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1.  Trends in Pre-Pregnancy Diabetes Among Deliveries in 19 U.S. States, 2000–2010 
Trends in state-level prevalence of pre-pregnancy diabetes mellitus (PDM; i.e., type 1 or type 2 diabetes diagnosed before pregnancy) among delivery hospitalizations are needed to inform healthcare delivery planning and prevention programs.
To examine PDM trends overall, by age group, race/ethnicity, primary payer, and with comorbidities such as pre-eclampsia and pre-pregnancy hypertension, and to report changes in prevalence over 11 years.
In 2014, State Inpatient Databases from the Agency for Healthcare Research and Quality were analyzed to identify deliveries with PDM and comorbidities using diagnosis-related group codes and ICD-9-CM codes. General linear regression with a log-link and binomial distribution was used to assess the annual change.
Between 2000 and 2010, PDM deliveries increased significantly in all age groups, all race/ethnicity groups, and in all states examined (p<0.01). The age-standardized prevalence of PDM increased from 0.65 per 100 deliveries in 2000 to 0.89 per 100 deliveries in 2010, with a relative change of 37% (p<0.01). Although PDM rates were highest in the South, some of the largest relative increases occurred in five Western states (≥9%). Non-Hispanic blacks had the highest PDM rates and the highest absolute increase (0.26 per 100 deliveries). From 2000 to 2010, the proportion of PDM deliveries with pre-pregnancy hypertension increased significantly (p<0.01) from 7.4% to 14.1%.
PDM deliveries are increasing overall and particularly among those with PDM who have hypertension. Effective diabetes prevention and control strategies for women of childbearing age may help protect their health and that of their newborns.
PMCID: PMC4486010  PMID: 25326417
2.  Galangin sensitizes TRAIL-induced apoptosis through down-regulation of anti-apoptotic proteins in renal carcinoma Caki cells 
Scientific Reports  2016;6:18642.
Galangin, bioflavonoids, has been shown anti-cancer properties in various cancer cells. In this study, we investigated whether galangin could enhance TRAIL-mediated apoptosis in TRAIL resistant renal carcinoma Caki cells. Galangin alone and TRAIL alone had no effect on apoptosis, while combined treatment with galangin and TRAIL significantly induced apoptosis in renal carcinoma (Caki, ACHN and A498) but not normal cells (normal mouse kidney cells and human normal mesangial cells). Galangin induced down-regulation of Bcl-2 protein at the transcriptional level via inhibition of NF-κB activation but not p53 pathway. Furthermore, galangin induced down-regulation of cFLIP, Mcl-1 and survivin expression at the post-translational levels, and the over-expression of Bcl-2, cFLIP, Mcl-1 and survivin markedly reduced galangin-induced TRAIL sensitization. In addition, galangin increased proteasome activity, but galangin had no effect on expression of proteasome subunits (PSMA5 and PSMD4). In conclusion, our investigation suggests that galangin is a potent candidate for sensitizer of TRAIL resistant cancer cell therapy.
PMCID: PMC4698673  PMID: 26725939
3.  Effect of Pneumoperitoneum on Oxidative Stress and Inflammation via the Arginase Pathway in Rats 
Yonsei Medical Journal  2015;57(1):238-246.
Oxidative stress during CO2 pneumoperitoneum is reported to be associated with decreased bioactivity of nitric oxide (NO). However, the changes in endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and arginase during CO2 pneumoperitoneum have not been elucidated.
Materials and Methods
Thirty male Sprague-Dawley rats were randomized into three groups. After anesthesia induction, the abdominal cavities of the rats of groups intra-abdominal pressure (IAP)-10 and IAP-20 were insufflated with CO2 at pressures of 10 mm Hg and 20 mm Hg, respectively, for 2 hours. The rats of group IAP-0 were not insufflated. After deflation, plasma NO was measured, while protein expression levels and activity of eNOS, iNOS, arginase (Arg) I, and Arg II were analyzed with aorta and lung tissue samples.
Plasma nitrite concentration and eNOS expression were significantly suppressed in groups IAP-10 and IAP-20 compared to IAP-0. While expression of iNOS and Arg I were comparable between the three groups, Arg II expression was significantly greater in group IAP-20 than in group IAP-0. Activity of eNOS was significantly lower in groups IAP-10 and IAP-20 than in group IAP-0, while iNOS activity was significantly greater in group IAP-20 than in groups IAP-0 and IAP-10. Arginase activity was significantly greater in group IAP-20 than in groups IAP-0 and IAP-10.
The activity of eNOS decreases during CO2 pneumoperitoneum, while iNOS activity is significantly increased, a change that contributes to increased oxidative stress and inflammation. Moreover, arginase expression and activity is increased during CO2 pneumoperitoneum, which seems to act inversely to the NO system.
PMCID: PMC4696960  PMID: 26632407
Arginase; nitric oxide synthase; oxidative stress; pneumoperitoneum
4.  Refractory pseudomembranous colitis that was treated successfully with colonoscopic fecal microbial transplantation 
Intestinal Research  2016;14(1):83-88.
Pseudomembranous colitis (PMC) is a nosocomial and opportunistic infection caused by Clostridium difficile. PMC is related to the use of antibiotics leading to intestinal dysbiosis and an overgrowth of C. difficile. Metronidazole or vancomycin is considered to be the standard therapy for the management of PMC. However, PMC has a 15%–30% recurrence rate and can be refractory to standard treatments, resulting in morbidity and mortality. Here we describe a patient who experienced refractory PMC who was treated with fecal microbiota transplantation. A 69-year-old woman was admitted to the hospital with consistent abdominal pain and diarrhea, which had been present for 5 months. She was diagnosed with PMC by colonoscopy and tested positive for C. difficile toxin. Even though she took metronidazole for 10 days, followed by vancomycin for 4 weeks, her symptoms did not improve. Because of her recurrent and refractory symptoms, we decided to perform fecal microbiota transplantation. Fifty grams of fresh feces from a donor were obtained on the day of the procedure, mixed with 500 mL of normal saline, and then filtered. The filtered solution was administered to the patient's colon using a colonoscope. After the procedure, her symptoms rapidly improved and a follow-up colonoscopy showed that the PMC had resolved without recurrence.
PMCID: PMC4754527  PMID: 26884739
Clostridium difficile; Fecal microbial transplantation; Colonoscopy; Enterocolitis, pseudomembranous
5.  The relationship between the number of natural teeth and airflow obstruction: a cross-sectional study using data from the Korean National Health and Nutrition Examination Survey 
Potential associations between oral health and respiratory disease, including chronic obstructive pulmonary disease (COPD), have been suggested in several studies. Among the indicators reflecting oral health, the number of natural teeth is an integrated and simple index to assess in the clinic. In this study, we examined the relationship between the number of natural teeth and airflow obstruction, which is a central feature of COPD.
A total of 3,089 participants over 40 years, who underwent reliable spirometry and oral health assessments were selected from the Korean National Health and Nutrition Examination Survey 2012, a cross-sectional and nationally representative survey. Spirometry results were classified as normal, restrictive, or obstructive pattern. Total number and pairs of natural teeth were counted after excluding third molars.
After adjusting for other variables, such as age, body mass index, socioeconomic factors, and oral health factors, the group with airflow obstruction showed significantly fewer natural teeth than the other groups in males (P=0.014 and 0.008 for total number and total pairs of natural teeth, respectively). Compared with participants with full dentition, the adjusted odds ratio for airflow obstruction in males with fewer than 20 natural teeth was 4.18 (95% confidence interval: 2.06–8.49) and with fewer than 10 pairs of natural teeth was 4.74 (95% confidence interval: 2.34–9.62). However, there was no significant association between the total number or pairs of natural teeth and airflow obstruction after adjustment in females.
Loss of natural teeth was significantly associated with the presence of airflow obstruction in males. Our finding suggests that the number of natural teeth could be one of the available indices for obstructive lung diseases, including COPD.
PMCID: PMC4694678  PMID: 26730184
tooth loss; oral health; airflow obstruction; chronic obstructive pulmonary disease
6.  A multi-channel device for high-density target-selective stimulation and long-term monitoring of cells and subcellular features in C. elegans 
Lab on a chip  2014;14(23):4513-4522.
Selective cell ablation can be used to identify neuronal functions in multicellular model organisms such as Caenorhabditis elegans. The optogenetic tool KillerRed facilitates selective ablation by enabling light-activated damage of cell or subcellular components in a temporally and spatially precise manner. However, the use of KillerRed requires stimulating (5 min-1 hr), culturing (~24 hrs) and imaging (often repeatedly) a large number of individual animals. Current manual manipulation methods are limited by their time-consuming, labor-intensive nature, and their usage of anesthetics. To facilitate large-scale selective ablation, culturing, and repetitive imaging, we developed a densely-packed multi-channel device and used it to perform high-throughput neuronal ablation on KillerRed-expressing animals. The ability to load worms in identical locations with high loading efficiency allows us to ablate selected neurons in multiple worms simultaneously. Our device also enables continuous observation of aminals for 24 hrs following KillerRed activation, and allows the animals to be recovered for behavioural assays. We expect this multi-channel device to facilitate a broad range of long-term imaging and selective illumination experiments in neuroscience.
PMCID: PMC4213302  PMID: 25257026
7.  Are Birth Certificate and Hospital Discharge Linkages Performed in 52 Jurisdictions in the United States? 
Maternal and child health journal  2015;19(12):2615-2620.
The purpose of this study was to determine the number and characteristics of US State Registrars of Vital Statistics (Vital Registrars) and State Systems Development Initiative (SSDI) Coordinators that link birth certificate and hospital discharge data as well as using linkage processes.
Vital Registrars and SSDI Coordinators in all 52 vital records jurisdictions (50 states, District of Columbia, and New York City) were asked to complete a 41-question survey. We examined frequency distributions among completed surveys using SAS 9.3.
The response rate was 100 % (N = 52) for Vital Registrars and 96 % (N = 50) for SSDI Coordinators. Nearly half of Vital Registrars (n = 22) and SSDI Coordinators (n = 23) reported that their jurisdiction linked birth certificate and hospital discharge records at least once in the last 4 years. Among those who link, the majority of Vital Registrars (77.3 %) and SSDI Coordinators (82.6 %) link both maternal and infant hospital discharge records to the birth certificate. Of those who do not link, 43 % of the Vital Registrars and 55 % of SSDI Coordinators reported an interest in linking birth certificate and hospital discharge data. Reasons for not linking included lack of staff time, inability to access raw data, high cost, and unavailability of personal identifiers to link the two sources.
Results of our analysis provide a national perspective on data linkage practices in the US. Our findings can be used to promote further data linkages, facilitate sharing of data and linkage methodologies, and identify uses of the resulting linked data.
PMCID: PMC4644195  PMID: 26140836
Birth certificate; Hospital discharge; Linkage; Survey
8.  Quantification and Application of Potential Epigenetic Markers in Maternal Plasma of Pregnancies with Hypertensive Disorders 
The aim of this study was to evaluate quantitative aberrations of novel fetal-specific epigenetic markers in maternal plasma of pregnancies with hypertensive disorders. We compared the concentrations of DSCR3, RASSF1A, and SRY as cell-free fetal DNA markers in 188 normal pregnancies, 16 pregnancies with early-onset preeclampsia (EO-PE), 47 pregnancies with late-onset preeclampsia (LO-PE), and 29 pregnancies with gestational hypertension (GH). The concentrations of all markers were significantly correlated with gestational age (p < 0.001 for all). Strong positive correlations were also observed between DSCR3 and SRY (r = 0.471, p < 0.001), as well as between RASSF1A and SRY (r = 0.326, p = 0.015) and between DSCR3 and RASSF1A (r = 0.673, p < 0.001). The concentrations of DSCR3 and RASSF1A in the EO-PE were significantly higher at 24–32 weeks and onwards (p < 0.05 for both). In the LO-PE, DSCR3 and RASSF1A concentrations were significantly higher only at 33–41 weeks compared with the controls. The concentrations of all markers in the GH group were not significantly different from those in the control group. This study is the first demonstration that DSCR3 is a novel epigenetic marker that can be an alternative to the RASSF1A for the prediction of EO-PE.
PMCID: PMC4691144  PMID: 26694356
epigenetic marker; cell-free fetal DNA; cell-free total DNA; pregnancies with hypertensive disorders
10.  Men With Severe Lower Urinary Tract Symptoms Are at Increased Risk of Depression 
Lower urinary tract symptoms (LUTS) comprise a set of common, bothersome symptoms in middle-aged and elderly men. Recent research suggests that depressive symptoms may influence the symptoms of benign prostatic hyperplasia (BPH). We performed a community-based cross-sectional study to evaluate the correlation between LUTS and depression.
The survey was conducted in a rural community during four periods in August 2009, 2010, 2011, and 2012. Two validated questionnaires were used to examine LUTS and depressive symptoms. These included the International Prostate Symptom Score/quality of life (IPSS/QoL) and the Korean version of the Center for Epidemiological Studies-Depression scale (CES-D-K). Patients were categorized in the depressive symptom group if their CES-D-K score was >16 points.
A total of 711 men were included in this study. Thirty-five participants (4.92%) were found to have depressive symptoms. There was a positive correlation between depressive symptoms and LUTS severity (P<0.001). As compared to the mild LUTS group, the odds ratio (OR) of depression was 2.868 (95% confidence interval [CI], 1.293–6.362; P for trend<0.001) in the moderate LUTS group, and 4.133 (95% CI, 1.510–11.313; P for trend<0.001) in the severe LUTS group. In a model considering multiple variables such as age, education level, smoking, and exercise, the OR in the moderate LUTS group was 2.534 (1.125–5.708, 95% CI, P for trend=0.005), while that in the severe LUTS group was 3.910 (95% CI, 5.708–11.154; P for trend=0.005). In addition, depression was related to voiding symptoms.
Men with severe LUTS are at higher risk of depression than those with less severe urinary symptoms. The severity of voiding symptoms worsens depression. More aggressive urological diagnosis and treatment is needed in patients with severe LUTS, due to the impact on depressive symptoms and QoL.
PMCID: PMC4703937  PMID: 26739184
Lower Urinary Tract Symptoms; Depression; Prostatic Hyperplasia
11.  Comparison of Antiretroviral Regimens: Adverse Effects and Tolerability Failure that Cause Regimen Switching 
Infection & Chemotherapy  2015;47(4):231-238.
The efficacy of antiretroviral therapy (ART) has improved, and the adverse effects of antiretroviral drugs have been reduced. However, these adverse effects still significantly influence patient compliance, increasing the risk of tolerability failure. Therefore, we investigated the adverse effects and tolerability failure causing changes in the first ART regimen, and identified the regimens that were most vulnerable to switching.
Materials and Methods
We enrolled patients with human immunodeficiency virus (HIV) who commenced their first ART between January 1, 2011 and July 30, 2014. Patients who started their first ART regimen at the Kyungpook National University Hospital were included in the study if they were aged ≥18 years and were followed-up for ≥12 weeks. The primary dependent variable was the duration of treatment on the same ART regimen. We analyzed the maintenance rate of the first ART regimen based on the treatment duration between these groups using survival analysis and log rank test. The frequency of the adverse effects of ART regimens was analyzed by multiple response data analysis.
During the investigation period, 137 patients were enrolled. Eighty-one patients were maintained on the initial treatment regimen (59.1%). In protease inhibitor (PI)-based regimen group, 54 patients were maintained on the initial treatment regimen (54/98, 55.1%). In non-nucleoside reverse transcriptase inhibitor (NNRTI)-and integrase inhibitor (II)-based regimen group, 15 (15/26, 57.7%) and 12 (12/13, 92.3%) patients were maintained on the initial treatment regimen, respectively. Adverse effects that induced ART switching included rash (16/35, 45.7%), gastrointestinal discomfort or pain (7/35, 20%), diarrhea (7/35, 20%), hyperbilirubinemia (6/35, 17.1%), headache or dizziness (3/35, 8.5%). Among the treatment regimens, the group receiving an II-based regimen showed the least switching. The group receiving PI-and NRTI-based regimens were most likely to switch due to adverse effects during the early treatment period. However, after about 18 months, switching was rarely observed in these groups. Among the PI drugs, darunavir/ritonavir showed fewer drug changes than atazanavir/ritonavir (P = 0.004, log rank test) and lopinavir/ritonavir (P = 0.010). Among the NNRTI drugs, rilpivirne produced less switching than efavirenz (P = 0.045).
Adverse effects to ART resulted in about a quarter of patients switching drugs during the early treatment period. II-based regimens were advantageous because they were less likely to induce switching within 18 months of treatment commencement. These findings indicated the importance of considering and monitoring the adverse effects of ART in order to improve adherence.
PMCID: PMC4716274  PMID: 26788406
Adherence; Antiretroviral drug; Adverse effect; Human immunodeficiency virus
12.  The Incidence and Clinical Characteristics of Acute Serum Creatinine Elevation more than 1.5 mg/dL among the Patients Treated with Tenofovir/Emtricitabine-containing HAART Regimens 
Infection & Chemotherapy  2015;47(4):239-246.
The combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) has been the first choice nucleoside reverse transcriptase inhibitor (NRTI) according to many reliable antiretroviral treatment (ART) guidelines because of its high efficacy. However, TDF-related renal toxicity reported in Western countries is a challenging issue regarding clinical use. We conducted this study to evaluate the incidence and characteristics of an acute increase in serum creatinine (Cr) level > 1.5 mg/dL among TDF/FTC-based highly active antiretroviral treatment (HAART)-treated patients.
Materials and Methods
We retrospectively reviewed the medical records of 205 HIV-infected patients treated with TDF/FTC-containing regimens between 1 February 2010 and 30 April 2014. Three groups of TDF/FTC + ritonavir-boosted protease inhibitor (PI/r), TDF/FTC + non-nucleoside reverse transcriptase inhibitor (NNRTI), and TDF/FTC + integrase strand transfer inhibitor (INSTI), and three PI/r subgroups of TDF/FTC + lopinavir (LPV)/r, TDF/FTC + atazanavir (ATV)/r, TDF/FTC + darunavir (DRV)/r were evaluated.
A total 136 patients (91 in the TDF/FTC + PI/r group, 20 in the TDF/FTC + NNRTI group and 25 in the TDF/FTC + INSTI group) were included in the statistical analysis. Four cases (4.9%; all in the TDF/FTC + PI/r group) among 136 patients showed an acute increase in serum Cr more than 1.5 mg/dL, so the overall incidence was 2.8 cases per 100 patient-years. One case was a patient treated with TDF/FTC + LPV/r, and the others were treated with TDF/FTC + ATV/r. No case of an acute increase in serum Cr was observed in the TDF/FTC + DRV/r group. The incidence of serum Cr increase more than 1.5 mg/dL in TDF/FTC + PI/r group was 4.0 cases per 100 patient-years.
Although only a small number of patients were evaluated retrospectively from a single center, the TDF/FTC + PI/r regimen may have been related with relatively higher tendency of increment of serum Cr level. These findings reinforce the importance of close follow-ups of HIV-infected patients treated with the TDF/FTC + PI/r regimens.
PMCID: PMC4716275  PMID: 26788407
Antiretroviral agents; Tenofovir; Nephrotoxicity; Protease inhibitors; Human immunodeficiency virus
13.  A Significant Increase in the Incidence of Central Precocious Puberty among Korean Girls from 2004 to 2010 
PLoS ONE  2015;10(11):e0141844.
Few studies have explored the trends in central precocious puberty (CPP) in Asian populations. This study assessed the prevalence and annual incidence of CPP among Korean children.
Using data from the Korean Health Insurance Review Agency from 2004 to 2010, we reviewed the records of 21,351 children, including those registered with a diagnosis of CPP for the first time and those diagnosed with CPP who were treated with gonadotropin-releasing hormone analogs.
The prevalence of CPP was 55.9 per 100,000 girls and 1.7 per 100,000 boys, respectively. The overall incidence of CPP was 15.3 per 100,000 girls, and 0.6 per 100,000 boys. The annual incidence of CPP in girls significantly increased from 3.3 to 50.4 per 100,000 girls; whereas in boys, it gradually increased from 0.3 to 1.2 per 100,000 boys. The annual incidence of CPP in girls consistently increased at all ages year by year, with greater increases at older ages (≥6 years of age), and smaller increases in girls aged < 6 years. In contrast, the annual incidence remained relatively constant in boys aged < 8 years, while a small increase was observed only in boys aged 8 years. The increase of annual incidence showed significant differences depending on age and gender (P <0.0001).
The annual incidence of CPP has substantially increased among Korean girls over the past 7 years. Continued monitoring of CPP trends among Korean children will be informative.
PMCID: PMC4634943  PMID: 26539988
15.  Risk Assessment of Mortality Following Intraoperative Cardiac Arrest Using POSSUM and P-POSSUM in Adults Undergoing Non-Cardiac Surgery 
Yonsei Medical Journal  2015;56(5):1401-1407.
The Physiological and Operative Severity Score for enUmeration of Mortality and morbidity (POSSUM) and its Portsmouth modification (P-POSSUM) are comprehensive assessment methods for evaluating patient and surgical factors widely used to predict 30-day mortality rates. In this retrospective study, we evaluated the usefulness of POSSUM and P-POSSUM in predicting 30-day mortality after intraoperative cardiac arrests in adult patients undergoing non-cardiac surgery.
Materials and Methods
Among 190486 patients who underwent anesthesia, 51 experienced intraoperative cardiac arrest as defined in our study protocol. Predicted mortality rates were calculated using POSSUM and P-POSSUM equations and were compared with actual outcomes using exponential and linear analyses. In addition, a receiver operating characteristic curve analysis was undertaken, and area-under-the-curve (AUC) values with confidence intervals (CIs) were calculated for POSSUM and P-POSSUM.
Among the 51 patients with intraoperative cardiac arrest, 32 (62.7%) died within 30 days postoperatively. The overall predicted 30-day mortality rates using POSSUM and P-POSSUM were 65.5% and 57.5%, respectively. The observed-to-predicted (O:E) ratio for the POSSUM 30-day mortality was 1.07, with no significant difference between the observed and predicted values (χ2=4.794; p=0.779). P-POSSUM predicted mortality equally well, with an O:E ratio of 1.10 (χ2=8.905; p=0.350). AUC values (95% CI) were 0.771 (0.634-0.908) and 0.785 (0.651-0.918) for POSSUM and P-POSSUM, respectively.
Both POSSUM and P-POSSUM performed well to predict overall 30-day mortality following intraoperative cardiac arrest in adults undergoing non-cardiac surgery at a university teaching hospital in Korea.
PMCID: PMC4541674  PMID: 26256987
Cardiac arrest; mortality; surgery
16.  Effects of Alveolar Recruitment and Positive End-Expiratory Pressure on Oxygenation during One-Lung Ventilation in the Supine Position 
Yonsei Medical Journal  2015;56(5):1421-1427.
Hypoxemia during one-lung ventilation (OLV) remains a serious problem, particularly in the supine position. We investigated the effects of alveolar recruitment (AR) and positive end-expiratory pressure (PEEP) on oxygenation during OLV in the supine position.
Materials and Methods
Ninety-nine patients were randomly allocated to one of the following three groups: a control group (ventilation with a tidal volume of 8 mL/kg), a PEEP group (the same ventilatory pattern with a PEEP of 8 cm H2O), or an AR group (an AR maneuver immediately before OLV followed by a PEEP of 8 cm H2O). The tidal volume was reduced to 6 mL/kg during OLV in all groups. Blood gas analyses, respiratory variables, and hemodynamic variables were recorded 15 min into TLV (TLVbaseline), 15 and 30 min after OLV (OLV15 and OLV30), and 10 min after re-establishing TLV (TLVend).
Ultimately, 92 patients were analyzed. In the AR group, the arterial oxygen tension was higher at TLVend, and the physiologic dead space was lower at OLV15 and TLVend than in the control group. The mean airway pressure and dynamic lung compliance were higher in the PEEP and AR groups than in the control group at OLV15, OLV30, and TLVend. No significant differences in hemodynamic variables were found among the three groups throughout the study period.
Recruitment of both lungs with subsequent PEEP before OLV improved arterial oxygenation and ventilatory efficiency during video-assisted thoracic surgery requiring OLV in the supine position.
PMCID: PMC4541677  PMID: 26256990
Alveolar recruitment; one-lung ventilation; positive end-expiratory pressure; supine position
17.  Two Cases of Allergy to Insulin in Gestational Diabetes 
Endocrinology and Metabolism  2015;30(3):402-407.
Allergic reaction to insulin is uncommon since the introduction of human recombinant insulin preparations and is more rare in pregnant than non-pregnant females due to altered immune reaction during pregnancy. Herein, we report two cases of allergic reaction to insulin in gestational diabetes that were successfully managed. One case was a 33-year-old female using isophane-neutral protamine Hagedorn human insulin and insulin lispro. She experienced dyspnea, cough, urticaria and itching sensation at the sites of insulin injection immediately after insulin administration. We discontinued insulin therapy and started oral hypoglycemic agents with metformin and glibenclamide. The other case was a 32-year-old female using insulin lispro and insulin detemer. She experienced pruritus and burning sensation and multiple nodules at the sites of insulin injection. We changed the insulin from insulin lispro to insulin aspart. Assessments including immunoglobulin E (IgE), IgG, eosinophil, insulin antibody level and skin biopsy were performed. In the two cases, the symptoms were resolved after changing the insulin to oral agents or other insulin preparations. We report two cases of allergic reaction to human insulin in gestational diabetes due to its rarity.
PMCID: PMC4595367  PMID: 26435137
Insulin allergy; Diabetes, gestational; Hypersensitivity, immediate
18.  Fraction of Gestational Diabetes Mellitus Attributable to Overweight and Obesity by Race/Ethnicity, California, 2007–2009 
American journal of public health  2013;103(10):e65-e72.
We calculated the racial/ethnic-specific percentages of gestational diabetes mellitus (GDM) attributable to overweight and obesity.
We analyzed 1 228 265 records of women aged 20 years or older with a live, singleton birth in California during 2007 to 2009. Using logistic regression, we estimated the magnitude of the association between prepregnancy body mass index and GDM and calculated the percentages of GDM attributable to overweight and obesity overall and by race/ethnicity.
The overall estimated GDM prevalence ranged from 5.4% among White women to 11.9% among Asian/Pacific Islander women. The adjusted percentages of GDM deliveries attributable to overweight and obesity were 17.8% among Asians/Pacific Islander, 41.2% among White, 44.2% among Hispanic, 51.2% among Black, and 57.8% among American Indian women. Select Asian subgroups, such as Vietnamese (13.0%), Asian Indian (14.0%), and Filipino (14.2%), had the highest GDM prevalence, but the lowest percentage attributable to obesity.
Elevated prepregnancy body mass index contributed to GDM in all racial/ethnic groups, which suggests that decreasing overweight and obesity among women of reproductive age could reduce GDM, associated delivery complications, and future risk of diabetes in both the mother and offspring.
PMCID: PMC3780749  PMID: 23947320
19.  Association of Maternal Body Mass Index, Excessive Weight Gain, and Gestational Diabetes Mellitus With Large-for-Gestational-Age Births 
Obstetrics and gynecology  2014;123(4):737-744.
To estimate the percentage of large-for-gestational age (LGA) neonates associated with maternal overweight and obesity, excessive gestational weight gain, and gestational diabetes mellitus (GDM)—both individually and in combination—by race or ethnicity.
We analyzed 2004–2008 linked birth certificate and maternal hospital discharge data of live, singleton deliveries in Florida. We used multivariable logistic regression to assess the independent contributions of mother’s prepregnancy body mass index (BMI), gestational weight gain, and GDM status on LGA (birth weight-for-gestational age 90th percentile or greater) risk by race and ethnicity while controlling for maternal age, nativity, and parity. We then calculated the adjusted population-attributable fraction of LGA neonates to each of these exposures.
Large-for-gestational age prevalence was 5.7% among normal-weight women with adequate gestational weight gain and no GDM and 12.6%, 13.5% and 17.3% among women with BMIs of 25 or higher, excess gestational weight gain, and GDM, respectively. A reduction ranging between 46.8% in Asian and Pacific Islanders and 61.0% in non-Hispanic black women in LGA prevalence might result if women had none of the three exposures. For all race or ethnic groups, GDM contributed the least (2.0–8.0%), whereas excessive gestational weight gain contributed the most (33.3–37.7%) to LGA.
Overweight and obesity, excessive gestational weight gain, and GDM all are associated with LGA; however, preventing excessive gestational weight gain has the greatest potential to reduce LGA risk.
PMCID: PMC4548850  PMID: 24785599
20.  Reprogramming Roadblocks Are System Dependent 
Stem Cell Reports  2015;5(3):350-364.
Since the first generation of induced pluripotent stem cells (iPSCs), several reprogramming systems have been used to study its molecular mechanisms. However, the system of choice largely affects the reprogramming efficiency, influencing our view on the mechanisms. Here, we demonstrate that reprogramming triggered by less efficient polycistronic reprogramming cassettes not only highlights mesenchymal-to-epithelial transition (MET) as a roadblock but also faces more severe difficulties to attain a pluripotent state even post-MET. In contrast, more efficient cassettes can reprogram both wild-type and Nanog−/− fibroblasts with comparable efficiencies, routes, and kinetics, unlike the less efficient reprogramming systems. Moreover, we attribute a previously reported variation in the N terminus of KLF4 as a dominant factor underlying these critical differences. Our data establish that some reprogramming roadblocks are system dependent, highlighting the need to pursue mechanistic studies with close attention to the systems to better understand reprogramming.
Graphical Abstract
•Distinct reprogramming cassettes yield different reprogramming intermediates•MET is not a major rate-limiting step in reprogramming with high KLF4 expression•A lack of endogenous Nanog becomes trivial in efficient reprogramming systems•Roadblocks toward iPSCs depend on the reprogramming systems
In this article, Kaji and colleagues demonstrate that different reprogramming systems with distinct reprogramming efficiencies yield clearly distinguishable intermediate populations and, thus, potentially biased mechanistic views. For example, mesenchymal-to-epithelial transition and lack of endogenous Nanog are obstacles for iPSC generation only in inefficient reprogramming systems. This work highlights the importance of re-assessing molecular mechanisms of reprogramming in the literature heeding the reprogramming systems.
PMCID: PMC4618455  PMID: 26278041
21.  Trends in Gestational Diabetes Among Hospital Deliveries in 19 U.S. States, 2000–2010 
Diabetes is one of the most common and fastest-growing comorbidities of pregnancy. Temporal trends in gestational diabetes mellitus (GDM) have not been examined at the state level. This study examines GDM prevalence trends overall and by age, state, and region for 19 states, and by race/ethnicity for 12 states. Sub-analysis assesses trends among GDM deliveries by insurance type and comorbid hypertension in pregnancy.
Using the Agency for Healthcare Research and Quality’s National and State Inpatient Databases, deliveries were identified using diagnosis-related group codes for GDM and comorbidities using ICD-9-CM diagnosis codes among all community hospitals. General linear regression with a log-link and binomial distribution was used in 2014 to assess annual change in GDM prevalence from 2000 through 2010.
The age-standardized prevalence of GDM increased from 3.71 in 2000 to 5.77 per 100 deliveries in 2010 (relative increase, 56%). From 2000 through 2010, GDM deliveries increased significantly in all states (p < 0.01), with relative increases ranging from 36% to 88%. GDM among deliveries in 12 states reporting race and ethnicity increased among all groups (p < 0.01), with the highest relative increase in Hispanics (66%). Among GDM deliveries in 19 states, those with pre-pregnancy hypertension increased significantly from 2.5% to 4.1% (relative increase, 64%). The burden of GDM delivery payment shifted from private insurers (absolute decrease of 13.5 percentage points) to Medicaid/Medicare (13.2–percentage point increase).
Results suggest that GDM deliveries are increasing. The highest rates of increase are among Hispanics and among GDM deliveries complicated by pre-pregnancy hypertension.
PMCID: PMC4532269  PMID: 26094225
22.  Prospective Cohort Study on the Effectiveness of Influenza and Pneumococcal Vaccines in Preventing Pneumonia Development and Hospitalization 
Pneumonia and acute exacerbation of chronic illness are leading causes of influenza-related hospitalization. Therefore, influenza and pneumococcal vaccinations are strongly recommended for adults with comorbidities. Using a hospital-based influenza surveillance system, we performed a multicenter, prospective cohort study of patients visiting emergency rooms with influenza-like illness (ILI) during the influenza epidemic period in 2013 to 2014. Patients aged ≥19 years were enrolled, and clinical data were collected. Multivariate analyses were performed to estimate the effectiveness of influenza and pneumococcal vaccination in preventing pneumonia development and hospitalization. During study periods, 2,262 patients with ILI were registered. Among 2,217 patients with available vaccination records, 31.9% (707 patients) and 9.7% (216 patients) had received influenza and pneumococcal vaccines, respectively. Among patients who had been administered a pneumococcal vaccine, 94.4% had received the 23-valent polysaccharide vaccine (PPV23). The adjusted rates of effectiveness of the influenza vaccine for preventing pneumonia development and hospitalization were 64.0% (95% confidence interval [CI] = 29% to 81%) and 35.0% (95% CI = 12% to 52%), respectively. Pneumococcal vaccination did not reduce pneumonia development or hospitalization. In conclusion, influenza rather than PPV23 vaccination may reduce pneumonia development and hospitalization in patients with preceding ILI.
PMCID: PMC4308868  PMID: 25540271
23.  Dicer Is Down-regulated and Correlated with Drosha in Idiopathic Sudden Sensorineural Hearing Loss 
Journal of Korean Medical Science  2015;30(8):1183-1188.
Previously, we reported the expression levels of specific microRNA machinery components, DGCR8 and AGO2, and their clinical association in patients with idiopathic sudden hearing loss (SSNHL). In the present study, we investigated the other important components of microRNA machinery and their association with clinical parameters in SSNHL patients. Fifty-seven patients diagnosed with SSNHL and fifty healthy volunteers were included in this study. We evaluated mRNA expression levels of Dicer and Drosha in whole blood of patients with SSNHL and the control group, using RT & real-time PCR analysis. The Dicer mRNA expression level was down-regulated in patients with SSNHL. However, the Drosha mRNA expression level was not significantly altered in patients with SSNHL. Neither the Dicer nor Drosha mRNA expression level was not associated with any clinical parameters, including age, sex, duration of initial treatment from onset (days), initial Pure tone average, Siegel's criteria, WBC, and Erythrocyte sedimentation rate. However, mRNA expression levels of Dicer and Drosha were positively correlated to each other in patients with SSNHL. In this study, we demonstrated for the first time that the Dicer mRNA expression level was down-regulated in patients with SSNHL, suggesting its important role in pathobiology of SSNHL development.
Graphical Abstract
PMCID: PMC4520951  PMID: 26240498
MicroRNA Biogenesis; Idiopathic Sudden Sensorineural Hearing Loss; Dicer; Drosha
24.  Insulin Resistance of Normal Weight Central Obese Adolescents in Korea Stratified by Waist to Height Ratio: Results from the Korea National Health and Nutrition Examination Surveys 2008–2010 
Background. To evaluate insulin resistance of normal weight central obese 13–18-year-old male and female adolescents stratified by waist to height ratio (WHR). Methods. Data were obtained from the Korea National Health and Nutrition Examination Survey (K-NHANES) conducted during 2008–2010. Central obesity was defined as that in the upper quartile of age and sex specific WHR. Subjects were classified into no central obesity normal weight (NW), central obesity normal weight (CONW), no central obesity overweight (OW), and central obesity overweight (COOW). Results. The prevalence of CONW was 9.6% (83/832) in female and 7.0% (61/909) in male. CONW showed higher levels of insulin (P < 0.006), HOMA-IR (P < 0.006), and ALT (P < 0.001) than NW in female. CONW had higher levels of insulin (P < 0.0001), HOMA-IR (P < 0.0001), and WBC count (P < 0.021) and lower level of HDL (P < 0.0001) than NW in male. WHR and BMI had similar significant correlations with MS components. CONW showed 2.5 times (95% confidence interval, 1.21–5.00) more likelihood to have high insulin resistance than NW in male. Conclusions. Screening for central obesity using WHR in clinical setting is recommended.
PMCID: PMC4519535  PMID: 26257779
25.  Are Birth Certificate and Hospital Discharge Linkages Performed in 52 Jurisdictions in the United States? 
Maternal and Child Health Journal  2015;19(12):2615-2620.
The purpose of this study was to determine the number and characteristics of US State Registrars of Vital Statistics (Vital Registrars) and State Systems Development Initiative (SSDI) Coordinators that link birth certificate and hospital discharge data as well as using linkage processes.
Vital Registrars and SSDI Coordinators in all 52 vital records jurisdictions (50 states, District of Columbia, and New York City) were asked to complete a 41-question survey. We examined frequency distributions among completed surveys using SAS 9.3.
The response rate was 100 % (N = 52) for Vital Registrars and 96 % (N = 50) for SSDI Coordinators. Nearly half of Vital Registrars (n = 22) and SSDI Coordinators (n = 23) reported that their jurisdiction linked birth certificate and hospital discharge records at least once in the last 4 years. Among those who link, the majority of Vital Registrars (77.3 %) and SSDI Coordinators (82.6 %) link both maternal and infant hospital discharge records to the birth certificate. Of those who do not link, 43 % of the Vital Registrars and 55 % of SSDI Coordinators reported an interest in linking birth certificate and hospital discharge data. Reasons for not linking included lack of staff time, inability to access raw data, high cost, and unavailability of personal identifiers to link the two sources.
Results of our analysis provide a national perspective on data linkage practices in the US. Our findings can be used to promote further data linkages, facilitate sharing of data and linkage methodologies, and identify uses of the resulting linked data.
PMCID: PMC4644195  PMID: 26140836
Birth certificate; Hospital discharge; Linkage; Survey

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