Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 1.897
Filter
Add more filters

Uruguay Oncology Collection
Publication year range
1.
EMBO J ; 43(14): 2878-2907, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38816652

ABSTRACT

In mice, γδ-T lymphocytes that express the co-stimulatory molecule, CD27, are committed to the IFNγ-producing lineage during thymic development. In the periphery, these cells play a critical role in host defense and anti-tumor immunity. Unlike αß-T cells that rely on MHC-presented peptides to drive their terminal differentiation, it is unclear whether MHC-unrestricted γδ-T cells undergo further functional maturation after exiting the thymus. Here, we provide evidence of phenotypic and functional diversity within peripheral IFNγ-producing γδ T cells. We found that CD27+ Ly6C- cells convert into CD27+Ly6C+ cells, and these CD27+Ly6C+ cells control cancer progression in mice, while the CD27+Ly6C- cells cannot. The gene signatures of these two subsets were highly analogous to human immature and mature γδ-T cells, indicative of conservation across species. We show that IL-27 supports the cytotoxic phenotype and function of mouse CD27+Ly6C+ cells and human Vδ2+ cells, while IL-27 is dispensable for mouse CD27+Ly6C- cell and human Vδ1+ cell functions. These data reveal increased complexity within IFNγ-producing γδ-T cells, comprising immature and terminally differentiated subsets, that offer new insights into unconventional T-cell biology.


Subject(s)
Antigens, Ly , Receptors, Antigen, T-Cell, gamma-delta , Tumor Necrosis Factor Receptor Superfamily, Member 7 , Animals , Mice , Antigens, Ly/metabolism , Antigens, Ly/genetics , Tumor Necrosis Factor Receptor Superfamily, Member 7/metabolism , Tumor Necrosis Factor Receptor Superfamily, Member 7/genetics , Tumor Necrosis Factor Receptor Superfamily, Member 7/immunology , Humans , Receptors, Antigen, T-Cell, gamma-delta/metabolism , Receptors, Antigen, T-Cell, gamma-delta/immunology , Receptors, Antigen, T-Cell, gamma-delta/genetics , Interferon-gamma/metabolism , Interferon-gamma/immunology , Interleukin-27/metabolism , Interleukin-27/genetics , Cell Differentiation/immunology , Mice, Inbred C57BL , T-Lymphocytes, Cytotoxic/immunology , T-Lymphocytes, Cytotoxic/metabolism
2.
PLoS Pathog ; 20(7): e1012336, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39018347

ABSTRACT

Cullin-1-RING ubiquitin ligases (CRL1) or SCF1 (SKP1-CUL1-RBX1) E3 ubiquitin ligases are the largest and most extensively investigated class of E3 ligases in mammals that regulate fundamental processes, such as the cell cycle and proliferation. These enzymes are multiprotein complexes comprising SKP1, CUL1, RBX1, and an F-box protein that acts as a specificity factor by interacting with SKP1 through its F-box domain and recruiting substrates via other domains. E3 ligases are important players in the ubiquitination process, recognizing and transferring ubiquitin to substrates destined for degradation by proteasomes or processing by deubiquitinating enzymes. The ubiquitin-proteasome system (UPS) is the main regulator of intracellular proteolysis in eukaryotes and is required for parasites to alternate hosts in their life cycles, resulting in successful parasitism. Leishmania UPS is poorly investigated, and CRL1 in L. infantum, the causative agent of visceral leishmaniasis in Latin America, is yet to be described. Here, we show that the L. infantum genes LINF_110018100 (SKP1-like protein), LINF_240029100 (cullin-like protein-like protein), and LINF_210005300 (ring-box protein 1 -putative) form a LinfCRL1 complex structurally similar to the H. sapiens CRL1. Mass spectrometry analysis of the LinfSkp1 and LinfCul1 interactomes revealed proteins involved in several intracellular processes, including six F-box proteins known as F-box-like proteins (Flp) (data are available via ProteomeXchange with identifier PXD051961). The interaction of LinfFlp 1-6 with LinfSkp1 was confirmed, and using in vitro ubiquitination assays, we demonstrated the function of the LinfCRL1(Flp1) complex to transfer ubiquitin. We also found that LinfSKP1 and LinfRBX1 knockouts resulted in nonviable L. infantum lineages, whereas LinfCUL1 was involved in parasite growth and rosette formation. Finally, our results suggest that LinfCul1 regulates the S phase progression and possibly the transition between the late S to G2 phase in L. infantum. Thus, a new class of E3 ubiquitin ligases has been described in L. infantum with functions related to various parasitic processes that may serve as prospective targets for leishmaniasis treatment.

3.
Chromosoma ; 133(3): 195-202, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38546866

ABSTRACT

Among the repetitive elements, satellite DNA (SatDNA) emerges as extensive arrays of highly similar tandemly repeated units, spanning megabases in length. Given that the satDNA PboSat01-176, previously characterized in P. boiei, prompted our interest for having a high abundance in P. boiei and potential for centromeric satellite, here, we employed various approaches, including low coverage genome sequencing, followed by computational analysis and chromosomal localization techniques in four Proceratophrys species and, investigating the genomic presence and sharing, as well as its potential for chromosomal centromere marker in Proceratophrys frog species. Our findings demonstrate that PboSat01-176 exhibits high abundance across all four Proceratophrys species, displaying distinct characteristics that establish it as the predominant repetitive DNA element in these species. The satellite DNA is prominently clustered in the peri/centromeric region of the chromosomes, particularly in the heterochromatic regions. The widespread presence of PboSat01-176 in closely related Proceratophrys species reinforces the validity of the library hypothesis for repetitive sequences. Thus, this study highlighted the utility of the satDNA family PboSat01-176 as a reliable centromeric marker in Proceratophrys species, with potential to be applied in other species of anuran amphibians. The observed sharing and maintenance of this sequence within the genus suggest possibilities for future research, particularly through expanded sampling to elucidate parameters that underlie the library hypothesis and the evolutionary dynamics of satDNA sequences.


Subject(s)
Anura , Centromere , DNA, Satellite , Animals , Centromere/genetics , DNA, Satellite/genetics , Anura/genetics , Genetic Markers , In Situ Hybridization, Fluorescence , Repetitive Sequences, Nucleic Acid , Species Specificity
4.
J Cell Sci ; 136(10)2023 05 15.
Article in English | MEDLINE | ID: mdl-37248991

ABSTRACT

Genomic replication is a critical, regulated process that ensures accurate genetic information duplication. In eukaryotic cells, strategies have evolved to prevent conflicts between replication and transcription. Giardia lamblia, a binucleated protozoan, alternates between tetraploid and octaploid genomes during its cell cycle. Using single-molecule techniques like DNA combing and nanopore-based sequencing, we investigated the spatio-temporal organization of DNA replication, replication fork progression and potential head-on replication-transcription collisions in Giardia trophozoites. Our findings indicate that Giardia chromosomes are replicated from only a few active origins, which are widely spaced and exhibit faster replication rates compared to those in other protozoan parasites. Immunofluorescence assays revealed that ∼20% of trophozoites show asynchronous replication between nuclei. Forksense and gene ontology analyses disclosed that genes in regions with potential head-on collisions are linked to chromatin dynamics, cell cycle regulation and DNA replication/repair pathways, possibly explaining the observed asynchronous replication in part of the population. This study offers the first comprehensive view of replication dynamics in Giardia, which is the pathogen that causes giardiasis, a diarrheal disease impacting millions worldwide.


Subject(s)
Giardia lamblia , Giardiasis , Humans , Giardia lamblia/genetics , Giardiasis/parasitology , Cell Cycle/genetics , Cell Nucleus , DNA Replication/genetics
5.
Hepatology ; 79(2): 502-523, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37540183

ABSTRACT

BACKGROUND AND AIMS: Fatty liver disease is a major public health threat due to its very high prevalence and related morbidity and mortality. Focused and dedicated interventions are urgently needed to target disease prevention, treatment, and care. APPROACH AND RESULTS: We developed an aligned, prioritized action agenda for the global fatty liver disease community of practice. Following a Delphi methodology over 2 rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the action priorities using Qualtrics XM, indicating agreement using a 4-point Likert-scale and providing written feedback. Priorities were revised between rounds, and in R2, panelists also ranked the priorities within 6 domains: epidemiology, treatment and care, models of care, education and awareness, patient and community perspectives, and leadership and public health policy. The consensus fatty liver disease action agenda encompasses 29 priorities. In R2, the mean percentage of "agree" responses was 82.4%, with all individual priorities having at least a super-majority of agreement (> 66.7% "agree"). The highest-ranked action priorities included collaboration between liver specialists and primary care doctors on early diagnosis, action to address the needs of people living with multiple morbidities, and the incorporation of fatty liver disease into relevant non-communicable disease strategies and guidance. CONCLUSIONS: This consensus-driven multidisciplinary fatty liver disease action agenda developed by care providers, clinical researchers, and public health and policy experts provides a path to reduce the prevalence of fatty liver disease and improve health outcomes. To implement this agenda, concerted efforts will be needed at the global, regional, and national levels.


Subject(s)
Delivery of Health Care , Liver Diseases , Humans
6.
J Hepatol ; 80(3): 419-430, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37984709

ABSTRACT

BACKGROUND & AIMS: Patients with fatty liver disease may experience stigma from the disease or comorbidities. In this cross-sectional study, we aimed to understand stigma among patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and healthcare providers. METHODS: Members of the Global NASH Council created two surveys about experiences/attitudes toward NAFLD and related diagnostic terms: a 68-item patient and a 41-item provider survey. RESULTS: Surveys were completed by 1,976 patients with NAFLD across 23 countries (51% Middle East/North Africa [MENA], 19% Europe, 17% USA, 8% Southeast Asia, 5% South Asia) and 825 healthcare providers (67% gastroenterologists/hepatologists) across 25 countries (39% MENA, 28% Southeast Asia, 22% USA, 6% South Asia, 3% Europe). Of all patients, 48% ever disclosed having NAFLD/NASH to family/friends; the most commonly used term was "fatty liver" (88% at least sometimes); "metabolic disease" or "MAFLD" were rarely used (never by >84%). Regarding various perceptions of diagnostic terms by patients, there were no substantial differences between "NAFLD", "fatty liver disease (FLD)", "NASH", or "MAFLD". The most popular response was being neither comfortable nor uncomfortable with either term (56%-71%), with slightly greater discomfort with "FLD" among the US and South Asian patients (47-52% uncomfortable). Although 26% of patients reported stigma related to overweight/obesity, only 8% reported a history of stigmatization or discrimination due to NAFLD. Among providers, 38% believed that the term "fatty" was stigmatizing, while 34% believed that "nonalcoholic" was stigmatizing, more commonly in MENA (43%); 42% providers (gastroenterologists/hepatologists 45% vs. 37% other specialties, p = 0.03) believed that the name change to metabolic dysfunction-associated steatotic liver disease (or MASLD) might reduce stigma. Regarding the new nomenclature, the percentage of providers reporting "steatotic liver disease" as stigmatizing was low (14%). CONCLUSIONS: The perception of NAFLD stigma varies among patients, providers, geographic locations and sub-specialties. IMPACT AND IMPLICATIONS: Over the past decades, efforts have been made to change the nomenclature of nonalcoholic fatty liver disease (NAFLD) to better align with its underlying pathogenetic pathways and remove any potential stigma associated with the name. Given the paucity of data related to stigma in NAFLD, we undertook this global comprehensive survey to assess stigma in NAFLD among patients and providers from around the world. We found there is a disconnect between physicians and patients related to stigma and related nomenclature. With this knowledge, educational programs can be developed to better target stigma in NAFLD among all stakeholders and to provide a better opportunity for the new nomenclature to address the issues of stigma.


Subject(s)
Gastroenterologists , Metabolic Diseases , Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/complications , Cross-Sectional Studies , Comorbidity , Obesity/metabolism , Metabolic Diseases/complications
7.
Gastroenterology ; 165(3): 696-716, 2023 09.
Article in English | MEDLINE | ID: mdl-37263305

ABSTRACT

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.


Subject(s)
Acute-On-Chronic Liver Failure , COVID-19 , Humans , Latin America/epidemiology , Liver Cirrhosis/diagnosis , Liver Cirrhosis/epidemiology , Liver Cirrhosis/genetics , Prospective Studies , COVID-19/complications , Acute-On-Chronic Liver Failure/diagnosis , Acute-On-Chronic Liver Failure/epidemiology , Acute-On-Chronic Liver Failure/genetics , Inflammation/complications , Prognosis
8.
Biochem Biophys Res Commun ; 706: 149748, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38460450

ABSTRACT

Angiogenesis is a process that is controlled by a delicate combination of proangiogenic and antiangiogenic molecules and can be disrupted in various illnesses, including cancer. Non-cancerous diseases can also have an abnormal or insufficient vascular growth, inflammation and hypoxia, which exacerbate angiogenesis. These conditions include atherosclerosis, psoriasis, endometriosis, asthma, obesity and AIDS. Based on that, the present work assessed the in vitro and ex vivo antiangiogenic properties stemming from BthMP, a P-I metalloproteinase from Bothrops moojeni snake venom, via the VEGF pathway. BthMP at a concentration of 5 and 40 µg/mL showed no toxicity to endothelial cells (HUVEC) in the MTT assay and was not able to induce necrosis and colony proliferation. Interestingly, BthMP inhibited adhesion, migration and invasion of HUVECs in Matrigel and arrested in vitro angiogenesis by reducing the average number of nodules in toxin-treated cells by 9.6 and 17.32 at 5 and 40 µg/mL, respectively, and the number of tubules by 15.9 at 5 µg/mL and 21.6 at 40 µg/mL in a VEGF-dependent way, an essential proangiogenic property. Furthermore, BthMP inhibited the occurrence of the angiogenic process in an ex vivo aortic ring test by decreasing new vessel formation by 52% at 5 µg/mL and by 66% at 40 µg/mL and by increasing the expression of an antiangiogenic gene, SFLT-1, and decreasing the expression of the proangiogenic genes VEGFA and ANGPT-1. Finally, this toxin reduces the production of nitric oxide, a marker that promotes angiogenesis and VEGF modulation, and decreases the protein expression of VEGFA in the supernatant of the HUVEC culture by about 30 %. These results suggest that BthMP has a promising antiangiogenic property and proves to be a biotechnological mechanism for understanding the antiangiogenic responses induced by snake venom metalloproteinases, which could be applied to a variety of diseases that exhibit an imbalance of angiogenesis mechanisms.


Subject(s)
Bothrops , Endothelial Cells , Venomous Snakes , Animals , Female , Humans , Endothelial Cells/metabolism , Vascular Endothelial Growth Factor A/metabolism , Bothrops/metabolism , Metalloproteases/metabolism , Snake Venoms , Human Umbilical Vein Endothelial Cells/metabolism , Angiogenesis Inhibitors/pharmacology
9.
Cytogenet Genome Res ; : 1-8, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38631304

ABSTRACT

INTRODUCTION: Eukaryotic genomes are composed of simple, repetitive sequences, including satellite DNAs (satDNA), which are noncoding sequences arranged in tandem arrays. These sequences play a crucial role in genomic functions and innovations, influencing processes such as the maintenance of nuclear material, the formation of heterochromatin and the differentiation of sex chromosomes. In this genomic era, advances in next-generation sequencing and bioinformatics tools have facilitated the exhaustive cataloging of repetitive elements in genomes, particularly in non-model species. This study focuses on the satDNA content of Ancistrus sp., a diverse species of fish from the Loricariidae family. The genus Ancistrus shows significant karyotypic evolution, with extensive variability from the ancestral diploid number. METHODS: By means of bioinformatic approaches, 40 satDNA families in Ancistrus sp., constituting 5.19% of the genome were identified. Analysis of the abundance and divergence landscape revealed diverse profiles, indicating recent amplification and homogenization of these satDNA sequences. RESULTS: The most abundant satellite, AnSat1-142, constitutes 2.1% of the genome, while the least abundant, AnSat40-52, represents 0.0034%. The length of the monomer repeat varies from 16 to 142 base pairs, with an average length of 61 bp. These results contribute to understanding the genomic dynamics and evolution of satDNAs in Ancistrus sp. CONCLUSION: The study underscores the variability of satDNAs between fish species and provides valuable information on chromosome organization and the evolution of repetitive elements in non-model organisms.

10.
Hepatology ; 78(3): 976-990, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37125643

ABSTRACT

Hepatitis B (HBV) is a major cause of global morbidity and mortality, and the leading cause of liver cancer worldwide. Significant advances have recently been made toward the development of a finite HBV treatment that achieves permanent loss of HBsAg and HBV DNA (so-called "HBV cure"), which could provide the means to eliminate HBV as a public health threat. However, the HBV cure is just one step toward achieving WHO HBV elimination targets by 2030, and much work must be done now to prepare for the successful implementation of the HBV cure. In this review, we describe the required steps to rapidly scale-up future HBV cure equitably. We present key actions required for successful HBV cure implementation, integrated within the World Health Organization (WHO) Global Health Sector Strategy (GHSS) 2022-2030 framework. Finally, we highlight what can be done now to progress toward the 2030 HBV elimination targets using available tools to ensure that we are preparing, but not waiting, for the cure.


Subject(s)
Hepatitis B, Chronic , Hepatitis B , Liver Neoplasms , Humans , Hepatitis B virus , Antiviral Agents/therapeutic use , Hepatitis B/epidemiology , Hepatitis B/prevention & control , Hepatitis B/drug therapy , Hepatitis B Surface Antigens , Liver Neoplasms/drug therapy , Hepatitis B, Chronic/drug therapy
11.
Hepatology ; 78(6): 1966-1986, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37363821

ABSTRACT

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms "nonalcoholic" and "fatty" were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease. There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and can improve awareness and patient identification.


Subject(s)
Non-alcoholic Fatty Liver Disease , Male , Female , Humans , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/metabolism , Delphi Technique , Hepatomegaly , Surveys and Questionnaires
12.
Eur J Vasc Endovasc Surg ; 68(1): 91-98, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38395382

ABSTRACT

OBJECTIVE: Understanding the causes of amputation is crucial for defining health policies that seek to avoid such an outcome, but only a few studies have investigated the epidemiology of patients submitted to amputations in developing countries. The objective of this study was to analyse all lower limb amputations performed in the public health system in Brazil over a 13 year period, evaluating trends in the number of cases, patient demographics, associated aetiologies, hospital length of stay, and in hospital mortality rate. METHODS: This was a retrospective, population based analysis of all lower limb amputations performed in the Brazilian public health system between 1 January 2008 and 31 December 2020. Using a public database, all types of amputations were selected, defining the number of procedures, their main aetiologies, anatomical level of limb loss, demographic data, regional distribution, and other variables of interest. RESULTS: A total of 633 455 amputations were performed between 2008 and 2020, mostly (55.6%) minor amputations, predominantly in males (67%). There was an upward trend in the number of amputations, determined mainly by the increase in major amputations (50.4% increase in the period). Elderly individuals have the highest rates of amputation. Diabetes mellitus (DM) is becoming the main primary diagnosis associated with amputations over the years. The highest in hospital mortality rate occurred after major amputations and was associated with peripheral arterial disease (PAD). CONCLUSION: Amputation rates in Brazil show an upward trend. DM is becoming the most frequent associated primary diagnosis, although PAD is the diagnosis most associated with major amputations and in hospital death.


Subject(s)
Amputation, Surgical , Hospital Mortality , Lower Extremity , Humans , Brazil/epidemiology , Amputation, Surgical/trends , Amputation, Surgical/statistics & numerical data , Amputation, Surgical/mortality , Male , Retrospective Studies , Female , Aged , Middle Aged , Hospital Mortality/trends , Lower Extremity/surgery , Lower Extremity/blood supply , Adult , Length of Stay/statistics & numerical data , Aged, 80 and over , Risk Factors , Time Factors
13.
BMC Infect Dis ; 24(1): 17, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38166763

ABSTRACT

BACKGROUND: An assessment of the factors that interfere with serum levels and the persistence of anti-SARs-CoV-2 IgG antibodies is essential in order to estimate the risk of reinfection and to plan vaccination. We analyzed the impact of the severity of coronavirus disease 2019 (COVID-19) and the clinical and biological factors regarding the persistence of SARs-CoV-2 anti-spike protein (IgG-S) antibodies at 12 months. METHODS: This was an observational, longitudinal study with individuals who had recovered from COVID-19 between August 2020 and June 2021. Peripheral blood samples were collected from volunteers who were hospitalized (SERIOUS COVID-19) and those who required no hospitalization (COVID-19 LIGHT). Samples were grouped according to days after symptom onset: up to 90, between 91 and 180, ≥ 180 days after symptom onset. A semiquantitative test for IgG anti-spike protein S1(IgG-S1) was used. RESULTS: We analyzed 238 individuals who had recovered from COVID-19, of whom 87 had been hospitalized and 151 had not. They provided 148 and 220 samples, respectively. Among those hospitalized, males (65.5%), volunteers aged over 60 years (41.1%), comorbidities such as arterial hypertension (67.8%) and diabetes mellitus (37.9%) were most frequent. We observed higher median serum IgG-S1 titers among those who had recovered from COVID-19 and had been hospitalized, at all collection time intervals (p < 0.001). We observed a weak correlation of increasing age with humoral IgG-S1 response (Spearman correlation = 0.298). There was a greater probability of IgG-S1 antibody persistence over time among samples from hospitalized individuals compared to samples from non-hospitalized participants (p = 0.001). CONCLUSION: This study has revealed higher titers and a higher probability of the persistence of IgG-S1 in severe cases after SARs-CoV-2 primary infection in unvaccinated recovered patients. Thus, in this study, the severe clinical presentation of COVID-19 was the main factor influencing serum levels and the persistence of IgG-S1 antibodies in COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Male , Humans , Middle Aged , Aged , Antibody Formation , Longitudinal Studies , Immunoglobulin G , Patient Acuity , Antibodies, Viral
14.
J Nat Prod ; 87(4): 1217-1221, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38630559

ABSTRACT

Two unusual naphthoquinones, named here as pleonotoquinones A (1) and B (2), were isolated along with two known anthraquinones (3 and 4) via chromatographic separations of an ethyl acetate extract of the roots of Pleonotoma jasminifolia. Compounds 1 and 2 are the first examples of quinones bearing a 2-methyloxepine moiety. The compounds were isolated with the aid of mass spectrometry and molecular networking, and their structures were resolved using 1D and 2D NMR and HRESIMS data. The isolated compounds were evaluated for their antiproliferative activity against human cancer cell lines, and compounds 1 and 2 displayed cytotoxicity against human colon cancer HCT116 cells (IC50 = 2.6 µM for compound 1 and IC50 = 4.3 µM for compound 2) and human liver cancer HepG2 cells (IC50 = 1.9 µM for compound 1 and IC50 = 6.4 µM for compound 2).


Subject(s)
Antineoplastic Agents, Phytogenic , Drug Screening Assays, Antitumor , Naphthoquinones , Plant Roots , Humans , Naphthoquinones/pharmacology , Naphthoquinones/chemistry , Naphthoquinones/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Molecular Structure , Plant Roots/chemistry , Hep G2 Cells , HCT116 Cells , Boraginaceae/chemistry
15.
Ann Vasc Surg ; 98: 7-17, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37717819

ABSTRACT

BACKGROUND: During the COVID-19 pandemic, there was a dramatic increase in healthcare demand. Resources were redirected to care patients with COVID-19. Therefore, surgical treatments were affected, including those of vascular diseases. There are no studies evaluating the whole impact of the COVID-19 pandemic, considering all types of vascular procedures, both elective and urgent, in a large country. The aim of the present study was to analyze the impact on all types of vascular procedures performed in Brazilian public hospitals during the COVID-19 pandemic. METHODS: Cross-sectional population-based analysis of publicly available data referring to vascular procedures. Surgeries 2 years before the pandemic onset (2018-2019) and 2 years during pandemic (2020-2021) were included. RESULTS: We observed a total of 521,069 procedures. Decrease was observed in elective abdominal aortic aneurysm repairs both open surgery (P = 0.001) and endovascular surgery (P < 0.001), emergency open abdominal repairs (P = 0.005), elective thoracic aortic aneurysm repairs (P = 0.007), elective open peripheral aneurysm repairs (P = 0.038), carotid endarterectomies (P < 0.001) and angioplasties (P = 0.001), open revascularizations for peripheral arterial disease (P < 0.001), surgical treatment of chronic venous disease (P < 0.001) and sympathectomies for hyperhidrosis (P < 0.001). However, there was an increase of lower limb amputations (P = 0.027) and vena cava filter placements (P = 0.005). There was a reduction of almost US$17 million in financial investments. CONCLUSIONS: The reorganization of health systems led to a significant reduction in vascular procedures and decrease in financial investments. On the other hand, there was a significant increase in the number of lower limb amputations and vena cava filter placements.


Subject(s)
Aortic Aneurysm, Abdominal , COVID-19 , Endovascular Procedures , Humans , Pandemics , Public Health , Cross-Sectional Studies , Treatment Outcome , COVID-19/epidemiology , Vascular Surgical Procedures/adverse effects , Aortic Aneurysm, Abdominal/surgery , Elective Surgical Procedures , Endovascular Procedures/methods , Retrospective Studies
16.
Ann Hepatol ; 29(1): 101133, 2024.
Article in English | MEDLINE | ID: mdl-37364816

ABSTRACT

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms "nonalcoholic" and "fatty" were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease. There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and can improve awareness and patient identification.


Subject(s)
Non-alcoholic Fatty Liver Disease , Female , Male , Humans , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/epidemiology , Delphi Technique , Ethanol , Cardiometabolic Risk Factors , Consensus , Hepatomegaly
17.
Eur Spine J ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38775819

ABSTRACT

OBJECTIVE: We aimed to prospectively evaluate the association between leisure-time physical activity and outcomes related to low back pain (LBP), such as pain intensity and daily activity limitation. METHODS: We analyzed data from the PAMPA (Prospective Study about Mental and Physical Health) cohort, a longitudinal study with adults residing in Southern Brazil. Participants answered an online-based, self-administered questionnaire. Physical activity was assessed as minutes per week, and those who reported engaging in 150 min/week or more were considered active. We also assessed the types of activities participants engaged. Pain intensity was assessed with a numeric pain rating scale (from 0 to 10), and participants reported whether their pain restricted their daily activities. Generalized linear models were used to investigate the association between physical activity and LBP outcomes. RESULTS: Data from 991 individuals (82.7% women) aged 38.9 ± 13.9 were analyzed. Pain intensity was higher in those inactive in waves one (ß: 0.54; 95 % CI 0.23, 0.86), three (ß: 0.38; 95% CI 0.02, 0.75), and four (ß: 0.48; 95% CI 0.06, 0.90). Also, being physically inactive at wave one was associated with a higher probability of daily activity limitation at waves two (IRR 1.77; 95% CI 1.27; 2.46), three (IRR 1.63; 95% CI 1.17, 2.29), and four (IRR 1.73; 95% CI 1.20, 2.50). CONCLUSION: Not practicing at least 150 min/week of physical activity resulted in higher levels of pain and an increased risk of daily activity limitation in individuals with LBP. Moreover, various forms of activities have shown to be advantageous in alleviating pain among this group.

18.
Food Microbiol ; 123: 104596, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39038898

ABSTRACT

This study evaluated the use of acerola (Malpighia glabra L., CACE), cashew (Anacardium occidentale L., CCAS), and guava (Psidium guayaba L., CGUA) fruit processing coproducts as substrates to promote the growth, metabolite production, and maintenance of the viability/metabolic activity of the probiotics Lactobacillus acidophilus LA-05 and Lacticaseibacillus paracasei L-10 during cultivation, freeze-drying, storage, and exposure to simulated gastrointestinal digestion. Probiotic lactobacilli presented high viable counts (≥8.8 log colony-forming units (CFU)/mL) and a short lag phase during 24 h of cultivation in CACE, CCAS, and CGUA. Cultivation of probiotic lactobacilli in fruit coproducts promoted sugar consumption, medium acidification, and production of organic acids over time, besides increasing the of several phenolic compounds and antioxidant activity. Probiotic lactobacilli cultivated in fruit coproducts had increased survival percentages after freeze-drying and during 120 days of refrigerated storage. Moreover, probiotic lactobacilli cultivated and freeze-dried in fruit coproducts had larger subpopulations of live and metabolically active cells when exposed to simulated gastrointestinal digestion. The results showed that fruit coproducts not only improved the growth and helped to maintain the viability and metabolic activity of probiotic strains but also enriched the final fermented products with bioactive compounds, being an innovative circular strategy for producing high-quality probiotic cultures.


Subject(s)
Fruit , Probiotics , Probiotics/metabolism , Fruit/microbiology , Lactobacillus acidophilus/growth & development , Lactobacillus acidophilus/metabolism , Lactobacillus acidophilus/physiology , Anacardium/microbiology , Anacardium/growth & development , Psidium/growth & development , Psidium/microbiology , Malpighiaceae/growth & development , Malpighiaceae/microbiology , Freeze Drying , Microbial Viability , Lacticaseibacillus paracasei/growth & development , Lacticaseibacillus paracasei/metabolism , Lacticaseibacillus paracasei/physiology , Fermentation , Food Handling/methods
19.
J Esthet Restor Dent ; 36(7): 1056-1067, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38581272

ABSTRACT

OBJECTIVE: To evaluate the effect of fluoride consistency and composition to protect enamel and dentin against the dental erosion. MATERIALS AND METHODS: Bovine enamel and dentin specimens were treated with artificial saliva, neutral fluoride gel (NFG), acidulated phosphate fluoride gel (AFG), neutral fluoride foam (NFF), and acidulated phosphate fluoride foam. The samples were subjected to cycling. Micro energy-dispersive X-ray fluorescence spectrometry, surface roughness (Ra), contact angle (CA), and scanning electron microscopy (SEM) were performed. Composition, CA and Ra data were analyzed by ANOVA and multiple comparison test (p < 0.05). RESULTS: The dentin protected had a significantly higher mineral content than in the control. Eroded unprotected enamel had higher Ra values than normal surfaces. Fluoride treatments increased the Ra in dentin samples. AFG increased the CA in enamel. Fluoride foams increased CA in dentin with reduced mineral loss. SEM analysis found a deposited layer on enamel treated with AFG and remnants of deposits on dentin treated with NFG and NFF. CONCLUSION: Regardless of the form of application, fluoride provided protection against erosion, however with different levels. CLINICAL SIGNIFICANCE: Applying the adequate fluoride form is relevant since the formulations have different effects on both enamel and dentin.


Subject(s)
Dental Enamel , Dentin , Fluorides , Microscopy, Electron, Scanning , Spectrometry, X-Ray Emission , Surface Properties , Tooth Erosion , Animals , Tooth Erosion/prevention & control , Cattle , Dental Enamel/drug effects , Dentin/drug effects , Fluorides/pharmacology , Acidulated Phosphate Fluoride/pharmacology , Saliva, Artificial , Fluorides, Topical/pharmacology
20.
J Esthet Restor Dent ; 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38563466

ABSTRACT

OBJECTIVE: This systematic review aimed to analyze the clinical (survival rate, failure risk, or fracture) and laboratory performance (fracture mode or failure) of rehabilitations of endodontically treated teeth, with and without posts. MATERIALS AND METHODS: A systematic search was conducted in the Pubmed, Scopus, Web of Science, Embase, Cochrane Library, and OpenGrey databases up to March 2023, according to PRISMA guidelines. In vitro and clinical studies that compared the clinical and laboratory performance of endodontically treated teeth with and without intraradicular posts were included. Studies selection, data extraction, and risk of bias analysis were performed. RESULTS: Thirty-one in vitro and 7 clinical studies were included. For in vitro studies, fiberglass post (n = 24) was the most mentioned. The follow-up time of the clinical studies ranged from 1 to 17 years, with the fiber-reinforced composite post (n = 3) being the most evaluated, and only failure risk proved to be more favorable for using intraradicular posts. CONCLUSION: Rehabilitations of endodontically treated teeth with and without intraradicular retainers showed no difference in fracture resistance and failure mode, evaluated by in vitro studies. Clinical studies showed no difference in survival rate, but failure risk proved to be more favorable for the use of posts. CLINICAL SIGNIFICANCE: This analysis revealed significant variability between results, however, most laboratory and clinical studies revealed no difference with using the post. Furthermore, it is important to emphasize the need to evaluate the coronary remnant and the general characteristics of the tooth in each situation.

SELECTION OF CITATIONS
SEARCH DETAIL