Recurrence of fusocellular subtype GIST with SDHB mutation: A case of SDHB-loss and therapeutic challenges.

Gastrointestinal stromal tumors (GISTs) are sarcomas affecting the stomach and small intestine, with a rare subtype characterized by succinate dehydrogenase B (SDHB)-loss posing significant diagnostic and therapeutic challenges. A 62-year-old man with weight loss and abdominal pain was diagnosed with a gastric GIST showing SDHB-loss. Initial treatment with Imatinib reduced the tumor size, but surgery revealed no residual tumor. Despite adjuvant Imatinib, recurrence occurred, necessitating further surgical intervention. While GISTs typically benefit from surgery and tyrosine kinase inhibitors (TKIs), those with SDHB-loss are resistant to TKIs, requiring a different management approach. This case emphasizes the importance of surgical intervention for SDHB-deficient GISTs and the need for ongoing research into effective treatments for this subtype.

Micro-osteoperforation for enhancement of orthodontic movement: A mechanical analysis using the finite element method.

BACKGROUND: Micro-osteoperforation is a minimally invasive technique aimed at accelerating tooth movement. The goal of this novel experimental study was to assess tooth movement and stress distribution produced by the force of orthodontic movement on the tooth structure, periodontal ligament, and maxillary bone structure, with and without micro-osteoperforation, using the finite element method. MATERIALS AND METHODS: Cone-beam computed tomography was used to obtain a virtual model of the maxilla and simulate the extraction of right and left first premolars. Three micro-osteoperforations (1.5 x 5 mm) were made in the hemiarch on the distal and mesial surfaces of upper canines, according to the power tip geometry of the Propel device (Propel Orthodontics, Ossining, New York, USA). An isotropic model of the maxilla was fabricated according to the finite element method by insertion of mechanical properties of the tooth structures, with orthodontic force (1.5 N) simulation in the distal movement on the upper canine of a hemiarch. RESULTS: Initial movement was larger when micro-osteoperforations were performed on the dental crown (24%) and on the periodontal ligament (29%). In addition, stress distribution was higher on the bone structure (31%) when micro-osteoperforations were used. CONCLUSIONS: Micro-osteoperforations considerably increased the movement of both the dental crown and periodontal ligament, which highlights their importance in the improvement of orthodontic movement, as well as in stress distribution across the bone structure. Important stress absorption regions were identified within micro-osteoperforations.

Computer-aided drug design supporting sunscreen research: a showcase study using previously synthesized hybrid UV filter-antioxidant compounds.

CONTEXT: Although quantum mechanical calculations have proven effective in accurately predicting UV absorption and assessing the antioxidant potential of compounds, the utilization of computer-aided drug design (CADD) to support sustainable synthesis research of new sunscreen active ingredients remains an area with limited exploration. Furthermore, there are ongoing concerns about the safety and effectiveness of existing sunscreens. Therefore, it remains crucial to investigate photoprotection mechanisms and develop enhanced strategies for mitigating the harmful effects of UVR exposure, improving both the safety and efficacy of sunscreen products. A previous study conducted synthesis research on eight novel hybrid compounds (I-VIII) for use in sunscreen products by molecular hybridization of trans-resveratrol (RESV), avobenzone (AVO), and octinoxate (OMC). Herein, time-dependent density functional theory (TD-DFT) calculations performed in the gas phase on the isolated hybrid compounds (I-VIII) proved to reproduce the experimental UV absorption. Resveratrol-avobenzone structure-based hybrids (I-IV) present absorption maxima in the UVB range with slight differences between them, while resveratrol-OMC structure-based hybrids (V-VIII) showed main absorption in the UVA range. Among RESV-OMC hybrids, compounds V and VI exhibited higher UV absorption intensity, and compound VIII stood out for its broad-spectrum coverage in our simulations. Furthermore, both in silico and in vitro analyses revealed that compounds VII and VIII exhibited the highest antioxidant activity, with compound I emerging as the most reactive antioxidant within RESV-AVO hybrids. The study suggests a preference for the hydrogen atom transfer (HAT) mechanism over single-electron transfer followed by proton transfer (SET-PT) in the gas phase. With a strong focus on sustainability, this approach reduces costs and minimizes effluent production in synthesis research, promoting the eco-friendly development of new sunscreen active ingredients. METHODS: The SPARTAN'20 program was utilized for the geometry optimization and energy calculations of all compounds. Conformer distribution analysis was performed using the Merck molecular force field 94 (MMFF94), and geometry optimization was carried out using the parametric method 6 (PM6) followed by density functional theory (DFT/B3LYP/6-31G(d)). The antioxidant behavior of the hybrid compounds (I-VIII) was determined using the highest occupied molecular orbital (εHOMO) and the lowest unoccupied molecular orbital (εLUMO) energies, as well as the bond dissociation enthalpy (BDE), ionization potential (IP), and proton dissociation enthalpy (PDE) values, all calculated at the same level of structural optimization. TD-DFT study is carried out to calculate the excitation energy using the B3LYP functional with the 6-31G(d) basis set. The calculated transitions were convoluted with a Gaussian profile using the Gabedit program.

Enhanced Diagnostic Precision: Assessing Tumor Differentiation in Head and Neck Squamous Cell Carcinoma Using Multi-Slice Spiral CT Texture Analysis.

This study explores the efficacy of texture analysis by using preoperative multi-slice spiral computed tomography (MSCT) to non-invasively determine the grade of cellular differentiation in head and neck squamous cell carcinoma (HNSCC). In a retrospective study, MSCT scans of patients with HNSCC were analyzed and classified based on its histological grade as moderately differentiated, well-differentiated, or poorly differentiated. The location of the tumor was categorized as either in the bone or in soft tissues. Segmentation of the lesion areas was conducted, followed by texture analysis. Eleven GLCM parameters across five different distances were calculated. Median values and correlations of texture parameters were examined in relation to tumor differentiation grade by using Spearman's correlation coefficient and Kruskal-Wallis and Dunn tests. Forty-six patients were included, predominantly female (87%), with a mean age of 66.7 years. Texture analysis revealed significant parameter correlations with histopathological grades of tumor differentiation. The study identified no significant age correlation with tumor differentiation, which underscores the potential of texture analysis as an age-independent biomarker. The strong correlations between texture parameters and histopathological grades support the integration of this technique into the clinical decision-making process.

Dysregulated microRNAs in type 2 diabetes and breast cancer: Potential associated molecular mechanisms.

Type 2 diabetes (T2D) is a multifaceted and heterogeneous syndrome associated with complications such as hypertension, coronary artery disease, and notably, breast cancer (BC). The connection between T2D and BC is established through processes that involve insulin resistance, inflammation and other factors. Despite this comprehension the specific cellular and molecular mechanisms linking T2D to BC, especially through microRNAs (miRNAs), remain elusive. miRNAs are regulators of gene expression at the post-transcriptional level and have the function of regulating target genes by modulating various signaling pathways and biological processes. However, the signaling pathways and biological processes regulated by miRNAs that are associated with T2D and BC have not yet been elucidated. This review aims to identify dysregulated miRNAs in both T2D and BC, exploring potential signaling pathways and biological processes that collectively contribute to the development of BC.

Raw milk cheeses from Beira Baixa, Portugal-A contributive study for the microbiological hygiene and safety assessment.

Due to specific bacterial microbiota, raw milk cheeses have appreciated sensory properties. However, they may pose a threat to consumer safety due to potential pathogens presence. This study evaluated the microbiological contamination of 98 raw milk cheeses from Beira Baixa, Portugal. Presence and enumeration of Coagulase Positive Staphylococci (CPS), Listeria monocytogenes, Salmonella spp., pathogenic Escherichia coli, and indicator microorganisms (non-pathogenic E. coli and Listeria spp.) was attained. E. coli antimicrobial resistance (AMR) was also evaluated. PCR and/or Whole genome sequencing (WGS) was used to characterize E. coli, Salmonella spp. and L. monocytogenes isolates. Sixteen cheeses (16.3%) were classified as Satisfactory, 59 (60.2%) as Borderline and 23 (23.5%) as Unsatisfactory/Potential Injurious to Health. L. monocytogenes, CPS > 104 cfu g-1, Extraintestinal pathogenic E. coli (ExPEC) and Salmonella spp. were detected in 4.1%, 6.1%, 3.1% and 1.0% of the samples, respectively. Listeria innocua (4.1%) and E. coli > 104 cfu g-1 (16.3%) were also detected. AMR E. coli was detected in 23/98 (23.5%) of the cheese samples, of which two were multidrug resistant. WGS identified genotypes already associated to human disease and Listeria spp. cluster analysis indicated that cheese contamination might be related with noncompliance with Good Hygiene Practices during cheese production.

Synthesis and In vitro and In silico Anti-inflammatory Activity of New Thiazolidinedione-quinoline Derivatives.

BACKGROUND: Inflammation is a series of complex defense-related reactions. The inflammation cascade produces various pro-inflammatory mediators. Unregulated production of these pro-inflammatory mediators can lead to a wide range of diseases, including rheumatoid arthritis, sepsis, and inflammatory bowel disease. In the literature, the anti-inflammatory action of quinoline and thiazolidinedione nuclei are well established, alone, and associated with other nuclei. The synthesis of hybrid molecules is a strategy for obtaining more efficient molecules due to the union of pharmacophoric nuclei known to be related to pharmacological activity. OBJECTIVES: Based on this, this work presents the synthesis of thiazolidinedione-quinoline molecular hybrids and their involvement in the modulation of cytokines involved in the inflammatory reaction cascade. METHODS: After synthesis and characterization, the compounds were submitted to cell viability test (MTT), ELISA IFN-γ and TNF-α, adipogenic differentiation, and molecular docking assay with PPARy and COX-2 targets. RESULTS: LPSF/ZKD2 and LPSF/ZKD7 showed a significant decrease in the concentration of IFN- γ and TNF-α, with a dose-dependent behavior. LPSF/ZKD4 at a concentration of 50 µM significantly reduced IL-6 expression. LPSF/ZKD4 demonstrates lipid accumulation with significant differences between the untreated and negative control groups, indicating a relevant agonist action on the PPARγ receptor. Molecular docking showed that all synthesized compounds have good affinity with PPARγ e COX-2, with binding energy close to -10,000 Kcal/mol. CONCLUSION: These results demonstrate that the synthesis of quinoline-thiazolidinedione hybrids may be a useful strategy for obtaining promising candidates for new anti-inflammatory agents.

Must a Knee with Anterior Cruciate Ligament Deficiency and High-grade Pivot Shift Test Present an Increase in Internal Rotation?

Objective: Rupture of the anterior cruciate ligament (ACL) is one of the most common injuries in athletes and is often associated with damage to anterolateral structures. This combination of injuries presents itself clinically as a high-grade pivot shift test. The hypothesis of this study is that patients with ACL deficiency and high-grade pivot shift test should have an increased internal knee rotation. Methods: Twenty-two patients were tested. After effective spinal anesthesia, two tests were performed with the patient in supine position. First, the bilateral pivot shift test was performed manually, and its grade was recorded. Then, with the knee flexed to 90 degrees, the examiner drew the projection of the foot in a neutral position and in maximum internal rotation, and the angle of internal rotation was measured from the axes built between the central point of the heel and the hallux. Results: In the ACL-deficient knee, it was observed that there is a statistically significant average internal rotation (IR) delta of 10.5 degrees between the groups when not adjusted for age, and 10.6 degrees when adjusted for age. Conclusions: Knees with ACL deficiency and with pivot shift test grade I do not show increased internal rotation in relation to knees with intact ACL. Knees with ACL deficiency and with pivot shift test grades II and III show increased internal rotation in comparison to healthy knees.

[Relationship between air temperature and dengue incidence: time series study in Minas Gerais, Brazil (2010-2019)]. / Relação entre temperatura do ar e incidência de dengue: estudo de séries temporais em Minas Gerais, Brasil (2010-2019).

Air temperature is a climatic factor that affects the incidence of dengue, with effects varying according to time and space. We investigated the relationship between minimum air temperature and dengue incidence in Minas Gerais, Brazil, and evaluated the influence of socioeconomic and geographic variables on this relationship. This is a time series study with analysis conducted in three distinct stages: modeling using a distributed lag non-linear model, meta-analysis of models obtained, and meta-regression with geographic and socioeconomic data. Minimum temperature was a protective factor at extreme cold temperatures (RR = 0.65; 95%CI: 0.56-0.76) and moderate cold temperatures (RR = 0.71; 95%CI: 0.64-0.79), and a risk factor at moderate hot temperatures (RR = 1.15; 95%CI: 1.07-1.24), but not at extreme hot temperatures (RR = 1.1; 95%CI: 0.99-1.22). Heterogeneity of the models was high (I2 = 60%), which was also observed in meta-regression. Moderate and extreme cold temperatures have a protective effect, while moderate hot temperatures increase the risk. However, minimum air temperature does not explain the variability in the region, not even with the other variables in meta-regression.

A temperatura do ar é um fator climático que afeta a incidência da dengue, com efeitos variando conforme o tempo e o espaço. Investigamos a relação entre a temperatura mínima do ar e a incidência da doença em Minas Gerais, Brasil, e avaliamos a influência de variáveis socioeconômicas e geográficas nessa relação, calculando-se o risco relativo (RR). Este é um estudo de série temporal com análise conduzida em três etapas distintas: modelagem por uso de distributed lag non-linear model (modelos não-lineares distributivos com defasagem), metanálise dos modelos obtidos e metarregressão com dados geográficos e socioeconômicos. A temperatura mínima foi um fator de proteção quando em temperaturas frias extremas (RR = 0,65; IC95%: 0,56-0,76) e moderadas (RR = 0,71; IC95%: 0,64-0,79) e fator de risco em temperaturas de calor moderado (RR = 1,15; IC95%: 1,07-1,24), mas não em extremo (RR = 1,1; IC95%: 0,99-1,22). A heterogeneidade dos modelos foi elevada (I2 = 60%) e essa medida não foi alterada em metarregressão. Temperaturas frias moderadas e extremas causam efeito protetivo, enquanto moderadas quentes aumentam o risco. No entanto, a temperatura mínima do ar não explica nem a variabilidade da região, nem mesmo com as outras variáveis em metarregressão.

La temperatura del aire es un factor climático que afecta la incidencia del dengue, con efectos que varían según el tiempo y el territorio. Investigamos la relación entre la temperatura mínima del aire y la incidencia de la enfermedad en Minas Gerais, Brasil, y evaluamos la influencia de variables socioeconómicas y geográficas en esta relación. Se trata de un estudio de serie temporal cuyo análisis se realiza en tres etapas distintas: modelación mediante el uso de distributed lag non-linear model (modelos distributivos no lineales con retraso), metaanálisis de los modelos obtenidos y metarregresión con datos geográficos y socioeconómicos. La temperatura mínima fue un factor de protección ante temperaturas extremadamente frías (RR = 0,65; IC95%: 0,56-0,76) y moderadas (RR = 0,71; IC95%: 0,64-0,79) y factor de riesgo en temperaturas de calor moderado (RR = 1,15; IC95%: 1,07-1,24), pero no en extremo (RR = 1,1; IC95%: 0,99-1,22). La heterogeneidad de los modelos fue alta (I2 = 60%), y esta medida no se modificó en la metarregresión. Las temperaturas frías moderadas y extremas tienen un efecto protector, mientras que las temperaturas moderadamente altas aumentan el riesgo. Sin embargo, la temperatura mínima del aire no explica la variabilidad de la región, ni siquiera con las demás variables en metarregresión.

Occurrence of arbovirus infections in two riverine populations in the municipality of Humaitá, Amazonas, Brazil.

BACKGROUND: The riverine communities of the Amazon comprise different social groups that inhabit the rural areas on the banks of rivers and lakes. Residents usually travel by river to rural and urban areas and are then exposed to urbanized diseases such as those caused by arbovirus infection. In Brazil, emerging diseases such as dengue, Zika, chikungunya, and those caused by infection with Oropouche and Mayaro viruses necessitate epidemiological surveillance. This study was aimed at determining the frequency of positivity for immunoglobulin (Ig)G and IgM antibodies against Zika, chikungunya, and dengue viruses and performing molecular analyses to detect viral RNA for the Zika, chikungunya, dengue virus, Oropouche, and Mayaro viruses, in the same serum samples obtained from riverside populations. METHODS: This cross-sectional study was conducted in a riverside population in the Humaitá municipality of the Brazilian Amazon. More than 80% of the local population participated in this study. Entomological samples were collected to identify local mosquito vectors. RESULTS: Analysis of 205 human serological samples revealed IgG antibodies against the dengue virus in 85 individuals. No molecular positivity was observed in human samples. Entomological analyses revealed 3,187 Diptera species, with Mansonia being the most frequent genus. Aedes aegypti and Aedes albopictus were not detected in the two collections. CONCLUSIONS: IgG antibodies against the dengue virus were highly prevalent, suggesting previous exposure. The absence of the arbovirus vectors Aedes aegypti and Aedes albopictus in the samples supports the hypothesis that the infections recorded likely occurred outside the riverside communities investigated.

Effect of topical application of ibuprofen/arginine on the in-office bleaching-induced tooth sensitivity: A randomized, triple-blind controlled trial.

OBJECTIVE: The application of anti-inflammatories as topical desensitizers before dental bleaching is an approach to reduce bleaching-induced tooth sensitivity (TS). This randomized controlled trial compared the risk and intensity of TS and the color change resulting from in-office dental bleaching after using an experimental desensitizing gel containing ibuprofen and arginine. METHODS: Sixty-two participants with upper canine shades A2 or darker were randomly assigned to either the ibuprofen-arginine desensitizing group or the placebo group. The desensitizing gel was applied for 15 min before in-office bleaching with 35 % hydrogen peroxide gel for 50 min (2 sessions). To assess the absolute risk and intensity of TS, visual (0-10) and numeric rating (0-5) scales were used, and group comparisons were made using the McNemar test, Wilcoxon test, and paired Student t-test (α = 0.05). Color change was evaluated using Vita Classical, Vita Bleachedguide (ΔSGU), and Vita EasyShade (ΔEab, ΔE00, and ΔWID) before and one month after the bleaching procedure. Group comparisons for color change were done using a paired t-test (α = 0.05). RESULTS: The odds ratio for TS was 0.14 [95 % CI 0.02 to 0.6], meaning lower odds of TS for the desensitizing gel. A lower intensity of TS was also observed for the experimental group (p < 0.005) up to 48 h after bleaching. All color evaluation tools demonstrated effective and similar whitening for both groups (p > 0.05). CONCLUSIONS: Using the experimental desensitizing gel containing ibuprofen and arginine effectively reduced the risk and intensity of TS without compromising the bleaching efficacy. CLINICAL RELEVANCE: The topical application of ibuprofen/arginine on the in-office bleaching reduced risk and intensity of bleaching-induced tooth sensitivity.

PPARγ partial agonist LPSF/GQ-16 prevents dermal and pulmonary fibrosis in HOCl-induced systemic sclerosis (SSc) and modulates cytokine production in PBMC of SSc patients.

Thiazolidinediones (TZD) are synthetic molecules that have a range of biological effects, including antifibrotic and anti-inflammatory, and they may represent a promising therapeutic strategy for systemic sclerosis (SSc). The aim of this study was to investigate the immunomodulatory and antifibrotic properties of LPSF/GQ-16, a TZD derivative, in peripheral blood mononuclear cells (PBMC) from SSc patients and in a murine model of SSc HOCl-induced. The PBMC of 20 SSc patients were stimulated with phytohemagglutinin (PHA) and treated with LPSF/GQ-16 for 48 h, later cytokines in the culture supernatants were quantified by sandwich enzyme-linked immunosorbent assay (ELISA) or cytometric bead array (CBA). Experimental SSc was induced by intradermal injections of hypochlorous acid (HOCl) for 6 weeks. HOCl-induced SSc mice received daily treatment with LPSF/GQ-16 (30 mg/kg) through intraperitoneal injections during the same period. Immunological parameters were evaluated by flow cytometry and ELISA, and dermal and pulmonary fibrosis were evaluated by RT-qPCR, hydroxyproline dosage and histopathological analysis. In PBMC cultures, it was possible to observe that LPSF/GQ-16 modulated the secretion of cytokines IL-2 (p < 0.001), IL-4 (p < 0.001), IL-6 (p < 0.001), IL-17A (p = 0.006), TNF (p < 0.001) and IFN-γ (p < 0.001). In addition, treatment with LPSF/GQ-16 in HOCl-induced SSc mice promoted a significant reduction in dermal thickening (p < 0.001), in the accumulation of collagen in the skin (p < 0.001), down-regulated the expression of fibrosis markers in the skin (Col1a1, α-Sma and Tgfß1, p < 0.001 for all) and lungs (Il4 and Il13, p < 0.001 for both), as well as reduced activation of CD4 + T cells (p < 0.001), B cells (p < 0.001) and M2 macrophages (p < 0.001). In conclusion, LPSF/GQ-16 showed immunomodulatory and antifibrotic properties, demonstrating the therapeutic potential of this molecule for SSc.

Relação entre temperatura do ar e incidência de dengue: estudo de séries temporais em Minas Gerais, Brasil (2010-2019) / Relationship between air temperature and dengue incidence: time series study in Minas Gerais, Brazil (2010-2019) / Relación entre la temperatura del aire y la incidencia del dengue: estudio de series temporales en Minas Gerais, Brasil (2010-2019)

Resumo A temperatura do ar é um fator climático que afeta a incidência da dengue, com efeitos variando conforme o tempo e o espaço. Investigamos a relação entre a temperatura mínima do ar e a incidência da doença em Minas Gerais, Brasil, e avaliamos a influência de variáveis socioeconômicas e geográficas nessa relação, calculando-se o risco relativo (RR). Este é um estudo de série temporal com análise conduzida em três etapas distintas: modelagem por uso de distributed lag non-linear model (modelos não-lineares distributivos com defasagem), metanálise dos modelos obtidos e metarregressão com dados geográficos e socioeconômicos. A temperatura mínima foi um fator de proteção quando em temperaturas frias extremas (RR = 0,65; IC95%: 0,56-0,76) e moderadas (RR = 0,71; IC95%: 0,64-0,79) e fator de risco em temperaturas de calor moderado (RR = 1,15; IC95%: 1,07-1,24), mas não em extremo (RR = 1,1; IC95%: 0,99-1,22). A heterogeneidade dos modelos foi elevada (I2 = 60%) e essa medida não foi alterada em metarregressão. Temperaturas frias moderadas e extremas causam efeito protetivo, enquanto moderadas quentes aumentam o risco. No entanto, a temperatura mínima do ar não explica nem a variabilidade da região, nem mesmo com as outras variáveis em metarregressão.

Abstract Air temperature is a climatic factor that affects the incidence of dengue, with effects varying according to time and space. We investigated the relationship between minimum air temperature and dengue incidence in Minas Gerais, Brazil, and evaluated the influence of socioeconomic and geographic variables on this relationship. This is a time series study with analysis conducted in three distinct stages: modeling using a distributed lag non-linear model, meta-analysis of models obtained, and meta-regression with geographic and socioeconomic data. Minimum temperature was a protective factor at extreme cold temperatures (RR = 0.65; 95%CI: 0.56-0.76) and moderate cold temperatures (RR = 0.71; 95%CI: 0.64-0.79), and a risk factor at moderate hot temperatures (RR = 1.15; 95%CI: 1.07-1.24), but not at extreme hot temperatures (RR = 1.1; 95%CI: 0.99-1.22). Heterogeneity of the models was high (I2 = 60%), which was also observed in meta-regression. Moderate and extreme cold temperatures have a protective effect, while moderate hot temperatures increase the risk. However, minimum air temperature does not explain the variability in the region, not even with the other variables in meta-regression.

Resumen La temperatura del aire es un factor climático que afecta la incidencia del dengue, con efectos que varían según el tiempo y el territorio. Investigamos la relación entre la temperatura mínima del aire y la incidencia de la enfermedad en Minas Gerais, Brasil, y evaluamos la influencia de variables socioeconómicas y geográficas en esta relación. Se trata de un estudio de serie temporal cuyo análisis se realiza en tres etapas distintas: modelación mediante el uso de distributed lag non-linear model (modelos distributivos no lineales con retraso), metaanálisis de los modelos obtenidos y metarregresión con datos geográficos y socioeconómicos. La temperatura mínima fue un factor de protección ante temperaturas extremadamente frías (RR = 0,65; IC95%: 0,56-0,76) y moderadas (RR = 0,71; IC95%: 0,64-0,79) y factor de riesgo en temperaturas de calor moderado (RR = 1,15; IC95%: 1,07-1,24), pero no en extremo (RR = 1,1; IC95%: 0,99-1,22). La heterogeneidad de los modelos fue alta (I2 = 60%), y esta medida no se modificó en la metarregresión. Las temperaturas frías moderadas y extremas tienen un efecto protector, mientras que las temperaturas moderadamente altas aumentan el riesgo. Sin embargo, la temperatura mínima del aire no explica la variabilidad de la región, ni siquiera con las demás variables en metarregresión.

Occurrence of arbovirus infections in two riverine populations in the municipality of Humaitá, Amazonas, Brazil

ABSTRACT Background: The riverine communities of the Amazon comprise different social groups that inhabit the rural areas on the banks of rivers and lakes. Residents usually travel by river to rural and urban areas and are then exposed to urbanized diseases such as those caused by arbovirus infection. In Brazil, emerging diseases such as dengue, Zika, chikungunya, and those caused by infection with Oropouche and Mayaro viruses necessitate epidemiological surveillance. This study was aimed at determining the frequency of positivity for immunoglobulin (Ig)G and IgM antibodies against Zika, chikungunya, and dengue viruses and performing molecular analyses to detect viral RNA for the Zika, chikungunya, dengue virus, Oropouche, and Mayaro viruses, in the same serum samples obtained from riverside populations. Methods: This cross-sectional study was conducted in a riverside population in the Humaitá municipality of the Brazilian Amazon. More than 80% of the local population participated in this study. Entomological samples were collected to identify local mosquito vectors. Results: Analysis of 205 human serological samples revealed IgG antibodies against the dengue virus in 85 individuals. No molecular positivity was observed in human samples. Entomological analyses revealed 3,187 Diptera species, with Mansonia being the most frequent genus. Aedes aegypti and Aedes albopictus were not detected in the two collections. Conclusions: IgG antibodies against the dengue virus were highly prevalent, suggesting previous exposure. The absence of the arbovirus vectors Aedes aegypti and Aedes albopictus in the samples supports the hypothesis that the infections recorded likely occurred outside the riverside communities investigated.

Must a Knee with Anterior Cruciate Ligament Deficiency and High-grade Pivot Shift Test Present an Increase in Internal Rotation? / Um joelho com deficiência de ligamento cruzado anterior e alto grau no teste de pivot shift deve apresentar aumento de rotação interna?

Abstract Objective: Rupture of the anterior cruciate ligament (ACL) is one of the most common injuries in athletes and is often associated with damage to anterolateral structures. This combination of injuries presents itself clinically as a high-grade pivot shift test. The hypothesis of this study is that patients with ACL deficiency and high-grade pivot shift test should have an increased internal knee rotation. Methods: Twenty-two patients were tested. After effective spinal anesthesia, two tests were performed with the patient in supine position. First, the bilateral pivot shift test was performed manually, and its grade was recorded. Then, with the knee flexed to 90 degrees, the examiner drew the projection of the foot in a neutral position and in maximum internal rotation, and the angle of internal rotation was measured from the axes built between the central point of the heel and the hallux. Results: In the ACL-deficient knee, it was observed that there is a statistically significant average internal rotation (IR) delta of 10.5 degrees between the groups when not adjusted for age, and 10.6 degrees when adjusted for age. Conclusions: Knees with ACL deficiency and with pivot shift test grade I do not show increased internal rotation in relation to knees with intact ACL. Knees with ACL deficiency and with pivot shift test grades II and III show increased internal rotation in comparison to healthy knees.

Resumo Objetivo: A ruptura do ligamento cruzado anterior (LCA) é uma das lesões mais comuns em atletas e está frequentemente associada a danos nas estruturas anterolaterais. Esta combinação de lesões apresenta-se clinicamente como um teste de pivot shift de alto grau. A hipótese deste estudo é que pacientes com deficiência de LCA e teste de pivot shift de alto grau tenham aumento da rotação interna (RI) do joelho. Métodos: Vinte e dois pacientes foram testados. Após raquianestesia efetiva, foram realizados dois testes com o paciente em posição supina. Primeiro, o teste de pivot shift bilateral foi realizado manualmente e seu grau foi registrado. Em seguida, com o joelho flexionado a 90 graus, o examinador traçou a projeção do pé em posição neutra e em RI máxima e mediu o ângulo de RI a partir dos eixos construídos entre o ponto central do calcanhar e o hálux. Resultados: Joelhos com deficiência de LCA apresentam delta da RI média estatisticamente significativo de 10,5 graus entre os grupos sem ajuste de idade e de 10,6 graus com ajuste de idade. Conclusões: Joelhos com deficiência do LCA e teste de pivot shift de grau I não apresentam aumento da RI em relação aos joelhos com LCA íntegro. Joelhos com deficiência do LCA e teste de pivot shift de graus II e III apresentam RI em comparação aos joelhos saudáveis.

Aerobic exercise training mitigates tumor growth and cancer-induced splenomegaly through modulation of non-platelet platelet factor 4 expression.

Exercise training reduces the incidence of several cancers, but the mechanisms underlying these effects are not fully understood. Exercise training can affect the spleen function, which controls the hematopoiesis and immune response. Analyzing different cancer models, we identified that 4T1, LLC, and CT26 tumor-bearing mice displayed enlarged spleen (splenomegaly), and exercise training reduced spleen mass toward control levels in two of these models (LLC and CT26). Exercise training also slowed tumor growth in melanoma B16F10, colon tumor 26 (CT26), and Lewis lung carcinoma (LLC) tumor-bearing mice, with minor effects in mammary carcinoma 4T1, MDA-MB-231, and MMTV-PyMT mice. In silico analyses using transcriptome profiles derived from these models revealed that platelet factor 4 (Pf4) is one of the main upregulated genes associated with splenomegaly during cancer progression. To understand whether exercise training would modulate the expression of these genes in the tumor and spleen, we investigated particularly the CT26 model, which displayed splenomegaly and had a clear response to the exercise training effects. RT-qPCR analysis confirmed that trained CT26 tumor-bearing mice had decreased Pf4 mRNA levels in both the tumor and spleen when compared to untrained CT26 tumor-bearing mice. Furthermore, exercise training specifically decreased Pf4 mRNA levels in the CT26 tumor cells. Aspirin treatment did not change tumor growth, splenomegaly, and tumor Pf4 mRNA levels, confirming that exercise decreased non-platelet Pf4 mRNA levels. Finally, tumor Pf4 mRNA levels are deregulated in The Cancer Genome Atlas Program (TCGA) samples and predict survival in multiple cancer types. This highlights the potential therapeutic value of exercise as a complementary approach to cancer treatment and underscores the importance of understanding the exercise-induced transcriptional changes in the spleen for the development of novel cancer therapies.

Effects of air temperature on the risk of death from COPD in major microregions in Brazil: a time series study.

OBJECTIVE: To evaluate the association between the risk of death from COPD and air temperature events in ten major Brazilian microregions. METHODS: This was a time series analysis of daily COPD deaths and daily mean air temperatures between 1996 and 2017. Using distributed nonlinear lag models, we estimated the cumulative relative risks of COPD mortality for four temperature percentiles (representing moderate and extreme cold and heat events) in relation to a minimum mortality temperature, with a lag of 21 days, in each microregion. RESULTS: Significant associations were found between extreme air temperature events and the risk of death from COPD in the southern and southeastern microregions in Brazil. There was an association of extreme cold and an increased mortality risk in the following microregions: 36% (95% CI, 1.12-1.65), in Porto Alegre; 27% (95% CI, 1.03-1.58), in Curitiba; and 34% (95% CI, 1.19-1.52), in São Paulo; whereas moderate cold was associated with an increased risk of 20% (95% CI, 1.01-1.41), 33% (95% CI, 1.09-1.62), and 24% (95% CI, 1.12-1.38) in the same microregions, respectively. There was an increased COPD mortality risk in the São Paulo and Rio de Janeiro microregions: 17% (95% CI, 1.05-1.31) and 12% (95% CI, 1,02-1,23), respectively, due to moderate heat, and 23% (95% CI, 1,09-1,38) and 32% (95% CI, 1,15-1,50) due to extreme heat. CONCLUSIONS: Non-optimal air temperature events were associated with an increased risk of death from COPD in tropical and subtropical areas of Brazil.

Hepatoprotective Effects of Four Brazilian Savanna Species on Acetaminophen-Induced Hepatotoxicity in HepG2 Cells.

We investigated four Cerrado plant species, i.e., Cheiloclinium cognatum (Miers) A.C.Sm, Guazuma ulmifolia Lam., Hancornia speciosa Gomes, and Hymenaea stigonocarpa Mart. ex Hayne, against acetaminophen toxicity using an in vitro assay with HepG2 cells. The activity against acetaminophen toxicity was evaluated using different protocols, i.e., pre-treatment, co-treatment, and post-treatment of the cells with acetaminophen and the plant extracts. HepG2 cell viability after treatment with acetaminophen was 39.61 ± 5.59% of viable cells. In the pre-treatment protocol, the extracts could perform protection with viability ranging from 50.02 ± 15.24% to 78.75 ± 5.61%, approaching the positive control silymarin with 75.83 ± 5.52%. In the post-treatment protocol, all extracts and silymarin failed to reverse the acetaminophen damage. In the co-treatment protocol, the extracts showed protection ranging from 50.92 ± 11.14% to 68.50 ± 9.75%, and silymarin showed 77.87 ± 4.26%, demonstrating that the aqueous extracts of the species also do not increase the toxic effect of acetaminophen. This protection observed in cell viability was accompanied by a decrease in ROS. The extracts' hepatoprotection can be related to antioxidant compounds, such as rutin and mangiferin, identified using HPLC-DAD and UPLC-MS/MS. The extracts were shown to protect HepG2 cells against future APAP toxicity and may be candidates for supplements that could be used to prevent liver damage. In the concomitant treatment using the extracts with APAP, it was demonstrated that the extracts do not present a synergistic toxicity effect, with no occurrence of potentiation of toxicity. The extracts showed considerable cytoprotective effects and important antioxidant characteristics.

Cochlear radiation dose and hearing loss in patients with vestibular schwannoma undergoing radiosurgery: systematic review

Abstract Objectives: To determine the cut-off point of the cochlear radiation dose as a risk factor for hearing loss in patients with vestibular schwannoma treated with radiosurgery. Methods: A systematic review of the literature was performed without language or publication year restrictions in the MEDLINE/PubMed, EMBASE, Web of Science, LILACS/VHL and Cochrane Library databases. Studies that met the following criteria were included: 1) population: adults of both sexes who underwent radiosurgery for vestibular schwannoma treatment; 2) exposure: cochlear radiation; 3) outcome: hearing loss; 4) type of study: cohort. Two independent reviewers conducted the entire review process. The registration number in PROSPERO was CRD42020206128. Results: From the 333 articles identified in the searches, seven were included after applying the eligibility criteria. There was no standardization as to how to measure exposure or outcome in the included studies, and most studies did not present sufficient data to enable meta-analysis. Conclusion: It was not possible to determine a cut-off point for high cochlear dose that could be considered a risk factor for hearing loss.

Effect of irrigation protocols on smear layer removal, bond strength and nanoleakage of fiber posts using a self-adhesive resin cement.

Objectives: This study aimed to investigate the effect of the application method of 2% chlorhexidine (CHX) and its influence on the adhesion of fiberglass posts cemented with a self-adhesive resin cement. Materials and Methods: Sixty human mandibular premolars were endodontically treated and divided into 5 groups (n = 12), according to the canal irrigant and its application method: 2 groups with conventional syringe irrigation (CSI)-2.5% sodium hypochlorite (NaOCl) (control) and 2% CHX- and 3 groups with 2% CHX irrigation/activation-by passive ultrasonic irrigation (PUI), Easy Clean file, and XP-Endo Finisher file. Two roots per group were evaluated for smear layer (SL) removal by scanning electron microscopy. For other roots, fiber posts were luted using a self-adhesive resin cement. The roots were sectioned into 6 slices for push-out bond strength (BS) (7/group) and nanoleakage (NL) (3/group). Data from SL removal were submitted to Kruskal-Wallis and Student-Newman-Keuls tests (α = 0.05). Data from BS and NL were evaluated by 2-way analysis of variance and Tukey's test (α = 0.05). Results: For SL removal and BS, the CHX irrigation/activation promoted better values than CSI with CHX (p < 0.05), but it was not significantly different from CSI with NaOCl (p > 0.05). For NL, the lowest values were obtained by the chlorhexidine irrigation/activation groups (p < 0.05). Conclusions: Active 2% CHX irrigation can be used to improve the post space cleaning and adhesion before fiber post cementation with self-adhesive resin cements.