Lack of information on gender differences in the package inserts of prescription drugs in Japan.

The package inserts of prescription drugs provide essential information for the proper administration of pharmacotherapy. The incidence of adverse reactions for several drugs is known to be higher in women than in men. However, no studies have examined whether information on gender differences is included in Japanese package inserts. Therefore, this study investigated information on gender differences in the package inserts of Japanese prescription drugs, using the drug information database JAMES provided by the Medical Information System Development Center and the Japan Pharmaceutical Information Center. Non-proprietary names of prescription drugs were yielded 1,679 in Japan. Of the 1,679 ingredients in package inserts of prescription drugs, 76 (4.5%) included information on gender differences. The number of inserts that contained information on gender differences in the "DOSAGE AND ADMINISTRATION," "ADVERSE REACTIONS," and "PHARMACOKINETICS" sections was 3, 16, and 62, respectively. Furthermore, in the "ADVERSE REACTIONS" section, 15 of the 16 inserts mentioned a higher frequency of adverse reactions in women compared with men. Importantly, most of the inserts with information on gender differences in the "PHARMACOKINETICS" section mentioned a higher area under the curve for women than for men. Most of the package inserts of prescription drugs with information on gender differences provide useful information aimed at preventing risks in women. However, there is an extreme lack of information on gender differences in the package inserts of prescription drugs in Japan, and we consider enhancing information on gender difference as an urgent issue.

Pathologically diagnosed early-stage gastric adenocarcinoma with enteroblastic differentiation after endoscopic submucosal dissection: A case report.

A 77-year-old male patient underwent esophagogastroduodenoscopy at his family doctor, and an easily hemorrhagic depressed lesion was noted near the anterior wall of the gastric antrum. A biopsy revealed moderately differentiated tubular adenocarcinoma > poorly differentiated adenocarcinoma, and the patient was referred to our department for further examination. A 15-mm 0-IIc lesion is seen near the anterior wall of the gastric antrum and narrow band imaging magnifying endoscopy revealed obscured glandular duct structures and corkscrew pattern vascular structures. We diagnosed the patient with early-stage gastric cancer [L, Ant, 15mm, cType0-IIc, cT1(M-SM1), cN0, cM0, cStage IA] after an esopahogastroduodenoscopy examination at our hospital, and endoscopic submucosal dissection was performed. Histopathological images with hematoxylin and eosin staining showed tumor cells with pale cytoplasm and the immunostaining for alpha-fetoprotein, sal-like protein 4, and Glypican3 was positive. The patient was pathologically diagnosed with gastric adenocarcinoma with enteroblastic differentiation, pT1b1 (SM, 0.4 mm), type 0-IIc, 15 mm, UL (-), Ly0, and V0. Gastric adenocarcinoma with enteroblastic differentiation is one of the representative histological types of alpah-fetoprotein-producing gastric cancer. Alpha-fetoprotein-producing gastric cancer is infrequent, accounting for at least 3% of all gastric cancers, and is generally highly malignant. Most cases are already advanced upon diagnosis, and finding them in the early stage is rare. Therefore, pathological findings that may indicate the gastric adenocarcinoma with enteroblastic differentiation should be noted even in early gastric cancer.

Hydrogen attenuates endothelial glycocalyx damage associated with partial cardiopulmonary bypass in rats.

Cardiopulmonary bypass (CPB) causes systemic inflammation and endothelial glycocalyx damage. Hydrogen has anti-oxidant and anti-inflammatory properties; therefore, we hypothesized that hydrogen would alleviate endothelial glycocalyx damage caused by CPB. Twenty-eight male Sprague-Dawley rats were randomly divided into four groups (n = 7 per group), as follows: sham, control, 2% hydrogen, and 4% hydrogen. The rats were subjected to 90 minutes of partial CPB followed by 120 minutes of observation. In the hydrogen groups, hydrogen was administered via the ventilator and artificial lung during CPB, and via the ventilator for 60 minutes after CPB. After observation, blood collection, lung extraction, and perfusion fixation were performed, and the heart, lung, and brain endothelial glycocalyx thickness was measured by electron microscopy. The serum syndecan-1 concentration, a glycocalyx component, in the 4% hydrogen group (5.7 ± 4.4 pg/mL) was lower than in the control (19.5 ± 6.6 pg/mL) and 2% hydrogen (19.8 ± 5.0 pg/mL) groups (P < 0.001 for each), but it was not significantly different from the sham group (6.2 ± 4.0 pg/mL, P = 0.999). The endothelial glycocalyces of the heart and lung in the 4% hydrogen group were thicker than in the control group. The 4% hydrogen group had lower inflammatory cytokine concentrations (interleukin-1ß and tumor necrosis factor-α) in serum and lung tissue, as well as a lower serum malondialdehyde concentration, than the control group. The 2% hydrogen group showed no significant difference in the serum syndecan-1 concentration compared with the control group. However, non-significant decreases in serum and lung tissue inflammatory cytokine concentrations, as well as in serum malondialdehyde concentration, were observed. Administration of 4% hydrogen via artificial and autologous lungs attenuated endothelial glycocalyx damage caused by partial CPB in rats, which might be mediated by the anti-inflammatory and anti-oxidant properties of hydrogen.

Modeled production, oxidation, and transport processes of wetland methane emissions in temperate, boreal, and Arctic regions.

Wetlands are the largest natural source of methane (CH4 ) to the atmosphere. The eddy covariance method provides robust measurements of net ecosystem exchange of CH4 , but interpreting its spatiotemporal variations is challenging due to the co-occurrence of CH4 production, oxidation, and transport dynamics. Here, we estimate these three processes using a data-model fusion approach across 25 wetlands in temperate, boreal, and Arctic regions. Our data-constrained model-iPEACE-reasonably reproduced CH4 emissions at 19 of the 25 sites with normalized root mean square error of 0.59, correlation coefficient of 0.82, and normalized standard deviation of 0.87. Among the three processes, CH4 production appeared to be the most important process, followed by oxidation in explaining inter-site variations in CH4 emissions. Based on a sensitivity analysis, CH4 emissions were generally more sensitive to decreased water table than to increased gross primary productivity or soil temperature. For periods with leaf area index (LAI) of ≥20% of its annual peak, plant-mediated transport appeared to be the major pathway for CH4 transport. Contributions from ebullition and diffusion were relatively high during low LAI (<20%) periods. The lag time between CH4 production and CH4 emissions tended to be short in fen sites (3 ± 2 days) and long in bog sites (13 ± 10 days). Based on a principal component analysis, we found that parameters for CH4 production, plant-mediated transport, and diffusion through water explained 77% of the variance in the parameters across the 19 sites, highlighting the importance of these parameters for predicting wetland CH4 emissions across biomes. These processes and associated parameters for CH4 emissions among and within the wetlands provide useful insights for interpreting observed net CH4 fluxes, estimating sensitivities to biophysical variables, and modeling global CH4 fluxes.

Most dentists approve of oral health check-ups for local residents at community pharmacies and desire collaboration with community pharmacists.

Community pharmacies are required to play a role in maintaining the health of local residents. Since September 2015, a national policy in Japan has allowed saliva tests to be used for oral health check-ups at community pharmacies. In the present study, we aimed to reveal dentists' perceptions and expectations for oral health check-ups provided at community pharmacies. A questionnaire survey was administered to dentists at 1,000 randomly selected dental clinics in Tokyo, Japan; 257 responses (25.7%) were included in the analysis and 85.2% of respondents approved of oral health check-ups at community pharmacies. Most respondents who approved of oral health check-ups expected that community pharmacists would recommend that local residents visit a dental clinic (85.8%) and provide a report to dentists (60.3%) after the check-up. Furthermore, 79.0% of respondents desired collaboration with community pharmacies. These findings suggested the potential for oral health check-ups to facilitate collaboration between community pharmacies and dental clinics aimed at maintaining and improving oral health of local residents.

Intraoperative Remifentanil Dosage in Surgery for Adolescent Idiopathic Scoliosis Does Not Increase Postoperative Opioid Consumption When Combined With Epidural Analgesia: A Retrospective Cohort Study.

Background In adults, high-dose remifentanil during surgery has been reported to increase postoperative opioid consumption, but this has not been well documented in children. Multimodal analgesia is recommended in the perioperative period for adolescent idiopathic scoliosis (AIS), but no report has examined opioid consumption under epidural analgesia, which is one of the most common types of analgesia. Aims To investigate the association between intraoperative remifentanil dosage and postoperative opioid consumption in AIS in the setting of combined epidural analgesia for postoperative multimodal analgesia. Methods In this retrospective cohort study, patients aged 10-18 years who underwent surgery for scoliosis and epidural analgesia for postoperative pain between July 2012 and April 2019 were included. The primary endpoint was the association between intraoperative cumulative weight-adjusted remifentanil dosage and logarithmic transformation of cumulative weight-adjusted fentanyl consumption in the intensive care unit (ICU). Nonopioid analgesics were investigated as secondary endpoints. An epidural catheter was inserted by the surgeon intraoperatively, and a local anesthetic was administered at the end of the surgery. Multivariate linear regression analysis with adjustment for confounders was performed for all analyses. Results In total, 142 patients were included, and the median intraoperative remifentanil dosage for all patients was 0.27 (interquartile range, 0.24-0.34) µg/kg/min. No association was observed between cumulative weight-adjusted intraoperative dosage of remifentanil and fentanyl, even after adjusting for potential confounders (slope = -1.25; 95% confidence interval [CI], -4.35 to 1.85; P = 0.43). No association was observed between nonopioid analgesic use and intraoperative remifentanil dosage. Conclusion No association was noted between remifentanil dosage during surgery for AIS and postoperative opioid consumption with epidural analgesia. However, this study has limitations due to its retrospective design; thus, further prospective studies are warranted.

Substantial hysteresis in emergent temperature sensitivity of global wetland CH4 emissions.

Wetland methane (CH4) emissions ([Formula: see text]) are important in global carbon budgets and climate change assessments. Currently, [Formula: see text] projections rely on prescribed static temperature sensitivity that varies among biogeochemical models. Meta-analyses have proposed a consistent [Formula: see text] temperature dependence across spatial scales for use in models; however, site-level studies demonstrate that [Formula: see text] are often controlled by factors beyond temperature. Here, we evaluate the relationship between [Formula: see text] and temperature using observations from the FLUXNET-CH4 database. Measurements collected across the globe show substantial seasonal hysteresis between [Formula: see text] and temperature, suggesting larger [Formula: see text] sensitivity to temperature later in the frost-free season (about 77% of site-years). Results derived from a machine-learning model and several regression models highlight the importance of representing the large spatial and temporal variability within site-years and ecosystem types. Mechanistic advancements in biogeochemical model parameterization and detailed measurements in factors modulating CH4 production are thus needed to improve global CH4 budget assessments.

Identifying dominant environmental predictors of freshwater wetland methane fluxes across diurnal to seasonal time scales.

While wetlands are the largest natural source of methane (CH4 ) to the atmosphere, they represent a large source of uncertainty in the global CH4 budget due to the complex biogeochemical controls on CH4 dynamics. Here we present, to our knowledge, the first multi-site synthesis of how predictors of CH4 fluxes (FCH4) in freshwater wetlands vary across wetland types at diel, multiday (synoptic), and seasonal time scales. We used several statistical approaches (correlation analysis, generalized additive modeling, mutual information, and random forests) in a wavelet-based multi-resolution framework to assess the importance of environmental predictors, nonlinearities and lags on FCH4 across 23 eddy covariance sites. Seasonally, soil and air temperature were dominant predictors of FCH4 at sites with smaller seasonal variation in water table depth (WTD). In contrast, WTD was the dominant predictor for wetlands with smaller variations in temperature (e.g., seasonal tropical/subtropical wetlands). Changes in seasonal FCH4 lagged fluctuations in WTD by ~17 ± 11 days, and lagged air and soil temperature by median values of 8 ± 16 and 5 ± 15 days, respectively. Temperature and WTD were also dominant predictors at the multiday scale. Atmospheric pressure (PA) was another important multiday scale predictor for peat-dominated sites, with drops in PA coinciding with synchronous releases of CH4 . At the diel scale, synchronous relationships with latent heat flux and vapor pressure deficit suggest that physical processes controlling evaporation and boundary layer mixing exert similar controls on CH4 volatilization, and suggest the influence of pressurized ventilation in aerenchymatous vegetation. In addition, 1- to 4-h lagged relationships with ecosystem photosynthesis indicate recent carbon substrates, such as root exudates, may also control FCH4. By addressing issues of scale, asynchrony, and nonlinearity, this work improves understanding of the predictors and timing of wetland FCH4 that can inform future studies and models, and help constrain wetland CH4 emissions.

Statistical upscaling of ecosystem CO2 fluxes across the terrestrial tundra and boreal domain: Regional patterns and uncertainties.

The regional variability in tundra and boreal carbon dioxide (CO2 ) fluxes can be high, complicating efforts to quantify sink-source patterns across the entire region. Statistical models are increasingly used to predict (i.e., upscale) CO2 fluxes across large spatial domains, but the reliability of different modeling techniques, each with different specifications and assumptions, has not been assessed in detail. Here, we compile eddy covariance and chamber measurements of annual and growing season CO2 fluxes of gross primary productivity (GPP), ecosystem respiration (ER), and net ecosystem exchange (NEE) during 1990-2015 from 148 terrestrial high-latitude (i.e., tundra and boreal) sites to analyze the spatial patterns and drivers of CO2 fluxes and test the accuracy and uncertainty of different statistical models. CO2 fluxes were upscaled at relatively high spatial resolution (1 km2 ) across the high-latitude region using five commonly used statistical models and their ensemble, that is, the median of all five models, using climatic, vegetation, and soil predictors. We found the performance of machine learning and ensemble predictions to outperform traditional regression methods. We also found the predictive performance of NEE-focused models to be low, relative to models predicting GPP and ER. Our data compilation and ensemble predictions showed that CO2 sink strength was larger in the boreal biome (observed and predicted average annual NEE -46 and -29 g C m-2  yr-1 , respectively) compared to tundra (average annual NEE +10 and -2 g C m-2  yr-1 ). This pattern was associated with large spatial variability, reflecting local heterogeneity in soil organic carbon stocks, climate, and vegetation productivity. The terrestrial ecosystem CO2 budget, estimated using the annual NEE ensemble prediction, suggests the high-latitude region was on average an annual CO2 sink during 1990-2015, although uncertainty remains high.

Patient satisfaction with oral health check-ups at a community pharmacy and their effect on oral self-care habits and dental consultation behavior.

Maintaining good oral health is important because oral diseases are related to systemic diseases, and community pharmacies play a key role in maintaining the health of local residents. This study aimed to examine the effects of oral health check-ups and information provision at community pharmacies on oral health-associated behaviors as well as patient satisfaction. We conducted oral health check-ups and provided information about oral health self-care to 84 patients at a community pharmacy, and then asked them to complete a questionnaire survey. One month later, we sent them a follow-up questionnaire and received responses from 66.7% (56/84) of the participants. The large majority were satisfied with the salivary test (95.2%) and the information (96.4%) we provided. Most of the participants (89.3%) indicated that they wanted to use the oral health check-up service again in the future. Compared with baseline, the ratio of participants restricting their intake of sugar-rich foods and drinks significantly increased 1 month later (p = 0.021). About 60% of those who had not undergone a regular dental examination at baseline reported newly visiting or planning to visit a dental clinic. The results revealed high satisfaction with the oral health check-up and information about oral self-care they received at the community pharmacy. The results suggested that oral health check-ups had the potential to change both oral self-care habits and dental consultation behavior. Our findings indicate that community pharmacies can contribute to the maintenance and promotion of oral health by providing oral health check-ups to local residents.

Expression of precipitating factors of pruritus found in humans in an imiquimod-induced psoriasis mouse model.

AIMS: To use a mouse model of imiquimod-induced psoriasis to investigate the relationship between pruritus and mast cells, nerve growth factor (NGF) and endogenous pruritogenic peptides, which are highly expressed in the skin of psoriasis patients. MAIN METHODS: We developed a mouse model of imiquimod-induced psoriasis and measured the frequency and duration of the model animals' self-scratching behavior using the SCLABA®-Real real-time scratch counting system. We then harvested the ears and subjected them to toluidine blue staining and real-time PCR. KEY FINDINGS: Topical application of imiquimod increased the Psoriasis Area and Severity Index score as well as the frequency and duration of self-scratching. Regarding internal factors, increases in mast cells number and mRNA expression of NGF and endogenous pruritogenic peptide precursor were confirmed. SIGNIFICANCE: Self-scratching behavior is accompanied by increased number of mast cells and expression of NGF and endogenous pruritogenic peptides in our imiquimod-induced psoriasis model. The expression of these factors was consistent with the features in patients with pruritic psoriasis, suggesting that our model reflects at least some of the precipitating factors of pruritus found in humans.

A survey on awareness of the "finger-tip unit" and medication guidance for the use of topical steroids among community pharmacists.

Atopic dermatitis (AD) is a common chronic, pruritic inflammatory skin condition. AD is most commonly treated with topical corticosteroids, and the finger-tip unit (FTU) should be used as a guideline for the amount to be used per application. In this study, we investigated the adequacy of pharmacists' instructions on the amount of topical steroids to be applied and the way in which they enhance the effect of pharmaceutical interventions. A self- administered anonymous questionnaire was distributed using QLifePro to 300 pharmacists working in insurance pharmacies that filled at least one dermatologist's prescription per month on average in Japan. Out of 300 pharmacists, 196 (65.3%) recognized the Japanese Dermatological Association's 2016 guidelines for the treatment AD, 107 (35.6%) gave instructions using the FTU as an index of external dose of topical steroids, 157 (52.3%) explained the amount of steroid application using an index other than FTU, and 61 (38.9% of 157) had inadequately instructed AD patients to apply steroids as a thin layer. Pharmacists who had read the guidelines for AD tended to give an appropriate instruction using FTU as an index of external dose of topical steroids (p < 0.001). We found that many pharmacists in pharmacies gave inadequate instructions on the amount of topical steroid application and deviated from the guidelines for AD, mainly because of inadequate knowledge of the guidelines.

Advanced dynamic statistical parametric mapping with MEG in localizing epileptogenicity of the bottom of sulcus dysplasia.

OBJECTIVE: To investigate whether advanced dynamic statistical parametric mapping (AdSPM) using magnetoencephalography (MEG) can better localize focal cortical dysplasia at bottom of sulcus (FCDB). METHODS: We analyzed 15 children with diagnosis of FCDB in surgical specimen and 3 T MRI by using MEG. Using AdSPM, we analyzed a ±50 ms epoch relative to each single moving dipole (SMD) and applied summation technique to estimate the source activity. The most active area in AdSPM was defined as the location of AdSPM spike source. We compared spatial congruence between MRI-visible FCDB and (1) dipole cluster in SMD method; and (2) AdSPM spike source. RESULTS: AdSPM localized FCDB in 12 (80%) of 15 children whereas dipole cluster localized six (40%). AdSPM spike source was concordant within seizure onset zone in nine (82%) of 11 children with intracranial video EEG. Eleven children with resective surgery achieved seizure freedom with follow-up period of 1.9 ±â€¯1.5 years. Ten (91%) of them had an AdSPM spike source in the resection area. CONCLUSION: AdSPM can noninvasively and neurophysiologically localize epileptogenic FCDB, whether it overlaps with the dipole cluster or not. SIGNIFICANCE: This is the first study to localize epileptogenic FCDB using MEG.

[A Case of Rocuronium Anaphylaxis in which Anesthesia was Safely Performed after Selection of an Alternative Drug after a Skin Test].

We report our experience of a patient with a history of anaphylactic shock suspected to be caused by rocuronium who was scheduled to undergo hepatic tumor resection. The patient was a 17-year-old female (height : 166 cm, weight : 46 kg). During general anesthesia at another hospital several years ago, she had an anaphylactic shock, and rocuronium was suspected to be the offending drug. To collect information and search for the cause, skin tests were performed for rocuronium, vecuronium and suxamethonium. She was positive for rocuronium, and negative for other drugs. At anesthesia induction, we administered vecuronium and confirmed no development of anaphylaxis before commencement of surgery. In the perioperative period, she had no symptoms that indicated anaphylaxis. Since there is potential high cross-reactivity among muscle relaxants, it is important to perform a test for alternative drugs when a muscle relaxant may be a cause of anaphylaxis. Selection and administration of an alternative drug should be carefully performed, even when a skin test is negative for the alternative drug.

[Changes in the Femoral Vein Diameter due to Lower Limb Flexion].

BACKGROUND: The purpose of this study was to in- vestigate the changes in the femoral vein (FV) diam- eter and the positional relationship during lower limb flexion using ultrasonography. METHODS: Twenty five male healthy volunteers were positioned in the supine and the hip joint was flexed to the target angles, followed by external rota- tion and abduction of the hip joint (hemi-frog-leg posi- tion). The flexion angle of the hip joint was mea- sured: before flexion (control), and at 30', 450, 60*, 75* flexion. The ultrasonograph transducer was held over the line which was 2 cm distal and parallel to the inguinal ligament Results: Compared with controls, the distance from the skin to the anterior wall of the FV was signifi- cantly shorter at 30 (15.1 mm vs 13.3 mm, P<0.01) and longer at 75" (15.1 mm vs 16.4 mm, P<0.03). The exposed width of the FV (length not overlapped by the femoral artery) was longest at 300(9.9 mm vs 12.1 mm, P<0.01). CONCLUSIONS: This study demonstrated that the hemi-frog-leg position was associated with significant increases in the diameter and exposed width of the FV. In particular, the most effective angle of the hip joint flexion was about 30*.

Relation between fentanyl dose and patient state index during spinal anesthesia for elective cesarean section.

BACKGROUND: In spinal anesthesia for cesarean section, the addition of fentanyl to the local anesthetic has been reported to improve perioperative analgesia. However, there is only limited knowledge on sedative effects of the added fentanyl. We examined whether the patient state index® (PSI) can detect and present the light sedated level with patients undergoing cesarean section. FINDINGS: We measured respiratory rate (RR), SpO2, and PSI values. Between child delivery and the completion of the operation, the proportions of time with the PSI values <90 and 80 were calculated. RR <8 breaths/min or SpO2 <95 % was defined as respiratory depression. Respiratory depression was not observed in any patient. At fentanyl doses of 10, 15, and 20 µg, the proportions of time with the PSI <90 were 14.5 ± 20.8, 49.4 ± 35.3, and 71.1 ± 22.9 %, respectively (P < 0.01). There were significant differences between 10 and 15 µg (P < 0.05), and 10 and 20 µg (P < 0.01). Similarly, the proportions of time with the PSI values <80 were 0.5 ± 1.8, 21.1 ± 24.1, and 31.8 ± 32.2 %, respectively (P < 0.05). There was a significant difference between 10 and 20 µg (P < 0.05). CONCLUSIONS: The PSI values decreased in a dose-dependent manner with increasing dose of fentanyl, but no respiratory depression was observed. The PSI values decreased to less than 90, when fentanyl was administered more than 15 µg. Furthermore, the PSI values decreased to less than 80, when fentanyl was administered 20 µg.

Autumn warming reduces the CO2 sink of a black spruce forest in interior Alaska based on a nine-year eddy covariance measurement.

Nine years (2003-2011) of carbon dioxide (CO2) flux were measured at a black spruce forest in interior Alaska using the eddy covariance method. Seasonal and interannual variations in the gross primary productivity (GPP) and ecosystem respiration (RE) were associated primarily with air temperature: warmer conditions enhanced GPP and RE. Meanwhile, interannual variation in annual CO2 balance was controlled predominantly by RE, and not GPP. During these 9 years of measurement, the annual CO2 balance shifted from a CO2 sink to a CO2 source, with a 9-year average near zero. The increase in autumn RE was associated with autumn warming and was mostly attributed to a shift in the annual CO2 balance. The increase in autumn air temperature (0.22 °C yr(-1)) during the 9 years of study was 15 times greater than the long-term warming trend between 1905 and 2011 (0.015 °C yr(-1)) due to decadal climate oscillation. This result indicates that most of the shifts in observed CO2 fluxes were associated with decadal climate variability. Because the natural climate varies in a cycle of 10-30 years, a long-term study covering at least one full cycle of decadal climate oscillation is important to quantify the CO2 balance and its interaction with the climate.

Karlotoxin synthetic studies: concise synthesis of a C(42-63) B-ring tetrahydropyran fragment.

Starting from natural D-mannose, a C(42-63) B-ring tetrahydropyran fragment in karlotoxin 2 has been prepared via a common THP intermediate in a concise manner. E-selective Julia-Kocienski olefination efficiently assembled a C(51-63) chlorodiene subunit and a C(42-50) tetrahydropyran segment.

Synergistic effect of combined treatment with gamma-tocotrienol and statin on human malignant mesothelioma cells.

The present study is the first to demonstrate the synergetic effect of statins (atorvastatin and simvastatin) and gamma-tocotrienol (γ-T3) on human malignant mesothelioma (MM). Statin + γ-T3 combinations induced greater cell growth inhibition more than each single treatment via inhibition of mevalonate pathway, a well-known target of both γ-T3 and statins. γ-T3 was necessary for endoplasmic reticulum stress markers CHOP and GRP78, whereas an intrinsic apoptotic marker, caspase 3 activation was induced only in the presence of statins. Overall, the combination of γ-T3 and statins could be useful for MM therapy and functions in a complementary style.

Growing season and spatial variations of carbon fluxes of Arctic and boreal ecosystems in Alaska (USA).

To better understand the spatial and temporal dynamics of CO2 exchange between Arctic ecosystems and the atmosphere, we synthesized CO2 flux data, measured in eight Arctic tundra and five boreal ecosystems across Alaska (USA) and identified growing season and spatial variations of the fluxes and environmental controlling factors. For the period examined, all of the boreal and seven of the eight Arctic tundra ecosystems acted as CO2 sinks during the growing season. Seasonal patterns of the CO2 fluxes were mostly determined by air temperature, except ecosystem respiration (RE) of tundra. For the tundra ecosystems, the spatial variation of gross primary productivity (GPP) and net CO2 sink strength were explained by growing season length, whereas RE increased with growing degree days. For boreal ecosystems, the spatial variation of net CO2 sink strength was mostly determined by recovery of GPP from fire disturbance. Satellite-derived leaf area index (LAI) was a better index to explain the spatial variations of GPP and NEE of the ecosystems in Alaska than were the normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI). Multiple regression models using growing degree days, growing season length, and satellite-derived LAI explained much of the spatial variation in GPP and net CO2 exchange among the tundra and boreal ecosystems. The high sensitivity of the sink strength to growing season length indicated that the tundra ecosystem could increase CO2 sink strength under expected future warming, whereas ecosystem compositions associated with fire disturbance could play a major role in carbon release from boreal ecosystems.