Improvement of the thalamocortical white matter network in people with stable treated relapsing-remitting multiple sclerosis over time.

Advanced imaging techniques (tractography) enable the mapping of white matter (WM) pathways and the understanding of brain connectivity patterns. We combined tractography with a network-based approach to examine WM microstructure on a network level in people with relapsing-remitting multiple sclerosis (pw-RRMS) and healthy controls (HCs) over 2 years. Seventy-six pw-RRMS matched with 43 HCs underwent clinical assessments and 3T MRI scans at baseline (BL) and 2-year follow-up (2-YFU). Probabilistic tractography was performed, accounting for the effect of lesions, producing connectomes of 25 million streamlines. Network differences in fibre density across pw-RRMS and HCs at BL and 2-YFU were quantified using network-based statistics (NBS). Longitudinal network differences in fibre density were quantified using NBS in pw-RRMS, and were tested for correlations with disability, cognition and fatigue scores. Widespread network reductions in fibre density were found in pw-RRMS compared with HCs at BL in cortical regions, with more reductions detected at 2-YFU. Pw-RRMS had reduced fibre density at BL in the thalamocortical network compared to 2-YFU. This effect appeared after correction for age, was robust across different thresholds, and did not correlate with lesion volume or disease duration. Pw-RRMS demonstrated a robust and long-distance improvement in the thalamocortical WM network, regardless of age, disease burden, duration or therapy, suggesting a potential locus of neuroplasticity in MS. This network's role over the disease's lifespan and its potential implications in prognosis and treatment warrants further investigation.

Increased Permeability of the Blood-Brain Barrier in a Diabetic Mouse Model (Leprdb/db Mice).

Type 2 Diabetes Mellitus (T2DM) is linked to multiple complications, including cognitive impairment, and the prevalence of memory-related neurodegenerative diseases is higher in T2DM patients. One possible theory is the alteration of the microvascular and macrovascular environment of the blood-brain barrier (BBB). In this study, we employed different approaches, including RT-PCR, functional pharmacokinetic studies using sodium fluorescein (NaFL), and confocal microscopy, to characterize the functional and molecular integrity of the BBB in a T2DM animal model, leptin receptor-deficient mutant mice (Leprdb/db mice). As a result, VCAM-1, ICAM-1, MMP-9, and S100b (BBB-related markers) dysregulation was observed in the Leprdb/db animal model compared to littermate wild-type mice. The brain concentration of sodium fluorescein (NaFL) increased significantly in Leprdb/db untreated mice compared to insulin-treated mice. Therefore, the permeability of NaFL was higher in Leprdb/db control mice than in all remaining groups. Identifying the factors that increase the BBB in Leprdb/db mice will provide a better understanding of the BBB microvasculature and present previously undescribed findings of T2DM-related brain illnesses, filling knowledge gaps in this emerging field of research.

APOE ε2-Carriers Are Associated with an Increased Risk of Primary Angle-Closure Glaucoma in Patients of Saudi Origin.

This study investigated the association between apolipoprotein E (APOE) gene polymorphisms (rs429358 and rs7412) and primary angle-closure glaucoma (PACG) and pseudoexfoliation glaucoma (PXG) in a Saudi cohort. Genotyping of 437 DNA samples (251 controls, 92 PACG, 94 PXG) was conducted using PCR-based Sanger sequencing. The results showed no significant differences in the allele and genotype frequencies of rs429358 and rs7412 between the PACG/PXG cases and controls. Haplotype analysis revealed ε3 as predominant, followed by ε4 and ε2 alleles, with no significant variance in PACG/PXG. However, APOE genotype analysis indicated a significant association between ε2-carriers and PACG (odds ratio = 4.82, 95% CI 1.52-15.26, p = 0.007), whereas no notable association was observed with PXG. Logistic regression confirmed ε2-carriers as a significant predictor for PACG (p = 0.008), while age emerged as significant for PXG (p < 0.001). These findings suggest a potential role of ε2-carriers in PACG risk within the Saudi cohort. Further validation and larger-scale investigations are essential to elucidate the precise role of APOE in PACG pathogenesis and progression.

Effectiveness of intra-thecal methotrexate in refractory Anti-N-methyl-d-aspartate receptor encephalitis.

BACKGROUND: Anti-N-methyl-d-aspartate "anti-NMDA" receptor encephalitis is one of the most common autoimmune encephalitis for which first- and second-line therapies have been recommended following international consensus. However, some refractory cases do not respond to the first- and second-line therapy and require further immune-modulatory therapies such as intra-thecal methotrexate. In this study, we reviewed six confirmed cases of refractory anti-NMDA receptor encephalitis from two tertiary centers in Saudi Arabia that required escalation of treatment and received a six-month course of intra-thecal methotrexate. The aim of this study was to evaluate the effectiveness of intra-thecal methotrexate as immunomodulatory therapy for refractory anti-NMDA receptor encephalitis. METHODS: We retrospectively evaluated six confirmed cases of refractory anti-NMDA receptor encephalitis who did not improve after first- and second-line therapy and received monthly intra-thecal methotrexate treatment course for six consecutive months. We reviewed patient demography, underlying etiologies, and compared their modified Rankin score prior to receiving intra-thecal methotrexate and six months after completing the treatment. RESULTS: Three of the six patients showed a marked response to intra-thecal methotrexate with a modified Rankin scale of 0-1 at 6-month follow-up. None of the patients experienced any side effects during or after intra-thecal methotrexate treatment, and no flareups were observed. CONCLUSION: Intra-thecal methotrexate may be a potentially effective and relatively safe escalation option for immunomodulatory therapy of refractory anti-NMDA receptor encephalitis. Future studies on intra-thecal methotrexate -specific treatment regimens may further support its utility, efficacy, and safety in treating refractory anti-NMDA receptor encephalitis.

Evaluation of Early Tocilizumab Effect on Multiorgan Dysfunction in Critically Ill Patients With COVID-19: A Propensity Score-Matched Study.

Background: Tocilizumab (TCZ) has been proposed as potential rescue therapy for severe COVID-19. No previous study has primarily assessed the role of TCZ in preventing severe COVID-19-related multiorgan dysfunction. Hence, this multicenter cohort study aimed to evaluate the effectiveness of TCZ early use versus standard of care in preventing severe COVID-19-related multiorgan dysfunction in COVID-19 critically ill patients during intensive care unit (ICU) stay. Methods: A multicenter, retrospective cohort study includes critically ill adult patients with COVID-19 admitted to the ICUs. Patients were categorized into two groups, the treatment group includes patients who received early TCZ therapy within 24 hours of ICU admission and the control group includes patients who received standard of care. The primary outcome was the multiorgan dysfunction on day three of the ICU admission. The secondary outcomes were 30-day, and in-hospital mortality, ventilator-free days, hospital length of stay (LOS), ICU LOS, and ICU-related complications. Results: After propensity score matching, 300 patients were included in the analysis based on predefined criteria with a ratio of 1:2. Patients who received TCZ had lower multiorgan dysfunction score on day three of ICU admission compared to the control group (beta coefficient: -0.13, 95% CI: -0.26, -0.01, P-value = 0.04). Moreover, respiratory failure requiring MV was statistically significantly lower in patients who received early TCZ compared to the control group (OR 0.52; 95% CI 0.31, 0.91, P-value = 0.02). The 30-day and in-hospital mortality were significantly lower in patients who received TCZ than those who did not (HR 0.56; 95% CI 0.37, 0.85, P-value = 0 .006 and HR 0.54; 95% CI 0.36, 0.82, P-value = 0.003, respectively). Conclusion: In addition to the mortality benefits associated with early TCZ use within 24 hours of ICU admission, the use of TCZ was associated with a significantly lower multiorgan dysfunction score on day three of ICU admission in critically ill patients with COVID-19.

Sternal Wound Infection Following Open Heart Surgery: Incidence, Risk Factor, Pathogen, and Mortality.

BACKGROUND: Due to its high morbidity and mortality after open-heart surgery, sternal wound infection (SWI) is one of the most important consequences to avoid and manage. AIM: To assess the incidence, risk factor, causative organisms, and mortality of SWIs in patients who had open-heart surgery over a 9-year period at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. METHODS: A retrospective study was done on 634 patients who underwent open heart surgery. Data was collected, including patient demographics, BMI, blood group, diabetes, hyperlipidemia, COPD, previous cardiac surgery, previous myocardial infarction, duration of the operation, blood transfusion during the operation, hospital length of stay, and bypass time with each type of sternal wound infection. RESULTS: The incidence of SSWI and DSWI was 8.6% and 4.1%, respectively. Coagulase-negative staphylococcus was the most frequently isolated organism from SSWI and DSWI patients. A concomitant diabetes mellitus that necessitates blood transfusion was identified as one of the risk variables for SSWI in a multivariate regression study. While concomitant diabetes, being a woman, and a lengthy hospital stay were independently linked with DSWI. Compared with the SSWI group, the 30-day mortality rate for DSWI patients was 3.8% as opposed to 3.7%, and the difference in survival was not statistically significant. Having an older, longer bypass time, and postoperative problems were independent risk factors for 30-day mortality. CONCLUSION: Future studies in various healthcare settings are required in order to generalize the results because this was a single center study.

Comparison of immobilization periods following open reduction and internal fixation of distal radius fracture: A systematic review and meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. INTRODUCTION: The use of volar locking plate (VLP) in the fixation of fracture fragments promised a new era in the management of distal radius fracture (DRF). PURPOSE OF THE STUDY: To compare the patient-reported outcomes, functional outcomes, pain, and adverse events between the different periods of immobilization following open reduction and internal fixation of DRFs with VLP. METHODS: We searched Medline/Pubmed, Web of Science, Ovid, and CINAHL. The inclusion criteria was randomized controlled trials that compared different immobilization periods after open reduction and internal fixation of DRFs with VLP. The last search was performed on 2 June 2020. The different immobilization periods were divided into the following 3 groups: ≤1-week group, 2-3-week group, and 5-6-week group. RESULTS: Seven eligible randomized controlled trials provided data on 509 patients. We found that compared to 5-6-week group, ≤1-week and 2-3-week groups showed a reduction in overall Patient-Reported Wrist Evaluation score (SMD = -0.48, 95% CI -0.73 to -0.22, P < .001; SMD = -0.69, 95% CI -0.97 to -0.41, P < .001, respectively). We also found that there were improvements in the other patient-reported outcomes including overall Disabilities of the Arm, Shoulder, and Hand score and pain; and functional outcomes including overall grip strength and range of motion measures in favor of ≤1-week and 2-3-week groups. CONCLUSION: This systematic review and meta-analysis showed that compared to immobilization for 5 to 6 weeks after DRF repair, immobilization for ≤1 week or 2-3 weeks showed improvements in the patients-reported outcomes and functional outcomes. The differences between the 3 immobilization groups may not be clinically important considering the small changes as follow up progresses.

Evaluation of Low-Dose Aspirin use among Critically Ill Patients with COVID-19: A Multicenter Propensity Score Matched Study.

BACKGROUND: Aspirin is widely used as a cardioprotective agent due to its antiplatelet and anti-inflammatory properties. The literature has assessed and evaluated its role in hospitalized COVID-19 patients. However, no data are available regarding its role in COVID-19 critically ill patients. This study aimed to evaluate the use of low-dose aspirin (81-100 mg) and its impact on outcomes in critically ill patients with COVID-19. METHOD: A multicenter, retrospective cohort study of all critically ill adult patients with confirmed COVID-19 admitted to intensive care units (ICUs) between March 1, 2020, and March 31, 2021. Eligible patients were classified into two groups based on aspirin use during ICU stay. The primary outcome was in-hospital mortality, and other outcomes were considered secondary. Propensity score matching was used (1:1 ratio) based on the selected criteria. RESULTS: A total of 1033 patients were eligible, and 352 patients were included after propensity score matching. The in-hospital mortality (HR 0.73 [0.56, 0.97], p = 0.03) was lower in patients who received aspirin during stay. Conversely, patients who received aspirin had a higher odds of major bleeding than those in the control group (OR 2.92 [0.91, 9.36], p = 0.07); however, this was not statistically significant. Additionally, subgroup analysis showed a possible mortality benefit for patients who used aspirin therapy prior to hospitalization and continued during ICU stay (HR 0.72 [0.52, 1.01], p = 0.05), but not with the new initiation of aspirin (HR 1.22 [0.68, 2.20], p = 0.50). CONCLUSION: Continuation of aspirin therapy during ICU stay in critically ill patients with COVID-19 who were receiving it prior to ICU admission may have a mortality benefit; nevertheless, it may be associated with an increased risk of significant bleeding. Appropriate evaluation for safety versus benefits of utilizing aspirin therapy during ICU stay in COVID19 critically ill patients is highly recommended.

Demographics, comorbidities, and outcomes among young and middle-aged COVID-19 patients in Saudi Arabia.

The impact of different sociodemographic and clinical characteristics on the COVID-19-related morbidity and mortality rates have been studied extensively around the world; however, there is a dearth of data on the impact of different clinical and sociodemographic variables on the COVID-19-related outcomes in Saudi Arabia. This study aimed to identify those at high risk of worse clinical outcomes, such as hospitalization and longer length of stay (LOS) among young and middle-aged adults (18 to 55 years). In this questionnaire-based cross-sectional study, 706 patients with real-time polymerase chain reaction (RT-PCR) confirmed COVID-19 infection were interviewed. Patients' demographic characteristics, dietary habits, medical history, and lifestyle choices were collected through phone interviews. Patients with chronic health conditions, such as diabetes and hypertension, reported a higher rate of hospitalization, ICU admission, oxygen-support needs, and a longer period of recovery and LOS. Multiple logistic regression showed that diabetes, hypertension, and pulmonary disease (e.g., asthma and chronic obstructive pulmonary disease (COPD)) were associated with a higher risk of hospitalization and longer LOS. Multiple logistic regression showed that symptoms of breathlessness, loss of smell and/or taste, diarrhea, and cough were associated with a longer recovery period. Similarly, breathlessness, vomiting, and diarrhea were associated with higher rates of hospitalization. The findings of this study confirm the similarity of the factors associated with worse clinical outcomes across the world. Future studies should use more robust designs to investigate the impact of different therapies on the COVID-19-related morbidity and mortality in Saudi Arabia.

Systemic TNF-α blockade attenuates anxiety and depressive-like behaviors in db/db mice through downregulation of inflammatory signaling in peripheral immune cells.

Research studies have indicated that the comorbidity burden of mood disorders and obesity is reasonably high. Insulin signaling has been shown to modulate multiple physiological functions in the brain, indicating its association with neuropsychiatric diseases, including mood disorders. Leptin is a hormone responsible for regulating body weight and insulin homeostasis. Previous studies on db/db mice (a mouse model that carries a spontaneous genetic mutation in leptin receptor Leprdb ) have shown that they exhibit inflammation as well as neurobehavioral traits associated with mood. Therefore, targeting inflammatory pathways such as TNF-α may be an effective strategy in the treatment of obesity-linked mood disorders. The objective of this study was to investigate the effect of long-term administration of etanercept (a TNF-α blocker) on anxiety and depressive-like behaviors in db/db mice. This was performed using light/dark box, forced swim, and open field tests with lean littermate wild type (WT) mice serving as a control group. Using flow cytometry in peripheral blood, we further examined the molecular effects of etanercept on NF-κB p65, TNF-α, IL-17A, and TLR-4 expressing CD4+, CD8+, and CD14+ cells in the peripheral blood. Our data show that peripheral administration of etanercept decreased these cells in db/db mice. Furthermore, our results indicated that peripheral administration of etanercept reduced anxiety and depressive-like behaviors. Therefore, targeting TNF-α signaling might be an effective strategy for modulating obesity-associated depression and anxiety.

Influence of electronic nicotine delivery systems (ENDS) in comparison to conventional cigarette on color stability of dental restorative materials.

OBJECTIVE: The use of Electronic Nicotine Delivery Systems (ENDS) is increasing rapidly. However, its discoloring effect on dental restorations is not known. This study aimed to evaluate the effect of ENDS aerosol when compared to conventional cigarette smoke (CS) on the color stability of dental ceramic (DC) and resin composite (RC). METHODS: This research project was conducted from November 2018 to May 2019. In this study 30 discs each for DC and RC materials were fabricated to be equally divided into groups of exposure to CS, ENDS aerosol and storage in distilled water (No smoke; NS) respectively (n=10). Specimens were exposed for a total of 7 days, with a rate of 10 cycles per day, each cycle represented 10 puffs. The color change was assessed using the CIELAB color space, by calculating ΔE. Data was analysed using ANOVA and multiple comparisons test. RESULTS: Ceramic specimens in CS (2.422 ± 0.771) and ENDS (2.396 ± 0.396) groups showed comparable ΔE (color change) (p=0.992). Similarly, composite specimens in CS (42.871 ± 2.442) and ENDS (46.866 ± 3.64) groups showed comparable ΔE (p>0.05). NS specimens in both composite and ceramic samples showed lower ΔE than CS and ENDS specimens respectively. CONCLUSIONS: Aerosol from Electronic nicotine delivery systems (ENDS) showed similar discoloration levels as cigarette smoking (CS). The level of discoloration for ceramic samples for both ENDS and CS was below clinically perceptible levels (Mean ΔE < 2.5). Discoloration of composite resin due to CS and ENDS was visually perceptible (Mean ΔE > 4.0).

Changes in the Fluorescence Tracking of NaV1.6 Protein Expression in a BTBR T+Itpr3tf/J Autistic Mouse Model.

The axon initial segment (AIS), the site of action potential initiation in neurons, is a critical determinant of neuronal excitability. Growing evidence indicates that appropriate recruitment of the AIS macrocomplex is essential for synchronized firing. However, disruption of the AIS structure is linked to the etiology of multiple disorders, including autism spectrum disorder (ASD), a condition characterized by deficits in social communication, stereotyped behaviors, and very limited interests. To date, a complete understanding of the molecular components that underlie the AIS in ASD has remained elusive. In this research, we examined the AIS structure in a BTBR T+Itpr3tf/J mouse model (BTBR), a valid model that exhibits behavioral, electrical, and molecular features of autism, and compared this to the C57BL/6J wild-type control mouse. Using Western blot studies and high-resolution confocal microscopy in the prefrontal frontal cortex (PFC), our data indicate disrupted expression of different isoforms of the voltage-gated sodium channels (NaV) at the AIS, whereas other components of AIS such as ankyrin-G and fibroblast growth factor 14 (FGF14) and contactin-associated protein 1 (Caspr) in BTBR were comparable to those in wild-type control mice. A Western blot assay showed that BTBR mice exhibited a marked increase in different sodium channel isoforms in the PFC compared to wild-type mice. Our results provide potential evidence for previously undescribed mechanisms that may play a role in the pathogenesis of autistic-like phenotypes in BTBR mice.

Comparing fatal crash risk factors by age and crash type by using machine learning techniques.

This study aims to use machine learning methods to examine the causative factors of significant crashes, focusing on accident type and driver's age. In this study, a wide-ranging data set from Jeddah city is employed to look into various factors, such as whether the driver was male or female, where the vehicle was situated, the prevailing weather conditions, and the efficiency of four machine learning algorithms, specifically XGBoost, Catboost, LightGBM and RandomForest. The results show that the XGBoost Model (accuracy of 95.4%), the CatBoost model (94% accuracy), and the LightGBM model (94.9% accuracy) were superior to the random forest model with 89.1% accuracy. It is worth noting that the LightGBM had the highest accuracy of all models. This shows various subtle changes in models, illustrating the need for more analyses while assessing vehicle accidents. Machine learning is also a transforming tool in traffic safety analysis while providing vital guidelines for developing accurate traffic safety regulations.

Examination of factors associated with the temporal stability assessment of crash severity by using generalised linear model-A case study.

Road crashes are a major public safety concern in Pakistan. Prior studies in Pakistan investigated the impact of different factors on road crashes but did not consider the temporal stability of crash data. This means that the recommendations based on these studies are not fully effective, as the impact of certain factors may change over time. To address this gap in the literature, this study aims to identify the factors contributing to crash severity in road crashes and examine how their impact varies over time. In this comprehensive study, we utilized Generalised Linear Model (GLM) on the crash data between the years 2013 to 2017, encompassing a total sample of 802 road crashes occurred on the N-5 road section in Pakistan, a 429-kilometer stretch connecting two big cities of Pakistan, i.e., Peshawar and Lahore. The purpose of the GLM was to quantify the temporal stability of the factors contributing crash severity in each year from 2013 to 2017. Within this dataset, 60% (n = 471) were fatal crashes, while the remaining 40% (n = 321) were non-fatal. The results revealed that the factors including the day of the week, the location of the crashes, weather conditions, causes of the crashes, and the types of vehicles involved, exhibited the temporal instability over time. In summary, our study provides in-depth insights aimed at reducing crash severity and potentially aiding in the development of effective crash mitigation policies in Pakistan and other nations having similar road safety problems. This research holds great promise in exploring the dynamic safety implications of emerging transportation technologies, particularly in the context of the widespread adoption of connected and autonomous vehicles.

Physiological Variability during Prehospital Stroke Care: Which Monitoring and Interventions Are Used?

Prehospital care is a fundamental component of stroke care that predominantly focuses on shortening the time between diagnosis and reaching definitive stroke management. With growing evidence of the physiological parameters affecting long-term patient outcomes, prehospital clinicians need to consider the balance between rapid transfer and increased physiological-parameter monitoring and intervention. This systematic review explores the existing literature on prehospital physiological monitoring and intervention to modify these parameters in stroke patients. The systematic review was registered on PROSPERO (CRD42022308991) and conducted across four databases with citation cascading. Based on the identified inclusion and exclusion criteria, 19 studies were retained for this review. The studies were classified into two themes: physiological-monitoring intervention and pharmacological-therapy intervention. A total of 14 included studies explored prehospital physiological monitoring. Elevated blood pressure was associated with increased hematoma volume in intracerebral hemorrhage and, in some reports, with increased rates of early neurological deterioration and prehospital neurological deterioration. A reduction in prehospital heart rate variability was associated with unfavorable clinical outcomes. Further, five of the included records investigated the delivery of pharmacological therapy in the prehospital environment for patients presenting with acute stroke. BP-lowering interventions were successfully demonstrated through three trials; however, evidence of their benefit to clinical outcomes is limited. Two studies investigating the use of oxygen and magnesium sulfate as neuroprotective agents did not demonstrate an improvement in patient's outcomes. This systematic review highlights the absence of continuous physiological parameter monitoring, investigates fundamental physiological parameters, and provides recommendations for future work, with the aim of improving stroke patient outcomes.

Shear strength and particle breakage of construction and demolition waste as a function of moisture state and compaction level: Insights for sustainable highway engineering.

In this study, the variation of shear strength behavior and particle breakage (after shearing), as a function of moisture state and compaction level, is investigated for recycled concrete aggregate blended with recycled clay masonry. Recycled masonry was blended with concrete aggregate in percentages ranging from 0% to 30% by total weight. Tests include; basic engineering characteristics (particle size, modified compaction, hydraulic conductivity, and California Bearing Ratio, CBR) as well as unconsolidated undrained static triaxial testing. In triaxial tests, moisture levels ranged from 60% to 100% of optimum moisture content, but compaction levels ranged from 90% to 98% of maximum dry density. The hydraulic conductivity for blends is approximately 2x10-6 cm/s, which indicates a relatively low hydraulic conductivity. Results show a proportional linear relationship between the shear strength of blends and the level of compaction. Despite this, both apparent cohesion and shear strength exhibited reverse linear trends. As expected, more compaction effort resulted in more particle breakage. Strict control should be performed over the compaction process to achieve the required compaction level which resulting in pavement materials being stiffer.

Diffusion tensor imaging changes of the cortico-thalamic-striatal tracts correlate with fatigue and disability in people with relapsing-remitting MS.

PURPOSE: To investigate how the microstructural neural integrity of cortico-thalamic-striatal (CTS) tracts correlate with fatigue and disability over time. The primary outcome was diffusion tensor imaging (DTI) metrics change over time, and the secondary outcome was correlations with fatigue and disability in people with RRMS (pw-RRMS). METHODS: 76 clinically stable pw-RRMS and 43 matched healthy controls (HCs). The pw-RRMS cohort consisted of three different treatment subgroups. All participants underwent disability, cognitive, fatigue and mental health assessments. Structural and diffusion scans were performed at baseline (BL) and 2-year follow-up (2-YFU) for all participants. Fractional anisotropy (FA), mean, radial and axial diffusivities (MD, RD, AD) of normal-appearing white matter (NAWM) and white matter lesion (WML) in nine tracts-of-interests (TOIs) were estimated using our MRtrix3 in-house pipeline. RESULTS: We found significant BL and 2-YFU differences in most diffusion metrics in TOIs in pw-RRMS compared to HCs (pFDR ≤ 0.001; false-detection-rate (FDR)-corrected). There was a significant decrease in WML diffusivities and an increase in FA over the follow-up period in most TOIs (pFDR ≤ 0.001). Additionally, there were no differences in DTI parameters across treatment groups. AD and MD were positively correlated with fatigue scores (r ≤ 0.33, p ≤ 0.01) in NAWM-TOIs, while disability (EDSS) was negatively correlated with FA in most NAWM-TOIs (|r|≤0.31, p ≤ 0.01) at both time points. Disability scores correlated with all diffusivity parameters (r ≤ 0.29, p ≤ 0.01) in most WML-TOIs at both time points. CONCLUSION: Statistically significant changes in diffusion metrics in WML might be indicative of integrity improvement over two years in CTS tracts in clinically stable pw-RRMS. This finding represents structural changes within lesioned tracts. Measuring diffusivity in pw-RRMS affected tracts might be a relevant measure for future remyelination clinical trials.

A Multi-Parametric Approach for Characterising Cerebral Haemodynamics in Acute Ischaemic and Haemorrhagic Stroke.

BACKGROUND AND PURPOSE: Early differentiation between acute ischaemic (AIS) and haemorrhagic stroke (ICH), based on cerebral and peripheral hemodynamic parameters, would be advantageous to allow for pre-hospital interventions. In this preliminary study, we explored the potential of multiple parameters, including dynamic cerebral autoregulation, for phenotyping and differentiating each stroke sub-type. METHODS: Eighty patients were included with clinical stroke syndromes confirmed by computed tomography within 48 h of symptom onset. Continuous recordings of bilateral cerebral blood velocity (transcranial Doppler ultrasound), end-tidal CO2 (capnography), electrocardiogram (ECG), and arterial blood pressure (ABP, Finometer) were used to derive 67 cerebral and peripheral parameters. RESULTS: A total of 68 patients with AIS (mean age 66.8 ± SD 12.4 years) and 12 patients with ICH (67.8 ± 16.2 years) were included. The median ± SD NIHSS of the cohort was 5 ± 4.6. Statistically significant differences between AIS and ICH were observed for (i) an autoregulation index (ARI) that was higher in the unaffected hemisphere (UH) for ICH compared to AIS (5.9 ± 1.7 vs. 4.9 ± 1.8 p = 0.07); (ii) coherence function for both hemispheres in different frequency bands (AH, p < 0.01; UH p < 0.02); (iii) a baroreceptor sensitivity (BRS) for the low-frequency (LF) bands that was higher for AIS (6.7 ± 4.2 vs. 4.10 ± 2.13 ms/mmHg, p = 0.04) compared to ICH, and that the mean gain of the BRS in the LF range was higher in the AIS than in the ICH (5.8 ± 5.3 vs. 2.7 ± 1.8 ms/mmHg, p = 0.0005); (iv) Systolic and diastolic velocities of the affected hemisphere (AH) that were significantly higher in ICH than in AIS (82.5 ± 28.09 vs. 61.9 ± 18.9 cm/s), systolic velocity (p = 0.002), and diastolic velocity (p = 0.05). CONCLUSION: Further multivariate modelling might improve the ability of multiple parameters to discriminate between AIS and ICH and warrants future prospective studies of ultra-early classification (<4 h post symptom onset) of stroke sub-types.

Characterization of Demographic, Clinical, and Laboratory Risk Factors for Stroke in a Tertiary Hospital in Riyadh, Saudi Arabia.

Background Stroke is a major cause of death and long-term disability worldwide, with varying incidence and risk factors across different populations. This study aims to analyze demographic, clinical, and laboratory risk factors for stroke among the Saudi Arabian population to enhance the understanding of its behavior and associated mortality. Methods In this retrospective cohort study, we analyzed data from 3586 patients diagnosed with hemorrhagic or non-hemorrhagic stroke at King Fahad Medical City from January 1, 2020, to November 11, 2022. We collected data on demographic variables, past medical history, social history, nationality, and laboratory components. Statistical analyses were performed using IBM SPSS Statistics for Windows, Version 27.0. (Armonk, NY: IBM Corp.), with significance set at p<0.05. Results The study population was predominantly male (57.86%) and within the age group of 51 to 80 years (58.8%). A significant portion of patients were Saudi nationals (99.6%), with hypertension (50.2%) and diabetes (40.4%) being the most common comorbidities. Laboratory abnormalities related to sodium and potassium levels were strongly linked to mortality rates. Notably, ischemic stroke was the most common type across all age groups, except for patients under age 16, where hemorrhagic stroke was more prevalent. Conclusions Our findings reveal significant associations between stroke risk factors and mortality within the Saudi Arabian population, highlighting the impact of hypertension, diabetes, and electrolyte imbalances. The study underscores the need for targeted stroke prevention and management strategies in Saudi Arabia, aligning with global trends to mitigate the burden of this disease.

Factors Underlying Vaccine Hesitancy and Their Mitigations in Saudi Arabia: Protocol for a Systematic Review.

BACKGROUND: Vaccine hesitancy is a growing concern in Saudi Arabia, impacting even well-educated parents. The decision-making process involves various factors such as accessibility, trustworthy information, and the influence of social networks, reflecting a complex interplay of emotional, cultural, social, spiritual, and political dimensions. OBJECTIVE: This review seeks to evaluate the prevalence and trends of vaccine hesitancy, identify contributing factors, and explore potential solutions to enhance immunization rates. This review aligns with global concerns, as the World Health Organization has identified vaccine hesitancy as a top global health threat. METHODS: Our systematic review will follow the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and PICOS (Population, Intervention, Comparison, Outcomes, and Study) criteria for comprehensive assessment. We will conduct a thorough search across various databases, encompassing a wide range of vaccines, and pay special attention to vaccination campaigns and refusals. Inclusion criteria involve descriptive, observational, and analytical studies focusing on factors influencing vaccine acceptance or hesitancy. The study will use the Crowe Critical Appraisal Tool for quality assessment and perform a narrative synthesis to summarize findings thematically. RESULTS: This systematic review is expected to unveil the prevalence and trends of vaccine hesitancy in diverse populations in Saudi Arabia, shedding light on cultural, religious, and social factors contributing to hesitancy. It aims to assess the effectiveness of implemented strategies, enable regional and global comparisons, and provide implications for tailored vaccination policies. Additionally, the review may pinpoint research gaps, guiding future investigations to address and mitigate vaccine hesitancy effectively. CONCLUSIONS: The findings are expected to have direct policy implications and guide interventions to strengthen vaccination programs and improve public health outcomes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/54680.