Ankle reflex and neurological symptom score: a primary level screening method for diabetic peripheral neuropathy.

Herein, we aimed to develop an easily available and efficient screening method for diabetic peripheral neuropathy (DPN) suitable for primary care settings, emphasizing simplicity, speed, and accuracy. Nerve conduction studies were conducted on 214 patients with diabetes, encompassing the outcomes of five distinct assessments: diabetic neuropathy symptom (DNS), vibration perception threshold (VPT), and nerve screening. The diagnostic accuracy of the VPT and nerve screening was evaluated by comparing them with that of the nerve conduction study. To assess diagnostic efficacy, various combinations were examined, including DNS combined with VPT, pain, temperature, touch, and ankle reflex. The diagnostic performance of DNS was superior to that of the five neurological screening items and VPT, with sensitivity, specificity, and accuracy of 0.68, 0.81, and 0.73, respectively. Among the two combined methods, "DNS + ankle reflex" was identified as having the highest diagnostic value, with an area under the curve, a sensitivity, a specificity, and an accuracy of 0.81, 0.89, 0.70, and 0.80, respectively. Furthermore, a combination of "DNS + ankle reflex + touch + pain + VPT" achieved the best performance among the five combinations, with an area under the curve, sensitivity, specificity, and accuracy of 0.85, 0.93, 0.68, and 0.81, respectively. The combination of DNS, ankle reflex, touch, pain, and VPT methods showed the highest diagnostic value for DPN. However, considering factors including accuracy, time, and economic cost, we recommend using a simpler combination of DNS and ankle reflex for large-scale screening of patients with DPN.

Machine learning models for diabetic neuropathy diagnosis using microcirculatory parameters in type 2 diabetes patients.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a primary cause of diabetic foot, early detection of DPN is essential. This study aimed to construct a machine learning model for DPN diagnosis based on microcirculatory parameters, and identify the most predictive parameters for DPN. METHODS: Our study involved 261 subjects, including 102 diabetics with neuropathy (DMN), 73 diabetics without neuropathy (DM), and 86 healthy controls (HC). DPN was confirmed by nerve conduction velocity and clinical sensory tests. Microvascular function was measured by postocclusion reactive hyperemia (PORH), local thermal hyperemia (LTH), and transcutaneous oxygen pressure (TcPO2). Other physiological information was also investigated. Logistic regression (LR) and other machine learning (ML) algorithms were used to develop the model for DPN diagnosis. Kruskal-Wallis Test (non-parametric) were performed for multiple comparisons. Several performance measures, such as accuracy, sensitivity and specificity, were used to access the efficacy of the developed model. All the features were ranked based on the importance score to find features with higher DPN predictions. RESULTS: There was an overall decrease in microcirculatory parameters in response to PORH and LTH, as well as TcPO2, in DMN group compared to DM group and HC group. Random forest (RF) was found to be the best model, and achieved 84.6% accuracy along with 90.2% sensitivity and 76.7% specificity. RF_PF% of PORH was the main predictor of DPN. In addition, diabetic duration was also an important risk factor. CONCLUSIONS: PORH Test is a reliable screening tool for DPN, which can accurately distinguish DPN from diabetics using RF.

Downregulation of REST in the cochlea contributes to age-related hearing loss via the p53 apoptosis pathway.

Age-related hearing loss (AHL) is the most common sensory disorder amongst the elderly population. Although the degeneration of spiral ganglion neurons (SGNs) and hair cells (HCs) is considered to play a critical role in AHL, the mechanism has not been fully outlined. The repressor element 1-silencing transcription factor (REST) has recently been associated with mediating cell death in neurodegenerative diseases. However, whether REST induces degeneration of cochlear HCs and SGNs to contribute to AHL remains unknown. Here, we report that REST expression was decreased in HCs and SGNs in AHL mice. Conditional deletion of Rest in HCs and SGNs of 2-month-old mice resulted in hearing loss accompanied by the upregulation of p53, TNFR1(tumor necrosis factor receptor-1), and cleaved caspase-3. The p53 inhibitor pifithrin-α significantly attenuated SGN and HC damage and rescued hearing impairment in Rest cKO mice. Furthermore, downregulation of REST by H2O2 treatment induced apoptosis in the House Ear Institute Organ of Corti 1 cell, through the upregulation of p53. In contrast, overexpression of REST reversed the changes in p53 expression. In addition, REST was further shown to bind directly to the p53 promoter site, thereby inhibiting the effect of p53. Finally, in aged mice, the p53 inhibitor significantly reduced loss of HCs and SGNs, and subsequently improved hearing. In summary, our findings indicate that REST has a protective role in AHL, and that its deficiency upregulates p53 and induces cochlear cell apoptosis, which that leads to deafness.

Repressor element 1-silencing transcription factor deficiency yields profound hearing loss through Kv7.4 channel upsurge in auditory neurons and hair cells.

Repressor element 1-silencing transcription factor (REST) is a transcriptional repressor that recognizes neuron-restrictive silencer elements in the mammalian genomes in a tissue- and cell-specific manner. The identity of REST target genes and molecular details of how REST regulates them are emerging. We performed conditional null deletion of Rest (cKO), mainly restricted to murine hair cells (HCs) and auditory neurons (aka spiral ganglion neurons [SGNs]). Null inactivation of full-length REST did not affect the development of normal HCs and SGNs but manifested as progressive hearing loss in adult mice. We found that the inactivation of REST resulted in an increased abundance of Kv7.4 channels at the transcript, protein, and functional levels. Specifically, we found that SGNs and HCs from Rest cKO mice displayed increased Kv7.4 expression and augmented Kv7 currents; SGN's excitability was also significantly reduced. Administration of a compound with Kv7.4 channel activator activity, fasudil, recapitulated progressive hearing loss in mice. In contrast, inhibition of the Kv7 channels by XE991 rescued the auditory phenotype of Rest cKO mice. Previous studies identified some loss-of-function mutations within the Kv7.4-coding gene, Kcnq4, as a causative factor for progressive hearing loss in mice and humans. Thus, the findings reveal that a critical homeostatic Kv7.4 channel level is required for proper auditory functions.