BACKGROUND
Prediabetes has garnered increasing attention due to its association with cardiovascular conditions, especially hypertension, which heightens the risk of prefrailty and frailty among older individuals.


METHODS
We screened elders with prefrail hypertension from March 2021 to January 2023. We assessed the correlation linking cognitive dysfunction (Montreal Cognitive Assessment score), insulin resistance (triglyceride-to-glucose index), and physical impairment (5-meter gait speed). Then, we measured the risk of developing frailty after a 1-year follow-up period, adjusting the outcome using multivariable Cox regression analysis. We also investigated the impact of administering 500 mg of metformin once daily to a subset of frail subjects for an additional 6 months.


RESULTS
We assessed the relationship between the triglyceride-to-glucose index and the Montreal Cognitive Assessment score, observing a significant correlation (r, 0.880; P<0.0001). Similarly, we analyzed the association between the triglyceride-to-glucose index and 5-meter gait speed, uncovering a significant link between insulin resistance and physical impairment (r, 0.809; P<0.0001). Prediabetes was found to significantly (P<0.0001) elevate the risk of frailty development compared with individuals without prediabetes by the end of the 1-year follow-up, a finding confirmed via multivariable analysis with Cox regression. Furthermore, among the subgroup of subjects who developed frailty, those who received metformin exhibited a significant decrease in frailty levels (P<0.0001).


CONCLUSIONS
Insulin resistance and prediabetes play substantial roles in the development of cognitive and physical impairments, highlighting their importance in managing hypertension, even before the onset of frank diabetes. Metformin, a well-established drug for the treatment of diabetes, has shown favorable effects in mitigating frailty.

Prediabetes Increases the Risk of Frailty in Older Adults With Prefrail Hypertension: Beneficial Effects of Metformin.

Global burden of disease attributable to metabolic risk factors in adolescents and young adults aged 15-39, 1990-2021

Evidence regarding the relationships between organophosphate flame retardants (OPFRs) and hyperuricemia and gout as well as the underlying mechanisms remains scarce, but some evidence indicates that inflammation might play a key role. Using an integrated approach, we aim to elucidate the associations of urinary metabolite OPFRs (m-OPFRs) with hyperuricemia and gout. Cross-sectional analyses using data from the National Health and Nutrition Examination Survey were performed to reveal the associations. Adults with complete data on five m-OPFRs with high detection frequencies and outcomes were enrolled. We used multivariate logistic regression, restricted cubic spline (RCS), and Bayesian kernel machine regression (BKMR) methods to account for single, nonlinear, and joint effects. The mediating effect of the inflammatory response was also estimated. Moreover, adverse outcome pathways (AOPs) based on network analysis were further constructed to reveal the underlying mechanism. Multivariate logistic models revealed that bis(2-chloroethyl) phosphate (BCEP) significantly increased risk of hyperuricemia (OR [95 % CI]: 1.165 [1.047, 1.296]) in the fully adjusted model. Elevated levels of bis(1-chloro-2-propyl) phosphate were associated with gout (OR [95 % CI]: 1.293 [1.015, 1.647]). No nonlinear relationship was observed in RCS. There was a positive association between mixed m-OPFRs and hyperuricemia risk in BMKR, with bis(1,3-dichloro-2-propyl) phosphate and BCEP being the main contributors (PIP > 0.5). We found that the inflammatory response significantly mediated the association between BCEP and hyperuricemia (P < 0.05). Network topology analysis identified seven genes and six phenotypes related to OPFR exposure and hyperuricemia. The AOP framework suggested that the inflammatory response, especially the activation of the TNF pathway, played a core role in the above relationships. Our results first revealed that individual and mixed OPFRs were associated with hyperuricemia, in which the inflammatory response plays an important role. Further longitudinal studies are warranted to consolidate or refute our main findings. 

The relationship of organophosphate flame retardants with hyperuricemia and gout via the inflammatory response: An integrated approach.

Gout flares have emerged as a significant public health concern. Colchicine (COL) is a first-line and standard drug for treating gout flares. However, its clinical use is limited due to various adverse effects. Besides, COL fails to adequately meet the needs of patients, particularly young patients. In this study, we investigate the therapeutic administration of Lactobacillus paracasei GY-1 (GY-1) to overcome the limitations of COL. Our results demonstrate that GY-1 attenuates COL toxicity in terms of body weight loss, decreased feed intake, mortality, reduced locomotor activity, colon shortening, increased oxidative stress, histological damage, and impaired gut permeability. Meanwhile, we demonstrate that GY-1 enhances the therapeutic effect for gout flares when combined with COL, as evidenced by the reduction in paw swelling, decreased levels of proinflammatory cytokines including IL-1β and TNF-α, and an increase in the anti-inflammatory cytokine IL-10. Additionally, the absolute quantification of the gut microbiota shows that GY-1 restores the gut microbiota imbalance caused by COL. Furthermore, GY-1 reduces the abundance of 4 Alistipes species and 6 Porphyromonadaceae species, which may be responsible for toxicity alleviation. At the same time, GY-1 increases the abundance of Bacteroides sartorii and Enterococcus sp., which may contribute to its therapeutic efficacy. This study demonstrates the feasibility of developing probiotic-based adjuvant therapy or bacteriotherapy for treating gout flares. To our knowledge, GY-1 is the first probiotic that could be used as an alternative synergetic agent with COL for the therapeutic treatment of gout flares.

Intestinal toxicity alleviation and efficacy potentiation through therapeutic administration of Lactobacillus paracasei GY-1 in the treatment of gout flares with colchicine.

Systemic lupus erythematosus (SLE) poses formidable challenges due to its multifaceted etiology while impacting multiple tissues and organs and displaying diverse clinical manifestations. Genetic and environmental factors contribute to SLE complexity, with relatively limited approved therapeutic options. Murine models offer insights into SLE pathogenesis but do not always replicate the nuances of human disease. This review critically evaluates spontaneous and induced animal models, emphasizing their validity and relevance to neuropsychiatric SLE (NPSLE). While these models undoubtedly contribute to understanding disease pathophysiology, discrepancies persist in mimicking some NPSLE intricacies. The lack of literature addressing this issue impedes therapeutic progress. We underscore the urgent need for refining models that truly reflect NPSLE complexities to enhance translational fidelity. We encourage a comprehensive, creative translational approach for targeted SLE interventions, balancing scientific progress with ethical considerations to eventually improve the management of NPSLE patients. A thorough grasp of these issues informs researchers in designing experiments, interpreting results, and exploring alternatives to advance NPSLE research.

Animal models of neuropsychiatric systemic lupus erythematosus: deciphering the complexity and guiding therapeutic development.

Objective To use data from the Global Burden of Disease (GBD) Study 2019 to report the global, regional and national rates and trends of annual incidence, point prevalence and years lived with disability (YLD) for gout in adolescents and young adults aged 15–39 years. Methods We conducted a serial cross-sectional study of gout burden in the young population aged 15–39 years using data from GBD Study 2019. We extracted rates per 100 000 population of incidence, prevalence and YLD of gout, then calculated their average annual percentage changes (AAPCs) at the global, regional and national level between 1990 and 2019 by sociodemographic index (SDI). Results The global gout prevalent cases in individuals aged 15–39 years was 5.21 million in 2019, with the annual incidence substantially increasing from 38.71 to 45.94 per 100 000 population during 1990–2019 (AAPC 0.61, 95% CI 0.57 to 0.65). This substantial increase was observed in all SDI quintiles (low, low-middle, middle, high-middle and high) and every age subgroup (15–19, 20–24, 25–29, 30–34 and 35–39 years). Males accounted for 80% of the gout burden. High-income North America and East Asia were facing a substantial increase in gout incidence and YLD simultaneously. Elimination of high body mass index can reduce 31.74% of the gout YLD globally in 2019, which varied from 6.97% to 59.31% regionally and nationally. Conclusion Gout incidence and YLD in the young population grew simultaneously and substantially in both developed and developing countries. Improving representative national-level data on gout, interventions for obesity and awareness in young populations are strongly suggested.

/pdf/global-regional-and-national-burdens-of-gout-in-the-young-1cj28lb7.pdf

Global, regional and national burdens of gout in the young population from 1990 to 2019: a population-based study

<h2>Summary</h2> China has hundreds of millions of children and adolescents aged 10–24 years, accounting for one-sixth of their total counterparts worldwide. We perform this study to clarify the priority of noncommunicable disease (NCD) control among youth in China via the Global Burden of Diseases Study 2019. The highest disability-adjusted life years (DALYs) from NCDs among youth in China remain in mental disorders, while the most increasing incidence is from diabetes and kidney diseases during 1990–2019. Bullying victimization and high BMI are the top risk factors for DALYs from mental disorders and diabetes mellitus, respectively. The most substantial gender differences are found for alcohol use disorders among the 20–24 age subgroup, which is also the top risk factor for neoplasm DALYs. Targeted interventions for NCDs among youth in China should focus on high body mass, alcohol usage, and bullying victimization, providing crucial information for resource-limited settings across the world. 

Burden of noncommunicable diseases among children and adolescents aged 10-24 years in China, 1990-2019: A population-based study.

BACKGROUND
Stroke is one of the leading causes of death among children, yet evidence on stroke incidence and prognosis in this population is largely neglected worldwide. The aim of this study was to estimate the latest burden of childhood stroke, as well as trends, risk factors, and inequalities from 1990 to 2019, at the global, regional, and national levels.


METHODS
The Global Burden of Disease 2019 study was utilized to evaluate the prevalence, incidence, years lived with disability, years of life lost (YLLs), and average annual percentage changes in stroke among populations aged 0 to 19 years from 1990 to 2019.


RESULTS
The global age-standardized incidence of stroke increased (average annual percentage change, 0.15% [95% uncertainty interval, 0.09%-0.21%]), while YLLs decreased substantially (average annual percentage change, -3.33% [95% uncertainty interval, -3.38% to -3.28%]) among children and adolescents between 1990 and 2019. Ischemic stroke accounted for 70% of incident cases, and intracerebral hemorrhage accounted for 63% of YLLs. Children under 5 years of age had the highest incidence of ischemic stroke, while adolescents aged 15 to 19 years had the highest incidence of hemorrhagic stroke. In 2019, low-income and middle-income countries were responsible for 84% of incident cases and 93% of YLLs due to childhood stroke. High-sociodemographic index countries had a reduction in YLLs due to stroke that was more than twice as fast as that of low-income and middle-income.


CONCLUSIONS
Globally, the burden of childhood stroke continues to increase, especially among females, children aged <5 years, and low-sociodemographic index countries, such as sub-Saharan Africa. The burden of childhood stroke is likely undergoing a significant transition from being fatal to causing disability. Global public health policies and the deployment of health resources need to respond rapidly and actively to this shift.

Global, Regional, and National Burdens of Stroke in Children and Adolescents From 1990 to 2019: A Population-Based Study.

Microglial cGAS-STING-TBK1 activation in paraventricular thalamus mediates sleep and emotional disturbances in lupus mice

The aim was to describe the diabetes regional burden, trends, and inequalities in the Western Pacific region.The Global Burden of Disease 2019 study was used to evaluate the prevalence, incidence, mortality, disability-adjusted life year (DALY) rates and average annual percentage changes (AAPCs) in diabetes in the Western Pacific region from 1990 to 2019. Cross-country inequalities in the DALY rates of diabetes were estimated between 1990 and 2019.The age-standardized incidence of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in the Western Pacific region increased from 2.6 to 3.8 per 100,000 population (AAPC, 0.97 [95% CI 0.84 to 1.1]) and from 174.8 to 207.3 per 100,000 population (AAPC, 0.63 [95% CI 0.48 to 0.77]) between 1990 and 2019, respectively. The most substantial increase in the incidence of T1DM and T2DM was found in the groups aged 70 years and older (AAPC, 2.38 [95% CI 2.19 to 2.58]) and 15-49 years (AAPC, 1.58 [95% CI 1.43 to 1.72]) from 1990 to 2019, respectively. Age-standardized DALYs for T1DM decreased but those for T2DM increased between 1990 and 2019. The relative concentration index of DALYs in T1DM and T2DM changed from 0.11 in 1990 to -0.08 in 2019 and from 0.03 in 1990 to -0.04 in 2019, respectively.Over three decades, diabetes incidence in the Western Pacific region rose substantially, with inequalities among countries. The burden shifted from higher to lower sociodemographic index countries. Diabetes remains a public health challenge, especially among young populations. Urgent interventions for prevention and early detection are crucial. 

Diabetes burden, trends, and inequalities in western pacific region, 1990–2019: A population-based study

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