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Background: General anesthesia is often necessary for dental treatment of outpatients with mental disabilities. Rapid recovery and effective management of postoperative nausea and vomiting (PONV) are critical for outpatients. This study aimed to investigate the effect of transitioning from propofol to remimazolam with flumazenil reversal administered toward the end of surgery during propofol-based total intravenous anesthesia (TIVA) on recovery. Methods: Adults with mental disabilities scheduled to undergo dental treatment were randomly assigned to receive either propofol-based TIVA (Group P) or propofol-remimazolam-based TIVA with flumazenil reversal (Group PR). Propofol was replaced with remimazolam 1 h before the end of surgery in Group PR; moreover, 0.5 mg of flumazenil was administered after the neuromuscular blockade reversal agent. The primary outcome was the duration of stay in the post-anesthesia care unit (PACU). The secondary outcomes included time to eye-opening, time to extubation, occurrence of PONV, and quality of recovery. Results: Fifty-four patients were included in this study. The duration of stay in the PACU in Group PR was significantly shorter than that in Group P (mean difference, 8.7 min; confidence interval [95% CI], 3.3–14.2; P = 0.002). Group PR exhibited a shorter time to eye opening (mean difference, 5.4 min; 95% CI, 3.3–8.1; P < 0.001) and time to extubation (mean difference, 5.5 min; 95% CI, 3.6–7.9; P < 0.001) than Group P. Neither group required the administration of rescue analgesics, and the incidence of PONV was not reported. Conclusions: Transitioning from propofol to remimazolam 1 h before the end of surgery followed by flumazenil reversal reduced the duration of stay in the PACU and the time to eye opening and extubation without affecting the incidence of PONV and quality of recovery. Trial registration number: Clinical Research Information Service (KCT0007794), Clinical trial first registration date: 12/10/2022. [ABSTRACT FROM AUTHOR]

Studies of mouse models of Alzheimer's disease (AD) have demonstrated that nitric oxide synthase 2 (NOS2) is involved in AD pathology. However, the effects of NOS2 on the pathology of Parkinson's disease (PD) are not well studied. To address this gap, we examined the impact of NOS2 on disease-associated phenotypes in a mouse model of PD. Transgenic mice carrying the A53T mutation of α-synuclein (SynA53T) and newly generated double transgenic mice with deletion of NOS2 (SynA53T/NOS2−/−) were used. Compared with SynA53T mice, the loss of nos2 decreased α-synuclein phosphorylation at serine 129 and reduced α-synuclein-induced microglial and astrocyte activation in SynA53T/NOS−/− mice. Additionally, neuroinflammation-related gene clusters in the deep mesencephalic nucleus (DpMe) were altered in SynA53T/NOS−/− mice compared with SynA53T mice. Taken together, our results suggest that deletion of nos2 alleviates α-synuclein pathology and α-synuclein-associated neuroinflammatory responses in the brain. [ABSTRACT FROM AUTHOR]

Background: In chronic myelogenous leukemia, reciprocal translocation between chromosome 9 and chromosome 22 generates a chimeric protein, Bcr-Abl, that leads to hyperactivity of tyrosine kinase-linked signaling transduction. The therapeutic agent nilotinib inhibits Bcr-Abl/DDR1 and can cross the blood-brain barrier, but its potential impact on neuroinflammatory responses and cognitive function has not been studied in detail.Methods: The effects of nilotinib in vitro and in vivo were assessed by a combination of RT-PCR, real-time PCR, western blotting, ELISA, immunostaining, and/or subcellular fractionation. In the in vitro experiments, the effects of 200 ng/mL LPS or PBS on BV2 microglial cells, primary microglia or primary astrocytes pre- or post-treated with 5 µM nilotinib or vehicle were evaluated. The in vivo experiments involved wild-type mice administered a 7-day course of daily injections with 20 mg/kg nilotinib (i.p.) or vehicle before injection with 10 mg/kg LPS (i.p.) or PBS.Results: In BV2 microglial cells, pre- and post-treatment with nilotinib altered LPS-induced proinflammatory/anti-inflammatory cytokine mRNA levels by suppressing AKT/P38/SOD2 signaling. Nilotinib treatment also significantly downregulated LPS-stimulated proinflammatory cytokine levels in primary microglia and primary astrocytes by altering P38/STAT3 signaling. Experiments in wild-type mice showed that nilotinib administration affected LPS-mediated microglial/astroglial activation in a brain region-specific manner in vivo. In addition, nilotinib significantly reduced proinflammatory cytokine IL-1β, IL-6 and COX-2 levels and P38/STAT3 signaling in the brain in LPS-treated wild-type mice. Importantly, nilotinib treatment rescued LPS-mediated spatial working memory impairment and cortical dendritic spine number in wild-type mice.Conclusions: Our results indicate that nilotinib can modulate neuroinflammatory responses and cognitive function in LPS-stimulated wild-type mice. [ABSTRACT FROM AUTHOR]

Background: Early adulthood is a significant period for preventive depression management for a healthy pregnancy. However, previous public health initiatives have not yet emphasized preparation for a healthy pregnancy in this population. In addition, pregnancy planning has traditionally been regarded as women's responsibility, so intervention strategies may differ by gender. This study explored intentions of preventive depression management for a healthy pregnancy among unmarried college students, as well as factors influencing those intentions, by applying the Theory of Planned Behavior (TPB) model. Methods: For this cross-sectional survey, 828 unmarried college students aged 18–29 were recruited from a national university in Korea from July to September 2019. The chi-square test and t-test were used to compare gender differences in general characteristics, the current level of depression, and constructs of the extended TPB. Hierarchical regression was performed to identify factors influencing the intention of preventive depression management for a healthy pregnancy. Results: The intention to manage depression was significantly higher in men than in women (t = 2.36, p = 0.019). The factors affecting the intention of preventive depression management for a healthy pregnancy were components of TPB in both women and men, of which self-efficacy had the greatest effect (female: β = 0.34, p < 0.001, male: β = 0.30, p < 0.001). The current level of depression was a significant factor for women only (β = 0.10, p = 0.014). Conclusions: Our study results underscore the need for nurses to perform preventive interventions and provide directions to develop interventions to improve the intention of depression management for unmarried college students. It is necessary to intervene with all the constructs of the TPB, especially self-efficacy, for both men and women. It is also important to check and address the current depression status of unmarried female college students. Plain English summary: Starting in early adulthood, such as college students in the preconception stage, it is necessary to take care of one's mental health (including depression) in order to have a healthy pregnancy in the future. The early identification of adults needing depression management is also a major challenge. In this study, an online survey was conducted to investigate levels of depression among Korean college students and their intention to manage depression for a healthy future pregnancy, as well as to identify the influencing factors. Convenience recruitment was conducted by e-mail at one university in Korea, and 828 male and female college students responded to the survey. An analysis of the factors affecting the intention to manage depression for a healthy future pregnancy identified the components of the Theory of Planned Behavior as influencing factors in both men and women. In particular, self-efficacy had the greatest influence. However, the current level of depression was only a significant factor among women. These findings could help nurses recognize differences in gender characteristics for the intention of preventive depression management for a healthy pregnancy, and provide evidence to develop and implement the intervention. These efforts will ultimately reduce high-risk pregnancies due to poor mental health. [ABSTRACT FROM AUTHOR]

Object: Measuring handgrip strength is a useful method to evaluate sarcopenia. No study has shown the trends of handgrip strength to weight ratio among Korean adolescents by year. This study aimed to determine the trends of handgrip strength among Korean adolescents using data from the Korea National Health and Nutrition Examination Survey (KNHANES). Data of 2304 adolescents who participated in the KNHANES between 2014 and 2017 were obtained. The handgrip-to-weight ratios were categorized by age, sex, and year. Results: Handgrip strength in adolescents decreased from 28.67 kg in 2014 to 27 kg in 2017 (P for trend < 0.05). The handgrip-to-weight ratio also decreased from 51.48 in 2014 to 48.18 in 2017 (P for trend < 0.05). The handgrip strength and handgrip-to-weight ratio also decreased among boys and girls over the years 2014–2017 (P for trend < 0.05). The results of the present study indicate that the handgrip-to-weight ratio decreased in Korean adolescents from the years 2014 to 2017, and a declining overall ratio indicates a decrease in the health status among Korean adolescents. Hence, there is a need to review the health status of Korean adolescents. [ABSTRACT FROM AUTHOR]

Background: Using reliable measurement tools is becoming increasingly important as the prevalence of obesity among children increases in Korea. The Dutch Eating Behavior Questionnaire for Children (DEBQ-C) measures three eating behaviors associated with overeating. This study aims to validate the DEBQ-C for use among Korean children and adolescents with high body weight. It examines the psychometric features of the Korean translation of the DEBQ-C and investigates the relationship between the subscale scores of the DEBQ-C and the weight status of participants (categorized into overweight, obese, and morbidly obese). Methods: A total of 233 children and adolescents (mean age: 11.4 ± 1.6 years) completed the questionnaire. The study verified the factor structure of the DEBQ-C using confirmatory factor analysis (CFA) and estimated its internal consistency with Cronbach's alpha. For convergent validity, it employed Pearson's correlation coefficient to assess relationships between the three eating behaviors of the DEBQ-C and the number of food addiction symptoms of the Yale Food Addiction Scale for Children (YFAS-C). Lastly, it examined the relationship between DEBQ-C scores and weight status via multinomial logistic regression analysis. Results: The three-factor model demonstrated goodness-of-fit (χ2 = 253, df = 167, χ2/df = 1.515, p < 0.001, CFI = 0.944; TLI = 0.937; RMSEA = 0.047). The internal consistency of the three eating behaviors was also satisfactory (Cronbach's alpha = 0.707–0.890). The emotional and external eating subscales of the DEBQ-C were positively correlated with the number of symptoms of food addiction of the YFAS-C. Emotional (OR: 2.008; 95% CI 1.973–2.043) and external (OR: 2.074; 95% CI 2.029–2.119) eating were positively associated with obesity status. Conclusion: The results suggest that the Korean version of the DEBQ-C is suitable for the examination of problematic eating behaviors in Korean children and adolescents with high body weight. Plain English Summary: The proportion of children and adolescents with obesity in Korea is increasing. Thus, the availability of a tool that can reliably identify problematic eating behavior linked to obesity would assist with prevention and management efforts. The Dutch Eating Behavior Questionnaire for Children (DEBQ-C) measures three types of overeating behavior in children that influence weight gain. This study examines the suitability of the Korean translation of the DEBQ-C questionnaire for use in studies on Korean children and adolescents with high body weight. The results of a survey on 233 adolescents (average age: 11.4 ± 1.6 years) suggest that the DEBQ-C translation would be useful in investigating overeating behavior in Korean children and adolescents. In addition, the findings suggest that eating in response to emotions and external cues are likely to play a role in the development of obesity among children and adolescents. [ABSTRACT FROM AUTHOR]

Background: Interventions to prepare for a healthy pregnancy from an early age can ensure the health of both mother and child. This study aims to compare the factors associated with healthy pregnancy preparation behavior (HPPB) among male and female adolescents. Methods: A total of 690 Korean adolescents participated in this cross-sectional study from July 11 to August 24, 2018. Determinants of the likelihood of engaging in HPPB were described using hierarchical regression about the importance of and confidence in HPPB, the gender equality related to pregnancy and birth, and the health belief model (HBM) constructs about HPPB. Results: Smoking experience (β = − 0.18, p < 0.001 for boys, β = − 0.25, p < 0.001 for girls), and HBM constructs were identified as factors correlated with HPPB in both genders. The significant factors in boys were perceived susceptibility (β = − 0.13, p = 0.005), perceived severity (β = 0.12, p = 0.015), perceived benefits (β = 0.23, p < 0.001), and perceived barriers (β = − 0.18, p < 0.001), whereas the corresponding factors in girls were perceived severity (β = 0.20, p = 0.001), and perceived barriers (β = − 0.23, p < 0.001). The importance of HPPB was identified as a factor only among girls (β = 0.19, p = 0.005), while confidence in HPPB (β = 0.12, p = 0.401), gender equality related to pregnancy and childbirth (β = − 0.20, p = 0.001 for women's responsibility variable, β = 0.14, p = 0.018 for men's responsibility variable), and alcohol (β = − 0.10, p = 0.022) were factors identified only among boys. Conclusions: The gender differences in opinions on HPPB identified in this study can help nurses and community health care professionals recognize issues for which they can develop and implement preventive interventions. For healthy pregnancy preparation, interventions based on HBM constructs and smoking should be presented for both male and female adolescents. Imparting education to females on the importance of HPPB and to males on confidence in HPPB, gender equality related to pregnancy and childbirth, and alcohol consumption, should be emphasized. In addition, as perceived susceptibility may be low in a disease prevention model using the health belief model, it is necessary to prioritize increasing the perceived susceptibility of school-age children as an intervention. Plain Language Summary: In the context of pregnancy preparation, attention has recently shifted from the period just before pregnancy to the early years, or even throughout one's life. The World Health Organization identifies adolescents as requiring specific attention. Adolescents' health behaviors can impact their adulthood years and have significant repercussions on the health of the future generation. In addition, recent studies consistently report that the preparedness of both men and women is essential to pregnancy preparation. Therefore, it is now time to present a new strategy by identifying and grasping the different factors that influence the two genders. This study can raise awareness of healthy pregnancy preparation behavior from adolescence onwards of both genders. There were differences in factors affecting HPPB by gender. For healthy pregnancy preparation, interventions based on HBM constructs and smoking should be presented for both male and female adolescents. Imparting education to females on the importance of HPPB (β = 0.19, p = 0.005) and males on confidence in HPPB (β = 0.12, p = 0.401), gender equality related to pregnancy and childbirth (β = − 0.20, p = 0.001 for women's responsibility variable, β = 0.14, p = 0.018 for men's responsibility variable), and alcohol consumption (β = − 0.10, p = 0.022) should be emphasized; and effective healthy pregnancy preventive strategies should be developed based on these findings. Interventions to prepare for a healthy pregnancy from an early age can ensure the health of both mother and child. [ABSTRACT FROM AUTHOR]

Background: Mild cognitive impairment (MCI) is defined as a decline in cognitive state with preservation of activities of daily living. Medications such as donepezil and rivastigmine have been commonly prescribed for MCI, but their use is controversial. Acupuncture has been widely used in Korea and has been shown to improve cognitive function. The aim of this study is to evaluate the efficacy of acupuncture for MCI and investigate the effect of acupuncture on structural and functional brain changes in patients with MCI.Methods: This study is a randomized, assessor-blinded, sham-controlled trial. Fifty participants with MCI will be randomly assigned to the acupuncture group (n = 25) or sham acupuncture group (n = 25). The acupuncture group will receive acupuncture treatment at nine acupuncture points (GV20, EX-HN1, bilateral LI4, and ST36) twice a week for 12 weeks. The sham acupuncture group will receive sham acupuncture treatment at the same points with non-penetrating sham needles. Both groups will be restricted from all other treatments for the improvement of cognitive function. The primary outcome measure is the Digit Span Test (DST). The secondary outcome measures are the Digit Symbol Substitution Test (DSST), Korean version of Montreal Cognitive Assessment (MoCA-K), Seoul Neuropsychological Screening Battery-II (SNSB-II), Beck Depression Inventory-II (BDI-II), State-Trait Anxiety Inventory (STAI), working memory (WM) task performance score, and structural/functional brain changes. Outcomes will be assessed at screening, baseline, 4 and 8 weeks, and after the end of treatment. We will also observe adverse events. In the statistical analysis, a full analysis set and per-protocol analysis will be performed.Discussion: This randomized clinical trial aims to examine the efficacy of acupuncture treatment for MCI. Neuropsychological tests, psychological inventories for measuring depression and anxiety, and magnetic resonance imaging will be performed to investigate the underlying neurological mechanisms and the association between cognition, emotion, and brain networks following acupuncture treatment. The results of the trial will provide evidence supporting the efficacy of acupuncture and also add to the neurobiological understanding of acupuncture treatment for MCI.Trial Registration: Clinical Research Information Service, KCT0002896 . Registered on 25 May 2018. [ABSTRACT FROM AUTHOR]

Background: Alexander disease is a rare neurological disease characterized by progressive spastic quadriparesis and bulbar palsy. Moreover, certain patients with adult-onset Alexander disease were often misdiagnosed as other neurodegenerative disorders.Case Presentation: Herein, we report an adult a 58-year-old woman presented with typical parkinsonism with good levodopa-responsiveness. The patient's dopamine transporter scanning showed significant striatal depletion, while her brain magnetic resonance imaging revealed bilateral tadpole shape of medulla oblongata and bilateral high signal intensity at both cerebellar dentate nuclei in T2-weighted images, suggesting the possibility of a genetic disorder beyond Parkinson's disease. The patient's genetic test resulted in known pathogenic glial fibrillary acidic protein variant, indicating Alexander disease.Conclusion: This unique case highlights genetically diagnosed Alexander disease may present with clinical Parkinson's disease. [ABSTRACT FROM AUTHOR]

Background: Numerous vaccine strategies are being advanced to control SARS-CoV-2, the cause of the COVID-19 pandemic. EuCorVac-19 (ECV19) is a recombinant protein nanoparticle vaccine that displays the SARS-CoV-2 receptor-binding domain (RBD) on immunogenic nanoliposomes.Methods: Initial study of a phase 2 randomized, observer-blind, placebo-controlled trial to assess the immunogenicity, safety, and tolerance of ECV19 was carried out between July and October 2021. Two hundred twenty-nine participants were enrolled at 5 hospital sites in South Korea. Healthy adults aged 19-75 without prior known exposure to COVID-19 were vaccinated intramuscularly on day 0 and day 21. Of the participants who received two vaccine doses according to protocol, 100 received high-dose ECV19 (20 μg RBD), 96 received low-dose ECV19 (10 μg RBD), and 27 received placebo. Local and systemic adverse events were monitored. Serum was assessed on days 0, 21, and 42 for immunogenicity analysis by ELISA and neutralizing antibody response by focus reduction neutralization test (FRNT).Results: Low-grade injection site tenderness and pain were observed in most participants. Solicited systemic adverse events were less frequent, and mostly involved low-grade fatigue/malaise, myalgia, and headache. No clinical laboratory abnormalities were observed. Adverse events did not increase with the second injection and no serious adverse events were solicited by ECV19. On day 42, Spike IgG geometric mean ELISA titers were 0.8, 211, and 590 Spike binding antibody units (BAU/mL) for placebo, low-dose and high-dose ECV19, respectively (p < 0.001 between groups). Neutralizing antibodies levels of the low-dose and high-dose ECV19 groups had FRNT50 geometric mean values of 129 and 316, respectively. Boosting responses and dose responses were observed. Antibodies against the RBD correlated with antibodies against the Spike and with virus neutralization.Conclusions: ECV19 was generally well-tolerated and induced antibodies in a dose-dependent manner that neutralized SARS-CoV-2. The unique liposome display approach of ECV19, which lacks any immunogenic protein components besides the antigen itself, coupled with the lack of increased adverse events during boosting suggest the vaccine platform may be amenable to multiple boosting regimes in the future. Taken together, these findings motivate further investigation of ECV19 in larger scale clinical testing that is underway.Trial Registration: The trial was registered at ClinicalTrials.gov as # NCT04783311. [ABSTRACT FROM AUTHOR]

Background: The germline mutations of DDX41, also known as DEAD box RNA helicase 41, have been found in about 1.5% of myeloid neoplasms (MNs). Development of MDS/AML is relatively common in germline DDX41 mutations. However, a variety of hematological malignancies (HMs) have been reported. Case presentation: We report a novel case of bi-alleleic DDX41 mutations in B-cell lymphoblastic leukemia (B-ALL), with unusual location of DDX41 mutations. The gene expression profile (GEP) of Ph + B-ALL with bi-alleleic DDX41 mutations showed heterogeneously transitional GEP and altered gene expression levels of genes involved in the process essential for red blood cells and myeloid cell differentiation were noted. Conclusions: We report that DDX41 mutations are unusual but can be an underlying event in Ph + B-ALL and screening DDX41 mutations can be also informative for patients awaiting for haploidentical stem cell transplantation and choosing the therapy. [ABSTRACT FROM AUTHOR]

Background: Inappropriate use of antibiotics not only increases antibiotic resistance as collateral damage but also increases clinical failure rates and medical costs. The purpose of this study was to determine the relationship between the appropriateness of antibiotic prescription and outcomes of community-acquired acute pyelonephritis (CA-APN).Methods: A multicenter prospective cohort study was conducted at eight hospitals in Korea between September 2017 and August 2018. All hospitalized patients aged ≥ 19 years who were diagnosed with CA-APN on admission were recruited. The appropriateness of empirical and definitive antibiotics, as well as the appropriateness of antibiotic treatment duration and route of administration, was evaluated in accordance with the guideline and expert opinions. Clinical outcomes and medical costs were compared between patients who were administered antibiotics 'appropriately' and 'inappropriately.'Results: A total of 397 and 318 patients were eligible for the analysis of the appropriateness of empirical and definitive antibiotics, respectively. Of them, 10 (2.5%) and 18 (5.7%) were administered 'inappropriately' empirical and definitive antibiotics, respectively. Of the 119 patients whose use of both empirical and definitive antibiotics was classified as 'optimal,' 57 (47.9%) received antibiotics over a longer duration than that recommended; 67 (56.3%) did not change to oral antibiotics on day 7 of hospitalization, even after stabilization of the clinical symptoms. Patients who were administered empirical antibiotics 'appropriately' had shorter hospitalization days (8 vs. 10 days, P = 0.001) and lower medical costs (2381.9 vs. 3235.9 USD, P = 0.002) than those who were administered them 'inappropriately.' Similar findings were observed for patients administered both empirical and definitive antibiotics 'appropriately' and those administered either empirical or definitive antibiotics 'inappropriately'.Conclusions: Appropriate use of antibiotics leads to better outcomes, including reduced hospitalization duration and medical costs. [ABSTRACT FROM AUTHOR]

Background: The objective of this study is to describe the changes in prescribing practices of antibiotics to treat acute pyelonephritis (APN) in Korea.Methods: The claim data base of the Health Insurance Review and Assessment Service in Korea was used to select patients with ICD-10 codes N10 (acute tubulo-interstitial nephritis) or N12 (tubulo-interstitial nephritis, not specified as acute nor chronic) as the primary discharge diagnosis during 2010-2014. Consumption of each class of antibiotics was converted to Defined Daily Dose (DDD)/event.Results: Throughout the five-year period, the average antibiotic consumption were 11.3 DDD per inpatient event and 6.0 DDD per outpatient event. The annual average antibiotic consumption increased for inpatients (P = 0.002), but remained stable for outpatients (P = 0.066). The use of parenteral antibiotics increased for inpatients (P < 0.001), but decreased for outpatients (P = 0.017). As for the the antibiotic classes, 3rd generation cephalosporins (3rd CEPs) was the most commonly prescribed (41.4%) for inpatients, followed by fluoroquinolones (FQs) (28.5%); for outpatient, FQs (54.8%) was the most commonly prescribed, followed by 3rd CEPs (13.1%). The use of 3rd CEPs (P < 0.001), beta-lactam/beta-lactamase inhibitors (P = 0.007), and carbapenems (P < 0.001) increased substantially for the treatment of hospitalized APN patients. In particular, carbapenems use increased 3.1-fold over the 5 years.Conclusions: Prescription of broad-spectrum antibiotics increased much for the treatment of APN in Korea during 2010-2014. [ABSTRACT FROM AUTHOR]

Background: Appropriate antibiotic use has become an important issue. However, collecting data on the use of all antibiotics in a hospital is difficult without an advanced computerized system and dedicated staff. This paper examines if 1-3 antibiotics can satisfactorily represent the total antibiotic consumption at the hospital level.Methods: We collected antibiotic data from six large university hospitals in Korea for some years between 2004 and 2012. Since the total antibiotics consist of a few chosen representative antibiotics and the rest, we used those chosen antibiotics along with additional variables constructed only with t (time) such as t, t 2 , and t 3 to capture the time trend and whether t belongs to each month or not to capture the monthly variations. The ordinary least squares method was used to explain the total antibiotic amount with these variables, and then the estimated model was employed to predict the use for 2013. To determine which antibiotics were the most representative in tracking general trends in antibiotic use over time, we tried various combinations of antibiotics to find the combination that best minimized the 2013 prediction error.Results: We found that fluoroquinolones and aminoglycosides were the most representative, followed by beta-lactam/beta-lactamase inhibitors and 4th-generation and 3rd-generation cephalosporins. The mean prediction error over 12 months in 2013 with these few antibiotics was only 1-3% of the monthly antibiotic consumption amount.Conclusions: The total antibiotic consumption amount at the hospital level can be represented sufficiently by a few antibiotics, such as fluoroquinolones and aminoglycosides, which means that hospitals can save resources by tracing only the usage of those few antibiotics instead of the entire inventory. Since the choice of fluoroquinolones and aminoglycosides is based solely on our Korean data, other hospitals may follow the same modelling methodology to find their own representative antibiotics. [ABSTRACT FROM AUTHOR]

Background: We intended to evaluate diagnostic utility of a targeted gene sequencing by using next generation sequencing (NGS) panel in patients with intractable early-onset epilepsy (EOE) and find the efficient analytical step for increasing the diagnosis rate. Methods: We assessed 74 patients with EOE whose seizures started before 3 years of age using a customized NGS panel that included 172 genes. Single nucleotide variants (SNVs) and exonic and chromosomal copy number variations (CNVs) were intensively examined with our customized pipeline and crosschecked with commercial or pre-built software. Variants were filtered and prioritized by in-depth clinical review, and finally classified according to the American College of Medical Genetics and Genomics guidelines. Each case was further discussed in a monthly consensus meeting that included the participation of all laboratory personnel, bioinformaticians, geneticists, and clinicians. Results: The NGS panel identified 28 patients (37.8%) with genetic abnormalities; 25 patients had pathogenic or likely pathogenic SNVs in 17 genes including SXTBP1 (n = 3), CDKL5 (n = 2), KCNQ2 (n = 2), SCN1A (n = 2), SYNGAP1 (n = 2), GNAO1 (n = 2), KCNT1 (n = 2), BRAT1, WWOX, ZEB2, CHD2, PRICKLE2, COL4A1, DNM1, SCN8A, MECP2, SLC9A6 (n = 1). The other 3 patients had pathogenic CNVs (2 duplications and 1 deletion) with varying sizes (from 2.5 Mb to 12 Mb). The overall diagnostic yield was 37.8% after following our step-by-step approach for clinical consensus. Conclusions: NGS is a useful diagnostic tool with great utility for patients with EOE. Diagnostic yields can be maximized with a standardized and team-based approach. [ABSTRACT FROM AUTHOR]

Background: We evaluated the incidence and spectrum of pathogenic and likely pathogenic variants of cancer susceptibility genes in BRCA1/2 mutation-negative Korean patients with a high risk for hereditary breast cancer using a comprehensive multigene panel that included 35 cancer susceptibility genes.Methods: Samples from 120 patients who were negative for BRCA1/2 mutations, but had been diagnosed with breast cancer that was likely hereditary, were prospectively evaluated for the prevalence of high-penetrance and moderate-penetrance germline mutations.Results: Nine patients (7.5%) had at least one pathogenic or likely pathogenic variant. Ten variants were identified in these patients: TP53 in two patients, PALB2 in three patients, BARD1 in two patients, BRIP1 in two patients, and MRE11A in one patient. We also identified 30 types of 139 variants of unknown significance (VUS). High-penetrance germline mutations, including TP53 and PALB2, tended to occur with high frequency in young (< 35 years) breast cancer patients (4/19, 21.1%) than in those diagnosed with breast cancer at ≥35 years of age (1/101, 1.0%; p = 0.003).Conclusions: These combined results demonstrate that multigene panels offer an alternative strategy for identifying veiled pathogenic and likely pathogenic mutations in breast cancer susceptibility genes. [ABSTRACT FROM AUTHOR]

Background: Functional dyspepsia (FD) is a prevalent gastric disorder that is difficult to manage due to lack of satisfactory treatments. Acupuncture has been studied with regard to the rising need for treating FD, but the mechanism verifying its efficacy has not yet been fully revealed. The aim of this study is to explore the efficacy and mechanism of acupuncture for FD compared with a sham group. Methods/design: We describe a proposal for a randomized, assessor-blind, sham-controlled trial with 70 eligible participants who will be randomly allocated either into an acupuncture or a sham group. Participants in the acupuncture group will receive 10 sessions of real acupuncture treatment and those in the sham group will be treated with identical sessions using a Streitberger needle. Functional magnetic resonance imaging (fMRI) and metabolomics studies will be implemented before and after 4 weeks of treatment to investigate the mechanism of acupuncture. The primary outcome is a proportion of responders with adequate symptom relief and the secondary outcomes include the Nepean Dyspepsia Index - Korean version, Functional Dyspepsia-Related Quality of Life questionnaire, Ways of Coping Questionnaire, Coping Strategies Questionnaire, perception of bodily sensation questionnaire, State-Trait Anxiety Inventory, and the Center for Epidemiological Studies - Depression Scale. The outcomes will be evaluated before and after the treatment. Discussion: This is the first large-scale trial evaluating the efficacy and mechanism of acupuncture with fMRI and metabolomic methods. We will compare real acupuncture with the Streitberger sham needle to verify the specific effect of acupuncture. The results of this trial are expected to be relevant evidences affecting policy and decision-makers associated with routine healthcare. Trial Registration: ClinicalTrials.gov Identifier: NCT02358486 . Date of Registration: 21 January 2015. [ABSTRACT FROM AUTHOR]

Background: Although overall survival for non-small cell lung cancer (NSCLC) has increased, survival rate for pathologically staged T2aN0M0 stage IB NSCLC remains low. Adjuvant chemotherapy is not a standard treatment for stage IB NSCLC. Our purpose was to determine the efficacy of platinum-based adjuvant chemotherapy in stage IB NSCLC.Methods: We retrospectively reviewed the medical records of 119 stage IB patients who underwent lobectomy and mediastinal lymph node dissection. Among these, 60 patients underwent platinum-based adjuvant chemotherapy (adjuvant group) and 59 did not receive chemotherapy (observation group).Results: Participants had a mean age of 62.12 ± 11.51 years and 73 (61.3%) were male. The median follow-up period was 49.04 months. Mean age was higher in the observation group whereas patients in the adjuvant group had larger tumors, more dissected lymph nodes, and better performance status. The 5-year overall survival was 64.7% in the observation group and 88.2% in the adjuvant group (p = 0.010). The 5-year disease-free survival was 51.3% in the observation group and 74.0% in the adjuvant group (p = 0.011). In multivariate analysis, only platinum-based adjuvant chemotherapy was a risk factor for overall survival [hazard ratio (HR) = 0.428, p = 0.049] and disease-free survival (HR = 0.57, p = 0.043). In subset analysis, patients with a larger tumor (greater than 3.2 cm), moderate to poor differentiation, and good performance status (Eastern Cooperative Oncology Group, 0) benefitted from platinum-based adjuvant chemotherapy.Conclusions: Platinum-based adjuvant chemotherapy for surgically treated stage IB NSCLC might offer better survival than observation alone. A large-scale randomized clinical trial is needed to validate these findings. [ABSTRACT FROM AUTHOR]