Metabolomics unveil key pathways underlying the synergistic activities of aztreonam and avibactam against multidrug-resistant Escherichia coli.

PURPOSE: Aztreonam/avibactam is effective against serious infections caused by Gram-negative bacteria including Enterobacterales harboring metallo-ß-lactamases. While the utility of this combination has been established in vitro and in clinical trials, the purpose of this study is to enhance our understanding of the underlying mechanism responsible for their activities through metabolomic profiling of a multidrug-resistant Escherichia coli clinical isolate. METHODS: Metabolomic analyses of time-dependent changes in endogenous bacterial metabolites in a clinical isolate of a multidrug-resistant E. coli treated with aztreonam and avibactam were performed. E. coli metabolomes were compared at 15 min, 1 h and 24 h following treatments with either avibactam (4 mg/L), aztreonam (4 mg/L), or aztreonam (4 mg/L) + avibactam (4 mg/L). RESULTS: Drug treatment affected 326 metabolites with magnitude changes of at least 2-fold, most of which are involved primarily in peptidoglycan biosynthesis, nucleotide metabolism, and lipid metabolism. The feedstocks for peptidoglycan synthesis were depleted by aztreonam/avibactam combination; a significant downstream increase in nucleotide metabolites and a release of lipids were observed at the three timepoints. CONCLUSION: The findings indicate that the aztreonam/avibactam combination accelerates structural damage to the bacterial membrane structure and their actions were immediate and sustained compared to aztreonam or avibactam alone. By inhibiting the production of crucial cell wall precursors, the combination may have inflicted damages on bacterial DNA.

Interventions based on salutogenesis for older adults: An integrative review.

AIMS: To synthesize the evidence of interventions based on salutogenesis for older adults. BACKGROUND: With the increasing tendency of global ageing and the progression of 'healthy ageing', salutogenesis has been adopted as a framework of health promotion for older adults. DESIGN: An integrative review following PRISMA guidelines. DATA SOURCES: Seven databases including PubMed, Cochrane Library, Web of Science, Embase, Scopus, PsycINFO and CINAHL Plus were systematically searched on 29 September 2022 and updated on 18 July 2023. RESULTS: Eighteen eligible studies were included in this review. Salutogenic-based interventions fell into three main categories: dialogue-based, health education courses based, and goal setting and achievement based. The intervention doses: length ranged from 4 weeks to 2 years, with most (n = 12) within 12 weeks; the duration of each session ranged from 30 to 150 min, with the majority (n = 7) within 1 h; the frequency ranged from five times weekly to three times in 10 months, and in six studies was once a week. Intervention providers were mostly multidisciplinary teams, while in four studies were nurses only. Most of the studies reported that salutogenic-based interventions could improve older adults' sense of coherence, quality of life, self-efficacy, self-management, meaning of life and mental health. CONCLUSIONS: This review synthesized the interventions based on salutogenesis for older adults, including salutogenesis application, intervention and its doses, intervention settings and providers, and intervention effects. Future research on the effectiveness of the intervention, the optimal dose of the intervention and the underlying mechanisms are still necessary to understand salutogenic-based interventions. NO PATIENT OR PUBLIC CONTRIBUTION: Not apply as it's a review paper. RELEVANCE TO CLINICAL PRACTICE: Salutogenic-based intervention is effective for older adults in different scenarios to improve their health outcomes. Nurses play a key role in salutogenic-based interventional programs and thus should be essential personnel as the intervention provider.

Factors associated with self-neglect from a salutogenic perspective among community-dwelling older adults: A cross-sectional correlational study.

OBJECTIVES: To identify the associated factors of self-neglect in older adults from a salutogenic perspective. METHODS: A cross-sectional correlational study was conducted in two communities in Beijing with 486 older adults recruited from April to December 2022. Data were collected by a set of questionnaires. RESULTS: Sense of coherence (ß=-0.138), socio-demographic generalized resistance resources (GRRs) (smoking: ß=0.156), social GRRs (living alone: ß=0.093), psychological GRRs (self-esteem: ß=-0.126), and motivational GRRs (powerful others locus of control: ß=-0.199, chance locus of control: ß=0.119) were all associated with self-neglect among older adults (p<0.05). CONCLUSIONS: Sense of coherence and GRRs are vital to improve self-neglect in older adults. It is suggested to increase the level of self-esteem and the tendency of the health locus of control to largely facilitate self-neglect management in older adults.

NIR Mitochondrial Fluorescent Probe for Visualizing SO2/Polarity in Drug Induced Inflammatory Mice.

SO2 and polarity are important microenvironmental parameters in cells, which are closely related to physiological activities in organisms. The intracellular levels of SO2 and polarity are abnormal in inflammatory models. To this end, a novel near-infrared fluorescent probe BTHP that can simultaneously detect SO2 and polarity was studied. BTHP can sensitively detect polarity change with emission peak change from 677 to 818 nm. BTHP can also detect SO2 with fluorescence change from red to green. After addition of SO2, the fluorescence emission intensity ratio I517/I768 of the probe increased by about 33.6 times. BTHP can determine bisulfite in single crystal rock sugar with high recovery rate (99.2%-101.7%). Fluorescence imaging of cells showed that BTHP could better target mitochondria and monitor exogenous SO2 in A549 cells. More importantly, BTHP has been successfully used for dual channel monitoring SO2 and polarity in drug-induced inflammatory cells and mice. In particular, the probe showed increased green fluorescence with the generation of SO2 and increased red fluorescence with the decrease of polarity in inflammatory cells and mice.

Perspectives and experiences of living with self-neglect among older adults: A systematic review and meta-synthesis.

PURPOSE: Given the global trajectory toward an aging population, renewed interest in the phenomena of self-neglect is needed if relevant stakeholders are to be adequately prepared for an expected increase in the number of elder self-neglect cases. This current study is designed to systematically review and synthesize the qualitative literature on the perspectives and experiences of older adults living with self-neglect. DESIGN: A narrative meta-synthesis was used. METHODS: Six English databases (PubMed, Web of Science, CINAHL Plus, Scopus, Embase, and PsycINFO) were comprehensively searched from inception to May 2022. The thematic synthesis method was applied to analyze and synthesize the findings of the included studies. The Critical Appraisal Skills Programme qualitative checklist was applied to evaluate the quality of the included studies. FINDINGS: A total of six qualitative studies were finally included with four studies conducted in the United States, one in Israel, and one in Ireland. Through meta-synthesis, five analytical themes were identified: attributes of self-neglect, life shaped by misery, insufficient social networks and resources, self-protection and preservation, and anchoring beliefs and practices. CONCLUSIONS: This qualitative synthesis provides profound insights into the self-neglect phenomenon from the standpoint of older adults with self-neglect and can provide guidance to relevant stakeholders on how to address elder self-neglect cases with respect to its assessment, reporting and management. Future research across geographical locations on the experiences of older adults with self-neglect are needed to provide a more global understanding of this significant and emerging public health issue. CLINICAL RELEVANCE: The development of future self-neglect management practices based on medical and sociocultural models of care can focus on supporting self-neglecters with positive coping mechanisms and supporting service providers with spiritual care competencies to ensure interventions achieve ethical principles of autonomy, beneficence, and nonmaleficence.

Changes in Lipidomics, Metabolomics, and the Gut Microbiota in CDAA-Induced NAFLD Mice after Polyene Phosphatidylcholine Treatment.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in most parts of the world. Although there is no first-line drug approved for the treatment of NAFLD, polyene phosphatidylcholine (PPC) is used by clinicians to treat NAFLD patients. This study aimed to evaluate the efficacy of PPC on a mice model of NAFLD, and to study the PPC's mechanism of action. The mice were fed a choline-deficient, L-amino acid-defined (CDAA) diet to induce NAFLD and were subsequently treated with PPC. The treatment effects were evaluated by the liver index, histopathological examination, and routine blood chemistry analyses. Lipidomics and metabolomics analyses of 54 samples were carried out using ultraperformance liquid chromatography (UPLC) coupled to a mass spectrometer to select for changes in metabolites associated with CDAA diet-induced NAFLD and the effects of PPC treatment. The intestinal flora of mice were extracted for gene sequencing to find differences before and after the induction of NAFLD and PPC treatment. PPC significantly improved the CDAA diet-induced NAFLD condition in mice. A total of 19 metabolites including 5 polar metabolites and 14 lipids showed marked changes. In addition, significant differences in the abundance of Lactobacillus were associated with NAFLD. We inferred that the protective therapeutic effect of PPC on the liver was related to the supplement of phosphatidylcholine, lysophosphatidylcholine, and sphingomyelin (PC, LPC, and SM, resectively) and acylcarnitine metabolism. This study developed a methodology for exploring the pathogenesis of NAFLD and can be extended to other therapeutic agents for treating NAFLD.

The role of frailty, social networks, and depression in self-neglect in an older Chinese population: A cross-sectional descriptive study.

OBJECTIVES: To identify the role of frailty, social networks, and depression in self-neglect in an older Chinese population. METHODS: The study was conducted in 521 older adults recruited from four community healthcare centers in a district in Beijing, China. Participants were investigated by a set of questionnaires. RESULTS: Frailty (ß=0.150, p=0.759) was not associated with self-neglect of older adults. Social isolation (ß=1.980, p<0.001) and depression (ß=3.606, p<0.001) were both factors associated with self-neglect in older adults. CONCLUSION: Management of depression and improvement of social networks of older adults should be incorporated into interventional strategies to effectively control self-neglect. Understanding self-neglect and its associated factors will ultimately contribute to the intervention development and well-being of older adults.

The association between loneliness and sleep quality among older adults: A systematic review and meta-analysis.

OBJECTIVE: To systematically review studies and explore the association between loneliness and sleep quality among older adults. METHODS: A comprehensive literature search was conducted in 8 databases from their inception to February 28, 2022. Studies that investigated the association between loneliness and sleep quality among older people were obtained. Comprehensive Meta-analysis was used to meta-analyze data in the included studies. RESULTS: In total, 16 studies with 23,485 participants were included in this review, and 6 of these studies were included in the meta-analysis. The meta-analysis showed that older adults who were lonely were significantly more likely to suffer from low sleep quality than their counterparts without loneliness (pooled OR = 1.750, 95% CI: 1.511-2.026, p < 0.01). CONCLUSIONS: Loneliness is associated with poor sleep quality among older adults. Loneliness reduction measures should be considered as one of the essential elements in sleep management programs for older people with low sleep quality.

Coumarin-based fluorescent probes toward viscosity in mitochondrion/lysosome.

Viscosity is an important microenvironmental indicator that plays an important role in the process of information transmission in various regions. Herein, two coumarin-based viscosity-sensitive fluorescent probes (CHB, CHN) were synthesized and the photophysical properties of the two probes were studied. The fluorescence quantum yields of CHB and CHN in glycerol can be as high as 25.2% and 18.3% respectively. The two probes can linearly detect viscosity in the viscosity logarithm range of 0.83-2.07, which is not interfered with pH, metal ions, anions and biomolecules. Fluorescent confocal cell experiments show CHB and CHN have good targeting ability to mitochondrion, lysosome, Endoplasmic reticulum and Golgi apparatus, and can be used to detect viscosity in mitochondrion/lysosome.

Adverse event profiles of PCSK9 inhibitors alirocumab and evolocumab: Data mining of the FDA adverse event reporting system.

BACKGROUND: Proprotein convertase subtilisin/kexin type (PCSK9) inhibitor is a new drug class approved for treating dyslipidemias. Herein, we aimed to investigate the safety profiles of PCSK9 inhibitors (alirocumab and evolocumab) using the Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: We included adverse event (AE) reports regarding alirocumab and evolocumab submitted to the FAERs between 2015Q3 to 2021Q1. Disproportionality analyses, including reporting odds ratio (ROR), were performed to detect risk signals from the FAERs data to identify potential drug-AE associations. A signal was considered when the lower limit of the 95% confidence interval of ROR exceeded 1 and ≥3 AEs were reported. The definition relied on system organ class and preferred terms established by the Medical Dictionary for Regulatory Activities. RESULTS: The FAERS database documented 31 475 reports regarding PCSK9 inhibitors (alirocumab and evolocumab) from July 1, 2015, to March 31, 2021. Although some differences were detected, alirocumab and evolocumab shared considerably similar safety profiles. The most significant RORs and most common reports were injection-site reactions (eg, injection-site pain, bruising, haemorrhage, erythema), muscle-related AEs (eg, myalgia, back pain, arthralgia, muscle spasms), influenza-like illness, pain and headache. CONCLUSION: Data mining of the FAERs is useful for examining PCSK9 inhibitor-induced AEs. Herein, our findings were largely consistent with clinical experience and could help clinicians improve the safety of PCSK9 inhibitors in clinical practice.

The pharmacokinetic characteristics and excretion studies of fucosterol from Sargasssum fusiforme in rats.

Fucosterol is the main phytosterol in brown algae with various pharmacological effects such as cholesterol-lowering, anticancer, hepatoprotection and neuroprotection. Little is known about the pharmacokinetics and excretion characteristics of fucosterol. In this study, a GC-MS method was developed and validated for the determination of fucosterol in rat plasma, urine and feces. The method effectively avoids the interference of Δ5 -avenasterol, a cis-trans-isomer of fucosterol derived from feed, by using a TG-5 capillary column (a nonpolar column with 5% phenyl-methylpolysilicone as stationary phase material). The linearity ranges were fucosterol 0.300-18.0 µg/ml (R2 = 0.9960) for plasma, 0.0500-2.50 µg/ml for the urine sample (R2 = 0.9963) and 0.100-8.00 µg/mg (R2 = 0.9923) for the feces sample. With good extraction recoveries and stability, this rapid and sensitive method was successfully applied to the pharmacokinetic and excretion studies of fucosterol in Sprague-Dawley rats. Fucosterol from Sargassum fusiforme had poor absorption and slow elimination with an absolute oral bioavailability of 0.74%, and was mainly eliminated through fecal excretion.

Lipidomic-based investigation into the therapeutic effects of polyene phosphatidylcholine and Babao Dan on rats with non-alcoholic fatty liver disease.

In recent years, with the improvement of people's living standards, non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in the world. In this paper, the metabolic disorders in Sprague Dawley (SD) rats were induced by a choline-deficient, l-amino acid-defined (CDAA) diet. The therapeutic effects of polyene phosphatidylcholine (PPC) and Babao Dan (BBD) on NAFLD were observed. Lipidomic analysis was performed using ultra-high-performance liquid chromatography-Orbitrap MS, and data analysis and lipid identification were performed using the software LipidSearch. Both PPC and BBD can reduce lipid accumulation in the liver and improve abnormal biochemical indicators in rats, including reduction of triglycerides, total cholesterol, alanine transaminase and aspartate transaminase in serum. In addition, lipids in rat serum were systematically analyzed by lipidomics. The lipidomic results showed that the most obvious lipids with abnormal metabolism in CDAA diet-induced rats were glycerides (triglycerides and diacylglycerols), phospholipids and cholesterol esters. Both BBD and PPC partly reversed the disturbance to lipids induced by the CDAA diet. PPC may be more effective than BBD in alleviating NAFLD because it has a better effect on inhibiting the abnormal accumulation of lipids and reducing the inflammatory reaction in the body.

A validated liquid chromatography-tandem mass spectrometry method for the determination of l-hyoscyamine in human plasma: Application in a clinical study.

Atropine is a racemic mixture of d- and l-hyoscyamine, but only l-hyoscyamine is the effective ingredient. In this study, a new, sensitive, stable, and selective LC/MS assay was developed for the determination of l-hyoscyamine and applied to a clinical study. The parent-product (m/z) transition pair of l-hyoscyamine was 290.1 → 124.1. Chromatographic separations were performed using a chiral MZ column (250 mm × 4.6 mm, 5.0 µm) by a stepwise gradient elution mode with n-hexane, isopropanol, and diethylamine as mobile phases. l-Hyoscyamine in human plasma was extracted by liquid-liquid extraction. This assay displayed a good linearity over a concentration range of 20.0-400 pg/mL for l-hyoscyamine. The accuracy of the validation assay for l-hyoscyamine ranged from -2.7% to 4.5%, and the precision was within 6.3% coefficient of variation. l-Hyoscyamine in human plasma remained stable at different storage conditions. The method has been successfully applied to plasma samples obtained from a safety study in humans.

"Jolly fat" or "sad fat": a systematic review and meta-analysis of the association between obesity and depression among community-dwelling older adults.

OBJECTIVE: To review the evidence and explore the association between obesity and depression in community-dwelling older adults. METHODS: We searched 6 electronic databases from inception to November 28, 2019. Observational studies investigating the association between obesity and depression among community-dwelling older adults aged 60 years or older were included. Two reviewers independently screened the studies, extracted the data and assessed the quality of the studies. The eligible studies were meta-analysed using the Comprehensive Meta-analysis Version 3.0. RESULTS: Among the 16,059 studies identified from these databases, 19 studies meeting the inclusion criteria were included, of which 14 were meta-analysed. Meta-analyses showed that older adults who were overweight (pooled odds ratio: 0.847, 95% CI:0.789-0.908, p < 0.001) or obesity (pooled odds ratio: 0.795, 95% CI:0.658-0.960, p = 0.017) - assessed using the body mass index - were significantly less likely to be depressed than their counterparts with a normal weight. No significant association between obesity (as measured via waist circumference) and depression was detected (pooled odds ratio: 0.722, 95% CI:0.465-1.119, p = 0.145) in this group population. The subgroup analyses demonstrated that both female and male older adults with overweight/obesity were significantly less likely to have depression. CONCLUSIONS: The "jolly fat" hypothesis is deemed to be applicable among community-dwelling older adults. Older adults might, therefore, be encouraged to increase their body weight above the normal level to be mentally healthy. Monitoring intentional weight loss among older adults should be reinforced for public health strategies.

Understanding professionals' perspectives and experiences of elder self-neglect: A systematic review and meta-synthesis of qualitative studies.

PURPOSE: To systematically review and synthesize the findings on various professionals' perspectives of elder self-neglect (ESN) and/or their experiences with ESN. DESIGN: A systematic qualitative review was used. METHODS: Primary qualitative studies published either in English or Chinese until August 2020 were systematically searched in the following databases: PubMed, Web of Science, Embase, CINAHL Plus, PsycINFO, Wanfang Data, and China National Knowledge Infrastructure (CNKI). FINDINGS: Eleven studies were included. Five subthemes including retaining a sense of normalcy/identity, service refusal, isolation, contributing factors in ESN, and manifestations and consequences of ESN were included in the overarching theme of ESN features. Another two subthemes, emotional and ethical dilemmas in caring for self-neglecters and management strategies, were included under the second overarching theme of complicated experiences managing cases of ESN. CONCLUSIONS: This qualitative synthesis provides a deep and comprehensive insight into professionals' perspectives and experiences of self-neglect in older adults. Understanding professionals' perspectives of ESN can help with the knowledge and theory development pertinent to this particular phenomenon. CLINICAL RELEVANCE: Findings are valuable in informing the provision of funds and structural, informational, and emotional support systems development for professionals managing ESN cases. Establishing a strong link between ESN case management and improved outcomes in older self-neglecters is essential to establish a definite need for the provision of support, resource, and stardardized guidelines for these professionals.

MFDroid: A Stacking Ensemble Learning Framework for Android Malware Detection.

As Android is a popular a mobile operating system, Android malware is on the rise, which poses a great threat to user privacy and security. Considering the poor detection effects of the single feature selection algorithm and the low detection efficiency of traditional machine learning methods, we propose an Android malware detection framework based on stacking ensemble learning-MFDroid-to identify Android malware. In this paper, we used seven feature selection algorithms to select permissions, API calls, and opcodes, and then merged the results of each feature selection algorithm to obtain a new feature set. Subsequently, we used this to train the base learner, and set the logical regression as a meta-classifier, to learn the implicit information from the output of base learners and obtain the classification results. After the evaluation, the F1-score of MFDroid reached 96.0%. Finally, we analyzed each type of feature to identify the differences between malicious and benign applications. At the end of this paper, we present some general conclusions. In recent years, malicious applications and benign applications have been similar in terms of permission requests. In other words, the model of training, only with permission, can no longer effectively or efficiently distinguish malicious applications from benign applications.

A comprehensive metabolomic and lipidomic analysis reveals the effect of temperature on flounder (Paralichthys olivaceus).

Temperature is a considerable stressor in aquatic environments. The objective of this study was to investigate the changes in endogenous compounds of flounder (Paralichthys olivaceus) at different temperatures based on a holistic metabolomic and lipidomic analysis. Accordingly, this study involved reversed-phase chromatography and hydrophilic interaction chromatography coupled with a mass spectrometry detection platform, and using a new database, and multivariate statistical analysis. In total, 954 unique masses were obtained, including 495 metabolites and 459 lipids, and 53 qualified differential metabolites were filtered. Specifically, among the highlighted biomarkers, 2'-Hydroxy-5'-methylacetophenone and FFA (17:1) were the metabolites and lipids with the largest Log2FC, respectively. In addition, 18-Hydroxycorticosterone showed the greatest downregulation. Hypoxia-inducible factor 1 signaling pathway, biosynthesis of amino acids, glycerophospholipid metabolism, and choline metabolism in cancer were enriched and noteworthy metabolic pathways, which were closely related. Overall, this study provides potential serum biomarkers and metabolic pathways for flounder as well as a reference for further studies on the physiological functions of flounder under different stressors.

A Redox-Activatable DNA Nanodevice for Spatially-Selective, AND-Gated Imaging of ATP and Glutathione in Mitochondria.

Design of biosensors capable of imaging ATP and glutathione (GSH) in mitochondria remains a challenge, despite their importance in elucidating their correlated pathophysiological events. Here, we report a new strategy that uses redox-activatable aptamer sensor design combined with nanoparticle-based targeting capability to achieve spatially controlled, AND-gated imaging of ATP and GSH in mitochondria. The DNA nanodevice was designed by the controlled assembly of the redox-responsive ATP aptamer probe on the nanoparticles and further decorated with mitochondria-targeting signals. We demonstrate that the system allows for mitochondria-specific, correlated imaging of ATP and GSH in living cells and in vivo. Furthermore, because the system can be lighted up only when meeting the "dual keys" (overexpressed ATP and GSH in mitochondria) simultaneously, the DNA nanodevice enables specific imaging of tumors in vivo with improved tumor-to-normal tissue ratio. This work illustrates the potential of the DNA nanodevices in the imaging of mitochondrial multivariate targets.

The Chinese version of the Abrams geriatric Self-neglect scale:Translation, validity, and reliability.

OBJECTIVES: To translate, cross-culturally adapt, and validate the Abrams Geriatric Self-neglect Scale (AGSS) for the older population in China. METHODS: The performance of the Chinese version of AGSS (C-AGSS) was evaluated among 334 older adults recruited from three community healthcare centers in Beijing, China. RESULTS: The Cronbach's α was 0.601 and the content validity index was 0.96 for the C-AGSS. The unidimensional model of the scale was supported by the confirmatory factor analysis with an excellent model fit. The concurrent validity was demonstrated by the significant correlation (r=0.614, p<0.001) between the C-AGSS and the Scale of the Elderly Self-neglect (Rural). The hypothesized validity and the discriminative validity of the C-AGSS were also approved. CONCLUSIONS: The C-AGSS has acceptable validity and reliability on self-neglect assessment in the Chinese older population. It can be used to classify and quantify the self-neglect of older adults in China.

Knowledge, attitudes, and barriers related to medication adherence of older patients with coronary heart disease in China.

OBJECTIVES: To investigate the knowledge, attitudes, and barriers related to medication adherence in older patients with coronary heart disease (CHD). METHODS: A total of 272 older patients with CHD were investigated by the Chinese version of the Medication Adherence Scale. The score ranges for the knowledge, attitudes, and barrier subscales were 0-30, 0-30, and 0-110, respectively. Higher scores indicate more knowledge, positive attitudes, and more barriers related to medication adherence. RESULTS: The median scores of knowledge, attitudes and barriers were 25.5, 28, and 8, respectively. Having stents, living alone, good financial status and fewer chronic diseases were related to more knowledge. Younger age, having no stent, and more chronic diseases were associated with more barriers. Patients with good financial status and higher age had more positive attitudes. CONCLUSIONS: Understanding older patients' knowledge, attitudes, and barriers related to medication adherence and their associated factors can help develop tailored interventions in medication adherence studies.