Intrasellar chordoma masquerading as a pituitary neuroendocrine tumor: Illustrative case.

Background: Chordomas are rare, locally aggressive neoplasms recognized as derivatives of the notochord vestiges. These tumors typically involve the midline axial skeleton, and intracranial chordomas exhibit proclivity for the spheno-occipital region. However, purely intrasellar occurrences are extremely rare. We report a case of intrasellar chordoma, which masqueraded as a pituitary neuroendocrine tumor. Case Description: An 87-year-old female presented with an acutely altered mental state after a few-week course of headaches and decreased left vision. Adrenal insufficiency was evident, and magnetic resonance imaging revealed an intrasellar lesion with heterogeneous contrast enhancement and marked T2 hyperintensity. Central adrenal insufficiency due to an intrasellar lesion was suspected. Cortisol replacement was initiated, and transsphenoidal surgery was performed. Anterosuperior displacement of the normal pituitary gland and the absence of the bony dorsum sellae were notable during the procedure. Histological examination led to a diagnosis of conventional chordoma, and upfront adjuvant stereotactic radiosurgery was executed. She has been free from tumor progression for 12 months. Conclusion: This case and literature review suggested that the pathognomonic features of intrasellar chordoma were heterogeneous contrast enhancement, marked T2 hyperintensity, osteolytic destruction of the dorsum sellae, and anterosuperior displacement of the pituitary gland. Clinical outcomes seemed slightly worse than those of all skull base chordomas, which were the rationale for upfront radiosurgery in our case. Neurosurgeons should include intrasellar chordomas in the differential diagnosis of intrasellar lesions, carefully dissect them from the adjacent critical anatomical structures, and consider upfront radiosurgery to achieve optimal patient outcomes.

No effect of whole-hand water flow stimulation on skill acquisition and retention during sensorimotor adaptation.

Introduction: Repetitive somatosensory stimulation (RSS) is a conventional approach to modulate the neural states of both the primary somatosensory cortex (S1) and the primary motor cortex (M1). However, the impact of RSS on skill acquisition and retention in sensorimotor adaptation remains debated. This study aimed to investigate whether whole-hand water flow (WF), a unique RSS-induced M1 disinhibition, influences sensorimotor adaptation by examining the hypothesis that whole-hand WF leads to M1 disinhibition; thereby, enhancing motor memory retention. Methods: Sixty-eight young healthy participants were randomly allocated to three groups based on the preconditioning received before motor learning: control, whole-hand water immersion (WI), and whole-hand WF. The experimental protocol for all the participants spanned two consecutive days. On the initial day (day 1), baseline transcranial magnetic stimulation (TMS) assessments (T0) were executed before any preconditioning. Subsequently, each group underwent their respective 30 min preconditioning protocol. To ascertain the influence of each preconditioning on the excitability of the M1, subsequent TMS assessments were conducted (T1). Following this, all participants engaged in the motor learning (ML) of a visuomotor tracking task, wherein they were instructed to align a cursor with a target trajectory by modulating the pinch force. Upon completion of the ML session, final TMS assessments (T2) were conducted. All participants were required to perform the same motor learning 24 h later on day 2. Results: The results revealed that whole-hand WF did not significantly influence skill acquisition during sensorimotor adaptation, although it did reduce intracortical inhibition. This phenomenon is consistent with the idea that S1, rather than M1, is involved in skill acquisition during the early stages of sensorimotor adaptation. Moreover, memory retention 24 h after skill acquisition did not differ significantly across the three groups, challenging our initial hypothesis that whole-hand WF enhances memory retention throughout sensorimotor adaptation. This could be due to the inability of whole-hand WF to alter sensorimotor connectivity and integration, as well as the nature of the plastic response elicited by the preconditioning. Discussion: In conclusion, these findings suggest that although whole-hand WF attenuates intracortical inhibition, it does not modulate skill acquisition or motor memory retention during sensorimotor adaptation.

Digital cognitive-behavioural therapy application compared with zolpidem for the treatment of insomnia: protocol for an exploratory randomised controlled trial.

INTRODUCTION: Insomnia is a common health problem and cognitive-behavioural therapy (CBT) is recommended as a treatment. As there is a critical shortage of CBT-trained therapists, we developed a digital CBT application (IIIP MED: Sleepy Med) as Software as a Medical Device for insomnia. This paper describes the study protocol for an exploratory randomised controlled trial (RCT) to evaluate effectiveness and safety of our developed digital CBT (dCBT) for 5 weeks compared with zolpidem tartrate for patients with insomnia disorder. METHODS AND ANALYSIS: This proposed multicentre exploratory RCT will be conducted at the outpatient clinic of Chiba University Hospital, Akita University Hospital and Yoyogi Sleep Disorder Center, Japan. The study population comprises two parallel groups (dCBT and zolpidem) consisting of 15 participants each (n=30 in total) diagnosed with insomnia disorder who remain symptomatic at 4 weeks after sleep hygiene education. We will evaluate the effectiveness at baseline, week 5 (post-intervention) and week 10 (follow-up). The primary outcome will be the change of subjective sleep onset latency at week 5 from baseline. Secondary outcomes include sleep-related outcomes, such as objective sleep onset latency measured by mobile electroencephalography, functional improvement during the daytime and quality of life. ETHICS AND DISSEMINATION: Ethics approval was granted by the Institutional Review Board of Chiba University Hospital (K2023001). All participants will be required to provide written informed consent. Results will be published in international journals. TRIAL REGISTRATION NUMBER: jRCT2032230353.

Anti-IgLON5 disease as a differential diagnosis of multiple system atrophy.

INTRODUCTION: Anti-immunoglobulin-like cell adhesion molecule 5 (IgLON5) disease is a rare autoimmune encephalitis that can mimic progressive supranuclear palsy or corticobasal syndrome. Moreover, anti-IgLON5 disease can present with symptoms characteristic of multiple system atrophy (MSA), such as cerebellar ataxia and autonomic dysfunction. However, the clinical features of anti-IgLON5 disease resembling MSA have not been well established. METHODS: We enrolled 35 patients with suspected MSA for whom anti-IgLON5 antibody tests were requested. We evaluated immunoglobulin G (IgG) against IgLON5 using cell-based assays. We also summarized the clinical characteristics of patients who were positive for anti-IgLON5 antibodies. RESULTS: We identified serum and cerebrospinal fluid anti-IgLON5 antibodies in three patients. These patients had many clinical features characteristic of MSA, including parkinsonism, cerebellar ataxia, severe orthostatic hypotension, acute respiratory failure, sleep parasomnia, vocal cord paralysis, and pyramidal tract signs. Clinical features atypical for MSA were myorhythmia, horizontal eye movement restriction, fasciculations, and painful muscle cramps. CONCLUSION: Anti-IgLON5 disease may be an important differential diagnosis of MSA. A comprehensive physical examination, including assessments of eye movement, lower motor neuron signs, and atypical involuntary movements, is important to avoid misdiagnosis.

Classification and comparison of the physical characteristics and functions of various age groups of community-dwelling elderly individuals participating in the Kayoi-no-ba program.

[Purpose] To classify and compare the physical characteristics and functions of community-dwelling elderly individuals of various age groups participating in the Kayoi-no-ba program. [Participants and Methods] A total of 176 community-dwelling elderly individuals living in six cities and towns in the Niigata Prefecture who participated in the Kayoi-no-ba program between 2018 and 2020 were recruited in this study. Physical characteristics, such as strength, balance, and mobility, were assessed. [Results] Among elderly females and males who participated in the Kayoi-no-ba program, those >80 years of age showed shorter height, lighter weight, and lower body muscle mass than the other age groups. Strength, balance, and mobility functions, including grip strength, sit-to-stand test, single-leg-stand test, and timed up-and-go test, were significantly decreased, especially in patients aged >80 years. [Conclusion] Among community-dwelling elderly individuals participating in the Kayoi-no-ba program, physical characteristics and functions were affected by aging, with significant decline particularly in those aged >80 years old. These findings suggest that early intervention is necessary to maintain muscle mass, strength, balance, and mobility in the elderly.

Secondary-tail formation during stolonization in the Japanese green syllid, Megasyllis nipponica.

Benthic annelids belonging to the family Syllidae show a distinctive sexual reproduction mode called "stolonization," in which posterior segments are transformed into a reproductive individual-like unit called a "stolon." Megasyllis nipponica forms a stolon head and a secondary tail in the middle of the trunk before a stolon detaches, while, in the case of posterior amputation, posterior regeneration initiates at the wound after amputation. To understand the difference between posterior regeneration and secondary-tail formation during stolonization, detailed comparisons between the developmental processes of these two tail-formation types were performed in this study. Morphological and inner structural observations (i.e., cell proliferation and muscular/nervous development) showed that some processes of posterior regeneration, such as blastema formation and muscular/nervous regeneration at the amputation site, are missing during secondary-tail formation. In contrast, the secondary tail showed some unique features, such as the formation of ventrolateral half-tail buds that later fused in the middle and muscle/nerve branches formed before the detachment of the stolon. These novel features in the process of stolonization are suggested to be adaptive since the animals need to recover a posterior end quickly to stolonize again.

Jump height ingenerated by countermovement and arm swing better correlates with proagility shuttle run tests but not with change of direction deficits in collegiate female athletes.

BACKGROUND: Jumping and linear sprinting performances show a moderate correlation with change of direction (COD) ability. However, the extent of these correlations remains unknown through statistical analysis. Thus, this study statistically compared correlation coefficients between COD, COD deficit (CODD), and jumping and linear sprint performances. METHODS: National-level basketball (29) and baseball (18) intercollegiate female athletes performed 20-m linear sprint, proagility (5-10-5) test, squat jump (SJ), countermovement jump with (CMJarm) and without (CMJ) arm swing and modified reactive strength index (RSImod). Correlation analysis was used to assess factors correlated with COD performance and CODD; subsequently, correlation coefficient comparison test was used to determine better correlations with COD and CODD performance. RESULTS: CMJ (r=-0.483) and CMJarm (r=-0.446) had stronger correlations with 10-m COD (both, P<0.018) than with 10-m linear sprint (r=0.431, P=0.002). For 20-m COD, RSImod, CMJ, and CMJarm (r=-0.491--0.543, P<0.001) better correlated with 20-m COD than with 20-m linear sprints (r=0.436, P=0.002), while RSI (both r=-0.317, P<0.030) and SJ (r=-0.359, r=-0.293, P=0.046) were weakly correlated with 10- and 20-m COD. The differences in correlation coefficients for RSImod, CMJ, and CMJarm were not significant in both 10- and 20-m COD. Ten-meter linear sprint performance only correlated with 10-m CODD, while no correlation was observed with 20-m CODD. CONCLUSIONS: Stronger correlations of RSImod, CMJ, and CMJarm with 10-/20-m COD than with linear sprinting, RSI, and SJ suggest that training focused on improving countermovement and arm swings with jumping may enhance COD performance in female athletes.

Impact of the coronavirus disease 2019 pandemic on primary and metastatic lung cancer treatments in Japan: A nationwide study using an interrupted time series analysis.

BACKGROUND: The coronavirus disease 2019 pandemic prompted healthcare providers to use different approaches from the current standards of care. We aimed to identify the changes in the number of treatments for primary non-small cell lung cancer (NSCLC) and metastatic lung cancer during the pandemic. METHODS: We used nationwide insurance claims data from January 2015 to January 2021, and estimated changes in the number of treatments using an interrupted time series analysis. RESULTS: The number of surgical resections for primary NSCLC significantly decreased in April 2020 (-888; 95% confidence interval [CI]: -1530 to -246) and July 2020 (-1314; 95% CI: -1935 to -694), while the number of stereotactic body radiotherapies (SBRTs) increased in April 2020 (95; 95% CI: 8-182) and July 2020 (111; 95% CI: 24-198). The total number of treatments for primary NSCLC remained unchanged; however, non-significant decreases were observed in 2020. The number of surgical resections for metastatic lung cancer significantly decreased in April 2020 (-201; 95% CI: -337 to -65), but it eventually increased in July 2020 (170; 95% CI: 32-308). Additionally, the number of SBRTs significantly increased in April 2020 (37; 95% CI: 3-71) and October 2020 (57; 95% CI: 23-91). The total number of treatments for metastatic lung cancer was maintained, with an initial decrease in April 2020 followed by a subsequent increase in July and October 2020. CONCLUSION: In Japan, surgical triage for primary and metastatic lung cancer are likely to have been implemented during the pandemic. Despite these proactive measures, patients with primary NSCLC may have been untreated, likely owing to their undiagnosed disease, potentially leading to a deterioration in prognosis. By contrast, patients diagnosed with cancer prior to the pandemic are presumed to have received standard management throughout the course of the pandemic.

Impact of the COVID-19 pandemic on gastric surgery in Japan: A nationwide study using interrupted time-series analyses.

BACKGROUND AND AIM: Changes in the number of surgeries for gastric cancer during the coronavirus disease 2019 (COVID-19) pandemic have been reported, but data are insufficient to understand the impact at the national level. This study aimed to determine the impact of the COVID-19 pandemic on gastric surgery in Japan. METHODS: Insurance claims data registered from January 2015 to January 2021 were used. Changes in the number of endoscopic resections and gastrectomies for gastric cancer were estimated using an interrupted time-series analysis. RESULTS: The number of endoscopic resections significantly decreased in July 2020 (-1565; 95% confidence interval [CI]: -2022, -1108) and January 2021 (-539; 95% CI: -970, -109), and the number of laparoscopic surgeries significantly decreased in July 2020 (-795; 95% CI: -1097, -492), October 2020 (-313; 95% CI: -606, -19), and January 2021 (-507; 95% CI: -935, -78). Meanwhile, the number of open gastrectomies remained unchanged, and the number of robot-assisted gastrectomies steadily increased since their coverage by public health insurance in April 2018. CONCLUSIONS: The decreased number of endoscopic resections and laparoscopic surgeries in Japan suggests a decline in early-stage gastric cancer diagnosis, likely due to the suspension of gastric cancer screening and diagnostic testing during the pandemic. Meanwhile, the number of open and robot-assisted gastrectomies remained unchanged and increased, respectively, indicating that these applications were not affected by the pandemic-related medical crisis. These findings highlight that procedures for cancer diagnosis, including screening, should still be provided during pandemics.

A Study of the Associated Risk Factors for Early Failure and the Effect of Photofunctionalisation in Full-Arch Immediate Loading Treatment Based on the All-on-Four Concept.

Early implant failure occurring within 1 year after implantation has been attributed to various factors. Particularly, early failure can lead to challenges in maintaining a full-arch prosthetic device, necessitating prompt intervention, including reoperation. This study aimed to retrospectively examine implant- and patient-related factors and the effects of photofunctionalisation associated with early failure in patients who underwent treatment using the all-on-four concept in both the maxilla and mandible. We conducted this retrospective study comprising 561 patients with 2364 implants who underwent implant-supported immediate loading with fixed full-arch rehabilitation using the all-on-four concept. We aimed to assess the survival rate within 1 year after implantation and determine the risk factors influencing early failure. The 1-year survival rates after implantation were 97.1% (patient level) and 98.9% (implant level) for the maxilla and 98.5% (patient level) and 99.6% (implant level) for the mandible. There was a significant difference in the implant-level survival rates between the maxilla and mandible, with a lower rate in the maxilla (p = 0.043). The risk factors associated with early implant failure according to the all-on-four concept included the maxilla (implant level) and smoking (patient level). We could not find a significant effect of photofunctionalisation on early failure (p = 0.25) following this treatment protocol.

Histopathological, Demographic, and Clinical Signatures of Medulla Oblongata Germ Cell Tumors: A Case Report With the Review of Literature.

The medulla oblongata is one of the rarest sites of occurrence for germ cell tumors (GCTs) of the central nervous system. As there is scant data regarding epidemiology, clinical presentations, optimal intervention, and long-term prognosis, we aimed to delineate the features of this rare entity by presenting our representative case and performing a quantitative review of the literature. A 24-year-old woman presented to our department with vertigo and swallowing difficulties. Magnetic resonance imaging revealed a homogenously enhanced exophytic lesion arising from the medulla oblongata and extending to the fourth ventricle. Surgical resection was performed and a histological diagnosis of pure germinoma was made. The patient underwent chemotherapy and whole-ventricular irradiation. No recurrence has been experienced for 4 months after the surgery. According to the literature, the prognosis of GCTs at the medulla oblongata seems no worse than those at typical sites. Striking features including occurrence at an older age, female preponderance, and a predominance of germinoma were noteworthy. The pattern of local recurrence suggests extensive radiation coverage is not a prerequisite. Special attention is needed for cardiac and respiratory functions as the main factors eliciting mortality.

Sodium-Glucose Cotransporter-2 Inhibitors Stabilize Coronary Plaques in Acute Coronary Syndrome With Diabetes Mellitus.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are widely used in cardiology and are effective in treating acute coronary syndrome (ACS). Their effects on unstable plaque in patients with ACS remains unclear. This study aimed to examine the effectiveness of SGLT2is in coronary plaque based on optical coherence tomography (OCT) images and the prognosis of ACS with type 2 diabetes mellitus. This retrospective study included 109 patients in the total cohort and 29 patients in the OCT cohort. Based on SGLT2i administration after ACS, the total cohort was categorized into non-SGLT2i (n = 69) and SGLT2i (n = 40) groups. The OCT cohort had 15 and 14 patients in the non-SGLT2i and SGLT2i groups, respectively. The OCT images of unstable plaque were analyzed in nonstented lesions during ACS catheterization and at the 6-month follow-up. The total cohort was assessed after 1 year for major adverse cardiovascular events, including all-cause mortality, revascularization, cerebrovascular disease, and heart failure hospitalization. SGLT2is improved unstable lesions with a significantly thicker fibrous cap (48 ± 15 µm vs 26 ± 24 µm, p = 0.005), reduced lipid arc (-29 ± 12° vs -18 ± 14°, p = 0.028), higher % decrease in total lipid arc (-35 ± 13% vs -19 ± 18%, p = 0.01), and lower major adverse cardiovascular event incidence (log-rank p = 0.023, hazard ratio 4.72 [1.08 to 20.63]) and revascularization rate (adjusted hazard ratio 6.77 [1.08 to 42.52]) than the non-SGLT2i group. In conclusion, SGLT2is can improve the markers of plaque stability and may improve the prognosis in patients with type 2 diabetes mellitus.

Trans-Distal Radial Artery Carotid Revascularization with Forearm Flow Reversal: An Alternative Option of CAS in the TCAR Era.

BACKGROUND: Transcarotid artery revascularization (TCAR) has emerged as an alternative to carotid artery stenting (CAS). TCAR demonstrated its superiority by avoiding femoral artery puncture and establishing proximal protection without crossing the stenotic lesion. In the TCAR era, we focused on the possibility of a trans-distal radial approach (DRA). A balloon-guide catheter was navigated via DRA to establish proximal protection before lesion crossing. The forearm subcutaneous vein was used as the flow-reversal circuit. METHODS: Six internal carotid artery stenosis patients underwent CAS using "the forearm flow reversal technique." Every procedure was performed under continuous flow reversal from the common carotid artery to the forearm cephalic vein. RESULTS: Successful revascularization was achieved without ischemic or access-site complications. The distal radial artery was patent at discharge in all cases. CONCLUSIONS: Trans-distal radial CAS with forearm flow reversal is a feasible and less invasive technical option.

A Case of Anti-IgLON5 Disease Showing an Improvement in Dysautonomia, Including Vocal Cord Palsy, via Combined Immunotherapy.

Anti-IgLON5 disease shows various neurological manifestations, of which dysautonomia is one of the major symptoms and is rarely improved by immunotherapy. We herein report a patient with anti-IgLON5 disease who showed several autonomic failures, including vocal cord palsy for four months. The patient presented with cognitive impairments, bulbar symptoms accompanied by myorhythmia in the pharynx and tongue, cerebellar ataxia with tremor, motor neuron symptoms in the limbs, gastrointestinal dysfunction, orthostatic hypotension, non-rapid eye movement sleep disorder on polysomnography, and severe vocal cord palsy. Combined immunotherapy improved his symptoms, including vocal cord palsy, suggesting that combined immunotherapy might improve dysautonomia in anti-IgLON5 disease.

Clinical Characteristics of Immediate Contralateral Ischemia Subsequent to Revascularization for Moyamoya Disease.

BACKGROUND: Moyamoya disease is a bilateral steno-occlusive disease involving the cerebral vasculature. While some patients are affected by procedure-related ipsilateral ischemia, ischemic complications contralateral to the revascularization are rarely observed. METHODS: We retrospectively investigated 135 hemispheres (103 patients) that underwent revascularization in our institution between April 2006 and September 2022. Revascularization surgery comprised single superficial temporal artery-middle cerebral artery anastomosis and encephalo-myo-synangiosis. Certain patients aged under 10 years underwent indirect revascularization. Bilateral revascularization was performed with an interval of >3 months. Medical records and neuroimages were reviewed, and patients with contralateral ischemic complications were identified. Some cases underwent genetic analysis. RESULTS: The mean age was 34.5 (range: 5-71) years, and 95 cases (70.4%) were in women. Of the 102 cases examined for the RNF213 c.14429 G > A (p.Arg4810Lys) variant, 33 (32.4%) and 69 (67.6%) showed the GG and GA genotype, respectively. Three cases (2.2%, all female, age range 44-71 years) were complicated with contralateral infarction. The infarcted area distributions of the 2 cases with RNF213 c.14429 G > A variant were patchy and peripheral. The other case showed on magnetic resonance imaging (MRI) angiography total occlusion of the internal carotid artery where patency had been confirmed preoperatively. CONCLUSIONS: Contralateral ischemia after revascularization occurred in 2.2% of cases. We classified them into peripheral and central types: peripheral type, an infarction owing to hemodynamic insufficiency or intracranial blood flow redistribution; central type, total occlusion of the contralateral internal carotid artery. Intensive preoperative management can minimize the risk of peripheral types, and neurosurgeons should beware of severe central types.

Effects of tafamidis on the left ventricular and left atrial strain in patients with wild-type transthyretin cardiac amyloidosis.

AIMS: Although tafamidis is used in patients with wild-type transthyretin cardiac amyloidosis (ATTRwt-CA), its specific effect on cardiac function is unclear. Thus, this study aimed to investigate the effect of tafamidis on left atrial (LA) and left ventricular function using speckle-tracking echocardiography for 1 year of treatment in patients with ATTRwt-CA. METHODS AND RESULTS: We included 23 patients (mean age, 76 years) with ATTRwt-CA confirmed via biopsy. We analysed the left ventricular and LA strain using 2D speckle-tracking echocardiography and compared these parameters before and 1 year after starting treatment with tafamidis between 16 patients with sinus rhythm (SR) and 7 patients with atrial fibrillation (AF). In ATTRwt-CA patients with SR, LA reservoir strain significantly improved by 1-year tafamidis treatment (10.5 ± 5.0% to 11.9 ± 5.3%, P = 0.0307) although global longitudinal strain (GLS) did not (-10.6 ± 3.1% to -11.3 ± 3.0%, P = 0.0608). In contrast, LA reservoir strain was not significantly changed (5.4 ± 2.9% to 4.9 ± 1.7%, P = 0.4571), and GLS deteriorated (-8.4 ± 2.3% to -6.8 ± 1.4%, P = 0.0267) in ATTRwt-CA patients with AF. CONCLUSION: LA function improved with tafamidis treatment in ATTRwt-CA patients with SR but not left ventricular function. However, these cardiac functions did not improve with tafamidis treatment in ATTRwt-CA patients with AF.

Long-term survival after cordectomy in a case of spinal cord diffuse midline glioma, H3K27-altered: illustrative case.

BACKGROUND: Spinal cord diffuse midline glioma, H3K27-altered, is an extremely rare entity with a poor prognosis. However, its optimal treatment remains poorly defined. Although cordectomy was introduced in the early 20th century, its efficacy has been questioned and shrouded behind the scenes. OBSERVATIONS: A 76-year-old male with recent-onset paraparesis of the lower extremities and paresthesia presented to our outpatient clinic. Magnetic resonance imaging revealed an intra-axial spinal cord tumor extending from T12 to L2. The patient underwent laminectomy and partial tumor resection, and the surgical specimen was histologically diagnosed as a diffuse midline glioma, H3K27-altered. Although standard chemoradiotherapy was implemented, the patient experienced local tumor recurrence 2 years later and underwent cordectomy at T9. The patient was alive at the 4-year follow-up after cordectomy without tumor recurrence. According to the literature, patients with lesions in the lower thoracic cord below T8 achieved a longer survival than those with lesions in the upper thoracic cord above T5. LESSONS: Cordectomy benefits selected cases of high-grade spinal cord gliomas. Maximal prevention of cerebrospinal fluid dissemination by tumor cells is indisputably important, and tumors located below the lower thoracic spine may be the key to success in establishing a long-term prognosis after cordectomy.

Morphological, histological and gene-expression analyses on stolonization in the Japanese Green Syllid, Megasyllis nipponica (Annelida, Syllidae).

Benthic annelids belonging to the family Syllidae (Annelida, Errantia, Phyllodocida) exhibit a unique reproduction mode called "schizogamy" or "stolonization", in which the posterior body part filled with gametes detaches from the original body, as a reproductive unit (stolon) that autonomously swims and spawns. In this study, morphological and histological observations on the developmental processes during stolonization were carried out in Megasyllis nipponica. Results suggest that the stolon formation started with maturation of gonads, followed by the formation of a head ganglion in the anteriormost segment of the developing stolon. Then, the detailed stolon-specific structures such as stolon eyes and notochaetae were formed. Furthermore, expression profiles of genes involved in the anterior-posterior identity (Hox genes), head determination, germ-line, and hormone regulation were compared between anterior and posterior body parts during the stolonization process. The results reveal that, in the posterior body part, genes for gonadal development were up-regulated, followed by hormone-related genes and head-determination genes. Unexpectedly, Hox genes known to identify body parts along the anterior-posterior axis showed no significant temporal expression changes. These findings suggest that during stolonization, gonad development induces the head formation of a stolon, without up-regulation of anterior Hox genes.

The formation of KV2.1 macro-clusters is required for sex-specific differences in L-type CaV1.2 clustering and function in arterial myocytes.

In arterial myocytes, the canonical function of voltage-gated CaV1.2 and KV2.1 channels is to induce myocyte contraction and relaxation through their responses to membrane depolarization, respectively. Paradoxically, KV2.1 also plays a sex-specific role by promoting the clustering and activity of CaV1.2 channels. However, the impact of KV2.1 protein organization on CaV1.2 function remains poorly understood. We discovered that KV2.1 forms micro-clusters, which can transform into large macro-clusters when a critical clustering site (S590) in the channel is phosphorylated in arterial myocytes. Notably, female myocytes exhibit greater phosphorylation of S590, and macro-cluster formation compared to males. Contrary to current models, the activity of KV2.1 channels seems unrelated to density or macro-clustering in arterial myocytes. Disrupting the KV2.1 clustering site (KV2.1S590A) eliminated KV2.1 macro-clustering and sex-specific differences in CaV1.2 cluster size and activity. We propose that the degree of KV2.1 clustering tunes CaV1.2 channel function in a sex-specific manner in arterial myocytes.

Deaths caused by osteoporotic fractures in Japan: An epidemiological study.

BACKGROUND: Osteoporosis is a global issue with a worldwide prevalence of 18.3%, and the presence of coexisting fragility fractures can reduce the survival rate by approximately 20%. In Japan, the prevalence of osteoporosis is estimated to be 12.8 million, and the annual occurrence of hip fractures is approximately 193,400. Remarkably, coexisting hip or spinal fragility fractures caused by slight external force meet the Japanese diagnostic criterion for osteoporosis regardless of bone mineral density. However, only 191 deaths due to osteoporosis were published in 2021 in Japan. With the concern that some cases of hip and spinal fragility fractures were assigned an underlying cause of death of traumatic fracture instead of osteoporosis, this study aimed to elucidate the actual number of deaths due to osteoporosis in Japan. METHODS: We used the data from Japan in 2018. First, the number of deaths due to osteoporosis and hip or spinal fractures was reviewed using published vital statistics. Second, we calculated the number of elderly deaths (age ≥80 years) resulting from hip or spinal fractures caused by falls on the same level using data from approximately 1.4 million annual individual death certificates. Combining the above data, the actual number of deaths due to osteoporosis was estimated. RESULTS: Only 190 deaths due to osteoporosis were reported in the published data. The individual certificate data revealed 3437 elderly deaths due to hip or spinal fractures caused by falls on the same level, which could meet the criteria of osteoporotic fragility fractures. Accordingly, the estimated number of deaths caused by osteoporosis was calculated as 3,627, approximately 19 times the published value. CONCLUSIONS: After researching the individual death certificate data focusing on the coexisting hip or spinal fragility fracture, it was implied that osteoporosis may have a higher mortality rate in Japan than what is published.