Procedural-Related Bleeding in Hospitalized Patients With Liver Disease (PROC-BLeeD): An International, Prospective, Multicenter Observational Study.

BACKGROUND & AIMS: Hospitalized patients with cirrhosis frequently undergo multiple procedures. The risk of procedural-related bleeding remains unclear, and management is not standardized. We conducted an international, prospective, multicenter study of hospitalized patients with cirrhosis undergoing nonsurgical procedures to establish the incidence of procedural-related bleeding and to identify bleeding risk factors. METHODS: Hospitalized patients were prospectively enrolled and monitored until surgery, transplantation, death, or 28 days from admission. The study enrolled 1187 patients undergoing 3006 nonsurgical procedures from 20 centers. RESULTS: A total of 93 procedural-related bleeding events were identified. Bleeding was reported in 6.9% of patient admissions and in 3.0% of the procedures. Major bleeding was reported in 2.3% of patient admissions and in 0.9% of the procedures. Patients with bleeding were more likely to have nonalcoholic steatohepatitis (43.9% vs 30%) and higher body mass index (BMI; 31.2 vs 29.5). Patients with bleeding had a higher Model for End-Stage Liver Disease score at admission (24.5 vs 18.5). A multivariable analysis controlling for center variation found that high-risk procedures (odds ratio [OR], 4.64; 95% confidence interval [CI], 2.44-8.84), Model for End-Stage Liver Disease score (OR, 2.37; 95% CI, 1.46-3.86), and higher BMI (OR, 1.40; 95% CI, 1.10-1.80) independently predicted bleeding. Preprocedure international normalized ratio, platelet level, and antithrombotic use were not predictive of bleeding. Bleeding prophylaxis was used more routinely in patients with bleeding (19.4% vs 7.4%). Patients with bleeding had a significantly higher 28-day risk of death (hazard ratio, 6.91; 95% CI, 4.22-11.31). CONCLUSIONS: Procedural-related bleeding occurs rarely in hospitalized patients with cirrhosis. Patients with elevated BMI and decompensated liver disease who undergo high-risk procedures may be at risk to bleed. Bleeding is not associated with conventional hemostasis tests, preprocedure prophylaxis, or recent antithrombotic therapy.

Genetic Ancestry, Race, and Severity of Acutely Decompensated Cirrhosis in Latin America.

BACKGROUND & AIMS: Genetic ancestry or racial differences in health outcomes exist in diseases associated with systemic inflammation (eg, COVID-19). This study aimed to investigate the association of genetic ancestry and race with acute-on-chronic liver failure (ACLF), which is characterized by acute systemic inflammation, multi-organ failure, and high risk of short-term death. METHODS: This prospective cohort study analyzed a comprehensive set of data, including genetic ancestry and race among several others, in 1274 patients with acutely decompensated cirrhosis who were nonelectively admitted to 44 hospitals from 7 Latin American countries. RESULTS: Three hundred ninety-five patients (31.0%) had ACLF of any grade at enrollment. Patients with ACLF had a higher median percentage of Native American genetic ancestry and lower median percentage of European ancestry than patients without ACLF (22.6% vs 12.9% and 53.4% vs 59.6%, respectively). The median percentage of African genetic ancestry was low among patients with ACLF and among those without ACLF. In terms of race, a higher percentage of patients with ACLF than patients without ACLF were Native American and a lower percentage of patients with ACLF than patients without ACLF were European American or African American. In multivariable analyses that adjusted for differences in sociodemographic and clinical characteristics, the odds ratio for ACLF at enrollment was 1.08 (95% CI, 1.03-1.13) with Native American genetic ancestry and 2.57 (95% CI, 1.84-3.58) for Native American race vs European American race CONCLUSIONS: In a large cohort of Latin American patients with acutely decompensated cirrhosis, increasing percentages of Native American ancestry and Native American race were factors independently associated with ACLF at enrollment.

Know-how of holding a Bioinformatics competition: Structure, model, overview, and perspectives.

The article presents a framework for a Bioinformatics competition that focuses on 4 key aspects: structure, model, overview, and perspectives. Structure represents the organizational framework employed to coordinate the main tasks involved in the competition. Model showcases the competition design, which encompasses 3 phases. Overview presents our case study, the League of Brazilian Bioinformatics (LBB) 2nd Edition. Finally, the section on perspectives provides a brief discussion of the LBB 2nd Edition, along with insights and feedback from participants. LBB is a biannual team competition launched in 2019 to promote the ongoing training of human resources in Bioinformatics and Computational Biology in Brazil. LBB aims to stimulate ongoing training in Bioinformatics by encouraging participation in competitions, promoting the organization of future Bioinformatics competitions, and fostering the integration of the Bioinformatics and Computational Biology community in the country, as well as collaboration among participants. The LBB 2nd Edition was launched in 2021 and featured 251 competitors forming 91 teams. Knowledge competitions promote learning, collaboration, and innovation, which are crucial for advancing scientific knowledge and solving real-world problems. In summary, this article serves as a valuable resource for individuals and organizations interested in developing knowledge competitions, offering a model based on our experience with LBB to benefit all levels of Bioinformatics trainees.

Neutrophil extracellular traps in rheumatoid arthritis and periodontitis: Contribution of PADI4 gene polymorphisms.

AIM: We sought to investigate the release of neutrophil extracellular traps (NETs) in neutrophils from individuals with rheumatoid arthritis (RA) and controls and compare the presence of NETs in gingival tissues according to periodontal status. Also, the association between single nucleotide polymorphisms (SNPs) of the peptidyl arginine deaminase type 4 (PADI4) gene and the GTG haplotype with RA, periodontitis and NETs was evaluated in vitro. MATERIALS AND METHODS: Peripheral neutrophils were isolated by density gradient, and NET concentration was determined by the PicoGreen method. Immunofluorescence was studied to identify NETs by co-localization of myeloperoxidase (MPO)-citrullinated histone H3 (H3Cit). Genotyping for SNPs (PADI4_89; PADI4_90; PADI4_92; and PADI4_104) was performed in 87 individuals with RA and 111 controls. RESULTS: The release of NETs in vitro was significantly higher in individuals with RA and periodontitis and when stimulated with Porphyromonas gingivalis. Gingival tissues from subjects with RA and periodontitis revealed increased numbers of MPO-H3Cit-positive cells. Individuals with the GTG haplotype showed a higher release of NETs in vitro and worse periodontal parameters. CONCLUSIONS: The release of NETs by circulating neutrophils is associated with RA and periodontitis and is influenced by the presence of the GTG haplotype.

Cannabidiol Recovers Dopaminergic Neuronal Damage Induced by Reserpine or α-synuclein in Caenorhabditis elegans.

Progressive neurodegenerative disorders such as Parkinson Disease (PD) lack curative or long-term treatments. At the same time, the increase of the worldwide elderly population and, consequently, the extension in the prevalence of age-related diseases have promoted research interest in neurodegenerative disorders. Caenorhabditis elegans is a free-living nematode widely used as an animal model in studies of human diseases. Here we evaluated cannabidiol (CBD) as a possible neuroprotective compound in PD using the C. elegans models exposed to reserpine. Our results demonstrated that CBD reversed the reserpine-induced locomotor alterations and this response was independent of the NPR-19 receptors, an orthologous receptor for central cannabinoid receptor type 1. Morphological alterations of cephalic sensilla (CEP) dopaminergic neurons indicated that CBD also protects neurons from reserpine-induced degeneration. That is, CBD attenuates the reserpine-induced increase of worms with shrunken soma and dendrites loss, increasing the number of worms with intact CEP neurons. Finally, we found that CBD also reduced ROS formation and α-syn protein accumulation in mutant worms. Our findings collectively provide new evidence that CBD acts as neuroprotector in dopaminergic neurons, reducing neurotoxicity and α-syn accumulation highlighting its potential in the treatment of PD.

Retrieval of HCV patients lost to follow-up as a strategy for Hepatitis C Microelimination: results of a Brazilian multicentre study.

BACKGROUND: Several HCV patients in Brazil were lost to follow-up (LTFU) in the last two decades before achievement of sustained virological response (SVR). Strategies to recall those diagnosed but untreated patients have been used elsewhere with different success rates. AIM: To identify and retrieve LTFU patients in order to offer them the treatment with the current highly effective direct acting antiviral agents (DAAs). METHODS: Registries ofall HCV patients from three large reference centers in Brazil were retrospectively reviewed to identify those with no registry of SVR. Reasons for non-achievement of SVR were elicited in HCV-RNA + patients. All patients who were not treated or cured were contacted to offer the therapy with DAAs. RESULTS: 10,289 HCV patients (50% males, mean age 52 ± 11 years) were identified. Only 4,293 (41.7%) had been successfully treated previously. From the remaining 5,996 most were LTFU (59%), were not treated for other reasons (14.7%) or were non-responders (26.3%). After revision of the charts 3,559 were considered eligible to be retrieved. The callback success of phone calls was 18%, 13% to cellphone messages (SMS or WhatsApp) and 7% to regular mail. Five-hundred sixty patients had been already treatedor were on treatment and 234 were reported to be dead or transplanted. Finally, 201 had made an appointment and initiated antiviral treatment. CONCLUSION: Even considering the low callback rate, retrieval of LTFU patients was shown to be an important strategy forhepatitis C micro-elimination in Brazil.

Preemptive effects of etoricoxib, acetaminophen, nimesulide, and ibuprofen on postoperative pain management after single-implant surgery: A randomized clinical trial.

BACKGROUND: There is insufficient evidence for pain control in preemptive analgesia (PA) after dental implant surgery, signaling the need for further studies. The objective of this study was to evaluate the efficacy of PA in single dental implant surgeries (SDIS), seeking to identify among the etoricoxib (ETOR), ibuprofen (IBU), nimesulide (NIME), and acetaminophen (ACETA)], which one has the higher efficacy effectiveness in relieving postoperative pain and reducing the use of rescue medication compared to placebo. METHODS: In this triple-blind, parallel, randomized controlled clinical trial, 135 individuals with a mean age of 57.6 years (±11.7), both genders, were randomly divided into five groups according to the test drug: I-PLACEBO; II-IBU (600 mg); III-NIME (100 mg); IV-ACETA (750 mg); and V-ETOR (90 mg). The occurrence, duration, and intensity of pain were analyzed using the Chi-square, Fisher's exact and ANOVA tests, and the generalized estimating equation models, when appropriate. RESULTS: Test drugs provided a reduction in postoperative pain scores and lower use of rescue medication when compared to placebo. The ETOR group presented significantly lower pain scores, when compared to other active treatments. The IBU group showed the highest mean number of rescue medication used. CONCLUSIONS: All test drugs provided a beneficial preemptive effect demonstrated by the reduced postoperative pain and reduced use of rescue medication. The ETOR group presented lower pain scores, and the IBU group showed the highest mean number of rescue medication used among the test groups.

NAADP-Evoked Ca2+ Signaling Leads to Mutant Huntingtin Aggregation and Autophagy Impairment in Murine Astrocytes.

Huntington's disease (HD) is a progressive neurodegenerative disease characterized by mutations in the huntingtin gene (mHtt), causing an unstable repeat of the CAG trinucleotide, leading to abnormal long repeats of polyglutamine (poly-Q) in the N-terminal region of the huntingtin, which form abnormal conformations and aggregates. Alterations in Ca2+ signaling are involved in HD models and the accumulation of mutated huntingtin interferes with Ca2+ homeostasis. Lysosomes are intracellular Ca2+ storages that participate in endocytic and lysosomal degradation processes, including autophagy. Nicotinic acid adenine dinucleotide phosphate (NAADP) is an intracellular second messenger that promotes Ca2+ release from the endo-lysosomal system via Two-Pore Channels (TPCs) activation. Herein, we show the impact of lysosomal Ca2+ signals on mHtt aggregation and autophagy blockade in murine astrocytes overexpressing mHtt-Q74. We observed that mHtt-Q74 overexpression causes an increase in NAADP-evoked Ca2+ signals and mHtt aggregation, which was inhibited in the presence of Ned-19, a TPC antagonist, or BAPTA-AM, a Ca2+ chelator. Additionally, TPC2 silencing revert the mHtt aggregation. Furthermore, mHtt has been shown co-localized with TPC2 which may contribute to its effects on lysosomal homeostasis. Moreover, NAADP-mediated autophagy was also blocked since its function is dependent on lysosomal functionality. Taken together, our data show that increased levels of cytosolic Ca2+ mediated by NAADP causes mHtt aggregation. Additionally, mHtt co-localizes with the lysosomes, where it possibly affects organelle functions and impairs autophagy.

The loss of molars in supportive periodontal care: A 10-year follow-up for tooth- and patient-related factors.

AIM: To determine the impact of the degree of furcation involvement (FI) on the longevity of molar teeth and assess the risk variables (tooth- and patient-related factors) associated with the loss of molars (LM) in individuals treated for periodontitis and monitored in a private programme of supportive periodontal care (SPC). MATERIALS AND METHODS: The present retrospective cohort study included 222 individuals with 1329 molars under a 10-year monitoring period in SPC. Periodontal clinical parameters, FI, the type of molar, pulp vitality, and other variables of interest were collected at approximately 50 days after active periodontal therapy and after 10 years. The association of tooth- and patient-related factors with LM was assessed using a multilevel Cox regression analysis. RESULTS: Two-hundred and thirty-five molars were extracted during the SPC period of 12.4 ± 1.9 years. Age >50 years, male gender, diabetes, smoking, and non-compliance were identified as relevant patient-related factors for LM during SPC (p < .05). Significant tooth-related factors for LM were bleeding on probing (BoP) and probing depth (PD) ≥5 mm, tooth non-vitality, and class II and III FI (p < .05). CONCLUSIONS: Class III FI, tooth non-vitality, higher mean PD and BoP, age, male gender, diabetes, and smoking all strongly influenced the prognosis of molars during SPC.

Association between liver cirrhosis and peri-implant diseases: a case-control study on implant- and patient-related risk factors.

OBJECTIVE: The objective of this study was to evaluate the potential association between liver cirrhosis and peri-implant diseases, as well as the influence of different risk indicators on this association. METHODS: This case-control study included 64 cases with liver cirrhosis and 128 controls without liver diseases that presented the same socio-demographic and economic profile. The specific inclusion criteria were the following: aged group of 35-55 years and presenting at least one osseointegrated implant functioning for >5 years. A full-mouth peri-implant and periodontal examination was performed and risk variables were recorded. The association between risk variables and the occurrence of peri-implant diseases was tested through univariate analysis and multivariate logistic regression, stratified by alcohol status. Additionally, a mediation analysis was performed to examine the mediating effect of age with peri-implantitis. RESULTS: A high prevalence of peri-implantitis (29.7%) was observed among cases when compared to controls (18.0%). Individuals with cirrhosis presented ~2.5 higher chance of having peri-implantitis than controls (p<0.001). Significant variables associated with the occurrence of peri-implantitis in the final logistic model were the following: cirrhosis, alcohol use, age (>55 years), male sex, smoking, periodontitis, and number of ≤14. CONCLUSIONS: An important risk association between liver cirrhosis and peri-implantitis was reported. Future studies with a larger sample size controlling for the patient- and implant-related confounders are needed to better understand the link between peri-implantitis and liver cirrhosis. CLINICAL RELEVANCE: Cirrhosis individuals, age, and periodontitis, as well as alcohol use and smoking interaction, should be considered as potential risk indicators for peri-implantitis.

Association between cumulative smoking exposure, span since smoking cessation, and peri-implantitis: a cross-sectional study.

OBJECTIVES: To investigate the association of cumulative smoking exposure and span since smoking cessation with the occurrence of peri-implantitis. METHODS: A sample of 350 individuals aged ≥ 35 years, with the presence of at least one osseointegrated implant functioning for > 5 years, were enrolled in the study. According to smoking habits, participants were categorized into 3 groups: non-smokers (NS; n = 212), former smokers (FC; n = 66), and current smokers (CS; n = 72). Complete peri-implant and periodontal examinations were evaluated. Associations between the occurrence of peri-implantitis and smoking habits, as well as potential confounders, were evaluated through univariate and multivariate analyses. RESULTS: The occurrence of peri-implantitis in the NS, FS, and CS groups was 18.2%, 19.7%, and 30.5%, respectively. A high prevalence of the overall number of cases with periodontitis (54.2%) was observed in the CS group when compared to the FS and NS groups. After adjusting for confounders, the odds ratio (OR) for the occurrence of peri-implantitis was 2.63 (1.39-6.77; p < 0.001) for CS compared to NS. There was a significant dose-response relationship between pack/year of smoking and the occurrence of peri-implantitis, as well as a significant decrease in the risk as the years of smoking cessation increased. CONCLUSIONS: The occurrence of peri-implantitis among CS was high. The cumulative smoking exposure in an incremental manner and the shorter smoking cessation span was directly associated with a higher risk for peri-implantitis. CLINICAL RELEVANCE: Educational and preventive strategies in general health services must attempt to reduce the adverse effects of cumulative smoking exposure and to explore the beneficial effects of smoking cessation on peri-implant status.

Disruption of Redox Homeostasis by Alterations in Nitric Oxide Synthase Activity and Tetrahydrobiopterin along with Melanoma Progression.

Cutaneous melanoma emerges from the malignant transformation of melanocytes and is the most aggressive type of skin cancer. The progression can occur in different stages: radial growth phase (RGP), vertical growth phase (VGP), and metastasis. Reactive oxygen species contribute to all phases of melanomagenesis through the modulation of oncogenic signaling pathways. Tetrahydrobiopterin (BH4) is an important cofactor for NOS coupling, and an uncoupled enzyme is a source of superoxide anion (O2•-) rather than nitric oxide (NO), altering the redox homeostasis and contributing to melanoma progression. In the present work, we showed that the BH4 amount varies between different cell lines corresponding to distinct stages of melanoma progression; however, they all presented higher O2•- levels and lower NO levels compared to melanocytes. Our results showed increased NOS expression in melanoma cells, contributing to NOS uncoupling. BH4 supplementation of RGP cells, and the DAHP treatment of metastatic melanoma cells reduced cell growth. Finally, Western blot analysis indicated that both treatments act on the PI3K/AKT and MAPK pathways of these melanoma cells in different ways. Disruption of cellular redox homeostasis by the altered BH4 concentration can be explored as a therapeutic strategy according to the stage of melanoma.

Overexpression of α-synuclein inhibits mitochondrial Ca2+ trafficking between the endoplasmic reticulum and mitochondria through MAMs by altering the GRP75-IP3R interaction.

Mitochondria-associated ER membranes (MAMs) are formed by close and specific components in the contact sites between the endoplasmic reticulum (ER) and mitochondria, which participate in several cell functions, including lipid metabolism, autophagy, and Ca2+ signaling. Particularly, the presence of α-synuclein (α-syn) in MAMs was previously demonstrated, indicating a physical interaction among some proteins in this region and a potential involvement in cell dysfunctions. MAMs alterations are associated with neurodegenerative diseases such as Parkinson's disease (PD) and contribute to the pathogenesis features. Here, we investigated the effects of α-syn on MAMs and Ca2+ transfer from the ER to mitochondria in WT- and A30P α-syn-overexpressing SH-SY5Y or HEK293 cells. We observed that α-syn potentiates the mitochondrial membrane potential (Δψm ) loss induced by rotenone, increases mitophagy and mitochondrial Ca2+ overload. Additionally, in α-syn-overexpressing cells, we found a reduction in ER-mitochondria contact sites through the impairment of the GRP75-IP3R interaction, however, with no alteration in VDAC1-GRP75 interaction. Consequently, after Ca2+ release from the ER, α-syn-overexpressing cells demonstrated a reduction in Ca2+ buffering by mitochondria, suggesting a deregulation in MAM activity. Taken together, our data highlight the importance of the α-syn/MAMs/Ca2+ axis that potentially affects cell functions in PD.

Angiotensin II modulates the murine hematopoietic stem cell and progenitors cocultured with stromal S17 cells.

Although the existence of the renin-angiotensin system (RAS) in the bone marrow is clear, the exact role of this system in hematopoiesis has not yet been fully characterized. Here the direct role of angiotensin II (AngII) in hematopoietic stem cells (HSCs), common myeloid progenitors (CMPs), granulocyte/monocyte progenitors (GMPs), and megakaryocytes/erythroid progenitors (MEPs), using a system of coculture with stromal S17 cells. Flow cytometry analysis showed that AngII increases the percentage of HSC and GMP, while reducing CMP with no effect on MEP. According to these data, AngII increased the total number of mature Gr-1+ /Mac-1+ cells without changes in Terr119+ cells. AngII does not induce cell death in the population of LSK cells. In these populations, treatment with AngII decreases the expression of Ki67+ protein with no changes in the Notch1 expression, suggesting a role for AngII on the quiescence of immature cells. In addition, exposure to AngII from murine bone marrow cells increased the number of CFU-GM and BFU-E in a clonogenic assay. In conclusion, our data showed that AngII is involved in the regulation of hematopoiesis with a special role in HSC, suggesting that AngII should be evaluated in coculture systems, especially in cases that require the expansion of these cells in vitro, still a significant challenge for therapeutic applications in humans.

CLIF-C AD Score Predicts Development of Acute Decompensations and Survival in Hospitalized Cirrhotic Patients.

BACKGROUND AND AIMS: Patients with decompensated cirrhosis are at increased risk of mortality, even in absence of ACLF. The CLIF-C AD score (CLIF-C ADs) was proposed as a prognostic score but lacks sufficient validation. Our aim was to describe clinical characteristics and hospital evolution according to score groups and evaluate prognostic capability of CLIF-C ADs alone or in combination with other scores. METHODS: Two hundred and sixty-six patients (55 ± 14 years, ascites in 63%, MELD 14 ± 5) were included, and classified as high, intermediate and low CLIF-C ADs in 13, 60 and 27% of cases. Development of new complications of cirrhosis during hospitalization and survival at 3 months were evaluated. RESULTS: Patients with high CLIF-C ADs had more severe systemic inflammation parameters and higher frequency of organ dysfunction. CLIF-C ADs ≥ 60, when compared to intermediate and low groups, was associated with higher incidence of complications of cirrhosis (90% vs 70% and 49%, p < 0.001) and lower survival (93%, 80% and 50%, p < 0.0001). In multivariate analysis, CLIF-C ADs, ascites and MELD were predictors of survival [(AUROC 0.76 (95% CI 0.69-0.83)]. Absence of ascites or MELD < 14 identified patients with intermediate CLIF-C ADs and good survival (89 and 84%, respectively). CONCLUSION: CLIF-C ADs predicts survival in cirrhotic patients with AD. High CLIF-C ADs is associated with higher frequency of organ dysfunction, increased risk of new complications of cirrhosis and high short-term mortality. On the contrary, individuals with low CLIF-C ADs, as well as those with intermediate score without ascites or with low MELD have excellent prognoses.

Is Implantoplasty Efficacious at Treating Peri-Implantitis? A Systematic Review and Meta-Analysis.

PURPOSE: Peri-implantitis is an inflammatory disease, characterized by the progressive loss of the peri-implant support bone tissue. The objective of this study was to assess whether implantoplasty is efficacious in promoting peri-implant health. METHODS: In this systematic review and meta-analysis, a search without restrictions regarding language or date of publication was conducted across different databases. Grey literature search, Google Scholar search and manual searches were also carried out. Studies evaluating periimplant clinical parameters of individuals with peri-implantitis who had been submitted to implantoplasty were included. Study selection, data extraction, and risk of bias assessment were conducted. The outcome variables were implant probing depth, the percentage of implants with bleeding on probing or suppuration on probing, and the success rate of implants after implantoplasty. The predictor variable was implantoplasty and the follow-up time after implantoplasty. Data on sample size, implant location, implant diameter, and diagnostic criteria for peri-implantitis were also collected during data extraction. Meta-analysis, sensitivity analysis, and analysis of the probability of implant success after implantoplasty with the Kalan-Meier method were performed. RESULTS: Ninety-four studies were assessed. Eight articles were included and 7 were incorporated into quantitative analyses. Subjects' mean age ranged between 50 to 70.7 years. The studies demonstrated that implantoplasty contributed to a significant improvement in the peri-implant condition, reducing the probing depth, bleeding and suppuration on probing. Overall, the included studies exhibited low risk of bias. Meta-analysis demonstrated that probing depth before implantoplasty was significantly higher than after implantoplasty (mean difference = -3.37 mm, confidence interval = -4.74; -2.00). This result was confirmed in the sensitivity analysis. The probability of success of implants at 6 months of follow-up after implantoplasty was 97.5% and at 24 months of follow-up was 94.7%. CONCLUSIONS: There is some evidence in the literature to recommend implantoplasty as a potential treatment for periimplantitis.

Pharmacological Modulators of Autophagy as a Potential Strategy for the Treatment of COVID-19.

The family of coronaviruses (CoVs) uses the autophagy machinery of host cells to promote their growth and replication; thus, this process stands out as a potential target to combat COVID-19. Considering the different roles of autophagy during viral infection, including SARS-CoV-2 infection, in this review, we discuss several clinically used drugs that have effects at different stages of autophagy. Among them, we mention (1) lysosomotropic agents, which can prevent CoVs infection by alkalinizing the acid pH in the endolysosomal system, such as chloroquine and hydroxychloroquine, azithromycin, artemisinins, two-pore channel modulators and imatinib; (2) protease inhibitors that can inhibit the proteolytic cleavage of the spike CoVs protein, which is necessary for viral entry into host cells, such as camostat mesylate, lopinavir, umifenovir and teicoplanin and (3) modulators of PI3K/AKT/mTOR signaling pathways, such as rapamycin, heparin, glucocorticoids, angiotensin-converting enzyme inhibitors (IECAs) and cannabidiol. Thus, this review aims to highlight and discuss autophagy-related drugs for COVID-19, from in vitro to in vivo studies. We identified specific compounds that may modulate autophagy and exhibit antiviral properties. We hope that research initiatives and efforts will identify novel or "off-label" drugs that can be used to effectively treat patients infected with SARS-CoV-2, reducing the risk of mortality.

Effects of Time of Day on Race Splits, Kinematics, and Blood Lactate During a 50-m Front Crawl Performance.

ABSTRACT: Lisbôa, FD, Raimundo, JAG, Pereira, GS, Ribeiro, G, de Aguiar, RA, and Caputo, F. Effects of time of day on race splits, kinematics, and blood lactate during a 50-m front crawl performance. J Strength Cond Res 35(3): 819-825, 2021-This study aimed to investigate the performance, race splits, metabolic, and stroke parameters during 2 successive 50-m front crawl under conditions simulating a competition. Eleven competitive male swimmers (20 ± 3 years, 182 ± 5 cm, and 77 ± 5 kg) performed 2 successive 50-m front crawl trials in a 50-m swimming pool at 10 am and 5 pm. Block time (tB), 15-m performance (t.15-m), and 50-m performance (t.50-m) were measured. Velocity (V), stroke rate (SR), stroke length (SL), and stroke index (SI) were measured at 3 time points during the trials. Pre-trial and post-trial blood samples were taken to determine blood lactate accumulation (Δ[Lac]). For t.50-m, the relative difference between 10 am and 5 pm reached 0.1% (p = 0.7; effect size [ES] = 0.02). Furthermore, no differences in tB (p = 0.12; ES = -0.28) and t.15-m (p = 0.39; ES = -0.16) were observed between periods. Both V (p = 0.11; ES = -0.14) and SI (p = 0.16; ES = 0.15) were also similar. Higher values of SR were recorded at 10 am (p = 0.03; ES = -0.32), whereas the morning values of SL were lower (p = 0.04; ES = 0.3). Δ[Lac] was not significantly different between periods (p = 0.07; ES = -0.27). Although time of the day did not impact performance in 2 successive 50-m front crawl performances, different stroke parameters profiles were observed during these trials. This may help coaches design specific warm-up exercises to enhance performance at different times of the day.

Anthocyanins Recovered from Agri-Food By-Products Using Innovative Processes: Trends, Challenges, and Perspectives for Their Application in Food Systems.

Anthocyanins are naturally occurring phytochemicals that have attracted growing interest from consumers and the food industry due to their multiple biological properties and technological applications. Nevertheless, conventional extraction techniques based on thermal technologies can compromise both the recovery and stability of anthocyanins, reducing their global yield and/or limiting their application in food systems. The current review provides an overview of the main innovative processes (e.g., pulsed electric field, microwave, and ultrasound) used to recover anthocyanins from agri-food waste/by-products and the mechanisms involved in anthocyanin extraction and their impacts on the stability of these compounds. Moreover, trends and perspectives of anthocyanins' applications in food systems, such as antioxidants, natural colorants, preservatives, and active and smart packaging components, are addressed. Challenges behind anthocyanin implementation in food systems are displayed and potential solutions to overcome these drawbacks are proposed.

Influence of Organic Matter in Sorption of the Saflufenacil in Ferralsols.

The saflufenacil herbicide has been applied in the agricultural areas as an efficient alternative for the control of resistant weeds to glyphosate. However, the environmental risks from the use of saflufenacil, especially in tropical soil, is not yet clearly known. We evaluated if the organic matter addition into the soil influences the sorption of saflufenacil in samples of a sandy and clayey texture soils. The sugarbeet was used as a species indicating the presence of saflufenacil in the solution of the substrates. We estimated the required dose of saflufenacil responsible for causing 50% of sugarbeet intoxication (C50) and the sorption ratio (SR) of this herbicide. The addition of organic matter increased the C50 and SR of saflufenacil in both soils. Here it is demonstrated that the soil organic matter content increases saflufenacil sorption in tropical soils and, consequently influences the dose of this herbicide to be applied in pre-emergence of weeds.