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There is little evidence in the literature about the relationship between frailty and falls in older adults. Our objective was to explore the relationship between frailty and falls, and to analyze the effect factors (e.g., gender, different frailty assessment tools, areas, level of national economic development, and year of publication) of the association between frailty and falls among older adults. Systematic review and meta-analysis. Cohort studies that evaluated the association between frailty and falls in the older adults were included. We excluded any literature outside of cohort studies. We did a systematic literature search of English databases PubMed, Scopus, Web of Science, EBSCOhost, and SciElO, as well as the Chinese databases CNKI, WANFANG, and VIP from 2001 until October 2022. The eligible studies were evaluated for potential bias using the Newcastle-Ottawa Scale (NOS). Study selection, data extraction and assessment of study quality were each conducted by two investigators. In Stata/MP 17.0 software, we calculated pooled estimates of the prevalence of falls by using a random-effects model, Subgroup analysis was conducted based on gender, different frailty assessment tools, areas, level of economic development, and year of publication. The results are presented using a forest plot. Twenty-nine studies were included in this meta-analysis and a total of 1,093,270 participants aged 65 years and above were enrolled. Among the older adults, frailty was significantly associated with a higher risk for falls, compared with those without frailty (combined RR-relative risk = 1.48, 95% CI-confidence interval: 1.27–1.73, I2=98.9%). In addition, the results of subgroup analysis indicated that men had a higher risk for falls than women among the older adults with frailty (RR 1.94, 95% CI: 1.18–3.2 versus RR 1.44, 95% CI: 1.24–1.67). Subgroup analysis by different frailty assessment tools revealed an increased risk of falls in older adults with frailty when assessed using the Frailty Phenotype (combined RR 1.32, 95%CI: 1.17–1.48), FRAIL score (combined RR 1.82, 95%CI: 1.36–2.43), and Study of Osteoporotic Fractures index (combined RR 1.54, 95%CI: 1.10–2.16). Furthermore, subgroup analysis by areas and level of national economic development found the highest fall risk in Oceania (combined RR 2.35, 95%CI: 2.28–2.43) and the lowest in Europe (combined RR 1.20, 95%CI: 1.05–1.38). Developed countries exhibited a lower fall risk compared to developing countries (combined RR 1.44, 95%CI: 1.21–1.71). Analysis by year of publication showed the highest fall risk between 2013–2019 (combined RR 1.79, 95%CI: 1.45–2.20) and the lowest between 2001–2013 (combined RR 1.21, 95%CI: 1.13–1.29). Frailty represents a significant risk factor for falls in older adults, with the degree of risk varying according to the different frailty assessment tools employed, and notably highest when using the FRAIL scale. Additionally, factors such as gender, areas, level of national economic development, and healthcare managers' understanding of frailty may all impact the correlation between frailty and falls. Thus, it's imperative to select suitable frailty diagnostic tools tailored to the specific characteristics of the population in question. This, in turn, facilitates the accurate identification of frailty in older adults and informs the development of appropriate preventive and therapeutic strategies to mitigate fall risk.

Treatment strategies for complex patients with pulmonary embolism (PE) are often debated given patient heterogeneity, multitude of available treatment modalities, and lack of consensus guidelines. Although multidisciplinary Pulmonary Embolism Response Teams (PERT) are emerging to address this lack of consensus, their impact on patient outcomes is not entirely clear. This analysis was conducted to compare outcomes of all patients with PE before and after PERT availability. We analyzed all adult patients admitted with acute PE diagnosed on computed tomography scans in the 18 months before and after the institution of PERT at a large tertiary care hospital. Among 769 consecutive inpatients with PE, PERT era patients had lower rates of major or clinically relevant nonmajor bleeding (17.0% vs 8.3%, p = 0.002), shorter time-to-therapeutic anticoagulation (16.3 hour vs 12.6 hour, p = 0.009) and decreased use of inferior vena cava filters (22.2% vs 16.4%, p = 0.004). There was an increase in the use of thrombolytics/catheter-based strategies, however, this did not achieve statistical significance (p = 0.07). There was a significant decrease in 30-day/inpatient mortality (8.5% vs 4.7%, p = 0.03). These differences in outcomes were more pronounced in intermediate and high-risk patients (mortality 10.0% vs 5.3%, p = 0.02). The availability of multidisciplinary PERT was associated with improved outcomes including 30-day mortality. Patients with higher severity of PE seemed to derive most benefit from PERT availability.

In principle, optical phase-sensitive amplifiers are known to be capable of realizing noiseless amplification, as well as improving the signal-to-noise-ratio of optical links by 3 dB compared to conventional, phase-insensitively amplified links. However, current state-of-the-art phase-sensitive amplifiers are still far from being practical, lacking, for example, significant noise performance improvement, broadband gain and modulation-format transparency. Here, we demonstrate experimentally, for the first time, an optical-fibre-based non-degenerate phase-sensitive amplifier link consisting of a phase-insensitive parametric copier followed by a phase-sensitive amplifier that provides broadband amplification, signal modulation-format independence, and nearly 6 dB link noise-figure improvement over conventional, erbium-doped fibre amplifier-based links. The PSA has a record-low 1.1 dB noise figure, and can be extended to work with multiple wavelength channels with modest system complexity. This concept can also be realized in other materials with third-order nonlinearities, and is useful in any attenuation-limited optical link. Scientists experimentally demonstrate an optical-fibre-based non-degenerate phase-sensitive amplifier link that offers broadband amplification, signal modulation-format independence and lower noise than links based on conventional erbium-doped fibre amplifiers.

This work provides a new method for pricing options under the generalized stochastic volatility models with Jacobi stochastic correlation. Our method is based on the observation that the generalized models belong to the class of polynomial diffusions and therefore the option prices can be efficiently computed via orthogonal polynomial expansions. We take the Heston and Schöbel-Zhu models with stochastic correlation as two specific examples and are able to derive the analytical formulas for the option prices. We also illustrate the accuracy of the proposed method through a number of numerical experiments.

The enhancer of zeste homolog 2 (EZH2) is upregulated and has an oncogenic role in several types of human cancer. However, the abnormalities of EZH2 and its underlying mechanisms in the pathogenesis of nasopharyngeal carcinoma (NPC) remain unknown. In this study, we found that high expression of EZH2 in NPC was associated closely with an aggressive and/or poor prognostic phenotype ( P <0.05). In NPC cell lines, knockdown of EZH2 by short hairpin RNA was sufficient to inhibit cell invasiveness/metastasis both in vitro and in vivo , whereas ectopic overexpression of EZH2 supported NPC cell invasive capacity with a decreased expression of E-cadherin. In addition, ablation of endogenous Snail in NPC cells virtually totally prevented the repressive activity of EZH2 to E-cadherin, indicating that Snail might be a predominant mediator of EZH2 to suppress E-cadherin. Furthermore, co-immunoprecipitation (IP), chromatin IP and luciferase reporter assays demonstrated that in NPC cells, (1) EZH2 interacted with HDAC1/HDAC2 and Snail to form a repressive complex; (2) these components interact in a linear fashion, not in a triangular fashion, that is, HDAC1 or HDAC2 bridge the interaction between EZH2 and Snail; and (3) the EZH2/HDAC1/2/Snail complex could closely bind to the E-cadherin promoter by Snail, but not YY1, to repress E-cadherin. The data provided in this report suggest a critical role of EZH2 in the control of cell invasion and/or metastasis by forming a co-repressor complex with HDAC1/HDAC2/Snail to repress E-cadherin, an activity that might be responsible, at least in part, for the development and/or progression of human NPCs.

Influenza A virus (IAV) is a common respiratory pathogen and a global cause of significant and often severe morbidity. Although inflammatory immune responses to IAV infections are well described, little is known about how neuroimmune processes contribute to IAV pathogenesis. In the present study, we employed surgical, genetic, and pharmacological approaches to manipulate pulmonary vagal sensory neuron innervation and activity in the lungs to explore potential crosstalk between pulmonary sensory neurons and immune processes. Intranasal inoculation of mice with H1N1 strains of IAV resulted in stereotypical antiviral lung inflammation and tissue pathology, changes in breathing, loss of body weight and other clinical signs of severe IAV disease. Unilateral cervical vagotomy and genetic ablation of pulmonary vagal sensory neurons had a moderate effect on the pulmonary inflammation induced by IAV infection, but significantly worsened clinical disease presentation. Inhibition of pulmonary vagal sensory neuron activity via inhalation of the charged sodium channel blocker, QX-314, resulted in a moderate decrease in lung pathology, but again this was accompanied by a paradoxical worsening of clinical signs. Notably, vagal sensory ganglia neuroinflammation was induced by IAV infection and this was significantly potentiated by QX-314 administration. This vagal ganglia hyperinflammation was characterized by alterations in IAV-induced host defense gene expression, increased neuropeptide gene and protein expression, and an increase in the number of inflammatory cells present within the ganglia. These data suggest that pulmonary vagal sensory neurons play a role in the regulation of the inflammatory process during IAV infection and suggest that vagal neuroinflammation may be an important contributor to IAV pathogenesis and clinical presentation. Targeting these pathways could offer therapeutic opportunities to treat IAV-induced morbidity and mortality.

High aerobic glycolysis not only provides energy to cancer cells, but also supports their anabolic growth. JMJD1A, a histone demethylase that specifically demethylates H3K9me1/2, is overexpressed in multiple cancers, including urinary bladder cancer (UBC). It is unclear whether JMJD1A could promote cancer cell growth through enhancing glycolysis. In this study, we found that downregulation of JMJD1A decreased UBC cell proliferation, colony formation and xenograft tumor growth. Knockdown of JMJD1A inhibited glycolysis by decreasing the expression of genes participated in glucose metabolism, including GLUT1, HK2, PGK1, PGM, LDHA and MCT4 . Mechanistically, JMJD1A cooperated with hypoxia inducible factor 1α (HIF1α), an important transcription factor for glucose metabolism, to induce the glycolytic gene expression. JMJD1A was recruited to the promoter of glycolytic gene PGK1 to demethylate H3K9me2. However, the JMJD1A (H1120Y) mutant, which loses the demethylase activity, failed to cooperate with HIF1α to induce the glycolytic gene expression, and failed to demethylate H3K9me2 on PGK1 promoter, suggesting that the demethylase activity of JMJD1A is essential for its coactivation function for HIF1α. Inhibition of glycolysis through knocking down HIF1α or PGK1 decelerated JMJD1A-enhanced UBC cell growth. Consistent with these results, a positive correlation between JMJD1A and several key glycolytic genes in human UBC samples was established by analyzing a microarray-based gene expression profile. In conclusion, our study demonstrates that JMJD1A promotes UBC progression by enhancing glycolysis through coactivation of HIF1α, implicating that JMJD1A is a potential molecular target for UBC treatment.

From a list of the top prescribed drugs in Canada, 11 pharmaceuticals and two metabolites were selected for study in municipal sewage treatment plant effluents and receiving waters. Wastewater samples were collected from 16 wastewater treatment plants across Southwest Nova Scotia including the Annapolis Valley, South Shore, and Metropolitan Halifax. Samples were also collected between 100 and 200 m downstream of effluent outflows. Seven pharmaceuticals were found above μg/L levels with their highest concentrations as follows: metformin (10.6 μg/L), acetaminophen (28.9 μg/L), paraxanthine (18.2 μg/L), cotinine (3.10 μg/L), caffeine (115 μg/L), naproxen (29.1 μg/L), and venlafaxine (2.65 μg/L). Metformin, paraxanthine, caffeine, naproxen, ramipril, and venlafaxine were detected in every wastewater effluent sample. Statistical analysis revealed significant differences in pharmaceutical occurrence by treatment methods, weak dependence of pharmaceutical concentrations on populations, and the co-occurrence of some pharmaceuticals. Experimental results might indicate the limitation of primary only treatment methods in breaking down pharmaceuticals.

Succinate is identified as a metabolite in innate immune signalling, which leads to enhanced interleukin-1β production during inflammation. Succinate is an innate immunity signal The bacterial endotoxin lipopolysaccharide activates macrophages, as part of the innate immunity response, by inducing a shift from oxidative to glycolytic metabolism. Gillian Tannahill et al . show here that lipopolysaccharide increases levels of the tricarboxylic acid cycle intermediate succinate in macrophages through a metabolic process not previously reported in macrophages, the 'GABA shunt'. Succinate in turn drives the key pro-inflammatory cytokine interleukin-1β. Macrophages activated by the Gram-negative bacterial product lipopolysaccharide switch their core metabolism from oxidative phosphorylation to glycolysis 1 . Here we show that inhibition of glycolysis with 2-deoxyglucose suppresses lipopolysaccharide-induced interleukin-1β but not tumour-necrosis factor-α in mouse macrophages. A comprehensive metabolic map of lipopolysaccharide-activated macrophages shows upregulation of glycolytic and downregulation of mitochondrial genes, which correlates directly with the expression profiles of altered metabolites. Lipopolysaccharide strongly increases the levels of the tricarboxylic-acid cycle intermediate succinate. Glutamine-dependent anerplerosis is the principal source of succinate, although the ‘GABA (γ-aminobutyric acid) shunt’ pathway also has a role. Lipopolysaccharide-induced succinate stabilizes hypoxia-inducible factor-1α, an effect that is inhibited by 2-deoxyglucose, with interleukin-1β as an important target. Lipopolysaccharide also increases succinylation of several proteins. We therefore identify succinate as a metabolite in innate immune signalling, which enhances interleukin-1β production during inflammation.