Brain clearance is reduced during sleep and anesthesia.

It has been suggested that the function of sleep is to actively clear metabolites and toxins from the brain. Enhanced clearance is also said to occur during anesthesia. Here, we measure clearance and movement of fluorescent molecules in the brains of male mice and show that movement is, in fact, independent of sleep and wake or anesthesia. Moreover, we show that brain clearance is markedly reduced, not increased, during sleep and anesthesia.

2D Tellurium Films Based Self-drive Near Infrared Photodetector.

To reduce the amount of energy consumed in integrated circuits, high efficiency with the lowest energy is always expected. Self-drive device is one of the options in the pursuit of low power nanodevices. It is a typical strategy to form an internal electric field by constructing a heterojunction in self-drive semiconductor system. Here, a two-step method is proposed to prepare high quality centimeter-sized 2D tellurium (Te) thin film with hall mobility as high as 37.3 cm2V-1s-1, and the 2D Te film is further assembled with silicon to form a heterojunction for self-drive photodetector, which can realize effective detection from visible to near infrared bands. The photodetectivity of the heterojunctions can reach 1.58 × 1011 Jones under the illumination of 400 nm@ 1.615 mW/cm2 and 2.08 x 108 Jones under the illumination of 1550 nm@ 1.511mW/cm2 without bias. Our experiments demonstrate the potential of 2D tellurium thin films for wide band and near infrared integrated device applications.

Effects of esketamine on postoperative negative emotions and early cognitive disorders in patients undergoing non-cardiac thoracic surgery: A randomized controlled trial.

STUDY OBJECTIVE: To investigate whether a single dosage of esketamine injection in the anesthesia period could improve postoperative negative emotions and early cognitive function in patients undergoing non-cardiac thoracic surgery. DESIGN: A prospective single center double blinded randomized placebo-controlled trial. SETTING: Perioperative period; operating room, post anesthesia care unit and hospital ward. PATIENTS: 129 adult patients that underwent elective non-cardiac thoracic surgery under general anesthesia. INTERVENTIONS: During the operation, pharmacologic prevention of postoperative negative emotion and early cognitive disorder with 0.2 mg/kg (Low esketamine group) and 0.5 mg/kg esketamine (High esketamine group) vs. placebo. MEASUREMENTS: Emotion and early cognitive performance were assessed on the day before surgery (POD-1), postoperative day 1 (POD1) and day 3 (POD3) using HADS-A, HADS-D, Pain Visual Analogue Scale (VAS), Confusion Assessment Method (CAM), Mini-Mental State Examination (MMSE), and serum biomarkers (S100ß, BDNF, IL-6, acetylcholine, and norepinephrine). MAIN RESULTS: The high esketamine group showed significantly lower HADS-A and HADS-D scores than control group on POD1 and POD3. No significant differences were observed between the low esketamine group and the control group. The esketamine-treated groups showed lower pain VAS scores than the control group at 2 h and on the first day after operation. There were no significant differences among the three groups in CAM and MMSE scores. However, the high esketamine group had lower S100ß and IL-6 levels, and higher BDNF levels postoperatively, while serum acetylcholine and norepinephrine were not significantly different. CONCLUSIONS: A single intraoperative injection of 0.5 mg/kg esketamine can alleviate postoperative anxiety, depression, and pain to some extent. Although cognitive function behavioral evaluation did not show obvious benefits, it can also reduce the production of pro-inflammatory and brain injury-related factors while promoting the generation of brain-derived neurotrophic factor. Registration Trial registry: http://www.chictr.org.cn/; Identifier: ChiCTR2100047067.

Hibernation-Like Behavior Induced by 2-Methyl-2-Thiazoline and Its Organ-Protective Effects and Mechanisms.

Hibernation is a prolonged state of low metabolism that animals enter in response to extreme environmental conditions to enhance their survival in harsh environments. Recent studies have shown that non-hibernating species can also be induced to enter a hibernation-like state. 2-methyl-2-thiazoline (2MT), a potent analog of fox odor, can induce fear-related behavior in mice with low body temperature and low metabolism, and has specific organ-protective effects. A systematic understanding of 2MT-induced hibernation and its underlying mechanisms may aid in expanding its applications in medicine and other fields.

MASCN Surface Treatment to Reduce Phase Transition Temperature and Regulate Strain for Efficient and Stable α-FAPbI3 Perovskite Solar Cells.

The fabrication of α-FAPbI3 perovskite films usually requires high temperature annealing above 150 °C, and the residual tensile strain in the films seriously affects the stability of α-FAPbI3 by converting to δ-phase FAPbI3. Here, we use MASCN surface treatment of FAPbI3 films to induce a rotation of the coplanar octahedron [PbI6]4- to the metric octahedron for the strong interaction of SCN- with Pb2+, converting δ-FAPbI3 into α-FAPbI3 highly crystalline films at room temperature. The optimized FAPbI3 films have high stability due to releasing residual tensile strains after MASCN treatment. The efficiency of the MASCN-treated unannealed FAPbI3 PSC is 19.03%, while the optimized FAPbI3 annealed at 100 °C shows a maximum PCE of 21.95% on a small area. The solar cell stability for humidity, light, and thermal stability are significantly improved. The MASCN treated FAPbI3 achieves a PCE of 15.32% on a PSC module with an effective area of 9.6 cm2 and maintains an initial efficiency of 94.1% after 100 days of ageing at 85 °C and 85% humidity.

Claustrum modulates behavioral sensitivity and EEG activity of propofol anesthesia.

AIMS: The claustrum has long been regarded as a vital center for conscious control. Electrical stimulation or damage to the claustrum can result in decreased awareness or loss of consciousness, suggesting that the claustrum may be a target for the action of general anesthetics. This study aimed to determine the role of the claustrum in propofol anesthesia. METHODS: We first applied a fiber photometry calcium signal recording system to record the claustral neuronal activity during the entire process of propofol anesthesia. Chemogenetic activation of claustral neurones was then performed to verify their role in anesthesia. Finally, muscimol (GABAa receptor agonist) and gabazine (GABAa receptor antagonist) were microinjected into the claustrum to determine whether their GABAa receptors were involved in modulating propofol anesthesia. EEG and behavioral indicators, such as anesthetic sensitivity and efficacy, were recorded and analyzed. RESULTS: An evident anesthesia-related change in claustrum neuronal activity was suppressed during propofol-induced unconsciousness and restored following recovery from anesthesia. Chemogenetic activation of claustrum neurons results in attenuated propofol sensitivity, a shorter anesthesia duration, and an EEG shift toward wakefulness. Manipulation of GABAa receptors in the claustrum showed bidirectional control of propofol sensitivity, as activation decreases anesthesia efficiency while inactivation augments it. Additionally, inhibiting claustrum GABAa receptors increases cortical EEG slow waves. CONCLUSIONS: Claustrum neurones and their GABAa receptors are implicated in the modulation of propofol anesthesia in both behavioral and EEG assessments. Our findings create scope to reveal the brain targets of anesthetic action further and add to the existing evidence on the consciousness-modulating role of the claustrum.

Omnibus or Ominous immigration laws? Immigration policy and mental health of the Hispanic population.

This study examines the impact of Omnibus Immigration Laws on the mental health of the Hispanic populations in the U.S. We use a Difference-in-Differences framework and data from the Behavioral Risk Factor Surveillance System Survey of Centers for Disease Control and Prevention for the 2000-2016 period that contains information on more than 400 thousand Hispanics residing in the U.S. We find that the most stringent provision, namely, "show me your papers" laws, adversely affects the mental health of Hispanics and contributes to an increase of 12%-16% in the number of unhealthy mental days and an increase of 13%-18% in the probability of having frequent mental distress in the states with "show me your papers" laws. OIL provisions that enforced the use of E-Verify or limited the use of public benefits to unauthorized immigrants did not have any effect on mental health. The study also examines (1) police stops, (2) physical health, insurance, and employment status, (3) co-ethnic density, and (4) immigration enforcement awareness as potential mechanisms that could lead to a deterioration in the mental health of Hispanics. The evidence indicates their vulnerability to strict immigration enforcement. The social and public health cost should be carefully evaluated when formulating and implementing immigration policies.

F-doping-Enhanced Carrier Transport in the SnO2/Perovskite Interface for High-Performance Perovskite Solar Cells.

SnO2 is widely used as the electron transport layer (ETL) in n-i-p perovskite solar cells. However, the deep-level defects at the interface between SnO2 and the perovskite film will lead to energy loss, reducing the open-circuit voltage. Therefore, the interface optimization is essential to raise the efficiency and enhance the stability of perovskite solar cells. In this work, we introduce NH4F into the SnO2 electron transport layers, and the optimized SnO2 films reduce the interface defect density, improve the charge extraction, and reveal a better energy-level arrangement. Compared to the conventional SnO2 perovskite solar cell, the average Voc is improved by 70 mV with the champion efficiency up to 22.12%. Moreover, the unencapsulated F-doped SnO2 perovskite solar cells show better thermal stability (maintained 86.2%) and humidity stability (maintained 80.8%) after 35 days.

The Obesity Effect of Arizona's State Immigration Law Among Hispanic Adolescents.

Since 2010, Arizona's immigration law (SB 1070) has produced unintended racial profiling consequences for Hispanics. Earlier empirical evidence establishes its adverse mental health effects on young Hispanics. This study expands the analysis by introducing obesogenic repercussions. Using Youth Risk Behavior Surveillance System data from 2001 to 2017, Synthetic Control Method techniques are employed to isolate the law's health consequences. Results indicate significant post-2010 deviations from indistinguishable pre-2010 trends in health indicators for Arizona and its synthetic states. After 2010, Arizona's Hispanic youths registered relatively significantly higher incidences of mutually reinforcing mental and physical (obesogenic) indicators, even after accounting for nutritional improvements. Our findings do not discredit weight reduction benefits of favorable diet choices, but rather emphasize the stronger offsetting influence of SB 1070-induced obesogenic health behaviors. Thus, there is a need for policy re-evaluation to curb the law's unintended ramifications and launch more targeted youth-oriented health support programs.

GABAA receptors in the basal forebrain mediates emergence from propofol anaesthesia in rats.

PURPOSE: The aim of the current study was to explore the role of the basal forebrain (BF) in propofol anaesthesia. METHODS: In the present study, we observed the neural activities of the BF during propofol anaesthesia using calcium fibre photometry recording. Subsequently, ibotenic acid was injected into the BF to verify the role of the BF in propofol anaesthesia. Finally, to test whether GABAA receptors in the BF were involved in modulating propofol anaesthesia, muscimol (GABAA receptor agonist) and gabazine (GABAA receptor antagonist) were microinjected into the BF. Cortical electroencephalogram (EEG), time to loss of righting reflex (LORR), and recovery of righting reflex (RORR) under propofol anaesthesia were recorded and analysed. RESULTS: The activity of BF neurons was inhibited during induction of propofol anaesthesia and activated during emergence from propofol anaesthesia. In addition, non-specifical lesion of BF neurons significantly prolonged the time to RORR and increased delta power in the frontal cortex under propofol anaesthesia. Next, microinjection of muscimol into the BF delayed emergence from propofol anaesthesia, increased delta power of the frontal cortex, and decreased gamma power under propofol anaesthesia. Conversely, infusion of gabazine accelerated emergence times and decreased EEG delta power. CONCLUSIONS: The basal forebrain is involved in modulating frontal cortex delta activity and emergence from propofol anaesthesia. Additionally, the GABAA receptors in the basal forebrain are involved in regulating emergence propofol anaesthesia.

Effect of basal forebrain somatostatin and parvalbumin neurons in propofol and isoflurane anesthesia.

AIMS: The basal forebrain (BF) plays an essential role in wakefulness and cognition. Two subtypes of BF gamma-aminobutyric acid (GABA) neurons, including somatostatin-expressing (GABASOM ) and parvalbumin-positive (GABAParv ) neurons, function differently in mediating the natural sleep-wake cycle. Since the loss of consciousness induced by general anesthesia and the natural sleep-wake cycle probably share similar mechanisms, it is important to clarify the accurate roles of these neurons in general anesthesia procedure. METHODS: Based on two transgenic mouse lines expressing SOM-IRES-Cre and PV-IRES-Cre, we used a combination of genetic activation, inactivation, and chronic ablation approaches to further explore the behavioral and electroencephalography (EEG) roles of BFSOM and BFParv neurons in general anesthesia. After a single intravenous injection of propofol and the induction and recovery times of isoflurane anesthesia, the anesthesia time was compared. The changes in cortical EEG under different conditions were also compared. RESULTS: Activation of BF GABASOM neurons facilitates both the propofol and isoflurane anesthesia, manifesting as a longer anesthesia duration time with propofol anesthesia and a fast induction time and longer recovery time with isoflurane anesthesia. Moreover, BF GABASOM -activated mice displayed a greater suppression of cortical electrical activity during anesthesia, showing an increase in δ power bands or a simultaneous decrease in high-frequency power bands. However, only a limited and nuanced effect on propofol and isoflurane anesthesia was observed with the manipulated BF GABAParv neurons. CONCLUSIONS: Our results suggested that BF GABASOM neurons play a critical role in propofol and isoflurane general anesthesia, while BF GABAParv neurons appeared to have little effect.

Lateral Habenula Glutamatergic Neurons Modulate Isoflurane Anesthesia in Mice.

Since their introduction in the 1840s, one of the largest mysteries of modern anesthesia are how general anesthetics create the state of reversible loss of consciousness. Increasing researchers have shown that neural pathways that regulate endogenous sleep-wake systems are also involved in general anesthesia. Recently, the Lateral Habenula (LHb) was considered as a hot spot for both natural sleep-wake and propofol-induced sedation; however, the role of the LHb and related pathways in the isoflurane-induced unconsciousness has yet to be identified. Here, using real-time calcium fiber photometry recordings in vivo, we found that isoflurane reversibly increased the activity of LHb glutamatergic neurons. Then, we selectively ablated LHb glutamatergic neurons in Vglut2-cre mice, which caused a longer induction time and less recovery time along with a decrease in delta-band power in mice under isoflurane anesthesia. Furthermore, using a chemogenetic approach to specifically activate LHb glutamatergic neurons shortened the induction time and prolonged the recovery time in mice under isoflurane anesthesia with an increase in delta-band power. In contrast, chemogenetic inhibition of LHb glutamatergic neurons was very similar to the effects of selective lesions of LHb glutamatergic neurons. Finally, optogenetic activation of LHb glutamatergic neurons or the synaptic terminals of LHb glutamatergic neurons in the rostromedial tegmental nucleus (RMTg) produced a hypnosis-promoting effect in isoflurane anesthesia with an increase in slow wave activity. Our results suggest that LHb glutamatergic neurons and pathway are vital in modulating isoflurane anesthesia.

Gastrodin promotes CNS myelination via a lncRNA Gm7237/miR-142a/MRF pathway.

Treatment of central nervous system (CNS) demyelination is greatly hindered by lack of the knowledge regarding to underlying molecular mechanisms as well as therapeutic agents. Here, we report a novel small molecule agent, gastrodin (GAS), which can significantly promote CNS myelination in in vivo mice models. By using high-throughput sequencing analysis, we discover a key long non-coding RNA Gm7237 that can enhance CNS myelination and is up-regulated by GAS. Through using bioinformatic analysis and experimental validations, we further unravel that microRNA-142a (miR-142a) and its target myelin gene regulatory factor (MRF) is under the direct regulation by Gm7237. Finally, we demonstrate that Gm7237/miR-142a/MRF axis is the key pathway involved in CNS myelination mediated by GAS. Overall, our results provide not only a novel agent for therapeutic treatment of CNS demyelination but also a molecular basis responsible for GAS-promoted CNS myelination.

Stringent immigration enforcement and the mental health and health-risk behaviors of Hispanic adolescent students in Arizona.

This study investigates the impact of the enforcement of SB 1070, a stringent immigration law, on the mental health, health-risk behaviors, and academic performance of Hispanic adolescent residents in Arizona. Using the difference-in-differences method, this study finds that SB 1070 increases their probability of feeling sad and decreases their physical activeness. The impact of SB 1070 on sad feelings and level of physical activity could have serious repercussions while it lasts. In addition, obese male Hispanic adolescents are more likely than their female or non-obese counterparts to develop mental health problems and engage in health-risk behaviors attributable to the stringent immigration policy. This study's empirical evidence on adverse mental health repercussions for Hispanic adolescents of state-level immigration enforcement suggests the need to be careful in formulating and implementing immigration policies.

Basal Forebrain Cholinergic Activity Modulates Isoflurane and Propofol Anesthesia.

Cholinergic neurons in the basal forebrain (BF) have long been considered to be the key neurons in the regulation of cortical and behavioral arousal, and cholinergic activation in the downstream region of the BF can arouse anesthetized rats. However, whether the activation of BF cholinergic neurons can induce behavior and electroencephalogram (EEG) recovery from anesthesia is unclear. In this study, based on a transgenic mouse line expressing ChAT-IRES-Cre, we applied a fiber photometry system combined with GCaMPs expression in the BF and found that both isoflurane and propofol inhibit the activity of BF cholinergic neurons, which is closely related to the consciousness transition. We further revealed that genetic lesion of BF cholinergic neurons was associated with a markedly increased potency of anesthetics, while designer receptor exclusively activated by designer drugs (DREADD)-activated BF cholinergic neurons was responsible for slower induction and faster recovery of anesthesia. We also documented a significant increase in δ power bands (1-4 Hz) and a decrease in ß (12-25 Hz) power bands in BF cholinergic lesioned mice, while there was a clearly noticeable decline in EEG δ power of activated BF cholinergic neurons. Moreover, sensitivity to anesthetics was reduced after optical stimulation of BF cholinergic cells, yet it failed to restore wake-like behavior in constantly anesthetized mice. Our results indicate a functional role of BF cholinergic neurons in the regulation of general anesthesia. Inhibition of BF cholinergic neurons mediates the formation of unconsciousness induced by general anesthetics, and their activation promotes recovery from the anesthesia state.

Activation of noradrenergic terminals in the reticular thalamus delays arousal from propofol anesthesia in mice.

Electroencephalogram monitoring during propofol (PRO) anesthesia typically features low-frequency oscillations, which may be involved with thalamic reticular nucleus (TRN) modulation. TRN receives noradrenergic inputs from the locus coeruleus (LC). We hypothesized that specific noradrenergic connections in the TRN may contribute to the emergence from PRO anesthesia. Intranuclei norepinephrine (NE) injections (n = 10) and designer receptors exclusively activated by designer drugs (DREADDs) (n = 10) were used to investigate the role of noradrenergic inputs from the LC to the TRN during PRO anesthesia. Whole-cell recording in acute brain slice preparations was used to identify the type of adrenoceptor that regulates noradrenergic innervation in the TRN. An intracerebral injection of NE into the TRN delays arousal in mice recovering from PRO anesthesia (means ± sd; 486.6 ± 57.32 s for the NE injection group vs. 422.4 ± 48.19 s for the control group; P = 0.0143) and increases the cortical-δ (0.1-4 Hz, 25.4 ± 2.9 for the NE injection group vs. 21.0 ± 1.7 for the control group; P = 0.0094) oscillation. An intra-TRN injection of NE also decreased the EC50 of PRO-induced unconsciousness (57.05 ± 1.78 mg/kg for the NE injection group vs. 72.44 ± 3.23 mg/kg for the control group; P = 0.0096). Moreover, the activation of LC-noradrenergic nerve terminals in the TRN using DREADDs increased the recovery time [466.1 ± 44.57 s for the clozapine N-oxide (CNO) injection group vs. 426.1 ± 38.75 s for the control group; P = 0.0033], decreased the EC50 of PRO-induced unconsciousness (64.77 ± 3.40 mg/kg for the CNO injection group vs. 74.00 ± 2.08 mg/kg for the control group; P = 0.0081), and increased the cortical-δ oscillation during PRO anesthesia (23.29 ± 2.58 for the CNO injection group vs. 19.56 ± 1.9 for the control group; P = 0.0213). In addition, whole-cell recording revealed that NE augmented the inhibitory postsynaptic currents in the TRN neurons via the α1-adrenoceptor. Our data indicated that enhanced NE signaling at the noradrenergic terminals of the LC-TRN projection delays arousal from general anesthesia, which is likely mediated by the α1-adrenoceptor activation. Our findings open a door for further understanding of the functions of various LC targets in both anesthesia and arousal.-Zhang, Y., Fu, B., Liu, C., Yu, S., Luo, T., Zhang, L., Zhou, W., Yu, T. Activation of noradrenergic terminals in the reticular thalamus delays arousal from propofol anesthesia in mice.

Parabrachial Neurons Promote Behavior and Electroencephalographic Arousal From General Anesthesia.

General anesthesia has been used clinically for more than 170 years, yet its underlying mechanisms are still not fully understood. The parabrachial nucleus (PBN) in the brainstem has been known to be crucial for regulating wakefulness and signs of arousal on the cortical electroencephalogram (EEG). Lesions of the parabrachial complex lead to unresponsiveness and a monotonous high-voltage, and a slow-wave EEG, which are the two main features of general anesthesia. However, it is unclear whether and how the PBN functions in the process of general anesthesia. By recording the levels of calcium in vivo in real-time, we found that the neural activity in PBN is suppressed during anesthesia, while it is robustly activated during recovery from propofol and isoflurane anesthesia. The activation of PBN neurons by "designer receptors exclusively activated by designer drugs" (DREADDs) shortened the recovery time but did not change the induction time. Cortical EEG recordings revealed that the neural activation of PBN specifically affected the recovery period, with a decrease of δ-band power or an increase in ß-band power; no EEG changes were seen in the anesthesia period. Furthermore, the activation of PBN elicited neural activation in the prefrontal cortex, basal forebrain, lateral hypothalamus, thalamus, and supramammillary nucleus. Thus, PBN is critical for behavioral and electroencephalographic arousal without affecting the induction of general anesthesia.

Health care service utilization of documented and undocumented hired farmworkers in the U.S.

This article analyzes issues related to U.S. hired farmworkers' utilization of health care services and their specific choices among health care provider and health bill payment method options. Using data from the National Agricultural Workers Surveys for the years 2000-2012, this article employs propensity score matching and probit estimation techniques to examine the health care utilization of hired farmworkers. This study's results indicate that undocumented hired farmworkers are 10.7 and 3% less likely to use U.S. and foreign health care, respectively, compared to documented farmworkers. Health insurance is found to significantly increase hired farmworkers' use of U.S. health care by 22.3%. Notably, compared to their documented working peers, undocumented workers are much less likely to patronize private clinics. They are even less likely to rely on migrant health centers even when these providers are their most viable sources of health care service.

Efficacy of different fluids preload on propofol injection pain: A randomized, controlled, double-blinded study.

Injection pain of propofol remains a common clinical problem. Previous studies demonstrated that propofol injection pain was alleviated by applying nitroglycerin ointment to the skin of injection site, which inspires us to test whether venous vasodilation induced by fluid preload could alleviate the pain. Different types or volumes of fluid preload were compared. 200 ASA I-II adult patients were randomly assigned to five groups of 40 each. A 20 G cannula was established on the dorsum or wrist of the hand. When fluid preload given with Plasma-Lyte A 100 mL (P100 group), 250 mL (P250 group), 500 mL (P500 group), 0.9% saline 500 mL (N500 group) or Gelofusine 500 mL (G500 group) was completed within 30 min, respectively, Propofol (0.5 mg/kg, 1%) was injected at a rate of 0.5 mL/s. A blind investigator assessed the pain using a four-point scale. Incidence of pain in P100, P250, and P500 groups was 87.5%, 57.5% and 35%, respectively (P<0.05). The median pain intensity score was significantly lower in P500 group than that in P250 and P100 groups (P<0.05 and P<0.01, respectively). Comparison of the effect of different types of solution preload indicated that the highest incidence of pain was in N500 group (62.5%) (N500 vs. P500, P=0.014; N500 vs. G500, P=0.007). The median pain intensity score in N500 group was higher than that in P500 group (P<0.05) and G500 group (P<0.05). There was no significant difference between P500 and G500 groups. It is suggested that Plasma-Lyte A or Gelofusine preload with 500 mL before propofol injection is effective in alleviating propofol-induced pain.