Advanced Glycation End Products and Health: A Systematic Review.

Advanced glycation end products (AGEs) have garnered significant attention due to their association with chronic diseases and the aging process. The prevalence of geriatric diseases among young individuals has witnessed a notable surge in recent years, potentially attributed to the accelerated pace of modern life. The accumulation of AGEs is primarily attributed to their inherent difficulty in metabolism, which makes them promising biomarkers for chronic disease detection. This review aims to provide a comprehensive overview of the recent advancements and findings in AGE research. The discussion is divided into two main sections: endogenous AGEs (formed within the body) and exogenous AGEs (derived from external sources). Various aspects of AGEs are subsequently summarized, including their production pathways, pathogenic mechanisms, and detection methods. Moreover, this review delves into the future research prospects concerning AGEs. Overall, this comprehensive review underscores the importance of AGEs in the detection of chronic diseases and provides a thorough understanding of their significance. It emphasizes the necessity for further research endeavors to deepen our comprehension of AGEs and their implications for human health.

SALVIANOLIC ACID A ATTENUATES ANGIOTENSIN II-INDUCED CARDIAC FIBROSIS THROUGH REGULATING THE TXNIP SIGNALING PATHWAY.

ABSTRACT: Cardiac fibrosis, characterized by excessive collagen accumulation in heart tissues, poses a significant clinical challenge in various heart diseases and complications. Although salvianolic acid A (Sal A) from Danshen ( Salvia miltiorrhiza ) has shown promise in the treatment of ischemic heart disease, myocardial infarction, and atherosclerosis, its effects on cardiac fibrosis remain unexplored. Our study investigated the efficacy of Sal A in reducing cardiac fibrosis and elucidated its underlying molecular mechanisms. We observed that Sal A demonstrated significant cardioprotective effects against Angiotensin II (Ang II)-induced cardiac remodeling and fibrosis, showing a dose-dependent reduction in fibrosis in mice and suppression of cardiac fibroblast proliferation and fibrotic protein expression in vitro . RNA sequencing revealed that Sal A counteracted Ang II-induced upregulation of Txnip, and subsequent experiments indicated that it acts through the inflammasome and ROS pathways. These findings establish the antifibrotic effects of Sal A, notably attenuated by Txnip overexpression, and highlight its significant role in modulating inflammation and oxidative stress pathways. This underscores the importance of further research on Sal A and similar compounds, especially regarding their effects on inflammation and oxidative stress, which are key factors in various cardiovascular diseases.

Loss of mGlu5 receptors in somatostatin-expressing neurons alters negative emotional states.

Subtype 5 metabotropic glutamate receptors (mGlu5) are known to play an important role in regulating cognitive, social and valence systems. However, it remains largely unknown at which circuits and neuronal types mGlu5 act to influence these behavioral domains. Altered tissue- or cell-specific expression or function of mGlu5 has been proposed to contribute to the exacerbation of neuropsychiatric disorders. Here, we examined how these receptors regulate the activity of somatostatin-expressing (SST+) neurons, as well as their influence on behavior and brain rhythmic activity. Loss of mGlu5 in SST+ neurons elicited excitatory synaptic dysfunction in a region and sex-specific manner together with a range of emotional imbalances including diminished social novelty preference, reduced anxiety-like behavior and decreased freezing during retrieval of fear memories. In addition, the absence of mGlu5 in SST+ neurons during fear processing impaired theta frequency oscillatory activity in the medial prefrontal cortex and ventral hippocampus. These findings reveal a critical role of mGlu5 in controlling SST+ neurons excitability necessary for regulating negative emotional states.

Breast Milk Excretion of Dinalbuphine Sebacate Injection Administered After Cesarean Section.

Ensuring the safety of analgesics during lactation is crucial for women of childbearing potential. Available data regarding the transfer of nalbuphine for postoperative acute pain via breast milk are limited to the postmarketing experience. This lactation study aimed to assess nalbuphine and dinalbuphine sebacate concentrations in breast milk from lactating women with postoperative pain treated with dinalbuphine sebacate extended-release injection (150 mg dinalbuphine sebacate/2 mL Naldebain). Breast milk was collected throughout the 5-day posthospitalization interval from 20 mothers injected with one dose of extended-release dinalbuphine sebacate intramuscularly. Maternal safety was assessed during the study period. Nalbuphine was detectable in 71% of milk samples collected from all mothers, whereas dinalbuphine sebacate was undetectable or below the quantitation limit (0.1 ng/mL). The mean nalbuphine concentration in milk was approximately 10.55 ng/mL, with the peak concentration reaching up to 12.7 ng/mL. The mean relative infant dose was 0.39% (coefficient of variation, 65%). The mean pain intensity at rest was reduced to mild pain from Day 2 morning to discharge. Overall, the maternal safety profile was tolerable. The breast milk of women who receive one dose of dinalbuphine sebacate injection postpartum contains low nalbuphine concentration. In addition, dinalbuphine sebacate injection potentially reduces maternal pain intensity during the first postpartum week and offers low toxicity risk among breastfed infants.

Instrument and Supply Variability: An Opportunity to Reduce the Carbon Footprint of the Operating Room.

INTRODUCTION: Reducing costs and carbon footprints are important, parallel priorities for the US health-care system. Within surgery, reducing the number of instruments that are sterilized and disposable supplies that are used for each operation may help achieve both goals. We wanted to measure the existing variability in surgical instrument and supply choices and assess whether standardization could have a meaningful cost and environmental impact. METHODS: We analyzed surgeon preference cards for common general surgery operations at our hospital to measure the number of sterilizable instrument trays and supplies used by each surgeon for each operation. From this data, we calculated supply costs, carbon footprint, and median operative time and studied the variability in each of these metrics. RESULTS: Among the ten operations studied, variability in sterilizable instrument trays requested on surgeon preference cards ranged from one to eight. Variability in disposable supplies requested ranged from 17 to 45. Variability in open supply costs ranged from $104 to $4184. Variability in carbon footprint ranged from 17 to 708 kg CO2e. If the highest-cost surgeon for each operation switched their preference card to that of the median-cost surgeon, $245,343 in open supply costs and 41,708 kg CO2e could be saved. CONCLUSIONS: There is significant variability in the instrument and supply choices of surgeons performing common general surgery operations. Standardizing this variability may lead to meaningful cost savings and carbon footprint reduction, especially if scaled across the entire health system.

Bicycle Data-Driven Application Framework: A Dutch Case Study on Machine Learning-Based Bicycle Delay Estimation at Signalized Intersections Using Nationwide Sparse GPS Data.

Data-driven approaches are helpful for quantitative justification and performance evaluation. The Netherlands has made notable strides in establishing a national protocol for bicycle traffic counting and collecting GPS cycling data through initiatives such as the Talking Bikes program. This article addresses the need for a generic framework to harness cycling data and extract relevant insights. Specifically, it focuses on the application of estimating average bicycle delays at signalized intersections, as this is an essential variable in assessing the performance of the transportation system. This study evaluates machine learning (ML)-based approaches using GPS cycling data. The dataset provides comprehensive yet incomplete information regarding one million bicycle rides annually across The Netherlands. These ML models, including random forest, k-nearest neighbor, support vector regression, extreme gradient boosting, and neural networks, are developed to estimate bicycle delays. The study demonstrates the feasibility of estimating bicycle delays using sparse GPS cycling data combined with publicly accessible information, such as weather information and intersection complexity, leveraging the burden of understanding local traffic conditions. It emphasizes the potential of data-driven approaches to inform traffic management, bicycle policy, and infrastructure development.

Transition to Reusable Surgical Gowns at a Hospital System.

This quality improvement study investigates the feasibility of transitioning back to reusable surgical gowns at a US tertiary hospital system and projected corresponding cost savings and solid waste reduction.

Knowledge Gaps in Anesthetic Gas Utilization in a Large Academic Hospital System: A Multicenter Survey.

Inhaled anesthetics account for a significant portion of the greenhouse gases generated by perioperative services within the healthcare systems. This cross-sectional study aimed to identify knowledge gaps and practice patterns related to carbon dioxide (CO2) absorbents and intraoperative delivery of fresh gas flows (FGF) for future sustainability endeavors. Secondary aims focused on differences in these knowledge gaps based on the level of training. Surveys were distributed at five large academic medical centers. In addition to site-specific CO2 absorbent use and practice volume and experience, respondents at each institution were queried about individual practice with FGF rates during anesthetic maintenance as well as the cost-effectiveness and environmental impact of different volatile anesthetics. Results were stratified and analyzed by the level of training. In total, 368 (44% physicians, 30% residents, and 26% nurse anesthetists) respondents completed surveys. Seventy-six percent of respondents were unaware or unsure about which type of CO2 absorbent was in use at their hospital. Fifty-nine percent and 48% of respondents used sevoflurane and desflurane with FGF ≥1 L/min, respectively. Most participants identified desflurane as the agent with the greatest environmental impact (89.9%) and a greater proportion of anesthesiologists correctly identified isoflurane as a cost-effective anesthetic (78.3%, p=0.02). Knowledge gaps about in-use CO2 absorbent and optimal FGF usage were identified within the anesthesia care team. Educational initiatives to increase awareness about the carbon emissions from anesthesia and newer CO2 absorbents will impact the environmental and economic cost per case and align anesthesia providers toward healthcare decarbonization.

A variety test platform for the standardization and data quality improvement of crop variety tests.

Variety testing is an indispensable and essential step in the process of creating new improved varieties from breeding to adoption. The performance of the varieties can be compared and evaluated based on multi-trait data from multi-location variety tests in multiple years. Although high-throughput phenotypic platforms have been used for observing some specific traits, manual phenotyping is still widely used. The efficient management of large amounts of data is still a significant problem for crop variety testing. This study reports a variety test platform (VTP) that was created to manage the whole workflow for the standardization and data quality improvement of crop variety testing. Through the VTP, the phenotype data of varieties can be integrated and reused based on standardized data elements and datasets. Moreover, the information support and automated functions for the whole testing workflow help users conduct tests efficiently through a series of functions such as test design, data acquisition and processing, and statistical analyses. The VTP has been applied to regional variety tests covering more than seven thousand locations across the whole country, and then a standardized and authoritative phenotypic database covering five crops has been generated. In addition, the VTP can be deployed on either privately or publicly available high-performance computing nodes so that test management and data analysis can be conveniently done using a web-based interface or mobile application. In this way, the system can provide variety test management services to more small and medium-sized breeding organizations, and ensures the mutual independence and security of test data. The application of VTP shows that the platform can make variety testing more efficient and can be used to generate a reliable database suitable for meta-analysis in multi-omics breeding and variety development projects.

A mixed-methods study on end-user perceptions of transitioning to reusable surgical gowns.

Background: Perioperative services contribute up to 70% of the US hospitals' solid waste generation. While surgical textiles are more environmentally friendly than their disposable counterparts, many US institutions have converted to disposable surgical wear in the last few decades. End-users' perception surrounding reusable textiles is currently unknown. Methods: Perioperative staff at the University of California San Francisco (UCSF) were surveyed to assess perceptions of reusable surgical gowns to guide potential implementation. The instrument included eight close-ended questions drawn from prior studies and a free-response section. The survey was piloted before dissemination. Descriptive statistics and qualitative inductive theme analysis were applied. Results: 205 participants or 19.8% of the workforce responded. 77.6% perceived reusable surgical gowns as better for the environment, while 34.1% were unsure or believed that switching to reusable surgical gowns would increase surgical site infections. If given an option, 39.8% preferred reusable gowns, 30.7% preferred disposable gowns, and 25.4% had no preference. Qualitatively, four themes were identified concerning reusable gowns' 1) functionality and safety, 2) user comfort, 3) environmental concern, and 4) cost, which hindered end-user buy-in. Laundering water utilization in a drought-prone area was of particular concern. Conclusions: While most perioperative staff in a US tertiary hospital believed reusable surgical gowns were environmentally friendly, ambivalence towards transitioning to reusable gowns stemmed from uncertainty in reusable textiles' environmental benefits, safety profile, and cost savings. These perceptions may prevent successful implementation of reusable surgical gowns and suggest a need for staff education and context-specific environmental impact analyses. Key message: End-user perceptions on transitioning to reusable surgical gowns are mixed and revolve around uncertainty in their environmental benefits, cost, and functionality, which may hinder their successful implementation.

Hereditary hemorrhagic telangiectasis with juvenile polyposis syndrome: a case report.

Hereditary hemorrhagic telangiectasis (HHT) and juvenile polyposis syndrome (JPS) are both relatively rare hereditary disorders. It has been reported that patients with SMAD4 mutations may suffer from both HHT and JPS, defined as JPS/HHT. To improve the understanding and diagnosis of these diseases, we herein report a case of a 17-year-old male with abdominal pain and hematochezia. Low-tension computed tomography (CT) of the small intestine showed intussusception. Combined with the patient's medical history of nasal bleeding and pulmonary arteriovenous fistula (pAVF) embolism, a final diagnosis of JPS/HHT was reached, according to the Curaçao Diagnostic Criteria. The possibility of JPS/HHT should be considered in patients with epistaxis and intussusception.

Salicylic Acid Enhances Cadmium Tolerance and Reduces Its Shoot Accumulation in Fagopyrum tataricum Seedlings by Promoting Root Cadmium Retention and Mitigating Oxidative Stress.

Soil cadmium (Cd) contamination seriously reduces the production and product quality of Tartary buckwheat (Fagopyrum tataricum), and strategies are urgently needed to mitigate these adverse influences. Herein, we investigated the effect of salicylic acid (SA) on Tartary buckwheat seedlings grown in Cd-contaminated soil in terms of Cd tolerance and accumulation. The results showed that 75-100 µmol L-1 SA treatment enhanced the Cd tolerance of Tartary buckwheat, as reflected by the significant increase in plant height and root and shoot biomass, as well as largely mitigated oxidative stress. Moreover, 100 µmol L-1 SA considerably reduced the stem and leaf Cd concentration by 60% and 47%, respectively, which is a consequence of increased root biomass and root Cd retention with promoted Cd partitioning into cell wall and immobile chemical forms. Transcriptome analysis also revealed the upregulation of the genes responsible for cell wall biosynthesis and antioxidative activities in roots, especially secondary cell wall synthesis. The present study determines that 100 µmol L-1 is the best SA concentration for reducing Cd accumulation and toxicity in Tartary buckwheat and indicates the important role of root in Cd stress in this species.

An Accessible Clinical Decision Support System to Curtail Anesthetic Greenhouse Gases in a Large Health Network: Implementation Study.

BACKGROUND: Inhaled anesthetics in the operating room are potent greenhouse gases and are a key contributor to carbon emissions from health care facilities. Real-time clinical decision support (CDS) systems lower anesthetic gas waste by prompting anesthesia professionals to reduce fresh gas flow (FGF) when a set threshold is exceeded. However, previous CDS systems have relied on proprietary or highly customized anesthesia information management systems, significantly reducing other institutions' accessibility to the technology and thus limiting overall environmental benefit. OBJECTIVE: In 2018, a CDS system that lowers anesthetic gas waste using methods that can be easily adopted by other institutions was developed at the University of California San Francisco (UCSF). This study aims to facilitate wider uptake of our CDS system and further reduce gas waste by describing the implementation of the FGF CDS toolkit at UCSF and the subsequent implementation at other medical campuses within the University of California Health network. METHODS: We developed a noninterruptive active CDS system to alert anesthesia professionals when FGF rates exceeded 0.7 L per minute for common volatile anesthetics. The implementation process at UCSF was documented and assembled into an informational toolkit to aid in the integration of the CDS system at other health care institutions. Before implementation, presentation-based education initiatives were used to disseminate information regarding the safety of low FGF use and its relationship to environmental sustainability. Our FGF CDS toolkit consisted of 4 main components for implementation: sustainability-focused education of anesthesia professionals, hardware integration of the CDS technology, software build of the CDS system, and data reporting of measured outcomes. RESULTS: The FGF CDS system was successfully deployed at 5 University of California Health network campuses. Four of the institutions are independent from the institution that created the CDS system. The CDS system was deployed at each facility using the FGF CDS toolkit, which describes the main components of the technology and implementation. Each campus made modifications to the CDS tool to best suit their institution, emphasizing the versatility and adoptability of the technology and implementation framework. CONCLUSIONS: It has previously been shown that the FGF CDS system reduces anesthetic gas waste, leading to environmental and fiscal benefits. Here, we demonstrate that the CDS system can be transferred to other medical facilities using our toolkit for implementation, making the technology and associated benefits globally accessible to advance mitigation of health care-related emissions.

Challenges to Student Interdisciplinary Learning Effectiveness: An Empirical Case Study.

In order to meet industrial demands, some colleges and universities have offered interdisciplinary programs that integrate design, engineering, and business. However, how many changes these programs have brought to students, and whether students participating in these programs have had better interdisciplinary ability than students involved in a single discipline study have always been questions that many researchers want to explore. In a university that offers an interdisciplinary program, we found that there is no significant difference in interdisciplinary integration ability between the students participating in the interdisciplinary program and the students involved in a single discipline study through quantitative comparisons of 91 student questionnaires and analyses of interviews with nine teachers of interdisciplinary courses and other related staff members. This may result from the students' lack of motivation, lack of prior experience, the influence of individual traits, the increase of learning pressure and academic burden, and the interference of disciplinary factors during interdisciplinary learning. The research finding is intended to improve student interdisciplinary learning effectiveness by facilitating interdisciplinary teachers' understanding of the influencing factors of student interdisciplinary learning, and by providing a reference for interdisciplinary teaching design.

GAHP: An integrated software package on genetic analysis with bi-parental immortalized heterozygous populations.

GAHP is a freely available software package for genetic analysis with bi-parental immortalized heterozygous and pure-line populations. The package is project-based and integrated with multiple functions. All operations and running results are properly saved in a project, which can be recovered when the project is re-open by the package. Four functionalities have been implemented in the current version of GAHP, i.e., 1) MHP: visualization of genetic linkage maps; 2) VHP: analysis of variance (ANOVA) and estimation of heritability on phenotypic data; 3) QHP: quantitative trait locus (QTL) mapping on both genotypic and phenotypic data; 4) SHP: simulation of bi-parental immortalized heterozygous and pure-line populations, and power analysis of QTL mapping. VHP and QHP can be conducted in individual populations, as well as in multiple populations by the combined analysis. Input files are arranged either in the plain text format with an extension name same as the functionality or in the MS Excel formats. Output files have the same prefix name as the input file, but with different extensions to indicate their contents. Three characters before the extension names stand for the types of populations used in analysis. In the interface of the software package, input files are grouped by functionality, and output files are grouped by individual or combined mapping populations. In addition to the text-format outputs, the constructed linkage map can be visualized per chromosome or for a number of selected chromosomes; line plots and bi-plots can be drawn from QTL mapping results and phenotypic data. Functionalities and analysis methods available in GAHP help the investigation of genetic architectures of complex traits and the mechanism of heterosis in plants.

AN INTER-COMPARISON OF PASSIVE DOSEMETERS FOR TERRESTRIAL GAMMA RADIATION MEASUREMENTS.

To evaluate the measurement method of passive dosemeters for terrestrial gamma radiation measurements. An inter-comparison of passive dosemeters for terrestrial gamma radiation measurements was organized alternately by the Japan Chemical Analysis Center, National Institute for Radiological Protection of Chinese Center for Disease Control and Prevention and Radiation Monitoring Technical Center of Ministry of Environmental Protection every 2 years. The procedures and exposure conditions of the field-exposure and reference irradiation test were provided by the organizer. During 2019-2020, the En values of Field-1 and Field-2 in three laboratories were lower than 1.0 and assigned 'acceptable' according to inter-comparison criteria. After the correction of the fading effect of dosemeter material, the En values of reference irradiation test (0.301 mGy, 1.000 mGy) in three laboratories were lower than 1.0 and assigned 'acceptable'.

Connectivity and synaptic features of hilar mossy cells and their effects on granule cell activity along the hippocampal longitudinal axis.

The hippocampus is an elongated brain structure which runs along a ventral-to-dorsal axis in rodents, corresponding to the anterior-to-posterior axis in humans. A glutamatergic cell type in the dentate gyrus (DG), the mossy cells (MCs), establishes extensive excitatory collateral connections with the DG principal cells, the granule cells (GCs), and inhibitory interneurons in both hippocampal hemispheres along the longitudinal axis. Although coupling of two physically separated GC populations via long-axis projecting MCs is instrumental for information processing, the connectivity and synaptic features of MCs along the longitudinal axis are poorly defined. Here, using channelrhodopsin-2 assisted circuit mapping, we showed that MC excitation results in a low synaptic excitation-inhibition (E/I) balance in the intralamellar (local) GCs, but a high synaptic E/I balance in the translamellar (distant) ones. In agreement with the differential E/I balance along the ventrodorsal axis, activation of MCs either enhances or suppresses the local GC response to the cortical input, but primarily promotes the distant GC activation. Moreover, activation of MCs enhances the spike timing precision of the local GCs, but not that of the distant ones. Collectively, these findings suggest that MCs differentially regulate the local and distant GC activity through distinct synaptic mechanisms. KEY POINTS: Hippocampal mossy cell (MC) pathways differentially regulate granule cell (GC) activity along the longitudinal axis. MCs mediate a low excitation-inhibition balance in intralamellar (local) GCs, but a high excitation-inhibition balance in translamellar (distant) GCs. MCs enhance the spiking precision of local GCs, but not distant GCs. MCs either promote or suppress local GC activity, but primarily promote distant GC activation.

Metal Tolerance Protein Encoding Gene Family in Fagopyrum tartaricum: Genome-Wide Identification, Characterization and Expression under Multiple Metal Stresses.

Metal tolerance proteins (MTP) as divalent cation transporters are essential for plant metal tolerance and homeostasis. However, the characterization and the definitive phylogeny of the MTP gene family in Fagopyrum tartaricum, and their roles in response to metal stress are still unknown. In the present study, MTP genes in Fagopyrum tartaricum were identified, and their phylogenetic relationships, structural characteristics, physicochemical parameters, as well as expression profiles under five metal stresses including Fe, Mn, Cu, Zn, and Cd were also investigated. Phylogenetic relationship analysis showed that 12 Fagopyrum tartaricum MTP genes were classified into three major clusters and seven groups. All FtMTPs had typical structural features of the MTP gene family and were predicted to be located in the cell vacuole. The upstream region of FtMTPs contained abundant cis-acting elements, implying their functions in development progress and stress response. Tissue-specific expression analysis results indicated the regulation of FtMTPs in the growth and development of Fagopyrum tataricum. Besides, the expression of most FtMTP genes could be induced by multiple metals and showed different expression patterns under at least two metal stresses. These findings provide useful information for the research of the metal tolerance mechanism and genetic improvement of Fagopyrum tataricum.

Surgeons' perspectives on operating room waste: Multicenter survey.

BACKGROUND: Waste is endemic in the U.S. health care system. Operating rooms are a source of significant solid waste. Surgeons are integral to many decisions in the operating room. METHOD: Online survey of surgeons at 2 major academic centers in the United States assessing perspectives on intraoperative waste and willingness to work to actively reduce intraoperative waste. RESULTS: We received responses from 219 surgeons: 90% agreed or strongly agreed that waste of sterile surgical items is an issue, and 95% agreed or strongly agreed to a willingness to change the operating room workflow to reduce waste. Surgeons estimated 26% of single-use, sterile supplies opened for surgery were unused at the end of the case. The barriers to waste reduction cited most frequently were: (1) lack of awareness of waste, (2) lack of concern for waste, and (3) lack of time to address the waste. CONCLUSION: Surgeons understand there is significant waste in the operating room and are willing to change their workflow to reduce waste. Changes in operating room practices that reduce waste will be beneficial to health systems' finances and their efforts to improve population health through a reduction in consumption and pollution. Efforts should be directed toward reducing operating room waste with an initial focus on the elimination of unnecessary waste of sterile surgical supplies. Further work is needed to determine the precise sources of perioperative waste and what initiatives can be implemented to reduce this burden while maintaining high-value patient care.