Application of Autofluorescence Endoscopy for Colorectal Cancer Screening: Rationale and an Update

As the result of basic researches, several intravital fluorophores have been determined so far in human colorectal tissue. Autofluorescence endoscopy (AFE) can detect slight alterations in their distribution and concentration during the colorectal carcinogenesis process and, thus facilitate noninvasive screening colonoscopies without the need for fluorescent substances or staining reagents to be administered. While detecting faint autofluorescence intensity by conventional fiberoptic endoscopy remains challenging, the latest AFE system with high-resolution videoendoscope capabilities enables such detection by using a false-color display algorithm. To this end, the diagnostic benefits of AFE have been reported in several multicenter randomized controlled studies of colorectal cancer (CRC) screening and differential diagnosis. CRC screening using the latest AFE technology could, therefore, lead to future reductions in CRC mortality

GABAergic Activities Control Spike Timing- and Frequency-Dependent Long-Term Depression at Hippocampal Excitatory Synapses

GABAergic interneuronal network activities in the hippocampus control a variety of neural functions, including learning and memory, by regulating θ and γ oscillations. How these GABAergic activities at pre- and postsynaptic sites of hippocampal CA1 pyramidal cells differentially contribute to synaptic function and plasticity during their repetitive pre- and postsynaptic spiking at θ and γ oscillations is largely unknown. We show here that activities mediated by postsynaptic GABAARs and presynaptic GABABRs determine, respectively, the spike timing- and frequency-dependence of activity-induced synaptic modifications at Schaffer collateral-CA1 excitatory synapses. We demonstrate that both feedforward and feedback GABAAR-mediated inhibition in the postsynaptic cell controls the spike timing-dependent long-term depression of excitatory inputs (“e-LTD”) at the θ frequency. We also show that feedback postsynaptic inhibition specifically causes e-LTD of inputs that induce small postsynaptic currents (<70 pA) with LTP-timing, thus enforcing the requirement of cooperativity for induction of long-term potentiation at excitatory inputs (“e-LTP”). Furthermore, under spike-timing protocols that induce e-LTP and e-LTD at excitatory synapses, we observed parallel induction of LTP and LTD at inhibitory inputs (“i-LTP” and “i-LTD”) to the same postsynaptic cells. Finally, we show that presynaptic GABABR-mediated inhibition plays a major role in the induction of frequency-dependent e-LTD at α and β frequencies. These observations demonstrate the critical influence of GABAergic interneuronal network activities in regulating the spike timing- and frequency-dependences of long-term synaptic modifications in the hippocampus

Complex and Transitive Synchronization in a Frustrated System of Calling Frogs

This letter reports synchronization phenomena and mathematical modeling on a frustrated system of living beings, or Japanese tree frogs (Hyla japonica). While an isolated male Japanese tree frog calls nearly periodically, he can hear sounds including calls of other males. Therefore, the spontaneous calling behavior of interacting males can be understood as a system of coupled oscillators. We construct a simple but biologically reasonable model based on the experimental results of two frogs, extend the model to a system of three frogs, and theoretically predict the occurrence of rich synchronization phenomena, such as triphase synchronization and 1:2 antiphase synchronization. In addition, we experimentally verify the theoretical prediction by ethological experiments on the calling behavior of three frogs and time series analysis on recorded sound data. Note that the calling behavior of three male Japanese tree frogs is frustrated because almost perfect antiphase synchronization is robustly observed in a system of two male frogs. Thus, nonlinear dynamics of the three-frogs system should be far from trivial

Effect of noise on mutually inhibiting pyramidal cells in visual cortex: foundation of stochasticity in bi-stable perception

Bi-stable perception has been an important tool to investigate how visual input is interpreted and how it reaches consciousness. To explain the mechanisms of this phenomenon, it has been assumed that a mutual inhibition circuit plays a key role. It is possible that this circuit functions to resolve ambiguity of input image by quickly shifting the balance of competing signals in response to conflicting features. Recently we established an in vitro neural recording system combined with computerized connections mediated by model neurons and synapses (“dynamic clamp” system). With this system, mutual inhibition circuit between two pyramidal cells from primary visual cortex were established by model inhibitory neurons and model synapses. Simultaneous injection of depolarizing current to the two pyramidal cells caused bi-stable activities: dominance of neural activities alternated between the two neurons with an interval of several seconds. We report the effect of adding noise to the (real) pyramidal cells and the (model) inhibitory neurons. Both excitatory and inhibitory synaptic conductance noise was modelled and given to these neurons while the pyramidal cells were exhibiting bi-stable activity. The histogram of the dominant activity durations showed gamma-like skewed distributions. The skewedness was enhanced by increasing the standard deviation of the conductance noise and the durations decreased overall. While adaptation of the dominant neuron and recovery (from adaptation) of the suppressed neuron caused a decrease and increase of their excitabilities, the fluctuation of membrane potentials due to the given conductance noise appeared to facilitate the reversal of the dominance

Reconstruction of GABAergic Transmission and Behavior by Striatal Cell Grafts in Rats with Ischemic Infarcts in the Middle Cerebral Artery

Fetal striatal cell suspensions were grafted stereotaxically into the infarcted striatum of rats, and reconstruction of striatopallidal GABA transmission and behavior were investigated. Occlusion of the middle cerebral artery (MCA) for one hour induced ischemic infarcts mainly in the lateral striatum, as detected by magnetic resonance imaging (MRI) and histology. Ischemic rats had deficits in the performance of a passive avoidance task, both acquisition and retention, but no changes in general circadian actograms. In these animals pallidal GABA, detected by microdialysis, decreased to about half of control levels. There were suggestions of an improvement in passive avoidance performance in the grafted animals. Pallidal GABA concentrations recovered almost to control levels, and were increased by infusions of the GABA uptake blocker nipecotic acid. These data indicate that neural transplantation is a promising approach to improve the deficits in chemical transmission and behavior following ischemic infarcts in rat striatum

Basal insulin ratio of type 1 diabetes

Aims/Introduction: To investigate the basal insulin requirement in patients with type 1 diabetes who are on multiple daily injections (MDI) and to assess the patient characteristics that affect the percent of total daily basal insulin dose to the total daily insulin dose (%TBD/TDD). Materials and Methods: The subjects of this study were 67 inpatients with type 1 diabetes who were served diabetic meals of 25–30 kcal/kg standard body weight during several weeks of hospitalization. The basal insulin requirement was adjusted to keep the blood glucose level from bedtime to before breakfast within a 30 mg/dL difference. The bolus insulin dose before the meal was adjusted to keep the blood glucose level below 140 and 200 mg/dL before and 2 h after each meal, respectively. The total daily insulin dose (TDD), the percent of total daily basal insulin dose (TBD) to TDD (%TBD/TDD), and clinical characteristics were collected. Results: The median (Q1, Q3) of TDD was 33.0 (26.0, 49.0) units, and the %TBD/TDD was 24.1 ± 9.8%. The %TBD/TDD was positively correlated with the body mass index (BMI) and negatively correlated with the age at the onset and at the examination according to a univariate analysis. However, the %TBD/TDD was dependent on the BMI (β = 0.340, P = 0.004) and the age at examination (β = −0.288, P = 0.012) according to the multiple regression analysis. Conclusions: The average %TBD/TDD in patients with type 1 diabetes on MDI was approximately 24% under inpatient conditions. The basal insulin requirement was dependent on the BMI and the age at examination

Dehydroepiandrosterone Sulfate, an Adrenal Androgen, Is Inversely Associated with Prevalence of Dynapenia in Male Individuals with Type 2 Diabetes

Dehydroepiandrosterone sulfate (DHEAS) is thought to be associated with life expectancy and anti-aging. Although skeletal muscle disorders are often found in diabetic people, the clinical significance of DHEAS in skeletal muscle remains unclear. Therefore, we aimed to determine whether DHEAS is associated with the development of skeletal muscle disorders in individuals with type 2 diabetes (T2D). A cross-sectional study was conducted in 361 individuals with T2D. Serum DHEAS levels, skeletal muscle mass index (SMI), handgrip strength (HS), and gait speed (GS) were measured in the participants. Pre-sarcopenia, sarcopenia, and dynapenia were defined according to the definitions of the AWGS 2019 criteria. DHEAS level was positively associated with HS but not with SMI or GS after adjustment of confounding factors. Multiple logistic regression analyses in total subjects showed that DHEAS level had an inverse association with the prevalence of dynapenia but not with the prevalence of pre-sarcopenia or sarcopenia. Furthermore, a significant association between DHEAS level and dynapenia was found in males but not in females. ROC curve analysis indicated that cutoff values of serum DHEAS for risk of dynapenia in males was 92.0 μg/dL. Therefore, in male individuals with T2D who have low serum levels of DHEAS, adequate exercise might be needed to prevent dynapenia

Canagliflozin reduces epicardial fat in patients with type 2 diabetes mellitus

Background: It is unknown whether canagliflozin, a selective sodium glucose co-transporter 2 inhibitor, reduces epicardial adipose tissue (EAT) thickness, which is associated with insulin resistance and is a risk factor for coronary artery disease. Methods and results: We administered 100 mg of canagliflozin for 6 months to 13 patients with type 2 diabetes mellitus. We evaluated glycemic control, visceral adipose tissue (VAT) area and subcutaneous adipose tissue (SAT) area, and skeletal muscle mass by using impedance methods, and EAT thickness by using echocardiography. Canagliflozin treatment for 6 months decreased hemoglobin A1c level from 7.1 ± 0.5% to 6.7 ± 0.6% (P < 0.05) and decreased EAT thickness from 9.3 ± 2.5 to 7.3 ± 2.0 mm (P < 0.001), along with a trend of decreasing VAT and SAT area. No association was found between any of these changes. Conclusion: Canagliflozin reduced EAT thickness in patients with type 2 diabetes mellitus independent of its effect on lowering blood glucose, suggesting that canagliflozin may have an effect in preventing cardiovascular events in these patients (UMIN000021327)

CHH with Early-Onset CAD

The patient with congenital hypogonadotropic hypogonadism (HH) shows low serum levels of androgen, which is a group of sex hormones including testosterone, caused by the decreased gonadotropin release in the hypothalamus. Recent reports showed androgens exert protective effects against insulin resistance or atherosclerotic diseases, such as diabetes mellitus or coronary artery disease. However, whether the juvenile hypogonadism affects the diabetes or cardiovascular disease is unclear. We report a case of a middle-aged man with congenital HH who had severe coronary artery disease complicated with metabolic disorders