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Heavy-chain deposition disease (HCDD) is a rare disorder characterized by the deposition of monoclonal immunoglobulin. Due to the disease's rarity and diagnostic challenges, its prognosis is generally poor. Herein, we report a case of successful treatment of HCDD coexisting with multiple myeloma. A 56-year-old man presented at an outpatient clinic with complaints of whole-body pain, edema, and dyspnea that had persisted for 2 weeks. Diagnostic tests confirmed nephrotic syndrome, hematuria, and progressive renal failure. Serum immunofixation electrophoresis identified the presence of IgG kappa paraprotein. A diagnosis of multiple myeloma was established following a bone marrow biopsy. A renal biopsy revealed antibodies specific to the heavy chains of IgG on immunofluorescence, and electron microscopy showed diffuse electron-dense "powdery" densities in the glomerular basement membrane. Based on these findings, the patient was diagnosed with both HCDD and multiple myeloma. Following the diagnosis, the patient immediately began anti-plasma cell therapy using bortezomib, lenalidomide, and dexamethasone. Intermittent hemodialysis was initiated due to persistent azotemia during the diagnostic process; however, renal function improved significantly after only 1 month of therapy, allowing the discontinuation of dialysis. Early intervention with anti-plasma cell therapy, such as bortezomib, is known to improve prognosis in the early stages of the disease. This case report is presented to enhance understanding of HCDD and underscore the importance of prompt diagnosis and treatment in managing this rare condition.

Mixed neuroendocrine-nonneuroendocrine neoplasms (MiNENs) of the gastrointestinal tract, particularly gastric MiNENs are rare, and a gastric adenoma that occurs concomitant with a neuroendocrine carcinoma (and not gastric adenocarcinoma) is extremely rare. The clinicopathologic and pathogenetic features of MiNENs remain unclear, and treatment guidelines are currently unavailable. A 75-year-old man patient was referred to our hospital for management of a gastric adenoma. Endoscopy revealed an elevated mucosal lesion (10 mm×10 mm) at the greater curvature of the lower gastric body. The patient underwent endoscopic submucosal dissection for removal of the gastric neoplasm. Histopathological evaluation revealed mixed epithelial dysplasia, low and partly high grade and a neuroendocrine tumor (grade 1). Immunohistochemical analysis showed neoplastic cells with immunopositivity for CD56, synaptophysin, and INSM1, and Ki-67 showed 2.2%. Therefore, the patient was diagnosed with a low-grade gastric MiNEN. We present a rare case of gastric MiNENs (adenoma-neuroendocrine tumor) together with a literature review.

The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.

Purpose The aim of this study was to analysis of the clinicopathological characteristics and prognosis of colorectal cancer (CRC) under the age of 50 years. Methods Between January 2009 and December 2018, 1,126 primary CRC patients were included from National Health Insurance Service Ilsan Hospital. The patients were divided into group 1 (n=111, ≤50 years) and group 2 (n=1,015, >50 years). The clinicopathologic features and prognostic outcomes were compared. In addition, to analyze whether there were any differences of those characteristics in 3 groups, patients aged under 50 years were divided into their 20s, 30s, and 40s. Results Group 1 had a slightly higher distribution in the left colon and rectum, lower T stage I and higher T stage IV rate, and a significantly higher distribution in stage N2 than group 2 (30.6%:16.3%, P

Extramedullary relapse in acute lymphoblastic leukemia (ALL) usually occurs in the central nervous system and testes those are known as sanctuary sites. Only a few cases of isolated breast relapse after allogeneic hematopoietic stem cell transplantation (HSCT) have been reported in pediatric ALL, with little known about the optimal treatment and prognosis of such cases. Herein, we report a pediatric case of isolated breast relapse with early T-cell precursor ALL after HSCT. We also describe a literature review of six pediatric cases, including our case.

Atypical chronic myeloid leukemia (aCML), BCR-ABL1-negative is a rare myeloid neoplasm, especially in pediatric patients. The mutations identified in aCML have overlapped with those of other myeloid neoplasms. In recent studies, ruxolitinib, a Janus kinase (JAK) inhibitor, was found efficient in some patients of aCML with CSF3R mutation. Here, we report a pediatric case of aCML with CSF3R mutation who did not respond to ruxoritinib, but was successfully rescued with hematopoietic stem cell transplantation (SCT). A stuporous 13-year-old boy was transferred with leukocytosis. Computed tomography showed an acute lobar intracranial hemorrhage in the left frontal lobe. The bone marrow aspirate demonstrated significant granulocytic proliferations with predominant dysplasia. Hydroxyurea and imatinib were initially administered to reduce leukocytosis. After BCR-ABL1 was found to be negative, imatinib was discontinued. After the identification of CSF3R mutation by customized targeted DNA sequencing (NGeneBio, Seoul, South Korea), ruxolitinib was added. He seemed to have hematologic and clinical responses on 2 months of ruxolitinib treatment, but the blast counts in the bone marrow increased. He underwent a full-matched unrelated peripheral blood SCT successfully 3 months after his diagnosis and has currently been disease-free 8 months since the transplantation. In conclusion, ruxolitinib for aCML with CSF3R mutation might not always induce a significant response but could be used as bridge to hematopoietic SCT.

Abstract The human fetal liver is a critical organ for prenatal hematopoiesis, the study of which offers insights into niche signals that regulate the fates of hematopoietic stem and progenitor cells (HSPCs) during fetal development. Here, we demonstrate that human fetal liver endothelium uniquely supports the maturation and expansion of multilineage HSPCs. Specifically, co-culture of fetal liver-derived immature CD43+CD45− hematopoietic cells with human fetal liver endothelial cells (ECs) led to a profound increase in the numbers of phenotypic CD45+CD34+ HSPCs and multilineage colony-forming progenitors generated in vitro, when compared to co-culture with ECs derived from other organs. We further identified a supportive role for EC-derived WNT5A in this process via gain- and loss-of-function studies within ECs. Our study emphasizes the importance of the organ-specific endothelial niche in supporting hematopoietic development and provides novel insight into signals that may facilitate HSPC expansion in vitro for clinical applications.

Purpose Although most colorectal malignancies are adenocarcinomas from mucosa, various types of malignant and benign tumors can develop. Due to extremely low incidence, little research has been conducted. The purpose was to assess incidence and compare it according to demographic factors. Methods Data from the Korea National Cancer Registry from 2007 to 2016 were used. The crude incidence, age-standard incidence rate (ASR) of colorectal nonadenocarcinomas were calculated. Results Over 11 years, there were 267,142 patients with colorectal malignancies. The patients of 14,495 (5.43%) were diagnosed with nonadenocarcinoma. The ASR was 2.52 per 100,000 in men and 1.56 in women. Lesions were classified according to histologic categories; neuroendocrine tumor (NET) was the most common malignancy (10,919 [75.33%]). Nonadenocarcinoma was the most common in 40s and 50s (40 to 49 years, 3,530 [24.35%]; 50 to 59 years, 3,991 [27.53%]). Lymphoma was high (54.46%) in patients in teenagers. Proportion of NET decreased with age and that of carcinoma increased with age. Carcinoma, sarcoma, and lymphoma were more common among men and melanoma was more common among women. The most common site was the rectum (11,066 [76.34%]). Lymphoma occurred more frequently in proximal colon. Melanoma, gastrointestinal stromal tumor, and NET occurred mostly in rectum. A total of 10,155 patients (70.06%) were classified as having localized disease. Conclusion This study is meaningful as it is the first study to examine incidence of colorectal nonadenocarcinoma. Differences in incidence of different lesions based on demographic factors were identified. This study will play a role in cancer prevention and diagnosis projects.

Abstract Background Staphylococcus aureus bacteremia (SAB) presents heterogeneously, owing to the differences in underlying host conditions and immune responses. Although Toll-like receptor 2 (TLR2) is important in recognizing S. aureus, its function during S. aureus infection remains controversial. We aimed to examine the association of TLR2 expression and associated cytokine responses with clinical SAB outcomes. Methods Patients from a prospective SAB cohort at two tertiary-care medical centers were enrolled. Blood was sampled at several timepoints (≤5 d, 6–9 d, 10–13 d, 14–19 d, and ≥ 20 d) after SAB onset. TLR2 mRNA levels were determined via real-time PCR and serum tumor necrosis factor [TNF]-α, interleukin [IL]-6, and IL-10 levels were analyzed with multiplex-high-sensitivity electrochemiluminescent ELISA. Results TLR2 levels varied among 59 SAB patients. On days 2–5, TLR2 levels were significantly higher in SAB survivors than in healthy controls (p = 0.040) and slightly but not significantly higher than non-survivors (p = 0.120), and SAB patients dying within 7 d had lower TLR2 levels than survivors (P = 0.077) although statistically insignificant. IL-6 and IL-10 levels were significantly higher in non-survivors than in survivors on days 2–5 post-bacteremia (P = 0.010 and P = 0.021, respectively), and those dying within 7 d of SAB (n = 3) displayed significantly higher IL-10/TNF-α ratios than the survivors did (P = 0.007). Conclusion TLR2 downregulation and IL-6 and IL-10 concentrations suggestive of immune dysregulation during early bacteremia may be associated with mortality from SAB. TLR2 expression levels and associated cytokine reactions during early-phase SAB may be potential prognostic factors in SAB, although larger studies are warranted.

Purpose Total mesorectal excision is a standard technique for rectal cancer. The whole-mount section can encompass the entire specimen, so it is a more appropriate for measuring circumferential margin than conventional section. We analyzed the clinical characteristics and prognosis based on lateral margins (LMs) measured by whole-mount sections. Methods Medical records of patients who were operated on for T3 rectal cancer from 2005 to 2015 were reviewed retrospectively. A total of 154 patients were included. The slides of the whole-mount sections were re-reviewed by a single pathologist. Results We divided the groups according to the length of the LM (1 mm, 1.5 mm, and 2 mm). There was significantly frequent lymphovascular invasion and N state was higher when LM was short in all groups. There were more micrometastasis in group LM ≤1 mm (53.3% ≤1 mm vs. 26.6% >1 mm, P=0.039), but not in other groups. When looking at local recurrence alone, there was no significant difference between groups, but the 5-year local recurrence-free survival was significantly worse when LM ≤2 mm (P=0.050). In each analysis based on 1 mm and 1.5 mm, overall survival was worse when LM was short. In all groups, disease-specific survival was worse when LM was short. Conclusion As previously known, securing a margin less than 1 mm negatively affects the prognosis. When LM was divided by 1.5 mm, there was a significant difference in overall survival. There was a significant difference in disease-specific survival when divided by 2 mm in T3 rectal cancer. However, further studies with more patients are necessary to secure the result.

Purpose Overall 5-year survival rates for colon and rectal cancer reported recently by the American Cancer Society were 89%, 90% for localized disease, 71%, 71% for regional disease, and 14%, 15% for distant disease. But the results of survival rate of colorectal cancer in a single institution were very rare. The aim of this study is to evaluate surgical results and survival rates of colorectal cancer. Methods We conducted a retrospective study with patients who underwent curative resection for a primary colorectal adenocarcinoma between 2009 and 2018. Results Five-year overall and disease-free survival were 79.5% and 69.9%, respectively. The overall 5-year survival by stages was 94.7% in stage I, 88.4% in stage II, 74.3% in stage III and 31.5% in stage IV. Five-year disease-free survival was 91% in stage I, 79.8% in stage II, 63.3% in stage III, and 18.9% in stage IV. The overall 5-year survival in rectal cancer was superior to colon cancer (P=0.014) while there was no difference in 5-year disease-free survival (P=0.338). Overall survival in female patients was better than male patient (P=0.029). Overall survival by age was worst in group of less than 40 years old (62.5%), and best in group between 41 and 65 years old (86.5%). Postoperative mortality within 30 days was 0.4%, and the recurrence rate was 19.2%. Conclusion With the development of surgical skills and various treatments, postoperative outcome of colorectal cancer is expected to improve. It may be helpful for surgeons to improve their surgical outcomes when they review their data and conduct active researches.

Objectives: To delineate clinical characteristics of asymptomatic and symptomatic patients confirmed with COVID-19 in South Korea. Methods: Data were obtained from the Korean National Health Insurance Service database linked to the Korea Centers for Disease Control and Prevention data. Results: Among 10,237 patients (mean [SD] age, 45.0 [19.8] years; 60.1% female) who met the eligibility criteria for the study, 6,350 (62.0%) patients were asymptomatic, and 3,887(38.0%) patients were symptomatic. The mean and median age were similar between asymptomatic and symptomatic patients. Notably, we observed a U-shaped association between age group and the proportion of asymptomatic patients, with the nadir at 57.3% in the 40-49 age group. This U-shaped distribution was largely similar between men and women. The overall prevalence of asymptomatic individuals was higher, regardless of sex, residential area, income levels, and comorbid conditions. Conclusions: In this national cohort of over 10,000 patients with COVID-19, more than 60% of all cases in South Korea reported no symptoms at the time of diagnosis. Expanding criteria for contact tracing and testing to capture potential transmission before symptom onset should be urgently considered to inform control strategies for COVID-19.

Purpose The incidence of colorectal cancer in Korea has recently increased, making it the second most common cancer in men and the third most common cancer in women. Risk factors for colorectal cancer have been studied worldwide, but risk factors specific for the Korean population have not been established. In this study, we investigated incidence trends and risk factors of colorectal cancer in Korea. Methods A total of 8,846,749 subjects were included. Colorectal cancer incidence was investigated using Korea National Health Insurance Service claim data from 2004 to 2014. Colorectal cancer diagnoses were obtained by evaluating colorectal cancer diagnostic codes and the cancer registry for cost sharing. Risk factor identification for colorectal cancer was obtained from National Health Examination data from 2004 to 2005. Cox proportional hazard model statistical analysis was used to determine risk factors of colorectal cancer. Results The incidence of colorectal cancer gradually increased from 2006 to 2014 (from 45.4/100,000 to 54.5/100,000). There was a predominance among men (1.47:1), but incidence trends were similar in both sexes. Old age, high body mass index, and no history of colonoscopy were identified as risk factors in both sexes. High fasting blood glucose, familial history of cancer, frequent alcohol intake, and current smoker were identified as risk factors, especially in men. Conclusion The incidence of colorectal cancer has been increasing in Korea. Colonoscopy screening was a protective factor for colorectal cancer, and active use of colonoscopy may reduce incidence. Early diagnosis and care are important, particularly for the high-risk group.

Purpose The objective of the current study was to compare surgical outcomes and prognosis based on the longitudinal location of stomach tumors in patients undergoing curative treatment. The specific focus was on the prognosis for adenocarcinomas in the proximal upper-third of the stomach, excluding tumors in the esophagogastric junction (EGJ). Methods Data from patients who underwent curative treatment for gastric adenocarcinoma between 2000 and 2010 at a single institution were analyzed retrospectively. Excluding tumors of EGJ origin, data from 797 patients were reviewed—686 with distal gastric cancer and 111 with proximal gastric cancer. Clinicopathology features, tumor stage, surgical outcomes, recurrence, and survival were compared between the groups. Results Gastric cancer recurred in 136 of the patients (17.1%). Although differences were detected between proximal and distal cancer patients in the prevalence in males versus females (74.8% vs. 63.4%, P=0.020) and in undifferentiated histology (60.4% vs. 47.7%, P=0.013), the prognosis for proximal gastric cancer did not differ from distal gastric cancer. The overall 5-year disease-free survival rate was 84.9% and 81.4% in proximal and distal cancer patients, respectively (P=0.389). Conclusion The prognosis of proximal cancer, excluding tumors of EGJ origin, did not differ from the prognosis of more distal gastric cancer. Clarifying the prognosis of proximal gastric cancer will require the large-scale comparison of an organized, multi-institution database.

The ultimate goal of the quality control program for special periodic health examination agencies is to diagnose the health condition of a worker correctly, based on accurate examination and analysis skills, leading to protect the worker’s health. The quality control program on three areas, chemical analysis for biological monitoring since 1995, and pneumoconiosis, audiometric testing since 1996, has contributed to improve the reliability of occupational health screenings by improving the issues including standardization of testing methods, tools, diagnostic opinions, and reliability of analysis for biological monitoring. It has contributed to improving the reliability of occupational health monitoring by rectifying the following issues associated with previous monitoring: absence of standardized testing methods, testing tools that are not upgraded, mismatching diagnostic opinions, and unreliable results of biological specimen analysis. Nevertheless, there are issues in need of further improvement such as lack of expertise or the use of inappropriate method for health examination, and passive and unwilling participation in the quality control. We suggested solutions to these problems for each area of quality control program. Above all, it is essential to provide active support for health examiners to develop their expertise, while encouraging all the health screening agencies, employers, and workers to develop the desire to improve the system and to maintain the relevance. Keywords: Audiometric test, Biological monitoring, Pneumoconiosis, Quality control program

Osteoma of the external auditory canal is a rare benign tumor with an estimated incidence of 0.05% of total otologic surgeries. In most cases, an osteoma in the external auditory canal does not cause symptoms because the tumor grows slowly and does not occlude the ear canal. However, if the mass grows to occlude the external auditory canal, several symptoms can occur, including conductive hearing loss, aural fullness, and keratin debris accumulation. We present two cases of this rare tumor in a 23-year-old woman and a 19-year-old man. The mass was surgically excised at the level of the peduncle under local anesthesia with microscope assistance. The base of the excised mass was drilled with a diamond burr to remove all osseous lesions. Histopathologic findings showed spongiotic osteomas. In these cases, patients had symptoms of aural fullness, although the osteomas did not completely occlude the external auditory canal, and the symptoms improved after surgical excision without recurrence.

Numerous recurrent genetic mutations are known to occur in acute myeloid leukemia (AML). Among these common mutations, Fms-like tyrosine kinase 3 remains as one of the most frequently mutated genes in AML. We observed apparent marrow expansion of megakaryocytes in three out of six patients with Flt3-mutated AML following treatment with a recently FDA-approved Flt3 inhibitor, gilteritinib which possesses activity against internal tandem duplication and tyrosine kinase domain Flt3 mutations and also inhibits tyrosine kinase AXL. To assess whether biopsy findings can be attributed to promotion of megakaryocytic (Mk) differentiation with gilteritinib, we devised a cellular assay by overexpressing double mutated Flt3-ITDY591F/Y919F in chronic myeloid leukemia cell line K562 to study Mk differentiation in the presence of Flt3 and AXL inhibitors with non-mutually exclusive mechanisms. These experiments demonstrated the lack of direct effect Flt3 inhibitors gilteritinib and quizartinib on megakaryocytic differentiation at either transcriptional or phenotypic levels, and highlighted antileukemic effects of AXL receptor tyrosine kinase inhibitor and its potential role in megakaryocytic development.

Summary: The endothelium first forms in the blood islands in the extra-embryonic yolk sac and then throughout the embryo to establish circulatory networks that further acquire organ-specific properties during development to support diverse organ functions. Here, we investigated the properties of endothelial cells (ECs), isolated from four human major organs—the heart, lung, liver, and kidneys—in individual fetal tissues at three months' gestation, at gene expression, and at cellular function levels. We showed that organ-specific ECs have distinct expression patterns of gene clusters, which support their specific organ development and functions. These ECs displayed distinct barrier properties, angiogenic potential, and metabolic rate and support specific organ functions. Our findings showed the link between human EC heterogeneity and organ development and can be exploited therapeutically to contribute in organ regeneration, disease modeling, as well as guiding differentiation of tissue-specific ECs from human pluripotent stem cells. : Stem Cells Research; Developmental Biology; Biology of Human Development Subject Areas: Stem Cells Research, Developmental Biology, Biology of Human Development

Lymph node metastasis in early colon cancer is relatively low. Furthermore, skip metastasis beyond principle lymph node is very rare. This is a case of early cecal cancer with skip metastasis to portocaval and retropancreatic space, without regional lymph node metastasis. A 69-year-old female diagnosed as cecal adenocarcinoma. The imaging study revealed as early cecal cancer without enlargement of regional lymph node. However, there is enlargement of portocaval lymph node and high fluorodeoxyglucose (FDG) uptake in positron emission tomography scan image. Right hemicolectomy with extended lymph node dissection was done including retropancreatic, portocaval and hepatoduodenal ligament lymph node. Though whole abdominal cavity exploration was done, there was no evidence of other synchronous cancer. The final pathologic findings revealed the poorly differentiated adenocarcinoma with invasion of submucosal layer and focally superficial layer of muscularis propria. Two of total 27 lymph nodes were involved by metastastatic adenocarcinoma which were from portocaval and retropancreatic space. The detailed preoperative imaging study could find unexpected lymph node metastasis beyond range of routine lymph node dissection. Even though the preoperative clinical stage is relatively early, the detailed and sufficient evaluation for clinical and imaging findings is important not to ignore skip metastasis.

Objectives The goal of this study was to investigate the short-term effect of ambient air pollution on emergency department (ED) visits in Seoul for asthma according to patients’ prior history of allergic diseases. Methods Data on ED visits from 2005 to 2009 were obtained from the Health Insurance Review and Assessment Service. To evaluate the risk of ED visits for asthma related to ambient air pollutants (carbon monoxide [CO], nitrogen dioxide [NO2], ozone [O3], sulfur dioxide [SO2], and particulate matter with an aerodynamic diameter

BackgroundFor detecting tumor recurrence of medullary thyroid carcinoma (MTC) in the neck, an appropriate frequency and interval of postoperative ultrasonography (US) surveillance remains unclear. This study aimed to assess an appropriate interval and frequency of postoperative neck US surveillance for detecting tumor recurrence in patients who had undergone thyroid surgery due to MTC.MethodsA total of 86 patients who had undergone thyroid surgery for the treatment of MTC and had at least one postoperative US follow-up examination at any of nine affiliated hospitals were included. Postoperative follow-up US, clinical, and histopathological results of patients were reviewed. The tumor recurrence/persistence rate of MTC was investigated, and the interval and session number of postoperative follow-up US and clinicopathologic factors were compared between tumor recurrence/persistence and non-recurrence groups.ResultsOf the 86 patients, 22 (25.6%) showed tumor recurrence/persistence. Of the 22 patients with tumor recurrence/persistence, 11 (50%) showed structural recurrence/persistence in the neck on follow-up US. In these 11 patients, the mean interval and session number of postoperative follow-up US between initial surgery and the first US detection of recurrence/persistence was 41.3 ± 39.3 months (range, 6–128 months) and 2.6 ± 2.3 (range, 1–8), respectively. On follow-up US, 6 (54.5%, 6/11) were diagnosed with tumor recurrence/persistence within 3 years of the initial surgery. Tumor recurrence/persistence was significantly correlated with TNM stage (p

Purpose: To evaluate the diagnostic accuracy of real-time neck computed tomography (CT)-guided ultrasonography (US) in detecting cervical neck lymph node metastasis (LNM) in patients with papillary thyroid cancer (PTC). Methods: We retrospectively reviewed data from 176 patients (mean age, 43 years; range, 23 to 74 years) with surgically confirmed PTC who underwent preoperative US, neck CT, and neck CTguided US. We then compared the sensitivities and diagnostic accuracies of each of the three above modalities in detecting cervical LNM. Results: Preoperative US showed 17.3% sensitivity and 58.5% diagnostic accuracy in detecting central LNM compared with 64.3% sensitivity and 89.2% diagnostic accuracy in detecting lateral neck LNM. Neck CT showed 23.5% sensitivity and 55.7% diagnostic accuracy in detecting central LNM and 71.4% sensitivity with 90.9% diagnostic accuracy in detecting lateral neck LNM. CT-guided US exhibited 37.0% sensitivity and 63.1% diagnostic accuracy in detecting central LNM compared with 92.9% sensitivity and 96.0% diagnostic accuracy in detecting lateral LNM. CT-guided US showed higher diagnostic accuracy with superior sensitivity in detecting central and lateral LNM than did US (P

BackgroundMetformin, an oral biguanide insulin-sensitizing agent, is well known to decrease appetite. Although there is evidence that metformin could affect the brain directly, the exact mechanism is not yet known.MethodsTo evaluate whether metformin induces anorexia via the hypothalamus, various concentrations of metformin were injected into the lateral ventricle of rats through a chronically implanted catheter and food intake was measured for 24 hours. The hypothalamic neuropeptides associated with regulation of food intake were also analyzed following 1 hour of intracerebroventricular (ICV) injections of metformin.ResultsAn ICV injection of metformin decreased food intake in a dose-dependent manner in unrestrained conscious rats. Hypothalamic phosphorylated AMP-activated protein kinase (pAMPK) increased by 3 µg with metformin treatment, but there was no further increase in pAMPK with increases in metformin dosage. The hypothalamic phosphorylated signal transducer and activator of transcription 3 (pSTAT3) increased by 3 µg with metformin treatment, but, there was no further increase in pSTAT3 level following increases of metformin dosage. Hypothalamic proopiomelanocortin was elevated with metformin treatment, while neuropeptide Y was not significantly changed.ConclusionOur results suggest that metformin induces anorexia via direct action in the hypothalamus and the increase in pSTAT3, at least in part, is involved in the process. However, hypothalamic pAMPK appears not to contribute to metformin-induced appetite reduction in normal rats. Further studies exploring new pathways connecting metformin and feeding regulation are needed.

This article sets out to study the FDI–environment nexus within a dynamic panel data framework. To that end, the pooled mean group (PMG) method of Pesaran et al. (1999) is used to assess the impact of FDI on CO2 emissions, controlling for income and energy consumption, using a panel of 17 Latin American countries. Our results using the full sample show that FDI increases CO2 emissions, confirming the pollution haven hypothesis. But when splitting the data into different income groups, FDI inflows only in high-income countries increase CO2 emissions. In addition, CO2 emissions with growth tend to increase monotonically within the full sample and middle-income countries. Finally, energy consumption is found to increase CO2 emissions in all cases: the full sample, high-, middle- and low-income countries.

The main contribution of this article is to examine the productivity spillover effects from India’s inward foreign direct investment (FDI), controlling for trade, in the framework of the cointegrated vector autoregression (CVAR). For this purpose, using the Solow residual approach the aggregate total factor productivity (TFP) in India is estimated to measure FDI-induced spillovers. The results show that the inflow of FDI to India indeed improves TFP growth through positive spillover effects. We also find that trade appears to have a detrimental effect on TFP growth in India.

Shear stress activates cellular signaling involved in cellular proliferation, differentiation, and migration. However, the mechanisms of mesenchymal stem cell (MSC) differentiation under interstitial flow are not fully understood. Here, we show the increased osteogenic differentiation of MSCs under exposure to constant, extremely low shear stress created by osmotic pressure-induced flow in a microfluidic chip. The interstitial level of shear stress in the proposed microfluidic system stimulated nuclear localization of TAZ (transcriptional coactivator with PDZ-binding motif), a transcriptional modulator of MSCs, activated TAZ target genes such as CTGF and Cyr61, and induced osteogenic differentiation. TAZ-depleted cells showed defects in shear stress-induced osteogenic differentiation. In shear stress induced cellular signaling, Rho signaling pathway was important forthe nuclear localization of TAZ. Taken together, these results suggest that TAZ is an important mediator of interstitial flow-driven shear stress signaling in osteoblast differentiation of MSCs.

The overexpression of vascular endothelial growth factor (VEGF) is known to be involved in the pathogenesis of diabetic nephropathy. In this study, the protective effects of taurine on diabetic nephropathy along with its underlying mechanism were investigated. Experimental animals were divided into three groups: LETO rats as normal group (n=10), OLETF rats as diabetic control group (n=10), and OLETF rats treated with taurine group (n=10). We treated taurine (200 mg/kg/day) for 20 weeks and treated high glucose (HG, 30 mM) with or without taurine (30 mM) in mouse cultured podocyte. After taurine treatment, blood glucose level was decreased and insulin secretion was increased. Taurine significantly reduced albuminuria and ACR. Also it decreased glomerular volume, GBM thickness and increased open slit pore density through decreased VEGF and increased nephrin mRNA expressions in renal cortex. The antioxidant effects of taurine were confirmed by the reduction of urine MDA in taurine treated diabetic group. Also reactive oxygen species (ROS) levels were decreased in HG condition with taurine treated podocytes compared to without taurine. These results indicate that taurine lowers glucose level via increased insulin secretion and ameliorates the progression of diabetic nephropathy through antifibrotic and antioxidant effects in type 2 diabetes rat model.

BACKGROUND: Although the socioeconomic burden of 2009 pandemic influenza A (H1N1) was considerable, no reliable estimates have been reported. Our aim was to compared medical costs and socioeconomic burden resulting from pandemic influenza A (H1N1) 2009 with that of previous seasonal influenza. METHODS: We estimated the medical costs and socioeconomic burden of influenza from May 2007 to April 2010. We used representative national data sources(data from the Health Insurance Review Agency, the National Health Insurance Corporation, the Korea Centers for Disease Control and Prevention, and the Korean National Statistics Office) including medical utilization, prescription of antivirals, and vaccination. Uncertainty of data was explored through sensitivity analysis using Monte Carlo simulation. RESULTS: Compared with the seasonal influenza, total medical costs (US$291.7 million) associated with pandemic (H1N1) 2009 increased more than 37-fold. Compared with the 2007-2008 season, outpatient diagnostic costs (US$135.3 million) were 773 times higher in the 2009-2010 season, and the mean diagnostic cost per outpatient visit was 58.8 times higher. Total socioeconomic burden of pandemic (H1N1) 2009 was estimated at US$1581.3 million (10%-90%: US$1436.0-1808.3 million) and those of seasonal influenza was estimated at US$44.7 million (10%-90%: US$32.4-57.9 million) in 2007-2008 season and US$42.3 million (10%-90%: US$31.5-53.8 million) in 2008-2009 season. Indirect costs accounted for 56.0% of total costs in pandemic (H1N1) 2009, and 66.48-68.09% in seasonal influenza. The largest contributors to total burden were productivity losses of caregiver in pandemic (H1N1) 2009, and productivity losses due to morbidity of outpatient in seasonal influenza. CONCLUSIONS: In the Republic of Korea, socioeconomic burden of pandemic (H1N1) 2009 were considerably higher than burden of the previous two influenza seasons, primarily because of high diagnostic costs and longer sick leave.

OBJECTIVE: In this multicenter study, we investigated the management algorithm for thyroid nodules with benign cytology using US features from data collected from 7 institutions. MATERIALS AND METHODS: The institutional review board approved this retrospective study. Data on 700 focal thyroid nodules in 673 consecutive patients were collected from 7 university-affiliated hospitals. This study included nodules that were diagnosed as benign at initial cytologic evaluation and that underwent pathologic or follow-up study. The risk of malignancy was compared according to the US assessments of each institution as well as looking at all the nodules together as a whole. RESULTS: Of the 700 nodules, 688 (98.3%) were benign and 12 (1.7%) were malignant. If initial cytologic results were benign, the likelihood of the nodule actually being malignant was from 1 to 3%, varying by institution. The likelihood of a cytologically benign nodule with positive US being malignant (4.7%, 8/169) was higher than that of one without positive US (0.8%, 4/531) (P = .002). CONCLUSION: Based on our multicenter study, repeat FNA should be performed in thyroid nodules with initial benign cytology showing suspicious US features in order to decrease the number of false negative cases.

Background: The increasing rate of excess body weight (EBW) in the global population has led to growing health concerns, including cancer-related EBW. We aimed to estimate the population attributable fraction (PAF) of cancer incidence and deaths linked to EBW in Korean individuals from 2015 to 2030 and to compare its value with various body mass index cutoffs. Methods: Levin's formula was used to calculate the PAF; the prevalence rates were computed using the Korean National Health and Nutrition Examination Survey data, while the relative risks of specific cancers related to EBW were estimated based on the results of Korean cohort studies. To account for the 15-year latency period when estimating the PAF in 2020, the prevalence rates from 2015 and attributable cases or deaths from 2020 were used. Results: The PAF attributed to EBW was similar for both cancer incidence and deaths using either the World Health Organization (WHO) Asian-Pacific region standard or a modified Asian standard, with the WHO standard yielding the lowest values. In the Korean population, the PAFs of EBW for cancer incidence were 2.96% in men and 3.61% in women, while those for cancer deaths were 0.67% in men and 3.06% in women in 2020. Additionally, PAFs showed a gradual increase in both sexes until 2030. Conclusion: The EBW continues to have a significant impact on cancer incidence and deaths in Korea. Effective prevention strategies targeting the reduction of this modifiable risk factor can substantially decrease the cancer burden. [ABSTRACT FROM AUTHOR]