Role of IL-18 in adipose tissue remodeling and metabolic dysfunction.

BACKGROUND/OBJECTIVES: Proinflammatory cytokines are increased in obese adipose tissue, including inflammasome key masters. Conversely, IL-18 protects against obesity and metabolic dysfunction. We focused on the IL-18 effect in controlling adipose tissue remodeling and metabolism. MATERIALS/SUBJECTS AND METHODS: We used C57BL/6 wild-type (WT) and interleukine-18 deficient (IL-18-/-) male mice fed a chow diet and samples from bariatric surgery patients. RESULTS: IL-18-/- mice showed increased adiposity and proinflammatory cytokine levels in adipose tissue, leading to glucose intolerance. IL-18 was widely secreted by stromal vascular fraction but not adipocytes from mice's fatty tissue. Chimeric model experiments indicated that IL-18 controls adipose tissue expansion through its presence in tissues other than bone marrow. However, IL-18 maintains glucose homeostasis when present in bone marrow cells. In humans with obesity, IL-18 expression in omental tissue was not correlated with BMI or body fat mass but negatively correlated with IRS1, GLUT-4, adiponectin, and PPARy expression. Also, the IL-18RAP receptor was negatively correlated with IL-18 expression. CONCLUSIONS: IL-18 signaling may control adipose tissue expansion and glucose metabolism, as its absence leads to spontaneous obesity and glucose intolerance in mice. We suggest that resistance to IL-18 signaling may be linked with worse glucose metabolism in humans with obesity.

Cluster-Based Multinomial Logistic Regression Model for Health-Related Quality of Life Among People Living with HIV in Brazil.

Improvement in treatment options has increased the survival of people living with HIV (PLHIV). Thus, we evaluated the factors associated with better health-related quality of life (HRQoL) among PLHIV in Brazil. This was a cross-sectional study carried out among 349 PLHIV. Data were collected using an interview-based questionnaire, and HRQoL was assessed by the Brazilian version of the WHOQOL HIV BREF instrument. We used non-hierarchical cluster analysis (K-means) to compile the WHOQOL HIV BREF's overall and domain scores into a unique more multidimensional measure for HRQoL consisting of three clusters: poor, fair and good; associations with clusters of better HRQoL were assessed using multinomial logistic regression models. The mean and median overall HRQoL scores were 15.13 (SD = 3.39) and 16, respectively. The reliability and validity of the Brazilian version of the WHOQOL HIV BREF instrument was confirmed among PLHIV in a non-metropolitan, medium-sized municipality of Brazil, which reaffirmed the cross-cultural validity of this instrument. The factors male sex; heterosexual and asexual orientations; higher individual income; undetectable viral load; absence of any comorbidity and presence of an infectious or a chronic comorbidity, with mental illness as the reference; and never having consumed illegal substances were independently associated with good HRQoL. Thus, the compilation of the WHOQOL HIV BREF's overall and domain scores into a unique multidimensional measure for HRQoL, which this study proposed for the first time, may facilitate more robust interpretations and models of predictors. These differentials could simplify HRQoL as an indicator of health and wellbeing to be routinely used as a key outcome in the clinical management of patients and in the global monitoring of health system responses to HIV.

RESUMEN: La mejora en las opciones de tratamiento ha aumentado la supervivencia de las personas que viven con el VIH (PVVIH). Por lo tanto, evaluamos los factores asociados con una mejor calidad de vida relacionada con la salud (CVRS) entre las PVVIH en Brasil. Se trata de un estudio transversal realizado con 349 PVVIH. Los datos se recopilaron mediante un cuestionario basado en entrevistas y la CVRS se evaluó mediante la versión brasileña del instrumento WHOQOL VIH BREF. Usamos un análisis de conglomerados no jerárquico (K-medias) para compilar las puntuaciones generales y de dominios del WHOQOL HIV BREF en una medida única más multidimensional para la CVRS que consta de tres conglomerados: deficiente, regular y bueno; y las asociaciones con grupos de mejor CVRS se evaluaron mediante modelos de regresión logística multinomial. Las puntuaciones de la CVRS global media y mediana fueron 15,13 (DE = 3,39) y 16. La confiabilidad y validez del WHOQOL VIH BREF versión brasileña fue confirmada entre personas que viven con el VIH en un municipio no metropolitano de mediana población de Brasil, lo que reafirma la validez transcultural de este instrumento. Los factores sexo masculino; orientaciones heterosexuales y asexuales; mayores ingresos individuales; carga viral indetectable; ausencia de comorbilidad y presencia de comorbilidad infecciosa o crónica, teniendo como referencia la enfermedad mental; y nunca haber consumido sustancias ilegales se asociaron de forma independiente con una buena CVRS. Por lo tanto, la compilación de las puntuaciones generales y de dominio del WHOQOL HIV BREF en una medida multidimensional única para la CVRS, que este estudio propuso por primera vez, puede facilitar interpretaciones y modelos de predictores más robustos. Estos diferenciales podrían simplificar la HRQoL como un indicador de salud y bienestar para ser utilizado de forma rutinaria como un resultado clave en el manejo clínico de los pacientes y en el monitoreo global de las respuestas del sistema de salud al VIH.

Protective Effect of Bovine Milk Extracellular Vesicles on Alveolar Bone Loss.

SCOPE: Bovine milk extracellular vesicles (MEVs) have demonstrated therapeutic potential in regulating bone cell activity. However, the outcome of their use on alveolar bone loss has not yet been demonstrated. METHODS AND RESULTS: This study evaluates the effect of oral administration of MEVs on ovariectomized (OVX) mice. There is a reduced height of the alveolar bone crest in OVX mice by MEVs treatment, but the alveolar bone parameters are not altered. OVX mice are then submitted to a force-induced bone remodeling model by orthodontic tooth movement (OTM). MEVs-treated mice have markedly less bone remodeling movement, unlike the untreated OVX mice. Also, OVX mice treated with MEVs show an increased number of osteoblasts and osteocytes associated with higher sclerostin expression and reduce osteoclasts in the alveolar bone. Although the treatment with MEVs in OVX mice does not show differences in root structure in OTM, few odontoclasts are observed in the dental roots of OVX-treated mice. Compared to untreated mice, maxillary and systemic RANKL/OPG ratios are reduced in OVX mice treated with MEVs. CONCLUSION: Treatment with MEVs results in positive bone cell balance in the alveolar bone and dental roots, indicating its beneficial potential in treating alveolar bone loss in the nutritional context.

Accuracy of serological tests for bovine brucellosis: A systematic review and meta-analysis.

The direct methods for diagnosis of bovine brucellosis have several limitations, therefore serological tests are the basis for the diagnosis of the disease. However, a meta-analysis estimating the diagnostic sensitivity (DSe) and diagnostic specificity (DSp) on the main tests used in bovine brucellosis control programs worldwide has not been performed. This systematic review and meta-analysis aimed to estimate the DSe, DSp and thereby accuracy of serological tests individually used in the diagnosis of bovine brucellosis. The databases CABI, Cochrane Library, PubMed/MEDLINE, SciELO, Scopus and Web of Science were used to select articles. The search resulted in 5308 studies, of which 71 were selected for systematic review using quality assessment tools and 65 studies were included in the meta-analysis. For the meta-analysis, 178 assays and 11 different serological tests were considered. To estimate DSe and DSp of the tests, studies were divided according to animal selection for the studies: (1) studies that carried out a random or consecutive selection of participants (noncasecontrol studies) and (2) all studies, including casecontrol studies. Considering only the non-case-control studies to estimate the DSe, the tests that exhibited the best and worst performance were the iELISA test (indirect enzyme immunoassay - bacterial suspension as antigen - BS) (96.5%, 95% CI: 94.1-97.9%) and 2ME (2- mercaptoethanol test) (85.0%, 95% CI: 79.6-89.1%), respectively; while for DSp, the FPA (fluorescence polarization assay) (99, 7%, 95% CI: 99.5-99.8%) and PCFIA tests (protein concentration fluorescence immunoassay) (78.5%, 95% CI: 70.0-85.1%) showed better and worse performance, respectively. Overall, our results showed an overestimation in the DSe and DSp of the eleven serological tests assessed when casecontrol studies were included in the meta-analysis, which is a concern considering its impacts on the time and costs associated with populational diagnosis of the diseases, since several of these tests are routinely used in the control and eradication programs of bovine brucellosis worldwide. Furthermore, the tests that exhibited the best DSe and DSp, iELISA (BS) and FPA, respectively, are relatively easy to perform and interpret and the test which showed the best overall accuracy was FPA.

Injection of freshly collected adipose tissue for the treatment complex cryptoglandular anal fistula: case report

Introduction: Perianal fistula is a common colorectal disease which is caused mainly by cryptoglandular disease. Although most cases are treated successfully by surgery, management of complex perianal fistulas (CPAF) remains a challenge with limited results in recurrence and sometimes associated with fecal incontinence. The CPAF treatment with autologous adipose-derived mesenchymal stem cells (ASCs) had become a research hotspot. The technique started to be used in the treatment of Crohn's disease (CD) fistulas, where the studies showed safe and goods result from the procedure. Cultured ASCs have been used but this approach requires the preceding collection of adipose tissue, time for isolation of ASCs and subsequent in vitro expansion, need for laboratory facilities, and expertise in cell culturing. These factors have been getting over by using the commercially available alternative, allogenic ASCs. Treatment with allogeneic ASCs has shown good results in patients with CD fistulas, however with the disadvantage of being expensive. Objective: To show that the injection with freshly collected adipose tissue is an alternative to treatment with autologous or allogenic ASCs with several advantages. Methods: In this case report, we show our first experience in the treatment of CPAF with the application of collected adipose tissue in a tertiary referral hospital from Belo Horizonte, Brazil. Results The patient had a good postoperative recuperation with a complete fistula healing after 8 months without adverse effects. Conclusion: Injection with freshly collected adipose tissue is a promising and apparently safe sphincter-sparing technique in the treatment of CPAF. (AU)

Trends in hospital admissions and mortality from diabetes mellitus in Rio Grande do Sul: historical series 2000-2020.

OBJECTIVE: To analyze the trends of hospital admissions and deaths from diabetes mellitus in the 18 host municipalities of the 19 regional health coordination offices and in Rio Grande do Sul, 2000-2020. METHOD: Ecological study with secondary data collected in the Hospital Information System, the Mortality Information System, and the Brazilian Institute of Geography and Statistics, from 2000-2020. Coefficients were standardized using the direct method and Prais-Winsten regression analysis. RESULTS: A downward trend wasfound in the coefficients of hospitalizations for diabetes mellitus in most cities and states. In 2020, for both areas, hospitalizations for diabetes mellitus were below the average of the period. The mortality trend remained stationary in almost all municipalities and in the state. CONCLUSION: There was evidence of a decrease in hospitalizations and stationary mortality by DM in most municipalities analyzed, possibly due to the policies and actions implemented in the period, despite the aging of the population.

Uncovering the neuroprotective effect of vitamin B12 in pneumococcal meningitis: insights into its pleiotropic mode of action at the transcriptional level.

Background: The interplay between bacterial virulence factors and the host innate immune response in pneumococcal meningitis (PM) can result in uncontrolled neuroinflammation, which is known to induce apoptotic death of progenitor cells and post-mitotic neurons in the hippocampal dentate gyrus, resulting in cognitive impairment. Vitamin B12 attenuates hippocampal damage and reduces the expression of some key inflammatory genes in PM, by acting as an epidrug that promotes DNA methylation, with increased production of S-adenosyl-methionine, the universal donor of methyl. Material and methods: Eleven-day-old rats were infected with S. pneumoniae via intracisternal injection and then administered either vitamin B12 or a placebo. After 24 hours of infection, the animals were euthanized, and apoptosis in the hippocampal dentate gyrus, microglia activation, and the inflammatory infiltrate were quantified in one brain hemisphere. The other hemisphere was used for RNA-Seq and RT-qPCR analysis. Results: In this study, adjuvant therapy with B12 was found to modulate the hippocampal transcriptional signature induced by PM in infant rats, mitigating the effects of the disease in canonical pathways related to the recognition of pathogens by immune cells, signaling via NF-kB, production of pro-inflammatory cytokines, migration of peripheral leukocytes into the central nervous system, and production of reactive species. Phenotypic analysis revealed that B12 effectively inhibited microglia activation in the hippocampus and reduced the inflammatory infiltrate in the central nervous system of the infected animals. These pleiotropic transcriptional effects of B12 that lead to neuroprotection are partly regulated by alterations in histone methylation markings. No adverse effects of B12 were predicted or observed, reinforcing the well-established safety profile of this epidrug. Conclusion: B12 effectively mitigates the impact of PM on pivotal neuroinflammatory pathways. This leads to reduced microglia activation and inflammatory infiltrate within the central nervous system, resulting in the attenuation of hippocampal damage. The anti-inflammatory and neuroprotective effects of B12 involve the modulation of histone markings in hippocampal neural cells.

CO2-plasma surface treatment of graphite sheet electrodes for detection of chloramphenicol, ciprofloxacin and sulphanilamide.

Graphite sheet (GS) electrodes are flexible and versatile substrates for sensing electrochemical; however, their use has been limited to incorporate (bio)chemical modifiers. Herein, we demonstrated that a cold (low temperature) CO2 plasma treatment of GS electrodes provides a substantial improvement of the electrochemical activity of these electrodes due to the increased structural defects on the GS surface as revealed by Raman spectroscopy (ID/IG ratio), and scanning electron microscopy images. XPS analyses confirmed the formation of oxygenated functional groups at the GS surface after the plasma treatment that are intrinsically related to the substantial increase in the electron transfer coefficient (K0 values increased from 1.46 × 10-6 to 2.09 × 10-3 cm s-1) and with reduction of the resistance to charge transfer (from 129.8 to 0.251 kΩ). The improved electrochemical activity of CO2-GS electrodes was checked for the detection of emerging contaminant species, such as chloramphenicol (CHL), ciprofloxacin (CIP) and sulphanilamide (SUL) antibiotics, at around + 0.15, + 1.10 and + 0.85 V (versus Ag/AgCl), respectively, by square wave voltammetry. Limit of detection values in the submicromolar range were achieved for CHL (0.08 µmol L-1), CIP (0.01 µmol L-1) and SFL (0.11 µmol L-1), which enabled the sensor to be successfully applied to natural waters and urine samples (recovery values from 85 to 119%). The CO2-GS electrode is highly stable and inexpensive ($0.09 each sensor) and can be easily inserted in portable 3D printed cells for environmental on-site analyses.

Extracellular Vesicles in Bone Remodeling and Osteoporosis.

Osteoporosis is a systemic disorder characterized by bone mass loss, leading to fractures due to weak and brittle bones. The bone tissue deterioration process is related to an impairment of bone remodeling orchestrated mainly by resident bone cells, including osteoblasts, osteoclasts, osteocytes, and their progenitors. Extracellular vesicles (EVs) are nanoparticles emerging as regulatory molecules and potential biomarkers for bone loss. Although the progress in studies relating to EVs and bone loss has increased in the last years, research on bone cells, animal models, and mainly patients is still limited. Here, we aim to review the recent advances in this field, summarizing the effect of EV components such as proteins and miRNAs in regulating bone remodeling and, consequently, osteoporosis progress and treatment. Also, we discuss the potential application of EVs in clinical practice as a biomarker and bone loss therapy, demonstrating that this rising field still needs to be further explored.

Neurotoxic effects of hallucinogenic drugs 25H-NBOMe and 25H-NBOH in organotypic hippocampal cultures.

Introduction: NBOMes and NBOHs are psychoactive drugs derived from phenethylamines and have hallucinogenic effects due to their strong agonism to serotonin 5-HT2A receptors. Although cases of toxicity associated with the recreational use of substituted phenethylamines are frequently reported, there is a lack of information on the possible neurotoxic effects of NBOMe and NBOH in the brain hippocampus, a major neurogenesis region. Objectives: This study aimed at assessing the phenotypic and molecular effects of prolonged exposure of the hippocampus to the drugs 25H-NBOMe and 25H-NBOH. Methods: The ex vivo organotypic culture model of hippocampal slices (OHC) was used to investigate, by immunofluorescence and confocal microscopy, and transcriptome analyses, the mechanisms associated with the neurotoxicity of 25H-NBOMe and 25H-NBOH. Results: Reduction in the density of mature neurons in the OHCs occurred after two and seven days of exposure to 25H-NBOMe and 25H-NBOH, respectively. After the withdrawal of 25H-NBOMe, the density of mature neurons in the OHCs stabilized. In contrast, up to seven days after 25H-NBOH removal from the culture medium, progressive neuron loss was still observed in the OHCs. Interestingly, the exposure to 25H-NBOH induced progenitor cell differentiation, increasing the density of post-mitotic neurons in the OHCs. Corroborating these findings, the functional enrichment analysis of differentially expressed genes in the OHCs exposed to 25H-NBOH revealed the activation of WNT/Beta-catenin pathway components associated with neurogenesis. During and after the exposure to 25H-NBOMe or 25H-NBOH, gene expression patterns related to the activation of synaptic transmission and excitability of neurons were identified. Furthermore, activation of signaling pathways and biological processes related to addiction and oxidative stress and inhibition of the inflammatory response were observed after the period of drug exposure. Conclusion: 25H-NBOMe and 25H-NBOH disrupt the balance between neurogenesis and neuronal death in the hippocampus and, although chemically similar, have distinct neurotoxicity mechanisms.

The Intervention of Diet on Energy Metabolism.

Food intake patterns determine changes in energy expenditure due to their influence on body size and composition (percentage of fat, bone, and muscle), which can modulate signaling pathways that optimize energy consumption [...].

Eosinophils protect from metabolic alterations triggered by obesity.

BACKGROUND: Eosinophils are generally related to helminth infections or allergies. Their association with metabolic alterations and adipose tissue (AT) remodeling has been demonstrated mainly in animal models of obesity. However, their physiological role in driving metabolic features has not yet been well described. Herein, we aimed to evaluate the participation of eosinophils in metabolic and adipose tissue homeostasis in mice and humans, focusing on a translational perspective. MATERIAL AND METHODS: Male BALB/c wild-type (WT) mice and GATA-1 knockout (Δdb/GATA-1-/-) mice were followed until 16-week-age in a regular diet or were fed with a high-refined-carbohydrate (HC) diet or high-fat (HF) diet for eight weeks. In subjects with obesity, clinical parameters and omental AT gene expression were evaluated. RESULTS: Eosinophils lack in mice fed a regular diet induced insulin resistance and increased adiposity. Their adipose tissue showed augmented cytokine levels, which could be attributed to increased leukocytes in the tissue, such as neutrophils and pro-inflammatory macrophages. Bone marrow transplant from WT mice to Δdb/GATA-1-/- mice showed some improvement in glucose metabolism with lower adipose tissue mass accretion. Upon an unhealthy diet challenge, Δdb/GATA-1-/- mice fed HC diet showed a mild degree of adiposity and glucose metabolic dysfunction severe in those mice fed HF diet. The expression of eosinophil markers in omental AT from humans with severe obesity was positively correlated to eosinophil cytokines and insulin sensitivity surrogate markers and negatively correlated to systemic insulin, HOMA-IR, and android fat mass. CONCLUSIONS: Eosinophils seem to have a physiological role by controlling systemic and adipose tissue metabolic homeostasis by modulating glucose metabolism, inflammation, and visceral fat expansion, even in lean mice. Indeed, eosinophils also seem to modulate glucose homeostasis in human obesity.

Organotypic hippocampal culture model reveals differential responses to highly similar Zika virus isolates.

INTRODUCTION: Zika virus (ZIKV) caused an outbreak in Brazil, in 2015, being associated to microcephaly. ZIKV has a strong neurotropism leading to death of infected cells in different brain regions, including the hippocampus, a major site for neurogenesis. The neuronal populations of the brain are affected differently by ZIKV from Asian and African ancestral lineages. However, it remains to be investigated whether subtle variations in the ZIKV genome can impact hippocampus infection dynamics and host response. OBJECTIVE: This study evaluated how two Brazilian ZIKV isolates, PE243 and SPH2015, that differ in two specific missense amino acid substitutions, one in the NS1 protein and the other in the NS4A protein, affect the hippocampal phenotype and transcriptome. METHODS: Organotypic hippocampal cultures (OHC) from infant Wistar rats were infected with PE243 or SPH2015 and analyzed in time series using immunofluorescence, confocal microscopy, RNA-Seq and RT-qPCR. RESULTS: Unique patterns of infection and changes in neuronal density in the OHC were observed for PE243 and SPH2015 between 8 and 48 h post infection (p.i.). Phenotypic analysis of microglia indicated that SPH2015 has a greater capacity for immune evasion. Transcriptome analysis of OHC at 16 h p.i. disclosed 32 and 113 differentially expressed genes (DEGs) in response to infection with PE243 and SPH2015, respectively. Functional enrichment analysis suggested that infection with SPH2015 activates mostly astrocytes rather than microglia. PE243 downregulated biological process of proliferation of brain cells and upregulated those associated with neuron death, while SPH2015 downregulated processes related to neuronal development. Both isolates downregulated cognitive and behavioral development processes. Ten genes were similarly regulated by both isolates. They are putative biomarkers of early hippocampus response to ZIKV infection. At 5, 7, and 10 days p.i., neuronal density of infected OHC remained below controls, and mature neurons of infected OHC showed an increase in the epigenetic mark H3K4me3, which is associated to a transcriptionally active state. This feature is more prominent in response to SPH2015. CONCLUSION: Subtle genetic diversity of the ZIKV affects the dynamics of viral dissemination in the hippocampus and host response in the early stages of infection, which may lead to different long-term effects in neuronal population.

Effect of high-refined carbohydrate diet on intestinal integrity.

OBJECTIVES: One of the leading causes of obesity is the consumption of excess nutrients. Obesity is characterized by adipose tissue expansion, chronic low-grade inflammation, and metabolic alterations. Although consumption of a high-fat diet has been demonstrated to be a diet-induced obesity model associated with gut disorders, the same effect is not well explored in a mild-obesity model induced by high-refined carbohydrate (HC) diet intake. The intestinal tract barrier comprises mucus, epithelial cells, tight junctions, immune cells, and gut microbiota. This system is susceptible to dysfunction by excess dietary components that could increase intestinal permeability and bacterial translocation. The aim of this study was to evaluate whether an HC diet and the alterations resulting from its intake are linked to small intestine changes. METHODS: Male BALB/c mice were fed a chow or an HC diet for 8 wk. RESULTS: Although differences in body weight gain were not observed between the groups, mice fed the HC diet showed increased adiposity associated with metabolic alterations. The interferon-γ expression and myeloperoxidase levels were increased in the small intestine in mice fed an HC diet. However, the intestinal villi length, the expression of tight junctions (zonula occludens-1 and claudin-4) and tumor necrosis factor-α cytokine, and the percentage of intraepithelial lymphocytes did not differ in the jejunum or ileum between the groups. We did not observe differences in intestinal permeability and bacterial translocation. CONCLUSION: Metabolic alterations caused by consumption of an HC diet lead to a mild obesity state that does not necessarily involve significant changes in intestinal integrity.

Vitamin B12 attenuates leukocyte inflammatory signature in COVID-19 via methyl-dependent changes in epigenetic markings.

COVID-19 induces chromatin remodeling in host immune cells, and it had previously been shown that vitamin B12 downregulates some inflammatory genes via methyl-dependent epigenetic mechanisms. In this work, whole blood cultures from moderate or severe COVID-19 patients were used to assess the potential of B12 as adjuvant drug. The vitamin normalized the expression of a panel of inflammatory genes still dysregulated in the leukocytes despite glucocorticoid therapy during hospitalization. B12 also increased the flux of the sulfur amino acid pathway, that regulates the bioavailability of methyl. Accordingly, B12-induced downregulation of CCL3 strongly and negatively correlated with the hypermethylation of CpGs in its regulatory regions. Transcriptome analysis revealed that B12 attenuates the effects of COVID-19 on most inflammation-related pathways affected by the disease. As far as we are aware, this is the first study to demonstrate that pharmacological modulation of epigenetic markings in leukocytes favorably regulates central components of COVID-19 physiopathology.

Exploring the Potential of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 as Promising Psychobiotics Using SHIME.

Psychobiotics are probiotics that have the characteristics of modulating central nervous system (CNS) functions or reconciled actions by the gut-brain axis (GBA) through neural, humoral and metabolic pathways to improve gastrointestinal activity as well as anxiolytic and even antidepressant abilities. The aim of this work was to evaluate the effect of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 on the gut microbiota of mildly anxious adults using SHIME®. The protocol included a one-week control period and two weeks of treatment with L. helveticus R0052 and B. longum R0175. Ammonia (NH4+), short chain fatty acids (SCFAs), gamma-aminobutyric acid (GABA), cytokines and microbiota composition were determined. Probiotic strains decreased significantly throughout the gastric phase. The highest survival rates were exhibited by L. helveticus R0052 (81.58%; 77.22%) after the gastric and intestinal phase when compared to B. longum (68.80%; 64.64%). At the genus level, a taxonomic assignment performed in the ascending colon in the SHIME® model showed that probiotics (7 and 14 days) significantly (p < 0.005) increased the abundance of Lactobacillus and Olsenella and significantly decreased Lachnospira and Escheria-Shigella. The probiotic treatment (7 and 14 days) decreased (p < 0.001) NH4+ production when compared to the control period. For SCFAs, we observed after probiotic treatment (14 days) an increase (p < 0.001) in acetic acid production and total SCFAs when compared to the control period. Probiotic treatment increased (p < 0.001) the secretion of anti-inflammatory (IL-6 and IL-10) and decreased (p < 0.001) pro-inflammatory cytokines (TNF-alpha) when compared to the control period. The gut-brain axis plays an important role in the gut microbiota, producing SCFAs and GABA, stimulating the production of anti-anxiety homeostasis. The signature of the microbiota in anxiety disorders provides a promising direction for the prevention of mental illness and opens a new perspective for using the psychobiotic as a main actor of therapeutic targets.

Influence of the Lennard-Jones Combination Rules on the Simulated Properties of Organic Liquids at Optimal Force-Field Parametrization.

We recently introduced the CombiFF scheme [Oliveira et al., J. Chem. Theory Comput. 2020, 16, 7525], an approach for the automated refinement of force-field parameters against experimental condensed-phase data for large compound families. Using this scheme, once the time-consuming task of target-data selection and curation has been performed, the force-field optimization itself is both straightforward and fast. As a result, CombiFF provides an ideal framework for evaluating the influence of functional-form decisions on the accuracy of a force field at an optimal level of parametrization. We already used this approach to assess the effect of using an all-atom representation compared to united-atom representations in the force field [Oliveira et al., J. Chem. Theory Comput. 2022, 18, 6757]. Here, CombiFF is applied to assess the effect of three Lennard-Jones combination rules, geometric-mean (GM), Lorentz-Berthelot (LB), or Waldman-Hagler (WH), on the simulated properties of organic liquids. The comparison is performed in terms of the experimental liquid density ρliq, vaporization enthalpy ΔHvap, surface-tension coefficient γ, static relative dielectric permittivity ϵ, and self-diffusion coefficient D. The calibrations of the three force-field variants are carried out independently against 2044 experimental values for ρliq, and ΔHvap concerning 1516 compounds. The resulting root-mean-square deviations from experiment are 30.0, 26.9, and 36.7 kg m-3 for ρliq and 2.8, 2.8, and 2.9 kJ mol-1 for ΔHvap, when applying the GM, LB, and WH combination rules, respectively. In terms of these (and the other) properties, the three combination rules perform comparatively well, with the GM and LB results being more similar to each other and slightly more accurate compared to experiment. In contrast, the use of distinct combination rules for the parameter calibration and property calculation leads to much larger errors.

Development of an open-source software for isomer enumeration.

This article documents enu, a freely-downloadable, open-source and stand-alone program written in C++ for the enumeration of the constitutional isomers and stereoisomers of a molecular formula. The program relies on graph theory to enumerate all the constitutional isomers of a given formula on the basis of their canonical adjacency matrix. The stereoisomers of a given constitutional isomer are enumerated as well, on the basis of the automorphism group of this matrix. The isomer list is then reported in the form of canonical SMILES strings within files in XML format. The specification of the molecule family of interest is very flexible and the code is optimized for computational efficiency. The algorithms and implementations underlying enu are described, and simple illustrative applications are presented. The enu code is freely available on GitHub at https://github.com/csms-ethz/CombiFF .

Clear aligners combined with orthognathic surgery: a case series.

The goal of this study was to describe a series of orthognathic surgery cases in which a clear aligner system was used for orthodontic treatment. A total of 16 cases were undertaken. A majority of the patients were female (68.75%), and the mean age of the patients was 26.78 years (SD 10.85 years). The most frequent malocclusion was Class II (56.25%), mainly caused by mandibular retrognathism (80.00%). Most of the patients were treated with single-jaw surgeries (56.15%). Orthodontic buttons and elastics were used for maxillomandibular fixation in 81.25% of the patients. The mean (SD) treatment period was 19.00 (1.11) months, and the postsurgical follow-up varied from 6 months to 10 years. Good results were achieved with orthognathic surgery and the adjunctive use of clear aligners, and no damage was noted during the orthosurgical treatment. Since clear aligners provide an esthetic, removable appliance and may be more acceptable to patients than conventional orthodontic appliances, the use of clear aligners in orthognathic surgery is a promising alternative to traditional orthodontics.

Surgical Treatment of the Five Most Common Types of Cancer in Brazil: 7 Years Analysis Overview.

BACKGROUND: Surgery is the main treatment for the majority of solid cancers. Studies investigating surgical interventions are a critical asset in improving patient health outcomes. We aim to analyze the temporal and spatial distribution of the surgical treatment of Brazil's 5 most common types of cancer. METHODS: The selected cancers were stomach, colorectal and rectosigmoid junction, bronchial and lung, breast, and prostatic. Surgical data were collected from the DATASUS database from 2013 to 2019. Statistical analyses included linear regression tests with a significance level of .05. RESULTS: From 2013 to 2019, 19.72% of the diagnoses of all cancers were treated surgically. Only breast cancer didn't have a significant linear increase in surgeries (P = .702). Prostatic cancer had the highest annual increase rate and breast the lowest. Analyzing the Brazilian regions, the Southeast had the highest incidence of oncological surgeries, and the Midwest had the lowest. DISCUSSION: Brazil's surgical oncology scenario is progressing positively through the analyzed period. The analysis of the 5 most common types of cancer in Brazil and their progression over the years provides an idea of the cancer surgery capacity in Brazil. There were disparities between the Brazilian regions in all types of cancer. Our study is the first step to better comprehending cancer care in Brazil and the access issues that some areas have. With that, it will be possible to provide better care to cancer patients needing surgical treatment.