Search Results for: Le sigarette light sono più pericolose di quelle normali

Annals of Internal Medicine, Volume 178, Issue 2, Page JC21, February 2025.

pearls slipping off a string, one slick diver followed by another, round and containing light, pried from a cool oyster shell and brought out to swelter in summer,

Background
The transition from traditional office work to telework has accelerated significantly since the late 20th century, especially in light of the COVID-19 pandemic. Despite its widespread adoption, the long-term health impacts of telework remain unclear. This study seeks to clarify the telework–health relationship by integrating longitudinal self-reported health data with health-related administrative records.

Methods and analysis
An online self-reported longitudinal survey with four follow-ups of 6 months each, starting in November 2024, will be set up and linked with administrative data sources. In total, a non-probabilistic sample of 5000 non-teleworkers and teleworkers will be recruited. This survey will mainly assess the effect of teleworking on mental (eg, depression and anxiety) and physical (eg, pain) health. Administrative data (eg, healthcare consumption contacts and socioeconomic status) will be extracted from Belgian administrative data sources (Statistics Belgium and the InterMutualistic Agency) for the same period. This administrative data will be linked to the survey data using the Social Security ID. The underlying relationships between telework and health will be analysed via regression models and mediation models embedded in the natural effects framework. The analysis will aim to (1) identify the impact of telework on self-reported health and administrative data, (2) identify the moderators and mediators between the telework–health relationship, (3) understand the long-term patterns of telework and health interaction and (4) predict the health outcomes of teleworkers. To mitigate biases associated with non-probabilistic samples and attrition, standardised probability weights scoring will be derived from the data.

Ethics and dissemination
This study involves human participants and has been approved by the Ethics Committee of Universitair Ziekenhuis Gent (Nr°. ONZ-2023–0630). The participants will participate in the study after signing an informed consent form. The study will be disseminated in academic journals, on (social) media and on the project website.

Introduction
Weight restoration is a primary goal in anorexia nervosa (AN) treatment. Recent studies suggest that addressing physical activity urges in patients with AN is a promising target to facilitate weight restoration. This trial will evaluate the feasibility of a virtual reality (VR)-based intervention as an add-on treatment to psychotherapy to improve activity urges and, consequently, initial treatment responses on core outcomes as targeted per AN treatment guidelines.

Methods and analysis
This single-centre feasibility trial adopts the single-blind, two-arm design and outcome measures of an intended full-scale randomised controlled trial (RCT) in order to establish that all necessary trial components work together as intended. It will evaluate feasibility as the primary endpoint and compare changes in ratings of the urge to be active between patients with AN randomly assigned to receiving VR intervention sessions and patients with AN in a control procedure. The feasibility of the full-scale RCT will depend on whether patients (1) will evaluate the experience as acceptable, (2) tolerate VR side effects and (3) will adhere to the intended intervention schedule. We define a set of three-tiered, formal progression criteria and employ a ‘traffic light system’ demarcating go (green), amend (amber) and stop (red) signals for advancing to the full-scale RCT.

Ethics and dissemination
The study was approved by the ethics committee of the Ruhr University Bochum’s Medical Faculty at Campus East-Westphalia (AZ 2024-1296, 9 December 2024). Patients have to provide written consent before taking part in the study. The findings will be published with open access.

Trial registration number
DRKS00035681, German Clinical Trials Register.

In a meta-analysis, bright light therapy was superior to placebo when added to antidepressant medication.

Stroke, Volume 56, Issue Suppl_1, Page A94-A94, February 1, 2025. Introduction:Ischemic stroke is a leading cause of death and disability worldwide, but there has been limited success in translating putative treatments from preclinical trials to patients. The Stroke Preclinical Assessment Network (SPAN) is a large-scale multicenter trial (six sites plus a coordinating center).Methods:SPAN implemented a multiparametric MRI protocol with minimal human input to assess tissue outcomes after mouse endovascular middle cerebral artery occlusion (MCAO). Imaging from 1766 mice was used in this study. The sample size includes three comorbidity models (Young mice, Aging mice, and diet-induced hyperglycemia/ obesity mice.Results:Infarct volumes were variable across the network but right-skewed at all sites. Striatal and cortical infarcts were more common than thalamic and hippocampal infarcts (present in 75%, 65%, 20%, and 22% of mice, respectively). Total lesion was more associated with striatal and cortical infarct volumes (R=0.94 and 0.97). Infarct volumes were strongly associated with midline shift on days 2 (R=0.74) and 30 (R=-0.80), reflecting ischemic swelling and encephalomalacia, respectively. Factor analysis identified the underpinnings of the covariance among MRI variables (Figure 1). We found 13 MRI readouts linked to the injury severity after MCAO. These included the total, striatal, and cortical infarct volumes, indices of ischemic edema on day 2, and indices of tissue loss on day 30. Five variables were linked to infarction involving the posterior cerebral artery. Another set of five variables was linked to ventricular volume, suggesting an independent contributing factor, such as age. Average R2ratein the contralateral tissue was lower in diet-induced obesity and aged mice compared with normal young mice, suggesting higher brain water content. Within the infarct, the R2ratewas significantly lower only in diet-induced obese mice versus the other groups.Conclusion:Our data revealed critical insight into the stroke model regarding lesion distribution, swelling, and atrophy. Our findings also shed light on previously underappreciated biological associations among these variables.

Stroke, Volume 56, Issue Suppl_1, Page ATP335-ATP335, February 1, 2025. Objective:Approximately 10%-17% of patients with a recent small subcortical infarction (RSSI) experience an adverse functional prognosis at three months. Identifying risk factors for poor prognosis in these patients and developing a predictive model are of significant clinical relevance.Methods:We conducted a prospective cohort study involving 630 patients with recent small subcortical infarction (RSSI). These patients were divided into training (70%) and internal validation (30%) cohorts. Additionally, for external validation, 103 patients from two other hospitals were included. To predict functional outcomes at three months, we employed eight different machine learning algorithms: Support Vector Machine, Decision Tree, Random Forest, Gradient Boosting, Extreme Gradient Boosting, Light Gradient Boosting Machine, Cat Boosting, and Logistic Regression. The interpretability of the best-performing model was enhanced with SHapley Additive exPlanations(SHAP).Results:Among the 630 patients included in the study, the average age of participants was 59.0 ±13.0 years and 65 (10.3%) exhibited poor functional outcomes at three months. The Cat Boosting model showed the highest performance among eight machine learning models. The final model could accurately predict outcome in both internal (AUC = 0.968) and external (AUC = 0.856) validations. SHAP analysis indicated that the initial NIHSS score was the most important variable. The web application is available at https://yrssiml.streamlit. app.Conclusions:Our research developed a predictive model using the Cat Boosting algorithm to forecast poor functional outcomes at three months in patients with RSSI. This model enables clinicians to identify patients at high risk and implement targeted interventions more effectively.

Stroke, Volume 56, Issue Suppl_1, Page AWMP3-AWMP3, February 1, 2025. Introduction:There is no established acute intervention for central retinal artery occlusion (CRAO) which often results in poor visual outcomes. Intravenous Alteplase (tPA) has emerged as a promising acute treatment for CRAO. Intravenous Tenecteplase (TNK) is non-inferior to tPA in the acute treatment of ischemic stroke. However, there is limited data on its use for CRAO.Methods:Retrospective data of patients from January 2016 to February 2024 with CRAO who received TNK or tPA and a medical management (MM) matched cohort were collected, including demographics, suspected etiology of CRAO, presenting and final central visual acuity, symptomatic intracranial hemorrhage (sICH), vitreous hemorrhage, and neovascularization. In cases where the presenting central visual acuity was not quantified, it was assigned a value by the investigator based on qualitative descriptions. Visual acuity was converted to LogMAR units to enable quantitative comparison, where the ability to count fingers was assigned a value of 1.85, hand motions 2.28, light perception 2.70, and no light perception 3.00. Functional visual recovery was defined as a final visual acuity of 20/100 or better. Patients without a documented final central visual acuity were excluded from the analysis. T-test, chi-square, and ANOVA were used for statistical analysis.Results:A total of 15 TNK, 19 tPA, and 31 MM patients were included. MM patients were older than the thrombolytic patients (74.5±8.8 vs. 68.2±14.4 yrs) p=0.04. More patients had diabetes in tPA (52.6%) vs TNK (13.3%) vs MM (29.0%) p=0.04. There was no difference in suspected etiologies of CRAO. Functional visual recovery trended toward improvement in TNK (33.3%) vs. tPA (5.3%) vs. MM (16.1%) p=0.09. Quantitative assessment of final visual acuity by LogMAR trended toward improvement in TNK (1.45±1.03) vs. tPA (1.97±0.55) vs. MM (2.04±0.86) p=0.07. Fewer patients were legally blind in TNK (60.0%) vs. tPA (94.7%) vs. MM (83.9%) p=0.03. There was no difference in sICH, vitreous hemorrhage, or neovascularization.Conclusions:This is the first case series comparing CRAO treated with TNK, tPA, and MM. There were fewer patients who were legally blind and there was a trend toward improved final visual acuity in the TNK group. There was no difference in sICH, vitreous hemorrhage, or neovascularization. This study adds to the growing body of evidence that TNK can be an effective and safe treatment for CRAO.

Stroke, Volume 56, Issue Suppl_1, Page AWMP12-AWMP12, February 1, 2025. Background:The trial of colchicine in high risk patients with acute minor-to-moderate ischaemic stroke or transient ischaemic attack (CHANCE-3) evaluated the efficacy and safety of low dose colchicine on reducing subsequent stroke within three month. The study did not provide any evidence showing that colchicine could reduce the risk of any stroke within three months after onset, possibly due to heterogeneity of treatment effect (HTE) across patients. Better assessing HTE could identify some subpopulations with derived benefit.Objective:In the post-hoc analysis, we aimed to assess HTE through different approaches and explore the subgroup of patients who may benefit from colchicine.Method:Exploratory analysis of a multicentre, double blind, randomised, controlled trial of low dose colchicine versus placebo in patients with a minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L. The primary outcome was any new stroke within three month after onset. Heterogeneity of treatment effect was assessed two ways: using a multivariable outcome prediction model, and a causal forest model. Cox proportional hazards models were used to evaluate the effect of colchicine in subgroup patients with specific characteristics.Results:The trial enrolled and assigned 8,343 patients to colchicine or placebo group and baseline characteristics were balanced between two groups (mean age, 65.6 years; 62.4% male). In the overall population, colchicine was not associated with an decreasing risk of stroke (HR: 0.98, 95%CI: 0.83-1.16, p =0.79). Based on causal forest models, mean corpusular volume, triglyceride, BMI, and the neutrophil count distinguished patients who differentially benefited from colchicine (interaction p =0.02). Cox proportional hazards models revealed a number needed to treat of 29.4 to prevent one stroke among participants with mean corpusular volume higher than 86.2 g/L, triglyceride higher than 1.39 mmol/L, BMI higher than 23.39 Kg/m2, and the neutrophil count higher than 4.35×109/L (HR: 0.65, 95%CI: 0.44-0.94, p =0.02).Conclusion:Among patients with acute minor-to-moderate ischaemic stroke or transient ischaemic attack, the effect of colchicine on stroke within three months was heterogeneous. Approaches to assessing HTE could identify individuals who might have derived benefit, which shed light on the design and analysis of further trials.

Stroke, Volume 56, Issue Suppl_1, Page AWMP42-AWMP42, February 1, 2025. Background:The Medical Research Council (MRC) scale is used to assess the impact of stroke on muscle strength. Shoulder abduction and finger extension, collectively (SAFE), have been suggested to have prognostic value for stroke outcomes (e.g. PREP-2), and been recommended for use in screening for clinical trials. Few studies have assessed the neuroanatomy associated with SAFE, and other upper extremity MRC scores after stroke. In this study, we used voxel-based lesion symptom mapping (VLSM) to assess lesion locations associated with worse SAFE scores, as well as other movements assessed by the MRC scale.Methods:A trained therapist assessed 12 individual MRC scores at the: shoulder (flexion, extension, abduction, internal and external rotation), elbow (flexion and extension), wrist (flexion and extension) and fingers (flexion, extension and abduction). Clinical neuroimaging (MRI and/or CT) was collected for all participants, and lesioned voxels traced by trained assessors and normalized to a standard template space. VLSM analysis was conducted for all 12 MRC scale scores, and SAFE score, using NiiStat. Only voxels lesioned in >10% of participants were tested.Results:We recruited 226 stroke participants at 2 weeks post-stroke (mean age=62.6; Males=147; Right Hemisphere=131; Ischemic=199, Hemorrhagic=27). VLSM analysis showed that worse SAFE scores were significantly associated with lesions in voxels in the left and right corona radiata, adjacent and dorsal to the lateral ventricles, and consistent with the upper portions of the corticospinal tract in each hemisphere. Additionally, voxels in the putamen were also significantly associated with worse SAFE scores. Interestingly, all other MRC scores were also associated with similar lesion topography to SAFE.Conclusion:This work demonstrates a consistent association between SAFE scores and corticospinal tract damage. The integrity of the corticospinal tract has frequently been suggested as a biomarker of stroke recovery. These findings shed light on why SAFE might be a valuable prognostic tool for stroke recovery, and a quick and efficient screening tool for clinical trials. Despite increasing use of SAFE, other muscle weakness, assessed by the MRC scale, is also represented by the same neuroanatomic regions and may share similar prognostic abilities. Continued investigation into effective prognostic tools for upper-limb recovery is warranted.

Stroke, Volume 56, Issue Suppl_1, Page AWP355-AWP355, February 1, 2025. Introduction:Variations in light exposure are associated with changes in inflammation. The risk of thrombotic events such as ischemic stroke have been found to oscillate with the day-light cycle.Aim:To investigate the impact of altering the light spectrum on ischemic stroke brain injury.Methods:Mice were exposed to ambient (mice-white, 300lux), red light (mice-red, 617nm) or blue light (mice-blue, 442 nm) with 12:12 hour light:dark cycle for 72 hours. After 72 hours of light exposure, male and female mice were subjected to transient middle cerebral artery occlusion. Stroke outcomes were assessed at 24 hours.Results:Exposure to long wavelength red light resulted in a significant reduction in infarct volume following stroke (mice-red 38.8±17.6 mm3 vs. mice-white 73.3±15.0 mm3; p

Stroke, Volume 56, Issue Suppl_1, Page AWMP95-AWMP95, February 1, 2025. Introduction:Isolated anterior cerebral artery occlusions (iACAo) in acute ischemic stroke (AIS) patients present significant challenges due to their rarity and complex symptomatology. The efficacy of endovascular therapy (EVT) versus best medical management (BMM) for iACAo remains unclear. In light of context we aim in this investigation to assess the outcomes of these treatments.Methods:This multinational, multicenter study analyzed data from the Multicenter Analysis of Distal Medium Vessel Occlusions: Effect of Mechanical Thrombectomy (MAD-MT) registry. We included 108 patients with iACAo, who underwent either EVT or BMM. Data were collected retrospectively from 37 sites across North America, Asia, and Europe. Inverse Probability of Treatment Weighting (IPTW) was applied to balance confounding variables between treatment groups. The primary outcome was functional independence at 90 days. Secondary outcomes included excellent outcomes (mRS 0-1), mortality, and NIHSS score on day one post-EVT. Safety outcomes assessed hemorrhagic complications.Results:Of the 108 patients, 36 received BMM and 72 underwent EVT. The median age was 75 years (IQR 67-87), with 60 (56%) male patients overall. The primary outcome of 90-day mRS 0-2 was achieved in 40% of the cohort, with no significant difference between the EVT and BMM groups (38% vs. 45%, p=0.46). Procedural success (TICI 2b-3) was high in EVT patients at 91%, with a low sICH rate of 2.9%. The IPTW-adjusted analysis showed no significant association between EVT and improved functional outcomes (OR 1.17, 95% CI 0.23-6.02, p=0.85) or reduced mortality (23% overall; 25% EVT vs. 21% BMM, p=0.71). However, EVT was associated with higher NIHSS scores on day one post-stroke in crude analyses (OR 4.8, 95% CI 1.2-8.5, p=0.012), though this was not significant in the IPTW model (OR 2.2, 95% CI -0.51 to 4.8, p=0.11).Conclusions:In this propensity score-weighted analysis, EVT did not demonstrate superior functional outcomes compared to BMM in patients with iACAo. Nonetheless, EVT achieved high procedural success and low rates of symptomatic hemorrhage, indicating its safety. These findings highlight the need for randomized controlled trials to further explore EVT’s potential role as a first-line or rescue therapy in iACAo patients, especially given the low recanalization rates with IV thrombolysis alone.

Stroke, Volume 56, Issue Suppl_1, Page AWP395-AWP395, February 1, 2025. Introduction:Polymorphonuclear Neutrophils (PMNs) are the first blood-derived immune cells to respond in ischemia/reperfusion injury (I/RI). PMNs exhibit spatial heterogeneity and play complex roles in injury progression and resolution. However, preclinical studies investigating the immune response have been limited to studying the area of maximal infarction or highly representative images throughout the stroke hemisphere. As a result, the spatial relationships of PMNs in the acute stages of I/RI throughout the whole brain remain largely unknown. To address this gap in knowledge, we applied light sheet microscopy (LSM) to fully map the spatial patterns of PMNs in relation to neuronal injury throughout the murine brain in I/RI.Methods:The transient middle cerebral artery occlusion (tMCAO) model was used to recapitulate I/RI in a Ly6G-tdTomato transgenic mouse line expressing an endogenous fluorescent marker for PMNs. Mice were subject to 60 min or 90 min of ischemia to model strokes of varying severity. Whole brains were collected 72h post-tMCAO, (the point of maximal PMN infiltration), cleared, and then imaged using LSM. Brains were co-labeled with NeuN (neurons), registered, and parcellated according to the Allen Brain Atlas. Relationships of PMNs to the M1 segment of the MCA were then mapped.Results:Following 60 min tMCAO, PMNs infiltrated predominantly in infarcted regions of the cerebral cortex (NeuN Negative). Further, the density of PMNs was higher in anatomic regions supplied by the middle cerebral artery (MCA) and negatively correlated with the distance from the M1. In the 90 min tMCAO, PMN infiltration followed a similar pattern with PMN accumulation predominantly in the ischemic cortex and increased with proximity to the M1. However, PMN densities in the 90 min tMCAO were significantly higher than in the 60 min tMCAO. Additionally, PMN-rich regions in the 90 min tMCAO were more concentrated than in the 60 min tMCAO.Conclusions:Our data demonstrate that PMNs exhibit spatial heterogeneity following experimental stroke and cluster in regions corresponding to increased neuronal death and proximity to the MCA. PMN distribution was also influenced by the duration of ischemia, suggesting that PMNs are highly responsive to both stroke topology and severity. These data enable a more in-depth understanding of neutrophil dynamics in I/RI that can be leveraged to inform future stroke therapies directed at limiting the immune response.

Stroke, Volume 56, Issue Suppl_1, Page AWP385-AWP385, February 1, 2025. Background:A damaged stroke area can affect both local and connected brain regions, leading to network-wide disruptions in brain functions. Increasing evidence shows that estrogen, particularly 17β-estradiol, plays a protective role after ischemic stroke. Understanding how hormonal levels impact brain stimulation may shed light on varying responses to neuromodulation therapies across estrous cycle phases. Previously, we demonstrated that optogenetic stimulations in the ipsilesional primary motor cortex (iM1) enhance functional recovery in male mice. In this study, we aim to expand upon these findings by exploring functional recovery and post-stroke neuroplasticity changes in in female mice.Methods:Female C57BL/6 mice (7-9 weeks old) underwent stereotaxic surgery to express channelrhodopsins-2 and implant an optical fiber in iM1. Four weeks later, transient middle cerebral artery occlusion (MCAO) was induced. Optogenetic stimulation was initiated on day 5 post-stroke and continued for 10 days. Estrous cycles were monitored via vaginal swabbing and estradiol ELISA measurements. Rotating beam tests were performed at pre-stroke, 4, 7, 10, and 14 days post-stroke (PD4, PD7, PD10, and PD14). Infarct size, astrocytic activation and microglia/macrophage activation were assessed.Results:Rotating beam tests showed that 71.4% of the stimulated mice significantly recovered by PD10 (p

Stroke, Volume 56, Issue Suppl_1, Page ADP14-ADP14, February 1, 2025. Background:PCSK9, a key regulator of cholesterol metabolism, has been implicated in atherosclerosis. However, its potential role in vascular cognitive impairment and dementia (VCID) remains elusive. We hypothesized that PCSK9 overexpression, exacerbated by a high-fat diet (HFD), would promote neurovascular inflammation and recapitulate VCID pathology.Methods:C57 mice were stratified into control, PCSK9 overexpression, HFD, and PCSK9+HFD groups. PCSK9 overexpression was induced via AAV injection, and mice were subjected to either a normal diet or HFD for 4 months. Laser speckle contrast imaging was employed to assess CBF response to whisker stimulation. Immunofluorescence analyses were conducted to evaluate neurovascular alterations, encompassing microvascular density, glial activation, neuronal density, arteriosclerosis, and blood-brain barrier integrity. Light sheet microscopy was utilized to provide ultra-high resolution 3D imaging of the cerebrovascular architecture. Cognitive function and exploratory behavior were investigated using novel object recognition and open field tests.Results:PCSK9+HFD mice exhibited significantly compromised neurovascular coupling, as evidenced by attenuated CBF response to whisker stimulation. Immunofluorescence revealed profound neurovascular alterations, including markedly reduced microvascular density, exacerbated astrogliosis and microglial activation, diminished neuronal density, heightened arteriosclerosis and inflammation, and severe blood-brain barrier disruption. These changes were most pronounced in the PCSK9+HFD group, followed by the HFD and PCSK9 groups, highlighting the synergistic detrimental effects of PCSK9 overexpression and HFD. Notably, light sheet fluorescence microscopy (LSFM) unveiled a dramatically sparser and less complex 3D cerebrovascular network in PCSK9+HFD mice. Moreover, PCSK9+HFD mice displayed the most severe neurocognitive changes, as shown by impaired recognition memory and reduced exploration.Conclusions:This study demonstrates that metabolic syndrome induced by PCSK9 overexpression and HFD synergistically converge upon neuroinflammatory mediators to recapitulate VCID pathology. Microglial and astrocytic activation in PCSK9 overexpression and HFD is strongly associated with altered cerebral blood flow regulation. Our findings provide a preclinical platform for discovery of new therapeutic approaches for neuroinflammatory and cerebrovascular alterations associated with VCID pathology.

Stroke, Volume 56, Issue Suppl_1, Page ADP37-ADP37, February 1, 2025. Object:The introduction of antiplatelet agents is essential in stent-assisted coil embolization (SACE) for the treatment of intracranial aneurysms, and preoperative drug efficacy assessment is important in reducing the risk of ischemic complications. Light Transmission Aggregometry (LTA) is used in our institution to assess drug efficacy, and we analyzed the association between patient background factors, including preoperative LTA values, and perioperative complications in patients who underwent SACE in a retrospective analysis.Methods:Patients who underwent SACE for unruptured cerebral aneurysms from 1 March 2017 to 30 June 2024 were included. Two antiplatelet drugs (aspirin 100 mg and clopidogrel 75 mg /or prasugrel 3.75 mg) were administered 7 days prior to the procedure, and LTA measurements were performed on the day of surgery. The association of each patient’s background factors with ischemic complications during the hospitalization period (≥1 mRS drop) and DWI and SWI positivity rates on the day after surgery was analyzed. To investigate whether LTA value affect DWI positive rate, propensity score-matched analysis was employed to control for age, sex, alcohol consumption, smoking, family history, medical history, aneurysm shape, multiple aneurysms, symptomatic aneurysms, maximum diameter, neck diameter, aneurysm site, left or right, first treatment or not, stent type, number of stents, clopidogrel or prasugrel.Results:During the observation period, 1021 unruptured cerebral aneurysms received endovascular treatment, of which 548 (453 Neuroform Atlas, 17 Enterprise, 78 LVIS) underwent coil embolization with stenting. The mean LTA value on the day of surgery was 44.2 (20-74). Symptomatic ischemic complications were present in two patients (0.4%), but no associated factors were found. Propensity score matching was successful for pairs of 184 aneurysms in the DWI negative group and 184 aneurysms in the DWI positive group. LTA value was still significantly higher in DWI positive group than in DWI negative group (46.96 vs 42.14, p