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Bundesgesundheitsblatt,... Jul 2024Out-of-home mobility, defined as active and passive movement through external environments, is a resource for autonomy, quality of life, and self-realization in older...
BACKGROUND
Out-of-home mobility, defined as active and passive movement through external environments, is a resource for autonomy, quality of life, and self-realization in older age. Various factors influence out-of-home mobility, primarily studied in urban settings. The study aims to examine associated factors in a study population aged 75 and above in rural areas.
METHODS
Baseline data from the MOBILE trial involving 212 participants aged 75 and above and collected between June 2021 and October 2022 were analyzed. Out-of-home mobility was measured temporally as time out of home (TOH) and spatially as convex hull (CHull) using GPS over seven days. Mixed models considered outpatient care parameters as well as personal, social, and environmental factors along with covariates such as age and gender.
RESULTS
Participants in the MOBILE study (average age 81.5; SD: 4.1; 56.1% female) exhibited average out-of-home mobility of TOH: 319.3 min (SD: 196.3) and CHull: 41.3 (SD: 132.8). Significant associations were found for age (TOH: ß = -0.039, p < 0.001), social network (TOH: ß = 0.123, p < 0.001), living arrangement (CHull: ß = 0.689, p = 0.035), health literacy (CHull: ß = 0.077, p = 0.008), sidewalk quality (ß = 0.366, p = 0.003), green space ratio (TOH: ß = 0.005, p = 0.047), outpatient care utilization (TOH: ß = -0.637, p < 0.001, CHull: ß = 1.532; p = 0.025), and active driving (TOH: ß = -0.361, p = 0.004).
DISCUSSION
Previously known multifactorial associations related to objectively measured out-of-home mobility in old age could be confirmed in rural areas. Novel and relevant for research and practice is the significant correlation between out-of-home mobility and outpatient care utilization.
PubMed: 38953972
DOI: 10.1007/s00103-024-03917-2 -
Der Nervenarzt Jul 2024While the neuronal mechanisms of epileptic hyperexcitability (HE) have been studied in detail, recent findings suggest that extraneuronal, mainly immune-mediated... (Review)
Review
OBJECTIVE
While the neuronal mechanisms of epileptic hyperexcitability (HE) have been studied in detail, recent findings suggest that extraneuronal, mainly immune-mediated inflammatory and vascular mechanisms play an important role in the development and progression of HE in epilepsy and the cognitive and behavioral comorbidities.
MATERIAL AND METHODS
Narrative review.
RESULTS
As in autoimmune (limbic) encephalitis (ALE/AIE) or Rasmussen's encephalitis (RE), the primary adaptive and innate immune responses and associated changes in the blood-brain barrier (BBB) and neurovascular unit (NVU) can cause acute cortical hyperexcitability (HE) and the development of hippocampal sclerosis (HS) and other structural cortical lesions with chronic HE. Cortical HE, which is associated with malformation of cortical development (MCD) and low-grade epilepsy-associated tumors (LEAT), for example, can be accompanied by secondary adaptive and innate immune responses and alterations in the BBB and NVU, potentially modulating the ictogenicity and epileptogenicity. These associations illustrate the influence of adaptive and innate immune mechanisms and associated changes in the BBB and NVU on cortical excitability and vice versa, suggesting a dynamic and complex interplay of these factors in the development and progression of epilepsy in general.
DISCUSSION
The described concept of a neuro-immune-vascular interaction in focal epilepsy opens up new possibilities for the pathogenetic understanding and thus also for the selective therapeutic intervention.
PubMed: 38953922
DOI: 10.1007/s00115-024-01695-5 -
JAMA Jul 2024
Topics: Humans; COVID-19
PubMed: 38953901
DOI: 10.1001/jama.2023.18332 -
JAMA Jul 2024
Topics: Humans; Female
PubMed: 38953900
DOI: 10.1001/jama.2023.18331 -
The Journal of Experimental Medicine Sep 2024Gain-of-function mutations in STING cause STING-associated vasculopathy with onset in infancy (SAVI) characterized by early-onset systemic inflammation, skin...
Gain-of-function mutations in STING cause STING-associated vasculopathy with onset in infancy (SAVI) characterized by early-onset systemic inflammation, skin vasculopathy, and interstitial lung disease. Here, we report and characterize a novel STING variant (F269S) identified in a SAVI patient. Single-cell transcriptomics of patient bone marrow revealed spontaneous activation of interferon (IFN) and inflammatory pathways across cell types and a striking prevalence of circulating naïve T cells was observed. Inducible STING F269S expression conferred enhanced signaling through ligand-independent translocation of the protein to the Golgi, protecting cells from viral infections but preventing their efficient immune priming. Additionally, endothelial cell activation was promoted and further exacerbated by cytokine secretion by SAVI immune cells, resulting in inflammation and endothelial damage. Our findings identify STING F269S mutation as a novel pathogenic variant causing SAVI, highlight the importance of the crosstalk between endothelial and immune cells in the context of lung disease, and contribute to a better understanding of how aberrant STING activation can cause pathology.
Topics: Membrane Proteins; Humans; Endothelial Cells; Lung Diseases, Interstitial; Signal Transduction; Vascular Diseases; Golgi Apparatus; Interferons; Male; Gain of Function Mutation; Mutation; Infant
PubMed: 38953896
DOI: 10.1084/jem.20232167 -
Journal of Vision Jul 2024Applications for eye-tracking-particularly in the clinic-are limited by a reliance on dedicated hardware. Here we compare eye-tracking implemented on an Apple iPad Pro... (Comparative Study)
Comparative Study
Applications for eye-tracking-particularly in the clinic-are limited by a reliance on dedicated hardware. Here we compare eye-tracking implemented on an Apple iPad Pro 11" (third generation)-using the device's infrared head-tracking and front-facing camera-with a Tobii 4c infrared eye-tracker. We estimated gaze location using both systems while 28 observers performed a variety of tasks. For estimating fixation, gaze position estimates from the iPad were less accurate and precise than the Tobii (mean absolute error of 3.2° ± 2.0° compared with 0.75° ± 0.43°), but fixation stability estimates were correlated across devices (r = 0.44, p < 0.05). For tasks eliciting saccades >1.5°, estimated saccade counts (r = 0.4-0.73, all p < 0.05) were moderately correlated across devices. For tasks eliciting saccades >8° we observed moderate correlations in estimated saccade speed and amplitude (r = 0.4-0.53, all p < 0.05). We did, however, note considerable variation in the vertical component of estimated smooth pursuit speed from the iPad and a catastrophic failure of tracking on the iPad in 5% to 20% of observers (depending on the test). Our findings sound a note of caution to researchers seeking to use iPads for eye-tracking and emphasize the need to properly examine their eye-tracking data to remove artifacts and outliers.
Topics: Humans; Eye-Tracking Technology; Fixation, Ocular; Saccades; Male; Adult; Female; Young Adult; Pursuit, Smooth; Computers, Handheld; Eye Movements
PubMed: 38953861
DOI: 10.1167/jov.24.7.1 -
Future Oncology (London, England) Jul 2024This is a summary describing the results from a phase 3 clinical trial called SUNLIGHT. The study looked at treatment with orally administered trifluridine/tipiracil...
WHAT IS THIS SUMMARY ABOUT?
This is a summary describing the results from a phase 3 clinical trial called SUNLIGHT. The study looked at treatment with orally administered trifluridine/tipiracil plus intravenously administered bevacizumab in people with metastatic colorectal cancer (mCRC) that is refractory to treatment.This study included people whose cancer had grown or spread beyond its original location after no more than two previous treatments. People in the study received either the combination of trifluridine/tipiracil plus bevacizumab or they received trifluridine/tipiracil alone. The aims of the study were to see how long people lived after treatment with trifluridine/tipiracil plus bevacizumab compared with trifluridine/tipiracil alone and to find out how well the combination of trifluridine/tipiracil plus bevacizumab worked at slowing down the spread of the cancer. Researchers also looked at side effects from taking the medicines and at how treatment affected people's physical functioning.
WHAT ARE THE KEY TAKEAWAYS?
People in the combination group lived longer (a median of 10.8 months) than people who received trifluridine/tipiracil alone (7.5 months). In addition, the time it took for the cancer to worsen was longer for those who received the combination treatment (a median of 5.6 months) compared with those who received trifluridine/tipiracil alone (2.4 months). People's physical functioning took longer to worsen with combination therapy (a median of 9.3 months) than it did with trifluridine/tipiracil alone (6.3 months), as measured by the impact of treatment on people's ability to carry out daily living activities. The most common side effects in both treatment groups were low levels of white blood cells, known as neutrophils (neutropenia), nausea, and low levels of healthy red blood cells (anemia).
WHAT WERE THE MAIN CONCLUSIONS REPORTED BY THE RESEARCHERS?
The results from the study suggest that treatment with oral trifluridine/tipiracil plus intravenous (IV) bevacizumab could help people with refractory mCRC live longer and maintain good physical functioning, and it could slow the worsening of their cancer. NCT04737187 (SUNLIGHT) (ClinicalTrials.gov).
PubMed: 38953855
DOI: 10.1080/14796694.2024.2366100 -
Translational Vision Science &... Jul 2024To identify the accelerometer-measured daily behaviors that mediate the association of refractive status with depressive disorders and enhance the understanding of...
PURPOSE
To identify the accelerometer-measured daily behaviors that mediate the association of refractive status with depressive disorders and enhance the understanding of behavioral differences in depression.
METHODS
Participants with baseline mean spherical equivalent (MSE) and 7-day accelerometer measurements from the UK Biobank were included in this cohort study. Refractive status was categorized as hyperopia and non-hyperopia. Four daily behaviors, including moderate to vigorous intensity physical activity (MVPA), light physical activity (LPA), sedentary, and sleep were recorded between 2013 and 2015. We also assessed 24-hour behavior patterns. Depression cases were defined through both questionnaires and hospital records over 10 years of follow-up.
RESULTS
Among 20,607 individuals, every 0.5-diopter increase in MSE was associated with a 6% higher risk of depressive disorders, with hyperopia participants at a higher risk than non-hyperopia participants (odds ratio, 1.14; 95% confidence interval, 1.05-1.23; P = 0.001). MVPA and sleep time significantly correlated with depressive disorders, with odds ratios of 0.79 and 1.14 (P < 0.05). MSE showed significant correlations with all four behaviors. The effects of MVPA and sleep duration on MSE and depressive disorders varied throughout the day. Mediation analyses showed that MVPA and sleep partially mediated the relationship between MSE and depressive disorders, with 35.2% of the association between moderate to high hyperopia and depression mediated by MVPA.
CONCLUSIONS
Physical activity and sleep significantly mediate the relationship between MSE and depressive disorders.
TRANSLATIONAL RELEVANCE
The mediation effect of MVPA highlights its therapeutic potential in reducing the risk of depression among individuals with moderate to severe hyperopia. Interventions aimed at increasing daytime MVPA and decreasing daytime sleep could enhance mental health in this vulnerable group.
Topics: Humans; Male; Female; Accelerometry; Middle Aged; Exercise; Depressive Disorder; Adult; Sleep; Aged; Sedentary Behavior; Surveys and Questionnaires; Hyperopia; Risk Factors
PubMed: 38953853
DOI: 10.1167/tvst.13.7.3 -
Investigative Ophthalmology & Visual... Jul 2024To investigate the correlation between apparent diffusion coefficient (ADC) histograms and high-risk clinicopathologic features related to uveal melanoma (UM) prognosis.
PURPOSE
To investigate the correlation between apparent diffusion coefficient (ADC) histograms and high-risk clinicopathologic features related to uveal melanoma (UM) prognosis.
METHODS
This retrospective study included 53 patients with UM who underwent diffusion-weighted imaging (DWI) between August 2015 and March 2024. Axial DWI was performed with a single-shot spin-echo echo-planar imaging sequence. ADC histogram parameters of ADCmean, ADC50%, interquartile range (IQR), skewness, kurtosis, and entropy were obtained from DWI. The relationships between histogram parameters and high-risk clinicopathological characteristics including tumor size, preoperative retinal detachment, histological subtypes, Ki-67 index, and chromosome status, were analyzed by Spearman correlation analysis, Mann-Whitney U test, or Kruskal-Wallis test.
RESULTS
A total of 53 patients (mean ± SD age, 55 ± 15 years; 22 men) were evaluated. The largest basal diameter (LBD) was correlated with kurtosis (r = 0.311, P = 0.024). Tumor prominence (TP) was correlated with entropy (r = 0.581, P < 0.001) and kurtosis (r = 0.273, P = 0.048). Additionally, significant correlations were identified between the Ki-67 index and ADCmean (r = -0.444, P = 0.005), ADC50% (r = -0.487, P = 0.002), and skewness (r = 0.394, P = 0.014). Finally, entropy was correlated with monosomy 3 (r = 0.541, P = 0.017).
CONCLUSIONS
The ADC histograms provided valuable insights into high-risk clinicopathologic features of UM and hold promise in the early prediction of UM prognosis.
Topics: Humans; Uveal Neoplasms; Male; Female; Middle Aged; Melanoma; Retrospective Studies; Prognosis; Diffusion Magnetic Resonance Imaging; Adult; Aged; Echo-Planar Imaging
PubMed: 38953846
DOI: 10.1167/iovs.65.8.3 -
Acta Ophthalmologica Jul 2024To characterise the retinal vasculometry of a Danish eye and vision cohort and examine associations with systolic blood pressure (BP), diastolic BP, mean arterial BP,...
Longitudinal associations of retinal vessel morphology with intraocular pressure and blood pressure at follow-up visit-Findings from a Danish eye and vision cohort, Project FOREVER.
PURPOSE
To characterise the retinal vasculometry of a Danish eye and vision cohort and examine associations with systolic blood pressure (BP), diastolic BP, mean arterial BP, and intraocular pressure (IOP).
DESIGN
Longitudinal study.
METHODS
The retinal vasculature of fundus images from the FOREVER (Finding Ophthalmic Risks and Evaluating the Value of Eye exams and their predictive Reliability) cohort was analysed using a fully automated image analysis program. Longitudinal associations of retinal vessel morphology at follow-up visit with IOP (baseline and follow-up) and BP (follow-up) were examined using multilevel linear regression models adjusting for age, sex and retinal vasculometry at baseline as fixed effects and person as random effect. Width measurements were additionally adjusted for the spherical equivalent.
RESULTS
A total of 2089 subjects (62% female) with a mean age of 61 (standard deviation 8) years and a mean follow-up period of 4.1 years (SD 0.6 years) were included. The mean arteriolar diameter was approximately 20% thinner than the mean venular diameter, and venules were about 21%-23% less tortuous than arterioles. BP at follow-up was associated with decreased arteriolar diameter from baseline to follow-up. After adjusting for baseline IOP, IOP at follow-up was associated with increased arteriolar tortuosity above baseline (0.59%, 95% CI 0.08-1.10, p-value 0.024).
CONCLUSION
In a Danish eye and vision cohort, variations in BP and alterations in IOP over time were associated with changes in the width and tortuosity of retinal vessels. Our findings contribute novel insights into retinal vascular alterations over time.
PubMed: 38953839
DOI: 10.1111/aos.16737