Increased nerve growth factor expression in the synovial tissues of patients with rotator cuff tears

BACKGROUND: Rotator cuff tears (RCTs) are often associated with severe shoulder pain. Non-steroidal anti-inflammatory drugs, not recommended for long-term use, do not effectively manage RCT-induced pain, resulting in reduced quality of life. To improve management, a better understanding of the fundamental properties of RCT pain is needed. Here, we aimed to compare the expression levels of nerve growth factor (NGF) and cyclooxygenase-2 (COX-2) mRNA in the synovial tissues of patients with RCT-induced pain and patients with non-painful recurrent shoulder dislocation (RSD). METHODS: The study included 32 patients with RCT who underwent arthroscopic rotator cuff repair and 28 patients with non-painful RSD who underwent arthroscopic Bankart repair. Synovial tissue samples were harvested from subacromial bursa and rotator interval of RCT patients and from the rotator interval of RSD patients. Samples were analyzed quantitatively expression levels for NGF and COX2 mRNA and NGF protein. RESULTS: NGF mRNA and protein levels were significantly higher in the rotator interval of RCT patients than in the rotator interval of RSD patients (p = 0.0017, p = 0.012, respectively), while COX2 mRNA levels did not differ significantly between the two patient groups. In RCT patients, COX2 mRNA was more highly expressed in the rotator interval than in the subacromial bursa (p = 0.038), whereas the mRNA and protein levels of NGF did not differ between the two tissues. The expression of NGF mRNA in the synovium of the rotator interval was significantly correlated with the numeric rating scale of pain (ρ = 0.38, p = 0.004). CONCLUSION: NGF mRNA and protein levels were elevated in patients with painful RCT compared with those in patients with non-painful RSD, whereas COX-2 levels were comparable in the two patient groups. These findings provide insights into novel potential strategies for clinical management of RCT

Syntactic Comprehension in Patients with Amyotrophic Lateral Sclerosis

Recent neuropsychological studies of patients with amyotrophic lateral sclerosis (ALS) have demonstrated that some patients have aphasic symptoms, including impaired syntactic comprehension. However, it is not known if syntactic comprehension disorder is related to executive and visuospatial dysfunction. In this study, we evaluated syntactic comprehension using the Syntax Test for Aphasia (STA) auditory comprehension task, frontal executive function using the Frontal Assessment Battery (FAB), visuospatial function using Raven’s Coloured Progressive Matrices (RCPM), and dementia using the Hasegawa Dementia Scale-Revised (HDS-R) in 25 patients with ALS. Of the 25 patients, 18 (72%) had syntactic comprehension disorder (STA score < IV), nine (36%) had frontal executive dysfunction (FAB score < 14), six (24%) had visuospatial dysfunction (RCPM score < 24), and none had dementia (HDS-R score < 20). Nine of the 18 patients with syntactic comprehension disorder (50%) passed the FAB and RCPM. Although sample size was small, these patients had a low STA score but normal FAB and RCPM score. All patients with bulbar onset ALS had syntactic comprehension disorder. These results indicate that it might be necessary to assess syntactic comprehension in patients with bulbar onset ALS. The implications of these findings are discussed in relation to the pathological continuum of ALS

Motor cortex-evoked activity in reciprocal muscles is modulated by reward probability.

Horizontal intracortical projections for agonist and antagonist muscles exist in the primary motor cortex (M1), and reward may induce a reinforcement of transmission efficiency of intracortical circuits. We investigated reward-induced change in M1 excitability for agonist and antagonist muscles. Participants were 8 healthy volunteers. Probabilistic reward tasks comprised 3 conditions of 30 trials each: 30 trials contained 10% reward, 30 trials contained 50% reward, and 30 trials contained 90% reward. Each trial began with a cue (red fixation cross), followed by blue circle for 1 s. The subjects were instructed to perform wrist flexion and press a button with the dorsal aspect of middle finger phalanx as quickly as possible in response to disappearance of the blue circle without looking at their hand or the button. Two seconds after the button press, reward/non-reward stimulus was randomly presented for 2-s duration. The reward stimulus was a picture of Japanese 10-yen coin, and each subject received monetary reward at the end of experiment. Subjects were not informed of the reward probabilities. We delivered transcranial magnetic stimulation of the left M1 at the midpoint between center of gravities of agonist flexor carpi radialis (FCR) and antagonist extensor carpi radialis (ECR) muscles at 2 s after the red fixation cross and 1 s after the reward/non-reward stimuli. Relative motor evoked potential (MEP) amplitudes at 2 s after the red fixation cross were significantly higher for 10% reward probability than for 90% reward probability, whereas relative MEP amplitudes at 1 s after reward/non-reward stimuli were significantly higher for 90% reward probability than for 10% and 50% reward probabilities. These results implied that reward could affect the horizontal intracortical projections in M1 for agonist and antagonist muscles, and M1 excitability including the reward-related circuit before and after reward stimulus could be differently altered by reward probability

Prediction of changes in functional ability of inpatients with schizophrenia using logarithmic and linear regression modelling

Background/Objective Few studies have addressed the type of time course regression that can predict changes in functional ability in inpatients with schizophrenia. This study investigated the possibility of predicting changes in functional ability by logarithmic and linear regression modelling when treating schizophrenia. Methods This longitudinal study included two analysis rounds. Analysis 1 comprised 40 inpatients (male/female: 16/24, mean age: 39.7 ± 13.5 years) for the identification of the time course of changes in functional ability based on the Activity Profile Scale for Patients with Psychiatric Disorders score from the group data. Analysis 2 comprised 17 inpatients (male/female: 9/8, mean age: 38.5 ± 9.4 years) to ensure correlation of the group data with the prediction of each individual’s degree of functional ability. Results In Analysis 1, Activity Profile Scale for Patients with Psychiatric Disorders score was assessed at the initial occupational therapy visit, one week and one month thereafter, and at discharge; logarithmic modelling using the scores at the initial visit, one month later and at discharge was more suitable (R 2  = .506, p  < .001) than the logarithmic and linear regression models using other score combinations. In Analysis 2, the individual’s predicted Activity Profile Scale for Patients with Psychiatric Disorders scores at discharge, as calculated by logarithmic modelling using scores from the initial visit and one month later, correlated moderately with actual Activity Profile Scale for Patients with Psychiatric Disorders scores (R 2  = .574, p  < .001; ICC = .747, p  < .001). Conclusion Logarithmic modelling based on Activity Profile Scale for Patients with Psychiatric Disorders score accurately predicted changes in the functional ability of inpatients with schizophrenia and is sufficiently uncomplicated to be adopted in daily clinical practice

Effect of renin–angiotensin system inhibitors in patients with cancer treated with anti-VEGF therapy

Background Cancer treatment with vascular endothelial growth factor signalling pathway (VSP) inhibitors frequently causes hypertension. Although previous reports suggested that the antihypertensive drug renin–angiotensin system inhibitor (RASI) may have a positive synergistic effect with VSP inhibitors, the actual impact on clinical outcomes is unknown.Objectives The study aims to clarify whether RASIs exhibit clinical benefits for patients with cancer with hypertension.Method From the Longevity Improvement and Fair Evidence Study database, comprising Japanese claims data between 2016 and 2020, we reviewed 2380 patients treated with VSP inhibitors who received antihypertensive treatment during cancer therapy. The patients were classified into two groups: with-RASI (n=883) and without-RASI (n=1497). In addition, 1803 of these patients treated for hypertension with RASI-only (n=707) or calcium channel blocker-only (n=1096) were also reviewed. The time-to-treatment failure (TTF), the interval from initiation of chemotherapy to its discontinuation, was applied as the primary endpoint.Results The median TTFs were 167 (60–382) days in the with-RASI group and 161 (63–377) days in the without-RASI group (p=0.587). All models, including Cox proportional hazard models and multiple propensity score models, did not reveal the superiority of with-RASI treatment. In the propensity score matching model, the HR for treatment with-RASI compared with that for without-RASI was 0.96 (95% CI 0.86 to 1.06, p=0.386). In addition, the TTFs of RASI-only were not superior to calcium channel blocker-only (p=0.584).Conclusions RASIs for hypertension do not benefit clinical outcomes during cancer therapy with VSP inhibitors. In addition, RASIs and calcium channel blockers have comparable clinical efficacy as first-line antihypertensive