Clin Infect Dis
August 2021
Background: Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) are associated with high mortality rates. We evaluated the efficacy and safety of tedizolid (administered as tedizolid phosphate) for treatment of gram-positive ventilated HABP/VABP.
Methods: In this randomized, noninferiority, double-blind, double-dummy, global phase 3 trial, patients were randomized 1:1 to receive intravenous tedizolid phosphate 200 mg once daily for 7 days or intravenous linezolid 600 mg every 12 hours for 10 days.
Background: Infections with Gram-positive bacteria, including acute bacterial skin and skin structure infections (ABSSSIs), are common in children. We describe a single-dose pharmacokinetics and safety study of tedizolid phosphate, a new oxazolidinone under investigation for the treatment of ABSSSIs in children, in hospitalized participants 2 to <12 years of age.
Methods: This open-label, multicenter, phase 1 trial (NCT02750761) enrolled hospitalized children 2 to <12 years of age receiving treatment for a confirmed/suspected Gram-positive bacterial infection.
Background: Tedizolid phosphate is an oxazolidinone prodrug approved in 2014 for treatment of adults with acute bacterial skin and skin structure infections (ABSSSIs); however, efficacy has not previously been evaluated in children. This study compared the safety and efficacy of tedizolid (administered as tedizolid phosphate) with active antibacterial comparators for the treatment of ABSSSIs in adolescents.
Methods: This was a randomized, assessor-blind, global phase 3 study of tedizolid versus active comparators for the treatment of Gram-positive ABSSSIs in adolescents (12 to <18 years of age; NCT02276482).
Chronic hepatitis B (CHB) is a precursor to liver cirrhosis and hepatocellular carcinoma, caused by a Hepatitis B viral infection. Genome-wide association studies (GWASs) have been conducted to find genes associated with CHB risk. In previous GWAS, EHMT2 was identified as one of the susceptibility genes for CHB.
View Article and Find Full Text PDFSchizophrenia is a debilitating mental disorder with a high heritability rate. Located on chromosome 1p31.3, the human cAMP-specific 3',5'-cyclic phosphodiesterase 4B (PDE4B) gene has been considered as an important candidate gene for the risk of schizophrenia.
View Article and Find Full Text PDFSchizophrenia is a serious mental disorder that is affected by genetic and environmental factors. As the disease has a high heritability rate, genetic studies identifying candidate genes for schizophrenia have been conducted in various populations. The gene for human Ran‑binding protein 9 (RANBP9) is a newly discovered candidate gene for schizophrenia.
View Article and Find Full Text PDFBackground: Uridine diphosphate glucuronyltransferase 1 family, A1 (UGT1A1) encodes for an enzyme that is a part of glucuronidation pathway, and a number of studies have shown that the promoter polymorphisms of UGT1A1 are associated with various diseases and drug response. In this study, we examined a possible association between UGT1A1 promoter haplotypes and the gene expression level.
Methods: To identify promoter haplotype structure population, we directly sequenced the promoter region of UGT1A1 in 192 healthy Korean to identify 10 UGT1A1 promoter single-nucleotide polymorphisms (SNPs).
Purpose: Melanocortin 3 Receptor (MC3R) is one of the families of seven-transmembrane G-protein-coupled receptors, and a recent study showed that MCR3 promoter polymorphism was significantly associated with the susceptibility of tuberculosis (TB) in South African population.
Methods: We analyzed six MC3R polymorphisms to examine the genetic effects on the risk of pulmonary TB in Korean subjects by using TaqMan assays and case-control analyses.
Results: Using statistical analyses, one common promoter polymorphism (MC3R rs11575886 T > C) was found to be associated with an increased risk of pulmonary TB.
The tyrosine-protein kinase Tec (TEC) is a member of non-receptor tyrosine kinases and has critical roles in cell signaling transmission, calcium mobilization, gene expression, and transformation. TEC is also involved in various immune responses, such as mast cell activation. Therefore, we hypothesized that TEC polymorphisms might be involved in aspirin-exacerbated respiratory disease (AERD) pathogenesis.
View Article and Find Full Text PDFLocated on 6q15 and 1p36.11, cannabinoid receptor 1 (CNR1) and cannabinoid receptor 2 (CNR2) genes are considered to be a positional and functional candidate gene for the development of mental disorders such as schizophrenia because CNR1 is known as a regulator of dopamine signaling in the hippocampus and the cerebral cortex. However, few genetic studies have been carried out to investigate an association of CNR1 and CNR2 polymorphisms and the risk of schizophrenia.
View Article and Find Full Text PDFPharmacogenomics is the study of the association between inter-individual genetic differences and drug responses. Researches in pharmacogenomics have been performed in compliance with the use of several genotyping technologies. In this study, a total of 392 single-nucleotide polymorphisms (SNPs) located in 141 pharmacogenes, including 21 phase I, 13 phase II, 18 transporter and 5 modifier genes, were selected and genotyped in 150 subjects using the GoldenGate assay or the SNaPshot technique.
View Article and Find Full Text PDFBackground: Neuromyelitis optica (NMO) is a serious inflammatory demyelinating disease (IDD), characterized by the inflammation and demyelination of optic nerves and spinal cords, which subsequently leads to the loss of function. In a previous genome-wide association study, cluster of differentiation 58 (CD58) region was found to be susceptible for the risk of multiple sclerosis (MS) in Caucasian, and the association between CD58 variants and MS was replicated in Americans. However, no study has been conducted to explore the possible association between CD58 and NMO yet.
View Article and Find Full Text PDFPurpose: UGT1A1, UGT2B7, and UGT2B15 are well-known pharmacogenes that belong to the uridine diphosphate glucuronyltransferase gene family. For personalized drug treatment, it is important to study differences in the frequency of core markers across various ethnic groups. Accordingly, we screened single nucleotide polymorphisms (SNPs) of these three genes and analyzed differences in their frequency among five ethnic groups, as well as attempted to predict the function of novel SNPs.
View Article and Find Full Text PDFMultiple sclerosis (MS) and neuromyelitis optica (NMO), which are referred to as inflammatory demyelinating diseases (IDDs), are autoimmune diseases affecting the central nervous system. Interleukin‑7 receptor (IL7R) encodes for a receptor protein that is important in the development of immune cells. Several studies have reported significant associations between IL7R polymorphisms and MS.
View Article and Find Full Text PDFBackground: Alcohol dependence (AD) is a common disorder with both environmental and genetic factors. Previous studies have shown that the genomic region from chromosome 4q22-q32 is closely associated with AD. Furthermore, a study with Irish subjects revealed that the polymorphisms of Dickkopf WNT signaling pathway inhibitor (DKK2), located at 4q25, showed a significant association with AD.
View Article and Find Full Text PDFDihydropyrimidine dehydrogenase (DPYD) is an enzyme that regulates the rate-limiting step in pyrimidine metabolism, especially catabolism of fluorouracil, a chemotherapeutic agent for cancer. In order to determine the genetic distribution of DPYD, we directly sequenced 288 subjects from five ethnic groups (96 Koreans, 48 Japanese, 48 Han Chinese, 48 African Americans, and 48 European Americans). As a result, 56 polymorphisms were observed, including 6 core polymorphisms and 18 novel polymorphisms.
View Article and Find Full Text PDFObjective: This study was conducted to find the possible association between CD226 polymorphisms and inflammatory demyelinating diseases in Korean population.
Methods: A total of 14 CD226 SNPs were selected based on their linkage disequilibrium, minor allele frequency, and location. Then, the SNPs were genotyped in 178 IDD patients and 237 healthy controls.
We hypothesized that ubiquitin-conjugating enzyme E2 E2 (UBE2E2) may be associated with gestational diabetes mellitus (GDM) and conducted association analyses. A total of 2071 subjects were recruited for the study, with 1104 cases and 967 controls. Two UBE2E2 single-nucleotide polymorphisms rs6780569 and rs7612463, and their haplotypes were analyzed for the study.
View Article and Find Full Text PDFThe DISC1 gene is considered to be a strong candidate gene for the development of schizophrenia. This study examines the association of DISC1 polymorphisms with schizophrenia in a Korean population. Although we fail to discover convincing evidence that DISC1 affects schizophrenia development, our findings may be useful for further genetic studies.
View Article and Find Full Text PDFPurpose: Aspirin exacerbated respiratory disease (AERD) results in a severe asthma attack after aspirin ingestion in asthmatics. The filamin A interacting protein 1 (FILIP1) may play a crucial role in AERD pathogenesis by mediating T cell activation and membrane rearrangement. We investigated the association of FILIP1 variations with AERD and the fall rate of forced expiratory volume in one second (FEV1).
View Article and Find Full Text PDFAspirin-exacerbated respiratory disease (AERD) is a respiratory disease characterized by acute bronchial responses upon the administration of non-steroidal anti‑inflammatory drugs (NSAIDs) and the immune response by mast cells is regarded as one of the noteworthy causes of AERD pathogenesis. The complement cascade is regarded as a key mechanism for clearing pathogens from the host. CD55 is one of the proteins involved in self-recognition, a central component of the complement system and autoimmunity.
View Article and Find Full Text PDFThe human receptor tyrosine-protein kinase erbB-4 (ERBB4) gene mediates neuregulin 1 (NRG1) signaling, and is involved in neuronal migration and differentiation. Despite the potential significance of ERBB4 in the development of schizophrenia, relatively few genetic studies for the association of ERBB4 with schizophrenia were performed in the populations including Ashkenazi Jews, Americans including Caucasians and African Americans, and Han Chinese. In this study, differences in ERBB4 variations were investigated to determine association with schizophrenia and smooth pursuit eye movement (SPEM) abnormality in a Korean population.
View Article and Find Full Text PDFPurpose: Underage drinking is common in the United States. This article presents nationally representative data on hospitalizations for alcohol use disorder (AUD) in youth.
Methods: Using the Nationwide Inpatient Sample database, discharge records of individuals between 15 and 20 years diagnosed with AUD were identified.