Continuous decision to wait for a future reward is guided by fronto-hippocampal anticipatory dynamics.

Deciding whether to wait for a future reward is crucial for surviving in an uncertain world. While seeking rewards, agents anticipate a reward in the present environment and constantly face a trade-off between staying in their environment or leaving it. It remains unclear, however, how humans make continuous decisions in such situations. Here, we show that anticipatory activity in the anterior prefrontal cortex, ventrolateral prefrontal cortex, and hippocampus underpins continuous stay-leave decision-making. Participants awaited real liquid rewards available after tens of seconds, and their continuous decision was tracked by dynamic brain activity associated with the anticipation of a reward. Participants stopped waiting more frequently and sooner after they experienced longer delays and received smaller rewards. When the dynamic anticipatory brain activity was enhanced in the anterior prefrontal cortex, participants remained in their current environment, but when this activity diminished, they left the environment. Moreover, while experiencing a delayed reward in a novel environment, the ventrolateral prefrontal cortex and hippocampus showed anticipatory activity. Finally, the activity in the anterior prefrontal cortex and ventrolateral prefrontal cortex was enhanced in participants adopting a leave strategy, whereas those remaining stationary showed enhanced hippocampal activity. Our results suggest that fronto-hippocampal anticipatory dynamics underlie continuous decision-making while anticipating a future reward.

Bone marrow-derived fibroblast migration via periostin causes irreversible arthrogenic contracture after joint immobilization.

Joint contracture causes distressing permanent mobility disorder due to trauma, arthritis, and aging, with no effective treatment available. A principal and irreversible cause of joint contracture has been regarded as the development of joint capsule fibrosis. However, the molecular mechanisms underlying contracture remain unclear. We established a mouse model of knee joint contracture, revealing that fibrosis in joint capsules causes irreversible contracture. RNA-sequencing of contracture capsules demonstrated a marked enrichment of the genes involved in the extracellular region, particularly periostin (Postn). Three-dimensional magnetic resonance imaging and immunohistological analysis of contracture patients revealed posterior joint capsule thickening with abundant type I collagen (Col1a2) and POSTN in humans. Col1a2-GFPTG ; Postn-/- mice and chimeric mice with Col1a2-GFPTG ; tdTomatoTG bone marrow showed fibrosis in joint capsules caused by bone marrow-derived fibroblasts, and POSTN promoted the migration of bone marrow-derived fibroblasts, contributing to fibrosis and contracture. Conversely, POSTN-neutralizing antibody attenuated contracture exacerbation. Our findings identified POSTN as a key inducer of fibroblast migration that exacerbates capsule fibrosis, providing a potential therapeutic strategy for joint contracture.

Timing of colonoscopy in acute lower GI bleeding: a multicenter retrospective cohort study.

BACKGROUND AND AIMS: We aimed to determine the optimal timing of colonoscopy and factors that benefit patients who undergo early colonoscopy for acute lower GI bleeding. METHODS: We identified 10,342 patients with acute hematochezia (CODE BLUE-J study) admitted to 49 hospitals in Japan. Of these, 6270 patients who underwent a colonoscopy within 120 hours were included in this study. The inverse probability of treatment weighting method was used to adjust for baseline characteristics among early (≤24 hours, n = 4133), elective (24-48 hours, n = 1137), and late (48-120 hours, n = 1000) colonoscopy. The average treatment effect was evaluated for outcomes. The primary outcome was 30-day rebleeding rate. RESULTS: The early group had a significantly higher rate of stigmata of recent hemorrhage (SRH) identification and a shorter length of stay than the elective and late groups. However, the 30-day rebleeding rate was significantly higher in the early group than in the elective and late groups. Interventional radiology (IVR) or surgery requirement and 30-day mortality did not significantly differ among groups. The interaction with heterogeneity of effects was observed between early and late colonoscopy and shock index (shock index <1, odds ratio [OR], 2.097; shock index ≥1, OR, 1.095; P for interaction = .038) and performance status (0-2, OR, 2.481; ≥3, OR, .458; P for interaction = .022) for 30-day rebleeding. Early colonoscopy had a significantly lower IVR or surgery requirement in the shock index ≥1 cohort (OR, .267; 95% confidence interval, .099-.721) compared with late colonoscopy. CONCLUSIONS: Early colonoscopy increased the rate of SRH identification and shortened the length of stay but involved an increased risk of rebleeding and did not improve mortality and IVR or surgery requirement. Early colonoscopy particularly benefited patients with a shock index ≥1 or performance status ≥3 at presentation.

Safety of early oral intake after endoscopic ultrasound-guided hepaticoenterostomy.

BACKGROUND: Techniques and devices for endoscopic ultrasound (EUS)-guided hepaticoenterostomy (EUS-HES) procedures, including EUS-guided hepaticogastrostomy (EUS-HGS) and EUS-guided hepaticojejunostomy (EUS-HJS), have been developed; however, the optimal timing to begin oral intake after EUS-HES remains unknown. This study aimed to evaluate the safety of early oral intake after EUS-HES. METHODS: We retrospectively investigated patients who underwent EUS-HES (EUS-HGS or EUS-HJS) between March 2015 and March 2022. Patients who had no problems with the results of blood tests and computed tomography examinations on the morning of day 1 after EUS-HES were classified as either the early intake group (started oral intake on day 1 after EUS-HES) or the late intake group (started oral intake on day 2 or later after EUS-HES). Patients' characteristics, procedure characteristics, and early postprocedural adverse events (within 14 days after the procedure) were compared between groups. RESULTS: Fifty patients were enrolled in this study. Forty-three patients had no problems with the results of examinations performed on the morning of day 1 after EUS-HES. Twenty-one patients comprised the early intake group and 22 comprised the late intake group. Adverse events that developed within 14 days after EUS-HES were not significantly different between groups (early 4.7% vs. late 9.0%; odds ratio, 0.50; 95% confidence interval, 0.0080-10.49; P = 1.00). CONCLUSIONS: Starting oral intake on day 1 after EUS-HES did not increase postprocedural adverse events compared with starting oral intake on day 2 or later after EUS-HES.

Evaluation and management of esophageal varices by through-the-scope endoscopic Doppler probe method.

OBJECTIVES: Objective assessments of esophageal varices (EVs) are inadequate. The recurrence of variceal bleeding after endoscopic variceal ligation (EVL) is associated with residual blood flow underlying EVL or incomplete treatment of a perforating vein by EVL. We aimed to assess our novel through-the-scope endoscopic Doppler probe method (DOP) for the evaluation and management of EVs. METHODS: This study included 20 patients (54 varices) with a history of esophageal variceal rupture from June 2019 to May 2021 who underwent DOP at a tertiary hospital. Variceal velocities were compared based on the size and endoscopic variceal findings. Additionally, we performed EVL assisted by DOP (EVL + DOP) in nine patients. RESULTS: Doppler imaging of EVs was observed in all 20 patients. The velocity of varices was significantly higher in EVs with a larger size, greater form, blue color, and red color sign positive. Perforating veins connecting to the EVs were identified in six out of nine patients who underwent EVL + DOP. Eight out of nine patients underwent repeat EVL. Repeat EVL was performed until the variceal velocity reached absent. No recurrence of variceal bleeding occurred during the follow-up period (mean 8.7 ± 3.2 months). No adverse events associated with DOP were observed. CONCLUSION: The evaluation of EVs using DOP is feasible and accurate. EV velocities are related to the variceal size, form, blue color, and red color sign. EVL + DOP may be a more reliable treatment for EVs. Further large-scale, long-term comparative studies are warranted.

Multiple non-polypoid mucosal Schwann cell hamartomas presenting as edematous and submucosal tumor-like lesions: a case report.

BACKGROUND: Mucosal Schwann cell hamartomas are rare neurogenic tumors which present most commonly in the distal colon. They are usually discovered as small, single polyps in asymptomatic patients. CASE PRESENTATION: An asymptomatic 64-year-old man was referred to us after a 12 mm subepithelial lesion was discovered incidentally on screening colonoscopy. Follow-up colonoscopy conducted 2 months later revealed that the tumor had disappeared, leaving multiple edematous, submucosal tumor-like elevations presenting as skip lesions throughout the sigmoid colon. Lesions had elongated pits on magnifying endoscopy and were limited to the first layer on endoscopic ultrasound. Biopsies revealed unclearly delineated foci of spindle-shaped cells limited to the lamina propria. On immunohistochemistry, all lesions were positive for S-100 protein and negative for CD34, CD56, and neurofilament protein. The patient was diagnosed with multiple mucosal Schwann cell hamartomas of the sigmoid colon. He remains asymptomatic after 18 months of follow-up, but the lesions have also remained unchanged. CONCLUSION: We report a case of multiple non-polypoid mucosal Schwann cell hamartomas. Endoscopic findings may assist in the differential diagnosis, particularly when presenting as non-polypoid, submucosal tumor-like lesions.

Safety and Effectiveness of Endoscopic Band Ligation for Colonic Diverticular Bleeding in Elderly Patients.

INTRODUCTION: Colonic diverticulosis increases with age, leading to a higher risk of colonic diverticular bleeding (CDB) in the elderly. As life expectancy continues to increase, the need for endoscopic hemostasis for CDB in the elderly can also be expected to increase. However, there have been no reports to date on the feasibility of endoscopic hemostasis for elderly CDB patients. Several recent studies have addressed the effectiveness of endoscopic band ligation (EBL) for CDB. In this study, we evaluate the safety and effectiveness of EBL in elderly CDB patients compared to younger CDB patients. METHODS: We retrospectively analyzed the medical records of consecutive patients treated with EBL for the first time at a tertiary referral center between March 2011 and November 2017. Patients were grouped according to age into those at least 75 years old (the Elderly) and those <75 years old (the Nonelderly). Patient characteristics, technical success, and complications were compared between the two groups. RESULTS: EBL was performed in 153 patients during the study period (49 Elderly patients and 104 Nonelderly patients). Elderly patients were less likely to be male (p < 0.001) and had lower hemoglobin levels on admission (p < 0.001). Bleeding on the right side of the splenic flexure was observed more frequently in the Nonelderly (p = 0.002). Charlson Comorbidity Index (CCI) and use of antithrombotic agents were significantly higher in the Elderly (p < 0.001 and p < 0.001, respectively). Active bleeding tended to be observed more frequently in the Elderly (p = 0.054), while the difference was not significant. There were no significant differences in the shock index, procedure time, or units of packed red blood cells transfused between the 2 groups. No significant differences in the technical success rate (97.1 vs. 98%, p = 0.76), early rebleeding rate (10.2 vs. 14.4%, p = 0.47), or other complications (2 vs. 1%, p = 0.58) were observed. Perforation and abscess formation were not observed in either group. Female gender, left-sidedness, higher CCI, and lower hemoglobin level were all significantly more frequently observed in the Elderly on multiple logistic regression analysis. DISCUSSION/CONCLUSION: EBL may be similarly safe and effective for the treatment of CDB in the elderly as in the nonelderly.

Effectiveness of risk scoring systems in predicting endoscopic treatment in colonic diverticular bleeding.

BACKGROUND AND AIMS: The identification of stigmata of recent hemorrhage (SRH) in colonic diverticular bleeding (CDB) enables an endoscopic treatment and can improve the clinical outcome. However, SRH identification rate remains low. This study aims to investigate whether NOBLADS and Strate scoring systems are useful for predicting SRH identification rate of CDB pre-procedurally via colonoscopy. METHODS: In this single-center retrospective observational study, 302 patients who experienced their first episode of CDB from April 2008 to March 2018 were included. Patients were classified into SRH-positive and SRH-negative groups. The primary outcome was SRH identification rate. The secondary outcomes were active bleeding in SRH and early rebleeding rates. The usefulness of the NOBLADS and Strate scores as predicted values of SRH identification was evaluated using the area under the receiver operating characteristic curve. RESULTS: There were 126 and 176 patients in the SRH-positive and SRH-negative groups, respectively. The area under the receiver operating characteristic curve for SRH identification using the NOBLADS score was 0.74 (95% confidence interval, 0.69-0.80) and that using the Strate score was 0.74 (95% confidence interval, 0.68-0.79). Active bleeding and early rebleeding rates increased according to each score. By setting the cut-off of the NOBLADS score to four points, treatment was possible in 70.2% (66/94) patients. Addition of extravasation at computed tomography to a NOBLADS score of ≧ 4 points allowed treatment of all patients (24/24). CONCLUSIONS: Severity scoring in acute lower gastrointestinal bleeding was effective for predicting SRH identification in CDB. We suggest that combination of these scorings and CT findings could offer a new therapeutic strategy.

Evaluation of a Novel Easy Loop-Forming Guidewire to Reduce Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis for Serial Pancreatic Juice Aspiration Cytologic Examination: A Propensity Score Matching Analysis.

OBJECTIVE: This study aimed to investigate whether a novel, easy loop-forming guidewire could reduce post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) in patients undergoing endoscopic nasopancreatic drainage tube placement for serial pancreatic juice aspiration cytologic examination (SPACE). METHODS: We evaluated patients with suspected pancreatic cancer who underwent SPACE at our institution between January 2015 and April 2023 retrospectively. The patients were divided into 2 groups based on the type of guidewire used, namely, easy loop-forming and control groups. Propensity score matching was used to compare the incidence of PEP between the groups. RESULTS: We included 101 patients, with 51 and 50 in the easy loop-forming and control groups, respectively. After propensity score matching, 29 pairs of patients were selected from each group. Intraductal ultrasonography of the pancreas was performed more frequently in the easy loop-forming group than in the control group (27.6% vs 0%; P = 0.004); however, PEP incidence was significantly lower in the easy loop-forming group than in the control group (3.4% vs 27.6%; odds ratio, 0.097; 95% confidence interval, 0.002-0.82; P = 0.025). CONCLUSIONS: The use of the novel easy loop-forming guidewire decreased PEP occurrence in patients who underwent endoscopic nasopancreatic drainage tube placement for SPACE.

Exploring the Potential of Lateral Wedge Insoles in Alleviating Bone Marrow Lesions in End-Stage Knee Osteoarthritis: A Preliminary Case Report.

The efficacy of lateral wedge insoles (LWIs) in patients with end-stage knee osteoarthritis (OA) is unclear. A 43-year-old male underwent two anterior cruciate ligament reconstructions in his right knee and was later diagnosed with end-stage knee OA. An LWI combining arch support with a lateral heel wedge was fabricated for this patient and used over 12 months. As a result, after 12 months, the bone marrow lesion (BML), as measured by the magnetic resonance imaging Osteoarthritis Knee Score (MOAKS), was downgraded from grade 2 to grade 1. The use of LWI in a patient with end-stage knee OA showed lower co-contraction ratios in knee muscles even after 12 months. The results provide preliminary evidence suggesting the use of LWI in patients with end-stage knee OA has potential benefits for reducing BML.

Cystic duct straightening using a fine-gauge balloon dilator for successful endoscopic transpapillary gallbladder stenting.

Endoscopic transpapillary gallbladder stenting is sometimes inhibited by a cystic duct loop, necessitating cystic duct straightening. Mandai and colleagues report a novel technique for straightening the looped cystic duct using a fine-gauge balloon dilator, which is useful during endoscopic gallbladder stenting when the double-guidewire technique fails.

Combination of rubber band traction and partial injection for effective under-gel endoscopic mucosal resection of an ileocecal valve lesion.

Video 1A 25-mm protruding polyp was detected on the proximal lip of the ileocecal valve, extending into the terminal ileum. The tumor was treated effectively with under-gel EMR and a combination of the double-clip and rubber band traction method and partial submucosal injection.

Neural underpinning of Japanese particle processing in non-native speakers.

Grammar acquisition by non-native learners (L2) is typically less successful and may produce fundamentally different grammatical systems than that by native speakers (L1). The neural representation of grammatical processing between L1 and L2 speakers remains controversial. We hypothesized that working memory is the primary source of L1/L2 differences, by considering working memory within the predictive coding account, which models grammatical processes as higher-level neuronal representations of cortical hierarchies, generating predictions (forward model) of lower-level representations. A functional MRI study was conducted with L1 Japanese speakers and highly proficient Japanese learners requiring oral production of grammatically correct Japanese particles. We assumed selecting proper particles requires forward model-dependent processes of working memory as their functions are highly context-dependent. As a control, participants read out a visually designated mora indicated by underlining. Particle selection by L1/L2 groups commonly activated the bilateral inferior frontal gyrus/insula, pre-supplementary motor area, left caudate, middle temporal gyrus, and right cerebellum, which constituted the core linguistic production system. In contrast, the left inferior frontal sulcus, known as the neural substrate of verbal working memory, showed more prominent activation in L2 than in L1. Thus, the working memory process causes L1/L2 differences even in highly proficient L2 learners.

Use of the NOBLADS Score to Predict Endoscopic Treatment in Patients with Colonic Diverticular Bleeding by Age Stratification.

Objective A high NOBLADS score reflecting the severity of lower gastrointestinal bleeding contributes to the identification of stigmata of recent hemorrhage (SRH) in colonic diverticular bleeding (CDB). The burden of colonoscopy is particularly high in elderly patients; therefore, we investigated the utility of the NOBLADS score for managing CDB by age stratification. The NOBLADS score performance in SRH prediction was estimated by the area under the receiver operating characteristic calculation and a multiple logistic regression model. Methods This was a single-center, retrospective cohort study. Patients who underwent initial colonoscopy with CDB between April 2008 and December 2019 were divided into a young group (<65 years old) and an elderly group (≥65 years old). We further categorized patients according to colonoscopy findings as SRH-positive, with successful endoscopic hemostasis performance, and SRH-negative, with suspected CDB. The main outcome measure was successful SRH identification. Results Four-hundred and seventeen CDB patients were included, of whom 250 (60.0%) were elderly. There were 72 (43.1%) SRH-positive patients in the young group and 94 (37.6%) in the elderly group. The areas under the receiver operating characteristic curves of the NOBLADS score predicting SRH identification were 0.76, 0.71, and 0.81 for all ages, young patients, and elderly patients, respectively. A multiple logistic regression analysis showed that SRH identification was significantly associated with NOBLADS scores in both groups. Eighty-one patients (32.4%) scored ≥4 in the elderly group, and 60 of those were SRH-positive (74.1%). All 27 patients (10.8%) who scored ≥4 with extravasation on computed tomography were found to have SRH. Conclusion The NOBLADS score is useful for predicting SRH identification, especially in elderly patients.

Coexistence of sensory qualities and value representations in human orbitofrontal cortex.

Despite the multiple regions and neural networks associated with value-based decision-making, the orbitofrontal cortex (OFC) is possible a particularly important one. Although the role of the OFC in reinforcer devaluation tasks, which assess the ability to represent identity, sensory qualities, and subjective values of the expected outcomes, has been established, the specific aspect represented in this area remains unclear. In this study, using functional magnetic resonance imaging, wherein participants rated the palatability of 128 food items using photographs, we investigated whether the human OFC represents object identity, sensory qualities, or value. Employing many items helped us dissociate object identity from sensory qualities and values; the inferred sensory qualities of identical items were manipulated by a change in metabolic state. Moreover, value differences between items were analytically controlled by employing a technique similar to age adjustment. The palatability ratings for food items significantly decreased after a meal. Using representational similarity analysis, we confirmed that the OFC represents value. Moreover, identical items were represented similarly in the lateral OFC in a given metabolic state; however, these representations were altered post-feeding. Importantly, this change was not explained by subjective value, suggesting that the OFC represents sensory quality and value, but not object identity.