Adults with Treacher Collins Syndrome Share Comparable 3D Upper Airway Dimensions with Nonsyndromic Individuals.

Purpose: Sleep apnea symptoms, such as snoring and daytime somnolence, are commonly observed in individuals with Treacher Collins Syndrome (TCS) and may be related to airway obstruction due to micro- and retro-gnathia. This study aims to three-dimensionally evaluate the upper airway using cone-beam computed tomography (CBCT) exams of adolescents (TCS-ADOL) and adults (TCS-ADUL) with TCS compared to a nonsyndromic group (CON). Materials and Methods: Twenty-six CBCT exams were divided into three groups: TCS-ADOL (n = 7) (13.14 ± 1.67 years): CBCT exams of TCS adolescents; TCS-ADUL (n = 10) (21.80 ± 4.39 years): CBCT exams of TCS adults; and CON (n = 9) (25.33 ± 8.57 years): CBCT exams of adult nonsyndromic individuals with Class II skeletal pattern. The variables analyzed were (1) total upper airway volume; (2) nasal cavity volume; (3) total pharyngeal volume; (4) nasopharyngeal volume; (5) oropharyngeal volume; (6) pharyngeal minimal cross-sectional area; (7) pharyngeal length; and (8) pharyngeal depth. Scans were analyzed by two examiners, and intra- and inter-rater agreement was calculated. A p-value of ≤0.05 was considered significant. Results: Although not statistically significant, the TCS-ADUL group showed decreased airway volume and minimal cross-sectional areas compared to the CON group. There were also significant differences between TCS-ADOL and TCS-ADUL, with significantly lower airway volumes in the TCS-ADOL group. Strong positive correlations were found between certain airway measurements in the TCS-ADOL group, which were not observed in adults. Conclusions: The upper airways of adults with TCS are dimensionally similar to those of nonsyndromic individuals, despite absolute value reductions found in the syndromic group. The reduced airway in the adolescent population suggests significant potential for growth, mainly in pharyngeal dimensions.

Photobiomodulation therapy for chronic knee pain in obese patients in pre-rehabilitation for bariatric surgery: randomised, placebo-controlled, double-blinded, clinical trial protocol.

INTRODUCTION: Obesity has become a worldwide public health problem and is directly linked to loss of quality of life, complications and comorbidities. One of them is chronic pain, especially in the knees, which increases significantly and proportionally with weight gain. In patients with severe obesity, with indication for bariatric surgery, the presence of chronic pain disables and often prevents their participation in a pre-surgical rehabilitation programme. As an analgesic therapy, photobiomodulation (PBM) has been studied with safety, efficacy, well-tolerated used and low costs. Thus, this study aims to evaluate the use of PBM for the treatment of chronic knee pain in obese patients undergoing a pre-surgical rehabilitation programme for bariatric surgery. METHODS AND ANALYSES: This is a double-blinded, randomised, placebo-controlled clinical, superiority, trial protocol. The PBM will be applied in bilateral knees and lumbar paraspinal points levels referring to the roots of innervation of the knee. The outcomes evaluated will be pain intensity, functionality, quality of life and clinical signs of neurological sensitization of chronic knee pain pathways. ETHICS AND DISSEMINATION: This protocol has already been approved by the Comitê de Ética em Pesquisa do Hospital das Clínicas da Universidade Federal de Goiás/EBSERH-Ethics Committee and it is following SPIRIT guidelines. The results will be statistically analysed and subsequently published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: Clinical Trials Platform (https://clinicaltrials.gov/) with the number NCT05816798.

A história de construção das Portarias de Consolidação do Sistema Único de Saúde: um marco normativo / The history of the construction of the Consolidation Ordinances of the Unified Health System: a normative milestone / La historia de la construcción de las Ordenanzas de Consolidación del Sistema Único de Salud: un hito normativo

Apresentar, por meio de resenha analítica, a obra 'Consolidação, Simplificação e Revisão do Arco Normativo Infralegal da Saúde: um projeto, muitas vozes', publicado pelo CONASS e que narra a história biográfica de um projeto pioneiro e inovador da consolidação do arco normativo infralegal do Sistema Único de Saúde.

To present, through an analytical review, the work 'Consolidation, Simplification, and Review of the Infralegal Normative Arch of Health: one project, many voices', published by CONASS, which narrates the biographical history of a pioneering and innovative project in consolidating the infralegal normative arch of the Unified Health System.

Presentar, a través de una reseña analítica, la obra 'Consolidación, Simplificación y Revisión del Arco Normativo Infralegal de la Salud: un proyecto, muchas voces', publicada por CONASS y que narra la historia biográfica de un proyecto pionero e innovador en la consolidación del arco normativo infralegal del Sistema Único de Salud.

Antimicrobial photodynamic therapy with methylene blue and its derivatives in animal studies: Systematic review.

BACKGROUND: Infections are complications in the wound healing process, and their treatment can lead to antibiotic overuse and bacterial resistance. Antimicrobial photodynamic therapy (aPDT) is used to treat infectious diseases caused by fungi, viruses, or bacteria. Methylene blue (MB) and its derivatives are commonly used dyes in antimicrobial photodynamic therapy (aPDT-MB). METHODS: This study is a PRISMA systematic review of animal models used to discuss the usefulness and therapeutic parameters of aPDT-MB or its derivatives for treating infected skin wounds. RESULTS: After an extensive literature review, 13 controlled trials totaling 261 animals were selected to evaluate skin infection by leishmaniasis and cutaneous bacterial and fungal infections. All studies found results favoring the use of aPDT-MB. Great variability in parameters was found for radiant exposure from 12 to 360 J/cm2, MB diluted in saline solution or distilled water, irradiation time from 40 to 3600 s, irradiance most commonly at a maximum of 100 mW/cm2, and wavelength used mainly in the 630-670 nm range. CONCLUSION: MB is a safe and promising agent used as a photosensitizer in aPDT for skin-infected lesions. There is great variability in the parameters found. Comparisons concerning concentration, irradiation time, and light intensity need to be performed.

Is There a Direct Effect Between the Plication of the Myoaponeurotic Layer and the Force of Inspiratory and Expiratory Muscles After Abdominoplasty?

OBJECTIVE: Abdominoplasty may generate an increase in the intra-abdominal pressure (IAP) and consequently an alteration in the pulmonary ventilation. The purpose of this study was to evaluate the potential alterations in the maximal static inspiratory pressure (MIP) and maximal static expiratory pressure (MEP) after abdominoplasty. METHODS: Thirty-three female patients, aged between 18 and 60, with type III/B Nahas abdominal deformity that underwent abdominoplasty with plication of the anterior rectus and external oblique aponeurosis were selected. The MIP and MEP were measured using a mouthpiece. This is a simple way to indirectly gauge inspiratory and expiratory muscle strength. Measurements were performed before surgery and on the 2nd, 7th, 15th, and 180th postoperative day. In addition, IAP was measured before abdominoplasty and after the placement of compression garment. The MIP and MEP were compared using analysis of variance, followed by the Bonferroni multiple comparison test pairing the different points in time. Paired Student's t test was used for comparing IAP measurements. Pearson's correlation test was used to compare MIP and MEP variations with IAP variation. Results were considered statistically significant when P ≤ 0.05. RESULTS: A decrease was observed in MEP on the 2nd day, with a return close to normal values on the 15th day. In opposition MIP had a surprisingly increase on the 15th postoperative day (129 cmH2O), normalizing 180 days after the operation. A leap in IAP values was revealed at the end of the surgical procedure. It was not possible to establish a positive correlation between the increase of IAP and the alterations of MIP and MEP. CONCLUSIONS: There is a decrease in maximum expiratory pressure on the very early postoperative day (2nd postoperative day) and an increase in maximum inspiratory pressure on the 15th postoperative day in patients who underwent abdominoplasty. There was no correlation between the IAP and maximum respiratory pressure variations, both inspiratory and expiratory.

Preventive and therapeutic vascular photobiomodulation decreases the inflammatory markers and enhances the muscle repair process in an animal model.

Photobiomodulation therapy (PBM) has shown positive effects when applied locally to modulate the inflammatory process and facilitate muscle repair. However, the available literature on the mechanisms of action of vascular photobiomodulation (VPBM), a non-invasive method of vascular irradiation, specifically in the context of local muscle repair, is limited. Thus, this study aimed to assess the impact of vascular photobiomodulation (VPBM) using a low-level laser (LLL) on the inflammatory response and the process of skeletal muscle repair whether administered prior to or following cryoinjury-induced acute muscle damage in the tibialis anterior (TA) muscles. Wistar rats (n = 85) were organized into the following experimental groups: (1) Control (n = 5); (2) Non-Injury + VPBM (n = 20); (3) Injured (n = 20); (4) Pre-VPBM + Injury (n = 20); (5) Injury + Post-VPBM (n = 20). VPBM was administered over the vein/artery at the base of the animals' tails (wavelength: 780 nm; power: 40 mW; application area: 0.04 cm2; energy density: 80 J/cm2). Euthanasia of the animals was carried out at 1, 2, 5, and 7 days after inducing the injuries. Tibialis anterior (TA) muscles were collected for both qualitative and quantitative histological analysis using H&E staining and for assessing protein expression of TNF-α, MCP-1, IL-1ß, and IL-6 via ELISA. Blood samples were collected and analyzed using an automatic hematological analyzer and a leukocyte differential counter. Data were subjected to statistical analysis (ANOVA/Tukey). The results revealed that applying VPBM prior to injury led to an increase in circulating neutrophils (granulocytes) after 1 day and a subsequent increase in monocytes after 2 and 5 days, compared to the Non-Injury + VPBM and Injured groups. Notably, an increase in erythrocytes and hemoglobin concentration was observed in the Non-Injury + VPBM group on days 1 and 2 in comparison to the Injured group. In terms of histological aspects, only the Prior VPBM + Injured group exhibited a reduction in the number of inflammatory cells after 1, 5, and 7 days, along with an increase in blood vessels at 5 days. Both the Prior VPBM + Injured and Injured + VPBM after groups displayed a decrease in myonecrosis at 1, 2, and 7 days, an increase in newly-formed and immature fibers after 5 and 7 days, and neovascularization after 1, 2, and 7 days. Regarding protein expression, there was an increase in MCP-1 after 1 and 5 days, TNF-α, IL-6, and IL-1ß after 1, 2, and 5 days in the Injured + VPBM after group when compared to the other experimental groups. The Prior VPBM + Injured group exhibited increased MCP-1 production after 2 days, in comparison to the Non-Injury + VPBM and Control groups. Notably, on day 7, the Injured group continued to show elevated MCP-1 protein expression when compared to the VPBM groups. In conclusion, VPBM effectively modulated hematological parameters, circulating leukocytes, the protein expression of the chemokine MCP-1, and the proinflammatory cytokines TNF-α and IL-1ß, ultimately influencing the inflammatory process. This modulation resulted in a reduction of myonecrosis, restoration of tissue architecture, increased formation of newly and immature muscle fibers, and enhanced neovascularization, with more pronounced effects when VPBM was applied prior to the muscle injury.

Prone positioning in awake patients without ventilatory support does not alter major clinical outcomes in severe COVID-19: results from a retrospective observational cohort study, systematic review and meta-analysis.

OBJECTIVES: During the Coronavirus disease (COVID-19) pandemic, clinicians recommended awake-prone positioning (APP) to avoid the worst outcomes. The objectives of this study were to investigate if APP reduces intubation, death rates, and hospital length of stay (HLOS) in acute COVID-19. METHODS: We performed a retrospective cohort with non-mechanically ventilated patients hospitalized in a reference center in Manaus, Brazil, 2020. Participants were stratified into APP and awake-not-prone positioning (ANPP) groups. Also, we conducted a systematic review and performed a meta-analysis to understand if this intervention had different outcomes in resource-limited settings (PROSPERO CRD42023422452). RESULTS: A total of 115 participants were allocated into the groups. There was no statistical difference between both groups regarding time to intubation (HR: 0.861; 95CI: 0.474-1.1562; p=0.622) and time to death (HR: 1.666; 95CI: 0.939-2.951; p=0.081). APP was not significantly associated with reduced HLOS. A total of 86 articles were included in the systematic review, of which 76 (88,3%) show similar findings after APP. Also, low/middle, and high-income countries were similar regarding such outcomes. CONCLUSION: APP in COVID-19 does not present clinical improvement that affects mortality, intubation rate and HLOS. The lack of a prone position protocol, obtained through a controlled study, is necessary. After 3 years, APP benefits are still inconclusive.

A Characterization of Biological Activities and Bioactive Phenolics from the Non-Volatile Fraction of the Edible and Medicinal Halophyte Sea Fennel (Crithmum maritimum L.).

Although the biochemical composition and biological properties of the volatile fraction of the halophyte sea fennel (Crithmum maritimum L.) have been largely described, little is known about its polar constituents and bioactivities. Here, a hydromethanolic extract of Crithmum maritimum (L.) leaves was fractionated, and the fractions were evaluated in vitro for antioxidant (using DPPH, ABTS, and FRAP bioassays), anti-inflammatory (inhibition of NO production in RAW 264.7 macrophages), antidiabetic (alpha-glucosidase inhibition), neuroprotective (inhibition of acetylcholinesterase), and skin-protective (tyrosinase and melanogenesis inhibitions) activities. Polar fractions of the extract were rich in phenolics and, correlatively, displayed a strong antioxidant power. Moreover, fractions eluted with MeOH20 and MeOH80 exhibited a marked inhibition of alpha-glucosidase (IC50 = 0.02 and 0.04 mg/mL, respectively), MeOH60 fractions showed a strong capacity to reduce NO production in macrophages (IC50 = 6.4 µg/mL), and MeOH80 and MeOH100 fractions had strong anti-tyrosinase activities (630 mgKAE/gDW). NMR analyses revealed the predominance of chlorogenic acid in MeOH20 fractions, 3,5-dicaffeoylquinic acid in MeOH40 fractions, and 3-O-rutinoside, 3-O-glucoside, 3-O-galactoside, and 3-O-robinobioside derivatives of quercetin in MeOH60 fractions. These compounds likely account for the strong antidiabetic, antioxidant, and anti-inflammatory properties of sea-fennel polar extract, respectively. Overall, our results make sea fennel a valuable source of medicinal or nutraceutical agents to prevent diabetes, inflammation processes, and oxidative damage.

Use of antidepressants in the treatment of chronic orofacial pain caused by temporomandibular disorders: A randomized controlled clinical trial.

BACKGROUND AND OBJECTIVE: Temporomandibular disorders (TMDs) are a common pathology, associated with pain in the facial territory and with associated psychological disorders, such as anxiety and depression. The aim of this study was to evaluate the efficacy of antidepressants in the treatment of pain associated with TMD. MATERIALS AND METHODS: Sixty four patients suffering from chronic orofacial pain, randomly distributed in 3 groups: control group treated with night splint, group treated with 10mg/day of citalopram and group treated with 25mg/day of amitriptyline. Pain intensity was assessed, randomly, by a single blinded evaluator, according to the VAS at baseline and after one, three, six and nine weeks. RESULTS: All groups showed a reduction of pain throughout the period of time evaluated, however, the group treated with amitriptyline showed the best pain reduction results 3.3±1.5, 1.5±1.4 and 0.9±1.3 at 3, 6 and 9 weeks, respectively. CONCLUSIONS: Low doses of amitriptyline appear to be a good therapeutic option in patients with TMDs suffering from chronic orofacial pain.

Associations between COVID-19 and Glucose-6-Phosphate Dehydrogenase Activity in Brazil.

Glucose-6 phosphate dehydrogenase deficiency (G6PDd) was suggested as a risk factor for severe disease in patients with COVID-19. We evaluated clinical outcomes and glucose-6 phosphate dehydrogenase (G6PD) activity during and after illness in patients with COVID-19. This prospective cohort study included adult participants (≥ 18 years old) who had clinical and/or radiological COVID-19 findings or positive reverse transcription-polymerase chain reaction results. Epidemiological and clinical data were extracted from electronic medical records. Glucose-6 phosphate dehydrogenase activity was measured using SD Biosensor STANDARD G6PD® equipment on admission and 1 year after discharge. Samples were genotyped for the three most common single nucleotide polymorphisms for G6PDd in the Brazilian Amazon. Seven hundred fifty-three patients were included, of whom 123 (16.3%) were G6PD deficient. There was no difference between groups regarding the risks of hospitalization (P = 0.740) or invasive mechanical ventilation (P = 0.31), but the risk of death was greater in patients with normal G6PD levels (P = 0.022). Only 29 of 116 participants (25%) carried the African G6PDd genotype. Of 30 participants tested as G6PD deficient during disease, only 11 (36.7%) results agreed 1 year after discharge. In conclusion, this study does not demonstrate an association of G6PDd with severity of COVID-19. Limitations of the test for detecting enzyme levels during COVID-19 illness were demonstrated by genotyping and retesting after the disease period. Care must be taken when screening for G6PDd in patients with acute COVID-19.

Lipolytic production from solid-state fermentation of the filamentous fungus Penicillium polonicum and its applicability as biocatalyst in the synthesis of ethyl oleate.

Lipases represent versatile biocatalysts extensively employed in transesterification reactions for ester production. Ethyl oleate holds significance in biodiesel production, serving as a sustainable alternative to petroleum-derived diesel. In this study, our goal was to prospect lipase and assess its efficacy as a biocatalyst for ethyl oleate synthesis. For quantitative analysis, a base medium supplemented with Rhodamine B, olive oil, and Tween 80 was used. Solid-state fermentation utilized crambe seeds of varying particle sizes and humidity levels as substrates. In the synthesis of ethyl oleate, molar ratios of 1:3, 1:6, and 1:9, along with a total enzymatic activity of 60 U in n-heptane, were utilized at temperatures of 30 °C, 37 °C, and 44 °C. Reactions were conducted in a shaker at 200 rpm for 60 min. As a result, we first identified Penicillium polonicum and employed the method of solid-state fermentation using crambe seeds as a substrate to produce lipase. Our findings revealed heightened lipolytic activity (22.5 Ug-1) after 96 h of fermentation using crambe cake as the substrate. Optimal results were achieved with crambe seeds at a granulometry of 0.6 mm and a fermentation medium humidity of 60%. Additionally, electron microscopy suggested the immobilization of lipase in the substrate, enabling enzyme reuse for up to 4 cycles with 100% enzymatic activity. Subsequently, we conducted applicability tests of biocatalysts for ethyl oleate synthesis, optimizing parameters such as the acid/alcohol molar ratio, temperature, and reaction time. We attained 100% conversion within 30 min at 37 °C, and our results indicated that the molar ratio proportion did not significantly influence the outcome. These findings provide a methodological alternative for the utilization of biocatalysts in ethyl oleate synthesis.

COVID-19-Associated Cognitive Biases on Pneumonia Differential Diagnosis.

The coronavirus disease 2019 (COVID-19) pandemic favors cognitive biases such as anchoring and availability biases. The first refers to overvaluing some of the initial information and establishing a diagnosis too early, with resistance to future adjustments. The latter happens when diagnoses more frequently considered are regarded as more common in reality. This case, in which the correct diagnosis was delayed due to these biases, highlights the need to remain aware of them as a means toward timely diagnosis and therapeutic success of pneumonia cases. An 84-year-old woman presented with a mild non-productive cough for two months and fever. She had a history of breast carcinoma treated with radiotherapy in the previous year. Computerized tomography (CT) showed extensive bilateral consolidation foci with ground-glass-opacification areas and bilateral pleural effusion, CO-RADS 3. COVID-19 with bacterial superinfection was suspected and levofloxacin was initiated. Nasopharyngeal swab polymerase chain reaction (PCR) was carried out three times, always negative for SARS-CoV-2. As the patient remained with fever and cough, the antibiotic was escalated to piperacillin/tazobactam and then to meropenem/vancomycin. She underwent bronchofibroscopy and alveolar lavage, with negative SARS-CoV-2 PCR. The re-evaluation CT scan maintained bilateral consolidations, with an aerial bronchogram. The biopsy of pulmonary consolidation allowed the diagnosis of radiation-induced organizing pneumonia. Prednisolone was initiated and achieved clinical remission and radiological improvement. This case highlights the need to remain aware of cognitive biases both when COVID-19 is suspected or ruled out and to consider other diagnoses when there is a lack of therapeutic response.

Diet-induced metabolic and immune impairments are sex-specifically modulated by soluble TNF signaling in the 5xFAD mouse model of Alzheimer's disease.

Emerging evidence indicates that high-fat, high carbohydrate diet (HFHC) impacts central pathological features of Alzheimer's disease (AD) across both human incidences and animal models. However, the mechanisms underlying this association are poorly understood. Here, we identify compartment-specific metabolic and inflammatory dysregulations that are induced by HFHC diet in the 5xFAD mouse model of AD pathology. We observe that both male and female 5xFAD mice display exacerbated adiposity, cholesterolemia, and dysregulated insulin signaling. Independent of biological sex, HFHC diet also resulted in altered inflammatory cytokine profiles across the gastrointestinal, circulating, and central nervous systems (CNS) compartments demonstrating region-specific impacts of metabolic inflammation. Interestingly, inhibiting the inflammatory cytokine, soluble tumor necrosis factor (TNF) with the brain-permeant soluble TNF inhibitor XPro1595 was able to restore aspects of HFHC-induced metabolic inflammation, but only in male mice. Targeted transcriptomics of CNS regions revealed that inhibition of soluble TNF was sufficient to alter expression of hippocampal and cortical genes associated with beneficial immune and metabolic responses. Collectively, these results suggest that HFHC diet impairs metabolic and inflammatory pathways in an AD-relevant genotype and that soluble TNF has sex-dependent roles in modulating these pathways across anatomical compartments. Modulation of energy homeostasis and inflammation may provide new therapeutic avenues for AD.

Qualidade da assistência ao parto na percepção da mulher assistida na rede pública de saúde / Quality of birth care in the perception of women assisted in the public health network

Levantar e analisar a perspectiva de mulheres acerca da assistência recebida durante o parto. Método: estudo epidemiológico, observacional, de abordagem quantitativa e transversal. Os dados coletados foram compilados em tabelas e gráficos, analisados comparativamente entre si e com dados levantados na literatura científica. Resultados: as 80 participantes, com idade média de 26,6 anos, foram assistidas, integralmente, por enfermeiras obstetras. Houve predomínio das pardas (55,0%), solteiras (53,7%) e com renda familiar inferior a salários-mínimos (77,5%). Constatou-se alto nível de satisfação relacionado à assistência recebida, entretanto, o toque vaginal e a falta liberdade de se posicionar ao dar à luz foram as queixas mais frequentes, e que gerou certo grau de insatisfação. Conclusão: a amostra analisada demonstrou satisfação com os cuidados recebidos, porém os dois indicadores, com menor grau de satisfação, precisam ser repensados na prática obstétrica de modo a promover o bem-estar e a segurança da mulher.(AU)

To survey and analyze women's perspectives on the care they received during childbirth. Method: an epidemiological, observational, quantitative, cross-sectional study. The data collected was compiled into tables and graphs and analyzed in comparison with each other and with data found in scientific literature. Results: the 80 participants, with an average age of 26.6 years, were attended entirely by obstetric nurses. There was a predominance of brown women (55.0%), single women (53.7%) and women with a family income of less than one minimum wage (77.5%). There was a high level of satisfaction with the care received; however, vaginal touch and the lack of freedom to position oneself when giving birth were the most frequent complaints, which generated a certain degree of dissatisfaction. Conclusion: The sample analyzed showed satisfaction with the care received, but the two indicators with the lowest level of satisfaction need to be rethought in obstetric practice in order to promote women's well-being and safety.(AU)

Encuestar y analizar las perspectivas de las mujeres sobre la atención recibida durante el parto. Método: estudio epidemiológico, observacional, cuantitativo y transversal. Los datos recogidos se compilaron en tablas y gráficos y se analizaron en comparación entre sí y con los datos encontrados en la literatura científica. Resultados: las 80 participantes, con edad media de 26,6 años, fueron atendidas en su totalidad por enfermeras obstétricas. Hubo predominio de mujeres morenas (55,0%), solteras (53,7%) y con renta familiar inferior a un salario mínimo (77,5%). Hubo un alto grado de satisfacción con la atención recibida; sin embargo, el tacto vaginal y la falta de libertad para colocarse al dar a luz fueron las quejas más frecuentes, lo que generó cierto grado de insatisfacción. Conclusión: La muestra analizada mostró satisfacción con la atención recibida, pero los dos indicadores con menor nivel de satisfacción necesitan ser repensados en la práctica obstétrica para promover el bienestar y la seguridad de las mujeres.(AU)

Cholesterol depletion induces mesenchymal properties in oral squamous cell carcinoma cell line.

BACKGROUND: Cholesterol in cell membranes is crucial for cell signaling, adhesion, and migration. Membranes feature cholesterol-rich caveolae with caveolin proteins, playing roles in epithelial-mesenchymal transition and cancer progression. Despite elevated cholesterol levels in tumors, its precise function and the effects of its depletion in oral squamous cell carcinoma remain unclear. The aim of this study was to evaluate the influence of cholesterol depletion in oral squamous cell carcinoma cell line and epithelial-mesenchymal transition process. METHODS: Cholesterol depletion was induced on SCC-9 cells by methyl-ß-cyclodextrin and cell viability, proliferation, apoptosis, and colony formation capacities were evaluated. Gene and protein expressions were evaluated by reverse transcription polymerase chain reaction (RT-qPCR) and Western Blot, respectively, and cell sublocalization was assessed by immunofluorescence. RESULTS: Cholesterol depletion resulted in alteration of oral squamous cell carcinoma cell morphology at different concentrations of methyl-ß-cyclodextrin, as well as decreased cell proliferation and viability rates. Analysis of CAV1 transcript expression revealed increased gene expression in the treated SCC-9 during the 24 h period, at different concentrations of methyl-ß-cyclodextrin: 5 , 7.5, 10, and 15 mM, in relation to parental SCC-9. CAV1 protein expression was increased, with subsequent dose-dependent decrease. A statistically significant difference was observed in samples treated with 5 mM of methyl-ß-cyclodextrin (p = 0.02, Kruskal-Wallis test). The immunofluorescence assay showed lower cytoplasmic and membrane labeling intensity in the treated samples for CAV1. CONCLUSION: These findings indicate the modulation of cholesterol as a possible mechanism underlying the regulation of these molecules and activation of epithelial-mesenchymal transition in oral squamous cell carcinoma.

Nutrient-efficient catfish-based aquaponics for producing lamb's lettuce at two light intensities.

BACKGROUND: Aquaponic systems are sustainable processes of managing water and nutrients for food production. An innovate nutrient-efficient catfish-based (Clarias gariepinus) aquaponics system was implemented for producing two cultivars of two leafy vegetables largely consumed worldwide: lamb's lettuce (Valerianella locusta var. Favor and Valerianella locusta var. de Hollande) and arugula (Eruca vesicaria var. sativa and Eruca sativa). Different growing treatments (4 × 2 factorial design) were applied to plants of each cultivar, grown at two light intensities (120 and 400 µmol m-2 s-1). During growth, several morphological characteristics (root length, plant height, leaf number, foliage diameter and biggest leaf length) were measured. At harvest, plants were weighed and examined qualitatively in terms of greenness and health status. Additionally, leaf extracts were obtained and used to determine total phenolic contents, antioxidant capacities, and levels of cytotoxicity to Caco-2 intestinal model cells. RESULTS: After a 5-week growth period, both lamb's lettuce cultivars presented high levels of greenness and health status, at both light intensities, particularly the var. de Hollande that also showed higher average performance in terms of plant morphology. In turn, arugula cultivars showed lower levels of greenness and health status, especially the cultivar E. vesicaria var. sativa submitted to direct sunlight during growth. In addition, plant specimens submitted to higher levels of light intensity showed higher contents in antioxidants/polyphenols. Cultivars with a higher content in antioxidants/polyphenols led to higher Caco-2 cell viability. CONCLUSION: For successful industrial implementation of the aquaponics technology, different and optimized acclimatizing conditions must be applied to different plant species and cultivars. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Diet-induced metabolic and immune impairments are sex-specifically modulated by soluble TNF signaling in the 5xFAD mouse model of Alzheimer's disease.

Emerging evidence indicates that high-fat, high carbohydrate diet (HFHC) impacts central pathological features of Alzheimer's disease (AD) across both human incidences and animal models. However, the mechanisms underlying this association are poorly understood. Here, we identify compartment-specific metabolic and inflammatory dysregulations that are induced by HFHC diet in the 5xFAD mouse model of AD pathology. We observe that both male and female 5xFAD mice display exacerbated adiposity, cholesterolemia, and dysregulated insulin signaling. Independent of biological sex, HFHC diet also resulted in altered inflammatory cytokine profiles across the gastrointestinal, circulating, and central nervous systems (CNS) compartments demonstrating region-specific impacts of metabolic inflammation. In male mice, we note that HFHC triggered increases in amyloid beta, an observation not seen in female mice. Interestingly, inhibiting the inflammatory cytokine, soluble tumor necrosis factor (TNF) with the brain-permeant soluble TNF inhibitor XPro1595 was able to restore aspects of HFHC-induced metabolic inflammation, but only in male mice. Targeted transcriptomics of CNS regions revealed that inhibition of soluble TNF was sufficient to alter expression of hippocampal and cortical genes associated with beneficial immune and metabolic responses. Collectively, these results suggest that HFHC diet impairs metabolic and inflammatory pathways in an AD-relevant genotype and that soluble TNF has sex-dependent roles in modulating these pathways across anatomical compartments. Modulation of energy homeostasis and inflammation may provide new therapeutic avenues for AD.

YY1 mutations disrupt corticogenesis through a cell-type specific rewiring of cell-autonomous and non-cell-autonomous transcriptional programs.

Germline mutations of YY1 cause Gabriele-de Vries syndrome (GADEVS), a neurodevelopmental disorder featuring intellectual disability and a wide range of systemic manifestations. To dissect the cellular and molecular mechanisms underlying GADEVS, we combined large-scale imaging, single-cell multiomics and gene regulatory network reconstruction in 2D and 3D patient-derived physiopathologically relevant cell lineages. YY1 haploinsufficiency causes a pervasive alteration of cell type specific transcriptional networks, disrupting corticogenesis at the level of neural progenitors and terminally differentiated neurons, including cytoarchitectural defects reminiscent of GADEVS clinical features. Transcriptional alterations in neurons propagated to neighboring astrocytes through a major non-cell autonomous pro-inflammatory effect that grounds the rationale for modulatory interventions. Together, neurodevelopmental trajectories, synaptic formation and neuronal-astrocyte cross talk emerged as salient domains of YY1 dosage-dependent vulnerability. Mechanistically, cell-type resolved reconstruction of gene regulatory networks uncovered the regulatory interplay between YY1, NEUROG2 and ETV5 and its aberrant rewiring in GADEVS. Our findings underscore the reach of advanced in vitro models in capturing developmental antecedents of clinical features and exposing their underlying mechanisms to guide the search for targeted interventions.

Acesso a Unidades Básicas de Saúde no município de Pelotas/Rio Grande do Sul

O objetivo do trabalho é analisar o fluxo de acesso às Unidades Básicas de Saúde no município de Pelotas/RS no ano de 2022. Metodologia: Estudo qualitativo observacional, exploratório e descritivo realizado através da coleta de dados na Secretaria Municipal de Saúde, e busca nas bases de dados referenciais. Resultados: Em Pelotas/RS, no ano de 2022, possuía 51 Unidades Básicas contempladas por 100 equipes de saúde. Em relação ao horário de funcionamento, 90% das unidades atuavam em horário comercial e, apenas 10%, em horário estendido. Quanto à territorialização, encontrava-se em processo de adesão à política de população adscrita, tendo, no momento do estudo, 45 de suas unidades com a área populacional total de abrangência. Além disso, nos últimos anos foi implementado o sistema de acolhimento como forma de primeiro atendimento. Conclusões: No que tange ao objeto de estudo - o acesso - viu-se que a principal barreira está no horário de funcionamento das unidades. A modificação na forma de atendimento, implementado o acolhimento, foi visivelmente benéfico à população, permitindo maior porta de entrada à saúde. Evidenciou-se, ainda, algumas lacunas que podem impedir o acesso integral dos indivíduos, como a falta de alguns profissionais nas unidades e a fragmentação do sistema, esse último podendo ser solucionado com o incentivo e o investimento à tecnologia, a favor da integração dos serviços.