Differential effects of sevoflurane and desflurane on frontal intraoperative electroencephalogram dynamics associated with postoperative delirium.

STUDY OBJECTIVE: Intraoperative electroencephalogram (EEG) patterns associated with postoperative delirium (POD) development have been studied, but the differences in EEG recordings between sevoflurane- and desflurane-induced anesthesia have not been clarified. We aimed to distinguish the EEG characteristics of sevoflurane and desflurane in relation to POD development. DESIGN AND PATIENTS: We collected frontal four-channel EEG data during the maintenance of anesthesia from 148 elderly patients who received sevoflurane (n = 77) or desflurane (n = 71); 30 patients were diagnosed with delirium postoperatively. The patients were divided into four subgroups based on anesthetics and delirium status: sevoflurane delirium (n = 17), sevoflurane non-delirium (n = 60), desflurane delirium (n = 13), and desflurane non-delirium (n = 58). We compared spectral power, coherence, and pairwise phase consistency (PPC) between sevoflurane and desflurane, and between non-delirium and delirium groups for each anesthetic. MAIN RESULTS: In patients without POD, the sevoflurane non-delirium group exhibited higher EEG spectral power across 8.5-35 Hz (99.5% CI bootstrap analysis) and higher PPC from alpha to gamma bands (p < 0.005) compared to the desflurane non-delirium group. Conversely, in patients with POD, no significant EEG differences were observed between the sevoflurane and desflurane delirium groups. For the sevoflurane-induced patients, the sevoflurane delirium group had significantly lower power within 7.5-31.5 Hz (99.5% CI bootstrap analysis), reduced coherence over 8.9-23.8 Hz (99.5% CI bootstrap analysis), and lower PPC values in the alpha band (p < 0.005) compared with the sevoflurane non-delirium group. For the desflurane-induced patients, there were no significant differences in the EEG patterns between delirium and non-delirium groups. CONCLUSIONS: In normal patients without POD, sevoflurane demonstrates a higher power spectrum and prefrontal connectivity than desflurane. Furthermore, reduced frontal alpha power, coherence, and connectivity of intraoperative EEG could be associated with an increased risk of POD. These intraoperative EEG characteristics associated with POD are more noticeable in sevoflurane-induced anesthesia than in desflurane-induced anesthesia.

Impact of Enforcement of the Act to Improve Training Conditions and the Status of Medical Residents in Emergency Abdominal Surgery.

PURPOSE: In 2018, the Act to Improve Training Conditions and the Status of Medical Residents (AITR) was fully implemented in South Korea. This study aimed to investigate the effects of AITR implementation on the clinical outcomes of patients who underwent emergency abdominal surgery. MATERIALS AND METHODS: A total of 2571 patients who underwent emergency abdominal surgery after visiting the emergency room (ER) between 2015 and 2019 was included. Electronic medical records were retrospectively reviewed. In addition, a comparative analysis was performed for patient groups treated before and after AITR implementation. RESULTS: The median patient age was 48.0 years, and 49.2% of them were male. Appendicitis was the most common diagnosis (82.6%), followed by major abdominal emergencies (9.9%) and cholecystitis (7.5%). The median time from arrival to surgery was 439 min, and 52 (2.0%) patients died. A comparison of patients who underwent surgery before (pre-AITR; 1453, 56.5%) and after (post-AITR; 1118, 43.5%) AITR implementation revealed a significant difference in age, number of residents on a 24-h shift, and diagnosis. The time from ER arrival to surgery was not significantly longer after AITR implementation than before AITR implementation (434 min vs. 443 min, p=0.230). AITR was not a significant risk factor for mortality (p=0.225). CONCLUSION: The time from ER arrival to emergency surgery did not increase significantly after AITR implementation, and there was no difference in the patients' clinical outcomes.

Total Synthesis of Eliglustat via Diastereoselective Amination of Chiral para-Methoxycinnamyl Benzyl Ether.

Eliglustat (Cerdelga®, Genzyme Corp. Cambridge, MA, USA) is an approved drug for a non-neurological type of Gaucher disease. Herein, we describe the total synthesis of eliglustat 1 starting from readily available 1,4-benzodioxan-6-carbaldehyde via Sharpless asymmetric dihydroxylation and diastereoselective amination of chiral para-methoxycinnamyl benzyl ethers using chlorosulfonyl isocyanate as the key steps. Notably, the reaction between syn-1,2-dibenzyl ether 6 and chlorosulfonyl isocyanate in the mixture of toluene and hexane (10:1) afforded syn-1,2-amino alcohol 5 at a 62% yield with a diastereoselectivity > 20:1. This observation can be explained by competition between the SNi and the SN1 mechanisms, leading to the retention of stereochemistry.

Laparoscopic radical distal pancreatosplenectomy with celiac axis excision following neoadjuvant chemotherapy for locally advanced pancreatic cancer.

A recent successful prospective randomized control study comparing open distal pancreatectomy with laparoscopic distal pancreatectomy (LDP) has shown that LDP is a safe and effective surgical modality in treating left-sided pancreatic pathological conditions requiring surgical extirpation. With the accumulating surgical experiences and improved surgical techniques, we recently reported several cases of successful LDP in advanced pancreatic cancer following neoadjuvant chemotherapy. Herein, we report a case of LDP with celiac axis resection (LDP-CAR) in locally advanced pancreatic cancer (LAPC) following neoadjuvant chemotherapy. A 58-year-old female with LAPC was referred to our institution. Computed tomography (CT) findings revealed a 24-mm mass in the pancreatic body that showed celiac artery (CA), common hepatic artery abutment. There was no abutment with superior mesenteric artery, superior mesenteric vein, and portal vein. From these findings, Neoadjuvant chemotherapy (FORFIRINOX) was performed biweekly. After 8 cycles of chemotherapy, the tumor size was slightly decreased (24 mm to 16 mm), but still abutting to CA. After 14 cycles of chemotherapy, CT revealed the same tumor size (16 mm) still abutting to CA. LDP-CAR was performed. Intraoperative ultrasonography gastric perfusion and hepatic perfusion were confirmed using indocyanine green. The patient recovered without complications and was discharged from the hospital nine days after the surgery.

Trends of forest and ecosystem services changes in the Mescalero Apache Tribal Lands.

Forests are critically important for the provision of ecosystem services. The Sacramento Mountains of New Mexico, USA, are a hotspot for conservation management and the Mescalero Apache Tribe's homeland. The multiple ecosystem services and functions and its high vulnerability to changes in climate conditions make their forests of ecological, cultural, and social importance. We used data from the Mescalero Apache Tribal Lands (MATL) Continuous Forest Inventory over 30 yr to analyze changes in the structure and composition of ecosystems as well as trends in ecosystem services. Many provisioning, regulating, cultural, and supporting services were shared among the MATL ecosystems and were tied to foundational species dominance, which could serve as a reliable indicator of ecosystem functioning. Our analysis indicates that the MATL are in an ongoing transition from conifer forests to woodlands with declines in two foundation species, quaking aspen and ponderosa pine, linked to past forest management and changing climate. In addition, we detected a decrease in species richness and tree size variability, amplifying the risk of forest loss in a rapid climatic change. Continuous permanent plots located on a dense grid (1 × 1 km) such as the ones monitored by the Bureau of Indian Affairs are the most detailed data available to estimate forests multiresource transitions over time. Native lands across the USA could serve as the leading edge of detecting decadal-scale forest changes and tracking climate impacts.

Synthesis and biological evaluation of novel purinyl quinazolinone derivatives as PI3Kδ-specific inhibitors for the treatment of hematologic malignancies.

Phosphatidylinositol 3-kinases (PI3Ks) mediate intracellular signal transduction. Aberrant PI3K signaling is associated with oncogenesis and disease progression in solid tumors and hematologic malignancies. Idelalisib (1), a first-in-class PI3Kδ inhibitor for the treatment of hematologic malignancies, was developed, but its sales were limited by black box warnings due to unexpected adverse effects. Therefore, to overcome these adverse events, various quinazolinone derivatives were synthesized and evaluated in vitro based on their inhibitory activity against the PI3K enzyme and the viability of cell lines such as MOLT and SUDHL. Among them, 6f (IC50 = 0.39 nM) and 6m (IC50 = 0.09 nM) showed excellent enzyme activity, and 6m displayed an approximately four-fold higher selectivity for PI3Kγ/δ compared with Idelalisib (1). Furthermore, in vivo PK experiments with 6f and 6m revealed that 6f (AUClast = 81.04 h*ng/mL, Cmax = 18.34 ng/mL, Tmax = 0.5 h, t1/2 = 10.2 h in 1 mpk dose) had improved PK compared with 1. Finally, further experiments will be conducted with 6f selected as a candidate, and the potential for it to be developed as a treatment with good efficacy for hematologic malignancies will be determined.

A cell-based FcRn-dependent recycling assay for predictive pharmacokinetic assessment of therapeutic antibodies.

Aim: Evaluation of suitable pharmacokinetic properties is critical for successful development of IgG-based biotherapeutics. The prolonged half-lives of IgGs depend on the intracellular trafficking function of neonatal Fc receptor, which rescues internalized IgGs from lysosomal degradation and recycles them back to circulation. Results: Here, we developed a novel cell-based assay to quantify recycling of monoclonal antibodies in a transwell culture system that uses a cell line that stably expresses human neonatal Fc receptor. We tested seven therapeutic antibodies and showed that the recycling output of the assay strongly correlated with the clearance in humans. Conclusion: This recycling assay has potential application as a pharmacokinetic prescreening tool to facilitate development and selection of IgG-based candidate therapeutic monoclonal antibodies.

Sequential power analysis framework in assessing social forestry outcomes.

We extend the Actor-Centred Power framework to consider dimensions beyond the life of community natural resource management partnership initiatives by examining social forestry partnership projects in Indonesia. We do this by examining how power constellations realign across the temporal phases that operationalize project partnerships. We propose a sequential power analysis framework that examines power in three parts. The framework first proposes a method for historicizing actors into their power background. Second, we present mode for examining the arrival of a partnership scheme, which we call the power delivery phase. Third, we highlight approaches for examining the way power relations are adjusted, whether reinforced or reconfigured, by introducing an approach for examining programmatic outcomes of social forestry partnership schemes. This article thus provides broadly applicable but targeted guide for the researchers collecting data and seeking to make sense of power relations on community forest partnership schemes in various contexts. This framework is particularly useful for analysing equity and justice dimensions by highlighting who benefits and who loses.•Sequential Power Analysis (SPA) methodology is rooted in interest based and historical power framework.•SPA is consisted of three parts: power background, power delivery, and power adjustment•SPA framing provides a protocol for researchers to collect data.

Synthesis and biological evaluation of quinoxaline derivatives as specific c-Met kinase inhibitors.

A series of novel quinoxaline derivatives were synthesized and evaluated for their inhibitory activity against c-Met kinase enzyme. Most of the tested compounds exhibited potent inhibitory activity. All the synthesized quinoxaline compounds were further examined against c-Met overexpressed human gastric cancer cell line (MKN-45), which showed good inhibitory activity. Among the synthesized compounds, compound 4 exhibited better tumor growth inhibition in the animal model study; we also confirmed its acceptable drug property and highly selective target activity.

Comparison of electroencephalogram between propofol- and thiopental-induced anesthesia for awareness risk in pregnant women.

There have been few comparative studies using electroencephalogram (EEG) spectral characteristics during the induction of general anesthesia for cesarean section. This retrospective study investigated the differences in the depth of anesthesia through EEG analysis between propofol- and thiopental-induced anesthesia. We reviewed data of 42 patients undergoing cesarean section who received either thiopental (5 mg/kg) or propofol (2 mg/kg). EEG data were extracted from the bispectral index (BIS) monitor, and 10-second segments were selected from the following sections: 1) Stage I, BIS below 60 after induction; 2) Stage II, after intubation completion; 3) Stage III, end-tidal sevoflurane above 0 vol%. The risk of awareness was represented by the BIS and entropy measures. In Stage III, the thiopental group (n = 20) showed significantly higher BIS value than the propofol group (n = 22) (67.9 [18.66] vs 44.5 [20.63], respectively, p = 0.002). The thiopental group had decreased slow-delta oscillations and increased beta-oscillations as compared to the propofol group in Stages II and III (p < 0.05). BIS, spectral entropy, and Renyi permutation entropy were also higher in the thiopental group at Stages II and III (p < 0.05). In conclusion, frontal spectral EEG analysis demonstrated that propofol induction maintained a deeper anesthesia than thiopental in pregnant women.

Diné kinship as a framework for conserving native tree species in climate change.

Climate change affects all ecosystems but despite increasing recognition for the needs to integrate Indigenous knowledge with modern climate science, the epistemological differences between the two make it challenging. In this study, we present how Indigenous belief and knowledge system can frame the application of a modeling tool (Climate-Forest Vegetation Simulator). We focus on managing forest ecosystem services of the Diné (Navajo) Nation as a case study. Most Diné tribal members depend directly on the land for their livelihoods and cultural traditions. The forest plays a vital role in Diné livelihoods through social, cultural, spiritual, subsistence, and economic factors. We simulated forest dynamics over time under alternative climate change scenarios and management strategies to identify forest management strategies that will maintain future ecosystem services. We initialized the Climate-Forest Vegetation Simulator model with data from permanent plots and site-specific growth models under multiple management systems (no-management, thinning, burning, and assisted migration planting) and different climate scenarios (no-climate-change, RCP 4.5, RCP 6.0). Projections of climate change show average losses of basal area by over 65% by 2105, a shift in tree species composition to drier-adapted species, and a decrease in species diversity. While substantial forest loss was inevitable under the warming climate scenarios, the modeling framework allowed us to evaluate the management treatments, including planting, for conserving multiple tree species in mixed conifer forests, thus providing an anchor for biodiversity. We presented the modeling results and management implications and discuss how they can complement Diné kinship concepts. Our approach is a useful step for framing modern science with Indigenous Knowledge and for developing improved strategies to sustain natural resources and livelihoods.

Fire regime on a cultural landscape: Navajo Nation.

Fire has played an important role in the evolutionary environment of global ecosystems, and Indigenous peoples have long managed natural resources in these fire-prone environments. We worked with the Navajo Nation Forestry Department to evaluate the historical role of fire on a 50 km2 landscape bisected by a natural mountain pass. We used fifty 5-ha circular plots to collect proxy fire history data on fire-scarred trees, stumps, logs, and snags in a coniferous forest centered on a key mountain pass. The fire history data were categorized into three groups: All (all 50 plots), Corridor (25 plots closest to Buffalo Pass drainage), and Outer (remaining 25 plots, farther from pass). We assessed spatial and temporal patterns of fire recurrence and fire-climate relationships. The landscape experienced frequent fires from 1644, the earliest fire date with sufficient sample depth, to 1920, after which fire occurrence was interrupted. The mean fire interval (MFI) for fire dates scarring 10% or more of the samples was 6.25 years; there were 13 large-scale fires identified with the 25% filter with an MFI of 22.6 years. Fire regimes varied over the landscape, with an early reduction in fire occurrence after 1829, likely associated with pastoralism, in the outer uplands away from the pass. In contrast, the pass corridor had continuing fire occurrence until the early 20th century.Synthesis. Fires were synchronized with large-scale top-down climatic oscillations (drought and La Niña), but the spatially explicit landscape sampling design allowed us to detect bottom-up factors of topography, livestock grazing, and human movement patterns that interacted in complex ways to influence the fire regime at fine scales. Since the early 20th century, however, fires have been completely excluded. Fuel accumulation in the absence of fire and warming climate present challenges for future management.

Downregulation of NO and PGE2 in LPS-stimulated BV2 microglial cells by trans-isoferulic acid via suppression of PI3K/Akt-dependent NF-κB and activation of Nrf2-mediated HO-1.

Little is known about whether trans-isoferulic acid (TIA) regulates the production of lipopolysaccharide (LPS)-induced proinflammatory mediators. Therefore, we examined the effect of TIA isolated from Clematis mandshurica on LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in BV2 microglial cells. We found that TIA inhibited the production of LPS-induced NO and PGE2 without accompanying cytotoxicity in BV2 microglial cells. TIA also downregulated the expression levels of specific regulatory genes such as inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) by suppressing LPS-induced NF-κB activity via dephosphorylation of PI3K/Akt. In addition, we demonstrated that a specific NF-κB inhibitor PDTC and a selective PI3K/Akt inhibitor, LY294002 effectively attenuated the expression of LPS-stimulated iNOS and COX-2 mRNA, while LY294002 suppressed LPS-induced NF-κB activity, suggesting that TIA attenuates the expression of these proinflammatory genes by suppressing PI3K/Akt-mediated NF-κB activity. Our results showed that TIA suppressed NO and PGE2 production through the induction of nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent heme oxygenase-1 (HO-1). Taken together, our data indicate that TIA suppresses the production of proinflammatory mediators such as NO and PGE2, as well as their regulatory genes, in LPS-stimulated BV2 microglial cells, by inhibiting PI3K/Akt-dependent NF-κB activity and enhancing Nrf2-mediated HO-1 expression.

Factors driving deforestation in common-pool resources in northern Mexico.

The theory of collective action has been extensively used to explain the relationship between common-based property regimes and the conservation of natural resources. However, there are two key components of the theory that literature reports as puzzles in which no consensus exists about their effect on the performance of common-pool resources. These are group size and heterogeneity. This study analyzes the effects of these two key components on the effectiveness of community-based forestry, called ejidos, to protect their forest resources in northern Mexico. We used a multinomial logit model to determine the contribution of 16 explanatory variables to the dependent variable, a measure of success of ejidos defined by the presence of deforested, degraded, or forested conditions. The results show that corn yield, marginality, percent of forest area, total population, a forest value index, distance to markets, roads and towns, were all statistically significant in driving deforested conditions. Deforestation becomes more attractive for poor communities and as corn yield and distance to towns, roads, and markets decrease. In general, group size and heterogeneity had no significant effects on the presence of deforested conditions. Deforestation is driven by resource-specific characteristics, such as location and soil productivity, not by ejidos' attributes, such as total area or number of members. We argue that current institutional policies focusing on the structure of property right arrangements should be shifted (1) to provide better technology for land cultivation; (2) to reduce the marginality problem in poor communities; and (3) to strengthen local institutions.

Regional economic impacts of Grand Canyon river runners.

Economic impact analysis (EIA) of outdoor recreation can provide critical social information concerning the utilization of natural resources. Outdoor recreation and other non-consumptive uses of resources are viewed as environmentally friendly alternatives to extractive-type industries. While outdoor recreation can be an appropriate use of resources, it generates both beneficial and adverse socioeconomic impacts on rural communities. The authors used EIA to assess the regional economic impacts of rafting in Grand Canyon National Park. The Grand Canyon region of northern Arizona represents a rural US economy that is highly dependent upon tourism and recreational expenditures. The purpose of this research is twofold. The first is to ascertain the previously unknown regional economic impacts of Grand Canyon river runners. The second purpose is to examine attributes of these economic impacts in terms of regional multipliers, leakage, and types of employment created. Most of the literature on economic impacts of outdoor recreation has focused strictly on the positive economic impacts, failing to illuminate the coinciding adverse and constraining economic impacts. Examining the attributes of economic impacts can highlight deficiencies and constraints that limit the economic benefits of recreation and tourism. Regional expenditure information was obtained by surveying non-commercial boaters and commercial outfitters. The authors used IMPLAN input-output modeling to assess direct, indirect, and induced effects of Grand Canyon river runners. Multipliers were calculated for output, employment, and income. Over 22,000 people rafted on the Colorado River through Grand Canyon National Park in 2001, resulting in an estimated $21,100,000 of regional expenditures to the greater Grand Canyon economy. However, over 50% of all rafting-related expenditures were not captured by the regional economy and many of the jobs created by the rafting industry are lower-wage and seasonal. Policy recommendations are given for increasing the regional retention of rafting expenditures and for understanding both the beneficial and adverse impacts that accompany outdoor recreation in rural areas.