-deoxykaempferol, berberine, guaiazulene, luteolin-4'-O-glucoside, myricetin, quercetagetin and sennoside B to modulate inflammatory signaling ER stress. Our results show that natural products are promising molecules for the discovery and pharmaceutical development of chemical entities able to modulate the inflammatory response, as well as proteostasis and the UPR.

Exploring structural determinants of neuroprotection bias on novel glypromate conjugates with bioactive amines.

Neurodegenerative disorders of the central nervous system (CNS) such as Alzheimer's and Parkinson's diseases, afflict millions globally, posing a significant public health challenge. Despite extensive research, a critical hurdle in effectively treating neurodegenerative diseases is the lack of neuroprotective drugs that can halt or reverse the underlying disease processes. In this work, we took advantage of the neuroprotective properties of the neuropeptide glycyl-l-prolyl-l-glutamic acid (Glypromate) for the development of new peptidomimetics using l-pipecolic acid as a proline surrogate and exploring their chemical conjugation with relevant active pharmaceutical ingredients (API) via a peptide bond. Together with prolyl-based Glypromate conjugates, a total of 36 conjugates were toxicologically and biologically evaluated. In this series, the results obtained showed that a constrained ring (l-proline) at the central position of the peptide motif accounts for enhanced toxicological profiles and biological effects using undifferentiated and differentiated human neuroblastoma SH-SY5Y cells. Additionally, it was shown that biased biological responses are API-dependent. Conjugation with (R)-1-aminoindane led to a 38-43% reduction of protein aggregation induced by Aß25-35 (10 µM), denoting a 3.2-3.6-fold improvement in comparison with the parent neuropeptide, with no significative difference between functionalization at α and γ-carboxyl ends. On the other hand, the best-performing neuroprotective conjugate against the toxicity elicited by 6-hydroxydopamine (6-OHDA, 125 µM) was obtained by conjugation with memantine at the α-carboxyl end, resulting in a 2.3-fold improvement of the neuroprotection capacity in comparison with Glypromate neuropeptide. Altogether, the chemical strategy explored in this work shows that the neuroprotective capacity of Glypromate can be modified and fine-tuned, opening a new avenue for the development of biased neurotherapeutics for CNS-related disorders.

Autologous anti-GD2 CAR T cells efficiently target primary human glioblastoma.

Glioblastoma (GBM) remains a deadly tumor. Treatment with chemo-radiotherapy and corticosteroids is known to impair the functionality of lymphocytes, potentially compromising the development of autologous CAR T cell therapies. We here generated pre-clinical investigations of autologous anti-GD2 CAR T cells tested against 2D and 3D models of GBM primary cells. We detected a robust antitumor effect, highlighting the feasibility of developing an autologous anti-GD2 CAR T cell-based therapy for GBM patients.

CD8+ Treg cells play a role in the obesity-associated insulin resistance.

Obesity-related chronic low-grade inflammation may trigger insulin resistance and type 2 diabetes (T2D) development. Cells with regulatory phenotype have been shown to be reduced during obesity, especially CD4+ Treg cells. However, little is known about the CD8+ Treg cells. Therefore, we aim to characterize the CD8+ Treg cells in human peripheral blood and adipose tissue, specifically, to address the effect of obesity and insulin resistance in this regulatory immune cell population. A group of 42 participants with obesity (OB group) were recruited. Fourteen of them were evaluated pre- and post-bariatric surgery. A group of age- and sex-matched healthy volunteers (n = 12) was also recruited (nOB group). CD8+ Treg cell quantification and phenotype were evaluated by flow cytometry, in peripheral blood (PB), subcutaneous (SAT), and visceral adipose tissues (VAT). The OB group displayed a higher percentage of CD8+ Treg cells in PB, compared to the nOB. In addition, they were preferentially polarized into Tc1- and Tc1/17-like CD8+ Treg cells, compared to nOB. Moreover, SAT displayed the highest content of CD8+ Tregs infiltrated, compared to PB or VAT, while CD8+ Tregs infiltrating VAT displayed a higher percentage of cells with Tc1-like phenotype. Participants with pre-diabetes displayed a reduced percentage of TIM-3+CD8+ Tregs in circulation, and PD-1+CD8+ Tregs infiltrated in the VAT. An increase in the percentage of circulating Tc1-like CD8+ Treg cells expressing PD-1 was observed post-surgery. In conclusion, obesity induces significant alterations in CD8+ Treg cells, affecting their percentage and phenotype, as well as the expression of important immune regulatory molecules.

Fatores associados à depressão e ansiedade em nutricionistas na pandemia por COVID-19 / Factors associated with depression and anxiety in nutritionists in the COVID-19 pandemic

O objetivo foi investigar os fatores associados à depressão e/ou ansiedade em nutricionistas durante a pandemia por COVID-19. Estudo transversal com aplicação das escalas GAD-7 e PHQ-9. Dos 1.018 participantes 60,2% manifestaram rastreio positivo para depressão e/ou ansiedade, com maior força de associação para conflitos muito frequentes nas relações (OR = 11,11; IC95% 6,61;18,67), uso de medicação para dor (OR = 7,42; IC95% 4,67;11,79) e pensar sempre sobre a pandemia (OR = 6,5; IC95% 4,14;10,32). Não estar em tratamento psicoterápico (OR = 0,39; IC95% 0,27;0,560) e não estar em uso de medicamento psicotrópico (OR = 0,40; IC95% 0,26;0,60) foram associados a menores chances de rastreio positivo. O estudo resulta em conhecimento epidemiológico aplicável a ações de vigilância, prevenção e controle da ansiedade e depressão entre nutricionistas.

The objective was to investigate the factors associated with depression and/or anxiety and depression in nutritionists during the COVID-19 pandemic. Cross-sectional study with the application of the GAD-7 and PHQ-9 scales. 1,018 participated, of which 60.2% showed positive screening for depression and/or anxiety, with a greater strength of association for very frequent conflicts in relationships (OR = 11.11; 95%CI 6.61;18.67), use of pain medication (OR = 7.42; 95%CI 4.67;11.79) and always thinking about the pandemic (OR = 6.5; 95%CI 4.14;10.32). Not being under psychotherapeutic treatment (OR = 0.39; 95%CI 0.27;0.560) and not using psychotropic medication (OR = 0.40; 95%CI 0.26;0.60) were associated with lower odds of positive screening. This study results in epidemiological knowledge applicable to surveillance, prevention and control of anxiety and depression among nutritionists.

Epigenetic regulation of TP53 is involved in prostate cancer radioresistance and DNA damage response signaling.

External beam radiotherapy (RT) is a leading first-line therapy for prostate cancer (PCa), and, in recent years, significant advances have been accomplished. However, RT resistance can arise and result in long-term recurrence or disease progression in the worst-case scenario. Thus, making crucial the discovery of new targets for PCa radiosensitization. Herein, we generated a radioresistant PCa cell line, and found p53 to be highly expressed in radioresistant PCa cells, as well as in PCa patients with recurrent/disease progression submitted to RT. Mechanism dissection revealed that RT could promote p53 expression via epigenetic modulation. Specifically, a decrease of H3K27me3 occupancy at TP53 gene promoter, due to increased KDM6B activity, was observed in radioresistant PCa cells. Furthermore, p53 is essential for efficient DNA damage signaling response and cell recovery upon stress induction by prolonged fractionated irradiation. Remarkably, KDM6B inhibition by GSK-J4 significantly decreased p53 expression, consequently attenuating the radioresistant phenotype of PCa cells and hampering in vivo 3D tumor formation. Overall, this work contributes to improve the understanding of p53 as a mediator of signaling transduction in DNA damage repair, as well as the impact of epigenetic targeting for PCa radiosensitization.

Effects of graphene oxide and reduced graphene oxide nanomaterials on porcine endothelial progenitor cells.

Graphene oxide (GO) and reduced graphene oxide (rGO) have been widely used in the field of tissue regeneration and various biomedical applications. In order to use these nanomaterials in organisms, it is imperative to possess an understanding of their impact on different cell types. Due to the potential of these nanomaterials to enter the bloodstream, interact with the endothelium and accumulate within diverse tissues, it is highly relevant to probe them when in contact with the cellular components of the vascular system. Endothelial progenitor cells (EPCs), involved in blood vessel formation, have great potential for tissue engineering and offer great advantages to study the possible angiogenic effects of biomaterials. Vascular endothelial growth factor (VEGF) induces angiogenesis and regulates vascular permeability, mainly activating VEGFR2 on endothelial cells. The effects of GO and two types of reduced GO, obtained after vacuum-assisted thermal treatment for 15 min (rGO15) and 30 min (rGO30), on porcine endothelial progenitor cells (EPCs) functionality were assessed by analyzing the nanomaterial intracellular uptake, reactive oxygen species (ROS) production and VEGFR2 expression by EPCs. The results evidence that short annealing (15 and 30 minutes) at 200 °C of GO resulted in the mitigation of both the increased ROS production and decline in VEGFR2 expression of EPCs upon GO exposure. Interestingly, after 72 hours of exposure to rGO30, VEGFR2 was higher than in the control culture, suggesting an early angiogenic potential of rGO30. The present work reveals that discrete variations in the reduction of GO may significantly affect the response of porcine endothelial progenitor cells.

Efeito da infecção por COVID-19 na via auditiva até tronco encefálico / Effect of COVID-19 infection on the auditory pathway to the brainstem / Efecto de la infección por COVID-19en la vía auditiva hacia el tronco del encéfalo

Introdução: A COVID-19 pode afetar o sistema auditivo, justificando a avaliação da audição de indivíduos infectados. Objetivo: analisar a via auditiva até o tronco encefálico de indivíduos acometidos por COVID-19 comparados ao grupo controle. Método: Estudo observacional transversal analítico realizado em uma amostra não probabilística de adultos que tiveram COVID-19, que foram comparados com um grupo controle, sem queixa auditiva. A avaliação consistiu em: medidas de imitância acústica, audiometria tonal liminar (ATL), emissões otoacústicas evocadas por estímulo transiente (EOET) e potencial evocado auditivo de tronco encefálico (PEATE). Resultados: Foram avaliados 77 indivíduos, sendo, 41 participantes do grupo COVID-19 (idade média de 26,3) e 36 do grupo controle (idade média de 25,8). Os limiares auditivos estavam dentro dos padrões da normalidade para todos os indivíduos do grupo COVID-19, sendo significativamente maiores para as frequências de 1000, 2000 e 3000 Hz à direita. A amplitude das EOET foi significativamente menor na banda de frequência de 1500 à direita. Houve correlação significativa e negativa para as frequências de 1000 Hz e 3000 Hz à direita e para as frequências de 1000, 2000 e 3000 Hz à esquerda, entre EOET e ATL. Foi verificado aumento da latência absoluta da onda I, do PEATE, na orelha esquerda. Conclusão: a COVID-19 afetou locais específicos do sistema auditivo. Houve diminuição da acuidade auditiva e do funcionamento das células ciliadas externas da cóclea, bem como aumento do tempo de condução neural do som na porção distal do VII par craniano à esquerda. (AU)

Introduction: COVID-19 can affect the auditory system, justifying the evaluation of the hearing of infected individuals. Objective: to analyze the auditory pathway to the brainstem of individuals affected by COVID-19 compared to the control group. Method: Analytical cross-sectional observational study carried out in a non-probabilistic sample of adults who had COVID-19, who were compared with a control group, without hearing complaints. The evaluation consisted of: acoustic immittance measurements, pure tone audiometry (PTA), transient stimulus-evoked otoacoustic emissions (TEOAE) and brainstem auditory evoked potential (BAEP). Results: 77 individuals were evaluated, 41 participants in the COVID-19 group (average age of 26.3) and 36 in the control group (average age of 25.8). Hearing thresholds were within normal limits for all individuals in the COVID-19 group, being significantly higher for the frequencies of 1000, 2000 and 3000 Hz on the right. TEOAE amplitude was significantly lower in the 1500 frequency band on the right. There was a significant and negative correlation for the frequencies of 1000 Hz and 3000 Hz on the right and for the frequencies of 1000, 2000 and 3000 Hz on the left, between TEOAE and PTA. An increase in the absolute latency of wave I, of the BAEP, was observed in the left ear. Conclusion: COVID-19 affected specific locations in the auditory system. There was a decrease in auditory acuity and the functioning of the outer hair cells of the cochlea, as well as an increase in the neural conduction time of sound in the distal portion of the VII cranial nerve on the left. (AU)

Introducción: COVID-19 puede afectar el sistema auditivo, justificando la evaluación de la audición de individuos infectados. Objetivo: analizar la vía auditiva hacia el tronco encefálico de individuos afectados por COVID-19 en comparación con el grupo control. Método: Estudio observacional analítico transversal realizado en una muestra no probabilística de adultos que padecieron COVID-19, quienes fueron comparados con un grupo control, sin escuchar quejas. La evaluación consistió en: mediciones de inmitancia acústica, audiometría de tonos puros (ATP), otoemisiones acústicas provocadas por estímulos transitorios (OAET) y potenciales evocados auditivos del tronco encefálico (PEATE). Resultados: Se evaluaron 77 individuos, 41 participantes en el grupo COVID-19 (edad promedio de 26,3 años) y 36 en el grupo control (edad promedio de 25,8 años). Los umbrales de audición estaban dentro de los límites normales para todos los individuos del grupo de COVID-19, siendo significativamente más altos para las frecuencias de 1000, 2000 y 3000 Hz de la derecha. La amplitud de OAET fue significativamente menor en la banda de frecuencia de 1500 de la derecha. Hubo correlación significativa y negativa para las frecuencias de 1000 Hz y 3000 Hz a la derecha y para las frecuencias de 1000, 2000 y 3000 Hz a la izquierda, entre OAET y ATP. Se observó un aumento de la latencia absoluta de la onda I, del PEATE, en el oído izquierdo. Conclusión: COVID-19 afectó ubicaciones específicas del sistema auditivo. Hubo una disminución de la agudeza auditiva y del funcionamiento de las células ciliadas externas de la cóclea, así como un aumento del tiempo de conducción neural del sonido en la porción distal del VII par craneal izquierdo. (AU)

OncoUroMiR: Circulating miRNAs for Detection and Discrimination of the Main Urological Cancers Using a ddPCR-Based Approach.

The three most common genitourinary malignancies (prostate/kidney/bladder cancers) constitute a substantial proportion of all cancer cases, mainly in the elderly population. Early detection is key to maximizing the patients' survival, but the lack of highly accurate biomarkers that might be used through non-/minimally invasive methods has impaired progress in this domain. Herein, we sought to develop a minimally invasive test to detect and discriminate among those urological cancers based on miRNAs assessment through ddPCR. Plasma samples from 268 patients with renal cell (RCC; n = 119), bladder (BlCa; n = 73), and prostate (PCa; n = 76) carcinomas (UroCancer group), and 74 healthy donors were selected. Hsa-miR-126-3p, hsa-miR-141-3p, hsa-miR-153-5p, hsa-miR-155-5p, hsa-miR-182-5p, hsa-miR-205-5p, and hsa-miR-375-3p levels were assessed. UroCancer cases displayed significantly different circulating hsa-miR-182-5p/hsa-miR-375-3p levels compared to healthy donors. Importantly, the hsa-miR-155-5p/hsa-miR-375-3p panel detected RCC with a high specificity (80.54%) and accuracy (66.04%). Furthermore, the hsa-miR-126-3p/hsa-miR-375-3p panel identified BlCa with a 94.87% specificity and 76.45% NPV whereas higher hsa-miR-126-3p levels were found in PCa patients. We concluded that plasma-derived miRNAs can identify and discriminate among the main genitourinary cancers, with high analytical performance. Although validation in a larger cohort is mandatory, these findings demonstrate that circulating miRNA assessment by ddPCR might provide a new approach for early detection and risk stratification of the most common urological cancers.

Noninvasive Red Laser Intervention before Radiotherapy of Triple-negative Breast Cancer in a Murine Model.

Radiotherapy is a well-established cancer treatment; it is estimated that approximately 52% of oncology patients will require this treatment modality at least once. However, some tumors, such as triple-negative breast cancer (TNBC), may present as radioresistant and thus require high doses of ionizing radiation and a prolonged period of treatment, which may result in more severe side effects. Moreover, such tumors show a high incidence of metastases and decreased survival expectancy of the patient. Thus, new strategies for radiosensitizing TNBC are urgently needed. Red light therapy, photobiomodulation, has been used in clinical practice to mitigate the adverse side effects usually associated with radiotherapy. However, no studies have explored its use as a radiosensitizer of TNBC. Here, we used TNBC-bearing mice as a radioresistant cancer model. Red light treatment was applied in three different protocols before a high dose of radiation (60 Gy split in 4 fractions) was administered. We evaluated tumor growth, mouse clinical signs, total blood cell counts, lung metastasis, survival, and levels of glutathione in the blood. Our data showed that the highest laser dose in combination with radiation arrested tumor progression, likely due to inhibition of GSH synthesis. In addition, red light treatment before each fraction of radiation, regardless of the light dose, improved the health status of the animals, prevented anemia, reduced metastases, and improved survival. Collectively, these results indicate that red light treatment in combination with radiation could prove useful in the treatment of TNBC.

Noninvasive Red Laser Intervention before Radiotherapy of Triple-negative Breast Cancer in a Murine Model.

Radiotherapy is a well-established cancer treatment; it is estimated that approximately 52% of oncology patients will require this treatment modality at least once. However, some tumors, such as triple-negative breast cancer (TNBC), may present as radioresistant and thus require high doses of ionizing radiation and a prolonged period of treatment, which may result in more severe side effects. Moreover, such tumors show a high incidence of metastases and decreased survival expectancy of the patient. Thus, new strategies for radiosensitizing TNBC are urgently needed. Red light therapy, photobiomodulation, has been used in clinical practice to mitigate the adverse side effects usually associated with radiotherapy. However, no studies have explored its use as a radiosensitizer of TNBC. Here, we used TNBC-bearing mice as a radioresistant cancer model. Red light treatment was applied in three different protocols before a high dose of radiation (60 Gy split in 4 fractions) was administered. We evaluated tumor growth, mouse clinical signs, total blood cell counts, lung metastasis, survival, and levels of glutathione in the blood. Our data showed that the highest laser dose in combination with radiation arrested tumor progression, likely due to inhibition of GSH synthesis. In addition, red light treatment before each fraction of radiation, regardless of the light dose, improved the health status of the animals, prevented anemia, reduced metastases, and improved survival. Collectively, these results indicate that red light treatment in combination with radiation could prove useful in the treatment of TNBC.

Genotoxic and mutagenic evaluation in Eisenia foetida annelids exposed to iron ore tailings from the region of Brumadinho, MG, Brazil.

Soils that have a disproportion of metallic elements due to anthropic activities endanger the terrestrial fauna. This study evaluated whether earthworms (Eisenia foetida) exposed to ore tailings from Brumadinho region presented a higher frequency of genotoxic and mutagenic damages than annelids from a reference area (control). The animals were exposed to substrates containing 0%, 25%, 50%, 75%, and 100% iron mining waste. The results indicated increased DNA damage (p < 0.05), detected by the comet assay at 25% and 50%. There was a three-fold increase in micronuclei in animals on the substrates with the highest concentrations (75% and 100%) [F = 3.095; p = 0.02]. The earthworms lost weight as the percentage of mining waste increased. We concluded that E. foetida presented DNA damage in the contaminated soils of Brumadinho. However, more research is fundamental, once the environmental disaster in Brumadinho was one of the biggest mining catastrophe in Brazil.