Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Background: This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination. Methods: In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (≥1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998). Results: Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, –0.65% and –0.55%; 95% confidence interval [CI], –0.79 to –0.51 and –0.71 to –0.39; P<0.0001). The proportion of patients achieving HbA1c <7% was higher in the triple combination group at week 52 (32.14% vs. 8.51% in placebo; odds ratio, 5.62; P<0.0001). Evogliptin significantly reduced the fasting glucose levels and mean daily glucose levels with improvement in homeostatic model assessment of β-cell function (LS mean difference, 9.04; 95% CI, 1.86 to 16.21; P=0.0138). Adverse events were similar between the groups, and no serious adverse drug reactions were reported in the evogliptin group. Conclusion Long-term triple combination with evogliptin added to DAPA/MET showed superior HbA1c reduction and glycemic control compared to placebo at 52 weeks and was well tolerated.

Background/Aims: Infectious complications are major concerns when treating patients with inflammatory bowel disease (IBD). This study evaluated clinical differences across countries/regions in the management of infectious diseases in patients with IBD. Methods: A multinational online questionnaire survey was administered to participants at the 8th meeting of the Asian Organization for Crohn’s and Colitis. The questionnaire included questions regarding surveillance, diagnosis, management, and prevention of infection in patients with IBD. Results: A total of 384 physicians responded to the questionnaire. The majority of Korean (n=70, 63.6%) and Chinese (n=51, 51.5%) physicians preferred vancomycin to metronidazole in the treatment of Clostridium difficile infection, whereas more than half of the Japanese physicians (n=62, 66.7%) preferred metronidazole. Physicians in Korea (n=88, 80.0%) and China (n=46, 46.5%) preferred a 3-month course of isoniazid and rifampin to treat latent tuberculosis infection, whereas most physicians in Japan (n=71, 76.3%) favored a 9-month course of isoniazid. Most Korean physicians (n=89, 80.9%) recommended hepatitis B virus (HBV) vaccination in patients lacking HBV surface antigen, whereas more than half of Japanese physicians (n=53, 57.0%) did not consider vaccination. Conclusions Differences in the diagnosis, prevention, and management of infections in patients with IBD across countries/regions reflect different prevalence rates of infectious diseases. This survey may broaden understanding of the real-world clinical settings across Asian countries/regions and provide information for establishing practical guidelines to manage patients with IBD.

PURPOSE: To describe the ultrasonographic (US) findings of type IIIa biliary atresia. METHODS: We retrospectively reviewed a medical database of patients pathologically confirmed to have biliary atresia, Kasai type IIIa, between January 2002 and May 2013 (n=18). We evaluated US findings including the visible common bile duct (CBD), triangular cord thickness, gallbladder size and shape, and subcapsular flow on color Doppler US; laboratory data; and pathological hepatic fibrosis grades. We divided them into two groups-those with visible (group A) and invisible (group B) CBD on US-and compared all parameters between the two groups. RESULTS: CBD was visible on US in five cases (27.8%; group A) and invisible in 13 cases (72.2%; group B). US was performed at an earlier age in group A than in group B (median, 27 days vs. 60 days; P=0.027) with the maximal age of 51 days. A comparison of the US findings revealed that the triangular cord thickness was smaller (4.1 mm vs. 4.9 mm; P=0.004) and the gallbladder length was larger (20.0 mm vs. 11.7 mm; P=0.021) in group A. The gallbladder shape did not differ between the two groups, and the subcapsular flow was positive in all cases of both groups. There was no significant difference in the laboratory data between the two groups. Upon pathological analysis, group A showed low-grade and group B showed low- to high-grade hepatic fibrosis. CONCLUSION: When CBD is visible on US in patients diagnosed with type IIIa biliary atresia, other US features could have a false negative status. A subcapsular flow on the color Doppler US would be noted in the type IIIa biliary atresia patients.
Biliary Atresia* ; Common Bile Duct ; Fibrosis ; Gallbladder ; Humans ; Retrospective Studies ; Ultrasonography

Tumor necrosis factor (TNF) -alpha induces pleiotropic cellular effects through a 55kDa, type 1 receptor (TNFR1) and a 75kDa type 2 receptor (TNFR2). Moreover, it participates in the pathogenesis of several CNS diseases, including demyelinating diseases. TNF- receptors are differentially expressed and are regulated in many cell types. However, data regarding the TNF-alpha receptor expression and regulation in human astrocytes is limited to date. We investigated TNF-alpha receptor expression, its regulation by cytokines, and its functional role in primary cultured human fetal astrocytes, which are the most abundant cellular population in the central nervous system and are known to be immunologically active. In this study, astrocytes were found to constitutively and predominantly transcribe, translate and shed TNFR1 rather than TNFR2, but TNFR2 expression was increased by adding TNF-alpha, IL-1, and IFN-gamma, but not by adding LPS. To determine the functional roles of TNFR1 and TNFR2 on TNF induction, we investigated NF-kappaB activation and TNF-alpha induction after neutralizing TNFR1 and TNFR2 by an antibody treatment. We found that NF-kappaB activation and TNF-alpha induction are blocked by TNFR1 neutralizing antibody treatments.
Receptors, Tumor Necrosis Factor, Type II/genetics/*metabolism/physiology ; Receptors, Tumor Necrosis Factor, Type I/genetics/*metabolism/physiology ; RNA, Messenger/metabolism ; NF-kappa B/metabolism ; Humans ; Gene Expression Regulation ; Fetus/cytology ; Cytokines/*pharmacology ; Cells, Cultured ; Astrocytes/drug effects/*metabolism

Candida albicans exhibits the ability to grow in either a yeast or a mycelia form in response to different environmental factors. The mycelia form, found in infected tissues, is important as a virulence factor in the adherence of the organism to the host epithelium. In vitro, the morphological transition can be induced by environmental shifts in the growing conditions, or by a variety of exogenous factors, including ambient pH, nutritional status and temperature. The differential-display reverse transcription polymerase chain reaction (DDRT-PCR) is a powerful technique for comparing gene expression between cell types, stages of development or differentiation. Hyphae related genes were identified and characterized using a PCR-based differential display. Candida albicans formed a germ tube when cultured in rabbit serum, RPMI 1640 medium or 39degrees C-YPD medium. We gained 21 cDNA bands showing a different expression pattern from that of the uninduced culture. DNA was extracted from the same location of the isolated bands, and PCR was performed under the same conditions, which reamplified the PCR product, showing the specific expression patterns according to the culture conditions. We cloned 18 germ tube-related cDNA clones (inserts average size is 80 - 700 bp) and sequenced them. The nucleotide sequences of the 18 clones were identified through in the present study from GenBank, and were found to have the accession number (AF405213-AF405230). We could not find any nucleotide sequence having a high homology with these clones. This study could form a part of the projects in the search for genes related to the germ tube formation of C. albicans.
Animals ; Base Sequence/genetics ; Candida albicans/genetics/*physiology ; Cloning, Molecular ; DNA, Complementary/genetics ; Molecular Sequence Data ; Rabbits ; Reverse Transcriptase Polymerase Chain Reaction/*methods ; Support, Non-U.S. Gov't

Astrocytes are ubiquitous in the brain and have multiple functions. It is becoming clear that they play an important role in monitoring the neuromicroenvironment, information processing, and signaling in the central nervous system (CNS) in normal conditions and respond to CNS injuries. During the development of the CNS, astrocytes play a key role as a substrate for neuronal migration and axonal growth. To identify genes that could participate in astrocyte maturation, we used the differential display reverse transcription-PCR (DDRT-PCR) method. Human fetal astrocytes were cultured and total RNAs are isolated at intervals of 5 days for 50 days. Using 24 primer combinations, we have identified a set of 18 candidate cDNAs deriving from excised DDRT-PCR bands. DNA sequencing revealed 16 genes that have been described already (HMGCR, thyroid receptor interactor gene, NPM, transglutaminase mRNA, and SPARC etc.). We have also found two novel genes (A3 and C8), which were expressed differently in culture stages. A3 expressed decreasingly and C8 expressed increasingly in accordance with to culture stages. We have analysed these two genes. A3 (3,626 bp) showed 93% homology with the Homo sapiens general transcription factor 3 (GTF3) and C8 (2,401 bp) had 97% homology with the transmembrane receptor Unc5H2. Temporal expression of these two genes in this study suggests that the proteins of these genes may have different roles in maturation of the human fetal astrocytes.
Astrocytes* ; Automatic Data Processing ; Axons ; Brain ; Central Nervous System ; DNA, Complementary ; Humans* ; Neurons ; RNA ; RNA, Messenger ; Sequence Analysis, DNA ; Thyroid Gland ; Transcription Factor 3

Parathyroid carcinoma is a very rare disease which comprising 0.1~5% of hyperparathyroidism, and it usually presents with marked hypercalcemia. Clinically, it shows hypercalcemia due to the effect of excessive secretion of parathyroid hormone, bone disease, renal involvement and palpable neck mass. It is known that hyperparathyroidism is induced mostly by parathyroid adenoma but it can be seen in parathyroid hyperplasia, hyperparathyroid carcinoma, rarely associated with familial or multiple endocrine neoplasia. Parathyroid carcinoma can be diagnosed with distant metastasis or local invasion. Treatment is complete resection of primary cancerous lesion and local tissue. Since recurrence or distant metastases are frequent, radiological studies should be done when hypercalcemia is recurred. Sometimes, other tumors can causes hypercalcemia. There are several reports of parathyroid cancer associated with multiple endocrine neoplasia, but has never been reported of parathyroid carcinoma associated with meningioma. We experienced a parathyroid carcinoma with meningioma in 68 year old woman and report the case with the review of literatures.
Aged ; Bone Diseases ; Female ; Humans ; Hypercalcemia ; Hyperparathyroidism ; Hyperplasia ; Meningioma* ; Multiple Endocrine Neoplasia ; Neck ; Neoplasm Metastasis ; Parathyroid Hormone ; Parathyroid Neoplasms* ; Rare Diseases ; Recurrence

Parathyroid carcinoma is a very rare disease which comprising 0.1~5% of hyperparathyroidism, and it usually presents with marked hypercalcemia. Clinically, it shows hypercalcemia due to the effect of excessive secretion of parathyroid hormone, bone disease, renal involvement and palpable neck mass. It is known that hyperparathyroidism is induced mostly by parathyroid adenoma but it can be seen in parathyroid hyperplasia, hyperparathyroid carcinoma, rarely associated with familial or multiple endocrine neoplasia. Parathyroid carcinoma can be diagnosed with distant metastasis or local invasion. Treatment is complete resection of primary cancerous lesion and local tissue. Since recurrence or distant metastases are frequent, radiological studies should be done when hypercalcemia is recurred. Sometimes, other tumors can causes hypercalcemia. There are several reports of parathyroid cancer associated with multiple endocrine neoplasia, but has never been reported of parathyroid carcinoma associated with meningioma. We experienced a parathyroid carcinoma with meningioma in 68 year old woman and report the case with the review of literatures.
Aged ; Bone Diseases ; Female ; Humans ; Hypercalcemia ; Hyperparathyroidism ; Hyperplasia ; Meningioma* ; Multiple Endocrine Neoplasia ; Neck ; Neoplasm Metastasis ; Parathyroid Hormone ; Parathyroid Neoplasms* ; Rare Diseases ; Recurrence

BACKGROUND: Osteoporosis in men is an important public health problem. Because of the incremental tendency of elderly population and age-specific incidence of fracture, it is inevitable that the health burden of fracture will increase. Also, the mortality of fracture in men is higher than in women. Alcohol consumption is a risk factor for osteoporosis based on the frequent finding of a low bone mass decreased bone formation rate and increased fracture incidence in alcoholics. Chronic alcohol consumption may reduce bone density but also increase bone density. It has been well established that liver cirrhosis also induces bone density changes and thus it is difficult to distinguish the role of liver disease from that of alcohol itself in bone alterations occurring in patients with chronic alcohol consumption. So we studied male chronic alcoholics which did not have liver cirrhosis to assess the effect of chronic alcohol consumption on bone mineral density. METHODS: We studied 18 chronic heavy drinkers of more than 40 g/day for at least 5 years and age-matched 18 control groups who had drunk alcohol less than 20 g/day. Serum and urinary parameters of bone and mineral metabolism were determined. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at four axial sites (lumbar spine, femoral neck, ward's triangle and trochanter). RESULTS: Alcoholic patients drank alcohol 97.7 g/day. Osteocalcin, a marker of bone formation, was slight decreased in alcoholic patients and deoxypyridinoline, a marker of bone resorption, was slight increased but not statistically significant (p > 0.05). The levels of 25-(OH)-vit D, parathyroid hormone, free testosterone, estradiol were not different between the two groups. Ward's triangle and trochanter BMD of femur were significantly lower than controls and L-spine BMD decreased parallel with total alcohol intake amount in the alcoholics (r=-0.62, p < 0.05). CONCLUSION: We suggest that chronic alcohol consumption induced low bone density on femur ward and trochanter. And there was significant inverse correlation between L-spine BMD and total alcohol consumption amount. The large scaled randomized and prospective studies are needed to clarify the pathogenesis of alcohol-induced male osteoporosis.
Absorptiometry, Photon ; Aged ; Alcohol Drinking ; Alcoholics ; Alcoholism ; Bone Density* ; Bone Resorption ; Eating* ; Estradiol ; Female ; Femur ; Femur Neck ; Humans ; Incidence ; Liver Cirrhosis* ; Liver Diseases ; Liver* ; Male* ; Metabolism ; Mortality ; Multiple Endocrine Neoplasia Type 1 ; Osteocalcin ; Osteogenesis ; Osteoporosis ; Parathyroid Hormone ; Public Health ; Risk Factors ; Spine ; Testosterone