KLHL3 deficiency in mice ameliorates obesity, insulin resistance, and nonalcoholic fatty liver disease by regulating energy expenditure.

Obesity is a growing global epidemic that can cause serious adverse health consequences, including insulin resistance (IR) and nonalcoholic fatty liver disease (NAFLD). Obesity development can be attributed to energy imbalance and metabolic inflexibility. Here, we demonstrated that lack of Kelch-like protein 3 (KLHL3) mitigated the development of obesity, IR, and NAFLD by increasing energy expenditure. KLHL3 mutations in humans cause Gordon's hypertension syndrome; however, the role of KLHL3 in obesity was previously unknown. We examined differences in obesity-related parameters between control and Klhl3-/- mice. A significant decrease in body weight concomitant with fat mass loss and improved IR and NAFLD were observed in Klhl3-/- mice fed a high-fat (HF) diet and aged. KLHL3 deficiency inhibited obesity, IR, and NAFLD by increasing energy expenditure with augmentation of O2 consumption and CO2 production. Delivering dominant-negative (DN) Klhl3 using adeno-associated virus into mice, thereby dominantly expressing DN-KLHL3 in the liver, ameliorated diet-induced obesity, IR, and NAFLD. Finally, adenoviral overexpression of DN-KLHL3, but not wild-type KLHL3, in hepatocytes revealed an energetic phenotype with an increase in the oxygen consumption rate. The present findings demonstrate a novel function of KLHL3 mutation in extrarenal tissues, such as the liver, and may provide a therapeutic target against obesity and obesity-related diseases.

Assessment of Pain Onset and Maximum Bearable Pain Thresholds in Physical Contact Situations.

With the development of robot technology, robot utilization is expanding in industrial fields and everyday life. To employ robots in various fields wherein humans and robots share the same space, human safety must be guaranteed in the event of a human-robot collision. Therefore, criteria and limitations of safety need to be defined and well clarified. In this study, we induced mechanical pain in humans through quasi-static contact by an algometric device (at 29 parts of the human body). A manual apparatus was developed to induce and monitor a force and pressure. Forty healthy men participated voluntarily in the study. Physical quantities were classified based on pain onset and maximum bearable pain. The overall results derived from the trials pertained to the subjective concept of pain, which led to considerable inter-individual variation in the onset and threshold of pain. Based on the results, a quasi-static contact pain evaluation method was established, and biomechanical safety limitations on forces and pressures were formulated. The pain threshold attributed to quasi-static contact can serve as a safety standard for the robots employed.

Analyzing climate change impacts on health, energy, water resources, and biodiversity sectors for effective climate change policy in South Korea.

This study analyzes how climate change affects the economy, society, and environment in South Korea. Then, the study explores the ways to strengthen capabilities that can alleviate climate change impacts. To find them, the study employs a system dynamics simulation method and builds a model with several sectors including the urban, rural, population, and social-environmental sectors. The study compares the size of climate change damages in rural and urban areas. The results with representative concentration path (RCP) 8.5 show that the size of climate change damage will continue to increase by 2050. The projected damages from the reduced industrial outputs in urban areas will be larger than that in rural areas. The results also show that the service sector will face stronger impacts from climate change than the manufacturing and agricultural sectors. However, the total size of damage in the rural areas will be bigger than that of the urban areas. It is because the size of reduced industrial outputs per capita in the rural areas is twice bigger than that of the urban areas. The climate change damage in the social and environmental sectors (including a loss of biodiversity and an increase in health costs) account for the largest part of the total damage. The study finally provides suggestions and policies that can improve the capabilities to reduce the climate change damages. One of the major suggestions of this study is that the increase in the climate change budget corresponding to the GDP growth can minimize the size of climate change impacts.

Cost-effectiveness analysis of micafungin versus fluconazole for prophylaxis of invasive fungal infections in patients undergoing hematopoietic stem cell transplantation in Korea.

BACKGROUND: Invasive fungal infections are often fatal complications in patients undergoing hematopoietic stem cell transplantation (HSCT), and prophylactic antifungal treatment has been recommended. Within budget-limited health care environments, choosing a cost-effective drug is very important. OBJECTIVE: This study was conducted to analyze the cost-effectiveness of micafungin and fluconazole for prophylaxis of invasive fungal infections from the payer's perspective in patients undergoing HSCT in a Korean health care setting. METHODS: We constructed a decision-analytic model to evaluate both total costs for each state of health and outcomes (such as the fungal-infection prevention rate and life expectancy) for 2 alternatives in a hypothetical cohort of 100 patients undergoing HSCT. The target population was aged 43 years, weighed >50 kg, and had normal renal function. For prophylaxis against systemic fungal infections, patients were administered either micafungin 50 mg/d or fluconazole 400 mg/d, without dose adjustment, as a 1-hour infusion for a mean of 19 consecutive days. Depending on the clinical outcomes with prophylactic therapy, different treatments were assumed. Patients with proven/ probable fungal infection received acute antifungal therapy, and those with suspected fungal infection received empiric antifungal therapy. All patients received general medical care during the analysis period. Results are expressed as Korean won (KW; US $1 = KW 925 as of December 1, 2007). RESULTS: The base-case analysis found that micafungin treatment, compared with fluconazole, saved KW 95,511,000, increased the number of infection-free patients by 0.5, and saved 4.8 life-years per 100 patients. Results with micafungin as the dominant strategy were found to be robust in sensitivity analyses for several parameters, including treatment success and failure rates; mortality risk ratio; and costs for general care, empiric therapy, and acute antifungal therapy. CONCLUSION: Micafungin was a cost-effective prophylactic antifungal strategy by providing lower medical costs and longer life expectancy than fluconazole from the payer's perspective in a hypothetical cohort of Korean adults undergoing HSCT.