Age and sex effects on paired-pulse suppression and prepulse inhibition of auditory evoked potentials.

Responses to a sensory stimulus are inhibited by a preceding stimulus; if the two stimuli are identical, paired-pulse suppression (PPS) occurs; if the preceding stimulus is too weak to reliably elicit the target response, prepulse inhibition (PPI) occurs. PPS and PPI represent excitability changes in neural circuits induced by the first stimulus, but involve different mechanisms and are impaired in different diseases, e.g., impaired PPS in schizophrenia and Alzheimer's disease and impaired PPI in schizophrenia and movement disorders. Therefore, these measures provide information on several inhibitory mechanisms that may have roles in clinical conditions. In the present study, PPS and PPI of the auditory change-related cortical response were examined to establish normative data on healthy subjects (35 females and 32 males, aged 19-70 years). We also investigated the effects of age and sex on PPS and PPI to clarify whether these variables need to be considered as biases. The test response was elicited by an abrupt increase in sound pressure in a continuous sound and was recorded by electroencephalography. In the PPS experiment, the two change stimuli to elicit the cortical response were a 15-dB increase from the background of 65 dB separated by 600 ms. In the PPI experiment, the prepulse and test stimuli were 2- and 10-dB increases, respectively, with an interval of 50 ms. The results obtained showed that sex exerted similar effects on the two measures, with females having stronger test responses and weaker inhibition. On the other hand, age exerted different effects: aging correlated with stronger test responses and weaker inhibition in the PPS experiment, but had no effects in the PPI experiment. The present results suggest age and sex biases in addition to normative data on PPS and PPI of auditory change-related potentials. PPS and PPI, as well as other similar paradigms, such as P50 gating, may have different and common mechanisms. Collectively, they may provide insights into the pathophysiologies of diseases with impaired inhibitory function.

Intraoperative hypotension affects postoperative acute kidney injury depending on the invasiveness of abdominal surgery: A retrospective cohort study.

Intraoperative hypotension (IOH) or highly invasive surgery adversely affects postoperative clinical outcomes. It is, however, unclear whether IOH affects postoperative acute kidney injury (AKI) depending on the invasiveness of abdominal surgery. We speculated that IOH in highly invasive abdominal surgery is a significant risk factor for postoperative AKI. We retrospectively reviewed the data of 448 patients who underwent abdominal surgery. Patients were divided into 3 groups: highly (such as pancreaticoduodenectomy and hepatectomy), moderately (open abdominal surgery), and minimally (laparoscopic surgery) invasive surgeries. The association between the time-weighted average (TWA) of mean arterial pressure (MAP) values (≤60 and ≤ 55 mm Hg) and AKI occurrences in each group was assessed. Postoperative AKI occurred after highly, moderately, and minimally invasive surgeries in 33 of 222 (14.9%), 14 of 110 (12.7%), and 12 of 116 (10.3%) cases, respectively (P = .526). The median [interquartile range] of TWA-MAP ≤ 60 mm Hg, as an IOH parameter, was 0.94 [0.33-2.08] mm Hg in highly, 0.54 [0.16-1.46] mm Hg in moderately, and 0.14 [0.03-0.57] mm Hg in minimally invasive surgeries (P < 0001). In addition, there was a significant association between TWA-MAP and AKI in highly invasive surgery, unlike in moderately and minimally invasive surgery, with adjusted odds ratios (95% confidence interval) for TWA-MAP ≤ 60 and ≤ 55 mm Hg associated with AKI of 1.23 [1.00-1.52] (P = .049) and 1.55 [1.02-2.36] (P = .041), respectively. Intraoperative MAP ≤ 60 mm Hg in highly invasive abdominal surgery is associated with postoperative AKI, compared to moderately and minimally invasive surgeries. Additionally, low MAP thresholds in highly invasive surgery increase postoperative AKI risk.

The proofreading exonuclease of leading-strand DNA polymerase epsilon prevents replication fork collapse at broken template strands.

Leading-strand DNA replication by polymerase epsilon (Polϵ) across single-strand breaks (SSBs) causes single-ended double-strand breaks (seDSBs), which are repaired via homology-directed repair (HDR) and suppressed by fork reversal (FR). Although previous studies identified many molecules required for hydroxyurea-induced FR, FR at seDSBs is poorly understood. Here, we identified molecules that specifically mediate FR at seDSBs. Because FR at seDSBs requires poly(ADP ribose)polymerase 1 (PARP1), we hypothesized that seDSB/FR-associated molecules would increase tolerance to camptothecin (CPT) but not the PARP inhibitor olaparib, even though both anti-cancer agents generate seDSBs. Indeed, we uncovered that Polϵ exonuclease and CTF18, a Polϵ cofactor, increased tolerance to CPT but not olaparib. To explore potential functional interactions between Polϵ exonuclease, CTF18, and PARP1, we created exonuclease-deficient POLE1exo-/-, CTF18-/-, PARP1-/-, CTF18-/-/POLE1exo-/-, PARP1-/-/POLE1exo-/-, and CTF18-/-/PARP1-/- cells. Epistasis analysis indicated that Polϵ exonuclease and CTF18 were interdependent and required PARP1 for CPT tolerance. Remarkably, POLE1exo-/- and HDR-deficient BRCA1-/- cells exhibited similar CPT sensitivity. Moreover, combining POLE1exo-/- with BRCA1-/- mutations synergistically increased CPT sensitivity. In conclusion, the newly identified PARP1-CTF18-Polϵ exonuclease axis and HDR act independently to prevent fork collapse at seDSBs. Olaparib inhibits this axis, explaining the pronounced cytotoxic effects of olaparib on HDR-deficient cells.

Intra-soft tissue and intramedullary antibiotic perfusion in combination with negative pressure wound therapy.

OBJECTIVE: Intra-soft tissue and intramedullary antibiotic perfusion (iSAP and iMAP), which combine continuous administration of antibiotic solution to the wound and negative pressure wound therapy (NPWT), have been reported to be a useful management approach for hard-to-heal ulcers in the field of orthopaedic surgery. We report the efficacy of this treatment and discuss the key points. METHOD: The recipients of this treatment had contaminated fresh severe trauma with a high risk of infection, or hard-to-heal ulcers which were expected to be difficult to manage with conventional NPWT alone. Continuous administration of 1200µg/ml of gentamicin (GM) solution to the wound was performed along with NPWT. The GM solution was administered subcutaneously using a small catheter for iSAP, while intramedullary administration used a bone marrow needle for iMAP. RESULTS: iSAP was employed in all 10 patients who took part, and iMAP in three of these patients. The average treatment time was 13.6 days with iSAP and 9.3 days with iMAP. The mean serum GM level during the therapy was 1.02µg/ml. Moderate GM-induced acute kidney injury was suspected in one case, but resolved spontaneously after GM administration was stopped. Favourable wound bed preparation was achieved in all cases without recurrence of infection. CONCLUSION: Combination with continuous suction by NPWT is able to keep the local concentration of antibiotic above the minimum inhibitory concentration of biofilm-coated bacteria within the wound. We have referred to this treatment as continuous local antibiotic perfusion. Further investigation of local pharmacodynamics in the wound and side-effects of this treatment are warranted.

CTF18-RFC contributes to cellular tolerance against chain-terminating nucleoside analogs (CTNAs) in cooperation with proofreading exonuclease activity of DNA polymerase ε.

Chemotherapeutic nucleoside analogs, such as cytarabine (Ara-C), are incorporated into genomic DNA during replication. Incorporated Ara-CMP (Ara-cytidine monophosphate) serves as a chain terminator and inhibits DNA synthesis by replicative polymerase epsilon (Polε). The proofreading exonuclease activity of Polε removes the misincorporated Ara-CMP, thereby contributing to the cellular tolerance to Ara-C. Purified Polε performs proofreading, and it is generally believed that proofreading in vivo does not need additional factors. In this study, we demonstrated that the proofreading by Polε in vivo requires CTF18, a component of the leading-strand replisome. We found that loss of CTF18 in chicken DT40 cells and human TK6 cells results in hypersensitivity to Ara-C, indicating the conserved function of CTF18 in the cellular tolerance of Ara-C. Strikingly, we found that proofreading-deficient POLE1D269A/-, CTF18-/-, and POLE1D269A/-/CTF18-/- cells showed indistinguishable phenotypes, including the extent of hypersensitivity to Ara-C and decreased replication rate with Ara-C. This observed epistatic relationship between POLE1D269A/- and CTF18-/- suggests that they are interdependent in removing mis-incorporated Ara-CMP from the 3' end of primers. Mechanistically, we found that CTF18-/- cells have reduced levels of chromatin-bound Polε upon Ara-C treatment, suggesting that CTF18 contributes to the tethering of Polε on fork at the stalled end and thereby facilitating the removal of inserted Ara-C. Collectively, these data reveal the previously unappreciated role of CTF18 in Polε-exonuclease-mediated maintenance of the replication fork upon Ara-C incorporation.

The 40-Hz auditory steady-state response enhanced by beta-band subharmonics.

The 40-Hz auditory steady-state response (ASSR) has received special attention as an index of gamma oscillations owing to its association with various neuropsychiatric disorders including schizophrenia. When a periodic stimulus is presented, oscillatory responses are often elicited not only at the stimulus frequency, but also at its harmonic frequencies. However, little is known about the effect of 40-Hz subharmonic stimuli on the activity of the 40-Hz ASSR. In the present magnetoencephalography study, we focused on the nature of oscillation harmonics and examined oscillations in a wide frequency range using a time-frequency analysis during the 6.67-, 8-, 10-, 13.3-, 20-, and 40-Hz auditory stimuli in 23 healthy subjects. The results suggested that the 40-Hz ASSR represents activation of a specific circuit tuned to this frequency. Particularly, oscillations elicited by 13.3- and 20-Hz stimuli exhibited significant enhancement at 40 Hz without changing those at the stimulus frequency. In addition, it was found that there was a non-linear response to stimulation in the beta band. We also demonstrated that the inhibition of beta to low-gamma oscillations by the 40-Hz circuit contributed to the violation of the rule that harmonic oscillations gradually decrease at higher frequencies. These findings can advance our understanding of oscillatory abnormalities in patients with schizophrenia in the future.

Accuracy of a noninvasive estimated continuous cardiac output measurement under different respiratory conditions: a prospective observational study.

PURPOSE: The estimated continuous cardiac output (esCCO) system was recently developed as a noninvasive hemodynamic monitoring alternative to the thermodilution cardiac output (TDCO). However, the accuracy of continuous cardiac output measurements by the esCCO system compared to TDCO under different respiratory conditions remains unclear. This prospective study aimed to assess the clinical accuracy of the esCCO system by continuously measuring the esCCO and TDCO. METHODS: Forty patients who had undergone cardiac surgery with a pulmonary artery catheter were enrolled. We compared the esCCO with TDCO from mechanical ventilation to spontaneous respiration through extubation. Patients undergoing cardiac pacing during esCCO measurement, those receiving treatment with an intra-aortic balloon pump, and those with measurement errors or missing data were excluded. In total, 23 patients were included. Agreement between the esCCO and TDCO measurements was evaluated using Bland-Altman analysis with a 20 min moving average of the esCCO. RESULTS: The paired esCCO and TDCO measurements (939 points before extubation and 1112 points after extubation) were compared. The respective bias and standard deviation (SD) values were 0.13 L/min and 0.60 L/min before extubation, and - 0.48 L/min and 0.78 L/min after extubation. There was a significant difference in bias before and after extubation (P < 0.001); the SD before and after extubation was not significant (P = 0.315). The percentage errors were 25.1% before extubation and 29.6% after extubation, which is the criterion for acceptance of a new technique. CONCLUSION: The accuracy of the esCCO system is clinically acceptable to that of TDCO under mechanical ventilation and spontaneous respiration.

Cortical activity during the wind-up of flexion reflex and pain: a magnetoencephalographic study using time-frequency analysis.

Wind-up is a nociceptive-specific phenomenon in which pain sensations are facilitated, in a frequency-dependent manner, by the repeated application of noxious stimuli of constant intensity, with invariant tactile sensations. Thus, cortical activities during wind-up could be an alteration associated with pain potentiation. We aimed to investigate somatosensory-evoked cortical responses and induced brain oscillations during wind-up by recording magnetoencephalograms. Wind-up was produced by the application of 11 consecutive electrical stimuli to the sural nerve, repeated at a frequency of 1 Hz without varying the intensity. The augmentation of flexion reflexes and pain rating scores were measured simultaneously as an index of wind-up. In the time-frequency analyses, the γ-band late event-related synchronization and the ß-band event-related desynchronization were observed in the primary somatosensory region and the bilateral operculo-insular region, respectively. Repetitive exposure to the stimuli enhanced these activities, along with an increase in the flexion reflex magnitude. The evoked cortical activity reflected novelty, with no alteration to these repetitive stimuli. Observed oscillations enhanced by repetitive stimulation at a constant intensity could reflect a pain mechanism associated with wind-up.

Application of neural network-based image analysis to detect sister chromatid cohesion defects.

Sister chromatid cohesion (SCC) is mediated by the cohesin complex and its regulatory proteins. To evaluate the involvement of a protein in cohesin regulation, preparations of metaphase chromosome spreads and classifications of chromosome shapes after depletion of the target protein are commonly employed. Although this is a convenient and approved method, the evaluation and classification of each chromosome shape has to be performed manually by researchers. Therefore, this method is time consuming, and the results might be affected by the subjectivity of researchers. In this study, we developed neural network-based image recognition models to judge the positional relationship of sister chromatids, and thereby detect SCC defects. Transfer learning models based on SqueeezeNet or ResNet-18 were trained with more than 600 chromosome images labeled with the type of chromosome, which were classified according to the positional relationship between sister chromatids. The SqueezeNet-based trained model achieved a concordance rate of 73.1% with the sample answers given by a researcher. Importantly, the model successfully detected the SCC defect in the CTF18 deficient cell line, which was used as an SCC-defective model. These results indicate that neural-network-based image recognition models are valuable tools for examining SCC defects in different genetic backgrounds.

Target Site of Prepulse Inhibition of the Trigeminal Blink Reflex in Humans.

Despite the clinical significance of prepulse inhibition (PPI), the mechanisms are not well understood. Herein, we present our investigation of PPI in the R1 component of electrically induced blink reflexes. The effect of a prepulse was explored with varying prepulse test intervals (PTIs) of 20-600 ms in 4 females and 12 males. Prepulse-test combinations included the following: stimulation of the supraorbital nerve (SON)-SON [Experiment (Exp) 1], sound-sound (Exp 2), the axon of the facial nerve-SON (Exp 3), sound-SON (Exp 4), and SON-SON with a long trial-trial interval (Exp 5). Results showed that (1) leading weak SON stimulation reduced SON-induced ipsilateral R1 with a maximum effect at a PTI of 140 ms, (2) the sound-sound paradigm resulted in a U-shaped inhibition time course of the auditory startle reflex (ASR) peaking at 140 ms PTI, (3) facial nerve stimulation showed only a weak effect on R1, (4) a weak sound prepulse facilitated R1 but strongly inhibited SON-induced late blink reflexes (LateRs) with a similar U-shaped curve, and (5) LateR in Exp 5 was almost completely absent at PTIs >80 ms. These results indicate that the principal sensory nucleus is responsible for R1 PPI. Inhibition of ASR or LateR occurs at a point in the startle reflex circuit where auditory and somatosensory signals converge. Although the two inhibitions are different in location, their similar time courses suggest similar neural mechanisms. As R1 has a simple circuit and is stable, R1 PPI helps to clarify PPI mechanisms.SIGNIFICANCE STATEMENT Prepulse inhibition (PPI) is a phenomenon in which the startle response induced by a startle stimulus is suppressed by a preceding nonstartle stimulus. This study demonstrated that the R1 component of the trigeminal blink reflex shows clear PPI despite R1 generation within a circuit consisting of the trigeminal and facial nuclei, without startle reflex circuit involvement. Thus, PPI is not specific to the startle reflex. In addition, PPI of R1, the auditory startle reflex, and the trigeminal late blink reflex showed similar time courses in response to the prepulse test interval, suggesting similar mechanisms regardless of inhibition site. R1 PPI, in conjunction with other paradigms with different prepulse-test combinations, would increase understanding of the underlying mechanisms.

Mechanisms of Short- and Long-Latency Sensory Suppression: Magnetoencephalography Study.

Prepulse inhibition (PPI) is sensory suppression whose mechanism (i.e., whether PPI originates from specific inhibitory mechanisms) remains unclear. In this study, we applied the combination of short-latency PPI and long-latency paired pulse suppression in 17 healthy subjects using magnetoencephalography to investigate the mechanisms of sensory suppression. Repeats of a 25-ms pure tone without a blank at 800 Hz and 70 dB were used for a total duration of 1600 ms. To elicit change-related cortical responses, the sound pressure of two consecutive tones in this series at 1300 ms was increased to 80 dB (Test). For the conditioning stimuli, the sound pressure was increased to 73 dB at 1250 ms (Pre 1) and 80 dB at 700 ms (Pre 2). Six stimuli were randomly presented as follows: (1) Test alone, (2) Pre 1 alone, (3) Pre 1 + Test, (4) Pre 2 + Test, (5) Pre 2 + Pre 1, and (6) Pre 2 + Pre 1 + Test. The inhibitory effects of the conditioning stimuli were evaluated using N100m/P200m components. The results showed that both Pre 1 and Pre 2 significantly suppressed the Test response. Moreover, the inhibitory effects of Pre 1 and Pre 2 were additive. However, when both prepulses were present, Pre 2 significantly suppressed the Pre 1 response, suggesting that the Pre 1 response amplitude was not a determining factor for the degree of suppression. These results suggested that the suppression originated from a specific inhibitory circuit independent of the excitatory pathway.

Risk factors for postoperative sore throat associated with i-gel™, a supraglottic airway device.

i-gel™ is a supraglottic airway device widely used for airway management during general anesthesia as an alternative to tracheal intubation. It sometimes results in a sore throat postoperatively; however, the risk factors for a postoperative sore throat caused by i-gel remain unclear. Here, we clarify the risk factors for a postoperative sore throat associated with i-gel insertion. We retrospectively reviewed the data of 426 adult patients who received general anesthesia with i-gel at our institution from January 2018 to December 2019. The incidence of postoperative sore throat and intraoperative data (size of i-gel, number of insertion attempts, total insertion time, and dose of the neuromuscular blocker and opioid) were evaluated. Logistic regression analysis was performed to identify the risk factors. Postoperative sore throat following i-gel insertion occurred in 24/426 patients (5.6%). The insertion time was significantly associated with the incidence of postoperative sore throat in the univariate analysis, but not in the multivariate analysis (P=0.519). Increased doses of neuromuscular blockers before i-gel insertion (odds ratio [OR], 5.46; 95% confidence interval [CI], 1.50-19.80; P=0.001) and reduced doses of intraoperative fentanyl (OR, 0.51; 95% CI, 0.28-0.93; P=0.028) were risk factors in the univariate and multivariate analyses. In the subgroup that used neuromuscular blockers before i-gel insertion, only an increased dose of neuromuscular blocker (OR, 17.2; 95%, CI 1.06-280; P=0.046) was an associated risk factor in the univariate and multivariate analyses. Overall, increased doses of neuromuscular blockers before i-gel insertion could contribute to the development of postoperative sore throat.

A Minimally Invasive Method for Observing Wind-Up of Flexion Reflex in Humans: Comparison of Electrical and Magnetic Stimulation.

Wind-up like pain or temporal summation of pain is a phenomenon in which pain sensation is increased in a frequency-dependent manner by applying repeated noxious stimuli of uniform intensity. Temporal summation in humans has been studied by observing the increase in pain or flexion reflex by repetitive electrical or thermal stimulations. Nonetheless, because the measurement is accompanied by severe pain, a minimally invasive method is desirable. Gradual augmentation of flexion reflex and pain induced by repetitive stimulation of the sural nerve was observed using three stimulation methods-namely, bipolar electrical, magnetic, and monopolar electrical stimulation, with 11 healthy male subjects in each group. The effects of frequency, intensity, and number of repetitive stimuli on the increase in the magnitude of flexion reflex and pain rating were compared among the three methods. The reflex was measured using electromyography (EMG) from the short head of the biceps femoris. All three methods produced a frequency- and intensity-dependent progressive increase in reflex and pain; pain scores were significantly lower for magnetic and monopolar stimulations than for bipolar stimulation (P < 0.05). The slope of increase in the reflex was steep during the first 4-6 stimuli but became gentler thereafter. In the initial phase, an increase in the reflex during the time before signals of C-fibers arrived at the spinal cord was observed in experiments using high-frequency stimulation, suggesting that wind-up was caused by inputs of A-fibers without the involvement of C-fibers. Magnetic and monopolar stimulations are minimally invasive and useful methods for observing the wind-up of the flexion reflex in humans. Monopolar stimulation is convenient because it does not require special equipment. There is at least a partial mechanism underlying the wind-up of the flexion reflex that does not require C-fibers.

Suppression of Low-Frequency Gamma Oscillations by Activation of 40-Hz Oscillation.

Gamma oscillations have received considerable attention owing to their association with cognitive function and various neuropsychiatric disorders. However, interactions of gamma oscillations at different frequency bands in humans remain unclear. In the present magnetoencephalographic study, brain oscillations in a wide frequency range were examined using a time-frequency analysis during the 20-, 30-, 40-, and 50-Hz auditory stimuli in 21 healthy subjects. First, dipoles for auditory steady-state response (ASSR) were estimated and interaction among oscillations at 10-60 Hz was examined using the source strength waveforms. Results showed the suppression of ongoing low-gamma oscillations at approximately 30 Hz during stimulation at 40 Hz. Second, multi-dipole analyses suggested that the main dipole for ASSR and dipoles for suppressed low-frequency gamma oscillations were distinct. Third, an all-sensor analysis was performed to clarify the distribution of the 40-Hz ASSR and suppression of low-frequency gamma oscillations. Notably, the area of suppression surrounded the center of the 40-Hz ASSR and showed a trend of extending to the vertex, indicating that different groups of neurons were responsible for these two gamma oscillations and that the 40-Hz oscillation circuit have specific inhibitory innervation to the low-gamma circuit.

Mechanisms of Long-Latency Paired Pulse Suppression: MEG Study.

Paired pulse suppression is an electrophysiological method used to evaluate sensory suppression and often applied to patients with psychiatric disorders. However, it remains unclear whether the suppression comes from specific inhibitory mechanisms, refractoriness, or fatigue. In the present study, to investigate mechanisms of suppression induced by an auditory paired pulse paradigm in 19 healthy subjects, magnetoencephalography was employed. The control stimulus was a train of 25-ms pure tones of 65 dB SPL for 2500 ms. In order to evoke a test response, the sound pressure of two consecutive tones at 2200 ms in the control sound was increased to 80 dB (Test stimulus). Similar sound pressure changes were also inserted at 1000 (CS2) and 1600 (CS1) ms as conditioning stimuli. Four stimulus conditions were used; (1) Test alone, (2) Test + CS1, (3) Test + CS1 + CS2, and (4) Test + CS2, with the four sound stimuli randomly presented and cortical responses averaged at least 100 times for each condition. The baseline-to-peak and peak-to-peak amplitudes of the P50m, N100m, and P200m components of the test response were compared among the four conditions. In addition, the response to CS1 was compared between conditions (2) and (3). The results showed significant test response suppression by CS1. While the response to CS1 was significantly suppressed when CS2 was present, it did not affect suppression of the test response by CS1. It was thus suggested that the amplitude of the response to a conditioning stimulus is not a factor to determine the inhibitory effects of the test response, indicating that suppression is due to an external influence on the excitatory pathway.

Conditioned Pain Modulation: Comparison of the Effects on Nociceptive and Non-nociceptive Blink Reflex.

Although conditioned pain modulation (CPM) is considered to represent descending pain inhibitory mechanisms triggered by noxious stimuli applied to a remote area, there have been no previous studies comparing CPM between pain and tactile systems. In this study, we compared CPM between the two systems objectively using blink reflexes. Intra-epidermal electrical stimulation (IES) and transcutaneous electrical stimulation (TS) were applied to the right skin area over the supraorbital foramen to evoke a nociceptive or a non-nociceptive blink reflex, respectively, in 15 healthy males. In the test session, IES or TS were applied six times and subjects reported the intensity of each stimulus on a numerical rating scale (NRS). Blink reflexes were measured using electromyography (R2). The first and second sessions were control sessions, while in the third session, the left hand was immersed in cold water at 10 °C as a conditioning stimulus. The magnitude of the R2 blink and NRS scores were compared among the sessions by 2-way ANOVA. Both the NRS score and nociceptive R2 were significantly decreased in the third session for IES, with a significant correlation between the two variables; whereas, TS-induced non-nociceptive R2 did not change among the sessions. Although the conditioning stimulus decreased the NRS score for TS, the CPM effect was significantly smaller than that for IES (p = 0.002). The present findings suggest the presence of a pain-specific CPM effect to a heterotopic noxious stimulus.

The Auditory Steady-State Response: Electrophysiological Index for Sensory Processing Dysfunction in Psychiatric Disorders.

Sensory processing is disrupted in several psychiatric disorders, including schizophrenia, bipolar disorder, and autism spectrum disorder. In this review, we focus on the electrophysiological auditory steady-state response (ASSR) driven by high-frequency stimulus trains as an index for disease-associated sensory processing deficits. The ASSR amplitude is suppressed within the gamma band (≥30 Hz) among these patients, suggesting an imbalance between GABAergic and N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission. The reduced power and synchronization of the 40-Hz ASSR are robust in patients with schizophrenia. In recent years, similar ASSR deficits at gamma frequencies have also been reported in patients with bipolar disorder and autism spectrum disorder. We summarize ASSR abnormalities in each of these psychiatric disorders and suggest that the observed commonalities reflect shared pathophysiological mechanisms. We reviewed studies on phase resetting in which a salient sensory stimulus affects ASSR. Phase resetting induces the reduction of both the amplitude and phase of ASSR. Moreover, phase resetting is also affected by rare auditory stimulus patterns or superimposed stimuli of other modalities. Thus, sensory memory and multisensory integration can be investigated using phase resetting of ASSR. Here, we propose that ASSR amplitude, phase, and resetting responses are sensitive indices for investigating sensory processing dysfunction in psychiatric disorders.

Label-free, chronological and selective detection of aggregation and fibrillization of amyloid ß protein in serum by microcantilever sensor immobilizing cholesterol-incorporated liposome.

To facilitate the early diagnosis of Alzheimer's disease and mild cognitive impairment patients, we developed a cantilever-based microsensor that immobilized liposomes of various phospholipids to detect a trace amount of amyloid ß (Aß) protein, and investigated its aggregation and fibrillization on model cell membranes in human serum. Three species of liposomes composed of different phospholipids of 1,2-dipalmtoyl-sn-glycero-3-phosphocholine (DPPC), DPPC/phosphatidyl ethanolamine and 1,2-dipalmitoyl-sn-glycero-3-phosphorylglycerol having varied hydrophilic groups were applied, which showed different chronological interactions with Aß(1-40) protein and varied sensitivities of the cantilever sensor, depending on their specific electrostatic charged conditions, hydrophilicity, and membrane fluidity. 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) having short hydrophobic carbon chains confirmed to show a large interaction with Aß(1-40) and a high sensitivity. Furthermore, the incorporation of cholesterol into DMPC was effective to selectively detect Aß(1-40) in human serum, which effect was also checked by quartz crystal microbalance. Finally, Aß detection of 100-pM order was expected selectively in the serum by using the developed biosensor.

Autopsy Case of a Penetrating Wound to the Left Cerebral Hemisphere Caused by an Accidental Shooting With a Crossbow.

A crossbow is a bow that shoots an arrow when a gun-like trigger is pulled. Deaths caused by accidental crossbow shootings are extremely rare. Here we describe an autopsy case of a penetrating wound to the left cerebral hemisphere caused by an accidental shooting with a crossbow. A man in his early 60s who lived with his wife and had used crossbows for 20 years as his hobby was found one early morning in the shed of his house, collapsed and bleeding from the head and neck. He was taken to a hospital and died after approximately 3 days of conservative treatment. At autopsy, a penetrating wound between the upper part of the left anterior neck and the left frontoparietal region was evident. Traumatic intracerebral hematoma was observed in the left frontal lobe, and severe traumatic subarachnoid hemorrhage was present throughout the brain. Cerebral contusion and hematoma without any organization were noted around the penetration. The cause of death was determined to be cerebral contusion and intracerebral hematoma due to the penetrating wound by the crossbow arrow. He was probably trying to load an arrow into the crossbow by placing it on the floor, pointing upward, and made a mistake in its operation that resulted in the shooting of the arrow. This case is unique because it was a rare accidental death caused by a crossbow arrow, and a detailed histopathological examination was performed.

Abrupt change of the superconducting gap structure at the nematic critical point in FeSe1-xSx.

The emergence of the nematic electronic state that breaks rotational symmetry is one of the most fascinating properties of the iron-based superconductors, and has relevance to cuprates as well. FeSe has a unique ground state in which superconductivity coexists with a nematic order without long-range magnetic ordering, providing a significant opportunity to investigate the role of nematicity in the superconducting pairing interaction. Here, to reveal how the superconducting gap evolves with nematicity, we measure the thermal conductivity and specific heat of FeSe1 - x S x , in which the nematicity is suppressed by isoelectronic sulfur substitution and a nematic critical point (NCP) appears at [Formula: see text] We find that, in the whole nematic regime ([Formula: see text]), the field dependence of two quantities consistently shows two-gap behavior; one gap is small but highly anisotropic with deep minima or line nodes, and the other is larger and more isotropic. In stark contrast, in the tetragonal regime ([Formula: see text]), the larger gap becomes strongly anisotropic, demonstrating an abrupt change in the superconducting gap structure at the NCP. Near the NCP, charge fluctuations of [Formula: see text] and [Formula: see text] orbitals are enhanced equally in the tetragonal side, whereas they develop differently in the orthorhombic side. Our observation therefore directly implies that the orbital-dependent nature of the nematic fluctuations has a strong impact on the superconducting gap structure and hence on the pairing interaction.