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Dehydration, characterized by the loss of total body water and/or electrolytes due to diseases or inadequate fluid intake, is prevalent globally but often underestimated. Its contribution to long-term chronic diseases and sarcopenia is recognized, yet the mechanisms involved in systemic and muscle protein metabolism during dehydration remain unclear. This study investigated metabolic adaptations in a 36-hour water deprivation (WD) model of mice. Male C57BL/6 mice underwent 36-h WD or pair-feeding at rest, with assessments of motor skills along with biochemical, and metabolic parameters. Dehydration was confirmed by hypernatremia, body mass loss, hyporexia, and increased activity of vasopressinergic and oxytocinergic neurons compared to controls. These results were associated with liver mass loss, decreased glycaemia, and increased cholesterolemia. Additionally, increased VO 2 and a decreased respiratory exchange ratio indicated reduced carbohydrate consumption and potentially increased protein use during dehydration. Thus, skeletal muscle protein metabolism was evaluated due to its high protein content. In the oxidative muscles of the WD group, total and proteasomal proteolysis increased, which was associated with decreased Akt-mediated intracellular signaling. Interestingly, there was an increase in fiber cross-sectional area, likely due to higher muscle water content caused by increased intracellular osmolality induced by protein catabolism products. Conversely, no changes were observed in protein turnover or water content in glycolytic muscles. These findings suggest that short-term WD imposes a pro-catabolic state, depleting protein content in skeletal muscle. However, skeletal muscle may respond differently to dehydration based on its phenotype and might adapt for a limited time.

Application of polyethylene glycol (PEG) to a peripheral nerve injury at the time of primary neurorrhaphy is thought to prevent Wallerian degeneration via direct axolemma fusion. The molecular mechanisms of nerve fusion and recovery are unclear. Our study tested the hypothesis that PEG alters gene expression in neural and muscular environments as part of its restorative properties. Lewis rats underwent unilateral sciatic nerve transection with immediate primary repair. Subjects were randomly assigned to receive either PEG treatment or standard repair at the time of neurorrhaphy. Samples of sciatic nerve distal to the injury and tibialis muscle at the site of innervation were harvested at 24 hours and 4 weeks postoperatively. Total RNA sequencing and subsequent bioinformatics analyses were used to identify significant differences in differentially expressed genes (DEGs) and their related biological pathways (p<0.05) in PEG-treated subjects compared to non-PEG controls. No significant DEGs were identified in PEG-treated sciatic nerve compared to controls after 24 hours, but 1,480 DEGs were identified in PEG-treated tibialis compared to controls. At 4 weeks, 918 DEGs were identified in PEG-treated sciatic nerve, whereas only 3 DEGs remained in PEG-treated tibialis compared to controls. DEGs in sciatic were mostly upregulated (79%) and enriched in pathways present during nervous system development and growth, whereas DEGs in muscle were mostly downregulated (77%) and related to inflammation and tissue repair. Our findings indicate that PEG application during primary neurorrhaphy leads to significant differential gene regulation in the neural and muscular environment that is associated with improved functional recovery in animals treated with PEG compared to sham non-PEG controls. A detailed understanding of key molecules underlying PEG function in recovery after peripheral nerve repair may facilitate amplification of PEG effects through systemic or focal treatments at the time of neurotmesis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Weiss 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.)

Purpose: We aim to evaluate the impact of surgical wound complications in the first 30 postoperative days after incisional hernia repair on the long-term quality of life of patients. In addition, the impact of the surgical technique and preoperative comorbidities on the quality of life of patients will also be evaluated., Method: Prospective cohort study, which evaluates 115 patients who underwent incisional hernioplasty between 2019 and 2020, using the onlay and retromuscular techniques. These patients were initially assessed with regard to surgical wound outcomes in the first 30 postoperative days (surgical site infection (SSI) or surgical site occurrence (SSO)), and then, assessed after three years, through a specific quality of life questionnaire, the Hernia Related Quality of Life Survey (HerQLes)., Results: After some patients were lost to follow-up during the study period, due to death, difficulty in contact, refusal to respond to the questionnaire, eighty patients were evaluated. Of these, 11 patients (13.8%) had SSI in the first 30 postoperative days and 37 (46.3%) had some type of SSO. The impact of both SSI and SSO on quality of life indices was not identified. When analyzing others variables, we observed that the Body Mass Index (BMI) had a significant impact on the patients' quality of life. Likewise, hernia size and mesh size were identified as variables related to a worse quality of life outcome. No difference was observed regarding the surgical techniques used., Conclusion: In the present study, no relationship was identified between surgical wound outcomes (SSO and SSI) and worse quality of life results using the HerQLes score. We observed that both BMI and the size of meshes and hernias showed an inversely proportional relationship with quality of life indices. However, more studies evaluating preoperative quality of life indices and comparing them with postoperative indices should be carried out to evaluate these correlations., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fibromyalgia (FM) is characterized by chronic widespread musculoskeletal pain accompanied by fatigue and muscle atrophy. Although its etiology is not known, studies have shown that FM patients exhibit altered function of the sympathetic nervous system (SNS), which regulates nociception and muscle plasticity. Nevertheless, the precise SNS-mediated mechanisms governing hyperalgesia and skeletal muscle atrophy in FM remain unclear. Thus, we employed two distinct FM-like pain models, involving intramuscular injections of acidic saline (pH 4.0) or carrageenan in prepubertal female rats, and evaluated the catecholamine content, adrenergic signaling and overall muscle proteolysis. Subsequently, we assessed the contribution of the SNS to the development of hyperalgesia and muscle atrophy in acidic saline-injected rats treated with clenbuterol (a selective β2-adrenergic receptor agonist) and in animals maintained under baseline conditions and subjected to epinephrine depletion through adrenodemedullation (ADM). Seven days after inducing an FM-like model with acidic saline or carrageenan, we observed widespread mechanical hyperalgesia along with loss of strength and/or muscle mass. These changes were associated with reduced catecholamine content, suggesting a common underlying mechanism. Notably, treatment with a β2-agonist alleviated hyperalgesia and prevented muscle atrophy in acidic saline-induced FM-like pain, while epinephrine depletion induced mechanical hyperalgesia and increased muscle proteolysis in animals under baseline conditions. Together, the results suggest that reduced sympathetic activity is involved in the development of pain and muscle atrophy in the murine model of FM analyzed., Competing Interests: Declaration of competing interest The 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 Elsevier Inc. All rights reserved.)

Carbohydrate (CHO) supplementation during endurance exercise can improve performance. However, it is unclear whether low glycemic index (GI) CHO leads to differential ergogenic and metabolic effects compared with a standard high GI CHO. This study investigated the ergogenic and metabolic effects of CHO supplementation with distinct GIs, namely, (a) trehalose (30 g/hr), (b) isomaltulose (30 g/hr), (c) maltodextrin (60 g/hr), and (d) placebo (water). In this double-blind, crossover, counterbalanced, placebo-controlled study, 13 male cyclists cycled a total of 100 min at varied exercise intensity (i.e., 10-min stages at 1.5, 2.0, and 2.5 W/kg; repeated three times plus two 5-min stages at 1.0 W/kg before and after the protocol), followed by a 20-min time trial on four separated occasions. Blood glucose and lactate (every 20 min), heart rate, and ratings of perceived exertion were collected throughout, and muscle biopsies were taken before and immediately after exercise. The results showed that trehalose improved time-trial performance compared with placebo (total work done 302 ± 39 vs. 287 ± 48 kJ; p = .01), with no other differences between sessions (all p ≥ .07). Throughout the 100-min protocol, blood glucose was higher with maltodextrin compared with the other supplements at all time points (all p < .05). Heart rate, ratings of perceived exertion, muscle glycogen content, blood glucose, and lactate were not different between conditions when considering the 20-min time trial (all p > .05). Trehalose supplementation throughout endurance exercise improved cycling performance and appears to be an appropriate CHO source for exercise tasks up to 2 hr. No ergogenic superiority between the different types of CHO was established.

Although it is well established that fibromyalgia (FM) syndrome is characterized by chronic diffuse musculoskeletal hyperalgesia, very little is known about the effect of this pathology on muscle tissue plasticity. Therefore, the present study aimed to characterize the putative alterations in skeletal muscle mass in female rats subjected to a FM model by inducing chronic diffuse hyperalgesia (CDH) through double injections of acidic saline (pH 4.0) into the left gastrocnemius muscle at 5-day intervals. To determine protein turnover, the total proteolysis, proteolytic system activities and protein synthesis were evaluated in oxidative soleus muscles of pH 7.2 (control) and pH 4.0 groups at 7 days after CDH induction. All animals underwent behavioural analyses of mechanical hyperalgesia, strength and motor performance. Our results demonstrated that, in addition to hyperalgesia, rats injected with acidic saline exhibited skeletal muscle loss, as evidenced by a decrease in the soleus fibre cross-sectional area. This muscle loss was associated with increased proteasomal proteolysis and expression of the atrophy-related gene (muscle RING-finger protein-1), as well as reduced protein synthesis and decreased protein kinase B/S6 pathway activity. Although the plasma corticosterone concentration did not differ between the control and pH 4.0 groups, the removal of the adrenal glands attenuated hyperalgesia, but it did not prevent the increase in muscle protein loss in acidic saline-injected animals. The data suggests that the stress-related hypothalamic-pituitary-adrenal axis is involved in the development of hyperalgesia, but is not responsible for muscle atrophy observed in the FM model induced by intramuscular administration of acidic saline. Although the mechanisms involved in the attenuation of hyperalgesia in rats injected with acidic saline and subjected to adrenalectomy still need to be elucidated, the results found in this study suggest that glucocorticoids may not represent an effective therapeutic approach to alleviate FM symptoms., (© 2024 John Wiley & Sons Australia, Ltd.)

Selenium-containing compounds have emerged as promising treatment for redox-based and inflammatory diseases. This study aimed to investigate the in vitro and in vivo anti-inflammatory activity of a novel diselenide named as dibenzyl[diselanediyIbis(propane-3-1diyl)] dicarbamate (DD). DD reacted with HOCl ( k  = 9.2 x 10 7 M -1 s -1 ), like glutathione ( k  = 1.2 x 10 8 M -1 s -1 ), yielding seleninic and selenonic acid derivatives, and it also decreased HOCl formation by activated human neutrophils (IC 50 =4.6 μM) and purified myeloperoxidase (MPO) (IC 50 =3.8 μM). However, tyrosine, MPO-I and MPO-II substrates, did not restore HOCl formation in presence of DD. DD inhibited the oxidative burst in d HL-60 cells with no toxicity up to 25 µM for 48h. Next, an intraperitoneal administration of 25, 50, and 75 mg/kg DD decreased total leukocyte, neutrophil chemotaxis, and inflammation markers (MPO activity, lipid peroxidation, albumin exudation, nitrite, TNF-α, IL-1β, CXCL1/KC, and CXCL2/MIP-2) on a murine model of carrageenan-induced peritonitis. Likewise, 50 mg/kg DD (i.p.) decreased carrageenan-induced paw edema over 5h. Histological and immunohistochemistry analyses of the paw tissue showed decreased neutrophil count, edema area, and MPO, carbonylated, and nitrated protein staining. Furthermore, DD treatment decreased the fMLP-induced chemotaxis of human neutrophils (IC 50 =3.7 μM) in vitro with no toxicity. Lastly, DD presented no toxicity in a single-dose model using mice (50 mg/kg, i.p.) over 15 days and in Artemia salina bioassay (50 to 2000 µM), corroborating findings from in silico toxicological study. Altogether, these results demonstrate that DD attenuates carrageenan-induced inflammation mainly by reducing neutrophil migration and the resulting damage from MPO-mediated oxidative burst.

We evaluated whether anserine, a methylated analog of the dipeptide carnosine, is present in the cardiac and skeletal muscles of humans and whether the CARNMT1 gene, which encodes the anserine synthesizing enzyme carnosine-N-methyltransferase, is expressed in human skeletal muscle. We found that anserine is present at low concentrations (low micromolar range) in both cardiac and skeletal muscles, and that anserine content in skeletal muscle is ~15 times higher than in cardiac muscle (cardiac muscle: 10.1 ± 13.4 μmol·kg -1 of dry muscle, n = 12; skeletal muscle: 158.1 ± 68.5 μmol·kg -1 of dry muscle, n = 11, p < 0.0001). Anserine content in the heart was highly variable between individuals, ranging from 1.4 to 45.4 μmol·kg -1 of dry muscle, but anserine content was not associated with sex, age, or body mass. We also showed that CARNMT1 gene is poorly expressed in skeletal muscle (n = 10). This is the first study to demonstrate that anserine is present in the ventricle of the human heart. The presence of anserine in human heart and the confirmation of its expression in human skeletal muscle open new avenues of investigation on the specific and differential physiological functions of histidine dipeptides in striated muscles., (© 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Viral respiratory tract infections are a significant public health concern, particularly in children. RSV is a prominent cause of lower respiratory tract infections among infants, whereas SARS-CoV-2 has caused a global pandemic with lower overall severity in children than in adults. In this review, we aimed to compare the innate and adaptive immune responses induced by RSV and SARS-CoV-2 to better understand differences in the pathogenesis of infection. Some studies have demonstrated that children present a more robust immune response against SARS-CoV-2 than adults; however, this response is dissimilar to that of RSV. Each virus has a distinctive mechanism to escape the immune response. Understanding the mechanisms underlying these differences is crucial for developing effective treatments and improving the management of pediatric respiratory infections.

Aim: To investigate the association between physical activity and immunogenicity among SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases prior to and following a 2-dose schedule of CoronaVac (Sinovac inactivated vaccine)., Methods: This was a prospective cohort study within an open-label, single-arm, phase 4 vaccination trial conducted in Sao Paulo, Brazil. In this substudy, only SARS-CoV-2 seropositive patients were included. Immunogenicity was assessed by seroconversion rates of total anti-SARS-CoV-2 S1/S2 immunoglobulin G (IgG), geometric mean titers of anti-S1/S2 IgG, frequency of positive neutralizing antibodies, and neutralizing activity before and after vaccination. Physical activity was assessed through a questionnaire. Model-based analyses were performed controlling for age (<60 or ≥60 y), sex, body mass index (<25, 25-30, and >30 kg/m2), and use of prednisone, immunosuppressants, and biologics., Results: A total of 180 seropositive autoimmune rheumatic disease patients were included. There was no association between physical activity and immunogenicity before and after vaccination., Conclusions: This study suggests that the positive association between physical activity and greater antibody responses seen in immunocompromised individuals following vaccination is overridden by previous SARS-CoV-2 infection, and does not extend to natural immunity.

Background: Physical activity associates with improved immunogenicity following a 2-dose schedule of CoronaVac (Sinovac's inactivated SARS-CoV-2 vaccine) in patients with autoimmune rheumatic diseases (ARD). This study evaluates whether physical activity impacts vaccine-induced antibody responses to a booster dose in this population., Methods: This was a phase-4 trial conducted in São Paulo, Brazil. Patients with ARD underwent a 3-dose schedule of CoronaVac. One month after the booster, we assessed seroconversion rates of anti-SARS-CoV-2 S1/S2 IgG, geometric mean titers of anti-S1/S2 IgG, frequency of positive neutralizing antibodies, and neutralizing activity. Physical activity was assessed through questionnaire., Results: Physically active (n = 362) and inactive (n = 278) patients were comparable for most characteristics; however, physically active patients were younger (P < .01) and had a lower frequency of chronic inflammatory arthritis (P < .01). Adjusted models showed that physically active patients had ∼2 times odds of seroconversion rates (OR: 2.09; 95% confidence interval, 1.22 to 3.61), ∼22% greater geometric mean titers of anti-S1/S2 IgG (22.09%; 95% confidence interval, 3.91 to 65.60), and ∼7% greater neutralizing activity (6.76%; 95% confidence interval, 2.80 to 10.72) than inactive patients., Conclusions: Patients with ARD who are physically active have greater odds of experiencing better immunogenicity to a booster dose of CoronaVac. These results support the recommendation of physical activity to improve vaccination responses, particularly for immunocompromised individuals.

Total absence of adipose tissue (lipoatrophy) is associated with the development of severe metabolic disorders including hepatomegaly and fatty liver. Here, we sought to investigate the impact of severe lipoatrophy induced by deletion of peroxisome proliferator-activated receptor gamma (PPARγ) exclusively in adipocytes on lipid metabolism in mice. Untargeted lipidomics of plasma, gastrocnemius and liver uncovered a systemic depletion of the essential linoleic (LA) and α-linolenic (ALA) fatty acids from several lipid classes (storage lipids, glycerophospholipids, free fatty acids) in lipoatrophic mice. Our data revealed that such essential fatty acid depletion was linked to increased: 1) capacity for liver mitochondrial fatty acid β-oxidation (FAO), 2) citrate synthase activity and coenzyme Q content in the liver, 3) whole-body oxygen consumption and reduced respiratory exchange rate in the dark period, and 4) de novo lipogenesis and carbon flux in the TCA cycle. The key role of de novo lipogenesis in hepatic steatosis was evidenced by an accumulation of stearic, oleic, sapienic and mead acids in liver. Our results thus indicate that the simultaneous activation of the antagonic processes FAO and de novo lipogenesis in liver may create a futile metabolic cycle leading to a preferential depletion of LA and ALA. Noteworthy, this previously unrecognized cycle may also explain the increased energy expenditure displayed by lipoatrophic mice, adding a new piece to the metabolic regulation puzzle in lipoatrophies., 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 © 2022 Elsevier B.V. All rights reserved.)

Predicting sugarcane yield by quality allows stakeholders from research centers to industries to decide on the precise time and place to harvest a product on the field; hence, it can streamline workflow while leveling up the cost-effectiveness of full-scale production. °Brix and Purity can offer significant and reliable indicators of high-quality raw material for industrial processing for food and fuel. However, their analysis in a relevant laboratory can be costly, time-consuming, and not scalable. We, therefore, analyzed whether merging multispectral images and machine learning (ML) algorithms can develop a non-invasive, predictive framework to map canopy reflectance to °Brix and Purity. We acquired multispectral images data of a sugarcane-producing area via unmanned aerial vehicle (UAV) while determining °Brix and analytical Purity from juice in a routine laboratory. We then tested a suite of ML algorithms, namely multiple linear regression (MLR), random forest (RF), decision tree (DT), and support vector machine (SVM) for adequacy and complexity in predicting °Brix and Purity upon single spectral bands, vegetation indices (VIs), and growing degree days (GDD). We obtained evidence for biophysical functions accurately predicting °Brix and Purity. Those can bring at least 80% of adequacy to the modeling. Therefore, our study represents progress in assessing and monitoring sugarcane on an industrial scale. Our insights can offer stakeholders possibilities to develop prescriptive harvesting and resource-effective, high-performance manufacturing lines for by-products., Competing Interests: The 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 Barbosa Júnior, Moreira, de Oliveira, Shiratsuchi and da Silva.)

Thoracic insufficiency syndromes are a genetically and phenotypically heterogeneous group of disorders characterized by congenital abnormalities or progressive deformation of the chest wall and/or vertebrae that result in restrictive lung disease and compromised respiratory capacity. We performed whole exome sequencing on a cohort of 42 children with thoracic insufficiency to elucidate the underlying molecular etiologies of syndromic and non-syndromic thoracic insufficiency and predict extra-skeletal manifestations and disease progression. Molecular diagnosis was established in 24/42 probands (57%), with 18/24 (75%) probands having definitive diagnoses as defined by laboratory and clinical criteria and 6/24 (25%) probands having strong candidate genes. Gene identified in cohort patients most commonly encoded components of the primary cilium, connective tissue, and extracellular matrix. A novel association between KIF7 and USP9X variants and thoracic insufficiency was identified. We report and expand the genetic and phenotypic spectrum of a cohort of children with thoracic insufficiency, reinforce the prevalence of extra-skeletal manifestations in thoracic insufficiency syndromes, and expand the phenotype of KIF7 and USP9X-related disease to include thoracic insufficiency., (© 2023. The Author(s).)

Aims: This work investigated the effects of creatine supplementation on different pathways related to the pathogenesis of non-alcoholic fatty liver disease and alcoholic liver disease., Main Methods: To induce alcoholic liver disease, male Swiss mice were divided into three groups: control, ethanol and ethanol supplemented with creatine. To induce non-alcoholic fatty liver disease, mice were divided into three groups: control, high-fat diet and high-fat diet supplemented with creatine. Each group consisted of eight animals. In both cases, creatine monohydrate was added to the diets (1 %; weight/vol)., Key Findings: Creatine supplementation prevented high-fat diet-induced non-alcoholic fatty liver disease progression, demonstrated by attenuated liver fat accumulation and liver damage. On the other hand, when combined with ethanol, creatine supplementation up-regulated key genes related to ethanol metabolism, oxidative stress, inflammation and lipid synthesis, and exacerbated ethanol-induced liver steatosis and damage, demonstrated by increased liver fat accumulation and histopathological score, as well as elevated oxidative damage markers and inflammatory mediators., Significance: Our results clearly demonstrated creatine supplementation exerts different outcomes in relation to non-alcoholic fatty liver disease and alcoholic liver disease, namely it protects against high-fat diet-induced non-alcoholic fatty liver disease but exacerbates ethanol-induced alcoholic liver disease. The exacerbating effects of the creatine and ethanol combination appear to be related to oxidative stress and inflammation-mediated up-regulation of ethanol metabolism., Competing Interests: Declaration of competing interest None of the authors have a potential conflict of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Biosensors are small devices known for their selectivity, high specificity and sensitivity to the respective analyte, at low concentrations. We developed an electrochemical biosensor using the crystalline polymer MOF-[Cu 3 (BTC) 2 (H 2 O) 2 ] n to characterize Cratylia mollis seed lectin (Cramoll) and its interaction with free carbohydrate (glucose) and carbohydrates on the surface of rabbit erythrocytes. The electrochemical potentials presented by the exponential curves that vary from 96 to 142 mV in relation to concentrations of 10 to 20 mM of glucose are decisive for the use of the system containing gold electrode/MOF/Cramoll for the characterization of biological models due to its high sensitivity. As well as the kinetic behavior presented in the cyclic voltammograms, with a cathodic current response of 0.000 3 A for a glucose concentration of 15 mM. These results were due to the high specificity of Cramoll under these conditions, promoting stability of surface charges at the Cramoll/electrode interface. This phenomenon facilitates the monitoring of the interaction with free glucose present in the electrolyte medium by potentiometric and amperometric methods and with carbohydrates present on the surface of rabbit erythrocytes through the potentiometric method. Through scanning electron microscopy (SEM) it was possible to observe Cramoll immobilized on the MOF surface, proving the specificity of the ligand (glucose-lectin) through the morphological lectin changes in this process. This electrochemical model, Cramoll/MOF biosensor, is effective for evaluating free lectin/carbohydrate or in the erythrocyte membrane., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

This prospective cohort study within an open-label, single-arm, phase 4 vaccination trial (clinicaltrials.gov #NCT04754698) aimed to investigate the association between physical activity and persistent anti-SARS-CoV-2 antibodies 6 months after two-dose schedule of CoronaVac in autoimmune rheumatic diseases (ARD) patients (n = 748). Persistent immunogenicity 6 months after the full-course vaccination was assessed using seroconversion rates of total anti-SARS-CoV-2 S1/S2 IgG, geometric mean titers of anti-S1/S2 IgG (GMT), and frequency of positive neutralizing antibodies (NAb). Physical activity was assessed trough questionnaire. Adjusted point estimates from logistic regression models indicated that physically active patients had greater odds of seroconversion rates (OR: 1.5 [95%CI: 1.1 to 2.1]) and NAb positivity (OR: 1.5 [95%CI: 1.0 to 2.1]), and approximately 43% greater GMT (42.8% [95%CI: 11.9 to 82.2]) than inactive ones. In conclusion, among immunocompromised patients, being physically active was associated with an increment in antibody persistence through 6 months after a full-course of an inactivated SARS-CoV-2 vaccine., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Incineration and landfilling offer possibilities for addressing high-rate management of COVID-waste streams. However, they can be costly and environmentally unsustainable. In addition, they do not allow to convert them to fuels and chemicals as waste-to-energy and waste-to-product technologies. Therefore, we analyzed whether integrating hydrothermal carbonization (HTC) and pelletization can allow converting the surgical face mask (SFM) and biomass to composite plastic-fiber fuel (CPFF). We blended the plastic material and corncob, peanut shell, or sugarcane bagasse at the proportion of 50:50 (%, dry mass basis) for HTC. We performed the thermal pretreatment of blends in an autoclaving reactor at 180 °C and 1.5 MPa. Then we pelletized the hydrochars in a presser machine at 200 MPa and 125 °C. By analyzing the evidence from our study, we recognized the viability of combining the SFM and agricultural residues for CPFF from comparable technical features of our products to standards for premium-grade wood pellets. For instance, the elemental composition of their low-meltable ash was not stoichiometrically sufficient to severely produce slagging and fouling in the equipment for thermal conversion. Although they contained synthetic polymers in their structures, such as polyethylene from filter layers and nylon from the earloop, they emitted CO and NO x below the critical limits of 200 and 500 mg m -3 , respectively, for occupational safety. Therefore, we extended the knowledge on waste-to-energy pathways to transform SFM into high-quality hybrid fuel by carbonization and pelletization. Our framework can provide stakeholders opportunities to address plastic and biogenic waste in the context of a circular economy., Supplementary Information: The online version contains supplementary material available at 10.1007/s13399-022-03285-4., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

This study aimed to integrate GWAS and structural variants to propose possible molecular biomarkers related to gastrointestinal nematode resistance traits in Santa Inês sheep. The phenotypic records FAMACHA, haematocrit, white blood cell count, red blood cell count, haemoglobin, platelets and egg counts per gram of faeces were collected from 700 naturally infected animals, belonging to four Brazilian flocks. A total of 576 animals were genotyped using the Ovine SNP12k BeadChip and were imputed using a reference population with Ovine SNP50 BeadChip. The GWAS approaches were based on SNPs, haplotypes, CNVs and ROH. The overlapping between the significant genomic regions detected from all approaches was investigated, and the results were integrated using a network analysis. Genes related to the immune system were found, such as ABCB1, IL6, WNT5A and IRF5. Genomic regions containing candidate genes and metabolic pathways involved in immune responses, inflammatory processes and immune cells affecting parasite resistance traits were identified. The genomic regions, biological processes and candidate genes uncovered could lead to biomarkers for selecting more resilient sheep and improving herd welfare and productivity. The results obtained are the start point to identify molecular biomarkers related to indicator traits of gastrointestinal nematode resistance in Santa Inês sheep., (© 2022 Wiley-VCH GmbH.)

Objectives/background: The prevalence of obstructive sleep apnea (OSA) in people over 70 years can reach up to 95%. Aerobic or combined exercise programs have been shown to impact positively on OSA severity. Resistance training changes leg fluid retention. We hypothesized that through this mechanism it may have an impact on the OSA severity in older adults., Patients/methods: We evaluated changes in the respiratory event index (REI) of older adults with moderate-severe obstructive sleep apnea in a randomized, masked, controlled, parallel group trial. Participants between the age of 65 and 80 years with REI between 20 and 50 events/hour were assigned randomly to 12 weeks of resistance training or healthy life-style recommendations. Change in REI was the primary outcome. Muscle thickness, maximum strength, and physical function were secondary outcomes and body mass index (BMI) and body water content were assessed as mediators., Results: Twenty-three subjects were included, 57% men, aged 71 ± 5 years, randomized to training (n = 12) and control intervention (n = 11). The baseline REI in the training and control groups were 30 ± 7/h and 29 ± 9/h; at follow-up, the delta REI were -3.6/hour (95% confidence interval -0.7 to -5.4) and 6.7/hour (5.2-8.6), respectively, with significant time × group interaction that remained significant after adjusting the generalized estimating equations model for delta BMI and delta body water content., Conclusions: Twelve weeks of resistance training in older adults significantly changed the respiratory event index and was well tolerated. Changes in body water content were slight but cannot be dismissed as contributing to REI reduction., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Uric acid is considered the main substrate for peroxidases in plasma. The oxidation of uric acid by human peroxidases generates urate free radical and urate hydroperoxide, which might affect endothelial function and explain, at least in part, the harmful effects of uric acid on the vascular system. Peroxidasin (PXDN), the most recent heme-peroxidase described in humans, catalyzes the formation of hypobromous acid, which mediates collagen IV crosslinks in the extracellular matrix. This enzyme has gained increasing scientific interest since it is associated with cardiovascular disease, cancer, and renal fibrosis. The main objective here was to investigate whether uric acid would react with PXDN and compromise the function of the enzyme in human endothelial cells. Urate decreased Amplex Red oxidation and brominating activity in the extracellular matrix (ECM) from HEK293/PXDN overexpressing cells and in the secretome of HUVECs. Parallelly, urate was oxidized to 5-hydroxyisourate. It also decreased collagen IV crosslink in isolated ECM from PFHR9 cells. Urate, the PXDN inhibitor phloroglucinol, and the PXDN knockdown impaired migration and adhesion of HUVECs. These results demonstrated that uric acid can affect extracellular matrix formation by competing for PXDN. The oxidation of uric acid by PXDN is likely a relevant mechanism in the endothelial dysfunction related to this metabolite.

Purpose: To improve outcomes for subretinal implantation surgery in pigs., Methods: Analysis of variables affecting the success of subretinal implantation surgery was performed on videos of 37 surgeries. Ex vivo experiments were conducted to measure intraocular pressure (IOP) and test various prototyped implanters for effectiveness at maintaining IOP., Results: A video analysis revealed a prolonged sclerotomy open time owing to a combination of uncontrolled bleeding and excessive fluid outflow often resulting in retinal prolapse. Precauterization of the choroid before full-thickness sclerotomy (n = 10) resulted in a reduced incidence of uncontrolled bleeding from 39.1% (9/23) versus 0% (0/10) (P = 0.005) and improved implantation success from 73% to 90%. An ex vivo analysis of the IOP revealed a mean decrease in the IOP from 30.2 ± 3.0 mm Hg to 5.0 ± 2.1 mm Hg after a fully penetrating sclerotomy. To address this situation, we produced a series of plugs that integrated with a custom implant insertion device to seal the sclerotomy during implantation. The use of the plugs was cumbersome, however, and so we opted instead to increase the width of the inserter tip to fill the open sclerotomy. This improved device restored and maintained IOP during implantation (27.1 ± 1.9 mm Hg). Combined with precauterization the improved inserter resulted in 100% successful implantation (n = 4)., Conclusions: For subretinal implantation in pigs, a modified procedure to precauterize the choroid before sclerotomy combined with an instrument that better fills the scleral opening decreases bleeding, hypotony, and open sclerotomy time, improving the success rate., Translational Relevance: Better management of IOP and bleeding from a sclerotomy will improve implant-based therapies.

This randomized controlled study aimed to investigate whether a single bout of exercise before the homologous booster dose of a SARS-CoV-2 inactivated vaccine could enhance immunogenicity in patients with spondyloarthritis. We selected 60 consecutive patients with spondyloarthritis (SpA). Patients assigned to the intervention group performed an exercise bout comprising three exercises. Then, they remained at rest for 1 h before vaccination. The control group remained at rest before vaccination. Immunogenicity was assessed before (Pre) and 1 mo after (Post) the booster using seropositivity rates of total anti-SARS-CoV-2 S1/S2 IgG, geometric mean titers of anti-S1/S2 IgG (GMT), frequency of neutralizing antibodies (NAb) positivity, and NAb activity. At Pre, 16 patients from the exercise group and 16 patients from the control group exhibited seropositivity for IgG (59% vs. 57.1%), and 1 mo after the booster dose, seropositivity occurred in 96% versus 100% of the cases. Only 10 patients from the exercise group and 12 patients from the control group showed positive NAb serology at Pre (37% vs. 42.8%). One month following the booster, NAb positivity was 96% versus 93%. GMT was comparable between groups at Pre. At Post, GMT increased similarly in both groups. Likewise, NAb activity was similar between groups at Pre and increased similarly in both of them as a result of the booster (47.5% vs. 39.9%). In conclusion, a single bout of exercise did not enhance immunogenicity to a homologous booster dose of an inactivated SARS-CoV-2 vaccine among patients with spondyloarthritis. NEW & NOTEWORTHY We tested the role of exercise as an adjuvant to a booster of a COVID-19 vaccine. Immunocompromised patients were immunized after an acute bout of exercise or not. Patients exhibited an excellent immunogenicity in response to the booster dose. Exercise did not add to the vaccine effects on IgG or neutralizing antibodies.

Invasive pulmonary aspergillosis (IPA) caused by the mold Aspergillus fumigatus is one of the most important life-threatening infections in immunocompromised patients. The alarming increase of isolates resistant to the first-line recommended antifungal therapy urges more insights into triazole-resistant A. fumigatus infections. In this study, we systematically optimized a longitudinal multimodal imaging-compatible neutropenic mouse model of IPA. Reproducible rates of pulmonary infection were achieved through immunosuppression (sustained neutropenia) with 150 mg/kg cyclophosphamide at day -4, -1 and 2, and an orotracheal inoculation route in both sexes. Furthermore, increased sensitivity of in vivo bioluminescence imaging for fungal burden detection, as early as the day after infection, was achieved by optimizing luciferin dosing and through engineering isogenic red-shifted bioluminescent A. fumigatus strains, one wild type and two triazole-resistant mutants. We successfully tested appropriate and inappropriate antifungal treatment scenarios in vivo with our optimized multimodal imaging strategy, according to the in vitro susceptibility of our luminescent fungal strains. Therefore, we provide novel essential mouse models with sensitive imaging tools for investigating IPA development and therapy in triazole-susceptible and triazole-resistant scenarios., Competing Interests: Competing interests K.L. has received consultancy fees from Merck Sharp & Dohme (MSD), SMB Laboratories Brussels and Gilead; travel support from Pfizer and MSD; and speaker fees from Gilead, MSD, FUJIFILM WAKO, Pfizer; and a services fee from Thermo Fisher Scientific. The remaining authors declare no conflict of interest., (© 2022. Published by The Company of Biologists Ltd.)

Creatine is an important energy metabolite that is concentrated in tissues such as the muscles and brain. Creatine is reversibly converted to creatine phosphate through a reaction with ATP or ADP, which is catalyzed by the enzyme creatine kinase. Dietary supplementation with relatively large amounts of creatine monohydrate has been proven as an effective sports supplement that can enhances athletic performance during acute high-energy demand physical activity. Some side effects have been reported with creatine monohydrate supplementation, which have stimulated research into new potential molecules that could be used as supplements to potentially provide bioavailable creatine. Recently, a popular supplement, creatyl-l-leucine, has been proposed as a potential dietary ingredient that may potentially provide bioavailable creatine. This study tests whether creatyl-l-leucine is a bioavailable compound and determines whether it can furnish creatine as a dietary supplement. Rats were deprived of dietary creatine for a period of two weeks and then given one of three treatments: a control AIN-93G creatine-free diet, AIN-93G supplemented with creatine monohydrate or AIN-93G with an equimolar amount of creatyl-l-leucine supplement in the diet for one week. When compared to the control and the creatine monohydrate-supplemented diet, creatyl-l-leucine supplementation resulted in no bioaccumulation of either creatyl-l-leucine or creatine in tissue.

While understanding molecular heterogeneity across patients underpins precision oncology, there is increasing appreciation for taking intra-tumor heterogeneity into account. Based on large-scale analysis of cancer omics datasets, we highlight the importance of intra-tumor transcriptomic heterogeneity (ITTH) for predicting clinical outcomes. Leveraging single-cell RNA-seq (scRNA-seq) with a recommender system (CaDRReS-Sc), we show that heterogeneous gene-expression signatures can predict drug response with high accuracy (80%). Using patient-proximal cell lines, we established the validity of CaDRReS-Sc's monotherapy (Pearson r>0.6) and combinatorial predictions targeting clone-specific vulnerabilities (>10% improvement). Applying CaDRReS-Sc to rapidly expanding scRNA-seq compendiums can serve as in silico screen to accelerate drug-repurposing studies. Availability: https://github.com/CSB5/CaDRReS-Sc ., (© 2021. The Author(s).)

The transformation of women's role in society has been systematically studied. Numerous authors point out that among the factors of extreme relevance to this fact, the main is the increased presence of women in the formal job market. Researches also reveal that the increase in quantity is not reflected equally in all productive sectors nor the egalitarian occupation of high hierarchical positions. The present study aimed to analyze how the presence of women, especially in leadership positions, has evolved at the Brazilian Federal Agency for the Support and Evaluation of Postgraduate Education (CAPES) and the National Council for Scientific and Technological Development (CNPq) over the last 20 years. For these analyzes, surveys were conducted in the people management systems of the Brazilian Federal Public Administration. The initial hypothesis was that female attendance had increased in both the total number of female servants and in management and auxiliary positions, known as DAS in Brazil; however, evidence shows that women reduced overall agency presence, especially in the number of female Analysts occupying DAS positions. These results indicate that the misogyny observed in the academic sphere of the Brazilian National Postgraduate and Science, Technology, and Innovation systems are replicated in the politic-bureaucratic sphere that manages and sponsors these systems.

Introduction: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, resulting in a range of clinical manifestations and outcomes. Laboratory and immunological alterations have been considered as potential markers of disease severity and clinical evolution. Type I interferons (IFN-I), mainly represented by IFN-α and β, are a group of cytokines with an important function in antiviral responses and have played a complex role in COVID-19. Some studies have demonstrated that IFN-I levels and interferon response is elevated in mild cases, while other studies have noted this in severe cases. The involvement of IFN-I on the pathogenesis and outcomes of SARS-CoV-2 infection remains unclear. In this study, we summarize the available evidence of the association of plasma protein levels of type I IFN with the severity of COVID-19., Methods: The PRISMA checklist guided the reporting of the data. A systematic search of the MEDLINE (PubMed), EMBASE, and Web of Science databases was performed up to March of 2021, looking for articles that evaluated plasma protein levels of IFN-I in mild, severe, or critical COVID-19 patients. Comparative meta-analyses with random effects were performed to compare the standardized mean differences in plasma protein levels of IFN-I of mild versus severe and mild versus critical patients. Meta-regressions were performed to test the moderating role of age, sex, time that the IFN-I was measured, and limit of detection of the assay used in the difference between the means., Results: There was no significant difference in plasma levels of IFN-α when comparing between mild and severe patients (SMD = -0.236, 95% CI -0.645 to 0.173, p = 0.258, I2 = 82.11), nor when comparing between patients mild and critical (SMD = 0.203, 95% CI -0.363 to 0.770, p = 0.481, I2 = 64.06). However, there was a significant difference between healthy individuals and patients with mild disease (SMD = 0.447, 95% CI 0.085 to 0.810, p = 0.016, I2 = 62.89)., Conclusions: Peripheral IFN-α cannot be used as a severity marker as it does not determine the clinical status presented by COVID-19 patients., Competing Interests: The 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 © 2021 da Silva, Gonçalves, Zanin, Schuch and de Souza.)

Macrophages perform the fundamental function of sensing cellular damage, initiating and mediating immune response and tissue repair. Adenine nucleotides are in relatively high abundance in cells and are released from cells during tissue damage that are converted to adenosine in the extracellular environment. The A 1 , A 2A , A 2B and A 3 adenosine receptors serve to regulate immune function. Despite characterization of the adenosine receptors, a comprehensive examination of adenosine receptor signaling in THP-1 macrophage cells has not been done. Moreover, previous studies employed chemical agonists and antagonists that have the potential for off-target affects. Here we systematically knockdown each of the four known adenosine receptors in THP-1 macrophages using validated siRNA and investigated their function under LPS stimulation. We demonstrate that the A 1 receptor is required for adenosine-stimulated IL-10 and IL-1β secretion indicating an important role of this receptor during resolution of inflammation and tissue repair in these cells. The A 1 and A 3 receptor were required for IL-6 and IL-1β secretion showing a net pro-inflammatory role for these receptors. Finally, we present the novel finding that THP-1 macrophages lacking the A 2B receptor undergo pyroptosis when exposed to LPS, demonstrating a novel role of the A 2B receptor in regulation of programmed cell death during inflammation. This work underscores the fundamental importance of adenosine signaling and provides insight into the independent roles of the adenosine receptors in modulating cytokine signaling., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This systematic review aimed to evaluate the accuracy of customized titanium plates in orthognathic surgery compared to standard outcome in virtual surgical planning. PRISMA and JBI guidelines were followed. Research protocol was registered in PROSPERO. Six databases and two gray literature repositories were used as sources of research articles. Descriptive clinical studies, that performed orthognathic surgery using custom titanium plates, were included. Risk of bias was assessed by "The Joanna-Briggs Institute Critical Appraisal tools for use in Systematic Reviews Checklist for Case Series". Of the 11,916 studies initially identified, seven met the eligibility criteria and were included. The studies were published between 2015 and 2019. Most of the studies (57%) had a low risk of bias, while one had a high risk of bias. Total sample included 74 patients with 63 bimaxillary surgeries and 11 unimaxillary surgeries. All studies showed acceptable accuracy within previously established clinical parameters. Although the eligible articles assessed the accuracy of the orthognathic surgery with respect to virtual planning, the wide variability of evaluation methodologies made it impossible to calculate a combined accuracy measure. It was not possible to perform a meta-analysis, so a pragmatic recommendation on the use of these plates is not possible., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: A spontaneous breathing trial (SBT) is commonly used to determine extubation readiness in patients receiving mechanical ventilation. However, the physiological impact of such a trial in preterm infants has not been well described. This study aimed to investigate the effects of a 3-min SBT on the cardiorespiratory stability of these infants., Methods: A retrospective analysis of prospectively collected data was done for infants < 37 weeks gestational age who were extubated after a successful 3-min SBT. Heart rate, [Formula: see text], breathing frequency, exhaled tidal volume, and Silverman Andersen Respiratory Severity Score (SA-RSS) to assess work of breathing, before and at the end of the SBT, were recorded and compared using nonparametric paired Mann-Whitney tests. A secondary analysis was done between extubation success (ie, 72 h without the need for re-intubation) and failure groups. Differences were considered statistically significant if P < .05., Results: A total of 90 SBTs were performed in 70 premature infants; 65 had a successful SBT, and 5 failed the SBT. Of the 65 infants who had a successful SBT and were extubated, 6 failed extubation (9.2%). Subjects had a median (interquartile range [IQR]) gestational age of 30 (27-33) weeks at birth, a birthweight of 1,240 (860-1,790) g, and weight at extubation of 1,790 (1,440-2,500) g. Cardiorespiratory stability was noted by a significant decrease in median (IQR) exhaled tidal volume (6.4 [4.9-8.4] mL/kg vs 5.2 (3.8-6.6] mL/kg, P < .001), a significant increase in mean ± SD breathing frequency (45.1 ± 11.4 vs 52.6 ± 14.4 breaths/min, P < .001), and a significant median (IQR) increase in work of breathing (SA-RSS of 1 [1-2] vs 2 [1-3], P < .001) at the end of the SBT. Respiratory instability was more remarkable in the success group., Conclusions: In preterm infants receiving prolonged mechanical ventilation, the performance of a 3-min SBT was associated with increased respiratory instability while still leading to a 10% extubation failure rate. Therefore, the routine use of SBTs to assess extubation readiness in this population is not recommended until there are clear standards and definitions, as well as good accuracy to identify failures., Competing Interests: This work was supported in part by Conselho Nacional de Desenvolvimento Científico e Tecnológico and Fundação Araucária/Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. The authors have disclosed no conflicts of interest., (Copyright © 2021 by Daedalus Enterprises.)

Objective: To verify the association of obesity with volume, intensity and types of physical activity in leisure time among Brazilian adults and elderly., Study Design: Cross-sectional study, with a secondary analysis of data from "Surveillance of Risk Factors and Protection for Chronic Diseases by Telephone Survey"., Methods: The target population comprised adults aged ≥18 years. The outcome was obesity (BMI≥30.0 ​​kg/m²) and the exposures were the volume, intensity, and main type of physical activity in leisure time. Binary logistic regression was used and the results were expressed as odds ratio (OR) and 95% confidence intervals (CI95%), with a significance level of 5%., Results: Compared to inactive, the highest volume of leisure time physical activity (≥300min/week) had a lower occurrence of obesity in adults (OR=0.76; CI95%: 0.63, 0.92; p=0.001) and elderly (OR=0.62; CI95%: 0.46, 0.82; p=0.001). In adults, vigorous activities (OR=0.65; CI95%: 0.55, 0.78; p<0.001) and, in the elderly, light/moderate activities (OR=0.75; CI95%: 0.62, 0.89; p<0.001) and vigorous (OR=0.54; CI95%: 0.37, 0.78; p<0.001) presented protective effect for obesity. Among the types of physical activity, running was the most strongly associated with a lower occurrence of obesity in adults (OR=0.54; CI95%: 0.32, 0.92; p=0.024) and elderly (OR=0.27; CI95%: 0.10, 0.69; p=0.006). In adults, strength training (p<0.001), gymnastics (p=0.032) and sports (p=0.013) and in elderly, walking (p=0.001) and sports (p=0.003) also had protective effect., Conclusion: A greater volume, vigorous intensity and physical activities of a structuring character and intensity progression, such as running, were associated with the lower occurrence of obesity., (Copyright © 2020 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to evaluate glycemic levels in diabetic patients before, during, and after extractions using 2% lidocaine with 1:100,000 epinephrine (Lido/Epi) and 3% prilocaine with 0.03 IU/mL felypressin (Prilo/Fely)., Materials and Methods: A double-blind, randomized clinical trial was conducted to evaluate changes in body parameters and glycemic levels in diabetic patients undergoing two anesthetic protocols during dental extractions. During surgery, we evaluated blood pressure (BP), heart rate (HR), saturation (SpO2), and capillary glycemic levels (Gly). These parameters were measured at the following surgical moments: basal, 30 min after medication, incision, tooth removal, suture, and 30 and 60 min after anesthesia., Results: Data analysis showed no differences between the groups considering age, weight, and time spent in surgery. Increased systolic BP and decreased diastolic BP were observed in the lido/epi group. No difference was observed in the prilo/fely group among the surgical moments or between the groups regarding BP. No difference was observed in HR and SpO2 between the groups at any surgical moment. However, differences were found when compared the differences in glycemic and basal levels in both groups with greater decreases in blood glucose values for the lido/epi group. In anxiety level evaluation, there was no difference between the different surgical moments., Conclusion: Thus, both lido/epi and prilo/fely (maximum 3.6 mL) can be safely used in controlled diabetic patients CLINICAL RELEVANCE: The use of lidocaine associated with epinephrine did not increase glycemic levels but leads to decrease over time when associated with an anxiety reduction protocol, offering some advantage over prilocaine plus felypressin for diabetic patients.

The temporomandibular joint (TMJ) ankylosis describes the bone or fibrous adhesion of the TMJ components, with functional impairment. The present report shows the surgical correction the TMJ ankylosis due to a condyle fracture in a child. A 12-year-old patient, female, attended to the Oral and Maxillofacial Surgery Department of the Clinical Hospital/Federal University of Uberlândia, showing severe mouth opening limitation (9 mm) and history of bilateral condyle fracture and symphysis fracture. The right TMJ ankylosis was diagnosed, removed, reshaped, and repositioned to form the reshaped condyle, by the sliding reconstruction of the condyle using posterior border of mandibular ramus and myofascial interposition of the temporal fascia. Five months of follow-up showed mouth opening of 44 mm maintained after 2 years, without complaints. The surgical treatment of the TMJ ankylosis is needed for the reestablishment of the immediate function; however, the patient must be watched until the end of development.

Fatty liver disease is increasing along with the prevalence of obesity and type-2 diabetes. Hepatic fibrosis is a major health complication for which there are no efficacious treatment options available. A better understanding of the fundamental mechanisms that contribute to the accumulation of fibrosis is needed. Glycine-N-methyltransferase (GNMT) is a critical enzyme in one-carbon metabolism that serves to regulate methylation and remethylation reactions. GNMT knockout (GNMT -/- ) mice display spontaneous hepatic fibrosis and later develop hepatocellular carcinoma. Previous literature supports the idea that hypermethylation as a consequence of GNMT deletion contributes to the hepatic phenotype observed. However, limited metabolomic information is available and the underlying mechanisms that contribute to hepatic fibrogenesis in GNMT -/- mice are still incomplete. Therefore, our goals were to use dietary intervention to determine whether increased lipid load exacerbates steatosis and hepatic fibrosis in this model and to employ both targeted and untargeted metabolomics to further understand the metabolic consequences of GNMT deletion. We find that GNMT mice fed high-fat diet do not accumulate more lipid or fibrosis in the liver and are in fact resistant to weight gain. Metabolomics analysis confirmed that pan-hypermethylation occurs in GNMT mice resulting in a depletion of nicotinamide intermediate metabolites. Further, there is a disruption in tryptophan catabolism that prevents adequate immune cell activation in the liver. The chronic cellular damage cannot be appropriately cleared due to a lack of immune checkpoint activation. This mouse model is an excellent example of how a disruption in small molecule metabolism can significantly impact immune function., (© 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

One-carbon metabolism is a collection of metabolic cycles that supports methylation and provides one-carbon bound folates for the de novo synthesis of purine and thymidine nucleotides. The methylation of phosphatidylethanolamine to form choline has been extensively studied in the context of fatty liver disease. However, the role of one-carbon metabolism in supporting nucleotide synthesis during liver damage has not been addressed. The objective of this study is to determine how the disruption of one-carbon metabolism influences nucleotide metabolism in the liver after dietary methionine and choline restriction. Mice (n=8) were fed a methionine-choline-deficient or control diet for 3 weeks. We treated mice with the compound alloxazine (0.5 mg/kg), a known adenosine receptor antagonist, every second day during the final week of feeding to probe the function of adenosine signaling during liver damage. We found that concentrations of several hepatic nucleotides were significantly lower in methionine- and choline-deficient mice vs. controls (adenine: 13.9±0.7 vs. 10.1±0.6, guanine: 1.8±0.1 vs. 1.4±0.1, thymidine: 0.0122±0.0027 vs. 0.0059±0.0027 nmol/mg dry tissue). Treatment of alloxazine caused a specific decrease in thymidine nucleotides, decrease in mitochondrial content in the liver and exacerbation of steatohepatitis as shown by the increased hepatic lipid content and altered macrophage morphology. This study demonstrates a role for one-carbon metabolism in supporting de novo nucleotide synthesis and mitochondrial function during liver damage., (Copyright © 2020 Elsevier Inc. All rights reserved.)

At present, small angle X-ray scattering (SAXS) studies of perfluorinated sulfonic-acid ionomers (PFSAs) are unable to fully determine the true shape of their building blocks, as recent SAXS modelling predicts disk- and rod-like nanoionic domains as being equally possible. This scenario requires evidence-based findings to unravel the real shape of PFSA building blocks. Herein, a SAXS pattern signature for a lamellar nanophase separation of the ionic domains of Nafion is presented, backed by mid and far infrared spectroscopy (MIR and FIR) and wide angle X-ray scattering (WAXS) data of Nafion in different ionic forms, a broad range of ionic phase contents (EW ∼ 859-42 252 g eq-1) and temperatures. The study indicates that the lamellar arrangement of the ionic domains is the most representative morphology that accounts for the physical properties of this ionomer. The lamellar SAXS reflections of Nafion are enhanced in electric and magnetic field-aligned membranes, as confirmed by atomic force microscopy (AFM). Electric and magnetic field-assisted casting of Nafion allowed producing nanostructured and anisotropic films with the lamellas stacked perpendicularly to the field vector, which is the direction of interest for several applications. Such nanostructured Nafion membranes are bestowed with advanced optical and proton transport properties, making them promising materials for solar and fuel cells.

Fatty liver involves ectopic lipid accumulation and dysregulated hepatic oxidative metabolism, which can progress to a state of elevated inflammation and fibrosis referred to as nonalcoholic steatohepatitis (NASH). The factors that control progression from simple steatosis to NASH are not fully known. Here, we tested the hypothesis that dietary vitamin E (VitE) supplementation would prevent NASH progression and associated metabolic alterations induced by a Western diet (WD). Hyperphagic melanocortin-4 receptor-deficient (MC4R -/- ) mice were fed chow, chow+VitE, WD, or WD+VitE starting at 8 or 20 weeks of age. All groups exhibited extensive hepatic steatosis by the end of the study (28 weeks of age). WD feeding exacerbated liver disease severity without inducing proportional changes in liver triglycerides. Eight weeks of WD accelerated liver pyruvate cycling, and 20 weeks of WD extensively upregulated liver glucose and oxidative metabolism assessed by 2 H/ 13 C flux analysis. VitE supplementation failed to reduce the histological features of NASH. Rather, WD+VitE increased the abundance and saturation of liver ceramides and accelerated metabolic flux dysregulation compared with 8 weeks of WD alone. In summary, VitE did not limit NASH pathogenesis in genetically obese mice, but instead increased some indicators of metabolic dysfunction., (Copyright © 2020 Hasenour et al.)

Nonalcoholic fatty liver disease (NAFLD) is a term used to characterize a range of disease states that involve the accumulation of fat in the liver but are not associated with excessive alcohol consumption. NAFLD is a prevalent disease that can progress to organ damage like liver cirrhosis and hepatocellular carcinoma. Many animal models have demonstrated that one-carbon metabolism is strongly associated with NAFLD. Phosphatidylcholine is an important phospholipid that affects hepatic lipid homeostasis and de novo synthesis of this phospholipid is associated with NAFLD. However, one-carbon metabolism serves to support all cellular methylation reactions and catabolism of methionine, serine, glycine, choline, betaine, tryptophan, and histidine. Several different pathways within one-carbon metabolism that play important roles in regulating energy metabolism and immune function have received less attention in the study of fatty liver disease and fibrosis. This review examines what we have learned about hepatic lipid metabolism and liver damage from the study of one-carbon metabolism thus far and highlights unexplored opportunities for future research., (Copyright © The Author(s) 2020.)

Background: Extracellular surface protein disulfide isomerase-A1 (PDI) is involved in platelet aggregation, thrombus formation and vascular remodeling. PDI performs redox exchange with client proteins and, hence, its oxidation by extracellular molecules might alter protein function and cell response. In this study, we investigated PDI oxidation by urate hydroperoxide, a newly-described oxidant that is generated through uric acid oxidation by peroxidases, with a putative role in vascular inflammation., Methods: Amino acids specificity and kinetics of PDI oxidation by urate hydroperoxide was evaluated by LC-MS/MS and by stopped-flow. Oxidation of cell surface PDI and other thiol-proteins from HUVECs was identified using impermeable alkylating reagents. Oxidation of intracellular GSH and GSSG was evaluated with specific LC-MS/MS techniques. Cell adherence, detachment and viability were assessed using crystal violet staining, cellular microscopy and LDH activity, respectively., Results: Urate hydroperoxide specifically oxidized cysteine residues from catalytic sites of recombinant PDI with a rate constant of 6 × 10 3  M -1  s -1 . Incubation of HUVECs with urate hydroperoxide led to oxidation of cell surface PDI and other unidentified cell surface thiol-proteins. Cell adherence to fibronectin coated plates was impaired by urate hydroperoxide, as well as by other oxidants, thiol alkylating agents and PDI inhibitors. Urate hydroperoxide did not affect cell viability but significantly decreased GSH/GSSG ratio., Conclusions: Our results demonstrated that urate hydroperoxide affects thiol-oxidation of PDI and other cell surface proteins, impairing cellular adherence., General Significance: These findings could contribute to a better understanding of the mechanism by which uric acid affects endothelial cell function and vascular homeostasis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: To investigate the effects of chronic beta-alanine (BA) supplementation on muscle taurine content, blood clinical markers and sensory side-effects., Methods: Twenty-five healthy male participants (age 27 ± 4 years, height 1.75 ± 0.09 m, body mass 78.9 ± 11.7 kg) were supplemented with 6.4 g day -1 of sustained-release BA (N = 16; CarnoSyn™, NAI, USA) or placebo (PL; N = 9; maltodextrin) for 24 weeks. Resting muscle biopsies of the m. vastus lateralis were taken at 0, 12 and 24 weeks and analysed for taurine content (BA, N = 12; PL, N = 6) using high-performance liquid chromatography. Resting venous blood samples were taken every 4 weeks and analysed for markers of renal, hepatic and muscle function (BA, N = 15; PL, N = 8; aspartate transaminase; alanine aminotransferase; alkaline phosphatase; lactate dehydrogenase; albumin; globulin; creatinine; estimated glomerular filtration rate and creatine kinase)., Results: There was a significant main effect of group (p = 0.04) on muscle taurine, with overall lower values in PL, although there was no main effect of time or interaction effect (both p > 0.05) and no differences between specific timepoints (week 0, BA: 33.67 ± 8.18 mmol kg -1  dm, PL: 27.75 ± 4.86 mmol kg -1  dm; week 12, BA: 35.93 ± 8.79 mmol kg -1  dm, PL: 27.67 ± 4.75 mmol kg -1  dm; week 24, BA: 35.42 ± 6.16 mmol kg -1  dm, PL: 31.99 ± 5.60 mmol kg -1  dm). There was no effect of treatment, time or any interaction effects on any blood marker (all p > 0.05) and no self-reported side-effects in these participants throughout the study., Conclusions: The current study showed that 24 weeks of BA supplementation at 6.4 g day -1 did not significantly affect muscle taurine content, clinical markers of renal, hepatic and muscle function, nor did it result in chronic sensory side-effects, in healthy individuals. Since athletes are likely to engage in chronic supplementation, these data provide important evidence to suggest that supplementation with BA at these doses for up to 24 weeks is safe for healthy individuals.