Wound fluid sampling methods and analysis of cytokine mRNA expression in ulcers from patients with diabetes mellitus.

The development of diabetic foot ulcers is a common and severe complication of diabetes that can significantly affect quality of life. The physiological healing cascade does not progress tissue repair in diabetic foot ulcerations in a timely manner. Serum markers from foot ulcers have been used to characterize the healing process of the diabetic foot using various collection techniques. This study aimed to compare the use of cervical brushes and the Levine technique to collect wound fluid from foot ulcers of people with diabetes in order to determine the presence of cytokines. The collected material was used for gene expression analysis of macrophage/monocyte-associated cytokines IL1-ß, IL-6, TNF-α, regulatory cytokine IL-10 and growth factor TGFß, via quantitative polymerase chain reaction (qPCR). Both collection methods produced sufficient amounts of RNA, but significantly more RNA was collected using a cervical brush (brush 224.82 ng/µL vs. Levine 80.90 ng/µL p = 0.0001). Significantly higher levels of expression of the following cytokine genes were detected in samples collected using a cervical brush: IL1-ß (p = 0.0001), IL-6 (p = 0.0106), IL-10 (p = 0.0277) and TGFß (p = 0.0002). Understanding why some wounds are difficult to heal is important for developing more effective treatments, and biomarkers may be useful for predicting the healing trajectory. These results demonstrate that it is possible to collect material from the wound bed for RT-qPCR analysis, and the cervical brush proved to be a simple and rapid method for monitoring cytokine gene expression.

The role of chaperone-mediated autophagy in drug resistance.

In the search for alternatives to overcome the challenge imposed by drug resistance development in cancer treatment, the modulation of autophagy has emerged as a promising alternative that has achieved good results in clinical trials. Nevertheless, most of these studies have overlooked a novel and selective type of autophagy: chaperone-mediated autophagy (CMA). Following its discovery, research into CMA's contribution to tumor progression has accelerated rapidly. Therefore, we now understand that stress conditions are the primary signal responsible for modulating CMA in cancer cells. In turn, the degradation of proteins by CMA can offer important advantages for tumorigenesis, since tumor suppressor proteins are CMA targets. Such mutual interaction between the tumor microenvironment and CMA also plays a crucial part in establishing therapy resistance, making this discussion the focus of the present review. Thus, we highlight how suppression of LAMP2A can enhance the sensitivity of cancer cells to several drugs, just as downregulation of CMA activity can lead to resistance in certain cases. Given this panorama, it is important to identify selective modulators of CMA to enhance the therapeutic response.

Using design thinking to create and implement a 3D digital library of anatomical specimens.

Design thinking (DT) is a five-stage process (empathize, define, ideate, prototype, and test) that guides the creation of user-centered solutions to complex problems. DT is in common use outside of science but has rarely been applied to anatomical education. The use of DT in this study identified the need for flexible access to anatomical specimens outside of the anatomy laboratory and guided the creation of a digital library of three-dimensional (3D) anatomical specimens (3D Anatomy Viewer). To test whether the resource was fit for purpose, a mixed-methods student evaluation was undertaken. Student surveys (n = 46) were employed using the system usability scale (SUS) and an unvalidated acceptability questionnaire. These verified that 3D Anatomy Viewer was usable (SUS of 72%) and acceptable (agreement range of 77%-93% on all Likert-type survey statements, Cronbach's alpha = 0.929). Supplementary interviews (n = 5) were analyzed through content analysis and revealed three main themes: (1) a credible online supplementary learning resource; (2) learning anatomy with 3D realism and interactivity; (3) user recommendations for expanding the number of anatomical models, test questions, and gamification elements. These data demonstrate that a DT framework can be successfully applied to anatomical education for creation of a practical learning resource. Anatomy educators should consider employing a DT framework where student-centered solutions to learner needs are required.

Topical agents for the prevention ofradiodermatitis in cancer patients: A systematic review / Agentes tópicos para prevenção de radiodermatiteem pacientes com câncer: revisão sistemática

Objetivo: Analisar as evidências sobre o efeito dos agentes tópicos empregados para a prevenção da radiodermatite em pacientes com câncer. Método: Revisão sistemática de estudos clínicos randomizados duplos-cegos construída conforme recomendações do Joanna Briggs Institute e busca nas bases de dados MEDLINE/PubMed, CINAHL, LILACS, Web of Science, Embase, Scopus, além da literatura cinzenta. Utilizaram-se a ferramenta de avaliação crítica do JBI para ensaios clínicos randomizados para avaliar a possibilidade de viés, o Grading of Recommendations, Assessment, Development and Evaluation para a qualidade das evidências e o Gradepro® para recomendá-las. Resultados: Selecionaram-se 13 estudos que avaliaram diferentes agentes tópicos para prevenir a radiodermatite, a saber: corticosteroides, de ação antioxidante e fitoterápicos. A qualidade metodológica de cada estudo foi apropriada, mas a qualidade da evidência gerada pela reunião deles foi baixa, independentemente do tipo de agente tópico empregado, sugerindo que a confiança no seu efeito é limitada e tornando a força de recomendação fraca. Conclusão: Alguns agentes tópicos mostraram-se promissores para a prevenção de radiodermatite, mas as evidências aqui reunidas sobre a eficácia deles não permitem indicar seu uso para a prevenção de radiodermatite em pacientes com câncer. (AU)

Objective: To analyze the evidence on the effect of topical agents to prevent radiodermatitis in cancer patients. Methods: Systematic review of double-blind randomized clinical studies built according to JBI recommendations and search in the databases MEDLINE/PubMed, CINAHL, LILACS, Web of Science, Embase and Scopus, in addition to the Gray Literature. The JBI critical assessment tool for randomized clinical trials was used to assess the possibility of bias, GRADE for the quality of evidence, and Gradepro® to recommend them. Results: Thirteen studies were selected that evaluated different topical agents to prevent radiodermatitis, namely: corticosteroids, with antioxidant action and herbal medicines. The methodological quality of each study was appropriate. Still, the quality of evidence generated by pooling them was low, regardless of the type of topical agent employed, suggesting that confidence in its effect is limited and weakening the strength of the recommendation. Conclusions: Some topical agents have shown promise for the prevention of radiodermatitis, but the evidence gathered here about their effectiveness does not indicate their use for the prevention of radiodermatitis in cancer patients. (AU)

Objetivo: Analizar la evidencia sobre el efecto de los agentes tópicos utilizados para la prevención de la radiodermatitis en pacientes con cáncer. Método: Revisión sistemática de estudios clínicos aleatorizados, doble ciego, elaborados según las recomendaciones del JBI y buscados en MEDLINE/PubMed, CINAHL, LILACS, Web of Science, Embase y Scopus, además de literatura gris. Se utilizó la herramienta de evaluación crítica JBI para ensayos clínicos aleatorios para evaluar la posibilidad de sesgo, GRADE para la calidad de la evidencia y Gradepro® para recomendarla. Resultados: Se seleccionaron trece estudios que evaluaron diferentes agentes tópicos para prevenir la radiodermatitis, a saber: corticosteroides, con acción antioxidante y fitoterapia. La calidad metodológica de cada estudio fue apropiada, pero la calidad de la evidencia generada al combinarlos fue baja, independientemente del tipo de agente tópico empleado, lo que sugiere que la confianza en su efecto es limitada y debilita la fuerza de la recomendación. Conclusión: Algunos agentes tópicos se han mostrado prometedores para la prevención de la radiodermatitis, pero la evidencia aquí reunida sobre su eficacia no nos permite indicar su uso para la prevención de la radiodermatitis en pacientes con cáncer. (AU)

Corrigendum: Rethinking immunization programs through the life course approach.

[This corrects the article DOI: 10.3389/fpubh.2024.1355384.].

Extracorporeal shock wave lithotripsy: retrospective study on possible predictors of treatment success and revisiting the role of non-contrast-enhanced computer tomography in kidney and ureteral stone disease.

Extracorporeal shock wave lithotripsy (ESWL) is a safe and efficient treatment option for urinary stone disease. The overall stone-free rate (SFR) varies significantly. This study aimed to assess the influence of stone size, location, stone density, and skin-to-stone distance (SSD), on the outcome of ESWL. We assessed whether pre-treatment non-contrast-enhanced CT scan (NCCT) confers significant advantages compared to kidney-ureter-bladder film (KUB) only. We reviewed the medical records of 307 cases (165 men, 142 women) with renal and ureteral stones treated consecutively at our institution with ESWL between 2020 and 2023. 44 of these underwent a NCCT. The outcome of ESWL was defined in two ways: visible stone fragmentation on KUB, and the need for further treatment. Overall success of fragmentation was 85% (261 patients). 61% of patients (n = 184) didn't need any further treatment. Stone size and location correlated significantly with treatment outcomes regarding the need for further treatment (p = 0.004) and stone fragmentation (p = 0.016), respectively. Unlike mean SSD (p = 0.462), the mean attenuation value (MAV) significantly correlated with the need for retreatment (p = 0.016). MAV seems to be a better predictor of treatment success (AUC of the ROC curve: 0.729), compared to stone size (AUC: 0.613). The difference between groups (with and without NCCT) in both treatment outcomes did not reach statistical significance. During decision-making, information regarding SSD and MAV can be useful in more dubious scenarios. However, it appears that their inclusion doesn't provide substantial advantages when compared to relying solely on KUB.

Hemograms and serial hemogram-derived ratios in survivors and non-survivors of COVID-19 in Campinas, Brazil

Introduction The hemogram and hemogram-derivative ratios (HDRs) are becoming markers of the severity and mortality of COVID-19. We evaluated the hemograms and serial weekly HDRs [neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), neutrophil-platelet ratio (NPR) and systemic immune-inflammatory index (SII)] in the survivors and non-survivors of COVID-19. Methods We retrospectively reviewed the medical notes and serial hemograms of real-time reverse-transcription polymerase chain reaction (RT-PCR)-confirmed COVID-19 adults hospitalized from April 2020 to March 2021 from the time of diagnosis to the 3rd week of diagnosis. Results Of the 320 adults, 257 (80.3%) were survivors and had a lower mean age than the non-survivors (57.73 vs. 64.65 years, p < 0.001). At diagnosis, the non-survivors had lower hematocrit (p = 0.021), and lymphocyte (p = 0.002) and basophil (p = 0.049) counts and the hematocrit showed a p-value (Is this what you meant???) of 0.021); higher NLR (p < 0.001), PLR (p = 0.047), NPR (p = 0.022) and SII (p = 0.022). Using general linear models, the survivors and non-survivors showed significant variations with weekly lymphocyte count (p < 0.001), neutrophil count (p = 0.005), NLR (p = 0.009), MLR (p = 0.010) and PLR (p = 0.035). All HDRs remained higher in the non-survivors in the 2nd week and 3rd week of diagnosis and the HDRs were higher in the intubated patients than in the non-intubated patients. The NLR and SII were more efficient predictors of mortality in COVID-19 patients. Conclusions This study shows that serial lymphocyte and neutrophil counts, NLR, PLR, MLR, NPR and SII could serve as good and easily accessible markers of severity and predictors of outcomes in COVID-19 patients and should be used for the monitoring of treatment response.

Amazon savannization and climate change are projected to increase dry season length and temperature extremes over Brazil.

Land use change and atmospheric composition, two drivers of climate change, can interact to affect both local and remote climate regimes. Previous works have considered the effects of greenhouse gas buildup in the atmosphere and the effects of Amazon deforestation in atmospheric general circulation models. In this study, we investigate the impacts of the Brazilian Amazon savannization and global warming in a fully coupled ocean-land-sea ice-atmosphere model simulation. We find that both savannization and global warming individually lengthen the dry season and reduce annual rainfall over large tracts of South America. The combined effects of land use change and global warming resulted in a mean annual rainfall reduction of 44% and a dry season length increase of 69%, when averaged over the Amazon basin, relative to the control run. Modulation of inland moisture transport due to savannization shows the largest signal to explain the rainfall reduction and increase in dry season length over the Amazon and Central-West. The combined effects of savannization and global warming resulted in maximum daily temperature anomalies, reaching values of up to 14 °C above the current climatic conditions over the Amazon. Also, as a consequence of both climate drivers, both soil moisture and surface runoff decrease over most of the country, suggesting cascading negative future impacts on both agriculture production and hydroelectricity generation.

Australian physiotherapists attitudes, perceptions, and behaviours towards psychosocial screening tools: a qualitative interpretive description study.

PURPOSE: Psychosocial factors are a barrier to recovery for people with musculoskeletal pain and psychosocial screening tools are consistently recommended by best practice guidelines to assist in identification. However, many physiotherapists do not use these tools. Presently, the perspectives on psychosocial screening tools of Australian physiotherapists are unknown. Exploration of these factors may create targets for increased uptake. The purpose of this paper is to qualitatively explore Australian physiotherapists' attitudes, perceptions, and behaviours towards psychosocial screening tools for musculoskeletal pain conditions. MATERIALS AND METHODS: An Interpretive description qualitative study design was employed. Seventeen Australian physiotherapists were interviewed about their attitudes, perceptions, and behaviours towards psychosocial screening tools. Interviews were transcribed verbatim and analysed according to interpretive description. RESULTS: Analysis highlighted three major themes: (1) understanding the patient through psychosocial screening, (2) confidence and competence with psychosocial factors, and (3) factors outside of my control influence screening. CONCLUSIONS: This study presents a deeper understanding of Australian physiotherapists' diverse attitudes and practices regarding psychosocial screening tools. The research highlights not only the variability in perspectives towards the relevance of psychosocial factors in patient assessments, but also the influence of external elements such as patient demographics and clinic culture on the utilization of these screening methods.

Australian physiotherapists' varying attitudes and limited understanding of the impact of psychosocial factors may hinder the use of recommended psychosocial screening.Concerns about scope of practice, tool appropriateness for different patients, and clinic culture further challenge the integration of psychosocial assessments.The findings from this study indicate the need to provide more education to Australian physiotherapists on the importance and use of psychosocial risk factor screening, as part of clinical care standards and best practice guidelines in the management of patients, with musculoskeletal pain conditions.The findings from this study can support the creation of targeted training/innovations to improve the uptake of screening tools in Australian musculoskeletal clinical practice, to improve the care of patients with musculoskeletal pain conditions.

Rethinking immunization programs through the life course approach.

The world continues to undergo a profound demographic shift toward increasing longevity -but quality of life is not improving correspondingly. At the same time, countries are taking stock of the negative impacts of the COVID-19 pandemic on national immunization programs. The pandemic exacerbated the declines in vaccination coverage for multiple vaccine-preventable diseases (VPD). To ensure that all persons receive all the vaccines for which they are eligible, it is time to consider how applying a life course approach (LCA) to immunization programs can help reinvigorate and redesign actions for greater vaccine uptake. In this mini review, we present the key concepts and principles of the LCA as applied to national immunization programs. Also, we offer recommendations on how health systems can achieve regional and national goals to ensure all people receive the recommended vaccine doses at every stage of life, thus ensuring the greatest benefits for individuals and societies.

Cafeteria Diet Can Affect Bone Microarchitecture in Sedentary and Trained Male Rats.

INTRODUCTION: Poor eating habits and a sedentary lifestyle can impair health. Regular physical activity improves the quality of life and is essential for bone health. Therefore, the present study aimed to evaluate the effects of the cafeteria diet on bone quality of sedentary and exercised rats. METHODS: Sixty young male Wistar rats were divided into six groups (n=10) according to diet composition and activity level, being: SD+CON, standard diet and control; SD+SED, standard diet and sedentary; SD+EX, standard diet and exercised; CD+CON, cafeteria diet and control; CD+SED, cafeteria diet and sedentary; CD+EX, cafeteria diet and exercised. The exercise protocol consisted of 10 ladder-climbing sessions/day, 5 days/week, and the sedentary rats were maintained in individual cages with limited mobility. Body mass and food intake were evaluated weekly. After 10 weeks, the animals were euthanized, and white adipose tissue was collected. The bone structure was evaluated by densitometry, mechanical tests, histomorphometric, and micro-computed tomography analyses. RESULTS: The cafeteria diet increased adipose tissue (p<0.001), decreased bone mineral density (p=0.004), and impaired biomechanical properties (p<0.05) and histomorphometry parameters (p=0.044). The sedentarism decreased bone mineral density (p<0.001) and biomechanical properties (p<0.05), and the exercise did not improve bone properties. CONCLUSION: In this experimental model, it was concluded that the cafeteria diet and a sedentary lifestyle negatively affect bone, and ladder-climbing exercise could not prevent the effects of the unhealthy diet.

Assessing the gene silencing potential of AuNP-based approaches on conventional 2D cell culture versus 3D tumor spheroid.

Three-dimensional (3D) cell culture using tumor spheroids provides a crucial platform for replicating tissue microenvironments. However, effective gene modulation via nanoparticle-based transfection remains a challenge, often facing delivery hurdles. Gold nanoparticles (AuNPs) with their tailored synthesis and biocompatibility, have shown promising results in two-dimensional (2D) cultures, nevertheless, they still require a comprehensive evaluation before they can reach its full potential on 3D models. While 2D cultures offer simplicity and affordability, they lack physiological fidelity. In contrast, 3D spheroids better capture in vivo conditions, enabling the study of cell interactions and nutrient distribution. These models are essential for investigating cancer behavior, drug responses, and developmental processes. Nevertheless, transitioning from 2D to 3D models demands an understanding of altered internalization mechanisms and microenvironmental influences. This study assessed ASO-AuNP conjugates for silencing the c-MYC oncogene in 2D cultures and 3D tumor spheroids, revealing distinctions in gene silencing efficiency and highlighting the microenvironment's impact on AuNP-mediated gene modulation. Herein, we demonstrate that increasing the number of AuNPs per cell by 2.6 times, when transitioning from a 2D cell model to a 3D spheroid, allows to attain similar silencing efficiencies. Such insights advance the development of targeted gene therapies within intricate tissue-like contexts.

A Survey on Environmental Sustainability Among Anesthesiologists: An Opportunity for Changing Behaviors.

Introduction  Environmental sustainability (ES) is a current issue related to natural resource scarcity, pollution and climate change. Although operating rooms (ORs) comprise a small proportion of the entire hospital infrastructure, they significantly impact the environment. Anesthesiologists are ideally positioned to assume leadership, mitigating this negative impact regarding OR waste in the environment. We created a Green Team, comprising multidisciplinary professionals from different areas of a tertiary Portuguese medical center, and conducted a survey that was sent to all the institution's anesthesiologists to assess the current state of ES. Results  From the sample of 133 participants, 101 responses were obtained. Concerning knowledge and training on ES, a significant portion of the respondents (66.7%) seem to attribute "great importance" to the subject. As to the greatest barrier to waste separation in the OR, several respondents highlighted the issues of "inadequate information/education/training" (62.6%) and "lack of support from hospital/OR in-chief/administration" (26.3%). Finally, among seven methods to raise awareness of ES, "training during residency" was the top choice for these professionals, with 52.5% of the votes. Discussion  Most anesthesiologists who responded to the survey recognize the utmost importance of ES and have perceived the environmental impact of their anesthetic practices in the OR. Overall, this tendency is consistent with other international studies. Moreover, most of those surveyed separate waste at home and want to extend this practice -in a more structured approach- to their workplace, with an effective separation of anesthetic and general waste in the OR. Conclusion Professionals perceive barriers to performing green practices, whether the lack of environmental education and awareness, the absence of recycling containers or waste separation bags, or the lack of protocols and guidelines implementing these circuits. With the publication of this work, we aim to encourage other institutions to implement ES projects in their hospitals and ORs.

Modeling of Human Rabies Cases in Brazil in Different Future Global Warming Scenarios.

Bat species have been observed to have the potential to expand their distribution in response to climate change, thereby influencing shifts in the spatial distribution and population dynamics of human rabies cases. In this study, we applied an ensemble niche modeling approach to project climatic suitability under different future global warming scenarios for human rabies cases in Brazil, and assessed the impact on the probability of emergence of new cases. We obtained notification records of human rabies cases in all Brazilian cities from January 2001 to August 2023, as reported by the State and Municipal Health Departments. The current and future climate data were sourced from a digital repository on the WorldClim website. The future bioclimatic variables provided were downscaled climate projections from CMIP6 (a global model ensemble) and extracted from the regionalized climate model HadGEM3-GC31-LL for three future socioeconomic scenarios over four periods (2021-2100). Seven statistical algorithms (MAXENT, MARS, RF, FDA, CTA, GAM, and GLM) were selected for modeling human rabies. Temperature seasonality was the bioclimatic variable with the highest relative contribution to both current and future consensus models. Future scenario modeling for human rabies indicated a trend of changes in the areas of occurrence, maintaining the current pace of global warming, population growth, socioeconomic instability, and the loss of natural areas. In Brazil, there are areas with a higher likelihood of climatic factors contributing to the emergence of cases. When assessing future scenarios, a change in the local climatic suitability is observed that may lead to a reduction or increase in cases, depending on the region.

Effects of plasma rich in growth factors on wound healing in patients with venous ulcers.

Introduction: Significant evidence suggests that plasma-rich in growth factors (PRGF) favor the repair of chronic wounds, enabling a rapid return to functionality. However, components of PRGF and their effects on persistent ulcers and epithelial tissues are not well characterized. The goals of this research were to analyze the biological properties of platelet-derived factors, to examine their effectiveness on healing of venous ulcers, and to establish a correlation with clinical and sociodemographic data. Methods: For the preparation of PRGF, the centrifugation technique was used, obtaining a 100 % autologous and biocompatible blood sample that was treated with sodium citrate and calcium chloride. The patients were attended weekly at the outpatient clinic for nursing consultation and wound dressing changes, with PRGF application every 15 days. The treatment protocols are described, and follow-up results are reported. Results: Initially, the patients' ulcers ranged in sizes from 4 to 84 cm2. After 12 weeks of treatment, there was a significant mean reduction of 46.2 % in ulcer area. At baseline, epithelial tissue was absent in all venous ulcers, but its presence grew significantly by the treatment period. However, the reduction of the area of the ulcers did not show significant correlation with the concentrations of the patient's growth factors. Conclusions: Using the established protocol for PRGF isolating, it was possible to obtain a product with the presence of the six growth factors related to tissue regeneration and observed a positive response on wound healing following treatment of venous ulcers, with capacity to accelerate re-epithelialization and restore the skin functional integrity.

Randomized adaptive selection trial of cryotherapy, compression therapy, and placebo to prevent taxane-induced peripheral neuropathy in patients with breast cancer.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating adverse effect of taxane therapy. Small non-randomized studies in patients with early-stage breast cancer (ESBC) suggest both cryotherapy and compression therapy may prevent CIPN. It is unknown which is more effective. METHODS: We conducted a randomized phase IIB adaptive sequential selection trial of cryotherapy vs. compression therapy vs. placebo ("loose" gloves/socks) during taxane chemotherapy. Participants were randomized in triplets. Garments were worn for 90-120 min, beginning 15 min prior and continuing for 15 min following the infusion. The primary goal was to select the best intervention based on a Levin-Robbins-Leu sequential selection procedure. The primary endpoint was a < 5-point decrease in the Functional Assessment of Cancer Therapy Neurotoxicity (FACT-NTX) at 12 weeks. An arm was eliminated if it had four or more fewer successes than the currently leading arm. Secondary endpoints included intervention adherence and patient-reported comfort/satisfaction. RESULTS: Between April 2019 and April 2021, 63 patients were randomized (cryotherapy (20); compression (22); placebo (21)). Most patients (60.3%) were treated with docetaxel. The stopping criterion was met after the 17th triplet (n = 51) was evaluated; success at 12 weeks occurred in 11 (64.7%) on compression therapy, 7 (41.1%) on cryotherapy, and 7 (41.1%) on placebo. Adherence to the intervention was lowest with cryotherapy (35.0%) compared to compression (72.7%) and placebo (76.2%). CONCLUSION: Compression therapy was the most effective intervention in this phase IIB selection trial to prevent CIPN and was well tolerated. Compression therapy for the prevention of CIPN should be evaluated in a phase III study. CLINICAL TRIAL REGISTRATION: ClinicaTrials.gov Identifier: NCT03873272.

Aqueous extract of the bark of Uncaria tomentosa, an amazonian medicinal plant, promotes gastroprotection and accelerates gastric healing in rats.

ETHNOPHARMACOLOGICAL IMPORTANCE: Uncaria tomentosa Willd. DC., is used in the Amazonian region of South America, wherein ethnic groups use the plant to treat diseases, including gastric disorders. However, despite its widespread popular use, this species has yet to be assessed for its anti-ulcer effects. AIM OF THE STUDY: In this study, we aimed to evaluate the in vivo gastroprotective and gastric healing activities of an aqueous extract of the bark of Uncaria tomentosa (AEUt) and sought to gain an understanding of the pharmacological mechanisms underlying these biological effects. MATERIALS AND METHODS: To verify the gastroprotective properties rats were treated with AEUt (30, 60, or 120 mg/kg) prior to inducing gastric ulceration with ethanol or piroxicam. Additionally, the involvement of nitric oxide, non-protein sulfhydryl compounds (NP-SH), α-2 adrenergic receptors, and prostaglandins was investigated. Furthermore, a pylorus ligature model was employed to investigate the antisecretory activity of AEUt. The gastric healing effects of AEUt (60 mg/kg) were examined in rats in which ulceration had been induced with 80% acetic acid, whereas the quality of healing was evaluated in mice with interleukin-induced recurrent ulcers. We also evaluated the in vivo thickness of the gastric wall using ultrasonography. Moreover, the levels of reduced glutathione (GSH) and malondialdehyde (MDA) were evaluated in ulcerated mucosa, and we determined the activities of the enzymes myeloperoxidase (MPO), N-acetyl-ß-D-glycosaminidase, superoxide dismutase, catalase, and glutathione S-transferase. In addition, we assessed the effects of AEUt on cell viability and subjected the AEUt to phytochemical analyses. RESULTS: Administration of the AEUt (60 or 120 mg/kg) prevented ethanol- and piroxicam-induced ulceration, which was also confirmed histologically. Moreover, we observed that pre-treatment with NEM and indomethacin abolished the gastroprotective effects of AEUt, thereby indicating the involvement of NP-SH and prostaglandins in these protective effects. In addition, we found that the administration of AEUt had no appreciable effects on the volume, acidity, or peptic activity of gastric juice. Furthermore, the AEUt (60 mg/kg) accelerated the gastric healing of acetic acid-induced ulcers by 46.2% and ultrasonographic findings revealed a reduction in the gastric wall thickness in this group. The gastric healing effect of AEUt was also accompanied by a reduction in MPO activity. The AEUt (60 mg/kg) also minimized ulcer recurrence in mice exposed to IL-1ß and was associated with the maintenance of GSH levels and a reduction in MDA contents. We deduce that the biological effects of AEUt could be associated with the activities of polyphenols and the alkaloids isomitraphylline and mitraphylline, identified as predominant constituents of the AEUt. Furthermore, we found no evidence to indicate that AEUt would have any cytotoxic effects. CONCLUSION: Collectively, our findings provide compelling evidence indicating the therapeutic efficacy of U. tomentosa. Our data indicate that compounds in AEUt confer gastroprotection and that this preventive effect of AEUt was accompanied by gastric healing and a reduction in gastric ulcer recurrence. Moreover, we provide evidence to indicate that the gastroprotective and gastric healing effects involve the antioxidant system and anti-inflammatory responses that contribute to preserving the gastric mucosa.

Eficácia da ivermectina e atazanavir no tempo de recuperação dos sintomas de covid-19: uma coorte prospectiva / Effectiveness of ivermectin and atazanavir on time to resolution from covid-19 symptoms: a prospective cohort / Eficacia de ivermectina y atazanavir en el tiempo hasta lá resolución de los síntomas de covid-19: una cohorte prospectiva

Objetivo: avaliar a eficácia da Ivermectina e do Atazanavir em comparação com placebo no tempo de resolução dos sintomas e no tempo de duração da doença por COVID-19. Método: estudo observacional, de coorte prospectivo, longitudinal, descritivo e analítico com pacientes sintomáticos ambulatoriais, acompanhados por 06 meses em duas Unidades Básicas de Saúde para atendimento de COVID-19 em Teresina- Piauí, Brasil, no período de novembro a abril de 2021 identificados por amostragem aleatória 1:1:1. Foram realizados exames Reverse transcription polymerase chain reaction (RT-PCR) para confirmação laboratorial da suspeita de infecção pelo novo coronavírus e avaliação sociodemográfica e clínica. Resultados: dos 87 pacientes randomizados, 62,1% (n=54) eram do sexo masculino, com média de idade de 35,1 anos, possuíam companheira (53,9%), baixa renda (50,6%), eutróficos (40,7%) e sem comorbidades de saúde (78,2%). Não houve diferença entre o tempo médio para resolução dos sintomas, que foi de 21 dias (IQR, 8-30) no grupo atazanavir, 30 dias (IQR, 5-90) no grupo ivermectina em comparação com 14 dias (IQR, 9-21) no grupo controle. No dia 180, houve resolução dos sintomas em 100% no grupo placebo, 93,9% no grupo atazanavir e 95% no grupo ivermectina. A duração mediana da doença foi de 08 dias em todos os braços do estudo. Conclusão: o tratamento com atazanavir (6 dias) e ivermectina (3 dias) não reduziu o tempo de resolução dos sintomas e nem o tempo de duração da doença entre os pacientes ambulatoriais com COVID-19 leve em comparação com o grupo placebo. Os resultados não suportam o uso de ivermectina e atazanavir para tratamento de COVID-19 leve a moderado.

Objective: to evaluate the effectiveness of Ivermectin and Atazanavir compared to placebo in the time to resolution of symptoms and duration of illness due to COVID-19. Method: observational, prospective, longitudinal, descriptive and analytical cohort study with symptomatic outpatients, followed for 06 months in two Basic Health Units for COVID-19 care in Teresina-Piauí, Brazil, from November to April 2021 identified by 1:1:1 random sampling. Reverse transcription polymerase chain reaction (RT-PCR) tests were performed for laboratory confirmation of suspected infection with the new coronavirus and sociodemographic and clinical evaluation. Results: of the 87 randomized patients, 62.1% (n=54) were male, with a mean age of 35.1 years, had a partner (53.9%), low income (50.6%), eutrophic (40.7%) and without health comorbidities (78.2%). There was no difference between the median time to resolution of symptoms, which was 21 days (IQR, 8-30) in the atazanavir group, 30 days (IQR, 5- 90) in the ivermectin group compared with 14 days (IQR, 9- 21) in the control group. At day 180, there was resolution of symptoms in 100% in the placebo group, 93.9% in the atazanavir group, and 95% in the ivermectin group. The median duration of illness was 8 days in all study arms. Conclusion: Treatment with atazanavir (6 days) and ivermectin (3 days) did not reduce the time to symptom resolution or the duration of illness among outpatients with mild COVID-19 compared to the placebo group. The results do not support the use of ivermectin and atazanavir for the treatment of mild to moderate COVID-19.

Objetivo: evaluar la efectividad de Ivermectina y Atazanavir en comparación con placebo en el tiempo de resolución de los síntomas y duración de la enfermedad por COVID-19. Método: estudio de cohorte observacional, prospectivo, longitudinal, descriptivo y analítico con pacientes ambulatorios sintomáticos, seguidos durante 06 meses en dos Unidades Básicas de Salud para atención de COVID-19 en Teresina-Piauí, Brasil, de noviembre a abril de 2021 identificados por 1:1:1 muestreo aleatorio. Se realizaron pruebas de reacción en cadena de la polimerasa con transcriptasa inversa (RT-PCR) para confirmación de laboratorio de sospecha de infección por el nuevo coronavirus y evaluación sociodemográfica y clínica. Resultados: de los 87 pacientes aleatorizados, 62,1% (n=54) eran del sexo masculino, con una edad media de 35,1 años, tenían pareja (53,9%), bajos ingresos (50,6%), eutróficos (40,7%) y sin comorbilidades de salud (78,2%). No hubo diferencia entre la mediana de tiempo hasta la resolución de los síntomas, que fue de 21 días (RIC, 8-30) en el grupo de atazanavir, 30 días (RIC, 5- 90) en el grupo de ivermectina en comparación con 14 días (RIC, 9 - 21) en el grupo control. En el día 180, hubo una resolución de los síntomas del 100 % en el grupo de placebo, del 93,9 % en el grupo de atazanavir y del 95 % en el grupo de ivermectina. La mediana de duración de la enfermedad fue de 8 días en todos los brazos del estudio. Conclusión: El tratamiento con atazanavir (6 días) e ivermectina (3 días) no redujo el tiempo de resolución de los síntomas ni la duración de la enfermedad entre los pacientes ambulatorios con COVID-19 leve en comparación con el grupo placebo. Los resultados no respaldan el uso de ivermectina y atazanavir para el tratamiento de la COVID-19 de leve a moderada.