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1.
J Korean Med Sci ; 39(21): e172, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38832477

RESUMO

BACKGROUND: We aimed to analyze the effects of an antimicrobial stewardship program (ASP) on the proportion of antimicrobial-resistant pathogens in bacteremia, antimicrobial use, and mortality in pediatric patients. METHODS: A retrospective single-center study was performed on pediatric inpatients under 19 years old who received systemic antimicrobial treatment from 2001 to 2019. A pediatric infectious disease attending physician started ASP in January 2008. The study period was divided into the pre-intervention (2001-2008) and the post-intervention (2009-2019) periods. The amount of antimicrobial use was defined as days of therapy per 1,000 patient-days, and the differences were compared using delta slope (= changes in slopes) between the two study periods by an interrupted time-series analysis. The proportion of resistant pathogens and the 30-day overall mortality rate were analyzed by the χ². RESULTS: The proportion of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bacteremia increased from 17% (39 of 235) in the pre-intervention period to 35% (189 of 533) in the post-intervention period (P < 0.001). The total amount of antimicrobial use significantly decreased after the introduction of ASP (delta slope value = -16.5; 95% confidence interval [CI], -30.6 to -2.3; P = 0.049). The 30-day overall mortality rate in patients with bacteremia did not increase, being 10% (55 of 564) in the pre-intervention and 10% (94 of 941) in the post-intervention period (P = 0.881). CONCLUSION: The introduction of ASP for pediatric patients reduced the delta slope of the total antimicrobial use without increasing the mortality rate despite an increased incidence of ESBL-producing gram-negative bacteremia.


Assuntos
Antibacterianos , Gestão de Antimicrobianos , Bacteriemia , Análise de Séries Temporais Interrompida , Klebsiella pneumoniae , Humanos , Estudos Retrospectivos , Criança , Bacteriemia/tratamento farmacológico , Bacteriemia/mortalidade , Bacteriemia/microbiologia , Feminino , Masculino , Pré-Escolar , Antibacterianos/uso terapêutico , Lactente , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Adolescente , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Hospitais Pediátricos
2.
Appl Microbiol Biotechnol ; 107(22): 6789-6798, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37725139

RESUMO

Congenital cytomegalovirus (CMV) infection is a common cause of sensorineural hearing loss and neurodevelopmental impairment in newborns. However, congenital CMV infection cannot be diagnosed using samples collected more than 3 weeks after birth because testing after this time cannot distinguish between congenital infection and postnatal infection. Herein, we developed a robust loop-mediated isothermal amplification (LAMP) assay for the large-scale screening of newborns for congenital CMV infection. In contrast to conventional quantitative polymerase chain reaction (qPCR), which detects CMV within a dynamic range of 1.0 × 106 to 1.0 × 102 copies/µL, our quantitative LAMP assay (qLAMP) detects CMV within a dynamic range of 1.1 × 108 to 1.1 × 103 copies/µL. Moreover, the turnaround time for obtaining results following DNA extraction is 90 min in qPCR but only 15 min in qLamp. The colorimetric LAMP assay can also detect CMV down to 1.1 × 103 copies/µL within 30 min, irrespective of the type of heat source. Our LAMP assay can be utilized in central laboratories as an alternative to conventional qPCR for quantitative CMV detection, or for point-of-care testing in low-resource environments, such as developing countries, via colorimetric naked-eye detection. KEY POINTS: • LAMP assay enables large-scale screening of newborns for congenital CMV infection. • LAMP allows colorimetric or quantitative detection of congenital CMV infection. • LAMP assay can be used as a point-of-care testing tool in low-resource environments.

3.
J Korean Med Sci ; 38(32): e248, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37582498

RESUMO

The pediatric population with comorbidities is a high-risk group for severe coronavirus disease 2019 (COVID-19). As of January 2023, the COVID-19 vaccination rate for at least two doses among Korean children 5-11 years is low at 1.1%. We summarized the COVID-19 vaccination status for the pediatric population (5-17 years) with comorbidities through July 2022 using the National Health Insurance Service database. Pediatric patients with comorbidities had higher vaccination rates than the general pediatric population (2.4% vs. 1.1% in 5-11-year-olds [P < 0.001], 76.5% vs. 66.1% in 12-17-year-olds [P < 0.001]). However, there were substantial differences according to comorbidity category, and the 2-dose vaccination rate was lowest among children with immunodeficiency in all age groups (1.1% in 5-11-year-olds, 51.2% in 12-17-year-olds). The COVID-19 vaccination rate among Korean children has remained stagnant at a low proportion despite ongoing outreach. Thus, more proactive strategies are needed alongside continuous surveillance.


Assuntos
COVID-19 , Humanos , Criança , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Comorbidade , Vacinação , República da Coreia/epidemiologia
4.
J Korean Med Sci ; 38(48): e361, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38084025

RESUMO

BACKGROUND: Pediatric urinary tract infection (UTI) caused by extended-spectrum ß-lactamase (ESBL)-positive gram-negative bacilli (GNB) has limited options for oral antibiotic treatment. The purpose of this study was to investigate the susceptibility of ESBL-positive Escherichia coli and Klebsiella pneumoniae isolates from pediatric urine samples to two oral antibiotics (fosfomycin and nitrofurantoin). METHODS: From November 2020 to April 2022, ESBL-positive E. coli and K. pneumoniae isolates from urine samples were collected at Samsung Medical Center, Seoul, Korea. Patients over 18 years of age or with malignancy were excluded. For repeated isolates from the same patient, only the first isolate was tested. Minimum inhibitory concentrations (MICs) were measured using agar (fosfomycin) or broth (nitrofurantoin) dilution methods. MIC50 and MIC90 were measured for fosfomycin and nitrofurantoin in both E. coli and K. pneumoniae. RESULTS: There were 117 isolates from 117 patients, with a median age of 7 months (range, 0.0-18.5 years). Among 117 isolates, 92.3% (108/117) were E. coli and 7.7% (9/117) were K. pneumoniae. Isolates from the pediatric intensive care unit (PICU) and general ward (GW) was 11.1% (13/117) and 88.9% (104/117), respectively. Among 108 E. coli isolates, MIC50 and MIC90 for fosfomycin were 0.5 µg/mL and 2 µg/mL, respectively. Fosfomycin susceptibility rate was 97.2% (105/108) with a breakpoint of 128 µg/mL. Fosfomycin susceptibility rate was significantly lower in PICU isolates than in GW isolates (81.8% vs. 99.0%, P = 0.027). For nitrofurantoin, both the MIC50 and MIC90 were 16 µg/mL. Nitrofurantoin susceptibility rate was 96.3% (104/108) with a breakpoint of 64 µg/mL based on Clinical and Laboratory Standards Institute guidelines. Among the nine K. pneumoniae isolates, the MIC50 and MIC90 for fosfomycin was 2 µg/mL and 32 µg/mL, respectively. MIC50 and MIC90 for nitrofurantoin were 64 µg/mL and 128 µg/mL, respectively. CONCLUSION: For uncomplicated UTI caused by ESBL-positive GNB in Korean children, treatment with fosfomycin and nitrofurantoin for E. coli infections can be considered as an effective oral therapy option.


Assuntos
Infecções por Escherichia coli , Fosfomicina , Infecções Urinárias , Humanos , Criança , Adolescente , Adulto , Recém-Nascido , Lactente , Fosfomicina/farmacologia , Fosfomicina/uso terapêutico , Nitrofurantoína/farmacologia , Nitrofurantoína/uso terapêutico , Escherichia coli , Klebsiella pneumoniae , beta-Lactamases , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções por Escherichia coli/tratamento farmacológico , Infecções Urinárias/tratamento farmacológico , Testes de Sensibilidade Microbiana
5.
J Korean Med Sci ; 38(1): e9, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36593690

RESUMO

BACKGROUND: We evaluated the household secondary attack rate (SAR) of the omicron and delta severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, according to the vaccination status of the index case and household contacts; further, in vaccinated index cases, we evaluated the effect of the antibody levels on household transmission. METHODS: A prospective cross-sectional study of 92 index cases and 197 quarantined household contacts was performed. Tests for SARS-CoV-2 variant type and antibody level were conducted in index cases, and results of polymerase chain reaction tests (during the quarantine period) were collected from contacts. Association of antibody levels in vaccinated index cases and SAR was evaluated by multivariate regression analysis. RESULTS: The SAR was higher in households exposed to omicron variant (42%) than in those exposed to delta variant (27%) (P = 0.040). SAR was 35% and 23% for unvaccinated and vaccinated delta variant exposed contacts, respectively. SAR was 44% and 41% for unvaccinated and vaccinated omicron exposed contacts, respectively. Booster dose immunisation of contacts or vaccination of index cases reduced SAR of vaccinated omicron variant exposed contacts. In a model with adjustment, anti-receptor-binding domain antibody levels in vaccinated index cases were inversely correlated with household transmission of both delta and omicron variants. Neutralising antibody levels had a similar relationship. CONCLUSION: Immunisation of household members may help to mitigate the current pandemic.


Assuntos
COVID-19 , Vacinas , Humanos , SARS-CoV-2/genética , Estudos Transversais , Estudos Prospectivos , COVID-19/prevenção & controle , Imunização Secundária
6.
J Community Psychol ; 49(7): 2383-2402, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34237159

RESUMO

The present study examines the associations between multiple measures of social trust and two outcomes of psychological wellbeing (happiness and depression) among South Korean adults (n = 1549) living in residential communities, that is, administrative districts (n = 77) in and around the capital city of Seoul. Based on multilevel modeling, we find that familial trust positively predicts happiness at both individual and contextual levels; and it negatively predicts depression at the individual level only. In comparison, peer trust is negatively related only to depression at the individual level, albeit marginally. Lastly, general trust significantly predicts both outcomes at the community, but not individual, level. These mixed findings suggest that the trust-wellbeing relationship depends critically on issues of definition (how the variables are conceptualized) and measurement (how they are operationalized according to different units of analysis). Our study offers implications for the literature on social determinants of mental health broadly and, more specifically, on the role of social trust.


Assuntos
Capital Social , Confiança , Adulto , Humanos , Saúde Mental , Análise Multinível , Inquéritos e Questionários
7.
Biochemistry ; 54(25): 3921-31, 2015 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-26053120

RESUMO

Antimicrobial peptides (AMPs) are important components of the host innate immune system. Papiliocin is a 37-residue AMP purified from larvae of the swallowtail butterfly Papilio xuthus. Magainin 2 is a 23-residue AMP purified from the skin of the African clawed frog Xenopus laevis. We designed an 18-residue hybrid peptide (PapMA) incorporating N-terminal residues 1-8 of papiliocin and N-terminal residues 4-12 of magainin 2, joined by a proline (Pro) hinge. PapMA showed high antimicrobial activity but was cytotoxic to mammalian cells. To decrease PapMA cytotoxicity, we designed a lysine (Lys) peptoid analogue, PapMA-k, which retained high antimicrobial activity but displayed cytotoxicity lower than that of PapMA. Fluorescent dye leakage experiments and confocal microscopy showed that PapMA targeted bacterial cell membranes whereas PapMA-k penetrated bacterial cell membranes. Nuclear magnetic resonance experiments revealed that PapMA contained an N-terminal α-helix from Lys(3) to Lys(7) and a C-terminal α-helix from Lys(10) to Lys(17), with a Pro(9) hinge between them. PapMA-k also had two α-helical structures in the same region connected with a flexible hinge residue at Nlys(9), which existed in a dynamic equilibrium of cis and trans conformers. Using lipopolysaccharide-stimulated RAW264.7 macrophages, the anti-inflammatory activity of PapMA and PapMA-k was confirmed by inhibition of nitric oxide and inflammatory cytokine production. In addition, treatment with PapMA and PapMA-k decreased the level of ultraviolet irradiation-induced expression of genes encoding matrix metalloproteinase-1 (MMP-1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in human keratinocyte HaCaT cells. Thus, PapMA and PapMA-k are potent peptide antibiotics with antimicrobial and anti-inflammatory activity, with PapMA-k displaying enhanced bacterial selectivity.


Assuntos
Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Magaininas/farmacologia , Peptoides/química , Proteínas de Xenopus/farmacologia , Sequência de Aminoácidos , Animais , Antibacterianos/química , Anti-Inflamatórios/química , Peptídeos Catiônicos Antimicrobianos/química , Bactérias/efeitos dos fármacos , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Desenho de Fármacos , Humanos , Interleucina-6/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Magaininas/química , Camundongos , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Peptoides/farmacologia , Estrutura Secundária de Proteína , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/imunologia , Proteínas de Xenopus/química
8.
Arch Insect Biochem Physiol ; 88(1): 31-44, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25319409

RESUMO

Cecropin A is a novel 37-residue cecropin-like antimicrobial peptide isolated from the cecropia moth, Hyalophora cecropia. We have demonstrated that cecropin A is an antibacterial agent and have investigated its mode of action. In this study, we show that cecropin A has potent antimicrobial activity against 2 multidrug resistant organisms-Acinetobacter baumanii and-Pseudomonas aeruginosa. Interactions between cecropin A and membrane phospholipids were studied using tryptophan blue shift experiments. Cecropin A has a strong interaction with bacterial cell mimetic membranes. These results imply that cecropin A has selectivity for bacterial cells. To address the potential the rapeutic efficacy of cecropin A, its anti-inflammatory activities and mode of action in mouse macrophage-derived RAW264.7 cells stimulated with lipopolysaccharide (LPS) were examined. Cecropin A suppressed nitrite production, mTNF-α, mIL-1ß, mMIP-1, and mMIP-2 cytokine release in LPS-stimulated RAW264.7 cells. Furthermore, cecropin A inhibited intracellular cell signaling via the ERK, JNK, and p38 MAPK pathway, leading to the prevention of COX-2 expression in LPS-stimulated RAW264.7 cells. These results strongly suggest that cecropin A should be investigated as a potential agent for the prevention and treatment of inflammatory diseases.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Animais , Anti-Infecciosos/farmacologia , Linhagem Celular , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Lipídeos de Membrana/metabolismo , Camundongos , Óxido Nítrico/biossíntese , Transdução de Sinais
9.
J Phys Ther Sci ; 27(4): 1091-6, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25995564

RESUMO

[Purpose] The aim of this study was to determine the effect of spatial target reaching training (TRT) based on visual biofeedback (VB) on the upper extremity (UE) function of hemiplegic subjects. [Subjects and Methods] Forty subjects between six and eighteen months post-stroke were enrolled in this study. They were randomly allocated to an experimental group (EG, n=20) and a control group (CG, n=20). All subjects received an hour of routine therapy for stroke three times a week for four weeks. Subjects in EG received additional spatial TRT based on VB using a 2-dimensional motion capture analysis system. Both groups were tested at pre and post-intervention. The motor function of each subject's UE was assessed using the Fugl-Meyer (FM) test of UE and the Wolf Motor Function Test (WMFT). The reaching speed, angle and maximum reach distance were recorded using the motion capture analysis system. The experimental data were analyzed using the paired and independent t-tests. [Results] The mean change scores of the FM Test of UE and WMFT show there was significantly more improvement at post-intervention in EG than in CG. Also, the speed and angle reached showed significantly more increase in the EG compared with the CG. [Conclusions] The findings indicate that UE motor recovery of hemiplegic stroke patients can be enhanced through the use of TRT based on VB.

10.
Biochemistry ; 53(29): 4814-25, 2014 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-24983822

RESUMO

Phosphatases of regenerating liver (PRLs) constitute a novel class of small, prenylated phosphatases with oncogenic activity. PRL-3 is particularly important in cancer metastasis and represents a potential therapeutic target. The flexibility of the WPD loop as well as the P-loop of protein tyrosine phosphatases is closely related to their catalytic activity. Using nuclear magnetic resonance spectroscopy, we studied the structure of vanadate-bound PRL-3, which was generated by addition of sodium orthovanadate to PRL-3. The WPD loop of free PRL-3 extended outside of the active site, forming an open conformation, whereas that of vanadate-bound PRL-3 was directed into the active site by a large movement, resulting in a closed conformation. We suggest that vanadate binding induced structural changes in the WPD loop, P-loop, helices α4-α6, and the polybasic region. Compared to free PRL-3, vanadate-bound PRL-3 has a longer α4 helix, where the catalytic R110 residue coordinates with vanadate in the active site. In addition, the hydrophobic cavity formed by helices α4-α6 with a depth of 14-15 Å can accommodate a farnesyl chain at the truncated prenylation motif of PRL-3, i.e., from R169 to M173. Conformational exchange data suggested that the WPD loop moves between open and closed conformations with a closing rate constant k(close) of 7 s(-1). This intrinsic loop flexibility of PRL-3 may be related to their catalytic rate and may play a role in substrate recognition.


Assuntos
Proteínas de Neoplasias/química , Proteínas Tirosina Fosfatases/química , Vanadatos/química , Humanos , Espectroscopia de Ressonância Magnética , Proteínas de Neoplasias/antagonistas & inibidores , Ligação Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Proteínas Tirosina Fosfatases/antagonistas & inibidores
11.
Biochim Biophys Acta ; 1828(2): 271-83, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23137439

RESUMO

The novel 43-residue, insect defensin-like peptide coprisin, isolated from the dung beetle, Copris tripartitus, is a potent antibiotic with bacterial cell selectivity, exhibiting antimicrobial activities against Gram-positive and Gram-negative bacteria without exerting hemolytic activity against human erythrocytes. Tests against Staphylococcus aureus using fluorescent dye leakage and depolarization measurements showed that coprisin targets the bacterial cell membrane. To understand structure-activity relationships, we determined the three-dimensional structure of coprisin in aqueous solution by nuclear magnetic resonance spectroscopy, which showed that coprisin has an amphipathic α-helical structure from Ala(19) to Arg(28), and ß-sheets from Gly(31) to Gln(35) and Val(38) to Arg(42). Coprisin has electropositive regions formed by Arg(28), Lys(29), Lys(30), and Arg(42) and ITC results proved that coprisin and LPS have electrostatically driven interactions. Using measurements of nitric oxide release and inflammatory cytokine production, we provide the first verification of the anti-inflammatory activity and associated mechanism of an insect defensin, demonstrating that the anti-inflammatory actions of the defensin-like peptide, coprisin, are initiated by suppressing the binding of LPS to toll-like receptor 4, and subsequently inhibiting the phosphorylation of p38 mitogen-activated protein kinase and nuclear translocation of NF-kB. In conclusion, we have demonstrated that an amphipathic helix and an electropositive surface in coprisin may play important roles in its effective interaction with bacterial cell membranes and, ultimately, in its high antibacterial activity and potent anti-inflammatory activity. In addition to elucidating the antimicrobial action of coprisin, this work may provide insight into the mechanism of action of insect defense systems.


Assuntos
Anti-Infecciosos/farmacologia , Proteínas de Insetos/química , Sequência de Aminoácidos , Animais , Linhagem Celular , Besouros , Citocinas/metabolismo , Humanos , Inflamação , Queratinócitos/citologia , Lipopolissacarídeos/metabolismo , Macrófagos/citologia , Espectroscopia de Ressonância Magnética/métodos , Camundongos , Dados de Sequência Molecular , NF-kappa B/metabolismo , Óxido Nítrico/química , Peptídeos/química , Conformação Proteica , Estrutura Secundária de Proteína , Homologia de Sequência de Aminoácidos , Staphylococcus aureus/metabolismo , Relação Estrutura-Atividade , Receptor 4 Toll-Like/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
12.
J Nat Prod ; 77(2): 258-63, 2014 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-24397781

RESUMO

Rhamnetin (1), a commonly occurring plant O-methylated flavonoid, possesses antioxidant properties. To address the potential therapeutic efficacy of 1, its anti-inflammatory activity and mode of action in mouse macrophage-derived RAW264.7 cells stimulated with lipopolysaccharide (LPS) or interferon (IFN)-γ were investigated. Rhamnetin (1) suppressed mouse tumor necrosis factor (mTNF)-α, mouse macrophage inflammatory protein (mMIP)-1, and mMIP-2 cytokine production in LPS-stimulated macrophages. A nontoxic dose of 1 suppressed nitric oxide production. It was found that the anti-inflammatory effects of 1 are mediated by actions on the p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and cyclooxygenase (COX)-2 pathways in LPS- or IFN-γ-stimulated RAW264.7 cells. It was determined that 1 binds to human JNK1 (9.7 × 10(8) M(-1)) and p38 MAPK (2.31 × 10(7) M(-1)) with good affinity. The binding model showed interactions with the 3'- and 4'-hydroxy groups of the B-ring and the 5-hydroxy group of the A-ring of 1. Further, 1 exerted an anti-inflammatory effect, reducing the levels of pro-inflammatory cytokines and mediators.


Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Ciclo-Oxigenase 2 , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Quercetina/análogos & derivados , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Anti-Inflamatórios/imunologia , Ciclo-Oxigenase 2/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Interferon gama/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Modelos Moleculares , Estrutura Molecular , NF-kappa B/metabolismo , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/biossíntese , Quercetina/química , Quercetina/farmacologia , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/farmacologia
13.
Molecules ; 19(9): 13200-11, 2014 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-25165860

RESUMO

Previously we have shown that 3,6-dihydroxyflavone (3,6-DHF) is a potent agonist of the human peroxisome proliferator-activated receptor (hPPAR) with cytotoxic effects on human cervical cancer cells. To date, the mechanisms by which 3,6-DHF exerts its antitumor effects on cervical cells have not been clearly defined. Here, we demonstrated that 3,6-DHF exhibits a novel antitumor activity against HeLa cells with IC50 values of 25 µM and 9.8 µM after 24 h and 48 h, respectively. We also showed that the anticancer effects of 3,6-DHF are mediated via the toll-like receptor (TLR) 4/CD14, p38 mitogen-activated protein kinase (MAPK), Jun-N terminal kinase (JNK), extracellular-signaling regulated kinase (ERK), and cyclooxygenase (COX)-2 pathways in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. We found that 3,6-DHF showed a similar IC50 (113 nM) value to that of the JNK inhibitor, SP600125 (IC50 = 118 nM) in a JNK1 kinase assay. Binding studies revealed that 3,6-DHF had a strong binding affinity to JNK1 (1.996 × 105 M-1) and that the 6-OH and the carbonyl oxygen of the C ring of 3,6-DHF participated in hydrogen bonding interactions with the carbonyl oxygen and the amide proton of Met111, respectively. Therefore, 3,6-DHF may be a candidate inhibitor of JNKs, with potent anticancer effects.


Assuntos
Flavonoides/administração & dosagem , Proteínas Quinases JNK Ativadas por Mitógeno/química , Proteínas de Neoplasias/biossíntese , Neoplasias do Colo do Útero/tratamento farmacológico , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Ligação de Hidrogênio/efeitos dos fármacos , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/biossíntese , Fosforilação/efeitos dos fármacos , Neoplasias do Colo do Útero/patologia
14.
Microbiol Spectr ; 12(4): e0424923, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38451228

RESUMO

The aim of this study was to compare the performance of the newly developed SMG HHV-6 Q Real-Time PCR Kit (SMG assay) with the RealStar HHV-6 PCR Kit (RealStar assay). The analytical sensitivity and specificity, linearity, and precision of the SMG assay were evaluated. The clinical performance of the SMG assay was assessed and compared with that of the RealStar assay using 207 clinical specimens (HHV-6A positive, n = 51; HHV-6B positive, n = 64; HHV-6A/B negative, n = 92). The limit of detection of the SMG assay was 2.92 log10 copies/mL for HHV-6A DNA and 2.88 log10 copies/mL for HHV-6B DNA. The linear range was determined to be 3.40-9.00 log10 copies/mL for both viruses. Intra- and inter-assay variability were below 5% at concentrations ranging from 4 to 9 log10 copies/mL. No cross-reactivity was observed with the 25 microorganisms included in the specificity panel. The clinical sensitivity and specificity of the SMG and RealStar assays compared to in-house polymerase chain reaction and sequencing were as follows: SMG assay, 98.0% and 100% for HHV-6A DNA, respectively, and 96.9% and 100% for HHV-6B DNA, respectively; RealStar assay, 98.0% and 100% for HHV-6A DNA, respectively, and 90.6% and 100% for HHV-6B DNA, respectively. The correlation coefficients between viral loads measured by the two assays were 0.948 and 0.975, with mean differences of 0.62 and 0.32 log10 copies/mL for HHV-6A and HHV-6B DNA, respectively. These results demonstrate that the SMG assay is a sensitive and reliable tool for the quantitative detection and differentiation of HHV-6A and HHV-6B DNA.IMPORTANCEQuantitative real-time PCR (qPCR) that can distinguish between HHV-6A and HHV-6B DNA is recommended for diagnosis of active infection. The SMG HHV-6 Q Real-Time PCR Kit (SMG assay) is a newly developed qPCR assay that can differentiate between HHV-6A and HHV-6B DNA; however, little is known about its performance. In this study, we assessed the performance of the SMG assay and compared it with that of a commercially available qPCR assay, the RealStar HHV-6 PCR Kit (RealStar assay). The SMG assay demonstrated excellent analytical sensitivity and specificity, precision, and linearity. Furthermore, the viral loads measured by the SMG assay were highly correlated with those measured by the RealStar assay. Our results suggest that the SMG assay is a useful diagnostic tool for quantitative detection and differentiation of HHV-6A and HHV-6B DNA.


Assuntos
Herpesvirus Humano 6 , Infecções por Roseolovirus , Humanos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Herpesvirus Humano 6/genética , DNA Viral/genética , Sensibilidade e Especificidade , Carga Viral/métodos , Infecções por Roseolovirus/diagnóstico
15.
Healthcare (Basel) ; 11(21)2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37957977

RESUMO

Rounded shoulder posture (RSP) causes shoulder pain and can lead to shoulder impingement and thoracic outlet syndromes, ultimately resulting in a frozen shoulder. Altered scapular positions in RSP patients affect muscle activity. Many studies have explored methods to correct and prevent RSP, including shoulder braces, muscle strengthening, stretching, and inhibition techniques. Using a shoulder brace reduces RSP and improves shoulder discomfort and function, similar to conventional rehabilitation. However, despite their effectiveness, these braces are bulky and inconvenient, which makes continuous daily wear challenging. This is especially true for women who are sensitive to their appearance. To address this issue, methods have been developed to convert women's underwear bra straps into braces. This study aimed to evaluate the immediate effects of three underwear-mounted rounded shoulder braces and to identify the brace that is most effective in decreasing RSP and upper trapezius (UT) muscle activity and increasing lower trapezius (LT) muscle activity in patients with RSP. The study included 18 patients with an RSP. The RSP amount and UT and LT muscle activities were measured before and after three interventions. The interventions were scapular posterior tilting (SPT) exercises with the X strap, X + 8 strap, and inner brace. Compared with the baseline value, the RSP amount was significantly lower with the three braces. The RSP was significantly lower with the X + 8 strap and the inner brace than with the X strap. The inner brace showed significantly lower UT muscle activity than those with the X strap and X + 8 straps and significantly greater LT muscle activity than that with the X + 8 strap. These results show underwear-mounted braces as a potential RSP solution, but long-term sustainability and improving comfort, especially for those concerned about appearance, require further research and development.

16.
Microbiol Spectr ; 11(6): e0167323, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-37800931

RESUMO

IMPORTANCE: This manuscript describes an occurrence of false-positive GM tests in patients receiving TPN products from a manufacturer who had recently changed the supplier of the glucose component. We describe the clinical presentation of nine false-positive cases and the results of serologic and microbiological investigations of the TPN products suspected of contamination with GM. Attempts to detect GM in parenteral nutrition products were made since the detection of GM in sodium gluconate-containing solutions in 2007, but none of them identified the source of elevated GM indexes in TPN products. However, the present study demonstrated that the glucose component of the TPN products contained a high level of GM antigen, which caused false-positive GM assay results. The source of GM was glucoamylase, which was derived from A. niger in the manufacturing process. Physicians and clinical microbiology laboratories should be aware of this issue to improve interpretation and patient care.


Assuntos
Aspergillus , Mananas , Humanos , Reações Falso-Positivas , Imunoensaio , Nutrição Parenteral Total , Antígenos de Fungos
17.
Open Forum Infect Dis ; 9(7): ofac262, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35855960

RESUMO

Background: Omicron variant viruses spread rapidly, even in individuals with high vaccination rates. This study aimed to determine the utility of the antibody against spike protein level as a predictor of the disease course of coronavirus disease 2019 (COVID-19) in vaccinated patients. Methods: Between December 11, 2021, and February 10, 2022, we performed a prospective observational cohort study in South Korea, which included patients infected with Delta and Omicron variants. A multivariable logistic regression analysis to determine the association between antibody levels and outcomes was conducted. The relationship between antibody levels and cycle threshold (Ct) values was confirmed using a generalized linear model. Results: From 106 vaccinated patients (39 Delta and 67 Omicron), the geometric mean titers of antibodies in patients with fever (≥37.5°C), hypoxia (≤94% of SpO2), pneumonia, C-reactive protein (CRP) elevation (>8 mg/L), or lymphopenia (<1100 cells/µL) were 1201.5 U/mL, 98.8 U/mL, 774.1 U/mL, 1335.1 U/mL, and 1032.2 U/mL, respectively. Increased antibody levels were associated with a decrease in the occurrence of fever (adjusted odds ratio [aOR], 0.23; 95% CI, 0.12-0.51), hypoxia (aOR, 0.23; 95% CI, 0.08-0.7), CRP elevation (aOR, 0.52; 95% CI, 0.29-0.0.94), and lymphopenia (aOR, 0.57; 95% CI, 0.33-0.98). Ct values showed a positive correlation between antibody levels (P = .02). Conclusions: Antibody levels are predictive of the clinical course of COVID-19 in vaccinated patients with Delta and Omicron variant infections. Our data highlight the need for concentrated efforts to monitor patients with severe acute respiratory syndrome coronavirus 2 infection who are at risk of low antibody levels.

18.
J Athl Train ; 56(9): 945-951, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33150402

RESUMO

CONTEXT: Weakness of the gluteus medius and gluteus maximus is associated with a variety of musculoskeletal disorders. However, activation of synergistic muscles that are not targeted should be considered when prescribing side-lying hip-abduction (SHA) exercises. Log-rolling positions may affect hip-abductor activity during SHA. OBJECTIVE: To determine the effects of log-rolling positions on gluteus medius, gluteus maximus, and tensor fasciae latae activity during SHA in participants with gluteus medius weakness. DESIGN: Controlled laboratory study. SETTING: University research laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty-one participants with gluteus medius weakness. INTERVENTION(S): Three types of SHA were performed: frontal-plane SHA in neutral position (SHA-neutral), frontal-plane SHA in anterior log-rolling position (SHA-anterior rolling), and frontal-plane SHA in posterior log-rolling position (SHA-posterior rolling). MAIN OUTCOME MEASURE(S): Surface electromyography was used to measure hip-abductor activity. One-way repeated-measures analysis of variance was calculated to assess the statistical significance of the muscle activity. RESULTS: The SHA-anterior rolling showed greater gluteus medius and gluteus maximus activation than the SHA-neutral (P = .003 and P < .001, respectively) and SHA-posterior rolling (P < .001 and P < .001, respectively). The SHA-neutral demonstrated greater gluteus medius and gluteus maximus activation than the SHA-posterior rolling (P < .001 and P = .001, respectively). The SHA-anterior rolling produced less tensor fasciae latae activation than the SHA-neutral (P < .001) and SHA-posterior rolling (P < .001). The SHA-neutral showed less tensor fasciae latae activation than the SHA-posterior rolling (P < .001). CONCLUSIONS: The SHA-anterior rolling may be an effective exercise for increasing activation of the gluteus medius and gluteus maximus while decreasing activation of the tensor fasciae latae in participants with gluteus medius weakness.


Assuntos
Articulação do Quadril , Músculo Esquelético , Nádegas , Eletromiografia , Exercício Físico , Humanos
19.
Medicine (Baltimore) ; 97(44): e12569, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30383625

RESUMO

Serratus anterior muscle weakness causes scapular winging, characterized by scapular downward rotation and scapular anterior tipping in the resting position. Knee push-up plus (KPP), a modified push-up plus that is generally used in early rehabilitation programs, is performed to elicit SA activation. However, excessive thoracic kyphosis can easily occur as a compensatory movement during KPP. Therefore, the aim of this study was to examine the effect of tactile cues during KPP on activities of the thoracic erector spinae, rectus abdominis, lower trapezius, serratus anterior, and upper trapezius; scapular winging; and thoracic kyphosis in subjects with scapular winging.Thirteen men with scapular winging performed KPP exercises under 3 different tactile cue conditions (no cue, to the thoracic spinous process [TSP], and to the interscapular region [ISR]). Electromyography was used to collect the muscle activity; in addition, a scapulometer and ImageJ software were used to measure the amount of scapular winging and thoracic kyphosis, respectively. One-way repeated-measures analysis of variance and Bonferroni correction were used to assess for statistical significance.The activity of the thoracic erector spinae, rectus abdominis, serratus anterior, and upper trapezius had significant difference among three conditions (P < .05). Lower trapezius activity was no significantly different among 3 conditions. Degrees of scapular winging and thoracic kyphosis had also significant difference among 3 conditions (P < .05).These results suggest that the tactile cue to the TSP and ISR in KPP exercise can be an effective method for decreasing scapular winging as well as correcting compensatory thoracic kyphosis during the KPP in subjects with scapular winging.


Assuntos
Cifose/fisiopatologia , Músculo Esquelético/fisiopatologia , Escápula/fisiopatologia , Adulto , Estudos Transversais , Sinais (Psicologia) , Eletromiografia , Exercício Físico/fisiologia , Teste de Esforço/métodos , Humanos , Articulação do Joelho/fisiopatologia , Masculino , Tronco/fisiopatologia
20.
Medicine (Baltimore) ; 97(14): e0348, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29620665

RESUMO

Scapular winging (SW) is defined as increased prominence of the whole medial border of the scapula. Many researchers recently recommended knee push-up plus (KPP) for enhancing serratus anterior (SA) activation. However, during push-up plus, thoracic kyphosis (TK) may usually occur as a compensatory movement. Thus, the purpose of this study was to investigate the effect of Thera-Band application during KPP on rectus abdominis (RA) activity, TK angle (TKA), SA activity, and amount of SW in subjects with SW.Fifteen subjects performed KPP with Thera-Band applied to different posterior body parts (no Thera-Band, in the occiput, and in the thoracic region). Electromyography was used to record the RA and SA activities. Image J software was used to calculate the compensatory TKA during KPP, and a scapulometer was used to measure SW in the quadruped position. One-way repeated-measures analysis of variance was used to test for significance.KPP with Thera-Band in the occiput showed significantly lower RA activity (P = .001) and TKA (P < .001) than KPP with no Thera-Band. SA activity (P = .020, P = .047) and SW (P < .001, P < .001) were significantly lower with Thera-Band applied to the occiput and thoracic regions than in KPP with no Thera-Band.Thera-Band applied to the occiput and thorax can be beneficial as it decreases RA and SA muscle activity and reduces TKA and SW during KPP in subjects with SW.


Assuntos
Fita Atlética , Discinesias/terapia , Terapia por Exercício/instrumentação , Músculos Intermediários do Dorso/fisiopatologia , Cifose/terapia , Reto do Abdome/fisiopatologia , Escápula/anormalidades , Estudos Transversais , Discinesias/complicações , Discinesias/fisiopatologia , Terapia por Exercício/métodos , Feminino , Humanos , Joelho , Cifose/etiologia , Cifose/fisiopatologia , Masculino , Movimento/fisiologia , Escápula/fisiopatologia , Resultado do Tratamento , Adulto Jovem
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