Non-alcoholic fatty liver disease risk with GLP-1 receptor agonists and SGLT-2 inhibitors in type 2 diabetes: a nationwide nested case-control study.

BACKGROUND: Non-alcoholic fatty liver diseases (NAFLDs)/non-alcoholic steatohepatitis (NASH) are the most common liver disorders among patients with type 2 diabetes. Newer classes of glucose-lowering agents (GLAs), such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is), have been shown to improve liver-related biomarkers. However, their effects on the development of NAFLD/NASH remain inconclusive. METHODS: A nested case-control study was conducted using Taiwan's National Health Insurance Research Database for 2011-2018. Patients aged ≥ 40 years, diagnosed with type 2 diabetes, having stable non-insulin GLA use, and without NAFLD/NASH history were included. Patients with incident NAFLD/NASH were matched up to 10 randomly sampled controls based on individual's age, gender, cohort entry date, type 2 diabetes diagnosis date, and disease risk score. Conditional logistic regression analyses were employed to estimate the association between liver risk and treatment exposure. Dose-response analysis was also performed. RESULTS: There were 621,438 study patients included for analysis. During 1.8 years of median follow-up, the incidence of NAFLD/NASH was 2.7 per 1000 person-years. After matching, 5,730 incident NAFLD cases (mean age: 57.6 years, male: 53.2%) and 45,070 controls (57.7 years, 52.7%) were identified. Using GLP-1RAs or SGLT2is was associated with an insignificantly lower NAFLD/NASH risk (i.e., odds ratios [95% CIs]: 0.84 [0.46-1.52] and 0.85 [0.63-1.14], respectively) and increased cumulative SGLT2i doses were significantly associated with a reduced NAFLD/NASH risk (0.61 [0.38-0.97]). CONCLUSION: GLP-1RA and SGLT2i therapies in type 2 diabetes patients might prevent NAFLD/NASH development, with a significantly lower risk related to greater treatment exposure.

Unveiling the molecular symphony: MicroRNA160a-Auxin Response Factor 18 module orchestrates low potassium tolerance in banana (Musa acuminata L.).

Potassium (K) is an essential nutrient for the growth and development of most plants. In banana (Musa acuminata L.), microRNA160a (miR160a) is suggested to potentially contribute to the response to low K+ stress by modulating the auxin signaling pathway. However, further investigation is required to elucidate its specific regulatory mechanism. This study presents evidence highlighting the critical role of the miR160a-Auxin Response Factor 18 (ARF18) module in conferring low K+ tolerance in banana. Both miR160a and its predicted target gene ARF18 displayed elevated expression levels in banana roots, with their expression profiles significantly altered under low K+ stress. The inhibitory effect of mac-miR160a on the expression of MaARF18-like-2 was confirmed through tobacco transient transformation and dual-Luciferase reporter assay. Surprisingly, Arabidopsis lines overexpressing mac-miR160a (mac-miR160a OE) exhibited enhanced tolerance to low K+ stress. Conversely, Arabidopsis lines overexpressing MaARF18-like-2 (MaARF18-like-2 OE) displayed increased sensitivity to K+ deficiency. Additionally, RNA sequencing (RNA-seq) analysis revealed that MaARF18-like-2 mediates the response of Arabidopsis to low K+ stress by influencing the expression of genes associated with Ca2+, ion transport, and reactive oxygen species (ROS) signaling. In conclusion, our study provides novel insights into the molecular mechanism of the miR160a-ARF18-like-2 module in the plant response to low K+ stress.

Cardiovascular Risks With SGLT2 Inhibitors in Clinical Practice Among Patients With Type 2 Diabetes.

Importance: Cardiovascular disease (CVD) can be recurrent during type 2 diabetes (T2D) progression in this aging population. The effectiveness of sodium-glucose cotransporter 2 inhibitor (SGLT2i) therapy on total (ie, first and subsequent) CVD among patients with T2D in clinical practice remains uncertain. Objective: To analyze the comparative association of SGLT2i vs dipeptidyl peptidase 4 inhibitor (DPP4i) therapy with total CVD among patients with T2D in clinical practice. Design, Setting, and Participants: This retrospective cohort study used electronic medical records at the National Cheng Kung University Hospital, a leading medical center in Taiwan, from 2015 through 2021. Adult patients with T2D who initiated first use of the study drugs from 2016 through 2019, with up to 6 years of follow-up, were identified. Main Outcomes and Measures: The primary outcomes included total composite CVD events and individual CVD subtypes (ie, atrial fibrillation, coronary heart disease, heart failure, stroke, myocardial infarction, and transient ischemic attack). A shared frailty model analysis was used to assess the association of treatment with repeat CVD events. Data from patients at high risk for CVD recurrence were further analyzed. Data were analyzed from September 1, 2022, to December 31, 2023. Results: Overall, 8384 patients with T2D were identified (mean [SD] age, 63.7 [12.4] years; 4645 [55.4%] male). A total of 1632 propensity score-matched pairs of SGLT2i (mean [SD] age, 57.8 [12.0] years; 673 [41.2%] female and 959 [58.8%] male) and DPP4i (mean [SD] age, 58.2 [12.9] years; 655 [40.1%] female and 977 [59.9%] male) users were included. SGLT2i was associated with reduced total CVD risk vs DPP4i therapy (hazard ratio [HR], 0.82 [95% CI, 0.69-0.98]) but not the first CVD event (with the use of SGLT2i therapy were more prominent for patients at high risk of CVD (ie, HR, 0.70 [95% CI, 0.62-0.80] for individuals with estimated glomerular filtration rate lower than 60 mL/min/1.73 m2; HR, 0.70 [95% CI, 0.64-0.78]; for individuals having any diabetes-related complications; and HR, 0.72 [95% CI, 0.65-0.80] for individuals with a history of CVD) compared with the overall cohort. Among patients at high risk of CVD, greater reduced total CVD burden associated with SGLT2i therapy was observed for women vs men (eg, HR, 0.59 [95% CI, 0.49-0.72] in the subgroup with CVD history). Conclusions and Relevance: In this cohort study of patients with T2D, the use of SGLT2is vs DPP4is was associated with reduced total cardiovascular burden, suggesting that long-term use of this therapy may optimize treatment benefit among patients with chronic CVD. The SGLT2i-associated benefit among patients with high risk of CVD encourages the prioritization of SGLT2i use for these vulnerable individuals.

Propofol improves sleep deprivation-induced sleep structural and cognitive deficits via upregulating the BMAL1 expression and suppressing microglial M1 polarization.

BACKGROUND: Sleep deprivation (SD) is a growing global health problem with many deleterious effects, such as cognitive impairment. Microglia activation-induced neuroinflammation may be an essential factor in this. Propofol has been shown to clear sleep debt after SD in rats. This study aims to evaluate the effects of propofol-induced sleep on ameliorating sleep quality impairment and cognitive decline after 48 h SD. METHODS: Almost 8-12-week-old rats were placed in the SD system for 48 h of natural sleep or continuous SD. Afterwards, rats received propofol (20 mg·kg-1·h-1, 6 h) via the tail or slept naturally. The Morris water maze (MWM) and Y-maze test assessed spatial learning and memory abilities. Rat EEG/EMG monitored sleep. The expression of brain and muscle Arnt-like protein 1 (BMAL1), brain-derived neurotrophic factor (BDNF) in the hippocampus and BMAL1 in the hypothalamus were assessed by western blot. Enzyme-linked immunosorbent assay detected IL-6, IL-1ß, arginase 1 (Arg1), and IL-10 levels in the hippocampus. Immunofluorescence was used to determine microglia expression as well as morphological changes. RESULTS: Compared to the control group, the sleep-deprived rats showed poor cognitive performance on both the MWM test and the Y-maze test, accompanied by disturbances in sleep structure, including increased total sleep time, and increased time spent and delta power in non-rapid eye movement sleep. In addition, SD induces abnormal expression of the circadian rhythm protein BMAL1, activates microglia, and causes neuroinflammation and nerve damage. Propofol reversed these changes and saved sleep and cognitive impairment. Furthermore, propofol treatment significantly reduced hippocampal IL-1ß and IL-6 levels, increased BDNF, Arg1, and IL-10 levels, and switched microglia surface markers from the inflammatory M1 type to the anti-inflammatory M2 type. CONCLUSION: Propofol reduces SD-induced cognitive impairment and circadian rhythm disruption, possibly by lowering neuronal inflammation and switching the microglia phenotype from an M1 to an M2 activated state, thus exerting neuroprotective effects.

Intermittent fasting alleviates postoperative cognitive dysfunction by reducing neuroinflammation in aged mice.

Elderly individuals undergoing surgical procedures are often confronted with the peril of experiencing postoperative cognitive dysfunction (POCD). Prior research has demonstrated the exacerbating effect of sevoflurane anesthesia on neuroinflammation, which can further deteriorate the condition of POCD in elderly patients. Intermittent fasting (IF) restricts food consumption to a specific time window and has been demonstrated to ameliorate cognitive dysfunction induced by neuropathic inflammation. We subjected 18-month-old male mice to 16 hours of fasting and 8 hours of unrestricted eating over a 24-hour period for 0, 1, 2, and 4 weeks, followed by abdominal exploration under sevoflurane anesthesia. In this study, we aim to explore the potential impact of IF on postoperative cognitive function in aged mice undergoing sevoflurane surgery through the preoperative implementation of IF measures. The findings indicate two weeks of IF leads to a significant enhancement of learning and memory capabilities in mice following surgery. The cognitive performance, as determined by the novel object recognition and Morris water maze tests, as well as the synaptic plasticity, as measured by in vivo electrophysiological recordings, has demonstrated marked improvements. Furthermore, the administration of IF markedly enhances the expression of synaptic-associated proteins in hippocampal neurons, concomitant with a decreasing expression of pro-inflammatory factors and a reduced density of microglial cells within the hippocampal brain region. To summarize, the results of this study indicate that IF may mitigate inflammation in the hippocampal area of the brain. Furthermore, IF appears to provide a safeguard against cognitive impairment and synaptic plasticity impairment brought on by sevoflurane anesthesia.

Crystal phase-driven performance of MnO2 in aqueous phase low-temperature thermal catalysis: Synergistic interactions between Mn3+ and surface lattice oxygen.

Catalytic oxidation at mild conditions is crucial for mitigating the high pressure and high temperature challenges associated with current catalytic wet air oxidation (CWAO) technologies in wastewater treatment. Among potential materials for catalytic oxidation reactions, polycrystalline MnO2 existed in natural minerals holds considerable promise. However, the relationships between different crystal phases of MnO2 and their catalytic activity sources in aqueous phase remain uncertain and subject to debate. In this research, we synthesized various MnO2 crystal phases, comprising α-, ß-, δ-, γ-, ε-, and λ-MnO2, and assessed their catalytic oxidation efficiency during low-temperature heating for treatment of organic pollutants. Our findings demonstrate that λ-MnO2 exhibits the highest catalytic activity, followed by δ-MnO2, γ-MnO2, α-MnO2, ε-MnO2, and ß-MnO2. The variations in catalytic activity among different MnO2 are attributed to variances in their oxygen vacancy abundance and redox activity. Furthermore, we identified the primary active species, which include Mn3+ and superoxide radicals (•O2-) generated by surface lattice oxygen of MnO2. This research highlights the critical role of crystal phases in influencing oxygen vacancy content, redox activity, and overall catalytic performance, providing valuable insights for the rational design of MnO2 catalysts tailored for effective organic pollutant degradation in CWAO applications.

Establishment and comparison of in situ detection models for foodborne pathogen contamination on mutton based on SWIR-HSI.

Introduction: Rapid and accurate detection of food-borne pathogens on mutton is of great significance to ensure the safety of mutton and its products and the health of consumers. Objectives: The feasibility of short-wave infrared hyperspectral imaging (SWIR-HSI) in detecting the contamination status and species of Escherichia coli (EC), Staphylococcus aureus (SA) and Salmonella typhimurium (ST) contaminated on mutton was explored. Materials and methods: The hyperspectral images of uncontaminated and contaminated mutton samples with different concentrations (108, 107, 106, 105, 104, 103 and 102 CFU/mL) of EC, SA and ST were acquired. The one dimensional convolutional neural network (1D-CNN) model was constructed and the influence of structure hyperparameters on the model was explored. The effects of different spectral preprocessing methods on partial least squares-discriminant analysis (PLS-DA), support vector machine (SVM) and 1D-CNN models were discussed. In addition, the feasibility of using the characteristic wavelength to establish simplified models was explored. Results and discussion: The best full band model was the 1D-CNN model with the convolution kernels number of (64, 16) and the activation function of tanh established by the original spectra, and its accuracy of training set, test set and external validation set were 100.00, 92.86 and 97.62%, respectively. The optimal simplified model was genetic algorithm optimization support vector machine (GA-SVM). For discriminating the pathogen species, the accuracies of SVM models established by full band spectra preprocessed by 2D and all 1D-CNN models with the convolution kernel number of (32, 16) and the activation function of tanh were 100.00%. In addition, the accuracies of all simplified models were 100.00% except for the 1D-CNN models. Considering the complexity of features and model calculation, the 1D-CNN models established by original spectra were the optimal models for pathogenic bacteria contamination status and species. The simplified models provide basis for developing multispectral detection instruments. Conclusion: The results proved that SWIR-HSI combined with machine learning and deep learning could accurately detect the foodborne pathogen contamination on mutton, and the performance of deep learning models were better than that of machine learning. This study can promote the application of HSI technology in the detection of foodborne pathogens on meat.

Sub-dose anesthetics combined with chloride regulators protect the brain against chronic ischemia-hypoxia injury.

BACKGROUND: Cerebral ischemia-hypoxia leads to excitotoxicity-mediated neuronal damage and cognitive dysfunction, especially in the elderly. Excessive intracellular [Cl- ]i accumulation weakens γ-aminobutyric acid (GABA) compensatory effects. Sub-anesthetic dose of propofol protected the brain against ischemia-hypoxia, which was abolished by blocking Cl- efflux transporter K+ /Cl- cotransporter 2 (KCC2). We aimed to determine whether low-dose anesthetic combined with [Cl- ]i regulators could restore the compensatory GABAergic system and improve cognitive function. METHODS: Chronic cerebral hypoxia (CCH) model was established by bilateral carotid artery ligation in aged rats. Sub-dose of anesthetics (propofol and sevoflurane) with or without KCC2 agonist N-ethylmaleimide (NEM) or Na+ /K+ /Cl- cotransporter 1 (NKCC1) antagonist bumetanide (BTN) was administered systemically 30 days post-surgery. Primary rat hippocampal neuronal cultures were subjected to hypoxic injury with or without drug treatment. Memory function, hippocampal neuronal survival, GABAergic system functioning, and brain-derived neurotrophic factor (BDNF) expressions were evaluated. RESULTS: Sub-anesthetic dose of combined propofol (1.2 µg mL-1 ) and sevoflurane [0.7 MAC (minimum alveolar concentration)] did not aggravate the hypoxic brain injury in rats or cell damage in neuronal cultures. Adding either BTN or NEM protected against hypoxic injury, associated with improved cognitive function in vivo, less intracellular accumulation of [Cl- ]i , reduced cell death, restored GABAergic compensation, and increased BDNF expression both in vivo and in vitro. CONCLUSION: Sub-anesthetic dose of propofol and sevoflurane is a recommended anesthesia regimen in at-risk patients. Restoration of [Cl- ]i homeostasis and GABAergic could further reduce the brain damage caused by ischemia-hypoxia.

Lower risks of cirrhosis and hepatocellular carcinoma with GLP-1RAs in type 2 diabetes: A nationwide cohort study using target trial emulation framework.

BACKGROUND: To assess the association of cirrhosis and hepatocellular carcinoma (HCC) with the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus long-acting insulins (LAIs), which are the two commonly prescribed injectable glucose-lowering agents (GLAs) for patients with type 2 diabetes (T2D) after the failure of multiple oral GLAs. METHODS: We emulated a target trial using the nationwide data of a Taiwanese cohort with T2D. Incident new users of GLP-1RAs and LAIs during 2013-2018 were identified, and propensity score (PS) matching was applied to ensure between-group comparability in baseline patient characteristics. The primary outcome was the composite liver disease including cirrhosis or HCC. Each patient was followed until the occurrence of a study outcome, death, or the end of 2019, whichever came first. Subdistribution hazard models were employed to assess the treatment-outcome association. Sensitivity (e.g., stabilized inverse probability of treatment weighting analysis, time-dependent analysis), E-value, and negative control outcome analyses were performed to examine the robustness of study findings. RESULTS: We included 7171 PS-matched pairs of GLP-1RA and LAI users with no significant between-group differences at baseline. Compared with LAIs, the use of GLP-1RAs was associated with significantly reduced risks of composite liver disease (subdistribution hazard ratio [95% confidence interval]: 0.56 [0.42-0.76]), cirrhosis (0.59 [0.43-0.81]), and HCC (0.47 [0.24-0.93]). Results were consistent across sensitivity analyses and among patients with different baseline characteristics. CONCLUSION: Among T2D patients who require injectable GLAs, the use of GLP-1RAs versus LAIs was associated with lower risks of cirrhosis and HCC.

Kapß2 Inhibits Perioperative Neurocognitive Disorders in Rats with Mild Cognitive Impairment by Reversing the Nuclear-Cytoplasmic Mislocalization of hnRNPA2/B1.

Harmful stimuli trigger mutations lead to uncontrolled accumulation of hnRNPA2/B1 in the cytoplasm, exacerbating neuronal damage. Kapß2 mediates the bidirectional transport of most substances between the cytoplasm and the nucleus. Kapß2 guides hnRNPA2/B1 back into the nucleus and restores its function, alleviating related protein toxicity. Here, we aim to explore the involvement of Kapß2 in neurodegeneration in rats with MCI following sevoflurane anesthesia and surgery. Firstly, novel object recognition test and Barnes maze were conducted to assess behavioral performances, and we found Kapß2 positively regulated the recovery of memory and cognitive function. In vivo electrophysiological experiments revealed that the hippocampal theta rhythm energy distribution was disrupted, coherence was reduced, and long-term potentiation was attenuated in MCI rats. LTP was greatly improved with positive modulation of Kapß2. Next, functional MRI and BOLD imaging will be employed to examine the AFLL and FC values of dynamic connectivity between the cortex and hippocampus of the brain. The findings show that regulating Kapß2 in the hippocampus region enhances functional activity and connections between brain regions in MCI rats. WB results showed that increasing Kapß2 expression improved the expression and recovery of cognitive-related proteins in the hippocampus of MCI rats. Finally, WB and immunofluorescence were used to examine the changes in hnRNPA2/B1 expression in the nucleus and cytoplasm after overexpression of Kapß2, and it was found that nucleocytoplasmic mis location was alleviated. Overall, these data show that Kapß2 reverses the nucleoplasmic misalignment of hnRNPA2/B1, which slows neurodegeneration towards dementia in MCI after sevoflurane anesthesia and surgery. Our findings may lead to new approaches for perioperative neuroprotection of MCI patients.

Endoscopic Anterior Lumbar Interbody Fusion: Systematic Review and Meta-Analysis.

Laparoscopic anterior lumbar interbody fusion (L-ALIF), which employs laparoscopic cameras to facilitate a less invasive approach, originally gained traction during the 1990s but has subsequently fallen out of favor. As the envelope for endoscopic approaches continues to be pushed, a recurrence of interest in laparoscopic and/or endoscopic anterior approaches seems possible. Therefore, evaluating the current evidence base in regard to this approach is of much clinical relevance. To this end, a systematic literature search was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using the following keywords: "(laparoscopic OR endoscopic) AND (anterior AND lumbar)." Out of the 441 articles retrieved, 22 were selected for quantitative analysis. The primary outcome of interest was the radiographic fusion rate. The secondary outcome was the incidence of perioperative complications. Meta-analysis was performed using RStudio's "metafor" package. Of the 1,079 included patients (mean age, 41.8±2.9 years), 481 were males (44.6%). The most common indication for L-ALIF surgery was degenerative disk disease (reported by 18 studies, 81.8%). The mean follow-up duration was 18.8±11.2 months (range, 6-43 months). The pooled fusion rate was 78.9% (95% confidence interval [CI], 68.9-90.4). Complications occurred in 19.2% (95% CI, 13.4-27.4) of L-ALIF cases. Additionally, 7.2% (95% CI, 4.6-11.4) of patients required conversion from L-ALIF to open surgery. Although L-ALIF does not appear to be supported by studies available in the literature, it is important to consider the context from which these results have been obtained. Even if these results are taken at face value, the failure of endoscopy to have a role in the ALIF approach does not mean that it should not be incorporated in posterior approaches.

Assessing survival outcomes and complication profiles following surgical excision and radiotherapy as interventions for skull base chordoma: a systematic review of operative margins and surgical approaches.

INTRODUCTION: Despite their precarious behavioral classification (benign and low grade on histopathology yet behaviorally malignant), great strides have been taken to improve prognostication and treatment paradigms for patients with skull base chordoma. With respect to surgical techniques, lateral transcranial (TC) approaches have traditionally been used, however endoscopic endonasal approaches (EEA) have been advocated for midline lesions. Nonetheless, due to the rarity of this pathology (0.2% of all intracranial neoplasms), investigations within the literature remain limited to small retrospective series. Furthermore, radiotherapeutic treatments investigated to date have proven largely ineffective. METHODS: Accordingly, we performed a systematic review in order to profile surgical and survival outcomes for skull base chordoma. Fixed and random-effect meta-analyses were performed for categorical variables including GTR, STR, 5-year OS, 10-year OS, 5-year PFS, and 10-year PFS. Additionally, we pooled eligible studies for formal meta-analysis to compare outcomes by surgical approach (lateral versus midline). Statistical analyses were performed using R Studio 'metafor' package or Cochrane Review Manager. Furthermore, meta-analysis of pooled mortality rates and sub-analyses of operative margin and surgical complications were used to compare midline versus lateral approaches via the Mantel-Haenszel method. We considered all p-values < 0.05 to be statistically significant. RESULTS: Following the systematic search and screen, 55 studies published between 1993 and 2022 reporting data for 2453 patients remained eligible for analysis. Sex distribution was comparable between males and females, with a slight predominance of male-identifying patients (0.5625 [95% CI: 0.5418; 0.3909]). Average age at diagnosis was 42.4 ± 12.5 years, while average age of treatment initiation was 43.0 ± 10.6 years. Overall, I2 value indicated notable heterogeneity across the 55 studies [I2 = 56.3% (95%CI: 44.0%; 65.9%)]. With respect to operative margins, the rate of GTR was 0.3323 [95% CI: 0.2824; 0.3909], I2 = 91.9% [95% CI: 90.2%; 93.4%], while the rate of STR was significantly higher at 0.5167 [95% CI: 0.4596; 0.5808], I2 = 93.1% [95% CI: 91.6%; 94.4%]. The most common complication was CSF leak (5.4%). In terms of survival outcomes, 5-year OS rate was 0.7113 [95% CI: 0.6685; 0.7568], I2 = 91.9% [95% CI: 90.0%; 93.5%]. 10-year OS rate was 0.4957 [95% CI: 0.4230; 0.5809], I2 = 92.3% [95% CI: 89.2%; 94.4%], which was comparable to the 5-year PFS rate of 0.5054 [95% CI: 0.4394; 0.5813], I2 = 84.2% [95% CI: 77.6%; 88.8%] and 10-yr PFS rate of 0.4949 [95% CI: 0.4075; 0.6010], I2 = 14.9% [95% CI: 0.0%; 87.0%]. There were 55 reported deaths for a perioperative mortality rate of 2.5%. The relative risk for mortality in the midline group versus the lateral approach group did not indicate any substantial difference in survival according to laterality of approach (-0.93 [95% CI: -1.03, -0.97], I2 = 95%, (p < 0.001). CONCLUSION: Overall, these results indicate good 5-year survival outcomes for patients with skull base chordoma; however, 10-year prognosis for skull base chordoma remains poor due to its radiotherapeutic resistance and high recurrence rate. Furthermore, mortality rates among patients undergoing midline versus lateral skull base approaches appear to be equivocal.

Applications of supraorbital keyhole craniotomy in pediatric cranial trauma: illustrative series of two cases and systematic literature review.

Minimally invasive (MIS) approaches to neurosurgical diseases continue to increase in popularity due to their association with decreased infection risk, shorter recovery time, and improved cosmesis. Cosmesis and lower morbidity are especially important for pediatric patients. The supraorbital keyhole craniotomy (SOKC) is one MIS approach shown to be effective for both neoplastic and vascular pathologies in pediatric patients. However, it is limited data on its use in pediatric trauma patients. Two cases employing SOKC in pediatric trauma patients are presented here along with a systematic review of the literature. We queried PubMed, Scopus, and Web of Science databases from inception to August 2022 using the Boolean search term: (supraorbital OR eyebrow OR transeyebrow OR suprabrow OR superciliary OR supraciliary) AND (craniotomy OR approach OR keyhole OR procedure) AND (pediatric OR children OR child OR young) AND "trauma". Studies that discussed the use of an SOKC in a pediatric patient having sustained trauma to the frontal calvarium and/or anterior fossa/sellar region of the skull base were included. Details were extracted on patient demographics, trauma etiology, endoscope use, and surgical and cosmetic outcomes. We identified 89 unique studies, of which four met inclusion criteria. Thirteen total cases were represented. Age and sex were reported for 12 patients, 25% of whom were male; the mean age was 7.5 years (range: 3-16). Pathologies included acute epidural hematoma (9), orbital roof fracture with dural tear (1), blowout fracture of the medial wall of the frontal sinus with supraorbital rim fracture (1), and compound skull fracture (1). Twelve patients were treated with a conventional operating microscope, while one underwent endoscope-assisted surgery. Only one significant complication (recurrent epidural hematoma) was reported. There were no reported cosmetic complications. The MIS SOKC approach is a reasonable option for select anterior skull base trauma in the pediatric population. This approach has been used previously for successful frontal epidural hematoma evacuation, which is often treated by a large craniotomy. Further study is merited.

Unraveling the significance of soil organic carbon-gravel parameterization: Insights into soil water and heat transport on the Tibetan Plateau.

In the Tibetan Plateau (TP) soil water and heat transfer process, soil organic carbon (SOC) and gravel content are considered as the most influential soil texture factors. However, the issues of underestimating SOC and neglecting gravel effect affected the simulation performance of CLM5.0 on soil moisture (SM) and soil temperature (ST). This paper proposed a new parameterization scheme, the organic carbon-gravel (OC-G) scheme, to simulate ST and SM from 1990 to 2018. The results showed that correlation between the simulated and observed ST or SM was higher, and the error was smaller, after the modification of the parameterization scheme. This improvement justifies the applicability of the scheme for soil hydrothermal simulations on the TP. The experiment described that ST and SM were more sensitive to changes in SOC content. And changes in gravel or SOC content had the "Same-Frequency" effect in the northeast and southeast TP. When the SOC and gravel content changed at the same time, the effects on ST and SM were a "cumulative" effect. The change directly affected the memory time of ST and SM in summer. Specifically, when the SOC content was increased, the memory time of SM increased in the northwest and decreased in the southeast. When gravel content was increased, the memory time of SM decreased in the northwest but increased in the southeast, but the memory time of ST remained largely unchanged. Changes to the abnormal duration may alter summer weather and climate in Eastern China.

Collaborative Learning Communities With Medical Students as Teachers.

In recent years, peer-assisted learning has emerged as a new and effective medical education modality. Near-peer tutoring utilizes a senior student serving as an instructor to a junior student. In 2019, the University of California, Irvine, School of Medicine (UCISOM) implemented a near-peer tutoring model beginning with first-year anatomy and physiology curricula. Following a successful pilot program, UCISOM launched a full-fledged near-peer tutoring program in 2020 named Collaborative Learning Communities (CLC) with Medical Students as Teachers. The rollout of CLC occurred in phases. In 2020, second-year medical students led the program for first-year students; in 2021, an additional program was led by third-year medical students for second-year students; in 2022, the program expanded to third-year medical students led by fourth-year students. Each program serves the unique learning needs of each student class, utilizing evidence-based teaching practices while allowing the opportunity for mentorship, interclass connectedness, and refinement of the tutor's teaching skills. In this paper, we describe the creation of CLC, its goals, leadership and curricular structure, and its various benefits, challenges, and limitations.

Estimating the Distribution and Convergence of County-level Healthcare Resources Allocative Efficiency in China Based on DEA and Spatial Panel Model.

Although China's 2009 New Healthcare Reform aimed to correct the imbalance in the spatial allocation of healthcare resources with a focus on the county level, its impact on county-level allocative efficiency evolution and convergence remains unclear. This paper for the first time performs a spatial analysis to explore the distribution, evolution, and convergence of the allocative efficiency of healthcare resources with county-level data. This paper uses the sample data of 158 countries in Henan Province, China, to evaluate the evolution and convergence of the allocative efficiency of healthcare resources. Based on the estimated Data Envelopment Analysis (DEA) allocative efficiency, analysis of variance (ANOVA), and spatial descriptive analysis, we explore the county heterogeneity and efficiency evolution; a spatial panel model is then utilized to test the county-level convergence of the allocative efficiency of healthcare resources. Although the number of efficient counties has not increased, the number of inefficient individuals keeps decreasing, and the allocative efficiency of municipal districts is lower than that of nonmunicipal counties. There exists a positive spatial correlation of allocative efficiency in Henan Province, and significant and robust convergence results can be found at the county level after China's 2009 reform. This study reveals a diversified picture of China's county-level spatial evolution of allocative efficiency in healthcare resources, showing a more balanced spatial distribution of allocative efficiency since the triggering of China's 2009 reform. However, long-term investment incentives and a targeted allocation of healthcare resources are still needed to promote further efficiency convergence and increase the number of counties with efficiency.

Calcium Dynamics of the Ventrolateral Preoptic GABAergic Neurons during Spontaneous Sleep-Waking and in Response to Homeostatic Sleep Demands.

The ventrolateral preoptic area (VLPO) contains GABAergic sleep-active neurons. However, the extent to which these neurons are involved in expressing spontaneous sleep and homeostatic sleep regulatory demands is not fully understood. We used calcium (Ca2+) imaging to characterize the activity dynamics of VLPO neurons, especially those expressing the vesicular GABA transporter (VGAT) across spontaneous sleep-waking and in response to homeostatic sleep demands. The VLPOs of wild-type and VGAT-Cre mice were transfected with GCaMP6, and the Ca2+ fluorescence of unidentified (UNID) and VGAT cells was recorded during spontaneous sleep-waking and 3 h of sleep deprivation (SD) followed by 1 h of recovery sleep. Although both VGAT and UNID neurons exhibited heterogeneous Ca2+ fluorescence across sleep-waking, the majority of VLPO neurons displayed increased activity during nonREM/REM (VGAT, 120/303; UNID, 39/106) and REM sleep (VGAT, 32/303; UNID, 19/106). Compared to the baseline waking, VLPO sleep-active neurons (n = 91) exhibited higher activity with increasing SD that remained elevated during the recovery period. These neurons also exhibited increased Ca2+ fluorescence during nonREM sleep, marked by increased slow-wave activity and REM sleep during recovery after SD. These findings support the notion that VLPO sleep-active neurons, including GABAergic neurons, are components of neuronal circuitry that mediate spontaneous sleep and homeostatic responses to sustained wakefulness.

Schizophrenia and neurosurgery: systematic review and theories.

OBJECTIVE: Despite its relatively low prevalence, schizophrenia has a high burden of illness due to its lifelong effects and the fact that it is often refractory to psychotropic treatment. This review investigated how neurosurgical interventions, primarily neuromodulation through deep brain stimulation (DBS), can mitigate treatment-refractory schizophrenia. Pathophysiological data and ongoing clinical trials were reviewed to suggest which targets hold promise for neurosurgical efficacy. METHODS: A systematic review of the literature was conducted via an electronic search of the PubMed, Scopus, and Web of Science databases. Included papers were human or animal studies of neurosurgical interventions for schizophrenia conducted between 2012 and 2022. An electronic search of ClinicalTrials.gov and the International Clinical Trials Registry Platform was conducted to find ongoing clinical trials. The ROBINS-I (Risk of Bias in Nonrandomized Studies of Interventions) assessment tool was used to evaluate risk of bias in the study. RESULTS: Eight human and 2 rat studies were included in the review. Of the human studies, 5 used DBS targeting the nucleus accumbens, subgenual anterior cingulate cortex, habenula, and substantial nigra pars reticulata. The remaining 3 human studies reported the results of subcaudate tractotomies and anterior capsulotomies. The rat studies investigated DBS of the nucleus accumbens and medial prefrontal cortex. Overall, human studies demonstrated long-term reduction in Positive and Negative Syndrome Scale scores in many participants, with a low incidence of surgical and psychological side effects. The rat studies demonstrated improved prepulse and latent inhibition in the targeted areas after DBS. CONCLUSIONS: As identified in this review, recent studies have investigated the potential effects of therapeutic DBS for schizophrenia, with varying results. DBS targets that have been explored include the hippocampus, subgenual anterior cingulate cortex, habenula, substantia nigra pars reticulata, and medial prefrontal cortex. In addition to DBS, other neuromodulatory techniques such as neuroablation have been studied. Current evidence suggests that neuroablation in the subcaudate tract and anterior capsulotomy may be beneficial for some patients. The authors recommend further exploration of neuromodulation for treatment-refractory schizophrenia, under the condition that rigorous standards be upheld when considering surgical candidacy for these treatments, given that their safety and efficacy remain to be determined.

The Effect of Descending Resources Reform on Reallocating Healthcare Resources: An Analysis Based on the Difference-in-Differences Method.

Since 2010, China has been exploring descending resources reform in order to correct the imbalanced allocation of healthcare resources and promote coordinated economic development among regions. This paper for the first time estimates the impact this reform has had on the reallocation of healthcare resources by using prefecture-level cities panel data from Zhejiang Province, China, which implemented the reform province-wide in 2013. The time-varying difference-in-differences (DID) method was used to estimate the reform's policy effects. The data used in this paper is from published statistical yearbooks and local governments, which include panel data from 11 prefecture-level and higher cities in Zhejiang Province as the treated group and 46 prefecture-level cities in Jiangsu, Henan, and Sichuan Province as the control group. The entropy weight method was used to construct the supply index and demand index to incorporate multiple inputs and outputs, and efficiency indicators were constructed using the ratio method. This research found that the reform has had a positive effect on outpatient visits in different prefecture-level cities with vast rural areas. However, this reform exerted no significant impact on inpatient services or supply-side or resource allocation efficiency. Several robust tests support the above conclusions, and one theoretical explanation is provided. The descending health resources reform can be a valuable reform path in promoting more balanced healthcare resource allocation; however, the resultant disparities in its effects should be considered when implementing it.