Baseline and Longitudinal MRI Markers Associated With 16-Year Mortality in Patients With Cerebral Small Vessel Disease.

BACKGROUND AND OBJECTIVES: Information on whether small vessel disease (SVD) reduces life expectancy is limited. Moreover, the excess mortality risk attributed specifically to SVD compared with controls from the general population has not been evaluated. This study aimed to investigate the baseline and progression of MRI markers of SVD associated with mortality in a 16-year follow-up cohort study and to determine the excess long-term mortality risk of patients with SVD. METHODS: Participants with SVD from the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort (RUN DMC) study (with MRI assessments in 2006, 2011, 2015, and 2020) were followed until their death or December 1, 2021. Adjusted Cox regression analyses and linear mixed-effect regression models were used to investigate the association between MRI markers of SVD and mortality. The excess mortality risk of SVD was calculated by comparing mortality data of the RUN DMC study with the general population matched by sex, age, and calendar year. RESULTS: 200 of 503 (39.9%) participants died during a follow-up period of 15.9 years. Cause of death was available for 182 (91%) participants. Baseline white matter hyperintensity volume (HR 1.3 per 1-SD increase [95% CI 1.1-1.5], p = 0.010), presence of lacunes (1.5 [95% CI 1.1-2.0], p = 0.008), mean diffusivity (HR 1.1 per 1-SD increase [95% CI 1.1-1.2], p = 0.001), and total brain volume (HR 1.5 per 1-SD decrease [95% CI 1.3-1.9], p < 0.001) were associated with all-cause mortality after adjusting for age, sex, and vascular risk factors. Total brain volume decrease over time was associated with all-cause mortality after adjusting for age, sex, and vascular risk factors (HR 1.3 per 1-SD decrease [95% CI 1.1-1.7], p = 0.035), and gray matter volume decrease remained significant after additionally adjusting for its baseline volume (1.3 per 1-SD decrease [1.1-1.6], p = 0.019). Participants with a Fazekas score of 3, presence of lacunes, or lower microstructural integrity had an excess long-term mortality risk (21.8, 15.7, 10.1 per 1,000 person-years, respectively) compared with the general population. DISCUSSION: Excess long-term mortality risk only exists in patients with severe SVD (Fazekas score of 3, presence of lacunes, or lower microstructural integrity). This could help in assisting clinicians to predict the clinical outcomes of patients with SVD by severity.

MiR-122, miR-133a, and miR-206 as potential biomarkers for post-mortem interval estimation.

BACKGROUD: Accurate estimation of post-mortem interval (PMI) is crucial in forensic investigations. MicroRNAs (miRNAs or miRs) are small non-coding RNAs that remain relatively stable within the cell nucleus despite post-mortem changes. OBJECTIVE: We assessed three target genes (miR-122, miR-133a, and miR-206) for PMI estimation using 72 healthy adult male BALB/c mice exposed to two different temperatures (4 and 21℃) at nine different time points over 10 days. METHODS: Initially, the stability of the two reference genes (RNU6B and 5 srRNA) was evaluated using gene stability analysis tools (Delta Ct, Best Keeper, and Genorm) to select the optimal reference gene. RNU6B was found to be the most stable endogenous control. Subsequently, the expression patterns of miR-122, miR-133a, and miR-206 were analyzed within a 10-day PMI period using the heart, skeletal muscle, liver, and brain tissues. RESULTS: At 4℃, miR-122 levels significantly decreased on days 8 and 10 in all tissues, with only the liver showing significant changes at 21℃. MiR-133a decreased over time in the heart, muscles, and brain, showing a dramatic decrease on days 8 and 10 in the heart and muscles at both temperatures. Although miR-206 levels decreased over time in muscles and liver at 4 â„ƒ, these increased in the brain at 21 â„ƒ, with no expression changes in other organs. CONCLUSION: In summary, miR-122, miR-133a, and miR-206 are potential PMI markers in heart and skeletal muscle tissues.

Can Older Adult Patients with Hip Fractures Have Their Discharge Destination Predicted by Physical Performance Measures?

Background and Objectives: The majority of patients who undergo hip fracture surgery do not recover their former level of physical function; hence, it is essential to establish a specific rehabilitation strategy for maximal functional recovery of patients after a hip fracture. Knowing which indicators of physical function in hip fracture patients have a significant impact on the decision regarding the place or timing of discharge would make it possible to plan and prepare for discharge as soon as possible. Therefore, this study aimed to investigate the relationship between physical function and discharge destination for older adult patients with hip fracture. Materials and Methods: In this retrospective cohort study, 150 hip fracture patients (mean age 78.9 ± 10.6 years) between January 2019 and June 2021 were enrolled. Patients were categorized into two groups according to their discharge destination, either home or facility. Demographic and disease-related characteristic data were collected from the medical records. All the patients completed performance-based physical function tests including the 10 Meter Walk Test (10MWT), Timed Up and Go test (TUG), Koval's grade, and Berg Balance Scale (BBS) at the start of rehabilitation and at discharge. A backward stepwise binary logistic regression analysis was then performed to determine the independent factors of the discharge destination. Results: The home discharge group had a significantly lower Koval's grade, lower TUG, higher BBS both at baseline and discharge, and younger age. Backward stepwise logistic binary regression analysis showed that TUG, BBS, and 10MWT at baseline and discharge were significant variables affecting the discharge destination after hip fracture. Conclusions: These results demonstrate that balance and gait in older adult patients with hip fractures are highly influential factors in the determining the discharge destination.

Bulk photovoltaic effect and high mobility in the polar 2D semiconductor SnP2Se6.

The growth of layered 2D compounds is a key ingredient in finding new phenomena in quantum materials, optoelectronics, and energy conversion. Here, we report SnP2Se6, a van der Waals chiral (R3 space group) semiconductor with an indirect bandgap of 1.36 to 1.41 electron volts. Exfoliated SnP2Se6 flakes are integrated into high-performance field-effect transistors with electron mobilities >100 cm2/Vs and on/off ratios >106 at room temperature. Upon excitation at a wavelength of 515.6 nanometer, SnP2Se6 phototransistors show high gain (>4 × 104) at low intensity (≈10-6 W/cm2) and fast photoresponse (< 5 microsecond) with concurrent gain of ≈52.9 at high intensity (≈56.6 mW/cm2) at a gate voltage of 60 V across 300-nm-thick SiO2 dielectric layer. The combination of high carrier mobility and the non-centrosymmetric crystal structure results in a strong intrinsic bulk photovoltaic effect; under local excitation at normal incidence at 532 nm, short circuit currents exceed 8 mA/cm2 at 20.6 W/cm2.

Long-term outcomes of magnetic sphincter augmentation in sleeve gastrectomy and Roux-en-Y gastric bypass patients: a comprehensive analysis.

INTRODUCTION: Management of gastroesophageal reflux disease after bariatric procedures can be challenging. There are very few long-term studies in this arena. This study aims to evaluate the long-term outcomes of the magnetic sphincter augmentation (MSA) reflux management system in a cohort of bariatric patients who had previously undergone sleeve gastrectomy and Roux-en-Y gastric bypass, with a focus on assessing gastroesophageal reflux disease (GERD) scores, medication use, and patient-reported symptoms. METHODS: We conducted a retrospective chart review of 16 consecutive bariatric patients who received MSA implants following sleeve gastrectomy (n = 14) or gastric bypass (n = 2) surgeries. Data were collected regarding BMI, GERD quality of life assessments (GERD-HRQL), reflux symptoms, and use of PPIs in the sleeve/RGB patients through an extended period with a mean follow-up of 48 months. RESULTS: Patients were followed up for a range of .5-84 months. Preoperative assessments included upper gastrointestinal imaging (UGI), high-resolution manometry, Bravo pH studies, and esophagogastroduodenoscopy (EGD). Three patients exhibited reflux on UGI, and 13/13 patients had positive Bravo studies preoperatively. Sixteen patients had a lower esophageal sphincter (LES) pressure under 18 mmHg, and eight patients had biopsy-proven esophagitis. Long-term outcomes are as follows. Daily PPI use fell from 88 to 25% at greater than three years. GERD-HRQL scores fell from 50.6 at baseline (range 27-70) and normalized at long-term follow-up. GERD symptom of regurgitation completely resolved. At long term, two patients had dysphagia and two patients had ongoing reflux. No adverse events were noted. CONCLUSION: This is the first long-term outcomes study of magnetic sphincter augmentation placement after bariatric surgery. Our study showed the majority of patients had long-term improvement in GERD-HRQL scores and resolution/ relief of their reflux symptoms, with decreased use of PPIs. MSA is a safe, effective and durable management tool for reflux after bariatric surgery in carefully selected patients.

Multiple-Junction-Based Traffic-Aware Routing Protocol Using ACO Algorithm in Urban Vehicular Networks.

The burgeoning interest in intelligent transportation systems (ITS) and the widespread adoption of in-vehicle amenities like infotainment have spurred a heightened fascination with vehicular ad-hoc networks (VANETs). Multi-hop routing protocols are pivotal in actualizing these in-vehicle services, such as infotainment, wirelessly. This study presents a novel protocol called multiple junction-based traffic-aware routing (MJTAR) for VANET vehicles operating in urban environments. MJTAR represents an advancement over the improved greedy traffic-aware routing (GyTAR) protocol. MJTAR introduces a distributed mechanism capable of recognizing vehicle traffic and computing curve metric distances based on two-hop junctions. Additionally, it employs a technique to dynamically select the most optimal multiple junctions between source and destination using the ant colony optimization (ACO) algorithm. We implemented the proposed protocol using the network simulator 3 (NS-3) and simulation of urban mobility (SUMO) simulators and conducted performance evaluations by comparing it with GSR and GyTAR. Our evaluation demonstrates that the proposed protocol surpasses GSR and GyTAR by over 20% in terms of packet delivery ratio, with the end-to-end delay reduced to less than 1.3 s on average.

Meso-cortical pathway damage in cognition, apathy and gait in cerebral small vessel disease.

Cerebral small vessel disease (SVD) is known to contribute to cognitive impairment, apathy, and gait dysfunction. Although associations between cognitive impairment and either apathy or gait dysfunction have been shown in SVD, the inter-relations among these three clinical features and their potential common neural basis remains unexplored. The dopaminergic meso-cortical and meso-limbic pathways have been known as the important brain circuits for both cognitive control, emotion regulation and motor function. Here, we investigated the potential inter-relations between cognitive impairment, apathy, and gait dysfunction, with a specific focus on determining whether these clinical features are associated with damage to the meso-cortical and meso-limbic pathways in SVD. In this cross-sectional study, we included 213 participants with SVD in whom MRI scans and comprehensive neurobehavioral assessments were administered. These assessments comprised of six clinical measures: processing speed, executive function, memory, apathy (based on the Apathy Evaluation Scale), and gait function (based on the time and steps in Timed Up and Go test). We reconstructed five tracts connecting ventral tegmental area (VTA) and the dorsolateral prefrontal cortex (dlPFC), ventral lateral PFC (vlPFC), medial orbitofrontal cortex (mOFC), anterior cingulate cortex (ACC) and nucleus accumbens (NAc) within meso-cortical and meso-limbic pathways using diffusion weighted imaging. The damage along the five tracts was quantified using the free water (FW) and FW-corrected mean diffusivity (MD-t) indices. Furthermore, we explored the inter-correlations among the six clinical measures and identified their common components using principal component analysis (PCA). Linear regression analyses showed that higher FW values of tracts within meso-cortical pathways were related to these clinical measures in cognition, apathy, and gait (all P-corrected values < 0.05). PCA showed strong inter-associations among these clinical measures and identified a common component wherein all six clinical measures loaded on. Higher FW values of tracts within meso-cortical pathways were related to the PCA-derived common component (all P-corrected values < 0.05). Moreover, FW values of VTA-ACC tract showed the strongest contribution to the PCA-derived common component over all other neuroimaging features. In conclusion, our study showed that the three clinical features (cognitive impairment, apathy, and gait dysfunction) of SVD are strongly inter-related and that the damage in meso-cortical pathway could be the common neural basis underlying the three features in SVD. These findings advance our understanding of the mechanisms behind these clinical features of SVD and have the potential to inform novel management and intervention strategies for SVD.

Anticholinergic Toxidrome due to Thorn Apple Seed Ingestion in an Elderly Couple.

Introduction: Sudden onset of reduced consciousness, psychomotor agitation and mydriasis are all indicative of an anticholinergic toxidrome. It is important to note that numerous drugs, as well as certain herbs and plants, possess anticholinergic properties. Case description: An 84-year-old female patient had sudden nocturnal onset of uncoordinated hand movements and altered mental status. Shortly after, the patient's 83-year-old husband developed symptoms of dysarthria, gait ataxia, vertigo, and delirium. Conclusion: Anticholinergic syndrome consists of a combination of central and peripheral anticholinergic symptoms. Physostigmine given intravenously resulted in rapid reversal of symptoms. Thorn apple seeds had been accidentally ingested and were identified as the cause. LEARNING POINTS: The clinical presentation of an anticholinergic toxidrome includes both central and peripheral symptoms such as altered consciousness, mydriasis, dry mucous membranes and skin, and tachycardia.Prompt recognition of anticholinergic toxidrome and the administration of physostigmine can lead to rapid reversal of symptoms and improved patient outcomes.Treatment with physostigmine is indicated when a patient with an agitated delirium does not respond adequately to titrated benzodiazepines.

Perivascular Spaces, Diffusivity Along Perivascular Spaces, and Free Water in Cerebral Small Vessel Disease.

BACKGROUND AND OBJECTIVES: Previous studies have linked the MRI measures of perivascular spaces (PVSs), diffusivity along the perivascular spaces (DTI-ALPS), and free water (FW) to cerebral small vessel disease (SVD) and SVD-related cognitive impairments. However, studies on the longitudinal associations between the three MRI measures, SVD progression, and cognitive decline are lacking. This study aimed to explore how PVS, DTI-ALPS, and FW contribute to SVD progression and cognitive decline. METHODS: This is a cohort study that included participants with SVD who underwent neuroimaging and cognitive assessment, specifically measuring Mini-Mental State Examination (MMSE), cognitive index, and processing speed, at 2 time points. Three MRI measures were quantified: PVS in basal ganglia (BG-PVS) volumes, FW fraction, and DTI-ALPS. We performed a latent change score model to test inter-relations between the 3 MRI measures and linear regression mixed models to test their longitudinal associations with the changes of other SVD MRI markers and cognitive performances. RESULTS: In baseline assessment, we included 289 participants with SVD, characterized by a median age of 67.0 years and 42.9% women. Of which, 220 participants underwent the follow-up assessment, with a median follow-up time of 3.4 years. Baseline DTI-ALPS was associated with changes in BG-PVS volumes (ß = -0.09, p = 0.030), but not vice versa (ß = -0.08, p = 0.110). Baseline BG-PVS volumes were associated with changes in white matter hyperintensity (WMH) volumes (ß = 0.33, p-corrected < 0.001) and lacune numbers (ß = 0.28, p-corrected < 0.001); FW fraction was associated with changes in WMH volumes (ß = 0.30, p-corrected < 0.001), lacune numbers (ß = 0.28, p-corrected < 0.001), and brain volumes (ß = -0.45, p-corrected < 0.001); DTI-ALPS was associated with changes in WMH volumes (ß = -0.20, p-corrected = 0.002) and brain volumes (ß = 0.23, p-corrected < 0.001). Furthermore, baseline FW fraction was associated with decline in MMSE score (ß = -0.17, p-corrected = 0.006); baseline FW fraction and DTI-ALPS were associated with changes in cognitive index (FW fraction: ß = -0.25, p-corrected < 0.001; DTI-ALPS: ß = 0.20, p-corrected = 0.001) and processing speed over time (FW fraction: ß = -0.29, p-corrected < 0.001; DTI-ALPS: ß = 0.21, p-corrected < 0.001). DISCUSSION: Our results showed that increased BG-PVS volumes, increased FW fraction, and decreased DTI-ALPS are related to progression of MRI markers of SVD, along with SVD-related cognitive decline over time. These findings may suggest that the glymphatic dysfunction is related to SVD progression, but further studies are needed.

Visit-to-visit blood pressure variability and progression of white matter hyperintensities over 14 years.

Purpose: There is evidence that blood pressure variability (BPV) is associated with cerebral small vessel disease (SVD) and may therefore increase the risk of stroke and dementia. It remains unclear if BPV is associated with SVD progression over years. We examined whether visit-to-visit BPV is associated with white matter hyperintensity (WMH) progression over 14 years and MRI markers after 14 years.Materials and methods: We included participants with SVD from the Radboud University Nijmegen Diffusion tensor Magnetic resonance-imaging Cohort (RUNDMC) who underwent baseline assessment in 2006 and follow-up in 2011, 2015 and 2020. BPV was calculated as coefficient of variation (CV) of BP at all visits. Association between WMH progression rates over 14 years and BPV was examined using linear-mixed effects (LME) model. Regression models were used to examine association between BPV and MRI markers at final visit in participants.Results: A total of 199 participants (60.5 SD 6.6 years) who underwent four MRI scans and BP measurements were included, with mean follow-up of 13.7 (SD 0.5) years. Systolic BPV was associated with higher progression of WMH (ß = 0.013, 95% CI 0.005 - 0.022) and higher risk of incident lacunes (OR: 1.10, 95% CI 1.01-1.21). There was no association between systolic BPV and grey and white matter volumes, Peak Skeleton of Mean Diffusivity (PSMD) or microbleed count after 13.7 years.Conclusions: Visit-to-visit systolic BPV is associated with increased progression of WMH volumes and higher risk of incident lacunes over 14 years in participants with SVD. Future studies are needed to examine causality of this association.

High blood pressure (BP) is very common, especially among older individuals. BP is not constant but tends to go up and down over time.Earlier studies have shown that when your BP fluctuates more, this can give a higher risk of dementia, stroke, cardiovascular events and even mortality. Large BP fluctuations are likely damaging for your brain, but it remains unknown if it leads to progression of brain damage over a longer period of time.This study examined if fluctuations in BP over 14 years are associated with progression of brain damage in older individuals with a mean age of 60.5 years.The results indicate that markers of brain damage progress more in participants with more variation in BP.This suggests that fluctuations in BP can cause damage in your brain to progress more.However, it is difficult to determine based on these results if BP fluctuations are a cause or a result of brain damage. More research is needed to determine what the temporal order of this association is.If variations in BP can indeed damage the brain, we need to focus not only on lowering BP, but also on keeping BP stable when considering treatments.

Early-Onset Colorectal Cancer in Egypt: Pathological Characters, Patterns of Care, and Survival Compared to Average-Age Onset Colorectal Cancer: A Retrospective Multicenter Study.

PURPOSE: Early-onset colorectal cancer (EOCRC) is a rising health problem. The incidence of EOCRC has increased over the past 2 decades all over the world. Reports from Egypt since the 1990s have reported a higher incidence among young populations with no identifiable risk factors. The aim of this study was to assess EOCRC in Egypt regarding incidence, characteristics, treatment pattern, and survival compared with average age onset and elderly patients. MATERIALS AND METHODS: This was a retrospective, record-based, cohort study combining data from four different cancer centers in Egypt. We grouped patients according to age into three categories: the EOCRC group for patients age ≤45 years and the average age onset and elderly cancer group (for patients age ≥65 years). RESULTS: The study included 1,310 patients with histopathologically proven colorectal cancer, representing four different geographical areas in Egypt. Patients with EOCRC represented 42.4% of the study population. Female patients were 50.6% among the EOCRC group and 52.5% among the average age group. Rectal tumors were significantly higher in EOCRC (54.7% v 40.6%; P < .001). There was no significant difference between both groups regarding the tumor stage at presentation, obstruction, or presence of metastases at presentation. Patients with EOCRC had a significantly higher rate of peritoneum/adnexa metastases than the average age ones (12.3% in EOCRC v 6.9% in the average age group; P < .001). No statistically significant differences between EOCRC and average age groups in both disease-free survival and overall survival were reported. CONCLUSION: A comprehensive framework for the study of EOCRC is required in Egypt as well as a genomic analysis to identify possible underlying genetic alterations responsible for the high incidence of EOCRC.

Long-Term Longitudinal Course of Cognitive and Motor Symptoms in Patients With Cerebral Small Vessel Disease.

BACKGROUND AND OBJECTIVES: Patients with cerebral small vessel disease (SVD) show a heterogenous clinical course. The aim of the current study was to investigate the longitudinal course of cognitive and motor function in patients who developed parkinsonism, dementia, both, or none. METHODS: Participants were from the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort study, a prospective cohort of patients with SVD. Parkinsonism and dementia were, respectively, diagnosed according to the UK Parkinson's Disease Society brain bank criteria and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for major neurocognitive disorder. Linear and generalized linear mixed-effect analyses were used to study the longitudinal course of motor and cognitive tasks. RESULTS: After a median follow-up of 12.8 years (interquartile range 10.2-15.3), 132 of 501 (26.3%) participants developed parkinsonism, dementia, or both. Years before diagnosis of these disorders, participants showed distinct clinical trajectories from those who developed none: Participant who developed parkinsonism had an annual percentage of 22% (95% CI 18%-27%) increase in motor part of the Unified Parkinson's Disease Rating Scale score. This was significantly higher than the 16% (95% CI 14%-18%) of controls, mainly because of a steep increase in bradykinesia and posture and gait disturbances. When they developed dementia as well, the increase in Timed Up and Go Test time of 0.73 seconds per year (95% CI 0.58-0.87) was significantly higher than the 0.20 seconds per year increase (95% CI 0.16-0.23) of controls. All groups, including the participants who developed parkinsonism without dementia, showed a faster decline in executive function compared with controls: Annual decline in Z-score was -0.07 (95% CI -0.10 to -0.05), -0.09 (95% CI -0.11 to -0.08), and -0.11 (95% CI -0.14 to -0.08) for participants who developed, respectively, parkinsonism, dementia, and both parkinsonism and dementia. These declines were all significantly faster than the annual decline in Z-score of 0.07 (95% CI -0.10 to -0.05) of controls. DISCUSSION: A distinct pattern in deterioration of clinical markers is visible in patients with SVD, years before the diagnosis of parkinsonism and dementia. This knowledge aids early identification of patients with a high risk of developing these disorders.

Age effects on autism heritability and etiological stability of autistic traits.

BACKGROUND: Autism and autistic traits onset in childhood but persist into adulthood. Little is known about how genetic and environmental factors influence autism and autistic traits into adulthood. We aimed to determine age effects on the heritability of clinically diagnosed autism and the etiological stability of autistic traits from childhood to adulthood using twin methods. METHODS: From 23,849 twin pairs in the Swedish Twin Register born between 1959 and 2010, we identified 485 individuals (1.01%, 31.5% female) with a clinical autism diagnosis. We estimated and compared the relative contribution of genetic, shared, and nonshared environmental influences to autism in childhood and adulthood. We further used multivariate twin analysis with four measurement points among 1,348 twin pairs in the longitudinal Twin Study of Child and Adolescent Development to assess the phenotypic and etiological stability of autistic traits - measured with three scales from the Child Behavior Checklist - from childhood to adulthood. RESULTS: Autism heritability was comparable from childhood, (96% [95% CI, 76-99%]) to adulthood (87% [67-96%]). Autistic traits were moderately stable (phenotypic correlation = 0.35-0.61) from childhood to adulthood, and their heritability varied between 52 and 71%. We observed stable as well as newly emerging genetic influences on autistic traits from ages 8-9 to 19-20, and unique nonshared environmental influences at each age. CONCLUSIONS: Genetic factors are important for autism and autistic traits in adulthood and separate genetic studies in adults are warranted.

Oral/taste sensitivity to non-esterified long-chain fatty acids with varying degrees of unsaturation.

Understanding human oral/taste sensitivity to long-chain non-esterified fatty acids (NEFA) with varying physicochemical properties is essential to reducing the intake of fats and altering the intake composition. This study investigated the differences in human taste sensitivity to two NEFA: oleic acid and linoleic acid. Twenty-four female subjects were divided into two equal sensitivity groups, and they performed discrimination tests for both fatty acids against bottled water using either the triangle or the DR A-Not A test. To achieve an accurate measurement of NEFA sensitivity, the stimulus was carefully prepared, avoiding additives that could interfere with the binding of fatty acids to receptors. Stimuli concentrations were selected to be within the lowest range (9.9 to 177.3 µM) evaluated in previous research. Through a systematic stimulus control process, this study confirmed that greater sensitivity was exhibited to linoleic acid than oleic acid, resulting in better discrimination than previous studies.

2D MXene electrochemical transistors.

The solid-state field-effect transistor, FET, and its theories were paramount in the discovery and studies of graphene. In the past two decades another transistor based on conducting polymers, called organic electrochemical transistor (ECT), has been developed and largely studied. The main difference between organic ECTs and FETs is the mode and extent of channel doping; while in FETs the channel only has surface doping through dipoles, the mixed ionic-electronic conductivity of the channel material in organic ECTs enables bulk electrochemical doping. As a result, organic ECTs maximize conductance modulation at the expense of speed. To date ECTs have been based on conducting polymers, but here we show that MXenes, a class of 2D materials beyond graphene, enable the realization of electrochemical transistors (ECTs). We show that the formulas for organic ECTs can be applied to these 2D ECTs and used to extract parameters like mobility. These MXene ECTs have high transconductance values but low on-off ratios. We further show that conductance switching data measured using ECT, in combination with other in situ-ex situ electrochemical measurements, is a powerful tool for correlating the change in conductance to that of the redox state, to our knowledge, this is the first report of this important correlation for MXene films. 2D ECTs can draw great inspiration and theoretical tools from the field of organic ECTs and have the potential to considerably extend the capabilities of transistors beyond those of conducting polymer ECTs, with added properties such as extreme heat resistance, tolerance for solvents, and higher conductivity for both electrons and ions than conducting polymers.

Structural Network Efficiency Predicts Conversion to Incident Parkinsonism in Patients With Cerebral Small Vessel Disease.

BACKGROUND: To investigate whether structural network disconnectivity is associated with parkinsonian signs and their progression, as well as with an increased risk of incident parkinsonism. METHODS: In a prospective cohort (Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort study) consisting of 293 participants with small vessel disease (SVD), we assessed parkinsonian signs and incident parkinsonism over an 8-year follow-up. In addition, we reconstructed the white matter network followed by graph-theoretical analyses to compute the network metrics. Conventional magnetic resonance imaging markers for SVD were assessed. RESULTS: We included 293 patients free of parkinsonism at baseline (2011), with a mean age 68.8 (standard deviation [SD] 8.4) years, and 130 (44.4%) were men. Nineteen participants (6.5%) developed parkinsonism during a median (SD) follow-up time of 8.3 years. Compared with participants without parkinsonism, those with all-cause parkinsonism had higher Unified Parkinson's Disease Rating scale (UPDRS) scores and lower global efficiency at baseline. Baseline global efficiency was associated with UPDRS motor scores in 2011 (ß = -0.047, p < .001) and 2015 (ß = -0.84, p < .001), as well as with the changes in UPDRS scores during the 4-year follow-up (ß = -0.63, p = .004). In addition, at the regional level, we identified an inter-hemispheric disconnected network associated with an increased UPDRS motor score. Besides, lower global efficiency was associated with an increased risk of all-cause and vascular parkinsonism independent of SVD markers. CONCLUSIONS: Our findings suggest that global network efficiency is associated with a gradual decline in motor performance, ultimately leading to incident parkinsonism in the elderly with SVD. Global network efficiency may have the added value to serve as a useful marker to capture changes in motor signs.

Shear stress in the intervillous space promotes syncytial formation of iPS cells-derived trophoblasts†.

The intervillous space of human placenta is filled with maternal blood, and villous trophoblasts are constantly exposed to the shear stress generated by maternal blood pressure and flow throughout the entire gestation period. However, the effects of shear stress on villous trophoblasts and their biological significance remain unknown. Here, using our recently established naïve human pluripotent stem cells-derived cytotrophoblast stem cells (nCTs) and a device that can apply arbitrary shear stress to cells, we investigated the impact of shear stress on early-stage trophoblasts. After 72 h of exposure to 10 dyn/cm2 shear stress, nCTs became fused and multinuclear, and mRNA expression of the syncytiotrophoblast (ST) markers, such as glial cell missing 1, endogenous retrovirus group W member 1 envelope, chorionic gonadotropin subunit beta 3, syndecan 1, pregnancy specific beta-1-glycoprotein 3, placental growth factor, and solute carrier family 2 member 1 were significantly upregulated compared to static conditions. Immunohistochemistry showed that shear stress increased fusion index, human chorionic gonadotropin secretion, and human placental lactogen secretion. Increased microvilli formation on the surface of nCTs under flow conditions was detected using scanning electron microscopy. Intracellular cyclic adenosine monophosphate significantly increased under flow conditions. Moreover, transcriptome analysis of nCTs subjected to shear stress revealed that shear stress upregulated ST-specific genes and downregulated CT-specific genes. Collectively, these findings indicate that shear stress promotes the differentiation of nCTs into ST.

Time to presentation and mortality outcomes among patients with diabetes and acute myocardial infarction.

BACKGROUND/AIMS: Due to limited real-world evidence on the association between time to presentation (T2P) and outcomes following acute myocardial infarction and diabetes (AMI-DM), we investigated the characteristics of patients with AMI-DM and their outcomes based on their T2P. METHODS: 4,455 patients with AMI-DM from a Korean nationwide observational cohort (2011-2015) were divided into early and late presenters according to symptom-to-door time. The effects of T2P on three-year all-cause mortality were estimated using inverse probability of treatment weighting (IPTW) and survival analysis. RESULTS: The incidence of all-cause mortality was consistently higher in late presenters than in early presenters (11.4 vs. 17.2%; p < 0.001). In the IPTW-adjusted dataset, the incidence of all-cause mortality was numerically higher in late presenters than in early presenters (9.1 vs. 12.4%; p = 0.072). In the survival analysis, the cumulative incidence of all-cause mortality was significantly higher in late presenters than in early presenters before and after IPTW. In the subgroup with ST-elevation myocardial infarction, late presenters had a higher incidence of cardiac death than early presenters before (4.8 vs. 10.5%; p < 0.001) and after IPTW (4.2 vs. 9.7%; p = 0.034). In the initial glycated hemoglobin (HbA1c)-stratified analysis, these effects were attenuated in patients with HbA1c ≥ 9.0% before (adjusted hazard ratio [HR]: 1.45, 95% confidence interval [CI]: 0.80-2.64) and after IPTW (adjusted HR: 0.82, 95% CI: 0.40-1.67). CONCLUSION: Late presentation was associated with higher mortality in patients with AMI-DM; therefore, multifaceted and systematic interventions are needed to decrease pre-hospital delays.

Revolutionizing trauma care: advancing coagulation management and damage control anesthesia

Despite advances in emergency transfer systems and trauma medicine, the incidence of preventable deaths due to massive hemorrhage remains high. Recent immunological research has elucidated key mechanisms underlying trauma-induced coagulopathy in the early stages of trauma, including sympathoadrenal stimulation, shedding of the glycocalyx, and endotheliopathy. Consequently, the condition progresses to fibrinogen depletion, hyperfibrinolysis, and platelet dysfunction. Coexisting factors such as uncorrected acidosis, hypothermia, excessive crystalloid administration, and a history of anticoagulant use exacerbate coagulopathy. This study introduces damage-control anesthetic management based on recent insights into damage-control resuscitation, emphasizing the importance of rapid transport, timely bleeding control, early administration of antifibrinolytics and fibrinogen concentrates, and maintenance of calcium levels and body temperature. Additionally, this study discusses brain-protective strategies for trauma patients with brain injuries and the utilization of cartridge-based viscoelastic assays for goal-directed coagulation management in trauma settings. This comprehensive approach may provide potential insights for anesthetic management in the fast-paced field of trauma medicine.

Prevalence and natural course of incidental gastric subepithelial tumors

Background/Aims@#Gastric subepithelial tumors (SETs) are often encountered during the upper gastrointestinal endoscopic screening. We assessed the prevalence of gastric SETs and the risk factors for their progression. @*Methods@#We reviewed the electronic medical records of 30,754 patients who underwent upper gastrointestinal endoscopic screening at our medical center between January 2013 and December 2016. @*Results@#Among the 30,754 patients examined, 599 (1.94%) had gastric SETs. The prevalence increased with age and was 9.56% in patients aged ≥70 years. In total, 262 patients underwent serial endoscopy for more than 6 months. The median age was 68 years (interquartile range [IQR], 61–74), and the number of females was 167 (63.7%). During a median follow-up of 58 months (IQR, 38–75), 22 patients (8.4%) showed significant changes in tumor size. An irregular border (odds ratio, 4.623; 95% confidence interval, 1.093–19.558; p=0.037) was a significant risk factor for progression. Seven patients underwent surgical or endoscopic resections. The pathologies of gastric SETs included leiomyomas (n=3), gastrointestinal stromal tumors (n=2), and lipomas (n=2). @*Conclusions@#The prevalence of gastric SETs increases with age. Most gastric SETs do not progress during long-term endoscopic examinations, and the risk of an increase in size is low in asymptomatic small SETs without irregular borders.