Assessment of lisdexamfetamine on executive function in rats: A translational cognitive research.

Executive function, including working memory, attention and inhibitory control, is crucial for decision making, thinking and planning. Lisdexamfetamine, the prodrug of d-amphetamine, has been approved for treating attention-deficit hyperactivity disorder and binge eating disorder, but whether it improves executive function under non-disease condition, as well as the underlying pharmacokinetic and neurochemical properties, remains unclear. Here, using trial unique non-matching to location task and five-choice serial reaction time task of rats, we found lisdexamfetamine (p.o) enhanced spatial working memory and sustained attention under various cognitive load conditions, while d-amphetamine (i.p) only improved these cognitive performances under certain high cognitive load condition. Additionally, lisdexamfetamine evoked less impulsivity than d-amphetamine, indicating lower adverse effect on inhibitory control. In vivo pharmacokinetics showed lisdexamfetamine produced a relative stable and lasting release of amphetamine base both in plasma and in brain tissue, whereas d-amphetamine injection elicited rapid increase and dramatical decrease in amphetamine base levels. Microdialysis revealed lisdexamfetamine caused lasting release of dopamine within the medial prefrontal cortex (mPFC), whereas d-amphetamine produced rapid increase followed by decline to dopamine level. Moreover, lisdexamfetamine elicited more obvious efflux of noradrenaline than that of d-amphetamine. The distinct neurochemical profiles may be partly attributed to the different action of two drugs to membranous catecholamine transporters level within mPFC, detecting by Western Blotting. Taken together, due to its certain pharmacokinetic and catecholamine releasing profiles, lisdexamfetamine produced better pharmacological action to improving executive function. Our finding provided valuable evidence on the ideal pharmacokinetic and neurochemical characteristics of amphetamine-type psychostimulants in cognition enhancement.

Nivolumab plus chemotherapy versus chemotherapy alone as first-line treatment for advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma: a cost-effectiveness analysis.

BACKGROUND: The aim of the study was to evaluate the cost-effectiveness of nivolumab plus chemotherapy as first-line treatment for patients with advanced gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma from the perspective of Chinese and US society. METHODS: To conduct the analysis, a state-transitioned Markov model, which included three mutually exclusive health states (progression-free survival (PFS), progressive disease (PD), and death), was developed. Cycle length was set at 3 weeks and lifetime horizon was set at 10 years. Costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) were calculated in the analysis. Willingness-to-pay (WTP) thresholds in the model were set at $37,653.00/QALY in China and $100,000.00/QALY in the US, respectively. Meanwhile, one-way sensitivity analyses and probabilistic sensitivity analyses were conducted to investigate the robustness of the model. RESULTS: Over a lifetime horizon, the ICERs of nivolumab plus chemotherapy versus chemotherapy alone were $430,185.04/QALY and $944,089.78/QALY in China and the US, respectively. Cost of nivolumab and utility for the PFS state had the most significant impact on ICERs both in the US and China based on the results of the one-way sensitivity analyses. In the probabilistic sensitivity analyses, the proportions of nivolumab plus chemotherapy being cost-effective compared with chemotherapy alone were 0%. CONCLUSIONS: In conclusion, nivolumab plus chemotherapy is unlikely to be a cost-effective treatment option compared with chemotherapy alone in the first-line setting of advanced gastric, GEJ, or esophageal adenocarcinoma.

Contrast-Enhanced Ultrasound Combined With 2D Strain Imaging and Histopathological Multimodal Assessment of Carotid Plaque Vulnerability.

OBJECTIVE: The aim of this study was to explore the value of contrast-enhanced ultrasound (CEUS) combined with 2-D strain imaging in evaluating carotid plaque vulnerability and the correlations among CEUS perfusion parameters, strain parameters and histopathological findings in different plaque segments. METHODS: Patients with carotid artery stenosis who underwent carotid endarterectomy (CEA) at the First Affiliated Hospital of Xinjiang Medical University from September 2020 to June 2021 underwent preoperative carotid artery 2-D ultrasonography and CEUS. The plaques were divided into three segments: the proximal end of the shoulder, central cap and distal end of the shoulder. The peak intensity (PI) value and strain rate parameters of the regions of interest were analyzed. Plaques were divided into a stable group (8 cases) and an unstable group (19 cases). The microvascular density (MVD) and vascular endothelial growth factor (VEGF) expression of each patch in the unstable group were analyzed. RESULTS: The peak strain during the systolic period in each plaque segment in both groups showed the following pattern: proximal end shoulder > distal end shoulder > top (p < 0.05). The PI value for CEUS is also represented. In the unstable group, the PI values of each segment of the plaque were positively correlated with the MVD, near-center PI value and VEGF average optical density value. The average optical density of each segment was positively correlated with the MVD (p < 0.05). There were positive correlations between the PI values of the proximal and distal shoulder and the strain values (p < 0.05), and the MVD value of each segment, VEGF value and strain value were positively correlated (p < 0.05). CONCLUSION: PI and the pathological tissue components represented by CEUS were positively correlated with the mechanical parameters of the plaque along the long axis. There may be overlap between the high shear stress area of the plaque and the neovascular aggregation area, and the combination of the two has certain significance for assessing the vulnerability of the plaque.

A comprehensive assessment of fungi in urban sewer biofilms: Community structure, environmental factors, and symbiosis patterns.

Sewers are important parts of wastewater treatment facilities and the fungal microbial communities therein make large contributions to the biotransformation of wastewater. Therefore, this experiment constructed an experimental sewer system and characterized the fungal microbial communities using ITS high-throughput sequencing technology in combination with network structure analysis and statistical correlation analysis methods. The results demonstrated that the overall diversity of the fungal communities gradually increased as growth phases progressed, but the dominant groups differed significantly among phases. In the early growth phase (RS1) the dominant genera were Apiotrichum and Inocybe, with abundances of 34% and 14%, respectively, while the middle and late growth phases (RS2 and RS3) were dominated by Candida, with a relative abundance of 47%-66%. CCA and correlation analysis showed that the fungal communities diversity from the artificial sewers had significant positive correlations with COD (r2 = 0.44, p < 0.05) and NH4+ (r2 = 0.64, p < 0.05) and that environmental factors significantly influenced the abundances of Fusarium and Aspergillus. Network analysis revealed differences in the fungal groups representing key nodes during different periods. Candida, Trichosporon, Fusarium, and Aspergillus played important roles in the microbial ecosystem of the simulated sewer systems. This study provides data-supported insight into the bacterial-fungal interaction mechanisms and associated pollutant biodegradation technologies in sewers.

Health risk assessment of PM2.5 on walking trips.

PM2.5 has an impact on residents' physical health during travelling, especially walking completely exposed to the environment. In order to obtain the specific impact of PM2.5 on walking, 368 healthy volunteers were selected and they were grouped according to gender and age. In the experiment, the heart rate change rate (HR%) is taken as test variable. According to receiver operating characteristic (ROC) curve, the travel is divided into two states: safety and risk. Based on this, a binary logit model considering Body Mass Index (BMI) is established to determine the contribution of PM2.5 concentration and body characteristics to travel risk. The experiment was conducted on Chang'an Middle Road in Xi'an City. The analysis results show that the threshold of HR% for safety and risk ranges from 31.1 to 40.1%, and that of PM2.5 concentration ranges from 81 to 168 µg/m3. The probability of risk rises 5.8% and 11.4%, respectively, for every unit increase in PM2.5 concentration and HR%. Under same conditions, the probability of risk for male is 76.8% of that for female. The probability of risk for youth is 67.5% of that for middle-aged people, and the probability of risk for people with BMI in healthy range is 72.1% of that for non-healthy range. The research evaluates risk characteristics of walking in particular polluted weather, which can improve residents' health level and provide suggestions for travel decision while walking.

Is the H2 economy realizable in the foreseeable future? Part III: H2 usage technologies, applications, and challenges and opportunities.

Energy enthusiasts in developed countries explore sustainable and efficient pathways for accomplishing zero carbon footprint through the H2 economy. The major objective of the H2 economy review series is to bring out the status, major issues, and opportunities associated with the key components such as H2 production, storage, transportation, distribution, and applications in various energy sectors. Specifically, Part I discussed H2 production methods including the futuristic ones such as photoelectrochemical for small, medium, and large-scale applications, while Part II dealt with the challenges and developments in H2 storage, transportation, and distribution with national and international initiatives. Part III of the H2 economy review discusses the developments and challenges in the areas of H2 application in chemical/metallurgical industries, combustion, and fuel cells. Currently, the majority of H2 is being utilized by a few chemical industries with >60% in the oil refineries sector, by producing grey H2 by steam methane reforming on a large scale. In addition, the review also presents the challenges in various technologies for establishing greener and sustainable H2 society.

α-Ketoglutarate Modulates Macrophage Polarization Through Regulation of PPARγ Transcription and mTORC1/p70S6K Pathway to Ameliorate ALI/ARDS.

As tissue-resident cells in the lung, alveolar macrophages display remarkable heterogeneity and play a crucial role in the development and control of septic acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Recent evidence suggests that α-ketoglutarate (α-KG) plays an important role in alternative activation of macrophage (M2) through metabolic and epigenetic reprogramming, and thus possesses anti-inflammatory properties. However, the underlying mechanisms of α-KG's effect on alveolar macrophage polarization and the potential effects of α-KG in ALI/ARDS remain unclear. Here, we examined the effects and mechanisms of α-KG on alveolar macrophage polarization, and investigated the possible effects of α-KG on lipopolysaccharide (LPS)-induced ALI/ARDS in a mouse model. We found that α-KG inhibited M1 macrophage polarization and promoted IL-4-induced M2 macrophage polarization in MH-S cells (a murine alveolar macrophage cell line). Further experiments showed that α-KG down-regulated the expression of M1-polarized marker genes and inhibited the activities of mammalian target of rapamycin complex 1 (mTORC1)/p70 ribosomal protein S6 kinase (p70S6K) signaling pathway in M1-polarized MH-S cells. Moreover, our results showed that α-KG promoted IL-4-induced M2 polarization of MH-S cells by augmenting nuclear translocation of peroxisome proliferator-activated receptor γ (PPARγ) and increasing expression of relevant fatty acid metabolic genes. Finally, using an LPS-induced ALI/ARDS mouse model, we found that α-KG ameliorated the LPS-induced inflammation and lung pathological damage, as well as α-KG pretreated mice had better clinical scores compared with the LPS group. These findings reveal new mechanisms of α-KG in regulating macrophage polarization which may provide novel strategies for the prevention and treatment of inflammatory diseases, including sepsis and septic ALI/ARDS.

A new comprehensive ecological risk index for risk assessment on Luanhe River, China.

With the enhancement of human activities which influence the physical and chemical integrity of ecosystem, it was bound to increase ecological risk to the ecosystem, and the risk assessment of small scale, single pollutant, or only on water quality have been not satisfied the demand of sustainable development of basin water environment. Based on the response relationship between environmental flow requirements guarantee ratio (GEF) and river ecological risk index (ERI), the Sediment Quality Guideline Quotient index (SQG-Q), and the Biotic Index (BI), we construct a new comprehensive ecological risk index (CERI) to evaluate the ecological risk of Luanhe River, China. According to the response relationship between GEF and ERI, upper and lower reaches of Luanhe River (Goutaizi to Hanjiaying) were at moderate risk level (0.41 < ERI < 0.56) in dry season, and all sites were at low risk level (ERI < 0.40) in wet season; considering the contribution of heavy metals contamination in the SQG-Q, the Luanhe River was the most influenced by higher levels of heavy metals in dry season and wet season; when this index was applied to the PAHs levels, only 30 and 20% of the sampling sites appeared to be moderately impacted (0.1 < SQG-Q PAHs < 0.5) by the PAHs in dry season and wet season, respectively. The results of BI showed that half of the sites appeared to be at moderately polluted level (50% of the sites, 0.25 < BI < 0.32) and heavily polluted level (Zhangbaiwan, BI = 0.36) in dry season, and 40% of the sites appeared to be at moderately polluted level (0.26 < BI < 0.29) in wet season. The CERI showed that 70 and 30% of the sites were at moderate risk level in dry season (0.25 < CERI < 0.36) and wet season (0.26 < CERI < 0.29), respectively. The results could give insight into risk assessment of water environment and decision-making for water source security.

Identifying the Uncertainty in Physician Practice Location through Spatial Analytics and Text Mining.

In response to the widespread concern about the adequacy, distribution, and disparity of access to a health care workforce, the correct identification of physicians' practice locations is critical to access public health services. In prior literature, little effort has been made to detect and resolve the uncertainty about whether the address provided by a physician in the survey is a practice address or a home address. This paper introduces how to identify the uncertainty in a physician's practice location through spatial analytics, text mining, and visual examination. While land use and zoning code, embedded within the parcel datasets, help to differentiate resident areas from other types, spatial analytics may have certain limitations in matching and comparing physician and parcel datasets with different uncertainty issues, which may lead to unforeseen results. Handling and matching the string components between physicians' addresses and the addresses of the parcels could identify the spatial uncertainty and instability to derive a more reasonable relationship between different datasets. Visual analytics and examination further help to clarify the undetectable patterns. This research will have a broader impact over federal and state initiatives and policies to address both insufficiency and maldistribution of a health care workforce to improve the accessibility to public health services.

Polycyclic aromatic hydrocarbons (PAHs) in water from three estuaries of China: Distribution, seasonal variations and ecological risk assessment.

The distribution, seasonal variations and ecological risk assessment of polycyclic aromatic hydrocarbons (PAHs) in water from three estuaries in Hai River Basin of China, which has been suffering from different anthropogenic pressures, were investigated. In three estuaries, the average concentration of ΣPAHs was the lowest in Luan River estuary, followed by Hai River estuary, and the highest in Zhangweixin River estuary. There were significant seasonal variations in ΣPAHs, the concentrations of ΣPAHs were higher in November than in May and August. The composition profiles of PAHs in different sites were significantly different, and illustrated seasonal variations. Generally, 2-ring (Nap) and 3-ring PAHs (Acp, Fl and Phe) were the most abundant components at most sampling sites in three estuaries. The PAHs in three estuaries were mainly originated from pyrogenic sources. A method based on toxic equivalency factors (TEFs) and risk quotient (RQ) was proposed to assess the ecological risk of ΣPAHs, with the ecological risk of individual PAHs being considered separately. The results showed that the ecological risks caused by ΣPAHs were high in Hai River estuary and Zhangweixin River estuary, and moderate in Luan River estuary. The mean values of ecological risk in August were lower than those in November. The contributions of individual PAHs to ecological risk were different in May, August and November. 3-ring and 4-ring PAHs accounted for much more ecological risk than 2-ring, 5-ring and 6-ring, although the contributions of 5-ring and 6-ring to ecological risk were higher than these to PAHs concentrations.

Assessment of Muscle Pain Induced by Elbow-Flexor Eccentric Exercise.

CONTEXT: Delayed-onset muscle soreness (DOMS) is a common muscle pain that many people experience and is often used as a model of acute muscle pain. Researchers have reported the effects of various interventions on DOMS, but different DOMS assessment protocols used in these studies make it difficult to compare the effects. OBJECTIVE: To investigate DOMS characteristics after elbow-flexor eccentric exercise to establish a standardized DOMS assessment protocol. DESIGN: Descriptive laboratory study. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: Ten healthy, untrained men (21-39 years). INTERVENTION(S): Participants performed 10 sets of 6 maximal isokinetic eccentric contractions of the elbow flexors. MAIN OUTCOME MEASURE(S): Indirect muscle-damage markers were maximal voluntary isometric contraction torque, range of motion, and serum creatine kinase activity. Muscle pain was assessed before exercise, immediately postexercise, and 1 to 5 days postexercise using (1) a visual analog scale (VAS), (2) a category ratio-10 scale (CR-10) when applying static pressure and palpation at different sites (3, 9, and 15 cm above the elbow crease), and (3) pressure-pain thresholds (PPTs) at 50 sites (pain mapping). RESULTS: Maximal voluntary isometric contraction and range of motion decreased and creatine kinase activity increased postexercise, indicating muscle damage. Palpation induced greater pain than static pressure, and longitudinal and transverse palpations induced greater pain than circular palpation (P < .05). The PPT was lower in the medial region before exercise, but the pain-sensitive regions shifted to the central and distal regions of the biceps brachii at 1 to 3 days postexercise (P < .05). The VAS was correlated with the CR-10 scale (r = 0.91, P < .05) but not with the PPT (r = -0.28, P = .45). CONCLUSIONS: The way in which muscles are assessed affects the pain level score. This finding suggests that pain level and pain threshold cannot be used interchangeably and that the central and distal regions of the biceps brachii should be included in DOMS assessment using the VAS, CR-10 scale, and PPT after elbow-flexor eccentric exercise.