Search

Changes in mitochondrial morphology are associated with nutrient utilization, but the precise causalities and the underlying mechanisms remain unknown. Here, using cellular models representing a wide variety of mitochondrial shapes, we show a strong linear correlation between mitochondrial fragmentation and increased fatty acid oxidation (FAO) rates. Forced mitochondrial elongation following MFN2 over-expression or DRP1 depletion diminishes FAO, while forced fragmentation upon knockdown or knockout of MFN2 augments FAO as evident from respirometry and metabolic tracing. Remarkably, the genetic induction of fragmentation phenocopies distinct cell type-specific biologicalfunctions of enhanced FAO. These include stimulation of gluconeogenesis in hepatocytes, induction of insulin secretion in islet β-cells exposed to fatty acids,and survival of FAO-dependent lymphoma subtypes. We find that fragmentation increases long-chain but not short-chain FAO,identifying carnitine O-palmitoyltransferase 1 (CPT1) as thedownstream effector of mitochondrial morphology in regulation of FAO.Mechanistically, we determined that fragmentation reduces malonyl-CoA inhibition of CPT1, while elongation increasesCPT1sensitivity to malonyl-CoA inhibition. Overall, these findings underscore a physiologic role for fragmentation as a mechanism whereby cellular fuel preference and FAO capacity are determined.

KIF5B-RET gene rearrangement occurs in ~1% of lung adenocarcinomas. Recently, targeted agents that inhibit RET phosphorylation have been evaluated in several clinical studies; however, little is known about the role of this gene fusion in driving lung cancer. Immunohistochemistry was used to evaluate the expression of the FOXA2 protein in tumor tissues of patients with lung adenocarcinoma. KIF5B-RET fusion cells proliferated in a cohesive form and grew tightly packed with variable-sized colonies. The expression of RET and its downstream signaling molecules, including p-BRAF, p-ERK, and p-AKT, increased. In KIF5B-RET fusion cells, the intracellular expression of p-ERK was higher in the cytoplasm than in the nucleus. Two transcription factors, STAT5A and FOXA2, exhibiting significantly different expressions at the mRNA level, were finally selected. p-STAT5A was highly expressed in the nucleus and cytoplasm, whereas the expression of the FOXA2 protein was lower; however, it was much higher in the nucleus than in the cytoplasm. Compared with the expression of FOXA2 in the RET rearrangement-wild NSCLC (45.0%), high expression (3+) were observed in most RET rearrangement NSCLCs (94.4%). Meanwhile, KIF5B-RET fusion cells began to increase belatedly from day 7 and only doubled on day 9 in 2D cell culture. However, tumors in mice injected with KIF5B-RET fusion cells began to rapidly increase from day 26. In cell cycle analyses, the KIF5B-RET fusion cells in G0/G1 were increased on day 4 (50.3 ± 2.6%) compared with the empty cells (39.3 ± 5.2%; P = 0.096). Cyclin D1 and E2 expressions were reduced, whereas CDK2 expression slightly increased. pRb and p21 expression was diminished compared with the empty cells, TGF-β1 mRNA was highly expressed, and the proteins were accumulated mostly in the nucleus. Twist mRNA and protein expression was increased, whereas Snail mRNA and protein expression was decreased. Particularly, in KIF5B-RET fusion cells treated with FOXA2 siRNA, the expression of TGF-β 1 mRNA was remarkably reduced but Twist1 and Snail mRNA were increased. Our data suggest that cell proliferation and invasiveness in KIF5B-RET fusion cells are regulated by the upregulation of STAT5A and FOXA2 through the continuous activation of multiple RET downstream signal cascades, including the ERK and AKT signaling pathways. We found that TGF-β1 mRNA, where significant increments were observed in KIF5B-RET fusion cells, is regulated at the transcriptional level by FOXA2.

Robotic prosthetic hands are a device that helps to improve the quality of life for patients without hands. Recently, robotic prosthetic hands can perform various grasping patterns because of improvement of bioengineering and robotics. The research that automatically selects the appropriate operation according to the situation is important. Many previous studies have used EMG signals. However, EMG signals are difficult to generalize because EMG signals vary depending on the position of the muscle. In this study, we developed a system for controlling robotic prosthetic hands using images and deep learning to facilitate generalization. We also proposed a method for selecting a grasping target to be held in the image. These results will help to improve the quality of life of the robotic prosthetic hand user.

By actively coping with changes, a government providing public services can also improve the quality of those public services and help citizens improve their quality of life in the face of rapidly changing social structures, environments, and values. Accordingly, this study will typologize public innovation capacity (PIC) in terms of the individual, middle manager, and organizational levels. This study typologizes public innovation capacity in terms of the individual, middle manager, and organizational levels through mini-round Delphi analysis and exploratory factor analysis and confirmatory factor analysis using survey. This capacity is a precondition of the specificity of the public sector (generating public interest by providing public services) and universal value of HR (human resource) research (creating performance). It provides the basic capacity within the public sector to enhance the quality of public services and create positive outcomes.

During the first outbreak of the coronavirus disease 2019 (COVID-19), many people expressed hatred toward others whom they believed were responsible for the situation. Such increase in negative affect could be resultant of the better-than-average effect (BTAE), which refers to the phenomenon of believing that one is superior to average others. This study investigated the relationship between the BTAE and emotional valence toward others and tested whether the relationship was moderated by allocentric goals (i.e., concerned with the interests of others rather than themselves) and culture. Participants from the U.S. (N = 210) and South Korea (N = 214) were asked about their perceptions on whether they were better than others at preventing the COVID-19 infection, how they felt about others regarding COVID-19, and for whom they were preventing COVID-19. The results indicated that people showing more BTAE in relation to preventing the COVID-19 infection reported more negative emotional valence toward others, but the relationship was moderated by allocentric goals. In particular, the U.S. participants with higher allocentric goals reported less negatively valenced emotions, while the same was not found in Korean participants. The findings suggest the power of allocentric goals in diminishing the BTAE in some cultures, which may possibly explain the negative emotions some people experience when following social distancing rules.

Additional file 1. List of rimers used for qRT-PCR.

본 연구는 의료사회복지사의 퇴원계획에 대한 개념 및 실태 등을 확인하고 이를 통해 의료사회복지사 퇴원계획 모델 개발과 수가 적용방안을 논의하는 것을 주요 목적으로 하고 있다. 연구목적달성을 위해 탐색적 설계를 기반으로 한 혼합방법을 활용하였다. 1단계에서는 퇴원계획과 관련된 개념을 도출하기 위해 10명의 의료사회복지사를 대상으로 2개의 초점집단 인터뷰(FGI)가 활용되었으며, 2단계에서는 총 114명의 종합병원 소속 의료사회복지사를 대상으로 설문조사를 실시하여 퇴원계획 관련 개념을 구체화시키는 과정을 거쳤다. 연구결과, 1단계 FGI에서는 1) 퇴원계획을 위한 선결과제, 2) 퇴원계획의 실제: 스크리닝부터 지역사회에 이르기까지, 3) 성공적인 퇴원계획을 위해서 라는 3개의 주제 하에 7개의 상위범주, 20개의 하위 범주, 156개의 개념이 도출되었다. 2단계에서는 퇴원계획의 목적, 퇴원계획에 대한 의료사회복지사의 역할 및 직무, 대상자 범위, 절차, 부서 간 협조체계, 수행업무 등 퇴원계획 수행을 위한 구체적인 사항을 확인하였다. 마지막 3단계에서는 1단계와 2단계 과정을 통합·분석하여 의료현장에서의 사회복지사를 위한 퇴원계획모델이 개발되었으며, 이를 근거로 퇴원계획 수가 적용 방안이 제시되었다. 결론에는 지역사회 통합 돌봄 정책 하에서 의료사회복지사의 퇴원계획이 전문적이고 체계적으로 수행되기 위한 방안이 논의되었다.

Background Cytomegalovirus (CMV) infection continues to cause morbidity in kidney transplant recipients, despite prophylaxis and pre-emptive therapy. Predictors of poor outcomes remain incompletely characterized. We questioned whether markers of CMV replication (CMV peak viral load, recurrent episodes, or duration of CMV DNAemia) are associated with adverse outcomes in the current era. Methods We studied 605 people who underwent kidney transplant at Johns Hopkins University (2010 – 2018). Mean follow-up was 45.5 months. The average age was 51.85 years and 39.7% were female. Donor-seropositive, recipient seronegative (D+/R-) patients received valganciclovir 900 mg/day for 6 months, while R+ patients received valganciclovir 450 mg/day for 3 months. CMV recurrence was defined as CMV DNAemia after two undetectable CMV PCR’s. Outcomes of acute rejection, graft failure, and death were evaluated in univariate analysis; p values were calculated by Fisher’s exact test. Results Peak CMV viral load was not associated with any outcomes (Table 1). There was a trend of increased graft failure in people who had long duration ( >6 month) DNAemia (Table 2). More than two episodes of CMV reactivation was associated with graft failure and rejection (Table 3). Conclusion CMV reactivation is associated with kidney rejection and failure in univariate models. Multivariate analyses and longitudinal modeling will provide increased data upon which to better instruct preventative strategies. Acknowledgments Funding for the research study was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA Disclosures Robin K. Avery, MD, Aicuris (Grant/Research Support)Astellas (Grant/Research Support)Chimerix (Research Grant or Support)Merck (Grant/Research Support)Oxford Immunotec (Grant/Research Support)Qiagen (Grant/Research Support)Takeda/Shire (Grant/Research Support) Yuexin Tang, PhD, JnJ (Other Financial or Material Support, Spouse’s employment)Merck & Co., Inc. (Employee, Shareholder) Kieren Marr, MD, Merck (Grant/Research Support, Advisor or Review Panel member)

Purpose of Review Insufficient knowledge about COVID-19 and the potential risks of COVID-19 are limiting organ transplantation in wait-listed candidates and deferring essential health care in solid organ transplant recipients. In this review, we expand the understanding and present an overview of the optimized management of COVID-19 in solid organ transplant recipients. Recent Findings Transplant recipients are at an increased risk of severe COVID-19. The unique characteristics of transplant recipients can make it more difficult to identify COVID-19. Based on the COVID-19 data to date and our experience, we present testing, management, and prevention methods for COVID-19. Comprehensive diagnostic tests should be performed to determine disease severity, phase of illness, and identify other comorbidities in transplant recipients diagnosed with COVID-19. Outpatients should receive education for preventative measures and optimal health care delivery minimizing potential infectious exposures. Multidisciplinary interventions should be provided to hospitalized transplant recipients for COVID-19 because of the complexity of caring for transplant recipients. Summary Transplant recipients should strictly adhere to infection prevention measures. Understanding of the transplant specific pathophysiology and development of effective treatment strategies for COVID-19 should be prioritized.

The ganglionated plexuses (GP) are dense epicardial nerves that are implicated in atrial fibrillation (AF). They can be functionally located from the endocardium using high frequency stimulation (HFS) which can locate distinct GP that trigger atrial ectopy/AF (ET-GP) or atrioventricular (AV) dissociating (AVD-GP). Our aim was to map and understand the histological, anatomical and functional properties of the different types of GP and ablate them with or without pulmonary vein isolation (PVI) in patients with AF. We hypothesised that ablating these specific GP sites is feasible, and prevents AF. Firstly, to investigate this, we mapped for AVD-GP and ET-GP using HFS in the left atrium of patients with AF. An automated process was used to merge and transform all patient maps onto one reference left atrial shell. A probability density function was applied at each tested site, including GP and negative HFS response sites, to create a probability distribution atlas of AVD-GP and ET-GP. There were distinct anatomical regions according to each GP sub-type, and ET-GP had preponderance to the PV ostia, roof, and mid-anterior wall. These are the areas that would usually be targeted with circumferential PVI. Therefore, a prospective, randomised, controlled study was performed (GANGLIA-AF) which assessed ET-GP ablation without PVI and PVI alone in patients with paroxysmal AF. Patients were followed-up for 12 months with multiple 48hr Holter monitors. The primary endpoint was any documented atrial arrhythmia >30s, and the secondary endpoints included complications and redo ablations. This showed that there was no statistically significant difference in AF prevention between the two arms, however the GP ablation arm required less ablation on average than the PVI arm. We also performed a smaller pilot study of redo AF ablation patients, assessing for feasibility and safety of GP ablation in addition to redo PVI. The same follow-up and endpoint criteria were used as in the GANGLIA-AF study. Some patients had permanent PVI, and non-PV triggers of AF were identifiable with HFS. We also developed a custom-built high frequency stimulator (Tau-20) that was used to identify ectopy-triggering (ET) sites in Langendorff-perfused porcine hearts. We were able to replicate the HFS responses used in the clinical setting in the porcine atria. Transmural cross-sectional dissections were taken from ET and non-ET sites, and the tissues were stained for parasympathetic and sympathetic nerves using immunohistochemistry methods. This showed that the mean density of nerves was greater in ET sites compare to non-ET sites. The Tau-20 has been successfully trialled in humans in the clinical setting, and with further improvements, it may replace the old Grass S88 stimulator for future GP ablation cases. In conclusion, ET-GP are upstream triggers of AF that can be ablated without PVI to prevent paroxysmal AF. GP ablation can be achieved with less RF energy than PVI implying a more specific technique on mechanistic grounds. The cross-over rate and clinical outcomes for GP ablation needs further improvement but GANGLIA-AF provides evidence that GP ablation may be an alternative or an adjunct technique to PVI. In addition, our ex-vivo evidence of increased nerve density at ET sites may account for the differential functional response of ET-GP stimulation in the clinical setting. Open Access

Additional file 2. Toxicity of low- or high-dose IR in BALB/c nude mice. (A) The shielding device was made of 4 mm thick lead. The anesthetized mice were fixed in a 50 mL tube and irradiated with a lead shield. (B) Tumor growth and (C) body weight according to radiation dose. (D) Tumor growth during long-term treatment with 4 Gy of IR.

Additional file 1. Short-term and long-term drug administration schedules.

Additional file 1.

Additional file 3. IHC staining with HIF-1α, VEGF, Glut-1, and Ki-67 antibodies in all five treatment groups (72 h after the end of treatment). Mice were divided into five groups according to the dosing and treatment schedule: vehicle (PBS), IR alone (4 Gy/day), CKD-516 alone (3 mg/kg), and CKD-516 (3 mg/kg, day 1 or days 1 and 5) combined with IR.Scale bar: 200 μm. Magnification: × 100.

Objectives: The aim of this study is to compare the characteristics of esthetic brackets and stainless steel braces used recently in orthodontic treatment. Methods: Articles were searched the PubMed databases from 2006 up to March 2017 with the key words or combinations: esthetic bracket, polycarbonate bracket, ceramic bracket. Data from the included studies were listed, including study name and author, year of publication, participations (plastic and ceramic brackets), intervention (tested mechanical and biomechanical properties) and outcome. Risk of Bias was included in the extraction procedure with ROB tool. Results: 20 studies were included in this systematic review and data for friction forces in 11 studies and date for shear bond strength from 3 studies were extracted for narrative analysis. Frictional forces of glass fiber or filler reinforced plastic brackets is significant higher than that of metallic brackets, however, brackets with metal slots created remarkable lower frictional force compared to stainless steel brackets. Polycrystalline brackets created significant higher frictional forces than stainless steel brackets, monocrystalline, metal slot reinforced and self ligating ceramic brackets. All designs of ceramic brackets have significant higher shear bond strength compared to stainless steel brackets, except for polycrystalline brackets with polymer mesh base. Bond strength of plastic brackets was significant lower than that of metallic brackets. Conclusions: This study is an overview about the properties of all esthetic brackets compared to traditional metallic ones, especially the frictional force and shear bond strength.

Background/ Objectives: Physically disabled workers have a higher employment rate than any other handicapped people. However, there is a lack of research over the usage of ICT equipment to help physically disabled workers. Hence, the purpose of this study is to determine the relationship of the ICT equipment on the physically disabled workers on their present satisfaction on work and life. Methods/Statistical Analysis: This study analyzed 5,515 disabled workers from the Ministry of Health and Welfare Panel Survey data in 2014. A t-test on SPSS 2.0 was used to determine any significance between the satisfaction of work and life. The effect size was determined using a regression analysis. Findings: The results showed significant difference between the usage of ICT equipment and non-usage of the equipment on the satisfaction of current life, work, and stress on disabled workers. Through the use of ICT equipment, their work satisfaction positively affected their life satisfaction. These findings revealed that the ICT machine is an important tool of everyday life for the people with disabled external body features, and also serves as an important tool for those with functional limitations due to the disability. Application/Improvements: A limitation of this study was that the panel data could not differentiate between the period of using the ICT tool and the ability to apply ICT to lives of the disabled, and did not reflect an influence factor on the physically disabled and the sensory impaired. In addition, a conclusion was presented based on the study’s implications.

Twenty-seven species of the genus Coleophora Hubner (Lepidoptera, Coleophoridae) are recognized in the Korean peninsula, including seven species that are new to Korea: C. albicans Zeller, C. falkovitshella Vives, C. honshuella Baldizzone & Oku, C. japonicella Oku, C. kononenkoi Baldizzone & Savenkov, C. rectimarginalis Li, and C. vestianella (Linnaeus). For all known species, bibliographies, collecting localities, distribution, biological information, and some taxonomic notes are provided, with illustrations of the male or the female genitalia.

Unilateral sensorineural hearing loss (USNHL)/single-side deafness (SSD) is a frequently encountered disability in children. The etiology of a substantial portion of USNHL/SSD still remains unknown, and genetic causes have not been clearly elucidated. In this study, the authors evaluated the heritability of USNHL/SSD. The authors sequentially recruited 50 unrelated children with SSD. For an etiologic diagnosis, we performed a rigorous review on the phenotypes of family members of all children and conducted, if necessary, molecular genetic tests including targeted exome sequencing of 129 deafness genes. Among the 50 SSD children cohort, the authors identify 4 (8%) unrelated SSD probands from 4 families (SH136, SB173, SB177, and SB199) with another hearing impaired family members. Notably, all 4 probands in our cohort with a familial history of SSD also have pigmentary abnormalities such as brown freckles or premature gray hair within first degree relatives, which may indicate that genes whose products are involved with pigmentary disorder could be candidates for heritable SSD. Indeed, SH136 and SB199 turned out to segregate a mutation in MITF and PAX3, respectively, leading to a molecular diagnosis of Waardenburg syndrome (WS). We report, for the first time in the literature, a significant heritability of pediatric SSD. There is a strong association between the heritability of USNHL/SSD and the pigmentary abnormality, shedding a new light on the understanding of the molecular basis of heritable USNHL/SSD. In case of children with congenital SSD, it would be mandatory to rigorously screen pigmentary abnormalities. WS should also be included in the differential diagnosis of children with USNHL/SSD, especially in a familial form.

A Satsuma mandarin (Citrus unshiu Marc. cv. Miyagawa) spontaneous mutant, Shinheungri, produces fruit with an abnormal red-coloured peel during ripening. The peel and pulp extracts of Shinheungri fruit were evaluated for polyphenolic contents and antioxidant activities by using various in vitro assays. Compared with those of wild type (WT), Shinheungri exhibited slightly higher total flavonoid content and antioxidant activities. The results of UPLC analyses indicate that the peel and pulp extracts of Shinheungri fruit were rich in mainly hesperidin, and they had different flavonoid composition. The present data on Shinheungri revealed a potential source of powerful flavonoids for further detailed phytochemical investigation.

We consider a model for two lasers that are mutually coupled optoelectronically by modulating the pump of one laser with the intensity deviations of the other. Signal propagation time in the optoelectronic loop causes a significant delay leading to the onset of oscillatory output. Multiscale perturbation methods are used to describe the amplitude and period of oscillations as a function of the coupling strength and delay time. For weak coupling the oscillations have the laser's relaxation period, and the amplitude varies as the one-fourth power of the parameter deviations from the bifurcation point. For order-one coupling strength the period is determined as multiples of the delay time, and the amplitude varies with a square-root power law. Because we allow for independent control of the individual coupling constants, for certain parameter values there is an atypical amplitude-resonance phenomena. Finally, our theoretical results are consistent with recent experimental observations when the inclusion of a low-pass filter in the coupling loop is taken into account., 26 pages 12 figures. SIAM J. Dynamical Systems, in press

Alkylanilines are a group of chemicals whose ubiquitous presence in the environment is a result of the multitude of sources from which they originate. Exposure assessments indicate that most individuals experience lifelong exposure to these compounds. Many alkylanilines have biological activity similar to that of the carcinogenic multi-ring aromatic amines. This review provides an overview of human exposure and biological effects. It also describes recent investigations into the biochemical mechanisms of action that lead to the assessment that they are most probably more complex than those of the more extensively investigated multi-ring aromatic amines. Not only is nitrenium ion chemistry implicated in DNA damage by alkylanilines but also reactions involving quinone imines and perhaps reactive oxygen species. Recent results described here indicate that alkylanilines can be potent genotoxins for cultured mammalian cells when activated by exogenous or endogenous phase I and phase II xenobiotic-metabolizing enzymes. The nature of specific DNA damage products responsible for mutagenicity remains to be identified but evidence to date supports mechanisms of activation through obligatory N-hydroxylation as well as subsequent conjugation by sulfation and/or acetylation. A fuller understanding of the mechanisms of alkylaniline genotoxicity is expected to provide important insights into the environmental and genetic origins of one or more human cancers and may reveal a substantial role for this group of compounds as potential human chemical carcinogens., National Institute of Environmental Health Sciences (PO1-ES006052), National Institute of Environmental Health Sciences (P30-ES002109)