Functional connectivity disruption of insular subregions in the cirrhotic patients with minimal hepatic encephalopathy.

We investigated abnormal functional connectivity (FC) patterns of insular subregions in patients with minimal hepatic encephalopathy (MHE) and examined their relationships with cognitive dysfunction using resting-state functional magnetic resonance imaging (fMRI). We collected resting-state fMRI data in 54 patients with cirrhosis [20 with MHE and 34 without MHE (NHE)] and 25 healthy controls. After defining six subregions of insula, we mapped whole-brain FC of the insular subregions and identified FC differences through three groups. FC of the insular subregions was correlated against clinical parameters (including venous blood ammonia level, Child-Pugh score, and cognitive score). The discrimination performance between the MHE and NHE groups was evaluated by performing a classification analysis using the FC index. Across three groups, the observed FC differences involved four insular subregions, including the left-ventral anterior insula, left-dorsal anterior insula, right-dorsal anterior insula, and left-posterior insula (P < 0.05 with false discovery rate correction). Moreover, the FC of these four insular subregions progressively attenuated from NHE to MHE. In addition, hypoconnectivity of insular subregions was correlated with the poor neuropsychological performance and the evaluated blood ammonia levels in patients (P < 0.05 with Bonferroni correction). The FC of insular subregions yielded moderate discriminative value between the MHE and NHE groups (AUC = 0.696-0.809). FC disruption of insular subregions is related to worse cognitive performance in MHE. This study extended our understanding about the neurophysiology of MHE and may assist for its diagnosis.

Anterior Talofibular Ligament All-Inside Arthroscopic Reconstruction with InternalBrace™ for Chronic Lateral Ankle Instability.

BACKGROUND Anterior talofibular ligament (ATFL) is the most easily injured or even broken of ankle sprain. Patients who fail to receive conservative treatment, resulting in persistent ankle swelling, painful and functional decline that it is so-called chronic lateral ankle instability (CLAI). It makes sense to investigate all-inside arthroscopic reconstruction of ATFL with InternalBrace™ for CLAI. MATERIAL AND METHODS We included 108 patients who underwent all-inside arthroscopic ATFL reconstruction with InternalBrace™ for CLAI from January 2018 to April 2020 through a retrospective study. Patients age ranged from 19 to 58 years (mean 35.6±8.7 years). Several elements are used to evaluate the clinical consequences of ankle function, including the American Orthopedic Foot and Ankle Society (AOFAS), Japanese Society for Surgery of the Foot Ankle-Hindfoot (JSSF), Kofoed, Tegner scores and complications, and the tilt angle of talus (TT) and the anterior displacement of talus (ADT) with stressing radiographs were taken to measure in follow-ups. RESULTS All 108 patients had all-inside arthroscopic procedures performed smoothly without serious complications. During the follow-up period (26.7±2.6 months on average), no recurrence of ankle instability and other serious complications happened. The AOFAS, JSSF, Kofoed, and Tegner scores significantly increased as time went by postoperatively, which proved statistically significant (P<0.01). Regarding stress-radiographic measurements, TT significantly decreased from (9.5±1.1)° preoperatively to (2.6±0.6)° at the latest follow-up (P<0.01), while ADT significantly decreased from (9.5±1.0) mm preoperatively to (2.6±0.6) mm at the latest examination (P<0.01). CONCLUSIONS All-inside arthroscopic ATFL reconstruction with the InternalBrace™ for CLAI is beneficial for ankle stability, allowing earlier return to activities.

Aberrant stability of brain functional architecture in cirrhotic patients with minimal hepatic encephalopathy.

To investigate the stability changes of brain functional architecture and the relationship between stability change and cognitive impairment in cirrhotic patients. Fifty-one cirrhotic patients (21 with minimal hepatic encephalopathy (MHE) and 30 without MHE (NHE)) and 29 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging and neurocognitive assessment using the Psychometric Hepatic Encephalopathy Score (PHES). Voxel-wise functional connectivity density (FCD) was calculated as the sum of connectivity strength between one voxel and others within the entire brain. The sliding window correlation approach was subsequently utilized to calculate the FCD dynamics over time. Functional stability (FS) is measured as the concordance of dynamic FCD. From HCs to the NHE and MHE groups, a stepwise reduction of FS was found in the right supramarginal gyrus (RSMG), right middle cingulate cortex, left superior frontal gyrus, and bilateral posterior cingulate cortex (BPCC), whereas a progressive increment of FS was observed in the left middle occipital gyrus (LMOG) and right temporal pole (RTP). The mean FS values in RSMG/LMOG/RTP (r = 0.470 and P = 0.001; r = -0.458 and P = 0.001; and r = -0.384 and P = 0.005, respectively) showed a correlation with PHES in cirrhotic patients. The FS index in RSMG/LMOG/BPCC/RTP showed moderate discrimination potential between the NHE and MHE groups. Changes in FS may be linked to neuropathological bias of cognitive impairment in cirrhotic patients and could serve as potential biomarkers for MHE diagnosis and monitoring the progression of hepatic encephalopathy.

Dynamic Alterations in Functional Connectivity Density in Amyotrophic Lateral Sclerosis: A Resting-State Functional Magnetic Resonance Imaging Study.

Background and Aims: Current knowledge on the temporal dynamics of the brain functional organization in amyotrophic lateral sclerosis (ALS) is limited. This is the first study on alterations in the patterns of dynamic functional connection density (dFCD) involving ALS. Methods: We obtained resting-state functional magnetic resonance imaging (fMRI) data from 50 individuals diagnosed with ALS and 55 healthy controls (HCs). We calculated the functional connectivity (FC) between a given voxel and all other voxels within the entire brain and yield the functional connection density (FCD) value per voxel. dFCD was assessed by sliding window correlation method. In addition, the standard deviation (SD) of dFCD across the windows was computed voxel-wisely to measure dFCD variability. The difference in dFCD variability between the two groups was compared using a two-sample t-test following a voxel-wise manner. The receiver operating characteristic (ROC) curve was used to assess the between-group recognition performance of the dFCD variability index. Results: The dFCD variability was significantly reduced in the bilateral precentral and postcentral gyrus compared with the HC group, whereas a marked increase was observed in the left middle frontal gyrus of ALS patients. dFCD variability exhibited moderate potential (areas under ROC curve = 0.753-0.837, all P < 0.001) in distinguishing two groups. Conclusion: ALS patients exhibit aberrant dynamic property in brain functional architecture. The dFCD evaluation improves our understanding of the pathological mechanisms underlying ALS and may assist in its diagnosis.

Characterizing Sensorimotor-Related Area Abnormalities in Amyotrophic Lateral Sclerosis: An Intravoxel Incoherent Motion Magnetic Resonance Imaging Study.

RATIONALE AND OBJECTIVES: To investigate the microperfusion and water molecule diffusion alterations in sensorimotor-related areas in amyotrophic lateral sclerosis (ALS) using intravoxel incoherent motion (IVIM) magnetic resonance imaging. MATERIALS AND METHODS: IVIM data were obtained from 43 ALS patients and 31 controls. This study employed the revised ALS Functional Rating Scale (ALSFRS-R) in evaluating disease severity. IVIM-derived metrics were calculated, including diffusion coefficient (D), pseudo-diffusion coefficient, and perfusion fraction. Conventional apparent diffusion coefficient was also computed. Atlas-based analysis was conducted to detect between-group difference in these metrics in sensorimotor-related gray/white matter areas. Spearman correlation analysis was employed to establish correlation between various metrics and ALSFRS-R. RESULTS: ALS patients had perfusion fraction (× 10-3) reduction in the left presupplementary motor area (60.72 ± 16.15 vs. 71.15 ± 12.98, p = 0.016), right presupplementary motor area (61.35 ± 17.02 vs. 72.18 ± 14.22, p = 0.016), left supplementary motor area (55.73 ± 12.29 vs. 64.12 ± 9.17, p = 0.015), and right supplementary motor area (56.53 ± 11.93 vs. 63.67 ± 10.03, p = 0.020). Patients showed D (× 10-6 mm2/s) increase in a white matter tract projecting to the right ventral premotor cortex (714.20 ± 39.75 vs. 691.01 ± 24.53, p = 0.034). A negative correlation between D of right ventral premotor cortex tract and ALSFRS-R score was observed (r = -0.316, p = 0.039). CONCLUSION: These findings suggest aberrant microperfusion and water molecule diffusion in the sensorimotor-related areas in ALS patients, which are associated with motor impairment in ALS.

Abnormal Stability of Dynamic Functional Architecture in Amyotrophic Lateral Sclerosis: A Preliminary Resting-State fMRI Study.

Purpose: Static and dynamic analyses for identifying functional connectivity (FC) have demonstrated brain dysfunctions in amyotrophic lateral sclerosis (ALS). However, few studies on the stability of dynamic FC have been conducted among ALS patients. This study explored the change of functional stability in ALS and how it correlates with disease severity. Methods: We gathered resting-state functional magnetic resonance data from 20 patients with ALS and 22 healthy controls (HCs). The disease severity was assessed with the Revised ALS Functional Rating Scale (ALSFRS-R). We used a sliding window correlation approach to identify dynamic FC and measured the concordance of dynamic FC over time to obtain the functional stability of each voxel. We assessed the between-group difference in functional stability by voxel-wise two-sample t-test. The correlation between the functional stability index and ALSFRS-R in ALS patients was evaluated using Spearman's correlation analysis. Results: Compared with the HC group, the ALS group had significantly increased functional stability in the left pre-central and post-central gyrus and right temporal pole while decreased functional stability in the right middle and inferior frontal gyrus. The results revealed a significant correlation between ALSFRS-R and the mean functional stability in the right temporal pole (r = -0.452 and P = 0.046) in the ALS patients. Conclusions: ALS patients have abnormal stability of brain functional architecture, which is associated with the severity of the disease.

White matter microstructural impairments in amyotrophic lateral sclerosis: A mean apparent propagator MRI study.

BACKGROUND: White matter (WM) impairment is a hallmark of amyotrophic lateral sclerosis (ALS). This study evaluated the capacity of mean apparent propagator magnetic resonance imaging (MAP-MRI) for detecting ALS-related WM alterations. METHODS: Diffusion images were obtained from 52 ALS patients and 51 controls. MAP-derived indices [return-to-origin/-axis/-plane probability (RTOP/RTAP/RTPP) and non-Gaussianity (NG)/perpendicular/parallel NG (NG⊥/NG||)] were computed. Measures from diffusion tensor/kurtosis imaging (DTI/DKI) and neurite orientation dispersion and density imaging (NODDI) were also obtained. Voxel-wise analysis (VBA) was performed to determine differences in these parameters. Relationship between MAP parameters and disease severity (assessed by the revised ALS Functional Rating Scale (ALSFRS-R)) was evaluated by Pearson's correlation analysis in a voxel-wise way. ALS patients were further divided into two subgroups: 29 with limb-only involvement and 23 with both bulbar and limb involvement. Subgroup analysis was then conducted to investigate diffusion parameter differences related to bulbar impairment. RESULTS: The VBA (with threshold of P < 0.05 after family-wise error correction (FWE)) showed that ALS patients had significantly decreased RTOP/RTAP/RTPP and NG/ NG⊥/NG|| in a set of WM areas, including the bilateral precentral gyrus, corona radiata, posterior limb of internal capsule, midbrain, middle corpus callosum, anterior corpus callosum, parahippocampal gyrus, and medulla. MAP-MRI had the capacity to capture WM damage in ALS, which was higher than DTI and similar to DKI/NODDI. RTOP/RTAP/NG/NG⊥/NG|| parameters, especially in the bilateral posterior limb of internal capsule and middle corpus callosum, were significantly correlated with ALSFRS-R (with threshold of FWE-corrected P < 0.05). The VBA (with FWE-corrected P < 0.05) revealed the significant RTAP reduction in subgroup with both bulbar and limb involvement, compared with those with limb-only involvement. CONCLUSIONS: Microstructural impairments in corticospinal tract and corpus callosum represent the consistent characteristic of ALS. MAP-MRI could provide alternative measures depicting ALS-related WM alterations, complementary to the common diffusion imaging methods.

Efficacy and safety of weekly rifapentine and isoniazid for tuberculosis prevention in Chinese silicosis patients: a randomized controlled trial.

OBJECTIVE: The aim was to evaluate the efficacy, safety and completion rate of 3-month, once-weekly rifapentine and isoniazid for tuberculosis (TB) prevention among Chinese silicosis patients. METHODS: Male silicosis patients without human immunodeficiency virus infection, aged 18 years to 65 years, with or without latent TB infection, were randomized 1:1 to receive rifapentine/isoniazid under direct observation (3RPT/INH group) or were untreated (observation group). Active TB incidence was compared between the two groups with 37 months of follow-up. Safety profile and complete rates were evaluated. RESULTS: A total of 1227 adults with silicosis were screened; 513 eligible participants were enrolled and assigned to 3RPT/INH (n = 254) vs. observation (n = 259). Twenty-eight participants were diagnosed with active TB, and 9 and 19 in the 3RPT/INH group and observation groups, respectively. In the intention-to-treat analysis, the cumulative active TB rate was 3.5% (9/254) in the 3RPT/INH group and 7.3% (19/259) in the observation group (log rank p 0.055). On per protocol analysis, the cumulative active TB rates were 0.7% (1/139) and 7.3% (19/259), respectively (log rank p 0.01). Owing to an unexpected high frequency of adverse events (70.4%) and Grade 3 or 4 AEs (7.9%), the completion rate of the 3RPT/INH regimen was 54.7% (139/254). Twenty-six (10.8%) participants had flu-like systemic drug reactions; five (2.1%) experienced hepatotoxicity. DISCUSSION: Weekly rifapentine/isoniazid prophylaxis prevented active TB among Chinese people with silicosis when taken, irrespective of LTBI screening; efficacy was reduced by lack of compliance. The regimen must be used with caution because of the high rates of adverse effects. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number: NCT02430259.

Liquiritin suppresses UVB­induced skin injury through prevention of inflammation, oxidative stress and apoptosis through the TLR4/MyD88/NF­κB and MAPK/caspase signaling pathways.

Solar ultraviolet B (UVB) radiation is known to trigger inflammation, oxidative stress and apoptotic responses through various signaling pathways, which eventually lead to skin cancer. The present study investigated whether liquiritin suppresses UVB­induced skin injury in vivo and in vitro using SKH­1 hairless mice and HACAT cells, respectively. The animals were exposed to UVB irradiation (180 mJ/cm2) for 20 min, followed by liquiritin treatment. The findings indicated that UVB exposure resulted in the excessive release of pro­inflammatory cytokines, including interleukin (IL)­1ß, tumor necrosis factor (TNF)­α, IL­18, IL­6 and cyclooxygenase (COX)2, which were dependent on the toll­like receptor (TLR)4/myeloid differentiation factor 88 (MyD88)/nuclear factor­κB (NF­κB) signaling pathway. Oxidative stress was also observed, evidenced by reduced antioxidants and elevated oxidants. Apoptosis, examined using terminal deoxynucleotidyl transferase dUTP nick end labeling and crystal violet staining, suggested that UVB irradiation caused cell death in vivo and in vitro, which was closely associated with p38/c­Jun N­terminal kinase and caspase activity. Of note, liquiritin treatment in mice and cells exposed to UVB showed reduced inflammatory response, oxidative stress and apoptosis through inhibiting the activation of TLR4/MyD88/NF­κB mitogen­activated protein kinases and caspase pathways, and downregulating the release of oxidants. Overall, the data revealed that liquiritin may be a useful compound against UVB­induced skin injury.