Increased serum HO-1 in hemophagocytic syndrome and adult-onset Still's disease: use in the differential diagnosis of hyperferritinemia

Heme oxygenase-1 (HO-1), an inducible heme-degrading enzyme, is expressed by macrophages and endothelial cells in response to various stresses. Because ferritin synthesis is stimulated by Fe(2+), which is a product of heme degradation, we examined the relation between HO-1 and ferritin levels in the serum of patients with hemophagocytic syndrome (HPS), adult-onset Still's disease (ASD), and other diseases that may cause hyperferritinemia. Seven patients with HPS, 10 with ASD, 73 with other rheumatic diseases, 20 with liver diseases, 10 recipients of repeated blood transfusion because of hematological disorders, and 22 healthy volunteers were enrolled. Serum HO-1 and ferritin levels were determined by ELISA. Expression of HO-1 mRNA and protein by peripheral blood mononuclear cells (PBMCs) was determined by real-time PCR and immunocytochemical techniques, respectively. Serum levels of HO-1 were significantly higher in patients with active HPS and ASD than in the other groups (P < 0.01). HO-1 levels were not elevated in patients with other causes of hyperferritinemia but were moderately elevated in patients with dermatomyositis/polymyositis. Among patients with HPS and ASD, serum HO-1 levels correlated closely with serum ferritin levels, and the levels of both returned to normal after therapy had induced remission. Increased expression of HO-1 mRNA was confirmed in PBMCs from some patients with HPS and ASD. Hyperferritinemia correlated closely with increased serum HO-1 in patients with HPS and ASD but not other conditions, indicating that measurement of serum HO-1 and ferritin levels would be useful in the differential diagnosis of hyperferritinemia and perhaps also in monitoring disease activity in HPS and ASD

IHTC14-22317 THE DEVELOPMENT OF PEFORMANCE PREDICTION METHODS FOR AN AUTOMOTIVE CO 2 AIR CONDITIONING CYCLE

ABSTRACT In previous researches, we have been focusing on the performance of the each element heat transfer and hydraulic performance of refrigeration cycle. Experimental investigations have been repeated several times and, finally, we have substantial data base including the effect of lubricant oil. Moreover, the mal-distribution of two-phase in an evaporator can be also predicted from the experimental data base. Under these circumstances, this study is intended to effectively put the construction of an automotive CO 2 air conditioning system into practical design use through the simulation using the abovementioned data base. This paper describes the refrigeration cycle performance prediction of each element (e.g. an evaporator, a gas-cooler, and so on) by a simulation using substantial data base and various available correlations proposed by us and several other researchers. In the performance prediction model of heat exchangers, local heat transfer and flow characteristics are considered and in addition, the effects of lubricant oil on heat transfer and pressure drop are duly considered. The comparison is also made between simulation results and bench test results using a real automotive air conditioning system. Finally, the developed simulation method can predict the cooling ability successfully within ±5%. By incorporating the lubricant oil effect, the simulation results are improved to ±5% and ±15% for the cooling ability and pressure drop respectively. INTRODUCION Due to the increasing environmental concern, the reduction of greenhouse effect gas, particularly, CO 2 emission and the direct leak of HCFC and HFC&apos;s have been considered to be among most important subjects in the field of refrigeration and airconditioning system. At present, the demand for the higher efficiency of a refrigeration system (COP) increases. More recently, the possibility of global warming potential (GWP) is extremely large, and the conventional refrigerant can go ahead through the policy that does not recognize a chlorofluorocarbon alternative to the refrigerant for car air-conditioners positively in EU particular, and the interest for natural refrigerant increases. Among various candidates of natural refrigerants, CO 2 is environmentally safe, being not toxic and non-flammable, so CO 2 has advantages for practical reasons. Moreover, CO 2 possesses a low viscosity, high specific heat, and high thermal conductivity. In general, it has excellent thermodynamic and transport properties as a refrigerant. On the other hand, however, since CO 2 has high critical pressure and its critical temperature is low, it becomes a transcritical cycle and the COP becomes low when compared with conventional refrigerants. Therefore, the high efficiency of heat exchangers is inevitable and it is necessary to grasp the plenary heat transfer coefficients and the basic characteristics of pressure drop in an evaporator and in a gas cooler. Moreover, it presents other problems; for example, the performance deteriorates because the lubricant oil contaminates into the refrigerant in a real working system. So various efforts have been made to investigate these aspects. Although a lot of evaporation heat transfer data are available in literature (Koyama 2004 (1) , Yamada 2004 (2) , Katsuta 2006 (3) ) and it is recognized that the evaporation heat transfer is very sensitive for lubricant oil concentration rate (OCR), few investigations have addressed to the effect of OCR and its prediction. The objective of this research, therefore, is to investigate the effect of oil mixing rate on the thermal and hydraulic characteristics using CO 2 as working refrigerant. In previous researches, we have been focusing on the performance of the each element heat transfer and hydraulic performance. Experimental investigations have been repeated several times and, finally, we have substantial data bas

Prognostic Factors for Post Recurrence Survival in Resected Pathological Stage I Non-small Cell Lung Cancer

[Background]Recurrence of lung cancer after surgical resection is a major obstacle in the cure and long-term survival of patients and has become the most common cause of death. However, prognostic factors and efficacy of therapy after recurrence remain controversial. We evaluated the prognostic factors of post recurrence survival (PRS) in patients of resected stage I non-small cell lung cancer (NSCLC). [Methods]Of the 551 patients who underwent surgery　for stage I NSCLC between 2005 and 2013, we reviewed 89 (16.2%) patients who had recurrence. We examined PRS using the Kaplan?Meier method and multivariate　Cox regression analyses. [Results]The median follow-up period after recurrence was 21.0 months. The median recurrence free interval (RFI) was 16.8 months. The 1-year PRS and 3-year PRS were 65.6% and 44.7%, respectively. Multivariate analysis revealed that size of primary lesion > 25 mm (P = 0.048), RFI ? 17 months (P = 0.048) and no treatment for recurrence (P < 0.001) were independent poor-prognosis factors of PRS. We further examined PRS in 66 patients who underwent any post recurrence therapy. For the patients who underwent treatment after recurrence, bone metastasis (P = 0.025) and treatment without epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) (P = 0.049) were independent poor prognostic factors. [Conclusion]PRS may be associated with characteristics of a recurrent lesion, including the biology of the recurrent tumor, RFI, recurrent site, the treatment for recurrence, rather than characteristics of primary lesion. Although further validation is needed, this information is important for the design of clinical trials for post-recurrence therapy

Degradation of Mutant Protein Aggregates within the Endoplasmic Reticulum of Vasopressin Neurons

Misfolded or unfolded proteins in the ER are said to be degraded only after translocation or isolation from the ER. Here, we describe a mechanism by which mutant proteins are degraded within the ER. Aggregates of mutant arginine vasopressin (AVP) precursor were confined to ER-associated compartments (ERACs) connected to the ER in AVP neurons of a mouse model of familial neurohypophysial diabetes insipidus. The ERACs were enclosed by membranes, an ER chaperone and marker protein of phagophores and autophagosomes were expressed around the aggregates, and lysosomes fused with the ERACs. Moreover, lysosome-related molecules were present within the ERACs, and aggregate degradation within the ERACs was dependent on autophagic-lysosomal activity. Thus, we demonstrate that protein aggregates can be degraded by autophagic-lysosomal machinery within specialized compartments of the ER

Initial Results of Robotic Surgery for Primary Lung Cancer: Feasibility, Safety and Learning Curve

[Background] At the end of 2016, robot-assisted thoracoscopic surgery (RATS) was still not covered by Japanese national health insurance. Therefore, few institutions in Japan perform RATS and even fewer have reported procedures as they occurred earlier. So, we decided to focus on the initial results of RATS for primary lung cancer. [Methods] We retrospectively reviewed 44 patients who underwent RATS for primary lung cancer from January 2011 to August 2016. After mastering the initial procedure, we introduced a completely portal robotic pulmonary resection procedure using a carbon dioxide insufflation system. Cases were divided into 2 groups: the early period (20 cases) and the later period (24 cases). [Results] There was no case of conversion to video-assisted thoracoscopic surgery or thoracotomy. In the 44 cases of primary lung cancer, median operating time was 239.5 min, console time was 179 min, blood loss was 10 mL, drainage period was 2 days, morbidity of Grade 2 or more (Clavien-Dindo classification) was 18.2%, morbidity of Grade 3 or more was only 4.6%, and there was no 30-day mortality. Median operating and console times were significantly shorter in the later period (215 min and 159.5 min, respectively) than in the initial period (300.5 min and 228 min, respectively). Median blood loss was significantly lower in the later period (5 mL) than in the initial period (50 mL). Fiveyear overall and disease-free survival rates were 100% and 88.9%, respectively. [Conclusion] RATS for primary lung cancer is feasible and safe, has a faster learning curve, and provides satisfactory. Studies with longer follow-ups and larger numbers of cases are necessary

A randomized phase III study of short-course radiotherapy combined with Temozolomide in elderly patients with newly diagnosed glioblastoma; Japan clinical oncology group study JCOG1910 (AgedGlio-PIII)

BACKGROUND: The current standard treatment for elderly patients with newly diagnosed glioblastoma is surgery followed by short-course radiotherapy with temozolomide. In recent studies, 40 Gy in 15 fractions vs. 60 Gy in 30 fractions, 34 Gy in 10 fractions vs. 60 Gy in 30 fractions, and 40 Gy in 15 fractions vs. 25 Gy in 5 fractions have been reported as non-inferior. The addition of temozolomide increased the survival benefit of radiotherapy with 40 Gy in 15 fractions. However, the optimal regimen for radiotherapy plus concomitant temozolomide remains unresolved. METHODS: This multi-institutional randomized phase III trial was commenced to confirm the non-inferiority of radiotherapy comprising 25 Gy in 5 fractions with concomitant (150 mg/m2/day, 5 days) and adjuvant temozolomide over 40 Gy in 15 fractions with concomitant (75 mg/m2/day, every day from first to last day of radiation) and adjuvant temozolomide in terms of overall survival (OS) in elderly patients with newly diagnosed glioblastoma. A total of 270 patients will be accrued from 51 Japanese institutions in 4 years and follow-up will last 2 years. Patients 71 years of age or older, or 71-75 years old with resection of less than 90% of the contrast-enhanced region, will be registered and randomly assigned to each group with 1:1 allocation. The primary endpoint is OS, and the secondary endpoints are progression-free survival, frequency of adverse events, proportion of Karnofsky performance status preservation, and proportion of health-related quality of life preservation. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in April 2020. Ethics approval was granted by the National Cancer Center Hospital Certified Review Board. Patient enrollment began in August 2020. DISCUSSION: If the primary endpoint is met, short-course radiotherapy comprising 25 Gy in 5 fractions with concomitant and adjuvant temozolomide will be a standard of care for elderly patients with newly diagnosed glioblastoma. TRIAL REGISTRATION: Registry number: jRCTs031200099 . Date of Registration: 27/Aug/2020. Date of First Participant Enrollment: 4/Sep/2020

Spatial and seasonal variability of the air-sea equilibration timescale of carbon dioxide

The exchange of carbon dioxide between the ocean and the atmosphere tends to bring waters within the mixed layer toward equilibrium by reducing the partial pressure gradient across the air-water interface. However, the equilibration process is not instantaneous; in general, there is a lag between forcing and response. The timescale of air-sea equilibration depends on several factors involving the depth of the mixed layer, wind speed, and carbonate chemistry. We use a suite of observational data sets to generate climatological and seasonal composite maps of the air-sea equilibration timescale. The relaxation timescale exhibits considerable spatial and seasonal variations that are largely set by changes in mixed layer depth and wind speed. The net effect is dominated by the mixed layer depth; the gas exchange velocity and carbonate chemistry parameters only provide partial compensation. Broadly speaking, the adjustment timescale tends to increase with latitude. We compare the observationally derived air-sea gas exchange timescale with a model-derived surface residence time and a data-derived horizontal transport timescale, which allows us to define two nondimensional metrics of equilibration efficiency. These parameters highlight the tropics, subtropics, and northern North Atlantic as regions of inefficient air-sea equilibration where carbon anomalies are relatively likely to persist. The efficiency parameters presented here can serve as simple tools for understanding the large-scale persistence of air-sea disequilibrium of CO2 in both observations and models

Outcomes in Transcatheter Aortic Valve Replacement for Bicuspid Versus Tricuspid Aortic Valve Stenosis

Cardiolog