Electrophysiological correlates of dentate nucleus deep brain stimulation for post-stroke motor recovery.

While ipsilesional cortical electroencephalography has been associated with post-stroke recovery mechanisms and outcomes, the role of cerebellum and its interaction with the ipsilesional cortex is still largely unknown. We have previously shown that post-stroke motor control relies on increased cortico-cerebellar coherence (CCC) in the low beta band to maintain motor task accuracy and to compensate for decreased excitability of the ipsilesional cortex. We now extend our work to investigate corticocerebellar network changes associated with chronic stimulation of the dentato-thalamo-cortical pathway aimed at promoting post-stroke motor rehabilitation. We investigated the excitability of ipsilesional cortex, dentate (DN), and their interaction as a function of treatment outcome measures. Relative to baseline, ten human participants (two women) at the end of 4-8 months of DN deep brain stimulation (DBS) showed 1) significantly improved motor control indexed by computerized motor tasks; 2) significant increase in ipsilesional premotor cortex event-related desynchronization that correlated with improvements in motor function; and 3) significant decrease in CCC, including causal interactions between the DN and ipsilesional cortex, which also correlated with motor function improvements. Furthermore, we show that the functional state of the DN in the post-stroke state and its connectivity with ipsilesional cortex were predictive of motor outcomes associated with DN-DBS. The findings suggest that as participants recovered, the ipsilesional cortex became more involved in motor control, with less demand on the cerebellum to support task planning and execution. Our data provide unique mechanistic insights into the functional state of cortico-cerebellar-cortical network after stroke and its modulation by DN-DBS.Significance Statement The study aims to understand the brain mechanisms underlying the effects of cerebellar dentate deep brain stimulation (DN-DBS), a novel upcoming therapy for chronic stroke. We provide evidence that functional improvements as a result of DN-DBS therapy were accompanied by significant improvements in task behavior and ipsilesional cortex excitability. More importantly.

Anatomic Referencing of the Distal Femur in Total Knee Arthroplasty: The Impact of Orientation on Femoral Component Size.

BACKGROUND: Anatomic referencing in total knee arthroplasty places the femoral component flush to the anterior cortex while maintaining posterior condylar offset (PCO). The intent of this study was to evaluate how component position influences the femoral component size. METHODS: Digital surface models were created using 446 femora from an established computed tomography database. Virtual bone resections, component sizing, and component placement were performed assuming neutral (0°) flexion and neutral (3°) rotation relative to the posterior condyles. The appropriately sized femoral component, which had 2 mm of incremental size, was placed flush with the anterior cortex for optimal restoration of the PCO. Sizing and placement were repeated using 3 and 6° flexion and 0, 5, and 7° external rotation (ER). RESULTS: At 0° flexion, decreasing ER from 3 to 0° resulted in an average decreased anterior-posterior height (APH) of 1.9 mm, corresponding to a component size decrease of 1 for 88% of patients. At 7° ER, component size increased by an average of 2.5 mm, corresponding to a size increase for 80% of patients. Flexing the femoral component to 3° with ER at 3° resulted in a decrease in APH of 2.2 mm (1 size decrease in 93% of patients). At 3° flexion and 3° ER, 86% had the same component size as at 0° flexion and 0° ER. Increasing ER at 3° flexion increased APH by 1.2 mm at 5° and 3.1 mm at 7° on average, relative to 3° ER. Increasing flexion from 3 to 6° extended this effect. CONCLUSIONS: Flexion decreases the APH when the ER is held constant. The ER of the femoral component increases the APH across all tested flexion angles, causing an increase in the ideal femoral component size to maintain PCO. With anatomic referencing, alterations in femoral component positioning and subsequent changes in component size can be accounted for.

An Evaluation of Anatomic Referencing for Femoral Component Sizing Using Computed Tomography-Based Computer Modeling.

One of the critical steps in total knee arthroplasty is femoral component positioning and sizing. Historically, there was wider variability between femoral component sizes, necessitating the concepts of anterior referencing (AR) and posterior referencing (PR). With the introduction of smaller increments between sizes, the concept of anatomic referencing has been introduced to replace AR and PR. The intent of this study was to validate the concept of anatomic referencing and show that with 2 mm increments in femoral sizes, the femoral component can be placed flush to the anterior cortex while maintaining posterior condylar offset (PCO). Digital surface models were created using 515 femurs from an established computed tomography database. Virtual bone resections, component sizing and placement were performed assuming neutral mechanical axis and a cartilage thickness of 2 mm. The appropriately sized femoral component, which had 2 mm incremental sizes, was placed flush with the anterior cortex with restoration of the PCO. The anterior-posterior distance from the posterior surface of the component to the medial and lateral surfaces of the posterior condylar cartilage were measured. The medial condyle was the limiting condyle in the majority of cases (73%). The average medial gap after appropriate femoral component matching was 0.6 mm (0.39-1.41 mm) across all sizes. The overall average condylar gap was 1.02 mm. The most common femoral component was a size 7 (57.2 mm) and the average femoral AP width was 55.9 mm. Anatomic referencing with an implant system that has 2-mm increments in femoral component sizing provides an alternative to AR and PR without compromise. Anatomic referencing allows for perfect alignment of the anterior flange of the femoral component to the anterior cortex of the femur while restoring the native PCO to within 1 mm. This avoids having to choose between AR or PR when in between femoral sizes.

Efficacy of Botulinum A Injection to the Laryngeal Adductor Compartment for Treatment of Cough.

OBJECTIVES: Studies examining electromyography (EMG)-guided laryngeal onobotulinumtoxinA (BTxA) injection for chronic cough reveal promising efficacy, however, are limited by small cohorts and absent quantifiable outcomes. It further remains unclear if pulmonary disease limits efficacy, or if vagal motor neuropathy prognosticates response. We hypothesize BTxA injection results in qualitative improvement in cough, decrease in Cough Severity Index (CSI), no change in Voice Handicap Index-10 (VHI-10), and complication rates comparable to historical data. We also examine the correlation of pulmonary comorbidities and vocal fold hypomobility with treatment efficacy. STUDY DESIGN: Retrospective review. METHODS: Charts for patients receiving percutaneous adductor compartment BTxA injection for cough were reviewed for the binary outcome of patient-reported presence or absence of improvement. Generalized estimating equations regression models were used to analyze the change in CSI (ΔCSI) and the correlation of ΔCSI with qualitative outcomes. Multivariable analyses were used to examine correlation of vocal fold hypomobility and pulmonary disease with qualitative outcomes and ΔCSI. RESULTS: Forty-seven patients underwent 197 BTxA injections from June 2012 to June 2022. A statistical proportion of 0.698 (0.599-0.813, p < 0.0001) or 69.8% of injections resulted in subjective improvement. Mean ΔCSI was -2.12 (0.22-4.02, p < 0.05), indicating overall improvement. With and without subjective improvement, estimated ΔCSI was -4.43 and +2.68, respectively (p < 0.0001). VHI-10 did not change (0.69, p = 0.483). Neither pulmonary disease nor vocal fold hypomobility correlated with subjective improvement or ΔCSI. Dysphagia occurred following 15 (7.6%) injections with no aspiration pneumonia or hospitalization. CONCLUSIONS: BTxA injection to the laryngeal adductors may effectively treat cough with limited risk for serious complications. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1749-1756, 2024.

Zone I Revision Finger Amputations Performed in the Emergency Department Compared With Those Performed in the Operating Room.

Finger amputations are commonly encountered. These may be revised in the emergency department (ED) or the operating room (OR). Previous studies have demonstrated the cost-effectiveness associated with procedures performed in the ED. Patient outcomes have not been described. We retrospectively reviewed patients who presented to our level 1 trauma center with a traumatic partial or complete finger amputation through flexor tendon zone I. All were treated with revision amputation performed in either the ED or the OR between January 2012 and December 2017. A total of 172 patient charts were included. Ninety-three of the revision amputations were performed in the ED, while 79 were performed in the OR. There was no difference in age, race, sex, having a manual labor job, medical comorbidities, or mechanism of injury between the groups. Compared with procedures performed in the ED, procedures performed in the OR had a higher rate of delayed healing, a longer stay in the hospital, and a higher referral to therapy postoperatively. Length of follow-up and number of follow-up visits were not statistically different based on location of procedure. There was no difference in post-procedural infection rate or need for revision procedure between the groups. Our data support the efficacy of performing revision amputation procedures in the ED. Recorded patient complications and subsequent treatment after revision amputations performed in the ED vs the OR were comparable. Those performed in the ED potentially decrease the burden placed on the patient and the health care system. [Orthopedics. 202x;4x(x):xx-xx.].

Myogenic and cortical evoked potentials vary as a function of stimulus pulse geometry delivered in the subthalamic nucleus of Parkinson's disease patients.

Introduction: The therapeutic efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease (PD) may be limited for some patients by the presence of stimulation-related side effects. Such effects are most often attributed to electrical current spread beyond the target region. Prior computational modeling studies have suggested that changing the degree of asymmetry of the individual phases of the biphasic, stimulus pulse may allow for more selective activation of neural elements in the target region. To the extent that different neural elements contribute to the therapeutic vs. side-effect inducing effects of DBS, such improved selectivity may provide a new parameter for optimizing DBS to increase the therapeutic window. Methods: We investigated the effect of six different pulse geometries on cortical and myogenic evoked potentials in eight patients with PD whose leads were temporarily externalized following STN DBS implant surgery. DBS-cortical evoked potentials were quantified using peak to peak measurements and wavelets and myogenic potentials were quantified using RMS. Results: We found that the slope of the recruitment curves differed significantly as a function of pulse geometry for both the cortical- and myogenic responses. Notably, this effect was observed most frequently when stimulation was delivered using a monopolar, as opposed to a bipolar, configuration. Discussion: Manipulating pulse geometry results in differential physiological effects at both the cortical and neuromuscular level. Exploiting these differences may help to expand DBS' therapeutic window and support the potential for incorporating pulse geometry as an additional parameter for optimizing therapeutic benefit.

Analgesic Trends in the Management of Pain Following Total Knee Arthroplasty: A Comparison of Peri-Articular Infiltration, Adductor Canal Block, and Adjuvant Treatment for Posterior Knee Pain.

The rising number of total knee arthroplasties (TKA's) in the United States increases demand for perioperative pain modalities, which can promote early mobilization and discharge. Over the decades, a focus has shifted from opioid-dominant regimens to motor-sparing multimodal protocols, which have not only improved pain scores and reduced opioid consumption but also improved overall patient outcomes. In this article, we briefly review the evolution of post-operative pain management in patients undergoing TKA and summarize the literature on the most popular modalities currently used including periarticular injections, adductor canal blocks, distal selective nerve blocks, as well as liposomal bupivacaine as part of a multimodal approach.

"The students keep me hopeful": Teacher hope during the COVID-19 pandemic.

This study examined teacher enactment of hope, specifically willpower, waypower, and agency in the shadow of the COVID-19 glare. Participants of this mixed methods study were K-12 public school classroom teachers (n = 233) in a Western US state. Quantitative survey results indicated teachers maintained moderate to high levels of hope. Qualitative survey results indicated themes of obstacles that were unique to this pandemic context as well as indicators of willpower, waypower, and agency. This study illustrates teacher resiliency and the ways in which they shifted instruction under highly strenuous circumstances. Teachers maintained hope because of their dedication to the students.

The impact of pulse timing on cortical and subthalamic nucleus deep brain stimulation evoked potentials.

The impact of pulse timing is an important factor in our understanding of how to effectively modulate the basal ganglia thalamocortical (BGTC) circuit. Single pulse low-frequency DBS-evoked potentials generated through electrical stimulation of the subthalamic nucleus (STN) provide insight into circuit activation, but how the long-latency components change as a function of pulse timing is not well-understood. We investigated how timing between stimulation pulses delivered in the STN region influence the neural activity in the STN and cortex. DBS leads implanted in the STN of five patients with Parkinson's disease were temporarily externalized, allowing for the delivery of paired pulses with inter-pulse intervals (IPIs) ranging from 0.2 to 10 ms. Neural activation was measured through local field potential (LFP) recordings from the DBS lead and scalp EEG. DBS-evoked potentials were computed using contacts positioned in dorsolateral STN as determined through co-registered post-operative imaging. We quantified the degree to which distinct IPIs influenced the amplitude of evoked responses across frequencies and time using the wavelet transform and power spectral density curves. The beta frequency content of the DBS evoked responses in the STN and scalp EEG increased as a function of pulse-interval timing. Pulse intervals <1.0 ms apart were associated with minimal to no change in the evoked response. IPIs from 1.5 to 3.0 ms yielded a significant increase in the evoked response, while those >4 ms produced modest, but non-significant growth. Beta frequency activity in the scalp EEG and STN LFP response was maximal when IPIs were between 1.5 and 4.0 ms. These results demonstrate that long-latency components of DBS-evoked responses are pre-dominantly in the beta frequency range and that pulse interval timing impacts the level of BGTC circuit activation.

Consistent Changes in Cortico-Subthalamic Directed Connectivity Are Associated With the Induction of Parkinsonism in a Chronically Recorded Non-human Primate Model.

Parkinson's disease is a neurological disease with cardinal motor signs including bradykinesia and tremor. Although beta-band hypersynchrony in the cortico-basal ganglia network is thought to contribute to disease manifestation, the resulting effects on network connectivity are unclear. We examined local field potentials from a non-human primate across the naïve, mild, and moderate disease states (model was asymmetric, left-hemispheric dominant) and probed power spectral density as well as cortico-cortical and cortico-subthalamic connectivity using both coherence and Granger causality, which measure undirected and directed effective connectivity, respectively. Our network included the left subthalamic nucleus (L-STN), bilateral primary motor cortices (L-M1, R-M1), and bilateral premotor cortices (L-PMC, R-PMC). Results showed two distinct peaks (Peak A at 5-20 Hz, Peak B at 25-45 Hz) across all analyses. Power and coherence analyses showed widespread increases in power and connectivity in both the Peak A and Peak B bands with disease progression. For Granger causality, increases in Peak B connectivity and decreases in Peak A connectivity were associated with the disease. Induction of mild disease was associated with several changes in connectivity: (1) the cortico-subthalamic connectivity in the descending direction (L-PMC to L-STN) decreased in the Peak A range while the reciprocal, ascending connectivity (L-STN to L-PMC) increased in the Peak B range; this may play a role in generating beta-band hypersynchrony in the cortex, (2) both L-M1 to L-PMC and R-M1 to R-PMC causalities increased, which may either be compensatory or a pathologic effect of disease, and (3) a decrease in connectivity occurred from the R-PMC to R-M1. The only significant change seen between mild and moderate disease was increased right cortical connectivity, which may reflect compensation for the left-hemispheric dominant moderate disease state.

Stability and Effect of Parkinsonian State on Deep Brain Stimulation Cortical Evoked Potentials.

OBJECTIVES: To characterize and compare the stability of cortical potentials evoked by deep brain stimulation (DBS) of the subthalamic nucleus (STN) across the naïve, parkinsonian, and pharmacologically treated parkinsonian states. To advance cortical potentials as possible biomarkers for DBS programming. MATERIALS AND METHODS: Serial electrocorticographic (ECoG) recordings were made more than nine months from a single non-human primate instrumented with bilateral ECoG grids spanning anterior parietal to prefrontal cortex. Cortical evoked potentials (CEPs) were generated through time-lock averaging of the ECoG recordings to DBS pulses delivered unilaterally in the STN region using a chronically implanted, six-contact, scaled DBS lead. Recordings were made across the naïve followed by mild and moderate parkinsonian conditions achieved by staged injections of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin. In addition to characterizing the spatial distribution and stability of the response within each state, changes in the amplitude and latency of CEP components as well as in the frequency content were examined in relation to parkinsonian severity and dopamine replacement. RESULTS: In the naïve state, the STN DBS CEP presented as a multiphase response maximal over M1 cortex, with components attributable to physiological activity distinguishable from stimulus artifact as early as 0.45-0.75 msec poststimulation. When delivered using therapeutically effective parameters in the parkinsonian state, the CEP was highly stable across multiple recording sessions within each behavioral state. Across states, significant differences were present with respect to both the latency and amplitude of individual response components, with greater differences present for longer-latency components (all p < 0.05). Power spectral density analysis revealed a high-beta peak within the evoked response, with significant changes in power between disease states across multiple frequency bands. CONCLUSIONS: Our findings underscore the spatiotemporal specificity and relative stability of the DBS-CEP associated with different disease states and with therapeutic benefit. DBS-CEP may be a viable biomarker for therapeutic programming.

The effect of race, socioeconomic status, and comorbidity on patients afflicted with COVID 19: A Local Perspective.

PURPOSE: The aim of this study is to further examine the associations of race, socioeconomic factors, and comorbidity with COVID-19 health outcomes. METHODS: This is a retrospective cohort study of 309 PCR confirmed COVID-19 positive adults who presented to Tulane Medical Center in New Orleans, LA, from March 9 to May 29, 2020. The primary outcomes investigated were need for invasive mechanical ventilation (IMV) and in-hospital mortality. A multivariate analysis was performed to determine socioeconomic and medical risk factors for IMV and in-hospital mortality. RESULTS: Compared to white patients, Black patients were more likely to present younger, female, obese, unemployed, and underinsured. However, when controlled for common risk factors, Black and white patients had similar risk for IMV and mortality. Increased age (≥65 years), obesity, and increased comorbidity were associated with increased risk for IMV and mortality. CONCLUSIONS: Race and socioeconomic factors may increase risk for COVID-19 infection but did not affect health outcomes within the hospital setting. Therefore, the higher rates of COVID-19 infection and mortality in vulnerable populations may be better explained by lower socioeconomic status, with subsequent higher comorbidity, in these populations. Community health initiatives should be prioritized in response to the COVID-19 pandemic.

Prediction of mild parkinsonism revealed by neural oscillatory changes and machine learning.

Neural oscillatory changes within and across different frequency bands are thought to underlie motor dysfunction in Parkinson's disease (PD) and may serve as biomarkers for closed-loop deep brain stimulation (DBS) approaches. Here, we used neural oscillatory signals derived from chronically implanted cortical and subcortical electrode arrays as features to train machine learning algorithms to discriminate between naive and mild PD states in a nonhuman primate model. Local field potential (LFP) data were collected over several months from a 12-channel subdural electrocorticography (ECoG) grid and a 6-channel custom array implanted in the subthalamic nucleus (STN). Relative to the naive state, the PD state showed elevated primary motor cortex (M1) and STN power in the beta, high gamma, and high-frequency oscillation (HFO) bands and decreased power in the delta band. Theta power was found to be decreased in STN but not M1. In the PD state there was elevated beta-HFO phase-amplitude coupling (PAC) in the STN. We applied machine learning with support vector machines with radial basis function (SVM-RBF) kernel and k-nearest neighbors (KNN) classifiers trained by features related to power and PAC changes to discriminate between the naive and mild states. Our results show that the most predictive feature of parkinsonism in the STN was high beta (∼86% accuracy), whereas it was HFO in M1 (∼98% accuracy). A feature fusion approach outperformed every individual feature, particularly in the M1, where ∼98% accuracy was achieved with both classifiers. Overall, our data demonstrate the ability to use various frequency band power to classify the clinical state and are also beneficial in developing closed-loop DBS therapeutic approaches.NEW & NOTEWORTHY Neurophysiological biomarkers that correlate with motor symptoms or disease severity are vital to improve our understanding of the pathophysiology in Parkinson's disease (PD) and for the development of more effective treatments, including deep brain stimulation (DBS). This work provides direct insight into the application of these biomarkers in training classifiers to discriminate between brain states, which is a first step toward developing closed-loop DBS systems.

Effects of variations in Dwyer calcaneal osteotomy determined by three-dimensional printed patient-specific modeling.

Dwyer (lateral calcaneal closing wedge) osteotomy is commonly used in surgical correction of heel varus deformity. The purpose of this study was to determine the effect of wedge size and angle of osteotomy on deformity correction using preoperative imaging analysis with three-dimensional (3D) printed modeling. Seven patients diagnosed with pes cavovarus deformity who underwent Dwyer calcaneal osteotomy were identified retrospectively. Preoperative computed tomogrphy scans were used to create 3D printed models of the foot. After18 variations of osteotomy and fixation performed for each foot, Harris heel and Saltzman images were obtained. The angle between the tibia-talus axis and calcaneal-tuber axis was measured and compared to pre-osteotomy state. Change in the calcaneal lengths was also analyzed. The average degree correction of deformity per mm of bone resected was 3.8 ± 0.2 degrees in the Harris Heel view and 2.7 ± 0.8 degrees in the Saltzman view. A significant increase in correction was obtained with 10 mm compared with 5 mm wide wedges (P < .001). The difference in correction was not statistically significant between 30 and 45 degree cuts or osteotomy distance from the posterior calcaneal tuberosity, but a 45 degree sagittal angle resulted in less calcaneal shortening compared to 30 degrees (P = .02). A clinically driven method using patient-specific 3D models for determining effects of calcaneal osteotomy variables in correcting hindfoot alignment was developed. In summary, the amount of wedge resected impacts hindfoot alignment more than location and sagittal angle of the cut. Calcaneal shortening depends on sagittal angle of the cut.

Feasibility and performance of a frameless stereotactic system for targeting subcortical nuclei in nonhuman primates.

OBJECTIVE: Deep brain stimulation (DBS) is an effective therapy for different neurological diseases, despite the lack of comprehension of its mechanism of action. The use of nonhuman primates (NHPs) has been historically important in advancing this field and presents a unique opportunity to uncover the therapeutic mechanisms of DBS, opening the way for optimization of current applications and the development of new ones. To be informative, research using NHPs should make use of appropriate electrode implantation tools. In the present work, the authors report on the feasibility and accuracy of targeting different deep brain regions in NHPs using a commercially available frameless stereotactic system (microTargeting platform). METHODS: Seven NHPs were implanted with DBS electrodes, either in the subthalamic nucleus or in the cerebellar dentate nucleus. A microTargeting platform was designed for each animal and used to guide implantation of the electrode. Imaging studies were acquired preoperatively for each animal, and were subsequently analyzed by two independent evaluators to estimate the electrode placement error (EPE). The interobserver variability was assessed as well. RESULTS: The radial and vector components of the EPE were estimated separately. The magnitude of the vector of EPE was 1.29 ± 0.41 mm and the mean radial EPE was 0.96 ± 0.63 mm. The interobserver variability was considered negligible. CONCLUSIONS: These results reveal the suitability of this commercial system to enhance the surgical insertion of DBS leads in the primate brain, in comparison to rigid traditional frames. Furthermore, our results open up the possibility of performing frameless stereotaxy in primates without the necessity of relying on expensive methods based on intraoperative imaging.

Decellularized Adipose Tissue: Biochemical Composition, in vivo Analysis and Potential Clinical Applications.

Decellularized tissues are gaining popularity as scaffolds for tissue engineering; they allow cell attachment, proliferation, differentiation, and are non-immunogenic. Adipose tissue is an abundant resource that can be decellularized and converted in to a bio-scaffold. Several methods have been developed for adipose tissue decellularization, typically starting with freeze thaw cycles, followed by washes with hypotonic/hypertonic sodium chloride solution, isopropanol, detergent (SDS, SDC and Triton X-100) and trypsin digestion. After decellularization, decellularized adipose tissue (DAT) can be converted into a powder, solution, foam, or sheet to allow for convenient subcutaneous implantation or to repair external injuries. Additionally, DAT bio-ink can be used to 3D print structures that closely resemble physiological tissues and organs. Proteomic analysis of DAT reveals that it is composed of collagens (I, III, IV, VI and VII), glycosaminoglycans, laminin, elastin, and fibronectin. It has also been found to retain growth factors like VEGF and bFGF after decellularization. DAT inherently promotes adipogenesis when seeded with adipose stem cells in vitro, and when DAT is implanted subcutaneously it is capable of recruiting host stem cells and forming adipose tissue in rodents. Furthermore, DAT has promoted healing in rat models of full-thickness skin wounds and peripheral nerve injury. These findings suggest that DAT is a promising candidate for repair of soft tissue defects, and is suitable for breast reconstruction post-mastectomy, wound healing, and adipose tissue regeneration. Moreover, since DAT's form and stiffness can be altered by physicochemical manipulation, it may prove suitable for engineering of additional soft and hard tissues.

Decellularized Adipose Tissue Hydrogel Promotes Bone Regeneration in Critical-Sized Mouse Femoral Defect Model.

Critical-sized bone defects fail to heal and often cause non-union. Standard treatments employ autologous bone grafting, which can cause donor tissue loss/pain. Although several scaffold types can enhance bone regeneration, multiple factors limit their level of success. To address this issue, this study evaluated a novel decellularized human adipose tissue (DAT) hydrogel as an alternative. In this study, DAT hydrogel alone, or in combination with adipose-derived stromal/stem cells (ASC), osteo-induced ASCs (OIASC), and hydroxyapatite were tested for their ability to mediate repair of a critical-sized (3 mm) femoral defect created in C57BL/6 mice. Micro-computed tomography results showed that all DAT hydrogel treated groups significantly enhanced bone regeneration, with OIASC + hydroxyapatite treated group displaying the most robust bone regeneration. Histological analyses revealed that all treatments resulted in significantly higher tissue areas with the relative mineralized tissue area significantly increased at 12 weeks; however, cartilaginous content was lowest among treatment groups with OIASC. Immunohistochemical analyses showed that DAT hydrogel enhanced collagen I and osteopontin expression, while the addition of OIASCs to the hydrogel reduced collagen II levels. Thus, DAT hydrogel promotes bone regeneration in a critical-sized femoral defect model that is further enhanced in the presence of OIASCs and hydroxyapatite.

Electrophysiologic mapping for deep brain stimulation for movement disorders.

Electrophysiologic mapping remains an integral component of deep brain stimulation (DBS) surgical procedures, particularly in movement disorder cases where functional maps are used to guide DBS lead placement in patients with Parkinson's disease, dystonia, or tremor. Overall, the goal of the surgical procedure is to implant the distal end of a chronic, multicontact depth electrode into a specific brain region for the purpose of delivering therapeutic electrical stimulation. Regions that are currently targeted for patients with movement disorders include the subthalamic nucleus, the ventral intermediate nucleus of the thalamus, and the globus pallidus. Multiple imaging modalities are used initially to derive a stereotactic plan and guide the initial microelectrode trajectory. Changes in neuronal firing rate and pattern, both spontaneous and in response to somatosensory stimulation, are used to establish the location of the tip of the microelectrode(s), while acute stimulation can be used to estimate the proximity of neighboring brain regions. In this chapter, we will provide an overview of the microelectrode recording process as it is commonly applied to refine image-based targeting of lead placement for DBS surgery.

Human Adipose-Derived Hydrogel Characterization Based on In Vitro ASC Biocompatibility and Differentiation.

Hydrogels serve as three-dimensional scaffolds whose composition can be customized to allow attachment and proliferation of several different cell types. Extracellular matrix-derived hydrogels are considered close replicates of the tissue microenvironment. They can serve as scaffolds for in vitro tissue engineering and are a useful tool to study cell-scaffold interaction. The aim of the present study was to analyze the effect of adipose-derived stromal/stem cells (ASCs) and decellularized adipose tissue-derived (DAT) hydrogel interaction on ASC morphology, proliferation, differentiation, and DAT hydrogel microstructure. First, the ASCs were characterized using flow cytometry, adipogenic/osteogenic differentiation, colony-forming unit fibroblast assay and doubling time. The viability and proliferation assays showed that ASCs seeded in DAT hydrogel at different concentrations and cultured for 21 days remained viable and displayed proliferation. ASCs were seeded on DAT hydrogel and cultured in stromal, adipogenic, or osteogenic media for 14 or 28 days. The analysis of adipogenic differentiation demonstrated the upregulation of adipogenic marker genes and accumulation of oil droplets in the cells. Osteogenic differentiation demonstrated the upregulation of osteogenic marker genes and mineral deposition in the DAT hydrogel. The analysis of DAT hydrogel fiber metrics revealed that ASC seeding, and differentiation altered both the diameter and arrangement of fibers in the matrix. Matrix metalloproteinase-2 (MMP-2) activity was assessed to determine the possible mechanism for DAT hydrogel remodeling. MMP-2 activity was observed in all ASC seeded samples, with the osteogenic samples displaying the highest MMP-2 activity. These findings indicate that DAT hydrogel is a cytocompatible scaffold that supports the adipogenic and osteogenic differentiation of ASCs. Furthermore, the attachment of ASCs and differentiation along adipogenic and osteogenic lineages remodels the microstructure of DAT hydrogel.