Prospective Connectomic-Based Deep Brain Stimulation Programming for Parkinson's Disease.

BACKGROUND: Efficacy of deep brain stimulation (DBS) relies on accurate lead placement as well as optimization of the stimulation parameters. Although clinical software tools are now available, programming still largely relies on a monopolar review, a tedious process for both patients and programmers. OBJECTIVE: This study investigates the safety and feasibility of prospective automated connectomic DBS programming (automated connectomic programming [ACP]), focusing on the recruitment of specific white matter pathways. METHODS: After DBS implantation, a detailed connectomic DBS model in patient-specific space was developed for each study participant. A driving-force model was used to quantify pathway recruitment across 2400 different DBS settings. Optimization algorithms maximized recruitment of therapeutic pathways while minimizing recruitment of side-effect pathways. Thirteen subjects were enrolled in two study phases that compared DBS settings derived from ACP to standard clinical DBS settings. RESULTS: Nine patients underwent reprogramming with ACP (5 globus pallidus interna [GPi], 4 subthalamic nucleus [STN]). Four patients underwent initial programming with ACP (3 GPi, 1 STN). All patients tolerated ACP without persistent side effects. In the reprogramming cohort, 3 patients preferred their ACP program, and 1 patient felt it was comparable to their clinical program. Unified Parkinson's Disease Rating Scale, Part III, scores for the initial ACP cohort (3 GPi, 1 STN) improved by an average of 43.5% (40.4-52.6 ± 5.6%). CONCLUSIONS: ACP appeared clinically safe and feasible. It provided reasonable motor improvement, which can be further optimized with subsequent clinical adjustment. Additional investigation is required to refine the optimization algorithm and to quantify the clinical benefit of ACP in a larger cohort. © 2024 International Parkinson and Movement Disorder Society.

Multimodal functional imaging and clinical correlates of pain regions in chronic low-back pain patients treated with spinal cord stimulation: a pilot study.

Objective: Spinal cord stimulation (SCS) is an invasive treatment option for patients suffering from chronic low-back pain (cLBP). It is an effective treatment that has been shown to reduce pain and increase the quality of life in patients. However, the activation of pain processing regions of cLBP patients receiving SCS has not been assessed using objective, quantitative functional imaging techniques. The purpose of the present study was to compare quantitative resting-state (rs)-fMRI and arterial spin labeling (ASL) measures between SCS patients and healthy controls and to correlate clinical measures with quantitative multimodal imaging indices in pain regions. Methods: Multi-delay 3D GRASE pseudo-continuous ASL and rs-fMRI data were acquired from five patients post-SCS with cLBP and five healthy controls. Three ASL measures and four rs-fMRI measures were derived and normalized into MNI space and smoothed. Averaged values for each measure from a pain atlas were extracted and compared between patients and controls. Clinical pain scores assessing intensity, sensitization, and catastrophizing, as well as others assessing global pain effects (sleep quality, disability, anxiety, and depression), were obtained in patients and correlated with pain regions using linear regression analysis. Results: Arterial transit time derived from ASL and several rs-fMRI measures were significantly different in patients in regions involved with sensation (primary somatosensory cortex and ventral posterolateral thalamus [VPL]), pain input (posterior short gyrus of the insula [PS]), cognition (dorsolateral prefrontal cortex [DLPC] and posterior cingulate cortex [PCC]), and fear/stress response (hippocampus and hypothalamus). Unidimensional pain rating and sensitization scores were linearly associated with PS, VPL, DLPC, PCC, and/or amygdala activity in cLBP patients. Conclusion: The present results provide evidence that ASL and rs-fMRI can contrast functional activation in pain regions of cLBP patients receiving SCS and healthy subjects, and they can be associated with clinical pain evaluations as quantitative assessment tools.

Simulated resections and responsive neurostimulator placement can optimize postoperative seizure outcomes when guided by fast ripple networks.

In medication-resistant epilepsy, the goal of epilepsy surgery is to make a patient seizure free with a resection/ablation that is as small as possible to minimize morbidity. The standard of care in planning the margins of epilepsy surgery involves electroclinical delineation of the seizure-onset zone and incorporation of neuroimaging findings from MRI, PET, single-photon emission CT and magnetoencephalography modalities. Resecting cortical tissue generating high-frequency oscillations has been investigated as a more efficacious alternative to targeting the seizure-onset zone. In this study, we used a support vector machine (SVM), with four distinct fast ripple (FR: 350-600 Hz on oscillations, 200-600 Hz on spikes) metrics as factors. These metrics included the FR resection ratio, a spatial FR network measure and two temporal FR network measures. The SVM was trained by the value of these four factors with respect to the actual resection boundaries and actual seizure-free labels of 18 patients with medically refractory focal epilepsy. Leave-one-out cross-validation of the trained SVM in this training set had an accuracy of 0.78. We next used a simulated iterative virtual resection targeting the FR sites that were of highest rate and showed most temporal autonomy. The trained SVM utilized the four virtual FR metrics to predict virtual seizure freedom. In all but one of the nine patients who were seizure free after surgery, we found that the virtual resections sufficient for virtual seizure freedom were larger in volume (P < 0.05). In nine patients who were not seizure free, a larger virtual resection made five virtually seizure free. We also examined 10 medically refractory focal epilepsy patients implanted with the responsive neurostimulator system and virtually targeted the responsive neurostimulator system stimulation contacts proximal to sites generating FR at highest rates to determine if the simulated value of the stimulated seizure-onset zone and stimulated FR metrics would trend towards those patients with a better seizure outcome. Our results suggest the following: (i) FR measures can accurately predict whether a resection, defined by the standard of care, will result in seizure freedom; (ii) utilizing FR alone for planning an efficacious surgery can be associated with larger resections; (iii) when FR metrics predict the standard-of-care resection will fail, amending the boundaries of the planned resection with certain FR-generating sites may improve outcome and (iv) more work is required to determine whether targeting responsive neurostimulator system stimulation contact proximal to FR generating sites will improve seizure outcome.

Long-Term Seizure Outcome With or Without Vagal Nerve Stimulation Therapy.

Background and Objectives: To compare long-term seizure control in patients with long-term VNS (vagal nerve stimulator) stimulation (VNS-on) with those who discontinued VNS after >3 years (VNS-off). Methods: Patients with refractory epilepsy with VNS therapy for >3 years (and follow-up for >2 years after VNS discontinuation for VNS-off patients) were included. Patients with brain surgery <3 years after VNS were excluded. We compared the percentage of patients with ≥50% seizure reduction (50% responder rate) and change in seizure frequency within and between groups in follow-up. Results: Thirty-three VNS-on and 16 VNS-off patients were evaluated. VNS-on patients underwent stimulation for 9.7 years (mean). VNS-off patients had VNS treatment for 6.5 years (mean), discontinued treatment, then had additional 8.0 years (mean) follow-up. 50% responder rates were similar between groups (VNS-on: 54.5% vs VNS-off at last-on: 37.5%, p = 0.26; vs VNS-off at the last follow-up: 62.5%, p = 0.60). VNS-on patients had a significant reduction in seizure frequency at the last follow-up compared with baseline (median [Mdn] = -4.5 seizures/month, interquartile range [IQR] = 14.0, 56% reduction, p = 0.013). VNS-off patients also showed significant seizure reduction while still continuing VNS therapy (Mdn = -1.0 seizures/month, IQR = 13.0, 35% reduction, p = 0.020) and, after discontinuing therapy, at the last follow-up compared with baseline (Mdn = -3.2, IQR = 11.0, 52% reduction, p = 0.020). The 2 groups were comparable in seizure frequency change both at the last-on visit (absolute change, p = 0.62; relative change, p = 0.50) at the last follow-up (absolute change, p = 0.67; relative change, p = 0.76). Discussion: Patients who discontinued VNS therapy and those who continued therapy had similar response during active treatment and similar long-term outcomes, suggesting that factors such as the natural disease course and/or medication treatment strongly affect long-term outcomes.

Microelectrode Recording During Deep Brain Stimulation Does Not Consistently Represent Lead Trajectory.

BACKGROUND AND OBJECTIVES: Long-term outcomes in deep brain stimulation (DBS) depend on accuracy of lead placement. Microelectrode recording (MER) is a long-used adjunct to leverage neurophysiological information to confirm satisfactory trajectory of implanted electrodes. The goal of this study was to evaluate the consistency in which electrodes are placed in sampled microelectrode trajectories. METHODS: This is a retrospective study using intraoperative computed tomography to measure final electrode deviation from MER probe placement during the DBS insertion targeting subthalamic nucleus. Fifteen patients had 29 DBS leads placed using MER assistance. Radial distance between the probe and the lead were measured for each patient using intraoperative imaging. In addition, the preoperative target to final lead error was measured in 14 patients undergoing subthalamic nucleus implants without the use of MER and compared with the 15 patients in which MER was used as an adjunct. RESULTS: There was no significant difference in the mean radial target error (1.2 vs 1.0 mm, P = .156) when comparing the leads placed with or without MER assistance, respectively. The mean difference in final position of microelectrode compared with DBS lead was 0.9 ± 0.1 (range 0.4-2.0 mm). Of all MER-assisted electrodes placed, 44.8% (13) of electrode final positions radially deviated 1.0 mm or more from the MER probe. CONCLUSION: Electrode placement may deviate significantly from MER trajectories. Given the concern that physiological data may not be representative of the final electrode trajectory, surgeons should consider using intraoperative imaging or other adjunctive techniques during DBS to confirm accuracy and satisfactory trajectory of DBS leads.

Thoracic canal morphology on preoperative magnetic resonance imaging in spinal cord stimulation patients.

INTRODUCTION: In high-frequency spinal cord stimulation anatomic placement targeting of the T9-10 disc space is based on "empiric" results that are best replicated with coverage broadly from T8 to T10. This study contains the largest cohort of patients evaluating low thoracic morphology and seeks to address the lack of MRI morphological analysis in literature. METHODS: This study was a retrospective review of a database of 101 consecutive patients undergoing permanent implant of thoracic SCS for chronic pain. Measurements were carried out on preoperative MRI imaging. Anteroposterior (AP) and lateral dimensions of the spinal cord as well as dural sac were measured. In addition, dorsal cerebrospinal fluid thickness and paddle depression distance were also measured. RESULTS: When comparing morphological dimensions by level, dorsal CSF thickness was smaller at T9-10 than T7-8 (p = 0.018). In addition, lateral dural and spinal cord diameters were larger at T10-11 than T9-10, contributing to larger dural surface area at T10-11 (p = 0.028). While trends of dorsal CSF thickness tend to decrease with lower thoracic levels, the ratio of surface area of spinal cord to dural sac appeared to remain relatively constant. CONCLUSIONS: Dorsal CSF thickness is smaller at T9-10 than T7-8 in chronic pain patients in this cohort. More ellipsoid, cord, and spinal canal diameter measurements were noted at lower levels of the thoracic spinal cord, particularly at T10-11. This may correlate with anatomical SCS placement. Future studies should evaluate efficacy of SCS therapy for pain based on these anatomical considerations.

Facile Electret-Based Self-Powered Soft Sensor for Noncontact Positioning and Information Translation.

Noncontact sensors have demonstrated significant potential in human-machine interactions (HMIs) in terms of hygiene and less wear and tear. The development of soft, stable, and simply structured noncontact sensors is highly desired for their practical applications in HMIs. This work reports on electret-based self-powered noncontact sensors that are soft, transparent, stable, and easy to manufacture. The sensors contain a three-layer structure with a thickness of 0.34 mm that is fabricated by simply stacking a polymeric electret layer, an electrode layer, and a substrate layer together. The fabricated sensors show high charge-retention capability, keeping over 98% of the initial surface potential even after 90 h, and can accurately and repeatedly sense external approaching objects with impressive durability. The intensity of the detected signal shows a strong dependence on the distance between the object and the sensor, capable of sensing a distance as small as 2 mm. Furthermore, the sensors can report stable signals in response to external objects over 3000 cycles. By virtue of the signal dependence on distance, an intelligent noncontact positioning system is developed that can precisely detect the location of an approaching object. Finally, by integrating with eyeglasses, the transparent sensor successfully captures the movements of blinks for information translation. This work may contribute to the development of stable and easily manufactured noncontact soft sensors for HMI applications, for instance, assisting with communication for locked-in syndrome patients.

Learning Curves during Implementation of Robotic Stereotactic Surgery.

INTRODUCTION: Adoption of robotic techniques is increasing for neurosurgical applications. Common cranial applications include stereoelectroencephalography (sEEG) and deep brain stimulation (DBS). For surgeons to implement robotic techniques in these procedures, realistic learning curves must be anticipated for surgeons to overcome the challenges of integrating new techniques into surgical workflow. One such way of quantifying learning curves in surgery is cumulative sum (CUSUM) analysis. METHODS: Here, the authors present retrospective review of stereotactic cases to perform a CUSUM analysis of operative time for robotic cases at a single institution performed by 2 surgeons. The authors demonstrate learning phase durations of 20 and 16 cases in DBS and sEEG, respectively. RESULTS: After plateauing of operative time, mastery phases started at cases 132 and 72 in DBS and sEEG. A total of 273 cases (188 DBS and 85 sEEG) were included in the study. The authors observed a learning plateau concordant with change of location of surgery after exiting the learning phase. CONCLUSION: This study demonstrates the learning curve of 2 stereotactic workflows when integrating robotics as well as being the first study to examine the robotic learning curve in DBS via CUSUM analysis. This work provides data on what surgeons may expect when integrating this technology into their practice for cranial applications.

Simulated resections and RNS placement can optimize post-operative seizure outcomes when guided by fast ripple networks.

In medication-resistant epilepsy, the goal of epilepsy surgery is to make a patient seizure free with a resection/ablation that is as small as possible to minimize morbidity. The standard of care in planning the margins of epilepsy surgery involves electroclinical delineation of the seizure onset zone (SOZ) and incorporation of neuroimaging findings from MRI, PET, SPECT, and MEG modalities. Resecting cortical tissue generating high-frequency oscillations (HFOs) has been investigated as a more efficacious alternative to targeting the SOZ. In this study, we used a support vector machine (SVM), with four distinct fast ripple (FR: 350-600 Hz on oscillations, 200-600 Hz on spikes) metrics as factors. These metrics included the FR resection ratio (RR), a spatial FR network measure, and two temporal FR network measures. The SVM was trained by the value of these four factors with respect to the actual resection boundaries and actual seizure free labels of 18 patients with medically refractory focal epilepsy. Leave one out cross-validation of the trained SVM in this training set had an accuracy of 0.78. We next used a simulated iterative virtual resection targeting the FR sites that were highest rate and showed most temporal autonomy. The trained SVM utilized the four virtual FR metrics to predict virtual seizure freedom. In all but one of the nine patients seizure free after surgery, we found that the virtual resections sufficient for virtual seizure freedom were larger in volume (p<0.05). In nine patients who were not seizure free, a larger virtual resection made five virtually seizure free. We also examined 10 medically refractory focal epilepsy patients implanted with the responsive neurostimulator system (RNS) and virtually targeted the RNS stimulation contacts proximal to sites generating FR at highest rates to determine if the simulated value of the stimulated SOZ and stimulated FR metrics would trend toward those patients with a better seizure outcome. Our results suggest: 1) FR measures can accurately predict whether a resection, defined by the standard of care, will result in seizure freedom; 2) utilizing FR alone for planning an efficacious surgery can be associated with larger resections; 3) when FR metrics predict the standard of care resection will fail, amending the boundaries of the planned resection with certain FR generating sites may improve outcome; and 4) more work is required to determine if targeting RNS stimulation contact proximal to FR generating sites will improve seizure outcome.

Demographics and PainDETECT as Predictors of 24-Month Outcomes for 10 kHz SCS in Nonsurgical Refractory Back Pain.

BACKGROUND: Nonsurgical refractory back pain (NSRBP) is broadly defined as chronic refractory back pain in patients who have not had previous spine surgery and, because they are deemed inappropriate candidates for surgery, are reliant on conventional medical management (CMM), which often provides poor long-term outcomes. High-frequency spinal cord stimulation (10kHz SCS) has demonstrated high rates of pain relief and improvements in functioning in patients with NSRBP. However, despite the use of temporary trial stimulation to select patients who will respond to therapy, some patients fail to achieve long-term therapy response with permanent implants. Prediction analysis founded on patients' baseline characteristics may enrich the appropriate selection of patients for permanent implantation. OBJECTIVES: To examine baseline patient characteristics to predict long-term pain and functional responses to treatment with 10 kHz SCS for NSRBP. STUDY DESIGN: A retrospective analysis of baseline patient characteristics as predictors of 24-month pain and functional outcomes from a previous multicenter randomized controlled trial of 10 kHz SCS in patients with NSRBP. PATIENTS: Patients diagnosed with chronic, neuropathic, axial, low back pain refractory to CMM who had had no previous spine surgery, were deemed unsuitable candidates for it according to a spine surgeon, were implanted with 10kHz SCS and continued with CMM for up to 24 months. METHODS: The baseline characteristics of and 24-month outcomes in the 125 implanted patients who participated in the NSRBP randomized controlled trial (RCT) were included in this analysis. The baseline characteristics included demographics, baseline pain on the visual analog scale (VAS), baseline function based on the Oswestry Disability Index (ODI), mental health according to the patient health questionnaire-9 (PHQ-9), neuropathic pain as measured by PainDETECT, and each patient's temporary trial response. Patient response at 24 months was defined as absolute change from the baseline on the VAS and ODI, and each patient was also classified as a pain responder (achieving at least a 50% decrease in VAS pain score from the baseline) and a function responder (at least a 10-point decrease in ODI or a 24-month score of no more than 20 points). Multivariate prediction models based on regression and classification and regression tree (CART) techniques were developed using the response variables discussed above as the dependent variables and the baseline characteristics as the independent variables. RESULTS: Different factors contributed to pain and functional outcomes. Patients presenting with neuropathic pain (PainDETECT >= 19) and female gender had higher odds of being pain responders to 10 kHz SCS therapy than did males and those without neuropathic pain. Both higher age and depression score (PHQ-9) independently reduced the odds that a patient would be an ODI responder. Years since diagnosis, the reason the patient was deemed unsuitable for spine surgery, and pain etiology were not predictive of pain or functional outcomes. LIMITATIONS: A retrospective sub-analysis of a single pragmatic randomized controlled trial. CONCLUSIONS: There may be an opportunity to increase pain relief and functional improvement if additional patient screening accompanies the temporary lead trial. The presence of neuropathic pain, female gender, age, and depression had some predictive value, but this analysis demonstrates the treatment efficacy of 10 kHz SCS across a wide range of patients with NSRBP.

The Temporal Lobe Club: Newer Approaches to Treat Temporal Lobe Epilepsy.

This brief review summarizes presentations at the Temporal Lobe Club Special Interest Group session held in December 2022 at the American Epilepsy Society meeting. The session addressed newer methods to treat temporal epilepsy, including methods currently in clinical use and techniques under investigation. Brief summaries are provided for each of 4 lectures. Dr Chengyuan Wu discussed ablative techniques such as laser interstitial thermal ablation, radiofrequency ablation, focused ultrasound; Dr Joon Kang reviewed neuromodulation techniques including electrical stimulation and focused ultrasound; Dr Julia Makhalova discussed network effects of the aforementioned techniques; and Dr Derek Southwell reviewed inhibitory interneuron transplantation. These summaries are intended to provide a brief overview and references are provided for the reader to learn more about each topic.

Magnolol extends lifespan and improves age-related neurodegeneration in Caenorhabditis elegans via increase of stress resistance.

Magnolol is a naturally occurring polyphenolic compound in many edible plants, which has various biological effects including anti-aging and alleviating neurodegenerative diseases. However, the underlying mechanism on longevity is uncertain. In this study, we investigated the effect of magnolol on the lifespan of Caenorhabditis elegans and explored the mechanism. The results showed that magnolol treatment significantly extended the  lifespan of nematode and alleviated senescence-related decline in the nematode model. Meanwhile, magnolol enhanced stress resistance to heat shock, hydrogen peroxide (H2O2), mercuric potassium chloride (MeHgCl) and paraquat (PQ) in nematode. In addition, magnolol reduced reactive oxygen species and malondialdehyde (MDA) levels, and increased superoxide dismutase and catalase (CAT) activities in nematodes. Magnolol also up-regulated gene expression of sod-3, hsp16.2, ctl-3, daf-16, skn-1, hsf-1, sir2.1, etc., down-regulated gene expression of daf-2, and promoted intranuclear translocation of daf-16 in nematodes. The lifespan-extending effect of magnolol were reversed in insulin/IGF signaling (IIS) pathway-related mutant lines, including daf-2, age-1, daf-16, skn-1, hsf-1 and sir-2.1, suggesting that IIS signaling is involved in the modulation of longevity by magnolol. Furthermore, magnolol improved the age-related neurodegeneration in PD and AD C. elegans models. These results indicate that magnolol may enhance lifespan and health span through IIS and sir-2.1 pathways. Thus, the current findings implicate magnolol as a potential candidate to ameliorate the symptoms of aging.

Mulberrin extends lifespan in Caenorhabditis elegans through detoxification function.

Mulberrin, a naturally occurring flavone found in mulberry and Romulus Mori, exhibits diverse biological functions. Here, we showed that mulberrin extended both the lifespan and healthspan in C. elegans. Moreover, mulberrin increased the worms' resistance to toxicants and activated the expression of detoxification genes. The longevity-promoting effect of mulberrin was attenuated in nuclear hormone receptor (NHR) homologous nhr-8 and daf-12 mutants, indicating that the lifespan extending effects of mulberrin in C. elegans may depend on nuclear hormone receptors NHR-8/DAF-12. Further analyses revealed the potential associations between the longevity effects of mulberrin and the insulin/insulin-like growth factor signaling (IIS) and adenosine 5'-monophosphate-activated protein kinase (AMPK) pathways. Together, our findings suggest that mulberrin may prolong lifespan and healthspan by activating detoxification functions mediated by nuclear receptors.

Robot-Assisted Minimally Invasive Asleep Single-Stage Deep Brain Stimulation Surgery: Operative Technique and Systematic Review.

BACKGROUND AND OBJECTIVES: Robotic assistance has garnered increased use in neurosurgery. Recently, this has expanded to include deep brain stimulation (DBS). Several studies have reported increased accuracy and improved efficiency with robotic assistance, but these are limited to individual robotic platforms with smaller sample sizes or are broader studies on robotics not specific to DBS. Our objectives are to report our technique for robot-assisted, minimally invasive, asleep, single-stage DBS surgery and to perform a meta-analysis comparing techniques from previous studies. METHODS: We performed a single-center retrospective review of DBS procedures using a floor-mounted robot with a frameless transient fiducial array registration. We compiled accuracy data (radial entry error, radial target error, and 3-dimensional target error) and efficiency data (operative time, setup time, and total procedure time). We then performed a meta-analysis of previous studies and compared these metrics. RESULTS: We analyzed 315 electrodes implanted in 160 patients. The mean radial target error was 0.9 ± 0.5 mm, mean target 3-dimensional error was 1.3 ± 0.7 mm, and mean radial entry error was 1.1 ± 0.8 mm. The mean procedure time (including pulse generator placement) was 182.4 ± 47.8 minutes, and the mean setup time was 132.9 ± 32.0 minutes. The overall complication rate was 8.8% (2.5% hemorrhagic/ischemic, 2.5% infectious, and 0.6% revision). Our meta-analysis showed increased accuracy with floor-mounted over skull-mounted robotic platforms and with fiducial-based registrations over optical registrations. CONCLUSION: Our technique for robot-assisted, minimally invasive, asleep, single-stage DBS surgery is safe, accurate, and efficient. Our data, combined with a meta-analysis of previous studies, demonstrate that robotic assistance can provide similar or increased accuracy and improved efficiency compared with traditional frame-based techniques. Our analysis also suggests that floor-mounted robots and fiducial-based registration methods may be more accurate.

CRISPR-powered microfluidic biosensor for preamplification-free detection of ochratoxin A.

The CRISPR technology, which does not require complex instruments, expensive reagents or professional operators, has attracted a lot of attention. When utilizing the CRISPR-Cas system for detection, the pre-amplification step is often necessary to enhance sensitivity. However, this approach tends to introduce complexity and prolong the time required. To address this issue, we employed Pd@PCN-222 nanozyme to label single-stranded DNA, referred to as Pd@PCN-222 CRISPR nanozyme, which serves as the reporter of the CRISPR system. Pd@PCN-222 nanozyme possess exceptional catalytic activity for the reduction of H2O2. Compared with traditional electrochemical probe ferrocene and methylene blue without catalytic activity, there is a significant amplification of the electrochemical signal. So the need for pre-amplification was eliminated. In this study, we constructed a CRISPR-Cas system for ochratoxin A, utilizing the Pd@PCN-222 CRISPR nanozyme to amplified signal avoiding pre-amplification with outstanding detection of 1.21 pg/mL. Furthermore, we developed a microfluidic electrochemical chip for the on-site detection of ochratoxin A. This achievement holds significant promise in establishing a practical on-site detection platform for identifying food safety hazards.

Durable responses at 24 months with high-frequency spinal cord stimulation for nonsurgical refractory back pain.

OBJECTIVE: The objective of this study was to evaluate the 24-month durability of pain relief, function, quality of life, and safety outcomes for patients with nonsurgical refractory back pain (NSRBP) treated with high-frequency spinal cord stimulation (SCS) within a large, national, multicenter randomized controlled trial (RCT). METHODS: Following the completion of an RCT comparing high-frequency SCS plus CMM with CMM alone for the treatment of NSRBP, patients gave additional consent for a follow-up extension to 24 months. Presented is the cohort analysis of all patients treated with high-frequency SCS following the optional crossover at 6 months. The outcomes assessed to 24 months included responder rate of ≥ 50% pain relief measured according to the visual analog scale [VAS]), disability (Oswestry Disability Index [ODI]), quality of life (EQ-5D 5-level [EQ-5D-5L]), opioid reduction. RESULTS: Of the 125 patients who received a permanent implant, 121 completed the 12-month follow-up, 101 gave additional consent for extended follow-up, and 98 completed the 24-month follow-up. At 24 months after implantation, the mean back pain VAS score was reduced by 73% and the responder rate was 82%. ODI and EQ-5D-5L both improved by at least double the minimal clinically important difference for each measure. No unexpected adverse events were observed, and the rates of serious adverse events (3.4%) and device explantations (4.8%) were low. CONCLUSIONS: The addition of high-frequency SCS to CMM in patients with NSRBP offers profound improvements at 24 months in pain, function, quality of life, and reduced opioid use. This study provides much-needed evidence to inform current clinical practice for managing patients with NSRBP.

MscI restriction enzyme cooperating recombinase-aided isothermal amplification for the ultrasensitive and rapid detection of low-abundance EGFR mutations on microfluidic chip.

The detection of low-abundance mutation genes of the epidermal growth factor receptor (EGFR) exon 21 (EGFR L858R) plays a crucial role in the diagnosis of non-small cell lung cancer (NSCLC), as it enables early cancer detection and facilitates the development of treatment strategies. A detection platform was developed by combining the MscI restriction enzyme with the recombinase-aided isothermal amplification (RAA) technique (MRE-RAA). During the RAA process, "TGG^CCA" site of the wild-type genes was cleaved by the MscI restriction enzyme, while only the low-abundance mutation genes underwent amplification. Notably, when the RAA product was combined with CRISPR-Cas system, the sensitivity of detecting the EGFR L858R mutation increased by up to 1000-fold for addition of the MscI restriction enzyme. This achievement marked the first instance of attaining an analytical sensitivity of 0.001%. Furthermore, a disk-shaped microfluidic chip was developed to automate pretreatment while concurrently analyzing four blood samples. The microfluidic features of the chip include DNA extraction, MRE-RAA, and CRISPR-based detection. The fluorescence signal is employed for detection in the microfluidic chip, which is visible to the naked eye upon exposure to blue light irradiation. Furthermore, this platform has the capability to facilitate early diagnosis for various types of cancer by enabling high-sensitivity detection of low-abundance mutation genes.

[Preparation of vitexin albumin nanoparticles and its pharmacokinetic study].

This study aims to prepare vitexin albumin nanoparticles(VT-BSA-NPs) to alleviate the low bioavailability of vitexin(VT) in vivo due to its poor water solubility. VT micro powders were prepared by the antisolvent crystallization method, and the morphology, size, and physicochemical properties of VT micro powders were studied. The results showed that the VT micro powder had a particle size of(187.13±7.15) nm, an approximate spherical morphology, and a uniform size distribution. Compared with VT, the chemical structure of VT micro powders has not changed. VT-BSA-NPs were prepared from VT micro powders by desolvation-crosslinking curing method. The preparation process was screened by single factor test and orthogonal test, and the quality evaluation of the optimal prescription particle size, PDI, Zeta potential, EE, and morphology was performed. The results showed that the average particle size of VT-BSA-NPs was(124.33±0.47) nm; the PDI was 0.184±0.012; the Zeta potential was(-48.83±2.20) mV, and the encapsulation rate was 83.43%±0.39%, all of which met the formulation-related requirements. The morphological results showed that the VT-BSA-NPs were approximately spherical in appearance, regular in shape, and without adhesion on the surface. In vitro release results showed a significantly reduced release rate of VT-BSA-NPs compared with VT, indicating a good sustained release effect. LC-MS/MS was used to establish an analytical method for in vivo analysis of VT and study the plasma pharmacokinetics of VT-BSA-NPs in rats. The results showed that the specificity of the analytical method was good, and the extraction recovery was more than 90%. Compared with VT and VT micro powders, VT-BSA-NPs could significantly increase AUC, MRT, and t_(1/2), which was beneficial to improve the bioavailability of VT.

Characteristic dynamic functional connectivity during sevoflurane-induced general anesthesia.

General anesthesia (GA) during surgery is commonly maintained by inhalational sevoflurane. Previous resting state functional MRI (rs-fMRI) studies have demonstrated suppressed functional connectivity (FC) of the entire brain networks, especially the default mode networks, transitioning from the awake to GA condition. However, accuracy and reliability were limited by previous administration methods (e.g. face mask) and short rs-fMRI scans. Therefore, in this study, a clinical scenario of epilepsy patients undergoing laser interstitial thermal therapy was leveraged to acquire 15 min of rs-fMRI while under general endotracheal anesthesia to maximize the accuracy of sevoflurane level. Nine recruited patients had fMRI acquired during awake and under GA, of which seven were included in both static and dynamic FC analyses. Group independent component analysis and a sliding-window method followed by k-means clustering were applied to identify four dynamic brain states, which characterized subtypes of FC patterns. Our results showed that a low-FC brain state was characteristic of the GA condition as a single featuring state during the entire rs-fMRI session; In contrast, the awake condition exhibited frequent fluctuations between three distinct brain states, one of which was a highly synchronized brain state not seen in GA. In conclusion, our study revealed remarkable dynamic connectivity changes from awake to GA condition and demonstrated the advantages of dynamic FC analysis for future studies in the assessments of the effects of GA on brain functional activities.

Current Neurostimulation Therapies for Chronic Pain Conditions.

PURPOSE OF REVIEW: Neurostimulation treatment options have become more commonly used for chronic pain conditions refractory to these options. In this review, we characterize current neurostimulation therapies for chronic pain conditions and provide an analysis of their effectiveness and clinical adoption. This manuscript will inform clinicians of treatment options for chronic pain. RECENT FINDINGS: Non-invasive neurostimulation includes transcranial direct current stimulation and repetitive transcranial magnetic stimulation, while more invasive options include spinal cord stimulation (SCS), peripheral nerve stimulation (PNS), dorsal root ganglion stimulation, motor cortex stimulation, and deep brain stimulation. Developments in transcranial direct current stimulation, repetitive transcranial magnetic stimulation, spinal cord stimulation, and peripheral nerve stimulation render these modalities most promising for the alleviating chronic pain. Neurostimulation for chronic pain involves non-invasive and invasive modalities with varying efficacy. Well-designed randomized controlled trials are required to delineate the outcomes of neurostimulatory modalities more precisely.