Genetic analysis of HAV strains isolated from patients with acute hepatitis in Korea, 2005-2006

Hepatitis A virus (HAV) is a causative agent of acute viral hepatitis, which represents a significant public health problem. HAV is usually transmitted by oral-fecal route and prevalent not only in developing countries but also in developed countries worldwide. To characterize the HAV wild type strains circulating in Korea, the VP3/VP1 and VP1/P2A junction regions were detected by RT-PCR from HAV IgM positives during 2005 and 2006. Among 160 HAV IgM positive sera, 30% (n = 48) were positive for HAV RNA. Additionally, the VP3/VP1 junction regions were detected all six stools, which collected from outbreak in Gyeonggi province. Phylogenetic analysis of the sequences obtained from 54 distinct HAV isolates revealed that most of the strains (n = 45) belonged to genotype IA and the others including nine strains belonged to genotype IIIA. Interestingly, a Q --> S amino acid change was dominantly observed at position 810 of the VP1/P2A junction region in 14 isolates. The molecular epidemiology of HAV infection in Korea has changed with the co-circulation of at least two genotypes and 810Q --> S amino acid substitutions were found to be prevalent. These results strongly suggest that various HAV strains, including genotype IIIA, might be imported from high-endemic countries into Korea.     

Association study of polymorphisms between DISC1 and schizophrenia in a Korean population

To further clarify schizophrenia (SCZ), disrupted in schizophrenia 1 (DISC1) is a promising candidate gene expressed predominantly within the hippocampus. Several lines of evidence suggest that DISC1 may be involved in susceptibility to SCZ. In this study, we investigated whether genetic polymorphisms in the coding region of DISC1 were associated with several SCZ clinical phenotypes in a Korean population. To examine any association between DISC1 and SCZ, we genotyped three clinical single nucleotide polymorphisms (SNPs) (rs3738401, R264Q; rs3738402, L465L; rs821616, S704C) in the coding region of the DISC1 gene using the Illumina Sentrix Array Matrix chip and direct sequencing in 303 patients with SCZ and 300 healthy controls. Our case-control analysis showed that none of these SNPs was associated with SCZ. In further endophenotype stratification, however, we found a significant association between rs821616 and the poor concentration subgroup of SCZ, determined using the Operational Criteria Checklist (codominant model, p=0.015). Our results suggest that DISC1 may be a susceptibility gene for poor concentration among Korean patients with SCZ.     

The contribution of skin blood flow in warming the skin after the application of local heat; the duality of the Pennes heat equation

As predicted by the Pennes equation, skin blood flow is a major contributor to the removal of heat from an external heat source. This protects the skin from erythema and burns. But, for a person in a thermally neutral room, the skin is normally much cooler than arterial blood. Therefore, if skin blood flow (BF) increases, it should initially warm the skin paradoxically. To examine this phenomenon, 10 young male and female subjects participated in a series of experiments to examine the contribution of skin blood flow in the initial warming the skin after the application of local heat. Heat flow was measured by the use of a thermode above the brachioradialis muscle. The thermode was warmed by constant temperature water at 44°C entering the thermode at a water flow rate of 100 cm(3)/min. Skin temperature was measured by a thermistor and blood flow in the underlying skin was measured by a laser Doppler imager in single point mode. The results of the experiments showed that, when skin temperature is cool (31-32°C), the number of calories being transferred to the skin from the thermode cannot account for the rise in skin temperature alone. A significant portion of the rise in skin temperature is due to the warm arterialized blood traversing the skin from the core areas of the body. However, as skin temperature approaches central core temperature, it becomes less of a heat source and more of a heat sync such that when skin temperature is at or above core temperature, the blood flow to the skin, as predicted by Pennes, becomes a heat sync pulling heat from the thermode.     

Expression of X-linked inhibitor of apoptosis protein in neoplastic thyroid disorder

X-linked inhibitor of apoptosis protein (XIAP) is associated with tumor genesis, growth, progression and metastasis, and acts by blocking caspase-mediated apoptosis. In the present study, we sought to evaluate the expression patterns of XIAP in various neoplastic thyroid disorders and determine the association between XIAP expression and clinicopathologic factors. Expression of XIAP was evaluated with immunohistochemical staining using monoclonal anti-XIAP in 164 specimens of conventional papillary thyroid carcinoma (PTC) and 53 specimens of other malignant or benign thyroid tumors. XIAP positivity was observed in 128 (78%) of the 164 conventional PTC specimens. Positive rates of XIAP expression in follicular variant PTC, follicular, medullary, poorly differentiated, and anaplastic thyroid carcinoma specimens were 20%, 25%, 38%, 67%, and 38%, respectively. Six nodular hyperplasia specimens were negative and 1 of 7 follicular adenomas (8%) was positive for XIAP. Lateral neck lymph node metastases were more frequent in patients negative for XIAP expression (P = 0.01). Immunohistochemical staining for XIAP as a novel molecular marker may thus be helpful in the differential diagnosis of thyroid cancer. Moreover, high XIAP expression in conventional PTC is strongly associated with reduced risk of lateral neck lymph node metastasis.     

Segmentation and reconstruction of hepatic veins and intrahepatic portal vein based on the coronal sectional anatomic dataset

Three-dimensional (3D) reconstruction of intrahepatic vessels is very useful in visualizing the complex anatomy of hepatic veins and intrahepatic portal vein. It also provides a 3D anatomic basis for diagnostic imaging and surgical operation on the liver. In the present study, we built a 3D digitized model of hepatic veins and intrahepatic portal vein based on the coronal sectional anatomic dataset of the liver. The dataset was obtained using the digital freezing milling technique. The pre-reconstructed structures were identified and extracted, and then were segmented by the method of manual intervention. The digitized model of hepatic veins and intrahepatic portal vein was established using 3D medical visualization software. This model facilitated a continuous and dynamic displaying of the hepatic veins and intrahepatic portal vein at different orientations, which demonstrated the complicated relationship of adjacent hepatic veins and intrahepatic portal vein realistically in the 3D space. This study indicated that high-quality 2D images, precise data segmentation, and suitable 3D reconstruction methods ensured the reality and accuracy of the digital visualized model of hepatic veins and intrahepatic portal vein.     

The impact of pretreatment thrombocytosis and persistent thrombocytosis after adjuvant chemotherapy in patients with advanced epithelial ovarian cancer

Objective

To evaluate the impact of both pretreatment thrombocytosis, and platelet count reduction post-adjuvant chemotherapy, on survival in patients with advanced epithelial ovarian cancer.

Methods

Records of 179 women who underwent cytoreductive surgery for FIGO stage III or IV epithelial ovarian cancer and received six cycles of platinum/paclitaxel-based chemotherapy between July1998 and March 2009 were retrospectively reviewed. Platelet ratio was defined as the preoperative platelet count divided by the platelet count after chemotherapy. The prognostic significance of thrombocytosis and platelet ratio, together with various clinicopathological factors, were evaluated by multivariate analysis.

Results

Sixty-two of 179 (34.6%) patients had thrombocytosis at primary diagnosis. Patients with preoperative thrombocytosis had greater elevations of CA-125 (p < 0.0001) and a greater volume of ascites (p = 0.007). On multivariate analysis, thrombocytosis and CA-125 elevation retained significance as indicators of poor prognosis in patients with stage III or IV disease. In patients with normal CA-125 after chemotherapy, a high platelet ratio was an independent risk factor for reduced survival (p = 0.05).

Conclusions

Preoperative thrombocytosis and a high platelet ratio appear to be poor prognostic factors of survival in patients with advanced epithelial ovarian cancer who were treated with cytoreductive surgery and adjuvant platinum/paclitaxel-based chemotherapy.     

Microglandular adenosis: a prime suspect in triple‐negative breast cancer development

Microglandular adenosis (MGA) and atypical MGA (AMGA) are unusual lesions of the breast. They were once regarded as benign proliferative lesions and innocent bystanders. Several lines of evidence suggested that they could be neoplastic, clonal lesions and a non‐obligate precursor for triple‐negative breast cancers (TNBC). Recent work published in The Journal of Pathology by Guerini‐Rocco and colleagues provided further evidence regarding the precursor–product relationship between MGA/AMGA and TNBC. Using a massively parallel sequencing approach, they demonstrated that MGA/AMGA, particularly those associated with TNBC, could be clonal neoplastic lesions showing clonal non‐synonymous mutations, but none in pure MGA. Importantly, those alterations were observed in the associated TNBC. They were also able to identify recurrent alterations in TP53 in those MGA/AMGA cases as well as their associated TNBC. The findings, in conjunction with others, underscore the significance for MGA in clinical diagnosis. The potential of a benign lesion to progress into an aggressive malignant tumour implies that modification of the current management approach may be necessary. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Does Age at Onset of First Major Depressive Episode Indicate the Subtype of Major Depressive Disorder?: The Clinical Research Center for Depression Study

Purpose

The purpose of this study was to evaluate the effects of age at onset of the first major depressive episode on the clinical features of individuals with major depressive disorder (MDD) in a large cohort of Korean depressed patients.

Materials and Methods

We recruited 419 MDD patients of age over 18 years from the Clinical Research Center for Depression study in South Korea. At the start of the study, the onset age of the first major depressive episode was self-reported by the subjects. The subjects were divided into four age-at-onset subgroups: childhood and adolescent onset (ages <18), early adult onset (ages 18-44), middle adult onset (ages 45-59), and late onset (ages 60+). Using analysis of covariance (ANCOVA) and ordinal logistic regression analysis with adjusting the effect of age, the relationships between clinical features and age at onset of MDD were evaluated.

Results

There was an apparent, but inconsistent correlation between clinical features and age at onset. Earlier onset MDD was significantly associated with higher proportion of female gender [adjusted odds ratio (AOR)=0.570, p=0.022], more previous suicide attempts (AOR=0.635, p=0.038), greater number of previous depressive episodes (F=3.475, p=0.016) and higher scores on the brief psychiatric rating scale (F=3.254, p=0.022), its negative symptom subscale (F=6.082, p<0.0001), and the alcohol use disorder identification test (F=7.061, p<0.0001).

Conclusion

Early age at onset may increase the likelihood of distinguishable MDD subtype, and age at onset of the first major depressive episode is a promising clinical indicator for the clinical presentation, course, and outcome of MDD.     

Tweet Content Related to Sexually Transmitted Diseases: No Joking Matter

Background

Online social media, such as the microblogging site Twitter, have become a space for speedy exchange of information regarding sexually transmitted diseases (STDs), presenting a potential risk environment for how STDs are portrayed. Examining the types of “tweeters” (users who post messages on Twitter) and the nature of “tweet” messages is important for identifying how information related to STDs is posted in online social media.

Objective

The intent of the study was to describe the types of message emitters on Twitter in relation to two different STDs—chlamydia and human immunodeficiency virus (HIV)—as well as the nature of content tweeted, including how seriously the topic was treated.

Methods

We used the Twitter search engine to look for tweets posted worldwide from August 1-7, 2013, and from September 1-7, 2013, containing the words “chlamydia” or “HIV”, and the hashtags “#chlamydia” or “#HIV”. Tweeters were classified by two independent reviewers according to the type of avatar of the user (human, logo, or fantasy), the identification of the emitter (identifiable, semi-identifiable, or non-identifiable), and the source (private company, general media, scientific media, non-governmental, individual account, academic institution, government department, or undefined). Tweet messages were also independently classified according to their nature (serious or jokes/funny), and whether their main message was factual or of a personal nature/experience.

Results

A total of 694 tweets were posted by 426 different users during the first 7 days of August and September, containing the hashtags and/or simple words “chlamydia” and/or “HIV”. Jokes or funny tweets were more frequently posted by individual users (89%, 66/74), with a human avatar (81%, 60/74), from a non-identifiable user (72%, 53/74), and they were most frequently related to chlamydia (76%, 56/74). Serious tweets were most frequently posted by the general media (20.6%, 128/620), using a logo avatar (66.9%, 415/620), and with identifiable accounts (85.2%, 528/620). No government departments, non-governmental organizations, scientific media, or academic institutions posted a joke on STDs. A total of 104 of these analyzed tweets were re-tweeted messages, belonging to 68 unique tweets. The content was serious (99%, 67/68), factual (90%, 52/58), and about HIV (85%, 58/68).

Conclusions

Social media such as Twitter may be an important source of information regarding STDs provided that the topic is presented appropriately. Reassuringly, the study showed that almost 9/10 of tweets on STDs (chlamydia and HIV) were of serious content, and many of the tweets that were re-tweeted were facts. The jokes that were tweeted were mainly about chlamydia, and posted by non-identifiable emitters. We believe social media should be used to an even larger extent to disseminate correct information about STDs.     

Collagen-based fibrous scaffold for spatial organization of encapsulated and seeded human mesenchymal stem cells

Living tissues consist of groups of cells organized in a controlled manner to perform a specific function. Spatial distribution of cells within a three-dimensional matrix is critical for the success of any tissue-engineering construct. Fibers endowed with cell-encapsulation capability would facilitate the achievement of this objective. Here we report the synthesis of a cell-encapsulated fibrous scaffold by interfacial polyelectrolyte complexation (IPC) of methylated collagen and a synthetic terpolymer. The collagen component was well distributed in the fiber, which had a mean ultimate tensile strength of 244.6 ± 43.0 MPa. Cultured in proliferating medium, human mesenchymal stem cells (hMSCs) encapsulated in the fibers showed higher proliferation rate than those seeded on the scaffold. Gene expression analysis revealed the maintenance of multipotency for both encapsulated and seeded samples up to 7 days as evidenced by Sox 9, CBFA-1, AFP, PPARγ2, nestin, GFAP, collagen I, osteopontin and osteonectin genes. Beyond that, seeded hMSCs started to express neuronal-specific genes such as aggrecan and MAP2. The study demonstrates the appeal of IPC for scaffold design in general and the promise of collagen-based hybrid fibers for tissue engineering in particular. It lays the foundation for building fibrous scaffold that permits 3D spatial cellular organization and multi-cellular tissue development.