Trauma-informed systems change training has transcultural, transcontinental transformative healing power: An analysis of leaders in the United States and Angola, Africa.

The Institute for Trauma-Informed Systems Change (ITISC) facilitated a 2-day, 12-hr trauma-informed workshop, delivered virtually, using the Training for Change curriculum. The workshop took place in Portuguese in September 2021 with a group of Angolan leaders (N = 51) and in May 2022, in English, with neonatal intensive care unit (NICU) workers from the United States (N = 73). Surveys were administered before (Time [T] 0) and after the workshop (T1) and consisted of demographic questions and the Survey for Trauma-Informed Systems Change (STISC), which assesses system-wide knowledge and attitudes about trauma-informed systems change and the intersection of culture, safety, and acceptance in the workplace. At T1, 18 (35.3%) participants in the Angolan leaders' group and 46 (63.0%) in the NICU group completed the surveys. Mean scores on the STISC Self-Assessed Knowledge and Attitudes subscale and STISC System-Wide Knowledge and Attitudes subscale increased significantly in both groups after the training. Effect sizes were large for self-assessed knowledge and attitudes, Angolan leaders: d = 1.11, NICU: d = 1.97, and small-to-medium for system-wide knowledge and attitudes, Angolan leaders: d = 0.52, NICU: d = 0.38. Limitations include the relatively small sample size and low participation rates for survey responses. Future research should examine the efficacy of the curriculum in larger samples that include individuals from diverse professions and additional countries. Together, the findings provide initial support that this training can be directly translated and implemented on a global scale.

A three-dimensional cell culture approach to investigate cytotoxic effects and production of inflammatory mediators by epoxy resin-based and calcium silicate-based endodontic sealer.

OBJECTIVES: The aim of the present study was to assess the cytocompatibility of epoxy resin-based AH Plus Jet (Dentsply De Trey, Konstanz, Germany), Sealer Plus (MK Life, Porto Alegre, Brazil), calcium silicate-based Bio-C Sealer (Angelus, Londrina, PR, Brazil), Sealer Plus BC (MK Life) and AH Plus BC (Dentsply) through a tridimensional (3D) culture model of human osteoblast-like cells. METHODS: Spheroids of MG-63 cells were produced and exposed to fresh root canal sealers extracts by 24 h, and the cytotoxicity was assessed by the Lactate Dehydrogenase assay (LDH). The distribution of dead cells within the microtissue was assessed by fluorescence microscopy, and morphological effects were investigated by histological analysis. The secreted inflammatory mediators were detected in cell supernatants through flow luminometry (XMap Luminex). RESULTS: Cells incubated with AH Plus Jet, AH Plus BC, Sealer Plus BC and Bio-C Sealer extracts showed high rates of cell viability, while the Sealer Plus induced a significant reduction of cell viability, causing reduction on the spheroid structure. Sealer Plus and Seaker Plus BC caused alterations on 3D microtissue morphology. The AH Plus BC extract was associated with the downregulation of secretion of pro-inflammatory cytokines IL-5, IL-7, IP-10 and RANTES. CONCLUSIONS: The new AH Plus BC calcium silicate-based endodontic sealer did not reduce cell viability in vitro, while led to the downregulation of pro-inflammatory cytokines. CLINICAL SIGNIFICANCE: Choosing the appropriate endodontic sealer is a crucial step. AH Plus BC demonstrated high cell viability and downregulation of pro-inflammatory cytokines, appearing reliable for clinical use, while Sealer Plus presented lower cytocompatibility.

Bamboo (Poales, Poaceae): An Important Maintainer of Immature Mosquitoes (Diptera: Culicidae) in a Biodiversity Hotspot in the City of Rio de Janeiro, Brazil.

Although tropical forests are home to most of the global diversity, they suffer from the most significant knowledge gaps concerning their fauna. Despite its high biodiversity, Brazil is facing an alarming destruction of habitats, with species becoming extinct before they can be discovered or described via science. Therefore, there is an urgent need to expand wildlife inventories, including entomofauna surveys. The present study aimed to analyze the bionomic aspects and the influence of abiotic factors on mosquito fauna whose immature phases develop in two bamboo species, Guadua tagoara and Bambusa vulgaris, in Tijuca National Park, Rio de Janeiro, Brazil. Immatures were collected in 10 artificially drilled bamboo plants, in five stalk internodes per plant, at two sampling points, from March 2022 to March 2023, during 23 collections. A total of 1845 immatures were obtained, 72.14% at sampling point 1 and 27.86% at sampling point 2. Of this, 1162 individuals reached adulthood, belonging to the following species: Culex iridescens, Culex neglectus, Haemagogus leucocelaenus, Orthopodomyia albicosta, Sabethes identicus, Sabethes melanonymphe, Sabethes purpureus, Toxorhynchites bambusicola, Toxorhynchites sp., Trichoprosopon compressum, Trichoprosopon pallidiventer, Wyeomyia arthrostigma, Wyeomyia codiocampa, Wyeomyia lutzi, Wyeomyia oblita, Wyeomyia personata, Wyeomyia serrata, and Wyeomyia sp. The Tijuca National Park is a tourist spot and receives a large number of visitors. Thus, humans can become an accessible food source for mosquitoes in this area, making the species survey critical since important arbovirus vectors have been recorded in Rio de Janeiro.

Zika virus infection impairs synaptogenesis, induces neuroinflammation, and could be an environmental risk factor for autism spectrum disorder outcome.

Zika virus (ZIKV) infection was first associated with Central Nervous System (CNS) infections in Brazil in 2015, correlated with an increased number of newborns with microcephaly, which ended up characterizing the Congenital Zika Syndrome (CZS). Here, we investigated the impact of ZIKV infection on the functionality of iPSC-derived astrocytes. Besides, we extrapolated our findings to a Brazilian cohort of 136 CZS children and validated our results using a mouse model. Interestingly, ZIKV infection in neuroprogenitor cells compromises cell migration and causes apoptosis but does not interfere in astrocyte generation. Moreover, infected astrocytes lost their ability to uptake glutamate while expressing more glutamate transporters and secreted higher levels of IL-6. Besides, infected astrocytes secreted factors that impaired neuronal synaptogenesis. Since these biological endophenotypes were already related to Autism Spectrum Disorder (ASD), we extrapolated these results to a cohort of children, now 6-7 years old, and found seven children with ASD diagnosis (5.14 %). Additionally, mice infected by ZIKV revealed autistic-like behaviors, with a significant increase of IL-6 mRNA levels in the brain. Considering these evidence, we inferred that ZIKV infection during pregnancy might lead to synaptogenesis impairment and neuroinflammation, which could increase the risk for ASD.

Approaches of marine compounds and relevant immune mediators in Autism Spectrum Disorder: Opportunities and challenges.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that affects social skills, language, communication, and behavioral skills, significantly impacting the individual's quality of life. Recently, numerous works have centered on the connections between the immune and central nervous systems and the influence of neuroinflammation on autism symptomatology. Marine natural products are considered as important alternative sources of different types of compounds, including polysaccharides, polyphenols, sterols, carotenoids, terpenoids and, alkaloids. These compounds present anti-inflammatory, neuroprotective and immunomodulatory activities, exhibiting a potential for the treatment of many diseases. Although many studies address the marine compounds in the modulation of inflammatory mediators, there is a gap regarding their use in the regulation of the immune system in ASD. Thus, this review aims to provide a better understanding regarding cytokines, chemokines, growth factors and immune responses in ASD, as well as the potential of bioactive marine compounds in the immune regulation in ASD. We expect that this review would contribute to the development of therapeutic alternatives for controlling immune mediators and inflammation in ASD.

Serum Magnesium Levels in Patients with Chronic Kidney Disease: Is There a Relationship with Inflammation Status?

BACKGROUND: Magnesium (Mg2+) is a fundamental mineral that maintains cellular function, and low levels may be linked to inflammation in patients with chronic kidney disease (CKD). This cross-sectional study evaluated the correlation between serum Mg2+ levels and the inflammatory status in patients undergoing dialysis. METHODS: Two hundred patients with CKD [150 undergoing hemodialysis (HD), 50 (18) years; BMI 24 (4.8) kg/m²; and 50 patients on peritoneal dialysis (PD), 54 (17.7) years; BMI, 27.5 (7.3) kg/m²] were included. Serum Mg2+ levels were evaluated using a colourimetric test and commercial kit. Inflammatory markers were assessed by ELISA and multiplex bead-based assay. Lipid peroxidation was evaluated using thiobarbituric acid-reactive substances. RESULTS: The median serum Mg2+ levels were 2.3 (0.5) mg/dL, and 21% of patients presented Mg2+ deficiency (< 2.07 mg/dL or 0.85 mmol/L). We found no difference in Mg2+ serum levels between the two groups. A significant negative correlation was observed between serum Mg2+ levels and plasma hs-CRP (r =-0.17, p = 0.01), IL-8 (r =-0.35, p = 0.01), and MCP-1 (r =-0.31, p = 0.03) levels. CONCLUSION: Mg2+ serum levels were negatively correlated with inflammatory status in patients with CKD on dialysis.

A Novel Approach to Increase Glial Cell Populations in Brain Microphysiological Systems.

Brain microphysiological systems (bMPS) recapitulate human brain cellular architecture and functionality more closely than traditional monolayer cultures and have become increasingly relevant for the study of neurological function in health and disease. Existing 3D brain models vary in reflecting the relative populations of different cell types present in the human brain. Most models consist mainly of neurons, while glial cells represent a smaller portion of the cell populations. Here, by means of a chemically defined glial-enriched medium (GEM), an improved method to expand the population of astrocytes and oligodendrocytes without compromising neuronal differentiation in bMPS, is presented. An important finding is that astrocytes also change in morphology when cultured in GEM, more closely recapitulating primary culture astrocytes. GEM bMPS are electro-chemically active and show different patterns of calcium staining and flux. Synaptic vesicles and terminals observed by electron microscopy are also present. No significant changes in neuronal differentiation are observed by gene expression, however, GEM enhanced neurite outgrowth and cell migration, and differentially modulated neuronal maturation in two different cell lines. These results have the potential to significantly improve functionality of bMPS for the study of neurological diseases and drug discovery, contributing to the unmet need for safe human models.

Clinical and Biochemical Evaluation of the Use of Alb-PRF versus L-PRF in Mandibular Third Molar Extractions: A Split-Mouth Randomized Clinical Trial.

Bone tissue engineering seeks biomaterials that enable cell migration, angiogenesis, matrix deposition, and tissue regeneration. Blood concentrates like platelet-rich fibrin (L-PRF) offer a cost-effective source of cells and growth factors to enhance healing. The present study aimed to evaluate heated serum albumin with liquid PRF (Alb-PRF) and L-PRF clinically and biochemically after placement in dental sockets following mandibular third molar extraction. In a controlled, split-mouth study involving 10 volunteers, 20 extracted molars were treated with either Alb-PRF or L-PRF. Post-extraction, pain, trismus, infection presence, and swelling were measured. The concentrations of different analytes in the surgical sites were also examined. The data were statistically analyzed, with significance defined at p < 0.05 (t-test). No significant difference was noted between the groups for pain and trismus, but Alb-PRF showed a significant reduction in swelling on day seven. The Alb-PRF group showed lower levels of pro-inflammatory cytokines (GM-CSF, IL-1b, IL-6, IFNy, IL-8, IL-15, RANTES, and MIP-1a) after seven days, with only higher expressions of MIP-1b, IL-1b, and MCP-1 found in the L-PRF group. Differences were observed in the release of analytes between L-PRF and Alb-PRF, with Alb-PRF significantly reducing edema after seven days. Alb-PRF reduced edema, while L-PRF increased inflammatory cytokines. When compared to L-PRF, Alb-PRF reduced edema and the release of inflammatory cytokines, suggesting promising effects in socket healing while underscoring the role of growth factors and cytokines in potential applications of blood concentrates.

A novel approach to increase glial cell populations in brain microphysiological systems.

Brain microphysiological systems (bMPS), which recapitulate human brain cellular architecture and functionality more closely than traditional monolayer cultures, have become a practical, non-invasive, and increasingly relevant platform for the study of neurological function in health and disease. These models include 3D spheroids and organoids as well as organ-on-chip models. Currently, however, existing 3D brain models vary in reflecting the relative populations of the different cell types present in the human brain. Most of the models consist mainly of neurons, while glial cells represent a smaller portion of the cell populations. Here, by means of a chemically defined glial-enriched medium (GEM), we present an improved method to expand the population of astrocytes and oligodendrocytes without compromising neuronal differentiation in bMPS. An important finding is that astrocytes not only increased in number but also changed in morphology when cultured in GEM, more closely recapitulating primary culture astrocytes. We demonstrate oligodendrocyte and astrocyte enrichment in GEM bMPS using a variety of complementary methods. We found that GEM bMPS are electro-chemically active and showed different patterns of Ca +2 staining and flux. Synaptic vesicles and terminals observed by electron microscopy were also present. No significant changes in neuronal differentiation were observed by gene expression, however, GEM enhanced neurite outgrowth and cell migration, and differentially modulated neuronal maturation in two different iPSC lines. Our results have the potential to significantly improve in vivo-like functionality of bMPS for the study of neurological diseases and drug discovery, contributing to the unmet need for safe human models.

Structure-based discovery of novel cruzain inhibitors with distinct trypanocidal activity profiles.

Over 110 years after the first formal description of Chagas disease, the trypanocidal drugs thus far available have limited efficacy and several side effects. This encourages the search for novel treatments that inhibit T. cruzi targets. One of the most studied anti-T. cruzi targets is the cysteine protease cruzain; it is associated with metacyclogenesis, replication, and invasion of the host cells. We used computational techniques to identify novel molecular scaffolds that act as cruzain inhibitors. First, with a docking-based virtual screening, we identified compound 8, a competitive cruzain inhibitor with a Ki of 4.6 µM. Then, aided by molecular dynamics simulations, cheminformatics, and docking, we identified the analog compound 22 with a Ki of 27 µM. Surprisingly, despite sharing the same isoquinoline scaffold, compound 8 presented higher trypanocidal activity against the epimastigote forms, while compound 22, against the trypomastigotes and amastigotes. Taken together, compounds 8 and 22 represent a promising scaffold for further development of trypanocidal compounds as drug candidates for treating Chagas disease.

SOCS2 regulates alveolar bone loss in Aggregatibacter actinomycetemcomitans-induced periodontal disease.

INTRODUCTION: The role of suppressor of cytokine signaling 2 (SOCS2) in Aggregatibacter actinomycetemcomitans (Aa)-induced alveolar bone loss is unknown; thus, it was investigated in this study. METHODS: Alveolar bone loss was induced by infecting C57BL/6 wild-type (WT) and Socs2-knockout (Socs2-/-) mice with Aa. Bone parameters, bone loss, bone cell counts, the expression of bone remodeling markers, and cytokine profile were evaluated by microtomography, histology, qPCR, and/or ELISA. Bone marrow cells (BMC) from WT and Socs2-/- mice were differentiated in osteoblasts or osteoclasts for analysis of the expression of specific markers. RESULTS: Socs2-/- mice intrinsically exhibited irregular phenotypes in the maxillary bone and an increased number of osteoclasts. Upon Aa infection, SOCS2 deficiency resulted in the increased alveolar bone loss, despite decreased proinflammatory cytokine production, in comparison to the WT mice. In vitro, SOCS2 deficiency resulted in the increased osteoclasts formation, decreased expression of bone remodeling markers, and proinflammatory cytokines after Aa-LPS stimulus. CONCLUSIONS: Collectively, data suggest that SOCS2 is a regulator of Aa-induced alveolar bone loss by controlling the differentiation and activity of bone cells, and proinflammatory cytokines availability in the periodontal microenvironment and an important target for new therapeutic strategies. Thus, it can be helpful in preventing alveolar bone loss in periodontal inflammatory conditions.

Effects of propolis on inflammation markers in patients undergoing hemodialysis: A randomized, double-blind controlled clinical trial.

BACKGROUND AND AIMS: Several studies have been performed in vitro and in animals showing that propolis (a resin made by bees) has excellent anti-inflammatory properties, but no study has been performed in patients with chronic kidney disease (CKD) on hemodialysis (HD). The present study aimed to evaluate the effects of propolis supplementation on inflammatory markers in patients with CKD on HD. METHODS: This is a longitudinal, double-blind, placebo-controlled trial with patients randomized into two groups: propolis (4 capsules of 100 mg/day containing concentrated and standardized dry EPP-AF® green propolis extract) or placebo (4 capsules of 100 mg/day containing microcrystalline cellulose, magnesium stearate and colloidal silicon dioxide) for two months. Routine parameters were analyzed using commercial kits. The plasma levels of inflammatory cytokines were evaluated by flow luminometry. RESULTS: Forty-one patients completed the follow-up, 21 patients in the propolis group (45 ± 12 years, 13 women, BMI, 22.8 ± 3.7 kg/m2) and 20 in the placebo group (45.5 ± 14 years, 13 women, BMI, 24.8 ± 6.8 kg/m2). The obtained data revealed that the intervention with propolis significantly reduced the serum levels of tumour necrosis factor α (TNFα) (p = 0.009) as well as had the tendency to reduce the levels of macrophage inflammatory protein-1ß (MIP-1ß) (p = 0.07). There were no significant differences in the placebo group. CONCLUSION: Short-term EPP-AF® propolis dry extract 400 mg/day supplementation seems to mitigate inflammation, reducing the plasma levels of TNFα and MIP-1ß in patients with CKD on HD. This study was registered at clinicaltrials.gov (NCT04411758).

Transcutaneous auricular vagus nerve stimulation effects on inflammatory markers and clinical evolution of patients with COVID-19: a pilot randomized clinical trial.

OBJECTIVE: To evaluate the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on inflammatory markers and clinical outcomes in patients with COVID-19. METHODS: A randomized blinded pilot study was carried out with 21 individuals hospitalized with COVID-19 who received 14 sessions of active (a-taVNS) or sham taVNS (s-taVNS). The level of interleukin-6 (IL-6), interleukin-10 (IL-10), cortisol, and C-reactive protein (CRP) in plasma and clinical evolution pre- and post-intervention were evaluated. The memory and attention levels were evaluated 14 days after the end of the treatment. RESULTS: After treatment, significant intragroup differences were found in the CRP (p = 0.01), IL-6 (p = 0.01), and cortisol (p = 0.01) levels; however, in the comparison between the groups, only the CRP level was statistically lower for the a-taVNS (p = 0.04). The impression of improvement in memory and attention was greater in the a-taVNS than in the s-taVNS (p = 0.01, p = 0.04, respectively). There was no difference between the other clinical outcomes. CONCLUSIONS: taVNS is a viable and safe intervention in the acute care of patients with COVID-19, which can modulate their inflammatory profile and improve cognitive symptoms. However, improvements in overall clinical outcomes were not detected. Larger sample sizes and longer follow-ups are needed to confirm the anti-inflammatory and clinical effects of taVNS in patients with COVID-19. TRIALS REGISTRY: The Brazilian Registry of Clinical Trials (RBR-399t4g5).

Occurrence of the Sylvatic Yellow Fever Vector Mosquito Haemagogus leucocelaenus (Diptera: Culicidae) in an Atlantic Forest Fragment of the Touristic State of Rio de Janeiro, Brazil.

The yellow fever virus is estimated to cause 30,000 deaths each year worldwide, with the majority of cases and deaths occurring in Africa. The virus is also endemic to Central and South America, including northern and western Brazil. The sylvatic cycle of the virus is related to wild and rural areas, with nonhuman primates as the primary host and wild mosquitoes, specifically from the genera Haemagogus, as vectors. The diversity of the mosquito community plays a significant role in the increase of pathogen transmission to humans. In the present study, we detected fluctuation in populations of vector mosquitoes using ovitraps for Culicidae egg collection. The study area is a forest fragment of the Atlantic Forest, one of the most threatened biomes in Brazil. This biome has been suffering significant deforestation due to anthropic activity. Worryingly, the proximity of human populations to forest environments increases the risk of spreading disease from forest fragments to urban areas. Our findings showed that the highest egg abundance occurred in December 2019, with a significant difference (p = 0.005) between rainy and dry seasons. Most eggs were collected during the rainy period. Subsequent quantification of specimens from epidemiologically relevant species hatched from field-collected eggs resulted in 1,131 (86%) Haemagogus leucocelaenus (Dyar & Shannon, 1924), 111 (8%) Aedes terrens (Walker, 1856), 47 (4%) Aedes albopictus (Skuse, 1894), and 21 (2%) Haemagogus janthinomys (Dyar, 1921). Finally, we assessed the behavior of different vector species performing oviposition on the same breeding site. The highest correlation coefficient was observed between Ae. albopictus and Ae. terrens (rho = 0.52) concerning other Culicidae species. Therefore, we believe that Culicidae population surveillance is crucial for disease monitoring since the increase in specimens of a number of vector species influences the emergence of yellow fever cases in nonhuman primates and human populations.

Report of Mosquito Vectors of Arboviruses from a Federal Conservation Unit in the Atlantic Forest, Rio de Janeiro State, Brazil.

Arbovirus infections, such as dengue, zika, chikungunya, and yellow fever, are a major public health problem worldwide. As the main vectors, mosquitoes have been classified by the Center for Disease Control and Prevention as one of the deadliest animals alive. In this ecological study, we analyzed the population dynamics of important genera and species of mosquito vectors. Mosquito immatures were collected using ovitraps and at natural breeding sites: bamboos and bromeliads. Adult mosquitoes were captured using CDC traps with CO2, Shannon traps, and manual suction tubes. Collections took place during the rainy and dry seasons from 2019 to 2020 in the Serra dos Órgãos National Park, Rio de Janeiro state, Brazil. The highest number of species was recorded in the ovitraps, followed by CDC and bromeliads. The breeding site with the lowest diversity was bamboo, though it showed the highest level of evenness compared to the other breeding sites. The medically important genera reported were Haemagogus spp., Aedes spp., Culex spp., and Wyeomyia spp. Culicid eggs increased in the rainy season, with a peak in November 2019 and January and February 2020, and lower abundance in the dry season, from September to October 2019. Mosquito eggs had a strong positive correlation (ρ = 0.755) with temperature and a moderate positive correlation (ρ = 0.625) with rainfall. This study shows how environmental variables can influence the ecology of disease-vector mosquitoes, which are critical in the maintenance of arbovirus circulation in a threatened biome within the most densely populated region of Brazil.

Efeito da estimulação elétrica transcutânea do nervo vago na inflamação, modulação autonômica cardíaca e evolução clínica dos pacientes com COVID-19: estudo de protocolo para um ensaio clínico, controlado, randomizado e cego / Efecto de la estimulación eléctrica transcutánea del nervio vago sobre la inflamación, la modulación autonómica cardiac y la evolución clínica de pacientes con COVID-19: estudio de protocolo para un ensayo clínico, controlado, aleatorizado y ciego / Effects of transcutaneous auricular vagus nerve stimulation on inflammation, cardiac autonomic modulation, and clinical evolution of patients with COVID-19: protocol for a clinical, controlled, randomized, and blind trial

RESUMO O objetivo deste estudo é avaliar o efeito da estimulação elétrica transcutânea do nervo vago (EETNV) na inflamação, modulação autonômica cardíaca e evolução clínica dos pacientes com COVID-19. Trata-se de um ensaio clínico, controlado por sham, randomizado e cego, no qual participarão 52 indivíduos hospitalizados com diagnóstico de COVID-19, que serão randomizados em dois grupos de tratamento: grupo experimental (tratamento médico usual associado à EETNV ativa) ou grupo-controle (tratamento médico usual associado à EETNV sham). A EETNV será realizada por meio de um estimulador elétrico neuromuscular (modelo Dualpex 071 da Quark Medical Products), com o eletrodo de estimulação posicionado sobre o tragus esquerdo, com corrente alternada, frequência de 30Hz e variação de 50%, intensidade ajustada para o limiar sensorial do paciente, com duração de 90 minutos cada sessão de estimulação, duas vezes ao dia, durante sete dias consecutivos, totalizando 14 sessões. Serão avaliados pré e pós-intervenção o nível de interleucina-6 (IL-6) e interleucina-10 (IL-10), cortisol e proteína C reativa (PCR), pressão arterial, variabilidade da frequência cardíaca pelos parâmetros de baixa frequência (BF), alta frequência (AF) e pela razão da baixa e alta frequência (BF/AF), além de evolução clínica dos pacientes, incluindo o nível de ansiedade e depressão, cujos dados serão obtidos por meio de prontuários e questionários. Será realizado também um acompanhamento 7 e 14 dias após o término das intervenções para verificar a evolução clínica, incluindo nível de ansiedade e depressão, e durante seis meses serão avaliadas memória e atenção.

RESUMEN El objetivo de este estudio es evaluar el efecto de la estimulación eléctrica transcutánea del nervio vago (EETNV) sobre la inflamación, la modulación autonómica cardíaca y la evolución clínica de pacientes con COVID-19. Se trata de un ensayo clínico, controlado por simulado, aleatorizado y ciego, en el que participarán 52 individuos hospitalizados diagnosticados de COVID-19, que serán aleatorizados en dos grupos de tratamiento: grupo experimental (tratamiento médico habitual asociado a la EETNV activa) o grupo control (tratamiento médico habitual asociado a la EETNV simulada). La EETNV se realizará mediante un estimulador eléctrico neuromuscular (modelo Dualpex 071 de Quark Medical Products), con el electrodo de estimulación colocado en el trago izquierdo, con corriente alterna, frecuencia de 30Hz y 50% de variación, intensidad ajustada al umbral sensorial del paciente, con una duración de 90 minutos cada sesión de estimulación, dos veces al día, durante siete días consecutivos, lo que totaliza 14 sesiones. Se evaluarán antes y después de la intervención la interleucina-6 (IL-6) y la interleucina-10 (IL-10), el cortisol y la proteína C reactiva (PCR), la presión arterial, la variabilidad de la frecuencia cardíaca por los parámetros de baja frecuencia (BF), alta frecuencia (AF) y razón de baja y alta frecuencia (BF/AF), así como la evolución clínica de los pacientes, incluidos los parámetros de ansiedad y depresión cuyos datos se obtendrán de historias clínicas y cuestionarios. También se realizará un seguimiento de 7 y 14 días tras finalizadas las intervenciones para verificar la evolución clínica, incluidos el nivel de ansiedad y de depresión, y durante seis meses se evaluará la memoria y la atención.

ABSTRACT This study aims to evaluate the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on inflammation, cardiac autonomic modulation, and clinical evolution of patients with COVID-19. This is a clinical, sham-controlled, randomized, and blind trial, in which 52 hospitalized individuals diagnosed with COVID-19 will participate. They will be randomized into: experimental group (usual medical treatment associated with active taVNS) and control group (usual medical treatment associated with sham taVNS). The taVNS will be performed by a neuromuscular electric stimulator (Dualpex model 071 of Quark Medical Products), with the stimulation electrode positioned on the left tragus, with alternating current, at a 30Hz frequency with 50% variation. Intensity will be adjusted to the patient's sensory threshold, with 90-minutes-long stimulation sessions, happening twice per day for seven consecutive days, totaling 14 sessions. Interleukin-6 (IL-6) and interleukin-10 (IL-10), cortisol and C-reactive protein (CRP), blood pressure, heart rate variability (HRV) by low frequency (LF), high frequency (HF) and low and high frequency ratio (LF/HF) parameters will be evaluated before and after the intervention, as well as patients' clinical evolution-including anxiety and depression levels-whose data will be obtained through medical records and questionnaires. A follow-up will also be performed seven and 14 days after the end of the interventions to verify the clinical evolution, including anxiety and depression levels. Memory and attention levels will be evaluated for six months.

Pro-Inflammatory Profile of Children Exposed to Maternal Chikungunya Virus Infection during the Intrauterine Period: A One-Year Follow-Up Study.

Chikungunya virus (CHIKV) vertical transmission occurs due to maternal viremia in the prepartum. Clinical presentation in neonates can be varied; however, the consequences of intrauterine exposure on the immune response are unclear. Thus, we aimed to analyze inflammatory alterations in children exposed to maternal CHIKV infection. This is a cross-sectional study that included children exposed to maternal CHIKV infection (confirmed by RT-qPCR and/or IgM). Circulant immune mediators were analyzed by a multiplex assay. RESULTS: We included 33 children, with a mean age of 3 ± 2.9 months-old, and 19 (57.6%) were male. Only one child presented neurological alterations. CHIKV-exposed infants showed elevated levels of MIP-1α, MIP-1ß, and CCL-2 (p < 0.05). Pro-inflammatory cytokines such as TNFα, IL-6, and IL-7 (p < 0.0001) were also increased. In addition, lower levels of PDGF-BB and GM-CSF were observed in the same group (p < 0.0001). Principal component (PC) analysis highlighted a distinction in the inflammatory profile between groups, where PC explained 56.6% of the alterations. Our findings suggest that maternal exposure to CHIKV can affect the circulating levels of pro-inflammatory cytokines during the infants' first year of life. The long-term clinical consequences of these findings should be investigated.

Interaction of Haemagogus leucocelaenus (Diptera: Culicidae) and Other Mosquito Vectors in a Forested Area, Rio de Janeiro, Brazil.

The yellow fever (YF) virus has been detected throughout Brazil, with the occurrence of human cases, cyclic epizootics, and its isolation from Haemagogus janthinomys and Hg. leucocelaenus. We assessed the seasonal occurrence, egg abundancy, and oviposition interaction of mosquito vector species captured at a Private Natural Heritage Reserve in the Atlantic Forest biome. A total of 2943 eggs and 1538 mosquito larvae were collected from which 1231 belonged to entomologically important species. Ovitraps were used to collect immature mosquitoes from September 2019 to January 2021. The Mann-Whitney test was used to assess the differences in the abundance of eggs between rainy and dry seasons. Kruskal-Wallis and Dunn's post hoc tests were used to evaluate the significance of the differences in the number of individuals from vector species. The highest percentage of mosquito vector eggs were collected during the rainy season, from December to February. Most eggs recovered from ovitraps belonged to the species Hg. leucocelaenus, representing 85% of all mosquito eggs identified. The other species had lower abundances and percentages: Aedes terrens (7%), Haemagogus janthinomys (5%) and Aedes albopictus (3%). The species that shared breeding sites with a higher frequency were Hg. leucocelaenus and Hg. janthinomys, with a statistically positive correlation (ρ = 0.74). This finding suggests that maybe the presence of Hg. leucocelaenus eggs acted as an attractant for Hg. janthinomys or vice versa. An understanding of mosquito oviposition behavior is necessary for the development of surveillance and control approaches directed against specific pathogen vectors of medical and veterinary importance.

The influence of methodology on the comparison of cytotoxicity of total-etch and self-etch adhesive systems.

OBJECTIVES: The present study aimed to compare the in vitro cytocompatibility of two etch-and-rinse (Adper Scothbond, Optibond) and two self-etch (Clearfill SE Bond and Single Bond Universal) dental adhesives through a dentin-barrier model with human pulp fibroblasts. METHODS: Human fibroblasts were placed on a plastic device containing 500µm human dentin discs treated with each adhesive or without treatment (control). Other groups were directly exposed to media conditioned with adhesive samples according to ISO 10993-5:2009. After 24h exposure, cell viability was assessed by XTT, and released inflammatory mediators were detected with a multiparametric immunoassay. RESULTS: The standardized test without barrier indicated both etch-and-rinse adhesives and self-etch as cytotoxic, promoting viabilities under 70% of the control group (p<0.05). The dentin-barrier model identified increased cell viability for self-etch adhesives, with Clearfill SE Bond identified as non-cytotoxic. The immunoassay evidenced high rates of cytokines by cells exposed to the conditioned media of Adper Scotchbond, Optibond S, and Single Bond Universal. CONCLUSIONS: The use of a dentin-barrier in vitro model detected a better biocompatibility for self-etching adhesives and, in the case of Clearfill SE Bond, with a reversion from cytotoxic to biocompatible when compared to the indirect standardized test. CLINICAL SIGNIFICANCE: The use of a dentin-barrier in vitro model was able to detect a better biocompatibility for self-etching adhesives when compared to the indirect standardized test and presents itself as a predictive in vitro method for assessing the cytotoxicity of dental restorative materials that may simulate the clinical condition more accurately.

"Sticky Bone" Preparation Device: A Pilot Study on the Release of Cytokines and Growth Factors.

Sticky bone, a growth factor-enriched bone graft matrix, is a promising autologous material for bone tissue regeneration. However, its production is strongly dependent on manual handling steps. In this sense, a new device was developed to simplify the confection of the sticky bone, named Sticky Bone Preparation Device (SBPD®). The purpose of this pilot study was to investigate the suitability of the SBPD® to prepare biomaterials for bone regeneration with autologous platelet concentrates. The SBPD® allows the blending of particulate samples from synthetic, xenograft, or autogenous bone with autologous platelet concentrates, making it easy to use and avoiding the need of further manipulations for the combination of the materials. The protocol for the preparation of sticky bone samples using the SBPD® is described, and the resulting product is compared with hand-mixed SB preparations regarding in vitro parameters such as cell content and the ability to release growth factors and cytokines relevant to tissue regeneration. The entrapped cell content was estimated, and the ability to release biological mediators was assessed after 7 days of incubation in culture medium. Both preparations increased the leukocyte and platelet concentrations compared to whole-blood samples (p < 0.05), without significant differences between SB and SBPD®. SBPD® samples released several growth factors, including VEGF, FGFb, and PDGF, at concentrations physiologically equivalent to those released by SB preparations. Therefore, the use of SBPD® results in a similar product to the standard protocol, but with more straightforward and shorter preparation times and less manipulation. These preliminary results suggest this device as a suitable alternative for combining bone substitute materials with platelet concentrates for bone tissue regeneration.