Antifungal activity of a trypsin inhibitor from Salvia hispanica L. (chia) seeds against fluconazole-resistant strains of Candida spp. and evaluation of its toxicity in vitro.

The incidence of Candida species resistant to traditional antifungal drugs is increasing globally. This issue significantly impacts patients' lives and increases healthcare expenses, confirming the need to develop novel therapeutic strategies. Recently, a thermostable trypsin inhibitor named ShTI (11.558 kDa), which has antibacterial effects on Staphylococcus aureus, was isolated from Salvia hispanica L. (chia) seeds. This study aimed to assess the antifungal effect of ShTI against Candida species and its synergism with fluconazole and to evaluate its mode of action. Preliminary toxicological studies on mouse fibroblasts were also performed. ShTI exhibited antifungal effects against C. parapsilosis (ATCC® 22,019), C. krusei (ATCC® 6258), and six clinical fluconazole-resistant strains of C. albicans (2), C. parapsilosis (2), and C. tropicalis (2). The minimum inhibitory concentration (MIC) values were 4.1 µM (inhibiting 50% of the isolates) and 8.2 µM (inhibiting 100% of the isolates). Additionally, when combined with fluconazole, ShTI had a synergistic effect on C. albicans, altering the morphological structure of the yeast. The mode of action of ShTI against C. krusei (ATCC® 6258) and C. albicans involves cell membrane permeabilization, the overproduction of reactive oxygen species, the formation of pseudohyphae, pore formation, and consequently, cell death. In addition, ShTI (8.65 and 17.3 µM) had noncytotoxic and nongenotoxic effects on L929 mouse fibroblasts. These findings suggest that ShTI could be a promising antimicrobial candidate, but further research is necessary to advance its application as a novel antifungal agent.

Exploring the Fluconazole-Resistance Modifying Activity and Potential Mechanism of Action of Fixed Oil from Caryocar coriaceum Wittm. (Caryocaraceae) against Candida Species.

The fixed oil from the inner mesocarp of Caryocar coriaceum Wittm. is used in the Chapada do Araripe region of Brazil for the treatment of genitourinary candidiasis. This study aimed to evaluate the chemical composition, antifungal activity, reduction of fungal virulence, and the preliminary toxicity of the fixed oil from the inner mesocarp of C. coriaceum tested against three Candida yeasts. The oil was characterized by gas chromatography (GC-MS and GC-FID). Antifungal activity was assessed using the serial microdilution method. Additionally, the potential of the oil as an enhancer of fluconazole action was tested at sub-inhibitory concentrations (MIC/8). The mechanism of action of C. coriaceum fixed oil was determined by evaluating the inhibition of morphological transition in Candida spp. The chemical composition of the fixed oil of C. coriaceum comprised both unsaturated and saturated fatty acids. Oleic (61 %) and palmitic (33 %) acids were the major constituents. Regarding its anti-Candida activity, the oil inhibited the growth of C. albicans (IC50 : 371 µg/mL) and C. tropicalis (IC50 : 830 µg/mL). Furthermore, the oil reversed the antifungal resistance of C. albicans and C. tropicalis, restoring the susceptibility to fluconazole and reducing their IC50 from 12.33 µg/mL and 362 µg/mL to 0.22 µg/mL and 13.93 µg/mL, respectively. The fixed oil of C. coriaceum completely inhibited the morphological transition of C. albicans and C. tropicalis at a concentration of 512 µg/mL, but exhibited limited low antifungal potential against C. krusei. The observed antifungal activity may be attributed to the overproduction of reactive oxygen species. Additionally, the oil showed no toxic effect on the Drosophila melanogaster in vivo model. The fixed oil from the inner mesocarp of C. coriaceum emerge as a strong candidate for the development of new pharmaceutical formulations to treat infections caused by Candida spp.

Spatial-temporal distribution of maxillofacial injuries resulting from intimate partner violence against women.

BACKGROUND/AIM: Maxillofacial trauma resulting from intimate partner violence (IPV) represents an important oral health problem. In this sense, the aim of this study was to investigate the spatial-temporal distribution of maxillofacial trauma resulting from IPV against women, using a geostatistical approach. MATERIALS AND METHODS: An ecological study was carried out including the analysis of confirmed IPV cases against women treated at a Center for Forensic Medicine and Dentistry over a four-year observation period, as well as the evaluation of population data from the victims' places of residence extracted from the last demographic census of the Brazilian Institute of Geography and Statistics. Statistical analysis included: (i) finite mixture modeling to establish incidence trajectory patterns; (ii) Getis-Ord indicator (Gi*) for spatial autocorrelation; (iii) spatial regression analysis (p < .05). RESULTS: Two distinct trajectory patterns (TP1 and TP2) related to IPV incidence were identified using finite mixture modeling, suggesting spatial-temporal disparities at the regional level. In TP1, it was observed that IPV incidence was relatively low and remained stable over time, covering almost two-thirds (62.0%) of investigated spatial units. TP2 was characterized by higher IPV incidence with a tendency to increase in the last year, including more than one-third of neighborhoods (38.0%). Autocorrelation analysis showed a predominance of hot areas (hotspots) in the Eastern zone (p < .05) and in the Western zone (p < .05); and cold areas (coldspots) in the Northern zone (p < .05). In addition, statistically significant association was observed among neighborhoods with higher percentage of households with family householder without income and higher incidence of maxillofacial trauma resulting from IPV against women (ß = 5.305; SE = 1.741; p = .002). CONCLUSIONS: The findings indicate an association between higher IPV incidence against women, maxillofacial trauma, and socio-spatial vulnerability.

Brazilian National Network of Alternative Methods (RENAMA) 10th Anniversary: Meeting of the Associated Laboratories, May 2022.

The Brazilian National Network of Alternative Methods (RENAMA), which is linked to the Ministry of Science, Technology and Innovation, is currently comprised of 51 laboratories from CROs, academia, industry and government. RENAMA's aim is to develop and validate new approach methodologies (NAMs), as well as train researchers and disseminate information on their use - thus reducing Brazilian, and consequently Latin American, dependence on external technology. Moreover, it promotes the adoption of NAMs by educators and trained researchers, as well as the implementation of good laboratory practice (GLP) and the use of certified products. The RENAMA network started its activities in 2012, and was originally comprised of three central laboratories - the National Institute of Metrology, Quality and Technology (INMETRO); the National Institute of Quality Control in Health (INCQS); and the National Brazilian Biosciences Laboratory (LNBio) - and ten associated laboratories. In 2022, RENAMA celebrated its 10th anniversary, a milestone commemorated by the organisation of a meeting attended by different stakeholders, including the RENAMA-associated laboratories, academia, non-governmental organisations and industry. Ninety-six participants attended the meeting, held on 26 May 2022 in Balneário Camboriú, SC, Brazil, as part of the programme of the XXIII Brazilian Congress of Toxicology 2022. Significant moments of the RENAMA were remembered, and new goals and discussion themes were established. The lectures highlighted recent innovations in the toxicological sciences that have translated into the assessment of consumer product safety through the use of human-relevant NAMs instead of the use of existing animal-based approaches. The challenges and opportunities in accepting such practices for regulatory purposes were also presented and discussed.

Calcineurin inhibitors in the management of recurrent miscarriage and recurrent implantation failure: Systematic review and meta-analysis.

Recurrent miscarriage (RM) affects up to 2.5% of couples of reproductive age. Up to 10% of couples using assisted reproductive technology experience recurrent implantation failure (RIF). Immunosuppressive drugs, such as calcineurin inhibitors (CNIs), has been proposed for RM and RIF management. This systematic review and meta-analysis (SRMA) aimed to evaluate the efficacy and safety of CNIs in RM and RIF treatment. We searched in the three databases. Review Manager 5.4.1 was used for statistical analysis. This review included 8 studies involving 1042 women (485 women in the CNIs group and 557 women in the control group). CNI treatment (cyclosporine [CsA] and tacrolimus [TAC]) increases live birth rate (LBR, odds ratio [OR]: 2.52; 95% confidence interval [CI]: 1.93-3.28, p < 0.00001) and clinical pregnancy rate (OR: 2.25; 95% CI: 1.54-4.40, p < 0.0001) and decreases miscarriage rate (OR: 0.45 95% CI: 0.32-0.63, p < 0.00001) when compared to the control. Side effects and obstetric and neonatal complications was similar in both groups. In conclusion, CNIs increased LBR in women with RM and RIF but there is a moderate risk of bias. Subgroup analysis revealed that CNIs improved LBR in women with RM with a low risk of bias. However, in women with RIF, with moderate to high risk of bias. The use of CsA and TAC, in low doses and for a short period, for managing reproductive failures in women seems to be safe, not causing serious side effects nor increasing the risk of obstetric and neonatal complications.

Caryocar coriaceum fruits as a potential alternative to combat fungal and bacterial infections: In vitro evaluation of methanolic extracts.

Caryocar coriaceum, commonly known as 'pequi', is a medicinal species used traditionally for the herbal treatment of infectious and parasitic diseases in the Brazilian Northeast region. In this study, we investigated whether the fruits of C. coriaceum have bioactive chemical constituents against etiological agents of infectious diseases. The methanolic extract of the internal mesocarp of the fruits of C. coriaceum (MECC) was chemically analyzed and evaluated for its antimicrobial and drug-enhancing activity against multidrug-resistant pathogenic bacteria (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus), and Candida spp. strains. The extract had flavones, flavonols, xanthones, catechins, and flavanones as major classes. A total of 11.26 mg GAE/g of phenolics, and 5.98 mg QE/g of flavonoids were found. No intrinsic antibacterial activity was observed; however, the extract was able to intensify the action of gentamicin and erythromycin against multi-resistant strains. The anti-Candida effect observed in this study was mainly due to the formation of reactive oxygen species. The extract was capable of causing damage to the plasmatic membrane of Candida tropicalis through pores formation. Our findings partially support the ethnopharmacological uses of the fruit pulp of C. coriaceum against infectious and parasitic diseases.

Tridimensional assessment of the mandibular angle in patients with different skeletal patterns by cone-beam computed tomography scans: a retrospective study.

BACKGROUND: Since the muscles of chewing are involved in the region of the mandibular angle, important structures in surgical and orthodontic procedures, to study its morphological aspects and the possible influence of different patterns of skeletal development would be of interest. Thus, this study aimed to assess the influence of patient characteristics - such as sex, skeletal malocclusion (Class I, Class II, and Class III) and facial type (brachycephalic, mesocephalic, and dolichocephalic) - on the width, height, thickness, and volume of the mandibular angle, using cone-beam computed tomography (CBCT) scans. METHODS: CBCT scans were assessed - 144 men and 154 women, total of 298 - and classified according to skeletal patterns (skeletal malocclusions and facial types). Width, height, and thickness of the mandibular angle were measured using OnDemand 3D software. The volumetric measures of the mandibular angle were obtained using the ITK-SNAP software. Analysis of Variance (multiway ANOVA) with Tukey's post-hoc test compared the data, with a 5% significance level. RESULTS: Among the factors studied, sex significantly influenced all the analyzed variables (height, width, thickness, and volume of the mandibular angle) (p < 0.05); in general, male individuals presented higher values than females. In some cases, the skeletal malocclusion and facial type factors influenced only the width and height variables (p < 0.05); in general, the Class III and dolichocephalic individuals presented higher values in relation to the other types of skeletal malocclusions and facial types. CONCLUSIONS: Variations in the craniofacial growth pattern, considering the different skeletal malocclusions and facial types, had some influence in the width and height dimensions of the mandibular angle. Furthermore, sex influenced all the studied variables.

Toxicity of copper and zinc alone and in combination in Caenorhabditis elegans model of Huntington's disease and protective effects of rutin.

Copper (Cu) and Zinc (Zn) are required in small concentrations for metabolic functions, but are also toxic. There is a great concern about soil pollution by heavy metals, which may exposure the population to these toxicants, either by inhalation of dust or exposure to toxicants through ingestion of food derived from contaminated soils. In addition, the toxicity of metals in combination is questionable, as soil quality guidelines only assess them separately. It is well known that metal accumulation is often found in the pathologically affected regions of many neurodegenerative diseases, including Huntington's disease (HD). HD is caused by an autosomal dominantly inherited CAG trinucleotide repeat expansion in the huntingtin (HTT) gene. This results in the formation of a mutant huntingtin (mHTT) protein with an abnormally long polyglutamine (polyQ) repeat. The pathology of HD results in loss of neuronal cells, motor changes, and dementia. Rutin is a flavonoid found in various food sources, and previous studies indicate it has protective effects in HD models and acts as a metal chelator. However, further studies are needed to unravel its effects on metal dyshomeostasis and to discern the underlying mechanisms. In the present study, we investigated the toxic effects of long-term exposure to copper, zinc, and their mixture, and the relationship with the progression of neurotoxicity and neurodegeneration in a C. elegans-based HD model. Furthermore, we investigated the effects of rutin post metal exposure. Overall, we demonstrate that chronic exposure to the metals and their mixture altered body parameters, locomotion, and developmental delay, in addition to increasing polyQ protein aggregates in muscles and neurons causing neurodegeneration. We also propose that rutin has protective effects acting through mechanisms involving antioxidant and chelating properties. Altogether, our data provides new indications about the higher toxicity of metals in combination, the chelating potential of rutin in the C. elegans model of HD and possible strategies for future treatments of neurodegenerative diseases caused by the aggregation of proteins related to metals.

Carbon dots: Types, preparation, and their boosted antibacterial activity by photoactivation. Current status and future perspectives.

Carbon dots (CDs) correspond to carbon-based materials (CBM) with sizes usually below 10 nm. These nanomaterials exhibit attractive properties such us low toxicity, good stability, and high conductivity, which have promoted their thorough study over the past two decades. The current review describes four types of CDs: carbon quantum dots (CQDs), graphene quantum dots (GQDs), carbon nanodots (CNDs), and carbonized polymers dots (CPDs), together with the state of the art of the main routes for their preparation, either by "top-down" or "bottom-up" approaches. Moreover, among the various usages of CDs within biomedicine, we have focused on their application as a novel class of broad-spectrum antibacterial agents, concretely, owing their photoactivation capability that triggers an enhanced antibacterial property. Our work presents the recent advances in this field addressing CDs, their composites and hybrids, applied as photosensitizers (PS), and photothermal agents (PA) within antibacterial strategies such as photodynamic therapy (PDT), photothermal therapy (PTT), and synchronic PDT/PTT. Furthermore, we discuss the prospects for the possible future development of large-scale preparation of CDs, and the potential for these nanomaterials to be employed in applications to combat other pathogens harmful to human health. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease.

ICU Nursing Team Mental Health in The Face of the COVID-19 Pandemic: An Integrative Review / Saúde mental da equipe de enfermagem intensivista ante a pandemia da covid-19: revisão integrativa / Salud mental de los profesionales de enfermería intensivistas ante la pandemia de la COVID-19: revisión integradora

Introduction: During the COVID-19 pandemic, health professionals were at an increased risk of developing psychological conditions, especially in Intensive Care Units. A gap is verified in the knowledge about ICU Nursing teams' mental health in the care provided to patients affected by COVID-19. Objective: To review the literature to identify the mental health conditions of ICU Nursing professionals during the COVID-19 pandemic. Materials and method: This is an integrative literature review with data collection from January to April 2022 in the Embase, Cumulative Index to Nursing and Allied Health Literature, PubMed, Scopus Content Overview and Web of Science databases. The following descriptors were listed: "Intensive Care Units," "COVID-19," "Mental Health," and "Nurse." The materials included were studies produced since 2020, available in full in the Spanish, English and Portuguese languages, and which answered the research question. Search and selection of the articles were the duty of two duly trained researchers, who worked independently through peer discussion. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations were followed. Results: From a sample of 16 articles, it was observed that the critical care of COVID-19 patients affected Nursing professionals' mental health with an emphasis on depression, anxiety, stress and fear. This was associated with a lack of evidence-based training, scarcity of human and physical resources, work overload and insufficient work experience. Conclusions: ICU Nursing professionals are mentally shaken; therefore, it is imperative to implement policies, strategies and methods to improve the psychological conditions of these professionals, to ensure the quality of services.

Introdução: durante a pandemia da covid-19, os profissionais de saúde apresentaram risco aumentado para o desenvolvimento de afecções psíquicas, especialmente na unidade de terapia intensiva. Verifica-se lacuna de conhecimento sobre a saúde mental da equipe de enfermagem intensivista no atendimento aos pacientes acometidos pela covid-19. Objetivo: identificar, na literatura científica, as condições da saúde mental do profissional de enfermagem intensivista durante a pandemia da covid-19. Materiais e método: esta é uma revisão integrativa da literatura; a coleta de dados ocorreu de janeiro a abril de 2022 nas fontes de dados Embase, Cumulative Index to Nursing and Allied Health Literature, PubMed, Scopus Content Overview e Web of Science. Elencaram-se os seguintes descritores: "Intensive Care Units", "Covid 19", "Mental Health", "Nurse". Incluíram-se estudos produzidos desde 2020, disponíveis na íntegra, em espanhol, inglês e português, e que respondessem à questão de pesquisa. A busca e seleção dos artigos foram executadas por dois pesquisadores treinados, de modo independente, mediante discussão por pares. As recomendações do Preferred Reporting Items for Systematic Reviews and Meta-Analyses foram seguidas. Resultados: a partir de uma amostra de 16 artigos, observou-se que o cuidado crítico de pacientes com covid-19 afetou a saúde mental dos profissionais de enfermagem com destaque para depressão, ansiedade, estresse e medo. Isso se associou à falta de tratamento baseado em evidências, à carência de recursos humanos e físicos, à sobrecarga de trabalho e às experiências de trabalho insuficientes. Conclusões: os profissionais de enfermagem intensivistas estão mentalmente abalados; portanto, é imperativa a implantação de políticas, estratégias e métodos para melhorar as condições psicológicas desses profissionais, para, assim, garantir a qualidade nos serviços.

Introducción: durante la pandemia de la covid-19, los profesionales de la salud han presentado riesgo aumentado para el desarrollo de afecciones psíquicas, especialmente en la unidad de terapia intensiva. Se encuentra vacío de conocimiento acerca de la salud mental de los profesionales de enfermería intensivistas en la atención a los pacientes acometidos por la covid-19. Objetivo: identificar, en la literatura científica, las condiciones de la salud mental del profesional de enfermería intensivista durante la pandemia de la covid-19. Materiales y método: se trata de una revisión integradora de la literatura; la recolección de datos ocurrió de enero a abril de 2022 en las fuentes de dados Embase, Cumulative Index to Nursing and Allied Health Literature, PubMed, Scopus Content Overview y Web of Science. Se han relacionado los siguientes descriptores: "Intensive Care Units", "Covid 19", "Mental Health", "Nurse". Se han incluido estudios producidos desde el 2020, disponibles de forma integral, en español, inglés y portugués, y que atendieran a la pregunta de investigación. La búsqueda y selección de los artículos se ejecutaron por dos investigadores capacitados, de modo independiente, mediante discusión por pares. Se siguieron las recomendaciones del Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Resultados: desde una amuestra de 16 artículos, se ha observado que la atención crítica a pacientes con covid-19 ha afectado la salud mental de los profesionales de enfermería con énfasis para depresión, ansiedad, estrés y miedo. Lo anterior se asocia a la falta de tratamiento basado en evidencia, la carencia de recursos humanos y físico, la sobrecarga de trabajo y las experiencias de trabajo insuficientes. Conclusiones: los profesionales de enfermería intensivistas están mentalmente debilitados; por lo tanto, urge la implantación de políticas, estrategias y métodos para mejorar las condiciones psicológicas de estos profesionales para, así, asegurar la calidad en los servicios.

Are history of falls and fear of falling associated with mobility in community-dwelling older adults?

Evidence has suggested that a history of falls and fear of falling (FOF) are associated with reduced mobility among older adults. Although many studies have explored the association between the history of falls and FOF in the context of decreased mobility, most have had small sample sizes, limiting the generalizability of the results. Therefore, this study sought to contribute to the body of knowledge around these constructs to further support the previous findings. To investigate the association between a history of falls and FOF with low mobility in community-dwelling older adults. This cross-sectional study included 308 older adults (69.9 ± 7.1 years, 57.8% female). The Timed Up and Go (TUG) test was used to classify mobility limitations in participants and the Falls Efficacy Scale-International - Brazil was used to quantify FOF. Participants were also asked if they had fallen in the previous 12 months. Multivariable logistic regression was used. The prevalence rates of a history of falls and FOF were 32.7 and 48.4%, respectively. Older adults with a history of falls and FOF had 2.20 (95%CI: 1.20; 4.02) and 3.80 (95%CI: 1.90; 7.58) greater odds of presenting low mobility than older adults without these health problems, respectively. History of falls and FOF are associated with higher odds of low mobility in community-dwelling older adults. Therefore, it is of the utmost importance to introduce public health programs aimed at preventing falls in older adults to reduce possible adverse health outcomes, including low mobility.

Chemical profile and cytotoxic evaluation of aerial parts of Euphorbia tirucalli L. on gastric adenocarcinoma (AGS cells).

Ethanol extract from the aerial parts of Euphorbia tirucalli L. as well as the latex of the plant suspended in water are used by the Brazilian population for the treatment of various diseases, including cancer. The purposes of this study were to determine if the ethanol extract is effective as cytotoxic agent against gastric adenocarcinoma cells (AGS) and its chemical composition by GC-MS, ESI-(-)-FT-ICR MS and (-)-ESI-LTQ-MS/MS. The results were compared with that of latex previously described by us. Hexane and aqueous fractions showed higher cytotoxicity on AGS cells. Nine triterpene compounds were detected by GC-MS in hexane fraction, including euphol and friedelin, while ellagic acid was identified as main phenolic compound in aqueous extract. Therefore, the greater cytotoxic activity of the ethanol extract of the aerial parts of Euphorbia tirucalli for gastric cancer, when compared to latex, seems to originate from the antiproliferative effects of ellagic acid and triterpenes.

Is waist circumference associated with fear of falling in community-dwelling older adults? A cross-sectional study.

INTRODUCTION: Fear of falling (FOF) is a prevalent condition among older adults and several variables have been pointed out as risk factors. OBJECTIVES: To identify the cut-off point on waist circumference (WC), capable of discriminating between older adults with and without FOF, and to test the association between WC and FOF. METHODS: A cross-sectional observational study was carried out with older adults of both sexes from Balneário Arroio do Silva, Brazil. We used Receiver Operating Characteristic (ROC) curves to determine the cut-off point on WC and logistic regression adjusted for potential confounding variables to test the association. RESULTS: Older women with WC >93.5 cm [area under the curve: 0.61 (95%CI 0.53; 0.68)] had 3.30 (95%CI 1.53; 7.14) greater chances of having FOF compared with older women with WC ≤93.5 cm. WC was not able to discriminate FOF in older men. CONCLUSION: WC values >93.5 cm are associated with higher chances of FOF in older women.

Combined reverse osmosis and UV/H2O2 treatment of aqueous solutions of bisphenol A and 17α-ethinylestradiol: assessment of estrogenic activity.

Bisphenol-A (BPA) and 17α-ethinylestradiol (EE2) are considered endocrine disrupting compounds (EDC) and they may be harmful to the normal functioning of endocrine systems of humans and animals. Moreover, the presence of these compounds in superficial and groundwater may represent serious risks, even in low concentrations like ng·L-1. The objectives of this study were to remove BPA and EE2 from solutions containing a mixture of these compounds in ultrapure water at low concentrations through reverse osmosis (RO) membrane combined with a UV/H2O2 process. Furthermore, to assess the estrogenic activity reduction after such treatments, in vitro recombinant yeast-estrogen screen (YES) assay was used. The removal efficiencies of target micropollutants increased with the increase of H2O2 dosage. For RO permeate stream, they enhanced from 91% to 96% for EE2 and from 76% to 90% for BPA while, for the concentrate stream, from 70% to 81% for EE2 and 41% to 84% for BPA as the H2O2 concentration were increased from 100 to 1000 µg·L-1. The OH radicals' generation was the dominant factor in the degradation of EDC during the UV/H2O2 treatment since the photolysis itself was not enough to degrade BPA or EE2. The estrogenic activity reduction after UV/H2O2 treatment was high, ranging from 92% to 98% for the permeate stream and from 50% to 93% for the concentrate stream. The EE2 was responsible for the whole observed estrogenic activity since BPA does not present estrogenicity, by in vitro YES assay, in the concentrations observed.

Potential of [11C](R)-PK11195 PET Imaging for Evaluating Tumor Inflammation: A Murine Mammary Tumor Model.

BACKGROUND: Breast tumor inflammation is an immunological process that occurs mainly by mediation of Tumor-Associated Macrophages (TAM). Aiming for a specific measurement of tumor inflammation, the current study evaluated the potential of Positron Emission Tomography (PET) imaging with [11C](R)-PK11195 to evaluate tumor inflammation in a mammary tumor animal model. METHODS: Female Balb/C mice were inoculated with 4T1 cells. The PET imaging with [11C](R)-PK11195 and [18F]FDG was acquired 3 days, 1 week, and 2 weeks after cell inoculation. RESULTS: The [11C](R)-PK11195 tumor uptake increased from 3 days to 1 week, and decreased at 2 weeks after cell inoculation, as opposed to the [18F]FDG uptake, which showed a slight decrease in uptake at 1 week and increased uptake at 2 weeks. In the control group, no significant differences occurred in tracer uptake over time. Tumor uptake of both radiopharmaceuticals is more expressed in tumor edge regions, with greater intensity at 2 weeks, as demonstrated by [11C](R)-PK11195 autoradiography and immunofluorescence with TSPO antibodies and CD86 pro-inflammatory phenotype. CONCLUSION: The [11C](R)-PK11195 was able to identify heterogeneous tumor inflammation in a murine model of breast cancer and the uptake varied according to tumor size. Together with the glycolytic marker [18F]FDG, molecular imaging with [11C](R)-PK11195 may provide a better characterization of inflammatory responses in cancer.

Platelet-derived growth factor (PDGF) cross-signaling via non-corresponding receptors indicates bypassed signaling in colorectal cancer.

Platelet-derived growth factor (PDGF) signaling, besides other growth factor-mediated signaling pathways like vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), seems to play a crucial role in tumor development and progression. We have recently provided evidence for upregulation of PDGF expression in UICC stage I-IV primary colorectal cancer (CRC) and demonstrated PDGF-mediated induction of PI3K/Akt/mTOR signaling in CRC cell lines. The present study sought to follow up on our previous findings and explore the alternative receptor cross-binding potential of PDGF in CRC. Our analysis of primary human colon tumor samples demonstrated upregulation of the PDGFRß, VEGFR1, and VEGFR2 genes in UICC stage I-III tumors. Immunohistological analysis revealed co-expression of PDGF and its putative cross-binding partners, VEGFR2 and EGFR. We then analyzed several CRC cell lines for PDGFRα, PDGFRß, VEGFR1, and VEGFR2 protein expression and found these receptors to be variably expressed amongst the investigated cell lines. Interestingly, whereas Caco-2 and SW480 cells showed expression of all analyzed receptors, HT29 cells expressed only VEGFR1 and VEGFR2. However, stimulation of HT29 cells with PDGF resulted in upregulation of VEGFR1 and VEGFR2 expression despite the absence of PDGFR expression and mimicked the effect of VEGF stimulation. Moreover, PDGF recovered HT29 cell proliferation under simultaneous treatment with a VEGFR or EGFR inhibitor. Our results provide some of the first evidence for PDGF cross-signaling through alternative receptors in colorectal cancer and support anti-PDGF therapy as a combination strategy alongside VEGF and EGF targeting even in tumors lacking PDGFR expression.

How much time in sedentary behavior is associated with probable sarcopenia in older adults?

Sedentary activities, such as watching television and using the computer, are frequent conditions in older adults and can be associated with sarcopenia. The objectives of this study were: (a) to establish sedentary behavior (SB) cutoff values for screening probable sarcopenia in community-dwelling older adults and (b) to verify the association between SB and probable sarcopenia according to the established cutoff point. This was a cross-sectional study including 1,165 community residents in Florianopolis/SC. SB was assessed using the International Physical Activity Questionnaire. The outcome was probable sarcopenia (assessed by time ≥ 15 s in the Five times sit-to-stand test). The cut-off points found for SB were time > 120 min/day [AUC: 0.54 (95%CI: 0.51; 0.57)] watching TV or video/DVD and ≤ 20 min/day [AUC: 0.59 (95%CI: 0.56;0.62)] using computer/internet. Older adults with SB had 1.30 (95% CI: 1.01; 1.66) and 1.46 (95% CI: 1.08; 1.96) greater chances of having sarcopenia, respectively.

Risk for postpartum depressive symptoms among pregnant women in a tertiary care setting with and without a positive COVID-19 test.

OBJECTIVE: This study systematically examines risk for postpartum depressive symptoms based on COVID-19 positivity status during pregnancy. METHODS: This is a retrospective matched cohort study of pregnant patients admitted to labor and delivery units from March through December 2020. Patients were administered three depression screening questions followed by the Edinburgh Postnatal Depression Scale (EPDS). RESULTS: 129 patients with positive COVID-19 tests (most with mild symptoms) were matched with 516 COVID-19 negative controls. We found no significant differences in rates of positive responses to screening questions (14/129, 10.9% vs. 72/516, 14.0%; p = .35) or EPDS scores >9 (6/97, 6.2% vs. 42/410, 10.2%; p = .22). Prior history of psychiatric illness was the only significant predictor of an EPDS score > 9 (adjOR 2.57, p = .002) or a positive brief screen for postpartum depressive symptoms (adjOR 2.93, p < .001). CONCLUSIONS: No significant differences in the rates for postpartum depressive symptoms were observed among pregnant women with and without a positive COVID-19 test during pregnancy, suggesting that testing positive for COVID-19 during pregnancy was not associated with an increased risk for the development of depressive symptoms during the acute postpartum period. Overall rates of postpartum depression symptoms were low, perhaps owing to the higher socioeconomic status of the sample.

Costus spiralis extract restores kidney function in cisplatin-induced nephrotoxicity model: Ethnopharmacological use, chemical and toxicological investigation.

ETHNOPHARMACOLOGICAL RELEVANCE: Costus spiralis (Jacq.). Roscoe (Costaceae) is traditionally used in Brazil for the treatment of kidney diseases such as pyelonephritis, urethra inflammation, kidney stones, and inflammatory conditions. There are reports of its use by Brazilian Indians since the 17th century when it was known as "pacocatinga." Currently, the use of the Costus species in Brazil is widespread, which was evidenced by the inclusion of the genus in the Brazilian National List of Medicinal Plants of Interest to the Unified Health System (RENISUS). AIM OF THE STUDY: This study aimed to confirm the ethnopharmacological use of Costus spiralis in the treatment of kidney diseases, toxicity study using animal models, and the phytochemistry of the species. MATERIALS AND METHODS: The chemical profile of Costus spiralis leaves extract (CSLE) was obtained for the hydroethanolic extract by ultra-performance liquid chromatography coupled to a mass spectrometer and ultraviolet detector with diode array (UPLC-UV/DAD-ESI-MS). The acute oral toxicity of the extract was predicted using the neutral red uptake cytotoxicity assay. Wistar rats were used in a model in vivo for confirmation of acute oral toxicity (2000 mg/kg p.o. for 14 days.) and determination of the effect on a cisplatin-induced nephrotoxicity model. RESULTS: The analysis by UPLC-UV/DAD-ESI-MS showed that the chemical composition of the extract is mostly di-glycosylated flavones of apigenin. In the extract were identified the flavones vicenin II and schaftoside. The quantification of total flavonoids by spectrometry showed 0.880%. CSLE proved to be safe for acute oral administration (2000 mg/kg) with an IC50 value of 222.9 µg/mL and predicted oral toxic dose of 523.82 µg/mL in a neutral red uptake cytotoxicity assay. The absence of death allows the classification of the extract in class 5 according to OECD 423 guidelines and therefore it can be considered as a high acute safety product, which is highly relevant, considering the wide popular use of the species. In the cisplatin-induced nephrotoxicity model, C. spiralis extract (5, 15, and 30 mg/kg) significantly improved renal function, reversing almost completely the effects on plasma creatinine levels and creatinine clearance (p < 0.001). CONCLUSIONS: This study demonstrates that oral administration of Costus spiralis extract leaves is safe and effective in restoring the renal function in rats in a cisplatin-induced nephrotoxicity. It is suggested that the observed activity is related to the flavonoids present. This hypothesis should be confirmed, and the participation of other secondary metabolites should be investigated in the future.