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Background/Aims@#A relationship between fatty liver and lung function impairment has been identified, and both are independently associated with metabolic dysfunction. However, the temporal relationship between changes in fatty liver status and lung function and their genome-wide association remain unclear. @*Methods@#This longitudinal cohort consisted of subjects who received serial health check-ups, including liver ultrasonography and spirometry, for ≥3 years between 2003 and 2015. Lung func-tion decline rates were classified as “slow” and “accelerated” and compared among four different sonographic changes in steatosis status: “normal,” “improved,” “worsened,” and “persistent.” A genome-wide association study was conducted between the two groups: normal/improved steatosis with a slow decline in lung function versus worsened/persistent steatosis with an accelerated decline in lung function. @*Results@#Among 6,149 individuals, the annual rates of decline in forced vital capacity (FVC) and forced expiratory volume measured in the first second of exhalation (FEV 1 ) were higher in the worsened/persistent steatosis group than in the normal/improved steatosis group. In multivariable analysis, persistent or worsened status of fatty liver was significantly associated with accelerated declines in FVC (persistent status, odds ratio [OR]=1.22, 95% confidence interval [CI]=1.04–1.44; worsened status, OR=1.30, 95% CI=1.12–1.50), while improved status of fatty liver was significantly associated with slow declines in FEV 1 (OR=0.77, 95% CI=0.64–0.92). The PNPLA3 risk gene was most strongly associated with steatosis status change and accelerated declines in FVC (rs12483959, p=2.61×10 -7 ) and FEV 1(rs2294433, p=3.69×10 -8 ). @*Conclusions@#Regression of fatty liver is related to lung function decline. Continuing efforts to improve fatty liver may preserve lung function, especially for subjects with a high genetic risk.
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Transarterial chemoembolization (TACE) was introduced in 1977 with the administration of chemotherapeutic agent to gelatin sponge particles through the hepatic artery in patients with hepatocellular carcinoma (HCC) and was established as conventional TACE using Lipiodol in the 1980s. In the 2000s, drug-eluting beads were developed and applied clinically. Currently, TACE is a commonly used non-surgical treatment modality for patients with HCC who are unsuitable for curative treatment. Considering the vital role of TACE in the management of HCC, it is crucial to organize current knowledge and expert opinions regarding patient preparation, procedural techniques, and post-treatment care in TACE, which can enhance therapeutic efficacy and safety. A group of 12 experts in the fields of interventional radiology and hepatology, convened by the Research Committee of the Korean Liver Cancer Association (KLCA), has developed expert consensus-based practical recommendations in TACE. These recommendations have been endorsed by the Korean Society of Interventional Radiology and provide useful information and direction in performing TACE procedure as well as pre- and post- procedural patient care.
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Background@#/Aim: Despite the increasing proportion of elderly patients with hepatocellular carcinoma (HCC) over time, treatment efficacy in this population is not well established. @*Methods@#Data collected from the Korean Primary Liver Cancer Registry, a representative cohort of patients newly diagnosed with HCC in Korea between 2008 and 2017, were analyzed. Overall survival (OS) according to tumor stage and treatment modality was compared between elderly and non-elderly patients with HCC. @*Results@#Among 15,186 study patients, 5,829 (38.4%) were elderly. A larger proportion of elderly patients did not receive any treatment for HCC than non-elderly patients (25.2% vs. 16.7%). However, OS was significantly better in elderly patients who received treatment compared to those who did not (median, 38.6 vs. 22.3 months; P0.05). After IPTW, in intermediate-stage HCC, surgery (median, 66.0 vs. 90.3 months) and transarterial therapy (median, 36.5 vs. 37.2 months), and in advanced-stage HCC, transarterial (median, 25.3 vs. 26.3 months) and systemic therapy (median, 25.3 vs. 26.3 months) yielded comparable OS between the elderly and non-elderly HCC patients (all P>0.05). @*Conclusions@#Personalized treatments tailored to individual patients can improve the prognosis of elderly patients with HCC to a level comparable to that of non-elderly patients.
ABSTRACT
Transarterial chemoembolization (TACE) was introduced in 1977 with the administration of chemotherapeutic agent to gelatin sponge particles through the hepatic artery in patients with hepatocellular carcinoma (HCC) and was established as conventional TACE using Lipiodol in the 1980s. In the 2000s, drug-eluting beads were developed and applied clinically. Currently, TACE is a commonly used non-surgical treatment modality for patients with HCC who are unsuitable for curative treatment. Considering the vital role of TACE in the management of HCC, it is crucial to organize current knowledge and expert opinions regarding patient preparation, procedural techniques, and post-treatment care in TACE, which can enhance therapeutic efficacy and safety. A group of 12 experts in the fields of interventional radiology and hepatology, convened by the Research Committee of the Korean Liver Cancer Association (KLCA), has developed expert consensus-based practical recommendations in TACE. These recommendations have been endorsed by the Korean Society of Interventional Radiology and provide useful information and direction in performing TACE procedure as well as pre- and post- procedural patient care.
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Background@#Muscle cramp is possibly related to peripheral nerve hyperexcitability (PNH), and one of the most debilitating symptoms frequently encountered in patients with liver cirrhosis. We investigated whether pregabalin, a gamma-aminobutyric acid analogue, can suppress neuronal excitability and reduce muscle cramps in cirrhotic patients. @*Methods@#We conducted a randomized, double-blind, placebo-controlled trial in which study participants with cirrhosis from a single tertiary center were enrolled. Primary endpoint was the relative change in cramp frequency from the run-in to standard dose treatment phase (4 weeks per each). Secondary endpoints included the responder rate, and the changes in cramp frequency during sleep, pain intensity, health-related quality of life (Liver Disease Quality of Life Instrument, Short Form-36) and electrophysiological measures of PNH. @*Results@#This study was terminated early because of insufficient accrual. 80% (n = 56) of the target number of participants (n = 70) were randomized to pregabalin (n = 29) or placebo (n = 27). Median baseline frequency of muscle cramps (interquartile range) was 5.8 (3.5–10) per week in the pregabalin group and 6.5 (4.0–10) in the placebo group (P = 0.970). The primary analysis showed a significant reduction in cramp frequency with pregabalin compared to placebo (−36% vs. 4.5% for the percentage change, P = 0.010). Secondary outcomes did not differ significantly between the two groups. Adverse effects with pregabalin were mainly dizziness and lethargy. @*Conclusion@#With multiple problems emerging from premature termination in mind, the results suggested an acceptable safety profile and favorable effect of pregabalin in reducing muscle cramps compared to placebo in cirrhotic patients.
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The genus Mitrula (Mitrulaceae, Helotiales), as also known as swamp beacons, inhabits submerged, decaying vegetation in standing or decaying needles, twigs, leaves, and shallow water. They play an important role in carbon cycling in some freshwater ecosystems. In the herbarium of the Korea National Arboretum (KH), seven Mitrula specimens were collected during mushroom forays in the period from 2019 to 2021. The Korean collections were found to be macromorphologically closely related to M. paludosa and M. elegans, but micromorphologically they could be distinguished by characteristics of slightly narrower asci and aseptate ascospores. Our molecular phylogenetic analyses of the internal transcribed spacer (ITS) and 28S rDNA regions also revealed that our specimens were related to M. paludosa and M. elegans, but formed a distinct clade. Based on these results, we reported our specimens as new to science and discussed the phylogeny and diversity ofMitrula species.
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The purpose of this study was to investigate the current status of interprofessional education (IPE) and the efforts required to promote, popularize, and implement it in Korea. The IPE status of 40 medical colleges was investigated using a survey with questions regarding the details of IPE, the future plans and necessary support required, and the reasons for not implementing IPE. Thirty-two medical colleges responded, of which 10 are implementing or have implemented IPE. Most of these colleges started IPE in 2018, and the duration of IPE was less than 9 hours. All medical colleges held classes with nursing students. As for the type of IPE, there were independent courses for IPE, one-time special lectures, or partial sessions in one course. Lectures, discussions and presentations, role playing, and high-fidelity simulations were mainly used as educational methods. The support and interest of the dean was the most important facilitating factor. No medical colleges were currently preparing to implement IPE, four colleges had planned IPE but failed to implement it, and 16 had no plans for IPE at all. All medical colleges cited scheduling or cooperation with other majors as the most significant barrier. All the colleges listed their requirements for educational materials, cases, guidelines, and teaching and learning methods for IPE from external institutions. To activate IPE, it is necessary to create an appropriate atmosphere and conditions for developing IPE competencies and a model suitable for the domestic situation. External medical education support organizations should distribute IPE development guidelines and educational materials, form a network between medical colleges with IPE experience, and make efforts to promote the importance of IPE.
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Background/Aims@#Accumulating evidence suggests a link between non-alcoholic fatty liver disease (NAFLD) and brain health. However, population-based evidence on the association between NAFLD and dementia remains unclear. This study was conducted to determine the association between NAFLD and incident dementia. @*Methods@#The study population included 608,994 adults aged ≥60 years who underwent health examinations between 2009 and 2010. Data were collected from the Korean National Health Insurance Service database. NAFLD was assessed using the fatty liver index (FLI). A Cox proportional hazards regression model was used to determine the association between NAFLD and dementia. @*Results@#During the 6,495,352 person-years of follow-up, 48,538 participants (8.0%) developed incident dementia. The participants were classified into low (FLI <30), intermediate (FLI ≥30 and <60), and high (FLI ≥60) groups. In the overall study population, the FLI groups were associated with a risk of dementia (P for trend <0.001). After propensity score matching, a low FLI was associated with a reduced risk of dementia (adjusted hazard ration [aHR], 0.96; 95% confidence interval [CI], 0.93–0.98; P=0.002), whereas a high FLI (NAFLD) was associated with an increased risk of dementia (aHR, 1.05; 95% CI, 1.02–1.08; P=0.001). A higher risk of dementia in the high FLI group than in the intermediate FLI group was attributed to Alzheimer’s disease (aHR, 1.04; 95% CI, 1.01–1.07; P=0.004) rather than vascular dementia (aHR, 0.94; 95% CI, 0.75–1.18; P=0.602). @*Conclusions@#NAFLD was associated with an increased risk of dementia, which was attributed to an increased risk of Alzheimer’s disease.
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Purpose@#This study aims to design that using formative assessment as an instructional strategy in real-time online classes, and to explore the application of Bloom’s taxonomy in the development of formative assessment items. @*Methods@#We designed the instruction using formative assessment in real-time online classes, developed the items of formative assessment, analyzed the items statistically, and investigated students' perceptions of formative assessment through a survey. @*Results@#It is designed to consist of 2–3 learning outcomes per hour of class and to conduct the formative assessment with 1–2 items after the lecture for each learning outcome. Formative assessment was 31 times in the physiology classes (total 48 hours) of three basic medicine integrated. There were nine “knowledge” items, 40 “comprehension” items, and 55 “application” items. There were 33 items (31.7%) with a correct rate of 80% or higher, which the instructor thought was appropriate. As a result of the survey on students’ perceptions of formative assessment, they answered that it was able to concentrate on the class and that it was helpful in achieving learning outcomes. @*Conclusion@#The students focused during class because they had to take formative assessment immediately after the learning outcome lecture. “Integration of lesson and assessments” was maximized by solving the assessment items as well as through the instructor’s immediate explanation of answers. Through formative assessment, the students were able to utilize metacognition by learning what content they understood or did not understand. Items that consider Bloom’s taxonomy allow students to remember, understand, and apply to clinical contexts.
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Purpose@#This study aims to design that using formative assessment as an instructional strategy in real-time online classes, and to explore the application of Bloom’s taxonomy in the development of formative assessment items. @*Methods@#We designed the instruction using formative assessment in real-time online classes, developed the items of formative assessment, analyzed the items statistically, and investigated students' perceptions of formative assessment through a survey. @*Results@#It is designed to consist of 2–3 learning outcomes per hour of class and to conduct the formative assessment with 1–2 items after the lecture for each learning outcome. Formative assessment was 31 times in the physiology classes (total 48 hours) of three basic medicine integrated. There were nine “knowledge” items, 40 “comprehension” items, and 55 “application” items. There were 33 items (31.7%) with a correct rate of 80% or higher, which the instructor thought was appropriate. As a result of the survey on students’ perceptions of formative assessment, they answered that it was able to concentrate on the class and that it was helpful in achieving learning outcomes. @*Conclusion@#The students focused during class because they had to take formative assessment immediately after the learning outcome lecture. “Integration of lesson and assessments” was maximized by solving the assessment items as well as through the instructor’s immediate explanation of answers. Through formative assessment, the students were able to utilize metacognition by learning what content they understood or did not understand. Items that consider Bloom’s taxonomy allow students to remember, understand, and apply to clinical contexts.
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During a survey of putative fungal pathogens infecting oak trees in the Gangwon Province of the Republic of Korea, a fungus resembling a Ceratocystis sp. was repeatedly isolated from natural wounds on Quercus variabilis. Morphological comparisons and DNA sequence comparisons based on partial b-tubulin and TEF-1a gene regions showed that the fungus resided in a distinct lineage. This novel Ceratocystis species is described here as C. quercicola sp. nov. This is the first novel species of Ceratocystis to be reported from Korea. A pathogenicity test showed that it can cause lesions on inoculated trees but that it had a very low level of aggressiveness. The discovery of this fungus suggests that additional taxa residing inCeratocystis are likely to be discovered in Korea in the future.
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Purpose@#The Advanced Prostate Cancer Consensus Conference (APCCC) 2015 was based on topics withcontroversy in the field of advanced prostate cancer. To understand the Korean urologists perspective regardingthe issues, we have conducted a questionnaire named Prostate Cancer Summit (PCAS) 2016, with 9 importantsubtopics. @*Materials and Methods@#Total 9 subtopics have been decided and questions were developed regarding eachsubtopic. The questions were based on that of APCCC 2015 and translated into Korean for better understanding.Total 51 panelists have voted online on 85 different questions. @*Results@#The survey concluded that testosterone should be measured as a diagnostic criterion for castrationresistance prostate cancer (CRPC) and that consensus was reached on issues such as the use of androgenreceptor pathway inhibitors in the treatment of predocetaxel and postdocetaxel in CRPC patients. In addition,76% of the participants agreed that imaging tests were needed before new treatment in CRPC patients, anda majority of participants agreed that periodic imaging tests are necessary regardless of symptoms during treatmentfor CRPC. However, some issues, such as the use of prostate-specific antigen-based triggers for remediationin CRPC patients, the endocrine manipulation in nonmetastatic CRPC patients, and the onset of treatment inasymptomatic metastatic CRPC patients, were not agreed. @*Conclusions@#The results from PCAS 2016 has addressed some of the issues with controversy. Although thevoting results are subjective, it will help guide treatment decisions in topics with less evidence.
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Background/Aims@#Considering the high prevalence and mortality of hepatocellular carcinoma (HCC) in Korea, accurate statistics for HCC are important. We evaluated the characteristics of Korean patients with newly diagnosed HCC. @*Methods@#We retrospectively evaluated data from the Korean Primary Liver Cancer Registry (KPLCR). The baseline characteristics, treatment modalities, and overall survival (OS) of 4,572 patients with HCC registered in the KPLCR between 2012 and 2014 were investigated. @*Results@#At the time of HCC diagnosis, the median age was 60.0 years, with male predominance (79.6%). Hepatitis B virus infection was the most common etiology (59.1%). The rates of Barcelona Clinic Liver Cancer (BCLC) stages 0, A, B, C, and D at diagnosis were 3.9%, 36.9%, 12.5%, 39.4%, and 7.3%, respectively. The proportion of very early or early stage HCC at diagnosis (BCLC stage 0 or A) in the 2012-2014 cohort was significantly lower than that in the 2008-2011 cohort (40.8% vs. 48.3%, P<0.001). Transarterial therapy (37.5%) was the most commonly performed initial treatment, followed by surgical resection (19.8%), best supportive care (19.1%), and local ablation (10.6%). The median OS was 2.9 years, and the 1-, 3-, and 5-year OS rates were 67.7%, 49.3% and 41.9%, respectively. The OS rate of the 2012-2014 cohort was significantly higher than that of the 2008-2011 cohort (log-rank, P<0.001). @*Conclusions@#The OS of HCC patients registered in the KPLCR between 2012 and 2014 significantly improved. Nevertheless, as about half of the HCC patients were diagnosed at an advanced stage, vigorous and optimized HCC screening strategies should be implemented.
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Background@#s/Aims: Backgrounds/Aims: In Korea, hepatocellular carcinoma (HCC) is the sixth most common cancer and results in the second-highest cancer death rate among all cancers. We aimed to describe the characteristics of patients who were newly diagnosed with HCC in Korea between 2008 and 2011. @*Methods@#The Korean Primary Liver Cancer Registry (KPLCR) is a random sample consisting of approximately 15% of patients with newly diagnosed primary liver cancer registered in the Korean Central Cancer Registry. We investigated the baseline characteristics, treatment modalities, and overall survival (OS) of patients with HCC registered in the KPLCR between 2008 and 2011. @*Results@#A total of 6,083 patients were histologically or radiologically diagnosed with HCC. The hepatitis B virus was the predominant HCC etiology (72.0%). According to the Barcelona Clinic Liver Cancer (BCLC) staging system, stages 0, A, B, C, and D accounted for 8.6%, 39.7%, 11.5%, 33.8%, and 6.9%, respectively. Transarterial therapy (41.7%) was the most commonly performed initial treatment, followed by best supportive care (21.7%), surgical resection (16.7%), and local ablation therapies (10.6%). The overall rate of adherence to the BCLC treatment guideline was only 37.7%. The 1-, 3-, and 5-year OS rates were 65.6%, 46.2%, and 36.8%, respectively. @*Conclusions@#Between 2008 and 2011, approximately half of patients with HCC (48.3%) were candidates for curative treatment (BCLC stage 0 or A), but one-third of patients (33.8%) had advanced HCC (BCLC stage C). Transarterial therapy was the most commonly conducted initial treatment and the 5-year OS rate was 36.8% in this period.
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Background/Aims@#The alcoholic hepatitis histologic score (AHHS) is a recently developed clinical model for predicting short-term mortality in Caucasian patients with alcoholic hepatitis (AH). The AHHS has not been extensively validated in other ethnic populations. This study validated the AHHS in a Korean patient cohort. @*Methods@#We conducted a pro-spective cohort study of hospitalized Korean patients with AH between January 2010 and August 2017. Histopatho-logical findings were assessed to determine the AHHS in all study subjects. Histopathological risk factors were examined by Cox regression analysis to predict overall survival (OS).Kaplan-Meier curves were plotted to assess the diagnostic performance of the AHHS. @*Results@#We recruited a total of 107 patients with biopsy-proven AH. None of the individual AHHS components were associated with 3-month mortality.However, the bilirubinostasis type and fibrosis severity were significantly associated with AH mortality beyond 6 months (all p<0.05, except fibrosis severity for 6-month mortality) and OS (all p<0.05). The modified AHHS classification as a binary variable (<5 vs ≥5) was also associated with OS (haz-ard ratio, 2.88; 95% confidence interval [CI], 1.50 to 5.56;p=0.002), and had higher predictive performance for OS (concordance index [C-index], 0.634; 95% CI, 0.561 to 0.707) than the original AHHS classification (mild vs moderate vs severe: C-index, 0.577; 95% CI, 0.498 to 0.656). This differ-ence was statistically significant (p=0.045). @*Conclusions@#In this prospective Korean AH cohort, the modified AHHS was significantly associated with OS. Therefore, the AHHS might be a useful histological prognosticator for long-term progno-sis in patients with nonsevere AH.
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BACKGROUND AND OBJECTIVES@#For patients with polyps and cysts, glottal gaps resulting from their lesions have negative respiratory effects when they vocalize. Phonatory Aerodynamic System is clinically used, but is often limited in the measurement of vowels. So the researchers attempted to verify the usefulness of Phonatory Aerodynamic System by comparing differences in respiratory characteristics and patterns which can be measured by the level of connected speech.MATERIALS AND METHOD: Among the subjects who were diagnosed through a stroboscopy, there were 33 patients with polyps and 23 patients with cysts. Then, 36 subjects who were found to have no specific findings through a stroboscopy and perceptual test were selected to the normal group. We compared respiratory characteristics and patterns. And compared vocal polyps and cysts before and after laryngeal micro surgery (LMS).@*RESULTS@#First, difference in respiratory patterns between the normal group and the patients with polyps and cysts were examined to show that breath groups, breath group syllables, and expiratory · inspiratory volume were significantly higher in the polyp/cyst group than those in the normal group, indicating that precision was lowered during the conversation, due to reduction in speech intelligibility and interruption of communication. Second, there were significant differences in maximum phonation time, mean flow rate, and subglottal pressure among respiratory characteristics, breath groups, breath group syllables, and inspiratory volume before and after LMS, which appeared to be similar to the normal group.@*CONCLUSION@#The understanding of respiratory characteristics and patterns produced by patients in connected speech which is most similar to natural speech was found to be the objective and useful method for examining characteristics of the subjects.
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PURPOSE: To investigate the effect of combined inhibition of protein kinase B (AKT) and SRC on the growth and metastatic potential of human pancreatic cancer cells. MATERIALS AND METHODS: AKT and SRC were inhibited using 10-DEBC and PP2, respectively. The expression of their messenger RNAs were down-regulated by specific small interfering RNA (siRNA). Changes in pancreatic cancer cell growth and metastatic potential were determined using a cell viability assay and a xenotransplant model of pancreatic cancer, as well as cell migration and invasion assays. Signal proteins were analyzed by Western blot. RESULTS: The inhibitors 10-DEBC and PP2 suppressed cell proliferation in a dose-dependent fashion in pancreatic cancer cell lines MIA PaCa-2 and PANC-1. The simultaneous inhibition of AKT and SRC at low concentrations resulted in a significant suppression of cell proliferation. Knockdown of AKT2 and SRC using siRNAs also significantly decreased cell proliferation. In a pancreatic cancer model, combined treatment with 10-DEBC and PP2 also significantly suppressed the growth of pancreatic cancer. Application of 10-DEBC with PP2 significantly reduced the metastatic potential of pancreatic cancer cells by inhibiting migration and invasion. The combined inhibition suppressed the phosphorylation of mTOR and ERK in pancreatic cancer cells. CONCLUSION: Combined targeting of AKT and SRC resulted in a synergistic efficacy against human pancreatic cancer growth and metastasis.
Subject(s)
Humans , Blotting, Western , Cell Line , Cell Movement , Cell Proliferation , Cell Survival , Neoplasm Metastasis , Pancreatic Neoplasms , Phosphorylation , Proto-Oncogene Proteins c-akt , RNA, Messenger , RNA, Small InterferingABSTRACT
Two-hundred and fifty-five strains of actinomycetes isolated from soil samples were screened for their antagonistic activities against four well-known wood decay fungi (WDF), including a brown rot fungus, Gloeophyllum trabeum and three white rot fungi Donkioporia expansa, Trametes versicolor, and Schizophyllum commune. A dual culture assay using culture media supplemented with heated or unheated culture filtrates of selected bacterial strains was used for the detection of their antimicrobial activity against four WDF. It was shown that Streptomyces atratus, S. tsukiyonensis, and Streptomyces sp. greatly inhibited the mycelial growth of the WDF tested compared with the control. To evaluate the biocontrol efficacy of S. atratus, S. tsukiyonensis, and Streptomyces sp., wood blocks of Pinus densiflora inoculated with three selected Streptomyces isolates were tested for weight loss, compression strength (perpendicular or parallel to the grain), bending strength, and chemical component changes. Of these three isolates used, Streptomyces sp. exhibited higher inhibitory activity against WDF, especially G. trabeum, as observed in mechanical and chemical change analyses. Scanning electron microscopy showed that cell walls of the wood block treated with Streptomyces strains were thicker and collapsed to a lesser extent than those of the non-treated control. Taken together, our findings indicate that Streptomyces sp. exhibits the potential to be used as a biocontrol agent for wood decay brown rot fungus that causes severe damage to coniferous woods.
Subject(s)
Actinobacteria , Cell Wall , Tracheophyta , Culture Media , Fungi , Hot Temperature , Mass Screening , Microscopy, Electron, Scanning , Pinus , Schizophyllum , Soil , Streptomyces , Trametes , Weight Loss , WoodABSTRACT
BACKGROUND/AIMS: A recent study reported that entecavir had inferior efficacy in nucleos(t)ide analogue (NA)-experienced chronic hepatitis B (CHB) patients compared to NA-naïve patients. We sought to compare the efficacy of tenofovir disoproxil fumarate (TDF) in NA-experienced and NA-naïve CHB patients. METHODS: We retrospectively enrolled 252 consecutive patients who had a serum hepatitis B virus (HBV) DNA level greater than 2,000 IU/mL at the initiation of TDF treatment and who received TDF for at least 6 months. Complete virologic suppression (CVS) was defined as undetectable serum HBV DNA. We generated a multivariate Cox proportional-hazard model to examine predictive factors that were independently associated with time to CVS. RESULTS: The mean age of patients was 48.2 years, and the cohort included 181 NA-naïve patients and 71 NA-experienced patients. The median duration of TDF treatment was 14.4 (interquartile range, 9.5-17.8) months. A total of 167 (92.3%) of 181 NA-naïve patients achieved CVS, and 60 (84.5%) of 71 NA-exposed patients achieved CVS. Forty-nine (89.1%) of 55 patients who previously took an NA aside from adefovir and 11 (68.8%) of 16 adefovir-experienced patients achieved CVS. In multivariable analysis, previous adefovir exposure significantly influenced time to CVS (hazard ratio, 0.37; 95% confidence interval, 0.19-0.72; P=0.003), after adjusting for HBeAg positivity, baseline HBV DNA level and cirrhosis. CONCLUSIONS: Tenofovir had inferior efficacy in adefovir-experienced CHB patients compared to NA-naïve patients. The response of patients with previous adefovir exposure to TDF monotherapy should be monitored closely.
Subject(s)
Humans , Cohort Studies , DNA , Fibrosis , Hepatitis B , Hepatitis B e Antigens , Hepatitis B virus , Hepatitis B, Chronic , Hepatitis, Chronic , Retrospective Studies , TenofovirABSTRACT
BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) can develop in chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) levels. Therefore, methods that can stratify an individual's HCC risk are needed. METHODS: A simple HCC risk score was developed from 971 patients with CHB who had elevated hepatitis B virus DNA levels (>2,000 IU/mL) with normal or mildly elevated ALT levels (<80 U/L). The score was validated from an independent cohort of 507 patients. RESULTS: A 4-point risk scale was developed, with HCC risk ranging from 0% to 17.8% at 5 years for the lowest and highest risk scores. The D2AS score had high area under the receiver operating curves (AUROCs) for predicting development of HCC at 3/5 years (0.895/0.884). The calculated AUROCs to predict the development of HCC at 3/5 years were 0.889/0.876 in the validation cohort, with 5-year HCC incidence rates ranging from 0% to 13.8% at 5 years for the lowest and highest risk scores. CONCLUSIONS: The D2AS risk score can play a valuable role in risk stratification and may be useful for guiding clinical decisions for enhanced surveillance or treatment to reduce the HCC risk in CHB patients with normal or mildly elevated ALT levels.