The clinical characteristics of cerebral small vessel disease patients with motoric cognitive risk syndrome during single- and dual-task walking.

Objective: We aimed to (1) identify neuroimaging biomarkers of distinguishing motoric cognitive risk syndrome (MCRS) risk among older Chinese adults with cerebral small vessel disease (CSVD) and (2) detect differences in gait parameters and neuroimaging biomarkers between CSVD individual with and without MCRS, especially during dual-task walking (DTW). Methods: We enrolled 126 inpatients with CSVD who were divided into two groups according to MCRS status. Data on basic parameters, variability, asymmetry, and coordination were collected during single-task walking (STW) and DTW. Neuroimaging features (white matter hyperintensities, lacunes, and microbleeds) and total disease burden were calculated. Analysis of variance and logistic regression analyses were applied to assess the role of STW, DTW, and neuroimaging biomarkers in MCRS. Results: In total, 126 consecutive inpatients with CSVD were included (84 and 42 patients were classified as MCRS-negative and MCRS-positive, respectively). The MCRS-positive group showed poorer performance for nearly all gait parameters compared with the MCRS-negative group during cognitive DTW. Meanwhile, all gait parameters except asymmetry were assessed in participants with MCRS for significant deterioration during cognitive DTW compared with that during STW. However, only basic parameters differed between STW and cognitive DTW in participants without MCRS. A significant independent association between total CSVD scores and MCRS was also detected. Conclusions: For CSVD patients, with higher total CSVD burden rather than any single neuroimaging marker, was linked to a greater risk of MCRS. In addition, CSVD individuals with MCRS had higher variability and phase coordination index (PCI), especially in cognitive DTW. Thus, they should concentrate more on their gait variability or coordination and reduce secondary task loads while walking in daily life, especially in cognitive secondary tasks.

Relationship between Body Composition and Gait Characteristics in Patients with Cerebral Small Vessel Disease.

BACKGROUND: This study aims to explore the correlation between body composition, encompassing factors such as muscle mass and fat distribution, and gait performance during both single-task walking (STW) and dual-task walking (DTW) in patients diagnosed with cerebral small vessel disease (CSVD). METHODS: The data of hospitalized patients diagnosed with CSVD, including cadence, stride time, velocity and stride length, as well as information on variability, asymmetry and coordination during both STW and DTW, were assessed. The number of falls reported by each participant was also assessed. RESULTS: A total of 95 CSVD patients were assessed, and the results showed that individuals with low appendicular skeletal muscle mass (ASM), which includes both the low ASM group and the combination of low ASM and high body fat (BF) group, had reduced velocity or cadence, shortened stride length, and prolonged stride time across all walking modalities compared to the control group. Only the combination of the low ASM and high BF group exhibited a deterioration in the coefficient of variation (CV) for all basic parameters and the Phase Coordination Index (PCI) compared to the control group across all walking patterns. Conversely, patients in the high BF group displayed a decline in basic parameters, primarily during cognitive DTW. Concurrently, the high BF group showed a significant increase in the CV and the PCI compared to the control group only during cognitive DTW. Furthermore, regardless of gender, both ASM and BF independently correlated with the occurrence of falls. CONCLUSIONS: CSVD patients with varying.

Performance of the walking trail making test in older adults with white matter hyperintensities.

BACKGROUND: Several studies have reported that the walking trail making test (WTMT) completion time is significantly higher in patients with developmental coordination disorders and mild cognitive impairments. We hypothesized that WTMT performance would be altered in older adults with white matter hyperintensities (WMH). AIM: To explore the performance in the WTMT in older people with WMH. METHODS: In this single-center, observational study, 25 elderly WMH patients admitted to our hospital from June 2019 to June 2020 served as the WMH group and 20 participants matched for age, gender, and educational level who were undergoing physical examination in our hospital during the same period served as the control group. The participants completed the WTMT-A and WTMT-B to obtain their gait parameters, including WTMT-A completion time, WTMT-B completion time, speed, step length, cadence, and stance phase percent. White matter lesions were scored according to the Fazekas scale. Multiple neuropsychological assessments were carried out to assess cognitive function. The relationships between WTMT performance and cognition and motion in elderly patients with WMH were analyzed by partial Pearson correlation analysis. RESULTS: Patients with WMH performed significantly worse on the choice reaction test (CRT) (0.51 ± 0.09 s vs 0.44 ± 0.06 s, P = 0.007), verbal fluency test (VFT, 14.2 ± 2.75 vs 16.65 ± 3.54, P = 0.012), and digit symbol substitution test (16.00 ± 2.75 vs 18.40 ± 3.27, P = 0.010) than participants in the control group. The WMH group also required significantly more time to complete the WTMT-A (93.00 ± 10.76 s vs 70.55 ± 11.28 s, P < 0.001) and WTMT-B (109.72 ± 12.26 s vs 82.85 ± 7.90 s, P < 0.001). WTMT-A completion time was positively correlated with CRT time (r = 0.460, P = 0.001), while WTMT-B completion time was negatively correlated with VFT (r = -0.391, P = 0.008). On the WTMT-A, only speed was found to statistically differ between the WMH and control groups (0.803 ± 0.096 vs 0.975 ± 0.050 m/s, P < 0.001), whereas on the WTMT-B, the WMH group exhibited a significantly lower speed (0.778 ± 0.111 vs 0.970 ± 0.053 m/s, P < 0.001) and cadence (82.600 ± 4.140 vs 85.500 ± 5.020 steps/m, P = 0.039), as well as a higher stance phase percentage (65.061 ± 1.813% vs 63.513 ± 2.465%, P = 0.019) relative to controls. CONCLUSION: Older adults with WMH showed obviously poorer WTMT performance. WTMT could be a potential indicator for cognitive and motor deficits in patients with WMH.

Research on safety evaluation of collapse risk in highway tunnel construction based on intelligent fusion.

To solve the problems of untimely and low accuracy of tunnel project collapse risk prediction, this study proposes a method of multi-source information fusion. The method uses the PSO-SVM model to predict the surrounding rock displacement. With the prediction index as the benchmark, the Cloud Model (CM) is used to calculate the basic probability assignment value. At the same time, the improved D-S theory is used to fuse the monitoring data, the advanced geological forecast, and the tripartite information indicators of site inspection patrol. This method is applied to the risk assessment of Jinzhupa Tunnel, and the decision-makers adjust the risk factors in time according to the prediction level. In the end, the tunnel did not collapse on a large scale.

Handwriting Movement Abnormalities in Older Adults with Silent Cerebral Small Vessel Disease-A Preliminary Study.

BACKGROUND: The features of cerebral small vessel disease (CSVD) range from occurrence of asymptomatic radiological markers to symptomatic characteristics that include cognitive deficits and gait decline. The aim of the present study was to examine whether handwriting movement is abnormal in older people with CSVD through handwriting and drawing tasks using digitized handwriting kinematic assessment technology. METHODS: Older subjects (n = 60) were grouped according to Fazekas score, with 16 in the Severe CSVD group, 12 in the Non-severe group and 32 in the Healthy group. Kinematic data were recorded and analyzed during handwriting and drawing tasks: signature; writing of Chinese characters ("" and ""); and Archimedes' spiral drawing. RESULTS: The Severe CSVD group showed lower velocity and higher tortuosity during signature writing, lower velocity of stroke #4 of "" and vertical size of "" than did the Non-severe and Healthy groups. Both Severe CSVD and Non-severe CSVD subjects displayed higher average normalized jerk than did the Healthy group. Partial correlation analysis adjusting for age, gender, education, and mini-mental state evaluation (MMSE) showed that CSVD burden was positively associated with tortuosity of signature and average normalized jerk of Archimedes' spiral, and was negatively associated with velocity of strokes #3 and #4 of "", as well as vertical size of "". CONCLUSIONS: Older adults with CSVD showed abnormal handwriting movement. And the handwriting abnormalities captured by digitized handwriting analysis were correlated with CSVD severity in users of simplified Chinese characters.

Variability, asymmetry and bilateral coordination of gait during single- and dual-task walking of patients with cerebral small vessel disease.

OBJECTIVE: We investigated coefficient of variation (CV), gait asymmetry (GA) and phase coordination index (PCI) in cerebral small vessel disease (CSVD) patients during single-task walking (STW) and dual-task walking (DTW) and explored the relationship between above parameters with disease severity and cognitive function. METHODS: This cross-sectional study collected cognitive function indices and gait parameters from 23 healthy controls and 94 patients with CSVD during STW and DTW. According to the Fazekas scales, the severity of CSVD valued by white matter hyperintensity (WMH) were divided into control, mild, moderate, severe and control group. MRIs were analyzed for WMHs, CMB, lacunes, etc. RESULTS: The control group showed lower PCI than CSVD patients during STW; no differences were detected among the disease severity groups. During DTW, all four groups exhibited significant differences in PCI and CV. For the moderate and severe groups, coordination and variation significantly differed between the two walking methods. There were correlations between the PCI and GA in the moderate and severe groups (R = 0.376, R = 0.573 during DTW; R = 0.414, R = 0.643 during STW) and no correlations in the control group and mild CSVD group. CONCLUSION: PCI and CV may be vital for detecting the symptoms in the early stage of CSVD disease. We also verified that the PCI could become the bridge across the cognition and motor disorder in CSVD, which was helpful for evaluating clinical symptoms comprehensively.

Preoperative CT-based deep learning radiomics model to predict lymph node metastasis and patient prognosis in bladder cancer: a two-center study.

OBJECTIVE: To establish a model for predicting lymph node metastasis in bladder cancer (BCa) patients. METHODS: We retroactively enrolled 239 patients who underwent three-phase CT and resection for BCa in two centers (training set, n = 185; external test set, n = 54). We reviewed the clinical characteristics and CT features to identify significant predictors to construct a clinical model. We extracted the hand-crafted radiomics features and deep learning features of the lesions. We used the Minimum Redundancy Maximum Relevance algorithm and the least absolute shrinkage and selection operator logistic regression algorithm to screen features. We used nine classifiers to establish the radiomics machine learning signatures. To compensate for the uneven distribution of the data, we used the synthetic minority over-sampling technique to retrain each machine-learning classifier. We constructed the combined model using the top-performing radiomics signature and clinical model, and finally presented as a nomogram. We evaluated the combined model's performance using the area under the receiver operating characteristic, accuracy, calibration curves, and decision curve analysis. We used the Kaplan-Meier survival curve to analyze the prognosis of BCa patients. RESULTS: The combined model incorporating radiomics signature and clinical model achieved an area under the receiver operating characteristic of 0.834 (95% CI: 0.659-1.000) for the external test set. The calibration curves and decision curve analysis demonstrated exceptional calibration and promising clinical use. The combined model showed good risk stratification performance for progression-free survival. CONCLUSION: The proposed CT-based combined model is effective and reliable for predicting lymph node status of BCa patients preoperatively. CRITICAL RELEVANCE STATEMENT: Bladder cancer is a type of urogenital cancer that has a high morbidity and mortality rate. Lymph node metastasis is an independent risk factor for death in bladder cancer patients. This study aimed to investigate the performance of a deep learning radiomics model for preoperatively predicting lymph node metastasis in bladder cancer patients. KEY POINTS: • Conventional imaging is not sufficiently accurate to determine lymph node status. • Deep learning radiomics model accurately predicted bladder cancer lymph node metastasis. • The proposed method showed satisfactory patient risk stratification for progression-free survival.

Deep learning signature based on multiphase enhanced CT for bladder cancer recurrence prediction: a multi-center study.

Background: Accurate stratification of recurrence risk for bladder cancer (BCa) is essential for precise individualized therapy. This study aimed to develop and validate a model for predicting the risk of recurrence in BCa patients postoperatively using 3-phase enhanced CT images. Methods: We retrospectively enrolled 874 BCa patients across four centers between January 2006 and December 2021. Patients from one center were used as training set, while the remaining patients went into the validation set. We trained a deep learning (DL) model based on convolutional neural networks using 3-phase enhanced CT images. The resulting prediction scores were entered into Cox regression analysis to obtain DL scores and construct a DL signature. DL scores and clinical features were then used as deep learning radioclinical signature. The predictive performance of DL signature was assessed according to concordance index and area under curve compared with deep learning radioclinical signature, clinical model and a widely accepted staging grading system. Recurrence-free survival (RFS) and overall survival (OS) were also predicted in order to further assess survival benefits. Findings: DL signature showed strong power for predicting recurrence (concordance index, 0.869; area under curve, 0.889) in validation set, outperforming other models and system. In addition, we divided RFS and OS into high and low risk groups by selecting appropriate cutoff values for DL signature, and calculated cumulative recurrence risk rates for both groups. Interpretation: Our proposed DL signature shows promising potential as clinical aid for predicting postoperative recurrence risk in BCa and for stratifying the risk of RFS and OS, which can be applied to guide personalized precision therapy. Funding: There are no sources of funding for this manuscript.

The relationship between apathy and nonparametric variables of rest activity rhythm in older adults with cerebral small vessel disease.

The goal of the current study was to demonstrate if the rest-activity rhythm (RAR) was altered in apathetic older adults with cerebral small vessel disease (CSVD) and find out the relationship between apathy/depression severity and RAR features in CSVD patients. This is a cross-sectional observational investigation including 53 CSVD cases (54.74% men), aged 70.70 ± 6.18 years old. The participants were assessed by neuropsychiatric inventory (NPI) subscale of apathy (NPI-apathy) and depression (NPI-depression) in succession, according to updated diagnostic criteria for apathy (DCA). Each subject wore an actigraph device (ActiGraph GT3X) in their nondominant hand for 7 days to collect raw data. Using a non-parametric methodological analysis, this study determined RAR variables such as interdaily stability (IS), intraday variability (IV) and relative amplitude (RA). Patients in the apathy-positive group had a higher Fazekas score than those in the apathy-negative group. IS, but not IV, RA, or objective sleep variables, differed between elderly patients with varying degrees of CSVD burden. Furthermore, apathy severity was statistically correlated with RA after adjusting for age, gender and education level, whereas depression severity was not associated with RAR variables. Finally, we discovered that the severity of apathy had no significant relationship with the severity of depression. All these findings indicated that the RAR altered in apathetic older adults with CSVD, and apathy was associated with decreased RAR amplitude.

Spatiotemporal gait characteristics during single- and dual-task walking are associated with the burden of cerebral small vessel disease.

Introduction: Gait impairment is a common symptom among individuals with cerebral small vessel disease (CSVD). However, performance differences between single-task walking (STW) and dual-task walking (DTW) among individuals with CSVD remain unclear. Therefore, we aimed to examine differences in gait characteristics during STW and DTW as well as the association between gait performance and neuroimaging markers. Methods: We enrolled 126 older individuals with CSVD. The speed, cadence, stride length, stride time, and their dual-task cost (DTC) or variability were measured under the STW, motor-cognitive DTW (cognitive DTW), and motor-motor DTW (motor DTW) conditions. We examined neuroimaging features such as white matter hyperintensities (WMHs), lacunes, microbleeds, and total burden. Further, we analysed the association of neuroimaging markers with gait performance, including gait variability and DTC. Results: Almost all spatiotemporal characteristics, as well as their DTCs or variabilities, showed significant among-group differences according to disease severity in the cognitive DTW condition; however, relatively lesser differences were observed in the STW and motor DTW conditions. The total CSVD burden score was moderately correlated with all the spatial parameters, as well as their DTCs or variabilities, in the cognitive DTW condition. Moreover, WMHs showed a correlation with speed, stride time, and cadence, as well as their DTCs, in the cognitive DTW condition. Furthermore, lacunes showed a moderate correlation with speed, stride length, and the DTC of speed, whilst microbleeds were only related to the DTC of stride length in the cognitive DTW condition. Neuroimaging biomarkers were not correlated with spatiotemporal parameters in STW and motor DTW conditions after Bonferroni correction. Moreover, the correlation coefficient between the total CSVD burden score and gait parameters was greater than those of other biomarkers. Discussion: Parameters in the cognitive DTW condition are more appropriate than those in the motor DTW condition for the evaluation of gait abnormalities in patients with CSVD. Moreover, the total CSVD burden score might have better predictive utility than any single neuroimaging marker. Patients with CSVD, especially those with moderate-to-severe disease, should concentrate more on their gait patterns and reduce the load of secondary cognitive tasks whilst walking in daily life.

[Droplet freeze-thawing system based on solid surface vitrification and laser rewarming].

Ultra-rapid cooling and rewarming rate is a critical technical approach to achieve ice-free cells during the freezing and melting process. A set of ultra-rapid solid surface freeze-thaw visualization system was developed based on a sapphire flim, and experiments on droplet freeze-thaw were carried out under different cryoprotectant components, volumes and laser energies. The results showed that the cooling rate of 1 µL mixed cryoprotectant [1.5 mol/L propylene glycol (PG) + 1.5 mol/L ethylene glycol (EG) + 0.5 mol/L trehalose (TRE)] could be 9.2×10 3 °C/min. The volume range of 1-8 µL droplets could be vitrified. After comparing the proportions of multiple cryoprotectants, the combination of equal proportion mixed permeability protectant and trehalose had the best vitrification freezing effect and more uniform crystallization characteristics. During the rewarming operation, the heating curve of glassy droplets containing gold nanoparticles was measured for the first time under the action of 400-1 200 W laser power, and the rewarming rate was up to the order of 10 6 °C/min. According to the droplet images of different power rewarming processes, the laser power range for ice-free rewarming with micron-level resolution was clarified to be 1 400-1 600 W. The work of this paper simultaneously realizes the ultra-high-speed temperature ramp-up, transient visual observation and temperature measurement of droplets, providing technical means for judging the ice free droplets during the freeze-thaw process. It is conducive to promoting the development of ultra-rapid freeze-thaw technology for biological cells and tissues.

CT-based deep learning radiomics nomogram for the prediction of pathological grade in bladder cancer: a multicenter study.

BACKGROUND: To construct and assess a computed tomography (CT)-based deep learning radiomics nomogram (DLRN) for predicting the pathological grade of bladder cancer (BCa) preoperatively. METHODS: We retrospectively enrolled 688 patients with BCa (469 in the training cohort, 219 in the external test cohort) who underwent surgical resection. We extracted handcrafted radiomics (HCR) features and deep learning (DL) features from three-phase CT images (including corticomedullary-phase [C-phase], nephrographic-phase [N-phase] and excretory-phase [E-phase]). We constructed predictive models using 11 machine learning classifiers, and we developed a DLRN by combining the radiomic signature with clinical factors. We assessed performance and clinical utility of the models with reference to the area under the curve (AUC), calibration curve, and decision curve analysis (DCA). RESULTS: The support vector machine (SVM) classifier model based on HCR and DL combined features was the best radiomic signature, with AUC values of 0.953 and 0.943 in the training cohort and the external test cohort, respectively. The AUC values of the clinical model in the training cohort and the external test cohort were 0.752 and 0.745, respectively. DLRN performed well on both data cohorts (training cohort: AUC = 0.961; external test cohort: AUC = 0.947), and outperformed the clinical model and the optimal radiomic signature. CONCLUSION: The proposed CT-based DLRN showed good diagnostic capability in distinguishing between high and low grade BCa.

EEG complexity correlates with residual consciousness level of disorders of consciousness.

BACKGROUND AND OBJECTIVE: Electroencephalography (EEG) and neuroimaging measurements have been highly encouraged to be applied in clinics of disorders of consciousness (DOC) to improve consciousness detection. We tested the relationships between neural complexity measured on EEG and residual consciousness levels in DOC patients. METHODS: Resting-state EEG was recorded from twenty-five patients with DOC. Lempel-Ziv complexity (LZC) and permutation Lempel-Ziv complexity (PLZC) were measured on the EEG, and their relationships were analyzed with the consciousness levels of the patients. RESULTS: PLZC and LZC values significantly distinguished patients with a minimally conscious state (MCS), vegetative state/unresponsive wakefulness syndrome (VS/UWS), and healthy controls. PLZC was significantly correlated with the Coma Recovery Scale-Revised (CRS-R) scores of DOC patients in the global brain, particularly in electrodes locating in the anterior and posterior brain regions. Patients with higher CRS-R scores showed higher PLZC values. The significant difference in PLZC values between MCS and VS/UWS was mainly located in the bilateral frontal and right hemisphere regions. CONCLUSION: Neural complexity measured on EEG correlates with residual consciousness levels of DOC patients. PLZC showed higher sensitivity than LZC in the classification of consciousness levels.

Leaky Gut Plays a Critical Role in the Pathophysiology of Autism in Mice by Activating the Lipopolysaccharide-Mediated Toll-Like Receptor 4-Myeloid Differentiation Factor 88-Nuclear Factor Kappa B Signaling Pathway.

Increased intestinal barrier permeability, leaky gut, has been reported in patients with autism. However, its contribution to the development of autism has not been determined. We selected dextran sulfate sodium (DSS) to disrupt and metformin to repair the intestinal barrier in BTBR T+tf/J autistic mice to test this hypothesis. DSS treatment resulted in a decreased affinity for social proximity; however, autistic behaviors in mice were improved after the administration of metformin. We found an increased affinity for social proximity/social memory and decreased repetitive and anxiety-related behaviors. The concentration of lipopolysaccharides in blood decreased after the administration of metformin. The expression levels of the key molecules in the toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-nuclear factor kappa B (NF-κB) pathway and their downstream inflammatory cytokines in the cerebral cortex were both repressed. Thus, "leaky gut" could be a trigger for the development of autism via activation of the lipopolysaccharide-mediated TLR4-MyD88-NF-κB pathway.

Motoric Cognitive Risk Syndrome Among Chinese Older Adults with White Matter Lesions: A Cross-Sectional Observational Study.

Brain aging is characterized by the declines in motor and cognitive features. The present study is to detect motor cognitive risk syndrome (MCRS) in older adults with white matter lesions (WML). 134 WML aged patients were recruited and diagnosed with the criteria for MCRS. Numerous cognitive function tests and walking tests were performed. The frequency of MCRS is 28.35%. Verbal fluency test, Mini-Mental State Examination, and dual-task walking speed were independent risk factor of MCRS. These findings indicated that MCRS was common in WML seniors. MCRS was associated with the pathologies of WML in older adults.

Aged Patients With Severe Small Vessel Disease Exhibit Poor Bimanual Coordination During the Anti-Phase Horizontal Line Drawing Task.

The present study explores whether SVD affects bimanual coordination, which is easier to detect than by conventional, MRI-based methods. We tested nine severe SVD patients, eight non-severe (i.e., moderate or mild) SVD patients, eleven healthy age-matched controls, and eight young adults. They were grouped according to Fazekas scale and by age. Participants performed horizontal line drawings with both hands simultaneously on two pen tablets. The movements consisted of rhythmic patterns where participants used both hands to draw horizontal lines in anti-phase on two pen tablets. Each participant underwent a series of neuropsychiatric assessments. Results showed that SVD patients exhibited in each hand smaller horizontal movement amplitudes with variability larger compared to the healthy age-matched controls. Only movement amplitudes appeared to decrease significantly with severity of SVD. Interestingly, we found no relevant differences between the age-matched, elderly controls and the young controls. Therefore, this effect appeared indicative of SVD. The variability of the lines orthogonal to the horizontal lines of the left, non-dominant hand differed only between the severe SVD group and the other groups. Furthermore, partial correlations demonstrated that the mean horizontal movement amplitude of the left hand was positively associated with the clock drawing test score, and the inter-manual asynchrony of the horizontal movements was positively associated with the Trail Making Test-B time. These results indicated that SVD patients show poor bimanual coordination, as reflected by spatial features such as movement amplitudes and variabilities, and abnormal bimanual coordination was associated with executive dysfunction.

Physical Activity Measurement in Children Accepting Table Tennis Training.

An increasing body of evidence now shows that the majority of children in China experience lower levels of physical activity (PA) than the recommended guideline. Table tennis is a compound and technically difficult game that is popular in China; undertaking table tennis training in clubs can help children to elevate their levels of PA. Given that children cannot complete self-evaluated questionnaires themselves and caregiver-based observations are not suitable for children, we hypothesized that an actigraphy-based method can be an objective method to measure PA. In the present study, we describe a procedure that can be used to evaluate PA levels using an actigraphic device and software. Furthermore, since hip-worn devices are known to reduce compliance, we attempted to assess the agreement between hip-worn and wrist-worn device data. Collectively, our results indicate that these devices are suitable for measuring PA and leisure time physical activity (LTPA) levels. Together with subjective questionnaires, both hip-worn and wrist-worn devices are highly suitable for evaluating PA in Chinese children undergoing table tennis training in clubs.

Detecting apathy in patients with cerebral small vessel disease.

Background: Apathy is attracting more and more attention in clinical practice. As one of the most common features of cerebral small vessel disease (CSVD), the assessment of apathy still mainly relies on observers. With the development of Information and Communication Technologies (ICTs), new objective tools take part in the early detection of apathy. Objectives: To detect apathy in patients with CSVD and find out the relationship between apathy and actigraphic data sampled from the diurnal and nocturnal periods. Methods: A total of 56 patients with CSVD were recruited for a cross-sectional observational study. Apathy was diagnosed by the diagnostic criteria for apathy in neurocognitive disorders. The presence of lacunes, white matter hyperintensities, cerebral microbleeds (CMBs), and perivascular spaces (PVS) in magnetic resonance imaging (MRI) images were rated independently. Actigraph devices were worn in the non-dominant hands of each subject for 7 consecutive days to collect samples of raw data, and diurnal vector magnitude (VM) and a series of sleep quality variables were obtained. Results: We found that the frequency of apathy in Chinese patients with CSVD reached 37.50%. Patients in the Apathy+ group showed more lacunes and CMBs, and higher Fazekas scores in comparison to apathy-group individuals. Diurnal VM, instead of other sleep quality variables, was lower in CSVD patients with apathy relative to those without apathy. Lastly, we discovered that diurnal VM and total time in bed (TTB) correlated negatively with apathy severity in patients with CSVD. Conclusion: Actigraphy is a promising choice to evaluate apathy in patients with CSVD.

Development of a borosilicate bioactive glass scaffold incorporating calcitonin gene-related peptide for tissue engineering.

Protein delivery and release from synthetic scaffold materials are major challenges within the field of bone tissue engineering. In this study, 13-93B1.5 borosilicate bioactive glass (BSG) base paste was 3D printed to produce BSG-based scaffolds with high porosity (59.85 ± 6.04%) and large pore sizes (350-400 µm) for functionalization with a sodium alginate (SA)/calcitonin gene-related peptide (CGRP) hydrogel mixture. SA/CGRP hydrogel was uniformly filled into the interconnected pores of 3D printed BSG constructs to produce BSG-SA/CGRP scaffolds which were subject to bioactivity and biocompatibility analysis. BSG scaffolds filled with SA hydrogel underwent dissolution in simulated body fluid (SBF), resulting in the precipitation of hydroxyapatite (HA) on the borosilicate glass evidenced by scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Around 90% of CGRP was released from scaffolds after 7 days of immersion in SBF, reaching a final released concentration of 893.00 ± 63.30 ng/mL. Cellular adhesion, proliferation, and differentiation of human bone marrow mesenchymal stem cells (HBMSCs) cultured with BSG-SA/CGRP scaffolds revealed improved biocompatibility and osteogenic capabilities compared with BSG-SA scaffolds in the absence of CGRP. When subcutaneously implanted in rat models, BSG-SA/CGRP scaffolds induced low localized inflammation without causing bodily harm in vivo. Findings revealed that bioactive glass scaffolds incorporating CGRP met the scaffold requirements for bone regeneration and that the addition of CGRP promoted osteogenic differentiation where it may potentially be utilized for future regenerative applications.

Cerebral small vessel disease alters neurovascular unit regulation of microcirculation integrity involved in vascular cognitive impairment.

Cerebral small vessel disease (CSVD) is a generic term used for intracranial vascular disorders caused by the structural changes of cerebral microvessels, including the small arteries, arterioles, capillaries and venules. CSVD exhibits various neuroimaging features and is associated clinical characteristics. Although CSVD is recognized as the leading cause of vascular cognitive impairment (VCI), the underlying mechanism(s) remains elusive. Growing evidence indicates a significant association between altered neurovascular unit (NVU) functioning and the pathophysiology of evolving CSVD-induced VCI. Therefore, research is required to understand how NVU dysregulation contributes to cognitive impairment due to CSVD. In this review, we describe the link between the neuroimaging focal lesions and cognitive alterations. We also discuss the potential pathological role of NVU dysregulation in the entry of pathogens from the blood into the parenchyma by altering the blood-brain barrier (BBB), affecting the cerebral microvascular and consequently cause VCI. Next, we review the coupling of neural activity with cerebral blood flow to control the microvascular perfusion; and the disrupted clearance of metabolic byproducts with CSF-ISF exchange via perivascular pathways and glymphatic system. Finally, we discussed the possible therapeutic interventions in CSVD.