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Entamoeba histolytica is a protozoan parasite belonging to the phylum Amoebozoa that causes amebiasis, a global public health problem. E. histolytica alternates its form between a proliferative trophozoite and a dormant cyst. Trophozoite proliferation is closely associated with amebiasis symptoms and pathogenesis whereas cysts transmit the disease. Drugs are available for clinical use; however, they have issues of adverse effects and dual targeting of disease symptoms and transmission remains to be improved. Development of new drugs is therefore urgently needed. An untargeted lipidomics analysis recently revealed structural uniqueness of the Entamoeba lipidome at different stages of the parasite's life cycle involving very long (26-30 carbons) and/or medium (8-12 carbons) acyl chains linked to glycerophospholipids and sphingolipids. Here, we investigated the physiology of this unique acyl chain diversity in Entamoeba, a non-photosynthetic protist. We characterized E. histolytica fatty acid elongases (EhFAEs), which are typically components of the fatty acid elongation cycle of photosynthetic protists and plants. An approach combining genetics and lipidomics revealed that EhFAEs are involved in the production of medium and very long acyl chains in E. histolytica. This approach also showed that the K3 group herbicides, flufenacet, cafenstrole, and fenoxasulfone, inhibited the production of very long acyl chains, thereby impairing Entamoeba trophozoite proliferation and cyst formation. Importantly, none of these three compounds showed toxicity to a human cell line; therefore, EhFAEs are reasonable targets for developing new anti-amebiasis drugs and these compounds are promising leads for such drugs. Interestingly, in the Amoebazoan lineage, gain and loss of the genes encoding two different types of fatty acid elongase have occurred during evolution, which may be relevant to parasite adaptation. Acyl chain diversity in lipids is therefore a unique and indispensable feature for parasitic adaptation of Entamoeba.
Assuntos
Entamoeba histolytica , Elongases de Ácidos Graxos , Elongases de Ácidos Graxos/metabolismo , Elongases de Ácidos Graxos/genética , Humanos , Entamoeba histolytica/efeitos dos fármacos , Entamoeba histolytica/genética , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/genética , Entamoeba/efeitos dos fármacos , Entamoeba/metabolismo , Amebíase/tratamento farmacológico , Amebíase/parasitologia , Entamebíase/parasitologia , Entamebíase/tratamento farmacológico , Entamebíase/metabolismo , Trofozoítos/efeitos dos fármacos , Trofozoítos/metabolismo , Antiprotozoários/farmacologia , Ácidos Graxos/metabolismoRESUMO
The study of propagation medium effects on lasers continues to be an active area of research. High energy laser (HEL) propagation through planetary atmosphere is particularly nuanced as the beam generates its own flow field and suffers from additional degrading effects. Herein, we construct experimental setups conducive to probing the physics of the laser-atmosphere interaction and generating validation datasets for high fidelity predictive software. Measured and derived parameters are presented, and predictive models are generated utilizing random forest regression.
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In this work, we report 14 novel quinazoline derivatives as immune checkpoint inhibitors, IDO1 and PD-L1. The antitumor screening of synthesized compounds on ovarian cancer cells indicated that compound V-d and V-l showed the most activity with IC50 values of about 5 µM. Intriguingly, compound V-d emerges as a stand out, triggering cell death through caspase-dependent and caspase-independent manners. More importantly, V-d presents its ability to hinder tumor sphere formation and re-sensitized cisplatin-resistant A2780 cells to cisplatin treatment. These findings suggest that compound V-d emerges as a promising lead candidate for the future development of immuno anticancer agents.
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Antineoplásicos , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores de Checkpoint Imunológico , Quinazolinas , Humanos , Quinazolinas/farmacologia , Quinazolinas/química , Quinazolinas/síntese química , Relação Estrutura-Atividade , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/síntese química , Inibidores de Checkpoint Imunológico/química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Estrutura Molecular , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Proliferação de Células/efeitos dos fármacos , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismoRESUMO
The epidemiology of vertebral fractures (VF) in underrepresented populations is not well-documented. This cohort study was part of a longitudinal osteoporosis research project with the aim of determining the prevalence, incidence, and risk factors for VF. 401 individuals (155 men) aged 50 years and older without a clinical diagnosis of VF were took radiographs at baseline and 2 years later. VF were ascertained using the Genant's semi-quantitative method. Bone mineral density (BMD) of femoral neck and lumbar spine were measured by dual-energy X-ray absorptiometry (Hologic Inc). The association between VF and risk factors was analyzed by the multiple logistic regression. The 95% confidence interval for prevalence and incidence was estimated by exact Poisson test. At baseline, the prevalence of VF was 12.2% (n = 49, 95% CI 9.0-16.2%) and increased with advancing age with one-fifth of those aged 70 and older having a VF. During the follow-up period, we observed 6 new VF, making the incidence of 6.6/1000 person-years (n = 6, 95% CI 2.4-14.3). The risk of prevalent VF was associated with male gender (OR: 2.67; 95% CI 1.28-5.87) and T-score at the femoral neck (OR per one SD decrease: 1.1; 1.03-1.17). These data indicate that VF is common among adults, and that lower femoral neck BMD was a risk factor for VF.
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Osteoporose , Fraturas da Coluna Vertebral , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Estudos de Coortes , Prevalência , Incidência , Vietnã , Osteoporose/diagnóstico por imagem , Osteoporose/epidemiologia , Osteoporose/complicações , Densidade Óssea , Absorciometria de Fóton/métodos , Fatores de Risco , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/lesõesRESUMO
Sarcopenia, a condition characterized by muscle mass decline, is one of the leading health problems in the elderly. This study determined the rate of sarcopenia according to criteria by Asian Working Group for Sarcopenia (AWGS) and related factors in elderly people. A community-based cross-sectional study was conducted in 632 people aged 60 years or over in Ho Chi Minh City. Data were collected through a predefined questionnaire and direct measurement. Sarcopenia was identified based on the Inbody 770 machine and AWGS criteria. The prevalence of sarcopenia was 32.0%. Participants with advanced age, low education, unemployment, low level of family economics and frailty were more likely to have sarcopenia. Among these, frailty had the highest impact on sarcopenia, with significantly higher odds of having sarcopenia found in participants with pre-frailty (OR = 4.80, 95% CI 2.75-8.38, p < 0.001) and frailty (OR = 21.16, 95% CI 8.96-49.97, p < 0.001). In contrast, BMI was inversely associated with sarcopenia. Sarcopenia is prevalent in the Vietnamese elderly. Apart from social demographic characteristics including age, education, employment and family economic status, frailty appeared to be an important risk factor. Early screening, referral, and treatment of sarcopenia among the elderly having a high risk of sarcopenia are recommended.
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Fragilidade , Sarcopenia , Idoso , Humanos , Sarcopenia/diagnóstico , Fragilidade/epidemiologia , Fragilidade/diagnóstico , Prevalência , Estudos Transversais , Vietnã/epidemiologiaRESUMO
'Drug abuse' has been recognized as one of the most pressing epidemics in contemporary society. Traditional research has primarily focused on understanding how drugs induce neurotoxicity or degeneration within the central nervous system (CNS) and influence systems related to reward, motivation, and cravings. However, recent investigations have increasingly shifted their attention toward the detrimental consequences of drug abuse on the blood-brain barrier (BBB). The BBB is a structural component situated in brain vessels, responsible for separating brain tissue from external substances to maintain brain homeostasis. The BBB's function is governed by cellular interactions involving various elements of the 'neurovascular unit (NVU),' such as neurons, endothelial cells, astrocytes, pericytes, and microglia. Disruption of the NVU is closely linked to serious neurodegeneration. This review provides a comprehensive overview of the harmful effects of psychostimulant drugs on the BBB, highlighting the mechanisms through which drugs can damage the NVU. Additionally, the review proposes novel therapeutic targets aimed at protecting the BBB. By understanding the intricate relationships between drug abuse, BBB integrity, and NVU function, researchers and clinicians may uncover new strategies to mitigate the damaging impact of drug abuse on brain health.
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Células Endoteliais , Transtornos Relacionados ao Uso de Substâncias , Humanos , Encéfalo , Barreira Hematoencefálica , Sistema Nervoso Central , Transtornos Relacionados ao Uso de Substâncias/etiologiaRESUMO
Human sterile α motif and HD domain-containing protein 1 (SAMHD1) has deoxyribonucleoside triphosphohydrolase (dNTPase) activity that allows it to defend against human immunodeficiency virus type I (HIV-1) infections and regulate the cell cycle. Although SAMHD1 mutations have been identified in various cancer types, their role in cancer is unclear. Here, we aimed to investigate the oncogenic role of SAMHD1 in human clear cell renal cell carcinoma (ccRCC), particularly as a core molecule promoting cancer cell migration. We found that SAMHD1 participated in endocytosis and lamellipodia formation. Mechanistically, SAMHD1 contributed to the formation of the endosomal complex by binding to cortactin. Thereafter, SAMHD1-stimulated endosomal focal adhesion kinase (FAK) signaling activated Rac1, which promoted lamellipodia formation on the plasma membrane and enhanced the motility of ccRCC cells. Finally, we observed a strong correlation between SAMHD1 expression and the activation of FAK and cortactin in tumor tissues obtained from patients with ccRCC. In brief, these findings reveal that SAMHD1 is an oncogene that plays a pivotal role in ccRCC cell migration through the endosomal FAK-Rac1 signaling pathway.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Cortactina , Proteína-Tirosina Quinases de Adesão Focal , Proteína 1 com Domínio SAM e Domínio HD , Pseudópodes , Transdução de Sinais , Neoplasias Renais/genética , Proteínas rac1 de Ligação ao GTP/genéticaRESUMO
BACKGROUND: Invasive gastrointestinal surgery may be performed as an open or endoscopic procedure, such as laparoscopic semi-colon surgery, laparoscopic appendectomy, laparoscopic gastrectomy, and anal surgery, among other such operations. Regardless of the approach, the operative procedure interferes with the patient's gastrointestinal tract, necessitating the rational use of prophylactic antibiotics to improve treatment outcomes and minimize postoperative infections. OBJECTIVE: To investigate the prophylactic and postoperative antibiotic usage in patients who underwent invasive gastrointestinal surgery, and to identify factors associated with postoperative infection. DESIGN: This descriptive, cross-sectional study included 112 patients who underwent invasive gastrointestinal surgery at the Department of Gastroenterology, Thong Nhat Hospital. We conducted a cross-sectional study in all inpatients aged 18 years and older, who underwent invasive gastrointestinal surgery between January 2020 and December 2020. We recorded patient characteristics, the administration and appropriateness of antibiotics, as well as treatment outcomes. The appropriateness of prophylactic and postoperative antibiotic usage was assessed based on 2015 Vietnamese national guideline for antibiotic use. Multivariable logistic regression analysis was used to determine the factors associated with postoperative infection. RESULTS: Patients' mean age was 59.7 ± 17.2 years. Most surgeries (89.3%) were clean-contaminated procedures. The rates of appropriate types of antibiotics selected, doses, and overall rates of appropriateness of antibiotic prophylaxis were 68.0%, 76.4% and 54.7%, respectively. Of the patients investigated, 34.8% had at least one sign of postoperative infection; the overall appropriate rate of postoperative antibiotic was 38.5%. Old age was associated with postoperative infection and longer length of hospitalization. CONCLUSION: Implementation of the guidelines recommended for the prophylactic and therapeutic use of antibiotics is essential to improve treatment outcomes.
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Antibacterianos , Hospitais , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Antibacterianos/uso terapêutico , Estudos Transversais , Complicações Pós-Operatórias , Gastrectomia/efeitos adversos , Povo AsiáticoRESUMO
Deep learning, in recent times, has made remarkable strides when it comes to impressive performance for many tasks, including medical image processing. One of the contributing factors to these advancements is the emergence of large medical image datasets. However, it is exceedingly expensive and time-consuming to construct a large and trustworthy medical dataset; hence, there has been multiple research leveraging medical reports to automatically extract labels for data. The majority of this labor, however, is performed in English. In this work, we propose a data collecting and annotation pipeline that extracts information from Vietnamese radiology reports to provide accurate labels for chest X-ray (CXR) images. This can benefit Vietnamese radiologists and clinicians by annotating data that closely match their endemic diagnosis categories which may vary from country to country. To assess the efficacy of the proposed labeling technique, we built a CXR dataset containing 9,752 studies and evaluated our pipeline using a subset of this dataset. With an F1-score of at least 0.9923, the evaluation demonstrates that our labeling tool performs precisely and consistently across all classes. After building the dataset, we train deep learning models that leverage knowledge transferred from large public CXR datasets. We employ a variety of loss functions to overcome the curse of imbalanced multi-label datasets and conduct experiments with various model architectures to select the one that delivers the best performance. Our best model (CheXpert-pretrained EfficientNet-B2) yields an F1-score of 0.6989 (95% CI 0.6740, 0.7240), AUC of 0.7912, sensitivity of 0.7064 and specificity of 0.8760 for the abnormal diagnosis in general. Finally, we demonstrate that our coarse classification (based on five specific locations of abnormalities) yields comparable results to fine classification (twelve pathologies) on the benchmark CheXpert dataset for general anomaly detection while delivering better performance in terms of the average performance of all classes.
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Aprendizado Profundo , Radiologia , Humanos , Tórax/diagnóstico por imagem , Radiografia Torácica/métodos , Povo AsiáticoRESUMO
In the presence of physiological monovalent cations, thousands of RNA G-rich sequences can form parallel G-quadruplexes (G4s) unless RNA-binding proteins inhibit, destabilize, or resolve the formation of such secondary RNA structures. Here, we have used a disease-relevant model system to investigate the biophysical properties of the RNA-binding protein HNRNPH1's interaction with G-rich sequences. We demonstrate the importance of two EWSR1-exon 8 G-rich regions in mediating the exclusion of this exon from the oncogenic EWS-FLI1 transcripts expressed in a subset of Ewing sarcomas, using complementary analysis of tumor data, long-read sequencing, and minigene studies. We determined that HNRNPH1 binds the EWSR1-exon 8 G-rich sequences with low nM affinities irrespective of whether in a non-G4 or G4 state but exhibits different kinetics depending on RNA structure. Specifically, HNRNPH1 associates and dissociates from G4-folded RNA faster than the identical sequences in a non-G4 state. Importantly, we demonstrate using gel shift and spectroscopic assays that HNRNPH1, particularly the qRRM1-qRRM2 domains, destabilizes the G4s formed by the EWSR1-exon 8 G-rich sequences in a non-catalytic fashion. Our results indicate that HNRNPH1's binding of G-rich sequences favors the accumulation of RNA in a non-G4 state and that this contributes to its regulation of RNA processing.
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Quadruplex G , Processamento Alternativo , Sequência de Bases , Oncogenes , RNA/química , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismoRESUMO
The dysregulation of fibroblast growth factor (FGF) signaling has been implicated in tumorigenesis, tumor progression, angiogenesis, and chemoresistance. The small-molecule AZD4547 is a potent inhibitor of FGF receptors. This study was performed to investigate the antitumor effects and determine the mechanistic details of AZD4547 in ovarian cancer cells. AZD4547 markedly inhibited the proliferation and increased the apoptosis of ovarian cancer cells. AZD4547 also suppressed the migration and invasion of ovarian cancer cells under nontoxic conditions. Furthermore, it attenuated the formation of spheroids and the self-renewal capacities of ovarian cancer stem cells and exerted an antiangiogenic effect. It also suppressed in vivo tumor growth in mice. Collectively, this study demonstrated the antitumor effect of AZD4547 in ovarian cancer cells and suggests that it is a promising agent for ovarian cancer therapy.
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Benzamidas/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Ovarianas/tratamento farmacológico , Piperazinas/farmacologia , Pirazóis/farmacologia , Receptores de Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Animais , Apoptose , Movimento Celular , Proliferação de Células , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Objectives: We explored the association of underlying health conditions (UHC) with depression and anxiety, and examined the modification effects of suspected COVID-19 symptoms (S-COVID-19-S), health-related behaviors (HB), and preventive behaviors (PB). Methods: A cross-sectional study was conducted on 8,291 outpatients aged 18-85 years, in 18 hospitals and health centers across Vietnam from 14th February to May 31, 2020. We collected the data regarding participant's characteristics, UHC, HB, PB, depression, and anxiety. Results: People with UHC had higher odds of depression (OR = 2.11; p < 0.001) and anxiety (OR = 2.86; p < 0.001) than those without UHC. The odds of depression and anxiety were significantly higher for those with UHC and S-COVID-19-S (p < 0.001); and were significantly lower for those had UHC and interacted with "unchanged/more" physical activity (p < 0.001), or "unchanged/more" drinking (p < 0.001 for only anxiety), or "unchanged/healthier" eating (p < 0.001), and high PB score (p < 0.001), as compared to those without UHC and without S-COVID-19-S, "never/stopped/less" physical activity, drinking, "less healthy" eating, and low PB score, respectively. Conclusion: S-COVID-19-S worsen psychological health in patients with UHC. Physical activity, drinking, healthier eating, and high PB score were protective factors.
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Ansiedade , COVID-19 , Comorbidade , Depressão , Pacientes Ambulatoriais , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/psicologia , Estudos Transversais , Depressão/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais/psicologia , Pacientes Ambulatoriais/estatística & dados numéricos , Vietnã/epidemiologia , Adulto JovemRESUMO
To extend the value of biosensor-SPR in the characterization of DNA recognition by nucleoproteins, we report a comparative analysis of DNA-facilitated target search by two ETS-family transcription factors: Elk1 and ETV6. ETS domains represent an attractive system for developing biosensor-based techniques due to a broad range of physicochemical properties encoded within a highly conserved DNA-binding motif. Building on a biosensor approach in which the protein is quantitatively sequestered and presented to immobilized cognate DNA as nonspecific complexes, we assessed the impact of intrinsic cognate and nonspecific affinities on long-range (intersegmental) target search. The equilibrium constants of DNA-facilitated binding were sensitive to the intrinsic binding properties of the proteins such that their relative specificity for cognate DNA were reinforced when binding occurred by transfer vs. without nonspecific DNA. Direct measurement of association and dissociation kinetics revealed ionic features of the activated complex that evidenced DNA-facilitated dissociation, even though Elk1 and ETV6 harbor only a single DNA-binding surface. At salt concentrations that masked the effects of nonspecific pre-binding at equilibrium, the dissociation kinetics of cognate binding were nevertheless distinct from conditions under which nonspecific DNA was absent. These results further strengthen the significance of long-range DNA-facilitated translocation in the physiologic environment.
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DNA/análise , Nucleoproteínas/química , Sítios de Ligação , Técnicas Biossensoriais , Escherichia coli/genética , Nucleoproteínas/genética , Ligação Proteica , Proteínas Proto-Oncogênicas c-ets/química , Proteínas Repressoras/química , Ressonância de Plasmônio de Superfície , Proteínas Elk-1 do Domínio ets/química , Variante 6 da Proteína do Fator de Translocação ETSRESUMO
Electrostatic protein/DNA interactions arise from the neutralization of the DNA phosphodiester backbone as well as coupled exchanges by charged protein residues as salt bridges or with mobile ions. Much focus has been and continues to be paid to interfacial ion pairs with DNA. The role of extra-interfacial ionic interactions, particularly as dynamic drivers of DNA sequence selectivity, remain poorly known. The ETS family of transcription factors represents an attractive model for addressing this knowledge gap given their diverse ionic composition in primary structures that fold to a tightly conserved DNA-binding motif. To probe the importance of extra-interfacial salt bridges in DNA recognition, we compared the salt-dependent binding by Elk1 with ETV6, two ETS homologs differing markedly in ionic composition. While both proteins exhibit salt-dependent binding with cognate DNA that corresponds to interfacial phosphate contacts, their nonspecific binding diverges from cognate binding as well as each other. Molecular dynamics simulations in explicit solvent, which generated ionic interactions in agreement with the experimental binding data, revealed distinct salt-bridge dynamics in the nonspecific complexes formed by the two proteins. Impaired DNA contact by ETV6 resulted in fewer backbone contacts in the nonspecific complex, while Elk1 exhibited a redistribution of extra-interfacial salt bridges via residues that are non-conserved between the two ETS relatives. Thus, primary structure variation in ionic residues can encode highly differentiated specificity mechanisms in a highly conserved DNA-binding motif.
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DNA/química , Simulação de Dinâmica Molecular , Proteínas Proto-Oncogênicas c-ets/química , Proteínas Repressoras/química , Proteínas Elk-1 do Domínio ets/química , Teoria da Densidade Funcional , Humanos , Variante 6 da Proteína do Fator de Translocação ETSRESUMO
Background: The COVID-19 pandemic causes a huge burden for affected countries. Several public health interventions were applied to contain the infection. However, the pandemic itself and the lockdown measure negatively influence people's lifestyles and psychological health. Purpose: To explore determinants of healthy dietary intake and depression, and examine the interaction between healthy dietary intake and COVID-19 lockdown on depression. Methods: A cross-sectional study was conducted at 18 hospitals and health centers from February 14 to May 31, 2020. Data of 8,291 outpatients were collected including patients' characteristics, clinical parameters, health literacy, healthy dietary intake (using the healthy eating score, HES), other health-related behaviors, and depression (using the patient health questionnaire, PHQ). Depression was defined as PHQ score ≥ 10. Results: Protective factors of healthy dietary intake and depression were higher education, better medication payment ability, higher social status, more physical activity, and higher health literacy, whereas older age, ever married, own business or other types of occupation, lockdown, suspected COVID-19 symptoms, and comorbidity were associated with lower HES scores and a higher depression likelihood. Besides, overweight/obesity and alcohol drinking were associated with lower HES scores. As compared with patients not under lockdown and with lowest HES score, those who were under lockdown and with lowest HES score had 10.6 times higher depression likelihood (odds ratio, OR, 10.60; 95% CI 6.88, 16.32; p < 0.001), whereas people with higher HES score had 15% lower depression likelihood (OR 0.85; 95% CI 0.82, 0.89; p < 0.001). Conclusions: Healthy dietary intake and depression were determined by several sociodemographic, clinical, and behavioral factors. Lockdown measure affects people's dietary intake behavior and depression. Importantly, healthy dietary intake potentially modifies the negative effect of lockdown on depression.
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OBJECTIVES: We examined impacts and interactions of COVID-19 response involvement, health-related behaviours and health literacy (HL) on anxiety, depression, and health-related quality of life (HRQoL) among healthcare workers (HCWs). DESIGN: A cross-sectional study was conducted. Data were collected 6 April to 19 April 2020 using online-based, self-administered questionnaires. SETTING: 19 hospitals and health centres in Vietnam. PARTICIPANTS: 7 124 HCWs aged 21-60 years. RESULTS: The COVID-19 response-involved HCWs had higher anxiety likelihood (OR (95% CI)=4.41 (3.53 to 5.51)), higher depression likelihood (OR(95% CI)=3.31 (2.71 to 4.05)) and lower HRQoL score (coefficient, b(95% CI)=-2.14 (-2.89 to -1.38)), compared with uninvolved HCWs. Overall, HCWs who smoked or drank at unchanged/increased levels had higher likelihood of anxiety, depression and lower HRQoL scores; those with unchanged/healthier eating, unchanged/more physical activity and higher HL scores had lower likelihood of anxiety, depression and higher HRQoL scores. In comparison to uninvolved HCWs who smoked or drank at never/stopped/reduced levels, involved HCWs with unchanged/increased smoking or drinking had lower anxiety likelihood (OR(95% CI)=0.34 (0.14 to 0.83)) or (OR(95% CI)=0.26 (0.11 to 0.60)), and lower depression likelihood (OR(95% CI)=0.33 (0.15 to 0.74)) or (OR(95% CI)=0.24 (0.11 to 0.53)), respectively. In comparison with uninvolved HCWs who exercised at never/stopped/reduced levels, or with those in the lowest HL quartile, involved HCWs with unchanged/increased exercise or with one-quartile HL increment reported lower anxiety likelihood (OR(95% CI)=0.50 (0.31 to 0.81)) or (OR(95% CI)=0.57 (0.45 to 0.71)), lower depression likelihood (OR(95% CI)=0.40 (0.27 to 0.61)) or (OR(95% CI)=0.63 (0.52 to 0.76)), and higher HRQoL scores (b(95% CI)=2.08 (0.58 to 3.58)), or (b(95% CI)=1.10 (0.42 to 1.78)), respectively. CONCLUSIONS: Physical activity and higher HL were found to protect against anxiety and depression and were associated with higher HRQoL. Unexpectedly, smoking and drinking were also found to be coping behaviours. It is important to have strategic approaches that protect HCWs' mental health and HRQoL.
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COVID-19/psicologia , Comportamentos Relacionados com a Saúde , Letramento em Saúde/estatística & dados numéricos , Pessoal de Saúde/psicologia , Qualidade de Vida , Adulto , Ansiedade/epidemiologia , Ansiedade/psicologia , Estudos Transversais , Depressão/epidemiologia , Depressão/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2 , Inquéritos e Questionários , Vietnã/epidemiologia , Adulto JovemRESUMO
BACKGROUND: The COVID-19 pandemic has imposed a heavy burden on health care systems and governments. Health literacy (HL) and eHealth literacy (as measured by the eHealth Literacy Scale [eHEALS]) are recognized as strategic public health elements but they have been underestimated during the pandemic. HL, eHEALS score, practices, lifestyles, and the health status of health care workers (HCWs) play crucial roles in containing the COVID-19 pandemic. OBJECTIVE: The aim of this study is to evaluate the psychometric properties of the eHEALS and examine associations of HL and eHEALS scores with adherence to infection prevention and control (IPC) procedures, lifestyle changes, and suspected COVID-19 symptoms among HCWs during lockdown. METHODS: We conducted an online survey of 5209 HCWs from 15 hospitals and health centers across Vietnam from April 6 to April 19, 2020. Participants answered questions related to sociodemographics, HL, eHEALS, adherence to IPC procedures, behavior changes in eating, smoking, drinking, and physical activity, and suspected COVID-19 symptoms. Principal component analysis, correlation analysis, and bivariate and multivariate linear and logistic regression models were used to validate the eHEALS and examine associations. RESULTS: The eHEALS had a satisfactory construct validity with 8 items highly loaded on one component, with factor loadings ranked from 0.78 to 0.92 explaining 76.34% of variance; satisfactory criterion validity as correlated with HL (ρ=0.42); satisfactory convergent validity with high item-scale correlations (ρ=0.80-0.84); and high internal consistency (Cronbach α=.95). HL and eHEALS scores were significantly higher in men (unstandardized coefficient [B]=1.01, 95% CI 0.57-1.45, P<.001; B=0.72, 95% CI 0.43-1.00, P<.001), those with a better ability to pay for medication (B=1.65, 95% CI 1.25-2.05, P<.001; B=0.60, 95% CI 0.34-0.86, P<.001), doctors (B=1.29, 95% CI 0.73-1.84, P<.001; B 0.56, 95% CI 0.20-0.93, P=.003), and those with epidemic containment experience (B=1.96, 95% CI 1.56-2.37, P<.001; B=0.64, 95% CI 0.38-0.91, P<.001), as compared to their counterparts, respectively. HCWs with higher HL or eHEALS scores had better adherence to IPC procedures (B=0.13, 95% CI 0.10-0.15, P<.001; B=0.22, 95% CI 0.19-0.26, P<.001), had a higher likelihood of healthy eating (odds ratio [OR] 1.04, 95% CI 1.01-1.06, P=.001; OR 1.04, 95% CI 1.02-1.07, P=.002), were more physically active (OR 1.03, 95% CI 1.02-1.03, P<.001; OR 1.04, 95% CI 1.03-1.05, P<.001), and had a lower likelihood of suspected COVID-19 symptoms (OR 0.97, 95% CI 0.96-0.98, P<.001; OR 0.96, 95% CI 0.95-0.98, P<.001), respectively. CONCLUSIONS: The eHEALS is a valid and reliable survey tool. Gender, ability to pay for medication, profession, and epidemic containment experience were independent predictors of HL and eHEALS scores. HCWs with higher HL or eHEALS scores had better adherence to IPC procedures, healthier lifestyles, and a lower likelihood of suspected COVID-19 symptoms. Efforts to improve HCWs' HL and eHEALS scores can help to contain the COVID-19 pandemic and minimize its consequences.
Assuntos
COVID-19/epidemiologia , Letramento em Saúde/métodos , Pessoal de Saúde/normas , Psicometria/métodos , SARS-CoV-2/patogenicidade , Telemedicina/métodos , Adulto , COVID-19/prevenção & controle , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Inquéritos e Questionários , Adulto JovemRESUMO
Targeting of genomic quadruplexes is an approach to treating complex human cancers. We describe a series of tetra-substituted naphthalene diimide (ND) derivatives with a phenyl substituent directly attached to the ND core. The lead compound (SOP1812) has 10 times superior cellular and in vivo activity compared with previous ND compounds and nanomolar binding to human quadruplexes. The pharmacological properties of SOP1812 indicate good bioavailability, which is consistent with the in vivo activity in xenograft and genetic models for pancreatic cancer. Transcriptome analysis shows that it down-regulates several cancer gene pathways, including Wnt/ß-catenin signaling.
RESUMO
Interactions are reported of three representative naphthalenediimide derivatives with three quadruplex targets, from the promoter region of the telomerase (hTERT) gene, a human telomeric DNA quadruplex, and a telomeric RNA quadruplex (TERRA). Thermal melting studies showed that these compounds strongly stabilize the quadruplexes, with weak stabilization of a duplex DNA. Binding studies by surface plasmon resonance and fluorescence spectroscopy found that the compounds bind to the quadruplexes with nanomolar equilibrium dissociation constants. Plausible topologies for the quadruplex complexes were deduced from CD spectra, which together with the surface plasmon resonance data indicate that the quadruplexes with parallel quadruplex folds are preferred by two compounds, which was confirmed by qualitative molecular modeling.
RESUMO
Arrest defective 1 (ARD1), also known as N(alpha)-acetyltransferase 10 (NAA10) was originally identified as an N-terminal acetyltransferase (NAT) that catalyzes the acetylation of N-termini of newly synthesized peptides. After that, mammalian ARD1/NAA10 expanded its' role to lysine acetyltransferase (KAT) that post-translationally acetylates internal lysine residues of proteins. ARD1/NAA10 is the only enzyme with both NAT and KAT activities. However, recent studies on the role of human ARD1/NAA10 (hARD1/NAA10) in lysine acetylation are contradictory, as crystal structure and in vitro acetylation assay results revealed the lack of KAT activity. Thus, the role of hARD1/NAA10 in lysine acetylation is still debating. Here, we found a clue that possibly explains these complicated and controversial results on KAT activity of hARD1/NAA10. Recombinant hARD1/NAA10 exhibited KAT activity, which disappeared soon in vitro. Size-exclusion analysis revealed that most recombinant hARD1/NAA10 formed oligomers over time, resulting in the loss of KAT activity. While oligomeric recombinant hARD1/NAA10 lost its ability for lysine acetylation, its monomeric form clearly exhibited lysine acetylation activity in vitro. We also characterized the KAT activity of hARD1/NAA10 that was influenced by several experimental conditions, including concentration of reactants and reaction time. Taken together, our study proves that recombinant hARD1/NAA10 exhibits KAT activity in vitro but only under accurate conditions, including reactant concentrations and reaction duration.