Association of polypharmacy with clinical outcomes and healthcare utilization in older adults with cardiometabolic diseases: a retrospective cohort study.

BACKGROUND: Limited knowledge exists on the association between polypharmacy among older patients diagnosed with cardiometabolic diseases and the risk of clinical outcomes and healthcare utilization. AIM: This study aimed to estimate the impact of polypharmacy on clinical outcomes and healthcare utilization in older adults with cardiometabolic diseases. METHOD: A retrospective cohort analysis was performed using data from the Beijing Municipal Medical Insurance Database. The study focused on polypharmacy prescribing patterns in community-dwelling adults 65 years and older with cardiometabolic diseases. Polypharmacy was defined as the use of five or more medications on the index date. The primary outcome included clinical outcomes, including hospitalizations and emergency department visits. The secondary outcome focuses on hospital utilization, specifically medication costs and length of stay. RESULTS: The study included a cohort of 405,608 patients. Among these, the most frequently used drug classes in the polypharmacy and non-polypharmacy groups were HMG-CoA reductase inhibitors and dihydropyridines, respectively. After adjustment for covariates, polypharmacy was not associated with an increased risk of hospitalization (odds ratio [OR] 1.09, 95% confidence interval [CI] 0.95-1.26, p = 0.23) or ED visits (OR 1.28, 95% CI 0.97-1.68, p = 0.08). Similarly, no significant association was found with an increase in inpatient medication costs ($2,620.5, 95% CI $2387.3-$2894.3, p = 0.97) or length of stay (3.98 days, 95% CI 3.68-4.30 days, p = 0.79). However, polypharmacy was associated with higher medication costs in outpatient settings ($73.07, 95% CI $72-$74, p < 0.05) and ED visits ($51.2, 95% CI $44.5-$59.1, p < 0.05). CONCLUSION: Although polypharmacy is associated with increased healthcare costs in outpatient settings and ED visits, it does not significantly increase the risk of hospitalization or ED visits when properly managed.

[Relationship between lipid metabolism molecules in plasma and carotid atheroscle-rotic plaques, traditional cardiovascular risk factors, and dietary factors].

OBJECTIVE: To explore the relationship between lipid metabolism molecules in plasma and carotid atherosclerotic plaques, traditional cardiovascular risk factors and possible dietary related factors. METHODS: Firstly, among 1 312 community people from those who participated in a 10-year follow-up study of subclinical atherosclerosis cohort in Shijingshan District, Beijing, 85 individuals with 2 or more carotid soft plaques or mixed plaques and 89 healthy individuals without plaques were selected according to the inclusive and the exclusive criteria (< 70 years, not having clinical cardiovascular disease and other diseases, etc.). Secondly, 10 cases and 10 controls were randomly selected in the above 85 and 89 individuals respectively. Carotid plaques were detected using GE Vivid i Ultrasound Machine with 8L detector. Lipid metabolism molecules were detected by high performance liquid chromatography-mass spectrometry. The detection indexes included 113 lipid metabolism molecules. Traditional cardiovascular risk factors were collected by unified standard questionnaires, and dietary related factors were collected by main dietary frequency and weight scale. The difference of lipid metabolism molecules between the case group and the control group was analyzed by Wilcoxin rank test. In the control group, the Spearman correlation method was used to analyze the correlation between statistically significant lipid metabolism molecules and traditional cardiovascular risk factors and dietary factors. RESULTS: Among the 113 lipid metabolism molecules, 53 lipid metabolism molecules were detected. C24:0 sphingomyelin (SM), C22:0/ C24:0 ceramide molecules, C18:0 phosphoethanolamine (PE) molecules, and C18:0/C18:2 (Cis) phosphatidylcholine (PC) were significantly higher in the carotid atherosclerotic plaque group than in the control group. The correlation analysis showed that C24:0 SM was significantly positively correlated with low density lipoprotein cholesterol (LDL-C, r=0.636, P < 0.05), C18:2 (Cis) PC (DLPC) was significantly positively correlated with systolic pressure (r=0.733, P < 0.05), C18:0 PE was significantly positively correlated with high sensitivity C-response protein (r=0.782, P < 0.01), C22:0, C24:0 ceramide and C18:0 PE were negatively correlated with vegetable intake (r=-0.679, P < 0.05;r=-0.711, P < 0.05;r=-0.808, P < 0.01), C24:0 ceramide was also negatively correlated with beans food intake (r=-0.736, P < 0.05) in the control group. CONCLUSIONS: The increase of plasma C24:0 SM, C22:0, C24:0 ceramide, C18:0 PE, C18:2 (Cis) PC (DLPC), C18:0 PC (DSPC) may be new risk factors for human atherosclerotic plaques. These molecules may be related to blood lipid, blood pressure or inflammatory level and the intake of vegetables and soy products, but the nature of the association needs to be verified in a larger sample population.

An emerging strategy: probiotics enhance the effectiveness of tumor immunotherapy via mediating the gut microbiome.

The occurrence and progression of tumors are often accompanied by disruptions in the gut microbiota. Inversely, the impact of the gut microbiota on the initiation and progression of cancer is becoming increasingly evident, influencing the tumor microenvironment (TME) for both local and distant tumors. Moreover, it is even suggested to play a significant role in the process of tumor immunotherapy, contributing to high specificity in therapeutic outcomes and long-term effectiveness across various cancer types. Probiotics, with their generally positive influence on the gut microbiota, may serve as effective agents in synergizing cancer immunotherapy. They play a crucial role in activating the immune system to inhibit tumor growth. In summary, this comprehensive review aims to provide valuable insights into the dynamic interactions between probiotics, gut microbiota, and cancer. Furthermore, we highlight recent advances and mechanisms in using probiotics to improve the effectiveness of cancer immunotherapy. By understanding these complex relationships, we may unlock innovative approaches for cancer diagnosis and treatment while optimizing the effects of immunotherapy.

Optimal audio beam pattern synthesis for an enhanced parametric array loudspeaker.

A parametric array loudspeaker (PAL) generates highly directional audible sound in air with a small aperture size compared to a conventional loudspeaker. But in indoor applications, the long propagation distance of a PAL causes reflections, which disturbs the reproduction of narrow audio beams. Moreover, sound distortion appears along the off-axis direction due to the frequency dependence of the beam width. This study proposed an optimal audio beam pattern synthesis for a PAL-based convex optimization, which can design the audio beam of a PAL with an optimal solution. The proposed method overcame the mentioned limitations by applying it to a length-limited PAL for audio spot control and a multichannel PAL array for a constant beam width audio beam. In a length-limited PAL, the proposed method restricts the audio spot to a smaller region and weakens the sound leakage along the off-axis direction. Whereas in a multichannel PAL array, the proposed method also achieves a constant beam width near the radiator axis. Simulations and experiments verify the effectiveness of the proposed method, which will enhance the performance of a PAL in scenarios where control of the audio beam is required.

Native microbiome dominates over host factors in shaping the probiotic genetic evolution in the gut.

Probiotics often acquire potentially adaptive mutations in vivo, gaining new functional traits through gut selection. While both the host and microbiome can contribute to probiotics' genetic evolution, separating the microbiome and the host's contribution to such selective pressures remains challenging. Here, we introduced germ-free (GF) and specific pathogen-free (SPF) mouse models to track how probiotic strains, i.e., Lactiplantibacillus plantarum HNU082 (Lp082) and Bifidobacterium animalis subsp. lactis V9 (BV9), genetically evolved under selection pressures derived from host factors alone and both host and microbial ecological factors. Notably, compared to the genome of a probiotic strain before consumption, the host only elicited <15 probiotic mutations in probiotic genomes that emerged in the luminal environment of GF mice, while a total of 840 mutations in Lp082 mutants and 21,579 mutations in BV9 were found in SPF mice, <0.25% of those derived from both factors that were never captured by other experimental evolution studies, indicating that keen microbial competitions exhibited the predominant evolutionary force in shaping probiotic genetic composition (>99.75%). For a given probiotic, functional genes occurring in potentially adaptive mutations induced by hosts (GF mice) were all shared with those found in mutants of SPF mice. Collectively, the native microbiome consistently drove a more rapid and divergent genetic evolution of probiotic strains in seven days of colonization than host factors did. Our study further laid a theoretical foundation for genetically engineering probiotics for better gut adaptation through in vitro artificial gut ecosystems without the selection pressures derived from host factors.

Lactobacillus gasseri CKCC1913 mediated modulation of the gut-liver axis alleviated insulin resistance and liver damage induced by type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by dysregulation of lipid metabolism, insulin resistance, and gut microbiota disorder. Compared to drug interventions, probiotic interventions may have a more enduring effect without producing any side effects. Thus, the potential of probiotics as a therapeutic approach for diabetes and other metabolic disorders has gained increasing attention in recent years. In this study, we evaluated the therapeutic efficacy of Lactobacillus gasseri CKCC1913, a potential probiotic strain, in high-fat diet-induced insulin-resistant diabetes using the C57BL/6J mouse animal model. From the results, L. gasseri CKCC1913 has been shown to increase glucose tolerance, reduce fasting blood glucose levels in diabetic mice, and reduce the expression of pro-inflammatory cytokines, such as TNF-α and IL-6. Besides, L. gasseri CKCC1913 intervention effectively alleviated oxidative stress damage by increasing SOD activity, decreasing MDA levels, reducing insulin resistance, and improving dyslipidemia caused by diabetes. The potential mechanism of L. gasseri CKCC1913 in improving metabolic health and alleviating diabetes involves an increased abundance of beneficial bacteria, such as Parabacteroides merdae, which directly produce short-chain fatty acids that help regulate immune cells and reduce inflammation. SCFAs also enter the bloodstream and promote antioxidant enzyme activity in the liver, protecting against oxidative damage. Additionally, L. gasseri CKCC1913 influences local bacterial metabolism pathways, such as the superpathway of unsaturated fatty acid biosynthesis, leading to an increase in unsaturated fatty acids, increasing high-density lipoprotein cholesterol (HDL-C) levels and improving lipid metabolism and glucose control in diabetic mice. In summary, in this study, L. gasseri CKCC1913 and its potential impact on metabolic health highlight the promising potential of probiotics as a therapeutic approach for diabetes. Future research should focus on identifying the optimal dose and duration, investigating the long-term effects and mechanisms of action, and exploring the potential use of probiotics as an adjunct to other therapies or in preventing metabolic disorders.

The strigolactone receptor SlDWARF14 plays a role in photosynthetic pigment accumulation and photosynthesis in tomato.

KEY MESSAGE: Tomato DWARF14 regulates the development of roots, shoot branches and leaves, and also plays a role in photosynthetic pigment accumulation and photosynthetic capacity. Strigolactones (SLs) are a novel class of plant hormones. DWARF14 (D14) is the only SL receptor identified to date, but it is not functionally analyzed in tomato (Solanum lycopersicum). In the present study, we identified the potential SL receptor in tomato by bioinformatic analysis, which was designated as SlD14. SlD14 was expressed in roots, stems, flowers and developing fruits, with the highest expression level in leaves. sld14 mutant plants produced by the CRISPR/Cas9 system displayed reduced plant height and root biomass, increased shoot branching and altered leaf shape comparing with WT plants. The cytokinin biosynthetic gene ISOPENTENYLTRANSFERASE 3 (SlIPT3), auxin biosynthetic genes FLOOZY (SlFZY) and TRYPTOPHAN AMINOTRANSFERASE RELATED 1 (SlTAR1) and several auxin transport genes SlPINs, which are involved in branch formation, showed higher expression levels in the sld14 plant stem. In addition, sld14 plants exhibited light-green leaves, reduced chlorophyll and carotenoid contents, abnormal chloroplast structure and reduced photosynthetic capacity. Transcriptomic analysis showed that the transcript levels of six chlorophyll biosynthetic genes, three carotenoid biosynthetic genes and numerous chlorophyll a/b-binding protein genes were decreased in sld14 plants. These results suggest that tomato SL receptor gene SlD14 not only regulates the development of roots, shoot branches and leaves, but also plays a role in regulating photosynthetic pigment accumulation and photosynthetic capacity.

Number-dependent association of potentially inappropriate medications with clinical outcomes and expenditures among community-dwelling older adults: A population-based cohort study.

AIMS: The aim of this study was to investigate the prevalence of potentially inappropriate medication (PIM) prescribing and its number-dependent association (PIM = 1, 2, ≥3) with all-cause hospitalizations, emergency department (ED) visits, and medication expenditures in Beijing, China. METHODS: A retrospective cohort analysis was conducted to analyse PIM prescribing in community-dwelling older adults aged ≥65 years within the Beijing Municipal Medical Insurance Database (data from July to September 2016). The prevalence of PIMs was estimated based on the 2015 Beers Criteria. Logistic models were utilized to investigate the associations between PIM use and all-cause hospitalizations and ED visits. Generalized linear models with the logic link and gamma distribution were used to analyse associations between PIM use and medication expenditures. RESULTS: Among the 506 214 older adults, the prevalence of PIM was 38.07%. After adjusting for covariables, prescribing two and three or more PIMs was associated with increased risks of hospitalizations (PIM = 2: odds ratio [OR] 1.34, 95% confidence interval [CI]: 1.22-1.47; PIM ≥ 3: OR = 1.47, 95% CI: 1.32-1.63) and ED visits (PIM = 2: OR = 1.29, 95% CI 1.12-1.48; PIM ≥ 3: OR = 1.23, 95% CI: 1.04-1.44). Exposures to two and three or more PIMs were associated with higher medication expenditures for inpatient visits (PIM = 2: incidence rate ratio [IRR] = 1.08, 95% CI 1.01-1.16; PIM ≥ 3: IRR = 1.18, 95% CI: 1.08-1.28). Vasodilators were the most frequent PIM prescribing group among patients who were hospitalized or had to visit the ED. CONCLUSIONS: PIMs were prescribed at a high rate among community-dwelling older adults in Beijing. Two or more PIMs were associated with increased risks of hospitalizations, ED visits, and increased inpatient medication expenditures. Effective interventions are needed to target unnecessary and inappropriate medications in older adults.

Comparison of oral physiological and salivary rheological properties of Chinese Mongolian and Han young adults.

OBJECTIVES: Consumers' oral physiology and salivary properties are greatly dependent on dietary backgrounds, and this in turn may impact food perception and preferences. Scarce studies are available on the oral physiology and salivary rheology of Chinese participants with different dietary and ethnic backgrounds. DESIGN: This study examined two ethnic groups, Chinese Han and Chinese Mongolian healthy young adults, and explored the differences in oral physiology and salivary rheological properties. Official data suggested that Chinese Mongolians tend to consume more red meat and dairy, and Chinese Han tend to consume more carbohydrates. 200 Han and 104 Mongolian participants were evaluated for the oral physiological and salivary rheological parameters (maximum bite force of incisor and molar teeth, maximum tongue pressure and maximum oral volume; the surface tension, shear viscosity and extensional viscosity of unstimulated and stimulated whole saliva samples). RESULTS: Distinct differences between two ethnic groups were found, particularly in their bite forces and salivary physical properties. Chinese Mongolian participants had significantly higher incisor bite force (168 N) than Chinese Han (146 N). In addition, Chinese Han had significantly lower unstimulated whole saliva flow rate than Chinese Mongolians; and significantly higher salivary surface tension, shear viscosity and extensional viscosity, in both unstimulated and stimulated whole saliva samples. CONCLUSIONS: Chinese Han and Chinese Mongolian participants exhibited different oral physiological and salivary rheological properties; and considering the dietary differences between the two ethnicities, the findings from this study suggest possible associations between dietary habits and oral physiological & saliva rheological properties.

Oral physiological and biochemical characteristics of different dietary habit groups II: Comparison of oral salivary biochemical properties of Chinese Mongolian and Han Young adults.

Saliva is an important component of food oral processing affecting the initial digestion and the formation of food bolus. It has been speculated that salivary biochemical properties could directly influence one's dietary habits, and vice versa. To date, there are few studies that investigate the possible relationships between dietary habits and salivary biochemical properties in Chinese participants from different dietary background. This study examined two Chinese ethnical groups of very different culture of food consumption, Han and Mongolian healthy young participants, as research participants to explore the differences in salivary biochemical properties and possible associations with dietary preferences. Chinese Mongolians tend to consume more red meat and dairy products, and Chinese Han tend to consume more carbohydrates as suggested by official data; therefore, a total of 304 healthy participants (200 Han and 104 Mongolian) were recruited for salivary compositional analysis. Results showed that for Mongolian participants' unstimulated salivary lipolytic activity (0.10 U/mL) and stimulated salivary lipolytic activity (0.09 U/mL) are significantly higher than those of the Han (0.03 U/mL, 0.04 U/mL) (p < 0.01), but their stimulated salivary α-amylase activity (2733 U/mL) was significantly lower than that of Han (3596 U/mL) (p < 0.01). Unstimulated and stimulated salivary total protein content of Chinese Han participants were significantly higher than those of Mongolian participants (p < 0.0001, p = 0.043). These findings have showed our initial hypothesis of possible associations between dietary habits and salivary biochemical properties.