Association between Stimulation-Site Pain and Clinical Improvement during Repetitive Transcranial Magnetic Stimulation for Patients with Major Depressive Disorders: A Prospective Observational Study at Two Sites.

INTRODUCTION: The clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD) in Japan has not been adequately investigated. Furthermore, the relationship between stimulation-site pain and the antidepressant effects of rTMS has not been thoroughly examined. Therefore, this study aimed to clarify (1) the real-world efficacy and safety of rTMS for TRD in Japan and (2) the relationship between stimulation-site pain and clinical improvement of depressive symptoms. METHODS: We conducted a retrospective observational study involving 50 right-handed patients with TRD. All patients received high-frequency rTMS for up to 6 weeks. Depressive symptoms were assessed using the Montgomery-Åsberg depression rating scale (MADRS). Pain at the stimulation site was reported by the patients using a visual analog scale (VAS) after each session. Remission and response rates at 3 and 6 weeks were calculated based on the MADRS scores. The correlation between changes in the MADRS and VAS scores was examined. RESULTS: Remission and response rates were 36% and 46%, respectively, at the end of 3 weeks, and 60% and 70%, respectively, at 6 weeks. At the end of the treatment, there was significant correlation between the reduction of MADRS and VAS scores (r = 0.42, p = 0.003). CONCLUSION: This study demonstrates the clinical efficacy of rTMS in Japan and the correlation between its antidepressant effects and stimulation-site pain.

Theta burst stimulation for depression: a systematic review and network and pairwise meta-analysis.

In clinical practice, theta burst stimulation (TBS) presents as a more efficient and potentially more effective therapeutic modality than conventional repetitive transcranial magnetic stimulation (rTMS), as it allows for the delivery of more stimuli in less time and at similar intensities. To date, accelerated treatment plans according to various continuous (cTBS) and intermittent TBS (iTBS) protocols for depression have been proposed. To investigate which of the TBS protocols provided a favorable risk-benefit balance for individuals with depression, this systematic review and random-effects model network meta-analysis was conducted. The study outcomes included response rate (primary), depression symptom improvement, remission rate, all-cause discontinuation rate, incidence of switch to mania, and incidence of headache/discomfort at treatment site. In this meta-analysis, a total of 23 randomized controlled trials (n = 960, mean age = 41.88 years, with 60.78% females) were included. Approximately 69.57% of the trials included individuals with an exclusive diagnosis of major depressive disorder. The following six TBS protocols (target) were evaluated: cTBS (right-dorsolateral prefrontal cortex [R-DLPFC]), cTBS (R-DLPFC) + iTBS (left-DLPFC [L-DLPFC]), iTBS (L-DLPFC), iTBS (L-DLPFC) + iTBS (R-DLPFC), iTBS (left-dorsomedial prefrontal cortex) + iTBS (right-dorsomedial prefrontal cortex), and iTBS (occipital lobe). Compared to sham, cTBS (R-DLPFC) + iTBS (L-DLPFC), iTBS (L-DLPFC), and iTBS (occipital lobe) had a higher response rate (k = 23); cTBS (R-DLPFC) + iTBS (L-DLPFC) and iTBS (L-DLPFC) dominated in the depression symptom improvement (k = 23); and iTBS (L-DLPFC) had a higher remission rate (k = 15). No significant differences were found for all-cause discontinuation rate (k = 17), incidence of switch to mania (k = 7), and incidence of headache/discomfort at treatment site (k = 10) between any TBS protocols and sham. Thus, cTBS (R-DLPFC) + iTBS (L-DLPFC) and iTBS (L-DLPFC) demonstrate favorable risk-benefit balance for the treatment of depression.

Newer antidepressant for Japanese adults with major depressive disorder: A systematic review and meta-analysis.

INTRODUCTION: The question remains to be elucidated: "Is treatment with antidepressants at doses approved in Japan effective for Japanese patients with MDD?" It is crucial to confirm this in order to provide appropriate treatments for Japanese patients with major depressive disorder (MDD). Therefore, we conducted a systematic review and random-effects pairwise meta-analysis including these nine double-blind, randomized, placebo-controlled trials. METHODS: We calculated the standardized mean difference (SMD) and risk ratio (RR) with a 95% confidence interval (95% CI). RESULTS: Pooled newer antidepressants outperformed placebo regarding improvement of depressive symptom scale scores [SMD (95% CI) = -0.20 (-0.27, -0.12), p < 0.00001], response to treatment [RR (95% CI) = 1.23 (1.13, 1.32), p < 0.00001], and remission rate [RR (95% CI) = 1.30 (1.16, 1.45), p < 0.00001]. Although all-cause discontinuation was not significantly different between the treatment groups, the pooled antidepressant group showed a higher discontinuation rate due to adverse event [RR (95% CI) = 1.60 (1.13, 2.26), p = 0.007] and a higher incidence of at least one adverse event than the placebo group [RR (95% CI) = 1.13 (1.08, 1.18), p < 0.00001]. DISCUSSION: We concluded that newer antidepressants are effective for Japanese adults with MDD although the clinicians must monitor the health conditions of these individuals.

A self-management system for preventing hyperglycemia through blood glucose level prediction and nudge-based food amount reduction.

In recent years, the number of diabetic patients has been increasing rapidly all over the world. Diabetes cannot be completely cured once it develops, so it is important to prevent diabetes before it develops. To prevent the onset of diabetes, it is necessary to avoid prolonged hyperglycemia after meals. In this paper, we propose a self-management system to help users prevent diabetes. The system monitors blood glucose levels in real time, calculates foods to be reduced taking into account the user's preferences, and presents them to the user as soon as the system predicts that the planned diet will cause high blood glucose. We designed and conducted two experiments to show the effectiveness of the proposed system. Experiment 1 was to construct and evaluate a model for predicting blood glucose levels two hours later. Experiment 2 was to evaluate the degree of satisfaction with the food and recommendations, and the acceptability of the recommendations by participants who actually used the proposed system. The results of Experiment 1 showed that the constructed model was able to predict blood glucose levels with an RMSE of 7.66 and MAE of 4.66. As a result of Experiment 2, we found the recommended intake was more acceptable if it reflected the user's preferences.

Circadian oscillation in primary cilium length by clock genes regulates fibroblast cell migration.

Various mammalian cells have autonomous cellular clocks that are produced by the transcriptional cycle of clock genes. Cellular clocks provide circadian rhythms for cellular functions via transcriptional and cytoskeletal regulation. The vast majority of mammalian cells possess a primary cilium, an organelle protruding from the cell surface. Here, we investigated the little-known relationship between circadian rhythm and primary cilia. The length and number of primary cilia showed circadian dynamics both in vitro and in vivo. The circadian rhythm of primary cilium length was abolished by SR9011 and Bmal1 knockout. A centrosomal protein, pericentrin, transiently accumulates in centriolar satellites, the base of primary cilia at the shortest cilia phase, and induces elongation of primary cilia at the longest cilia phase in the circadian rhythm of primary cilia. In addition, rhythmic cell migration during wound healing depends on the length of primary cilia and affects the rate of wound healing. Our findings demonstrate that the circadian dynamics of primary cilium length by clock genes control fibroblast migration and could provide new insights into chronobiology.

Intermittent theta burst stimulation vs. high-frequency repetitive transcranial magnetic stimulation for major depressive disorder: A systematic review and meta-analysis.

Our meta-analysis demonstrated that intermittent theta burst stimulation (iTBS)/bilateral-TBS (Bi-TBS) and high-frequency repetitive transcranial magnetic stimulation (HF-rTMS)/bilateral-rTMS (Bi-rTMS) had similar efficacy, acceptability, and safety profiles for antidepressant treatment-resistant major depressive disorder (AD-TRD). In our sensitivity analysis that excluded a study that compared Bi-TBS with Bi-rTMS for older adults, all efficacy outcomes were also comparable between iTBS and HF-rTMS. Because iTBS does not require higher stimulation intensity and a longer stimulus time than conventional HF-rTMS protocols, we speculated that for those with AD-TRD, iTBS/Bi-TBS is a more helpful therapeutic modality in clinical practice than HF-rTMS/Bi-rTMS.

Movement recognition via channel-activation-wise sEMG attention.

CONTEXT: Surface electromyography (sEMG) signals contain rich information recorded from muscle movements and therefore reflect the user's intention. sEMG has seen dominant applications in rehabilitation, clinical diagnosis as well as human engineering, etc. However, current feature extraction methods for sEMG signals have been seriously limited by their stochasticity, transiency, and non-stationarity. OBJECTIVE: Our objective is to combat the difficulties induced by the aforementioned downsides of sEMG and thereby extract representative features for various downstream movement recognition. METHOD: We propose a novel 3-axis view of sEMG features composed of temporal, spatial, and channel-wise summary. We leverage the state-of-the-art architecture Transformer to enforce efficient parallel search and to get rid of limitations imposed by previous work in gesture classification. The transformer model is designed on top of an attention-based module, which allows for the extraction of global contextual relevance among channels and the use of this relevance for sEMG recognition. RESULTS: We compared the proposed method against existing methods on two Ninapro datasets consisting of data from both healthy people and amputees. Experimental results show the proposed method attains the state-of-the-art (SOTA) accuracy on both datasets. We further show that the proposed method enjoys strong generalization ability: a new SOTA is achieved by pretraining the model on a different dataset followed by fine-tuning it on the target dataset.

Development of Machine Learning-Based Web System for Estimating Pleural Effusion Using Multi-Frequency Bioelectrical Impedance Analyses.

BACKGROUND: Transthoracic impedance values have not been widely used to measure extravascular pulmonary water content due to accuracy and complexity concerns. Our aim was to develop a foundational model for a novel system aiming to non-invasively estimate the intrathoracic condition of heart failure patients. METHODS: We employed multi-frequency bioelectrical impedance analysis to simultaneously measure multiple frequencies, collecting electrical, physical, and hematological data from 63 hospitalized heart failure patients and 82 healthy volunteers. Measurements were taken upon admission and after treatment, and longitudinal analysis was conducted. RESULTS: Using a light gradient boosting machine, and a decision tree-based machine learning method, we developed an intrathoracic estimation model based on electrical measurements and clinical findings. Out of the 286 features collected, the model utilized 16 features. Notably, the developed model demonstrated high accuracy in discriminating patients with pleural effusion, achieving an area under the receiver characteristic curves (AUC) of 0.905 (95% CI: 0.870-0.940, p < 0.0001) in the cross-validation test. The accuracy significantly outperformed the conventional frequency-based method with an AUC of 0.740 (95% CI: 0.688-0.792, and p < 0.0001). CONCLUSIONS: Our findings indicate the potential of machine learning and transthoracic impedance measurements for estimating pleural effusion. By incorporating noninvasive and easily obtainable clinical and laboratory findings, this approach offers an effective means of assessing intrathoracic conditions.

Genomic adaptive potential to cold environments in the invasive red swamp crayfish.

Biological invasion refers to the introduction, spread, and establishment of non-native species in a novel habitat. The ways in which invasive species successfully colonize new and different environments remain a fundamental topic of research in ecology and evolutionary biology. Here, we investigated the genomic and transcriptomic characteristics of the red swamp crayfish (Procambarus clarkii), a widespread invader in freshwater environments. Targeting a recently colonized population in Sapporo, Japan that appears to have acquired a high degree of cold tolerance, RNA-seq analysis revealed differentially expressed genes in response to cold exposure, and those involved in protease inhibitors and cuticle development were considered top candidates. We also found remarkable duplications for these gene families during evolution and their concerted expression patterns, suggesting functional amplification against low temperatures. Our study thus provides clues to the unique genetic characteristics of P. clarkii, possibly related to cold adaptation.

Maintenance repetitive transcranial magnetic stimulation (rTMS) therapy for treatment-resistant depression: a study protocol of a multisite, prospective, non-randomized longitudinal study.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a widely used treatment for major depressive disorder (MDD), and its effectiveness in preventing relapse/recurrence of MDD has been explored. Although few small sample controlled studies exist, the protocols of maintenance rTMS therapy were heterogeneous and evidence of its effectiveness is not sufficient. Thus, this study aims to evaluate whether maintenance rTMS is effective in maintaining the treatment response in patients with MDD with a large sample size and feasible study design. METHODS: In this multicenter open-labelled parallel-group trial we plan to recruit 300 patients with MDD who have responded or remitted to acute rTMS therapy. Participants would be classified into two groups according to their preference; the maintenance rTMS and pharmacotherapy group, and the pharmacotherapy only group. The protocol of maintenance rTMS therapy is once a week for the first six months and once biweekly for the second six months. The primary outcome is the relapse/recurrence rates during 12 months following enrollment. Other measures of depressive symptoms and recurrence/relapse rates at different time points are the secondary outcomes. The primary analysis is the between-group comparison adjusted for background factors using a logistic regression model. We will perform the group comparison with inverse probability of treatment weighting as the sensitivity analysis to ensure the comparability of the two groups. DISCUSSION: We hypothesize that maintenance rTMS therapy could be an effective and safe treatment for preventing depressive relapse/recurrence. Considering the limitation of potential bias owing to the study design, we plan to use statistical approaches and external data to avoid overestimation of the efficacy. TRIAL REGISTRATION: Japan Registry of Clinical Trials, ID: jRCT1032220048 . Registered 1 May 2022.

Effectiveness of medical fee revisions for psychotropic polypharmacy in patients with mood disorders in Japan: An interrupted time-series analysis using a nationwide inpatient database.

BACKGROUND: This study aimed to evaluate the effects of medical fee revisions aimed to reduce psychotropic polypharmacy in Japan on the proportion of psychotropic polypharmacy in discharge prescriptions for patients with major depressive disorder (MDD) or bipolar disorder (BD) using a nationwide inpatient database. METHODS: In this retrospective cohort study, we used the Diagnosis Procedure Combination database to identify patients with MDD or BD discharged between April 2012 and March 2021. We targeted medical fee revisions in October 2014, April 2016, and April 2018. The major outcome was the monthly proportion of psychotropic polypharmacy in prescription at discharge using the criteria following the April 2018 revision (antidepressants ≥3, antipsychotics ≥3, anxiolytics ≥3, hypnotics ≥3, or sum of anxiolytics and hypnotics ≥4). We performed interrupted time series analyses to evaluate the changes in level and trend between pre- and post-revisions. RESULTS: We identified 63,289 and 33,780 patients with MDD and BD respectively in the entire study period. In both the patient groups, there were significant decreases in the proportion of psychotropic polypharmacy at revision in October 2014, and no significant trend and level change at revision were observed in April 2016 and April 2018, with a few exceptions. CONCLUSIONS: The medical fee revisions aimed to reduce psychotropic polypharmacy in Japan might have had a limited impact on discharge prescriptions for patients with MDD and BD.

Transvenous embolization of the direct carotid-cavernous fistula via the pterygoid plexus: illustrative case.

BACKGROUND: Endovascular treatment is the mainstay of treatment for carotid-cavernous fistulas, but endovascular approaches vary widely. The authors report a rare case of a direct carotid-cavernous fistula with cranial nerve symptoms caused by rupture of a giant aneurysm in which selective transvenous embolization via the pterygoid plexus was performed. OBSERVATIONS: An 81-year-old man presented with headache and various progressive cranial nerve symptoms due to a direct carotid-cavernous fistula caused by a ruptured giant aneurysm. All the draining veins visualized on preoperative examination immediately before the treatment were occluded except for the pterygoid plexus. Therefore, the authors chose the dilated pterygoid plexus to approach the shunted pouch at the cavernous sinus and achieve shunt obliteration by selective embolization with coils and n-butyl cyanoacrylate. LESSONS: Careful study of the three-dimensional rotational images in the preoperative examination is important when considering the various approaches to surgery. The pterygoid plexus can be an effective venous approach route to reach the cavernous sinus area.

A Case of Radiation-Induced Osteosarcoma with RB1 Gene Alteration Treated by Skull Base Surgery and Craniofacial Reconstruction.

A 35-year-old female presented with headache, photophobia and developed sudden loss of vision after having undergone right-side ophthalmectomy and radiochemotherapy for retinoblastoma in infancy. A neoplastic lesion was found in the left middle cranial fossa and was surgically removed. The diagnosis was radiation-induced osteosarcoma with RB1 gene alteration. Although she received chemotherapy for the residual tumor, it progressed 17 months later. Maximal surgical resection with craniofacial reconstruction was required. We utilized two three-dimensional models for surgical planning. She was discharged without neurological deficits other than loss of light perception subsequent to left ophthalmectomy. In cases where retinoblastoma is treated with radiotherapy, long-term follow-up is necessary to monitor for radiation-induced tumor development.

Antidepressants for the treatment of adults with major depressive disorder in the maintenance phase: a systematic review and network meta-analysis.

A systematic review and random-effects model network meta-analysis were conducted to compare the efficacy, acceptability, tolerability, and safety of antidepressants to treat adults with major depressive disorder (MDD) in the maintenance phase. This study searched the PubMed, Cochrane Library, and Embase databases and included only double-blind, randomized, placebo-controlled trials with an enrichment design: patients were stabilized on the antidepressant of interest during the open-label study and then randomized to receive the same antidepressant or placebo. The outcomes were the 6-month relapse rate (primary outcome, efficacy), all-cause discontinuation (acceptability), discontinuation due to adverse events (tolerability), and the incidence of individual adverse events. The risk ratio with a 95% credible interval was calculated. The meta-analysis comprised 34 studies (n = 9384, mean age = 43.80 years, and %females = 68.10%) on 20 antidepressants (agomelatine, amitriptyline, bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, tianeptine, venlafaxine, vilazodone, and vortioxetine) and a placebo. In terms of the 6-month relapse rate, amitriptyline, citalopram, desvenlafaxine, duloxetine, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, tianeptine, venlafaxine, and vortioxetine outperformed placebo. Compared to placebo, desvenlafaxine, paroxetine, sertraline, venlafaxine, and vortioxetine had lower all-cause discontinuation; however, sertraline had a higher discontinuation rate due to adverse events. Compared to placebo, venlafaxine was associated with a lower incidence of dizziness, while desvenlafaxine, sertraline, and vortioxetine were associated with a higher incidence of nausea/vomiting. In conclusion, desvenlafaxine, paroxetine, venlafaxine, and vortioxetine had reasonable efficacy, acceptability, and tolerability in the treatment of adults with stable MDD.