Nomo1 deficiency causes autism-like behavior in zebrafish.

Patients with neuropsychiatric disorders often exhibit a combination of clinical symptoms such as autism, epilepsy, or schizophrenia, complicating diagnosis and development of therapeutic strategies. Functional studies of novel genes associated with co-morbidities can provide clues to understand the pathogenic mechanisms and interventions. NOMO1 is one of the candidate genes located at 16p13.11, a hotspot of neuropsychiatric diseases. Here, we generate nomo1-/- zebrafish to get further insight into the function of NOMO1. Nomo1 mutants show abnormal brain and neuronal development and activation of apoptosis and inflammation-related pathways in the brain. Adult Nomo1-deficient zebrafish exhibit multiple neuropsychiatric behaviors such as hyperactive locomotor activity, social deficits, and repetitive stereotypic behaviors. The Habenular nucleus and the pineal gland in the telencephalon are affected, and the melatonin level of nomo1-/- is reduced. Melatonin treatment restores locomotor activity, reduces repetitive stereotypic behaviors, and rescues the noninfectious brain inflammatory responses caused by nomo1 deficiency. These results suggest melatonin supplementation as a potential therapeutic regimen for neuropsychiatric disorders caused by NOMO1 deficiency.

Influence of Transcutaneous Vagus Nerve Stimulation on Motor Planning: A Resting-State and Task-State EEG Study.

Transcutaneous vagus nerve stimulation (tVNS) shows a potential regulatory role for motor planning. Still, existing research mainly focuses on behavioral studies, and the neural modulation mechanism needs to be clarified. Therefore, we designed a multi-condition (active or sham, pre or under, difficult or easy, left-hand or right-hand) motor planning experiment to explore the effect of online tVNS (i.e., tVNS and tasks synchronized). Twenty-eight subjects were recruited and randomly assigned to active and sham groups. Both groups performed the same tasks in the experiment and separately collected task-state EEG and 5-min eye-open resting-state EEG. The results showed that the changes in event-related potential (ERP) and movement-related cortical potential (MRCP) amplitudes were more significant for the left-hand difficult task (LD) under active-tVNS. According to the power spectrum results, active-tVNS significantly modulated the activities of the contralateral motor cortex at beta and gamma bands in the resting state. The functional connectivity based on partial directed coherence (PDC) showed significant changes in the parietal lobe after active-tVNS. These findings suggest that tVNS is a promising way to improve motor planning ability.

Enhancing Motor Sequence Learning via Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): An EEG Study.

Motor learning plays a crucial role in human life, and various neuromodulation methods have been utilized to strengthen or improve it. Transcutaneous auricular vagus nerve stimulation (taVNS) has gained increasing attention due to its non-invasive nature, affordability and ease of implementation. Although the potential of taVNS on regulating motor learning has been suggested, its actual regulatory effect has yet been fully explored. Electroencephalogram (EEG) analysis provides an in-depth understanding of cognitive processes involved in motor learning so as to offer methodological support for regulation of motor learning. To investigate the effect of taVNS on motor learning, this study recruited 22 healthy subjects to participate a single-blind, sham-controlled, and within-subject serial reaction time task (SRTT) experiment. Every subject involved in two sessions at least one week apart and received a 20-minute active/sham taVNS in each session. Behavioral indicators as well as EEG characteristics during the task state, were extracted and analyzed. The results revealed that compared to the sham group, the active group showed higher learning performance. Additionally, the EEG results indicated that after taVNS, the motor-related cortical potential amplitudes and alpha-gamma modulation index decreased significantly and functional connectivity based on partial directed coherence towards frontal lobe was enhanced. These findings suggest that taVNS can improve motor learning, mainly through enhancing cognitive and memory functions rather than simple movement learning. This study confirms the positive regulatory effect of taVNS on motor learning, which is particularly promising as it offers a potential avenue for enhancing motor skills and facilitating rehabilitation.

Acoustoelectric brain imaging with different conductivities and acoustic distributions.

Objective: Acoustoelectric brain imaging (AEBI) is a promising imaging method for mapping brain biological current densities with high spatiotemporal resolution. Currently, it is still challenging to achieve human AEBI with an unclear acoustoelectric (AE) signal response of medium characteristics, particularly in conductivity and acoustic distribution. This study introduces different conductivities and acoustic distributions into the AEBI experiment, and clarifies the response interaction between medium characteristics and AEBI performance to address these key challenges. Approach: AEBI with different conductivities is explored by the imaging experiment, potential measurement, and simulation on a pig's fat, muscle, and brain tissue. AEBI with different acoustic distributions is evaluated on the imaging experiment and acoustic field measurement through a deep and surface transmitting model built on a human skullcap and pig brain tissue. Main results: The results show that conductivity is not only inversely proportional to the AE signal amplitude but also leads to a higher AEBI spatial resolution as it increases. In addition, the current source and sulcus can be located simultaneously with a strong AE signal intensity. The transcranial focal zone enlargement, pressure attenuation in the deep-transmitting model, and ultrasound echo enhancement in the surface-transmitting model cause a reduced spatial resolution, FFT-SNR, and timing correlation of AEBI. Under the comprehensive effect of conductivity and acoustics, AEBI with skull finally shows reduced imaging performance for both models compared with no-skull AEBI. On the contrary, the AE signal amplitude decreases in the deep-transmitting model and increases in the surface-transmitting model. Significance: This study reveals the response interaction between medium characteristics and AEBI performance, and makes an essential step toward developing AEBI as a practical neuroimaging technique.

Hypothermic Protection in Neocortex Is Topographic and Laminar, Seizure Unmitigating, and Partially Rescues Neurons Depleted of RNA Splicing Protein Rbfox3/NeuN in Neonatal Hypoxic-Ischemic Male Piglets.

The effects of hypothermia on neonatal encephalopathy may vary topographically and cytopathologically in the neocortex with manifestations potentially influenced by seizures that alter the severity, distribution, and type of neuropathology. We developed a neonatal piglet survival model of hypoxic-ischemic (HI) encephalopathy and hypothermia (HT) with continuous electroencephalography (cEEG) for seizures. Neonatal male piglets received HI-normothermia (NT), HI-HT, sham-NT, or sham-HT treatments. Randomized unmedicated sham and HI piglets underwent cEEG during recovery. Survival was 2-7 days. Normal and pathological neurons were counted in different neocortical areas, identified by cytoarchitecture and connectomics, using hematoxylin and eosin staining and immunohistochemistry for RNA-binding FOX-1 homolog 3 (Rbfox3/NeuN). Seizure burden was determined. HI-NT piglets had a reduced normal/total neuron ratio and increased ischemic-necrotic/total neuron ratio relative to sham-NT and sham-HT piglets with differing severities in the anterior and posterior motor, somatosensory, and frontal cortices. Neocortical neuropathology was attenuated by HT. HT protection was prominent in layer III of the inferior parietal cortex. Rbfox3 immunoreactivity distinguished cortical neurons as: Rbfox3-positive/normal, Rbfox3-positive/ischemic-necrotic, and Rbfox3-depleted. HI piglets had an increased Rbfox3-depleted/total neuron ratio in layers II and III compared to sham-NT piglets. Neuronal Rbfox3 depletion was partly rescued by HT. Seizure burdens in HI-NT and HI-HT piglets were similar. We conclude that the neonatal HI piglet neocortex has: (1) suprasylvian vulnerability to HI and seizures; (2) a limited neuronal cytopathological repertoire in functionally different regions that engages protective mechanisms with HT; (3) higher seizure burden, insensitive to HT, that is correlated with more panlaminar ischemic-necrotic neurons in the somatosensory cortex; and (4) pathological RNA splicing protein nuclear depletion that is sensitive to HT. This work demonstrates that HT protection of the neocortex in neonatal HI is topographic and laminar, seizure unmitigating, and restores neuronal depletion of RNA splicing factor.

[Gut microbial dysbiosis under space environment: a review].

Unique factors in the space environment can cause dysbiosis of astronauts' gut microbiota and its metabolites, which may exert systematic physiological effects on human body. Recent progress regarding the effect of space flight/simulated space environment (SF/SPE) on the composition of gut microbiota and its metabolites was reviewed in this paper. SF/SPE may cause the increase of invasive pathogenic bacteria and the decrease of beneficial bacteria, aggravating intestinal inflammation and increasing intestinal permeability. SF/SPE may also cause the decrease of beneficial metabolites or the increase of harmful metabolites of gut microbiota, leading to metabolism disorder in vivo, or inducing damage of other systems, thus not beneficial to the health and working efficiency of astronauts. Summarizing the effects of SF/SPE on gut microbiota may provide scientific basis for further researches in this field and the on-orbit health protection of astronauts.

An Atypical Incontinentia Pigmenti Female with Persistent Mucocutaneous Hyperinflammation and Immunodeficiency Caused by a Novel Germline IKBKG Missense Mutation.

While most missense mutations of the IKBKG gene typically result in Ectodermal Dysplasia with Immunodeficiency, there have been rare reported instances of missense mutations of the IKBKG gene causing both Incontinentia Pigmenti (IP) and immunodeficiency in female patients. In this study, we described an atypical IP case in a 19-year-old girl, characterized by hyperpigmented and verrucous skin areas over the entire body. Remarkably, she experienced recurrent red papules whenever she had a feverish upper respiratory tract infection. Immunohistochemical staining unveiled a substantial accumulation of CD68+ macrophages alongside the TNF-α positive cells in the dermis tissue of new pustules, with increased apoptotic basal keratinocytes in the epidermis tissue of these lesions. Starting from the age of 8 years old, the patient suffered from severe and sustained chronic respiratory mucous membrane scar hyperplasia and occluded subglottic lumen. In addition to elevated erythrocyte sedimentation rate values, inflammatory cells were observed in the pathologic lesions of endobronchial biopsies and Bronchoalveolar Lavage Fluid (BALF) smear. Further histological analysis revealed a destructive bronchus epithelium integrity with extensive necrosis. Simultaneously, the patient experienced recurrent incomplete intestinal obstructions and lips contracture. The patient's BALF sample displayed an augmented profile of proinflammatory cytokines and chemokines, suggesting a potential link to systemic hyperinflammation, possibly underlying the pathogenic injuries affecting the subglottic, respiratory, and digestive systems. Furthermore, the patient presented with recurrent pneumonias and multiple warts accompanied by a T+BlowNKlow immunophenotype. Next generation sequencing showed that the patient carried a novel de novo germline heterozygous missense mutation in the IKBKG gene (c. 821T>C, p. L274P), located in the highly conserved CC2 domain. TA-cloning sequencing of patient's cDNA yielded 30 mutant transcripts out of 44 clones. In silico analysis indicated that the hydrogen bond present between Ala270 and Leu274 in the wild-type NEMO was disrupted by the Leu274Pro mutation. However, this mutation did not affect NEMO expression in peripheral blood mononuclear cells (PBMCs). Moreover, patient PBMCs exhibited significantly impaired TNF-α production following Lipopolysaccharide (LPS) stimulation. X-chromosome inactivation in T cells and neutrophils were not severely skewed. Reduced levels of IκBα phosphorylation and degradation in patient's PBMCs were observed. The NF-κB luciferase reporter assay conducted using IKBKG-deficient HEK293T cells revealed a significant reduction in NF-kB activity upon LPS stimulation. These findings adds to the ever-growing knowledge on female IP that might contribute to the better understanding of this challenging disorder.

Mortality prediction using medical time series on TBI patients.

BACKGROUND AND OBJECTIVE: Traumatic Brain Injury (TBI) is one of the leading causes of injury-related mortality in the world, with severe cases reaching mortality rates of 30-40%. It is highly heterogeneous both in causes and consequences making more complex the medical interpretation and prognosis. Gathering clinical, demographic, and laboratory data to perform a prognosis requires time and skill in several clinical specialties. Artificial intelligence (AI) methods can take advantage of existing data by performing helpful predictions and guiding physicians toward a better prognosis and, consequently, better healthcare. The objective of this work was to develop learning models and evaluate their capability of predicting the mortality of TBI. The predictive model would allow the early assessment of the more serious cases and scarce medical resources can be pointed toward the patients who need them most. METHODS: Long Short Term Memory (LSTM) and Transformer architectures were tested and compared in performance, coupled with data imbalance, missing data, and feature selection strategies. From the Medical Information Mart for Intensive Care III (MIMIC-III) dataset, a cohort of TBI patients was selected and an analysis of the first 48 hours of multiple time series sequential variables was done to predict hospital mortality. RESULTS: The best performance was obtained with the Transformer architecture, achieving an AUC of 0.907 with the larger group of features and trained with class proportion class weights and binary cross entropy loss. CONCLUSIONS: Using the time series sequential data, LSTM and Transformers proved to be both viable options for predicting TBI hospital mortality in 48 hours after admission. Overall, using sequential deep learning models with time series data to predict TBI mortality is viable and can be used as a helpful indicator of the well-being of patients.

Calcium Imaging Characterize the Neurobiological Effect of Terahertz Radiation in Zebrafish Larvae.

(1) Objective: To explore the neurobiological effects of terahertz (THz) radiation on zebrafish larvae using calcium (Ca2+) imaging technology. (2) Methods: Zebrafish larvae at 7 days post fertilization (dpf) were exposed to THz radiation for 10 or 20 min; the frequency was 2.52 THz and the amplitude 50 mW/cm2. The behavioral experiments, neural Ca2+ imaging, and quantitative polymerase chain reaction (qPCR) of the dopamine-related genes were conducted following the irradiation. (3) Results: Compared with the control group, the behavioral experiments demonstrated that THz radiation significantly increased the distance travelled and speed of zebrafish larvae. In addition, the maximum acceleration and motion frequency were elevated in the 20 min radiation group. The neural Ca2+ imaging results indicated a substantial increase in zebrafish neuronal activity. qPCR experiments revealed a significant upregulation of dopamine-related genes, such as drd2b, drd4a, slc6a3 and th. (4) Conclusion: THz radiation (2.52 THz, 50 mW/cm2, 20 min) upregulated dopamine-related genes and significantly enhanced neuronal excitability, and the neurobiological effect of THz radiation can be visualized using neural Ca2+ imaging in vivo.

NKG2D-CAR T cells eliminate senescent cells in aged mice and nonhuman primates.

Cellular senescence, characterized by stable cell cycle arrest, plays an important role in aging and age-associated pathologies. Eliminating senescent cells rejuvenates aged tissues and ameliorates age-associated diseases. Here, we identified that natural killer group 2 member D ligands (NKG2DLs) are up-regulated in senescent cells in vitro, regardless of stimuli that induced cellular senescence, and in various tissues of aged mice and nonhuman primates in vivo. Accordingly, we developed and demonstrated that chimeric antigen receptor (CAR) T cells targeting human NKG2DLs selectively and effectively diminish human cells undergoing senescence induced by oncogenic stress, replicative stress, DNA damage, or P16INK4a overexpression in vitro. Targeting senescent cells with mouse NKG2D-CAR T cells alleviated multiple aging-associated pathologies and improved physical performance in both irradiated and aged mice. Autologous T cells armed with the human NKG2D CAR effectively delete naturally occurring senescent cells in aged nonhuman primates without any observed adverse effects. Our findings establish that NKG2D-CAR T cells could serve as potent and selective senolytic agents for aging and age-associated diseases driven by senescence.

EEG dynamics induced by zolpidem forecast consciousness evolution in prolonged disorders of consciousness.

OBJECTIVE: To explore whether the EEG dynamics induced by zolpidem can predict consciousness evolution in patients with prolonged disorders of consciousness (PDOC). METHODS: We conducted a prospective explorative analysis on thirty-six patients with PDOC and eleven healthy controls. The EEG power spectrum was analyzed and categorized into 'ABCD' patterns at baseline and one hour after zolpidem administration at 10 mg. The clinical outcome was defined as consciousness improvement and no improvement six months after enrollment using the Coma Recovery Scale-Revised (CRS-R) score. RESULTS: Zolpidem administration significantly increased the EEG power in the delta & theta bands and decreased EEG power in the beta bands in healthy controls. Further follow-up studies indicated that the increased EEG beta-band power induced by zolpidem can predict an improved consciousness six months after enrollment with an area under the receiver operating characteristic curve (AUC) of 0.829, the sensitivity of 94.38% and an accuracy of 81.48%. CONCLUSIONS: Our work revealed that the specific EEG responses to zolpidem can predict consciousness recovery in PDOC patients. SIGNIFICANCE: The zolpidem-induced specific EEG responses could potentially predict the recovery of PDOC patients, which may help clinicians and patients' families in their decision-making process.

Enhancing Motor Imagery Performance by Antiphasic 10 Hz Transcranial Alternating Current Stimulation.

Motor imagery (MI), as a cognitive motor process, involves the coordinated activation of frontal and parietal cortices and has been widely studied as an effective way to improve motor functions. However, there are large inter-individual differences in MI performance, with many subjects unable to elicit sufficiently reliable MI brain patterns. It has been shown that dual-site transcranial alternating current stimulation (tACS) applied on two brain sites can modulate functional connectivity between the targeted regions. Here, we investigated whether electrically stimulating frontal and parietal regions using dual-site tACS at mu frequency will modulate motor imagery performance. Thirty-six healthy participants were recruited and randomly divided into in-phase (0° lag), anti-phase (180° lag) and sham stimulation group. All groups performed the simple (grasping movement) and complex (writing movement) motor imagery tasks before and after tACS. Simultaneously collected EEG data showed that the event-related desynchronization (ERD) of mu rhythm and classification accuracy during complex task were significantly improved after anti-phase stimulation. In addition, anti-phase stimulation resulted in decreased event-related functional connectivity between regions within frontoparietal network in the complex task. In contrast, no beneficial after-effects of anti-phase stimulation were found in the simple task. These findings suggest that dual-site tACS effects on MI dependent on the phase lag of the stimulation and the complexity of the task. Anti-phase stimulation applied to the frontoparietal regions is a promising way to foster demanding MI task.

Right versus left eye asymmetry of microvasculature in diabetes revealed by optical coherence tomography angiography.

In this study, we explored inter-ocular asymmetry (between the two eyes of the same patient) using optical coherence tomography angiography (OCTA) in patients with diabetes mellitus (DM) at different retinopathy stages. A total of 258 patients were divided into four groups: no DM, DM without diabetic retinopathy (DR), non-proliferative DR (NPDR), and proliferative DR (PDR). Superficial and deep vessel density (SVD, DVD), superficial and deep perfusion density (SPD, DPD), foveal avascular zone (FAZ) area, perimeter and circularity were calculated, and asymmetry index (AI) was used to evaluate the asymmetry of two eyes of the same subject. AIs of SPD, SVD, FAZ area and FAZ perimeter in the PDR group were larger than all other 3 groups (all p < 0.05). The AIs of DPD, DVD, FAZ area and FAZ perimeter in males were larger than in females (p = 0.015, p = 0.023, p = 0.006 and p = 0.017). Hemoglobin A1c (HbA1c) was positively correlated with AI of FAZ perimeter (p = 0.02) and circularity (p = 0.022). In conclusion, PDR patients' eyes were significantly asymmetric in both vascular density and FAZ metrics. Male sex and HbA1c are risk factors that influenced symmetry. This study highlights that right-left asymmetry should be taken into account in DR-related studies, particularly those analyzing microvascular changes with OCTA.

Juvenile idiopathic arthritis presenting as diffuse alveolar hemorrhage at onset: A case series.

OBJECTIVE: The etiology of diffuse alveolar hemorrhage (DAH) in childhood is often unknown, and it may be an early manifestation of rheumatic disease. Juvenile idiopathic arthritis (JIA) is one of the most common rheumatic diseases in children, but DAH as an onset manifestation of JIA is rare. This study summarizes the clinical characteristics of patients with JIA presenting as DAH. METHODS: We retrospectively analyzed the age of onset, clinical manifestations, imaging features, treatments, and prognosis of five cases of JIA presenting as DAH. RESULTS: Themedian age at DAH onset was 6 months (range, 2 months-3 years). Pallor was the most common manifestation of onset (5/5). Other symptoms included cough (2/5), tachypnea (2/5), hemoptysis (1/5), cyanosis (1/5), and fatigue (1/5). Imaging showed ground-glass opacity (GGO) (5/5), subpleural or intrapulmonary honeycombing (4/5), consolidation (3/5), interlobular septal thickening (2/5), and nodules (1/5). Anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF) were positive in five children (5/5), and antinuclear antibody (ANA) was positive in four children (4/5). ANA in three children and ACPA/RF in one child were positive before the onset of joint symptoms. The median age at the onset of joint symptoms was 3 years and 9 months (2 years and 6 months-8 years). Joint symptoms were mainly characterized by joint swelling, pain, and difficulty walking, and the most commonly affected joints were the knees, ankles, and wrists. After the diagnosis of DAH, the five patients were treated with glucocorticoids. Alveolar hemorrhage was effectively controlled in three cases, but the other two patients still had anemia and poor improvements in chest imaging. After joint symptoms, the patients were treated with glucocorticoids combined with diclofenac, disease-modifying antirheumatic drugs, and biological agents. Alveolar hemorrhage was in remission, and joint symptoms were relieved in the five cases. CONCLUSION: DAH can be the first clinical manifestation of JIA, and joint involvement occurs 1-5 years later. Children with DAH who are positive for RF, ACPA, and/or ANA and have GGO accompanied by honeycombing on imaging should be concerned about their joint involvement in future.

EPAS1 prevents telomeric damage-induced senescence by enhancing transcription of TRF1, TRF2, and RAD50.

Telomeres are nucleoprotein structures located at the end of each chromosome, which function in terminal protection and genomic stability. Telomeric damage is closely related to replicative senescence in vitro and physical aging in vivo. As relatively long-lived mammals based on body size, bats display unique telomeric patterns, including the up-regulation of genes involved in alternative lengthening of telomeres (ALT), DNA repair, and DNA replication. At present, however, the relevant molecular mechanisms remain unclear. In this study, we performed cross-species comparison and identified EPAS1, a well-defined oxygen response gene, as a key telomeric protector in bat fibroblasts. Bat fibroblasts showed high expression of EPAS1, which enhanced the transcription of shelterin components TRF1 and TRF2, as well as DNA repair factor RAD50, conferring bat fibroblasts with resistance to senescence during long-term consecutive expansion. Based on a human single-cell transcriptome atlas, we found that EPAS1 was predominantly expressed in the human pulmonary endothelial cell subpopulation. Using in vitro-cultured human pulmonary endothelial cells, we confirmed the functional and mechanistic conservation of EPAS1 in telomeric protection between bats and humans. In addition, the EPAS1 agonist M1001 was shown to be a protective compound against bleomycin-induced pulmonary telomeric damage and senescence. In conclusion, we identified a potential mechanism for regulating telomere stability in human pulmonary diseases associated with aging, drawing insights from the longevity of bats.

Polynitroxylated PEGylated hemoglobin protects pig brain neocortical gray and white matter after traumatic brain injury and hemorrhagic shock.

Polynitroxylated PEGylated hemoglobin (PNPH, aka SanFlow) possesses superoxide dismutase/catalase mimetic activities that may directly protect the brain from oxidative stress. Stabilization of PNPH with bound carbon monoxide prevents methemoglobin formation during storage and permits it to serve as an anti-inflammatory carbon monoxide donor. We determined whether small volume transfusion of hyperoncotic PNPH is neuroprotective in a porcine model of traumatic brain injury (TBI) with and without accompanying hemorrhagic shock (HS). TBI was produced by controlled cortical impact over the frontal lobe of anesthetized juvenile pigs. Hemorrhagic shock was induced starting 5 min after TBI by 30 ml/kg blood withdrawal. At 120 min after TBI, pigs were resuscitated with 60 ml/kg lactated Ringer's (LR) or 10 or 20 ml/kg PNPH. Mean arterial pressure recovered to approximately 100 mmHg in all groups. A significant amount of PNPH was retained in the plasma over the first day of recovery. At 4 days of recovery in the LR-resuscitated group, the volume of frontal lobe subcortical white matter ipsilateral to the injury was 26.2 ± 7.6% smaller than homotypic contralateral volume, whereas this white matter loss was only 8.6 ± 12.0% with 20-ml/kg PNPH resuscitation. Amyloid precursor protein punctate accumulation, a marker of axonopathy, increased in ipsilateral subcortical white matter by 132 ± 71% after LR resuscitation, whereas the changes after 10 ml/kg (36 ± 41%) and 20 ml/kg (26 ± 15%) PNPH resuscitation were not significantly different from controls. The number of cortical neuron long dendrites enriched in microtubules (length >50 microns) decreased in neocortex by 41 ± 24% after LR resuscitation but was not significantly changed after PNPH resuscitation. The perilesion microglia density increased by 45 ± 24% after LR resuscitation but was unchanged after 20 ml/kg PNPH resuscitation (4 ± 18%). Furthermore, the number with an activated morphology was attenuated by 30 ± 10%. In TBI pigs without HS followed 2 h later by infusion of 10 ml/kg LR or PNPH, PNPH remained neuroprotective. These results in a gyrencephalic brain show that resuscitation from TBI + HS with PNPH protects neocortical gray matter, including dendritic microstructure, and white matter axons and myelin. This neuroprotective effect persists with TBI alone, indicating brain-targeting benefits independent of blood pressure restoration.

Transcutaneous Electrical Acupoints Stimulation Improves Spontaneous Voiding Recovery After Laparoscopic Cholecystectomy: A Randomized Clinical Trial.

BACKGROUND: Facilitating the recurrence of spontaneous voiding is considered to be a way to prevent urinary retention after surgery, which is of great importance in cholecystectomy. This study aimed to assess the effect of transcutaneous electrical acupoint stimulation (TEAS) on spontaneous voiding recovery after laparoscopic cholecystectom. METHODS: Participants who underwent elective laparoscopic cholecystectomy were randomly assigned to either the TEAS group or the sham group. Active TEAS or sham TEAS at specific acupuncture points was conducted intraoperatively and postoperatively. The primary outcome was the recovery speed of spontaneous voiding ability after surgery and secondary outcomes included postoperative urinary retention (POUR), voiding dysfunction, pain, anxiety and depression, and early recovery after surgery. RESULTS: A total of 1,948 participants were recruited and randomized to TEAS (n = 975) or sham (n = 973) between August 2018 and June 2020. TEAS shortens the time delay of the first spontaneous voiding after laparoscopic cholecystectomy (5.6 h [IQR, 3.7-8.1 h] in the TEAS group vs 7.0 h [IQR, 4.7-9.7 h] in the sham group) (p < 0.001). The TEAS group experienced less POUR (p = 0.020), less voiding difficulty (p < 0.001), less anxiety and depression (p < 0.001), reduced pain (p = 0.007), and earlier ambulation (p = 0.01) than the sham group. CONCLUSIONS: Our results showed that TEAS is an effective approach to accelerate the recovery of spontaneous voiding and reduce POUR which facilitates recovery for patients after laparoscopic cholecystectomy.