Pioneering a chick embryo model to explore the intrauterine etiology of developmental dysplasia of the hip in oligohydramnios conditions.

OBJECTIVE: To explore the impact of oligohydramnios on fetal movement and hip development, given its association with developmental dysplasia of the hip (DDH) but unclear mechanisms. METHODS: Chick embryos were divided into four groups based on the severity of oligohydramnios induced by amniotic fluid aspiration (control, 0.2 mL, 0.4 mL, 0.6 mL). Fetal movement was assessed by detection of movement and quantification of residual amniotic fluid volume. Hip joint development was assessed by gross anatomic analysis, micro-computed tomography (micro-CT) for cartilage assessment, and histologic observation at multiple time points. In addition, a subset of embryos from the 0.4 mL aspirated group underwent saline reinfusion and subsequent evaluation. RESULTS: Increasing volumes of aspirated amniotic fluid resulted in worsening of fetal movement restrictions (e.g., 0.4 mL aspirated and control group at E10: frequency difference -7.765 [95% CI: -9.125, -6.404]; amplitude difference -0.343 [95% CI: -0.588, -0.097]). The 0.4 mL aspirated group had significantly smaller hip measurements compared to controls, with reduced acetabular length (-0.418 [95% CI: -0.575, -0.261]) and width (-0.304 [95% CI: -0.491, -0.117]) at day E14.5. Histological analysis revealed a smaller femoral head (1.084 ±â€¯0.264 cm) and shallower acetabulum (0.380 ±â€¯0.106 cm) in the 0.4 mL group. Micro-CT showed cartilage matrix degeneration (13.6% [95% CI: 0.6%, 26.7%], P = 0.043 on E14.5). Saline reinfusion resulted in significant improvements in the femoral head to greater trochanter (0.578 [95% CI: 0.323, 0.833], P = 0.001). CONCLUSIONS: Oligohydramnios can cause DDH by restricting fetal movement and disrupting hip morphogenesis in a time-dependent manner. Timely reversal of oligohydramnios during the fetal period may prevent DDH.

Comparison of uncut Roux-en-Y anastomosis and Billroth-II with Braun anastomosis after distal gastrectomy.

Background: This study aimed to compare the clinical outcomes and patient benefits of uncut Roux-en-Y (URY) anastomosis and Billroth-II with Braun (BB) anastomosis after distal gastrectomy. Methods: We retrospectively reviewed the data of patients who underwent URY or BB anastomosis after distal gastrectomy between March 2015 and December 2017. Clinical characteristics, survival data, postoperative recovery data, and long-term outcomes were recorded and compared between the two groups. Results: A total of 231 patients were included, with 167 in the URY group and 64 in the BB group. Kaplan-Meier curves for overall survival showed no differences after propensity score matching (p = 0.488). Long-term postoperative quality of life evaluation also showed no significant differences. Compared to the BB group, patients in the URY group had a significantly shorter time to start a liquid diet after propensity score matching (67.6 h vs. 46.5 h, p = 0.003), and a lower occurrence of bile reflux on follow-up gastroscopy (p < 0.001). Conclusion: The URY anastomosis appears to be a feasible method for digestive tract reconstruction after distal gastrectomy, resulting in less bile reflux and better postoperative recovery. However, there is no significant difference between URY and BB anastomosis in terms of overall survival and long-term quality of life.

Temporal Single-Cell Sequencing Analysis Reveals That GPNMB-Expressing Macrophages Potentiate Muscle Regeneration.

Macrophages play a crucial role in coordinating the skeletal muscle repair response, but their phenotypic diversity and the transition of specialized subsets to resolution-phase macrophages remain poorly understood. To address this issue, we induced injury and performed single-cell RNA sequencing on individual cells in skeletal muscle at different time points. Our analysis revealed a distinct macrophage subset that expressed high levels of Gpnmb and that coexpressed critical factors involved in macrophage-mediated muscle regeneration, including Igf1, Mertk, and Nr1h3. Gpnmb gene knockout inhibited macrophage-mediated efferocytosis and impaired skeletal muscle regeneration. Functional studies demonstrated that GPNMB acts directly on muscle cells in vitro and improves muscle regeneration in vivo. These findings provide a comprehensive transcriptomic atlas of macrophages during muscle injury, highlighting the key role of the GPNMB macrophage subset in regenerative processes. Targeting GPNMB signaling in macrophages could have therapeutic potential for restoring skeletal muscle integrity and homeostasis.

Prognostic and clinical significance of tumor-associated macrophages in esophageal squamous cell carcinoma after surgery: do biomarkers and distributions matter?

BACKGROUND: The role of tumor-associated macrophages (TAMs) in patients with esophageal squamous cell carcinoma (ESCC) following surgery remains controversial. Hence, we performed the present study to systematically analyze the prognostic and clinical significance of distinct TAMs biomarkers and distributions in ESCC patients underwent surgery. METHODS: PubMed, Web of Science, and EMBASE databases were searched up to March 31, 2023. The pooled analysis was conducted to evaluate the effects of TAMs on overall survival (OS), disease-free survival (DFS), and clinicopathological characteristics using fixed-effects or random-effect model. RESULTS: Involving a total of 2,502 ESCC patients underwent surgery from 15 studies, the results suggested that the total count of CD68+ TAMs was inversely associated with OS and DFS in ESCC patients, which was also noticed in the relationship of CD68+ TAMs in tumor islet (TI) with OS (all P<0.05), although no association between CD68+ TAMs in tumor stroma (TS) and OS (P>0.05). Moreover, either islet or stromal CD163+ TAMs density was a prognostic factor ESCC (all P<0.05). Similarly, an elevated CD204+ TAMs density in TI predicted a poor DFS (P<0.05), although CD204+ TAMs in TI had no relationship with OS (P>0.05). Besides, a high CD68+ TAMs density was significantly associated with lymphatic vessel invasion, vascular invasion, and lymph node metastasis (all P<0.05). CONCLUSION: Our results demonstrated the prognostic and clinical significance of TAMs in ESCC patients underwent surgery. TAMs should be considered a target that could improve prognostic stratification and clinical outcomes in ESCC after surgery.

Endoscopic ultrasonography-related diagnostic accuracy and clinical significance on small rectal neuroendocrine neoplasms.

This research aimed to examine the diagnostic accuracy and clinical significance of endoscopic ultrasonography (EUS) in the context of small rectal neuroendocrine neoplasms (NENs). A total of 108 patients with rectal subepithelial lesions (SELs) with a diameter of < 20 mm were included in the analysis. The diagnosis and depth assessment of EUS was compared to the histology findings. The prevalence of NENs in rectal SELs was 78.7% (85/108). The sensitivity of EUS in detecting rectal NENs was 98.9% (84/85), while the specificity was 52.2% (12/23). Overall, the diagnostic accuracy of EUS in identifying rectal NENs was 88.9% (96/108). The overall accuracy rate for EUS in assessing the depth of invasion in rectal NENs was 92.9% (78/84). Therefore, EUS demonstrates reasonable diagnostic accuracy in detecting small rectal NENs, with good sensitivity but inferior specificity. EUS may also assist physicians in assessing the depth of invasion in small rectal NENs before endoscopic excision.

Exploration of Pharmacological Mechanisms of Dapagliflozin against Type 2 Diabetes Mellitus through PI3K-Akt Signaling Pathway based on Network Pharmacology Analysis and Deep Learning Technology.

BACKGROUND: Dapagliflozin is commonly used to treat type 2 diabetes mellitus (T2DM). However, research into the specific anti-T2DM mechanisms of dapagliflozin remains scarce. OBJECTIVE: This study aimed to explore the underlying mechanisms of dapagliflozin against T2DM. METHODS: Dapagliflozin-associated targets were acquired from CTD, SwissTargetPrediction, and SuperPred. T2DM-associated targets were obtained from GeneCards and DigSee. VennDiagram was used to obtain the overlapping targets of dapagliflozin and T2DM. GO and KEGG analyses were performed using clusterProfiler. A PPI network was built by STRING database and Cytoscape, and the top 30 targets were screened using the degree, maximal clique centrality (MCC), and edge percolated component (EPC) algorithms of CytoHubba. The top 30 targets screened by the three algorithms were intersected with the core pathway-related targets to obtain the key targets. DeepPurpose was used to evaluate the binding affinity of dapagliflozin with the key targets. RESULTS: In total, 155 overlapping targets of dapagliflozin and T2DM were obtained. GO and KEGG analyses revealed that the targets were primarily enriched in response to peptide, membrane microdomain, protein serine/threonine/tyrosine kinase activity, PI3K-Akt signaling pathway, MAPK signaling pathway, and AGE-RAGE signaling pathway in diabetic complications. AKT1, PIK3CA, NOS3, EGFR, MAPK1, MAPK3, HSP90AA1, MTOR, RELA, NFKB1, IKBKB, ITGB1, and TP53 were the key targets, mainly related to oxidative stress, endothelial function, and autophagy. Through the DeepPurpose algorithm, AKT1, HSP90AA1, RELA, ITGB1, and TP53 were identified as the top 5 anti-targets of dapagliflozin. CONCLUSION: Dapagliflozin might treat T2DM mainly by targeting AKT1, HSP90AA1, RELA, ITGB1, and TP53 through PI3K-Akt signaling.

Modulation of experimental acute lung injury by exosomal miR-7704 from mesenchymal stromal cells acts through M2 macrophage polarization.

Acute lung injury (ALI) is a life-threatening condition with limited treatment options. The pathogenesis of ALI involves macrophage-mediated disruption and subsequent repair of the alveolar barriers, which ultimately results in lung damage and regeneration, highlighting the pivotal role of macrophage polarization in ALI. Although exosomes derived from mesenchymal stromal cells have been established as influential modulators of macrophage polarization, the specific role of exosomal microRNAs (miRNAs) remains underexplored. This study aimed to elucidate the role of specific exosomal miRNAs in driving macrophage polarization, thereby providing a reference for developing novel therapeutic interventions for ALI. We found that miR-7704 is the most abundant and efficacious miRNA for promoting the switch to the M2 phenotype in macrophages. Mechanistically, we determined that miR-7704 stimulates M2 polarization by inhibiting the MyD88/STAT1 signaling pathway. Notably, intra-tracheal delivery of miR-7704 alone in a lipopolysaccharide-induced murine ALI model significantly drove M2 polarization in lung macrophages and remarkably restored pulmonary function, thus increasing survival. Our findings highlight miR-7704 as a valuable tool for treating ALI by driving the beneficial M2 polarization of macrophages. Our findings pave the way for deeper exploration into the therapeutic potential of exosomal miRNAs in inflammatory lung diseases.

Regional GABA levels modulate abnormal resting-state network functional connectivity and cognitive impairment in multiple sclerosis.

More evidence shows that changes in functional connectivity with regard to brain networks and neurometabolite levels correlated to cognitive impairment in multiple sclerosis. However, the neurological basis underlying the relationship among neurometabolite levels, functional connectivity, and cognitive impairment remains unclear. For this purpose, we used a combination of magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging to study gamma-aminobutyric acid and glutamate concentrations in the posterior cingulate cortex, medial prefrontal cortex and left hippocampus, and inter-network functional connectivity in 29 relapsing-remitting multiple sclerosis patients and 34 matched healthy controls. Neuropsychological tests were used to evaluate the cognitive function. We found that relapsing-remitting multiple sclerosis patients demonstrated significantly reduced gamma-aminobutyric acid and glutamate concentrations and aberrant functional connectivity involving cognitive-related networks compared to healthy controls, and both alterations were associated with specific cognition decline. Moreover, mediation analyses indicated that decremented hippocampus gamma-aminobutyric acid levels in relapsing-remitting multiple sclerosis patients mediated the association between inter-network functional connectivity in various components of default mode network and verbal memory deficits. In summary, our findings shed new lights on the essential function of GABAergic system abnormalities in regulating network dysconnectivity and functional connectivity in relapsing-remitting multiple sclerosis patients, suggesting potential novel approach to treatment.

Immunotherapy-associated symptoms, distress, financial toxicity and unmet supportive care needs of patients with cancer.

PURPOSE: To examine the unmet care needs (i.e., overall needs and need subdomains [physical and daily living needs, psychological and emotional needs, care and support needs, and health-system and informational needs]) of patients with cancer undergoing immunotherapy alone or in combination with other anticancer therapies, as well as related influencing factors. METHODS: A cross-sectional design was adopted. Cancer patients who received immunotherapy completed consent and questionnaires. Unmet care needs were evaluated with the Chinese version of the Supportive Care Needs Survey Screening Tool, symptom severity with the Symptom Severity Scale, distress severity with the Distress Thermometer Scale, and financial toxicity using the Financial Toxicity - Functional Assessment of Chronic Illness Therapy Questionnaire. RESULTS: In total, 105 patients were surveyed. The most frequently reported unmet needs were psychological and emotional needs (56.2%) followed by health-system and informational needs (36.2%). The major factors associated with unmet care needs and their subdomains were years of education, symptoms, distress, and financial toxicity. Years of education predicted overall unmet care needs, psychological and emotional needs, and care and support needs; symptoms predicted overall unmet care needs and all four subdomains; distress predicted psychological and emotional needs and health-system and informational needs; and financial toxicity predicted overall needs and psychological and emotional needs. CONCLUSIONS: Patients with higher education, severe symptoms, distress, and financial toxicity reported more unmet care needs. The findings of this study could be incorporated into immunotherapy-related clinical practice guidelines and future interventions to improve the quality of cancer care.

Nomogram for preoperative estimation of symptomatic subdural hygroma risk in pediatric intracranial arachnoid cysts.

OBJECTIVE: The occurrence and predictors of symptomatic subdural hygroma (SSH) subsequent to the fenestration of pediatric intracranial arachnoid cysts (IACs) are unclear. In this study, the authors aimed to investigate the likelihood of an SSH following IAC fenestration and the impact on operative efficacy with the ultimate goal of constructing a nomogram. METHODS: The medical records of 1782 consecutive patients who underwent surgical treatment at the Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were reviewed. Among these patients, a training cohort (n = 1214) underwent surgery during an earlier period and was used for the development of a nomogram. The remaining patients formed the validation cohort (n = 568) and were used to confirm the performance of the developed model. The development of the nomogram involved the use of potential predictors, while internal validation was conducted using a bootstrap-resampling approach. RESULTS: SSH was detected in 13.2% (160 of 1214) of patients in the training cohort and in 11.1% (63 of 568) of patients in the validation cohort. Through multivariate analysis, several factors including Galassi type, IAC distance to the basal cisterns, temporal bulge, midline shift, IAC shape in the coronal view, area of the stoma, and artery location near the stoma were identified as independent predictors of SSH. These 7 predictors were used to construct a nomogram, which exhibited a concordance statistic (C-statistic) of 0.826 and demonstrated good calibration. Following internal validation, the nomogram maintained good calibration and discrimination with a C-statistic of 0.799 (95% CI 0.665-0.841). Patients who had nomogram scores < 30 or ≥ 30 were considered to be at low and high risk of SSH occurrence, respectively. CONCLUSIONS: The predictive model and derived nomogram achieved satisfactory preoperative prediction of SSH. Using this nomogram, the risk for an individual patient can be estimated, and the appropriate surgery can be performed in high-risk patients.

Enhancing biocathode denitrification performance with nano-Fe3O4 under polarity period reversal.

The presence of excessive concentrations of nitrate poses a threat to both the environment and human health, and the bioelectrochemical systems (BESs) are attractive green technologies for nitrate removal. However, the denitrification efficiency in the BESs is still limited by slow biofilm formation and nitrate removal. In this work, we demonstrate the efficacy of novel combination of magnetite nanoparticles (nano-Fe3O4) with the anode-cathode polarity period reversal (PPR-Fe3O4) for improving the performance of BESs. After only two-week cultivation, the highest cathodic current density (7.71 ± 1.01 A m-2) and NO3--N removal rate (8.19 ± 0.97 g m-2 d-1) reported to date were obtained in the PPR-Fe3O4 process (i.e., polarity period reversal with nano-Fe3O4 added) at applied working voltage of -0.2 and -0.5 V (vs Ag/AgCl) under bioanodic and biocathodic conditions, respectively. Compared with the polarity reversal once only process, the PPR process (i.e., polarity period reversal in the absence of nano-Fe3O4) enhanced bioelectroactivity through increasing biofilm biomass and altering microbial community structure. Nano-Fe3O4 could enhance extracellular electron transfer as a result of promoting the formation of extracellular polymers containing Fe3O4 and reducing charge transfer resistance of bioelectrodes. This work develops a novel biocathode denitrification strategy to achieve efficient nitrate removal after rapid cultivation.

Get the win-win: Sustainable circular model of 'generation-value-technology' of industrial solid waste management.

The management of industrial solid waste (ISW) and promoting sustainable circular development of the industrial economy is an urgent priority today. Therefore, this article constructs a sustainable circular model of 'generation-value-technology' of ISW management through the lens of industrial added value (IAV) and technology level. Also, the importance of the role of government is considered in the model. Based on actual data of China, this article simulates the future trend of the model using a system dynamics approach. The chief findings of the study are as follows: (1) under the current policy, China's future industrialization is increasing and the technological level of industrial enterprises is rising, but this is accompanied by a climb in ISW generation. (2) The win-win situation of ISW decrease and IAV increase can be achieved through enhanced information disclosure, technology innovation and government incentives. (3) Government subsidy should be oriented towards supporting technology innovation in industrial enterprises while reducing the proportion of incentives for ISW management results. Based on the results, this study proposes targeted policy implications for government and industrial enterprises.

Laser Speckle Contrast Imaging Guides Needling Treatment of Vascular Complications from Dermal Fillers.

BACKGROUND: Although laser Doppler imaging (LDI) accurately delineates a hypoperfused area to help target hyaluronidase treatment, laser speckle contrast imaging (LSCI) is more appropriate for assessing microvascular hemodynamics and has greater reproducibility than LDI. This study investigated the use of LSCI in the evaluation and treatment of six patients who developed vascular complications after facial dermal filler injections. METHODS: The areas of vascular occlusion were accurately defined in real time by LSCI and were more precise than visual inspections or photographic evidence for guiding needling and hyaluronidase treatment. RESULTS: All patients had achieved satisfactory outcomes as early as Day 2 of treatment and no procedure-related complications were reported after a median follow-up of 9.5 (7-37) days. CONCLUSION: LSCI accurately and noninvasively delineated vascular occlusions in real time among patients experiencing complications of facial dermal filler injections. Moreover, LSCI was more accurate than visual and photographic evaluations. Clinicians can use LSCI to reliably follow-up therapeutic outcomes after salvage interventions for vascular occlusions. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Effect of examining lymph nodes count on mortality risk in resected T1 non-small-cell lung cancer.

OBJECTIVES: This study aims to estimate the effect of the examined lymph node count (ELNC) on the cancer-related mortality risk and non-cancer-related mortality risk in patients with resected T1 non-small-cell lung cancer (NSCLC). METHODS: Patients diagnosed as primary T1 NSCLC between 2000 and 2017 were extracted from the Surveillance, Epidemiology and End Results database. Patients were divided into 2 groups according to the ELNC cutoff value, which was calculated based on overall survival outcomes. Propensity score matching was used to equalize the differences in baseline characteristics between groups. RESULTS: A total of 38 242 resected T1 NSCLC patients were extracted from the database with the ELNC cutoff value of 8. After propensity score matching, 27 676 patients were included in this study. Examining ≥8 ELNC was associated with a more accurate assessment of lymph node (LN) metastasis and significantly improving the prognosis. These trends remained consistent in subgroup analysis by histology type. In competing risk mode, examining ≥8 LNs could significantly reduce the risk of death from lung cancer, risk of death from chronic obstructive pulmonary disease, and risk of death from cardiac diseases. In the subgroup analysis, these trends were consistent. CONCLUSIONS: Given the mortality risk associated with lung cancer, chronic obstructive pulmonary disease, and cardiac diseases, at least 8 LNs should be examined in surgery for T1 NSCLC.

Enhanced axon outgrowth of spinal motor neurons in co-culturing with dorsal root ganglions antagonizes the growth inhibitory environment.

Introduction: Forming a bridge made of functional axons to span the lesion is essential to reconstruct the motor circuitry following spinal cord injury (SCI). Dorsal root ganglion (DRG) axons are robust in axon growth and have been proved to facilitate the growth of cortical neurons in a process of axon-facilitated axon regeneration. However, whether DRG transplantation affects the axon outgrowth of spinal motor neurons (SMNs) that play crucial roles in motor circuitry remains unclear. Methods: We investigated the axonal growth patterns of co-cultured DRGs and SMN aggregates (SMNAs) taking advantage of a well-designed 3D-printed in vitro system. Chondroitin sulphate proteoglycans (CSPG) induced inhibitory matrix was introduced to imitate the inhibitory environment following SCI. Axonal lengths of DRG, SMNA or DRG & SMNA cultured on the permissive or CSPG induced inhibitory matrix were measured and compared. Results: Our results indicated that under the guidance of full axonal connection generated from two opposing populations of DRGs, SMNA axons were growth-enhanced and elongated along the DRG axon bridge to distances that they could not otherwise reach. Quantitatively, the co-culture increased the SMNA axonal length by 32.1 %. Moreover, the CSPG matrix reduced the axonal length of DRGs and SMNAs by 46.2 % and 17.7 %, respectively. This inhibitory effect was antagonized by the co-culture of DRGs and SMNAs. Especially for SMNAs, they extended the axons across the CSPG-coating matrix, reached the lengths close to those of SMNAs cultured on the permissive matrix alone. Conclusions: This study deepens our understanding of axon-facilitated reconstruction of the motor circuitry. Moreover, the results support SCI treatment utilizing the enhanced outgrowth of axons to restore functional connectivity in SCI patients.

sLASER and PRESS perform similarly at revealing metabolite-age correlations at 3 T.

PURPOSE: To compare the respective ability of PRESS and sLASER to reveal biological relationships, using age as a validation covariate at 3 T. METHODS: MRS data were acquired from 102 healthy volunteers using PRESS and sLASER in centrum semiovale and posterior cingulate cortex (PCC). Acquisition parameters included TR/TE = 2000/30 ms, 96 transients, and 2048 datapoints sampled at 2 kHz. Spectra were analyzed using Osprey. SNR, FWHM linewidth of total creatine, and metabolite concentrations were extracted. A linear model was used to compare SNR and linewidth. Paired t-tests were used to assess differences in metabolite measurements between PRESS and sLASER. Correlations were used to evaluate the relationship between PRESS and sLASER metabolite estimates, as well as the strength of each metabolite-age relationship. Coefficients of variation were calculated to assess inter-subject variability in each metabolite measurement. RESULTS: SNR and linewidth were significantly higher (p < 0.01) for sLASER than PRESS in PCC. Paired t-tests showed significant differences between PRESS and sLASER in most metabolite measurements. PRESS-sLASER measurements were significantly correlated (p < 0.05) for most metabolites. Metabolite-age relationships were consistently identified using both methods. Similar coefficients of variation were observed for most metabolites. CONCLUSION: The study results suggest strong agreement between PRESS and sLASER in identifying relationships between brain metabolites and age in centrum semiovale and PCC data acquired at 3 T. sLASER is technically desirable due to the reduced chemical shift displacement artifact; however, PRESS performed similarly in homogeneous brain regions at clinical field strength.

Does enhanced cognitive performance reduce fracture risk? a Mendelian randomization study.

OBJECTIVE: While observational studies have suggested a link between cognitive performance and fracture risk, the causality and site-specific nature are unclear. We applied Mendelian randomization (MR) to elucidate these associations. METHODS: 147 single-nucleotide polymorphisms (SNPs) tied strongly to cognitive performance (p< 5e-8) were selected. We performed MR analysis to investigate the causal relationship between cognitive performance and fractures at specific sites, including the wrist, upper arm, shoulder, ribs, sternum, thoracic spine, lumbar spine, pelvis, femur, leg, and ankle. The primary estimate was determined using the inverse variance-weighted method. Additionally, we examined heterogeneity using the MR Pleiotropy RESidual Sum Outlier test and Cochran Q, and employed MR-Egger regression to identify horizontal pleiotropy. RESULTS: MR analysis identified a causal association between cognitive performance and fractures at the lumbar-spine-pelvis (odds ratio [OR] = 0.727, 95% CI = 0.552-0.956, p = 0.023), and ribs-sternum-thoracic spine sites (OR = 0.774, 95% CI = 0.615-0.974, p = 0.029). However, no causal association was found for fractures at other sites. CONCLUSIONS: This study provided evidence of a causal connection between cognitive performance and fracture risk at certain locations. These findings underline the potential of cognitive enhancement strategies as innovative and effective methods for fracture prevention.

Three-dimensional magnetic resonance neurography aids in detection of brachial plexus nerve root signal and size alterations in patients with amyotrophic lateral sclerosis: a case-control study.

Background: Since previous histopathological studies have shown a distal to proximal gradient of axonal damage in peripheral nerves of patients with amyotrophic lateral sclerosis (ALS), it would be worthwhile to evaluate consequence of such changes on magnetic resonance imaging (MRI). The aim of this study was to assess proximal-distal longitudinal signal and size alterations of brachial plexus nerve roots in ALS patients using 3-dimensional (3D) magnetic resonance neurography (MRN). Methods: A total of 21 ALS patients and 19 controls were evaluated. The diameters and signal-to-noise (SNR) ratio values of C5-C8 roots were measured at five points from proximal to distal sites. Student's t-test was performed to compare the differences at each point between two groups. Linear regression was performed for each nerve root, and the differences in linear regression slopes between two groups were analyzed. Receiver operating characteristic (ROC) analysis was performed for the diameter and SNR value ratio of the distal to the proximal points. Results: Interobserver agreement was excellent [intraclass correlation coefficient (ICC): 0.802-0.913]. The diameters and SNR values of C5-C8 roots showed a significant decrease (P<0.05) from proximal to distal except SNR value of C5 root in controls. The slope values of diameters in ALS were -0.01924 for C5, -0.04404 for C6, -0.06228 for C7, and -0.06464 for C8. The slope values of SNR values in ALS were -10.14 for C5, -12.86 for C6, -15.99 for C7, and -19.06 for C8. The slope of nerve diameters and SNR values for ALS patients were more negatively sloped than controls (P<0.05) except SNR values of C5 and C7 roots. The ROC analysis confirmed that the diameter and SNR value ratio could differentiate ALS patients from controls with high accuracy. The cutoff values of diameter ratio were 0.7418 for C5, 0.6952 for C6, 0.6431 for C7, and 0.7147 for C8. The cutoff values of SNR value ratio were 0.5989 for C5, 0.6516 for C6, 0.6065 for C7, and 0.6758 for C8. Conclusions: Proximal-distal longitudinal diameters and SNR values decreased significantly for brachial plexus nerve roots in ALS patients with larger differences in slopes compared to controls. These results reflect pathophysiological changes of ALS and may be helpful in improving the diagnosis of ALS.

Use of a Digital Conversational Agent for the Management of Overactive Bladder.

IMPORTANCE: Conservative therapy is effective for the treatment of overactive bladder (OAB) but may be limited by accessibility to care. OBJECTIVE: The objective of this study was to evaluate the efficacy of a digital conversational agent (CeCe) for the treatment of OAB. STUDY DESIGN: This was a prospective observational trial utilizing a digital conversational agent developed by Renalis University Hospitals (Cleveland, Ohio) for the treatment of OAB. Patients were given access to CeCe over an 8-week period and were instructed on how to perform bladder training and pelvic floor exercises and taught about bladder health. The primary outcome was a decrease in the International Consultation on Incontinence-Overactive Bladder Quality-of-Life Questionnaire (ICIQ-OAB-QoL) score from week 1 to week 8. Patients also completed the 36-item Short-Form Health Survey and Generalized Anxiety Disorder Questionnaire at the same intervals and voiding diaries at weeks 1, 4, and 8. A power analysis was performed and determined that a total of 30 patients would be needed to demonstrate a significant difference in symptom scores after use of CeCe with 80% power and an α error of 5%. RESULTS: Twenty-nine patients completed all data collection. The ICIQ-OAB-QoL scores were significantly different between weeks 1 and 8 (62 [IQR], 49-75) vs 32 [IQR, 24-43]; P < 0.001). Patients also reported a decrease in frequency pretreatment and posttreatment (7 [IQR, 6-10] vs 5 [IQR, 4-7]; P = -0.04), nocturia (2 [IQR, 1-3] vs 1 [IQR, 1-2]; P = 0.03), and urge urinary incontinence (2 [IQR, 1-5] vs 0 [IQR, 0-3]; P = 0.04). Consumption of alcohol decreased from week 1 to week 8 (24 oz [IQR, 12-36 oz) to 14 oz (IQR, 9-22 oz]; P = 0.02). CONCLUSION: The use of a digital conversational agent effectively reduced the severity of symptoms and improved quality of life in patients with OAB.