Inhibition of NKCC1 Ameliorates Anxiety and Autistic Behaviors Induced by Maternal Immune Activation in Mice.

Autism spectrum disorder (ASD) is thought to result from susceptibility genotypes and environmental risk factors. The offspring of women who experience pregnancy infection have an increased risk for autism. Maternal immune activation (MIA) in pregnant animals produces offspring with autistic behaviors, making MIA a useful model for autism. However, how MIA causes autistic behaviors in offspring is not fully understood. Here, we show that NKCC1 is critical for mediating autistic behaviors in MIA offspring. We confirmed that MIA induced by poly(I:C) infection during pregnancy leads to autistic behaviors in offspring. We further demonstrated that MIA offspring showed significant microglia activation, excessive dendritic spines, and narrow postsynaptic density (PSD) in their prefrontal cortex (PFC). Then, we discovered that these abnormalities may be caused by overexpression of NKCC1 in MIA offspring's PFCs. Finally, we ameliorated the autistic behaviors using PFC microinjection of NKCC1 inhibitor bumetanide (BTN) in MIA offspring. Our findings may shed new light on the pathological mechanisms for autism caused by pregnancy infection.

Study on the Consistency Between Automatic Measurement Based on Convolutional Neural Network Technology and Manual Visual Evaluation in Intracavitary Ultrasonic Cine of Anterior Pelvic.

OBJECTIVES: This study was to evaluate the application of automatic measurement based on convolutional neural network (CNN) technology in intracavitary ultrasound cine of anterior pelvic. METHODS: A total of 500 patients who underwent pelvic floor ultrasound examination at Peking University Shenzhen Hospital from July 2021 to February 2022 were retrospectively retrieved by the picture archiving and communication system (PACS) system, and 300 cases were used as a training set. The training set was labeled by three experienced ultrasound physicians to train CNN models and develop an automatic measurement software. The remaining 200 cases were used as a test set. Automatic measurement software identified relevant anatomical structures frame by frame and determined the two frames with the greatest difference, calculated the bladder neck descent (BND), urethral rotation angle (URA), and retrovesical angle (RA). Meanwhile, two experienced ultrasound physicians evaluated the resting frame and the maximum Valsalva frame on the cines by manual visual evaluation, labeled the anatomical structures in the corresponding frame, such as the inferoposterior margin of pubic symphysis, the mid-axis of pubic symphysis, bladder contour, and urethra in the front, and calculated BND, URA, and RA. Considering that the residual urine volume (RUV) in the bladder may affect the results, enrolled patients were grouped according to the RUV (10-50 mL, 50-100 mL, and >100 mL). The consistency of the results by automatic measurement and manual visual evaluation was evaluated using the intraclass correlation coefficient (ICC) and the Bland-Altman graph. RESULTS: Of the 200 cases in the test set, 120 cases were successfully identified by the CNN automatic software with a 60% recognition rate. In the case of successful identification, the ICC of manual visual evaluation measurement and automatic measurement was 0.936 (BND), 0.911 (URA), 0.756 (RA in rest), and 0.877 (RA at maximum Valsalva), respectively. In addition, the RUV had a negligible effect on the consistency. The Bland-Altman plot shows the proportion of samples outside the limit was below 5%. CONCLUSIONS: CNN-based automatic measurement software exhibited high reliability in anterior pelvic measurement, which results in a significantly enhanced measurement efficiency.

Feasibility of a kinect-based system in assessing physical function of the elderly for home-based care.

BACKGROUND: With concerns about accurate diagnosis through telehealth, the Kinect sensor offers a reliable solution for movement analysis. However, there is a lack of practical research investigating the suitability of a Kinect-based system as a functional fitness assessment tool in homecare settings. Hence, the objective of this study was to evaluate the feasibility of using a Kinect-based system to assess physical function changes in the elderly. METHODS: The study consisted of two phases. Phase one involved 35 young healthy adults, evaluating the reliability and validity of a Kinect-based fitness evaluation compared to traditional physical examination using the intraclass correlation coefficient (ICC). Phase two involved 665 elderly subjects, examining the correlation between the Kinect-based fitness evaluation and physical examination through Pearson's correlation coefficients. A Kinect sensor (Microsoft Xbox One Kinect V2) with customized software was employed to capture and compute the movement of joint centers. Both groups performed seven functional assessments simultaneously monitored by a physical therapist and the Kinect system. System usability and user satisfaction were assessed using the System Usability Scale (SUS) and Questionnaire for User Interface Satisfaction (QUIS), respectively. RESULTS: Kinect-based system showed overall moderate to excellent within-day reliability (ICC = 0.633-1.0) and between-day reliability (ICC = 0.686-1.0). The overall agreement between the two devices was highly correlated (r ≧ 0.7) for all functional assessment tests in young healthy adults. The Kinect-based system also showed a high correlation with physical examination for the functional assessments (r = 0.858-0.988) except functional reach (r = 0.484) and walking speed(r = 0.493). The users' satisfaction with the system was excellent (SUS score = 84.4 ± 18.5; QUIS score = 6.5-6.7). CONCLUSIONS: The reliability and validity of Kinect for assessing functional performance are generally favorable. Nonetheless, caution is advised when employing Kinect for tasks involving depth changes, such as functional reach and walking speed tests for their moderate validity. However, Kinect's fundamental motion detection capabilities demonstrate its potential for future applications in telerehabilitation in different healthcare settings.

Assessing Risk for Relapse among Children with Infantile Spasms Using the Based Score after ACTH Treatment: A Retrospective Study.

INTRODUCTION: Even though adrenocorticotropic hormone (ACTH) demonstrated powerful efficacy in the initially successful treatment of infantile spasms (IS), nearly one-half of patients whose spasms were once suppressed experienced relapse. There is currently no validated method for the prediction of the risk of relapse. The Burden of Amplitudes and Epileptiform Discharges (BASED) score is an electroencephalogram (EEG) grading scale for children with infantile spasms. We sought to determine whether an association exists between the BASED score after ACTH treatment and relapse after initial response with ACTH. METHODS: Children with IS who achieved initial response after ACTH treatment were selected as the study subjects. Those who experienced relapse within 12 months after ACTH treatment were categorized as the relapse group, and those who did not were categorized as the non-relapse group. Their general clinical data and EEG data (using BASED scoring) after ACTH treatment were collected, and compared between groups. Cox proportional hazards models were fit to determine factors associated with relapse. RESULTS: A total of 64 children with IS were enrolled in the study, of which 37 (57.8%) experienced a relapse, and the median duration after ACTH treatment was 3 (1.5, 6) months. The BASED score was significantly higher in the relapse group than in the non-relapse group. Cox modeling demonstrated that BASED score was independently associated with relapse. The patients with a score greater than or equal to 3 showed a high rate (89.3%) of relapse. The relapse group had stronger, more stable EEG functional networks than the non-relapse group, and there were obvious correlations between BASED score and functional connectivity. CONCLUSION: This study suggests the BASED score after ACTH treatment has potential value as a predictor for relapse after initial response. Children with IS who have a BASED score greater than or equal to 3 after the initial response of ACTH carry a high risk of relapse within 1 year.

Foveal pit morphological changes in asymptomatic carriers of the G11778A mutation with Leber's hereditary optic neuropathy.

AIM: To investigate the foveal pit morphology changes in unaffected carriers and affected Leber's hereditary optic neuropathy (LHON) patients with the G11778A mutation from one family. METHODS: This study was a prospective cross-sectional study. Both eyes from 16 family members (age from 9 to 47y) with the G11778A mutation were analyzed and compared with 1 eye from 20 normal control subjects. Eleven family members with the G11778A mutation but without optic neuropathy were classified as unaffected carriers (n=22 eyes). Five family members (n=10 eyes) expressed the LHON phenotype and were classified as affected patients. Retinal images of all the subjects were taken by optical coherence tomography (OCT), and an automatic algorithm was used to segment the retina to eight layers. Horizontal and vertical OCT images centered on the fovea were used to measure intra-retinal layer thicknesses and foveal morphometry. RESULTS: Thicker foveal thickness, thinner foveal pit depth, and flatter foveal slopes were observed in unaffected carriers and affected LHON patients (all P<0.001). Further, the slopes of all four sectors in the LHON were flatter than those in the unaffected carriers (all P<0.001). Compared with the control group, affected LHON patients had a thinner retinal nerve fiber layer (RNFL), ganglion cell layer and inner plexiform layer (GCL+IPL), and total retina (all P<0.01). The retinal nerve fiber layer (RNFL) of affected patients was 38.0% thinner than that of controls while the GCL+IPL was 40.1% thinner. CONCLUSION: The foveal pit morphology shows changes in both unaffected carriers and affects patients. RNFL and GCL+IPL are thinner in affected LHON patients but not in unaffected carriers.

Immunogenicity of oral vaccination with Lactococcus lactis derived vaccine candidate antigen (UreB) of Helicobacter pylori fused with the human interleukin 2 as adjuvant.

Helicobacter pylori (H. pylori) infection remains a significant global public health problem. Vaccine, especially edible vaccine, is considered to be effective in the management of H. pylori infections. By using recombinant technology, Lactococcus lactis (L. lactis) could serve as an antigen-delivering vehicle for the development of edible vaccine. The aim of this study was to produce edible UreB (urease B) vaccine derived from L. lactis against H. pylori. The UreB subunit is the most effective and common immunogen of all strains of H. pylori. The UreB was produced as a chimeric protein fused with IL-2 (human interleukin 2) as the mucosal adjuvant. Mucosal immunization of mice with recombinant L. lactis NZ9000 containing the UreB-IL-2 protein elicited more anti-UreB antibody that specifically bounded to the purified bacterial UreB protein and more cytokines such as IFN-γ, IL-4, and IL-17, and had a lower H. pylori burden and urease activity than control mice. These results suggest that the recombinant L. lactis expressing UreB-IL-2 can be potentially used as an edible vaccine for controlling H. pylori infection.