Background. Although Middle East Respiratory Syndrome coronavirus (MERS-CoV) is characterized by a risk of nosocomial transmission, the detailed mode of transmission and period of virus shedding from ...infected patients are poorly understood. The aims of this study were to investigate the potential role of environmental contamination by MERS-CoV in healthcare settings and to define the period of viable virus shedding from MERS patients. Methods. We investigated environmental contamination from 4 patients in MERS-CoV units of 2 hospitals. MERS-CoV was detected by reverse transcription polymerase chain reaction (PCR) and viable virus was isolated by cultures. Results. Many environmental surfaces of MERS patient rooms, including points frequently touched by patients or healthcare workers, were contaminated by MERS-CoV. Viral RNA was detected up to five days from environmental surfaces following the last positive PCR from patients' respiratory specimens. MERS-CoV RNA was detected in samples from anterooms, medical devices, and air-ventilating equipment. In addition, MERS-CoV was isolated from environmental objects such as bed sheets, bedrails, IV fluid hangers, and X-ray devices. During the late clinical phase of MERS, viable virus could be isolated in 3 of the 4 enrolled patients on day 18 to day 25 after symptom onset. Conclusions. Most of touchable surfaces in MERS units were contaminated by patients and health care workers and the viable virus could shed through respiratory secretion from clinically fully recovered patients. These results emphasize the need for strict environmental surface hygiene practices, and sufficient isolation period based on laboratory results rather than solely on clinical symptoms.
Since the report of the first confirmed case in Daegu on February 18, 2020, local transmission of coronavirus disease 2019 (COVID-19) in Korea has continued. In this study, we aimed to identify the ...pattern of local transmission of COVID-19 using mathematical modeling and predict the epidemic size and the timing of the end of the spread.
We modeled the COVID-19 outbreak in Korea by applying a mathematical model of transmission that factors in behavioral changes. We used the Korea Centers for Disease Control and Prevention data of daily confirmed cases in the country to estimate the nationwide and Daegu/Gyeongbuk area-specific transmission rates as well as behavioral change parameters using a least-squares method.
The number of transmissions per infected patient was estimated to be about 10 times higher in the Daegu/Gyeongbuk area than the average of nationwide. Using these estimated parameters, our models predicts that about 13,800 cases will occur nationwide and 11,400 cases in the Daegu/Gyeongbuk area until mid-June.
We mathematically demonstrate that the relatively high per-capita rate of transmission and the low rate of changes in behavior have caused a large-scale transmission of COVID-19 in the Daegu/Gyeongbuk area in Korea. Since the outbreak is expected to continue until May, non-pharmaceutical interventions that can be sustained over the long term are required.
BACKGROUNDFor protection against coronavirus disease 2019 (COVID-19), the Korean government recommended the KF94 mask or that a mask at the same level as the KF94 should be worn when contacting a ...patient with COVID-19. Furthermore, adequately fitted N95 respirators and KF94 masks are essential. We investigated the fit tests to determine whether healthcare workers had adequate protection with N95 respirators and KF94 masks. METHODSIn this prospective single-center simulation study, five N95 respirators (two made in the USA by 3M and three made in Korea) and six KF94 masks, the Korean standard medical masks, were tested. The fit factor (FF) and leakage rate were evaluated using a two-fit test device. Adequate protection (defined as FF ≥ 100 or leakage rate ≤ 5) rates were compared between N95 respirators and KF94 masks, and between made in Korea and the 3M N95 respirators. For KF94 masks, adequate protection rates were compared before and after ear strap fixation. RESULTSOverall, 30 participants were enrolled, and 330 fit tests were performed for FF and leakage rate. Adequate protection rates of all tested N95 respirators and KF94 masks were 22.7% (n = 75) by FF and 20.6% (n = 68) by leakage rate. N95 respirators showed a significantly higher adequate protection rate than KF94 masks for FF (48.7% vs. 1.1%, P < 0.001) and leakage rate (42.0% vs. 2.8%, P < 0.001). Adequate protection rate of 3M-made N95 respirators was significantly higher than that of those made in Korea (83.3% vs. 25.6% in FF, P < 0.001; 73.3% vs. 21.1% in leakage rate, P < 0.001). In KF94 masks, after fixation of ear strap with a hook, adequate protection rate improved significantly (1.1% vs. 12.8% in FF, P < 0.001; 2.8% vs. 11.1%, P < 0.001). CONCLUSIONAlthough adequate protection rate of N95 respirators was higher than that of KF94 masks, N95 respirator protection rate was not optimum. Thus, it is necessary to minimize exposure to risk by selecting an appropriate mask or respirator that adequately fits each person, and by wearing respirators or masks appropriately, before contacting the patients. With their superior protection rate, wearing N95 respirators is recommended instead of KF94 masks, especially when performing aerosol-generating procedures.
In this study, we investigated the effect of material composition on the selector-only memory (SOM) characteristics of ovonic threshold switch (OTS) device. By controlling the selenium (Se) ...concentration within the chalcogenide film, we were able to optimize the electrical properties. OTS devices co-sputtered with Se exhibited excellent characteristics, including a sufficient memory window (MW > 1.2 V) and fast operation speed (<inline-formula> <tex-math notation="LaTeX">\sim </tex-math></inline-formula>10 ns). Furthermore, we found that the desired MW could be obtained by varying the pulse height during the write process. The optical bandgap and bond nature of chalcogenide film were analyzed by UV-vis and Raman spectroscopy, revealing that the Se is the key element to the SOM operation of the OTS device. To understand the correlation between electrical properties and modification of the bond topology, we employed density functional theory (DFT) calculations. Finally, we explained the mechanism of SOM operation by introducing a thermally assisted hopping (TAH) model and analyzing the trap behavior in OTS devices. From our experimental results, we have demonstrated that the stability of delocalized traps formed depending on the polarity of the write pulse plays a crucial role in the operation of the SOM device. Our findings provide valuable insights into the complex relationship between material composition and the electrical characteristics of SOM devices.
The interaction between statins and omega-3 fatty acids remains controversial. The aim of this phase 1 trial was to evaluate the pharmacokinetics of drug-drug interaction between atorvastatin and ...omega-3 fatty acids. Treatments were once-daily oral administrations of omega-3 (4 g), atorvastatin (40 mg), and both for 14 days, 7 days, and 14 days, respectively, with washout periods. The concentrations of atorvastatin, 2-OH-atorvastatin, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) were determined with LC-MS/MS. Parameters of DHA and EPA were analyzed after baseline correction. A total of 37 subjects completed the study without any major violations. The geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of the co-administration of a single drug for the area under the concentration–time curve during the dosing interval at steady state of atorvastatin, 2-OH-atorvastatin, DHA, and EPA were 1.042 (0.971–1.118), 1.185 (1.113–1.262), 0.157 (0.091–0.271), and 0.557 (0.396–0.784), respectively. The GMRs (90% Cis) for the co-administration at steady state of atorvastatin, 2-OH-atorvastatin, DHA, and EPA were 1.150 (0.990–1.335), 1.301 (1.2707–1.1401), 0.320 (0.243–0.422), and 0.589 (0.487–0.712), respectively. The 90% CIs for most primary endpoints were outside the range of typical bioequivalence, indicating a pharmacokinetic interaction between atorvastatin and omega-3.
Abstract
Background
Despite use of the 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) over the last decade, the disease burden of ...pneumococcal pneumonia is still high. We evaluated the field effectiveness of PCV13, PPSV23, and sequential vaccination against pneumococcal pneumonia in older adults.
Methods
This prospective multicenter study was conducted in adults aged ≥65 years hospitalized with community-acquired pneumonia (CAP) between September 2015 and August 2017. The case-control test-negative design was used to estimate vaccine effectiveness (VE) against pneumococcal CAP.
Results
Of 1525 cases with CAP hospitalization, 167 (11.0%) were identified as pneumococcal CAP. In the elderly aged ≥65 years, the adjusted VE of pneumococcal vaccines against pneumococcal CAP was statistically insignificant: 40.0% (95% confidence interval CI, –10.8% to 67.5%) for PCV13 and 11.0% (95% CI, –26.4% to 37.3%) for PPSV23. However, in the younger subgroup (aged 65–74 years), sequential PCV13/PPSV23 vaccination showed the highest adjusted VE of 80.3% (95% CI, 15.9%–95.4%), followed by single-dose PCV13 (adjusted VE, 66.4% 95% CI, .8%–88.6%) and PPSV23 (adjusted VE, 18.5% 95% CI, –38.6% to 52.0%).
Conclusions
Sequential PCV13/PPSV23 vaccination is most effective for preventing pneumococcal CAP among the elderly aged 65–74 years.
Sequential pneumococcal conjugate vaccine (PCV13)/23-valent pneumococcal polysaccharide vaccine (PPSV23) vaccination showed the highest adjusted vaccine effectiveness of 80.3% in the elderly (age 65–74 years), compared with single-dose PCV13 (66.4%) or PPSV23 (18.5%).
With the global increase in the older population, the proportion of those receiving care in long-term care facilities (LTCFs) has also been increasing. We assessed the epidemiology, antibiotic ...susceptibility, and colonization status of drug-resistant organisms in patients transferred from LTCFs.
We retrospectively reviewed the medical records of patients transferred from LTCFs between 2017 and 2022. The reasons for admission, antimicrobial susceptibility, and colonization rates of carbapenem-resistant Enterobacterales (CRE), methicillin-resistant Staphylococcus aureus (MRSA), and carbapenem-resistant Acinetobacter baumannii (CRAB) were recorded. We analyzed the susceptibility and colonization rates by year to identify trends.
Of the 936 patients transferred from LTCFs, 54.3% were admitted to the intensive care unit and 12.5% died. The most common reason for admission was infection (n = 573, 61.2%), followed by gastrointestinal bleeding (n = 67, 7.2%) and cerebrovascular disorder (n = 65, 6.9%). A total of 452 Enterobacterales strains were isolated, and their susceptibility rates to ciprofloxacin and cefotaxime were 33.3% and 35.6%, respectively. A total of 54.9% were extended-spectrum beta-lactamase-producing strains, and 4.9% of them were carbapenem-resistant, both of which showed an increasing trend (P = 0.024 and P < 0.001, respectively). The prevalence rates of CRE, CRAB, and MRSA colonization were 9.2%, 7.1%, and 23.1%, respectively. CRE colonization showed a significant increase (P < 0.001), with carbapenemase-producing Enterobacterales accounting for 75.9% of cases.
Patients transferred from LTCFs are primarily affected by infections and exhibit high resistance rates. The increasing trend in CRE colonization rates each year highlights the need for the implementation of rigorous infection control measures for effective management.
•Serotype 3 and 19A were still most prevalent in adults in the era vaccines.•Ceftriaxone non-susceptible rate was high (32.5%) in invasive pneumococci.•Serotypes 11A/E and 19A pneumococci showed low ...ceftriaxone susceptibility.•Ceftriaxone non-susceptibility was related to sequence type 166 and 320.
Invasive pneumococcal disease (IPD) is associated with substantial morbidity and mortality in children and elderly populations. Serotype distribution and antibiotic susceptibility of IPD isolates are changing with the implementation of pneumococcal vaccination and increasing antibiotic use worldwide. We aimed to determine serotype distribution, antibiogram, and molecular epidemiology of pneumococci in the late stage of PCV13 era.
Prospective multicenter IPD surveillance study was conducted for adults aged ≥ 19 years from July 2019 to June 2021. Clinical and epidemiologic data were collected. In addition, antibiotic susceptibility test, serotype identification and multi-locus sequence typing (MLST) was taken for pneumococcal isolates.
A total of 160 IPD cases were collected with mean age of 65.1 years (male, 72.5%). Serotyping was taken for 116 available pneumococcal isolates. PCV13 and PPSV23 serotypes were 32.8% (n = 38) and 56.0% (n = 65), respectively. Serotype 3 (13.8%) and 19A (9.5%) were the most common causative agents of IPD, followed by serogroup 11 (6.9%), 23A (6.9%), 10A (4.3%), and 15B (4.3%). Notably, 32.5% of invasive pneumococcal isolates were non-susceptible to ceftriaxone. Serotypes 11A, 11E and 19A pneumococci showed high ceftriaxone non-susceptible rate (80%, 100% and 81.8% respectively), and they were related to sequence type (ST) 166 and ST320. In comparison, most serotype 3 isolates were ceftriaxone susceptible and related to ST180.
PCV serotypes, especially 3 and 19A, are still prevalent in adult IPDs, suggesting that individual PCV13 immunization would be necessary for the elderly people and chronically ill patients. Ceftriaxone non-susceptible rate was remarkably high in invasive pneumococcal isolates.
Fulminant hepatitis is characterized by rapid and massive immune-mediated liver injury. Dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX1;
) ...represses the transcription of various genes. Here, we determine whether DAX1 serves as a regulator of inflammatory liver injury induced by concanavalin A (ConA). C57BL/6J (WT), myeloid cell-specific
knockout (MKO), and hepatocyte-specific
knockout (LKO) mice received single intravenous administration of ConA. Histopathological changes in liver and plasma alanine aminotransferase and aspartate aminotransferase levels in
MKO mice were comparable with those in WT mice following ConA administration. Unlike
MKO mice,
LKO mice were greatly susceptible to ConA-induced liver injury, which was accompanied by enhanced infiltration of immune cells, particularly CD4
and CD8
T cells, in the liver. Factors related to T-cell recruitment, including chemokines and adhesion molecules, significantly increased following enhanced and prolonged phosphorylation of NF-κB p65 in the liver of ConA-administered
LKO mice. This is the first study to demonstrate that hepatocyte-specific DAX1 deficiency exacerbates inflammatory liver injury via NF-κB p65 activation, thereby causing T-cell infiltration by modulating inflammatory chemokines and adhesion molecules. Our results suggest DAX1 as a therapeutic target for fulminant hepatitis treatment.
Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, but its overdose can cause acute liver failure. The dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on ...the X chromosome, gene 1 (DAX-1, NR0B1), is an orphan nuclear receptor that acts as a transcriptional co-repressor of various genes. In this study, we identified the role of DAX-1 in APAP-induced liver injury using hepatocyte-specific Dax-1 knockout (Dax-1 LKO) mice. Mouse primary hepatocytes were used as a comparative in vitro study. APAP overdose led to decreased plasma alanine aminotransferase and aspartate aminotransferase levels in Dax-1 LKO mice compared to C57BL/6J (WT) controls, accompanied by reduced liver necrosis. The expression of the genes encoding the enzymes catalyzing glutathione (GSH) synthesis and metabolism and antioxidant enzymes was increased in the livers of APAP-treated Dax-1 LKO mice. The rapid recovery of GSH levels in the mitochondrial fraction of APAP-treated Dax-1 LKO mice led to reduced reactive oxygen species levels, resulting in the inhibition of the prolonged JNK activation. The hepatocyte-specific DAX-1 deficiency increased the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) compared with WT controls after APAP administration. These results indicate that DAX-1 deficiency in hepatocytes protects against APAP-induced liver injury by Nrf2-regulated antioxidant defense.
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