COVID-19-Related Functional Impairment in a Community Sample of Korean Adults: Associations With Depression, COVID-19 Infection Fear, and Resilience.

OBJECTIVE: We aimed to determine the effects of depression, COVID-19 infection fear, and resilience on COVID-19-related functional impairment. METHODS: We obtained data from 476 community-dwelling adults aged 20-69 years living in Jeju, South Korea, and evaluated the relationships between COVID-19-related functional impairment (work/school, social, and home life) and sociodemographic and healthrelated characteristics, COVID-19-related life changes (financial difficulties since the pandemic, employment change, interpersonal conflict), and clinical characteristics, including depression, COVID-19 infection fear, and resilience. RESULTS: Functional impairment in the home life domain was associated with marital status and monthly income. Greater work/school, social, and home life functional impairment was significantly associated with all COVID-19-related life changes. Regression analysis indicated that resilience modulated the positive associations of COVID-19-related functional impairment with symptoms of depression and COVID-19 infection fear when relevant factors were controlled for. CONCLUSION: Our results suggest the importance of clinical characteristics, including depression, COVID-19 infection fear, and resilience for understanding functional impairment related to COVID-19. These results have important implications for interventions aimed at reducing depression and COVID-19 infection fear, and enhancing resilience.

Inverse PCR for subtyping of Acinetobacter baumannii carrying ISAba1.

Acinetobacter baumannii has been prevalent in nosocomial infections, often causing outbreaks in intensive care units. ISAba1 is an insertion sequence that has been identified only in A. baumannii and its copy number varies among strains. It has been reported that ISAba1 provides a promoter for bla(OXA-51-like), bla(OXA-23-like), and bla(ampC), which are associated with the resistance of A. baumannii to carbapenems and cephalosporins. The main purpose of this study was to develop a novel inverse PCR method capable of typing A. baumannii strains. The method involves three major steps: cutting of genomic DNA with a restriction enzyme, ligation, and PCR. In the first step, bacterial genomic DNA was digested with DpnI. In the second step, the digested genomic DNAs were ligated to form intramolecular circular DNAs. In the last step, the ligated circular DNAs were amplified by PCR with primers specific for ISAba1 and the amplified PCR products were electrophoresed. Twenty-two clinical isolates of A. baumannii were used for the evaluation of the inverse PCR (iPCR) typing method. Dendrogram analysis revealed two major clusters, similar to pulsed-field gel electrophoresis (PFGE) results. Three ISAba1-associated genes--bla(ampC), bla(OXA-66-like), and csuD--were amplified and detected in the clinical isolates. This novel iPCR typing method is comparable to PFGE in its ability to discriminate A. baumannii strains, and is a promising molecular epidemiological tool for investigating A. baumannii carrying ISAba1.

A hemagglutinin quantification method for development of an influenza pandemic vaccine using size exclusion high performance liquid chromatography.

Single radial immunodiffusion (SRID) assay requires a reference antigen and an antibody to the hemagglutinin (HA) of an influenza vaccine. As it takes 2­3 months to develop the reference antigen, vaccine development is delayed in cases of an influenza pandemic. In the present study, the measurement of the HA content of influenza vaccines was assessed using size exclusion high performance liquid chromatography (SE­HPLC) for the rapid development of a pandemic vaccine. When the 2009 H1N1 reference antigen, pandemic 2009 H1N1 vaccine and 2010 seasonal influenza vaccines were analyzed by SE­HPLC, the HA of the reference antigen and vaccines was specifically separated. The presence and specificity of HA were evidenced with immunoprecipitation and ELISA assays. For the influenza vaccines, the chromatogram pattern and retention time of HA were similar among the antigen types (2009 H1N1, 2010 H3N2 and 2010 B). In addition, when SE­HPLC was applied, the ratio of HA chromatogram to peak area revealed a significant correlation with HA concentration for the reference antigen and vaccine. The result of the HA content calculation based on SE­HPLC exhibited 99.91­100% similarity, compared with that of SRID. These findings suggest that the measurement of peak area ratio/HA content using SE­HPLC may be a substitute for SRID and rapidly measure HA content to enable faster development of a vaccine during an influenza pandemic.

The genetic effect of copy number variations on the risk of type 2 diabetes in a Korean population.

BACKGROUND: Unlike Caucasian populations, genetic factors contributing to the risk of type 2 diabetes mellitus (T2DM) are not well studied in Asian populations. In light of this, and the fact that copy number variation (CNV) is emerging as a new way to understand human genomic variation, the objective of this study was to identify type 2 diabetes-associated CNV in a Korean cohort. METHODOLOGY/PRINCIPAL FINDINGS: Using the Illumina HumanHap300 BeadChip (317,503 markers), genome-wide genotyping was performed to obtain signal and allelic intensities from 275 patients with type 2 diabetes mellitus (T2DM) and 496 nondiabetic subjects (Total n = 771). To increase the sensitivity of CNV identification, we incorporated multiple factors using PennCNV, a program that is based on the hidden Markov model (HMM). To assess the genetic effect of CNV on T2DM, a multivariate logistic regression model controlling for age and gender was used. We identified a total of 7,478 CNVs (average of 9.7 CNVs per individual) and 2,554 CNV regions (CNVRs; 164 common CNVRs for frequency>1%) in this study. Although we failed to demonstrate robust associations between CNVs and the risk of T2DM, our results revealed a putative association between several CNVRs including chr15:45994758-45999227 (P = 8.6E-04, P(corr) = 0.01) and the risk of T2DM. The identified CNVs in this study were validated using overlapping analysis with the Database of Genomic Variants (DGV; 71.7% overlap), and quantitative PCR (qPCR). The identified variations, which encompassed functional genes, were significantly enriched in the cellular part, in the membrane-bound organelle, in the development process, in cell communication, in signal transduction, and in biological regulation. CONCLUSION/SIGNIFICANCE: We expect that the methods and findings in this study will contribute in particular to genome studies of Asian populations.

Leukemia inhibitory factor promotes olfactory sensory neuronal survival via phosphoinositide 3-kinase pathway activation and Bcl-2.

Leukemia inhibitory factor (LIF), a neuropoietic cytokine, has been implicated in the control of neuronal development. We previously reported that LIF plays a critical role in regulating the terminal differentiation of olfactory sensory neurons (OSNs). Here, we demonstrate that LIF plays a complementary role in supporting the survival of immature OSNs. Mature OSNs express LIF, which may be elaborated in a paracrine manner to influence adjacent neurons. LIF null mice display more apoptotic immature neurons than do their wild-type littermates. LIF treatment of dissociated OSNs in vitro significantly reduces the apoptosis of immature OSNs. Double immunocytochemical analysis indicates that the survival of immature OSNs is dependent on the presence of LIF. LIF activates the phosphoinositide 3-kinase (PI3K) pathways and induces the expression of the antiapoptotic molecule Bcl-2 in OSNs, whereas inhibition of the PI3K pathway blocks LIF-dependent OSN survival and Bcl-2 induction. Thus, LIF plays a central role in maintaining the size and integrity of the population of immature neurons within the olfactory epithelium; this population is critical to the rapid recovery of olfactory function after injury. LIF may play a similar role elsewhere in the CNS and thus be important for manipulation of stem cell populations for therapeutic interventions.

The vomeronasal organ and adjacent glands express components of signaling cascades found in sensory neurons in the main olfactory system.

The vomeronasal organ (VNO) is a sensory organ that influences social and/or reproductive behavior and, in many cases, the survival of an organism. The VNO is believed to mediate responses to pheromones; however, many mechanisms of signal transduction in the VNO remain elusive. Here, we examined the expression of proteins involved in signal transduction that are found in the main olfactory system in the VNO. The localization of many signaling molecules in the VNO is quite different from those in the main olfactory system, suggesting differences in signal transduction mechanisms between these two chemosensory organs. Various signaling molecules are expressed in distinct areas of VNO sensory epithelium. Interestingly, we found the expressions of groups of these signaling molecules in glandular tissues adjacent to VNO, supporting the physiological significance of these glandular tissues. Our finding of high expression of signaling proteins in glandular tissues suggests that neurohumoral factors influence glandular tissues to modulate signaling cascades that in turn alter the responses of the VNO to hormonal status.

Inhibitory effects of ochratoxin A on nerve growth factor-induced neurite extension through downregulation of p38 MAP kinase and AP-1 activation in cultured pheochromocytoma cells.

Ochratoxin A (OTA) induces microcephaly in animals and in vitro cultured whole embryos. Inhibition of neuronal cell differentiation was proposed as underlying mechanisms responsible for OTA-induced microcephaly. Previously it was found that OTA inhibited differentiation of cultured rat embryonic midbrain cells into neurons. In this study, the influence of OTA on differentiation in PC-12 cells, a widely accepted model cells for study of neuronal differentiation was examined. Cell differentiation was assessed by measurement of neurite extension and quantified by the number of neurites extended. OTA decreased serum and nerve growth factor (NGF)-induced neurite extension in a concentration-dependent manner. Since MAP kinase and transcription factors have been implicated in cell differentiation of neuronal cells, and our previous study demonstrated that p38 MAP kinase and AP-1 are activated during PC 12 cell differentiation, the effect of OTA on NGF-induced p38 MAP kinase and transcription factor activation was examined. Co-treatment of OTA with NGF resulted in inhibition of NGF-induced p38 MAP kinase and AP-1 activation. Moreover, SB203580, a specific inhibitor of p38 MAP kinase blocked p38 MAP kinase and AP-1 activation accompanied by further inhibition of neurite extension. The present study shows that OTA inhibited cell differentiation of PC-12 cells, and this inhibitory effect may be related to inhibition of the activation of the p38 MAP kinase in conjunction with transcription factors AP-1. This finding suggests that the inhibitory effect on neuronal cell differentiation by OTA might be a mechanism responsible for OTA-induced microcephaly.