This study describes the epidemiology of hemorrhagic fever with renal syndrome (HFRS) in the past 10 yr (2001-2010) in Korea. During this period, a total of 3,953 HFRS patients and an average prevalence rate of 0.81 per 100,000 population were recorded, with a total of 40 fatal cases, corresponding to a case fatality rate of 1.01%. More HFRS cases were found in men than in women (57% vs 43%), and a higher prevalence rate of HFRS was observed in patients older than 40 yr (82.1%). The highest numbers of HFRS cases were found amongst farmers (35.6%). The majority of HFRS cases (71.3%) occurred in the last quarter of the calendar year (October to December). More HFRS cases occurred in the western part than in the eastern part of Korea (68.9% vs 31.1%). The incidence of HFRS was significantly higher (P < 0.001) in rural areas than in urban areas (80.3% vs 19.7%). HFRS still occurs commonly among men, in autumn, and in western rural area of Korea.
Hemorrhagic Fever with Renal Syndrome; Epidemiology; Autumn; Rural Area
Induced pluripotent stem cells (iPSCs) hold great promise for the development of patient-specific therapies for cardiovascular disease. However, clinical translation will require preclinical optimization and validation of large animal iPSC models.
To successfully derive endothelial cells from porcine iPSCs and demonstrate their potential utility for the treatment of myocardial ischemia.
Methods and Results
Porcine adipose stromal cells were reprogrammed to generate porcine iPSCs (piPSCs). Immunohistochemistry, quantitative PCR, microarray hybridization, and angiogenic assays confirmed that piPSC-derived endothelial cells (piPSC-ECs) shared similar morphological and functional properties as endothelial cells isolated from the autologous pig aorta. To demonstrate their therapeutic potential, piPSC-ECs were transplanted into mice with myocardial infarction (MI). Compared to control, animals transplanted with piPSC-ECs showed significant functional improvement measured by echocardiography (fractional shortening at week 4: 27.2±1.3% vs. 22.3±1.1%; P<0.001) and magnetic resonance imaging (ejection fraction at week 4: 45.8±1.3% vs. 42.3±0.9%; P<0.05). Quantitative protein assays and microfluidic single cell PCR profiling showed that piPSC-ECs released pro-angiogenic and anti-apoptotic factors in the ischemic microenvironment, which promoted neovascularization and cardiomyocyte survival, respectively. Release of paracrine factors varied significantly among subpopulations of transplanted cells, suggesting that transplantation of specific cell populations may result in greater functional recovery.
In summary, this is the first study to successfully differentiate piPSCs-ECs from piPSCs and demonstrate that transplantation of piPSC-ECs improved cardiac function following MI via paracrine activation. Further development of these large animal iPSC models will yield significant insights into their therapeutic potential and accelerate the clinical translation of autologous iPSC-based therapy.
Induced pluripotent stem cells; large animal models; paracrine activation; myocardial infarction; molecular imaging; ischemic heart disease; vascular biology
Microscale engineering plays a significant role in developing tools for biological applications by miniaturizing devices and providing controllable microenvironments for in vitro cell research. Miniaturized devices offer numerous benefits in comparison to their macroscale counterparts, such as lower use of expensive reagents, biomimetic environments, and the ability to manipulate single cells. Microscale electroporation is one of the main beneficiaries of microscale engineering as it provides spatial and temporal control of various electrical parameters. Microscale electroporation devices can be used to reduce limitations associated with the conventional electroporation approaches such as variations in the local pH, electric field distortion, sample contamination, and the difficulties in transfecting and maintaining the viability of desired cell types. Here, we present an overview of recent advances of the microscale electroporation methods and their applications in biology, as well as current challenges for its use for clinical applications. We categorize microscale electroporation into microchannel and microcapillary electroporation. Microchannel-based electroporation can be used for transfecting cells within microchannels under dynamic flow conditions in a controlled and high-throughput fashion. In contrast, microcapillary-based electroporation can be used for transfecting cells within controlled reaction chambers under static flow conditions. Using these categories we examine the use of microscale electroporation for clinical applications related to HIV-1, stem cells, cancer and other diseases and discuss the challenges in further advancing this technology for use in clinical medicine and biology.
Recent studies have suggested that metabolic health may contribute more to the atherosclerosis than obesity. The aim of this study is to compare coronary artery calcium scores (CACS) among patients with different metabolic health and obesity status.
A health-screening program of 24,063 participants (mean age 41 years) was conducted, and CACS was assessed by multi-detector computerized tomography (MDCT). Being metabolically healthy was defined as having fewer than two of the following risk factors: high blood pressure, high fasting blood glucose, high triglyceride, low high-density lipoprotein cholesterol, highest decile of homeostasis model assessment-insulin resistance (HOMA-IR) index, and highest decile of high-sensitivity C-reactive protein (hs-CRP). Obesity status was defined as body mass index (BMI) higher than 25 kg/m2. Analyses were performed in four groups divided according to metabolic health and obesity: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUHNO), and metabolically unhealthy obese (MUHO).
Mean values of CACS in the four groups were significantly different, except those between MHNO and MHO and between MUHNO and MUHO. When multinomial logistic regression analysis was performed with five CACS categories as the dependent variables and after adjusting for age, sex, and smoking status, the MHO, MUHNO, and MUHO groups showed significantly increased odds ratio for increasing CACS categories compared with no calcification status (5.221 for CACS >400 in MUHO group with 95% CI 2.856∼5.032 with MHNO group as the reference). When other variables including the metabolic parameters were included in the same model, the risks were attenuated.
Metabolic health is more closely associated with subclinical atherosclerosis than obesity as assessed by CACS.
We evaluated oncologic outcomes following radical prostatectomy (RP) in patients with a Gleason score (GS) of 7 with tertiary Gleason pattern 5 (TGP5).
Materials and Methods
We retrospectively reviewed the medical records of 310 patients who underwent RP from 2005 to 2010. Twenty-four patients who received neoadjuvant or adjuvant antiandrogen deprivation or radiation therapy were excluded. Just 239 (GS 6 to 8) of the remaining 286 patients were included in the study. Patients were classified into four groups: GS 6, GS 7 without TGP5, GS 7 with TGP5, and GS 8. We analyzed preoperative clinical factors, postoperative pathological outcomes, and biochemical recurrence (BCR).
TGP5 in GS 7 was an independent predictor of primary Gleason pattern 4, tumor volume larger than 10%, positive surgical margin, and lymphovascular invasion. The presence of TGP5 in GS 7 was not associated with BCR-free survival. Subgroup analyses revealed that BCR-free survival did not differ significantly between patients with GS 7 with TGP5 and those with GS 8 (p=0.120). In addition, time to BCR in patients with a higher percentage of TGP5 was shorter than that in patients with a lower percentage of TGP5. TGP5 in GS 7 was not a significant predictive factor for BCR, whereas prostate-specific antigen density and a positive surgical margin were shown to be independent predictors of BCR.
TGP5 in GS 7 was an independent predictor of unfavorable pathologic outcomes. The rate of BCR was similar in GS 7 disease with TGP5 and in GS 8 disease, even though TGP5 was not a significant predictive factor for BCR in Cox proportional hazards models.
Disease progression; Neoplasm grading; Prostatectomy
Tight junctions (TJs) are a mode of cell-to-cell adhesion in epithelial or endothelial cells, and serve as a physical barrier to maintenance of homeostasis in body by controlling paracellular transport. Claudins are the most important molecules of the TJs, but paradoxically these proteins are frequently over-expressed in cancers and their overexpression is implicated in the invasive potential of cancer. Hence, we investigated the effects of flavonoids extracted from Orostachys japonicus A. Berger (FEOJ) on TJs and the expression of claudins as well as cancer invasion along with in LnCaP human prostate cancer. FEOJ suppressed cancer cell motility and invasiveness at the concentrations where FEOJ did not show anti-proliferative activity. FEOJ increased transepithelial electrical resistance (TER) associated with tightening TJs, and suppressed expression of claudin proteins. Furthermore, FEOJ suppressed the activities of MMP-2 and -9 in a dose-dependent manner, which came from the activation of tissue inhibitor of metalloproteinases (TIMPs) by FEOJ. FEOJ suppressed migration and invasion by suppressing PI3K/Akt signaling pathway. Taken together, this study suggest that FEOJ suppresses cancer migration and invasion by tightening TJs through the suppression of claudin expression, and by suppressing MMPs in LnCaP human prostate cancer cells, which at least in part results from the suppression of PI3K/Akt signaling pathway.
Orostachys japonicus; flavonoids; LnCaP cells; tight junctions; Akt
This study compared the expression of genes involved in pluripotency, segregation of inner cell mass (ICM) and trophectoderm (TE), and primitive endoderm (PE) formation in porcine embryos produced by in vitro fertilization (IVF), parthenogenetic activation (PA), and nuclear transfer (NT) using either fetal fibroblasts (FF-NT) or mesenchymal stem cells (MSC-NT).
Blastocyst formation and total cell number were analyzed. The expression patterns of transcripts, including SRY-related HMG-box gene 2 (SOX2), reduced expression gene 1 (REX1/ZFP42), LIN28, caudal type homeobox 2 (CDX2), TEA domain family member 4 (TEAD4), integrin beta 1 (ITGB1) and GATA6 were assessed at the 4–8 cell and blastocyst stage embryos by real-time PCR.
Developmental rates to blastocyst stage and total cell number were higher in IVF and PA embryos than in NT embryos. But MSC-NT embryos had increased blastocyst formation and higher total cell number compared to FF-NT embryos. The relative expressions of transcripts were higher in blastocysts than in 4–8 cell stage embryos. The mRNA expression levels of SOX2 and REX1 were largely similar in embryos of different origins. However, the genes such as LIN28, CDX2, TEAD4, ITGB1 and GATA6 showed the differential expression pattern in PA and NT embryos compared to IVF embryos. Importantly, the transcript levels in MSC-NT embryos were relatively less variable to IVF than those in FF-NT embryos.
MSCs seem to be better donors for porcine NT as they improved the developmental competency, and influenced the expression pattern of genes quite similar with IVF embryos than that of FFs.
Gene expression; Preimplantation embryos; Nuclear transfer; Porcine
Tuberculous infection of the hand is a rare form of extrapulmonary tuberculosis that, left untreated, can cause serious joint and tendon damage. We report the case of a 65-year-old male patient who presented with an insidious flexor weakness of the fifth finger but without any history of trauma. Magnetic resonance imaging revealed a partial tear of the fifth finger flexor tendon with a fluid collection in the tendon sheath and in the flexor compartment along the ulnar side. Under ultrasound guidance, this fluid collection was aspirated and analyzed for Mycobacterium tuberculosis using polymerase chain reaction. The assay was positive for the microorganism, confirming the diagnosis of tuberculous tenosynovitis and ulnar bursitis of the wrist. The early suspicion and diagnosis of this extrapulmonary disease facilitated anti-tuberculous chemotherapy and helped avoid a hasty injection of corticosteroid.
Tenosynovitis; Tuberculosis; Polymerase chain reaction
Direct observations of the primary mouse CD4 T cell morphologies, e.g., cell adhesion and cell spreading by culturing CD4 T cells in a short period of incubation (e.g., 20 min) on streptavidin-functionalized quartz nanopillar arrays (QNPA) using a high-content scanning electron microscopy method were reported. Furthermore, we first demonstrated cross-sectional cell traction force distribution of surface-bound CD4 T cells on QNPA substrates by culturing the cells on top of the QNPA and further analysis in deflection of underlying QNPA via focused ion beam-assisted technique.
Cell traction force; Cell adhesion; CD4 T cell; Cell migration; Focused ion beam
Dynamic cell-microenvironment interactions regulate many biological events and play a critical role in tissue regeneration. Cell homing to targeted tissues requires well balanced interactions between cells and adhesion molecules on blood vessel walls. However, many stem cells lack affinity with adhesion molecules. It is challenging and clinically important to engineer these stem cells to modulate their dynamic interactions with blood vessels. In this study, a new chemical strategy was developed to engineer cell-microenvironment interactions. This method allowed the conjugation of peptides onto stem cell membranes without affecting cell viability, proliferation or multipotency. Mesenchymal stem cells (MSCs) engineered in this manner showed controlled firm adhesion and rolling on E-selectin under physiological shear stresses. For the first time, these biomechanical responses were achieved by tuning the binding kinetics of the peptide-selectin interaction. Rolling of engineered MSCs on E-selectin is mediated by a Ca2+ independent interaction, a mechanism that differs from the Ca2+ dependent physiological process. This further illustrates the ability of this approach to manipulate cell-microenvironment interactions, in particular for the application of delivering cells to targeted tissues. It also provides a new platform to engineer cells with multiple functionalities.
Robots have allowed head and neck surgeons to extirpate oropharyngeal tumors safely without the need for lip-split incision or mandibulotomy. Using robots in oropharyngeal reconstruction is new but essential for oropharyngeal defects that result from robotic tumor excision. We report our experience with robotic free-flap reconstruction of head and neck defects to exemplify the necessity for robotic reconstruction.
We investigated head and neck cancer patients who underwent ablation surgery and free-flap reconstruction by robot. Between July 1, 2011 and March 31, 2012, 5 cases were performed and patient demographics, location of tumor, pathologic stage, reconstruction methods, flap size, recipient vessel, necessary pedicle length, and operation time were investigated.
Among five free-flap reconstructions, four were radial forearm free flaps and one was an anterolateral thigh free-flap. Four flaps used the superior thyroid artery and one flap used a facial artery as the recipient vessel. The average pedicle length was 8.8 cm. Flap insetting and microanastomosis were achieved using a specially manufactured robotic instrument. The total operation time was 1,041.0 minutes (range, 814 to 1,132 minutes), and complications including flap necrosis, hematoma, and wound dehiscence did not occur.
This study demonstrates the clinically applicable use of robots in oropharyngeal reconstruction, especially using a free flap. A robot can assist the operator in insetting the flap at a deep portion of the oropharynx without the need to perform a traditional mandibulotomy. Robot-assisted reconstruction may substitute for existing surgical methods and is accepted as the most up-to-date method.
Robotics; Free tissue flaps; Head and neck neoplasms
Gabapentin is a safe and well-tolerated anticonvulsant with a wide therapeutic index, and it is used for neuropathic pain. The aim of this study was to compare previous dosing methods with the administration of four different doses of gabapentin while maintaining the same maximum daily dose for the safe administration of high doses of the medication.
The subjects were outpatients with various neuropathic pain syndromes, with at least two of the following symptoms: allodynia, burning pain, shooting pain, or hyperalgesia. The TID group received equal doses of gabapentin 3 times per day, while the QID group received 4 different doses of gabapentin per day. The pain score, frequency of breakthrough pain (BTP), severity and the duration of pain, sleep disturbance due to nocturnal pain, and adverse effects were recorded each day.
The average daily pain score and sleep disturbance were significantly reduced in the QID group between days 3 and 10 of the experiment. The adverse effects of the medication were also reduced in the QID group. However, the frequency of BTP and severity and duration of pain were not significantly different between two groups.
Administration of 4 different doses of gabapentin during the initial titration in outpatients with neuropathic pain resulted in a significant reduction in awakening from breakthrough pain and a reduction in the adverse effects of the medication.
Ambulatory care; Drug administration schedule; Gabapentin; Neuropathic pain
Branchio-oto-renal (BOR) or branchio-otic (BO) syndrome is one of the most common forms of autosomal dominant syndromic hearing loss. Mutations in EYA1, SIX1 and SIX5 genes have been associated with BOR syndrome. In this study, clinical and genetic analyses were performed in patients with BOR/BO syndrome focusing on auditory manifestations and rehabilitation.
The audiologic manifestations were reviewed in 10 patients with BOR/BO syndrome. The operative findings and hearing outcome were analyzed in patients who underwent middle ear surgeries. The modality and outcome of auditory rehabilitation were evaluated. Genetic analysis was performed for EYA1, SIX1, and SIX5 genes.
All patients presented with mixed hearing loss. Five patients underwent middle ear surgeries without successful hearing gain. Cochlear implantation performed in two patients resulted in significant hearing improvement. Genetic analysis revealed four novel EYA1 mutations and a large deletion encompassing the EYA1 gene.
Auditory rehabilitation in BOR/BO syndrome should be individually tailored keeping in mind the high failure rate after middle ear surgeries. Successful outcome can be expected with cochlear implantations in patients with BOR/BO syndrome who cannot benefit from hearing aids. The novel EYA1 mutations may add to the genotypic and phenotypic spectrum of BOR syndrome in the East Asian population.
Brucella abortus is an intracellular zoonotic pathogen which causes undulant fever, endocarditis, arthritis and osteomyelitis in human and abortion and infertility in cattle. This bacterium is able to invade and replicate in host macrophage instead of getting removed by this defense mechanism. Therefore, understanding the interaction between virulence of the bacteria and the host cell is important to control brucellosis. Previously, we generated internalization defective mutants and analyzed the envelope proteins. The present study was undertaken to evaluate the changes in early transcriptional responses between wild type and internalization defective mutants infected mouse macrophage, RAW 264.7.
Both of the wild type and mutant infected macrophages showed increased expression levels in proinflammatory cytokines, chemokines, apoptosis and G-protein coupled receptors (Gpr84, Gpr109a and Adora2b) while the genes related with small GTPase which mediate intracellular trafficking was decreased. Moreover, cytohesin 1 interacting protein (Cytip) and genes related to ubiquitination (Arrdc3 and Fbxo21) were down-regulated, suggesting the survival strategy of this bacterium. However, we could not detect any significant changes in the mutant infected groups compared to the wild type infected group.
In summary, it was very difficult to clarify the alterations in host cellular transcription in response to infection with internalization defective mutants. However, we found several novel gene changes related to the GPCR system, ubiquitin-proteosome system, and growth arrest and DNA damages in response to B. abortus infection. These findings may contribute to a better understanding of the molecular mechanisms underlying host-pathogen interactions and need to be studied further.
Brucella abortus; Infection; Macrophage; Response; Transcription
The low-sodium diet is a known preventive factor for hypertension and cardiovascular disease. Factors associated with low-sodium diets should be identified to reduce sodium intake effectively. This study was conducted to identify factors correlated with a low-sodium diet.
This cross-sectional study analyzed data from a total of 14,539 Koreans aged 20 years or older, who participated in the Fourth (2007-2009) Korean National Health and Nutrition Examination Survey. A low-sodium diet was defined as having ≤2,000 mg/day based on 24-hour recalls. Multiple logistic regression models were used to assess sex, age, education, number of family members, household income, occupation, alcohol drinking, total energy intake, frequency of eating out, and hypertension management status for their associations with low-sodium diets.
Among all participants, only 13.9% (n=2,016) had low-sodium diets. In the multivariate analysis, 40-49 years of age, clerical work jobs, higher total energy intake, and frequent eating out were inversely associated with low-sodium diets. And female sex and living-alone were associated with low-sodium diets. Lower frequency of eating out was significantly associated with low-sodium diets, even after adjusting for total energy intake and other potential confounders. Adjusted odds ratios (95% confidence interval) for a low-sodium diet were 1.97 (1.49-2.61), 1.47 (1.13-1.91), 1.24 (0.96-1.61), and 1.00 (reference) in people who eat out <1 time/month, 1-3 times/month, 1-6 times/week, and ≥1 time/day, respectively.
Our study suggests that sex, age, number of family members, occupation, total energy intake, and lower frequency of eating out were associated with a low-sodium diet in Korean adults.
Food services; Low-sodium diet; Population surveillance; Republic of Korea; Sodium intake
Recently we have demonstrated that anthocyanins from fruits of Vitis coignetiae Pulliat (AIMs) have anticancer effects. Here, we investigate the effects of AIMs on cell proliferation and invasion as well as epithelial-mesenchymal transition (EMT) which have been linked to cancer metastasis in human uterine cervical cancer HeLa cells. AIMs inhibited the invasion of HeLa cells in a dose-dependent manner. AIMs inhibited MMP-9 expression in a dose-dependent manner. AIMs inhibited the motility of HeLa cells in a wound healing test. AIMs still suppressed NF-κB activation induced by TNF. AIMs also inhibited EMT in HeLa cells. AIMs suppressed vimentin, N-cadherin, and β-catenin expression and induced E-cadherin. AIMs also suppressed expression of β-catenin and Snail, which was regulated by GSK-3. These effects of AIMs were also limited in the HeLa cells treated with TNF. In conclusion, this study indicates that AIMs have anticancer effects by suppressing NF-κB-regulated genes and EMT, which relates to suppression of IκBα phosphorylation and GSK-3 activity, respectively. However, the effects of AIMs were attenuated in the TNF-high condition.
The IL-7 receptor alpha (IL-7Rα) is the high affinity receptor for IL-7 which is essential for T cell homeostasis. We recently reported an age-associated expansion of human effector memory (EM) CD8+ T cells expressing IL-7Rα low (IL-7Rαlow), which could be detrimental to hosts by occupying “immunological space”. We investigated the potential mechanisms for this phenomenon, focusing on cytomegalovirus (CMV) infection and INF-α. In the elderly (age≥65), CMV infection was associated with a decreased frequency of naïve CD8+ T cells as well as with an increased frequency of total EM and IL-7Rαlow EM CD8+ T cells. However, in the young (age≤40), this viral infection was associated only with an increased frequency of IL-7Rαlow EM CD8+ T cells. There was no association found between CMV immune status and plasma levels of IFN-α. In CMV-infected young and elderly people, INF-α levels had no correlation with the frequency of IL-7Rαlow EM CD8+ T cells although this cytokine levels correlated with the frequency of IL-7Rαlow CD45RA+ EM CD8+ T cells in CMV-uninfected elderly people. Our findings suggest that the effect of CMV infection on the frequency of CD8+ T cell subsets may begin with IL-7Rαlow EM CD8+ T cells and spread to other subsets with aging. Also, IFN-α could be associated with the expansion of IL-7Rαlow CD45RA+ EM CD8+ T cells in the CMV-uninfected elderly.
Human; aging; cytomegalovirus (CMV); IL-7; CD8+ T cells
Forkhead box P3 (FOXP3)-positive regulatory T cells (Treg) are a unique subset of T cells with immune regulatory properties. Treg cells can be induced from non-Treg CD4+ T cells (induced Treg, iTreg) by T cell receptor (TCR) triggering, IL-2 and TGF-β or retinoic acid. 1,25(OH)2 vitamin D3 (VD3) affects the functions of immune cells including T cells. 1,25(OH)2VD3 binds the nuclear vitamin D receptor (VDR) that binds target DNA sequences known as the vitamin D response element (VDRE). Although 1,25(OH)2VD3 can promote FOXP3 expression in CD4+ T cells with TCR triggering and IL-2, it is unknown whether this effect of 1,25(OH)2VD3 is mediated through direct binding of VDR to the FOXP3 gene without involving other molecules. Also, it is unclear whether FOXP3 expression in 1,25(OH)2VD3-induced Treg (VD-iTreg) cells is critical for the inhibitory function of these cells. Here we demonstrated the presence of VDREs in the intronic conserved non-coding sequence (CNS) region +1714 to +2554 of the human FOXP3 gene and the enhancement of the FOXP3 promoter activity by such VDREs in response to 1,25(OH)2VD3. In addition, VD-iTreg cells suppressed the proliferation of target CD4+ T cells and this activity was dependent on FOXP3 expression. These findings suggest that 1,25(OH)2VD3 can affect human immune responses by regulating FOXP3 expression in CD4+ T cells through direct VDR binding to the FOXP3 gene which is essential for inhibitory function of VD-iTreg cells.
The genomes of three South Korean Rinderpest virus vaccine strains (L72, LA77, and LA96) were analyzed in order to investigate their genetic variability. These three vaccine strains were all derived from the same virus strain origin (Fusan) through repeated passages in different culture systems. The full genome length of the three strains was 15,882 nucleotides, and the sequence similarity between the three South Korean RPV strains at the nucleotide level was 98.1 to 98.9%. The genetic distance between Nakamura III, L72, LA77, LA96, and LATC06 and the Kabete strain was greater than that between the Fusan and Kabete strains for the P, V, and C genes. The difference in pathogenicity among these strains might be due to the V gene, which has a positive (>1) selection ratio based on the analysis of synonymous (dS) and nonsynonymous (dN) substitution rates (dN/dS ratio [ω]).
The incidence of early colorectal epithelial neoplasm (ECEN) is increasing, and its pathologic diagnosis is important for patient care. We investigated the incidence of ECEN and the current status of its pathologic diagnosis.
We collected datasheets from 25 institutes in Korea for the incidence of colorectal adenoma with high grade dysplasia (HGD) and low grade dysplasia in years 2005, 2007, and 2009; and early colorectal carcinoma in the year 2009. We also surveyed the diagnostic terminology of ECEN currently used by the participating pathologists.
The average percentage of diagnoses of adenoma HGD was 7.0%, 5.0%, and 3.4% in years 2005, 2007, and 2009, respectively. The range of incidence rates of adenoma HGD across the participating institutes has gradually narrowed over the years 2005 to 2009. The incidence rate of early colorectal carcinoma in the year 2009 was 21.2%. The participants did not share a single criterion or terminology for the diagnosis of adenoma HGD. The majority accepted the diagnostic terms that distinguished noninvasive, mucosal confined, and submucosal invasive carcinoma.
Further research requirements suggested are a diagnostic consensus for the histopathologic diagnosis of ECEN; and standardization of diagnostic terminology critical for determining the disease code.
Colorectal neoplasms; Pathology, surgical; Multicenter study; Incidence; Diagnosis
There are approximately 20 known species of the genus Cryptosporidium, and among these, 8 infect immunocompetent or immunocompromised humans. C. hominis and C. parvum most commonly infect humans. Differentiating between them is important for evaluating potential sources of infection. We report here the development of a simple and accurate real-time PCR-based restriction fragment length polymorphism (RFLP) method to distinguish between C. parvum and C. hominis. Using the CP2 gene as the target, we found that both Cryptosporidium species yielded 224 bp products. In the subsequent RFLP method using TaqI, 2 bands (99 and 125 bp) specific to C. hominis were detected. Using this method, we detected C. hominis infection in 1 of 21 patients with diarrhea, suggesting that this method could facilitate the detection of C. hominis infections.
Cryptosporidium parvum; Cryptosporidium hominis; real-time PCR; RFLP; TaqI
Several epidemiological surveys have reported the prevalence of Toxoplasma gondii infection in stray cats in Korea, but little information is available on T. gondii infection in household cats. The aim of the present study was to assess the prevalence and risk factors of T. gondii infection among household cats reared in Seoul, Korea. A total of 474 blood samples were collected from clinically healthy household cats. All samples were tested using ELISA and PCR. The risk factor analysis was based on a questionnaire filled out by the owners. The overall positive rate for ELISA and PCR assays was 2.2% (10/437) and 2.1% (10/474), respectively. With regard to the origin of cats, the positive rates among cats adopted from the animal shelter and veterinary clinic for stray cats were significantly different (P<0.05). Our study demonstrated that the positive rate of T. gondii infection in household cats was low and that this low prevalence was assumed to be associated with keeping the cats indoors and restriction of eating raw food and uncooked meat. Therefore, we suggest that the owners check the origin of the cats prior to adoption to prevent infection of other animals, including humans.
Toxoplasma gondii; risk factor; household cat; PCR; ELISA
To investigate outcomes of stimulated IVF cycles in which GnRH antagonist was omitted on the ovulation triggering day.
A total of 86 women who underwent controlled ovarian hyperstimulation with recombinant FSH and GnRH antagonist flexible multiple-dose protocols were recruited and prospectively randomized into the conventional group (group A) or cessation group (group B). The GnRH antagonist, 0.25 mg/day of cetrorelix, was started when the leading follicle reached 14 mm in diameter and was continuously administered until the hCG triggering day (group A, 43 cycles) or until the day before hCG administration (group B, 43 cycles). The maturity of oocytes, fertilization rate, embryo quality, and implantation and clinical pregnancy rates were evaluated.
The duration of ovarian stimulation, total dose of gonadotropins, serum estradiol levels on hCG administration day, and number of oocytes retrieved were not significantly different between the two groups. The total dose of GnRH antagonist was significantly lower in group B than group A (2.5±0.9 vs. 3.2±0.8 ampoules, p<0.05). There was no premature luteinization in any of the subjects. The proportion of mature oocytes and fertilization rate were not significantly different in group B than group A (70.7% vs. 66.7%; 71.1% vs. 66.4%, respectively). There were no significant differences in the implantation or clinical pregnancy rates.
Our prospective randomized study suggested that cessation of GnRH antagonist on the hCG administration day during a flexible multiple-dose protocol could reduce the total dose of GnRH antagonist without compromising its effects on pregnancy rates.
GnRH antagonist; Ovarian stimulation; Oocyte maturation; Fertilization in vitro; Pregnancy rate
Recent advance in sequencing technology has enabled comprehensive profiling of genetic alterations in cancer. We have established a targeted sequencing platform using next-generation sequencing (NGS) technology for clinical use, which can provide mutation and copy number variation data. NGS was performed with paired-end library enriched with exons of 183 cancer-related genes. Normal and tumor tissue pairs of 60 colorectal adenocarcinomas were used to test feasibility. Somatic mutation and copy number alteration were analyzed. A total of 526 somatic non-synonymous sequence variations were found in 113 genes. Among these, 278 single nucleotide variations were 232 different somatic point mutations. 216 SNV were 79 known single nucleotide polymorphisms in the dbSNP. 32 indels were 28 different indel mutations. Median number of mutated gene per tumor was 4 (range 0–23). Copy number gain (>X2 fold) was found in 65 genes in 40 patients, whereas copy number loss (
Results 1-25 (422)
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