RESUMO
Individual's risk perception regarding specific hazards is a dynamic process that evolves over time. This study analyzed the relationship between the number of COVID-19 cases and the South Korean public's risk perceptions from the outset of the pandemic to the recent past. More than 70 repeated cross-sectional surveys were conducted biweekly to measure individuals' risk perception. An autoregressive integrated moving average with explanatory variable time series analysis was used to characterize the relationship between the number of COVID-19 cases and level of risk perceptions. It revealed that individuals' risk perception and the number of COVID-19 cases were not linearly related but were logarithmically correlated. This finding can be understood as a psychic numbing effect, suggesting that people's perception of risk is not linear but rather exponentially sensitive to changes. The findings also revealed a significant influence of individuals' trust in local governments on their risk perceptions, highlighting the substantial role played by local governments in direct risk management during the COVID-19 pandemic.
Assuntos
COVID-19 , Pandemias , Percepção , SARS-CoV-2 , COVID-19/psicologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Humanos , República da Coreia/epidemiologia , Medição de Risco/métodos , Estudos Transversais , Masculino , Feminino , Inquéritos e Questionários , Adulto , Confiança , Pessoa de Meia-IdadeRESUMO
BACKGROUND: This study aimed to evaluate exposure to various hazardous substances emitted by incineration facilities and their likely effect on the health for residents of Bugi-myeon, Cheongju, Korea, which has three incineration facilities. METHODS: Heavy metals, polycyclic aromatic hydrocarbons (PAHs), and dioxin concentrations in the air and soil of exposed and control areas were measured. Moreover, the exposure levels to harmful substances and its effects on health were investigated in 1,124 exposed and 232 control adults. RESULTS: PAHs and dioxin concentrations in the air in the exposed area were significantly higher than in the control area. Urinary cadmium and PAHs metabolite concentrations were significantly higher in the exposed group than in the control group. The exposure group also had a higher prevalence of depression and self-reported allergic symptoms than the control group. CONCLUSION: The possibility of residents in Bugi-myeon being exposed to hazardous substances at incineration facilities cannot be ruled out. To prevent them from further exposure to hazardous substances, it is necessary to prohibit the expansion of additional incineration facilities in this area and to implement continuous monitoring projects for residents.
Assuntos
Dioxinas , Dibenzodioxinas Policloradas , Hidrocarbonetos Policíclicos Aromáticos , Adulto , Humanos , Dioxinas/toxicidade , Incineração , Resíduos Industriais , Substâncias Perigosas/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , República da Coreia/epidemiologiaRESUMO
A method has been developed and validated for the determination of polycyclic aromatic hydrocarbons (PAHs) in the electronic liquid/gas (e-liquid/e-gas) of electronic cigarettes (e-cigarettes) and ignitable/non-ignitable smokeless cigarettes by high-performance liquid chromatography-fluorescence detection. The proposed method was further applied to detect the presence of PAHs in 16 commercially available smoking cessation aids. The analytical method for benz [a]anthracene, chrysene, benzo [b]fluoranthene, benzo [k]fluoranthene, benzo [a]pyrene, dibenz [a,h]anthracene, and benzo [g,h,i]perylene (BghiP) was validated in terms of linearity, limit of detection, limit of quantification, recovery (%), accuracy (%), and precision (%). Results showed low levels of PAHs in all samples, except for the non-ignitable cigarettes. In particular, BghiP was detected in e-liquid even though a mixture of food-grade propylene glycol and vegetable glycerin was used, and at least one PAH was present in the e-gas of all e-cigarettes, except for one. From these results, it is necessary to prepare an accurate quantitative analysis method and investigate unexpected hazardous materials generated from smoking cessation aids to prevent health problems and provide the scientific basis for safety management.
Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Hidrocarbonetos Policíclicos Aromáticos/análise , Abandono do Hábito de Fumar , Cromatografia Líquida de Alta PressãoRESUMO
BACKGROUND: Prenatal exposure to heavy metals during critical developmental phases has been implicated in allergic phenotypes. However, few studies have been conducted on the gender-specific association of prenatal heavy metal exposure with atopic dermatitis (AD) in infants. OBJECTIVE: To examine the gender-specific association of prenatal exposure to multiple heavy metals with AD incidence in 6-month-old infants using data from the Mothers and Children's Environmental Health (MOCEH). METHODS: We evaluated 738 mother-child pairs from the MOCEH study, an ongoing prospective birth cohort. The concentrations of three heavy metals (lead, mercury and cadmium) in maternal blood samples were measured during early and late pregnancy. Each quartile of heavy metal concentration was used to consider the possible nonlinear association with AD. For assessing the multi-pollutant model, we constructed the multivariate regression model including all three heavy metals at both early and late pregnancy. Further, the group Lasso model was used to perform the variable selection with categorized exposures and assess the effect of multiple pollutants including their pairwise interactions. RESULTS: A total of 200 incident cases of AD were diagnosed in 6-month-old infants. In the multivariate regression model of the boy group, adjusted odds ratios comparing the second, third and fourth quartile of lead exposure in boys with the first quartile were 1.83 (95% CI: 1.00, 3.38), 1.04 (0.91, 3.32) and 2.40 (1.18, 4.90), respectively. However, the only second quartile of lead exposure compared to first quartile was significantly associated with AD in girls. In addition, the results of the group Lasso model were similar with the results of multivariate regression model. CONCLUSION: The results suggest that lead exposure in late pregnancy increases risk of AD in 6-month-old boys although the strength of association is weak. Further studies are needed to confirm the susceptibility window and gender differences in lead-induced AD.
Assuntos
Dermatite Atópica , Metais Pesados , Efeitos Tardios da Exposição Pré-Natal , Criança , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/epidemiologia , Feminino , Humanos , Lactente , Masculino , Exposição Materna/efeitos adversos , Metais Pesados/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estudos Prospectivos , Caracteres SexuaisRESUMO
N-phenylpiperazine analogs can bind selectively to the D3 versus the D2 dopamine receptor subtype despite the fact that these two D2-like dopamine receptor subtypes exhibit substantial amino acid sequence homology. The binding for a number of these receptor subtype selective compounds was found to be consistent with their ability to bind at the D3 dopamine receptor subtype in a bitopic manner. In this study, a series of the 3-thiophenephenyl and 4-thiazolylphenyl fluoride substituted N-phenylpiperazine analogs were evaluated. Compound 6a was found to bind at the human D3 receptor with nanomolar affinity with substantial D3 vs. D2 binding selectivity (approximately 500-fold). Compound 6a was also tested for activity in two in-vivo assays: (1) a hallucinogenic-dependent head twitch response inhibition assay using DBA/2J mice and (2) an L-dopa-dependent abnormal involuntary movement (AIM) inhibition assay using unilateral 6-hydroxydopamine lesioned (hemiparkinsonian) rats. Compound 6a was found to be active in both assays. This compound could lead to a better understanding of how a bitopic D3 dopamine receptor selective ligand might lead to the development of pharmacotherapeutics for the treatment of levodopa-induced dyskinesia (LID) in patients with Parkinson's disease.
Assuntos
Piperazinas/química , Receptores de Dopamina D2/química , Receptores de Dopamina D3/química , Animais , Benzamidas/química , Ligação Competitiva , Agonistas de Dopamina/química , Antagonistas de Dopamina/química , Desenho de Fármacos , Humanos , Cinética , Levodopa , Ligantes , Masculino , Camundongos , Camundongos Endogâmicos DBA , Doença de Parkinson/tratamento farmacológico , Ligação Proteica , RatosRESUMO
The specific detection of eosinophil peroxidase (EPO) activity requires the difficult distinction between hypobromous acid generated by EPO and hypochlorous acid generated by other haloperoxidases. Here we report a fluorogenic probe that is halogenated with high kinetic selectivity (≥1200:1) for HOBr over HOCl. Heavy-atom effects do not quench the dibrominated product because of its self-assembly into emissive J-aggregates that provide a turn-on signal. Applications of this fluorogen to EPO activity assays, dipstick sensors, fluorescence imaging of EPO activity, assays of oxidative stress in cancer cells, and immune response detection in live mice are reported.
Assuntos
Peroxidase de Eosinófilo/análise , Corantes Fluorescentes/química , Imagem Óptica , Animais , Bromatos/química , Peroxidase de Eosinófilo/metabolismo , Corantes Fluorescentes/síntese química , Ácido Hipocloroso/química , Cinética , Camundongos , Estrutura Molecular , Tamanho da Partícula , Células RAW 264.7 , Propriedades de SuperfícieRESUMO
A strictly aerobic, catalase-negative and oxidase-positive bacterium (HR-BBT), isolated from a water sample of the Han River, was taxonomically studied using a polyphasic approach. Cells were Gram-stain-negative motile rods with a polar flagellum. The strain grew at 20-35 °C and pH 7-8 and in the absence of NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain HR-BBT belonged to the family Nevskiaceae in the phylum Proteobacteria and formed a phylogenic lineage with members of the genus Solimonas. A comparison of the 16S rRNA gene sequences of strain HR-BBT and the type strains of closely related species of the genus Solimonas showed that it shared highest sequence similarity with Solimonas terrae KIS83-12T (94.9â%), Solimonas soli DCY12T (94.8â%), Solimonas variicoloris MN28T (94.4â%) and Solimonas flava CW-KD 4T (94.2â%). The fatty acids of the strain consisted of summed features 8 (comprising C18â:â1ω6c and/or C18â:â1ω7c) and 3 (comprising C16â:â1ω6c and/or C16â:â1ω7c), C16â:â0 and C12â:â0 as major components. The polar lipids comprised phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, three unidentified phospholipids and an unidentified lipid. Ubiquinone-8 was detected as the sole respiratory quinone. The DNA G+C content of strain HR-BBT was 68.5 mol%. Based on the genotypic, chemotaxonomic and phenotypic analyses, strain HR-BBT represents a novel species of the genus Solimonas, for which the name Solimonas fluminis sp. nov. is proposed. The type strain is HR-BBT (=KACC 19410T=JCM 32268T).
Assuntos
Gammaproteobacteria/classificação , Filogenia , Rios/microbiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Gammaproteobacteria/genética , Gammaproteobacteria/isolamento & purificação , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Ubiquinona/químicaRESUMO
BACKGROUND: Based on data obtained from pregnant women who participated in the Mothers and Children's Environmental Health (MOCEH) study in South Korea, we aimed to determine whether maternal intake of fruits and vegetables or vitamin C is associated with fetal and infant growth. METHODS: A total of 1138 Korean pregnant women at 12-28 weeks gestation with their infants were recruited as study participants for the MOCEH. Intake of fruits and vegetables or vitamin C during pregnancy was assessed by a 1-day 24-h recall method. Fetal biometry was determined by ultrasonography at late pregnancy. Infant weight and length were measured at birth and 6 months. RESULTS: A multiple regression analysis after adjusting for covariates showed that maternal intake of fruits and vegetables was positively associated with the biparietal diameter of the fetus and infant's weight from birth to 6 months. Also, maternal vitamin C intake was positively associated with the abdominal circumference of the fetus and infant birth length. In addition, there was a significant inverse relationship between consumption of fruits and vegetables (below the median compared to above the median of ≥519 g/d) and the risk of low growth (<25th percentile) of biparietal diameter (odds ratio (OR): 2.220; 95% confidence interval (CI): 1.153-4.274) and birth weight (OR: 1.434; 95% CI: 1.001-2.056). A significant inverse relationship also existed between vitamin C consumption (below vs above the estimated average requirement (EAR) of ≥85 mg/d) and the risk of low growth (<25th percentile) of birth weight (OR: 1.470; 95% CI: 1.011-2.139), weight from birth to 6 months (OR: 1.520; 95% CI: 1.066-2.165), and length at birth (OR: 1.579; 95% CI: 1.104-2.258). CONCLUSIONS: An increased intake of fruits and vegetables or vitamin C at mid-pregnancy is associated with increased fetal growth and infant growth up to 6 months of age.
Assuntos
Ácido Ascórbico/administração & dosagem , Desenvolvimento Infantil/fisiologia , Dieta/métodos , Desenvolvimento Fetal/fisiologia , Frutas , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Verduras , Adulto , Peso ao Nascer/fisiologia , Estudos de Coortes , Dieta/estatística & dados numéricos , Saúde Ambiental , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mães , Gravidez , República da Coreia , Vitaminas/administração & dosagemRESUMO
BACKGROUND: Mercury is a toxic heavy metal and is known to affect many diseases. However, few studies have examined the effects of mercury exposure on liver function in the general population. We examined the association between blood mercury concentrations and liver enzyme levels in the elderly. METHODS: We included 560 elderly participants (60 years or older) who were recruited from 2008 to 2010 and followed up to 2014. Subjects visited a community welfare center and underwent a medical examination and measurement of mercury levels up to five times. Analyses using generalized estimating equations model were performed after adjusting for age, sex, education, overweight, alcohol consumption, smoking, regular exercise, high-density lipoproteins cholesterol, and total calorie intake. Additionally, we estimated interaction effects of alcohol consumption with mercury and mediation effect of oxidative stress in the relationship between mercury levels and liver function. RESULTS: The geometric mean (95% confidence interval (CI)) of blood mercury concentrations was 2.81 µg/L (2.73, 2.89). Significant relationships were observed between blood mercury concentrations and the level of liver enzymes, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT), after adjusting for potential confounders (P < 0.05). The odds ratios of having abnormal ALT levels were statistically significant in the highest mercury quartile compared to those with the lowest quartile. Particularly, regular alcohol drinkers showed greater effect estimates of mercury on the liver function than non-drinkers groups. There was no mediation effect of oxidative stress in the relationship between blood mercury concentrations and liver function. CONCLUSIONS: Our results suggest that blood mercury levels are associated with elevated liver enzymes and interact with alcohol consumption for the association in the elderly.
Assuntos
Consumo de Bebidas Alcoólicas/sangue , Poluentes Ambientais/sangue , Hepatopatias/sangue , Mercúrio/sangue , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Consumo de Bebidas Alcoólicas/urina , Aspartato Aminotransferases/sangue , Feminino , Humanos , Estilo de Vida , Hepatopatias/urina , Masculino , Malondialdeído/urina , Pessoa de Meia-Idade , Obesidade/sangue , República da Coreia , gama-Glutamiltransferase/sangueRESUMO
The objective of the present study was to investigate the relationship of IQ in children with maternal blood mercury concentration during late pregnancy. The present study is a component of the Mothers and Children's Environmental Health (MOCEH) study, a multi-center birth cohort project in Korea that began in 2006. The study cohort consisted of 553 children whose mothers underwent testing for blood mercury during late pregnancy. The children were given the Korean language version of the Wechsler Preschool and Primary Scale of Intelligence, revised edition (WPPSI-R) at 60 months of age. Multivariate linear regression analysis, with adjustment for covariates, was used to assess the relationship between verbal, performance, and total IQ in children and blood mercury concentration of mothers during late pregnancy. The results of multivariate linear regression analysis indicated that a doubling of blood mercury was associated with the decrease in verbal and total IQ by 2.482 (95% confidence interval [CI], 0.749-4.214) and 2.402 (95% CI, 0.526-4.279), respectively, after adjustment. This inverse association remained after further adjustment for blood lead concentration. Fish intake is an effect modifier of child IQ. In conclusion, high maternal blood mercury level is associated with low verbal IQ in children.
Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , Inteligência/efeitos dos fármacos , Mercúrio/efeitos adversos , Mercúrio/sangue , Alimentos Marinhos/efeitos adversos , Pré-Escolar , Estudos de Coortes , Dieta/efeitos adversos , Feminino , Humanos , Inteligência/fisiologia , Testes de Inteligência , Masculino , GravidezRESUMO
Our objective is to evaluate the relationships between prenatal maternal stress and depressive symptoms, respectively, and infant neurodevelopment at 6 months, adjusted for heavy metals and oxidative stress. This research is a part of a multi-center birth cohort study in South Korea. Information on stress and depressive symptoms was collected during the first trimester using Psychosocial Well-Being Index Short Form (PWI-SF) and Center for Epidemiological Studies Depression Scale (CES-D). The Korean Bayley Scales of Infant Development-II assessment (BSID-II), which includes the standardized mental development index (MDI) and psychomotor developmental index (PDI), and Korean Ages & Stages Questionnaires (K-ASQ) were applied to infants at six months of age. A higher index score indicates better development. Among 641 babies, 320 were female (50%). Maternal PWI ≥ 29 (vs. PWI ≤ 18) during early pregnancy was associated with a decrease in MDI scores of 5.37 points (P = 0.02) after adjusting for socioeconomic factors. Maternal CES-D ≥ 26 (vs. CES-D ≤ 10) during early pregnancy was associated with a decrease in MDI scores of 8.18 points (P = 0.01). The associations remained significant even after adjustment for lead, cadmium, and MDA levels (P < 0.05). However, no association was found between maternal PWI/CES-D and PDI score. No interaction was observed between stress and lead exposure. We found an inverse association between prenatal maternal stress and depressive symptoms, and MDI scores in 6-month-old infants after adjustment for prenatal lead exposure, which is known to affect cognitive function negatively.
Assuntos
Desenvolvimento Infantil/fisiologia , Depressão/patologia , Mães/psicologia , Estresse Psicológico , Adulto , Cádmio/sangue , Estudos de Coortes , Depressão/epidemiologia , Feminino , Humanos , Lactente , Chumbo/sangue , Modelos Lineares , Masculino , Malondialdeído/sangue , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
We investigated the association between breastfeeding and cognitive development in infants during their first 3 years. The present study was a part of the Mothers' and Children's Environmental Health (MOCEH) study, which was a multi-center birth cohort project in Korea that began in 2006. A total of 697 infants were tested at age 12, 24, and 36 months using the Korean version of the Bayley Scales of Infant Development II (K-BSID-II). The use and duration of breastfeeding and formula feeding were measured. The relationship between breastfeeding and the mental development index (MDI) score was analyzed by multiple linear regression analysis. The results indicated a positive correlation between breastfeeding duration and MDI score. After adjusting for covariates, infants who were breastfed for ≥ 9 months had significantly better cognitive development than those who had not been breastfed. These results suggest that the longer duration of breastfeeding improves cognitive development in infants.
Assuntos
Aleitamento Materno , Desenvolvimento Infantil/fisiologia , Cognição/fisiologia , Adulto , Pré-Escolar , Demografia , Feminino , Seguimentos , Humanos , Lactente , Entrevistas como Assunto , Modelos Lineares , Masculino , Mães/psicologia , Análise Multivariada , Avaliação de Programas e Projetos de Saúde , Estudos Prospectivos , República da CoreiaRESUMO
MdsABC is a Salmonella-specific tripartite efflux pump that has been implicated in the virulence of Salmonella enterica serovar Typhimurium; however, little is known about the virulence factors associated with this pump. We observed MdsABC expression-dependent alterations in the degree of resistance to extracellular oxidative stress and macrophage-mediated killing. Thin-layer chromatography and tandem mass spectrometry analyses revealed that overexpression of MdsABC led to increased secretion of 1-palmitoyl-2-stearoyl-phosphatidylserine (PSPS), affecting the ability of the bacteria to invade and survive in host cells. Overexpression of MdsABC and external addition of PSPS similarly rendered the mdsABC deletion strain resistant to diamide. Diagonal gel analysis showed that PSPS treatment reduced the diamide-mediated formation of disulfide bonds, particularly in the membrane fraction of the bacteria. Salmonella infection of macrophages induced the upregulation of MdsABC expression and led to an increase of intracellular bacterial number and host cell death, similar to the effects of MdsABC overexpression and PSPS pretreatment on the mdsABC deletion strain. Our study shows that MdsABC mediates a previously uncharacterized pathway that involves PSPS as a key factor for the survival and virulence of S. Typhimurium in phagocytic cells.
Assuntos
Proteínas de Bactérias/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Infecções por Salmonella/microbiologia , Salmonella typhimurium/metabolismo , Salmonella typhimurium/patogenicidade , Proteínas de Bactérias/genética , Regulação Bacteriana da Expressão Gênica , Humanos , Macrófagos/metabolismo , Macrófagos/microbiologia , Proteínas de Membrana Transportadoras/genética , Salmonella typhimurium/genética , VirulênciaRESUMO
The delivery of biologically functional peptides into mammalian cells can be a direct and effective method for cancer therapy and treatment of other diseases. Discoidin domain receptor 2 (DDR2) is a collagen-induced receptor tyrosine kinase recently identified as a novel therapeutic target in lung cancer. In this study, we report that peptides containing the functional domain of DDR2 can be efficiently delivered into lung malignant cancer cells via a gold nanoparticle-DNA aptamer conjugate (AuNP-Apt)-based system. Peptide delivery resulted in the abrogation of DDR2 activation triggered by collagen. Moreover, the peptide delivered by the AuNP-Apt system inhibited cancer cell proliferation and invasion mediated by DDR2 activation. Thus, these results suggest that peptide loaded onto AuNP-Apt conjugates can be used for the development of peptide-based biomedical applications for the treatment of DDR2-positive cancer.
Assuntos
Aptâmeros de Nucleotídeos , Carcinoma Pulmonar de Células não Pequenas/patologia , Ouro/química , Neoplasias Pulmonares/patologia , Nanopartículas Metálicas , Peptídeos/administração & dosagem , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Mitogênicos/antagonistas & inibidores , Linhagem Celular Tumoral , Membrana Celular , Receptores com Domínio Discoidina , Humanos , Peptídeos/química , Receptores Proteína Tirosina Quinases/fisiologia , Receptores Mitogênicos/fisiologiaRESUMO
OBJECTIVES: ß-Lactam antibiotics are commonly used in outpatient parenteral antimicrobial therapy (OPAT), but data regarding outcomes of long-term therapy are limited. The purpose of this study was to compare treatment success, readmission and antibiotic switch rates in patients treated with ß-lactam antibiotics as OPAT. METHODS: We carried out a retrospective review of all patients, discharged from Tufts Medical Center with cefazolin, ceftriaxone, ertapenem or oxacillin, between January 2009 and June 2013. A competing risks analysis was used to compare the cumulative incidence of first occurrence of treatment success, antibiotic switch and 30 day readmission for each drug. RESULTS: Four hundred patients were identified (cefazolin nâ=â38, ceftriaxone nâ=â104, ertapenem nâ=â128 and oxacillin nâ=â130). Baseline demographics were similar. Treatment success rates were higher for ceftriaxone and ertapenem (cefazolin 61%, ceftriaxone 81%, ertapenem 73% and oxacillin 58%; Pâ<â0.001). Thirty-day all-cause readmissions were similar (cefazolin 21%, ceftriaxone 14%, ertapenem 20% and oxacillin 15%; Pâ=â0.46). In 400 OPAT courses, 37 out of 50 antibiotic switches were accomplished without readmission. Adverse drug events (ADEs) were the most common reason for outpatient antibiotic switches (31/37, 84%). The ADE rate was higher for the oxacillin group (cefazolin 2.0 versus ceftriaxone 1.5 versus ertapenem 2.9 versus oxacillin 8.4 per 1000 OPAT days; Pâ<â0.001). CONCLUSIONS: OPAT with ß-lactam antibiotics is effective, but antibiotic switches for adverse events were more frequent with oxacillin use. Clinicians should be cognizant of the risk of readmissions and ADEs in OPAT patients, as the value of OPAT lies in reducing patient morbidity and readmissions by managing ADEs and preventing clinical failures.
Assuntos
Assistência Ambulatorial/métodos , Antibacterianos/uso terapêutico , beta-Lactamas/uso terapêutico , Administração Intravenosa , Adulto , Idoso , Antibacterianos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , beta-Lactamas/efeitos adversosRESUMO
PURPOSE OF REVIEW: Pathogen-directed therapy targeting multidrug-resistant bacteria in pneumonia can be a challenge. We reviewed the recent literature on bacterial resistance, diagnostic methods, and treatment strategies to guide pathogen-directed therapy of respiratory infections. RECENT FINDINGS: Antibiotic resistance is a growing problem in both community and nosocomial settings. Macrolide resistance in Streptococcus pneumoniae varies geographically, ranging from 45 to 88%, and has been associated with prior antibiotic use. Methicillin-resistant Staphylococcus aureus and multidrug-resistant Gram-negative bacilli remain the main targets for pathogen-directed therapy in patients with hospital-acquired and ventilator-associated pneumonia. Rapid molecular tests show promise to facilitate pathogen-directed therapy. Improved antibiotic use with the right drug and optimal dose is a key strategy in tackling antimicrobial resistance. Evidence supporting de-escalation for hospital-acquired and ventilator-associated pneumonia has been increasing. To date, no convincing evidence exists to support combination therapy for severe infections due to carbapenem-resistant Gram-negative bacilli. Aerosolized therapy might provide additive benefits to parenteral therapy, but requires further study. SUMMARY: Pathogen-directed therapy guided by in-vitro microbiological data is a safe approach for the treatment of respiratory infections due to antibacterial-resistant bacteria. Further research should focus on the role of rapid diagnostic tools, new antibiotics, and novel immunotherapy for respiratory infection.
Assuntos
Infecções Respiratórias/microbiologia , Infecções Respiratórias/terapia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Humanos , Imunoterapia/métodos , Pneumonia Pneumocócica/microbiologia , Pneumonia Pneumocócica/terapia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/terapia , Staphylococcus aureus/isolamento & purificação , Streptococcus pneumoniae/isolamento & purificaçãoRESUMO
Dokdonella koreensis is a non-spore-forming, aerobic, Gram-negative bacillus that was initially isolated from soil. The pathogenicity of this organism in humans remains unclear. The authors report a case of successfully treated D koreensis bacteremia in a patient with a hematological malignancy who presented with a fever and palmar-plantar erythrodysesthesia.
Le Dokdonella koreensis est un bacille à Gram négatif aérobie non sporogène qui, à l'origine, était isolé dans le sol. On en comprend mal la pathogénicité chez l'humain. Les auteurs rendent compte d'un cas de bactériémie à D koreensis traitée avec succès chez un patient ayant un cancer hématologique malin qui a consulté à cause de fièvre et d'érythrodysesthésie palmo-plantaire.
RESUMO
PURPOSE: This study aimed to develop the ultrasonography (US) criteria for risk stratification of the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) 4 nodules, and to evaluate the diagnostic yield of a modified biopsy criterion in a multicenter cohort. METHODS: In total, 1,542 K-TIRADS 4 nodules (≥1 cm) were included in the study. US criteria for the subcategorization of K-TIRADS 4 nodules were developed based on high-risk US features. The diagnostic yields and false referral rates of biopsy criterion 1 (size cut-off of 1 cm), biopsy criterion 2 (size cut-off of 1.5 cm), and modified biopsy criterion 3 (size cut-off of 1 cm for K-TIRADS 4B and 1.5 cm for K-TIRADS 4A) were evaluated. RESULTS: The five high-risk US features (solid composition, marked hypoechogenicity, macrocalcification, punctate echogenic foci, and irregular margin) independently increased the malignancy risk of the K-TIRADS 4 nodules (P<0.001). The K-TIRADS 4 nodules could be subcategorized into higher- and lower-risk subcategories according to the number of high-risk US features: K-TIRADS 4B (≥2 US features) and K-TIRADS 4A (≤1 US feature). The modified biopsy criterion increased the diagnostic yield by 7.8% compared with criterion 2 and reduced the false referral rate by 15.3% compared with criterion 1 (P<0.001). CONCLUSION: The K-TIRADS 4 nodules were subcategorized as K-TIRADS 4B and K-TIRADS 4A based on high-risk US features. The modified biopsy criterion 3 showed a similar diagnostic yield and reduced false referral rate compared to criterion 1.
RESUMO
New water soluble antofine C-13a analogues were designed, synthesized, and evaluated for antiproliferative activity against cancer cells. Particularly, (-)-(R)-13a-hydroxymethylantofine ((-)-(R)-4b) demonstrated notable growth inhibition against a panel of human cancer cell lines. This growth inhibition was associated with the arrest of the cell cycle in the G0/G1 phases and suppression of mTOR signaling in human lung A549 cancer cells. Compound (-)-(R)-4b also overcame paclitaxel-resistance in human lung cancer cells (A549-Pa) by suppressing P-glycoprotein expression. Furthermore, compound (-)-(R)-4b significantly inhibited the tumor growth of A549 and A549-Pa xenografts in a nude mouse model, which suggests it is a promising novel antitumor agent with sufficient aqueous solubility.
Assuntos
Antineoplásicos/síntese química , Desenho de Fármacos , Indóis/química , Fenantrolinas/química , Animais , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Células HCT116 , Células HEK293 , Humanos , Indóis/uso terapêutico , Indóis/toxicidade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , Fenantrolinas/uso terapêutico , Fenantrolinas/toxicidade , Transdução de Sinais/efeitos dos fármacos , Estereoisomerismo , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Transplante Heterólogo , Água/químicaRESUMO
Polymeric film coatings were applied by dip coating on two magnesium alloy systems, AZ31 and Mg4Y, in an attempt to slow the degradation of these alloys under in vitro conditions. Poly(lactic-co-glycolic acid) polymer in solution was explored at various concentrations, yielding coatings of varying thicknesses on the alloy substrates. Electrochemical corrosion studies indicate that the coatings initially provide some corrosion protection. Degradation studies showed reduced degradation over 3 days, but beyond this time point however, do not maintain a reduction in corrosion rate. Scanning electron microscopy indicates inhomogeneous coating durability, with gas pocket formation in the polymer coating, resulting in eventual detachment from the alloy surface. In vitro studies of cell viability utilizing mouse osteoblast cells showed improved biocompatibility of polymer coated substrates over the bare AZ31 and Mg4Y substrates. Results demonstrate that while challenges remain for long term degradation control, the developed polymeric coatings nevertheless provide short term corrosion protection and improved biocompatibility of magnesium alloys for possible use in orthopedic applications.