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Bruno L Raposo,1,* Sueden O Souza,1,* Gleyciane S Santana,1 Max TA Lima,2 José F Sarmento-Neto,3 Júlio S Reboucas,3 Goreti Pereira,2,4 Beate S Santos,5 Paulo E Cabral Filho,1 Martha S Ribeiro,6 Adriana Fontes1 1Departamento de Biofísica e Radiobiologia, Universidade Federal de Pernambuco, Recife, PE, Brazil; 2Departamento de Química Fundamental, Universidade Federal de Pernambuco, Recife, PE, Brazil; 3Departamento de Química, Universidade Federal da Paraíba, João Pessoa, PB, Brazil; 4Departamento de Química & CESAM, Universidade de Aveiro, Aveiro, Portugal; 5Departamento de Ciências Farmacêuticas, Universidade Federal de Pernambuco, Recife, PE, Brazil; 6Centro de Lasers e Aplicações, Instituto de Pesquisas Energéticas e Nucleares (IPEN-CNEN/SP), São Paulo, SP, Brazil*These authors contributed equally to this workCorrespondence: Adriana Fontes; Sueden O Souza, Departamento de Biofísica e Radiobiologia, Universidade Federal de Pernambuco, Recife, PE, 50670-901, Brazil, Email adriana.fontes@ufpe.br; eden.su.souza@gmail.comBackground: Photodynamic inactivation (PDI) is an attractive alternative to treat Candida albicans infections, especially considering the spread of resistant strains. The combination of the photophysical advantages of Zn(II) porphyrins (ZnPs) and the plasmonic effect of silver nanoparticles (AgNPs) has the potential to further improve PDI. Here, we propose the novel association of polyvinylpyrrolidone (PVP) coated AgNPs with the cationic ZnPs Zn(II) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin or Zn(II) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin to photoinactivate C. albicans.Methods: AgNPs stabilized with PVP were chosen to allow for (i) overlap between the NP extinction and absorption spectra of ZnPs and (ii) favor AgNPs-ZnPs interaction; prerequisites for exploring the plasmonic effect. Optical and zeta potential (ζ) characterizations were performed, and reactive oxygen species (ROS) generation was also evaluated. Yeasts were incubated with individual ZnPs or their respective AgNPs-ZnPs systems, at various ZnP concentrations and two proportions of AgNPs, then irradiated with a blue LED. Interactions between yeasts and the systems (ZnP alone or AgNPs-ZnPs) were evaluated by fluorescence microscopy.Results: Subtle spectroscopic changes were observed for ZnPs after association with AgNPs, and the ζ analyses confirmed AgNPs-ZnPs interaction. PDI using ZnP-hexyl (0.8 μM) and ZnP-ethyl (5.0 μM) promoted a 3 and 2 log10 reduction of yeasts, respectively. On the other hand, AgNPs-ZnP-hexyl (0.2 μM) and AgNPs-ZnP-ethyl (0.6 μM) systems led to complete fungal eradication under the same PDI parameters and lower porphyrin concentrations. Increased ROS levels and enhanced interaction of yeasts with AgNPs-ZnPs were observed, when compared with ZnPs alone.Conclusion: We applied a facile synthesis of AgNPs which boosted ZnP efficiency. We hypothesize that the plasmonic effect combined with the greater interaction between cells and AgNPs-ZnPs systems resulted in an efficient and improved fungal inactivation. This study provides insight into the application of AgNPs in PDI and helps diversify our antifungal arsenal, encouraging further developments toward inactivation of resistant Candida spp.Keywords: photodynamic inactivation, fungi, plasmon, photosensitizer

Despite the large number of studies discussing the prevalence of psychiatry disorders in the general population, only a few compare patients with minor/moderate disorders with those with more severe ones, chiefly at the primary/secondary level interface. This article compares patients with minor/moderate psychiatric disorders to those with more severe ones, as refers to demographic, socioeconomic, psycho-pathological and treatment variables. This was an observational study, evaluating 876 patients, referred by five primary care units from Juiz de Fora- MG, Brazil, to a first consultation at the mental health secondary service that is a referral center for the western area of the city. Bivariate analyses were performed in order to establish possible associations (p < 0.05) between severe mental disorders and 69 variables included in the study. Of the variables, 6 demographic, 3 socioeconomic, 22-psycho-pathological and interactive, and 5 related to treatment or the referral/counter-referral process were associated with severe mental disorders. The variables analyzed came from the semi-structured clinical files of the Juiz de Fora Municipal Health System, were generated from a combination of variables, or were collected from the referral form to the secondary level, filled out by the basic health unit staff. Besides being a baseline for studies comparing patients with severe mental disorders to those with less severe ones, the results may help to improve the quality of mental health care. [ABSTRACT FROM AUTHOR]

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Background: Bedside ultrasonography, also known as point-of-care ultrasound (PoCUS), is a promising technological tool that enhances clinical assessment, enriching diagnostic capabilities and clinical reasoning. Its use in nursing spans various patient populations and health care settings, providing nurses with a valuable health assessment tool to improve care quality and patient safety. Despite its growing integration into clinical practice, PoCUS training has mainly focused on physicians, leaving a gap for trained nurses who demonstrate similar proficiency in conducting scans and interpreting images. Previous research highlights the value of digital tools in PoCUS training, showing their role in improving professionals' and students' knowledge, image interpretation skills, and clinical acumen., Objective: This study aimed to (1) establish an assessment instrument gauging nurses' competency milestones in PoCUS and evaluate its content and appearance validity, (2) develop a series of 5 educational videos focused on PoCUS and assess their content and appearance validity, and (3) construct an online learning environment tailored to nurses' PoCUS training needs and evaluate its content and appearance validity., Methods: We will conduct a methodological study of technological production guided by Rogers' diffusion of innovations theory. Subproject 1 will design and validate a comprehensive assessment tool for evaluating nurses' competency milestones in PoCUS use. For this purpose, a scoping review will be conducted. The review will be based on JBI Collaboration guidelines and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extended for Scoping Reviews (PRISMA-ScR) checklist. Subproject 2 involves an evaluation of content and appearance validity for a series of 5 educational videos on PoCUS, designed specifically for nurses about applying peripherally inserted central catheter lines, inserting nasogastric feeding tubes, assessing gastric residual volume, assessing pressure injuries and soft tissue conditions, and assessing muscle mass to monitor patient nutritional status. In subproject 3, a comprehensive online learning environment dedicated to PoCUS training for nurses will be developed and validated. The launch of an online learning environment represents a cornerstone of our dissemination strategy, scheduled to coincide with the inaugural Brazilian PoCUS symposium for nurses, an event organized by the project members. This platform will serve as a pivotal resource for continuous learning and professional development., Results: Subproject 1 will start in the second half of 2024 and is expected to be completed by mid-2025. Subproject 2 is currently ongoing and is expected to be completed in early 2026. Subproject 3 is set to begin in early 2025 and is planned to be completed by 2026., Conclusions: Through these concerted efforts, the project aims to bridge the existing gap in PoCUS training for nurses, thereby fostering their proficiency and enhancing patient care outcomes., International Registered Report Identifier (irrid): PRR1-10.2196/58030., (©Fernanda Raphael Escobar Gimenes, Angelita Maria Stabile, Rodrigo Magri Bernardes, Vinicius Batista Santos, Mayra Gonçalves Menegueti, Patricia Rezende do Prado, Mauricio Serra Ribeiro, Flavia Giron Camerini, Soraia Assad Nasbine Rabeh. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 23.10.2024.)

Introduction: Human aortic tissues in vitro are tools to clarify the pathophysiological mechanisms of the cardiovascular system, cell culture, and transplants. Therefore, this study aims to analyze and compare the preservation of human aneurysmatic aortic tissues in three different solutions., Methods: Six human abdominal aortic aneurysms were obtained from patients after surgical ablation. The aorta samples were incubated in different solutions - 0.9% normal physiological saline solution, Ringer's lactate solution, and histidine-tryptophan-ketoglutarate solution (Custodiol®). Segments were collected at 0, 6, 24, and 48 hours. Creatine kinase and nitrate/nitrite were quantified for each incubation time. The tissue's alpha-smooth muscle actin was analyzed by immunofluorescence., Results: There was a significant increase in creatine kinase formation in the normal saline group at 0 and 48 hours and in the Ringer's lactate group at 0 and 48 hours (P=0.018 and P=0.028). The lower levels of creatine kinase and nitrate/nitrite and the aortic tissues' morphological integrity show that histidine-tryptophan-ketoglutarate has better tissue protection. These data suggest that histidine-tryptophan-ketoglutarate induces a protective effect on smooth muscle cells, with less tissue depletion in the aortic aneurysm., Conclusion: This study compared three preservation solutions with the potential for human abdominal aortic aneurysm tissue preservation. The histidine-tryptophan-ketoglutarate solution reduced tissue injury and improved tissue preservation in human abdominal aortic aneurysm tissue samples.

Cutaneous leishmaniasis (CL) is a neglected disease caused by Leishmania parasites. The oral drug miltefosine is effective, but there is a growing problem of drug resistance, which has led to increasing treatment failure rates and relapse of infections. Photodynamic therapy (PDT) combines a light source and a photoactive drug to promote cell death by oxidative stress. Although PDT is effective against several pathogens, its use against drug-resistant Leishmania parasites remains unexplored. Herein, we investigated the potential of organic light-emitting diodes (OLEDs) as wearable light sources, which would enable at-home use or ambulatory treatment of CL. We also assessed its impact on combating miltefosine resistance in Leishmania amazonensis-induced CL in mice. The in vitro activity of OLEDs combined with 1,9-dimethyl-methylene blue (DMMB) (OLED-PDT) was evaluated against wild-type and miltefosine-resistant L. amazonensis strains in promastigote (EC 50 = 0.034 μM for both strains) and amastigote forms (EC 50 = 0.052 μM and 0.077 μM, respectively). Cytotoxicity in macrophages and fibroblasts was also evaluated. In vivo, we investigated the potential of OLED-PDT in combination with miltefosine using different protocols. Our results demonstrate that OLED-PDT is effective in killing both strains of L. amazonensis by increasing reactive oxygen species and stimulating nitric oxide production. Moreover, OLED-PDT showed great antileishmanial activity in vivo, allowing the reduction of miltefosine dose by half in infected mice using a light dose of 7.8 J/cm 2 and 15 μM DMMB concentration. In conclusion, OLED-PDT emerges as a new avenue for at-home care and allows a combination therapy to overcome drug resistance in cutaneous leishmaniasis., Competing Interests: Declaration of Competing Interest Competing Interests: I.D.W.S. is a founder and shareholder of Lustre Skin Ltd, which develops wearable light sources for the treatment of acne., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The end of South American isolation during the Great American Biotic Interchange (GABI) promoted the contact between South and North American saber-tooth forms that evolved in isolation. This contact may have driven saber-tooth species to a competitive interaction, resulting in the extinction of the South American saber-tooth form. Here, we used paleoclimatic data to compare the climatic niche of the saber-tooth forms Thylacosmilus atrox (from South America), Smilodon fatalis, and Smilodon populator (both originally from North America). We evaluated niche width, overlap, and similarity to infer potential geographic distribution overlap and competition between these North and South American predators. To do so, we obtained the climatic variables from sites where occurrence fossil records were available. Our results suggest that T. atrox had a narrower climatic niche compared to Smilodon species. Although we found a significant climatic niche overlap and similarity between S. fatalis and T. atrox, it seems unlikely that both species have co-occurred. Low niche overlap and similarity between T. atrox and S. populator dismiss competitive interaction between them. Moreover, climatic niche and low tolerance for environmental changes may have been the cause of the South American saber-tooth extinction., (© 2024. The Author(s).)

Objective: We sought to examine the association between chronic Benzodiazepine (BZD) use and brain metabolism obtained from 2-deoxy-2-fluoro-D-glucose (FDG) positron emission tomography (PET) in the MEMENTO clinical cohort of nondemented older adults with an isolated memory complaint or mild cognitive impairment at baseline., Methods: Our analysis focused on 3 levels: (1) the global mean brain standardized uptake value (SUVR), (2) the Alzheimer's disease (AD)-specific regions of interest (ROIs), and (3) the ratio of total SUVR on the brain and different anatomical ROIs. Cerebral metabolism was obtained from 2-deoxy-2-fluoro-D-glucose-FDG-PET and compared between chronic BZD users and nonusers using multiple linear regressions adjusted for age, sex, education, APOE ε 4 copy number, cognitive and neuropsychiatric assessments, history of major depressive episodes and antidepressant use., Results: We found that the SUVR was significantly higher in chronic BZD users (n = 192) than in nonusers (n = 1,122) in the whole brain (beta = 0.03; p = 0.038) and in the right amygdala (beta = 0.32; p = 0.012). Trends were observed for the half-lives of BZDs (short- and long-acting BZDs) (p = 0.051) and Z-drug hypnotic treatments (p = 0.060) on the SUVR of the right amygdala. We found no significant association in the other ROIs., Conclusion: Our study is the first to find a greater global metabolism in chronic BZD users and a specific greater metabolism in the right amygdala. Because the acute administration of BZDs tends to reduce brain metabolism, these findings may correspond to a compensatory mechanism while the brain adapts with global metabolism upregulation, with a specific focus on the right amygdala., (Copyright © 2023 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

The aims of the present study were to identify strongyles in the feces of Thoroughbred horses based on larval morphology; to detect Strongylus vulgaris using molecular diagnosis and compare results to those of feces culture; and to determine the association between the presence of S. vulgaris with corresponding animal information (age range, gender, and anthelmintic use). Feces of horses kept in six Training Centers in Rio de Janeiro State, that showed the presence of ≥500 eggs per gram of feces (EPG) were subjected to strongyle identification. Of the 520 fecal samples collected, 35 had an EPG ≥ 500. After fecal culture for L3 larvae identification, DNA was extracted, subjected to PCR to amplify the ITS2 region DNA fragment of S. vulgaris, and sequenced. A total of 3500 larvae were analyzed. Most were classified as small strong (99.7%), with an emphasis on the type A subfamily of Cyathostominae. Forms of S. vulgaris only corresponded to 0.2%. In all, 25 samples showed amplified S. vulgaris DNA products and 11 showed nucleotide sequences with high sequence identity. Fecal culture and PCR results showed poor agreement (kappa = 0.105) for S. vulgaris diagnosis. Age, gender, anthelmintic use, and anthelmintic administration interval were not statistically significant. The present study showed the presence of S. vulgaris in the feces of horses kept in Rio de Janeiro Training Centers, mainly seen via PCR, which has emerged as the most effective tool for diagnosis. This study made it possible to identify strongyles that infect horses in the region, emphasizing upon the necessity for constant monitoring of the animals., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To evaluate whether the continuous support provided by doulas influences the endogenous release of serotonin in parturients., Methods: This pilot study included 24 primigravidae at term. Of these, 12 women received continuous doula support (Experimental Group), whereas the other 12 received the usual assistance without doula support (Control Group). Blood samples were collected from all the women at the active and expulsion stages of labor and at the fourth period of labor (Greenberg period) for evaluation of their serotonin levels using high-performance liquid chromatography., Results: The average serotonin concentrations in the control and experimental groups were respectively 159.33 and 150.02 ng/mL at the active stage, 179.13 and 162.65 ng/mL at the expulsion stage, and 198.94 and 221.21 ng/mL at the Greenberg period. There were no statistically significant differences in serotonin concentrations between the two groups at the active and expulsion stages of labor. By contrast, within the experimental group, a significant increase in serotonin concentration was observed in the Greenberg period compared with the levels in the active and expulsion stages (p < 0.05)., Conclusion: The novelty of this study relies on the ability to correlate the influence of the continuous support offered by doulas with the release of serotonin in parturients, with the results suggesting that the assistance received during labor can modulate the levels of hormone release in the Greenberg period., Brazilian Registry of Clinical Trials: RBR-4zjjm4h., Competing Interests: Conflicts to interest: none to declare., (© 2023. Federação Brasileira de Ginecologia e Obstetrícia. All rights reserved.)

Orosomucoid, or alpha-1 acid glycoprotein (AGP), is a major acute-phase protein expressed in response to systemic injury and inflammation. AGP has been described as an inhibitor of neutrophil migration on sepsis, particularly its immunomodulation effects. AGP's biological functions in coronavirus disease 2019 (COVID-19) are not understood. We sought to investigate the role of AGP in severe COVID-19 infection patients and neutrophils infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Epidemiological data, AGP levels, and other laboratory parameters were measured in blood samples from 56 subjects hospitalized in the ICU with SARS-CoV-2 infection. To evaluate the role of AGP in NETosis in neutrophils, blood samples from health patients were collected, and neutrophils were separated and infected with SARS-CoV-2. Those neutrophils were treated with AGP or vehicle, and NETosis was analyzed by flow cytometry. AGP was upregulated in severe COVID-19 patients (p<0.05). AGP level was positively correlated with IL-6 and C-reactive protein (respectively, p=0.005, p=0.002) and negatively correlated with lactate (p=0.004). AGP treatment downregulated early and late NETosis (respectively, 35.7% and 43.5%) in neutrophils infected with SARS-CoV-2 and up-regulated IL-6 supernatant culture expression (p<0.0001). Our data showed increased AGP in COVID-19 infection and contributed to NETosis regulation and increased IL-6 production, possibly related to the Cytokine storm in COVID-19., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In this study, videothermometry's application in detecting mammary tumors in dogs is explored in-depth. The research hypothesizes that this technique can effectively identify cancerous tissues during surgery by analyzing thermal patterns. The methodology involved comparing thermal imaging results from dogs with palpable mammary nodules against a control group, focusing on capturing real-time thermal patterns. Results were significant, showing distinct thermal patterns in carcinomas. This indicates videothermometry's capability in accurately identifying micro metastases and differentiating between neoplastic and non-neoplastic changes. The study concludes that videothermometry has considerable potential in enhancing surgical precision, especially in tumor resection and safety margin definition, but emphasizes the need for further research to thoroughly understand the thermal signatures of various mammary tumors in dogs.

Primary cell cultures are essential tools for elucidating the physiopathological mechanisms of the cardiovascular system. Therefore, a primary culture growth protocol of cardiovascular smooth muscle cells (VSMCs) obtained from human abdominal aortas was standardized. Ten abdominal aorta samples were obtained from patients diagnosed with brain death who were organ and tissue donors with family consent. After surgical ablation to capture the aorta, the aortic tissue was removed, immersed in a Custodiol® solution, and kept between 2 and 8 °C. In the laboratory, in a sterile environment, the tissue was fragmented and incubated in culture plates containing an enriched culture medium (DMEM/G/10% fetal bovine serum, L-glutamine, antibiotics and antifungals) and kept in an oven at 37 °C and 5% CO 2 . The aorta was removed after 24 h of incubation, and the culture medium was changed every six days for twenty days. Cell growth was confirmed through morphological analysis using an inverted optical microscope (Nikon®) and immunofluorescence for smooth muscle alpha-actin and nuclei. The development of the VSMCs was observed, and from the twelfth day, differentiation, long cytoplasmic projections, and adjacent cell connections occurred. On the twentieth day, the morphology of the VSMCs was confirmed by actin fiber immunofluorescence, which is a typical characteristic of VSMCs. The standardization allowed VSMC growth and the replicability of the in vitro test, providing a protocol that mimics natural physiological environments for a better understanding of the cardiovascular system. Its use is intended for investigation, tissue bioengineering, and pharmacological treatments., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: This study is a systematic review with meta-analysis comparing radioactive seed localization (RSL) versus radio-guided occult lesion localization (ROLL) and wire-guided localization (WGL) for patients with impalpable breast cancer undergoing breast-conserving surgery and evaluating efficacy, safety, and logistical outcomes. The protocol is registered in PROSPERO with the number CRD42022299726., Methods: A search was conducted in the Embase, Lilacs, Pubmed, Scielo, Web of Science, and clinicaltrials.gov databases, in addition to a manual search in the reference list of relevant articles, for randomized clinical trials and cohort studies. Studies selected were submitted to their own data extraction forms and risk of bias analysis according to the ROB 2 and ROBINS 1 tools. A meta-analysis was performed, considering the random effect model, calculating the relative risk or the mean difference for dichotomous or continuous data, respectively. The quality of the evidence generated was analyzed by outcome according to the GRADE tool. Overall, 46 articles met the inclusion criteria and were included in this systematic review; of these, 4 studies compared RSL and ROLL with a population of 1550 women, and 43 compared RSL and WGL with a population of 19,820 women., Results: The results showed that RSL is a superior method to WGL in terms of surgical efficiency in the impalpable breast lesions' intraoperative localization, and it is at least equivalent to ROLL. Regarding security, RSL obtained results equivalent to the already established technique, the WGL. In addition to presenting promising results, RSL has been proven to be superior to WGL and ROLL technologies.

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., (©2023 by Radiation Research Society. All rights of reproduction in any form reserved.)

Background: Carnivore mammals are animals vulnerable to human interference, such as climate change and deforestation. Their distribution and persistence are affected by such impacts, mainly in tropical regions such as the Amazon. Due to the importance of carnivores in the maintenance and functioning of the ecosystem, they are extremely important animals for conservation. We evaluated the impact of climate change on the geographic distribution of carnivores in the Amazon using Species Distribution Models (SDMs). Do we seek to answer the following questions: (1) What is the effect of climate change on the distribution of carnivores in the Amazon? (2) Will carnivore species lose or gain representation within the Protected Areas (PAs) of the Amazon in the future?, Methods: We evaluated the distribution area of 16 species of carnivores mammals in the Amazon, based on two future climate scenarios (RCP 4.5 and RCP 8.5) for the year 2070. For the construction of the SDMs we used bioclimatic and vegetation cover variables (land type). Based on these models, we calculated the area loss and climate suitability of the species, as well as the effectiveness of the protected areas inserted in the Amazon. We estimated the effectiveness of PAs on the individual persistence of carnivores in the future, for this, we used the SDMs to perform the gap analysis. Finally, we analyze the effectiveness of PAs in protecting taxonomic richness in future scenarios., Results: The SDMs showed satisfactory predictive performance, with Jaccard values above 0.85 and AUC above 0.91 for all species. In the present and for the future climate scenarios, we observe a reduction of potencial distribution in both future scenarios (RCP4.5 and RCP8.5), where five species will be negatively affected by climate change in the RCP 4.5 future scenario and eight in the RCP 8.5 scenario. The remaining species stay stable in terms of total area. All species in the study showed a loss of climatic suitability. Some species lost almost all climatic suitability in the RCP 8.5 scenario. According to the GAP analysis, all species are protected within the PAs both in the current scenario and in both future climate scenarios. From the null models, we found that in all climate scenarios, the PAs are not efficient in protecting species richness., Competing Interests: The authors declare there are no competing interests., (©2023 Ferreira Leão et al.)

The emergence of drug resistance in cutaneous leishmaniasis (CL) has become a major problem over the past decades. The spread of resistant phenotypes has been attributed to the wide misuse of current antileishmanial chemotherapy, which is a serious threat to global health. Photodynamic therapy (PDT) has been shown to be effective against a wide spectrum of drug-resistant pathogens. Due to its multi-target approach and immediate effects, it may be an attractive strategy for treatment of drug-resistant Leishmania species. In this study, we sought to evaluate the activity of PDT in vitro using the photosensitizer 1,9-dimethyl methylene blue (DMMB), against promastigotes of two Leishmania amazonensis strains: the wild-type (WT) and a lab induced miltefosine-resistant (MFR) strain. The underlying mechanisms of DMMB-PDT action upon the parasites was focused on the changes in the lipid metabolism of both strains, which was conducted by a quantitative lipidomics analysis. We also assessed the production of ROS, mitochondrial labeling and lipid droplets accumulation after DMMB-PDT. Our results show that DMMB-PDT produced high levels of ROS, promoting mitochondrial membrane depolarization due to the loss of membrane potential. In addition, both untreated strains revealed some differences in the lipid content, in which MFR parasites showed increased levels of phosphatidylcholine, hence suggesting this could also be related to their mechanism of resistance to miltefosine. Moreover, the oxidative stress and consequent lipid peroxidation led to significant phospholipid alterations, thereby resulting in cellular dysfunction and parasite death. Thus, our results demonstrated that DMMB-mediated PDT is effective to kill L. amazonensis MFR strain and should be further studied as a potential strategy to overcome antileishmanial drug resistance., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Cabral et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The aims of this study were to determine the prevalence of helminths in Thoroughbred horses in Rio de Janeiro; make correlations with risk factors for these infections; and compare the efficiency of three floatation solutions applied in the quantitative Mini-FLOTAC technique. Fecal samples from 520 horses were collected from six training centers between 2019 and 2021. These were subjected to the Mini-FLOTAC technique using three solutions: NaCl (density = 1.200 g/mL), ZnSO 4 (1.350 g/mL) and ZnSO 4 (1.200 g/mL); and also to qualitative techniques. Information on the horses' sex and age of horses was retrieved from the studbook; data on management from a questionnaire. The overall prevalence of intestinal parasites was 71.9%, with significant differences between training centers (P ≤ .05). On farm C, 87.7% of the samples presented strongylids and 38.7% had Parascaris spp., with the highest egg counts per gram of feces (EPG), of 358.33 and 40.41 respectively. Horses less than 3 years of age were about eight times more likely to be parasitized by strongylids and eleven times more likely to have EPG ≥500. The NaCl solution used in Mini-FLOTAC enabled recovery of the greatest number of samples with high EPG and reached the highest sensitivity values in the diagnosis when compared to the other solutions. Moreover, in the diagnoses, the levels of agreement between the results from the solutions used in Mini-FLOTAC were substantial. However, in estimating the EPG, full agreement between the results from the solutions used in Mini-FLOTAC was not obtained., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Melanoma is a serious and aggressive type of skin cancer with growing incidence, and it is the leading cause of death among those affected by this disease. Although surgical resection has been employed as a first-line treatment for the early stages of the tumor, noninvasive topical treatments might represent an alternative option. However, they can be irritating to the skin and result in undesirable side effects. In this context, the potential of topical polymeric hydrogels has been investigated for biomedical applications to overcome current limitations. Due to their biocompatible properties, hydrogels have been considered ideal candidates to improve local therapy and promote wound repair. Moreover, drug combinations incorporated into the polymeric-based matrix have emerged as a promising approach to improve the efficacy of cancer therapy, making them suitable vehicles for drug delivery. In this work, we demonstrate the synthesis and characterization of Pluronic F-127 hydrogels (PL) containing the nitric oxide donor S-nitrosoglutathione (GSNO) and copper oxide nanoparticles (CuO NPs) against melanoma cells. Individually applied NO donor or metallic oxide nanoparticles have been widely explored against various types of cancer with encouraging results. This is the first report to assess the potential and possible underlying mechanisms of action of PL containing both NO donor and CuO NPs toward cancer cells. We found that PL + GSNO + CuO NPs significantly reduced cell viability and greatly increased the levels of reactive oxygen species. In addition, this novel platform had a huge impact on different organelles, thus triggering cell death by inducing nuclear changes, a loss of mitochondrial membrane potential, and lipid peroxidation. Thus, GSNO and CuO NPs incorporated into PL hydrogels might find important applications in the treatment of skin cancer.

Background: Venous thromboembolism is the third most common cardiovascular disease and the main cause of preventable death in hospitalized patients. Prophylaxis is still underused, despite well-established guidelines in the literature. Studies show a worldwide prophylaxis adequacy rate close to 50%., Objectives: To assess the adequacy of risk stratification and prophylactic measures for venous thromboembolism in a tertiary university hospital., Methods: A cross-sectional observational study was carried out, collecting data from medical records. Adult patients hospitalized by different specialties were enrolled and divided into surgical and clinical groups. The risk stratification of venous thromboembolism performed by the attending physicians was compared with stratification based on recent guidelines performed by the research physicians. Prophylaxis measures prescribed by the attending physicians were compared with guideline recommendations, thus obtaining the prophylaxis adequacy rate., Results: 400 patients were analyzed, 169 (42.3%) surgical and 231 (57.7%) clinical. The overall stratification adequacy rate was 50.8%. Adequacy rates were 39.1% and 59.3% in the surgical and clinical groups respectively (P < 0.0001). The overall prophylaxis adequacy rate was 71.5%, with 78.1% in the surgical group and 66.7% in the clinical group (P=0.0137)., Conclusions: Risk stratification adequacy is low, demonstrating a low awareness among prescribing physicians of the need for adequate stratification for prescription of prophylaxis. However, the prophylaxis prescription adequacy rates are higher than those in global data., Competing Interests: Conflicts of interest: No conflicts of interest declared concerning the publication of this article., (Copyright© 2023 The authors.)

Dengue (DENV), chikungunya (CHIKV), and Zika (ZIKV) virus infections are widespread throughout the Rio de Janeiro state. The co-circulation of these emergent arboviruses constitutes a serious public health problem, resulting in outbreaks that can spatially and temporally overlap. Environmental conditions favor the presence, maintenance, and expansion of Aedes aegypti , the primary vector of these urban arboviruses. This study assessed the detection of clusters of urban arboviruses in the Rio de Janeiro state from 2010 to 2019. Notified cases of dengue, chikungunya, and Zika were grouped by year according to the onset of symptoms and their municipality of residence. The study period recorded the highest number of dengue epidemics in the state along with the simultaneous circulation of chikungunya and Zika viruses. The analyzes showed that the central municipalities of the metropolitan regions were associated with higher risk areas. Central municipalities in metropolitan regions were the first most likely clusters for dengue and Zika, and the second most likely cluster for chikungunya. Furthermore, the northwest and north regions were comprised clusters with the highest relative risk for the three arboviruses, underscoring the impact of these arboviruses in less densely populated regions of Brazil. The identification of high-risk areas over time highlights the need for effective control measures, targeted prevention and control interventions for these urban arboviral diseases.

In recent years, Candida auris has emerged as a hazardous hospital-acquired pathogen. Its resistance to antifungal treatments makes it challenging, requiring new approaches to manage it effectively. Herein, we aimed to assess the impact of photodynamic inactivation mediated by methylene blue (MB-PDI) or 1,9-dimethyl MB (DMMB-PDI) combined with a red LED against C. auris . To evaluate the photoinactivation of yeasts, we quantified colony-forming units and monitored ROS production. To gain some insights into the differences between MB and DMMB, we assessed lipid peroxidation (LPO) and mitochondrial membrane potential (ΔΨm). After, we verified the effectiveness of DMMB against biofilms by measuring metabolic activity and biomass, and the structures were analyzed through scanning electron microscopy and optical coherence tomography. We also evaluated the cytotoxicity in mammalian cells. DMMB-PDI successfully eradicated C. auris yeasts at 3 μM regardless of the light dose. In contrast, MB (100 μM) killed cells only when exposed to the highest dose of light. DMMB-PDI promoted higher ROS, LPO and ΔΨm levels than those of MB. Furthermore, DMMB-PDI was able to inhibit biofilm formation and destroy mature biofilms, with no observed toxicity in fibroblasts. We conclude that DMMB-PDI holds great potential to combat the global threat posed by C. auris .

The frequency of gastrointestinal parasites with an emphasis on Strongylus vulgaris was investigated among the Brazilian Pony breed kept on farms in the municipality of Teresópolis, state of Rio de Janeiro. Fecal samples were collected in three stud farms: A (n= 22 animals), B (n= 3), and C (n= 2). Fecal samples were subjected to the quantitative Mini-FLOTAC technique, using three different solutions, and to qualitative techniques. The parasite prevalence was found to be 81.4%. Eggs from strongylids were identified in 74% of the ponies. Eggs of Parascaris spp. were detected in 22.7% of the animals, which were all females of farm A. At this locality, mares were kept with their foals in fenced paddocks all the time. The NaCl solution of d = 1.200 g/ml was generally the one that presented the highest frequency of diagnosis of nematode eggs and the highest mean of fecal eggs per gram. The fecal samples were also subjected to the polymerase chain reaction for amplification of DNA from the ITS2 region for Strongylus vulgaris. Twelve samples presented nucleotide sequences for S. vulgaris. In the end, this study revealed the high frequency (96.3%) of S. vulgaris among ponies on farms in Teresópolis, Rio de Janeiro, Brazil.

Background: Cutaneous leishmaniasis (CL) is an important tropical neglected disease with broad geographical dispersion. The lack of effective drugs has raised an urgent need to improve CL treatment, and antimicrobial photodynamic therapy (APDT) has been investigated as a new strategy to face it with positive outcomes. Natural compounds have emerged as promising photosensitizers (PSs), but their use in vivo remains unexplored., Purpose: In this work, we investigated the potential of three natural anthraquinones (AQs) on CL induced by Leishmania amazonensis in BALB/c mice., Study Design/methods: ANIMALS WERE INFECTED AND RANDOMLY DIVIDED INTO FOUR GROUPS: CG (control, non-treated group), G5ClSor-gL (treated with 5-chlorosoranjidiol and green LED, 520±10 nm), GSor-bL and GBisor-bL (treated with soranjidiol and bisoranjidiol, respectively, exposed to violet-blue LED, 410±10 nm). All AQs were assayed at 10 μM and LEDs delivered a radiant exposure of 45 J/cm 2 with an irradiance of 50 mW/cm 2 . We assessed the parasite burden in real time for three consecutive days. Lesion evolution and pain score were assessed over 3 weeks after a single APDT session., Results: G5ClSor-gL was able to sustain low levels of parasite burden over time. Besides, GSor-bL showed a smaller lesion area than the control group, inhibiting the disease progression., Conclusion: Taken together, our data demonstrate that monoAQs are promising compounds for pursuing the best protocol for treating CL and helping to face this serious health problem. Studies involving host-pathogen interaction as well as monoAQ-mediated PDT immune response are also encouraged., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The unbridled use of antimicrobial drugs over the last decades contributed to the global dissemination of drug-resistant pathogens and increasing rates of life-threatening infections for which limited therapeutic options are available. Currently, the search for safe, fast, and effective therapeutic strategies to combat infectious diseases is a worldwide demand. Antimicrobial photodynamic therapy (APDT) rises as a promising therapeutic approach against a wide range of pathogenic microorganisms. APDT combines light, a photosensitizing drug (PS), and oxygen to kill microorganisms by oxidative stress. Since the APDT field involves branches of biology and physics, the strengthening of interdisciplinary collaborations under the aegis of biophysics is welcome. Given this scenario, Brazil is one of the global leaders in the production of APDT science. In this review, we provide detailed reports of APDT studies published by the Laboratory of Optical Therapy (IPEN-CNEN), Group of Biomedical Nanotechnology (UFPE), and collaborators over the last 10 years. We present an integrated perspective of APDT from basic research to clinical practice and highlight its promising use, encouraging its adoption as an effective and safe technology to tackle important pathogens. We cover the use of methylene blue (MB) or Zn(II) porphyrins as PSs to kill bacteria, fungi, parasites, and pathogenic algae in laboratory assays. We describe the impact of MB-APDT in Dentistry and Veterinary Medicine to treat different infectious diseases. We also point out future directions combining APDT and nanotechnology. We hope this review motivates further APDT studies providing intuitive, vivid, and insightful information for the readers., Competing Interests: Conflict of interestThe authors declare no competing interests., (© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Cutaneous leishmaniasis is a neglected parasitic disease that leads to destructive lesions. The emergence of drug resistance has been a global concern over the past years. Photodynamic therapy (PDT) mediated by a red LED and methylene blue (MB) involves the overproduction of oxidative stress, which oxidizes several cellular biomolecules and prevents the selection of resistant strains. Herein, we investigated the potential of PDT mediated by MB against wild-type and miltefosine-resistant strains of Leishmania amazonensis. As a result, both strains were susceptible to PDT, thus encouraging us to seek the best conditions to overcome the drug resistance problem in cutaneous leishmaniasis.

The unbridled dissemination of multidrug-resistant pathogens is a major threat to global health and urgently demands novel therapeutic alternatives. Antimicrobial photodynamic therapy (aPDT) has been developed as a promising approach to treat localized infections regardless of drug resistance profile or taxonomy. Even though this technique has been known for more than a century, discussions and speculations regarding the biochemical mechanisms of microbial inactivation have never reached a consensus on what is the primary cause of cell death. Since photochemically generated oxidants promote ubiquitous reactions with various biomolecules, researchers simply assumed that all cellular structures are equally damaged. In this study, biochemical, molecular, biological and advanced microscopy techniques were employed to investigate whether protein, membrane or DNA damage correlates better with dose-dependent microbial inactivation kinetics. We showed that although mild membrane permeabilization and late DNA damage occur, no correlation with inactivation kinetics was found. On the other hand, protein degradation was analyzed by three different methods and showed a dose-dependent trend that matches microbial inactivation kinetics. Our results provide a deeper mechanistic understanding of aPDT that can guide the scientific community toward the development of optimized photosensitizing drugs and also rationally propose synergistic combinations with antimicrobial chemotherapy., (© 2022 American Society for Photobiology.)

Several diseases or conditions cause dermatological disorders that hinder the process of skin repair. The search for novel technologies has inspired the combination of stem cell (SC) and light-based therapies to ameliorate skin wound repair. Herein, we systematically revised the impact of photobiomodulation therapy (PBM) combined with SCs in animal models of skin wounds and quantitatively evaluated this effect through a meta-analysis. For inclusion, SCs should be irradiated in vitro or in vivo, before or after being implanted in animals, respectively. The search resulted in nine eligible articles, which were assessed for risk of bias. For the meta-analysis, studies were included only when PBM was applied in vivo, five regarding wound closure, and three to wound strength. Overall, a positive influence of SC + PBM on wound closure (mean difference: 9.69; 95% CI: 5.78-13.61, P < 0.00001) and strength (standardized mean difference: 1.7, 95% CI: 0.68-2.72, P = 0.001) was detected, although studies have shown moderate to high heterogeneity and a lack of information regarding some bias domains. Altogether, PBM seems to be an enabling technology able to be applied postimplantation of SCs for cutaneous regeneration. Our findings may guide future laboratory and clinical studies in hopes of offering wound care patients a better quality of life., (© 2022 American Society for Photobiology.)

The database presented in this data article is related to the paper "Megafauna kill sites in South America: a critical review" [1]. It includes a list of 134 publications on human-megafauna interaction, with 69 archaeological sites showing human-megafauna interaction. From these sites, 44 present a minimum human-megafauna association, from which up to 17 megafauna kill sites were classified, with up to 15 exploited extinct megafauna taxa. It also provides a list of current taxonomic classifications of extinct megafauna that humans have exploited according to empirical evidence presented in the related paper. The megafauna kill sites were classified based on five restrictive criteria according to Grayson and Meltzer's (2015, 2002), Borrero's (2009) and Mothé et al.'s (2020) protocol. The kill sites database reflects the empirical evidence on megafauna exploitation by humans available in scientific literature and is useful to understand the human-megafauna interactions in the late Quaternary. Finally, we also provide our online repository (www.killsitedatabase.com), an initiative to unify the evidence on megafauna kill sites (and their related data) worldwide, starting in South America., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Antimicrobial blue light (aBL) offers efficacy and safety in treating infections. However, the bacterial targets for aBL are still poorly understood and may be dependent on bacterial species. Here, we investigated the biological targets of bacterial killing by aBL (λ = 410 nm) on three pathogens: Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Initially, we evaluated the killing kinetics of bacteria exposed to aBL and used this information to calculate the lethal doses (LD) responsible for killing 90 and 99.9% of bacteria. We also quantified endogenous porphyrins and assessed their spatial distribution. We then quantified and suppressed reactive oxygen species (ROS) production in bacteria to investigate their role in bacterial killing by aBL. We also assessed aBL-induced DNA damage, protein carbonylation, lipid peroxidation, and membrane permeability in bacteria. Our data showed that P. aeruginosa was more susceptible to aBL (LD 99.9 = 54.7 J/cm 2 ) relative to S. aureus (LD 99.9 = 158.9 J/cm 2 ) and E. coli (LD 99.9 = 195 J/cm 2 ). P. aeruginosa exhibited the highest concentration of endogenous porphyrins and level of ROS production relative to the other species. However, unlike other species, DNA degradation was not observed in P. aeruginosa. Sublethal doses of blue light (90 ) could damage the cell membrane in Gram-negative species but not in S. aureus. In all bacteria, oxidative damage to bacterial DNA (except P. aeruginosa), proteins, and lipids occurred after high aBL exposures (>LD 99.9 ). We conclude that the primary targets of aBL depend on the species, which are probably driven by variable antioxidant and DNA-repair mechanisms. IMPORTANCE Antimicrobial-drug development is facing increased scrutiny following the worldwide antibiotic crisis. Scientists across the world have recognized the urgent need for new antimicrobial therapies. In this sense, antimicrobial blue light (aBL) is a promising option due to its antimicrobial properties. Although aBL can damage different cell structures, the targets responsible for bacterial inactivation have still not been completely established and require further exploration. In our study, we conducted a thorough investigation to identify the possible aBL targets and gain insights into the bactericidal effects of aBL on three relevant pathogens: Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. This research not only adds new content to blue light studies but opens new perspectives to antimicrobial applications.

Type I and III interferons (IFN-I/λ) are important antiviral mediators against SARS-CoV-2 infection. Here, we demonstrate that plasmacytoid dendritic cells (pDC) are the predominant IFN-I/λ source following their sensing of SARS-CoV-2-infected cells. Mechanistically, this short-range sensing by pDCs requires sustained integrin-mediated cell adhesion with infected cells. In turn, pDCs restrict viral spread by an IFN-I/λ response directed toward SARS-CoV-2-infected cells. This specialized function enables pDCs to efficiently turn-off viral replication, likely via a local response at the contact site with infected cells. By exploring the pDC response in SARS-CoV-2 patients, we further demonstrate that pDC responsiveness inversely correlates with the severity of the disease. The pDC response is particularly impaired in severe COVID-19 patients. Overall, we propose that pDC activation is essential to control SARS-CoV-2-infection. Failure to develop this response could be important to understand severe cases of COVID-19., (© 2023. The Author(s).)

Dendritic cells (DCs) are key regulators of both innate and adaptive immunity via varied functions, including cytokine production and antigen presentation. Plasmacytoid DC (pDC) is a DC subset specialized in the production of type I and III interferons (IFNs). They are thus pivotal players of the host antiviral response during the acute phase of infection by genetically distant viruses. The pDC response is primarily triggered by the endolysosomal sensors Toll-like receptors, which recognize nucleic acids from pathogens. In some pathologic contexts, pDC response can also be triggered by host nucleic acids, hereby contributing to the pathogenesis of autoimmune diseases, such as, e.g., systemic lupus erythematosus. Importantly, recent in vitro studies from our laboratory and others uncovered that pDCs sense viral infections when a physical contact is established with infected cells. This specialized synapse-like feature enables a robust type I and III IFN secretion at the infected site. Therefore, this concentrated and confined response likely limits the correlated deleterious impacts of excessive cytokine production to the host, notably due to tissue damages. Here we provide a pipeline of methods for ex vivo studies of pDC antiviral functions, designed to address how pDC activation is regulated by cell-cell contact with virally infected cells and the current approaches enabling to decipher the underlying molecular events leading to an efficient antiviral response., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The aim of this study was to analyze the outcomes of a standardized protocol using routine CSFD, neuromonitoring, LL reperfusion, and selective TASP to prevent SCI during F-BEVAR., Background: SCI is to be the most devastating complication for the patient, family, and surgeon, with impact on patient's quality of life and long-term prognosis. An optimal standardized protocol may be used to improve outcomes., Methods: Patients enrolled in a prospective, nonrandomized single-center study between 2013 and 2018. A SCI prevention protocol was used for TAAAS or complex abdominal aneurysms with ≥5-cm supraceliac coverage including CSFD, neuromonitoring, LL reperfusion, and selective TASP. Endpoints included mortality and rates of SCI., Results: SCI prevention protocol was used in 170 of 232 patients (73%) treated by F-BEVAR. Ninety-one patients (55%) had changes in neuromonitoring, which improved with maneuvers in all except for 9 patients (10%) who had TASP. There was one 30-day or in-hospital mortality (0.4%). Ten patients (4%) developed SCIs including in 1% (1/79) of patients with normal neuromonitoring and 10% (9/91) of those who had decline in neuromonitoring ( P = 0.02). Permanent paraplegia occurred in 2 patients (1%). Factors associated with SCI included total operating time (odds ratio 1.5, 95% confidence interval 1.1-2.2, P = 0.02) and persistent changes in neuromonitoring requiring TASP (odds ratio 15.7, 95% confidence interval 2.9-86.2, P = 0.001)., Conclusion: This prospective nonrandomized study using a standardized strategy to prevent SCI was associated with low incidence of the SCI during F-BEVAR. Permanent paraplegia occurred in 1%., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Melanoma is a highly aggressive skin cancer that requires new approaches for its management. Low-level laser therapy, currently named photobiomodulation therapy (PBM), has been used to improve different conditions but its effects and safe use on melanoma remain unexplored. Herein, we investigated the PBM impact on melanoma cells differing by pigmentation using near-infrared (NIR) and red lasers in vitro. In vivo, we evaluated the effects of the red laser on melanoma-bearing mice. Amelanotic (SK-MEL-37) and melanotic (B16F10) cells were exposed in vitro to a NIR (780 nm, 40 mW) or a red laser (660 nm, 40 mW) in 3 different light doses: 30, 90, and 150 J/cm 2 and responses were assessed regarding mitochondrial activity, invasiveness, migration, and VEGF production. In vivo, melanoma-bearing mice received the red laser delivering 150 J/cm 2 directly to the tumor on 3 consecutive days. Mice were monitored for 15 days regarding tumor progression and mouse survival. We noticed that amelanotic cells were unresponsive to NIR light. In contrast, NIR irradiation at 30 J/cm 2 promoted an increase in the invasiveness of pigmented cells, even though all light doses have inhibited cell migration. Regarding the red laser on pigmented cells, the highest light dose (150 J/cm 2 ) decreased the VEGF production and migration. In vivo, melanoma-bearing mice treated with red laser showed smaller tumor volume and longer survival than controls. We conclude that PBM appears to be safe for amelanotic non-pigmented melanoma but triggers different responses in melanotic pigmented cells depending on light parameters. Additionally, a high dose of red laser impairs the invasive behavior of melanoma cells, probably due to the decrease in VEGF synthesis, which may have contributed to tumor arrest and increased mouse survival. These findings suggest that red laser therapy could be a new ally in the supportive care of melanoma patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Regulation of inflammation is a critical process for maintaining physiological homeostasis. The λ-carrageenan (λ-CGN) is a mucopolysaccharide extracted from the cell wall of red algae ( Chondrus crispus ) capable of inducing acute intestinal inflammation, which is translated into the production of acute phase reactants secreted into the blood circulation. However, the associated mechanisms in vertebrates are not well understood. Here, we investigated the crucial factors behind the inflammatory milieu of λ-CGN-mediated inflammation administered at 0, 1.75, and 3.5% (v/w) by i.p. injection into the peritoneal cavity of adult zebrafish (ZF) ( Danio rerio ). We found that polymorphonuclear leukocytes (neutrophils) and lymphocytes infiltrating the ZF peritoneal cavity had short-term persistence. Nevertheless, they generate a strong pattern of inflammation that affects systemically and is enough to produce edema in the cavity. Consistent with these findings, cell infiltration, which causes notable tissue changes, resulted in the overexpression of several acute inflammatory markers at the protein level. Using reversed-phase high-performance liquid chromatography followed by a hybrid linear ion-trap mass spectrometry shotgun proteomic approach, we identified 2938 plasma proteins among the animals injected with PBS and 3.5% λ-CGN. First, the bioinformatic analysis revealed the composition of the plasma proteome. Interestingly, 72 commonly expressed proteins were recorded among the treated and control groups, but, surprisingly, 2830 novel proteins were differentially expressed exclusively in the λ-CGN-induced group. Furthermore, from the commonly expressed proteins, compared to the control group 62 proteins got a significant ( p < 0.05) upregulation in the λ-CGN-treated group, while the remaining ten proteins were downregulated. Next, we obtained the major protein-protein interaction networks between hub protein clusters in the blood plasma of the λ-CGN induced group. Moreover, to understand the molecular underpinnings of these effects based on the unveiled protein sets, we performed a bioinformatic structural similarity analysis and generated overlapping 3D reconstructions between ZF and humans during acute inflammation. Biological pathway analysis pointed to the activation and abundance of diverse classical immune and acute phase reactants, several catalytic enzymes, and varied proteins supporting the immune response. Together, this information can be used for testing and finding novel pharmacological targets to treat human intestinal inflammatory diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Charlie-Silva, Feitosa, Pontes, Fernandes, Nóbrega, Gomes, Prata, Ferraris, Melo, Conde, Rodrigues, Aracati, Corrêa-Junior, Manrique, Superio, Garcez, Conceição, Yoshimura, Núñez, Eto, Fernandes, Freitas, Ribeiro, Nedoluzhko, Lopes-Ferreira, Borra, Barcellos, Perez, Malafaia, Cunha, Belo and Galindo-Villegas.)

Background: Transfemoral carotid artery stenting (TF-CAS) and carotid endarterectomy (CEA) are alternative strategies for stroke prevention in patients with atherosclerotic carotid disease. Because their main objective is to prevent future ischemic events, regular reassessment of the outcomes is mandatory for providing the best therapy. The purpose of this study was to describe the practice and the outcomes of TF-CAS and CEA in symptomatic patients in public university hospitals in Brazil, using data from a prospective multicentric registry., Methods: A prospective 8-year observational study of patients with symptomatic carotid artery atherosclerotic disease that underwent TF-CAS and CEA in 5 public university hospitals affiliated with the RHEUNI (Registry Project of Vascular Disease in the Public University Hospitals of São Paulo). All consecutive procedures were included. The indications for the procedures were determined by each surgeon's individual discretion, in accordance with a preoperative risk evaluation. The outcome measures were any 30-day follow-up death, stroke, myocardial infarction (MI), and their combined outcome (major adverse cardiovascular events [MACE]). The registration of the study was made at clinicaltrials.gov NCT02538276., Results: From January 2012 through December 2019, 376 consecutive and symptomatic patients were included in the study records. There were 152 TF-CAS procedures (40.4%) and 224 CEA procedures (59.5%). All completed the 30-day follow-up period. Occurrence of death (TF-CAS: 0.66% × CEA: 0.66%, P = 0.99), stroke (TF-CAS: 4.61% × CEA: 4.46%, P = 0.99), and MI (TF-CAS: 0.66% × CEA: 0%, P = 0.403) were similar in both groups, without statistically significant differences. MACE rate did not differ in both groups (TF-CAS: 5.92% × CEA: 4.46%, P = 0.633)., Conclusions: Data from a prospective registry of 5 Brazilian university hospitals showed that TF-CAS and CEA in symptomatic patients had similar 30-day perioperative rates of death, stroke, and MI and their combination., (Copyright © 2022 Elsevier Inc. All rights reserved.)

During the first semester of 2021, all of Brazil has suffered an intense wave of COVID-19 associated with the Gamma variant. In July, the first cases of Delta variant were detected in the state of Rio de Janeiro. In this work, we have employed phylodynamic methods to analyse more than 1 600 genomic sequences of Delta variant collected until September in Rio de Janeiro to reconstruct how this variant has surpassed Gamma and dispersed throughout the state. After the introduction of Delta, it has initially spread mostly in the homonymous city of Rio de Janeiro, the most populous of the state. In a second stage, dispersal occurred to mid- and long-range cities, which acted as new close-range hubs for spread. We observed that the substitution of Gamma by Delta was possibly caused by its higher viral load, a proxy for transmissibility. This variant turnover prompted a new surge in cases, but with lower lethality than was observed during the peak caused by Gamma. We reason that high vaccination rates in the state of Rio de Janeiro were possibly what prevented a higher number of deaths.

Simultaneous spatial circulation of urban arboviral diseases, such as dengue, chikungunya, and Zika, is a major challenge. In this ecological study of urban arboviruses performed from 2015 to 2019, we analyzed the spatial and temporal dynamics of these arboviruses in all 92 municipalities and nine health regions of Rio de Janeiro state. Annual cumulative incidences are presented for all three arboviruses throughout the study period. Spatial analyses of the three studied arboviruses showed distinct behaviors among municipalities and health regions. Co-circulation of the three arboviruses in the state and a heterogeneous spatiotemporal pattern was observed for each disease and region, with dengue having a higher annual incidence during the five years of the study, as well as two consecutive epidemic years in the state. The increase in transmission in different regions of the state in one year culminated in an epidemic in the state in the following year. A high annual cumulative incidence of chikungunya occurred in municipalities from 2017 to 2019 and of Zika only in 2016. Some municipalities with higher population densities showed higher incidences for some arboviruses and appeared to contribute to the dissemination to cities of lower demographic density and maintenance of these urban arboviruses. Thus, regions recording increased incidences of the three diseases in their territories for long periods should be considered municipal poles, as they initiated and sustained high transmission within their region.

Background: Methylene blue (MB)-mediated photodynamic inactivation (PDI) has shown good results in killing Candida spp. Although MB solutions are commonly used, new formulations have been designed to improve PDI. However, chemical substances in the formulation may interfere with the PDI outcome. In this sense, different methodologies should be used to evaluate PDI in vitro. Herein, we report different methodologies to evaluate the effects of PDI with an oral formulation (OF) containing 0.005% MB on Candida albicans biofilm., Methods: Biofilms were treated using the MB-OF, with 5 min pre-irradiation time and exposure to a 640 nm LED device (4.7 J/cm 2 ). PDI was evaluated by the XTT reduction test, counting the colony forming units (CFU), a filamentation assay, crystal violet (CV) staining, and scanning electronic microscopy (SEM)., Results: PDI was able to reduce around 1.5 log 10 CFU/mL, even though no significant differences were noted in metabolic activity in comparison to the control immediately after PDI. A significant decrease in yeast to hyphae transition was observed after PDI, while the biofilm exhibited flattened cells and a reduced number of yeasts in SEM. The CV assay showed increased biomass., Conclusion: MB-OF-mediated PDI was effective in C. albicans biofilms, as it significantly reduced the CFU/mL and the virulence of surviving cells. The CV data were inconclusive, since the OF components interacted with the CV, making the data useless. Taken together, our data suggest that the association of different methods allows complementary responses to assess how PDI mediated by a formulation impacts biofilms., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Candida albicans is the main cause of superficial candidiasis. While the antifungals available are defied by biofilm formation and resistance emergence, antimicrobial photodynamic inactivation (aPDI) arises as an alternative antifungal therapy. The tetracationic metalloporphyrin Zn(II) meso -tetrakis( N -n-hexylpyridinium-2-yl)porphyrin (ZnTnHex-2-PyP 4+ ) has high photoefficiency and improved cellular interactions. We investigated the ZnTnHex-2-PyP 4+ as a photosensitizer (PS) to photoinactivate yeasts and biofilms of C. albicans strains (ATCC 10231 and ATCC 90028) using a blue light-emitting diode. The photoinactivation of yeasts was evaluated by quantifying the colony forming units. The aPDI of ATCC 90028 biofilms was assessed by the MTT assay, propidium iodide (PI) labeling, and scanning electron microscopy. Mammalian cytotoxicity was investigated in Vero cells using MTT assay. The aPDI (4.3 J/cm 2 ) promoted eradication of yeasts at 0.8 and 1.5 µM of PS for ATCC 10231 and ATCC 90028, respectively. At 0.8 µM and same light dose, aPDI-treated biofilms showed intense PI labeling, about 89% decrease in the cell viability, and structural alterations with reduced hyphae. No considerable toxicity was observed in mammalian cells. Our results introduce the ZnTnHex-2-PyP 4+ as a promising PS to photoinactivate both yeasts and biofilms of C. albicans , stimulating studies with other Candida species and resistant isolates.