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Sensitivity Analysis of dVm/dtMax_repol to Ion Channel Conductance for Prediction of Torsades de Pointes Risk (다형 심실빈맥의 예측을 위한 dVm/dtMax_repol의 이온채널 전도도에 대한 민감도 분석)

  • Jeong, Da Un;Yoo, Yedam;Marcellinus, Aroli;Lim, Ki Moo
    • Journal of Biomedical Engineering Research
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    • v.43 no.5
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    • pp.331-340
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    • 2022
  • Early afterdepolarization (EAD), a significant cause of fatal ventricular arrhythmias including Torsade de Pointes (TdP) in long QT syndromes, is a depolarizing afterpotential at the plateau or repolarization phase in action potential (AP) profile early before completing one pace. AP duration prolongation is related to EAD but is not necessarily accounted for EAD. Several computational studies suggested EAD can form from an abnormality in the late plateau and/or repolarization phase of AP shape. In this sense, we hypothesized the slope during repolarization has the characteristics to predict TdP risk, mainly focusing on the maximum slope during repolarization (dVm/dtmax_repol). This study aimed to predict the sensitivity of dVm/dtmax_repol to ion channel conductances as a TdP risk metric through a population simulation considering multiple effects of simultaneous reduction in six ion channel conductances of gNaL, gKr, gKs, gto, gK1, and gCaL. Additionally, we verified the availability of dVm/dtmax_repol for TdP risk prediction through the correlation analysis with qNet, the representative TdP metric. We performed the population simulations based on the methodology of Gemmel et al. using the human ventricular myocyte model of Dutta et al. Among the sixion channel conductances, dVm/dtmax_repol and qNet responded most sensitively to the change in gKr, followed by gNaL. Furthermore, dVm/dtmax_repol showed a statistically significant high negative correlation with qNet. The dVm/dtmax_repol values were significantly different according to three TdP risk levels of high, intermediate, and low by qNet (p<0.001). In conclusion, we suggested dVm/dtmax_repol as a new biomarker metric for TdP risk assessment.

Isolation and Cloning of Porcine SLC27A2 Gene and Detection of Its Polymorphism Associated with Growth and Carcass Traits

  • Wang, Tao;Liu, Chang;Xiong, Yuan-Zhu;Deng, Chang-Yan;Zuo, Bo;Xie, Hong-Tao;Xu, De-Quan
    • Asian-Australasian Journal of Animal Sciences
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    • v.20 no.8
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    • pp.1169-1173
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    • 2007
  • The protein encoded by SLC27A2 gene is an isozyme of long-chain fatty-acid-coenzyme A ligase family, and it converts free long-chain fatty acids into fatty acyl-CoA esters, and thereby plays a key role in lipid biosynthesis and fatty acid degradation. In the present study, SLC27A2 located on human chromosome 15 was selected as candidate gene and we isolated and cloned partial fragments of mRNA sequence and genomic fragments of porcine SLC27A2 gene. The coding region of the gene as determined by alignments shared 90% and 82% identity with human and mouse cDNAs, respectively. Detection in LargeWhite and Meishan breeds showed that a single nucleotide polymorphism (SNP) ($A{\rightarrow}G$) existed in exon 7, which caused corresponding amino acid changed for encoding. In LargeWhite pigs it encoded for Val while in Meishan pigs it encoded for Ile, so we developed the PCR-RFLP genotype method for detection of this polymorphism. Association study in 135 $F_2$ reference family indicated that significant correlation existed between the polymorphism and growth and carcass traits.

Formation of Chitin Oligasaccharides during Long fermentation of Toha-jeot(Salt-Fermented Toha Shrimp)

  • Park, Bock-Hee;Park, Won-Ki;Kim, Hee-Kyung;Park, Young-Hee
    • Preventive Nutrition and Food Science
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    • v.3 no.3
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    • pp.221-224
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    • 1998
  • Toha-jeot, salt-fermented Toha shirmp(caridina denticulata denticulata DeHAAN) is a traditional fermented food in Korea. Samples of Toha-jeot used in the present study were a low-salt group of 15% sodium chloride(L), a high-salt group of 23% sodium chloride(H), a 50% conventional soybean sauce group(S), a low-salt group contraining 2% wheat bran (W2%-L) , a high -salt group containing 2% wheat bran(W2%-H), a low-salt group containing 4% wheat bran(W4%-L)and a high-salt group containing 4% wheat bran (W4%-H). These seven groups were refrigerated at 4 $\pm$1$^{\circ}C$ and then taken out for analysis at theree month intervals. We investigated the functional components of Toha-jeot during fermentation . Long fermentation of Toha-jeot lowered the viscosity of chitin and tended to reduce the distribution of molecular weight. THe formation of chitin oligosaccharides on the other hand, increased significantly. After nine months of fermenttion, chitin oligosaccharides(M.W. 823~1789) constituting 24.75% of Toha chitin were produced in the sample of W2%-H. During the same period, chitin oligosaccharides(M.W.1436-1879) constituting 66.30% of Toha chitin were produced in the samples of S. However, chitin oligosaccharides were not produced in Jeotsaeu-jeot made of sea-water shrimp when fermented for six months.

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Self-Reported Recovery from 2-Week 12-Hour Shift Work Schedules: A 14-Day Follow-Up

  • Merkus, Suzanne L.;Holte, Kari Anne;Huysmans, Maaike A.;van de Ven, Peter M.;van Mechelen, Willem;van der Beek, Allard J.
    • Safety and Health at Work
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    • v.6 no.3
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    • pp.240-248
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    • 2015
  • Background: Recovery from fatigue is important in maintaining night workers' health. This study compared the course of self-reported recovery after 2-week 12-hour schedules consisting of either night shifts or swing shifts (i.e., 7 night shifts followed by 7 day shifts) to such schedules consisting of only day work. Methods: Sixty-one male offshore employees-20 night workers, 16 swing shift workers, and 25 day workers-rated six questions on fatigue (sleep quality, feeling rested, physical and mental fatigue, and energy levels; scale 1-11) for 14 days after an offshore tour. After the two night-work schedules, differences on the $1^{st}$ day (main effects) and differences during the follow-up (interaction effects) were compared to day work with generalized estimating equations analysis. Results: After adjustment for confounders, significant main effects were found for sleep quality for night workers (1.41, 95% confidence interval 1.05-1.89) and swing shift workers (1.42, 95% confidence interval 1.03-1.94) when compared to day workers; their interaction terms were not statistically significant. For the remaining fatigue outcomes, no statistically significant main or interaction effects were found. Conclusion: After 2-week 12-hour night and swing shifts, only the course for sleep quality differed from that of day work. Sleep quality was poorer for night and swing shift workers on the $1^{st}$ day off and remained poorer for the 14-day follow-up. This showed that while working at night had no effect on feeling rested, tiredness, and energy levels, it had a relatively long-lasting effect on sleep quality.

The effect of electronic commerce on the economy - logistics industry perspective - (전자상거래가 경제에 미치는 효과 - 물류 정보화를 중심으로 -)

  • 김범환
    • Proceedings of the Technology Innovation Conference
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    • 1999.12a
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    • pp.281-295
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    • 1999
  • This paper analyses the effects of the increase of logistics outsourcing on the economy which are largely classified into three parts. The firm level and industry level are two among them which will be summarized below. The another is consumers level. On the fm level, the logistics outsourcing of a manufacturing firm not only helps to increase the efficiency of itself and but also confront the competitive environments by weakening the entry barriers, i.e., the emergence of contestable market. The reasons why the efficiency of the firm enhances are also largely divided into two parts. One is due to the reduction of inventory cost by replacing it by the information cost resulting from internet use. The other is owing to reducing the life cycle of production process by the emergence of virtual enterprises which are located in one point in De process of supply chain management. The weakening of entry barriers is directly affected by the drastic increase of internet users in twofold reasons: one is based on the restricted competitive characteristics due to the long-term transaction relationship between logistics providers and the companies who offer logistics services and the other, due to the weakening of the restriction of space and time. The effect of industry level is due to the transition of traditional to virtual vertical integration system The firms corresponding to a connection point in the process of supply chain management would try to realize both the scale of economy and the scope of economy for strengthening the competitiveness. We indicated above the emergence of contestable market however, it is a short-term phenomenon and result in the oligopoly market due to the entry barriers in the long-run sense.

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Short-course Versus Long-course Preoperative Radiotherapy plus Delayed Surgery in the Treatment of Rectal Cancer: a Meta-analysis

  • Liu, Shi-Xin;Zhou, Zhi-Rui;Chen, Ling-Xiao;Yang, Yong-Jing;Hu, Zhi-De;Zhang, Tian-Song
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.5755-5762
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    • 2015
  • Background: Short-course preoperative radiation (SCRT) with delayed surgery was found to increase pathologic complete response (pCR) rates in several trials. However, there was no clear answer on whether SCRT or long-course chemo-radiotherapy (LCRT) is more effective. Therefore we conducted this meta-analysis to evaluate the safety and efficacy of SCRT versus LCRT, both with delayed surgery, for treatment of rectal cancer. Materials and Methods: The literature was searched from PubMed, EMBASE, Web of Science, Cochrane Library and clinicaltrials.gov up to November, 2014. Quality of the randomized controlled trials (RCTs) was evaluated according to the Cochrane's risk of bias tool of RCT. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to rate the level of evidence. Review Manager 5.3 was employed for statistical analysis. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. Results: Three RCTs, with a total of 357 rectal cancer patients, were included in this systematic review. Metaanalysis results demonstrated there were no significantly differences in sphincter preservation rate, local recurrence rate, grade 3~4 acute toxicity, R0 resection rate and downstaging rate. Compared with SCRT, LCRT was associated with significant increase in the pCR rate [RR=0.49, 95%CI (0.31, 0.78), P=0.003]. Conclusions: In terms of sphincter preservation rate, local recurrence rate, grade 3~4 acute toxicity, R0 resection rate and downstaging rate, SCRT with delayed surgery is as effective as LCRT with delayed surgery for management of rectal cancer. LCRT significantly increased pCR rate compared with SCRT. Due to risk of bias and imprecision, further multi-center large sample RCTs were needed to confirm this conclusion.

A Case of Short Arm Deletion and Long Arm Duplication at Chromosome 3 (3번 염색체 단완 결실과 장완 중복을 동반한 1례)

  • Kong, Seung Hyun;Seo, Jeong Il;Kang, Jang Hui;Jung, So Young;Mok, Ji Sun
    • Clinical and Experimental Pediatrics
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    • v.48 no.12
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    • pp.1389-1389
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    • 2005
  • The long arm duplication of chromosome 3 was reported for the first time in 1966 by Falek et al., and Hirschhorn et al. came to identify the duplication of 3q21${\rightarrow}$qter region in 1973. In most cases of duplication 3q syndrome patients, pure duplication of 3qter is believed to be rare and is often reported accompanied with deletion of another segment of the chromosome. Approximately 75 percent of parents of the patient in the meantime have been demonstrated to have unbalanced translocations or inversions of the chromosome. Partial deletion of the distal part of the short arm of chromosome 3 was first reported by Verjaal and De Nef in 1978 and terminal deletion of chromosome 3 (3p25-qter) has been observed in most cases. In karyotyping of chromosomes of immature infants showing the manifestations of flat occiputs, low set ears, hypertelorism, broad nasal roots, thin lips, web necks, hypotonia, hypertrichosis skin, cryptorchidism etc, we experienced a case diagnosed as 46,XY, rec(3)dup(3)(q21)del(3)(p25)inv(3)(p25q21).

Comparison of the Efficacy of Caudal, Interlaminar, and Transforaminal Epidural Injections in Managing Lumbar Disc Herniation: Is One Method Superior to the Other?

  • Manchikanti, Laxmaiah;Singh, Vijay;Pampati, Vidyasagar;Falco, Frank J.E.;Hirsch, Joshua A.
    • The Korean Journal of Pain
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    • v.28 no.1
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    • pp.11-21
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    • 2015
  • Background: Epidural injections are performed utilizing 3 approaches in the lumbar spine: caudal, interlaminar, and transforaminal. The literature on the efficacy of epidural injections has been sporadic. There are few high-quality randomized trials performed under fluoroscopy in managing disc herniation that have a long-term follow-up and appropriate outcome parameters. There is also a lack of literature comparing the efficacy of these 3 approaches. Methods: This manuscript analyzes data from 3 randomized controlled trials that assessed a total of 360 patients with lumbar disc herniation. There were 120 patients per trial either receiving local anesthetic alone (60 patients) or local anesthetic with steroids (60 patients). Results: Analysis showed similar efficacy for caudal, interlaminar, and transforaminal approaches in managing chronic pain and disability from disc herniation. The analysis of caudal epidural injections showed the potential superiority of steroids compared with local anesthetic alone a 2-year follow-up, based on the average relief per procedure. In the interlaminar group, results were somewhat superior for pain relief in the steroid group at 6 months and functional status at 12 months. Interlaminar epidurals provided improvement in a significantly higher proportion of patients. The proportion of patients nonresponsive to initial injections was also lower in the group for local anesthetic with steroid in the interlaminar trial. Conclusions: The results of this assessment show significant improvement in patients suffering from chronic lumbar disc herniation with 3 lumbar epidural approaches with local anesthetic alone, or using steroids with long-term follow-up of up to 2 years, in a contemporary interventional pain management setting.

Reconstruction of a long defect of the median nerve with a free nerve conduit flap

  • Campodonico, Andrea;Pangrazi, Pier Paolo;De Francesco, Francesco;Riccio, Michele
    • Archives of Plastic Surgery
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    • v.47 no.2
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    • pp.187-193
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    • 2020
  • Upper limb nerve damage is a common condition, and evidence suggests that functional recovery may be limited following peripheral nerve repair in cases of delayed reconstruction or reconstruction of long nerve defects. A 26-year-old man presented with traumatic injury from a wide, blunt wound of the right forearm caused by broken glass, with soft tissue loss, complete transection of the radial and ulnar arteries, and a large median nerve gap. The patient underwent debridement and subsequent surgery with a microsurgical free radial fasciocutaneous flap to provide a direct blood supply to the hand; the cephalic vein within the flap was employed as a venous vascularized chamber to wrap the sural nerve graft and to repair the wide gap (14 cm) in the median nerve. During the postoperative period, the patient followed an intensive rehabilitation program and was monitored for functional performance over 5 years of follow-up. Our assessment demonstrated skin tropism and sufficient muscle power to act against strong resistance (M5) in the muscles previously affected by paralysis, as well as a good localization of stimuli in the median nerve region and an imperfect recovery of two-point discrimination (S3+). We propose a novel and efficient procedure to repair >10-cm peripheral nerve gap injuries related to upper limb trauma.

Clozapine-related Sudden Pericarditis in a Patient Taking Long Acting Aripiprazole and Valproate: A Case Report

  • De Berardis, Domenico;Fornaro, Michele;Orsolini, Laura;Olivieri, Luigi;Nappi, Francesco;Rapini, Gabriella;Vellante, Federica;Napoletano, Cosimo;Serroni, Nicola;Di Giannantonio, Massimo
    • Clinical Psychopharmacology and Neuroscience
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    • v.16 no.4
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    • pp.505-507
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    • 2018
  • Clozapine may be associated with cardiovascular adverse effects including QTc prolongation and, more rarely, with myocarditis and pericarditis. Although rare, these latter cardiovascular adverse effects may be life-threatening and must be immediately recognized and treated. Several cases of clozapine related-pericarditis have been described and often it has a subtle and insidious onset with symptoms that may be often misdiagnosed with psychiatric manifestations (e.g. anxiety, panic or somatization) leading to a delayed correct diagnosis with potential fatal consequences. In the present report we describe the case of a 27-year-old girl with schizoaffective disorder taking long acting aripiprazole and valproate who developed a sudden onset clozapine-related pericarditis during titration phase that resolved with immediate clozapine discontinuation and indomethacin administration. We underline the importance of an early diagnosis of clozapine-related pericarditis and the need to have monitoring protocols to prevent this potentially fatal adverse effect especially when polypharmacy is administered to patients taking clozapine.