Regulated Cell Death Pathways in Pathological Cardiac Hypertrophy.

Cardiac hypertrophy is characterized by an increased volume of individual cardiomyocytes rather than an increase in their number. Myocardial hypertrophy due to pathological stimuli encountered by the heart, which reduces pressure on the ventricular walls to maintain cardiac function, is known as pathological hypertrophy. This eventually progresses to heart failure. Certain varieties of regulated cell death (RCD) pathways, including apoptosis, pyroptosis, ferroptosis, necroptosis, and autophagy, are crucial in the development of pathological cardiac hypertrophy. This review summarizes the molecular mechanisms and signaling pathways underlying these RCD pathways, focusing on their mechanism of action findings for pathological cardiac hypertrophy. It intends to provide new ideas for developing therapeutic approaches targeted at the cellular level to prevent or reverse pathological cardiac hypertrophy.

Corrigendum: Serum TRPA1 mediates the association between olfactory function and cognitive function.

[This corrects the article DOI: 10.3389/fnagi.2024.1411031.].

Understanding the Relationships Between Physical Activity and Climate Change: An Umbrella Review.

BACKGROUND: Physical activity is crucial for maintaining health and preventing chronic diseases. However, climate conditions can impact physical activity patterns, and conversely, physical activity can impact climate change. This umbrella review aims to summarize the existing evidence regarding the relationships between physical activity and climate change, as revealed in previous reviews. METHODS: Systematic reviews and meta-analyses were analyzed. Searches were conducted across GreenFILE, PubMed, and Web of Science databases for peer-reviewed articles published in English. A 2-stage independent screening process was conducted, and methodological quality was assessed using the JBI framework. Standardized data extraction methods were then applied. RESULTS: Out of 1292 articles retrieved, 7 met all eligibility criteria and were included in the review. Three articles examined physical activity as a primary exposure, 3 focused on the impacts of climate change, and one considered both physical activity and climate change as primary exposures. CONCLUSIONS: Findings reveal an interplay between climate change and physical activity. While rising temperatures may prompt outdoor activities up to a certain temperature threshold, air pollution and extreme heat can have harmful effects. Active transportation and improved logistics around large-scale sporting events can mitigate climate change by reducing greenhouse gas emissions, but transportation systems linked to sports venues may increase emissions. Research on the reciprocal relationship between climate change and physical activity domains, and integrating the community into climate discussions, is crucial for equity, especially for marginalized communities. Incorporating climate adaptation and mitigation strategies in physical activity infrastructure to minimize environmental impacts is critical.

Dose-Response Independent and Joint Associations of Physical Activity and Sedentary Behavior With Mortality Risk in 40 156 Australian Adults With Coronary Heart Disease.

BACKGROUND: Little is known about the relationship between physical activity (PA) and sedentary behavior (SB) with death in people with coronary heart disease. The aim was to examine the independent and joint associations of PA and SB with death. METHODS AND RESULTS: This is a prospective cohort study including Australian participants aged ≥45 years with self-reported coronary heart disease (2006-2020). Self-reported PA (min/wk) and SB (h/d) were the exposures. Cardiac and all-cause death were the main outcomes. The cohort included 40 156 participants (mean age, 70.3 (SD, 10.3) years; 15 278 women [38%]). During a median follow-up of 11.1 (interquartile range, 6.2-14.4) years, 2497 cardiac and 12 240 all-cause deaths were recorded. Compared with no PA, a 20% to 30% lower risk of cardiac and all-cause death was associated with any level of PA. Walking and moderate to vigorous PA at 150 to 300 min/wk was associated with a 43% to 44% lower risk of cardiac death and 35% to 40% lower risk of all-cause death. Compared with ≥10.5 h/d of SB, participants who were sedentary for 7 to 10.4 h/d experienced an ≈25% reduced associated risk of cardiac and all-cause death. A 56% associated reduction in all-cause mortality risk was found if SB was limited to <3.4 h/d. If participants completed >150 min/wk moderate to vigorous PA and spent <7 h/d in SB, the associated risk of cardiac and all-cause death was reduced by ≈70%. CONCLUSIONS: All people with coronary heart disease should be encouraged to meet the PA guidelines and limit SB to <7 h/d, noting any increase in physical activity and decrease in SB is better than none to prevent premature death.

An iron-binding protein of entomopathogenic fungus suppresses the proliferation of host symbiotic bacteria.

BACKGROUND: Entomopathogenic fungal infection-induced dysbiosis of host microbiota offers a window into understanding the complex interactions between pathogenic fungi and host symbionts. Such insights are critical for enhancing the efficacy of mycoinsecticides. However, the utilization of these interactions in pest control remains largely unexplored. RESULTS: Here, we found that infection by the host-specialist fungus Metarhizium acridum alters the composition of the symbiotic microbiota and increases the dominance of some bacterial symbionts in locusts. Meanwhile, M. acridum also effectively limits the overgrowth of the predominant bacteria. Comparative transcriptomic screening revealed that the fungus upregulates the production of MaCFEM1, an iron-binding protein, in the presence of bacteria. This protein sequesters iron, thereby limiting its availability. Functionally, overexpression of MaCFEM1 in the fungus induces iron deprivation, which significantly suppresses bacterial growth. Conversely, MaCFEM1 knockout relieves the restriction on bacterial iron availability, resulting in iron reallocation. Upon ΔMaCFEM1 infection, some host bacterial symbionts proliferate uncontrollably, turning into opportunistic pathogens and significantly accelerating host death. CONCLUSIONS: This study elucidates the critical role of pathogenic fungal-dominated iron allocation in mediating the shift of host microbes from symbiosis to pathogenicity. It also highlights a unique biocontrol strategy that jointly exploits pathogenic fungi and bacterial symbionts to increase host mortality. Video Abstract.

Clinical efficacy of unilateral laminotomy for bilateral decompression in the treatment of adjacent segment disease after lumbar fusion.

Objective: To assess the clinical impact of unilateral laminotomy for bilateral decompression (ULBD) in managing patients with adjacent vertebrae following lumbar fusion. Methods: A retrospective analysis was conducted on 21 patients, with a mean age of 67.4 years, who underwent ULBD for adjacent vertebra disease at our department from January 2021 to November 2023. We reviewed demographic data, surgical techniques, imaging studies, and patient-reported outcomes. The study compared Visual Analog Scale (VAS) scores, Numeric Rating Scale (NRS) scores, Japanese Orthopaedic Association (JOA) scores, Short Form-36 (SF-36) scores, and imaging outcomes before surgery, immediately post-surgery, and at 1 month, 6 months, and 12 months post-surgery. Results: Evaluation of 21 patients with adjacent segment disease (ASD) (13 males, 8 females; mean age 67.42 years) was performed with follow-ups at various intervals post-surgery. Postoperative VAS, NRS, JOA, and SF-36 scores showed significant improvements compared to preoperative scores. Immediately after surgery, there were significant improvements in NRS score (2.76 ± 0.70 vs. 3.71 ± 0.85, P < 0.05) and JOA score (15.38 ± 1.02 vs. 9.29 ± 1.01, P < 0.05) compared to preoperative scores. Similarly, at 12 months post-surgery, significant improvements were observed in NRS score (1.52 ± 0.51 vs. 3.71 ± 0.85, P < 0.05) and JOA score (25.0 ± 1.10 vs. 9.29 ± 1.01, P < 0.05) compared to preoperative scores. The clinical satisfaction rate was 95.0% among all patients, with postoperative imaging examinations revealing a significant decompression effect. No complications were reported among the surgical patients. Conclusions: This study suggests that endoscopic ULBD can be a safe and effective technique for managing symptomatic ASD, providing satisfactory clinical outcomes for patients with ASD. Endoscopic ULBD may serve as an alternative treatment option for ASD with lumbar stenosis.

Functional investigation and two-sample Mendelian randomization study of primary biliary cholangitis hub genes.

BACKGROUND: The identification of specific gene expression patterns is crucial for understanding the mechanisms underlying primary biliary cholangitis (PBC) and finding relevant biomarkers for diagnosis and therapeutic evaluation. AIM: To determine PBC-associated hub genes and assess their clinical utility for disease prediction. METHODS: PBC expression data were obtained from the Gene Expression Omnibus database. Overlapping genes from differential expression analysis and weighted gene co-expression network analysis (WGCNA) were identified as key genes for PBC. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses were performed to explore the potential roles of key genes. Hub genes were identified in protein-protein interaction (PPI) networks using the Degree algorithm in Cytoscape software. The relationship between hub genes and immune cells was investigated. Finally, a Mendelian randomization study was conducted to determine the causal effects of hub genes on PBC. RESULTS: We identified 71 overlapping key genes using differential expression analysis and WGCNA. These genes were primarily enriched in pathways related to cytokine-cytokine receptor interaction, and Th1, Th2, and Th17 cell differentiation. We utilized Cytoscape software and identified five hub genes (CD247, IL10, CCL5, CCL3, and STAT3) in PPI networks. These hub genes showed a strong correlation with immune cell infiltration in PBC. However, inverse variance weighting analysis did not indicate the causal effects of hub genes on PBC risk. CONCLUSION: Hub genes can potentially serve as valuable biomarkers for PBC prediction and treatment, thereby offering significant clinical utility.

The co-benefits of active travel interventions beyond physical activity: a systematic review.

Active travel is a widely recognised strategy for promoting active living but its co-benefits beyond increasing physical activity, such as broader health, environmental, and social benefits, have rarely been synthesised. We conducted a systematic review to examine the co-benefits of active travel interventions. Following a preregistered protocol (PROSPERO CRD42022359059), we identified 80 studies for the search period from Jan 1, 2000, to Sept 13, 2022. Across studies, there was consistent evidence that active travel interventions offered co-benefits beyond physical activity. Particularly, 25 (71%) of 35 studies favoured improved safety outcomes, 20 (67%) of 30 showed improved health, 17 (85%) of 20 supported economic benefits, 16 (84%) of 19 highlighted improved transport quality, 12 (92%) of 13 showed environmental benefits, and four (80%) of five documented social benefits. Despite the overall low-certainty evidence, mostly limited by the quasi-experimental design and natural-experimental design of many of the studies, active travel interventions offer unique opportunities to engage stakeholders across sectors to jointly address major societal issues, such as physical inactivity, traffic safety, and carbon emissions. This evidence can inform the design, implementation, and evaluation of active travel interventions.

Risk factors and clinical significance of posterior slip of the proximal vertebral body after lower lumbar fusion.

BACKGROUND: Adjacent segment disease (ASD) after fusion surgery is frequently manifests as a cranial segment instability, disc herniation, spinal canal stenosis, spondylolisthesis or retrolisthesis. The risk factors and mechanisms of ASD have been widely discussed but never clearly defined. AIM: To investigate the risk factors and clinical significance of retrograde movement of the proximal vertebral body after lower lumbar fusion. METHODS: This was a retrospective analysis of the clinical data of patients who underwent transforaminal lumbar interbody fusion surgery between September 2015 and July 2021 and who were followed up for more than 2 years. Ninety-one patients with degenerative lumbar diseases were included (22 males and 69 females), with an average age of 52.3 years (40-73 years). According to whether there was retrograde movement of the adjacent vertebral body on postoperative X-rays, the patients were divided into retrograde and nonretrograde groups. The sagittal parameters of the spine and pelvis were evaluated before surgery, after surgery, and at the final follow-up. At the same time, the Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS) were used to evaluate the patients' quality of life. RESULTS: Nineteen patients (20.9%) who experienced retrograde movement of proximal adjacent segments were included in this study. The pelvic incidence (PI) of the patients in the retrograde group were significantly higher than those of the patients in the nonretrograde group before surgery, after surgery and at the final follow-up (P < 0.05). There was no significant difference in lumbar lordosis (LL) between the two groups before the operation, but LL in the retrograde group was significantly greater than that in the nonretrograde group postoperatively and at the final follow-up. No significant differences were detected in terms of the |PI-LL|, and there was no significant difference in the preoperative lordosis distribution index (LDI) between the two groups. The LDIs of the retrograde group were 68.1% ± 11.5% and 67.2% ± 11.9%, respectively, which were significantly lower than those of the nonretrograde group (75.7% ± 10.4% and 74.3% ± 9.4%, respectively) (P < 0.05). Moreover, the patients in the retrograde group had a greater incidence of a LDI < 50% than those in the nonretrograde group (P < 0.05). There were no significant differences in the ODI or VAS scores between the two groups before the operation, but the ODI and VAS scores in the retrograde group were significantly worse than those in the nonretrograde group after the operation and at the last follow-up, (P < 0.05). CONCLUSION: The incidence of posterior slippage after lower lumbar fusion was approximately 20.9%. The risk factors are related to a higher PI and distribution of lumbar lordosis. When a patient has a high PI and insufficient reconstruction of the lower lumbar spine, adjacent segment compensation via posterior vertebral body slippage is one of the factors that significantly affects surgical outcomes.

Pilot implementation of the revised criteria for staging of Alzheimer's disease by the Alzheimer's Association Workgroup in a tertiary memory clinic.

INTRODUCTION: We aimed to evaluate the feasibility of the 2024 Alzheimer's Association Workgroup's integrated clinical-biological staging scheme in outpatient settings within a tertiary memory clinic. METHODS: The 2018 syndromal cognitive staging system, coupled with a binary biomarker classification, was implemented for 236 outpatients with cognitive concerns. The 2024 numeric clinical staging framework, incorporating biomarker staging, was specifically applied to 154 individuals within the Alzheimer's disease (AD) continuum. RESULTS: The 2024 staging scheme accurately classified 95.5% AD. Among these, 56.5% exhibited concordant clinical and biological stages (canonical), 34.7% demonstrated more advanced clinical stages than biologically expected (susceptible), and 8.8% displayed the inverse pattern (resilient). The susceptible group was characterized by a higher burden of neurodegeneration and inflammation than anticipated from tau, whereas the resilient group showed the opposite. DISCUSSION: The 2024 staging scheme is generally feasible. A discrepancy between clinical and biological stages is relatively frequent among symptomatic patients with AD. HIGHLIGHTS: The 2024 AA staging scheme is generally feasible in a tertiary memory clinic. A discrepancy between clinical and biological stages is relatively frequent in AD. The mismatch may be influenced by a non-specific pathological process involved in AD. Individual profiles like aging and lifestyles may contribute to such a mismatch. Matched and mismatched cases converge toward similar clinical outcomes.

Diagnosis, Treatment Patterns, and Outcomes in Real-World Patients with RET Fusion-Positive Non-small Cell Lung Cancer in China.

INTRODUCTION: Epidemiological studies on non-small cell lung cancer (NSCLC) have noted RET fusions as an oncogenic driver. However, real-world data on RET biomarker testing and treatment patterns in China remain limited. This study aimed to examine demographics, clinical and molecular features, and RET testing and treatment patterns and outcomes in patients with RET fusion-positive NSCLC. METHODS: Utilizing real-world data from the Chinese Multi-center Lung Cancer Precision Medicine Registry, this retrospective cohort study focused on Chinese patients diagnosed with RET fusion-positive NSCLC between January 1, 2016, and November 30, 2021. The cohort was divided into early-stage and advanced-stage subgroups. Demographics, clinical and molecular profiles, treatment received, and outcomes including real-world event free survival (rwEFS), real-world progression free survival (rwPFS), and overall survival (OS) were assessed. RESULTS: The study included 121 patients with RET fusion-positive NSCLC, comprising 80 early-stage and 58 advanced-stage patients. High biomarker testing rates were observed at diagnosis (75% for early-stage, 78% for advanced-stage). RET testing was often conducted via tissue samples (95.9%) and next-generation sequencing (89.3%). KIF5B (57.0%) and CCDC6 (20.7%) were the most common gene fusion partners. The most frequent oncogenic mutations were TP53 (15.7%) and EGFR (6.6%). Platinum-based chemotherapy was the most common first-line treatment among advanced-stage patients. Median rwPFS was 9.22 months for advanced-stage patients on first-line chemotherapy, and median OS was 30.7 months for all advanced-stage patients. The 2-year rwEFS rate for early-stage patients was 86.0%, with a median OS of 91.9 months. CONCLUSIONS: The study observed high biomarker testing rates at initial diagnosis for early- and advanced-stage RET fusion-positive NSCLC patients in China. The heterogeneous treatment pattern of advanced patients suggests the need for more precise, evidence-based treatment to guide clinical decisions. Given the existing therapeutic regimens fall short of adequately addressing treatment needs, targeted therapies are essential to improve outcomes.

The impact of COVID-19 on people with epilepsy: Global results from the coronavirus and epilepsy study.

OBJECTIVE: To characterize the experience of people with epilepsy and aligned healthcare workers (HCWs) during the first 18 months of the COVID-19 pandemic and compare experiences in high-income countries (HICs) with non-HICs. METHODS: Separate surveys for people with epilepsy and HCWs were distributed online in April 2020. Responses were collected to September 2021. Data were collected for COVID-19 infections, the effect of COVID-related restrictions, access to specialist help for epilepsy (people with epilepsy), and the impact of the pandemic on work productivity (HCWs). The frequency of responses for non-HICs and HICs were compared using non-parametric Chi-square tests. RESULTS: Two thousand one hundred and  five individuals with epilepsy from 53 countries and 392 HCWs from 26 countries provided data. The same proportion of people with epilepsy in non-HICs and HICs reported COVID-19 infection (7%). Those in HICs were more likely to report that COVID-19 measures had affected their health (32% vs. 23%; p < 0.001). There was no difference between non-HICs and HICs in the proportion who reported difficulty in obtaining help for epilepsy. HCWs in non-HICs were more likely to report COVID-19 infection than those in HICs (18% vs 6%; p = 0.001) and that their clinical work had been affected by concerns about contracting COVID-19, lack of personal protective equipment, and the impact of the pandemic on mental health (all p < 0.001). Compared to pre-pandemic practices, there was a significant shift to remote consultations in both non-HICs and HICs (p < 0.001). SIGNIFICANCE: While the frequency of COVID-19 infection was relatively low in these data from early in the pandemic, our findings suggest broader health consequences and an increased psychosocial burden, particularly among HCWs in non-HICs. Planning for future pandemics should prioritize mental healthcare alongside ensuring access to essential epilepsy services and expanding and enhancing access to remote consultations. PLAIN LANGUAGE SUMMARY: We asked people with epilepsy about the effects of COVID-19 on their health and healthcare. We wanted to compare responses from people in high-income countries and other countries. We found that people in high-income countries and other countries had similar levels of difficulty in getting help for their epilepsy. People in high-income countries were more likely to say that their general health had been affected. Healthcare workers in non-high-income settings were more likely to have contracted COVID-19 and have the care they deliver affected by the pandemic. Across all settings, COVID-19 associated with a large shift to remote consultations.

Sport Participation Trajectories and Loneliness: Evidence From the Longitudinal Study of Australian Children.

BACKGROUND: This study aimed to identify patterns of overall, team, and individual sport participation and examine the prospective associations between these patterns and loneliness in young people. METHODS: We analyzed data from 4241 young people, from waves 3 (8-9 y) to 9 (20-21 y) of the Longitudinal Study of Australian Children. We conducted latent class analyses to identify overall and team versus individual sport participation trajectories and used adjusted log-Poisson regression models to examine the associations between these trajectories and loneliness at wave 9. RESULTS: Latent class analyses identified 4 distinct overall sport participation classes which were labeled: nonparticipants (24%), dropouts (42%), initiators (7%), and consistent participants (27%). Compared with nonparticipants, consistent participants had a lower risk of loneliness (risk ratios = 0.69; 95% CIs, 0.59-0.81). Latent class analyses also identified 4 distinct team versus individual sport participation classes: team and individual sport nonparticipants (38%), individual sport participants (14%), moderate team sport participants (14%), and high team sport participants (34%). Compared with the team and individual sport nonparticipants, the high team sports participants had a lower risk of loneliness (risk ratios = 0.70; 95% CIs, 0.53-0.92). CONCLUSIONS: Young people who continued participating in sport in general, and particularly in team sport, had a reduced risk of loneliness. Continued participation in sports should be promoted to improve a range of physical, mental, and social health benefits. Furthermore, team-based sport can provide additional health and well-being benefits, including reduced loneliness due to the group nature of participation.

Degradation and preservation of nitrites in whole blood.

Understanding the factors that influence nitrite degradation in whole blood and developing methods for its stable preservation are crucial for ensuring accurate and reliable forensic identification in cases of nitrite poisoning. This study systematically monitored nitrite degradation and changes in hemoglobin proportions across different initial nitrite concentrations and blood samples. It was revealed that high nitrite concentrations rapidly reduced deoxyhemoglobin levels within the first 15 minutes and subsequently reacted with oxyhemoglobin at a slower rate. Therefore, the proportions of these two hemoglobin forms are key factors in determining nitrite degradation rates. Regarding preservation, the study examined the effects of low temperatures (4°C and -20°C) and various preservatives (potassium ferricyanide, N-ethylmaleimide) on nitrite stability. The results indicate that adding 6.6 g/L potassium ferricyanide can rapidly eliminate all deoxyhemoglobin and reduce oxyhemoglobin proportions to below 60 %, enabling stable preservation of high nitrite concentrations in whole blood for over 30 days at -20°C. The efficacy of potassium ferricyanide was further validated in forensic-acquired postmortem heart blood samples.

Nicotinamide Mononucleotide: Research Process in Cardiovascular Diseases.

Nicotinamide adenine dinucleotide (NAD+) is an essential metabolite that plays a crucial role in diverse biological processes, including energy metabolism, gene expression, DNA repair, and mitochondrial function. An aberrant NAD+ level mediates the development of cardiovascular dysfunction and diseases. Both in vivo and in vitro studies have demonstrated that nicotinamide mononucleotide (NMN), as a NAD+ precursor, alleviates the development of cardiovascular diseases such as heart failure, atherosclerosis, and myocardial ischemia/reperfusion injury. Importantly, NMN has suggested pharmacological activities mostly through its involvement in NAD+ biosynthesis. Several clinical studies have been conducted to investigate the efficacy and safety of NMN supplementation, indicating its potential role in cardiovascular protection without significant adverse effects. In this review, we systematically summarize the impact of NMN as a nutraceutical and potential therapeutic drug on cardiovascular diseases and emphasize the correlation between NMN supplementation and cardiovascular protection.

Low Intake of Total Antioxidant Nutrients as a Risk Factor for Incident Dementia in Older Adults: The Shanghai Aging Study.

INTRODUCTION: Previous longitudinal studies reported the impact of antioxidant nutrients (ANs) on cognitive impairment in the older population, but the conclusions were inconsistent. This study aimed to verify the hypothesis that dietary intake of total AN was associated with incident dementia among older individuals. METHODS: Community residents without dementia aged ≥60 years were prospectively followed up for an average of 5.2 years in the Shanghai Aging Study. At baseline, daily intakes of total dietary AN (the sum of carotene, vitamin C, vitamin E, lutein, and flavonoids) and energy were calculated based on an interviewer-administered food frequency questionnaire measuring the dietary intake over the past 1 year for each participant. A battery of neuropsychological tests was used to evaluate cognitive function, and a consensus diagnosis of dementia was made according to the DSM-IV criteria at baseline and follow-up. RESULTS: Among 1,550 dementia-free participants, 135 (8.7%) incident dementia cases were identified during the average of 5.2 years of follow-up. Participants with low AN intake (<112 mg/day) had a significantly higher risk of incident dementia than those with high AN intake (≥112 mg/day) (hazard ratio 1.87, 95% confidence interval 1.26-2.77) after adjusting for age, gender, education, obesity, APOE-ε4, hypertension, diabetes, depression, baseline Mini-Mental State Examination score, and total energy intake. The significant association of total AN intake with incident dementia was only found in individuals ≥70 years. CONCLUSION: Low total AN intake may be a risk factor for incident dementia among older adults. Maintaining sufficient AN intake may be beneficial against age-related cognitive decline.

A Holistic Way to Understand the Determinants of Physical Activity in Urban New South Wales, Australia: A Codesigned Systems Mapping Project.

BACKGROUND: To meet the World Health Organization goal of reducing physical inactivity by 15% by 2030, a multisectoral system approach is urgently needed to promote physical activity (PA). We report the process of and findings from a codesigned systems mapping project to present determinants of PA in the context of urban New South Wales, Australia. METHODS: A participatory conceptual mapping workshop was held in May 2023 with 19 participants working in education, transportation, urban planning, community, health, and sport and recreation. Initial maps were developed and refined using online feedback from the participants. Interviews were conducted with 10 additional policymakers from relevant sectors to further refine the maps. RESULTS: Two systems maps were cocreated, identifying over 100 variables influencing PA and their interconnections. Five settings emerged from the adults' map-social and community, policy, built environment and transportation, health care, and workplace-and 4 for the young people's map-family, school, transportation, and community and environment. The maps share similarities, such as regarding potential drivers within the transportation, community, and built environment sectors; however, the young people's map has a specific focus on the school setting and the adults' map on workplace and health care settings. Interviews with policymakers provided further unique insights into understanding and intervening in the PA system. CONCLUSIONS: This codesigned participatory systems mapping process, supplemented by stakeholder interviews, provided a unique opportunity to bring together stakeholders across sectors to understand the complexity within the PA system and begin to identify leverage points for tackling physical inactivity in New South Wales.

Risk factor differences in five-year progression of Intracranial artery stenosis and cerebral small vessel disease in general population.

BACKGROUND: Intracranial artery stenosis (ICAS) and cerebral small vessel disease (CSVD) are associated with a heavy socioeconomic burden; however, their longitudinal changes remain controversial. METHODS: We conducted a longitudinal analysis on 756 participants of Shunyi Cohort who underwent both baseline and follow-up brain magnetic resonance imaging (MRI) and MR angiography in order to investigate the risk factors for ICAS and CSVD progression in community population. Incident ICAS was defined as new stenosis occurring in at least one artery or increased severity of the original artery stenosis. CSVD markers included lacunes, cerebral microbleeds (CMB), and white matter hyperintensities (WMH). RESULTS: After 5.58 ± 0.49 years of follow-up, 8.5% of the 756 participants (53.7 ± 8.0 years old, 65.1% women) had incident ICAS. Body mass index (BMI) (OR = 1.09, 95% CI = 1.01-1.17, p = 0.035) and diabetes mellitus (OR = 2.67, 95% CI = 1.44-4.93, p = 0.002) were independent risk factors for incident ICAS. Hypertension was an independent risk factor for incident lacunes (OR = 2.12, 95% CI = 1.20-3.77, p = 0.010) and CMB (OR = 2.32, 95% CI = 1.22-4.41, p = 0.011), while WMH progression was primarily affected by BMI (ß = 0.108, SE = 0.006, p = 0.002). A higher LDL cholesterol level was found to independently protect against WMH progression (ß = -0.076, SE = 0.027, p = 0.019). CONCLUSIONS: Modifiable risk factor profiles exhibit different in patients with ICAS and CSVD progression. Controlling BMI and diabetes mellitus may help to prevent incident ICAS, and antihypertensive therapy may conduce to mitigate lacunes and CMB progression. LDL cholesterol may play an inverse role in large arteries and small vessels.

Correlation between Circle of Willis configuration and intracranial arterial dolichoectasia, and genetic contributions.

OBJECTIVES: Intracranial arterial dolichoectasia (IADE) is characterized by the dilation, elongation, and tortuosity of intracranial arteries. We aimed to investigate the association between variations of the Circle of Willis (COW) and IADE in the general population, as well as estimate the genetic correlation between COW variations and IADE. METHODS: A total of 981 individuals from a population-based cohort were included. Brain magnetic resonance angiography was performed to assess COW variants and measure the diameters of intracranial arteries. IADE was defined as a total intracranial volume-adjusted diameter ≥ 2 standard deviations. Logistic regression models were used to analyze the association between COW variations and IADE. The heritability and genetic correlation were estimated using genome-wide complex trait analysis (GCTA) based on single nucleotide polymorphism (SNP) array data. RESULTS: The prevalence of IADE was 6.2 %. Hypoplastic/absent A1 segments were associated with an increase in contralateral ICA diameter (ß ± SE, 0.279 ± 0.049; p = 0.001) and a decrease in ipsilateral ICA diameter (ß ± SE, -0.300 ± 0.050; p = 0.001). Fetal-type posterior cerebral artery (FTP) was associated with a larger ICA diameter (ß ± SE, 0.326 ± 0.048; p = 0.001) and a smaller BA diameter (ß ± SE, -0.662 ± 0.043; p = 0.001). FTP revealed a positive genetic correlation with ICA dilation (rG = 0.259 ± 0.175; p = 0.0009) and a negative genetic correlation with BA dilation (rG = -0.192 ± 0.153, p = 0.015). CONCLUSIONS: There was an association between COW variations and larger intracranial arterial diameters in the general population. Genetic factors may play a role in the development of intracranial arterial dilation and the formation of COW variants.