Novel Selective PPARα Modulator Pemafibrate for Dyslipidemia, Nonalcoholic Fatty Liver Disease (NAFLD), and Atherosclerosis

Statins, the intestinal cholesterol transporter inhibitor (ezetimibe), and PCSK9 inhibitors can reduce serum LDL-C levels, leading to a significant reduction in cardiovascular events. However, these events cannot be fully prevented even when maintaining very low LDL-C levels. Hypertriglyceridemia and reduced HDL-C are known as residual risk factors for ASCVD. Hypertriglyceridemia and/or low HDL-C can be treated with fibrates, nicotinic acids, and n-3 polyunsaturated fatty acids. Fibrates were demonstrated to be PPARα agonists and can markedly lower serum TG levels, yet were reported to cause some adverse effects, including an increase in the liver enzyme and creatinine levels. Recent megatrials of fibrates have shown negative findings on the prevention of ASCVD, which were supposed to be due to their low selectivity and potency for binding to PPAR α. To overcome the off-target effects of fibrates, the concept of a selective PPARα modulator (SPPARMα) was proposed. Kowa Company, Ltd. (Tokyo, Japan), has developed pemafibrate (K-877). Compared with fenofibrate, pemafibrate showed more favorable effects on the reduction of TG and an increase in HDL-C. Fibrates worsened liver and kidney function test values, although pemafibrate showed a favorable effect on liver function test values and little effect on serum creatinine levels and eGFR. Minimal drug-drug interactions of pemafibrate with statins were observed. While most of the fibrates are mainly excreted from the kidney, pemafibrate is metabolized in the liver and excreted into the bile. It can be used safely even in patients with CKD, without a significant increase in blood concentration. In the megatrial of pemafibrate, PROMINENT, for dyslipidemic patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia, and low HDL-C and LDL-C levels, the incidence of cardiovascular events did not decrease among those receiving pemafibrate compared to those receiving the placebo; however, the incidence of nonalcoholic fatty liver disease was lower. Pemafibrate may be superior to conventional fibrates and applicable to CKD patients. This current review summarizes the recent findings on pemafibrate

The effect of lunar cycle, tidal condition and wind direction on the catches and profitability of Japanese common squid Todarodes pacificus jigging and trap-net fishing

Jigging with artificial lights (squid jigging) and deploying of large scale trap-net (also known as a set-net in Japan), are the major methods to capture Japanese common squid Todarodes pacificus in western Japan. Squid jigging is a highly selective fishing method. However, it consumes large amount of energy for steaming to the fishing ground and for lighting. In contrast, trap-net fishing requires substantially less energy but its capture efficiency is strongly influenced by its stationary mode of capture. The primary objective of this study was to analyze how various environmental and biological factors such as the lunar cycle, tidal condition, wind direction and squid abundance affect the capture efficiency of squid jigging and trap-net fishing. We analyzed the effect of these factors on squid catch in five Fisheries Cooperative Associations located on four islands in Nagasaki Prefecture, western Japan. Our analysis shows that squid catch in jigging and trap-net fishing is mainly influenced by the lunar cycle but also tide and wind direction play a marked role. In addition, squid abundance significantly affects the catches in trap-net fishing. Recommendations are made to improve the overall profitability of squid fishing by proper choice of the capture method, location and season

Etiler'de Locanda

Taha Toros Arşivi, Dosya No: 112-Lokantalarİstanbul Kalkınma Ajansı (TR10/14/YEN/0033) İstanbul Development Agency (TR10/14/YEN/0033

Ectopic adrenal adenoma causing gross hematuria: Steroidogenic enzyme profiling and literature review

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149375/1/iju512068.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149375/2/iju512068_am.pd

上部消化管出血における血液凝固第XIII因子活性の低下

We report on blood coagulation factor XⅢ（F１３）activity in upper gastrointestinal bleeding （UGIB）due to peptic ulcer（PU）. 【Methods】From January ２０１１ to December ２０１６, 42 patients who had UGIB with PU, performed endoscopic hemostasis（EH）, and measured F１３ activity （normal range：７０‐１４０％）, were retrospectively studied. The clinical signs, peripheral blood, biochemistry, coagulation, F１３ activity, and endoscopic findings were examined by logistic regression analysis（LRA）in３２patients with successful hemostasis and１０patients with rebleeding. 【Results】There were２５elderly patients aged７０ and over. The average F１３ activity was ６５．７±２２．５％, ６８．３±２２．１％ in the case of successful hemostasis, below the lower limit of normal, and further decreased to ５７．５±１８．１％ in the case of rebleeding. LRA showed association with rebleeding in Forrest classification and F１３activity. 【Conclusion】F１３activity decreased in many cases of UGIB due to PU, and associated with rebleeding after EH

Clinical Significance of Serum Soluble T Cell Regulatory Molecules in Clear Cell Renal Cell Carcinoma

To clarify the role of serum soluble T cell regulatory molecules in clear cell renal cell carcinoma (CCRCC), we measured the serum levels of soluble interleukin-2 receptor (sIL-2R), soluble B7-H3 (sB7-H3), and soluble cytotoxic T lymphocyte associated antigen-4 (sCTLA-4) in 70 CCRCC patients and 35 healthy controls. We investigated correlations between the serum levels of these soluble T cell regulatory molecules and the pathological grade, clinical stage, and prognosis of CCRCC. We also assessed the relations among each of these soluble molecules. As a result, the serum level of sIL-2R was significantly higher in CCRCC patients than in healthy controls ( < 0.05). In addition, elevation of serum sIL-2R was significantly correlated with the clinical stage ( < 0.001), and the survival of patients with high sIL-2R levels was shorter than that of patients with low sIL-2R levels ( < 0.05). Furthermore, the serum level of sB7-H3 was also significantly correlated with the clinical stage ( < 0.05), while the sIL-2R and sB7-H3 levels showed a positive correlation with each other ( = 0.550, < 0.0001). These results indicate that the serum level of sIL-2R reflects tumor progression in CCRCC patients. In addition, the possibility was suggested that the IL-2/IL-2R and B7-H3 pathways may be involved in the progression of CCRCC

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life