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In this study, we introduce a pioneering approach that leverages advanced machine learning and ultrahigh-resolution Fourier transform ion cyclotron mass spectrometry (FT-ICR MS) data to predict the distribution of the total acid number (TAN) in true boiling point (TBP) distillation cuts from crude oil. By employing partial least-squares (PLS) regression and ordered predictor selection (OPS), we achieved robust predictive models with high accuracy, evidenced by low root-mean-square error of calibration (RMSEC) and strong correlation coefficients (Rc). Our analysis of 36 diverse crude oil samples revealed significant variations in chemical composition, with nitrogen- and oxygen-containing compounds playing key roles in influencing TAN values. Through the use of volcano plots, we identified critical molecular classes that drive changes in TAN. The predictive models demonstrated remarkable consistency between predicted and actual TAN values, particularly in samples with a higher TAN, further validating their reliability. Significantly, our method overcomes the limitations of traditional ASTM testing by requiring smaller sample volumes while still providing accurate TAN predictions. This novel approach offers a powerful new tool for the molecular characterization and behavioral forecasting of complex mixtures, enabling a more efficient pathway for sample analysis when resources are limited.

Background: Sexual health is influenced by a complex interplay of biological, psychological, and social factors, all of which can be impacted by Parkinson's disease (PD). Female sexual dysfunction includes reduced sexual desire and/or arousal, pain during sexual activity, or difficulty achieving orgasm. Despite its impact on quality of life, sexual health in women with PD remains poorly understood., Objective: To investigate the impact of motor, non-motor, and social PD aspects on sexual health of women with PD., Methods: We conducted a cross-sectional study with 100 women with PD (Hoehn and Yahr stages 1-3) who reported an active sex life in the last six months. Data were collected via remote interviews and included demographic and clinical features, cognitive capacity, motor and non-motor experiences, fatigue, self-esteem, sleep disorders, couple relationship quality, depressive symptoms, and sexual health assessments using the Female Sexual Function Index (FSFI) and Sexual Quotient-Female (SQ-F). Multiple regression models were used to identify predictors of FSFI and SQ-F scores., Results: Results indicated that while several motor, non-motor, and social factors correlated with sexual health, only couple relationship quality and sleep quality significantly predicted both short-term (FSFI) and long-term (SQ-F) sexual health. No significant associations were observed with age, disease onset, postmenopausal status, or daily medication dosage., Conclusions: The present study's evidence identifies multiple key areas, such as couple's relationship quality and sleep quality that could be targeted for intervention to improve sexual health in women with PD., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This study aimed to determine the total phenolic content, antioxidant and anti-inflammatory activities, and metabolomic profiling of Jabuticaba beverages. The metabolomic profiling showed a greater abundance of flavonoids in liqueur samples, while sweet wine predominantly contained phenolic acids. On the other hand, dry wine was characterized by a higher abundance of terpenes. The total phenolic content (TPC) was determined by the Folin-Ciocalteu method, while antioxidant activity was evaluated using the DPPH radical-scavenging assay. Notably, dry wine was rich in anthocyanins and tannins and demonstrated the highest TPC (2985.08 ± 0.23 mg GAE/L). Furthermore, this sample exhibited superior antioxidant activity (IC 50 0.83 ± 0.005 μg/mL). All beverages' samples displayed excellent antioxidant potential and TPC ranking as: dry wine > liqueur > sweet wine > juice. In terms of anti-inflammatory activity, treatments with 5 % dry wine led to reduce NO production. Molecular networking and chemometric tools, including HCA and PLS-DA, were employed to differentiate the samples and identify key metabolites. Chemometric analysis showed similar molecular composition between liqueur and dry wine samples, with the primary differences observed in their content of phenolic acids and simple phenols., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Background: The impact of ankyloglossia (tongue-tie) on breastfeeding outcomes may be overestimated and surgical treatment in newborns remains a controversial topic. The aim of the present study was to assess and quantify the impact of ankyloglossia in newborns on breastfeeding self-efficacy at 14 days of life., Methods: A birth cohort study was conducted involving mothers and newborns soon after childbirth at a public hospital in the city of Canoas, southern Brazil. At the hospital, the lingual frenum of newborns were clinically examined and classified using the Bristol Tongue Assessment Tool. For every newborn with defined or suspected ankyloglossia, two newborns without ankyloglossia were co-enrolled for the study. At 14 days of the children's lives, the mothers were interviewed at home to collect data on breastfeeding self-efficacy using the Breastfeeding Self-Efficacy Scale-Short Form (BSES-SF). Poisson regression with robust variance was conducted to quantify differences in the Breastfeeding Self-Efficacy scores between exposed and nonexposed newborns after adjusting for maternal sociodemographic variables (mother's completed years of schooling, mother's age, family structure, progenitor status of child, mother's smoking status), the gestational variables (number of prenatal appointments, gestational age, comorbidities, type of childbirth), and child related variables (sex, birth weight, birth length) as confounders., Results: The final sample was composed of 31 children with ankyloglossia (exposed) and 57 without ankyloglossia (nonexposed). No significant differences were found in the BSEF-SF scores between the 31 children with ankyloglossia (mean BSEF-SF scores: 56.0; median BSEF-SF scores: 60; 95% CI: 51.9-60.1) and the 57 children without ankyloglossia (mean BSEF-SF scores: 59.6; median BSEF-SF scores: 60; 95% CI: 57.5-61.7). The Poisson regression analysis showed no significant difference in the BSEF-SF scores between newborns with ankyloglossia and those without ankyloglossia (Ratio = 0.95; 95% CI: 0.88-1.02; p = 0.139)., Conclusion: Ankyloglossia at birth exerted no clinically relevant impact on breastfeeding self-efficacy in children at 14 days of life., Competing Interests: Declarations. Ethics approval and consent to participate: This study was performed in line with the principles of the Declaration of Helsinki and approved by the Human Research Ethics Committee of the Lutheran University of Brazil (certificate number: 5.378.250). All parents signed a statement of informed consent after receiving clarifications regarding the intervention and all phases of the data collection process. Consent for publication: Not applicable. Competing interests: Morẹ́nikẹ́ Oluwátóyìn Foláyan is a Senior Editor Board member with BMC Oral Health. All other authors declare no conflict of interest., (© 2025. The Author(s).)

Prosthetic gait differs considerably from the unimpaired gait. Studying alterations in the gait patterns could help to understand different adaptation mechanisms adopted by these populations. This study investigated the effects of induced stiff-knee gait (SKG) on prosthetic and healthy gait patterns and the capabilities of predictive simulation. Self-selected speed gait of two participants was measured: one healthy subject and one knee disarticulation subject using a variable-damping microprocessor controlled knee prosthesis. Both performed unperturbed gait and gait with restricted knee flexion. Experimental joint angles and moments were computed using OpenSim and muscle activity was measured using surface electromyography (EMG). The differences between the conditions were analyzed using statistical parametric mapping (SPM). Predictive models based on optimal control were created to represent the participants. Additionally, a hypothetical unimpaired predictive model with the same anthropometric characteristics as the amputee was created. Some patterns observed in the experimental prosthetic gait were predicted by the models, including increased knee flexion moment on the contralateral side caused by SKG in both participants, which was statistically significant according to SPM. With the exception of the rectus femoris muscle, we also found overall good agreement between measured EMG and predicted muscle activation. We predicted more alterations in activation of the hip flexors than other muscle groups due to the amputation and in the activation of the biceps femoris short head, quadratus femoris, and tibialis anterior due to SKG. In summary, we demonstrated that the method applied in this study could predict gait alterations due to amputation of the lower limb or due to imposed SKG., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Santos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Clostridium perfringens alpha toxin (CPA) is an important enterotoxemic pathogen linked to gastrointestinal disorders and previously associated with pulmonary disease in other mammals. A young female neotropical otter presented with lethargy, anorexia and steatorrhea, which developed within 24 hours. Veterinary care was provided under anesthesia, during which dehydration, intestinal hypermotility and pulmonary crackling sounds were identified. Hematological tests revealed normochromic normocytic anemia, and a quantitative RT-PCR assay for Clostridium perfringens alpha toxin detected a markedly elevated CPA count (43,789 copies of pathogen DNA/uL) in fecal samples, confirming the diagnosis. An abdominal ultrasound exhibited intestinal gas and mucous fecal contents, with normal wall stratification and evolving peristalsis. Chest X-rays and bronchoscopy revealed diffuse serous secretion associated with an underlying inflammatory process, predominantly affecting the left lung. Treatment included hydroelectrolyte replacement, analgesia, antibiotics, and antiemetics, with close monitoring during the critical stage. The patient improved gradually, with regression of clinical signs and the emergence of innate behaviors, and was discharged to the original enclosure after two weeks, supported by updated test results. In conclusion, this study analyzes and details the veterinary approach, diagnosis, and treatment of an acute infectious enteric condition with pulmonary involvement in a neotropical otter under human care., Competing Interests: Conflict of interest: BAS, BEPB, ACTA, BPM, GFS, DAB – No conflict of interest

Paper spray ionization (PSI-MS) and tissue spray ionization (TSI-MS) mass spectrometry are simple and rapid ambient ionization mass spectrometry techniques that offer numerous advantages over conventional analysis methods. This study aims to analyze the efficiency of detecting anthocyanins from Eugenia jambolana fruit peel and Inga edulis seeds using PSI-MS, TSI-MS, and DI-MS (direct infusion). DI-MS exhibited high efficiency, detecting all compounds in abundance, with anthocyanins malvidin 3,5-O-diglucoside (1) and petunidin 3,5-O-diglucoside (2) being the most prevalent. PSI-MS, however, struggled to detect delphinidin 3-O-glucoside and showed lower abundances for compounds 1, 2, 3 (delphinidin 3,5-O-diglucoside), and 4 (petunidin 3-O-glucoside) compared to DI-MS, attributed to the technique's challenges with molecular weight and polarity. TSI-MS was least effective, detecting only compounds 1, 2, and 3 at low intensities. The overall unique compounds identified across techniques were 134, emphasizing the importance of comprehensively employing multiple methods to analyze anthocyanins in these edible plants., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Naphthenic acids (NAs) naturally occur in crude oil and its associated produced water, presenting significant challenges, such as corrosion, in refinery apparatus and ecotoxicity in aquatic habitats. This study delineates a multivariate method to quantify NAs in produced water via electrospray ionization coupled with high-resolution Orbitrap mass spectrometry (ESI-Orbitrap MS). By employing liquid-liquid extraction, followed by direct infusion ESI(-)-Orbitrap MS, we characterized and quantified NAs employing a partial least-squares regression (PLS) model enhanced by the ordered predictor selection (OPS) algorithm. Thirty-six produced water samples were utilized, with 24 allocated for calibration and 12 designated for validation. The PLS-OPS model demonstrated notable accuracy in predicting NA concentrations in simulated and actual produced water samples ranging from ∼30 to 300 mg·L -1 . This methodology offers a rapid yet robust alternative for quantifying NAs using mass spectrometry augmented by PLS and the OPS. Its significance is underscored by its potential to equip the petroleum industry with a swift and reliable monitoring mechanism for NAs in produced water, thereby aiding in mitigating environmental and operational risks.

The chemical composition, antioxidant capacity and functional properties of mixtures of baru by-products, named baru food ingredients (BFI), were investigated and applied in a plant-based burger formulation. BFI were prepared from wasted baru by-products - partially defatted baru nut cake and baru pulp plus peel. A plant-based burger was developed and its chemical composition, antioxidant capacity, cooking and texture parameters were determined. BFI 1 (50% partially defatted baru nut cake + 50% baru pulp plus peel) had the highest content of carbohydrate (31.9%), and dietary fibre (28.3%). BFI 2 (75% partially defatted baru nut cake + 25% baru pulp plus peel) and BFI 3 (90% partially defatted baru nut cake + 10% baru pulp plus peel) showed high concentration of protein and dietary fibre, and BFI 3 had the highest protein content (29.5%). All BFI showed high concentration of total phenolics (402-443 mg GAE/100 g). Replacing textured pea protein of control burger (PPB) with 35% of BFI 3 in the formulation of baru protein burger (BPB) resulted in a low-fat product (2.9%), with protein content (19.2%) comparable to the PPB (15.9%) and the commercial burger (mixed plant proteins - 16.3%). The BPB also showed a higher concentration of dietary fibre (4.9%) and phenolic compounds (128 mg GAE/100 g) than the control burger. BPB's cooking yield was the highest among the tested burgers. BPB had a softer texture when compared to other burgers. Baru food ingredients can be used as nutritive ingredients of health-promoting foods, especially in plant-based products, such as burger and meat analogues, or in hybrid meat products. BPB showed a healthy and nutritious profile., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Small-cell lung cancer (SCLC) is characterized by rapid proliferation and early dissemination. The objective of this study was to examine the demographic trends and outcomes in SCLC., Methods: The authors queried the National Cancer Institute's Surveillance, Epidemiology, and End Results database to assess the trends in incidence, demographics, staging, and survival for SCLC from 1975 to 2019. Trends were determined using joinpoint analysis according to the year of diagnosis., Results: Among the 530,198 patients with lung cancer, there were 73,362 (13.8%) with SCLC. The incidence per 100,000 population peaked at 15.3 in 1986 followed by a decline to 6.5 in 2019. The percentage of SCLC among all lung tumors increased from 13.3% in 1975 to a peak of 17.5% in 1986, declining to 11.1% by 2019. There was an increased median age at diagnosis from 63 to 69 years and an increased percentage of women from 31.4% to 51.2%. The percentage of stage IV increased from 58.6% in 1988 to 70.8% in 2010, without further increase. The most common sites of metastasis at diagnosis were mediastinal lymph nodes (75.3%) liver (31.6%), bone (23.7%), and brain (16.4%). The 1-year and 5-year overall survival rate increased from 23% and 3.6%, respectively, in 1975-1979 to 30.8% and 6.8%, respectively, in 2010-2019., Conclusions: The incidence of SCLC peaked in 1988 followed by a gradual decline. Other notable changes include increased median age at diagnosis, the percentage of women, and the percentage of stage IV at diagnosis. The improvement in 5-year overall survival has been statistically significant but clinically modest., (© 2024 American Cancer Society.)

Introduction: Bone metastases are associated with increased morbidity and decreased quality of life in patients with solid tumors. Identifying patients at increased risk of bone metastases at diagnosis could lead to earlier interventions. We sought to retrospectively identify the incidence and predictive factors for bone metastases at initial diagnosis in a large population-based dataset., Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients 18 years-old or older diagnosed with solid cancers from 2010 to 2019. Patients with hematologic malignancies and primary tumors of the bone were excluded. We calculated the incidence and predictive factors for bone metastases according to demographic and tumor characteristics., Results: Among 1,132,154 patients identified, 1,075,070 (95.0%) had known bone metastasis status and were eligible for the study. Bone metastases were detected in 55,903 patients (5.2% of those with known bone metastases status). Among patients with bone metastases, the most common primary tumors arose from lung (44.4%), prostate (19.3%), breast (12.3%), kidney (4.0%), and colon (2.2%). Bone metastases at presentation were most common in small cell lung cancer (25.2%), non-small cell lung cancer (18.0%), and esophageal adenocarcinoma (9.4%). In addition to stage classification, predictors for bone metastases included Gleason score (OR 95.7 (95% CI 73.1 - 125.4) for Grade Group 5 vs 1 and OR 42.6 (95% CI 32.3 - 55.9) for Group 4 vs 1) and PSA (OR 14.2 (95% CI 12.6 - 16.0) for PSA > 97 vs 0 - 9.9) for prostate cancer, HER2 and hormonal receptor (HR) status (OR 2.2 (95% CI 1.9 - 2.6) for HR+/HER2+ vs HR-/HER2-) for breast cancer, histology (OR 2.5 (95% CI 2.3 - 2.6) for adenocarcinoma vs squamous) for lung cancer, and rectal primary (OR 1.2 (95% 1.1 - 1.4) vs colon primary) and liver metastases (OR 8.6 (95% CI 7.3 - 10.0) vs no liver metastases) for colorectal tumors., Conclusions: Bone metastases at presentation are commonly seen in solid tumors, particularly lung, prostate, breast, and kidney cancers. Clinical and pathologic factors are associated with a significantly increased risk for bone metastases., Competing Interests: PS reports speaking honorarium from Varian Medical Systems. DM reports consulting or advisory roles from Abbvie, G1 Therapeutics, Lilly Medical, Mirati Therapeutics, Arcus Biosciences, stock or other ownership interests from Bristol-Myers Squibb and Abbot Laboratories, and institutional research funding from Heat Biologics, Merck, Celgene, AstraZeneca, Baxter, Incyte, Abbvie, Bristol-Myers Squibb, EpicentrX, Pfizer, Roche, Lilly, Altum Pharmaceuticals, Array Biopharma, Surface Oncology, Arcus Biosciences, Boehringer Ingelheim, and Y-mAbs Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Knapp, Cittolin-Santos, Flanagan, Grandhi, Gao, Samson, Govindan and Morgensztern.)

Malaria is the leading parasitic disease worldwide, with P. vivax being a major challenge for its control. Several studies have indicated metabolomics as a promising tool for combating the disease. The study evaluated plasma metabolomic profiles of patients with recurrent and non-recurrent P. vivax malaria in the Brazilian Amazon. Metabolites extracted from the plasma of P. vivax-infected patients were subjected to LC-MS analysis. Untargeted metabolomics was applied to investigate the metabolic profile of the plasma in the two groups. Overall, 51 recurrent and 59 non-recurrent patients were included in the study. Longitudinal metabolomic analysis revealed 52 and 37 significant metabolite features from the recurrent and non-recurrent participants, respectively. Recurrence was associated with disturbances in eicosanoid metabolism. Comparison between groups suggest alterations in vitamin B6 (pyridoxine) metabolism, tyrosine metabolism, 3-oxo-10-octadecatrienoate β-oxidation, and alkaloid biosynthesis II. Integrative network analysis revealed enrichment of other metabolic pathways for the recurrent phenotype, including the butanoate metabolism, aspartate and asparagine metabolism, and N-glycan biosynthesis. The metabolites and metabolic pathways predicted in our study suggest potential biomarkers of recurrence and provide insights into targets for antimalarial development against P. vivax., (© 2024. The Author(s).)

Background: Sexual health (SH) is influenced by several biological, mental, and social factors that may be negatively impacted by Parkinson's disease (PD). Despite its prevalence and relevance for quality of life, the factors that affect SH in men with PD (MwPD) are still poorly understood., Objectives: To investigate the impact of motor, non-motor, and social aspects on the SH in MwPD., Methods: We conducted a cross-sectional study of 80 men (mean-age 53.55±10.8) in stages 1-3 of Hoehn and Yahr classification (H&Y), who reported having an active sex life in the last six months. The following data were collected for each person: 1) Demographic and clinical features; 2) global cognitive capacity (T-MoCA); 3) Non-Motor Aspects of Experiences of Daily Living (MDS-UPDRS, part I); 4) Motor Aspects of Experiences of Daily Living (MDS-UPDRS, part II); 5) Fatigue (FSS); 6) Self-esteem (RSES); 7) Sleep disorder (PDSS); 8) Couple relationship quality (DAS); 9) Depressive signals (BDI); 10) Short-term sexual health by International Index of Erectile Function (IIFE); and 11) Long-term sexual health by Sexual Quotient-Male (SQ-M)., Results: Our results showed that although several motor, non-motor, and social factors were correlated with SH, only motor disability levels in daily living predicted short-term SH and erectile dysfunction, while only depression predicted long-term SH in MwPD. Age, disease onset, and medication daily dosage were not correlated with SH., Conclusions: Our findings confirm that multidimensional factors can affect the SH of MwPD and emphasize that only a multi-professional team can offer proper care to improve SH in MwPD.

Importance: The SARS-CoV-2 virus infection in humans induces significant inflammatory and systemic reactions and complications of which corticosteroids like methylprednisolone have been recommended as treatment. Our understanding of the metabolic and metabolomic pathway dysregulations while using intravenous corticosteroids in COVID-19 is limited. This study will help enlighten the metabolic and metabolomic pathway dysregulations underlying high daily doses of intravenous methylprednisolone in COVID-19 patients compared to those receiving placebo. The information on key metabolites and pathways identified in this study together with the crosstalk with the inflammation and biochemistry components may be used, in the future, to leverage the use of methylprednisolone in any future pandemics from the coronavirus family., Competing Interests: The authors declare no conflict of interest.

This paper examines scaling behaviors of urban landscape and street design metrics with respect to city population in Latin America. We used data from the SALURBAL project, which has compiled and harmonized data on health, social, and built environment for 371 Latin American cities above 100,000 inhabitants. These metrics included total urbanized area, effective mesh size, area in km2 and number of streets. We obtained scaling relations by regressing log(metric) on log (city population). The results show an overall sub-linear scaling behavior of most variables, indicating a relatively lower value of each variable in larger cities. We also explored the potential influence of colonization on the current built environment, by analyzing cities colonized by Portuguese (Brazilian cities) or Spaniards (Other cities in Latin America) separately. We found that the scaling behaviors are similar for both sets of cities., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Paiva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

There is an increasing need for developing a strategy to analyze the penetration of pesticides in cultures during postharvest control with minimal or no sample preparation. This study explores the combined use of laser ablation electrospray ionization mass spectrometry imaging (LAESI imaging) and tissue spray ionization mass spectrometry (TSI-MS) to investigate the penetration of thiabendazole (TBZ) in fruits, simulating a postharvest procedure. Slices of guava and apple were prepared, and an infrared laser beam was used, resulting in the ablation of TBZ directly ionized by electrospray and analyzed by mass spectrometry. The experiments were conducted for 5 days of fruit storage after TBZ administration to simulate a postharvest treatment. During postharvest treatment, TBZ is applied directly to the fruit peel after harvesting. Consequently, TBZ residues may remain on the peel if the consumer does not wash the fruit properly before its consumption. To evaluate the effectiveness of household washing procedures, TSI-MS was employed as a rapid and straightforward technique to monitor the remaining amount of TBZ in guava and apple peels following fruit washing. This study highlights the advantages of LAESI imaging for evaluating TBZ penetration in fruits. Moreover, the powerful capabilities of TSI-MS are demonstrated in monitoring and estimating TBZ residues after pesticide application, enabling the comprehensive unveiling of pesticide contaminants in fruits.

Foodborne diseases are characterized by conditions that can induce symptomatic illnesses in their carriers, and therefore represent a serious problem. They are important conditions from a clinical and epidemiological point of view, and are associated with the occurrence of serious public health problems, with a strong impact on morbidity and mortality. The Escherichia coli (E. coli) is an enterobacterium associated with enteric conditions of variable intensity and which are accompanied by blood. The transmission routes are mainly based on the consumption of contaminated food and water sources. Shiga toxin-producing E. coli (STEC) are considered a serogroup of E. coli, are capable of producing Shiga-type toxins (Stx 1 and Stx 2) and the O157:H7 strain is one of the best-known serotypes. The early detection of this pathogen is very important, especially due to the capacity of contamination of carcasses destined for food consumption and supply of productive markets. Sanitary protocols must be developed and constantly reviewed in order to prevent/control the presence of the pathogen., (© 2023. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

This paper aims to identify typologies of Latin American cities based on socioeconomic urban environment patterns. We used census data from 371 urban agglomerations in 11 countries included in the SALURBAL project to identify socioeconomic typologies of cities in Latin America. Exploratory factor analysis was used to select a set of variables, and finite mixture modelling (FMM) was applied to identify clusters to define the typology of cities. Despite the heterogeneities among the Latin American cities, we also found similarities. By exploring intersections and contrasts among these clusters, it was possible to define five socioeconomic regional typology patterns. The main features of each one are low-education cities in Northeast Brazil; low-unemployment cities in Peru and Panama; high-education cities in Argentina, Chile, Colombia, Costa Rica, Nicaragua and Mexico; high female labor participation, with high primary education in Argentina and low primary education in Brazil; and low female labor participation and low education in Brazil, Colombia, El Salvador, Guatemala, and Mexico. Identifying clusters of cities with similar features underscores understanding of the urban social and economic development dynamics and assists in studying how urban features affect health, the environment, and sustainability., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Employing a combination of liquid chromatography electrospray ionization and paper spray ionization high-resolution tandem mass spectrometry, extracts from cupuassu ( Theobroma grandiflorum ) pulp prepared with either water, methanol, acetonitrile or combinations thereof were subjected to metabolite fingerprinting. Among the tested extractors, 100% methanol extracted preferentially phenols and cinnamic acids derivatives, whereas acetonitrile and acetonitrile/methanol were more effective in extracting terpenoids and flavonoids, respectively. And while liquid chromatography- mass spectrometry detected twice as many metabolites as paper spray ionization tandem mass spectrometry, the latter proved its potential as a screening technique. Comprehensive structural annotation showed a high production of terpenes, mainly oleanane triterpene derivatives. of the mass spectra Further, five major metabolites with known antioxidant activity, namely catechin, citric acid, epigallocatechin-3'-glucuronide, 5,7,8-trihydroxyflavanone, and asiatic acid, were subjected to molecular docking analysis using the antioxidative enzyme peroxiredoxin 5 (PRDX5) as a model receptor. Based on its excellent docking score, a pharmacophore model of 5,7,8-trihydroxyflavanone was generated, which may help the design of new antioxidants.

Severe manifestations of coronavirus disease 2019 (COVID-19) and mortality have been associated with physiological alterations that provide insights into the pathogenesis of the disease. Moreover, factors that drive recovery from COVID-19 can be explored to identify correlates of protection. The cellular metabolism represents a potential target to improve survival upon severe disease, but the associations between the metabolism and the inflammatory response during COVID-19 are not well defined. We analyzed blood laboratorial parameters, cytokines, and metabolomes of 150 individuals with mild to severe disease, of which 33 progressed to a fatal outcome. A subset of 20 individuals was followed up after hospital discharge and recovery from acute disease. We used hierarchical community networks to integrate metabolomics profiles with cytokines and markers of inflammation, coagulation, and tissue damage. Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) promotes significant alterations in the plasma metabolome, whose activity varies according to disease severity and correlates with oxygen saturation. Differential metabolism underlying death was marked by amino acids and related metabolites, such as glutamate, glutamyl-glutamate, and oxoproline, and lipids, including progesterone, phosphocholine, and lysophosphatidylcholines (lysoPCs). Individuals who recovered from severe disease displayed persistent alterations enriched for metabolism of purines and phosphatidylinositol phosphate and glycolysis. Recovery of mild disease was associated with vitamin E metabolism. Data integration shows that the metabolic response is a hub connecting other biological features during disease and recovery. Infection by SARS-CoV-2 induces concerted activity of metabolic and inflammatory responses that depend on disease severity and collectively predict clinical outcomes of COVID-19. IMPORTANCE COVID-19 is characterized by diverse clinical outcomes that include asymptomatic to mild manifestations or severe disease and death. Infection by SARS-CoV-2 activates inflammatory and metabolic responses that drive protection or pathology. How inflammation and metabolism communicate during COVID-19 is not well defined. We used high-resolution mass spectrometry to investigate small biochemical compounds (<1,500 Da) in plasma of individuals with COVID-19 and controls. Age, sex, and comorbidities have a profound effect on the plasma metabolites of individuals with COVID-19, but we identified significant activity of pathways and metabolites related to amino acids, lipids, nucleotides, and vitamins determined by disease severity, survival outcome, and recovery. Furthermore, we identified metabolites associated with acute-phase proteins and coagulation factors, which collectively identify individuals with severe disease or individuals who died of severe COVID-19. Our study suggests that manipulating specific metabolic pathways can be explored to prevent hyperinflammation, organ dysfunction, and death.

Introduction: Yangambin and epi-yangambin are the main lignans found in Louro-de-Cheiro [ Ocotea fasciculata (Nees) Mez], a tree native to the Atlantic forests of northeastern Brazil whose leaves and bark are widely used in folk medicine. The present study investigated the leishmanicidal and immunomodulatory effects of both lignans in in vitro models of infection by Leishmania amazonensis or Leishmania braziliensis , both etiological agents of Cutaneous Leishmaniasis in Brazil., Methods: Bone marrow-derived mouse macrophages were infected with L. amazonensis or L. braziliensis and then treated for 48 h at varying concentrations of yangambin or epi-yangambin., Results: Yangambin and epi-yangambin were found to reduce the intracellular viability of either Leishmania species in a concentration-dependent manner, with respective IC 50 values of: 43.9 ± 5 and 22.6 ± 4.9 µM for L. amazonensis , compared to IC 50 values of 76 ± 17 and 74.4 ± 9.8 µM for L. braziliensis . In this context, epi-yangambin proved more selective and effective against in vitro infection by L. amazonensis . However, both lignans were found to distinctly modulate the production of inflammatory mediators and other cytokines by macrophages infected by either of the Leishmania species evaluated. While yangambin increased the production of IL-10 by L. braziliensis- infected macrophages, both compounds were observed to lower the production of NO, PGE 2 , IL-6 and TNF-α in both Leishmania species., Discussion: The present results serve to encourage the development of novel studies aimed at screening natural bioactive compounds with the hope of discovering new therapeutic options for the treatment of Cutaneous Leishmaniasis., Competing Interests: Author AB was employed by Apis Flora Industrial e Comercial Ltda. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rebouças-Silva, Santos, Filho, Berretta, Marquele-Oliveira and Borges.)

Lithium has proven its efficacy in treating bipolar disorder. Severe side effects caused by lithium, including renal and endocrine outcomes, have already been amply documented. The impact of lithium on sexual function, however, is less well known. A 33-year-old man, with no past medical history, diagnosed with bipolar disorder, developed premature ejaculation after short-term use of lithium. The dose of lithium was reduced, leading to a rapid clinical resolution. Retrospectively, lithium-induced premature ejaculation was deemed the most likely diagnosis. Premature ejaculation is a rare side effect of lithium. Changing the time of medication administration and lowering dose could be considered as alternatives. Given lithium's pharmacological profile, it is likely that the pathophysiologic mechanism behind premature ejaculation is altered levels or altered serotonin receptor sensitivity in the ejaculatory modulating centers of the central nervous system. Given the reluctance to spontaneously report sexual adverse effects, clinicians should be aware of this possible side effect., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Pedro Amadeu Almeida et al.)

Highly selective and sensitive analytical techniques are necessary for microbial metabolomics due to the complexity of the microbial sample matrix. Hence, mass spectrometry (MS) has been successfully applied in microbial metabolomics due to its high precision, versatility, sensitivity, and wide dynamic range. The different analytical tools using MS have been employed in microbial metabolomics investigations and can contribute to the discovery or accelerate the search for bioactive substances. The coupling with chromatographic and electrophoretic separation techniques has resulted in more efficient technologies for the analysis of microbial compounds occurring in trace levels. This book chapter describes the current advances in the application of mass spectrometry-based metabolomics in the search for new biologically active agents from microbial sources; the development of new approaches for in silico annotation of natural products; the different technologies employing mass spectrometry imaging to deliver more comprehensive analysis and elucidate the metabolome involved in ecological interactions as they enable visualization of the spatial dispersion of small molecules. We also describe other ambient ionization techniques applied to the fingerprint of microbial natural products and modern techniques such as ion mobility mass spectrometry used to microbial metabolomic analyses and the dereplication of natural microbial products through MS., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

The liquid chromatography-mass spectrometry (LC-MS)-based metabolomics approach is a powerful technology for discovering novel biologically active molecules. In this study, we investigated the metabolic profiling of Orchidaceae species using LC-HRMS/MS data combined with chemometric methods and dereplication tools to discover antifungal compounds. We analyze twenty ethanolic plant extracts from Vanda and Cattleya (Orchidaceae) genera. Molecular networking and chemometric methods were used to discriminate ions that differentiate healthy and fungal-infected plant samples. Fifty-three metabolites were rapidly annotated through spectral library matching and in silico fragmentation tools. The metabolomic profiling showed a large production of polyphenols, including flavonoids, phenolic acids, chromones, stilbenoids, and tannins, which varied in relative abundance across species. Considering the presence and abundance of metabolites in both groups of samples, we can infer that these constituents are associated with biochemical responses to microbial attacks. In addition, we evaluated the metabolic dynamic through the synthesis of stilbenoids in fungal-infected plants. The tricin derivative flavonoid- and the loliolide terpenoidfound only in healthy plant samples, are promising antifungal metabolites. LC-HRMS/MS, combined with state-of-the-art tools, proved to be a rapid and reliable technique for fingerprinting medicinal plants and discovering new hits and leads.

Socioeconomic factors have exacerbated the impact of COVID-19 worldwide. Brazil, already marked by significant economic inequalities, is one of the most affected countries, with one of the highest mortality rates. Understanding how inequality and income segregation contribute to excess mortality by COVID-19 in Brazilian cities is essential for designing public health policies to mitigate the impact of the disease. This paper aims to fill in this gap by analyzing the effect of income inequality and income segregation on COVID-19 mortality in large urban centers in Brazil. We compiled weekly COVID-19 mortality rates from March 2020 to February 2021 in a longitudinal ecological design, aggregating data at the city level for 152 Brazilian cities. Mortality rates from COVID-19 were compared across weeks, cities and states using mixed linear models. We estimated the associations between COVID-19 mortality rates with income inequality and income segregation using mixed negative binomial models including city and week-level random intercepts. We measured income inequality using the Gini index and income segregation using the dissimilarity index using data from the 2010 Brazilian demographic census. We found that 88.2% of COVID-19 mortality rates variability was between weeks, 8.5% between cities, and 3.3% between states. Higher-income inequality and higher-income segregation values were associated with higher COVID-19 mortality rates before and after accounting for all adjustment factors. In our main adjusted model, rate ratios (RR) per 1 SD increases in income inequality and income segregation were associated with 17% (95% CI 9% to 26%) and 11% (95% CI 4% to 19%) higher mortality. Income inequality and income segregation are long-standing hallmarks of large Brazilian cities. Risk factors related to the socioeconomic context affected the course of the pandemic in the country and contributed to high mortality rates. Pre-existing social vulnerabilities were critical factors in the aggravation of COVID-19, as supported by the observed associations in this study., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Sousa Filho et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Naphthenic acids comprise one of the most toxic compounds of the produced water released from offshore oil platforms. Therefore, developing and applying faster, simpler, and more efficient analytical methods for analyzing naphthenic acids are urgently needed. Electromembrane extraction (EME) uses the electrokinetic migration of target ions through a porous membrane. Herein, the EME method was applied to extract naphthenic acids from produced water. The EME method was optimized, and the optimal conditions encompassed decanol as the organic solvent, the sample with pH 10.0, 5 min of extraction at 200 V, and the ratio 4:1 (borate buffer/matrix, v/v). Electrochemical impedance spectroscopy confirmed charged species' migration from produced water through the EME. Subsequently, all extracts were analyzed by ultra-high-resolution mass spectrometry. The EME efficiency was assessed by comparing the extraction results to the liquid-liquid extraction (LLE) method results. Analytical results showed good linearity for both solvent and matrix curves ( R 2 > 0.98). Low detection limits ranged from 0.10 to 0.13 μg mL -1 and quantification limits from 0.36 to 0.45 μg mL -1 . Precision and accuracy values ranged from -13.3% to 16.5%. These values fit the proposed method, demonstrating that the EME was more efficient than LLE in naphthenic acid extraction. The EME method preferably extracted aromatic compounds with double-bond equivalence from 6 to 8. The EME coupled with ultra-high-resolution mass spectrometry was demonstrated as a promising analytical approach to naphthenic acid extraction as an efficient and more environmentally friendly alternative to conventional extraction methods.

The indiscriminate utilization of agrochemicals causes environmental and animal life impacts. In this regard, methodologies have been developed to offer efficiency and quickness for agrochemicals detection. Due to their selectivity and molecular recognition sites, Molecular Imprinted Polymer (MIPs) have been widely employed in some areas, including biotechnology, waste analyses, foodstuff, biological fluids, and others. This work proposed developing a method to determine aminocarb, pirimicarb, dimethoate, omethoate, pyridaphenthion, and fenitrothion pesticides using molecularly imprinted polymer combined with solid-phase extraction (MIP-SPE) for clean-up and paper spray ionization mass spectrometry for their analysis. Extractions analysis for Aminocarb, Pirimicarb, and Omethoate using MIP-SPE showed better performance when compared with MIP and NIP. The R 2 values were found with R 2  > 0.98 for all pesticides, and LODs and LOQs values were 50 and 100 µg kg -1 , respectively. The precision and accuracy were assessed at three concentration levels-low, medium, and high. The precision values (interday and intraday) were below 10%, and the variation of recovery was between 80 and 120% for all pesticides. Therefore, it was possible to verify the presence of two carbamates and five organophosphorus without the necessity of preconcentration samples with precision and good recovery., Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05464-7., Competing Interests: Conflict of interestThe authors declare no competing financial interest., (© Association of Food Scientists & Technologists (India) 2022.)

Pulmonary atelectasis is a disease characterized by the collapse of the pulmonary alveoli, leading to partial or total loss of function in the affected lung, and is mostly described in older dogs. It occurs due to chronic inflammatory and obstructive processes such as pneumonia. In infants who do not feed directly from the mother, it is common to develop aspiration pneumonia due to inhalation of a milk replacer. Once aspirated, food generates an inflammatory process in the airway that alters the function of the pulmonary surfactant, increases mucus production, and causes consequent airway obstruction, which may progress to alveolar and bronchial collapse. The aim of the present study was to report a case of a 4-month-old canine with pulmonary atelectasis secondary to bronchopneumonia and the outcome of the clinical case. The patient presented with cough, exercise intolerance, tachypnea, and progressive weight loss. Thoracic radiographic examination was performed to identify displacement of the mediastinum and heart overlapping the collapsed lung, interstitial-alveolar pattern associated with atelectasis of the middle lobe of the right lung, and a diffuse interstitial bronchial pattern throughout the other lung fields. Pulmonary support treatment was administered with antibiotics, bronchodilators, mucolytics, and inhaled corticosteroids, with resolution of clinical and radiographic symptoms after 60 days of treatment. Therefore, adequate treatment of chronic bronchopneumonia is effective in resolving pulmonary atelectasis and its associated clinical complications., Competing Interests: Conflict of interests: DAM, SB, DCS, GFS, LCFJ, COA, AJRB and BA had no conflict of interest., (Copyright Mendonça et al.)

Residential segregation has brought significant challenges to cities worldwide and has important implications for health. This study aimed to assess income segregation in the 152 largest Brazilian cities in the SALURBAL Project. We identify specific socioeconomic characteristics related to residential segregation by income using the Brazilian demographic census of 2010 and calculated the income dissimilarity index (IDI) at the census tract level for each city, subsequently comparing it with Gini and other local socioeconomic variables. We evaluated our results' robustness using a bootstrap correction to the IDI to examine the consequences of using different income cut-offs in substantial urban and regional inequalities. We identified a two minimum wage cut-off as the most appropriate. We found little evidence of upward bias in the calculation of the IDI regardless of the cut-off used. Among the ten most segregated cities, nine are in the Northeast region, with Brazil's highest income inequality and poverty. Our results indicate that the Gini index and poverty are the main variables associated with residential segregation., Supplementary Information: The online version contains supplementary material available at 10.1007/s43545-022-00491-9., Competing Interests: Conflict of interestWe declare no competing interest., (© The Author(s) 2022.)

We explored how mortality scales with city population size using vital registration and population data from 742 cities in 10 Latin American countries and the United States. We found that more populated cities had lower mortality (sublinear scaling), driven by a sublinear pattern in U.S. cities, while Latin American cities had similar mortality across city sizes. Sexually transmitted infections and homicides showed higher rates in larger cities (superlinear scaling). Tuberculosis mortality behaved sublinearly in U.S. and Mexican cities and superlinearly in other Latin American cities. Other communicable, maternal, neonatal, and nutritional deaths, and deaths due to noncommunicable diseases were generally sublinear in the United States and linear or superlinear in Latin America. Our findings reveal distinct patterns across the Americas, suggesting no universal relation between city size and mortality, pointing to the importance of understanding the processes that explain heterogeneity in scaling behavior or mortality to further advance urban health policies.

This work describes the surface coating of wooden toothpicks with amino groups (NH 2 ) for electrospray ionization mass spectrometry (MS) analysis of naphthenic acids (NAs) in produced water samples and crude oil fractions. NH 2 was introduced into the cellulosic material through a silanization reaction using aminopropyltriethoxysilane. An NH 2 -modified toothpick was inserted into the analyte extraction sample and was subsequently used as an electrospray emitter for MS analysis. The extraction conditions were optimized by analyzing NAs (benzoic acid, 1-naphthoic acid, decanoic acid, 3,5-dimethyladamantane-1-carboxylic acid, and 3,5-dimethyladamantane-1-acetic acid) in pure water, and the best condition was using 5 min of extraction time with the samples under agitation. Modified and unmodified wooden toothpicks were compared, and the intensities of all NAs were higher when using the modified substrates than when using the unmodified ones. Limit of detection (LOD), limit of quantification (LOQ), linearity, precision, and recovery were determined by analyzing decanoic acid in seawater samples. The LOD and LOQ were 2 and 5 μg mL -1 , respectively, and a linear correlation ( R 2 = 0.9927) was obtained with concentrations ranging from 5 to 250 μg mL -1 . Precision values ranged from 6 to 13% and recoveries from 89 to 106%. The technique was also employed to analyze three produced water samples, in which decanoic acid was semi-quantified, and the concentrations ranged from 10 to 13 μg mL -1 . High abundances of acidic compounds of class O2 with DBEs (double bond equivalents) ranging from 1 to 3 and carbon numbers going from 8 to 12 were detected in the produced water samples. The results suggest that the modification of wooden toothpicks with NH 2 might offer a significant advancement in the knowledge of cheap substrates that can improve the sensitivity of analysis of NAs in water samples.

Post-stroke patients present various gait abnormalities such as drop foot, stiff-knee gait (SKG), and knee hyperextension. Functional electrical stimulation (FES) improves drop foot gait although the mechanistic basis for this effect is not well understood. To answer this question, we evaluated the gait of a post-stroke patient walking with and without FES by inverse dynamics analysis and compared the results to an optimal control framework. The effect of FES and cause-effect relationship of changes in knee and ankle muscle strength were investigated; personalized muscle-tendon parameters allowed the prediction of pathologic gait. We also predicted healthy gait patterns at different speeds to simulate the subject walking without impairment. The passive moment of the knee played an important role in the estimation of muscle force with knee hyperextension, which was decreased during FES and knee extensor strengthening. Weakening the knee extensors and strengthening the flexors improved SKG. During FES, weak ankle plantarflexors and strong ankle dorsiflexors resulted in increased ankle dorsiflexion, which reduced drop foot. FES also improved gait speed and reduced circumduction. These findings provide insight into compensatory strategies adopted by post-stroke patients that can guide the design of individualized rehabilitation and treatment programs., (© 2021. The Author(s).)

We report a 64-year-old caucasian woman diagnosed with membranous nephropathy secondary to alpha-1 antitrypsin deficiency (AATD). AATD is a rare autosomal codominant genetic disorder. Its clinical manifestations are mostly observed in the lungs, with early-onset emphysema. Nephropathy due to AATD is still very rare and only a few cohort studies have been reported. It has been recognised that alpha-1 antitrypsin has a protective role in the kidneys which enhances the possibility of development of kidney failure, such as nephrotic syndrome, in cases of AATD. Further clinical investigation is needed to understand the relationship between the development of nephropathy, namely membranous nephropathy, and AATD., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

The recent efforts dedicated to understanding important features and consequences of city growth have profited from the scaling approach to urban indicators. This kind of analysis can be conveniently used to investigate the impact of geo-economic transformations, like fast urbanization and industrial development, which occurred in continental size countries (e.g., India, China, and Brazil) during the past half-century. Profiting from high quality data, this work explores how scaling relationships among urban indicators are influenced by strong regional heterogeneities in Brazil. It is based on economic, infrastructure and violence related data sets for the time interval 2002-2016. Results indicate that regional specificities related to infrastructure, economic development, and geography have a larger influence on the absolute value of the urban indexes. Regional scaling similarities and differences among Brazilian regions were also uncovered. Interesting enough, the results indicate that the richest and poorest Brazilian regions share similar scaling behavior, despite all huge different local influences. By contrast, the results for the two richest regions, with similar average values of urban indexes and the same kind of local influences have rather different scaling properties. Thus, scaling analysis suggests that distinct political solutions might be necessary to improve life's quality, even for two regions with similar average values of urban indicators., Competing Interests: The authors have declared that no competing interests exist.

Background: Selecting the optimal treatment strategy for coronary revascularization is challenging. A crucial endpoint to be considered when making this choice is the necessity to repeat revascularization since it is much more frequent after percutaneous coronary intervention (PCI) than after coronary artery bypass grafting (CABG)., Objective: This study intends to provide insights on patients' preferences for revascularization, strategies in the perspective of patients who had to repeat revascularization., Methods: We selected a sample of patients who had undergone PCI and were hospitalized to repeat coronary revascularization and elicited their preferences for a new PCI or CABG. Perioperative death, long-term death, myocardial infarction, and repeat revascularization were used to design scenarios describing hypothetical treatments that were labeled as PCI or CABG. PCI was always presented as the option with lower perioperative death risk and a higher necessity to repeat procedure. A conditional logit model was used to analyze patients' choices using R software. A p value < 0.05 was considered statistically significant., Results: A total of 144 patients participated, most of them (73.7%) preferred CABG over PCI (p < 0.001). The regression coefficients were statistically significant for PCI label, PCI long-term death, CABG perioperative death, CABG long-term death and repeat CABG. The PCI label was the most important parameter (p < 0.05)., Conclusion: Most patients who face the necessity to repeat coronary revascularization reject a new PCI, considering realistic levels of risks and benefits. Incorporating patients' preferences into benefit-risk calculation and treatment recommendations could enhance patient-centered care.

Bovine papillomavirus (BPV) can cause damage to the epithelial and mucosal tissue and currently presents 28 known types. Not all BPV types are associated with the development of cancer in cattle. Studies have shown that variants of human papillomavirus types can present different pathogenic profiles. However, despite the similarity, it is not yet known whether variants of BPV types can also present varying degrees of pathogenicity. Thus, the aim of this study was to evaluate the genetic variability of BPV types and variants isolated in Northeastern Brazil. Samples were obtained from animals with papillomatous lesions. BPV DNA was detected by the amplification of the L1 gene and genotyping was performed by sequencing. Mutations were analyzed in a phylogenetic, structural and functional context. In total, 52 positive samples were obtained and 11 different BPV types were identified in the samples. Ten putative new BPV types were also identified. In addition, several non-synonymous mutations were identified and predicted to alter protein stability, having an impact on immune evasion. The study demonstrated a high genetic diversity of BPV in the region with a large number of mutations identified, serving as a basis for more efficient control measures to be adopted for bovine papillomatosis.

A 28-year-old Caucasian male with Hashimoto's disease and vitiligo presented with two weeks of dizziness on exertion following pharyngitis which was treated with prednisone 40 mg by mouth once a day for five days. Initial workup revealed anemia, elevated lactate dehydrogenase (LDH), and low haptoglobin. He underwent workup for causes of hemolytic anemia which was remarkable for a peripheral blood smear with hypersegmented neutrophils and low vitamin B12 levels concerning for pernicious anemia. Parietal cell and intrinsic factor antibodies were negative, and he then underwent an esophagogastroduodenoscopy with biopsy. The biopsy was negative for Helicobacter pylori , and the immunohistochemical stains were suggestive of chronic atrophic gastritis. He was started on vitamin B12 1,000 mcg intramuscular injections daily. His hemoglobin, LDH, and haptoglobin normalized. Given the absence of the parietal cell antibody and intrinsic factor antibody, this is a rare case of seronegative pernicious anemia., Competing Interests: The authors declare that they have no conflicts of interest to declare., (Copyright © 2020 G. F. Cittolin-Santos et al.)

Passion fruit green spot and passion fruit sudden death are two reportedly distinct viral diseases that recurrently affect passion fruit ( Passiflora spp.) groves in Brazil. Here we used a systematic approach that interconnects symptoms, transmission electron microscopy, RT-PCR detection assays followed by Sanger sequencing, and high-throughput sequencing of the RNA of affected passion fruit plants to gain insights about these diseases. Our data confirmed not only the involvement of cileviruses in these two pathologies, as previously suggested, but also that these viruses belong to the same tentative species: passion fruit green spot virus (PfGSV). Results revealed that PfGSV has a positive-sense RNA genome split into two molecules of approximately 9 kb (RNA1) and 5 kb (RNA2), which share about 50-70% nucleotide sequence identity with other viruses in the genus Cilevirus . Genome sequences of five PfGSV isolates suggest that they have more conserved RNA1 (<5% of nucleotide sequence variability) compared to RNA2 (up to 7% of variability) molecules. The highest nucleotide sequence divergence among PfGSV isolates and other cileviruses is in the genomic segment covering from the 5'-end of the RNA2 until the 5'-end of the open reading frame (ORF) p61 , which includes the ORF p15 and the intergenic region. This genomic stretch also harbors a novel orphan ORF encoding a 13 kDa protein presenting a cysteine-rich domain. High variability of 5'-end of the RNA2 in cileviruses is discussed in an evolutionary context assuming that they share putative common ancestors with unclassified arthropod-infecting single-strand positive RNA viruses, including mosquito-specific viruses of the group Negevirus (clades Nelorpivirus and Sandwavirus), and other viruses in the family Kitaviridae., (Copyright © 2020 Ramos-González, Santos, Chabi-Jesus, Harakava, Kitajima and Freitas-Astúa.)

Quaternary or spirocyclic 3-substituted-3-hydroxy-2-oxindole is considered a privileged scaffold. In other words, it is a molecular core present on several compounds with a wide spectrum of biological activities. Among its precursors, activated ketones (isatin nucleus) can be used as interesting starting points to Morita-Baylis-Hillman adducts derivatives, a class of compounds with good cytotoxic potential. In this paper, we present the synthesis, anti-proliferative activity against lung cancer cell line and a theoretical conformational study of 21 of Morita-Baylis-Hillman adducts from isatin derivatives, by DFT quantum chemical calculations, followed by a SAR and QSAR analysis. Besides, an efficient synthetic protocol and good biological activity profile were highlighted interesting observations about 1 H NMR experimental spectra, molecular modeling results and crystallographic data available.

Acute liver failure (ALF) implies a severe and rapid liver dysfunction that leads to impaired liver metabolism and hepatic encephalopathy (HE). Recent studies have suggested that several brain alterations such as astrocytic dysfunction and energy metabolism impairment may synergistically interact, playing a role in the development of HE. The purpose of the present study is to investigate early alterations in redox status, energy metabolism and astrocytic reactivity of rats submitted to ALF. Adult male Wistar rats were submitted either to subtotal hepatectomy (92% of liver mass) or sham operation to induce ALF. Twenty-four hours after the surgery, animals with ALF presented higher plasmatic levels of ammonia, lactate, ALT and AST and lower levels of glucose than the animals in the sham group. Animals with ALF presented several astrocytic morphological alterations indicating astrocytic reactivity. The ALF group also presented higher mitochondrial oxygen consumption, higher enzymatic activity and higher ATP levels in the brain (frontoparietal cortex). Moreover, ALF induced an increase in glutamate oxidation concomitant with a decrease in glucose and lactate oxidation. The increase in brain energy metabolism caused by astrocytic reactivity resulted in augmented levels of reactive oxygen species (ROS) and Poly [ADP-ribose] polymerase 1 (PARP1) and a decreased activity of the enzymes superoxide dismutase and glutathione peroxidase (GSH-Px). These findings suggest that in the early stages of ALF the brain presents a hypermetabolic state, oxidative stress and astrocytic reactivity, which could be in part sustained by an increase in mitochondrial oxidation of glutamate., (Copyright © 2020 Guazzeli, Cittolin-Santos, Meira-Martins, Grings, Nonose, Lazzarotto, Nogara, da Silva, Fontella, Wajner, Leipnitz, Souza and de Assis.)

We report a clinical case of a 39-year old male, without any known previous medical condition but with occupational exposure to paints and dust cement, who presented an autoimmune pulmonary alveolar proteinosis (PAP) triggered by exposure to toxic inhalation at his workplace. PAP is a rare lung disease characterized by intra-alveolar abnormal accumulation of surfactant. The presence of a crazy-paving pattern in high-resolution computed tomography scan brings the suspicion of PAP although histopathology results of bronchoalveolar lavage are always required for its final diagnosis. The autoimmune form of PAP due to toxic inhalation, such as the one here described, is rare and it is usually difficult to establish a causal relationship., Competing Interests: None, (© 2020 The Authors.)

Obesity has a positive relation to non-alcoholic fatty liver disease (NAFLD) and studies have demonstrated that strength training can regulate lipid accumulation in the hepatocytes of obese rats., Aims: Our aim is to evaluate the effects of high fat diet and strength training on markers of oxidation and lipogenesis in the liver of Wistar rats., Main Methods: Forty Wistar rats were divided into four groups (n = 10): control (CTL), strength training (TR), high fat diet consumption (HF) and high fat diet consumption with strength training (HFT). Animals were subjected to physical strength training and high fat diet consumption for 12 weeks, 3 session per week. Then, the animals were euthanized, and liver markers were evaluated via immunolabeling., Key Findings: Our results indicated that strength training reduced the expression of adiposity as well as the accumulation of glycogen and lipids in the liver. This reduction of fatty acid (FA) stored in hepatocytes is related to reduction of proteins linked to β-oxidation such as Fas/CD95, LIMP-II and CD36, as well as other proteins linked to lipogeneses such as SREBP-1., Significance: Finally, we observed that high fat diet can alter lipogenesis and reduce β-oxidation promoted hepatic fat accumulation. In conclusion, there was a reduction of obesity-related hepatic lipogenesis after 12 weeks of strength training., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Glucocorticoids (GC) increase food intake and body weight in humans and rodents and chronic stress and GC treatment-induced enhancement of the plasma concentration of GC lead to obesity and metabolic changes. In response to hypercaloric treatment, males were shown to be more susceptible to obesity than females, demonstrating that sex differences may affect energy homeostasis. The objective of the current study was to evaluate the effects of prolonged (28 days) treatment with dexamethasone or corticosterone on food intake and body weight gain in intact rats, both male and female. Also examined were Lee index, weights and area of adipocytes of retroperitoneal and perigonadal+perirenal adipose tissues, glucose tolerance test (GTT) and plasma concentrations of free fatty acids, cholesterol and triglycerides. Treatment with dexamethasone was able to increase body weight, food intake, area of adipocytes and weight of retroperitoneal adipose tissue in males. Prolonged treatment with corticosterone also stimulated body weight gain and food intake in males. In addition, it induced an increase in the area of adipocytes and weight of perirenal+perigonadal adipose tissue and higher glycemia after GTT in these animals, without changes on Lee index and plasma parameters after both GC treatments. No parameter was changed by dexamethasone or corticosterone treatment in female rats. Thus, it can be concluded that male rats are more susceptible to the anabolic effects of glucocorticoids than female rats, and these responses can be due to the protective effects of circulating estrogens in females, and/or the difference between males and females in the expression/activity of corticosteroids receptors., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Hepatic encephalopathy (HE) represents a brain dysfunction caused by both acute and chronic liver failures, and its severity deeply affects the prognosis of patients with impaired liver function. In its pathophysiology, ammonia levels and glutamatergic system hyperactivity seem to play a pivotal role in the disruption of brain homeostasis. Here, we investigate important outcomes involved in behavioral performance, electroencephalographic patterns, and neurochemical parameters to better characterize the well-accepted animal model of acute liver failure (ALF) induced by subtotal hepatectomy (92% removal of tissue) that produces ALF. This study was divided into three cohorts: (1) rats clinically monitored after hepatectomy every 6 h for 96 h or until death; (2) rats tested in an open-field task (OFT) before and after surgery and had blood, cerebrospinal fluid, and brain tissue collected after the last OFT; and (3) rats that had continuous EEGs recorded before and after surgery for 3 days. The hepatectomized rats presented significant motor behavioral changes accompanied by important abnormalities in classical blood laboratory parameters of ALF, and EEG features suggestive of HE and deep disturbances in the brain glutamatergic system. Using an animal model of ALF induced via subtotal hepatectomy, this work provides a comprehensive and reliable experimental model that increases the opportunity for studying the effects of new treatment strategies to be explored in an unprecedented way. It also presents insights into the pathophysiology of HE in a reproducible model of ALF, which correlates important neurochemical and EEG aspects of the syndrome., (Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.)