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Abstract Adrenoleukodystrophy (ALD), an X-linked leukodystrophy caused by pathogenic variants in ABCD1, exhibits a broad range of phenotypes from childhood-onset cerebral forms to adult-onset adrenomyeloneuropathy (AMN). We report a rare in-frame ABCD1 deletion c.1469_71delTGG (p.Val490del) in a man with AMN. Although this variant has been interpreted as ‘uncertain significance’ in ClinVar, biochemical analysis along with clinical evaluation confirmed the pathogenicity of this variant, underscoring the importance of functional assessment of in-frame deletions.

Abstract Objective Amyotrophic lateral sclerosis (ALS) is a devastating, incurable neurodegenerative disease. A subset of ALS patients manifests with early‐onset and complex clinical phenotypes. We aimed to elucidate the genetic basis of these cases to enhance our understanding of disease etiology and facilitate the development of targeted therapies. Methods Our research commenced with an in‐depth genetic and biochemical investigation of two specific families, each with a member diagnosed with early‐onset ALS (onset age of

Objective: This study aimed to determine the maximum safe dose of intranasal insulin administration during cardiac surgery. Methods: This open-label, Phase 1, single-center, dose-escalation clinical trial recruited patients scheduled to undergo elective cardiac surgery or major vascular surgery requiring cardiopulmonary bypass between February and September 2021. They were grouped into 5 dose-escalation cohorts and administered 0, 40, 80, 160, and 240 IU insulin (n = 6 in each group) via a metered nasal dispenser after the induction of general anesthesia. Blood samples were collected at 10-minute intervals for the first 60 minutes and at 30-minute intervals thereafter. Hypoglycemia was defined as a blood glucose level

ABSTRACT Objective Adrenoleukodystrophy (ALD) has a poor prognosis when it progresses to the cerebral form (CALD). The aim of this study is to investigate whether cerebrospinal fluid (CSF) neurofilament light chain (cNfL) is a sensitive biomarker for detecting CALD and assessing response to hematopoietic stem cell transplantation (HSCT). Methods We conducted a cross‐sectional study of 41 male ALD patients. The cNfL levels in patients with the cerebral form of ALD (CALD) or the cerebello‐brainstem form of ALD were compared with those in patients with adrenomyeloneuropathy (AMN). The correlation between cNfL levels and MRI‐based Loes severity scores was investigated. A longitudinal analysis was performed on patients who underwent multiple CSF examinations. Results The cNfL levels in 22 patients with CALD were significantly higher than those in 14 patients with AMN (median, 5545 vs. 1490 pg/mL; p

Abstract Background Idiopathic basal ganglia calcification (IBGC), also known as Farh's disease, is a rare neurodegenerative disorder characterized by calcification of the basal ganglia and other brain regions. This disease usually occurs in middle‐aged patients and presents with various neurological and psychiatric symptoms. The exact prevalence is unknown; however, population genomic data analysis suggests a prevalence of at least 4.5/10,000 to 3.3/1000, indicating that the disease is more common than previously thought and remains underdiagnosed. Case Presentation We report the case of a middle‐aged Japanese man who attempted suicide twice because of obsessive‐compulsive ideation caused by trivial triggers. The patient's psychiatric symptoms resolved relatively quickly after hospitalization, and imaging and genetic testing led to a diagnosis of IBGC. Conclusion This case report illustrates the importance of including IBGC in the differential diagnosis of psychiatric symptoms that initially develop in middle‐aged patients.

Abstract Background Postoperative pain and inflammation are significant complications following surgery. Strategies that aim to prevent excessive inflammation without hampering natural wound-healing are required for the management of postoperative pain and inflammation. However, the knowledge of the mechanisms and target pathways involved in these processes is lacking. Recent studies have revealed that autophagy in macrophages sequesters pro-inflammatory mediators, and it is therefore being recognized as a crucial process involved in regulating inflammation. In this study, we tested the hypothesis that autophagy in macrophages plays protective roles against postoperative pain and inflammation and investigated the underlying mechanisms. Methods Postoperative pain was induced by plantar incision under isoflurane anesthesia in mice lacking macrophage autophagy (Atg5flox/flox LysMCre +) and their control littermates (Atg5flox/flox). Mechanical and thermal pain sensitivity, changes in weight distribution, spontaneous locomotor activity, tissue inflammation, and body weight were assessed at baseline and 1, 3, and 7 days after surgery. Monocyte/macrophage infiltration at the surgical site and inflammatory mediator expression levels were evaluated. Results Atg5flox/flox LysMCre + mice compared with the control mice exhibited lower mechanical and thermal pain thresholds and surgical/non-surgical hindlimb weight-bearing ratios. The augmented neurobehavioral symptoms observed in the Atg5flox/flox LysMCre + mice were associated with more severe paw inflammation, higher pro-inflammatory mediator mRNA expression, and more monocytes/macrophages at the surgical site. Conclusion The lack of macrophage autophagy augmented postoperative pain and inflammation, which were accompanied by enhanced pro-inflammatory cytokine secretion and surgical-site monocyte/macrophage infiltration. Macrophage autophagy plays a protective role in postoperative pain and inflammation and can be a novel therapeutic target.

Abstract Background With recent advances in robot-assisted techniques, an increasing number of surgeries are being performed with pneumoperitoneum and head-down maneuver (HDM) that may affect the cerebral microcirculation. For the first time, this study investigated the direct influence of pneumoperitoneum and HDM on the cerebral microvasculature in rabbits. Methods Adult male rabbits were randomly allocated to the following groups (n = 7 each): control, pneumoperitoneum alone (P), and pneumoperitoneum with HDM (P + HDM) for 120 min. A closed cranial window was installed above the parietal bone to visualize the pial microvasculature. Pial arteriolar diameter and hemodynamic and blood gas parameters were measured during the 140-min observation period. Brain edema was assessed by evaluation of the brain water content at the end of the experiment. Results Rabbits in the P and P + HDM groups exhibited a similar degree of immediate pial arteriolar dilation following the initiation of both P and P + HDM (P: 1.11 ± 0.03, p = 0.0044 and P + HDM: 1.07 ± 0.02, p = 0.0004, relative changes from the baseline value by defining the baseline as one). In the P + HDM group, pial arteriole diameter returned to the baseline level following the discontinuation of pneumoperitoneum and HDM (1.05 ± 0.03, p = 0.0906, vs. baseline). In contrast, the pial arterioles remained dilated as compared to the baseline level in the P group after discontinuation of pneumoperitoneum. There were no changes in pial arteriole diameter in the animals in the control group. Heart rate, blood gas parameters, and brain water content were not significantly different between the groups. Conclusion The pial arterioles dilated immediately after pneumoperitoneum with or without HDM. The pial arterioles remained dilated 20 min after discontinuation of pneumoperitoneum alone but constricted upon discontinuation of pneumoperitoneum plus HDM. Pneumoperitoneum and HDM for 2 h did not cause brain edema.

Abstract Background During cardiopulmonary resuscitation, the brain becomes ischemic. Adrenaline and vasopressin have been recommended for use during cardiopulmonary resuscitation. We aimed to investigate the direct effects of adrenaline and vasopressin on the cerebral microvasculature at baseline and during ischemia and reperfusion in rabbits. Methods The closed cranial window method was used to visualize the cerebral microcirculation and changes in the pial arteriole diameter in rabbits. Adrenaline and vasopressin were administered topically on the brain tissue. First, the effects of adrenaline and vasopressin on pial arterioles were evaluated in 7 rabbits that were given 4 different concentrations of adrenaline, and another 7 rabbits that received 4 different concentrations of vasopressin. Second, the effects of adrenaline and vasopressin were determined during the global brain ischemia and reperfusion, which was induced by clamping the brachiocephalic, left common carotid, and left subclavian arteries for 15 min. An additional 21 rabbits were randomly assigned to receive artificial cerebrospinal fluid (aCSF) (n = 7), adrenaline 10–5 mol/L (n = 7), or vasopressin 10–7 mol/L (n = 7). Each drug was continuously infused from 5 min after the initiation of ischemia until 120 min after reperfusion. The pial arteriole diameters were recorded before and during ischemia, and after reperfusion. Results At baseline, adrenaline and vasopressin did not affect the cerebral pial arterioles. During ischemia, vasopressin, but not aCSF and adrenaline constricted the pial vessels. Late in the reperfusion phase, pial diameter became reduced in the vasopressin and aCSF groups whereas pial diameter was higher in the animals treated with adrenaline. Conclusions Adrenaline and vasopressin did not affect pial arterioles at baseline. During reperfusion, adrenaline may counteract the cerebral vasoconstriction.

Abstract Background: Lactoferrin, an iron-binding glycoprotein, is known to have protective effects against intestinal and cerebral ischemia-reperfusion (IR) injuries; however, its cardioprotective effects against the stunned myocardium are unknown. This study aimed to test the hypothesis that lactoferrin has cardioprotective effects against stunned myocardium. Methods: Using isolated rat hearts (Langendorff system), we determined the effects of lactoferrin administered enterally and by direct cardiac perfusion. Rat hearts were perfused using the Langendorff system, and two experiments were performed. In experiment 1, the hearts were divided into the enteral lactoferrin (E-LF) 7.5 m, 15 m, 30 m, and 60 m groups, where lactoferrin (1000 mg/kg) was administered enterally 7.5, 15, 30, and 60 min, respectively, before perfusion; and a control group, where saline was administered 30 min before perfusion. In experiment 2, hearts were allocated to the perfusate lactoferrin (P-LF) 15 and 100 groups, where 15 mg/L and 100 mg/L lactoferrin were respectively added to the perfusate, and a control group. Each group was perfused for 20 min prior to 15 min of no-flow ischemia with pacing, followed by 20 min of reperfusion. The primary outcome was the maximum left ventricular derivative of pressure development (LV dP/dt max) 15 min after reperfusion. Myocardial phospho-protein kinase B (p-Akt) was assayed using western blotting. Results: The LV dP/dt max 15 min after reperfusion in the E-LF 15 and 30 m groups was significantly higher than that in the control group. However, the effects disappeared in the E-LF 60 m group. In the second experiment, there were no significant differences in LV dP/dt max. Myocardial p-Akt was not significantly activated in any lactoferrin group. Conclusion: Cardioprotection was observed 15–30 min after enteral lactoferrin but not by direct cardiac perfusion with lactoferrin. Myocardial p-Akt was not associated with the cardioprotective effect. The cardioprotective effect may be induced by enteral lactoferrin-induced substances.

Abstract Insulin exerts positive inotropic effects on cardiac muscle; however, the relationship between cardiac contractility and phosphoinositol-3-kinase/Akt (PI3K/Akt) activation remains unclear. We hypothesized that the positive inotropic effects of insulin are dose-dependent and mediated via the PI3K/Akt pathway in isolated normal rat hearts. The Institutional Animal Investigation Committee approved the use of hearts excised from rats under pentobarbital anesthesia. The hearts were perfused at a constant pressure using the Langendorff technique. After stabilization (baseline), the hearts were randomly divided into the following four insulin (Ins) groups: 1) Ins0 (0 IU/L), 2) Ins0.5 (0.5 IU/L), 3) Ins5 (5 IU/L), and 4) Ins50 (50 IU/L) (n = 8 in each group). To clarify the role of the PI3K/Akt pathway in insulin-dependent inotropic effects, we also treated the insulin groups with the PI3K inhibitor wortmannin (InsW): 5) InsW0 (0 IU/L), 6) InsW0.5 (0.5 IU/L), 7) InsW5 (5 IU/L), and 8) InsW50 (50 IU/L). Hearts were perfused with Krebs–Henseleit buffer solution with or without wortmannin for 10 min, followed by 20 min perfusion with the solution containing each concentration of insulin. The data were recorded as the maximum left ventricular derivative of pressure development (LV dP/dt max). Myocardial p-Akt levels were measured at 3 min, 5 min, and at the end of the perfusion. In the Ins groups, LV dP/dt max in Ins5 and Ins50 increased by 14% and 48%, respectively, 3 min after insulin perfusion compared with the baseline. Tachyphylaxis was observed after 10 min in the Ins5 and Ins50 treatment groups. Wortmannin partially inhibited the positive inotropic effect of insulin; although insulin enhanced p-Akt levels at all time points compared with the control group, this increase was suppressed in the presence of wortmannin. The positive inotropic effect of insulin is dose-dependent and consistent with Akt activation. This effect mediated by high doses of insulin on cardiac tissue was temporary and caused tachyphylaxis, potentially triggered by Akt overactivation, which leads beta 1 deactivation.

Abstract Background Accidental dural puncture (ADP), which is a complication of epidural anesthesia, still exists and leads to worse outcomes in surgical patients. While residency training is important for epidural competency, it remains unknown whether anesthetic experience reduces ADP in surgical patients. Using an incident reporting system along with anesthetic records, this case-controlled study retrospectively investigated risk factors associated with ADP in surgical patients. Methods Patients who experienced ADP during epidural anesthesia who were registered in the incident reporting system of our institution between April 2012 and March 2019 were enrolled. Patients with ADP were control-matched with those who without ADP in a 1:3 ratio, to compare the potential risk factors and calculated odds ratios (ORs) for ADP. The primary hypothesis was that anesthesiologists’ experience reduces the incidence of ADP. The secondary hypothesis was that there are risk factors for ADP. Between-group differences in anesthesiologists’ experience were compared using the Mann–Whitney U test. Significance was set at P

Shivering after surgery or during therapeutic hypothermia can lead to serious complications, such as myocardial infarction and respiratory failure. Although several anesthetics and opioids are shown to have anti-shivering effects, their sedative and respiratory side effects dampen the usefulness of these drugs for the prevention of shivering. In the present study, we explored the potential of a novel ultrashort-acting benzodiazepine, remimazolam, in the prevention of shivering using a rabbit model of hypothermia. Adult male Japanese white rabbits were anesthetized with isoflurane. The rabbits received saline (control), remimazolam (either 0.1 or 1 mg/kg/h), or remimazolam + flumazenil, a selective γ-aminobutyric acid (GABA) type A receptor antagonist (n = 6 each). Thirty minutes after discontinuation of the drugs, cooling was initiated by perfusing 10°C water via a plastic tube positioned in the colon until the animal shivered. Core body temperature and hemodynamic and physiological parameters were recorded. Remimazolam at 1 mg/kg/h significantly lowered the core temperature change during shivering (−2.50 ± 0.20°C vs. control: −1.00 ± 0.12°C, p = 0.0009). The effect of 1 mg/kg/h remimazolam on the core temperature change was abolished by flumazenil administration (−0.94 ± 0.16°C vs. control: −1.00 ± 0.12°C, p = 0.996). Most of the hemodynamic and physiological parameters did not differ significantly among groups during cooling. Remimazolam at a clinically relevant dose successfully suppressed shivering in rabbits via the GABA pathway even after its anesthetic effects likely disappeared. Remimazolam may have the potential to prevent shivering in patients undergoing surgery or therapeutic hypothermia.

Abstract Cerebellar hemorrhage after surgery is a rare but critical complication requiring prompt diagnosis and intervention. However, anesthetics can mask most brain compression signs. Prolonged coma with apnea after tumor resection under general anesthesia may indicate the need for prompt imaging to detect or exclude cerebellar lesions.

As the world is rapidly aging, and the number of elderly patients who undergo surgery is rising, postoperative cognitive decline among those patients has become an increasing healthcare problem. Although understanding the risk factors and mechanisms underlying the pathogenesis of postoperative cognitive decline is critically important from a preventative viewpoint, such knowledge and evidence are lacking. A growing body of evidence suggest an association between cognitive function and sleep duration. The purpose of this study was to investigate the association between postoperative cognitive function and sleep duration on the night before surgery using a wearable sleep tracker. In this 6-month prospective cohort study, we analyzed data from 194 patients aged ≥ 65 years who underwent elective non-cardiac and non-cranial surgery under general anesthesia. According to the sleep duration on the night before surgery, patients were categorized into following four groups: 9 h. Perioperative cognitive function and domains were assessed using a neuropsychological test battery, and the incidence and prevalence of cognitive decline over 6 months after surgery were analyzed using the multiple logistic regression analysis. During the 6-month follow-up period, 41 patients (21%) developed cognitive decline. The incidence of cognitive decline was significantly elevated for the patients with sleep duration < 5 h (vs. 7–9 h; surgical duration-adjusted odds ratio, 3.50; 95% confidence interval, 1.20–10.2; P < 0.05). The association between sleep duration and prevalence of cognitive decline was limited to the early postoperative period (at 1 week and 1 month). Among the cognitive domains assessed, attentional function was significantly impaired in patients with a sleep duration < 5 h [vs. 7–9 h at 1 week; 4/37 (10.8%) vs. 0/73 (0%); P < 0.05]. In conclusion, sleep duration < 5 h on the night before surgery was significantly associated with worse attentional function after surgery and higher incidence of cognitive decline. The present results indicate that sleep deprivation on the night before surgery may have a temporary but significantly negative influence on the patient's postoperative cognitive function and is a potential target for preventing cognitive decline.

Abstract Background Although recent studies using experimental models of ischemic brain injury indicate that systemically-administered β1-blockers have potential protective effects on the cerebrovascular system, the precise mechanisms remain unclear. In addition to their cardiovascular effects, water-soluble β1-blockers can pass the blood–brain barrier and may exert their vascular action on cerebral microvessels. The aim of this study was to investigate the direct effects of β1-blockade on the cerebral microvasculature both in the normal state and ischemia/reperfusion state using the cranial window method. Methods The closed cranial window method was used to visualize the cerebral microcirculation and changes in the pial arteriole diameter in adult male rabbits. In the first experiment, various concentrations of the selective β1-blocker landiolol were administered into the cranial window to evaluate the dose-response. In the second experiment, the effect of β1-blockade on the brain during ischemic/reperfusion injury was investigated. Global brain ischemia/reperfusion was induced by clamping the brachiocephalic, left common carotid, and left subclavian arteries for 15 min. Either landiolol or artificial cerebrospinal fluid was infused 5 min after initiation of ischemia through 120 min after reperfusion. Pial arteriole diameter and hemodynamic and physiological parameters were recorded before ischemia, during ischemia, and 5, 10, 20, 40, 60, 80, 100, and 120 min after reperfusion. Results In the first experiment, topical administration of landiolol at higher concentrations produced slight pial arteriole dilation (10− 8 mol/L: 4.3 ± 3.4%, 10− 6 mol/L: 8.0 ± 5.8%, 10− 4 mol/L: 7.3 ± 4.0%). In the second experiment, the topical administration of landiolol significantly dilated the pial arteriole diameters during ischemia/reperfusion injury (ischemia: 30.6 ± 38.6%, 5 min: 47.3 ± 42.2%, 10 min: 47.8 ± 34.2%, 20 min: 38.0 ± 39.0%). There were no statistical differences in hemodynamic and physiological parameters between the landiolol and control groups. Conclusions The blockade of β1-adrenergic receptors induced significant vasodilation of pial arterioles during ischemia/reperfusion injury. By contrast, only a slight dilation of the arterioles was observed in the normal state, indicating that ischemic cerebral microvessels are more susceptible to the vasodilatory effect induced by selective blockade of β1-adrenergic receptors than normal microvessels.

We have examined impacts of gate insulator (Al2O3 or HfO2) and gate electrode (TiN or W) on electrical performance of ZnSnO/Si bilayer tunneling field-effect transistors (TFETs). It is found from the capacitance-voltage (C-V) characteristics that the W gate is effective to reduce the counter-clockwise hysteresis. Additionally, the optimal temperature of post-metallization annealing (PMA) is different for each gate stack, and this optimization is critically important for the high ON-state current (ION) and steep ON/OFF switching. The W/Al2O3/ZnSnO/Si bilayer TFET provides the hysteresis-free steep ON/OFF switching with the minimum sub-threshold swing (SS) of 65.4 mV/dec. and average SS of 72.0 mV/dec. in a gate-voltage swing of 0.3 V, which are 19% and 18% lower than the control TiN/Al2O3/ZnSnO/Si bilayer TFET. When the gate stack is replaced by W/HfO2/Al2O3, the TFET exhibits less steep ON/OFF switching in spite of thinning capacitance equivalent thickness (CET) from 5.9 and 2.3 nm. These results indicate the importance of improvement in the gate stack quality on the sub-threshold characteristics of the bilayer TFETs.

Abstract Background Sodium ion transportation plays a crucial role in the pathogenesis of hypoxic–ischemic brain injury. Amiodarone, a Vaughan-Williams class III antiarrhythmic drug, has been widely used to treat life-threatening arrhythmia and cardiac arrest worldwide. In addition to its inhibitory effects on the potassium channel, amiodarone also blocks various sodium ion transporters, including the voltage-gated sodium channel, sodium pump, and Na+/Ca+ exchanger. Considering these pharmacological profile, amiodarone may affect the influx–efflux balance of sodium ion in the hypoxic–ischemic brain. Previous studies suggest that the blockade of the voltage-gated sodium channel during hypoxic–ischemic brain injury exerts neuroprotection. On the contrary, the blockade of sodium pump or Na+/Ca+ exchanger during hypoxia–ischemia may cause further intracellular sodium accumulation and consequent osmotic cell death. From these perspectives, the effects of amiodarone on sodium ion balance on the hypoxic–ischemic brain can be both protective and detrimental depending on the clinical and pathophysiological conditions. In this study, we therefore investigated the effect of amiodarone on hypoxic–ischemic brain injury using a murine experimental model. Results Compared with the control group mice, mice that received amiodarone after induction of 40-min hypoxic–ischemic brain injury exhibited lower survival rates over 7 days and worse neurological function. After 25-min hypoxic–ischemic brain injury, amiodarone treated mice exhibited larger infarct volumes (16.0 ± 6.9 vs. 24.2 ± 6.8 mm3, P

Abstract Background We previously reported that each 100 mg dL− 1 reduction in blood glucose over the range from ≈90 to > 300 mg dL− 1 decreases the shivering threshold (triggering core temperature) in rabbits by 1 °C. However, the effects of lower blood glucose concentrations has yet to be evaluated. We thus evaluated the relationship between the shivering threshold and blood glucose concentration over the mild-to-severe hypoglycemic range. Methods Thirty-nine rabbits were lightly anaesthetized with isoflurane and randomly assigned to one of the three groups: 1) severe hypoglycemia, insulin and dextrose infusions titrated to achieve blood glucose concentration at 45–75 mg dL− 1; 2) mild hypoglycemia, insulin and dextrose infusions titrated to achieve blood glucose concentration at 75–100 mg dL− 1; and 3) saline infusion. Cooling by colonic perfusion of water at 10 °C was continued until shivering occurred or esophageal core temperatures reached to 34 °C. Results The shivering threshold in the severe hypoglycemic rabbits was 35.7 ± 1.1 °C (mean ± SD); the thresholds in the mild hypoglycemic rabbits was 37.0 ± 0.7 °C; and the threshold in the control rabbits was 37.9 ± 1.0 °C. The shivering threshold increased linearly with blood glucose concentration: shivering threshold (°C) = 0.032 ∙ [blood glucose concentration (mg dL− 1)] + 34.1, R2 = 0.45. The shivering threshold thus decreased by approximately 1 °C for each 31 mg dL− 1 decrease in blood glucose concentration. Conclusions There was a linear relationship between blood glucose and the shivering threshold over the range from severe hypoglycemia to normoglycemia. Blood glucose perturbations in the hypoglycemic range reduced the shivering threshold about three times as much as previously reported for the hyperglycemic range.

Abstract Background Involuntary muscle contraction caused by extracardiac stimulation is a rare complication induced by a pacemaker. We report a case who developed sudden onset diaphragmatic contractions during general anesthesia caused by a DDD mode pacemaker. Case presentation A 74-year-old woman with a permanent pacemaker was scheduled to undergo mastectomy. The pacing mode was switched from DDD to VOO intraoperatively to avoid electromagnetic interference. Immediately after returning the pacing mode to DDD after surgery, diaphragmatic contractions occurred, mimicking bucking type of movements. After switching the pacing to A-sense V-pace, the twitching ceased. Because no structural problems were noted, and the twitching disappeared after terminating atrial pacing, diaphragmatic contractions might be caused by stimulation of the right phrenic nerve located near the right appendage where the electrode was installed. Conclusion The potential risk of muscle twitching should be carefully evaluated preoperatively especially in patients with atypical position of pacemaker leads.

Abstract Background We evaluated the change of cerebral regional tissue oxygen saturation (rSO2) along with the pneumoperitoneum and the Trendelenburg position. We also assessed the relationship between the change of rSO2 and the changes of mean arterial blood pressure (MAP), heart rate (HR), arterial carbon dioxide tension (PaCO2), arterial oxygen tension (PaO2), or arterial oxygen saturation (SaO2). Methods Forty-one adult patients who underwent a robotic assisted endoscopic prostatic surgery under propofol and remifentanil anesthesia were involved in this study. During the surgery, a pneumoperitoneum was established using carbon dioxide. Measurements of rSO2, MAP, HR, PaCO2, PaO2, and SaO2 were performed before the pneumoperitoneum (baseline), every 5 min after the onset of pneumoperitoneum, before the Trendelenburg position. After the onset of the Trendelenburg position, rSO2, MAP, HR were recorded at 5, 10, 20, 30, 45, and 60 min, and PaCO2, PaO2, and SaO2 were measured at 10, 30, and 60 min. Results Before the pneumoperitoneum, left and right rSO2 were 67.9 ± 6.3% and 68.5 ± 7.0%. Ten minutes after the onset of pneumoperitoneum, significant increase in the rSO2 was observed (left: 69.6 ± 5.9%, right: 70.6 ± 7.4%). During the Trendelenburg position, the rSO2 increased initially and peaked at 5 min (left: 72.2 ± 6.5%, right: 73.1 ± 7.6%), then decreased. Multiple regression analysis showed that change of rSO2 correlated with MAP and PaCO2. Conclusions Pneumoperitoneum and the Trendelenburg position in robotic-assisted endoscopic prostatic surgery did not worsen cerebral oxygenation. Arterial blood pressure is the critical factor in cerebral oxygenation. Trial registration Japan Primary Registries Network (JPRN); UMIN-CTR ID; UMIN000026227 (retrospectively registered).

Abstract Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a fatal cardiac ion channelopathy that causes sudden unexpected death in the young. Case presentation The patient was a 3-year-old girl with CPVT. Insertion of an implantable cardioverter defibrillator (ICD) using epicardial pacing was scheduled. After premedication of rectal midazolam was given, general anesthesia was induced with midazolam, fentanyl, and rocuronium, and maintained with midazolam, fentanyl, remifentanil, and rocuronium. The operation was performed without any complications. Dexmedetomidine and fentanyl were continuously infused after the operation until she was extubated in the morning of postoperative day 1. Fatal arrhythmia due to perioperative stress did not occur. Conclusions We report the anesthetic management of a child with CPVT who underwent insertion of an ICD. CPVT-induced fatal arrhythmia did not occur perioperatively by carefully avoiding perioperative stress with premedication and post-operative sedation.

For harvesting energy from waste heat, the power generation densities and fabrication costs of thermoelectric generators (TEGs) are considered more important than their conversion efficiency because waste heat energy is essentially obtained free of charge. In this study, we propose a miniaturized planar Si-nanowire micro-thermoelectric generator (SiNW-μTEG) architecture, which could be simply fabricated using the complementary metal–oxide–semiconductor–compatible process. Compared with the conventional nanowire μTEGs, this SiNW-μTEG features the use of an exuded thermal field for power generation. Thus, there is no need to etch away the substrate to form suspended SiNWs, which leads to a low fabrication cost and well-protected SiNWs. We experimentally demonstrate that the power generation density of the SiNW-μTEGs was enhanced by four orders of magnitude when the SiNWs were shortened from 280 to 8 μm. Furthermore, we reduced the parasitic thermal resistance, which becomes significant in the shortened SiNW-μTEGs, by optimizing the fabrication process of AlN films as a thermally conductive layer. As a result, the power generation density of the SiNW-μTEGs was enhanced by an order of magnitude for reactive sputtering as compared to non-reactive sputtering process. A power density of 27.9 nW/cm2 has been achieved. By measuring the thermal conductivities of the two AlN films, we found that the reduction in the parasitic thermal resistance was caused by an increase in the thermal conductivity of the AlN film and a decrease in the thermal boundary resistance.

Abstract Background Ion channels play a crucial role in the development of ischemic brain injury. Recent studies have reported that the blockade of various types of ion channels improves outcomes in experimental stroke models. Amiodarone, one of the most effective drugs for life-threatening arrhythmia, works as a multiple channel blocker and its characteristics cover all four Vaughan-Williams classes. Although it is known that amiodarone indirectly contributes to preventing ischemic stroke by maintaining sinus rhythm in patients with atrial fibrillation, the direct neuroprotective effect of amiodarone has not been clarified. The purpose of this study was to investigate the direct effect of amiodarone on ischemic stroke in mice. Methods Focal cerebral ischemia was induced via distal permanent middle cerebral artery occlusion (MCAO) in adult male mice. The amiodarone pre-treatment group received 50 mg/kg of amiodarone 1 h before MCAO; the amiodarone post-treatment groups received 50 mg/kg of amiodarone immediately after MCAO; the control group received vehicle only. In addition, the sodium channel opener veratrine and selective beta-adrenergic agonist isoprotelenol were used to elucidate the targeted pathway. Heart rate and blood pressure were monitored perioperatively. Infarct volume analysis was conducted 48 h after MCAO. The body asymmetry test and the corner test were used for neurological evaluation. Results Amiodarone pre-treatment and post-treatment reduced the heart rate but did not affect the blood pressure. No mice showed arrhythmia. Compared with the control group, the amiodarone pre-treatment group had smaller infarct volumes (8.9 ± 2.1% hemisphere [mean ± SD] vs. 11.2 ± 1.4%; P

Abstract Background While acute hyperglycemia has been shown to mitigate the beneficial effects of ischemic preconditioning, its effect on insulin-induced preconditioning remains unclear. Methods The study was designed to test the hypothesis that acute hyperglycemia diminishes the cardioprotective effects following a 20-min pre-ischemic pre-conditioning with insulin in the isolated rat heart using the Langendorff system. Forty hearts were assigned to receive modified Krebs–Henseleit (KH) buffer containing 0.5 U/L insulin and 100 mg/dL glucose (InsG100, n = 10), KH buffer with 100 mg/dL glucose (G100, n = 10), KH buffer supplemented with 0.5 U/L insulin and 600 mg/dL glucose (InsG600, n = 10), or with 600 mg/dL glucose (G600, n = 10). To match the osmotic pressure of the InsG600 group, 27.5 mmol/L of mannitol was added to KH solution in the InsG100 and G100 group. The four groups were perfused with each solution for 20 min prior to 15 min of no-flow ischemia, and during 20 min of reperfusion. Only during the ischemic period the heart was paced at 222 beats/min. Measurements of heart rate, coronary flow and maximum of LV derivative of pressure development (dP/dt max) were recorded. Myocardial phospho-protein kinase B (p-Akt) and tumor necrosis factor-α (TNF-α) levels were assayed by enzyme-linked immunosorbent assay and sandwich ELISA, respectively following reperfusion. Results After reperfusion, LV dP/dt max and heart rate in the InsG100 group was significantly higher than that in the other three groups. The myocardial p-Akt level in the InsG100 group was significantly elevated when compared to the InsG600 group at the end of reperfusion. The p-Akt levels in the InsG600 and InsG100 group were significantly higher than in the corresponding non-insulin groups. Conclusions Acute hyperglycemia diminishes the cardioprotective effects of insulin preconditioning in the isolated rat heart, possibly mediated through the suppression of myocardial Akt phosphorylation.

We propose a tunnel field-effect transistor (TFET) having a trimmed gate (TG) structure, which considerably improves the subthreshold swing (SS). The TG structure truncates the needless long band-to-band tunneling (BTBT) paths to a “channel”, which normally appear in a conventional TFET, and realize a sudden switching to the on-state arising from a short BTBT path. Our simulations demonstrate that the TG-TFET can achieve an extremely steep SS, less than 10 mV/decade, in the double-gated Si-channel configuration. The TG structure also improves the ratio ION/IOFF to a value higher than that of ideal MOSFETs in the operation voltage range up to 0.35 V. The mechanism of steep switching is based on a simple modification of the gate electrostatic control; therefore, in addition to the demonstrated TFETs, the TG structure is universally applicable to many types of TFETs.

The effect of post-implantation annealing (PIA) on Al–N isoelectronic trap (IET) formation in silicon has been experimentally investigated to discuss the Al–N IET formation and implantation-induced defect recovery mechanisms. We performed a photoluminescence study, which indicated that self-interstitial clusters and accompanying vacancies are generated in the ion implantation process. It is supposed that Al and N atoms move to the vacancy sites and form stable Al–N pairs in the PIA process. Furthermore, the PIA process recovers self-interstitial clusters while transforming their atomic configuration. The critical temperature for the formation/dissociation of Al–N pairs was found to be 450 °C, with which we describe the process integration for devices utilizing Al–N IET technology.

The scaled charge trapping (CT) type silicon on insulator (SOI) FinFET flash memories with different blocking layer materials of Al2O3 and SiO2 have successfully been fabricated, and their electrical characteristics including short-channel effect (SCE) immunity, threshold voltage (Vt) variability, and the memory characteristics have been comparatively investigated. It was experimentally found that the better SCE immunity and a larger memory window are obtained by introducing a high-k Al2O3 blocking layer instead of a SiO2 blocking layer. It was also confirmed that the variability of Vt before and after one program/erase (P/E) cycle is almost independent of the blocking layer materials.

A threshold voltage (Vth) controllable multigate FinFET on a 10-nm-thick ultrathin BOX (UTB) SOI substrate have been investigated. It is revealed that the Vth of the FinFET on the UTB SOI substrate is effectively modulated thanks to the improved coupling between the Si channel and the back gate. We have also carried out analysis of the Vth controllability in terms of the size dependence such as the gate length (LG) and the fin width (TFin).

BACKGROUND: There is accumulating evidence that the activation of spinal glial cells, especially microglia, is a key event in the pathogenesis of neuropathic pain. However, the inhibition of microglial activation is often ineffective, especially for long-lasting persistent neuropathic pain. So far, neuropathic pain remains largely intractable and a new therapeutic strategy for the pain is still required. METHODS/PRINCIPAL FINDINGS: Using Seltzer model mice, we investigated the temporal aspect of two types of neuropathic pain behaviors, i.e., thermal hyperalgesia and mechanical allodynia, as well as that of morphological changes in spinal microglia and astrocytes by immunohistochemical studies. Firstly, we analyzed the pattern of progression in the pain behaviors, and found that the pain consisted of an "early induction phase" and subsequent "late maintenance phase". We next analyzed the temporal changes in spinal glial cells, and found that the induction and the maintenance phase of pain were associated with the activation of microglia and astrocytes, respectively. When Bushi, a Japanese herbal medicine often used for several types of persistent pain, was administered chronically, it inhibited the maintenance phase of pain without affecting the induction phase, which was in accordance with the inhibition of astrocytic activation in the spinal cord. These analgesic effects and the inhibition of astrocytic activation by Bushi were mimicked by the intrathecal injection of fluorocitrate, an inhibitor of astrocytic activation. Finally, we tested the direct effect of Bushi on astrocytic activation, and found that Bushi suppressed the IL-1β- or IL-18-evoked ERK1/2-phosphorylation in cultured astrocytes but not the ATP-evoked p38- and ERK1/2-phosphorylation in microglia in vitro. CONCLUSIONS: Our results indicated that the activation of spinal astrocytes was responsible for the late maintenance phase of neuropathic pain in the Seltzer model mice and, therefore, the inhibition of astrocytic activation by Bushi could be a useful therapeutic strategy for treating neuropathic pain.