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.

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.

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.

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.

Cost-effectiveness of Novel Macrophage-Regulating Treatment for Wound Healing in Patients With Diabetic Foot Ulcers From the Taiwan Health Care Sector Perspective.

Importance: Diabetic foot ulcers (DFUs) and subsequent amputation incur enormous health and economic burdens to patients, health care systems, and societies. As a novel macrophage-regulating drug, ON101 is a breakthrough treatment for DFUs, which demonstrated significant complete wound healing effects in a phase 3 randomized clinical trial, but its economic value remains unknown. Objective: To assess the cost-effectiveness of an ON101 cream added on to general wound care (GWC; ie, conventional treatments for DFUs, which comprised initial and regular foot examinations, ulcer management, comorbidity control, patient education, and multidisciplinary care) vs GWC alone for DFUs from the Taiwan health care sector perspective. Design, Setting, and Participants: This economic evaluation used a hypothetical cohort of patients with diabetes, with characteristics mirroring those of the participants in the ON101 trial. A Markov state-transition simulation model was constructed to estimate costs and health outcomes associated with the ON101 with GWC and GWC alone strategies over a 5-year time horizon, discounting costs and effectiveness at 3% annually. Costs were in 2021 US dollars. Data were sourced from the ON101 trial and supplemented from published literature. Deterministic and probabilistic sensitivity analyses were performed to assess the uncertainty of input parameters and study generalizability. The analysis was designed and conducted from September 1, 2020, to January 31, 2022. Exposures: ON101 with GWC vs GWC alone. Main Outcomes and Measures: DFU-related complications, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio. Results: Patients in the hypothetical cohort had a mean age of 57 years and an uninfected DFU of 1 to 25 cm2 that was present for 4 or more weeks with a Wagner grade of 1 or 2. Over 5 years, the ON101 with GWC group vs the GWC alone group experienced more healing events, stayed for a longer time in the healing state, and had fewer infected DFUs, gangrene, and amputations (eg, 2787 additional healing events and 2766 fewer infected DFU, 72 fewer amputation, and 7 fewer gangrene events in the ON101 with GWC group vs GWC alone group). The ON101 with GWC strategy vs GWC alone yielded an additional 0.038 QALYs at an incremental cost of $571, resulting in $14 922/QALY gained. Economic results were most sensitive to healing efficacy, drug cost, and health utility of the healing state. Cost-saving results were observed in patient subgroups with poor glycemic control, larger ulcer sizes, longer ulcer durations, and current smoking. The ON101 with GWC strategy was considered cost-effective in 60% to 82% of model iterations against willingness-to-pay thresholds of $32 787/QALY gained to $98 361/QALY gained. Conclusions and Relevance: In this economic evaluation study using a simulated patient cohort, the ON101 with GWC strategy represented good value compared with GWC alone for patients with DFUs from the Taiwan health care sector perspective and may be prioritized for those with high risks for disease progression of DFUs.

Staphylococcus Aureus Swabbing and Decolonization Before Neuromodulation Procedures: A Systematic Review and Meta-Analysis.

INTRODUCTION: Staphylococcus aureus (S aureus) is the foremost bacterial cause of surgical-site infection (SSI) and is a common source of neuromodulation SSI. Endogenous colonization is an independent risk factor for SSI; however, this risk has been shown to diminish with screening and decolonization. MATERIALS AND METHODS: A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the PubMed, Cochrane Library, and Embase data bases from inception to January 1, 2022, for the purposes of identifying all studies reporting on the use of S aureus swabbing and/or decolonization before neuromodulation procedures. A random-effects meta-analysis was performed using the metaphor package in R to calculate odds ratios (OR). RESULTS: Five observational cohort studies were included after applying the inclusion and exclusion criteria. The average study duration was 6.6 ± 3.8 years. Three studies included nasal screening as a prerequisite for subsequent decolonization. Type of neuromodulation included spinal cord stimulation in two studies, deep brain stimulation in two studies, intrathecal baclofen in one study, and sacral neuromodulation in one study. Overall, 860 and 1054 patients were included in a control or intervention (ie, screening and/or decolonization) group, respectively. A combination of nasal mupirocin ointment and a body wash, most commonly chlorhexidine gluconate soap, was used to decolonize throughout. Overall infection rates were observed at 59 of 860 (6.86%) and ten of 1054 (0.95%) in the control and intervention groups, respectively. Four studies reported a significant difference. The OR for intervention (screen and/or decolonization) vs no intervention was 0.19 (95% CI, 0.09-0.37; p < 0.001). Heterogeneity between studies was nonsignificant (I2 = 0.43%, τ2 = 0.00). CONCLUSIONS: Preoperative S aureus swabbing and decolonization resulted in significantly decreased odds of infection in neuromodulation procedures. This measure may represent a worthwhile tool to reduce neuromodulation SSI, warranting further investigation.

Heterogeneous nuclear ribonucleoprotein A2/B1 as a novel biomarker in elderly patients for the prediction of postoperative neurocognitive dysfunction: A prospective nested case-control study.

Background and objective: Postoperative neurocognitive dysfunction (PND) occurs in up to 54% of older patients, giving rise to the heavy psychological and economic burdens to patients and society. To date, the development of PND biomarkers remains a challenge. Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) is an RNA-binding protein whose prion-like structure is prone to mutation and hence leads to neurodegenerative diseases, but its expression changes in PND remains unclear. Here, we detect the preoperative hnRNPA2/B1 level in patients with PND, and to explore its value in the prediction and diagnosis of PND. Methods: The study included 161 elderly patients undergoing lumbar decompression and fusion in Nankai University Affinity the Third Central Hospital from September 2021 to July 2022. Neuropsychological and psychometric evaluations were performed before surgery, 1 week and 3 months after surgery to diagnose the occurrence of PND, then the peripheral blood was collected from patients before induction of anesthesia. The concentration in plasma of hnRNPA2/B1 and amyloid-ß 42 were determined by enzyme-linked immunosorbent assay. The median fluorescence intensity and mRNA levels of hnRNPA2/B1 in peripheral blood mononuclear cells was detected by indirect intracellular staining flow cytometry and quantitative real-time PCR, respectively. Results: The preoperative hnRNPA2/B1 level in patients with PND was higher both in short-time and long-time follow-up. We found significantly higher concentrations of hnRNPA2/B1 in PND at 7 days after surgery (median, 72.26 pg/mL vs. 54.95 pg/mL, p = 0.022) compared with patients without PND, and so as 3 months after surgery (median, 102.93 pg/mL vs. 56.38 pg/mL, p = 0.012). The area under the curve (AUC) was predicted to be 0.686 at 7 days after surgery and 0.735 at 3 months. In addition, when combining several clinical information, the diagnostic efficiency of hnRNPA2/B1 for PND could further increase (AUC, 0.707 at 7 days, 0.808 at 3 months). Conclusion: Based on the findings reported here, hnRNPA2/B1 may serve as a new and powerful predictive biomarker to identify elderly patients with PND.

Dissociable effects of oxycodone on behavior, calcium transient activity, and excitability of dorsolateral striatal neurons.

Opioids are the most common medications for moderate to severe pain. Unfortunately, they also have addictive properties that have precipitated opioid misuse and the opioid epidemic. In the present study, we examined the effects of acute administration of oxycodone, a µ-opioid receptor (MOR) agonist, on Ca2+ transient activity of medium-sized spiny neurons (MSNs) in freely moving animals. Ca2+ imaging of MSNs in dopamine D1-Cre mice (expressing Cre predominantly in the direct pathway) or adenosine A2A-Cre mice (expressing Cre predominantly in the indirect pathway) was obtained with the aid of miniaturized microscopes (Miniscopes) and a genetically encoded Cre-dependent Ca2+ indicator (GCaMP6f). Systemic injections of oxycodone (3 mg/kg) increased locomotor activity yet, paradoxically, reduced concomitantly the number of active MSNs. The frequency of Ca2+ transients was significantly reduced in MSNs from A2A-Cre mice but not in those from D1-Cre mice. For comparative purposes, a separate group of mice was injected with a non-Cre dependent Ca2+ indicator in the cerebral cortex and the effects of the opioid also were tested. In contrast to MSNs, the frequency of Ca2+ transients in cortical pyramidal neurons was significantly increased by oxycodone administration. Additional electrophysiological studies in brain slices confirmed generalized inhibitory effects of oxycodone on MSNs, including membrane hyperpolarization, reduced excitability, and decreased frequency of spontaneous excitatory and inhibitory postsynaptic currents. These results demonstrate a dissociation between locomotion and striatal MSN activity after acute administration of oxycodone.

Self-adjusting inverse design method for nanophotonic devices.

Nanophotonic devices, which consist of multiple cell structures of the same size, are easy to manufacture. To avoid the optical proximity effect in the ultraviolet lithography process, the cell structures must be maintained at a distance from one another. In the inverse design process, the distance is maintained by limiting the optimized range of the location. However, this implementation can weaken the performance of the devices designed during transmission. To solve this problem, a self-adjusting inverse design method based on the adjoint variable method is developed. By introducing artificial potential field method, the location of one cell structure is modified only when the distances between this cell structure and other cell structures are smaller than a threshold. In this case, the range of the location can be expanded, and thus the performance of the designed devices can be improved. A wavelength demultiplexer with a channel spacing of 1.6 nm is designed to verify the performance of the proposed method. The experiment reveals that the transmission of the designed devices can be improved by 20%, and the self-adjusting inverse design process is 100 times faster than the inverse-design process based on the genetic algorithm.

Effectiveness of Deep Brain Stimulation in Treatment of Anorexia Nervosa and Obesity: A Systematic Review.

OBJECTIVE: Anorexia nervosa and obesity are common appetite disorders, which may be life threatening if not treated and often coincide with psychiatric disorders. We sought to investigate whether deep brain stimulation (DBS) of specific regions within the brain could aid in the treatment of these disorders. This review aims to organize the literature regarding the feasibility of DBS via clinical outcomes and synthesize the data on patient demographics and electrode parameters for future optimization. METHODS: PubMed, Scopus, and Web of Science databases were all queried on 7 June 2022 to identify studies reporting the effect of DBS in treatment of either anorexia nervosa or obesity. We included studies involving 1) DBS, 2) treatment of anorexia nervosa or obesity, and 3) body mass index (BMI) as the primary outcome variable. Case reports, retrospective cohort studies, and randomized controlled trials were all eligible for inclusion. Exclusion of articles was based on the following criteria: 1) meta-analyses or systematic reviews or 2) describes diseases other than only anorexia or obesity. Screening of the 999 articles returned by an initial search yielded 23 studies for inclusion and further data extraction. Qualitative assessment of included studies was subsequently conducted in accordance with Newcastle-Ottawa Scale criteria. RESULTS: We included 23 articles (17 anorexia, 5 obesity) that met our inclusion and exclusion criteria, which included 8 case reports, 13 case series, and 1 case-control study. Our primary variables of interest were location of DBS, change in BMI after intervention, electrode parameters, and psychiatric comorbidities. A total of 131 patients were included and analyzed, 118 of those belonging in the anorexia cohort. For patients with anorexia, we found that the most common place for DBS was the subcallosal cingulate followed by the nucleus accumbens, resulting in an overall increase in BMI by 24.82% over the span of a mean 17.1 months. Psychiatric comorbidities (major depressive disorder, obsessive-compulsive disorder, and anxiety) were common in the anorexia cohort. For patients with obesity, DBS was most common in the lateral hypothalamus followed by the nucleus accumbens, resulting in a small decrease in BMI by 3.97% over a mean 17.2 months. Data were insufficient for this cohort to report on additional psychiatric comorbidities or calculate the duration from diagnosis to treatment. CONCLUSIONS: DBS seems to be a promising solution in addressing treatment-refractory anorexia, but additional prospective studies are still needed to confirm this same usefulness for the treatment of obesity. Primary limitations included the apparent lack of data on DBS for obesity as well as the dearth of cohort studies assessing efficacy of DBS compared with control treatments. Although these limitations could not be addressed in the current review, this study may incentivize future trials to assess DBS in patients with appetite disorders in a more controlled fashion.