Noradrenaline activation of hippocampal dopamine D1 receptors promotes antidepressant effects.

Dopamine D1 receptors (D1Rs) in the hippocampal dentate gyrus (DG) are essential for antidepressant effects. However, the midbrain dopaminergic neurons, the major source of dopamine in the brain, only sparsely project to DG, suggesting possible activation of DG D1Rs by endogenous substances other than dopamine. We have examined this possibility using electrophysiological and biochemical techniques and found robust activation of D1Rs in mouse DG neurons by noradrenaline. Noradrenaline at the micromolar range potentiated synaptic transmission at the DG output and increased the phosphorylation of protein kinase A substrates in DG via activation of D1Rs and ß adrenergic receptors. Neuronal excitation preferentially enhanced noradrenaline-induced synaptic potentiation mediated by D1Rs with minor effects on ß-receptor-dependent potentiation. Increased voluntary exercise by wheel running also enhanced noradrenaline-induced, D1R-mediated synaptic potentiation, suggesting a distinct functional role of the noradrenaline-D1R signaling. We then examined the role of this signaling in antidepressant effects using mice exposed to chronic restraint stress. In the stressed mice, an antidepressant acting on the noradrenergic system induced a mature-to-immature change in the DG neuron phenotype, a previously proposed cellular substrate for antidepressant action. This effect was evident only in mice subjected to wheel running and blocked by a D1R antagonist. These results suggest a critical role of noradrenaline-induced activation of D1Rs in antidepressant effects in DG. Experience-dependent regulation of noradrenaline-D1R signaling may determine responsiveness to antidepressant drugs in depressive disorders.

UDP-Glucose/P2Y14 Receptor Signaling Exacerbates Neuronal Apoptosis After Subarachnoid Hemorrhage in Rats.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a severe subtype of stroke with poor outcomes. Abnormal glucose metabolism often occurs after SAH, but the strict control of blood glucose levels is not always beneficial. This study aimed to investigate the contribution of uridine diphosphate glucose (UDP-G), an intermediate of glucose/glycogen metabolism, and its receptor P2Y14 (P2Y purinoceptor 14) to SAH pathology and explored the potential targeted treatments in rats. METHODS: A total of 218 Sprague-Dawley male rats were used. SAH was induced by endovascular perforation. Brain expressions of P2Y14, uridine diphosphate glucose (UDP-G), and its converting enzyme UGP2 (UDP-G pyrophosphorylase-2) were evaluated. Exogenous UDP-G or selective P2Y14 inhibitor was administered intranasally at 1 hour after SAH to explore their potential effects. Intranasal Ugp2 or P2ry14 siRNA was delivered 24 hours before SAH for mechanistic evaluation. Primary neuron culture and hemoglobin stimulation were used as in vitro model of SAH. Post-SAH evaluation included liquid chromatography-mass spectrometry measurement of brain endogenous UDP-G level, neurobehavioral assessments, Western blotting, immunohistochemistry, TUNEL staining, and Nissl staining. RESULTS: There was an acute elevation of endogenous brain UDP-G and UGP2 after SAH, and P2Y14 was expressed in neurons. Although P2Y14 inhibitor decreased neurological dysfunction, neuronal apoptosis, and proapoptotic molecules, exogenous UDP-G exacerbated these outcomes at 24 hours after SAH. Early inhibition of P2Y14 preserved long-term neuronal survival in the hippocampus, amygdala, and cortex with improved neurocognition and depressive-like behavior. In addition, in vivo knockdown of Ugp2- and P2ry14-reduced neurological deficits and proapoptotic molecules at 24 hours after SAH, and furthermore in vitro knockdown of P2ry14-reduced apoptosis in hemoglobin stimulated primary neuron. CONCLUSIONS: These findings suggest a detrimental role of brain UDP-G/P2Y14 signaling in SAH, as a part of glucose metabolic pathology at the tissue level. P2Y14 inhibitor 4-[4-(4-piperidinyl)phenyl]-7-[4-(trifluoromethyl)phenyl]-2-naphthalenecarboxylic acid hydrochloride may serve as a potential therapeutic target in treating patients with SAH.

The role of left insula mediating impaired error processing in response inhibition in adult heavy drinkers.

Identification of neurobiological mechanisms underlying development of alcohol use disorder is critical to ensuring the appropriate early-phase treatment and prevention of the disorder. To this aim, we tried to elucidate the disturbance of neural functions in heavy drinking, which can lead to alcohol use disorder. Because response inhibition is affected by alcohol use disorder, we examined neural activation and task performance for response inhibition using the Go/No-Go task in an fMRI paradigm in adult non-dependent heavy and light drinkers. We examined the neural activation for error processing and inhibitory control, components of response inhibition. We then investigated the mediating effect of the relevant neural substrate on the relationship between the level of alcohol drinking and task performance using mediation analysis. We found that heavy drinking significantly decreased activation in the left insula during error processing and increased the mean commission error rate for No-Go trials compared with light drinking. Mediation analysis demonstrated full mediation of the left insula activation during error processing for the relationship between drinking level and commission error rate. Our results suggested that left insula activation may be a neural marker pivotal for potential conversion to alcohol use disorder in individuals with high clinical risk such as heavy drinking.

Survival impact of sequential chemotherapy following pembrolizumab for recurrent or metastatic head and neck squamous cell carcinoma.

BACKGROUND: Pembrolizumab alone or combined with chemotherapy is the standard of care for first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) with positive programmed death-ligand 1 combined positive scores. However, data on second-line chemotherapy following pembrolizumab are scarce. METHODS: A single-center, retrospective study was conducted to determine the efficacies of pembrolizumab and pembrolizumab plus chemotherapy as first-line treatments and the efficacy of second-line chemotherapy for patients with R/M HNSCC who were refractory or intolerant to first-line treatment. RESULTS: Fifty-four patients were treated with pembrolizumab, and 29 received second-line therapy, with 27 opting for cetuximab-containing regimens. The median progression-free survival (PFS), overall survival (OS), and PFS on next-line therapy for first-line treatment were 4.7 (95% confidence interval [CI], 2.1-8.7), 22.1 (95% CI, 12.6-not reached), and 15.6 months (95% CI, 9.7-not reached) in the pembrolizumab group and 5.4 (95% CI, 3.3-6.8), 15.8 (95% CI, 8.6-not reached), and 13.7 months (95% CI, 8.1-not reached) in the pembrolizumab plus chemotherapy group, respectively. The overall response rate and median PFS for second-line treatment were 48.3% (95% CI, 30.4-67.0) and 6.1 months (95% CI, 2.30-8.84). The median OS for patients who received second-line treatment was 18.4 months, which was superior to the median OS of 6.0 months for patients who received the best supportive care (log-rank p = 0.10). CONCLUSION: This study indicates that cetuximab-containing second-line chemotherapy can improve outcomes in R/M HNSCC, even after first-line therapy failure or intolerance.

Neurological recovery rate and predictive factors of incomplete AIS grade C spinal cord injury in the older aged population.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To define the prognosis and predictive factors for neurological improvement in older patients with incomplete spinal cord injury (SCI) of American Spinal Injury Association Impairment Scale grade C (AIS-C). SETTINGS: Multi-institutions in Japan. METHODS: We included patients aged ≥65 years with traumatic SCI of AIS-C who were treated conservatively or surgically with >3 follow-up months. To identify factors related to neurological improvement, patients were divided into three groups according to their neurological status at the final follow-up, with univariate among-group comparisons of demographics, radiographic, and therapeutic factors. Significant variables were included in the multivariate logistic regression analysis. RESULTS: Overall, 296 older patients with SCI of AIS-C on admission were identified (average age: 75.2 years, average follow-up: 18.7 months). Among them, 190 (64.2%) patients improved to AIS-D and 21 (7.1%) patients improved to AIS-E at final follow-up. There were significant among-group differences in age (p = 0.026), body mass index (p = 0.007), status of pre-traumatic activities of daily living (ADL) (p = 0.037), and serum albumin concentrations (p = 0.011). Logistic regression analysis showed no significant differences in variables in the stratified group of patients who improved to AIS-D. Meanwhile, serum albumin was a significant variable in patients who improved to AIS-E (p = 0.026; OR: 6.20, pre-traumatic ADL was omitted due to data skewness). CONCLUSIONS: Most older patients with incomplete AIS-C SCI demonstrated at least 1 grade of neurological improvement. However, <10% of patients achieved complete recovery. Key predictors of complete recovery were high serum albumin levels on admission and independent pre-traumatic ADL. SPONSORSHIP: No funding was received for this study.

Influence of the timing of surgery for cervical spinal cord injury without bone injury in the elderly: A retrospective multicenter study.

BACKGROUND: Although previous studies have demonstrated the advantages of early surgery for traumatic spinal cord injury (SCI), the appropriate surgical timing for cervical SCIs (CSCIs) without bone injury remains controversial. Here, we investigated the influence of relatively early surgery within 48 h of injury on the neurological recovery of elderly patients with CSCI and no bone injury. METHODS: In this retrospective multicenter study, we reviewed data from 159 consecutive patients aged ≥65 years with CSCI without bone injury who underwent surgery in participating centers between 2010 and 2020. Patients were followed up for at least 6 months following CSCI. We divided patients into relatively early (≤48 h after CSCI, n = 24) and late surgery (>48 h after CSCI, n = 135) groups, and baseline characteristics and neurological outcomes were compared between them. Multivariate analysis was performed to identify factors associated with neurological recovery. RESULTS: The relatively early surgery group demonstrated a lower prevalence of cardiac disease, poorer baseline American Spinal Injury Association (ASIA) impairment scale grade, and lower baseline ASIA motor score (AMS) than those of the late surgery group (P < 0.030, P < 0.001, and P < 0.001, respectively). Although the AMS was lower in the relatively early surgery group at 6 months following injury (P = 0.001), greater improvement in this score from baseline to 6-months post injury was observed (P = 0.010). Multiple linear regression analysis revealed that relatively early surgery did not affect postoperative improvement in AMS, rather, lower baseline AMS was associated with better AMS improvement (P < 0.001). Delirium (P = 0.006), pneumonia (P = 0.030), and diabetes mellitus (P = 0.039) negatively influenced postoperative improvement. CONCLUSIONS: Although further validation by future studies is required, relatively early surgery did not show a positive influence on neurological recovery after CSCI without bone injury in the elderly.

Cerebral activation caused by dental sounds: a functional magnetic resonance imaging study.

Dental drilling sounds can induce anxiety in some patients. This study aimed to use functional magnetic resonance imaging (fMRI) to assess the relationship between dental fear and auditory stimuli. Thirty-four right-handed individuals (21 women and 13 men; average age, 31.2 years) were selected. The level of dental fear was assessed using the dental fear survey (DFS). Based on a threshold DFS score > 52, participants were categorized into two groups: dental fear (DF) group (n = 12) and control group (n = 22). Two types of stimuli were presented in a single session: dental and neutral sounds. Cerebral activation during the presentation of these sounds was evaluated using contrast-enhanced blood oxygenation level-dependent fMRI. In the DF group, dental sounds induced significantly stronger activation in the left inferior frontal gyrus and left caudate nucleus (one-sample t test, P < 0.001). In contrast, in the control group, significantly stronger activation was observed in the bilateral Heschl's gyri and left middle frontal gyrus (one-sample t test, P < 0.001). Additionally, a two-sample t test revealed that dental sounds induced a significantly stronger activation in the left caudate nucleus in the DF group than in the control group (P < 0.005). These findings suggest that the cerebral activation pattern in individuals with DF differs from that in controls. Increased activation of subcortical regions may be associated with sound memory during dental treatment.

Acute-Phase Plasma Pigment Epithelium-Derived Factor Predicting Outcomes after Aneurysmal Subarachnoid Hemorrhage in the Elderly.

Aneurysmal subarachnoid hemorrhage (SAH) has increased with the aging of the population, but the outcome for elderly SAH patients is very poor. Therefore, predicting the outcome is important for determining whether to pursue aggressive treatment. Pigment epithelium-derived factor (PEDF) is a matricellular protein that is induced in the brain, and the plasma levels could be used as a biomarker for the severity of metabolic diseases. This study investigated whether acute-phase plasma PEDF levels could predict outcomes after aneurysmal SAH in the elderly. Plasma samples and clinical variables were collected over 1-3 days, post-SAH, from 56 consecutive elderly SAH patients ≥75 years of age registered in nine regional stroke centers in Japan between September 2013 and December 2016. The samples and variables were analyzed in terms of 3-month outcomes. Acute-phase plasma PEDF levels were significantly elevated in patients with ultimately poor outcomes, and the cutoff value of 12.6 µg/mL differentiated 3-month outcomes with high sensitivity (75.6%) and specificity (80.0%). Acute-phase plasma PEDF levels of ≥12.6 µg/mL were an independent and possibly better predictor of poor outcome than previously reported clinical variables. Acute-phase plasma PEDF levels may serve as the first biomarker to predict 3-month outcomes and to select elderly SAH patients who should be actively treated.

Epidermal Growth Factor Receptor Mediates Neuronal Apoptosis After Subarachnoid Hemorrhage in Mice.

BACKGROUND: Early brain injury including neuronal apoptosis is a main contributor to neurological deterioration after subarachnoid hemorrhage (SAH). This study was aimed to investigate whether EGFR (epidermal growth factor receptor)/NFκB (nuclear factor-kappa B) inducing kinase (NIK)/NFκB (p65 and p50) pathway is involved in the neuronal apoptosis after SAH in mice. METHODS: C57BL/6 adult male mice underwent endovascular perforation SAH modeling or sham-operation (n=286), and 86 mild SAH mice were excluded. In experiment 1, vehicle or an EGFR inhibitor (632.0 ng AG1478) was administered intraventricularly at 30 minutes postmodeling. At 24 or 72 hours, after neurological score was tested, brain water content, double immunolabeling with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and a neuronal marker antimicrotubule-associated protein-2 antibody, Western blotting using whole tissue lysate or nuclear protein extraction of the left cortex, and immunohistochemistry for cleaved caspase-3, phosphorylated (p-) EGFR, NIK, p-NFκB p65, and NFκB p105/50 were evaluated. In experiment 2, after sham or SAH modeling, AG1478+vehicle or AG1478+4.0 ng EGF was administered intraventricularly. The brain was used for TUNEL staining and immunohistochemistry after 24-hour observation. RESULTS: SAH group showed deteriorated neurological score (P<0.01, Mann-Whitney U test), more TUNEL- and cleaved caspase-3-positive neurons (P<0.01, ANOVA), and higher brain water content (P<0.01, Mann-Whitney U test), and these observations were improved in SAH-AG1478 group. Western blotting showed that expression levels of p-EGFR, p-p65, p50, and nuclear-NIK were increased after SAH (P<0.05, ANOVA), and decreased by AG1478 administration. Immunohistochemistry revealed these molecules localized in degenerating neurons. EGF administration resulted in neurological deterioration, increased TUNEL-positive neurons, and activation of EGFR, NIK, and NFκB. CONCLUSIONS: Activated EGFR, nuclear-NIK, and NFκB expressions were observed in cortical degenerating neurons after SAH, and were decreased by administration of AG1478, associated with suppression of TUNEL- and cleaved caspase-3-positive neurons. EGFR/NIK/NFκB pathway is suggested to be involved in neuronal apoptosis after SAH in mice.

TSLP in DRG neurons causes the development of neuropathic pain through T cells.

BACKGROUND: Peripheral nerve injury to dorsal root ganglion (DRG) neurons develops intractable neuropathic pain via induction of neuroinflammation. However, neuropathic pain is rare in the early life of rodents. Here, we aimed to identify a novel therapeutic target for neuropathic pain in adults by comprehensively analyzing the difference of gene expression changes between infant and adult rats after nerve injury. METHODS: A neuropathic pain model was produced in neonatal and young adult rats by spared nerve injury. Nerve injury-induced gene expression changes in the dorsal root ganglion (DRG) were examined using RNA sequencing. Thymic stromal lymphopoietin (TSLP) and its siRNA were intrathecally injected. T cells were examined using immunofluorescence and were reduced by systemic administration of FTY720. RESULTS: Differences in changes in the transcriptome in injured DRG between infant and adult rats were most associated with immunological functions. Notably, TSLP was markedly upregulated in DRG neurons in adult rats, but not in infant rats. TSLP caused mechanical allodynia in adult rats, whereas TSLP knockdown suppressed the development of neuropathic pain. TSLP promoted the infiltration of T cells into the injured DRG and organized the expressions of multiple factors that regulate T cells. Accordingly, TSLP caused mechanical allodynia through T cells in the DRG. CONCLUSION: This study demonstrated that TSLP is causally involved in the development of neuropathic pain through T cell recruitment.

An alternative method to evaluate lumbar interbody fusion status focusing on position change of screw-rod constructs.

OBJECTIVES: The evaluation of lumbar interbody fusion status is generally subjective and may differ among raters. The authors examined whether the assessment of position change of screw-rod constructs could be an alternative method for the evaluation of fusion status. METHODS: Sixty-three patients undergoing lumbar interbody single-level fusion were retrospectively reviewed. Three-dimensional images of screw-rod constructs were created from baseline CT examination on the day after surgery and follow-up CT examinations (3-5 months, 6-11 months, and ≥ 12 months) and superposed, with position change of screw-rod constructs being evaluated by the distance between the 3-dimensional images at baseline and follow-up. The evaluation was repeated twice to confirm the reproducibility. Fusion status on follow-up CT examinations was assessed by three raters, where inter-rater reliability was evaluated with Fleiss' kappa. The results of the fusion status were classified into fusion and incomplete fusion groups in each timing of follow-up CT examinations, where the amount of position change was compared between the two groups. RESULTS: The evaluation of position change was completely reproducible. The Fleiss' kappa (agreements) was 0.481 (69.4%). The medians of the amount of position change in fusion and incomplete fusion groups were 0.134 mm and 0.158 mm at 3-5 months (p = 0.21), 0.160 mm and 0.190 mm at 6-11 months (p = 0.02), and 0.156 mm and 0.314 mm at ≥ 12 months (p = 0.004). CONCLUSIONS: The assessment of position change of screw-rod constructs at 6 months or more after surgery can be an alternative method for evaluating lumbar interbody fusion status. KEY POINTS: • Lumbar interbody fusion status (satisfactory, incomplete, or failed) is associated with the quantification of position change of screw-rod in this study. • Reference values for the evaluation of position change in identifying interbody fusion status are provided. • Position change of screw-rod could be a supportive method for evaluating interbody fusion status.

Prognostic impact of respiratory dysfunction in elderly patients with cervical spinal cord injury and/or fractures: a multicenter survey.

PURPOSE: To investigate the impact of early post-injury respiratory dysfunction for neurological and ambulatory ability recovery in patients with cervical spinal cord injury (SCI) and/or fractures. METHODS: We included 1,353 elderly patients with SCI and/or fractures from 78 institutions in Japan. Patients who required early tracheostomy and ventilator management and those who developed respiratory complications were included in the respiratory dysfunction group, which was further classified into mild and severe respiratory groups based on respiratory weaning management. Patient characteristics, laboratory data, neurological impairment scale scores, complications at injury, and surgical treatment were evaluated. We performed a propensity score-matched analysis to compare neurological outcomes and mobility between groups. RESULTS: Overall, 104 patients (7.8%) had impaired respiratory function. In propensity score-matched analysis, the respiratory dysfunction group had a lower home discharge and ambulation rates (p = 0.018, p = 0.001, respectively), and higher rate of severe paralysis (p < 0.001) at discharge. At the final follow-up, the respiratory dysfunction group had a lower ambulation rate (p = 0.004) and higher rate of severe paralysis (p < 0.001). Twenty-six patients with severe disability required respiratory management for up to 6 months post-injury and died of respiratory complications. The mild and severe respiratory dysfunction groups had a high percentage of severe paraplegic cases with low ambulatory ability; there was no significant difference between them. The severe respiratory dysfunction group tended to have a poorer prognosis. CONCLUSION: Respiratory dysfunction in elderly patients with SCI and/or cervical fracture in the early post-injury period reflects the severity of the condition and may be a useful prognostic predictor.

Effect of posterior decompression with and without fixation on a kyphotic cervical spine with ossification of the posterior longitudinal ligament.

STUDY DESIGN: Biomechanical study. OBJECTIVE: Cervical ossification of the posterior longitudinal ligament (C-OPLL) causes myelopathy. Though posterior decompression for C-OPLL showed positive results, poor outcomes were seen in patients with a kyphotic alignment. Posterior decompression with fusion (PDF) tends to show better results compared to posterior decompression. The aim of this study is to evaluate the effects of the posterior procedures for C-OPLL. SETTING: Yamaguchi University. METHODS: Based on 3D finite element C2-C7 spine created from medical images and a spinal cord, the following compression models were created: the intact model, K-line 0 mm model, and K-line 2 mm model. These models were used to analyze the effects of posterior decompression with varied lengths of fixation. The stress of the spinal cord was calculated for intact, K-line 0 mm, and K-line 2 mm as preoperative models, and laminectomy (LN)-K-line 0 mm, PDF (C4-C5)-K-line 0 mm, PDF (C3-C6)-K-line 0 mm, LN-K-line 2 mm, PDF (C4-C5)-K-line 2 mm, and PDF (C3-C6)-K-line 2 mm model as operative models in a neutral, flexion, and extension. RESULTS: As the compression increased, stress on the spinal cord increased compared to the intact model. In the neutral, posterior decompression decreased the stress of the spinal cord. However, in flexion and extension, the stress on the spinal cord for LN-K-line 0 or 2 mm, PDF (C4-C5)-K-line 0 or 2 mm, and PDF (C3-C6)-K-line 0 or 2 mm models decreased by more than 40%, 43%, and 70% respectively compared to the K-line 0 or 2 mm model. CONCLUSIONS: In kyphotic C-OPLL, it is essential to control intervertebral mobility in the posterior approach.

Hemodynamic differences of posterior communicating artery aneurysms between adult and fetal types of posterior cerebral artery.

BACKGROUND: The recanalization of posterior communicating artery (PCoA) aneurysms after endovascular treatment has been analyzed by various factors. However, the differences between adult and fetal types of posterior cerebral artery (PCA) have not been fully investigated. The main aim of this study was to investigate hemodynamic differences of PCoA aneurysms between adult and fetal types using computational fluid dynamics (CFD). METHODS: Fifty-five PCoA aneurysms were evaluated by 3D CT angiography and divided into unruptured aneurysms with adult-type or fetal-type PCAs (19 cases, UA group; 9 cases, UF group) and ruptured aneurysms with adult-type or fetal-type PCAs (17 cases, RA group; 10 cases, RF group). These native aneurysms were analyzed by CFD regarding morphological and hemodynamic characteristics. To evaluate simulated endovascular treatment of aneurysms, CFD was performed using porous media modeling. RESULTS: Morphologically, the RA group had significantly smaller parent artery diameter (2.91 mm vs. 3.49 mm, p=0.005) and higher size ratio (2.54 vs. 1.78, p=0.023) than the RF group. CFD revealed that the UA group had significantly lower oscillatory shear index (OSI) (0.0032 vs. 0.0078, p=0.004) than the UF group and that the RA group had lower WSS (3.09 vs. 11.10, p=0.001) and higher OSI (0.014 vs. 0.006, p=0.031) than the RF group, while the RF group presented significantly higher intra-aneurysmal flow velocity (0.19 m/s vs. 0.061 m/s, p=0.002) than the RA group. Porous media modeling of simulated treatment revealed higher residual flow volume in the fetal-type groups. CONCLUSIONS: These results suggested that PCoA aneurysms with fetal-type PCAs had different morphological features and hemodynamic characteristics compared with those with adult-type PCAs, leading to high risks of recanalization.

Factors associated with improvement in tibialis anterior weakness due to lumbar degenerative disease.

BACKGROUND: The weakness of the tibialis anterior remains to be a controversial topic. There has been no study that used electrophysiological assessment of the function of the lumbar and sacral peripheral motor nerves. The aim is to evaluate surgical outcomes in patients with weakness of the tibialis anterior using neurological and electrophysiological assessments. METHODS: We enrolled 53 patients. Tibialis anterior weakness was quantified by muscle strength, as assessed using a manual muscle test on a scale of 1 through 5, with scores <5 indicating weakness. Postoperative improvement in muscle strength was classified as excellent (5 grades recovered), good (more than one grade recovered), or fair (less than one grade recovered). RESULTS: Surgical outcomes for tibialis anterior function were categorized as "excellent" in 31, "good" in 8, "fair" in 14 patients. Significant difference in outcomes were observed depending on diabetes mellitus status, type of surgery, and the compound muscle action potentials amplitudes of the abductor hallucis and extensor digitorum brevis (p < 0.05). Surgical outcomes were classified into two groups, patients with excellent and good outcomes (Group 1) and patients with fair outcome (Group 2). Using the forward selection stepwise method, sex and the compound muscle action potentials amplitudes of the extensor digitorum brevis were identified as significant factors for their positive association with Group 1 status. The diagnostic power of the predicted probability was as high as 0.87 in terms of area under curve of the receiver operating characteristic curve. CONCLUSIONS: There was a significant correlation between the prognosis of tibialis anterior weakness and sex and the compound muscle action potentials amplitude of extensor digitorum brevis, suggesting that recording the compound muscle action potentials amplitude of extensor digitorum brevis will aid the outcome assessment of future surgical interventions for tibialis anterior weakness.

Worsening ambulation in elderly patients with cervical odontoid fractures: A nationwide multicenter study in Japan.

BACKGROUND: Despite the increasing prevalence of cervical odontoid fractures in older adults, the treatment strategy is controversial. The objectives of the current study are to investigate the prognosis and complications of cervical odontoid fractures in elderly patients and to identify factors associated with worsening of ambulation after 6 months. METHODS: This multicenter, retrospective study included 167 patients aged 65 years or older with odontoid fractures. Patient demographic and treatment data were investigated and compared according to the treatment strategy. To determine associations with worsening ambulation after 6 months, we focused on the treatment strategies (nonsurgical treatment [collar immobilization or halo vest], conversion to surgery, or initial surgery) and patients' background. RESULTS: Patients who received nonsurgical treatment were significantly older, and patients who underwent surgery had more Anderson-D'Alonzo type 2 fractures. Of the patients initially treated nonsurgically, 26% later underwent surgery. Numbers of complications, including death, and degrees of ambulation after 6 months did not differ significantly among treatment strategies. Patients who had worsened ambulation after 6 months were significantly more likely to be older than 80 years, to have needed assistance with walking before injury, and to have cerebrovascular disease. Multivariable analysis showed that a score of ≥2 on the 5-item modified frailty index (mFI-5) was significantly associated with worsening ambulation. CONCLUSIONS: Preinjury mFI-5 scores of ≥2 were significantly associated with worsening ambulation 6 months after treatment of cervical odontoid fractures in older adults.

Current Concepts of Biomaterial Scaffolds and Regenerative Therapy for Spinal Cord Injury.

Spinal cord injury (SCI) is a catastrophic condition associated with significant neurological deficit and social and financial burdens. It is currently being managed symptomatically, with no real therapeutic strategies available. In recent years, a number of innovative regenerative strategies have emerged and have been continuously investigated in preclinical research and clinical trials. In the near future, several more are expected to come down the translational pipeline. Among ongoing and completed trials are those reporting the use of biomaterial scaffolds. The advancements in biomaterial technology, combined with stem cell therapy or other regenerative therapy, can now accelerate the progress of promising novel therapeutic strategies from bench to bedside. Various types of approaches to regeneration therapy for SCI have been combined with the use of supportive biomaterial scaffolds as a drug and cell delivery system to facilitate favorable cell-material interactions and the supportive effect of neuroprotection. In this review, we summarize some of the most recent insights of preclinical and clinical studies using biomaterial scaffolds in regenerative therapy for SCI and summarized the biomaterial strategies for treatment with simplified results data. One hundred and sixty-eight articles were selected in the present review, in which we focused on biomaterial scaffolds. We conducted our search of articles using PubMed and Medline, a medical database. We used a combination of "Spinal cord injury" and ["Biomaterial", or "Scaffold"] as search terms and searched articles published up until 30 April 2022. Successful future therapies will require these biomaterial scaffolds and other synergistic approaches to address the persistent barriers to regeneration, including glial scarring, the loss of a structural framework, and biocompatibility. This database could serve as a benchmark to progress in future clinical trials for SCI using biomaterial scaffolds.

Inflammatory Skin Disease Causes Anxiety Symptoms Leading to an Irreversible Course.

Intense itching significantly reduces the quality of life, and atopic dermatitis is associated with psychiatric conditions, such as anxiety and depression. Psoriasis, another inflammatory skin disease, is often complicated by psychiatric symptoms, including depression; however, the pathogenesis of these mediating factors is poorly understood. This study used a spontaneous dermatitis mouse model (KCASP1Tg) and evaluated the psychiatric symptoms. We also used Janus kinase (JAK) inhibitors to manage the behaviors. Gene expression analysis and RT-PCR of the cerebral cortex of KCASP1Tg and wild-type (WT) mice were performed to examine differences in mRNA expression. KCASP1Tg mice had lower activity, higher anxiety-like behavior, and abnormal behavior. The mRNA expression of S100a8 and Lipocalin 2 (Lcn2) in the brain regions was higher in KCASP1Tg mice. Furthermore, IL-1ß stimulation increased Lcn2 mRNA expression in astrocyte cultures. KCASP1Tg mice had predominantly elevated plasma Lcn2 compared to WT mice, which improved with JAK inhibition, but behavioral abnormalities in KCASP1Tg mice did not improve, despite JAK inhibition. In summary, our data revealed that Lcn2 is closely associated with anxiety symptoms, but the anxiety and depression symptoms caused by chronic skin inflammation may be irreversible. This study demonstrated that active control of skin inflammation is essential for preventing anxiety.

Influence of nervous tendencies on oral health status and lifestyle habits.

OBJECTIVE: It is presumed that people with nervous tendencies brush their teeth for long durations, and, we aimed to investigate how nervous tendencies affect oral health status and lifestyle habits. SUBJECTS AND METHODS: Three hundred and sixty patients who visited the Senri Dental Clinic, affiliated with the Sunstar Foundation, and were being treated for periodontal diseases between 11 January 2017 and 10 April 2017 were enrolled. A total of 323 respondents (101 men and 222 women) were considered eligible. Nervous tendencies were investigated using the Fujinami neurotic index (FNI) and its derivative, the neurotic index (NI). Patients with NIs of ≥20 were included in the 'needs caution' group, whereas those with NIs of <19 comprised the 'healthy' group. The plaque score; periodontal pocket depth; bleeding on probing degree; gingival recession; crevice defects; oral conditions, such as cervical fillings and lifestyle habits were compared between the groups. RESULTS AND DISCUSSION: No statistically significant differences in oral status were observed between the groups. On the other hand, the needs caution group had significantly longer brushing durations and lower usage of auxiliary teeth cleaning tools than the healthy group. Sleep duration was significantly shorter in the needs caution group than in the healthy group. CONCLUSIONS: Patients with strong nervous tendencies had long oral brushing durations and low usage of auxiliary cleaning tools. However, these factors did not negatively affect oral health status. These results could aid in understanding patients with strong nervous tendencies and in developing appropriate dental health guidance measures.

Should the Supraclavicular Lymph Nodes be Considered Regional Lymph Nodes in Cervical Esophageal Cancer?

BACKGROUND: The importance of supraclavicular lymph node (SCLN) metastases in esophageal cancer (EC) remains unknown. Few studies have reported on the prognostic impact of SCLN metastases on patients with cervical EC (CEC). This study aimed to investigate whether SCLNs should be considered regional lymph nodes and be dissected in patients with CEC. METHODS: This retrospective study enrolled 835 consecutive patients who underwent radical esophagectomy. Of these patients, 67 underwent radical surgery for CEC. These 67 patients were divided into three groups based on the presence of lymph node metastases with or without metastatic SCLNs or the absence of lymph node metastases. RESULTS: Of the 67 patients, 23 (34.3%) did not have metastatic lymph nodes (pN-negative group), 27 (40.3%) had metastatic lymph nodes except for metastatic SCLNs (pN-positive group without metastatic SCLN), and 17 (25.4%) had metastatic lymph nodes including metastatic SCLNs (pN-positive group with metastatic SCLNs). The 5-year overall survival rate was 58.4% for the pN-negative group, 46.2% for the pN-positive group without metastatic SCLNs, and 7.8% for the pN-positive group with metastatic SCLNs. The pN-positive group with metastatic SCLNs tended to show residual tumor cells and complications after surgery. The presence of metastatic SCLNs was a significantly poor prognostic factor (p = 0.004). The efficacy index was lowest for the lymph nodes in the supraclavicular region. CONCLUSIONS: The prognosis of the CEC patients with metastatic SCLNs was dismal. Although the cervical esophagus is located adjacent to the SCLNs, the SCLNs may be considered extra-regional lymph nodes in patients with CEC.