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.

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.

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.

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.

Electrophysiological and functional signs of Guillain-Barré syndrome predicted by a multiscale neuromuscular computational model.

Objective.The diagnosis of nerve disorders in humans has relied heavily on the measurement of electrical signals from nerves or muscles in response to electrical stimuli applied at appropriate locations on the body surface. The present study investigated the demyelinating subtype of Guillain-Barré syndrome using multiscale computational model simulations to verify how demyelination of peripheral axons may affect plantar flexion torque as well as the ongoing electromyogram (EMG) during voluntary isometric or isotonic contractions.Approach.Changes in axonal conduction velocities, mimicking those found in patients with the disease at different stages, were imposed on a multiscale computational neuromusculoskeletal model to simulate subjects performing unipodal plantar flexion force and position tasks.Main results.The simulated results indicated changes in the torque signal during the early phase of the disease while performing isotonic tasks, as well as in torque variability after partial conduction block while performing both isometric and isotonic tasks. Our results also indicated changes in the root mean square values and in the power spectrum of the soleus EMG signal as well as changes in the synchronization index computed from the firing times of the active motor units. All these quantitative changes in functional indicators suggest that the adoption of such additional measurements, such as torques and ongoing EMG, could be used with advantage in the diagnosis and be relevant in providing extra information for the neurologist about the level of the disease.Significance.Our findings enrich the knowledge of the possible ways demyelination affects force generation and position control during plantarflexion. Moreover, this work extends computational neuroscience to computational neurology and shows the potential of biologically compatible neuromuscular computational models in providing relevant quantitative signs that may be useful for diagnosis in the clinic, complementing the tools traditionally used in neurological electrodiagnosis.

Most meal and snack patterns are stable over a 3-year period in schoolchildren in southern Brazil.

This study aimed to identify meal and snack patterns in Brazilian schoolchildren and assess their stability over 3 years. This is a repeated cross-sectional study carried out in 2013, 2014 and 2015 with 6353 schoolchildren aged 7-12 years from public schools in Florianópolis, Brazil. Previous-day food consumption data for six pre-defined meals (breakfast, mid-morning snack, lunch, mid-afternoon snack, dinner and evening snack) were collected using the validated Web-CAAFE (Food Consumption and Physical Activity of Schoolchildren) questionnaire. Latent class analysis was performed to derive meal and snack patterns. The stability of patterns was analysed using multinomial logistic regression, and the probability of belonging to a meal pattern was calculated for each year. Three patterns were identified for breakfast and four patterns for a mid-morning snack, lunch, mid-afternoon snack, dinner and evening snack. Most meal and snack patterns were stable over the 3-year evaluation period. In the total sample, for a mid-afternoon snack, there was an increase in the probability of the children belonging to the 'Fruits and porridge' pattern (14.5%, 95% CI 12%-17% in 2015 vs. 9.2%, 95% CI 6.8%-11.7% in 2013) and a reduction in the 'Ultra-processed' pattern (42.5%, 95% CI 39.4%-45.6% in 2015 vs. 51.3%, 95% CI 46.5%-56.1% in 2013). These results appear to be in line with the recommendations of the Brazilian Dietary Guidelines and regional policies to increase the intake of healthy foods and limit that of ultra-processed, high fat, sugar and salt foods.

Heart rate variability as a biomarker in patients with Chronic Chagas Cardiomyopathy with or without concomitant digestive involvement and its relationship with the Rassi score.

BACKGROUND: Dysautonomia plays an ancillary role in the pathogenesis of Chronic Chagas Cardiomyopathy (CCC), but is the key factor causing digestive organic involvement. We investigated the ability of heart rate variability (HRV) for death risk stratification in CCC and compared alterations of HRV in patients with isolated CCC and in those with the mixed form (CCC + digestive involvement). Thirty-one patients with CCC were classified into three risk groups (low, intermediate and high) according to their Rassi score. A single-lead ECG was recorded for a period of 10-20 min, RR series were generated and 31 HRV indices were calculated. The HRV was compared among the three risk groups and regarding the associated digestive involvement. Four machine learning models were created to predict the risk class of patients. RESULTS: Phase entropy is decreased and the percentage of inflection points is increased in patients from the high-, compared to the low-risk group. Fourteen patients had the mixed form, showing decreased triangular interpolation of the RR histogram and absolute power at the low-frequency band. The best predictive risk model was obtained by the support vector machine algorithm (overall F1-score of 0.61). CONCLUSIONS: The mixed form of Chagas' disease showed a decrease in the slow HRV components. The worst prognosis in CCC is associated with increased heart rate fragmentation. The combination of HRV indices enhanced the accuracy of risk stratification. In patients with the mixed form of Chagas disease, a higher degree of sympathetic autonomic denervation may be associated with parasympathetic impairment.

Endothelial dysfunction biomarkers in sickle cell disease: is there a role for ADMA and PAI-1?

Within the spectrum of sickle cell disease (SCD) are sickle cell anemia (SCA), presence of hemoglobin SS (HbSS), hemoglobin SC disease (HbSC), and sickle cell ß-thalassemia (Sß-thal). Asymmetric dimethylarginine (ADMA) competitively inhibits the binding of arginine to NOS, reducing NO production. In patients with HbSS, increased levels of ADMA have been reported, as well as changes in many hemostatic biomarkers, including the plasminogen activator inhibitor type 1 (PAI-1). We hypothesized that high levels of ADMA and PAI-1 may be associated with more severe SCD. Thus, ADMA and PAI-1 levels were determined in 78 individuals including 38 adult patients with SCD and 40 control subjects. Higher levels of ADMA were shown in HbSS and Sß-thal patients compared to controls. Concerning PAI-1, all patients showed high levels of PAI-1 compared to controls. As a role of NO in the pathogenesis of SCD has already been established, we concluded that high levels of ADMA should compromise, at least in part, NO synthesis, resulting in endothelial dysfunction. Elevated plasma levels of PAI-1 in all patients may indicate not only endothelial dysfunction but also a hypofibrinolytic state favoring thrombotic complications. Finally, high levels of ADMA and PAI-1 may be associated with more severe SCD.

Efficacy of Brucella abortus S19 and RB51 vaccine strains: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to recalculate the efficacy of Brucella abortus S19 and RB51 vaccine strains and discuss the main variables associated with controlled trials to evaluate bovine brucellosis vaccine efficacy (VE). The most commonly used vaccine strain was S19, at a dose of 1010 colony forming units (CFU), followed by RB51 at 1010 CFU. The most commonly used challenge strain was B. abortus 2308, at a dose of 107 CFU, by the intraconjunctival route. Regarding the meta-analysis, trials were grouped according to the vaccine strain and dose to recalculate protection against abortion (four groups) or infection (five groups) using pooled risk ratio (RR) and VE. Regarding protection against abortion (n = 15 trials), the S19 vaccine at 109 CFU exhibited the highest protection rate (RR = 0.25, 95% confidence interval (CI) : 0.12-0.52; VE = 75.09%, 95% CI: 48.08-88.05), followed by RB51 at 1010 CFU (RR = 0.31, 95% CI: 0.16-0.61; VE = 69.25%, 95% CI: 39.48-84.38). Regarding protection against infection (n = 23 trials), only two subgroups exhibited significant protection: S19 at 109 CFU (RR = 0.28, 95% CI: 0.14-0.55; VE = 72.03%, 95% CI: 57.70- 81.50) and RB51 at 1010 CFU (RR = 0.43, 95% CI: 0.22-0.84; VE = 57.05%, 95% CI: 30.90-73.30). In conclusion, our results suggest that a dose of 109 CFU for S19 and 1010 CFU for RB51 are the most suitable for the prevention of abortion and infection caused by B. abortus.

Efficiency of eDNA and iDNA in assessing vertebrate diversity and its abundance.

Environmental DNA (eDNA) and invertebrate-derived DNA (iDNA) have been increasingly recognized as powerful tools for biodiversity assessment and conservation management. However, eDNA/iDNA efficiency for vertebrate diversity assessment remains uncertain, and comparisons to conventional methods are still rare. Through a meta-analysis of previously published vertebrate diversity surveys, we compared the efficiency of eDNA/iDNA against conventional methods across several types of samplers, vertebrate groups, and locations (tropical vs. temperate zones). We also assess eDNA/iDNA efficiency to estimate relative abundance or biomass over different molecular methods (qPCR and metabarcoding) and type of experiment (in the laboratory or in the field). We showed that for water sampler, fish as a target species, and studies achieved in temperate zones, eDNA presents lower risk of not detecting a species or a site with a target species than conventional methods. These results show that eDNA is an efficient tool to assess fish diversity. Moreover, eDNA data presents positive correlation with fish abundance or biomass. However, such correlation was higher in laboratory experiments than in the field. For the other samplers, vertebrate groups, and in tropical zones we were not able to draw general conclusion, highlighting the urgency of conducting more comparative studies.

Impregnation and drying to develop a melon snack enriched in calcium.

Melon fortification with calcium by impregnation techniques using a vacuum and/or ultrasound and drying were combined to obtain a snack product. For the impregnation step, samples were immersed in a 2 g 100 mL-1 calcium chloride solution at 25 °C. The samples were dried at 60 °C and an air velocity of 2 m s-1. The influence of the impregnation method on drying kinetics, mass variation, calcium content, water activity, color, and texture was evaluated. All dried samples had reduced water activity. The vacuum impregnated (VI) melons presented higher mass gain and drying time. It resulted in the highest calcium incorporation, increasing up to 13 times the calcium concentration of the samples. The samples dried after submitted to VI showed the greatest differences in color and hardness. However, VI was the most effective technique for calcium incorporation, being the only one capable of producing fortified dried melon.

Meal and snack patterns of 7-13-year-old schoolchildren in southern Brazil.

OBJECTIVE: The aim of the current study was to identify and describe the meal and snack patterns (breakfast, mid-morning snack, lunch, mid-afternoon snack, dinner and evening snack) of public schoolchildren. DESIGN: Cross-sectional study. Information on the previous day's food intake was obtained through the Web-CAAFE (Food Intake and Physical Activity of Schoolchildren), an interactive questionnaire, which divides daily food consumption into three meals (breakfast, lunch and dinner) and three snacks (mid-morning, mid-afternoon and evening). Each meal contains thirty-one food items and the schoolchildren clicked on the food items consumed in each meal. Factor analysis was used to identify meal and snack patterns. The descriptions of the dietary patterns (DP) were based on food items with factor loads ≥ 0·30 that were considered representative of each DP. SETTING: Schoolchildren, Florianopolis, Brazil. PARTICIPANTS: Children (n 1074) aged 7-13 years. RESULTS: Lunch was the most consumed meal (96·0 %), followed by dinner (86·4 %), breakfast (85·3 %) and mid-afternoon snack (81·7 %). Four DP were identified for breakfast, mid-morning snack, lunch, dinner and evening snack, and three for mid-afternoon snack. Breakfast, lunch and dinner patterns included traditional Brazilian foods. DP consisting of fast foods and sugary beverages were also observed, mainly for the evening snack. CONCLUSIONS: The results of the current study provide important information regarding the meal and snack patterns of schoolchildren to guide the development of nutrition interventions in public health.

Neuroprotective effect of ACTH on collagenase-induced peri-intraventricular hemorrhage in newborn male rats.

Peri-intraventricular hemorrhage (PIVH) is a common and serious prematurity-related complication in neonates. Adrenocorticotropic hormone (ACTH) has neuroprotective actions and is a candidate to ameliorate brain damage following PIVH. Here, we tested the efficacy of ACTH1-24 on a collagenase-induced lesion of the germinal matrix (GM) in newborn male rats. Animals received microinjection of the vehicle (PBS, 2 µl) or collagenase type VII (0.3 IU) into the GM/periventricular tissue on postnatal day (PN) 2. Twelve hours later pups received microinjection of either the agonist ACTH1-24 (0.048 mg/kg), or the antagonist SHU9119 (antagonist of MCR3/MCR4 receptors, 0.01 mg/kg), or their combination. Morphological outcomes included striatal injury extension, neuronal and glial cells counting, and immunohistochemical expression of brain lesion biomarkers ipsilateral and contralateral to the hemorrhagic site. Data were evaluated on PN 8. Collagenase induced PIVH and severe ipsilateral striatal lesion. ACTH1-24 dampened the deleterious effects of collagenase-induced hemorrhage in significantly reducing the extension of the damaged area, the striatal neuronal and glial losses, and the immunoreactive expression of the GFAP, S100ß, and NG2-glia biomarkers in the affected periventricular area. SHU9119 blocked the glial density rescuing effect of ACTH1-24. ACTH1-24 could be further evaluated to determine its suitability for preclinical models of PVH in premature infants.

Association between sleep period time and dietary patterns in Brazilian schoolchildren aged 7-13 years.

OBJECTIVES: To assess the association between sleep period time and dietary patterns (DPs) in Brazilian schoolchildren aged 7-13 years. METHODS: Sleep data of 1019 children were obtained from a questionnaire completed by parents/guardians. Food consumption, physical activity, and screen-based activity were assessed through the validated Web-CAAFE questionnaire. Latent profile analysis was used to identify dietary patterns. Associations between sleep period time and dietary patterns were analyzed by multinomial logistic regression, and the average marginal effect of sleep period time on the probability of adherence to dietary patterns was determined. RESULTS: Overall, 11.4% of children had inadequate sleep period time (<9 h per day). Three mutually exclusive dietary patterns were identified: "Monotonous" characterized by high consumption of pasta, instant pasta, sweets, and hamburgers/hot dog/pizza/salty snacks; "Traditional" characterized by high consumption of rice, vegetables, green leaves, beans, manioc flour, maize/potatoes, and meats; and "Dairy, bread, green leaves, maize/potatoes and sausage". The likelihood of adherence to the "Dairy, bread, green leaves, maize/potatoes and sausages" DP decreased by 0.026 as sleep period time increased by 1 h per day. For a sleep period time of more than 10 h per day, the average marginal effect of sleep period time on the likelihood of adherence to the this dietary pattern was significant and negative. CONCLUSIONS: Sleep period time was inversely associated with adherence to the "Dairy, bread, green leaves, maize/potatoes and sausages" DP; children who slept more than 10 h per day were less likely to present this pattern.

Melanonychia associated with subungual follicular inclusions: report of three cases.

Melanonychia is the change in the coloration of the nail plate resulting from the deposition of melanin. Among its causes are melanocytic hyperplasia, melanocytic activation and nail melanoma. Subungual follicular inclusions are histological findings of unknown etiology, possibly related to trauma. We present three cases of melanonychia of different etiologies with subungual follicular inclusions, an association that has not been well described and with an indefinite pathogenesis.

Melanonychia associated with subungual follicular inclusions: report of three cases

Abstract Melanonychia is the change in the coloration of the nail plate resulting from the deposition of melanin. Among its causes are melanocytic hyperplasia, melanocytic activation and nail melanoma. Subungual follicular inclusions are histological findings of unknown etiology, possibly related to trauma. We present three cases of melanonychia of different etiologies with subungual follicular inclusions, an association that has not been well described and with an indefinite pathogenesis.

SOCS2 modulates adipose tissue inflammation and expansion in mice.

INTRODUCTION: Obesity is usually triggered by a nutrient overload that favors adipocyte hypertrophy and increases the number of pro-inflammatory cells and mediators into adipose tissue. These mediators may be regulated by suppressors of cytokine signaling (SOCS), such as SOCS2, which is involved in the regulation of the inflammatory response of many diseases, but its role in obesity is not yet known. We aimed to investigate the role of SOCS2 in metabolic and inflammatory dysfunction induced by a high-refined carbohydrate-containing diet (HC). MATERIAL AND METHODS: Male C57BL/6 wild type (WT) and SOCS2 deficient (SOCS2-/-) mice were fed chow or an HC diet for 8 weeks. RESULTS: In general, SOCS2 deficient mice, independent of the diet, showed higher adipose tissue mass compared with their WT counterparts that were associated with decreased lipogenesis rate in adipose tissue, lipolysis in adipocyte culture and energy expenditure. An anti-inflammatory profile was observed in adipose tissue of SOCS2-/- by reduced secretion of cytokines, such as TNF and IL-6, and increased M2-like macrophages and regulatory T cells compared with WT mice. Also, SOCS2 deficiency reduced the differentiation/expansion of pro-inflammatory cells in the spleen but increased Th2 and Treg cells compared with their WT counterparts. CONCLUSION: The SOCS2 protein is an important modulator of obesity that regulates the metabolic pathways related to adipocyte size. Additionally, SOCS2 is an inflammatory regulator that appears to be essential for controlling the release of cytokines and the differentiation/recruitment of cells into adipose tissue during the development of obesity.

Increases in dendritic spine density in BLA without metabolic changes in a rodent model of PTSD.

Imaging studies have shown abnormal amygdala function in patients with posttraumatic stress disorder (PTSD). In addition, alterations in synaptic plasticity have been associated with psychiatric disorders and previous reports have indicated alterations in the amygdala morphology, especially in basolateral (BLA) neurons, are associated with stress-related disorders. Since, some individuals exposed to a traumatic event develop PTSD, the goals of this study were to evaluate the early effects of PTSD on amygdala glucose metabolism and analyze the possible BLA dendritic spine plasticity in animals with different levels of behavioral response. We employed the inescapable footshock protocol as an experimental model of PTSD and the animals were classified according to the duration of their freezing behavior into distinct groups: "extreme behavioral response" (EBR) and "minimal behavioral response". We evaluated the amygdala glucose metabolism at baseline (before the stress protocol) and immediately after the situational reminder using the microPET and the radiopharmaceutical 18F-FDG. The BLA dendritic spines were analyzed according to their number, density, shape and morphometric parameters. Our results show the EBR animals exhibited longer freezing behavior and increased proximal dendritic spines density in the BLA neurons. Neither the amygdaloid glucose metabolism, the types of dendritic spines nor their morphometric parameters showed statistically significant differences. The extreme behavior response induced by this PTSD protocol produces an early increase in BLA spine density, which is unassociated with either additional changes in the shape of spines or metabolic changes in the whole amygdala of Wistar rats.

The worst is yet to come: probable sporadic Creutzfeldt-Jakob disease in a well-controlled HIV patient.

We describe a case of probable sporadic Creutzfeldt-Jakob disease in the setting of well-controlled HIV and discuss whether exist, in fact, HIV-related factors that may predispose to the development of prion disease. To the best of our knowledge, this is the third report of this association.