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Background Scrub typhus is a mite-borne infectious rickettsial disease that can occur in rural and urban areas, with an especially high prevalence in older populations. This disease causes systemic vasculitis that can invade the central nervous system. Considering these characteristics, here we examined whether scrub typhus was associated with the occurrence of dementia, using large population-based cohort data. Method This population-based cohort study enrolled patients aged 60–89 years using data from the Health Insurance Review and Assessment database of South Korea between 2009 and 2018. We defined scrub typhus and dementia using International Classification of Diseases, Tenth Edition diagnostic codes. The control group was stratified according to age and sex at a ratio of 1:5 to the case group in the study population. The index date was set after 90 days beyond the date of the scrub typhus diagnosis, while the observation period was from the time of the index appointment to December 31, 2020. The primary outcome was newly diagnosed dementia. The secondary outcome was dementia classification, such as Alzheimer’s disease, vascular dementia, and other. All analyses were conducted by matching age, gender, and comorbidity. Results During the observation period, 10,460 of 71,047 (14.7%) people who had a history of scrub typhus versus 42,965 of 355,235 (12.1%) people in the control group, that is, with no history of scrub typhus, were diagnosed with dementia (adjusted hazard ratio, 1.12; 95% confidence interval, 1.10–1.15, p Conclusion In conclusion, a history of scrub typhus infection in old age is significantly associated with an increase in dementia, especially Alzheimer’s disease. Our results suggest that prevention and appropriate treatment of scrub typhus should be emphasized as a dementia prevention measure.

Background. Biomarkers for the diagnosis and prognosis of sepsis are urgently needed. Myokines secreted from muscles play a key role in the immune system. In the present study, we evaluated two myokines, brain-derived neurotrophic factor (BDNF) and oncostatin M, for their potential use as diagnostic and prognostic biomarkers for patients with sepsis. We also evaluated the association between myokines and muscle mass. Methods. BDNF and oncostatin M levels were measured upon the initial diagnosis of sepsis, and again at the end of treatment, in patients who visited the emergency room between January 2016 and January 2020. On abdomen/pelvis computed tomography (CT) performed during the hospital stay, muscle mass was measured as an index of the total abdominal muscle area index (TAMAI). We evaluated the relationship between mortality due to sepsis, myokine levels, and muscle mass. Results. A total of 210 participants (168 patients and 42 healthy controls) were enrolled in the present study. Median BDNF levels in patients diagnosed with sepsis and septic shock were significantly lower than in healthy controls. In contrast, median oncostatin M levels in patients with sepsis and septic shock were significantly higher than in healthy controls. BDNF and oncostatin M levels showed a statistically significant negative correlation. TAMAI in patients with sepsis and septic shock were 34.6 cm2/m2 and 34.2 cm2/m2, respectively; however, the TAMAI had no correlation with either BDNF or oncostatin M levels. BDNF level was significantly higher in the 28-day survivors than in those that died. Increased oncostatin M levels were associated with higher 14- and 28-day mortalities. At the end of treatment, BDNF levels and muscle mass were significantly higher in survivors than in deceased patients. Conclusions. BDNF levels were significantly lower, and oncostatin M levels were significantly higher in patients with sepsis and septic shock than in healthy controls. Muscle mass was significantly lower in patients who died as the result of sepsis; however, the levels of myokines were not associated with muscle mass. These results highlight the potential of BDNF and oncostatin M as diagnostic and prognostic biomarkers of sepsis.

Background Brain-derived neurotrophic factor (BDNF) is a pleiotropic cytokine that not only acts on the central nervous system, but is also implicated in metabolic regulation, development of lung diseases, and support of hematopoiesis. Recently, a study report that the plasma levels of BDNF were independently associated with mortality in critically ill patients. We aimed to evaluate the role of BDNF in sepsis patients and animal sepsis model. Methods Prospectively enrolled adult sepsis patients (n=168) who visited the emergency room (ER) of Korea University Ansan Hospital from January 2017 to December 2018., and healthy volunteers (n=48) were included in the present study. Serum BDNF level was determined and analyzed in septic patients and healthy volunteers. The effects of BDNF on pro-inflammatory cytokines, AMP-activated protein kinase (AMPK) and NF-κB signaling in septic condition of RAW264.7 cells and mouse peritoneal macrophage, and mouse sepsis model by cecal ligation and puncture (CLP). Results Serum BDNF levels (mean) were significantly decreased in sepsis patients compared to healthy controls (11.78ng/ml vs 18.91ng/ml, p< 0.001) and significantly decreased in non-survivors compared to survivors at discharge (3.16ng/ml vs 13.86ng/ml, p< 0.05). BDNF treatment suppressed LPS-induced pro-inflammatory cytokine (TNF-α, iL-6, and iL-1β) in RAW264.7 cells. Although LPS stimulation diminished AMPK phosphorylation, BDNF was able to decrease the effects of LPS/toll-like receptor 4 (TLR4) engagement on down stream signaling events, particularly LPS-induced IκBα degradation in RAW cells and peritoneal macrophage. In CLP model, intra-muscular injection of BDNF after CLP significantly decreased serum levels of TNF-α which was increased compared to sham, and significantly improved survival of mouse (p< 0.01). Conclusion Sepsis results in a decreased production of BDNF, which might be a potential prognostic biomarker and therapeutic target through AMPK signal pathway for sepsis. Disclosures All Authors: No reported disclosures.

Background Scrub typhus causes systemic vasculitis and can lead to complications ranging from pneumonia and acute renal injury to meningitis or encephalitis. In South Korea, it occurs not only in rural areas but also in urban areas, and especially high in older people. We hypothesized that patients with scrub typhus are predisposed to increased risks for developing dementia. Methods We performed a population-based cohort study, in which persons aged between 60∼89 years, used the Health Insurance Review and Assessment database of South Korea between 2009 and 2018. The case definition of scrub typhus was based on the ICD-10 diagnostic code and prescription of doxycycline more than three days. Dementia was defined as patients with the code in expending benefit coverage or patients with the ICD-10 codes, examination codes and drug codes. The control group was selected as stratifying by age and gender at a ratio of 1:5 to the number of the case group in study population. Results During the observational periods, Of 76,073 patients had diagnosed with scrub typhus, 5,026 excluded due to diagnosed with scrub typhus during window period, with dementia or died before index date, 71,047 patients were included as case group. 355,235 patients were included as controls. During a mean follow-up of 5.6±2.9 years, 14,089 (19.8%) patients with previous scrub typhus and 61,807 (15.2%) controls had been developed dementia. Scrub typhus was significantly associated with dementia (adjusted hazard ratio [aHR], 1.12; 95% confidential interval [CI], 1.10-1.15, P< 0.001). Of dementia classification, the risk of Alzheimer dementia was significantly higher in the case group (17.8% vs 15.2%; aHR, 1.15; 95%CI, 1.13-1.18, p< 0.001), however, there was no significant difference in the risk of vascular dementia (2.1% vs 2.2%; aHR, 0.98; 95%CI, 0.83-1.16, p=0.82). Cumulative incidence of dementia during the follow-up period by the history of scrub typhus It shows in both groups dementia incidence increased over time and the case group had higher incident dementia compared with control group. Conclusion History of scrub typhus infection in elderly was associated with increased risk for dementia, especially Alzheimer’s dementia. Our results suggest that prevent measures of dementia could be improved by preventing and treating scrub typhus. Disclosures All Authors: No reported disclosures.

Metal chalcogenides have attracted attention as potential thermoelectric materials due to their intrinsically low thermal conductivity arising from their layered structure with weak van der Waals atomic bonding. InSe, one of the post transition metal chalcogenides, also has low thermal conductivity and doping of InSe with elements such as Sn, Si, and As is known to improve the electronic transport properties. Herein, we investigated Te doping in Si-doped InSe (In0.9Si0.1Se) and report enhanced thermoelectric properties, mainly the increased Seebeck coefficient due to the increase in effective mass. Due to the increase in effective mass, the magnitude of the Seebeck coefficient systematically increased with Te doping from 234 µV/K to 405 µV/K. Eventually, the zT at 700 K was enhanced from 0.040 for the pristine sample to 0.069–0.096 for the Te-doped samples.

Background Despite high vaccination coverage, measles outbreaks have been reported in measles elimination countries, especially among healthcare workers in their 20 and 30 s. This study was designed to identify measles-susceptible individuals and to evaluate whether primary or secondary vaccine failure occurred during measles outbreak response immunization (ORI) activities. Methods The study population was divided into three groups as follows: natural immunity group (Group 1), vaccine-induced immunity group (Group 2), and vaccine failure group (Group 3). We evaluated the immunogenicity of measles among healthcare workers using three methods—enzyme-linked immunoassays, plaque reduction neutralization tests, and avidity assays. The results were assessed at baseline, 4 weeks after, and 6 months after the completion of measles-mumps-rubella (MMR) vaccination. Results In total, 120 subjects were enrolled, with 40 subjects in each group. The median age of Group 3 was 29 years, which was significantly lower than that of the other groups. The baseline negative measles virus (MeV) IgG in Group 3 increased to a median value of 165 AU/mL at 4 weeks after ORI and was lower than that in Groups 1 and 2. The median neutralizing antibody titer was highest in Group 1, and this was significantly different from that in Group 2 or Group 3 at 4 weeks (944 vs. 405 vs. 482 mIU/mL, P = 0.001) and 6 months (826 vs. 401 vs. 470, P = 0.011) after ORI. The rates of high MeV avidity IgG were highest in Group 2, and these were significantly different from those in Groups 1 or 3 at 4 weeks (77.5 vs. 90% vs. 88.6%, P = 0.03) and 6 months (81 vs. 94.8 vs. 82.1%, P = 0.01) after ORI. Conclusions Considering the MeV-neutralizing antibodies and IgG avidity after MMR vaccination in measles-susceptible group, vaccine failure is inferred as secondary vaccine failure, and further data regarding the maintenance of immunogenicity are needed based on long-term data. The MeV-neutralizing antibody levels were highest in the natural immunity group, and the primary vaccine-induced immunity group showed the highest rates of high MeV IgG avidity.

A biopolymer film serving as a wound-healing substitute was fabricated using keratin and fibrin (extracted from a goat hoof and blood, respectively) via modified Shindai techniques. The importance ...

Memory T cells contribute to rapid viral clearance during re-infection, but the longevity and differentiation of SARS-CoV-2-specific memory T cells remain unclear. Here we conduct ex vivo assays to evaluate SARS-CoV-2-specific CD4+ and CD8+ T cell responses in COVID-19 convalescent patients up to 317 days post-symptom onset (DPSO), and find that memory T cell responses are maintained during the study period regardless of the severity of COVID-19. In particular, we observe sustained polyfunctionality and proliferation capacity of SARS-CoV-2-specific T cells. Among SARS-CoV-2-specific CD4+ and CD8+ T cells detected by activation-induced markers, the proportion of stem cell-like memory T (TSCM) cells is increased, peaking at approximately 120 DPSO. Development of TSCM cells is confirmed by SARS-CoV-2-specific MHC-I multimer staining. Considering the self-renewal capacity and multipotency of TSCM cells, our data suggest that SARS-CoV-2-specific T cells are long-lasting after recovery from COVID-19, thus support the feasibility of effective vaccination programs as a measure for COVID-19 control., T cells are instrumental to protective immune responses against SARS-CoV-2, the pathogen responsible for the COVID-19 pandemic. Here the authors show that, in convalescent COVID-19 patients, memory T cell responses are detectable up to 317 days post-symptom onset, in which the presence of stem cell-like memory T cells further hints long-lasting immunity.

A new series of proton-conducting solid polymer electrolytes with different compositions, comprising polyvinylpyrrolidone (PVPK40) and polymethylmethacrylate (PMMA) as host polymers, methanesulfonic acid (MSA) as a proton-conducting salt, and alumina (Al2O3) as the nanofiller, were prepared using solution casting. High proton-conducting samples were identified and utilized for the construction of primary proton batteries. The electrical properties of the prepared electrolytes were investigated through AC impedance analysis. The highest proton conductivity (2.51 × 10−5 S/cm) was achieved at room temperature by PMMA-PVPK40-MSA-based blended polymer electrolytes (BS3). The discharge characteristics of filler-dispersed solid polymer electrolytes were better than those of other solid polymer electrolytes. The estimated energy density of the constructed proton battery using solid polymer electrolytes with blended polymers and nanofillers was 0.66 and 3.25 Wh kg−1, respectively.

A simple solution cast route was used to prepare proton conducting solid polymer electrolytes using poly(methyl methacrylate) and poly(vinylpyrrolidone) as polymer hosts and methanesulfonic acid as a proton provider. Fourier transform infrared spectra confirmed functional group interactions between polymers, blended polymers, and acid. Polymer glass transition temperature shifted with increasing acid content in the blend electrolytes provide thermal stability up to 290 °C, verified by differential scanning calorimetry and thermogravimetry analyses. Proton conductivity achieved = 1.16 × 10−4 S/cm at room temperature with an ionic transport number of 0.98. Discharge profiles verified oxidation current

We investigated potential nosocomial aerosol transmission of severe fever with thrombocytopenia syndrome virus (SFTSV) with droplet precautions. During aerosol generating procedures, SFTSV was be transmitted from person to person through aerosols. Thus, airborne precautions should be added to standard precautions to avoid direct contact and droplet transmission.

Objective: To evaluate the impact of enhanced environmental cleaning (two times per day) compared with conventional cleaning on the acquisition of carbapenem-resistant Acinetobacter baumannii (CRAB) in a highly endemic intensive care unit (ICU). Methods: The intervention consisted of alternating environmental cleaning and conventional cleaning every 3 months during the study period from July 2018 to June 2019. CRAB acquisition was assessed using incidence and prevalence rates, and colonization pressure. Results: The incidence rates of CRAB with and without enhanced cleaning were 16.3 and 13.9 cases per 1000 population, respectively; and the prevalence rates were 66.9 and 61.7 cases per 1000 population, respectively. Colonization pressure was 53.3% with enhanced cleaning and 51.3% without enhanced cleaning. No association was found between enhanced environmental cleaning and the incidence (P=0.156), prevalence (P=0.888) and colonization pressure (P=0.825) of CRAB acquisition. The ventilator utilization ratio increased the colonization pressure of CRAB acquisition (P=0.010, β coefficient=0.37). The proportion of new nurses with

Few studies have focused on clinical courses or viral loads in young asymptomatic or mild patients with COVID-19 infection. We sought to better understand the clinical course and association between viral load and prevalence of pneumonia in young COVID-19 patients with asymptomatic or mild disease severity. In this retrospective study, 106 COVID-19 young patients with asymptomatic or mild disease severity were analyzed for clinical characteristics, clinical course, prevalence of radiologically proven pneumonia and viral load. The cut-off value of viral load for presence of pneumonia was also investigated. The mean age was 28.0±9.3 years. Eleven patients (10.4%) experienced viral remission within one week of diagnosis, but one (0.9%) transferred to the hospital due to aggravation of pneumonia. Patients with pneumonia had significantly higher viral load than those without, and the cut-off value of the Ct value for presence of pneumonia were 31.38. The patients with pneumonia had significantly slower recovery times than those without. Diarrhea was significantly more common in patients with pneumonia than patients without pneumonia. In conclusion, most young asymptomatic and mildly symptomatic patients showed stable clinical course. There were significant differences in viral load and recovery times between patients with and without pneumonia.

Memory T cells contribute to rapid viral clearance during re-infection, but the longevity and differentiation of SARS-CoV-2-specific memory T cells remain unclear. We conducted direct ex vivo assays to evaluate SARS-CoV-2-specific CD4+ and CD8+ T cell responses in COVID-19 convalescents up to 254 days post-symptom onset (DPSO). Here, we report that memory T cell responses were maintained during the study period. In particular, we observed sustained polyfunctionality and proliferation capacity of SARS-CoV-2-specific T cells. Among SARS-CoV-2-specific CD4+ and CD8+ T cells detected by activation-induced markers, the proportion of stem cell-like memory T (TSCM) cells increased, peaking at approximately 120 DPSO. Development of TSCM cells was confirmed by SARS-CoV-2-specific MHC-I multimer staining. Considering the self-renewal capacity and multipotency of TSCM cells, our data suggest that SARS-CoV-2-specific T cells are long-lasting after recovery from COVID-19. The current study provides insight for establishing an effective vaccination program and epidemiological measurement.

Next-generation electronic and optoelectronic devices require a high-quality channel layer. Graphene is a good candidate because of its high carrier mobility and unique ambipolar transport characteristics. However, the on/off ratio and photoresponsivity of graphene are typically low. Transition metal dichalcogenides (e.g., MoSe2) are semiconductors with high photoresponsivity but lower mobility than that of graphene. Here, we propose a graphene/MoSe2 barristor with a high-k ion-gel gate dielectric. It shows a high on/off ratio (3.3 × 104) and ambipolar behavior that is controlled by an external bias. The barristor exhibits very high external quantum efficiency (EQE, 66.3%) and photoresponsivity (285.0 mA/W). We demonstrate that an electric field applied to the gate electrode substantially modulates the photocurrent of the barristor, resulting in a high gate tuning ratio (1.50 μA/V). Therefore, this barristor shows potential for use as an ambipolar transistor with a high on/off ratio and a gate-tunable photodetector with a high EQE and responsivity. An approach that enhances control over charge carrier movement in graphene-based transistors may be useful in applications such as bendable circuits and light sensors. The difference in current flow when a transistor turns from on to off plays a critical role in determining device performance. Bae Ho Park from Konkuk University in Seoul, South Korea, and colleagues report that stacking graphene on top of another two-dimensional (2D) film of molybdenum selenide can lead to larger on/off current ratios than conventional graphene transistors. Optical and electrical characterizations revealed that the interface between the 2D films created a potential barrier that blocked current flow in the device’s off state without compromising graphene’s mechanical flexibility. Using an external voltage to modulate current flow through the barrier region also allowed the stacked device to serve as a high-efficiency photodetector. we report a field-effect device with a graphene/MoSe2 channel layer and high-k ion-gel gate dielectric. The device shows a high carrier mobility (~247 cm2/V ∙ s), a high on/off ratio (3.3 × 104), and ambipolar behavior that are controlled by an applied gate voltage. The strong gating effect of the device results in higher external quantum efficiency (EQE) (66.3%), photoresponsivity (285.0 mA/W), and gate-tuning ratio (1.50 μA/V) compared to pristine devices. Therefore, our graphene/MoSe2 barristor device can be a suitable candidate for use in ambipolar transistors and gate-tunable broad-area photodetectors.

The formation of secondary phases of NiTe2 and NbTe2 in p-type Bi0.5Sb1.5Te3 thermoelectric alloys was investigated through in situ phase separation by using the melt spinning process. Adding stoichiometric Ni, Nb, and Te in a solid-state synthesis process of Bi0.5Sb1.5Te3, followed by rapid solidification by melt spinning, successfully segregated NiTe2 and NbTe2 in the Bi0.5Sb1.5Te3 matrix. Since heterointerfaces of Bi0.5Sb1.5Te3 with NiTe2 and NbTe2 form potential barriers of 0.26 and 0.08 eV, respectively, a low energy carrier filtering effect can be expected, higher Seebeck coefficients and power factors were achieved for Bi0.5Sb1.5Te3(NiTe2)0.01 (250 &mu, V/K and 3.15 mW/mK2), compared to those of Bi0.5Sb1.5Te3 (240 &mu, V/K and 2.69 mW/mK2). However, there was no power factor increase for NbTe2 segregated samples. The decrease in thermal conductivity was seen due to the possible additional phonon scattering by the phase segregations. Consequently, zT at room temperature was enhanced to 0.98 and 0.94 for Bi0.5Sb1.5Te3(NiTe2)0.01 and Bi0.5Sb1.5Te3(NbTe2)0.01, respectively, compared to 0.79 for Bi0.5Sb1.5Te3. The carrier filtering effect induced by NiTe2 segregations with an interface potential barrier of 0.26 eV effectively increased the Seebeck coefficient and power factor, thus improving the zT of p-type Bi0.5Sb1.5Te3, while the interface potential barrier of 0.08 eV of NbTe2 segregation appeared to be too small to induce an effective carrier filtering effect.

Background Olfactory and gustatory dysfunction has been reported as characteristic symptoms of coronavirus disease 2019 (COVID-19). This study evaluated olfactory and gustatory dysfunction in mild COVID-19 patients using validated assessment methods. Methods A prospective surveillance study was conducted for mild COVID-19 patients who were isolated at the Gyeonggi International Living and Treatment Support Center (LTSC), Korea. Olfactory function was assessed using the Korean version of the Questionnaire of Olfactory Disorders (QOD) and Cross-Cultural Smell Identification Test (CC-SIT). Gustatory function was assessed using an 11-point Likert scale and 6-n-propylthiouracil, phenylthiocarbamide, and control strips. All patients underwent nasal and oral cavity endoscopic examination. Results Of the 62 patients at the LTSC, 15 patients (24.2%) complained of olfactory or gustatory dysfunction on admission. Four of 10 patients who underwent functional evaluation did not have general symptoms and 2 were asymptomatic. The mean short version of QOD-negative statements and QOD-visual analogue scale scores were 13 ± 6 and 4.7 ± 3.6, respectively. The mean CC-SIT score was 8 ± 2. No patients showed anatomical abnormalities associated with olfactory dysfunction on endoscopic examination. The mean Likert scale score for function was 8 ± 2, and there were no abnormal lesions in the oral cavity of any patient. Conclusions The prevalence of olfactory and gustatory dysfunction was 24.2% in mild COVID-19 patients. All patients had hyposmia due to sensorineural olfactory dysfunction, which was confirmed using validated olfactory and gustatory evaluation methods and endoscopic examination. Olfactory and gustatory dysfunction may be characteristic indicators of mild COVID-19., Graphical Abstract

SummaryBackgroundAngiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) have anti-inflammatory effects. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the membrane protein angiotensin-converting enzyme 2 (ACE2), which is increased by ARB/ACEI treatment, as a cell entry receptor. Therefore, the use of ARBs/ACEIs for COVID-19 remains controversial.MethodsA retrospective case-control study was conducted using COVID-19 patients previously diagnosed with hypertension before COVID-19 onset. The primary outcome was severe infection or all-cause mortality. Cases included ARB/ACEI use for ≥30 days during the 6 months before COVID-19 onset. Primary controls included antihypertensive use other than ARBs/ACEIs (narrow control); secondary controls included all other hypertension patients (broad control). We investigated ARB/ACEI association with outcomes in general and by subgroups (age, sex, and presence of diabetes) using logistic regression models with propensity score matching.FindingsOf 234427 suspected COVID-19 patients we screened, 1585 hypertension patients were analyzed. In the 892 cases, 428 narrow controls, and 693 broad controls, severe infection or death occurred in 8·6%, 22·2%, and 16·7%, respectively. ARB/ACEI use was associated with a reduced risk of severe infection or death relative to the narrow control group (adjusted odds ratio [aOR] 0·43, 95% confidence interval [CI] 0·28 – 0·65) and broad control group (aOR 0·49, 95% CI 0·33 – 0·71). The association was smaller for newly diagnosed hypertension patients (aOR 0·11, 95% CI 0·03 – 0·42 compared to narrow control group). ARB/ACEI protective effects against severe infection or death were significantly observed in male and diabetic patients.InterpretationARB/ACEI use was associated with a lower risk of severe infection or mortality compared to other antihypertensives or ARB/ACEI nonuse.FundingNoneResearch in contextEvidence before this studyAnimal studies reported that ACE2 attenuates lung injury and provides a protective effect against severe pneumonia. Additionally, retrospective studies found that ARBs/ACEIs may have beneficial effects on ARDS patient survival. Previous observational studies have reported no potential harmful association of either ARBs or ACEIs with COVID-19 outcomes.Added value of this studyBy analyzing nationwide claims data in South Korea, we found that previous use of ARB/ACEI was associated with improved outcomes in COVID-19 compared with either nonuse or use of a different class of antihypertensive drugs. The risk of severe infection or death was consistently about 55% lower in those treated with ARB/ACEIs than those who were not exposed to ARB/ACEIs. The protective effect of ARB/ACEI was remained significantly among the male subgroup and patients with diabetes. This association was also observed among COVID-19 patients with newly diagnosed hypertension.Implications of all the available evidenceThese results provide supporting evidence for the continued use of ARBs/ACEIs among patients with COVID-19. Moreover, for newly diagnosed hypertension patients, initiation of ARB/ACEI use may not adversely affect COVID-19 prognosis. Given the poor prognosis of COVID-19 patients with hypertension and lack of curable strategy, these findings may have considerable clinical implications in prevention of poor outcome in patients with hypertension.

Since sepsis was first defined, sepsis management has remained challenging. To improve mortality rates for sepsis and septic shock, an accurate diagnosis and prompt administration of appropriate antibiotics are essential. The goals of antimicrobial stewardship are to achieve optimal clinical outcomes and to ensure cost-effectiveness and minimal unintended consequences, such as toxic effects and development of resistant pathogens. A combination of inadequate diagnostic criteria for sepsis and time pressure to provide broad-spectrum antimicrobial therapy remains an obstacle for antimicrobial stewardship. Efforts such as selection of appropriate empirical antibiotics and de-escalation or determination of whether or not to stop antibiotics may help to improve a patient's clinical prognosis as well as the successful implementation of antimicrobial stewardship.

Background: Olfactory and gustatory dysfunction have been reported as characteristic symptoms of coronavirus disease 2019 (COVID-19). This study evaluated olfactory and gustatory dysfunction in mild COVID-19 patients using validated assessment methods. Methods: A prospective surveillance study was conducted for mild COVID-19 patients who were isolated at the Gyeonggi International Living and Treatment Support Center (LTSC), Korea. Olfactory function was assessed using the Korean version of the Questionnaire of Olfactory Disorders (QOD) and Cross-Cultural Smell Identification Test (CC-SIT). Gustatory function was assessed using an 11-point Likert scale and 6-n-propylthiouracil, phenylthiocarbamide, and control strips. All patients underwent nasal and oral cavity endoscopic examination. Findings: Of the 62 patients at the LTSC, 15 patients (24.2%) complained of olfactory or gustatory deterioration on admission. Four of 10 patients who underwent functional evaluation did not have general symptoms and 2 patients were asymptomatic. The mean sQOD-NS and QOD-VAS scores were 13 ± 6 and 4.7 ± 3.6, respectively. The mean CC-SIT score was 8 ± 2. No patients showed anatomical abnormalities associated with olfactory dysfunction on endoscopic examination. The mean Likert scale score for function was 8 ± 2, and there were no abnormal lesions in the oral cavity of any patient. Interpretation: The prevalence of olfactory and gustatory dysfunction was 24.2% in mild COVID-19 patients. All patients had hyposmia due to sensorineural olfactory deterioration, which was confirmed using validated olfactory and gustatory evaluation methods and endoscopic examination. Olfactory and gustatory dysfunction may be characteristic indicators of mild COVID-19. Funding Statement: No funding. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study protocol was approved by the Institutional Review Board of the Korea University Ansan Hospital (2020AS0122).

After publication of the original article [1], we were notified that an author’s name has been incorrectly spelled. Soon You Kwon’s correct full name is Soon Young Kwon.

Yersinia pseudotuberculosis is a causative agent of foodborne zoonosis that usually causes self-limiting pseudoappendicitis. Y. pseudotuberculosis infection also causes systemic spread or extraintestinal manifestations in patients with predisposing conditions. Here, we present a case of acute hepatitis with Y. pseudotuberculosis bacteremia in a 30-year-old man. He was previously healthy without significant medical history other than obesity and current smoking. At the time of admission, he presented with high fever accompanied by chills, jaundice, abdominal pain, and watery diarrhea. Laboratory studies revealed leukocytosis and elevated liver function parameters. A stool culture showed no causative pathogens. Empiric antibiotic therapy with ceftriaxone and metronidazole was administered. Y. pseudotuberculosis was later isolated from the initial blood culture performed on the day of admission using MALDI-TOF mass spectrometry. Antibiotic treatment was continued based on the susceptibility testing results from MALDI-TOF MS and VITEk®2, as well as clinical and laboratory improvements. The patient was discharged on the tenth day of admission and remained healthy with no recurrence during the 12-month follow-up. Here, we review the literature on the systemic infection caused by Y. pseudotuberculosis, including extraintestinal manifestations. This case highlights that Y. pseudotuberculosis may be considered a differential causative organism in patients with acute colitis and hepatitis.

The Third International Consensus Definitions for Sepsis and Septic Shock (SEPSIS-3) task force assessed the latest pathophy-siological parameters associated with sepsis and septic shock and defined sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection. This SEPSIS-3 definition may be applied using relevant clinical and biological criteria in-cluding changes in the Sequential Organ Failure Assessment score and serum lactate levels. The new definition does not include cri-teria for systemic inflammatory response syndrome or the concept of `severe sepsis.` The SEPSIS-3 definition aims to devise more precise descriptions of sepsis and to improve clinical care. However, there are important questions relating to the clinical applica-tion of the new definition. We review the main characteristics and limitations of previous definitions and discuss some of the poten-tial controversies raised by the new framework. (Korean J Med 2017;92:342-348)

The aim of this study was to develop a new method, using a vibration sensor, to address the drawbacks of preexisting methods for monitoring soil ecological toxicity. A novel method was designed by inspiration from seismometers, which record signals originating from the ground motion caused by earthquake events. Similarly, the newly developed method using a vibration sensor detects the signals generated by earthworm activity, which reflects the soil ecological toxicity. To establish the new method, a stepwise approach was adopted: (1) the effects of operational conditions on the overall performance of the system were evaluated, and (2) the feasibility of the method was tested by an application study. A number of crucial factors influencing the overall performance of the method were evaluated. These were categorized based on three features: soil, tested organism, and instrumentation. The soil properties evaluated included soil type (artificial and natural), moisture content, and bulk density. In terms of the organism, the effect of the number of earthworms was investigated. Finally, with regard to instrumentation, appropriate soil chamber specifications and monitoring duration were identified. The most effective conditions for each factor were determined based on a comparative evaluation of changes in the activity levels and body weights of the earthworms. After the first step of the study, an application study was carried out to demonstrate the feasibility of the proposed method. Zinc (Zn)-contaminated soils were tested under the most efficient operational conditions identified in the preceding study. The results of the study confirm that the method is applicable to natural soils, and the best performance was achieved under soil conditions of 50–60% maximum water holding capacity and 0.95 g/cm3 bulk density. Furthermore, the optimal number of earthworms was found to be five, which corresponds 19.84 g soil per earthworm. With respect to the instrumental conditions, the most efficient specification was a cylindrical soil chamber with a diameter of 94 mm and height of 54 mm. Additionally, the most relevant monitoring duration was found to be 7 days. The results indicate that the method can shorten the testing period, reduce the soil amount and earthworm number required, and facilitate the real-time monitoring of mortality. Based on the results of the application study, we validated the proposed vibration sensor-based method for characterizing earthworm behavior in terms of its feasibility for monitoring the ecological toxicity of soil. The results indicate that dermal contact and feeding activity of earthworms decreased significantly with increasing Zn concentrations in the soil. The EC50 value of Zn calculated based on the earthworm behavior was 340.97 mg/kg. Based on the results, it is concluded that the proposed method cannot only overcome the shortcomings of traditional test methods using earthworms, but also enable real-time ecotoxicity in soil environments.

The use of organic conjugated polymers in sensors has attracted greater attention due to their application in materials technology. In the present communication, we utilized Schiff's condensation polymerization reaction for the synthesis of a novel conjugated polymer poly(tetrahexadecyl-dihydroindacenodithiophene)-alt-(p-phenylenediimine) (PIDTPD) consisting of indacenodithiophene (IDT) and p-phenylene diamine (PDA) units for use in acid vapor sensing. Conventionally, the characteristics and applications of conjugated polymers are affected by their constituents. The imine bond between the components of organic materials has received little attention compared to their active counterparts. In order to explore the practical application of conjugated polymers in sensors, we employed PIDTPD in a paper sensor and illustrated the impact of mono- and bis-protonation on the pristine material in driving a noteworthy protonation-induced color shift toward the longer wavelength region via acidochromism.

Memory T cell responses have been demonstrated in COVID-19 convalescents, but ex vivo phenotypes of SARS-CoV-2-specific T cells have been unclear. We detected SARS-CoV-2-specific CD8+ T cells by MHC class I multimer staining and examined their phenotypes and functions in acute and convalescent COVID-19. Multimer+ cells exhibited early differentiated effector-memory phenotypes in the early convalescent phase. The frequency of stem-like memory cells was increased among multimer+ cells in the late convalescent phase. Cytokine secretion assays combined with MHC class I multimer staining revealed that the proportion of interferon-I³ (IFN-I³)-producing cells was significantly lower among SARS-CoV-2-specific CD8+ T cells than those specific to influenza A virus. Importantly, the proportion of IFN-I³-producing cells was higher in PD-1+ cells than PD-1- cells among multimer+ cells, indicating that PD-1-expressing, SARS-CoV-2-specific CD8+ T cells are not exhausted, but functional. Our current findings provide information for understanding of SARS-CoV-2-specific CD8+ T cells elicited by infection or vaccination.

Nitrogen functionalized graphitic carbon (NGC), aside from being a distinctive support material for catalyst integration, is also intrinsically active for various electrochemical reactions especially in energy storage and conversion devices. Given the admirable conductivity and graded pore structure, the strategy of hybridizing metal oxides with NGC skeleton is reckoned to be highly compelling in the design of electrode materials. In this work, carboxy methylcellulose and melamine derived – Co3O4 NGC is used as an active electrode material for high performance asymmetric supercapacitors (ASC). The synthesized Co3O4 NGC exhibits microglobules with mesoporous network and maximum surface area of 445.3 m2 g−1 at 77 K. A solid state ASC is fabricated with activated carbon and Co3O4 NGC microglobules as negative and positive electrodes, respectively based on charge balancing theory, delivering ultra-high capacitance (128.43 F. g−1), energy density (45.66 Wh.kg−1) and power density (399.9 W.kg−1). Further, excellent capacitance retention (92.1%) over 5000 cycles confirms their long-term stability, which in turn enlightening the energy storage device progress for future generation electronics.

Lead-free (100 − x)BiFeO3–xBaTiO3 (BFBTx, x = 0, 30, 33, 40 and 50) piezoelectric thin films were deposited on platinized silicon substrates by using a pulsed laser deposition method. The BFBTx thin films has a single-phase perovskite structure with (111) preferred orientations. Atomic force microscopy images showed the dense morphology, and large piezoresponses were observed in the piezoelectric force microscope measurements. The best local piezoelectric coefficient, value of 259 pm V−1, was observed in the BFBT40 thin film. This result is one of the best values in lead-free piezoelectric thin films with a simple geometry. The BFBT40 piezoelectric thin film can be considered as a strong candidate to replace lead-based piezoelectric thin films for piezoelectric-based microelectromechanical systems.

Background Even after the introduction of the Sepsis-3 definition, there is still debate on the ideal antibiotic administration time in patients with sepsis. This study was performed to evaluate the association between the timing of antibiotic administration and mortality in sepsis patients who visited the emergency room. Methods A prospective cohort study was conducted on patients who were diagnosed as sepsis with Sepsis-3 definition among patients who visited the emergency department (ED) of Korea University Ansan Hospital from September 2017 to January 2019. The timing of antibiotic administration was defined as the time in hours from ED arrival until the first antibiotic administration. Cox logistic regression analysis was used to estimate the association between time to antibiotics and 7-, 14-, and 28-day mortality. Results During the study period, a total of 251 patients were enrolled with a 7-, 14-, and 28-day mortality of 16.7%, 36.3%, and 57.4%, respectively. The median time to antibiotic administration was 247 minutes (interquartile range 72 – 202 minutes). The mean age was 72 ± 15 years old and 122 patients (48.6%) were female. The most common site of infection was respiratory infection. The timing of antibiotic administration were not associated with 7-, 14-, and 28-day mortality. Female (adjusted hazard ratio [HR] 2.06 [95% confidence interval (CI) 1.21 – 3.53]; P value = 0.008), SOFA score (aHR 1.17 [95% CI 1.05 - 1.31]; P = 0.005), and initial lactate level (aHR 1.13 [95% CI 1.05 - 1.22]; P = 0.001) increased the risk of 7-day mortality. Female (aHR 2.07 [95% CI 1.48 – 2.89]; P ≤ 0.001), Charlson comorbidity index (aHR 1.12 [95% CI 1.02 - 1.24]; P = 0.025), and initial lactate level (aHR 1.19 [95% CI 1.02 - 1.16]; P = 0.011) increased the risk of 14-day mortality. Female (aHR 1.95 [95% CI 1.50 – 2.54]; P = 0.001) increased the risk of 28-day mortality in patients with sepsis. Conclusion The timing of antibiotic administration did not increase the risk of mortality in the treatment of sepsis patients who visited ED. Rather, the SOFA score, lactate, female, and comorbidity increased the mortality associated with sepsis. Disclosures All authors: No reported disclosures.

Selectively activated inorganic synaptic devices, showing a high on/off ratio, ultrasmall dimensions, low power consumption, and short programming time, are required to emulate the functions of high-capacity and energy-efficient reconfigurable human neural systems combining information storage and processing (Li et al. Sci. Rep. 2014, 4, 4096). Here, we demonstrate that such a synaptic device is realized using a Ag/PbZr0.52Ti0.48O3 (PZT)/La0.8Sr0.2MnO3 (LSMO) ferroelectric tunnel junction (FTJ) with ultrathin PZT (thickness of ∼4 nm). Ag ion migration through the very thin FTJ enables a large on/off ratio (107) and low energy consumption (potentiation energy consumption = ∼22 aJ and depression energy consumption = ∼2.5 pJ). In addition, the simple alignment of the downward polarization in PZT selectively activates the synaptic plasticity of the FTJ and the transition from short-term plasticity to long-term potentiation.

The cooperative effect of pyridine catalysis with photoenhanced electrochemical reduction by CdTe/FTO of CO2 is explored. The enhancement of overall formic acid production and high faradaic efficiency is due to the increased photocurrent of CdTe/FTO upon irradiation and the decrease in activation barrier due to the formation of a pyridine–CO2 intermediate.

Temozolomide is the current first-line treatment for glioblastoma patients but, because many patients are resistant to it, there is an urgent need to develop antitumor agents to treat temozolomide-resistant glioblastoma. Gossypol, a natural polyphenolic compound, has been studied as a monotherapy or combination therapy for the treatment of glioblastoma. The combination of gossypol and temozolomide has been shown to inhibit glioblastoma, but it is not clear yet whether gossypol alone can suppress temozolomide-resistant glioblastoma. We find that gossypol suppresses the growth of temozolomide-resistant glioblastoma cells in both tumor sphere and adherent culture conditions, with tumor spheres showing the greatest sensitivity. Molecular docking and binding energy calculations show that gossypol has a similar affinity to the Bcl2 (B-cell lymphoma 2) family of proteins and several dehydrogenases. Gossypol reduces mitochondrial membrane potential and cellular ATP levels before cell death, which suggests that gossypol inhibits several dehydrogenases in the cell&rsquo, s metabolic pathway. Treatment with a Bcl2 inhibitor does not fully explain the effect of gossypol on glioblastoma. Overall, this study demonstrates that gossypol can suppress temozolomide-resistant glioblastoma and will be helpful for the refinement of gossypol treatments by elucidating some of the molecular mechanisms of gossypol in glioblastoma.

Background Fosfomycin is one of the antibiotics that may be a candidate for the next-generation antimicrobial agents againt multidrug-resistant bacteria. To date, it is known that the resistance rate is not high for Escherichia coli. However, it is necessary to update the fosfomycin resistance rates in E. coli according to the studies that extended spectrum β-lactamase (ESBL) producing E. coli strains are highly resistance to fosfomycin. We evaluated the resistance rate of fosfomycin, the resistant mechanism of fosfomycin in E. coli, and the activity of fosfomycin against susceptible and resistant strains of E. coli. Methods A total of 283 clinical isolates was collected from patients with Escherichia coli species during the period of January 2018 to June 2018, in three tertiary hospitals of Republic of Korea. In vitro antimicrobial susceptibility tests were performed in all E. coli isolates using the broth microdilution method according to the Clinical and Laboratory Standard Institute (CLSI). Multilocus sequence typing (MLST) of the Oxford scheme was conducted to determine the genotypes of E. coli isolated. Fosfomycin genes were investigated for all fosfomycin-resistant E. coli strains. Results The overall resistance rate to fosfomycin was 10.2%, compared with 53.4%, 46.3%, 41.3%, 31.1%, 10.6%, 2.5%, and 2.1% for ciprofloxacin, cefixime, cefepime, piperacillin/tazobactam, colistin, ertapenem, and amikacin, respectively. The 29 fosfomycin-resistant isolates did not show a clonal pattern on the phylogenetic tree. MurA and glp genes were identified in all strains. FosA3 were identified in two strains and uhp gene were identified in 4 strains. In time-kill curve studies, fosfomycin was more bactericidal than cefixime against all sensitive E. coli strain. Morever, fosfomycin was more bactericidal than piperacillin/tazobactam against ESBL-producing E. coli strain. Conclusion The resistant rate of fosfomycin to E. coli is still low. Fosfomycin was active against E. coli including ESBL producing strains. Disclosures All authors: No reported disclosures.

We investigated the role of glucosamine (GlcN) on the integrin β4/plectin complex and its role in the regulation of mouse embryonic stem cell (mESC) migration and proliferation. GlcN significantly decreased integrin β4 mRNA/protein expression, whereas plectin protein expression did not change. Also, decrease of integrin β4 expression caused reduction of integrin β4/plectin complex formation, and then increased cell migration. GlcN increased intracellular calcium influx and protein kinase C (PKC) phosphorylation followed by integrin β4 serine phosphorylation and reduction of the integrin β4/plectin complex. GlcN entered into the cell through glucose transporter 1 and then increased O-GlcNAc transferase (OGT) and the level of glycosylation (CTD110.6). Inhibition of OGT (OGT inhibitor; ST045849) increased integrin β4/plectin complex opposite with decreased cell migration. Moreover, GlcN increased O-GlcNAc-specificity protein 1 (Sp1) and nuclear translocated p-Sp1 stimulated calmodulin (CaM) expression, which combined with plectin. In addition, GlcN increased Akt glycosylation and glycogen synthase kinase-3β (GSK-3β) phosphorylation, and then Snail1 glycosylation. Snail small interfering ribonucleic acid (siRNA) reversed the reduction of integrin β4/plectin complex and dissociation of cell junctions (tight and adherent junction). GlcN increased cell migration, cell cycle regulatory proteins [cyclinD1, cyclin-dependent kinase 4 (CDK4), cyclinE, and CDK2], and the percentage of S phase cells, which were inhibited by a PKC inhibitor, CaM siRNA, or Snail1 siRNA. Additionally, GlcN maintained the undifferentiation status of ESCs. In conclusion, GlcN contributed to migration and proliferation of mESCs through integrin β4/plectin complex reduction via Ca²⁺/PKC, as well as the Sp1/CaM and Akt/GSK-3β/Snail1 signaling pathway.

Delphinidin, gallic acid, betulinic acid, and ursolic acid, which are bio-active ingredients in a variety of fruits, vegetables, and herbs, have potent antioxidant activity and various biological activities. However, it is not clear whether these bio-active ingredients can significantly contribute to the protection of embryonic stem (ES) cells from hypoxia-induced apoptosis. In the present study, hypoxia-induced ES cells apoptosis with time, which were abrogated by pretreatment with all ingredients. Hypoxia-induced ROS generation was blocked by pretreatment with all ingredients in a dose-dependent manner, with the maximum ROS scavenging effect observed for delphinidin. Hypoxia increased phosphorylation of JNK and NF-κB were blocked by pretreatment of delphinidin as well as NAC. Hypoxia decreased phosphorylation of Akt(thr308) and (ser473); these decreases were reversed by pretreatment with delphinidin or NAC. However, Akt inhibition did not affect NF-κB phosphorylation. Delphinidin attenuated the hypoxia-induced increase in Bax, cleaved caspase-9, cleaved caspase-3, and decrease in Bcl-2, which were diminished by pretreatment of Akt inhibitor. Hypoxia induced Bax translocation from the cytosol to mitochondria. Furthermore, hypoxia induced mitochondria membrane potential loss and cytochrome c release in cytosol, which were blocked by delphinidin pretreatment. Hypoxia induced cleavage of procaspase-9 and procaspase-3 which were blocked by delphinidin or SP600125, but Akt inhibitor abolished the protection effect of delphinidin. Moreover, inhibition of JNK and NF-κB abolished hypoxia-induced ES cell apoptosis and inhibition of Akt attenuated delphinidin-induced blockage of apoptosis. The results indicate that delphinidin can prevent hypoxia-induced apoptosis of ES cells through the inhibition of JNK and NF-κB phosphorylation, and restoration of Akt phosphorylation.