Ablation of oligodendrogenesis in adult mice alters brain microstructure and activity independently of behavioral deficits.

Oligodendrocytes continue to differentiate from their precursor cells even in adulthood, a process that can be modulated by neuronal activity and experience. Previous work has indicated that conditional ablation of oligodendrogenesis in adult mice leads to learning and memory deficits in a range of behavioral tasks. The current study replicated and re-evaluated evidence for a role of oligodendrogenesis in motor learning, using a complex running wheel task. Further, we found that ablating oligodendrogenesis alters brain microstructure (ex vivo MRI) and brain activity (in vivo EEG) independent of experience with the task. This suggests a role for adult oligodendrocyte formation in the maintenance of brain function and indicates that task-independent changes due to oligodendrogenesis ablation need to be considered when interpreting learning and memory deficits in this model.

A novel NODAL variant in a young embolic stroke patient with visceral heterotaxy.

BACKGROUND: Ischemic stroke in young adults can be caused by a variety of etiologies including the monogenic disorders. Visceral heterotaxy is a condition caused by abnormal left-right determinations during embryonic development. We aimed to determine the cause of a young ischemic stroke patient with visceral heterotaxy. CASE PRESENTATION: We performed neurological, radiological, and genetic evaluations in a 17-year-old male patient presenting ischemic stroke and visceral heterotaxy to determine the underlying cause of this rare disease combination. Brain magnetic resonance imaging (MRI) showed evidence of embolic stroke, abdominal computed tomography (CT) showed visceral heterotaxy, and echocardiogram showed cardiac anomaly with right-to-left-shunt (RLS). Whole genome sequencing (WGS) revealed a heterozygous missense variant (NM_018055.5: c.1016 T > C, p.(Met339Val)) in the NODAL gene, which is essential to the determination of the left-right body axis. CONCLUSIONS: Our study highlights the importance of evaluating genetic etiology in young ischemic stroke and the need for stroke risk management in visceral heterotaxy patients with RLS. To the best of our knowledge, we report the first genetically-confirmed case of visceral heterotaxy with young embolic stroke reported to date.

Brain carbon monoxide can suppress the rat micturition reflex through brain γ-aminobutyric acid receptors.

OBJECTIVES: To investigate roles of brain carbon monoxide (CO), an endogenous gasotransmitter, in regulation of the rat micturition reflex. METHODS: In urethane-anesthetized (0.8 g/kg, ip) male rats, evaluation of urodynamic parameters was started 1 h before intracerebroventricular administration of CORM-3 (CO donor) or ZnPP (non-selective inhibitor of heme oxygenase, a CO producing enzyme) and continued for 2 h after the administration. We also investigated effects of centrally pretreated SR95531 (GABAA receptor antagonist) or SCH50911 (GABAB receptor antagonist) on the CORM-3-induced response. RESULTS: CORM-3 significantly prolonged intercontraction intervals (ICIs) without changing maximal voiding pressure (MVP), while ZnPP significantly shortened ICI and reduced single-voided volume and bladder capacity without affecting MVP, post-voided residual volume, or voiding efficiency. The ZnPP-induced ICI shortening was reversed by CORM-3. The CORM-3-induced ICI prolongation was significantly attenuated by centrally pretreated SR95531 or SCH50911, respectively. CONCLUSIONS: Brain CO can suppress the rat micturition reflex through brain γ-aminobutyric acid (GABA) receptors.

Negative regulation of thyroid adenoma-associated protein (THADA) in the cardiac glycoside-induced anti-cancer effect.

Cardiac glycosides, known as inhibitors of Na+,K+-ATPase, have anti-cancer effects such as suppression of cancer cell proliferation and induction of cancer cell death. Here, we examined the signaling pathway elicited by cardiac glycosides in the human hepatocellular carcinoma HepG2 cells and human epidermoid carcinoma KB cells. Three kinds of cardiac glycosides (ouabain, oleandrin, and digoxin) inhibited the cancer cell proliferation and decreased the expression level of thyroid adenoma-associated protein (THADA). Interestingly, the knockdown of THADA inhibited cancer cell proliferation, and the proliferation was significantly rescued by re-expression of THADA in the THADA-knockdown cells. In addition, the THADA-knockdown markedly decreased the expression level of L-type amino acid transporter LAT1. Cardiac glycosides also reduced the LAT1 expression. The LAT1 inhibitor, JPH203, significantly weakened the cancer cell proliferation. These results suggest that the binding of cardiac glycosides to Na+,K+-ATPase negatively regulates the THADA-LAT1 pathway, exerting the anti-proliferative effect in cancer cells.

Innovative hemostasis technique for cesarean section in placenta previa: A retrospective study.

OBJECTIVE: To evaluate hemostatic efficacy, complications, and subsequent pregnancy outcomes in women with placenta previa who underwent combined vertical compression sutures in the lower uterine segment and intrauterine balloon tamponade (Hot-Dog method) to achieve hemostasis after cesarean section. METHODS: We retrospectively reviewed data for 117 women with singleton pregnancy diagnosed with placenta previa who underwent cesarean section between 29 and 38 weeks' gestation. Treatments were as follows: (1) conventional-intravenous oxytocin administration after placental detachment and suturing of bleeding points at the detachment site as needed (conventional group) (n = 47). (2) Intrauterine balloon tamponade alone (balloon group) (n = 41). (3) Vertical compression sutures + intrauterine balloon tamponade (Hot-Dog group) (n = 29). RESULTS: The placenta accreta spectrum prevalence was significantly higher in the balloon and Hot-Dog groups versus the conventional group. The prevalence of anteriorly located placenta was significantly higher in the Hot-Dog versus balloon groups. Intraoperative and total blood loss were significantly higher in the Hot-Dog versus conventional groups. Postoperative blood loss was significantly lower in the Hot-Dog versus balloon groups. Fewer additional procedures for managing postoperative hemorrhage were required in the Hot-Dog versus conventional and balloon groups. The number of subsequent pregnancies in the conventional, balloon, and Hot-Dog groups was 11 (23.4%), 8 (19.5%), and 4 (13.8%), respectively; all resulted in live births at term without serious obstetric complications. CONCLUSION: The Hot-Dog method is a straightforward and safe hemostasis technique for placenta previa that preserves fertility and controls severe bleeding.

Stage at diagnosis of colorectal cancer through diagnostic route: Who should be screened?

BACKGROUND: Colorectal cancer (CRC) is a global health concern, with advanced-stage diagnoses contributing to poor prognoses. The efficacy of CRC screening has been well-established; nevertheless, a significant proportion of patients remain unscreened, with > 70% of cases diagnosed outside screening. Although identifying specific subgroups for whom CRC screening should be particularly recommended is crucial owing to limited resources, the association between the diagnostic routes and identification of these subgroups has been less appreciated. In the Japanese cancer registry, the diagnostic routes for groups discovered outside of screening are primarily categorized into those with comorbidities found during hospital visits and those with CRC-related symptoms. AIM: To clarify the stage at CRC diagnosis based on diagnostic routes. METHODS: We conducted a retrospective observational study using a cancer registry of patients with CRC between January 2016 and December 2019 at two hospitals. The diagnostic routes were primarily classified into three groups: Cancer screening, follow-up, and symptomatic. The early-stage was defined as Stages 0 or I. Multivariate and univariate logistic regressions were exploited to determine the odds of early-stage diagnosis in the symptomatic and cancer screening groups, referencing the follow-up group. The adjusted covariates were age, sex, and tumor location. RESULTS: Of the 2083 patients, 715 (34.4%), 1064 (51.1%), and 304 (14.6%) belonged to the follow-up, symptomatic, and cancer screening groups, respectively. Among the 2083 patients, CRCs diagnosed at an early stage were 57.3% (410 of 715), 23.9% (254 of 1064), and 59.5% (181 of 304) in the follow-up, symptomatic, and cancer screening groups, respectively. The symptomatic group exhibited a lower likelihood of early-stage diagnosis than the follow-up group [P < 0.001, adjusted odds ratio (aOR), 0.23; 95% confidence interval (95%CI): 0.19-0.29]. The likelihood of diagnosis at an early stage was similar between the follow-up and cancer screening groups (P = 0.493, aOR for early-stage diagnosis in the cancer screening group vs follow-up group = 1.11; 95%CI = 0.82-1.49). CONCLUSION: CRCs detected during hospital visits for comorbidities were diagnosed earlier, similar to cancer screening. CRC screening should be recommended, particularly for patients without periodical hospital visits for comorbidities.

Rare Co-occurrence of Spinal Cord Hemorrhage from Radiation-induced Cavernous Hemangioma and Classical Hodgkin Lymphoma Post-transplant Lymphoproliferative Disorder.

Post-transplant lymphoproliferative disorders (PTLDs) are lymphoproliferative diseases that occur after solid organ transplantation or hematopoietic stem cell transplantation (HSCT). The development of PTLD is often associated with reactivation of Epstein-Barr virus (EBV). A 26-year-old woman with a history of HSCT and total-body irradiation developed spinal cord hemorrhage from a radiation-induced cavernous hemangioma (RICH) shortly after the development of classical Hodgkin lymphoma PTLD with EBV reactivation. Although little is known about the factors leading to hemorrhagic events from spinal cord RICH, we suspect that EBV reactivation may have been a factor contributing to the hemorrhage in the present case.

Roles of the cerebellum and basal ganglia in temporal integration: Insights from a synchronized tapping task.

OBJECTIVE: The aim of this study was to clarify the roles of the cerebellum and basal ganglia for temporal integration. METHODS: We studied 39 patients with spinocerebellar degeneration (SCD), comprising spinocerebellar atrophy 6 (SCA6), SCA31, Machado-Joseph disease (MJD, also called SCA3), and multiple system atrophy (MSA). Thirteen normal subjects participated as controls. Participants were instructed to tap on a button in synchrony with isochronous tones. We analyzed the inter-tap interval (ITI), synchronizing tapping error (STE), negative asynchrony, and proportion of delayed tapping as indicators of tapping performance. RESULTS: The ITI coefficient of variation was increased only in MSA patients. The standard variation of STE was larger in SCD patients than in normal subjects, especially for MSA. Negative asynchrony, which is a tendency to tap the button before the tones, was prominent in SCA6 and MSA patients, with possible basal ganglia involvement. SCA31 patients exhibited normal to supranormal performance in terms of the variability of STE, which was surprising. CONCLUSIONS: Cerebellar patients generally showed greater STE variability, except for SCA31. The pace of tapping was affected in patients with possible basal ganglia pathology. SIGNIFICANCE: Our results suggest that interaction between the cerebellum and the basal ganglia is essential for temporal processing. The cerebellum and basal ganglia and their interaction regulate synchronized tapping, resulting in distinct tapping pattern abnormalities among different SCD subtypes.