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Background: About 10% of patients with gallbladder (GB) stones also have concurrent common bile duct (CBD) stones. Laparoscopic cholecystectomy (LC) after removal of CBD stones using endoscopic retrograde cholangiopancreatography (ERCP) is the most widely used method for treating coexisting gallbladder and common bile duct stones. We evaluated the optimal timing of LC after ERCP according to clinical factors, focusing on preoperative relief of jaundice. Methods: A total of 281 patients who underwent elective LC after ERCP because of choledocholithiasis and cholecystolithiasis from January 2010 to April 2018 were retrospectively reviewed. We compared the hospital stay, perioperative morbidity, and rate of surgical conversion to open cholecystectomy according to the relief of jaundice before surgery. These enrolled patients were divided into two groups: relief of jaundice before surgery (group 1, n = 125) or not (group 2, n = 156). Results: The initial total bilirubin level was higher in group 1; however, there were no significant differences in the other baseline characteristics including age, sex, American Society of Anesthesiologists score, previous surgical history, white blood cell count, C-reactive protein, and operative time between the two groups. There was also no significant difference in postoperative hospital stay between the two groups (4.5 ± 3.3 vs. 5.5 ± 5.6 days, p = 0.087). However, after ERCP, the waiting time until LC was significantly longer in group 1 (5.0 ± 4.9 vs. 3.5 ± 2.4 days, p < 0.001). There were no statistical differences in the conversion rate (3.2% vs. 3.8%, p = 0.518) or perioperative morbidity (4.0% vs. 5.8%, p = 0.348), either. Conclusions: LC would not be delayed until the relief of jaundice after ERCP since there were no significant differences in perioperative morbidity or surgical conversion rate to open cholecystectomy. Early LC after ERCP may be feasible and safe in patients with cholangitis and cholecystolithiasis. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

An acoustic finite element model of a bridge is developed to evaluate the noise generated by the traffic-induced vibration of the bridge. The dynamic response of a multi-girder bridge, modeled by a three-dimensional (3-D) frame element model, is analyzed with a 3-axle (8 degrees of freedom (DOF)) truck model and a 5-axle (13 DOF) tractor-trailer. The flat plate element is used to analyze the acoustic pressure due to the fluid–structure interactions between the vibrating surface and contiguous acoustic fluid medium. The radiation fields of noise with a specified distribution of vibrating velocity and pressure on the structural surface are also computed using the Kirchhoff–Helmholtz integral. Among the diverse parameters affecting the dynamic response of a bridge, vehicle velocity, vehicle weight, and spatial distribution of the road surface roughness are found to be the main factors that increase the level of vibration noise. In an attempt to illustrate the influence of the structural vibration noise of a bridge to total noise level around the bridge, the random function is used to generate the vehicle noise source including the engine noise and the rolling noise between the road and tire. The results show that the low-frequency noise produced by the vibrating bridge members amplifies the high-frequency vehicle noise by 4–7 dB. In addition, the amplification rate of noise increases with traveling speed and vehicle weight. [ABSTRACT FROM AUTHOR]

Glia contribute to synapse elimination through phagocytosis in the central nervous system. Despite the important roles of this process in development and neurological disorders, the identity and regulation of the "eat‐me" signal that initiates glia‐mediated phagocytosis of synapses has remained incompletely understood. Here, we generated conditional knockout mice with neuronal‐specific deletion of the flippase chaperone Cdc50a, to induce stable exposure of phosphatidylserine, a well‐known "eat‐me" signal for apoptotic cells, on the neuronal outer membrane. Surprisingly, acute Cdc50a deletion in mature neurons causes preferential phosphatidylserine exposure in neuronal somas and specific loss of inhibitory post‐synapses without effects on other synapses, resulting in abnormal excitability and seizures. Ablation of microglia or the deletion of microglial phagocytic receptor Mertk prevents the loss of inhibitory post‐synapses and the seizure phenotype, indicating that microglial phagocytosis is responsible for inhibitory post‐synapse elimination. Moreover, we found that phosphatidylserine is used for microglia‐mediated pruning of inhibitory post‐synapses in normal brains, suggesting that phosphatidylserine serves as a general "eat‐me" signal for inhibitory post‐synapse elimination. SYNOPSIS: Neuronal‐specific deletion of the flippase chaperone Cdc50a leads to exposure of phosphatidylserin on neuronal outer membranes causing specific loss of inhibitory post‐synapses and seizures. Microglial phagocytosis via the phagocytic receptor MERTK promotes inhibitory post‐synapse elimination in Cdc50a cKO brains. Inhibitory post‐synapses in normal juvenile brains also use phosphatidylserine for synapse elimination, suggesting that phosphatidylserine exposure functions as an "eat‐me" signal for microglia‐dependent inhibitory post‐synapse elimination. Neuronal Cdc50a deletion induces rapid lethality with appearance of audiogenic seizure.Neuronal Cdc50a deletion causes the specific loss of inhibitory post‐synapses without affecting other synapses.Ablating microglia or deleting microglial Mertk rescues the loss of inhibitory post‐synapses and seizure behaviors in Cdc50a cKO mice.Microglial Mertk deletion increases the number of phosphatidylserine‐exposed inhibitory post‐synapses in the wild‐type juvenile brains. [ABSTRACT FROM AUTHOR]

• Enhanced environmental cleaning alone failed to reduce carbapenem-resistant Acinetobacter baumannii (CRAB) acquisition in an intensive care unit. • The ventilator utilization ratio increased the CRAB colonization pressure. • Inexperienced nurses may be associated with increased CRAB acquisition. 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). 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. 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 <3 years of clinical practice experience was positively correlated with the incidence and prevalence of CRAB acquisition. Enhanced environmental cleaning alone failed to reduce CRAB acquisition in a highly endemic ICU. The ventilator utilization ratio may be of more importance than environmental cleaning. Inexperienced nurses may need to be monitored regarding infection control activities in addition to hand hygiene adherence. [ABSTRACT FROM AUTHOR]

Neutralizing antibodies targeted at the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have been developed and now under evaluation in clinical trials. The US Food and Drug Administration currently issued emergency use authorizations for neutralizing monoclonal antibodies in non-hospitalized patients with mild to moderate coronavirus disease 2019 (COVID-19) who are at high risk for progressing to severe disease and/or hospitalization. In terms of this situation, there is an urgent need to investigate the clinical aspects and to develop strategies to deploy them effectively in clinical practice. Here we provide guidance for the use of anti-SARS-CoV-2 monoclonal antibodies for the treatment of COVID-19 based on the latest evidence. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Despite the global effort to mitigate the spread, coronavirus disease 2019 (COVID-19) has become a pandemic that took more than 2 million lives. There are numerous ongoing clinical studies aiming to find treatment options and many are being published daily. Some effective treatment options, albeit of variable efficacy, have been discovered. Therefore, it is necessary to develop an evidence-based methodology, to continuously check for new evidence, and to update recommendations accordingly. Here we provide guidelines on pharmaceutical treatment for COVID-19 based on the latest evidence. [ABSTRACT FROM AUTHOR]

배경 In sepsis, the systemic response systemic inflammatory response of the host to pathogens, host factors with poor prognosis include old age, frailty, and sarcopenia. Biomarkers to evaluate the diagnosis and severity of sepsis may be critical for adequate clinical decision and help improve the prognosis of sepsis. Among biomarkers, this study was conducted to evaluate the association between the myokine, cytokines produced and secreted by muscle cells, and the diagnosis and prognosis of sepsis, and also to evaluate whether myokine is associated with muscle mass. 방법 A prospective cohort study was conducted among adult sepsis patients who visited the emergency room of Korea University Ansan Hospital from January 2016 to January 2020. The myokines measured in this study were brain-derived neutrotrophic factor oncostatin M. Muscle mass index was measured by a board-certified radiologist on axial images of L3 vertebra level in patients underwent abdomen CT scan at the time of admission for sepsis. 결과 During the study population, 627 sepsis patients were included in the study. Of these, myokines were measured in 168 patients, and 66 patients (39.2%) were diagnosed as septic shock. The median SOFA score was 8 in sepsis group and 11 in septic shock group. The initial lactate levels were 2.5 and 5.6 mmol/L in sepsis and septic shock, respectively. In-hospital mortality rate was 39.3%, and the 7-, 14-, and 28-day mortality rates were 13.7%, 21.4%, and 26.8%, respectively. Among myokines, the median value of BDNF were 11.2ng/mL and 10ng/mL in sepsis and septic shock, respectively. The median value of oncostatin M were 102pg/mL and 111.6pg/mL in sepsis and septic shock, respectively. Total abdomi- nal muscle area index (TAMAI) were 34.6㎠/㎡ and 34.2㎠/㎡ in sepsis and septic shock, respectively. BDNF was statistically significantly different from sepsis (P < 0.001) and septic shock (P <0.001) com- pared with the control group, respectively. Oncostatin M in sepsis (P <0.001) and septic shock (P <0.001) were significantly different from the control group, respectively. Higher oncostatin M were asso- ciated with increased 14-day mortality (adjusted hazard ratio [aHR]: 1.01, 95% confidence interval [CI]: 1.00-1.02, P = 0.028) and 28-day mortality (aHR: 1.01, 95% CI 1.00-1.02, P = 0.010). BDNF at the di- agnosis of sepsis was statistically higher in survivors (12.15 ng/mL) than in deaths (8.19 ng/mL), where as oncostatin M showed no difference between the two groups. TAMAI showed higher value in the sur- vivors (35.23㎠/㎡) than in the deaths (30.6㎠/㎡). TAMAI did not show any association with myokines. 결론 In patients with sepsis and septic shock, BDNF was lower than that of healthy controls and oncostatin M was higher than that of healthy controls. Oncostatin M was associated with higher mortality in sepsis patients, and BDNF was significantly higher in sepsis survivors. Muscle mass did not show a significant association with myokine levels. [ABSTRACT FROM AUTHOR]

Glycyl‐tRNA synthetase 1 (GARS1), a cytosolic enzyme secreted from macrophages, promotes apoptosis in cancer cells. However, the mechanism underlying GARS1 secretion has not been elucidated. Here, we report that GARS1 is secreted through unique extracellular vesicles (EVs) with a hydrodynamic diameter of 20–58 nm (mean diameter: 36.9 nm) and a buoyant density of 1.13–1.17 g/ml. GARS1 was anchored to the surface of these EVs through palmitoylated C390 residue. Proteomic analysis identified 164 proteins that were uniquely enriched in the GARS1‐containing EVs (GARS1‐EVs). Among the identified factors, insulin‐like growth factor II receptor, and vimentin also contributed to the anti‐cancer activity of GARS1‐EVs. This study identified the unique secretory vesicles containing GARS1 and various intracellular factors that are involved in the immunological defence response against tumorigenesis. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a major global public health issue. SARS-CoV-2 infection is confirmed by the detection of viral RNA using reverse transcription polymerase chain reaction (RT-PCR). Prolonged viral shedding has been reported in patients with SARS-CoV-2 infection, but the presence of viral RNA does not always correlate with infectivity. Therefore, the present study aimed to confirm the presence of viable virus in asymptomatic or mildly symptomatic patients in the later phase of the disease, more than two weeks after diagnosis. Method: Asymptomatic or mildly symptomatic COVID-19 patients who had been diagnosed with the disease at least two weeks previously and admitted to a community treatment center (CTC) from 15 March to 10 April 2020 were enrolled in this study. Nasopharyngeal and salivary swab specimens were collected from each patient. Using these specimens, RT-PCR assay and viral culture were performed. Result: In total, 48 patients were enrolled in this study. There were no significant differences in baseline characteristics between the asymptomatic and mildly symptomatic patient groups. RT-PCR assay and viral culture of SARS-CoV-2 were performed using nasopharyngeal and salivary swabs. The results of RT-PCR performed using salivary swab specimens, in terms of cycle threshold (Ct) values, were similar to those of RT-PCR using nasopharyngeal swab specimens. In addition, no viable virus could be cultured from swab specimens collected from the late-phase COVID-19 patients with prolonged viral RNA shedding. Conclusions: In conclusion, our study suggests that even if viral shedding is sustained in asymptomatic or mildly symptomatic patients with later phase of COVID-19, it can be expected that the transmission risk of the virus is low. In addition, saliva can be used as a reliable specimen for the diagnosis of SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Background: No studies have investigated the association between self-rated health (SRH) and high-sensitivity C-reactive protein (hs-CRP) levels in South Koreans. We explored this association and analyzed differences between sexes.Methods: Using cross-sectional data from the 2015-2017 Korea National Health and Nutrition Examination Survey, we analyzed the association between SRH and high hs-CRP levels (> 1.0 mg/L) in 14,544 Koreans aged ≥ 19 years who responded to the SRH survey and had available hs-CRP test results. Differences in sociodemographic factors were analyzed using the Pearson's chi-square test for categorical variables or the Mann-Whitney U test for continuous variables. Multiple logistic regression analysis was used to measure the association between hs-CRP levels and SRH according to sex while adjusting for other possible confounders.Results: The percentage of very poor to poor SRH was higher in the high hs-CRP group (22.4%) than in the low hs-CRP group (17.66%). Among men, the risk of a high hs-CRP level increased with worse SRH (adjusted for confounders; P for trend < 0.001). After adjusting for all confounders, including chronic diseases, men with very poor SRH showed a higher odds ratio (OR) for high hs-CRP levels than those with very good SRH (fully adjusted OR, 1.74; 95% CI, 1.04-2.90). Significant correlations were absent among women.Conclusions: Poor SRH was correlated with low-grade inflammation (high hs-CRP levels) among Korean male adults. These findings could be useful for developing health improvement programs and in goal setting at a national scale. [ABSTRACT FROM AUTHOR]

Glycyl‐tRNA synthetase 1 (GARS1), a cytosolic enzyme secreted from macrophages, promotes apoptosis in cancer cells. However, the mechanism underlying GARS1 secretion has not been elucidated. Here, we report that GARS1 is secreted through unique extracellular vesicles (EVs) with a hydrodynamic diameter of 20–58 nm (mean diameter: 36.9 nm) and a buoyant density of 1.13–1.17 g/ml. GARS1 was anchored to the surface of these EVs through palmitoylated C390 residue. Proteomic analysis identified 164 proteins that were uniquely enriched in the GARS1‐containing EVs (GARS1‐EVs). Among the identified factors, insulin‐like growth factor II receptor, and vimentin also contributed to the anti‐cancer activity of GARS1‐EVs. This study identified the unique secretory vesicles containing GARS1 and various intracellular factors that are involved in the immunological defence response against tumorigenesis. [ABSTRACT FROM AUTHOR]

The article discusses the results of a study that examines the concurrence of active pulmonary tuberculosis (TB) and influenza A(H1N1)pdm09 virus infection in South Korea. The study shows the sensitivity to anti-TB drugs by all Mycobacterium tuberculosis isolates. Lifetime risk for development of active TB is 5 percent to 10 percent for persons infected with Mycobacterium tuberculosis and increases for those with immunocopromising conditions.

Premise: When plants are exposed to stress conditions, irreversible damage can occur, negatively impacting yields. It is therefore important to detect stress symptoms in plants, such as the accumulation of anthocyanin, as early as possible. Methods and Results: Twenty‐two regression models in five color spaces were trained to develop a prediction model for plant anthocyanin levels from digital color imaging data. Of these, a quantile random forest regression model trained with standard red, green, blue (sRGB) color space data most accurately predicted the actual anthocyanin levels. This model was then used to noninvasively monitor the spatial and temporal accumulation of anthocyanin in Arabidopsis thaliana leaves. Conclusions: The digital imaging–based nature of this protocol makes it a low‐cost and noninvasive method for the detection of plant stress. Applying a similar protocol to more economically viable crops could lead to the development of large‐scale, cost‐effective systems for monitoring plant health. [ABSTRACT FROM AUTHOR]

Since the first case was reported in Wuhan, Hubei Province, China on December 12, 2019, Coronavirus disease 2019 (COVID-19) has spread widely to other countries since January 2020. As of April 16, 2020, 10635 confirmed cases have been reported, with 230 deaths in Korea. COVID-19 patients may be asymptomatic or show various clinical manifestations, including acute symptoms such as fever, fatigue, sore throat; pneumonia presenting as acute respiratory distress syndrome; and multiple organ failure. As COVID-19 has such varied clinical manifestations and case fatality rates, no standard antiviral therapy regimen has been established other than supportive therapy. In the present guideline, we aim to introduce potentially helpful antiviral and other drug therapies based on in vivo and in vitro research and clinical experiences from many countries. [ABSTRACT FROM AUTHOR]

To develop a clinical practice guideline for vaccination in patients with autoimmune inflammatory rheumatic disease (AIIRD), the Korean College of Rheumatology and the Korean Society of Infectious Diseases developed a clinical practice guideline according to the clinical practice guideline development manual. Since vaccination is unlikely to cause AIIRD or worsen disease activities, required vaccinations are recommended. Once patients are diagnosed with AIIRD, treatment strategies should be established and, at the same time, monitor their vaccination history. It is recommended to administer vaccines when the disease enters the stabilized stage. Administering live attenuated vaccines in patients with AIIRD who are taking immunosuppressants should be avoided. Vaccination should be considered in patients with AIIRD, prior to initiating immunosuppressants. It is recommended to administer influenza, Streptococcus pneumoniae, hepatitis A, hepatitis B, herpes zoster, measlesmumps- rubella virus, human papillomavirus, and tetanus-diphtheria-pertussis vaccines in patients with AIIRD; such patients who planned to travel are generally recommended to be vaccinated at the recommended vaccine level of healthy adults. Those who live in a household with patients with AIIRD and their caregivers should also be vaccinated at levels that are generally recommended for healthy adults. [ABSTRACT FROM AUTHOR]

Background: ERCP training models are very different in terms of anatomical differences, ethical issues, storage problems, realistic tactile sensation, durability and portability. There is no easy way to select an optimized model for ERCP training. If the ERCP training model could be made as a soft silicone model using 3D printing technique, it would have numerous advantages over the models presented so far. The purpose of this study was to develop an optimized ERCP training model using a 3D printing technique and to try to find ways for implementing various practical techniques.Methods: All organ parts of this model were fabricated using silicone molding techniques with 3D printing. Especially, various anatomy of the ampulla of Vater and common bile duct (CBD) were creatively designed for different diagnostic and therapeutic procedures. In order to manufacture each of the designed organ parts with silicone, a negative part had to be newly designed to produce the molder. The negative molders were 3D printed and then injection molding was applied to obtain organ parts in silicone material. The eight different types of ampulla and CBD were repeatedly utilized and replaced to the main system as a module-type.Results: ERCP training silicone model using 3D technique was semi-permanently used to repeat various ERCP procedures. All ERCP procedures using this model could be observed by real-time fluoroscopic examination as well as endoscopic examination simultaneously. Using different ampulla and CBD modules, basic biliary cannulation, difficult cannulation, stone extraction, mechanical lithotripsy, metal stent insertion, plastic stent insertion, and balloon dilation were successfully and repeatedly achieved. Endoscopic sphincterotomy was also performed on a specialized ampulla using a Vienna sausage. After repeat procedures and trainings, all parts of organs including the ampulla and CBD modules were not markedly damaged or deformed.Conclusions: We made a specialized ERCP training silicon model with 3D printing technique. This model is durable, relatively cheap and easy to make, and thus allows the users to perform various specialized ERCP techniques, which increases its chances of being a good ERCP training model. [ABSTRACT FROM AUTHOR]

Objective: To determine the association of radiological and symptomatic osteoarthritis with sleep duration in a representative sample of the Korean population. Methods: Using data from the national cross-sectional fifth Korea National Health and Nutrition Examination Survey 2010–2012. Of the 16,528 participants in KNHANES-V, 8,918 were adults aged≥ 50 years who had completed the survey questions on sleep duration and osteoarthritis, and had diagnostic X-ray results. We evaluated the association between sleep duration as the primary predictor for osteoarthritis involving the hip, knee, and spinal joints. A complex sample logistic regression analysis was performed to adjust for the covariates. Results: Proportions of participants with total daily sleep duration of ≤6 hours, 7–8 hours, and ≥9 hours were 47.1%, 45.2, and 7.7%, respectively. The rate of osteoarthritis diagnoses in the ≤6 hours, 7–8 hours, and ≥9 hours of sleep duration groups was 24.1%, 17.6%, and 21.8%, respectively (p <0.0001). The odds ratios (OR) were significantly higher in the ≤6 hours of sleep group than in the 7–8 hours of sleep group (OR, 1.20; 95% confidence interval [CI], 1.03–1.39; p = 0.02), but no significant difference in the ≥9 hours of sleep group was found after adjusting the confounding variables. When we compared knee joint pain (Numeric Rating Scale 0 versus 1–10) in participants with grade 2–4 Kellgren-Lawrence (KL) classification after adjusting these same confounding variables, the ≤6 hours of sleep group (OR, 1.32; 95% CI, 1.10–1.58) and the ≥9 hours of sleep group (OR, 1.41; 95% CI, 1.03–1.95) showed significantly higher ORs. Conclusion: This study confirmed the significant association between sleep duration and osteoarthritis in adults aged ≥50 years. Participants' positive for both radiological (KL grade ≥2) and symptomatic osteoarthritis showed a strong association between knee joint pain and not enough sleep duration. [ABSTRACT FROM AUTHOR]

Background and Purpose: We recently reported that AAV1-Rheb(S16H) transduction could protect hippocampal neurons through the induction of brain-derived neurotrophic factor (BDNF) in the rat hippocampus in vivo. It is still unclear how neuronal BDNF produced by AAV1-Rheb(S16H) transduction induces neuroprotective effects in the hippocampus and whether its up-regulation contributes to the enhance of a neuroprotective system in the adult brain.Experimental Approach: To determine the presence of a neuroprotective system in the hippocampus of patients with Alzheimer's disease (AD), we examined the levels of glial fibrillary acidic protein, BDNF and ciliary neurotrophic factor (CNTF) and their receptors, tropomyocin receptor kinase B (TrkB) and CNTF receptor α(CNTFRα), in the hippocampus of AD patients. We also determined whether AAV1-Rheb(S16H) transduction stimulates astroglial activation and whether reactive astrocytes contribute to neuroprotection in models of hippocampal neurotoxicity in vivo and in vitro.Key Results: AD patients may have a potential neuroprotective system, demonstrated by increased levels of full-length TrkB and CNTFRα in the hippocampus. Further AAV1-Rheb(S16H) transduction induced sustained increases in the levels of full-length TrkB and CNTFRα in reactive astrocytes and hippocampal neurons. Moreover, neuronal BDNF produced by Rheb(S16H) transduction of hippocampal neurons induced reactive astrocytes, resulting in CNTF production through the activation of astrocytic TrkB and the up-regulation of neuronal BDNF and astrocytic CNTF which had synergistic effects on the survival of hippocampal neurons in vivo.Conclusions and Implications: The results demonstrated that Rheb(S16H) transduction of hippocampal neurons could strengthen the neuroprotective system and this intensified system may have a therapeutic value against neurodegeneration in the adult brain. [ABSTRACT FROM AUTHOR]

Background/Aims: Using an appropriate guidewire can increase the success rate of selective cannulation in endoscopic retrograde cholangiopancreatography. The purpose of this technical study was to investigate the characteristics of each guidewire type and to evaluate its efficiency and rapidity of insertion. Methods: We conducted a three-point bending test using a universal testing machine to investigate the flexibility and bending features of each guidewire. 3D-printed silicone tubes with various types of stricture and a hand-made biliary tree silicone model with sixstranded intrahepatic ducts were used to evaluate the success rate and insertion time of each guidewire. Results: In the three-point bending test, the characteristics of each guidewire were classified. We found that the bending strengths and times were independent of shaft thickness. Using two in vitro biliary duct models, we determined that the success rate and total insertion time were better for guidewires with a resilient shaft and angled tip than for other types of guidewires (p<0.001). Although thickness of the guidewire affected the success rate (p<0.05), it did not affect the total insertion time (p≥0.05). Conclusions: Among several types of guidewire, some factors (resilient shaft, highly flexible, and angled tip) appeared to be associated with the efficiency and rapidity of the guidewire insertion. [ABSTRACT FROM AUTHOR]

Aim: Stearoyl-CoA desaturase (SCD)-1 and elongase-6 (Elovl-6) are associated with fatty acid (FA) synthesis. We evaluated the effect of omega-3 FA on erythrocyte membrane FA contents through SCD-1 and Elovl-6 expression in the liver and kidney of a cyclosporine (CsA)-induced rat model. Methods: Male Sprague Dawley rats were divided into control, CsA, and CsA treated with omega-3 FA groups. We measured SCD-1 and Elovl-6 expression levels via western blot and immunohistochemistry analysis. Results: Erythrocyte membrane oleic acid content was lower in the CsA with omega-3 FA group compared to the CsA group. Compared to the control group, CsA-induced rats showed elevated SCD-1 expression in the kidney and liver, which omega-3 FA treatment reversed. Elovl-6 expression was increased in the liver, but decreased in the kidney in CsA group compared to control, which omega-3 FA treatment also reversed. Conclusions: Omega-3 FA supplementation decreased erythrocyte membrane oleic acid content by modulating SCD-1 and Elovl-6 expression in the kidney and liver of CsA-induced rats. [ABSTRACT FROM AUTHOR]

Background: We evaluated the optimal radiotherapy (RT) plan for synchronous bilateral breast cancer (SBBC), especially treatment plans including the regional lymph node (LN) area.Methods: This study was conducted using 15 patients with SBBC (5 with small breasts, 5 with large breasts, and 5 who underwent a left total mastectomy). The clinical target volume (CTV) was defined as the volume enveloping the bilateral whole breasts/chest wall and left regional LN area. We established the following plans: 1) volumetric-modulated arc therapy (VMAT)-the only plan using two pairs of partial arcs for the whole target volume, 2) VMAT using one partial arc for the left CTV followed by a 3D tangential technique for the right breast (primary hybrid plan), and 3) VMAT for the left CTV followed by a tangential technique using an automatically calculated prescription dose for the right breast, considering the background dose from the left breast VMAT plan (modified hybrid plan). The Tukey test and one-way analysis of variance were used to compare the target coverage and doses to organs at risk (OARs) of the three techniques.Results: For target coverage, the VMAT-only and modified hybrid plans showed comparable target coverage in terms of Dmean (50.33 Gy vs. 50.53 Gy, p = 0.106). The primary hybrid plan showed the largest distribution of the high-dose volume, with V105% of 25.69% and V110% of 6.37% for the planning target volume (PTV) (p < 0.001). For OARs including the lungs, heart, and left anterior descending artery, the percentages of volume at various doses (V5Gy, V10Gy, V20Gy, V30Gy) and Dmean were significantly lower in both the primary and modified hybrid plans compared to those of the VMAT-only plan. These results were consistent in subgroup analyses of breast size and morphological variation.Conclusions: The modified hybrid plan, using an automatically calculated prescription dose for the right breast and taking into consideration the background dose from the left breast VMAT plan, showed comparable target coverage to that of the VMAT-only plan, and was superior for saving OARs. However, considering that VMAT can be adjusted according to the physician's intention, further evaluation is needed for developing a better plan. [ABSTRACT FROM AUTHOR]

Pathologic fibrosis around silicone implants is problematic, and thus, these implants have been coated with a mixture of a biocompatible polymer and antifibrotic drug for sustained drug release to prevent fibrosis. However, a coating applied over an entire surface would be subject to mechanical instability as the implant would be severely crumpled for implant insertion. Therefore, in this work, we proposed localized, patterned coating dots, each composed of poly(lactic-co-glycolic acid) (PLGA) and tranilast, to be applied on the surface of silicone implants. The drug loaded in the pattern-coated implant herein was well retained after a cyclic tensile test. Due to the presence of PLGA in each coating dot, the tranilast could be released in a sustained manner for more than 14 days. When implanted in a subcutaneous pocket in living rats for 12 weeks, compared with the intact implant, the pattern-coated implant showed a decreased capsule thickness and collagen density, as well as less transforming growth factor-β (TGF-β) expression and fewer fibroblasts; importantly, these changes were similar between the surfaces with and without the coating dots. Therefore, we conclude that the pattern-coating strategy proposed in this study can still effectively prevent fibrosis by maintaining the physical stability of the coatings. [ABSTRACT FROM AUTHOR]

Cloud computing is a type of Internet-based computing that allows users to access computing resources that are connected to the Internet anytime and anywhere. Recently, as the Internet-of-Things market using the cloud has grown, a tremendous amount of data has been generated, and services requiring low latency are increasing. To solve these problems, a new architecture called fog computing has been proposed. Fog computing can process data on a network device close to the user, drastically reducing the bandwidth required from the network and providing near real-time response. However, not much research has been done on which network devices should be used to deploy the fog server. In this article, we propose a fog server deployment technique to minimize the data movement path in a fog computing environment and a technique to make full use of the computing resources of a fog device through a vector bin packing algorithm in a situation where many services are concentrated on one network device. Experimental results show that the proposed algorithm can reduce the data movement distance and maximize the utilization of the computing resources of the fog device. [ABSTRACT FROM AUTHOR]

Established fear memory becomes vulnerable to disruption after memory retrieval and extinction; this labile state is critical for inhibiting the return of fear memory. However, the labile state has a very narrow time window after retrieval, and underlying molecular mechanisms are not well known. To that end, we isolated the hippocampus immediately after fear memory retrieval and performed proteomics. We identified Neurobeachin (NBEA), an autism-related regulator of synaptic protein trafficking, to be upregulated after contextual fear memory retrieval. NBEA protein expression was rapid and transient after fear memory retrieval at the synapse. Nbea mRNA was enriched at the synapses, and the rapid induction of NBEA expression was blocked by inhibition of the mammalian target of rapamycin (mTOR)-dependent signaling pathway. Mice with cornu ammonis 1 (CA1)-specific Nbea shRNA knockdown showed normal fear acquisition and contextual fear memory but impaired extinction, suggesting an important role of Nbea in fear memory extinction processes. Consistently, Nbea heterozygotes showed normal fear acquisition and fear memory recall but showed impairment in extinction. Our data suggest that NBEA is necessary either for induction of memory lability or for the physiological process of memory extinction. [ABSTRACT FROM AUTHOR]

Background: The mental V-Y advancement flap method is useful for reconstruction of lower lip defect because of its many advantages. However, it is not easy to select the optimal reconstructive method for the vermilion defect that remains after application of the mental V-Y advancement flap. In choosing the representative surgical method for vermilion mucosal reconstruction including mucosal V-Y advancement flap, buccal mucosal flap, and buccal mucosal graft. We describe an efficient technique to large lower lip defects combining mental V-Y advancement flap and buccal mucosal graft. Methods: This study included 16 patients who underwent reconstructive surgery for full-thickness and large defect (> half the entire width) of the lower lip from October 2006 to September 2017. The operation was conducted using mental V-Y advancement flap with various vermilion mucosal reconstruction methods considering the location of the defect and the amount of residual tissue of the lip coloboma after excision. Results: All patients underwent mental V-Y advancement flap. In vermilion mucosal reconstruction, five patients underwent mucosal V-Y advancement flap, three underwent buccal mucosal flap, and eight underwent buccal mucosal graft. There were good aesthetic and functional results in all patients who underwent buccal mucosal graft. However, two patients who underwent mucosal V-Y advancement flap complained of oral incompetence, and all patients who underwent buccal mucosal flap had oral commissure deformity. Conclusion: Buccal mucosal graft combined with mental V-Y advancement flap can produce suitable functional and aesthetic outcomes in near total lower lip reconstruction in patient with large mucosal defect including vermilion portion. [ABSTRACT FROM AUTHOR]

Background: Lamivudine and abacavir sulfate are widely used nucleoside/tide reverse transcriptase inhibitors (NRTI) backbone agents, which are recommended in major international treatment guidelines. The fixed-dose combination of lamivudine and abacavir sulfate has been developed to contribute to low pill burden of antiretroviral therapy (ART) regimen and patient adherence. A mandatory post-marketing surveillance was conducted in Korea to monitor the safety of Kivexa (lamivudine 300 mg/abacavir 600 mg). Materials and Methods An open label, multi-center, non-interventional post-marketing surveillance was conducted to monitor the safety of Kivexa from July 2011 to July 2017 in 23 hospitals in Korea. Subjects over 12 years old taking Kivexa per prescribing information were enrolled. The primary outcome was defined as the occurrence of any adverse events during the study period. Secondary outcomes included the occurrence of adverse drug reaction, the occurrence of serious adverse events and the effectiveness of Kivexa. Result A total of 600 patients from 23 hospitals were enrolled within the 6 years of study. The total observation period was 1,004 person-years. Three hundred and ten patients reported 674 adverse events. The incidence of upper respiratory infection (65 cases, 10.9%) was the highest, followed by diarrhea (20 cases, 3.3%), and nausea (18 cases, 3.0%). 109 subjects reported 71 events of adverse drug reactions, and the most common reaction was nausea in 2.33% of the subjects. Thirty-one subjects reported serious adverse events, none of them were considered drug related. From the total of 600 subjects, excluding 48 subjects who were 'effectiveness unassessable' by investigators, 552 patients were eligible for the subjective effectiveness analysis. 459 (83.2%) were evaluated as 'improved'. Proportion of subjects whose human immunodeficiency virus-RNA is <50 copies/ml was 61.2% (309/505) at the beginning of observation and increased to 91.9% (464/505) at the end of study period. Conclusions: The post-marketing surveillance showed the safety of Kivexa in HIV-1 patients in Korea. Ischemic cardiovascular events and hypersensitivity associated with Kivexa were few. There was no significant new safety information. This data may be helpful in implementing Kivexa and lamivudine/abacavir sulfate containing drugs in Korea. [ABSTRACT FROM AUTHOR]

Background: Watson for oncology (WFO) is a cognitive computing system providing decision support. We evaluated the concordance rates between the treatment options determined by WFO and those determined by a multidisciplinary team (MDT). Methods: We reviewed the medical charts of patients diagnosed with colorectal cancer who visited the MDT at a single tertiary medical center from November 2016 to April 2017. WFO classified the treatment options for specific patients into three categories: ‘Recommended’, ‘For consideration’, and ‘Not recommended’. Concordance rates between the WFO- and MDT-determined chemotherapy options, and the factors that potentially influence the concordance rate, were analyzed. Results: Sixty-nine patients with colorectal cancer met with the MDT from Nov. 2016 to Feb. 2017. The mean age of the patients was 62 years (range: 34–86 years), and more patients were male (47/69) than female. Of the 69 patients, 51 (73.9%) were diagnosed with colon cancer, of whom 46.4% received the same regimen recommendation from WFO (‘Recommended’) as they did from the MDT. After inclusion of the ‘For consideration’ category from WFO, the concordance rate increased to 87.0%. The concordance rate between MDT and NCCN guidelines was 97.1%, and that between the WFO and NCCN guidelines was 88.4%. The concordance rates between WFO and MDT were significantly lower in patients with stage II, IIIC, or IV disease (P<0.001), and the colorectal cancer stage was the only statistically significant factor discriminating between WFO and MDT. Conclusions: The concordance rate between chemotherapy regimens for colorectal cancer determined by MDT versus WFO recommendations was 46.4%. After including the ‘For consideration’ category from WFO, the concordance rate increased to 88.4%. Further modification and improvement of the WFO prioritizing algorithm used to recommend treatment may increase the usefulness of WFO in the clinic. [ABSTRACT FROM AUTHOR]

Background: Influenza and pneumonia are leading causes of morbidity and mortality among the elderly. Although vaccination is a main strategy to prevent these infectious diseases, concerns remain with respect to vaccine effectiveness. Methods: During three influenza seasons (2014–2015, 2015–2016 and 2016–2017), we evaluated the effectiveness of the influenza and pneumococcal vaccines against pneumonia and acute exacerbation of cardiopulmonary diseases among the elderly aged ≥65 years with influenza-like illness (ILI). Demographic and clinical data were collected prospectively. Results: Among 2,119 enrolled cases, 1,302 (61.4%) and 871 (41.1%) received the influenza vaccine and 23-valent pneumococcal polysaccharide vaccine (PPV23), respectively. During an A/H3N2-dominant season with poor influenza vaccine effectiveness (2014–2015 season), neither the influenza vaccine nor PPV23 showed significant effectiveness against pneumonia or acute exacerbation of cardiopulmonary diseases. During seasons with good influenza vaccine effectiveness (2015–2016 and 2016–2017 seasons), the influenza vaccine was effective in preventing pneumonia, but PPV23 was not. In particular, the influenza vaccine was effective in preventing acute exacerbation of heart diseases (75.0%) during the A/H1N1-dominant 2015–2016 season. Conclusion: The influenza vaccine was effective in preventing pneumonia only during vaccine-matched seasons with good effectiveness against circulating influenza viruses. In addition, the influenza vaccine was cardio-protective during a vaccine-matched A/H1N1-dominant season. [ABSTRACT FROM AUTHOR]

The efficiency of a heterojunction with intrinsic thin‐layer (HIT) solar cell with an insulator/ITO structure was discussed in this paper. First, the efficiency was analyzed by OPAL 2 simulations. Second, an insulator/ITO structure was experimentally applied to a HIT solar cell. The OPAL 2 simulations using an insulator/ITO/Si structure and a TCO/ITO/Si structure showed that the generation current density in the Si substrate increased when the insulator or TCO layer had a proper thickness. Experimentally, HfO2, a type of insulator, was deposited on a HIT solar cell with a thickness varying from 3 to 15 nm. The average efficiency of the HIT solar cell improved from 18.21% to 20.75% after HfO2 deposition. The highest efficiency was achieved for the 3‐nm‐thick HfO2/HIT solar cell structure, which exhibited the best improvement in the current density of approximately 1.5 mA/cm2. For the external quantum efficiency of the HfO2/HIT solar cell, the total absorption was improved by HfO2 deposition. The results suggest that the HfO2 layer improves the solar cell efficiency of the HIT solar cell by increasing light absorption. The simulations using an insulator or TCO/ITO/Si structures showed that the generation current density increased when the insulator or TCO layer had a proper thickness. Experimentally, the average efficiency of the HIT solar cell improved from 18.21% to 20.75% after HfO2 deposition, a type of insulator. The highest efficiency was achieved for the 3‐nm‐thick HfO2/HIT solar cell structure, which exhibited the best improvement in the current density of approximately 1.5 mA/cm2. [ABSTRACT FROM AUTHOR]

Background: Guidelines recommend a break-in period of 2 weeks before starting peritoneal dialysis (PD), but PD within 14 days is also an acceptable and safe alternative to hemodialysis (HD) in patients with an urgent need. However, the effect of the break-in period within 48 hours or later had not been evaluated for early technical complications, long-term maintenance, and survival in patients starting urgent PD. Methods: Of 360 patients with a surgically inserted PD catheter, we evaluated 190 patients who needed urgent PD and 29 patients who received conventional PD at a single center between January 2007 and December 2014 in this retrospective observational study. Enrolled patients were divided according to break-in period of <48 hours (P1) or 2–13 days (P2) before starting urgent PD. The primary endpoint was incidence of early technical complications and secondary endpoints included long-term PD maintenance, and patient survival. Results: PD was started in 103 patients (54.2%) within 48 hours and in 87 patients (45.8%) within 2 to 13 days. The incidence of early technical complication was significantly higher in P1 group (28.2%) than in P2 group (10.3%) (P = 0.002). The need for a repositioning procedure was significantly greater in P1 group (14.6%) than in P2 group (3.4%) (P = 0.009). However, we observed no significant differences between the two groups with respect to the prevalence of catheter dysfunction requiring change to HD within 6 months or incidence of peritonitis or exit-site infection. There was no significant difference in PD maintenance and patient survival according to the break-in period between P1 and P2 as well as against the control group. Conclusion: Urgent PD was associated with a low incidence of early technical complications if start was avoided within 48 hours after catheter insertion, and long-term PD maintenance was independent of the break-in period. [ABSTRACT FROM AUTHOR]

A fast computational method for modeling and simulation of large projector arrays is presented. The method is based on the array equations that account for the acoustic interaction among the projector elements as well as the individual characteristics of each projector. Unlike the existing solution method in which the acoustic interaction must be known a priori in the form of interaction impedance matrix Z, the present method seeks the solution of modified array equations through iterations without explicitly evaluating the Z matrix. This significantly speeds up the analysis of complex arrays with surrounding structures, where the evaluation of the Z matrix may require a large number of time-consuming finite element computations. The method is compared with the traditional Z-matrix method for the case of a cylindrical array of 72 × 8 Tonpilz transducers. For the same level of accuracy, the iterative method is shown to be up to 2 orders-of-magnitude faster than the Z-matrix method. The method can be used for rapid design and analysis of active sonar arrays and medical ultrasonic transducers, often made of hundreds and even thousands of elements. [ABSTRACT FROM AUTHOR]

Highlights • National immunization of the elderly with the 23-valent polysaccharide vaccine (PPSV23) was implemented in Korea in 2013. • Overall in-hospital mortality was 34.2% for adult invasive pneumococcal disease (IPD) and 51.0% for patients ≥75 years of age. • Mortality risks were older age, higher bacteremia score, and immunocompromised status. • An effective vaccination strategy for those at higher risk of IPD is needed. Abstract Objectives This study aimed to characterize the risk factors for mortality in adult patients with invasive pneumococcal disease (IPD) stratified by age groups, after implementation of the national immunization program of 23-valent polysaccharide vaccine (PPSV23) for those aged ≥65 years in the Republic of Korea (ROK). Methods Clinical data and pneumococcal isolates from adult patients with IPD (≥18 years of age) were collected prospectively from 20 hospitals through the nationwide surveillance program from March 2013 to October 2015. Results A total of 319 patients with IPD were enrolled. Median age was 69 years. Overall in-hospital mortality was 34.2%: 17.1% in those aged 18–49 years, 23.7% in those aged 50–64 years, 33.0% in those aged 65–74 years, and 51.0% in those aged ≥75 years (p < 0.001). In particular, early death within 7 days of hospitalization accounted for 60.6% (66/109). While old age (≥65 years), higher Pitt bacteremia score (≥4), and bacteremic pneumonia were independently associated with IPD mortality in all age groups, an additional mortality risk factor of immunocompromised status was identified for patients aged 50–64 years. PPSV23 serotypes accounted for 64.4% (122/189) of the pneumococcal isolates serotyped. Conclusions This study suggests that vaccine-type IPD continues to place a substantial burden on older adults in the ROK, necessitating an effective vaccination strategy for those at higher risk. [ABSTRACT FROM AUTHOR]

The production of a large amount of high-quality transition metal dichalcogenides is critical for their use in industrial applications. Here, we demonstrate the scalable exfoliation of bulk molybdenum disulfide (MoS2) powders into single- or few-layer nanosheets using the Taylor-Couette flow. The toroidal Taylor vortices generated in the Taylor-Couette flow provide efficient mixing and high shear stresses on the surfaces of materials, resulting in a more efficient exfoliation of the layered materials. The bulk MoS2 powders dispersed in N-methyl-2-pyrrolidone (NMP) were exfoliated with the Taylor-Couette flow by varying the process parameters, including the initial concentration of MoS2 in the NMP, rotation speed of the reactor, reaction time, and temperature. With a batch process at an optimal condition, half of the exfoliated MoS2 nanosheets were thinner than ~3 nm, corresponding to single to ~4 layers. The spectroscopic and microscopic analysis revealed that the exfoliated MoS2 nanosheets contained the same quality as the bulk powders without any contamination or modification. Furthermore, the continuous exfoliation of MoS2 was demonstrated by the Taylor-Couette flow reactor, which produced an exfoliated MoS2 solution with a concentration of ~0.102 mg/mL. This technique is a promising way for the scalable production of single- or few-layer MoS2 nanosheets without using hazardous intercalation materials. [ABSTRACT FROM AUTHOR]

Background: The influenza virus is reportedly associated with 3‐5 million cases of severe illness and 250 000‐500 000 deaths annually worldwide. Objectives: We investigated the variation of influenza A virus in Korea and examined the association with death. Methods: A total of 13 620 cases were enrolled in the Hospital‐based Influenza Morbidity & Mortality surveillance system in Korea during 2011‐2016. Among these cases, a total of 4725 were diagnosed with influenza using RT‐PCR (influenza A; n = 3696, influenza B; n = 928, co‐infection; n = 101). We used 254 viral sequences from the 3696 influenza A cases for phylogenetic analysis using the BioEdit and MEGA 6.06 programs. Results: We found that the sequences of A/H3N2 in the 2011‐2012 season belong to subgroup 3C.1, whereas the sequences in the 2012‐2013 season pertain to subgroup 3C.2. The sequences in the 2013‐2014 and 2014‐2015 seasons involve subgroups 3C.3a and 3C.2a. The A/H1N1pdm09 subtype belongs to subgroup 6 and contains two clusters. In addition, sequence analysis confirmed the several substitutions of internal genes and gene substitutions associated with drug resistance (I222V in NA and S31N in M2) in the fatal cases. While statistical analysis found no significant associations between genetic differences in the viruses and mortality, mortality was associated with certain host factors, such as chronic lung disease. Conclusions: In conclusion, influenza A virus clade changes occurred in Korea during the 2011‐2016 seasons. These data, along with antigenic analysis, can aid in selecting effective vaccine strains. We confirmed that fatality in influenza A cases was related to underlying patient diseases, such as chronic lung disease, and further studies are needed to confirm associations between mortality and viral genetic substitutions. [ABSTRACT FROM AUTHOR]

A class of metasurfaces for underwater sound absorption, based on a design principle that maximizes thermoviscous loss, is presented. When a sound meets a solid surface, it leaves a footprint in the form of thermoviscous boundary layers in which energy loss takes place. Considered to be a nuisance, this acoustic to vorticity/entropy mode conversion and the subsequent loss are often ignored in the existing designs of acoustic metamaterials and metasurfaces. The metasurface created is made of a series of topographic meta-atoms, i.e., intaglios and reliefs engraved directly on the solid object to be concealed. The metasurface is acoustically sticky in that it rather facilitates the conversion of the incident sound to vorticity and entropy modes, hence the thermoviscous loss, leading to the desired anechoic property. A prototype metasurface machined on a brass object is tested for its anechoicity, and shows a multitude of absorption peaks as large as unity in the 2–5 MHz range. Computations also indicate that a topographic metasurface is robust to hydrostatic pressure variation, a quality much sought-after in underwater applications. [ABSTRACT FROM AUTHOR]

Radiation-induced skin injury can take the form of serious cutaneous damage and have specific characteristics. Asymptomatic periods are classified as the latent stage. The skin barrier plays a critical role in the modulation of skin permeability and hydration and protects the body against a harsh external environment. However, an analysis on skin barrier dysfunction against radiation exposure in the latent stage has not been conducted. Thus, we investigated whether the skin barrier is impaired by irradiation in the latent stage and aimed to identify the molecules involved in skin barrier dysfunction. We analyzed skin barrier function and its components in SKH1 mice that received 20 and 40 Gy local irradiation. Increased transepidermal water loss and skin pH were observed in the latent stage of the irradiated skin. Skin barrier components, such as structural proteins and lipid synthesis enzymes in keratinocyte, increased in the irradiated group. Interestingly, we noted sebaceous gland atrophy and increased serine protease and inflammatory cytokines in the irradiated skin during the latent period. This finding indicates that the main factor of skin barrier dysfunction in the latent stage of radiation-induced skin injury is sebaceous gland deficiency, which could be an intervention target for skin barrier impairment. [ABSTRACT FROM AUTHOR]

Campylobacter infection causes gastrointestinal symptoms such as abdominal pain or diarrhea. Occasionally, Campylobacter bacteremia affects immunocompromised patients; however, serious outcomes are known to be rare. Here, we present a case of a patient with Campylobacter bacteremia who had underlying liver cirrhosis. The patient had fever and diarrhea. These symptoms subsided after treatment with cefotaxime. Campylobacter jejuni was isolated in the blood culture after 10 days. In addition, previously reported cases of Campylobacter bacteremia in Asian countries were reviewed with respect to antimicrobial sensitivities. [ABSTRACT FROM AUTHOR]

Background and Objective: Studies focusing on pulmonary tuberculosis in advanced age (≥80 years) are lacking. This study aimed to explore treatment delay, outcomes and their predictors in this group.Methods: Adult (≥20 years) patients with pulmonary tuberculosis were identified from the National Health Insurance Research Database of Taiwan from 2004 to 2009. Treatment completion and mortality rates were noted at one year after treatment.Results: Among the 81,081 patients with pulmonary tuberculosis identified, 13,923 (17.2%) were aged ≥80 years, and 26,897 (33.2%) were aged 65-79 years. The treatment completion, mortality rates and treatment delay were 54.8%, 34.7% and 61 (12-128) [median, (1st-3rd quartiles)] days in patients aged ≥80 years, 68.3%, 18.5% and 53 (8-122) days in patients aged 65-79 years, and 78.9%, 6.5% and 21 (1-84) days in patients aged <65 years, respectively. The elder patients were more likely to receive second-line anti-tuberculosis agents. The treatment completion rate decreased with older age, female sex, comorbidities, low income, requiring second-line anti-tuberculosis agents, severity of pulmonary tuberculosis and longer treatment delay. Older age, female sex, comorbidities, low income, and not undergoing rapid molecular diagnostic tests were independently associated with longer treatment delays.Conclusions: Pulmonary tuberculosis in advanced age has a longer treatment delay and a higher mortality rate. Applying rapid molecular diagnostic tools may reduce treatment delay and should be integrated into the diagnostic algorithm for pulmonary tuberculosis, particularly in elderly patients. [ABSTRACT FROM AUTHOR]

In the 2016–2017 season, the A(H3N2) influenza epidemic presented an unusual early peak pattern compared with past seasons in South Korea. The interim vaccine effectiveness (VE) of influenza vaccination in preventing laboratory-confirmed influenza was estimated using test-negative design through the tertiary hospital-based influenza surveillance system in South Korea. From 1 September, 2016 to 7 January, 2017, adjusted VE of influenza vaccination in preventing laboratory-confirmed A(H3N2) was -52.1% (95% confidence interval [CI], -147.2 to 6.4); -70.0% (95% CI, -212.0 to 7.4) in 19–64 years and 4.3% (95% CI, -137.8 to 61.5) in the elderly. Circulating A(H3N2) viruses belonged to the three phylogenetic subclades of 3C.2a, differently to A/Hong Kong/4801/2014, the current vaccine strain. Amino acid substitutions in hemagglutinin of circulating viruses seem to contribute to low VE. In conclusion, interim VE analysis presented that the protection of laboratory-confirmed influenza by seasonal influenza vaccination did not show the statistical significance in South Korea in the 2016–2017 influenza season. [ABSTRACT FROM AUTHOR]

Purpose. Radiation-induced lung fibrosis (RILF) is a serious late complication of radiotherapy. In vitro studies have demonstrated that pentoxifylline (PTX) has suppressing effects in extracellular matrix production in fibroblasts, while the antifibrotic action of PTX alone using clinical dose is yet unexplored. Materials and Methods. We used micro-computed tomography (micro-CT) and histopathological analysis to evaluate the antifibrotic effects of PTX in a rat model of RILF. Results. Micro-CT findings showed that lung density, volume loss, and mediastinal shift are significantly increased at 16 weeks after irradiation. Simultaneously, histological analysis demonstrated thickening of alveolar walls, destruction of alveolar structures, and excessive collagen deposition in the irradiated lung. PTX treatment effectively attenuated the fibrotic changes based on both micro-CT and histopathological analyses. Western analysis also revealed increased levels of plasminogen activator inhibitor- (PAI-) 1 and fibronectin (FN) and PTX treatment reduced expression of PAI-1 and FN by restoring protein kinase A (PKA) phosphorylation but not TGF-β/Smad in both irradiated lung tissues and epithelial cells. Conclusions. Our results demonstrate the antifibrotic effect of PTX on radiation-induced lung fibrosis and its effect on modulation of PKA and PAI-1 expression as possible antifibrotic mechanisms. [ABSTRACT FROM AUTHOR]

Aim:Coronary artery calcification (CAC) score on computed tomography (CT) or vascular calcification (VC) scores on plain radiographs are associated with cardiovascular events and fracture. We investigated which VC score among several VC scores on plain radiographs is predictor of CAC, and whether VC scores are related with bone mineral density (BMD) in dialysis patients. Methods:We checked several plain radiographs (hands and pelvis [HP], feet and lateral lumbar spine), BMD and multidetector CT scans of 55 patients maintaining dialysis in this cross-sectional study. We analyzed data to find predictors for severe CAC which was defined as CAC scores >400 on CT. Results:Patients with severe CAC on CT had a higher proportion of abdominal aortic calcification (AAC) score ≥5, HP score ≥3 and feet ≥1 than those without severe CAC. The CAC score on CT was positively correlated with all VC scores on plain radiographs. The AAC and CAC scores were negatively correlated with T-scores for the BMD at the forearm and positively correlated with osteoprotegerin levels. Among several VC scores on plain radiographs, the AAC ≥5 were independently associated with severe CAC on CT. Conclusions:Several plain radiographs evaluating VC scores, including a lateral lumbar spine view at the very least, can replace CT checking CAC score in dialysis patients. The AAC score ≥5 may not only reveal severe CAC but also give a hint of low bone mass at the forearm. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization recommends the surveillance of influenza-like illness (ILI) and severe acute respiratory infection (SARI) to respond effectively to both seasonal influenza epidemics and pandemics. In Korea, the “Hospital-based Influenza Morbidity and Mortality (HIMM)” surveillance system has been operated to monitor ILI and SARI occurrences. Materials and Methods: A multi-center prospective observational study was conducted. Adult patients with acute respiratory infection (ARI) were enrolled during the 2011-12, 2012-2013, and 2013-2014 influenza seasons at the 10 university hospitals using the HIMM surveillance system. With respect to SARI and pneumonia development, risk profiles were analyzed in patients with ARI in Korea. Results: A total of 5,459 cases were eligible for this analysis. Among 5,459 cases with ARI, 2,887 cases (52.9%) were identified that they had influenza infection. Among enrolled cases, 750 cases belonged to the SARI group, while 4,709 cases belonged to the non-SARI group. With respect to pneumonia development, 317 cases were accompanied by pneumonia, and 5,142 cases were not. Multivariate analyses revealed that the following factors were associated with an increased risk of SARI: Old age (≥65 years) (odds ratio [OR] 2.69, 95% confidence interval [CI] 2.2-3.32), chronic heart disease (CHD) (OR 2.24, 95% CI 1.68-2.98), cerebrovascular disease (CVD) (OR 1.49, 95% CI 1.05-2.10), chronic obstructive pulmonary disease (COPD) (OR 2.34, 95% CI 1.48-3.69), asthma (OR 2.33, 95% CI 1.62-3.36), chronic kidney disease (CKD) (OR 2.62, 95% CI 1.73-3.99), chronic liver disease (OR 1.71, 95% CI 1.04-2.81), and autoimmune diseases (OR 2.53, 1.57-4.08). Multivariate analyses revealed that the following factors were independent risk factors for pneumonia development: Old age (≥65 years) (OR 5.71, 95% CI 4.10-7.94), CHD (OR 1.54, 95% CI 1.07-2.22), COPD (OR 2.34, 95% CI 1.48-3.69), asthma (OR 2.33, 95% CI 1.62-3.36), CKD (OR 2.62, 95% CI 1.73-3.99), immunocompromised conditions (OR 3.12, 95% CI 1.47-6.62), and autoimmune diseases (OR 3.35, 95% CI 1.79-6.27). The risk of SARI and pneumonia was increased by the number of concurrent chronic medical conditions. Conclusion: The risk of SARI and pneumonia development among adult patient with ARI was significantly increased by the presence or number of concurrent chronic medical conditions in Korea. [ABSTRACT FROM AUTHOR]

Background: For more effective and safer usage of antibiotics, the dosing strategy should be individualized based on the patients' characteristics, including race. The aim of this study was to investigate the population pharmacokinetic (PK) profiles of piperacillin and tazobactam in Korean patients with acute infections. Materials and Methods: At least four consecutive 2/0.25 g or 4/0.5 g doses of piperacillin/tazobactam (TZP) were intravenously infused over 1 h every 8 h for patients with creatinine clearance (CLcr) ≤50 ml/min or CLcr >50 mL/min, respectively. Blood samples from 33 patients at a steady-state were taken pre-dose and at 0 min, 30 min, and 4-6 h after the fourth infusion. The population PK analysis was conducted using a non-linear mixed-effects method. A likelihood ratio test was used to select significant covariates, with significance levels of P <0.05 for selection and P <0.01 for elimination. Results: Both piperacillin PK and tazobactam PK were well described by a two-compartment model with first-order elimination. Creatinine clearance and body weight, as covariates on clearance (CL) and volume of central compartment (V1), were selected among the covariates possibly affecting PK parameters of both drugs. CL was defined as CL = 2.9 + 4.03 × CLcr /47 for piperacillin and CL = 1.76 + 4.81 × CLcr /47 for tazobactam. V1 was defined as V1 = 19.5 × weight/60 for piperacillin and V1 = 22.6 × weight/60 for tazobactam. Conclusion: The PK profiles of TZP at a steady-state in Korean patients with acute infections were well described by a two-compartment model with first-order elimination. Both piperacillin and tazobactam clearances were significantly influenced by creatinine clearance. [ABSTRACT FROM AUTHOR]

A new and mild synthetic approach for the N-arylation of 2-pyridones with diaryliodonium salts has been developed. Most reactions proceed readily at room temperature in the presence of 10 mol % of copper chloride. As a result, a wide range of N-arylpyridine-2-ones were synthesized in yields of 23% to 99%. With this method, an antifibrotic drug, Pirfenidone, was successfully synthesized in 99% yield within 30 min at room temperature. [ABSTRACT FROM AUTHOR]

We assessed humoral responses and reactogenicity following the heterologous vaccination compared to the homologous vaccination groups. We enrolled healthcare workers (HCWs) who were either vaccinated with ChAdOx1 followed by BNT162b2 (heterologous group) or 2 doses of ChAdOx1 (ChAdOx1 group) or BNT162b2 (BNT162b2 group). Immunogenicity was assessed by measuring antibody titers against receptor-binding domain (RBD) of SARS-CoV-2 spike protein in all participants and neutralizing antibody titer in 100 participants per group. Reactogenicity was evaluated by a questionnaire-based survey. We enrolled 499 HCWs (ChAdOx1, n = 199; BNT162b2, n = 200; heterologous ChAdOx1/BNT162b2, n = 100). The geometric mean titer of anti–receptor-binding domain antibody at 14 days after the booster dose was significantly higher in the heterologous group (11 780.55 binding antibody unit (BAU)/mL [95% CI, 10 891.52–12 742.14]) than in the ChAdOx1 (1561.51 [95% CI, 1415.03–1723.15]) or BNT162b2 (2895.90 [95% CI, 2664.01–3147.98]) groups (both p < 0.001). The neutralizing antibody titer of the heterologous group (geometric mean ND 50 , 2367.74 [95% CI, 1970.03–2845.74]) was comparable to that of the BNT162b2 group (2118.63 [95% CI, 1755.88–2556.32]; p > 0.05) but higher than that of the ChAdOx1 group (391.77 [95% CI, 326.16–470.59]; p < 0.001). Compared with those against wild-type SARS-CoV-2, the geometric mean neutralizing antibody titers against the Delta variant at 14 days after the boosting were reduced by 3.0-fold in the heterologous group (geometric mean ND 50 , 872.01 [95% CI, 685.33–1109.54]), 4.0-fold in the BNT162b2 group (337.93 [95% CI, 262.78–434.57]), and 3.2-fold in the ChAdOx1 group (206.61 [95% CI, 144.05–296.34]). The local or systemic reactogenicity after the booster dose in the heterologous group was higher than that of the ChAdOx1 group but comparable to that of the BNT162b2 group. Heterologous ChAdOx1 followed by BNT162b2 vaccination with a 12-week interval induced a robust humoral immune response against SARS-CoV-2, including the Delta variant, that was comparable to the homologous BNT162b2 vaccination and stronger than the homologous ChAdOx1 vaccination, with a tolerable reactogenicity profile. [ABSTRACT FROM AUTHOR]