To Bet, or Not to Bet: That Is the Question of SEF Spikes

The ability of animals to monitor their own cognitive processes is called metacognition. In this issue of Neuron, Middlebrooks and Sommer (2012) show that single-unit activity of SEF neurons exhibit a metacognitive signal while monkeys perform a postdecision wagering task

Chemotherapy for elderly patients with GI cancer

Chemotherapy for cancer has significantly improved owing to the increasing number of effective chemotherapeutic agents and supportive care. Recently, the number of older cancer patients has rapidly increased owing to the aging of the global population. However, in most cases, it is difficult to treat those using similar dosages or schedules as that of younger patients because older patients generally have unfavorable factors, such as decreased performance status and physical and cognitive conditions, thus increasing the incidence of complications and side effects. Chemotherapy for gastrointestinal cancers has made significant progress in recent years with the introduction of molecular-targeted agents and immunotherapy. However, clinical trials showed limited evidence regarding the efficacy of chemotherapy in older cancer patients, accounting for half of all patients, making it difficult to develop a well-established treatment strategy. This review aimed to evaluate the current state of chemotherapy for gastrointestinal cancer in older adults. Furthermore, the limitations and future perspectives were discussed

Treatment Response Predictors of Neoadjuvant Therapy for Locally Advanced Gastric Cancer : Current Status and Future Perspectives

Neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (LAGC) has been recognized as an effective therapeutic option because it is expected to improve the curative resection rate by reducing the tumor size and preventing recurrence of micrometastases. However, for patients resistant to NAC, not only will operation timing be delayed, but they will also suffer from side effects. Thus, it is crucial to develop a comprehensive strategy and select patients sensitive to NAC. However, the therapeutic effect of NAC is unpredictable due to tumor heterogeneity and a lack of predictive biomarkers for guiding the choice of optimal preoperative treatment in clinical practice. This article summarizes the related research progress on predictive biomarkers of NAC for gastric cancer. Among the many investigated biomarkers, metabolic enzymes for cytotoxic agents, nucleotide excision repair, and microsatellite instability, have shown promising results and should be assessed in prospective clinical trials. Noninvasive liquid biopsy detection, including miRNA and exosome detection, is also a promising strategy

Male Infertility and Its Causes in Human

Infertility is one of the most serious social problems facing advanced nations. In general, approximate half of all cases of infertility are caused by factors related to the male partner. To date, various treatments have been developed for male infertility and are steadily producing results. However, there is no effective treatment for patients with nonobstructive azoospermia, in which there is an absence of mature sperm in the testes. Although evidence suggests that many patients with male infertility have a genetic predisposition to the condition, the cause has not been elucidated in the vast majority of cases. This paper discusses the environmental factors considered likely to be involved in male infertility and the genes that have been clearly shown to be involved in male infertility in humans, including our recent findings

Dystonia and Cerebellum : From Bench to Bedside

Dystonia pathogenesis remains unclear; however, findings from basic and clinical research suggest the importance of the interaction between the basal ganglia and cerebellum. After the discovery of disynaptic pathways between the two, much attention has been paid to the cerebellum. Basic research using various dystonia rodent models and clinical studies in dystonia patients continues to provide new pieces of knowledge regarding the role of the cerebellum in dystonia genesis. Herein, we review basic and clinical articles related to dystonia focusing on the cerebellum, and clarify the current understanding of the role of the cerebellum in dystonia pathogenesis. Given the recent evidence providing new hypotheses regarding dystonia pathogenesis, we discuss how the current evidence answers the unsolved clinical questions

Functional Differentiation of Memory Retrieval Network in Macaque Posterior Parietal Cortex

SummaryHuman fMRI studies revealed involvement of the posterior parietal cortex (PPC) during memory retrieval. However, corresponding memory-related regions in macaque PPC have not been established. In this monkey fMRI study, comparisons of cortical activity during correct recognition of previously seen items and rejection of unseen items revealed two major PPC activation sites that were differentially characterized by a serial probe recognition paradigm: area PG/PGOp in inferior parietal lobule, along with the hippocampus, was more active for initial item retrieval, while area PEa/DIP in intraparietal sulcus was for the last item. Effective connectivity analyses revealed that connectivity from hippocampus to PG/PGOp, but not to PEa/DIP, increased during initial item retrieval. The two parietal areas with differential serial probe recognition profiles were embedded in two different subnetworks of the brain-wide retrieval-related regions. These functional dissociations in the macaque PPC imply the functional correspondence of retrieval-related PPC networks in macaques and humans

アキレス腱付着部症に対しアキレス腱モーメントアーム長が及ぼす影響

Insertional Achilles tendinopathy (IAT) is caused by traction force of the tendon. The effectiveness of the suture bridge technique in correcting it is unknown. We examined the moment arm in patients with IAT before and after surgery using the suture bridge technique, in comparison to that of healthy individuals. We hypothesized that the suture bridge method influences the moment arm length. An IAT group comprising 10 feet belonging to 8 patients requiring surgical treatment for IAT were followed up postoperatively and compared with a control group comprising 15 feet of 15 healthy individuals with no ankle complaints or history of trauma or surgery. The ratio of the moment arm (MA) length/foot length was found to be statistically significant between the control group, the IAT group preoperatively and the IAT group postoperatively (p < 0.01). Despite no significant difference in the force between the control and preoperative IAT groups, a significantly higher force to the Achilles tendon was observed in the IAT group postoperatively compared to the other groups (p < 0.05). This study demonstrates that a long moment arm may be one of the causes of IAT, and the suture bridge technique may reduce the Achilles tendon moment arm.博士（医学）・甲第845号・令和4年9月28日© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)

上皮成長因子受容体を標的とした結腸直腸腫瘍の分子イメージング : 動物モデルにおける腫瘍の検出と治療評価

To overcome the problem of overlooking colorectal tumors, a new and highly sensitive modality of colonoscopy is needed. Moreover, it is also important to establish a new modality to evaluate viable tumor volume in primary lesions of colorectal cancer (CRC) during chemotherapy. Therefore, we carried out molecular imaging of colorectal tumors targeting epidermal growth factor receptor (EGFR), which is highly expressed on tumor cells, for evaluating chemotherapeutic efficacy and for endoscopic detection of colorectal adenomas. We first attempted to image five CRC cell lines with various levels of EGFR expression using an Alexa Fluor‐labeled anti‐EGFR monoclonal antibody (AF‐EGFR‐Ab). A strong fluorescence signal was observed in the cells depending on the level of EGFR expression. When nude mice xenografted with LIM1215 CRC cells, which highly express EGFR, were i.v. injected with AF‐EGFR‐Ab, a strong fluorescence signal appeared in the tumor with a high signal to noise ratio, peaking at 48 hours after injection and then gradually decreasing, as shown using an IVIS Spectrum system. When the xenografted mice were treated with 5‐fluorouracil, fluorescence intensity in the tumor decreased in proportion to the viable tumor cell volume. Moreover, when the colorectum of azoxymethane‐treated rats was observed using a thin fluorescent endoscope with AF‐EGFR‐Ab, all 10 small colorectal adenomas (≤3 mm) were detected with a clear fluorescence signal. These preliminary results of animal experiments suggest that EGFR‐targeted fluorescent molecular imaging may be useful for quantitatively evaluating cell viability in CRC during chemotherapy, and also for detecting small adenomas using a fluorescent endoscope

Transcriptomic Profile of Distal Middle Cerebral Artery from Moyamoya Disease Patients Reveals a Potential Unique Pathway

BACKGROUND: Moyamoya disease (MMD) is a peculiar disease, characterized by progressive steno-occlusion of the distal ends of bilateral internal carotid arteries and their proximal branches. Numerous studies of MMD investigated as a singular pathway, thus overlooked the complexity of MMD pathobiology. AIM: In this study, we sought to investigate the gene expression in the involved arteries to reveal the novel mechanism of MMD. MATERIALS AND METHODS: Eight middle cerebral artery (MCA) specimens were obtained from six patients underwent surgical procedure superficial temporal artery to MCA (STA-MCA bypass) for MMD and two control patients. We performed RNA extraction and microarray analysis with Agilent Whole Human Genome DNA microarray 4x44K ver.2.0 (Agilent Tech., Inc., Wilmington, DE, USA). RESULTS: From 42,405 gene probes assayed, 921 gene probes were differentially regulated in MCA of patients with MMD. Subsequent pathway analysis with PANTHER database revealed that angiogenesis, inflammation, integrin, platelet-derived growth factor (PDGF), and WNT pathways were distinctly regulated in MMD. Among genes in aforementioned pathways, SOS1 and AKT2 were the mostly distinctly regulated genes and closely associated with RAS pathway. CONCLUSION: The gene expression in MCA of patients with MMD was distinctly regulated in comparison with control MCA; presumably be useful for elucidating MMD pathobiology

Claw sign predicts first-pass effect in MT

Background: Mechanical thrombectomy (MT) is an effective treatment for acute cerebral large vessel occlusion (LVO). Complete recanalization of vessels in a single procedure is defined as the first-pass effect (FPE) and is associated with good prognosis. In this study, angiographic clot protruding sign termed the “claw sign,” was examined as candidate preoperative imaging factor for predicting the FPE. Methods: We retrospectively analyzed data from 91 consecutive patients treated for acute LVO in the anterior circulation by MT between January 2014 and December 2019. The claw sign was defined as a thrombus that protruded proximally by more than half of the diameter of the parent artery. Radiological findings such as claw sign, clinical and etiological features, and outcomes were compared between groups with and without successful FPE. Multivariate analysis was conducted to evaluate perioperative factors associated with FPE. Results: FPE was achieved in 26 of 91 (28.6%) patients and the claw sign was observed in 34 of 91 (37.4%) patients. The claw sign was significantly more frequent in the successful FPE group than in the failed FPE group (53.8% vs. 30.8%; P = 0.040). After the multivariate analysis, the claw sign was the only pretreatment parameter that could predict FPE (odds ratio, 2.67; 95% confidence interval, 1.01–7.06; P = 0.047). Conclusion: The claw sign is an angiographic imaging factor that might predict FPE after MT for anterior circulation acute ischemic stroke