Acute kidney injury associated with anti-PD-1 and anti-PD-L1 drugs: a meta-analysis of randomized clinical trials.

BACKGROUND: Immune Checkpoint Inhibitors (ICI) have been widely used in treating different types of cancer. They increase survival in many oncologic patients and enable cancer-specific therapy. Acute Kidney Injury (AKI) is one of the adverse effects associated with using ICI, where knowledge of the prevalence and renal histological findings are still reasons for discussion. OBJECTIVE: Therefore, this meta-analysis evaluates the association between ICI use and AKI. METHODS: The search was performed in PubMed, Lilacs, and Cochrane platforms. Studies published up to December 1, 2022, were included. RESULTS: A total of 16 studies met the established PICOT criteria and were included in this review. Comparing the ICI plus chemotherapy against chemotherapy alone, the relative risk (RR) for AKI's development with ICI use was 2.89 (95%CI 1.37-6.10). In the analyses by class and drug type, programmed cell death 1 monoclonal antibody (anti-PD-1) showed an increased risk of 2.11 (95%CI 1.26-3.52), and pembrolizumab demonstrated a risk of AKI (RR= 2.77, 95%CI 1.46-5.26). Likewise, regarding the severity of AKI, AKI grade 3 or higher was more common in the ICI plus chemotherapy compared to the chemotherapy group: 3.66 (95%CI 1.19-11.30), while the subgroup analyses pooled studies comparing ICI alone versus chemotherapy alone in the control group did not demonstrate an association with AKI. CONCLUSIONS: These findings suggest that ICI use is associated with an increased risk of AKI and that anti-PD-1 use is associated with a higher incidence of renal adverse events than programmed cell death ligand 1 monoclonal antibody (anti-PD-L1). Studies with adequate power and well-defined criteria for acute interstitial nephritis, nowadays taken as a synonym for AKI related to ICI, are necessary.

From capillaries to microchips, green electrophoretic features for enantiomeric separations: A decade review (2013-2022).

Enantioseparation by the electromigration-based method is well-established and widely discussed in the literature. Electrophoretic strategies have been used to baseline resolve complex enantiomeric mixtures, typically using a selector substance into the background electrolyte (BGE) from capillaries to microchips. Along with developing new materials/substances for enantioseparations, it is the concern about the green analytical chemistry (GAC) principles for method development and application. This review article brings a last decade's update on the publications involving enantioseparation by electrophoresis for capillary and microchip systems. It also brings a critical discussion on GAC principles and new green metrics in the context of developing an enantioseparation method. Chemical and green features of native and modified cyclodextrins are discussed. Still, given the employment of greener substances, ionic liquids and deep-eutectic solvents are highlighted, and some new selectors are proposed. For all the mentioned selectors, green features about their production, application, and disposal are considered. Sample preparation and BGE composition in GAC perspective, as well as greener derivatization possibilities, were also addressed. Therefore, one of the goals of this review is to aid the electrophoretic researchers to look where they have not.

Fipronil Tablets: Development and Pharmacokinetic Profile in Beagle Dogs.

Increased human-pet interactions have led to concerns related to the prevention and treatment of ectoparasite infestations. Fipronil (FIP) is a widely used ectoparasiticide in veterinary medicine available for topical administration; however, its use may cause damage to the owners and the environment. The aim of the study was to develop immediate-release tablets of FIP, as well as to determine its pharmacokinetic properties after oral administration in beagle dogs. The prepared FIP tablets were evaluated for pre-compression (angle of repose, speed flow, and Carr's index) and post-compression (weight variation, friability, thickness, hardness, disintegration time, and dissolution rate) parameters. Orally administered FIP at a dose of 2 mg/kg was rapidly absorbed with Cmáx of 3.13 ± 1.39 µg/mL at 1.83 ± 0.40 h post treatment (P.T.) and metabolized with 1.27 ± 1.04 µg/mL at 2.33 ± 0.82 h P.T. for fipronil sulfone (SULF) (the primary metabolite). The elimination of FIP and SULF occurred slowly and had maintained quantifiable plasma levels in the blood for up to 28 days P.T. The goal of the study is aligned with the concept of One Health, which aims to collaboratively achieve the best health for people, animals, and the environment. Therefore, the use of FIP tablets for the control of ectoparasites in dogs may be a safer alternative for owners and the environment.

Evaluation of Rosin Gum and Eudragit® RS PO as a Functional Film Coating Material.

Polymers are essential tools in the research and development of new therapeutic devices. The diversity and flexibility of these materials have generated high expectations in the composition of new materials with extraordinary abilities, especially in the design of new systems for the modified release of pharmaceutically active ingredients. The natural polymer rosin features moisture protection and pH-dependent behavior (i.e., it is sensitive to pH > 7.0), suggesting its possible use in pharmaceutical systems. The synthetic polymer Eudragit® RS PO is a low-permeability material, the disintegration of which depends on the time of residence in the gastrointestinal tract. The present study developed a polymeric material with desirable physicochemical characteristics and synergistic effects that resulted from the inherent properties of the associated polymers. Isolated films were obtained by solvent evaporation and subjected to a water vapor transmission test, scanning electron microscopy, calorimetry, Fourier transform-infrared (FT-IR) spectroscopy, micro-Raman spectroscopy, and mechanical analysis. The new polymeric material was macroscopically continuous and homogeneous, was appropriately flexible, had low water permeability, was vulnerable in alkaline environments, and was thermally stable, maintaining an unchanged structure up to temperatures of ∼400°C. The new material also presented potentially suitable characteristics for application in film coatings for oral solids, suggesting that it is capable of carrying therapeutic substances to distal regions of the gastrointestinal tract. These findings indicate that this new material may be added to the list of functional excipients.

Whistle comparison of four delphinid species in Southeastern Brazil.

The present study evaluates variations in frequency and duration parameters of whistles of four dolphin species (Sotalia guianensis, Steno bredanensis, Stenella frontalis, and Tursiops truncatus), recorded in the Rio de Janeiro State Coast, Southeastern Brazil. A total of 487 whistles were analyzed. Acoustic parameters of the whistles were classified to species by discriminant function analysis. Overall classification score was 72.5%, with the highest classification score obtained for whistles of S. bredanensis and the lowest obtained for S. frontalis. Most differences were among S. bredanensis and S. guianensis, species that did not have their repertoires compared in other studies.

High-frequency whistles of Guiana dolphins (Sotalia guianensis) in Guanabara Bay, southeastern Brazil.

Guiana dolphins produce whistles with a higher frequency and less complexity than most other delphinid species. The present study used a recording system with sampling rate of 192 kHz to describe the high-frequency whistles of Sotalia guianensis in Guanabara Bay, Rio de Janeiro. Eleven acoustic parameters (start, end, minimum, maximum, delta, center and peak frequency, duration, and frequency at 14, 12, and 34 of duration) were measured for all whistles. Whistles with a fundamental frequency up to 66.7 kHz were reported, thereby expanding the known frequency range of this species.

Corporal artistic training influences attention: a pilot study.

This study assessed the effect of the Body Rhythmics (BRIM) on actors' attentional processes. BRIM is a combination of exercises using numbers and rules that enact musical parameters in the moving body through displacements. Male actors (N = 22) participated in the study: 7 in the BRIM (Study) group and 15 in the Control group (groups were equivalent on mean Raven's IQ). The Continuous Performance Test (CPT-II) was administered before and after an intensive period of BRIM training. There was no significant difference on the CPT-II before training. Group results for before vs after training showed a significant difference for reaction time for the Study group. There was also a trend to increased errors of commission in the Study group after BRIM training.

Redirection of palatally ectopic maxillary canines: Case report and proposition of an interceptive sequential guideline.

The eruptive deviation of the permanent maxillary canine must be identified early, at the beginning of the second transitional period of the mixed dentition. Acting at this moment is fundamental for its spontaneous redirection and eruption. The aim of the paper is to present a case where the extraction of the deciduous canines was the choice for redirecting the maxillary permanent canines with eruptive palatal deviation, as well as to suggest a sequence of procedures for diagnosis and choice of treatment. The success of deciduous canine extraction in redirecting the ectopic permanent canines is discussed in this case, as well as aspects that might lead to failure. Still, it highlights the importance of computed tomography for choosing conservative treatment or traction, including it in the sequential guideline for acting in these cases.

Long-Term Sustainability of Peri-Operative Infection Control Practices: Implementation of "Clean Cut," a Checklist-Based Quality Improvement Program in India.

Introduction: Surgical site infections (SSIs) are a substantial healthcare burden in low- and middle- income countries. "Clean Cut" is a checklist-based infection prevention and control (IPC) program intended to improve compliance to peri-operative IPC standards. We aim to study the short-term and long-term impact of its implementation in a tertiary care cancer referral center. Methods: This was a single institute, prospective interventional study. Patients undergoing elective head-neck surgical procedures were included. The "Clean Cut" program consisting of surveillance, audits, and IPC training was implemented for 6 months, after which there was no active oversight. Post-intervention (T2) and 1-year follow-up (T3) data regarding compliance to core IPC practices and SSI rates were compared with baseline (T1). Results: One hundred eighty six patients were included with 50 (26.9%), 86 (46.2%), and 50 (26.9%) patients at T1, T2, and T3, respectively. At baseline, teams complied with a mean of 3.56 of the six critical components of infection control processes which rose to 4.66 (p < 0.001) at T2, but decreased to 4.02 at T3 (p = 0.053). The SSI rate at baseline decreased significantly after Clean Cut implementation [16 (32%) vs. 12 (13.95%), p = 0.012], but returned to baseline levels after 1 year [17 (34%), p = 0.006]. Conclusion: Implementation of the "Clean Cut" program increases compliance to infection control processes and reduces SSI rates in the short term. Without continuing oversight, these rates return to baseline values after 1 year.

Impact of quality and transparency in scientific writing on the reduction of animal usage in experimental protocols: a review based in pertinent literature.

The irreproducibility in scientific research has become a critical issue. Despite the essential role of rigorous methodology in constructing a scientific article, more than half of publications, on average, are considered non-reproducible. The implications of this irreproducibility extend to reliability problems, hindering progress in technological production and resulting in substantial financial losses. In the context of laboratory animal research, this work emphasizes the importance of choosing an appropriate experimental model within the 3R's principle (Refine, Reduce, Replace). This study specifically addresses a deficiency in data specification in scientific articles, revealing inadequacies in the description of crucial details, such as environmental conditions, diet, and experimental procedures. For this purpose, 124 articles from journals with relevant impact factors were analyzed, conducting a survey of data considered important for the reproducibility of studies. Important flaws in the presentation of data were identified in most of the articles evaluated. The results of this study highlight the need to improve the description of essential information, standardizing studies, and ensuring the reproducibility of experiments in areas such as metabolism, immunity, hormones, stress, among others, to enhance the reliability and reproduction of experimental results, aligning with international guidelines such as ARRIVE and PREPARE.

Perspectives of FTIR as Promising Tool for Pathogen Diagnosis, Sanitary and Welfare Monitoring in Animal Experimentation Models: A Review Based on Pertinent Literature.

Currently, there is a wide application in the literature of the use of the Fourier Transform Infrared Spectroscopy (FTIR) technique. This basic tool has also proven to be efficient for detecting molecules associated with hosts and pathogens in infections, as well as other molecules present in humans and animals' biological samples. However, there is a crisis in science data reproducibility. This crisis can also be observed in data from experimental animal models (EAMs). When it comes to rodents, a major challenge is to carry out sanitary monitoring, which is currently expensive and requires a large volume of biological samples, generating ethical, legal, and psychological conflicts for professionals and researchers. We carried out a survey of data from the relevant literature on the use of this technique in different diagnostic protocols and combined the data with the aim of presenting the technique as a promising tool for use in EAM. Since FTIR can detect molecules associated with different diseases and has advantages such as the low volume of samples required, low cost, sustainability, and provides diagnostic tests with high specificity and sensitivity, we believe that the technique is highly promising for the sanitary and stress and the detection of molecules of interest of infectious or non-infectious origin.

Eugenol attenuates ischemia-mediated oxidative stress in cardiomyocytes via acetylation of histone at H3K27.

Despite clinical advances, ischemia-induced cardiac diseases remain an underlying cause of death worldwide. Epigenetic modifications, especially alterations in the acetylation of histone proteins play a pivotal role in counteracting stressful conditions, including ischemia. In our study, we found that histone active mark H3K27ac was significantly reduced and histone repressive mark H3K27me3 was significantly upregulated in the cardiomyocytes exposed to the ischemic condition. Then, we performed a high throughput drug screening assay using rat ventricular cardiomyocytes during the ischemic condition and screened an antioxidant compound library comprising of 84 drugs for H3K27ac by fluorescence microscopy. Our data revealed that most of the phenolic compounds like eugenol, apigenin, resveratrol, bis-demethoxy curcumin, D-gamma-tocopherol, ambroxol, and non-phenolic compounds like l-Ergothioneine, ciclopirox ethanolamine, and Tanshinone IIA have a crucial role in maintaining the cellular H3K27ac histone marks during the ischemic condition. Further, we tested the role of eugenol on cellular protection during ischemia. Our study shows that ischemia significantly reduces cellular viability and increases total reactive oxygen species (ROS), and mitochondrial ROS in the cells. Interestingly, eugenol treatment significantly restores the cellular acetylation at H3K27, decreases cellular ROS, and improves cellular viability. To explore the mechanism of eugenol-medicated inhibition of deacetylation, we performed a RNAseq experiment. Analysis of transcriptome data using IPA indicated that eugenol regulates several cellular functions associated with cardiovascular diseases, and metabolic processes. Further, we found that eugenol regulates the expression of HMGN1, CD151 and Ppp2ca genes during ischemia. Furthermore, we found that eugenol might protect the cells from ischemia through modulation of HMGN1 protein expression, which plays an active role in regulation of histone acetylation and cellular protection during stress. Thus, our study indicated that eugenol can be exploited as an agent to protect the ischemic cells and also could be used to develop a novel drug for treating cardiac disease.

A multi-level approach reveals key physiological and molecular traits in the response of two rice genotypes subjected to water deficit at the reproductive stage.

Rice is more vulnerable to drought than maize, wheat, and sorghum because its water requirements remain high throughout the rice life cycle. The effects of drought vary depending on the timing, intensity, and duration of the events, as well as on the rice genotype and developmental stage. It can affect all levels of organization, from genes to the cells, tissues, and/or organs. In this study, a moderate water deficit was applied to two contrasting rice genotypes, IAC 25 and CIRAD 409, during their reproductive stage. Multi-level transcriptomic, metabolomic, physiological, and morphological analyses were performed to investigate the complex traits involved in their response to drought. Weighted gene network correlation analysis was used to identify the specific molecular mechanisms regulated by each genotype, and the correlations between gene networks and phenotypic traits. A holistic analysis of all the data provided a deeper understanding of the specific mechanisms regulated by each genotype, and enabled the identification of gene markers. Under non-limiting water conditions, CIRAD 409 had a denser shoot, but shoot growth was slower despite better photosynthetic performance. Under water deficit, CIRAD 409 was weakly affected regardless of the plant level analyzed. In contrast, IAC 25 had reduced growth and reproductive development. It regulated transcriptomic and metabolic activities at a high level, and activated a complex gene regulatory network involved in growth-limiting processes. By comparing two contrasting genotypes, the present study identified the regulation of some fundamental processes and gene markers, that drive rice development, and influence its response to water deficit, in particular, the importance of the biosynthetic and regulatory pathways for cell wall metabolism. These key processes determine the biological and mechanical properties of the cell wall and thus influence plant development, organ expansion, and turgor maintenance under water deficit. Our results also question the genericity of the antagonism between morphogenesis and organogenesis observed in the two genotypes.

Antimicrobial photodynamic therapy for the treatment of oral mucositis-A comparative study.

OBJECTIVES: The aim was to evaluate the effectiveness of photobiomodulation and antimicrobial photodynamic therapy in the treatment of oral mucositis. BACKGROUND: Oral Mucositis is a frequent complication of oral cavity and oropharynx cancer. Considering the OM aggravation by microorganisms contamination, disinfection provide by antimicrobial photodynamic therapy could be an effective approach. MATERIAL AND METHODS: This comparative study included fourteen patients undergoing radiochemotherapy for oral cavity and oropharynx cancer treatment, who developed oral mucositis. CONTROL GROUP: photobiomodulation. Intervention group: photobiomodulation and antimicrobial photodynamic therapy. The lesion size, duration, pain, and identification of microorganisms were evaluated. RESULTS: The mean reduction in oral mucositis size in the intervention group was 0.70 cm² (±0.35) and 0.30 cm² (±1.10) for the control group. The mean duration of oral mucositis was 18.37 days (±12.12) for the intervention group and 23 days (±14.78) for the control group. The intervention group had a mean reduction of 3.40 points on the pain scale (±2.44), while the control group had 0.17 (±2.28). In the intervention group, the predominant isolated microbiota was featured as mixed culture (n = 4/ 50%), followed of Gram Positive (n = 3/ 37.50%), and Gram Negative (n = 1/ 12.55%). In the control group, mixed culture was also more frequent (n = 4 / 66%), followed by Gram Positive (n = 2 /34%). Gram Negative was not predominantly isolated in the control group. CONCLUSION: No statistical significance was found between PBM-T alone and PBM-T + PDT. However, the better outcomes reached by PBM-T + PDT group would suggest there could be a role for combined treatment in the management of OM lesions.

Characteristics of whistles from rough-toothed dolphins (Steno bredanensis) in Rio de Janeiro coast, southeastern Brazil.

There is no information about the whistles of rough-toothed dolphins in the South Atlantic Ocean. This study characterizes the whistle structure of free-ranging rough-toothed dolphins recorded on the Rio de Janeiro coast, southeastern Brazil, and compares it to that of the same species in other regions. A total of 340 whistles were analyzed. Constant (N = 115; 33.8%) and ascending (N = 99; 29.1%) whistles were the most common contours. The whistles recorded had their fundamental frequencies between 2.24 and 13.94 kHz. Whistles without inflection points were frequently emitted (N = 255; 75%). Some signals presented breaks or steps in their contour (N = 97; 28.5%). Whistle duration was short (347 ± 236 ms and 89.7% of the whistles lasted <600 ms). Seventy-eight whistle contour types were found in the total of whistles analyzed, and 27 (7.9%) of these occurred only once. Most of the whistle types were unique to a particular recording session (N = 43). The signals emitted by the rough-toothed dolphins in southeastern Brazil were characterized by low frequency modulation, short duration, low number of inflection points, and breaks. Differences in the mean values of the whistle parameters were found between this and other studies that recorded Steno bredanensis, but as in other localities, whistles above 14 kHz are rare.

Development of an innovative nutraceutical fermented beverage from herbal mate (Ilex paraguariensis A.St.-Hil.) extract.

Herbal mate (Ilex paraguariensis A.St.-Hil.) leaves are traditionally used for their stimulant, antioxidant, antimicrobial, and diuretic activity, presenting as principal components polyphenolic compounds. The aim of this work was to develop an innovative, non-dairy, functional, probiotic, fermented beverage using herbal mate extract as a natural ingredient which would also be hypocholesterolemic and hepatoprotective. Among different strains used, Lactobacillus acidophilus was selected as the best for fermentation. The addition of honey positively affected the development of L. acidophilus and the formulated beverage maintained microbial stability during shelf life. Key ingredients in the extract included xanthines, polyphenols and other antioxidants with potential health benefits for the consumer. Caffeine levels and antioxidant activity were also studied. Acceptable levels of caffeine and large antioxidant capacity were observed for the formulation when compared to other antioxidant beverages. An advantage of this product is the compliance to organic claims, while providing caffeine, other phyto-stimulants and antioxidant compounds without the addition of synthetic components or preservatives in the formulation. Sensorial analysis demonstrated that the beverage had good consumer acceptance in comparison to two other similar commercial beverages. Therefore, this beverage could be used as a new, non-dairy vehicle for probiotic consumption, especially by vegetarians and lactose intolerant consumers. It is expected that such a product will have good market potential in an era of functional foods.

Clean and Confident: Impact of Sterile Instrument Processing Workshops on Knowledge and Confidence in Five Low- and Middle-Income Countries.

Background: Proper sterilization of surgical instruments is essential for safe surgery, yet re-processing methods in low-resource settings can fall short of standards. Training of Trainers (TOT) workshops in Ethiopia and El Salvador instructed participants in sterile processing concepts and prepared participants to teach others. This study examines participants' knowledge and confidence post-TOT workshop, and moreover discusses subsequent non-TOT workshops and observed sterile processing practices. Methods: Five TOT workshops were conducted between 2018 and 2020 in Ethiopia and Central America. Participant trainers then led nine non-TOT workshops in El Salvador, Guatemala, Honduras, and Nicaragua. Interactive sessions covered instrument cleaning, packaging, disinfection, sterilization, and transportation. Participants completed pre- and post-tests, demonstrated skill competencies, and shared feedback. Peri-operative sterile processing metrics were also observed in Ethiopian hospitals pre- and post-workshops. Results: Ninety-five trainees participated in TOT workshops, whereas 169 participated in non-TOT workshops. Knowledge on a 10-point scale increased substantially after all training sessions (+2.3 ± 2.8, +2.9 ± 1.7, and 2.7 ± 2.5 after Ethiopian, Central American, and non-TOT workshops, respectively; all p < 0.05). Scores on tests of sterile processing theory also increased (Ethiopian TOT, +68% ± 92%; Central American TOT, +26% ± 20%; p < 0.01). Most respondents felt "very confident" about teaching (Ethiopian TOT, 72%; Central American TOT, 83%; non-TOT, 70%), whereas fewer participants felt "very confident" enacting change (Ethiopian TOT, 36%; Central American TOT, 58%; non-TOT, 38%). Reasons included resource scarcity and inadequate support. Nonetheless, observed instrument compliance improved after Ethiopian TOT workshops (odds ratio [OR], 1.47; 95% confidence interval [CI], 1.21-1.78; p < 0.01). Conclusions: Sterile processing workshops can improve knowledge, confidence, and sterility compliance in selected low- and middle-income countries. Training of Trainers models empower participants to adapt programs locally, enhancing sterile processing knowledge in different communities. However, national guidelines, physical and administrative resources, and long-term follow-up must improve to ensure effective sterile processing.

Efficacy of a dinotefuran, permethrin and pyriproxyfen combination product in the treatment of rabbits (Oryctolagus cuniculus) naturally infested by Psoroptes ovis.

The main of this study was to evaluate the efficacy of dinotefuran, pyriproxyfen and permethrin-combination (Vectra 3D-CEVA) in the topical treatment of rabbits naturally infested with P. ovis. Adult New Zealand rabbits (n = 18) with plaques of crust in both ears were divided into three groups (one control and two treated). On day 0, the animals belonging to the treated groups received a single dose of a commercial ectoparasiticide formulation, recommended for use in dogs. The control group (G1) (n = 6) received no treatment, the treated group (G2) (n = 6) received one drop in each ear, and the remaining volume was applied along the back of the animal in the dorsal midline with the commercial formulation. In the other treated group (G3) (n = 6), animals received the same product used in G2, but all the volumes of 0.5 mL were applied only to the back of the animal (dorsal midline). On days 0, +7, +14, +21, +28 and +35, lesion scores and mites per gram (MPG) of each ear scab were evaluated. Statistical analysis was performed using the statistical software Bioestat 5.01. As the Shapiro-Wilk test determined that the data were nonparametrically distributed, the Kruskal-Wallis test was performed, followed by the Student-Newman-Keuls test, to determine the significance levels among the mean values of mite counts per gram of crusts compared to the three experimental groups. The efficacies for remission of lesion scores were 19.87 % on day +7 to 83.44 % on day +35 for G2 and 70.67 % on day +7 to 92.20 % on day +35 for G3. The efficacies obtained by evaluation of MPG were 100 % on day +7 to 99.86 % on day +35 for G2 and from 93.05 % on day +7 to 99.89 on day +35 for G3. The topical administration of the combination of dinotefuran (4.95 %), pyriproxifen (0.44 %) and permethrin (36 %) on the ears and back or only on the back in rabbits was shown to be effective in naturally controlling mite infestations by P. ovis.

A Serious Game (Immunitates) About Immunization: Development and Validation Study.

BACKGROUND: Vaccination is a fundamental part of all levels-local to worldwide-of public health, and it can be considered one of humanity's greatest achievements in the control and elimination of infectious diseases. Teaching immunization and vaccination can be monotonous and tiring. It is necessary to develop new approaches for teaching these themes in nursing school. OBJECTIVE: We aimed to develop and validate a serious game about immunization and vaccination for Brazilian nursing students. METHODS: We developed a quiz-type game, Immunitates, using design and educational theoretical models and Brazilian National Health Guidelines. The game's heuristics and content were evaluated with 2 different instruments by a team of experts. A sample of nursing students evaluated the validity of the game's heuristics only. We calculated the content validity index (CVI) for each evaluation. RESULTS: The study included 49 experts and 15 nursing students. All evaluations demonstrated high internal consistency (Cronbach α≥.86). The game's heuristics (experts: CVI 0.75-1.0; students: CVI 0.67-1.0) and the game's contents demonstrated validity (experts: CVI 0.73-1.0). Participants identified some specific areas for improvement in the next version. CONCLUSIONS: The serious game appears to be valid. It is intended as a support tool for nursing students in the teaching-learning process and as a tool for continuing education for nurses.

Burnout syndrome in healthcare workers during the COVID-19 pandemic: a systematic review.

There is evidence that harm to the mental health of healthcare workers has occurred during the pandemic caused by COVID-19. The burnout syndrome is a form of exhaustion that occurs in occupational settings and is a condition caused by long-term stress in the workplace. The objectives of this systematic review of observational studies were to present data from research into the prevalence of burnout syndrome in healthcare workers during the COVID-19 pandemic and observe its prevalence among frontline workers. The search was conducted on the MEDLINE, LILACS, and Embase databases from 2019 to May of 2021 and returned 538 publications, which underwent a two-stage process of selection by independent peers, resulting in selection of a sample of 29 articles. Data were then extracted and synthesized for presentation in narrative form. Cross-sectional designs were more prevalent (n = 26) than longitudinal studies (n = 3). The sample included research from 19 different countries, with one Brazilian study. A wide range of different instruments were administered by study authors to assess burnout syndrome, the most common of which was the Maslach Burnout Inventory (n = 13). The prevalence of burnout syndrome in the studies varied from 76 to 14.7%. Data on the relationship between development of burnout syndrome and working on the frontline were controversial. The lack of standardization of burnout syndrome assessment was a source of considerable difficulty, compromising comparability of the results, and should therefore be targeted for improvement by researchers. We suggest that more investigations should be conducted into prevalence and the associated factors of risk and protection.