Publications by authors named "Bora Lee"

191 Publications

Home-Based Up-Dosing in Build-Up Phase of Oral Immunotherapy of Egg Allergy Is Safe and Feasible in Real-World Practice.

Allergy Asthma Immunol Res 2021 Sep;13(5):791-798

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Oral immunotherapy (OIT) has emerged to build sustained unresponsiveness or tolerance in patients with egg allergy. However, it is important to increase compliance and ensure safety because OIT requires an extended period of time and has a risk of side effects like anaphylaxis. We aimed to show the feasibility and safety of OIT during the build-up phase using a home-based, up-dosing method in children with egg allergy. Sixteen patients aged 4 to 12 years with egg allergy were enrolled. Patients increased the dose of boiled egg white (EW) by 5% per day at home and 25% per month at the hospital, with a target dose of 40 g of boiled EW (4.0 g of EW proteins). A historical control group (n = 16) was matched for age, sex, and clinical characteristics for comparisons with the OIT group. Oral food challenge (OFC) tests were performed after completing the build-up phase. In the OIT group, 93.8% (15/16) of patients achieved desensitization, with only 1 patient discontinuing OIT before the maintenance phase due to repeated allergic reactions. Mild allergic reactions and anaphylaxis occurred in 12 (75.0%) and 2 patients (12.5%), respectively. However, there were no significant adverse reactions such as serious anxiety or life-threatening events that required discontinuation of treatment. On the contrary, only 1 patient (6.3%) in the control group passed an OFC of 40 g of boiled EW during the same period ( < 0.001). Our results suggest that home-based up-dosing protocols using boiled eggs may be safe and feasible for the build-up phase of OIT in children with egg allergy.
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http://dx.doi.org/10.4168/aair.2021.13.5.791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419648PMC
September 2021

DeepCUBIT: Predicting Lymphovascular Invasion or Pathological Lymph Node Involvement of Clinical T1 Stage Non-Small Cell Lung Cancer on Chest CT Scan Using Deep Cubical Nodule Transfer Learning Algorithm.

Front Oncol 2021 5;11:661244. Epub 2021 Jul 5.

Division of Oncology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea.

The prediction of lymphovascular invasion (LVI) or pathological nodal involvement of tumor cells is critical for successful treatment in early stage non-small cell lung cancer (NSCLC). We developed and validated a Deep Cubical Nodule Transfer Learning Algorithm (DeepCUBIT) using transfer learning and 3D Convolutional Neural Network (CNN) to predict LVI or pathological nodal involvement on chest CT images. A total of 695 preoperative CT images of resected NSCLC with tumor size of less than or equal to 3 cm from 2008 to 2015 were used to train and validate the DeepCUBIT model using five-fold cross-validation method. We also used tumor size and consolidation to tumor ratio (C/T ratio) to build a support vector machine (SVM) classifier. Two-hundred and fifty-four out of 695 samples (36.5%) had LVI or nodal involvement. An integrated model (3D CNN + Tumor size + C/T ratio) showed sensitivity of 31.8%, specificity of 89.8%, accuracy of 76.4%, and AUC of 0.759 on external validation cohort. Three single SVM models, using 3D CNN (DeepCUBIT), tumor size or C/T ratio, showed AUCs of 0.717, 0.630 and 0.683, respectively on external validation cohort. DeepCUBIT showed the best single model compared to the models using only C/T ratio or tumor size. In addition, the DeepCUBIT model could significantly identify the prognosis of resected NSCLC patients even in stage I. DeepCUBIT using transfer learning and 3D CNN can accurately predict LVI or nodal involvement in cT1 size NSCLC on CT images. Thus, it can provide a more accurate selection of candidates who will benefit from limited surgery without increasing the risk of recurrence.
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http://dx.doi.org/10.3389/fonc.2021.661244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287408PMC
July 2021

A high degree of knee flexion after TKA promotes the ability to perform high-flexion activities and patient satisfaction in Asian population.

BMC Musculoskelet Disord 2021 Jun 21;22(1):565. Epub 2021 Jun 21.

Department of Orthopaedic Surgery, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.

Background: This study investigated whether achieving a higher degree of knee flexion after TKA promoted the ability to perform high-flexion activities, as well as patient satisfaction and quality of life.

Methods: Clinical data on 912 consecutive primary TKA cases involving a single high-flexion posterior stabilized fixed-bearing prosthesis were retrospectively analyzed. Demographic and clinical data were collected, including knee flexion angle, the ability to perform high-flexion activities, and patient satisfaction and quality of life.

Results: Of the cases, 619 (68%) achieved > 130° of knee flexion after TKA (high flexion group). Knee flexion angle and clinical scores showed significant annual changes, with the maximum improvement seen at 5 years and slight deterioration observed at 10 years postoperatively. In the high flexion group, more than 50% of the patients could not kneel or squat, and 35% could not stand up from on the floor. Multivariate analysis revealed that > 130° of knee flexion, the ability to perform high-flexion activities (sitting cross-legged and standing up from the floor), male gender, and bilateral TKA were significantly associated with patient satisfaction after TKA, while the ability to perform high-flexion activities (sitting cross-legged and standing up from the floor), male gender, and bilateral TKA were significantly associated with patient quality of life after TKA.

Conclusions: High knee flexion angle (> 130°) after TKA increased the ease of high-flexion activities and patient satisfaction. The ease of high-flexion activities also increased quality of life after TKA in our Asian patients, who frequently engage in these activities in daily life.
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http://dx.doi.org/10.1186/s12891-021-04369-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215776PMC
June 2021

The Effect of Tranexamic Acid Administration on Early Endothelial Damage Following Posterior Lumbar Fusion Surgery.

J Clin Med 2021 Apr 1;10(7). Epub 2021 Apr 1.

Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul 03722, Korea.

Tranexamic acid (TXA) protects against endothelial glycocalyx injury in vitro. We aimed to evaluate whether TXA could protect against endothelial glycocalyx degradation in patients undergoing posterior lumbar fusion surgery. Patients aged 30-80 years were enrolled. The TXA group was administered a loading dose of 10 mg/kg, followed by a 1 mg/kg/h infusion. Serum syndecan-1 and heparan sulfate concentrations, which are biomarkers of glycocalyx degradation, were measured at preoperative baseline (T0), immediately post-surgery (T1), and 2 h post-surgery (T2). Postoperative complications were assessed, including hypotension, desaturation, and acute kidney injury. Among the 121 patients who completed the study, 60 received TXA. There were no significant differences in the marker concentrations at each time point. However, the postoperative increase in syndecan-1 levels from baseline was significantly attenuated in the TXA group compared with the control group (median (interquartile range); T1 vs. T0: -1.6 (-5.3-2.6) vs. 2.2 (-0.7-4.8), = 0.001; T2 vs. T0: 0.0 (-3.3-5.5) vs. 3.6 (-0.1-9.3), = 0.013). Postoperative complications were significantly associated with the magnitude of the change in syndecan-1 levels (for T2 vs. T0: odds ratio: 1.08, 95% confidence interval: 1.02-1.14, = 0.006). TXA administration was associated with reduced syndecan-1 shedding in patients undergoing posterior lumbar fusion surgery.
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http://dx.doi.org/10.3390/jcm10071415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037070PMC
April 2021

Increased Carotid Intima-Media Thickness was not Associated With Cognitive Dysfunction After Off-Pump Coronary Surgery in Older Adult Patients Without Carotid Stenosis.

Semin Thorac Cardiovasc Surg 2021 Mar 10. Epub 2021 Mar 10.

Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea; Severance Cardiovascular Hospital, Yonsei University Health System, Seoul, Republic of Korea. Electronic address:

Increased carotid intima-media thickness (C-IMT), a marker of atherosclerosis, is known to be associated with cerebrovascular and cortical abnormalities and cognitive impairment. This prospective observational study investigated the association between increased C-IMT and postoperative cognitive dysfunction (POCD) in older adult patients undergoing off-pump coronary artery bypass surgery. A total of 201 patients (57 females, 144 males; >60 years) were classified into increased (n = 105) or normal (n = 96) C-IMT groups by a cut-off value of 0.9 mm (bilateral C-IMT mean). Cognitive function was serially assessed with the Korean Mini-Mental State Examination, and Korean Montreal Cognitive Assessment scores preoperatively and at 7 days and 3 months postoperatively. POCD was defined as the deterioration of 1 standard deviation in at least one of the postoperative tests compared with their corresponding baseline scores. Independent risk factors for POCD were evaluated using multivariable analysis. Overall, POCD occurred in 46 patients (23%) over the 3 months. The incidences of POCD at 7 days and 3 months after surgery were similar, and there was no difference in both Korean Mini-Mental State Examination and Korean Montreal Cognitive Assessment test scores before and after surgery between groups. Chronic obstructive lung disease and intraoperative hyperglycemia episodes (>180 mg/dL), but not increased C-IMT, were independent risk factors for POCD. Unlike in nonsurgical cohorts, increased C-IMT was not significantly associated with the occurrence of POCD in older adult patients undergoing off-pump coronary artery bypass surgery.
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http://dx.doi.org/10.1053/j.semtcvs.2021.03.004DOI Listing
March 2021

Decoding neuronal composition and ontogeny of individual hypothalamic nuclei.

Neuron 2021 04 17;109(7):1150-1167.e6. Epub 2021 Feb 17.

Department of Neuroscience and Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; The Epigenetic Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

The hypothalamus plays crucial roles in regulating endocrine, autonomic, and behavioral functions via its diverse nuclei and neuronal subtypes. The developmental mechanisms underlying ontogenetic establishment of different hypothalamic nuclei and generation of neuronal diversity remain largely unknown. Here, we show that combinatorial T-box 3 (TBX3), orthopedia homeobox (OTP), and distal-less homeobox (DLX) expression delineates all arcuate nucleus (Arc) neurons and defines four distinct subpopulations, whereas combinatorial NKX2.1/SF1 and OTP/DLX expression identifies ventromedial hypothalamus (VMH) and tuberal nucleus (TuN) neuronal subpopulations, respectively. Developmental analysis indicates that all four Arc subpopulations are mosaically and simultaneously generated from embryonic Arc progenitors, whereas glutamatergic VMH neurons and GABAergic TuN neurons are sequentially generated from common embryonic VMH progenitors. Moreover, clonal lineage-tracing analysis reveals that diverse lineages from multipotent radial glia progenitors orchestrate Arc and VMH-TuN establishment. Together, our study reveals cellular mechanisms underlying generation and organization of diverse neuronal subtypes and ontogenetic establishment of individual nuclei in the mammalian hypothalamus.
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http://dx.doi.org/10.1016/j.neuron.2021.01.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035319PMC
April 2021

Dental students' perceptions on a simulated practice using patient-based customised typodonts during the transition from preclinical to clinical education.

Eur J Dent Educ 2021 Jan 29. Epub 2021 Jan 29.

Department of Prosthodontics, Yonsei University College of Dentistry, Seoul, Korea.

Purpose/objectives: Dental students experience difficulties during the transition from preclinical to clinical curriculum. In order to help the students to adapt to the clinical education programme, a simulated practice using patient-based customised models was introduced in this study to prepare for their first clinical practice.

Methods: This study included 45 third-year predoctoral students (D3 students) who were about to perform the preparation of a single crown abutment on their first patient. After practicing abutment preparation using simulated models and providing the actual treatment to their own patient, the students were surveyed to investigate their perceptions on the simulated practice using the 3D-printed customised typodont model. The statistical analysis of the quantitative data and the thematic analysis of the qualitative data were conducted.

Results: Regarding this simulation, more than 80% of the students gave positive feedback on their practice of (a) operative positions and postures, (b) finger rest, (c) occlusal reduction, (d) axial reduction and (e) proximal reduction. Student responses on the open-ended questions about how they perceived the usefulness of this simulation were categorised as "First clinical case," "Patient-based model" and "Realistic simulation environment." In addition, a number of improvements of the simulation were also suggested by the students including the typodont and the manikin.

Conclusions: This study gives insights into the significance of simulated practice using patient-based customised typodonts as a transitional education tool and its direction of development in the field of restorative treatments accompanied by irreversible tooth preparations.
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http://dx.doi.org/10.1111/eje.12672DOI Listing
January 2021

Gene regulatory networks controlling differentiation, survival, and diversification of hypothalamic Lhx6-expressing GABAergic neurons.

Commun Biol 2021 01 21;4(1):95. Epub 2021 Jan 21.

Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.

GABAergic neurons of the hypothalamus regulate many innate behaviors, but little is known about the mechanisms that control their development. We previously identified hypothalamic neurons that express the LIM homeodomain transcription factor Lhx6, a master regulator of cortical interneuron development, as sleep-promoting. In contrast to telencephalic interneurons, hypothalamic Lhx6 neurons do not undergo long-distance tangential migration and do not express cortical interneuronal markers such as Pvalb. Here, we show that Lhx6 is necessary for the survival of hypothalamic neurons. Dlx1/2, Nkx2-2, and Nkx2-1 are each required for specification of spatially distinct subsets of hypothalamic Lhx6 neurons, and that Nkx2-2+/Lhx6+ neurons of the zona incerta are responsive to sleep pressure. We further identify multiple neuropeptides that are enriched in spatially segregated subsets of hypothalamic Lhx6 neurons, and that are distinct from those seen in cortical neurons. These findings identify common and divergent molecular mechanisms by which Lhx6 controls the development of GABAergic neurons in the hypothalamus.
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http://dx.doi.org/10.1038/s42003-020-01616-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820013PMC
January 2021

Limitations of rapid diagnostic tests in malaria surveys in areas with varied transmission intensity in Uganda 2017-2019: Implications for selection and use of HRP2 RDTs.

PLoS One 2020 31;15(12):e0244457. Epub 2020 Dec 31.

College of Health Sciences, Makerere University, Kampala, Uganda.

Background: Plasmodium falciparum histidine-rich protein 2 (HRP2)-based rapid diagnostic tests (RDTs) are exclusively recommended for malaria diagnosis in Uganda; however, their functionality can be affected by parasite-related factors that have not been investigated in field settings.

Methods: Using a cross-sectional design, we analysed 219 RDT-/microscopy+ and 140 RDT+/microscopy+ dried blood spots obtained from symptomatic children aged 2-10 years from 48 districts in Uganda between 2017 and 2019. We aimed to investigate parasite-related factors contributing to false RDT results by molecular characterization of parasite isolates. ArcGIS software was used to map the geographical distribution of parasites. Statistical analysis was performed using chi-square or Fisher's exact tests, with P ≤ 0.05 indicating significance. Odds ratios (ORs) were used to assess associations, while logistic regression was performed to explore possible factors associated with false RDT results.

Results: The presence of parasite DNA was confirmed in 92.5% (332/359) of the blood samples. The levels of agreement between the HRP2 RDT and PCR assay results in the (RDT+/microscopy+) and (RDT-/microscopy+) sample subsets were 97.8% (137/140) and 10.9% (24/219), respectively. Factors associated with false-negative RDT results in the (RDT-/microscopy+) samples were parasite density (<1,000/μl), pfhrp2/3 gene deletion and non-P. falciparum species (aOR 2.65, 95% CI: 1.62-4.38, P = 0.001; aOR 4.4, 95% CI 1.72-13.66, P = 0.004; and aOR 18.65, 95% CI: 5.3-38.7, P = 0.001, respectively). Overall, gene deletion and non-P. falciparum species contributed to 12.3% (24/195) and 19.0% (37/195) of false-negative RDT results, respectively. Of the false-negative RDTs results, 80.0% (156/195) were from subjects with low-density infections (< 25 parasites per 200 WBCs or <1,000/μl).

Conclusion: This is the first evaluation and report of the contributions of pfhrp2/3 gene deletion, non-P. falciparum species, and low-density infections to false-negative RDT results under field conditions in Uganda. In view of these findings, the use of HRP2 RDTs should be reconsidered; possibly, switching to combination RDTs that target alternative antigens, particularly in affected areas, may be beneficial. Future evaluations should consider larger and more representative surveys covering other regions of Uganda.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244457PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774953PMC
March 2021

Bleeding properties according to surgical sites during pediatric craniotomy: a retrospective study comparing the two stages of epilepsy surgery.

Anesth Pain Med (Seoul) 2020 Jul;15(3):283-290

Department of Anesthesiology and Pain Medicine, Severance Hospital and Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Korea.

Background: During pediatric epilepsy surgery, due to low circulating blood volume, intraoperative bleeding can result in significant hemodynamic instability, thereby requiring meticulous hemodynamic and transfusion strategies. Knowing the source of bleeding during the procedure would allow medical staff to better prepare the perioperative protocols for these patients. We compared intraoperative bleeding between the first (involving skin to meninges) and second (involving brain parenchyma) stages of epilepsy surgery to investigate the differences between various anatomical sites.

Methods: We reviewed the electronic medical records of 102 pediatric patients < 14 years old who underwent two-stage epilepsy surgeries during January 2012-December 2016. Invasive subdural grids were placed via craniotomy during Stage 1 and the epileptogenic zone was removed during Stage 2 of the surgery. We compared the volume of intraoperative bleeding between these two surgeries and identified variables associated with bleeding using multivariate regression analysis.

Results: Both surgeries resulted in similar intraoperative bleeding (24 vs. 26 ml/kg, P = 0.835), but Stage 2 required greater volumes of blood transfusion than Stage 1 (18.4 vs. 14.8 ml/kg, P = 0.011). Massive bleeding was associated with patients < 7 years of age in Stage 1 and weighing < 18 kg in Stage 2.

Conclusions: The volume of intraoperative bleeding was similar between the two stages of pediatric epilepsy surgery and was large enough to require blood transfusions. Thus, blood loss during pediatric epilepsy surgery occurred at both anatomic sites. This indicates the necessity of early preparation for blood transfusion in both stages of pediatric epilepsy surgery.
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http://dx.doi.org/10.17085/apm.20010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713839PMC
July 2020

CT-based nomogram for predicting survival after R0 resection in patients with gallbladder cancer: a retrospective multicenter analysis.

Eur Radiol 2021 May 13;31(5):3336-3346. Epub 2020 Nov 13.

Institute of Public Health and Environment, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea.

Objectives: To establish a prognostic nomogram for patients undergoing R0 resection for gallbladder cancer based on preoperative CT.

Methods: A total of 151 patients (64 males, 87 females; mean age, 73.26 years) with gallbladder cancer who underwent CT and surgery with margin-negative resection were retrospectively collected at two tertiary institutions. The demographic and radiologic parameters were analyzed using univariate and multivariate Cox regression analyses to identify independent prognostic factors. The final CT-based nomogram was constructed to predict prognosis after curative resection of gallbladder cancer. Calibration curves for the survival probabilities were obtained for internal validation.

Results: Mass-forming type (hazard ratio [HR], 28.80), bile duct invasion (HR, 4.76), duodenal invasion (HR, 6.32), colon invasion (HR, 4.37), gallstones (HR, 0.09), and cholecystitis (HR, 2.56) were significant independent predictors for recurrence-free survival (p < .05). Mass-forming type (HR, 8.16, p < .001), bile duct invasion (HR, 2.92, p = .013), duodenal invasion (HR, 3.72, p = .012), and regional lymph node metastasis (HR, 2.07, p = .043) were independent predictors of poor cancer-specific survival (CSS) and were used to construct the nomogram. The nomogram showed a good predictive ability for the probabilities of survival on the calibration curves, and the concordance index of the model in predicting CSS was .768.

Conclusion: Preoperative CT findings could predict the prognosis of gallbladder cancer, and the CT-based nomogram accurately predicted CSS in patients with gallbladder cancer after attempted curative resection.

Key Points: • Among the preoperative imaging features, mass-forming type, bile duct invasion, duodenal invasion, and regional lymph node metastasis were independent predictors of poor cancer-specific survival. • The nomogram constructed using preoperative CT findings showed a good predictive ability for the survival on calibration curves, and the concordance index of the model in predicting cancer-specific survival was 0.768.
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http://dx.doi.org/10.1007/s00330-020-07402-7DOI Listing
May 2021

Influence of age at complementary food introduction on the development of asthma and atopic dermatitis in Korean children aged 1-3 years.

Clin Exp Pediatr 2021 Aug 1;64(8):408-414. Epub 2020 Nov 1.

Institute of Health & Environment, Graduate School of Public Health, Seoul National University, Seoul, Korea.

Background: Complementary food in infancy is necessary for human growth, neurodevelopment, and health. However, the role of allergen consumption in early infancy and its effects on the development of food allergy or tolerance remain unclear.

Purpose: To investigate the influence of age at the time of complementary food introduction on the development of asthma and atopic dermatitis in Korean children aged 1-3 years.

Methods: We combined data from the Korea National Health and Nutrition Examination Survey collected from 2010 to 2014 and analyzed 1619 children aged 1-3 years who were included in the survey. Multivariate regression analysis was used to identify associations among type of feeding, age at the time of complementary food introduction, and doctor-diagnosed atopic dermatitis and asthma.

Results: Age at the time of complementary food introduction was not significantly associated with doctor-diagnosed atopic dermatitis and asthma in children aged 1-3 years. In the univariate analysis, children with asthma showed higher water and sodium intake levels than nonasthmatic children. However, this relationship was not significant in the multivariate regression analysis.

Conclusion: The present study revealed no statistically significant relationship between age at the time of complementary food introduction and the risk of atopic dermatitis and asthma in young Korean children. A national prospective study is needed to clarify the influence of age at the time of complementary food introduction on the development of allergic diseases.
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http://dx.doi.org/10.3345/cep.2020.01382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342876PMC
August 2021

A randomised trial evaluating the effect of intraoperative iron administration.

Sci Rep 2020 09 28;10(1):15853. Epub 2020 Sep 28.

Department of Anesthesiology and Pain Medicine, Severance Hospital and Anesthesia and Pain Research Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea.

Perioperative anaemia increases postoperative morbidity and mortality, and iron deficiency is anaemia's most common cause in surgical patients. Preoperative intravenous iron increases postoperative haemoglobin; however, data regarding intraoperative intravenous iron's effectiveness are inadequate. This study examined intraoperative intravenous iron's effects on postoperative haemoglobin levels in adults. Fifty-seven healthy subjects (aged 19-40 years) scheduled for bimaxillary orthognathic surgery were assigned randomly to the iron (n = 28) or control (n = 29) groups. The iron group received intravenous ferric derisomaltose (1,000 mg) after anaesthetic induction. The control group received an identical volume of intravenous normal saline. The primary outcome was postoperative haemoglobin level. Secondary outcomes included other postoperative haematologic and iron parameters. Laboratory data were obtained preoperatively and at 1 day, 2 weeks, and 4 weeks postoperatively. Haemoglobin was higher in the iron group 2 weeks postoperatively (12.9 g/dL vs. 12.2 g/dL), but the between-group difference was not significant after adjustment for multiple testing. However, the reticulocyte production index was significantly higher in the iron group 2 weeks postoperatively. Intraoperative intravenous iron maintains postoperative haemoglobin values in patients undergoing bimaxillary orthognathic surgery by increasing haematopoietic function and iron bioavailability and therefore appears to be a useful strategy for blood management.
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http://dx.doi.org/10.1038/s41598-020-72827-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522208PMC
September 2020

Molecular surveillance reveals the presence of pfhrp2 and pfhrp3 gene deletions in Plasmodium falciparum parasite populations in Uganda, 2017-2019.

Malar J 2020 Aug 26;19(1):300. Epub 2020 Aug 26.

QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.

Background: Histidine-rich protein-2 (HRP2)-based rapid diagnostic tests (RDTs) are the only RDTs recommended for malaria diagnosis in Uganda. However, the emergence of Plasmodium falciparum histidine rich protein 2 and 3 (pfhrp2 and pfhrp3) gene deletions threatens their usefulness as malaria diagnostic and surveillance tools. The pfhrp2 and pfhrp3 gene deletions surveillance was conducted in P. falciparum parasite populations in Uganda.

Methods: Three-hundred (n = 300) P. falciparum isolates collected from cross-sectional malaria surveys in symptomatic individuals in 48 districts of eastern and western Uganda were analysed for the presence of pfhrp2 and pfhrp3 genes. Presence of parasite DNA was confirmed by PCR amplification of the 18s rRNA gene, msp1 and msp2 single copy genes. Presence or absence of deletions was confirmed by amplification of exon1 and exon2 of pfhrp2 and pfhrp3 using gene specific PCR.

Results: Overall, pfhrp2 and pfhrp3 gene deletions were detected in 29/300 (9.7%, 95% CI 6.6-13.6%) parasite isolates. The pfhrp2 gene was deleted in 10/300 (3.3%, 95% CI 1.6-6.0%) isolates, pfhrp3 in 9/300 (3.0%, 95% CI 1.4-5.6%) while both pfhrp2 and pfhrp3 were deleted in 10/300 (3.3%, 95% CI 1.6-6.0%) parasite isolates. Proportion of pfhrp2/3 deletions was higher in the eastern 14.7% (95% CI 9.7-20.0%) compared to the western region 3.1% (95% CI 0.8-7.7%), p = 0.001. Geographical location was associated with gene deletions aOR 6.25 (2.02-23.55), p = 0.003.

Conclusions: This is the first large-scale survey reporting the presence of pfhrp2/3 gene deletions in P. falciparum isolates in Uganda. Roll out of RDTs for malaria diagnosis should take into consideration the existence of pfhrp2/3 gene deletions particularly in areas where they were detected. Periodic pfhrp2/3 surveys are recommended to inform future decisions for deployment of alternative RDTs.
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http://dx.doi.org/10.1186/s12936-020-03362-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449024PMC
August 2020

Modulation of Gut Microbiota in Korean Navy Trainees following a Healthy Lifestyle Change.

Microorganisms 2020 Aug 20;8(9). Epub 2020 Aug 20.

School of Applied Biosciences, Kyungpook National University, Daegu 41566, Korea.

Environmental factors can influence the composition of gut microbiota, but understanding the combined effect of lifestyle factors on adult gut microbiota is limited. Here, we investigated whether changes in the modifiable lifestyle factors, such as cigarette smoking, alcohol consumption, sleep duration, physical exercise, and body mass index affected the gut microbiota of Korean navy trainees. The navy trainees were instructed to stop smoking and alcohol consumption and follow a sleep schedule and physical exercise regime for eight weeks. For comparison, healthy Korean civilians, who had no significant change in lifestyles for eight weeks were included in this study. A total of 208 fecal samples were collected from navy trainees ( = 66) and civilians ( = 38) at baseline and week eight. Gut flora was assessed by sequencing the highly variable region of the 16S rRNA gene. The α-and β -diversity of gut flora of both the test and control groups were not significantly changed after eight weeks. However, there was a significant difference among individuals. Smoking had a significant impact in altering α-diversity. Our study showed that a healthy lifestyle, particularly cessation of smoking, even in short periods, can affect the gut microbiome by enhancing the abundance of beneficial taxa and reducing that of harmful taxa.
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http://dx.doi.org/10.3390/microorganisms8091265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569816PMC
August 2020

Association between Inflammatory Biomarkers and Nutritional Status in Fatty Liver.

Clin Nutr Res 2020 Jul 28;9(3):182-194. Epub 2020 Jul 28.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon 14854, Korea.

The prevalence and progression of non-alcoholic fatty liver disease (NAFLD) is mediated via several factors correlating with hepatic necroinflammation (adipokines/cytokines). This study was performed to analyze the level of inflammatory markers according to the presence of NAFLD and to identify related nutritional factors. A total of 80 adults were classified into 2 groups (healthy and NAFLD), and their body composition, blood tests, and eating habits were evaluated. In addition, inflammatory markers (adiponectin, high-sensitivity C-reactive protein [CRP], and tumor necrosis factor-alpha [TNF-α]), nutrient intake status, and dietary quality were compared. The quality of diet was assessed according to the nutrient adequacy ratio and the mean adequacy ratio (MAR). The NAFLD group had a higher body mass index (p < 0.001) than the healthy group and also carried significantly higher CRP levels (p < 0.001) but lower adiponectin (p = 0.001). TNF-α levels increased significantly with fatty liver grade (p = 0.023). The NAFLD group showed significantly higher intake of energy, carbohydrates, iron, sodium, vitamin A and saturated fatty acids, but significantly lower intake of zinc and vitamin E than the healthy group. The MAR values were slightly higher in the NAFLD group but without any significant difference. The levels of adiponectin and vitamin E showed a significant inverse correlation (p < 0.05). Nutritional management of NAFLD patients is important, and the intake of antioxidant and anti-inflammatory nutrients such as zinc and vitamin E should be emphasized.
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http://dx.doi.org/10.7762/cnr.2020.9.3.182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402975PMC
July 2020

Sexually Dimorphic Crosstalk at the Maternal-Fetal Interface.

J Clin Endocrinol Metab 2020 12;105(12)

Division of Reproductive Endocrinology and Infertility; Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California.

Context: Crosstalk through receptor ligand interactions at the maternal-fetal interface is impacted by fetal sex. This affects placentation in the first trimester and differences in outcomes. Sexually dimorphic signaling at early stages of placentation are not defined.

Objective: Investigate the impact of fetal sex on maternal-fetal crosstalk.

Design: Receptors/ligands at the maternal-fetal surface were identified from sexually dimorphic genes between fetal sexes in the first trimester placenta and defined in each cell type using single-cell RNA-Sequencing (scRNA-Seq).

Setting: Academic institution.

Samples: Late first trimester (~10-13 weeks) placenta (fetal) and decidua (maternal) from uncomplicated ongoing pregnancies.

Main Outcome Measures: Transcriptomic profiling at tissue and single-cell level; immunohistochemistry of select proteins.

Results: We identified 91 sexually dimorphic receptor-ligand pairs across the maternal-fetal interface. We examined fetal sex differences in 5 major cell types (trophoblasts, stromal cells, Hofbauer cells, antigen-presenting cells, and endothelial cells). Ligands from the CC family chemokine ligand (CCL) family were most highly representative in females, with their receptors present on the maternal surface. Sexually dimorphic trophoblast transcripts, Mucin-15 (MUC15) and notum, palmitoleoyl-protein carboxylesterase (NOTUM) were also most highly expressed in syncytiotrophoblasts and extra-villous trophoblasts respectively. Gene Ontology (GO) analysis using sexually dimorphic genes in individual cell types identified cytokine mediated signaling pathways to be most representative in female trophoblasts. Upstream analysis demonstrated TGFB1 and estradiol to affect all cell types, but dihydrotestosterone, produced by the male fetus, was an upstream regulator most significant for the trophoblast population.

Conclusions: Maternal-fetal crosstalk exhibits sexual dimorphism during placentation early in gestation.
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http://dx.doi.org/10.1210/clinem/dgaa503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571453PMC
December 2020

Iterative Suzuki-Miyaura Cross-coupling/Bromo-desilylation Reaction Sequences for the Assembly of Chemically Well-defined, Acyclic Oligopyrrole/Benzenoid Hybrids Embodying Mixed Modes of Connectivity.

Chem Asian J 2020 Oct 9;15(19):3059-3081. Epub 2020 Sep 9.

Research School of Chemistry, Institute of Advanced Studies, The Australian National University, Canberra, ACT 2601, Australia.

Syntheses of a range of chemically well-defined oligopyrrole/benzenoid hybrids are described using tandem Suzuki-Miyaura cross-coupling/bromo-desilyation reaction sequences for linking borylated pyrroles, halogenated pyrroles and/or dibromobenzenes to one another. By such means, including iterative variants, a range of all α-linked, all β-linked oligopyrroles as well as certain combinations thereof have been assembled, some of them for the first time. The conductivities of iodine-treated thin films formed from certain such systems have been determined.
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http://dx.doi.org/10.1002/asia.202000740DOI Listing
October 2020

Risk of fatty liver after long-term use of tamoxifen in patients with breast cancer.

PLoS One 2020 30;15(7):e0236506. Epub 2020 Jul 30.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University School of Medicine Bucheon Hospital, Bucheon, Korea.

Background: Few studies report the effects of tamoxifen intake and the occurrence of de novo fatty liver and the deterioration of existing fatty liver. The aim of this study was to investigate the effects of tamoxifen on fatty change of liver over time and also the impact of fatty liver on the prognosis of patients with breast cancer.

Methods: This was a single-center, retrospective study of patients who were diagnosed with primary breast cancer from January 2007 to July 2017. 911 consecutive patients were classified into three groups according to treatment method: tamoxifen group, aromatase inhibitor (AI) group, and control group.

Results: Median treatment duration was 49 months (interquartile range, IQR; 32-58) and median observational period was 85 months (IQR; 50-118). Long-term use of tamoxifen significantly aggravated fatty liver status compared to AI or control groups [hazard ratio (HR): 1.598, 95% confidence interval (CI): 1.173-2.177, P = 0.003] after adjusting other factors. When analyzed separately depending on pre-existing fatty liver at baseline, tamoxifen was involved in the development of de novo fatty liver [HR: 1.519, 95% CI: 1.100-2.098, P = 0.011) and had greater effect on fatty liver worsening (HR: 2.103, 95% CI: 1.156-3.826, P = 0.015). However, the progression of fatty liver did not significantly affect the mortality of breast cancer patients.

Conclusions: Tamoxifen had a significant effect on the fatty liver status compared to other treatment modalities in breast cancer patients. Although fatty liver did not affect the prognosis of breast cancer, meticulous attention to cardiovascular disease or other metabolic disease should be paid when used for a long time.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236506PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392315PMC
September 2020

Community Assessment of the Predictability of Cancer Protein and Phosphoprotein Levels from Genomics and Transcriptomics.

Cell Syst 2020 08 24;11(2):186-195.e9. Epub 2020 Jul 24.

Joint Research Centre for Computational Biomedicine (JRC-COMBINE), RWTH Aachen University, Faculty of Medicine, 52074 Aachen, Germany; European Molecular Biology Laboratory-The European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK; Institute for Computational Biomedicine, Heidelberg University Hospital and Heidelberg University, Faculty of Medicine, Bioquant Heidelberg, Hedelberg 69120, Germany. Electronic address:

Cancer is driven by genomic alterations, but the processes causing this disease are largely performed by proteins. However, proteins are harder and more expensive to measure than genes and transcripts. To catalyze developments of methods to infer protein levels from other omics measurements, we leveraged crowdsourcing via the NCI-CPTAC DREAM proteogenomic challenge. We asked for methods to predict protein and phosphorylation levels from genomic and transcriptomic data in cancer patients. The best performance was achieved by an ensemble of models, including as predictors transcript level of the corresponding genes, interaction between genes, conservation across tumor types, and phosphosite proximity for phosphorylation prediction. Proteins from metabolic pathways and complexes were the best and worst predicted, respectively. The performance of even the best-performing model was modest, suggesting that many proteins are strongly regulated through translational control and degradation. Our results set a reference for the limitations of computational inference in proteogenomics. A record of this paper's transparent peer review process is included in the Supplemental Information.
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http://dx.doi.org/10.1016/j.cels.2020.06.013DOI Listing
August 2020

Bacteria-derived metabolite, methylglyoxal, modulates the longevity of through TORC2/SGK-1/DAF-16 signaling.

Proc Natl Acad Sci U S A 2020 07 7;117(29):17142-17150. Epub 2020 Jul 7.

Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Korea;

Gut microbes play diverse roles in modulating host fitness, including longevity; however, the molecular mechanisms underlying their mediation of longevity remain poorly understood. We performed genome-wide screens using 3,792 mutants and identified 44 mutants that modulated longevity. Three of these mutants modulated longevity via the bacterial metabolite methylglyoxal (MG). Importantly, we found that low MG-producing mutants, , extended the lifespan of through activation of the DAF-16/FOXO family transcription factor and the mitochondrial unfolded protein response (UPR). Interestingly, the lifespan modulation by did not require insulin/insulin-like growth factor 1 signaling (IIS) but did require TORC2/SGK-1 signaling. Transcriptome analysis revealed that activated novel class 3 DAF-16 target genes that were distinct from those regulated by IIS. Taken together, our data suggest that bacteria-derived MG modulates host longevity through regulation of the host signaling pathways rather than through nonspecific damage on biomolecules known as advanced glycation end products. Finally, we demonstrate that MG enhances the phosphorylation of hSGK1 and accelerates cellular senescence in human dermal fibroblasts, suggesting the conserved role of MG in controlling longevity across species. Together, our studies demonstrate that bacteria-derived MG is a novel therapeutic target for aging and aging-associated pathophysiology.
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http://dx.doi.org/10.1073/pnas.1915719117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382248PMC
July 2020

Nutritional and Clinical Factors Affecting Weight and Fat-Free Mass Loss after Gastrectomy in Patients with Gastric Cancer.

Nutrients 2020 Jun 27;12(7). Epub 2020 Jun 27.

Department of Surgery, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon 14584, Korea.

After a gastrectomy, the nutritional status of patients with gastric cancer has great effect on the treatment outcome and patients' quality of life. We investigated the changes in body composition and nutrient intake after gastrectomy in 288 gastric cancer patients. A multiple linear regression analysis was used for each time period to verify the effects of nutritional and clinical factors on weight and fat-free mass loss rates. Gastric cancer patients who underwent a gastrectomy continued to experience weight and fat-free mass loss until three months after surgery and became stagnant at six months. The marginal mean of calorie intake per weight was 24.5, 26.8, and 29.4 kcal at one, three, and six months. The protein intake per kg lean mass was 1.14, 1.14, and 1.16 g at one, three, and six months, respectively. One month after surgery, the rate of weight loss increased significantly in females who received chemotherapy ( < 0.001). At one to three months postoperative, females who had undergone chemotherapy tended to significantly lose weight ( = 0.016). Females with a history of chemotherapy also showed a reduction in fat-free mass for one to three months ( = 0.036). Calorie intake was a significant factor in preventing fat-free mass weight loss at one month after surgery. Chemotherapy was an independent factor affecting the weight and fat-free mass loss rate up to six months after gastrectomy. Careful monitoring of weight and muscle mass changes following active nutritional intervention for sufficient nutrition support could be helpful for patients after gastrectomy.
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http://dx.doi.org/10.3390/nu12071905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400091PMC
June 2020

An autophagic deficit in the uterine vessel microenvironment provokes hyperpermeability through deregulated VEGFA, NOS1, and CTNNB1.

Autophagy 2021 07 17;17(7):1649-1666. Epub 2020 Jun 17.

Department of Biomedical Science & Technology, Konkuk University, Seoul, Korea.

The uterus undergoes vascular changes during the reproductive cycle and pregnancy. Steroid hormone deprivation induces macroautophagy/autophagy in major uterine cell types. Herein, we explored the functions of uterine autophagy using the -driven deletion model. Deletion of was confirmed by functional deficit of autophagy in uterine stromal, myometrial, and vascular smooth muscle cells, but not in endothelial cells. uteri exhibited enhanced stromal edema accompanied by dilation of blood vessels. Ovariectomized uteri showed decreased expression of endothelial junction-related proteins, such as CTNNB1/beta-catenin, with increased vascular permeability, and increased expression of VEGFA and NOS1. Nitric oxide (NO) was shown to mediate VEGFA-induced vascular permeability by targeting CTNNB1. NO involvement in maintaining endothelial junctional stability in uteri was confirmed by the reduction in extravasation following treatment with a NOS inhibitor. We also showed that uterine phenotype improved the fetal weight:placental weight ratio, which is one of the indicators of assessing the status of preeclampsia. We showed that autophagic deficit in the uterine vessel microenvironment provokes hyperpermeability through the deregulation of VEGFA, NOS1, and CTNNB1. ACTA2: actin, alpha 2, smooth muscle, aortic; : anti-Mullerian hormone type 2 receptor; ANGPT1: angiopoietin 1; ATG: autophagy-related; CDH5: cadherin 5; CLDN5: claudin 5; COL1A1: collagen, type I, alpha 1; CSPG4/NG2: chondroitin sulfate proteoglycan 4; CTNNB1: catenin (cadherin associated protein), beta 1; DES: desmin; EDN1: endothelin 1; EDNRB: endothelin receptor type B; F3: coagulation factor III; KDR/FLK1/VEGFR2: kinase insert domain protein receptor; LYVE1: lymphatic vessel endothelial hyaluronan receptor 1; MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MCAM/CD146: melanoma cell adhesion molecule; MYL2: myosin, light polypeptide 2, regulatory, cardiac, slow; MYLK: myosin, light polypeptide kinase; NOS1/nNOS: nitric oxide synthase 1, neuronal; NOS2/iNOS: nitric oxide synthase 2, inducible; NOS3/eNOS: nitric oxide synthase 3, endothelial cell; OVX: ovariectomy; PECAM1/CD31: platelet/endothelial cell adhesion molecule 1; POSTN: periostin, osteoblast specific factor; SQSTM1: sequestosome 1; TEK/Tie2: TEK receptor tyrosine kinase; TJP1/ZO-1: tight junction protein 1; TUBB1, tubulin, beta 1 class VI; USC: uterine stromal cell; VEGFA: vascular endothelial growth factor A; VSMC: vascular smooth muscle cell.
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http://dx.doi.org/10.1080/15548627.2020.1778292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354601PMC
July 2021

Distribution and genetic diversity of the toxic benthic dinoflagellate genus Ostreopsis in Korea.

Harmful Algae 2020 06 15;96:101820. Epub 2020 May 15.

LOHABE, Department of Oceanography, Chonnam National University, Gwangju 61186, Republic of Korea. Electronic address:

Species belonging to the toxic dinoflagellate genus Ostreopsis are widespread, occurring from tropical to temperate waters. As mainly benthic/epiphytic species, they would be expected to show distinct geographical patterns. In this study, ribosomal DNA (rDNA) sequences from partial nuclear LSU D8-D10, 5.8S, and ITS regions were determined for 169 isolates of Ostreopsis species collected from three coastal sites (i.e., Jeju Island, Chuja Island, and Pohang) within Korea. The phylogenetic tree inferred from the LSU rDNA D8-D10 sequences showed that Korean Ostreopsis species corresponded to either Ostreopsis sp. 1 or sp. 6, with Ostreopsis sp. 1 being relatively predominant regarding their distribution. While Ostreopsis sp. 1 occurred throughout all the three sampling sites within Korea, Ostreopsis sp. 6 was confined to the northern part of Jeju Island. When further investigated, the genetic diversity of Ostreopsis sp. 1 in Korea based on ITS sequences showed a total of 21 haplotypes. The presumed ancestral haplotype H3, was also present in the Japanese and Russian populations of Ostreopsis sp. 1. Although the overall demographic history of all the Korean populations of Ostreopsis sp. 1 could not be clearly identified, probably due to a mixture of different regional demographic patterns within Korea, each Ostreopsis sp. 1 population showed a characteristic demographic pattern at a regional scale. While the Jeju Island Ostreopsis sp. 1 population showed a signal in agreement with population equilibrium, the Chuja Island and Pohang Ostreopsis sp. 1 populations showed distribution patterns that are expected in a sudden population expansion model. The results from this study provide a basis for a better understanding of the distribution and genetic structure of the Asian Ostreopsis sp. 1 populations.
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http://dx.doi.org/10.1016/j.hal.2020.101820DOI Listing
June 2020

Establishment of Adequate Nutrient Intake Criteria to Achieve Target Weight Loss in Patients Undergoing Bariatric Surgery.

Nutrients 2020 Jun 14;12(6). Epub 2020 Jun 14.

Department of Statistics, Chung-Ang University, Seoul 06911, Korea.

Although bariatric surgery is the best treatment modality for morbidly obese patients, a 10-30% rate of weight recidivism has been reported in various specialized centers. We examined changes in energy and macronutrients after bariatric surgery and performed analysis to establish appropriate nutritional guidelines for reaching the target percentage of weight loss after surgery. A total of 189 subjects who underwent bariatric surgery were classified into success and failure groups depending on whether or not they reached 50% loss of excess weight at 12 months after bariatric surgery. Physical examinations and dietary surveys were completed before and 1, 6, and 12 months after surgery. Using receiver operating characteristic (ROC) analysis, the optimal cutoff points for nutrient intakes for determining success after bariatric surgery were computed based on maximal Youden's index. At 6 and 12 months after surgery, the success group had significantly lower carbohydrate and fat intakes than the failure group. The cutoff calorie intake for success in weight loss was <835.0, <1132.5, and <1523.0 kcal/day at 1, 6, and 12 months post operation, respectively. With regard to protein, the cutoff intakes were >44.5, >41.5, and >86.5 g/day at 1, 6, and 12 months post operation, respectively. At 12 months, the cutoff ratio for energy obtained from carbohydrates, protein, and fat was <49.0, >24.5, and <28.0%, respectively. Our findings confirm that the level of diet control and nutrition restriction affect the achievement of target weight loss, emphasizing that long-term weight loss is related to compliance with nutrient recommendations.
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http://dx.doi.org/10.3390/nu12061774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353322PMC
June 2020

A subset of microRNAs in the Dlk1-Dio3 cluster regulates age-associated muscle atrophy by targeting Atrogin-1.

J Cachexia Sarcopenia Muscle 2020 10 3;11(5):1336-1350. Epub 2020 Jun 3.

Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea.

Background: The microRNAs (miRNAs) down-regulated in aged mouse skeletal muscle were mainly clustered within the delta-like homologue 1 and the type III iodothyronine deiodinase (Dlk1-Dio3) genomic region. Although clustered miRNAs are coexpressed and regulate multiple targets in a specific signalling pathway, the function of miRNAs in the Dlk1-Dio3 cluster in muscle aging is largely unknown. We aimed to ascertain whether these miRNAs play a common role to regulate age-related muscle atrophy.

Methods: To examine anti-atrophic effect of miRNAs, we individually transfected 42 miRNA mimics in fully differentiated myotubes and analysed their diameters. The luciferase reporter assay using target 3' untranslated region (UTR) and RNA pull-down assay were employed to ascertain the target predicted by the TargetScan algorithm. To investigate the therapeutic potential of the miRNAs in vivo, we generated adeno-associated virus (AAV) serotype 9 expressing green fluorescent protein (GFP) (AAV9-GFP) bearing miR-376c-3p and infected it into the tibialis anterior muscle of old mice. We performed morphometric analysis and measured ex vivo isometric force using a force transducer. Human gluteus maximus muscle tissues (ages ranging from 25 to 80 years) were used to investigate expression levels of the conserved miRNAs in the Dlk1-Dio3 cluster.

Results: We found that the majority of miRNAs (33 out of 42 tested) in the cluster induced anti-atrophic phenotypes in fully differentiated myotubes with increasing their diameters. Eighteen of these miRNAs, eight of which are conserved in humans, harboured predicted binding sites in the 3' UTR of muscle atrophy gene-1 (Atrogin-1) encoding a muscle-specific E3 ligase. Direct interactions were identified between these miRNAs and the 3' UTR of Atrogin-1, leading to repression of Atrogin-1 and thereby induction of eIF3f protein content, in both human and mouse skeletal muscle cells. Intramuscular delivery of AAV9 expressing miR-376c-3p, one of the most effective miRNAs in myotube thickening, dramatically ameliorated skeletal muscle atrophy and improved muscle function, including isometric force, twitch force, and fatigue resistance in old mice. Consistent with our findings in mice, the expression of miRNAs in the cluster was significantly down-regulated in human muscle from individuals > 50 years old.

Conclusions: Our study suggests that genetic intervention using a muscle-directed miRNA delivery system has therapeutic efficacy in preventing Atrogin-1-mediated muscle atrophy in sarcopenia.
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http://dx.doi.org/10.1002/jcsm.12578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567143PMC
October 2020

Clinical application of ultrasonography-guided percutaneous liver biopsy and its safety over 18 years.

Clin Mol Hepatol 2020 07 25;26(3):318-327. Epub 2020 May 25.

Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea.

Background/aims: Liver biopsy (LB) remains the gold standard for the evaluation of liver disease. However, over the past two decades, many noninvasive tests have been developed and utilized in clinical practice as alternatives to LB. The aim of this study was to evaluate the clinical use and safety of LB in the era of noninvasive assessment of liver fibrosis.

Methods: This retrospective study included 1,944 consecutive cases of LB performed between 2001 and 2018 in a tertiary hospital. All of the LBs were conducted under ultrasonography guidance with 18-gauge cutting needles.

Results: LBs were performed an average of approximately 108 times per year during the study period. Chronic hepatitis B (25.3%) and suspected malignancy (20.5%) were the two most common indications for LB. The use of LB for nonalcoholic fatty liver disease increased from 8.1% to 17.2% in the past 5 years compared to the last 10 years, while that for viral hepatitis decreased from 40.3% to 18.9%. Discordance rate between the suspected diagnosis and the final diagnosis was 2.6% (51 cases). The overall rate of major adverse events was 0.05% (one case), which involved delayed bleeding at the biopsy site. Liver cirrhosis was observed in 563 cases (28.9%), and the presence of cirrhosis did not affect the frequency of complications (P=0.289).

Conclusion: LB is widely used in clinical practice as an irreplaceable diagnostic tool, even in the era of noninvasiveness. Ultrasonography-guided LB can be performed safely in patients with liver cirrhosis.
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http://dx.doi.org/10.3350/cmh.2019.0019nDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364354PMC
July 2020

miR-3074-3p promotes myoblast differentiation by targeting Cav1.

BMB Rep 2020 May;53(5):278-283

Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141; Department of Biomolecular Science, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon 34113, Korea.

Muscle fibers are generally formed as multinucleated fibers that are differentiated from myoblasts. Several reports have identified transcription factors and proteins involved in the process of muscle differentiation, but the roles of microRNAs (miRNAs) in myogenesis remain unclear. Here, comparative analysis of the miRNA expression profiles in mouse myoblasts and gastrocnemius (GA) muscle uncovered miR-3074-3p as a novel miRNA showing markedly reduced expression in fully differentiated adult skeletal muscle. Interestingly, elevating miR-3074-3p promoted myogenesis in C2C12 cells, primary myoblasts, and HSMMs, resulting in increased mRNA expression of myogenic makers such as Myog and MyHC. Using a target prediction program, we identified Caveolin-1 (Cav1) as a target mRNA of miR-3074-3p and verified that miR-3074-3p directly interacts with the 3' untranslated region (UTR) of Cav1 mRNA. Consistent with the findings in miR-3074-3p-overexpressing myoblasts, knockdown of Cav1 promoted myogenesis in C2C12 cells and HSMMs. Taken together, our results suggest that miR-3074-3p acts a positive regulator of myogenic differentiation by targeting Cav1. [BMB Reports 2020; 53(5): 278-283].
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262514PMC
May 2020

Short Term Intake of Does Not Affect Bone Biomarkers in Young Korean Women with Low Calcium Intake.

Clin Nutr Res 2020 Apr 22;9(2):90-96. Epub 2020 Apr 22.

Department of Integrative Medicine, Korea University College of Medicine, Seoul 02841, Korea.

Calcium intake is essential for bone health, but young Korean women have low calcium intakes. Seaweeds have high calcium content, which may affect calcium metabolism. Twenty nine females aged 18-39 years with low calcium intake (< 400 mg/day) participated in a 19-day open-label randomized controlled trial. During the first five days, participants adhered to a controlled-feeding protocol followed by a two-week supplementation period in free-living conditions. The treatment group (n = 14) received an additional 200 mg Ca/day through and in meals during the controlled-feeding period, and as noodles during days 6-19. Mineral intake (Ca, P, Mg, Na, and K) was assessed from diet composites and three 24-hour recalls during the controlled-feeding and free-living periods, respectively. Fasting serum levels of calcium, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D (1,25[OH]D), phosphorus, parathyroid hormone (PTH), and alkaline phosphatase (ALP) were assessed at baseline, day 6, and day 19. Statistical analyses were performed by Student's -test and mixed ANOVA. Mean intakes of all minerals during days 1-5 and mean Ca and Mg intakes during days 6-19 were greater in the treatment group compared to the control group. No group effect or group and time interaction was observed in serum biomarkers. Serum 1,25(OH)D increased while PTH and ALP tended to decrease on day 6 but returned to baseline values on day 20. Short-term intake of and does not affect calcium metabolism in young Korean women with low calcium intakes.

Trial Registration: Clinical Research Information Service Identifier: KCT0003307.
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http://dx.doi.org/10.7762/cnr.2020.9.2.90DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192671PMC
April 2020

Epidural bolus versus continuous epidural infusion analgesia on optic nerve sheath diameter in paediatric patients: A prospective, double-blind, randomised trial.

Sci Rep 2020 03 25;10(1):5477. Epub 2020 Mar 25.

Department of Anaesthesiology and Pain Medicine, Severance Hospital and Anaesthesia and Pain Research Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea.

The use of programmed intermittent epidural bolus for postoperative analgesia may have greater analgesic efficacy than continuous epidural infusion. However, the rapid delivery speed used with an epidural bolus is more likely to increase intracranial pressure. We compared the effects of lumbar epidural bolus versus continuous infusion epidural analgesia on intracranial pressure in children using optic nerve sheath diameter as a marker. We randomly assigned 40 paediatric patients to bolus or infusion groups. Epidural analgesia (0.15% ropivacaine 0.3 ml·kg) was administered via bolus or infusion. Ultrasonography was used to measure the optic nerve sheath diameter before (T0), at 3 min (T1), 10 min (T2), and 70 min (T3) after starting the pump. There were statistically significant between-group differences in optic nerve sheath diameter over time (P = 0.045). From T0-T3, the area under the curve values were similar between the two groups. Although there were differences in the patterns of optic nerve sheath diameter change according to the delivery mode, the use of lumbar epidural bolus did not increase the risk of intracranial pressure increase over that of continuous infusion. Further research is needed to investigate intracranial pressure changes after continuous application of each delivery mode.
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http://dx.doi.org/10.1038/s41598-020-62273-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096447PMC
March 2020
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