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Background: Protease-activated receptor 1 (PAR1) is expressed in human platelets and can be activated by low concentrations of thrombin. Vorapaxar, a selective antagonist of PAR1, inhibits thrombin-induced calcium mobilization in human platelet, which is associated with an increased risk of bleeding. Conversely, the administration of a positive allosteric modulator (PAM) of PAR1 may pose a substantial risk of thrombosis due to inducing excessive platelet activation. In this study, we discovered a novel PAM of PAR1 and investigated the effect of enhanced PAR1 activation by PAM of PAR1 on platelet activation. Methods: To find PAMs of PAR1, a cell-based screen was performed in HT29 cells, and finally, gestodene, an oral contraceptive drug (OC), was identified as a novel PAM of PAR1. The mechanism of action of gestodene and its effects on platelet activation were investigated in human megakaryocytic leukemia cell line MEG-01 cells and human platelet. Results: Gestodene enhanced both thrombin- and PAR1-activating peptide (AP)-induced intracellular calcium levels in a dose-dependent manner without altering PAR2 and PAR4 activity. Gestodene significantly increased PAR1-AP-induced internalization of PAR1 and phosphorylation of ERK1/2, and the enhancing effects were significantly blocked by vorapaxar. Furthermore, gestodene potently increased PAR1-AP induced morphological changes in MEG-01 cells. Remarkably, in human blood, gestodene exerted a robust augmentation of PAR1-AP-induced platelet aggregation, and vorapaxar effectively attenuated the gestodene-induced enhancement of platelet aggregation mediated by PAR1. Conclusion: Gestodene is a selective PAM of PAR1 and suggest one possible mechanism for the increased risk of venous thromboembolism associated with OCs containing gestodene.
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Spinal cord injury (SCI) is associated with substantial healthcare challenges, frequently resulting in enduring sensory and motor deficits alongside various chronic complications. While advanced regenerative therapies have shown promise in preclinical research, their translation into clinical application has been limited. In response, this study utilized a comprehensive network meta-analysis to evaluate the effectiveness of neural stem/progenitor cell (NSPC) transplantation across animal models of SCI. We analyzed 363 outcomes from 55 distinct studies, categorizing the treatments into NSPCs alone (cell only), NSPCs with scaffolds (cell + scaffold), NSPCs with hydrogels (cell + hydrogel), standalone scaffolds (scaffold), standalone hydrogels (hydrogel), and control groups. Our analysis demonstrated significant enhancements in motor recovery, especially in gait function, within the NSPC treatment groups. Notably, the cell only group showed considerable improvements (standardized mean difference [SMD], 2.05; 95 % credible interval [CrI]: 1.08 to 3.10, p < 0.01), as did the cell + scaffold group (SMD, 3.73; 95 % CrI: 2.26 to 5.22, p < 0.001) and the cell + hydrogel group (SMD, 3.37; 95 % CrI: 1.02 to 5.78, p < 0.05) compared to controls. These therapeutic combinations not only reduced lesion cavity size but also enhanced neuronal regeneration, outperforming the cell only treatments. By integrating NSPCs with supportive biomaterials, our findings pave the way for refining these regenerative strategies to optimize their potential in clinical SCI treatment. Although there is no overall violation of consistency, the comparison of effect sizes between individual treatments should be interpreted in light of the inconsistency. STATEMENT OF SIGNIFICANCE: This study presents a comprehensive network meta-analysis exploring the efficacy of neural stem cell (NSC) transplantation, with and without biomaterials, in animal models of spinal cord injury (SCI). We demonstrate that NSCs, particularly when combined with biomaterials like scaffolds or hydrogels, significantly enhance motor and histological recovery post-SCI. These findings underscore the potential of NSC-based therapies, augmented with biomaterials, to advance SCI treatment, offering new insights into regenerative strategies that could significantly impact clinical practices.
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Materiais Biocompatíveis , Células-Tronco Neurais , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/patologia , Células-Tronco Neurais/transplante , Células-Tronco Neurais/citologia , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Humanos , Transplante de Células-Tronco , Hidrogéis/química , Hidrogéis/farmacologia , Recuperação de Função Fisiológica , Metanálise em Rede , Alicerces Teciduais/químicaRESUMO
Anoctamin1 (ANO1), a calcium-activated chloride channel, is overexpressed in a variety of cancer cells, including prostate cancer, and is involved in cancer cell proliferation, migration, and invasion. Inhibition of ANO1 in these cancer cells exhibits anticancer effects. In this study, we conducted a screening to identify novel ANO1 inhibitors with anticancer effects using PC-3 human prostate carcinoma cells. Screening of 2978 approved and investigational drugs revealed that hemin is a novel ANO1 inhibitor with an IC50 value of 0.45 µM. Notably, hemin had no significant effect on intracellular calcium signaling and cystic fibrosis transmembrane conductance regulator (CFTR), a cyclic AMP (cAMP)-regulated chloride channel, and it showed a weak inhibitory effect on ANO2 at 3 µM, a concentration that completely inhibits ANO1. Interestingly, hemin also significantly decreased ANO1 protein levels and strongly inhibited the cell proliferation and migration of PC-3 cells in an ANO1-dependent manner. Furthermore, it strongly induced caspase-3 activation, PARP degradation, and apoptosis in PC-3 cells. These findings suggest that hemin possesses anticancer properties via ANO1 inhibition and could be considered for development as a novel treatment for prostate cancer.
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Anoctamina-1 , Antineoplásicos , Hemina , Proteínas de Neoplasias , Neoplasias da Próstata , Humanos , Masculino , Anoctamina-1/metabolismo , Anoctamina-1/antagonistas & inibidores , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Hemina/farmacologia , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/antagonistas & inibidores , Células PC-3 , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologiaRESUMO
OBJECTIVE: This study aimed to examine maternal and neonatal factors in cesarean deliveries due to dystocia, including cephalopelvic disproportion, latent-phase prolongation, and fetal malposition or malpresentation. Additionally, we sought to compare the differences between the dystocia subgroups. METHOD AND MATERIALS: This retrospective case-control study included women who delivered between January 2010 and June 2021 after 37 weeks of pregnancy and underwent abdominal-pelvic CT scans within 5 years before and after delivery. Neonatal factors were extracted from medical charts immediately after delivery. RESULTS: Among the 292 women studied, those with cesarean deliveries for dystocia were older (mean ± SD, 34.2 ± 4.27 vs. 32.2 ± 3.8, p-value = 0.002), had higher pre-pregnancy BMI (22.7 ± 3.67 vs. 21.4 ± 3.48, p-value = 0.012) and term-BMI (27.4 ± 3.72 vs. 25.9 ± 3.66, p-value = 0.010), shorter interspinous distance (ISD, the distance between ischial spine) (10.8 ± 0.76 vs. 11.2 ± 0.85 cm, p-value = 0.003), and longer head circumference (HC) (35 ± 1.47 vs. 34.4 ± 1.36 cm, p-value = 0.003) compared to those who had vaginal deliveries. Univariate logistic regression for dystocia revealed associations between HC/maternal height and HC/ISD ratios (OR, 2.02 [95% confidence interval, CI, 1.4 ~ 2.92], 12.13 [3.2 ~ 46.04], respectively). Multivariate logistic analysis indicated that maternal age, ISD, and HC were significant factors for dystocia (OR, 1.11 [95% CI, 1.01 ~ 1.21], 0.49 [0.26 ~ 0.91], 1.53 [1.07 ~ 2.19], respectively). The subgroup with latent-phase prolongation exhibited the lowest birthweight/term-BMI ratio (124 ± 18.8 vs. 113 ± 10.3 vs. 134 ± 19.1, p-value = 0.013). CONCLUSION: The HC/ISD ratio emerged as a crucial predictor of dystocia, suggesting that reducing term-BMI could potentially mitigate latent-phase prolongation. Further research assessing the maternal mid-pelvis during pregnancy and labor is warranted, along with efforts to reduce BMI during pregnancy.
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Distocia , Cabeça , Humanos , Feminino , Gravidez , Estudos Retrospectivos , Adulto , Estudos de Casos e Controles , Recém-Nascido , Cabeça/diagnóstico por imagem , Desproporção Cefalopélvica/diagnóstico por imagem , Pelve/diagnóstico por imagem , Cesárea/estatística & dados numéricos , CefalometriaRESUMO
(1) Background: This study investigated the epidemiology and viral connections of Henoch-Schönlein purpura (HSP) using information from the Korea Disease Control and Prevention Agency and the Health Insurance Review and Assessment database. (2) Method: Between 2016 and 2019, a total of 25,443 patients with HSP were identified, with 51.3% of patients under the age of 20 years and the highest incidence in March. (3) Results: The autoregressive integrated moving average model and Granger causality test were used to analyze the association between the virus positivity detection rate and HSP incidence. (4) Conclusions: The incidence of HSP was associated with rotavirus, bocavirus, parainfluenza virus, and respiratory syncytial virus in individuals under 20 years of age, whereas adenovirus, respiratory syncytial virus, and norovirus were associated with individuals above that age.
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The epidermal growth factor receptor (EGFR), also known as ErbB1 and HER1, belongs to the receptor tyrosine kinase family. EGFR serves as the primary driver in non-small-cell lung cancer (NSCLC) and is a promising therapeutic target for NSCLC. In this study, we synthesized a novel chemical library based on a benzofuran-indole hybrid scaffold and identified 8aa as a potent and selective EGFR inhibitor. Interestingly, 8aa not only showed selective anticancer effects against NSCLC cell lines, PC9, and A549, but it also showed significant inhibitory effects against the double mutant L858R/T790M EGFR, which frequently occurs in NSCLC. In addition, in PC9 and A549 cells, 8aa potently blocked the EGFR signaling pathway, cell viability, and cell migration. These findings suggest that 8aa, a benzofuran-indole hybrid derivative, is a novel EGFR inhibitor that may be a potential candidate for the treatment of NSCLC patients with EGFR mutations.
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Following 3R (reduction, refinement, and replacement) principles, we employed the rat liver S9 fraction to mimic liver metabolism of curcumol having high in vitro IC50 on cancer cells. In HCT116 and HT29 colon cancer cells, the metabolites of curcumol by S9 fraction exerted more enhanced activity in inducing cell cycle arrest and apoptosis via regulating the expression of cyclin D1, CDK1, p21, PARP and Bcl-2 than curcumol. In addition, oral administration of curcumol at 4 mg/kg BW significantly suppressed the development of colon tumor induced by azoxymethane/dextran sulfate sodium, and induced cell cycle arrest and apoptosis in tumor tissues. In mass analysis, curcumenol and curzerene were identified as the metabolites of curcumol by S9 fraction metabolism. Taken together, curcumol metabolites showed the enhanced suppressive effect on colon cancer, suggesting that S9 fraction can be considered as simple, fast, and bio-mimicking platform for the screening of chemical libraries on different chronic diseases.
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Highly prevalent hepatitis B and hepatitis C virus (HBV and HCV) infections have been reported among individuals with diabetes. Given the frequently asymptomatic nature of hepatitis and the challenges associated with screening in some vulnerable populations such as diabetes patients, we conducted an investigation into the performance of various machine learning models for the identification of hepatitis in diabetic patients while also evaluating the significance of features. Analyzing NHANES data from 2013 to 2018, machine learning models were evaluated; random forest (RF), support vector machine (SVM), eXtreme Gradient Boosting (XGBoost), and least absolute shrinkage and selection operator (LASSO) along with stacked ensemble model. We performed hyperparameter tuning to improve the performance of the model, and selected important predictors using the best performance model. LASSO showed the highest predictive performance (AUC-ROC = 0.810) rather than other models. Illicit drug use, poverty, and race were highly ranked as predictive factors for developing hepatitis in diabetes patients. Our study demonstrated that a machine-learning-based model performed optimally in the detection of hepatitis among diabetes patients, achieving high performance. Furthermore, models and predictors evaluated from the current study, we expect, could be supportive information for developing screening or treatment methods for hepatitis care in diabetes patients.
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Diabetes Mellitus , Hepatite A , Hepatite B , Hepatite C , Viroses , Humanos , Inquéritos Nutricionais , Hepatite B/diagnóstico , Hepatite B/epidemiologia , Hepatite C/complicações , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Diabetes Mellitus/epidemiologia , Aprendizado de MáquinaRESUMO
OBJECTIVE: To predict the interspinous distance (ISD) using the relationship between female height and pelvimetric measures on magnetic resonance (MR) images. METHODS: We obtained measurements of the pubic arch angle (PAA), inlet-anteroposterior (AP) distance, mid-pelvis AP distance, outlet-AP distance, ISD, and ischial tuberosity distance using 710 pelvic MR images from nonpregnant reproductive-aged (21-50 years) women from January 2014 to June 2020. Patient height was also assessed from medical records. We determined the formula for predicting ISD using multiple regression analysis. RESULTS: The mean ± standard deviation of the height, PAA, inlet-AP distance, mid-pelvis AP distance, outlet-AP distance, ISD, and ischial tuberosity distance were 160.0 ± 5.5 cm, 87.31 ± 6.6°, 129.7 ± 9.0 mm, 119.7 ± 8.5 mm, 111.71 ± 8.90 mm, 108.88 ± 8.0 mm, and 121.97 ± 11.8 mm, respectively. Two significant regression formulas for predicting ISD were identified as follows: ISD = 0.24973 × height - 0.06724 × inlet-AP distance + 0.12166 × outlet-AP distance + 0.29233 × ischial tuberosity distance + 0.32524 × PAA (P < 0.001, R2 = 0.9973 [adjusted R2 = 0.9973]) and ISD = 0.40935 × height + 0.49761 × PAA (P < 0.001, R2 = 0.9965 [adjusted R2 = 0.9965]). CONCLUSION: ISD is the best predictor of obstructed labor. This study predicted ISD with 99% explanatory power using only the height and PAA. The PAA can be measured by transperineal ultrasound. This formula may successfully predict vaginal delivery or cephalopelvic disproportion.
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Distocia , Pelve , Gravidez , Humanos , Feminino , Adulto , Pelve/diagnóstico por imagem , Parto Obstétrico/métodos , Pelvimetria/métodos , Imageamento por Ressonância Magnética/métodosRESUMO
Amyloid generation plays essential roles in various human diseases, biological functions, and nanotechnology. However, developing efficient chemical and biological candidates for regulating amyloid fibrillation remains difficult because information on the molecular actions of modulators is insufficient. Thus, studies are needed to understand how the intermolecular physicochemical properties of the synthesised molecules and amyloid precursors influence amyloidogenesis. In this study, we synthesised a novel amphiphilic sub-nanosized material, arginine-arginine (RR)-bile acid (BA), by conjugating positively charged RR to hydrophobic BA. The effects of RR-BA on amyloid formation were investigated on α-synuclein (αSN) in Parkinson's disease and on K18 and amyloid-ß (1-42) (Aß42) in Alzheimer's disease. RR-BA showed no appreciable effect on the kinetics of K18 and Aß42 amyloid fibrillation because of their weak and non-specific interactions. However, RR-BA specifically bound to αSN with moderate binding affinity through electrostatic interactions between the positively charged RR and the negatively charged cluster in the C-terminus of αSN. In addition, hydrophobic BA in the αSN-RR-BA complex transiently condensed αSN for primary nucleation, thereby accelerating αSN amyloid fibrillation. We propose an electrostatic binding and hydrophobic condensation model of RR-BA-driven amyloid formation of αSN, which will contribute to the rational design and development of molecules for controlling amyloid aggregation in diverse fields.
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Doença de Alzheimer , Doença de Parkinson , Humanos , alfa-Sinucleína/química , Doença de Parkinson/metabolismo , Amiloide/química , Doença de Alzheimer/metabolismo , Peptídeos beta-AmiloidesRESUMO
A 9-month-old, female Pomeranian dog presented with vomiting and lethargy. Ultrasonography revealed multilobulated anechoic round shape structures at the ovarian and uterine locations. Through computed tomography scan, an extensive non-contrast multilobulated fluid-filled mass suspected of originating from the walls of the ovary, uterus, urinary bladder and rectum was observed. Ovariohysterectomy and urinary bladder biopsy were performed. Histopathological examination revealed numerous cystic lesions lined by plump cuboidal cells believed to be of epithelial origin. Immunohistochemical staining showed that the cyst-like lesions lining cells were strongly positive for lymphatic vessel endothelial hyaluronan receptor 1. Based on these results, lesions were identified as generalized lymphatic anomaly (GLA), in which lymphangiomas develop in multiple organs. After 6 months follow-up, the size of the cysts remaining in the region of the bladder did not undergo much change. GLA should be included in the differential diagnosis when multiple cystic lesions are interspersed in multiple organs.
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Numerous cathepsin B inhibitors have been developed and are under investigation as potential cancer treatments. They have been evaluated for their ability to inhibit cathepsin B activity and reduce tumor growth. However, they have shown critical limitations, including low anticancer efficacy and high toxicity, due to their low selectivity and delivery problems. In this study, we developed a novel peptide and drug conjugate (PDC)-based cathepsin B inhibitor using cathepsin-B-specific peptide (RR) and bile acid (BA). Interestingly, this RR and BA conjugate (RR-BA) was able to self-assemble in an aqueous solution, and as a result, it formed stable nanoparticles. The nano-sized RR-BA conjugate showed significant cathepsin B inhibitory effects and anticancer effects against mouse colorectal cancer (CT26) cells. Its therapeutic effect and low toxicity were also confirmed in CT26 tumor-bearing mice after intravenous injection. Therefore, based on these results, the RR-BA conjugate could be developed as an effective anticancer drug candidate for inhibiting cathepsin B in anticancer therapy.
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The Maf polymorphic toxin system is involved in conflict between strains found in pathogenic Neisseria species such as Neisseria meningitidis and Neisseria gonorrhoeae. The genes encoding the Maf polymorphic toxin system are found in specific genomic islands called maf genomic islands (MGIs). In the MGIs, the MafB and MafI encode toxin and immunity proteins, respectively. Although the C-terminal region of MafB (MafB-CT) is specific for toxic activity, the underlying enzymatic activity that renders MafB-CT toxic is unknown in many MafB proteins due to lack of homology with domain of known function. Here we present the crystal structure of the MafB2-CTMGI-2B16B6/MafI2MGI-2B16B6 complex from N. meningitidis B16B6. MafB2-CTMGI-2B16B6 displays an RNase A fold similar to mouse RNase 1, although the sequence identity is only ~ 14.0%. MafB2-CTMGI-2B16B6 forms a 1:1 complex with MafI2MGI-2B16B6 with a Kd value of ~ 40 nM. The complementary charge interaction of MafI2MGI-2B16B6 with the substrate binding surface of MafB2-CTMGI-2B16B6 suggests that MafI2MGI-2B16B6 inhibits MafB2-CTMGI-2B16B6 by blocking access of RNA to the catalytic site. An in vitro enzymatic assay showed that MafB2-CTMGI-2B16B6 has ribonuclease activity. Mutagenesis and cell toxicity assays demonstrated that His335, His402 and His409 are important for the toxic activity of MafB2-CTMGI-2B16B6, suggesting that these residues are critical for its ribonuclease activity. These data provide structural and biochemical evidence that the origin of the toxic activity of MafB2MGI-2B16B6 is the enzymatic activity degrading ribonucleotides.
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Ilhas Genômicas , Neisseria meningitidis , Animais , Camundongos , Interleucina-6 , Neisseria , Ribonucleases , Proteínas Proto-Oncogênicas c-mafRESUMO
Anoctamin1 (ANO1), a calcium-activated chloride channel, is involved in the proliferation, migration, and invasion of various cancer cells including head and neck squamous cell carcinoma, lung cancer, and prostate cancer. Inhibition of ANO1 activity or downregulation of ANO1 expression in these cancer cells is known to exhibit anticancer effects. Resveratrol, a natural polyphenol abundant in wines, grapes, berries, soybeans, and peanuts, shows a wide variety of biological effects including anti-inflammatory, antioxidant, and anticancer activities. In this study, we investigated the effects of two stereoisomers of resveratrol on ANO1 activity and found that cis- and trans-resveratrol inhibited ANO1 activity with different potencies. Cis- and trans-resveratrol inhibited ANO1 channel activity with IC50 values of 10.6 and 102 µM, respectively, and had no significant effect on intracellular calcium signaling at 10 and 100 µM, respectively. In addition, cis-resveratrol downregulated mRNA and protein expression levels of ANO1 more potently than trans-resveratrol in PC-3 prostate cancer cells. Cis- and trans-resveratrol significantly reduced cell proliferation and cell migration in an ANO1-dependent manner, and both resveratrol isomers strongly increased caspase-3 activity, PARP cleavage, and apoptotic sub-G1 phase ratio in PC-3 cells. These results revealed that cis-resveratrol is a potent inhibitor of ANO1 and exhibits ANO1-dependent anticancer activity against human metastatic prostate cancer PC-3 cells.
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Neoplasias de Cabeça e Pescoço , Neoplasias da Próstata , Masculino , Humanos , Resveratrol/farmacologia , Células PC-3 , Anoctamina-1/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Proteínas de Neoplasias/metabolismoRESUMO
A highly efficient approach to a new indolizine scaffold fused with pyrrolo[1,2-c]pyrimidine was achieved via one-pot three-component coupling followed by an oxidative cyclization reaction. The simple two-step sequence allowed rapid access to various tetracyclic compounds from commercially available starting materials with the formation of five new bonds. Here, we observed the effects of these compounds on cell viability in HepG2, H1299, HT29, AGS, and A549 cancer cell lines. Interestingly, this fused scaffold had more potent anticancer activity in hepatocellular carcinoma HepG2 and Huh7 cells than other cancer cells. In particular, 5r strongly decreased cell viability in HepG2 and Huh7 cells with an IC50 value of 0.22 ± 0.08 and 0.10 ± 0.11 µM, respectively, but had a very weak inhibitory effect on the cell viability of other cancer cell lines. In addition, 5r significantly inhibited cell migration and induced apoptosis in HepG2 and Huh7 cells via the activation of caspase-3 and cleavage of PARP in a dose-dependent manner. Notably, the co-treatment of 5r with gemcitabine resulted in the significant additional inhibition of cell viability in HepG2 and Huh7 cells. Our results suggest that 5r could be used to develop new chemotype anticancer agents against liver cancers.
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As an enveloped virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delivers its viral genome into host cells via fusion of the viral and cell membranes. Here, we show that ANO6/TMEM16F-mediated cell surface exposure of phosphatidylserine is critical for SARS-CoV-2 entry and that ANO6-selective inhibitors are effective against SARS-CoV-2 infections. Application of the SARS-CoV-2 Spike pseudotyped virus (SARS2-PsV) evokes a cytosolic Ca2+ elevation and ANO6-dependent phosphatidylserine externalization in ACE2/TMPRSS2-positive mammalian cells. A high-throughput screening of drug-like chemical libraries identifies three different structural classes of chemicals showing ANO6 inhibitory effects. Among them, A6-001 displays the highest potency and ANO6 selectivity and it inhibits the single-round infection of SARS2-PsV in ACE2/TMPRSS2-positive HEK 293T cells. More importantly, A6-001 strongly inhibits authentic SARS-CoV-2-induced phosphatidylserine scrambling and SARS-CoV-2 viral replications in Vero, Calu-3, and primarily cultured human nasal epithelial cells. These results provide mechanistic insights into the viral entry process and offer a potential target for pharmacological intervention to protect against coronavirus disease 2019 (COVID-19).
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Tratamento Farmacológico da COVID-19 , Enzima de Conversão de Angiotensina 2 , Animais , Anoctaminas , Humanos , Mamíferos/metabolismo , Fosfatidilserinas , Proteínas de Transferência de Fosfolipídeos/metabolismo , SARS-CoV-2 , Internalização do VírusRESUMO
BACKGROUND: Meditation has been increasingly adapted for healthy populations and participants with diseases. Its beneficial effects are still challenging to determine due to the heterogeneity and methodological obstacles regarding medical applications. This study aimed to integrate the features of therapeutic meditation in randomized controlled trials (RCTs). METHODS: We conducted a systematic review of RCTs with meditation for populations with diseases using the PubMed database through June 2021. We analyzed the characteristics of the diseases/disorders, participants, measurements, and their overall benefits. RESULTS: Among a total of 4855 references, 104 RCTs were determined and mainly applied mindfulness-based (51 RCTs), yoga-based (32 RCTs), and transcendental meditation (14 RCTs) to 10,139 patient-participants. These RCTs were conducted for participants with a total of 45 kinds of disorders; the most frequent being cancer, followed by musculoskeletal and connective tissue diseases and affective mood disorder. Seven symptoms or signs were frequently assessed: depressive mood, feeling anxious, quality of life, stress, sleep, pain, and fatigue. The RCTs showed a higher ratio of positive outcomes for sleep (73.9%) and fatigue (68.4%). CONCLUSIONS: This systematic review produced the comprehensive features of RCTs for therapeutic meditation. These results will help physicians and researchers further study clinical adaptations in the future as reference data.
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Meditação , Atenção Plena , Yoga , Ansiedade/terapia , Humanos , Meditação/psicologia , Atenção Plena/métodos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
STATEMENT OF PROBLEM: Selective laser melting (SLM) additive manufacturing (AM) technologies provide an alternative to conventional casting and milling procedures in fabricating metal-ceramic dental prostheses. However, the quality of porcelain bond strength to the SLM AM cobalt-chromium (Co-Cr) metal framework of a dental restoration is unclear. PURPOSE: The purpose of this systematic review and meta-analysis was to identify in vitro studies that reported the porcelain bond strength to SLM AM Co-Cr dental metal alloys and compare the porcelain bond strength values to cast, milled, and additively manufactured Co-Cr dental alloys. MATERIAL AND METHODS: An electronic systematic review was performed in different databases: MEDLINE/PubMed, EMBASE, World of Science, Cochrane, and Scopus. A manual search was also conducted. Studies that reported the porcelain bond strength to SLM Co-Cr metal alloys and in the English language were included. Two investigators evaluated the quality assessment of the studies by applying the JBI critical appraisal checklist for quasi-experimental studies (nonrandomized experimental studies). A third investigator was consulted to resolve lack of consensus. Two subgroups were created based on the test used, 3-point bend and shear bond strength tests. The porcelain bond strength of cast, milled, and AM Co-Cr dental alloys were compared. The I2 statistic and its associated P value were used to assess the heterogeneity between studies. The Eger test was used for determining significance of the funnel pots. RESULTS: A total of 216 studies were collected from the electronic and manual searches. After independently evaluating the titles and abstracts by the reviewers, 26 articles were identified. Three of these were excluded after full-text revision. The porcelain bond strength comparison between the cast and AM alloys for the 3-point bend subgroup revealed a significant result for overall effect (P<.001) favoring the SLM method with considerable heterogeneity (I2=83%, P<.001). Furthermore, the porcelain bond strength comparison between cast and milled alloys for the shear bond strength subgroup revealed a significant test for overall effect (P=.04) favoring milled procedures with a nonsignificant unimportant heterogeneity (I2= 0%, P<.47) and for the 3-point bend subgroup (P<.001) favoring milled specimens with a significant considerable heterogeneity (I2=79%, P<.001). CONCLUSIONS: The metal manufacturing method had no effect on the porcelain bond strength to Co-Cr dental metal alloys.
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Colagem Dentária , Porcelana Dentária , Porcelana Dentária/química , Ligas de Cromo/química , Ligas Metalo-Cerâmicas/química , Teste de Materiais , Propriedades de Superfície , Cobalto , Cromo , Ligas DentáriasRESUMO
The rapid increase in carbapenemase-producing Enterobacterales is a global health concern. During 2017-2020, a total of 44 Escherichia coli isolates co-harbouring blaNDM-5 and blaOXA-181 were collected from patients at 17 hospitals in Seoul and characterized based on antimicrobial susceptibility, resistance genes and plasmid replicons detected using polymerase chain reaction (PCR). Clonal relatedness was estimated using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). All isolates had an identical multidrug resistance profile, including resistance to carbapenems, cephalosporins, ciprofloxacin, tetracycline, and trimethoprim/sulfamethoxazole, and susceptibility to amikacin, colistin, and tigecycline. Resistance genes (blaCTX-M-15, blaCMY-2, blaTEM-1B, blaOXA-1, aac(6')-Ib-cr, and qnrS) and plasmid replicons (IncFIA, IncFIB, and IncX3) was observed in almost all isolates. All isolates belonged to ST410 and were genetically similar (>88% similarity), with some PFGE types shared among isolates from different hospitals. Analysis of the whole genome revealed that the isolates clustered together with other strains of the international high-risk clone ST410 B4/H24RxC from other countries. These findings underline the ongoing spread of the high-risk clone of NDM-5- and OXA-181-producing E. coli ST410 B4/H24RxC among hospitals in Seoul. Continuous monitoring and implementation of infection control measures are crucial to track and prevent further spread of these resistant strains.
Assuntos
Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Proteínas de Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , beta-Lactamases/genética , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/crescimento & desenvolvimento , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Carbapenêmicos/metabolismo , Eletroforese em Gel de Campo Pulsado , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/epidemiologia , Genoma Bacteriano/genética , Humanos , Testes de Sensibilidade Microbiana , Epidemiologia Molecular , Tipagem de Sequências Multilocus , República da Coreia/epidemiologia , Sequenciamento Completo do GenomaRESUMO
Colistin is often used as a drug of last resort against infections caused by multi-drug-resistant Gram-negative bacteria, including carbapenem-resistant Enterobacterales (CRE). Recently, the acquisition of mobile colistin resistance (mcr) genes by CRE has become a cause for concern. This study investigated the prevalence of mcr genes in CRE isolates in Seoul, Republic of Korea. In total, 3675 CRE strains were collected from patients between 2018 and 2019, and initially screened for mcr genes using multiplex polymerase chain reaction assays. Upon the identification of mcr-harbouring strains, colistin susceptibility tests, identification of carbapenemase and ß-lactamase genes, and plasmid replicon typing were performed. Clonal analysis was conducted using pulsed-field gel electrophoresis. mcr genes were detected in 2.2% (80/3675) of CRE strains. There were three mcr-1 carriers, one mcr-4.3 carrier, one mcr-4.3/mcr-9 carrier, 58 mcr-9 carriers, one mcr-9/mcr-10 carrier and 16 mcr-10 carriers among various Enterobacterales species, of which 60 were Enterobacter cloacae complex (ECC) strains. The prevalence of mcr genes in ECC strains was 20.5%. Molecular detection confirmed that 21.3% and 13.8% of mcr-harbouring strains shared blaNDM-1 or blaKPC-2, respectively. In addition, an IncHI2 replicon was identified in 71.7% of mcr-9 strains. Comparative analysis revealed not only a notable diversity of mcr carriers, but also clonal spreading or nosocomial outbreaks of some ECC strains. These findings revealed a silent distribution of mcr genes in CRE strains with high genetic heterogeneity in Seoul, underscoring the urgent need for timely intervention to control and prevent mcr dissemination.