Altered pupil light and darkness reflex and eye-blink responses in late-life depression.

BACKGROUND: Late-life depression (LLD) is a prevalent neuropsychiatric disorder in the older population. While LLD exhibits high mortality rates, depressive symptoms in older adults are often masked by physical health conditions. In younger adults, depression is associated with deficits in pupil light reflex and eye blink rate, suggesting the potential use of these responses as biomarkers for LLD. METHODS: We conducted a study using video-based eye-tracking to investigate pupil and blink responses in LLD patients (n = 25), older (OLD) healthy controls (n = 29), and younger (YOUNG) healthy controls (n = 25). The aim was to determine whether there were alterations in pupil and blink responses in LLD compared to both OLD and YOUNG groups. RESULTS: LLD patients displayed significantly higher blink rates and dampened pupil constriction responses compared to OLD and YOUNG controls. While tonic pupil size in YOUNG differed from that of OLD, LLD patients did not exhibit a significant difference compared to OLD and YOUNG controls. GDS-15 scores in older adults correlated with light and darkness reflex response variability and blink rates. PHQ-15 scores showed a correlation with blink rates, while MoCA scores correlated with tonic pupil sizes. CONCLUSIONS: The findings demonstrate that LLD patients display altered pupil and blink behavior compared to OLD and YOUNG controls. These altered responses correlated differently with the severity of depressive, somatic, and cognitive symptoms, indicating their potential as objective biomarkers for LLD.

Antiemetic prophylaxis with droperidol in morphine-based intravenous patient-controlled analgesia: a propensity score matched cohort study.

BACKGROUND: There are limited real-world data regarding the use of droperidol for antiemetic prophylaxis in intravenous patient-controlled analgesia (IV-PCA). This study aimed to evaluate the antiemetic benefits and sedation effects of droperidol in morphine-based IV-PCA. METHODS: Patients who underwent major surgery and used morphine-based IV-PCA at a medical center from January 2020 to November 2022 were retrospectively analyzed. The primary outcome was the rate of any postoperative nausea and/or vomiting (PONV) within 72 h after surgery. Propensity score matching was used to match patients with and without the addition of droperidol to IV-PCA infusate in a 1:1 ratio. Multivariable conditional logistic regression models were used to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CIs). RESULTS: After matching, 1,104 subjects were included for analysis. The addition of droperidol to IV-PCA reduced the risk of PONV (aOR: 0.49, 95% CI: 0.35-0.67, p < 0.0001). The antiemetic effect of droperidol was significant within 36 h after surgery and attenuated thereafter. Droperidol was significantly associated with a lower risk of antiemetic uses (aOR: 0.58, 95% CI: 0.41-0.80, p = 0.0011). The rate of unintentional sedation was comparable between the patients with (9.1%) and without (7.8%; p = 0.4481) the addition of droperidol. Postoperative opioid consumption and numeric rating scale acute pain scores were similar between groups. CONCLUSIONS: The addition of droperidol to IV-PCA reduced the risk of PONV without increasing opiate consumption or influencing the level of sedation. However, additional prophylactic therapies are needed to prevent late-onset PONV.

Non-invasive ventilation for preoxygenation before general anesthesia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Preoxygenation is crucial for providing sufficient oxygen reservoir to a patient before intubation and enables the extension of the period between breathing termination and critical desaturation (safe apnoea time). Conventionally, face mask ventilation is used for preoxygenation. Non-invasive ventilation is a new preoxygenation method. The study objective was to compare the outcomes of non-invasive ventilation and face mask ventilation for preoxygenation. METHOD: PubMed, Embase, Cochrane Library, and the ClinicalTrials.gov registry were searched for eligible studies published from database inception to September 2021. Individual effect sizes were standardized, and a meta-analysis was conducted using random effects models to calculate the pooled effect size. Inclusion criteria were randomised controlled trials of comparing the outcomes of non-invasive ventilation or face mask ventilation for preoxygenation in patients scheduled for surgeries. The primary outcome was safe apnea time, and the secondary outcomes were post-operative complications, number of patients who achieved the expired O2 fraction (FeO2) after 3 min of preoxygenation, minimal SpO2 during tracheal intubation, partial pressure of oxygen in the arterial blood (PaO2) and partial pressure of carbon dioxide (PaCO2) after preoxygenation, and PaO2 and PaCO2 after tracheal intubation. RESULTS: 13 trials were eligible for inclusion in this study. Significant differences were observed in safe apnoea time, number of patients who achieved FeO2 90% after preoxygenation for 3 min, and PaO2 and PaCO2 after preoxygenation and tracheal intubation. Only in the non-obese subgroup, no significant difference was observed in safe apnoea time (mean difference: 125.38, 95% confidence interval: - 12.26 to 263.03). CONCLUSION: Non-invasive ventilation appeared to be more effective than conventional methods for preoxygenation. We recommend non-invasive ventilation based on our results.

Enzalutamide Induces Apoptotic Insults to Human Drug-Resistant and -Sensitive Glioblastoma Cells via an Intrinsic Bax-Mitochondrion-Cytochrome C Caspase Cascade Activation Pathway.

Glioblastoma multiforme (GBM) is the most common and malignant brain tumor. Temozolomide (TMZ) is the first-line chemotherapeutic drug for treating GBM. However, drug resistance is still a challenging issue in GBM therapy. Our preliminary results showed upregulation of androgen receptor (AR) gene expression in human GBM tissues. This study was designed to evaluate the effects of enzalutamide, a specific inhibitor of the AR, on killing drug-resistant and -sensitive glioblastoma cells and the possible mechanisms. Data mining from The Cancer Genome Atlas (TCGA) database revealed upregulation of AR messenger (m)RNA and protein expressions in human GBM tissues, especially in male patients, compared to normal human brains. In addition, expressions of AR mRNA and protein in human TMZ-sensitive U87 MG and -resistant U87 MG-R glioblastoma cells were elevated compared to normal human astrocytes. Exposure of human U87 MG and U87 MG-R cells to enzalutamide concentration- and time-dependently decreased cell viability. As to the mechanism, enzalutamide killed these two types of glioblastoma cells via an apoptotic mechanism. Specifically, exposure to enzalutamide augmented enzyme activities of caspase-9 rather than those of caspase-8. Moreover, enzalutamide successively triggered an elevation in levels of the proapoptotic Bax protein, a reduction in the mitochondrial membrane potential, release of cytochrome c, cascade activation of caspases-3 and -6, DNA fragmentation, and cell apoptosis in human TMZ-sensitive and -resistant glioblastoma cells. Pretreatment with Z-VEID-FMK, an inhibitor of caspase-6, caused significant attenuations in enzalutamide-induced morphological shrinkage, DNA damage, and apoptotic death. Taken together, this study showed that enzalutamide could significantly induce apoptotic insults to human drug-resistant and -sensitive glioblastoma cells via an intrinsic Bax-mitochondrion-cytochrome c-caspase cascade activation pathway. Enzalutamide has the potential to be a drug candidate for treating GBM by targeting the AR signaling axis.

Effects of preoperative oral carbohydrate on postoperative discomfort in patients undergoing elective surgery: a meta-analysis of randomized controlled trials.

PURPOSE: Fasting is a standard preoperative procedure performed to prevent vomiting and pulmonary aspiration during anaesthesia and surgery. However, fasting can cause postoperative physical and psychological discomfort. Intake of oral carbohydrate (CHO) may mimic the intake of food, which prevents postoperative discomfort. We conducted a meta-analysis to evaluate the effect and safety of preoperative oral CHO in adult surgical patients. METHODS: Randomized controlled trials (RCTs) were searched for in the PubMed, EMBASE, and Cochrane Library databases. A meta-analysis was performed to calculate a pooled effect size by using random-effects models. The satisfaction outcomes were mouth dryness, hunger, thirst, pain severity, duration of hospitalization, homeostatic model assessment for insulin resistance (HOMA-IR), and the incidence of postoperative nausea and vomiting. The safety outcomes were the incidence of aspiration and infection. RESULTS: In total, 57 RCTs involving 5606 patients were included. The outcomes of mouth dryness, thirst, hunger, and pain were assessed by a 10-point visual analogue scale (0 = best, 10 = worst). The severity of mouth dryness (weighted mean difference [WMD]: -1.26, 95% CI: -2.36 to -0.15), thirst (WMD: -1.36, 95% CI: -2.05 to -0.67), hunger (WMD: -1.66, 95% CI: -2.53 to -0.80), pain (WMD: -0.68, 95% CI: -1.01 to -0.35), duration of hospitalization (WMD: -0.39 day, 95% CI: -0.66 to -0.12), and HOMA-IR (WMD: -1.80, 95% CI: -2.84 to -0.76) were significantly lower in the CHO group than in the control group. The incidence of postoperative nausea and vomiting did not differ between the CHO and control groups. No aspiration was recorded in any of the groups. CONCLUSIONS: Preoperative CHO can alleviate patient's discomfort without safety concerns. Surgeons and anaesthesiologists should strongly promote preoperative CHO as a strategy to enhance recovery after surgery protocols.

Periodontal disease and risk of mortality and kidney function decline in advanced chronic kidney disease: a nationwide population-based cohort study.

OBJECTIVES: Periodontal disease is prevalent in patients with chronic kidney disease (CKD) and potentially associated with kidney function decline. However, it is uncertain whether periodontal disease affects the risk of mortality and morbidity in patients with advanced CKD. MATERIALS AND METHODS: Taiwan's National Health Insurance Research Database was used to conduct a nationwide population-based cohort study. Propensity score matching procedures were performed to select people with stage 5 CKD and to compare the long-term risk of mortality, end-stage renal disease, and major adverse cardiovascular events (MACE) between people with and without periodontal disease. Multivariable Cox regression analyses were conducted to calculate the adjusted hazard ratio (aHR) with 95% confidence interval (CI) for the outcome of interest. RESULTS: A total of 8119 subjects with stage 5 CKD were initially included. After matching to demographic and clinical covariates, 1254 subjects with 7099 person-years of follow-up were selected for analyses. Periodontal disease was not associated with long-term risks of all-cause mortality (aHR: 0.77, 95% CI: 0.49-1.22), progression to end-stage renal disease (aHR: 0.91, 95% CI: 0.75-1.10), or MACE (aHR: 1.18, 95% CI: 0.91-1.53). These findings were generally consistent across subgroups of age, sex, comorbid diabetes, uses of systemic antibiotic, and different dental procedures. CONCLUSIONS: Periodontal disease is not a predictor for long-term mortality or morbidity in patients with advanced CKD. CLINICAL RELEVANCE: These results provide important evidence to elucidate the relationship between periodontitis and critical clinical outcomes of advanced CKD.

Methylpiperidinopyrazole Attenuates Estrogen-Induced Mitochondrial Energy Production and Subsequent Osteoblast Maturation via an Estrogen Receptor Alpha-Dependent Mechanism.

An estrogen deficiency is the main cause of osteoporosis in postmenopausal women. In bone remodeling, estrogen receptors (ERs) can mediate estrogen-transducing signals. Methylpiperidinopyrazole (MPP) is a highly specific antagonist of ER-alpha (ERα). This study was designed to evaluate the effects of MPP on estrogen-induced energy production, subsequent osteoblast maturation, and the possible mechanisms. Exposure of primary osteoblasts isolated from neonatal rat calvarias to MPP did not affect cell morphology or survival. Estradiol can induce translocation of ERα into mitochondria from the cytoplasm. Interestingly, pretreatment of rat calvarial osteoblasts with MPP lowered estrogen-induced ERα translocation. Sequentially, estrogen-triggered expressions of mitochondrial energy production-linked cytochrome c oxidase (COX) I and COX II messenger (m)RNAs were inhibited following pretreatment with MPP. Consequently, MPP caused decreases in estrogen-triggered augmentation of the activities of mitochondrial respiratory complex enzymes and levels of cellular adenosine phosphate (ATP). During progression of osteoblast maturation, estrogen induced bone morphogenetic protein (BMP)-6 and type I collagen mRNA expressions, but MPP treatment inhibited such induction. Consequently, estrogen-induced osteoblast activation and mineralization were attenuated after exposure to MPP. Taken together, MPP suppressed estrogen-induced osteoblast maturation through decreasing chromosomal osteogenesis-related BMP-6 and type I collagen mRNA expressions and mitochondrial ATP synthesis due to inhibiting energy production-linked COX I and II mRNA expressions. MPP can appropriately be applied to evaluate estrogen-involved bioenergetics and osteoblast maturation.

Protection of Dexmedetomidine Against Ischemia/Reperfusion-Induced Apoptotic Insults to Neuronal Cells Occurs Via an Intrinsic Mitochondria-Dependent Pathway.

Dexmedetomidine, an agonist of alpha2-adrenergic receptors, is used for critically ill patients to induce and maintain sedation and analgesia. Brain ischemia/reperfusion (I/R) usually causes severe neuronal injuries to intensive care unit patients. This study was aimed to evaluate the effects of dexmedetomidine on I/R-induced insults to neuronal cells and the possible mechanisms. Treatment of neuro-2a cells with dexmedetomidine did not affect cell viability but could protect against I/R-induced cell death. Separately, the I/R-triggered cell shrinkage, DNA fragmentation, and apoptosis in neuro-2a cells were alleviated by dexmedetomidine. As to the mechanisms, exposure of neuro-2a cells to dexmedetomidine substantially attenuated I/R-induced translocation of Bax protein from the cytosol to mitochondria and reduction in the mitochondrial membrane potential (MMP). Successively, dexmedetomidine decreased cytochrome c release from mitochondria to the cytoplasm and consequent cascade activations of caspases-9, -3, and -6 in I/R-treated neuro-2a cells. Interestingly, downregulating caspase-6 activity synergistically improved dexmedetomidine-induced defense against I/R-induced apoptosis of neuro-2a cells. The dexmedetomidine-involved neuroprotection was further confirmed in the other NB41A3 neuronal cells by significantly attenuating I/R-induced changes in the MMP, caspase-3 activation, DNA fragmentation, and cell apoptosis. Taken together, this study has shown the neuroprotective effects of dexmedetomidine against I/R-induced apoptotic insults via an intrinsic Bax-mitochondria-cytochrome c-caspase protease pathway. J. Cell. Biochem. 118: 2635-2644, 2017. © 2016 Wiley Periodicals, Inc.

Human microsaccade cueing modulation in visual- and memory-delay saccade tasks after theta burst transcranial magnetic stimulation over the frontal eye field.

Microsaccades that occur during periods of fixation are modulated by various cognitive processes and have an impact on visual processing. A network of brain areas is involved in microsaccade generation, including the superior colliculus and frontal eye field (FEF) which are involved in modulating microsaccade rate and direction after the appearance of a visual cue (referred to as microsaccade cueing modulation). Although the neural mechanisms underlying microsaccade cueing modulations have been demonstrated in monkeys, limited research has investigated a causal role of these areas in humans. By applying continuous theta-burst transcranial magnetic stimulation (cTBS) over the right FEF and vertex, we investigated the role of human FEF in modulating microsaccade responses after the appearance of a visual target in a visual- and memory-delay saccade task. After target appearance, microsaccade rate was initially suppressed but then increased in both cTBS conditions. More importantly, in the visual-delay task, microsaccades after target appearance were directed to the ipsilateral side more often with FEF, compared to vertex stimulation. Moreover, microsaccades were directed towards the target location, then to the opposite location of the target in both tasks, with larger effects in the visual-, compared to, memory-delay task. This microsaccade direction modulation was delayed after FEF stimulation in the memory-delay task. Overall, some microsaccade cueing modulations were moderately disrupted after FEF cTBS, suggesting a causal role for involvement of the human FEF in microsaccade generation after presentation of salient stimuli.

Resveratrol triggers the ER stress-mediated intrinsic apoptosis of neuroblastoma cells coupled with suppression of Rho-dependent migration and consequently prolongs mouse survival.

Neuroblastoma, the most common childhood tumor, are highly malignant and fatal because neuroblastoma cells extremely defend against apoptotic targeting. Traditional treatments for neuroblastomas are usually ineffective and lead to serious side effects and poor prognoses. In this study, we investigated the molecular mechanisms of resveratrol-induced insults to neuroblastoma cells and survival extension of nude mice with neuroblastomas, especially in the endoplasmic reticular (ER) stress-intracellular reactive oxygen species (iROS) axis-mediated signals. Resveratrol specifically killed neuroblastoma cells mainly via apoptosis and autophagy rather than necrosis. As to the mechanisms, resveratrol time-dependently triggered productions of Grp78 protein and iROS in neuroblastoma cells. Attenuating the ER stress-iROS signaling axis significantly suppressed resveratrol-induced autophagy, DNA damage, and cell apoptosis. Successively, resveratrol decreased phosphorylation of retinoblastoma protein and induced cell cycle arrest at the S phase, translocation of Bak protein to mitochondria, a reduction in the mitochondrial membrane potential, cascade activation of caspases-9, -3, and -6, and DNA fragmentation. Moreover, weakening the ER stress-iROS axis concomitantly overcome resveratrol-induced decreases in translocation of Rho protein to membranes and succeeding cell migration. Interestingly, administration of resveratrol did not cause significant side effects but could protect the neuroblastoma-bearing nude mice from body weight loss and consequently extended the animal survival. In parallel, resveratrol elevated levels of Grp78 and then induced cell apoptosis in neuroblastoma tissues. This study has shown that resveratrol could kill neuroblastoma cells and extend survival of animals with neuroblastomas by triggering the ER stress-iROS-involved intrinsic apoptosis and suppression of Rho-dependent cell migration. Our results imply the potential of resveratrol as a drug candidate for chemotherapy of neuroblastoma patients.

Effect of patient decision aids on choice between sugammadex and neostigmine in surgeries under general anesthesia: a multicenter randomized controlled trial.

BACKGROUND: Shared decision making using patient decision aids (PtDAs) was established over a decade ago, but few studies have evaluated its efficacy in Asian countries. We therefore evaluated the application of PtDAs in a decision conflict between two muscle relaxant reversal agents, neostigmine and sugammadex, and sequentially analyzed the regional differences and operating room turnover rates. METHODS: This multicenter, outcome-assessor-blind, randomized controlled trial included 3,132 surgical patients from two medical centers admitted between March 2020 and August 2020. The patients were randomly divided into the classical and PtDA groups for pre-anesthesia consultations. Their clinicodemographic characteristics were analyzed to identify variables influencing the choice of reversal agent. On the day of the pre-anesthesia consultation, the patients completed the four SURE scale (sure of myself, understand information, risk-benefit ratio, encouragement) screening items. The operating turnover rates were also evaluated using anesthesia records. RESULTS: Compared with the classical group, the PtDA group felt more confident about receiving sufficient medical information (P < 0.001), felt better informed about the advantages and disadvantages of the medications (P < 0.001), exhibited a superior understanding of the benefits and risks of their options (P < 0.001), and felt surer about their choice (P < 0.001). Moreover, the PtDA group had a significantly greater tendency to choose sugammadex over neostigmine (P < 0.001). CONCLUSIONS: PtDA interventions in pre-anesthesia consultations provided surgical patients with clear knowledge and better support. PtDAs should be made available in other medical fields to enhance shared clinical decision-making.

Cigarette smoking, opioid consumption, and pain intensity after major surgery: An observational study.

BACKGROUND: Chronic exposure to nicotine may change pain perception and promote opioid intake. This study aimed to evaluate the putative effect of cigarette smoking on opioid requirements and pain intensity after surgery. METHODS: Patients who underwent major surgery and received intravenous patient-controlled analgesia (IV-PCA) at a medical center between January 2020 and March 2022 were enrolled. Patients' preoperative smoking status was assessed using a questionnaire by certified nurse anesthetists. The primary outcome was postoperative opioid consumption within 3 days after surgery. The secondary outcome was the mean daily maximum pain score, assessed using a self-report 11-point numeric rating scale, and the number of IV-PCA infusion requests within three postoperative days. Multivariable linear regression models were used to calculate the regression coefficient (beta) and 95% confidence interval (CI) for the association between smoking status and outcomes of interest. RESULTS: A total of 1162 consecutive patients were categorized into never smokers (n = 968), former smokers (n = 45), and current smokers (n = 149). Current smoking was significantly associated with greater postoperative opioid consumption (beta: 0.296; 95% CI, 0.068-0.523), higher pain scores (beta: 0.087; 95% CI, 0.009-0.166), and more infusion requests (beta: 0.391; 95% CI, 0.073-0.710) compared with never smokers. In a dose-dependent manner, smoking quantity (cigarette per day) was positively correlated with both intraoperative (Spearman's rho: 0.2207, p = 0.007) and postoperative opioid consumption (Spearman's rho: 0.1745, p = 0.033) among current smokers. CONCLUSION: Current cigarette smokers experienced higher acute pain, had more IV-PCA infusion requests, and consumed more opioids after surgery. Multimodal analgesia with nonopioid analgesics and opioid-sparing techniques, along with smoking cessation should be considered for this population.

Cost-Effectiveness of Sugammadex Versus Neostigmine to Reverse Neuromuscular Blockade in a University Hospital in Taiwan: A Propensity Score-Matched Analysis.

Sugammadex has several pharmacological advantages over neostigmine, including faster reversal of neuromuscular blockade and fewer adverse effects. However, the economic impact of sugammadex remains controversial due to the considerable heterogeneity of study designs and clinical settings in previous studies. In a post-hoc analysis of a randomized controlled trial, we evaluated patients who underwent elective surgeries and general anesthesia with endotracheal intubation in a medical center in Taiwan between March 2020 and August 2020. Patients were divided into either the sugammadex or neostigmine group based on the neuromuscular blocking drug used. Propensity score matching was used to balance the baseline patient characteristics between the two groups. The patient's recovery from anesthesia and the putative cost-effectiveness of sugammadex versus neostigmine was assessed. Derived cost-effectiveness using personnel costs in the operating room and the post-anesthesia care unit was estimated using multiple linear regression models. A total of 2587 and 1784 patients were included before and after matching, respectively. Time to endotracheal extubation was significantly shorter in the sugammadex group (mean 6.0 ± standard deviation 5.3 min) compared with the neostigmine group (6.6 ± 6.3 min; p = 0.0032). In addition, the incidence of bradycardia was significantly lower in the sugammadex group (10.2%) compared with the neostigmine group (16.9%; p < 0.001). However, the total costs were significantly lower in the neostigmine group (50.6 ± 21.4 United States dollars) compared with the sugammadex group (212.0 ± 49.5 United States dollars). Despite improving postoperative recovery, the benefits of sugammadex did not outweigh its higher costs compared with neostigmine, possibly due to the low costs of labor in Taiwan's healthcare system.

Contribution of the Testosterone Androgen Receptor-PARD3B Signaling Axis to Tumorigenesis and Malignance of Glioblastoma Multiforme through Stimulating Cell Proliferation and Colony Formation.

BACKGROUND: Glioblastoma multiforme (GBM) is the most common and malignant brain tumor with very poor prognoses. After surgical resection of the primary tumor, rapid proliferation of residual glioblastoma cells is a critical cause explaining tumor malignance and recurrence. In this study, we evaluated de novo roles of the testosterone androgen receptor (AR)-PARD3B signaling axis in the tumorigenesis and malignance of human GBM and the possible related mechanisms. METHODS: AR and PARD3B gene expressions and their correlations were mined from The Cancer Genome Atlas (TCGA) database and analyzed using the UALCAN system. Analyses using a real-time PCR, cell proliferation, and colony formation and a loss-of-function strategy by suppressing AR activity with its specific inhibitor, enzalutamide, were then carried out to determine roles of the testosterone AR-PARD3B signaling axis in tumor malignance. RESULTS: Expressions of AR, PARD3B mRNA, and proteins in human GBM tissues were upregulated compared to normal human brain tissues. In contrast, levels of AR and PARD3B mRNA in most TCGA pan-cancer types were downregulated compared to their respective normal tissues. Interestingly, a highly positive correlation between AR and PARD3B gene expressions in human GBM was identified. The results of a bioinformatics search further showed that there were five AR-specific DNA-binding elements predicted in the 5' promoter of the PARD3B gene. Regarding the mechanisms, exposure of human glioblastoma cells to testosterone induced AR and PARD3B gene expressions and successively stimulated cell proliferation and colony formation. Suppressing AR activity concurrently resulted in significant attenuations of testosterone-induced PARD3B gene expression, cell proliferation, and colony formation in human glioblastoma cells. CONCLUSIONS: This study showed the contribution of the testosterone AR-PARD3B signaling axis to the tumorigenesis and malignance of human GBM through stimulating cell proliferation and colony formation. Therefore, the AR-PARD3B signaling axis could be targeted for potential therapy for human GBM.

Fatigue and Arousal Modulations Revealed by Saccade and Pupil Dynamics.

Saccadic eye movements are directed to the objects of interests and enable high-resolution visual images in the exploration of the visual world. There is a trial-to-trial variation in saccade dynamics even in a simple task, possibly attributed to arousal fluctuations. Previous studies have showed that an increase of fatigue level over time, also known as time-on-task, can be revealed by saccade peak velocity. In addition, pupil size, controlled by the autonomic nervous system, has long been used as an arousal index. However, limited research has been done with regards to the relation between pupil size and saccade behavior in the context of trial-to-trial variation. To investigate fatigue and arousal effects on saccadic and pupillary responses, we used bright and emotional stimuli to evoke pupillary responses in tasks requiring reactive and voluntary saccade generation. Decreased voluntary saccade peak velocities, reduced tonic pupil size and phasic pupillary responses were observed as time-on-task increased. Moreover, tonic pupil size affected saccade latency and dynamics, with steeper saccade main sequence slope as tonic pupil size increased. In summary, saccade dynamics and tonic pupil size were sensitive to fatigue and arousal level, together providing valuable information for the understanding of human behavior.

Investigating the role of human frontal eye field in the pupil light reflex modulation by saccade planning and working memory.

The pupil constricts in response to an increase in global luminance level, commonly referred to as the pupil light reflex. Recent research has shown that these reflex responses are modulated by high-level cognition. There is larger pupil constriction evoked by a bright stimulus when the stimulus location spatially overlaps with the locus of attention, and these effects have been extended to saccade planning and working memory (here referred to as pupil local-luminance modulation). Although research in monkeys has further elucidated a central role of the frontal eye field (FEF) and superior colliculus in the pupil local-luminance modulation, their roles remain to be established in humans. Through applying continuous theta-burst transcranial magnetic stimulation over the right FEF (and vertex) to inhibit its activity, we investigated the role of the FEF in human pupil local-luminance responses. Pupil light reflex responses were transiently evoked by a bright patch stimulus presented during the delay period in the visual- and memory-delay tasks. In the visual-delay task, larger pupil constriction was observed when the patch location was spatially aligned with the target location in both stimulation conditions. More interestingly, after FEF stimulation, larger pupil constriction was obtained when the patch was presented in the contralateral, compared to the ipsilateral visual field of the stimulation. In contrast, FEF stimulation effects were absence in the memory-delay task. Linear mixed model results further found that stimulation condition, patch location consistency, and visual field significantly modulated observed pupil constriction responses. Together, our results constitute the first evidence of FEF modulation in human pupil local-luminance responses.

A comparison of high-flow nasal cannula and standard facemask as pre-oxygenation technique for general anesthesia: A PRISMA-compliant systemic review and meta-analysis.

BACKGROUND: Current practice guidelines recommend the use of nasal cannula as an alternative pre-oxygenation method for tracheal intubation. However, the efficacy of high-flow nasal oxygenation versus standard facemask oxygenation has not been fully evaluated. METHODS: We searched PubMed, Cochrane Library, and ClinicalTrials.gov for English-language studies published from January 1, 2000 to November 30, 2021. We included randomized controlled trials which compared high-flow nasal oxygenation and facemask oxygenation as the pre-oxygenation maneuver. Primary outcome was arterial partial pressure of oxygen (PaO2) after pre-oxygenation. Secondary outcomes were safe apnea time, arterial desaturation during intubation, lowest peripheral capillary oxygen saturation during intubation, and patient comfort score. Random-effects models and Mantel-Haenszel method were used for data synthesis. RESULTS: A total of 16 randomized controlled trials and 1148 patients were included. High-flow nasal oxygenation achieved a higher PaO2 compared with facemask, mean difference: 64.86 mm Hg (95% confidence interval [CI]: 32.33-97.40, P < .0001). Safe apnea time was longer in high-flow nasal oxygenation, mean difference: 131.03 seconds (95% CI: 59.39-202.66, P < .0001). There was no difference in the risk of peri-intubation desaturation or lowest peripheral capillary oxygen saturation between groups. Patient comfort score was higher in high-flow nasal oxygenation, mean difference: 1.00 (95% CI: 0.46-1.54, P = .0003). CONCLUSION: High-flow nasal oxygenation better enhanced PaO2 and extended safe apnea time and is not inferior to facemask oxygenation in preventing desaturation during tracheal intubation. High-flow nasal oxygenation may be considered as an alternative method, especially for patients with a potential difficult airway.

The Association between General Anesthesia and New Postoperative Uses of Sedative-Hypnotics: A Nationwide Matched Cohort Study.

Sedative−hypnotic misuse is associated with psychiatric diseases and overdose deaths. It remains uncertain whether types of anesthesia affect the occurrence of new postoperative uses of sedative−hypnotics (NPUSH). We used reimbursement claims data of Taiwan's National Health Insurance and conducted propensity score matching to compare the risk of NPUSH between general and neuraxial anesthesia among surgical patients who had no prescription of oral sedative−hypnotics or diagnosis of sleep disorders within the 12 months before surgery. The primary outcome was NPUSH within 180 days after surgery. Multivariable logistic regression models were used to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI). A total of 92,222 patients were evaluated after matching. Among them, 15,016 (16.3%) had NPUSH, and 2183 (4.7%) were made a concomitant diagnosis of sleep disorders. General anesthesia was significantly associated both with NPUSH (aOR: 1.17, 95% CI: 1.13−1.22, p < 0.0001) and NPUSH with sleep disorders (aOR: 1.11, 95% CI: 1.02−1.21, p = 0.0212) compared with neuraxial anesthesia. General anesthesia was also linked to NPUSH that occurred 90−180 days after surgery (aOR: 1.12, 95% CI: 1.06−1.19, p = 0.0002). Other risk factors for NPUSH were older age, female, lower insurance premium, orthopedic surgery, specific coexisting diseases (e.g., anxiety disorder), concurrent medications (e.g., systemic steroids), postoperative complications, perioperative blood transfusions, and admission to an intensive care unit. Patients undergoing general anesthesia had an increased risk of NPUSH compared with neuraxial anesthesia. This finding may provide an implication in risk stratification and prevention for sedative−hypnotic dependence after surgery.

Spectral Entropy Monitoring Accelerates the Emergence from Sevoflurane Anesthesia in Thoracic Surgery: A Randomized Controlled Trial.

The clinical efficacy of spectral entropy monitoring in improving postoperative recovery remains unclear. This trial aimed to investigate the impact of M-Entropy (GE Healthcare, Helsinki, Finland) guidance on emergence from anesthesia and postoperative delirium in thoracic surgery. Adult patients undergoing video-assisted thoracoscopic surgery for lung resection at a medical center were randomly allocated into the M-Entropy guidance group (n = 39) and the control group (n = 37). In the M-Entropy guidance group, sevoflurane anesthesia was titrated to maintain response and state entropy values between 40 and 60 intraoperatively. In the control group, the dosing of sevoflurane was adjusted based on clinical judgment and vital signs. The primary outcome was time to spontaneous eye opening. M-Entropy guidance significantly reduced the time proportion of deep anesthesia (entropy value <40) during surgery, mean difference: −21.5% (95% confidence interval (CI): −32.7 to −10.3) for response entropy and −24.2% (−36.3 to −12.2) for state entropy. M-Entropy guidance significantly shortened time to spontaneous eye opening compared to clinical signs, mean difference: −154 s (95% CI: −259 to −49). In addition, patients of the M-Entropy group had a lower rate of emergence agitation (absolute risk reduction: 0.166, 95% CI: 0.005−0.328) and delirium (0.245, 0.093−0.396) at the postanesthesia care unit. M-Entropy-guided anesthesia hastened awakening and potentially prevented emergence agitation and delirium after thoracic surgery. These results may provide an implication for facilitating postoperative recovery and reducing the complications associated with delayed emergence and delirium.