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1.
Artigo em Inglês | MEDLINE | ID: mdl-38310346

RESUMO

BACKGROUND AND OBJECTIVES: Nonhuman primates (NHPs) are important preclinical models for evaluating therapeutics because of their anatomophysiological similarities to humans, and can be especially useful for testing new delivery targets. With the growing promise of cell and gene therapies for the treatment of neurological diseases, it is important to ensure the accurate and safe delivery of these agents to target structures in the brain. However, a standard guideline or method has not been developed for stereotactic targeting in NHPs. In this article, we describe the safe use of a magnetic resonance imaging-guided frameless stereotactic system to target bilateral cerebellar dentate nuclei for accurate, real-time delivery of viral vector in NHPs. METHODS: Seventeen rhesus macaques (Macaca mulatta) underwent stereotactic surgery under real-time MRI guidance using the ClearPoint® system. Bilateral cerebellar dentate nuclei were targeted through a single parietal entry point with a transtentorial approach. Fifty microliters of contrast-impregnated infusate was delivered to each dentate nucleus, and adjustments were made as necessary according to real-time MRI monitoring of delivery. Perioperative clinical outcomes and postoperative volumes of distribution were recorded. RESULTS: All macaques underwent bilateral surgery successfully. Superficial pin site infection occurred in 4/17 (23.5%) subjects, which resolved with antibiotics. Two episodes of transient neurological deficit (anisocoria and unilateral weakness) were recorded, which did not require additional postoperative treatment and resolved over time. Volume of distribution of infusate achieved satisfactory coverage of target dentate nuclei, and only 1 incidence (2.9%) of cerebrospinal fluid penetration was recorded. Mean volume of distribution was 161.22 ± 39.61 mm3 (left, 173.65 ± 48.29; right, 148.80 ± 23.98). CONCLUSION: MRI-guided frameless stereotactic injection of bilateral cerebellar dentate nuclei in NHPs is safe and feasible. The use of this technique enables real-time modification of the surgical plan to achieve adequate target coverage and can be readily translated to clinical use.

2.
Neurosurgery ; 94(3): 529-537, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37795983

RESUMO

BACKGROUND AND OBJECTIVES: The Accreditation Council for Graduate Medical Education has approved 117 neurological surgery residency programs which develop and educate neurosurgical trainees. We present the current landscape of neurosurgical training in the United States by examining multiple aspects of neurological surgery residencies in the 2022-2023 academic year and investigate the impact of program structure on resident academic productivity. METHODS: Demographic data were collected from publicly available websites and reports from the National Resident Match Program. A 34-question survey was circulated by e-mail to program directors to assess multiple features of neurological surgery residency programs, including curricular structure, fellowship availability, recent program changes, graduation requirements, and resources supporting career development. Mean resident productivity by program was collected from the literature. RESULTS: Across all 117 programs, there was a median of 2.0 (range 1.0-4.0) resident positions per year and 1.0 (range 0.0-2.0) research/elective years. Programs offered a median of 1.0 (range 0.0-7.0) Committee on Advanced Subspecialty Training-accredited fellowships, with endovascular fellowships being most frequently offered (53.8%). The survey response rate was 75/117 (64.1%). Of survey respondents, the median number of clinical sites was 3.0 (range 1.0-6.0). Almost half of programs surveyed (46.7%) reported funding mechanisms for residents, including R25, T32, and other in-house grants. Residents received a median academic stipend of $1000 (range $0-$10 000) per year. Nearly all programs (93.3%) supported wellness activities for residents, which most frequently occurred quarterly (46.7%). Annual academic stipend size was the only significant predictor of resident academic productivity (R 2 = 0.17, P = .002). CONCLUSION: Neurological surgery residency programs successfully train the next generation of neurosurgeons focusing on education, clinical training, case numbers, and milestones. These programs offer trainees the chance to tailor their career trajectories within residency, creating a rewarding and personalized experience that aligns with their career aspirations.


Assuntos
Internato e Residência , Humanos , Estados Unidos , Estudos Transversais , Educação de Pós-Graduação em Medicina , Neurocirurgiões , Inquéritos e Questionários
3.
Brain Sci ; 13(12)2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38137103

RESUMO

Neural transplantation represents a promising approach to repairing damaged brain circuitry. Cellular grafts have been shown to promote functional recovery through "bystander effects" and other indirect mechanisms. However, extensive brain lesions may require direct neuronal replacement to achieve meaningful restoration of function. While fetal cortical grafts have been shown to integrate with the host brain and appear to develop appropriate functional attributes, the significant ethical concerns and limited availability of this tissue severely hamper clinical translation. Induced pluripotent stem cell-derived cells and tissues represent a more readily scalable alternative. Significant progress has recently been made in developing protocols for generating a wide range of neural cell types in vitro. Here, we discuss recent progress in neural transplantation approaches for two conditions with distinct design needs: Parkinson's disease and cortical injury. We discuss the current status and future application of injections of dopaminergic cells for the treatment of Parkinson's disease as well as the use of structured grafts such as brain organoids for cortical repair.

4.
Nat Commun ; 14(1): 7346, 2023 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-37963886

RESUMO

Genomic DNA (gDNA) undergoes structural interconversion between single- and double-stranded states during transcription, DNA repair and replication, which is critical for cellular homeostasis. We describe "CHEX-seq" which identifies the single-stranded DNA (ssDNA) in situ in individual cells. CHEX-seq uses 3'-terminal blocked, light-activatable probes to prime the copying of ssDNA into complementary DNA that is sequenced, thereby reporting the genome-wide single-stranded chromatin landscape. CHEX-seq is benchmarked in human K562 cells, and its utilities are demonstrated in cultures of mouse and human brain cells as well as immunostained spatially localized neurons in brain sections. The amount of ssDNA is dynamically regulated in response to perturbation. CHEX-seq also identifies single-stranded regions of mitochondrial DNA in single cells. Surprisingly, CHEX-seq identifies single-stranded loci in mouse and human gDNA that catalyze porphyrin metalation in vitro, suggesting a catalytic activity for genomic ssDNA. We posit that endogenous DNA enzymatic activity is a function of genomic ssDNA.


Assuntos
Reparo do DNA , DNA de Cadeia Simples , Humanos , DNA de Cadeia Simples/genética , DNA/genética , Proteínas de Ligação a DNA/metabolismo , Genômica , Replicação do DNA
5.
Curr Biol ; 33(24): 5275-5287.e5, 2023 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-37924807

RESUMO

The human olfactory system has two discrete channels of sensory input, arising from olfactory epithelia housed in the left and right nostrils. Here, we asked whether the primary olfactory cortex (piriform cortex [PC]) encodes odor information arising from the two nostrils as integrated or distinct stimuli. We recorded intracranial electroencephalogram (iEEG) signals directly from PC while human subjects participated in an odor identification task where odors were delivered to the left, right, or both nostrils. We analyzed the time course of odor identity coding using machine-learning approaches and found that uni-nostril odor inputs to the ipsilateral nostril are encoded ∼480-ms faster than odor inputs to the contralateral nostril on average. During naturalistic bi-nostril odor sampling, odor information emerged in two temporally segregated epochs, with the first epoch corresponding to the ipsilateral and the second epoch corresponding to the contralateral odor representations. These findings reveal that PC maintains distinct representations of odor input from each nostril through temporal segregation, highlighting an olfactory coding scheme at the cortical level that can parse odor information across nostrils within the course of a single inhalation.


Assuntos
Córtex Olfatório , Percepção Olfatória , Córtex Piriforme , Humanos , Odorantes , Condutos Olfatórios , Olfato
6.
World Neurosurg ; 180: e765-e773, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37839567

RESUMO

INTRODUCTION: Technological advancements are reshaping medical education, with digital tools becoming essential in all levels of training. Amidst this transformation, the study explores the potential of ChatGPT, an artificial intelligence model by OpenAI, in enhancing neurosurgical board education. The focus extends beyond technology adoption to its effective utilization, with ChatGPT's proficiency evaluated against practice questions from the Primary Neurosurgery Written Board Exam. METHODS: Using the Congress of Neurologic Surgeons (CNS) Self-Assessment Neurosurgery (SANS) Exam Board Review Prep questions, we conducted 3 rounds of analysis with ChatGPT. We developed a novel ChatGPT Neurosurgical Evaluation Matrix (CNEM) to assess the output quality, accuracy, concordance, and clarity of ChatGPT's answers. RESULTS: ChatGPT achieved spot-on accuracy for 66.7% of prompted questions, 59.4% of unprompted questions, and 63.9% of unprompted questions with a leading phrase. Stratified by topic, accuracy ranged from 50.0% (Vascular) to 78.8% (Neuropathology). In comparison to SANS explanations, ChatGPT output was considered better in 19.1% of questions, equal in 51.6%, and worse in 29.3%. Concordance analysis showed that 95.5% of unprompted ChatGPT outputs and 97.4% of unprompted outputs with a leading phrase were aligned. CONCLUSIONS: Our study evaluated the performance of ChatGPT in neurosurgical board education by assessing its accuracy, clarity, and concordance. The findings highlight the potential and challenges of integrating AI technologies like ChatGPT into medical and neurosurgical board education. Further research is needed to refine these tools and optimize their performance for enhanced medical education and patient care.


Assuntos
Neurocirurgia , Humanos , Inteligência Artificial , Escolaridade , Procedimentos Neurocirúrgicos , Idioma
7.
ArXiv ; 2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37547655

RESUMO

Introduction: Intracranial EEG (IEEG) is used for 2 main purposes, to determine: (1) if epileptic networks are amenable to focal treatment and (2) where to intervene. Currently these questions are answered qualitatively and sometimes differently across centers. There is a need for objective, standardized methods to guide surgical decision making and to enable large scale data analysis across centers and prospective clinical trials. Methods: We analyzed interictal data from 101 patients with drug resistant epilepsy who underwent presurgical evaluation with IEEG. We chose interictal data because of its potential to reduce the morbidity and cost associated with ictal recording. 65 patients had unifocal seizure onset on IEEG, and 36 were non-focal or multi-focal. We quantified the spatial dispersion of implanted electrodes and interictal IEEG abnormalities for each patient. We compared these measures against the "5 Sense Score (5SS)," a pre-implant estimate of the likelihood of focal seizure onset, and assessed their ability to predict the clinicians' choice of therapeutic intervention and the patient outcome. Results: The spatial dispersion of IEEG electrodes predicted network focality with precision similar to the 5SS (AUC = 0.67), indicating that electrode placement accurately reflected pre-implant information. A cross-validated model combining the 5SS and the spatial dispersion of interictal IEEG abnormalities significantly improved this prediction (AUC = 0.79; p<0.05). The combined model predicted ultimate treatment strategy (surgery vs. device) with an AUC of 0.81 and post-surgical outcome at 2 years with an AUC of 0.70. The 5SS, interictal IEEG, and electrode placement were not correlated and provided complementary information. Conclusions: Quantitative, interictal IEEG significantly improved upon pre-implant estimates of network focality and predicted treatment with precision approaching that of clinical experts. We present this study as an important step in building standardized, quantitative tools to guide epilepsy surgery.

8.
World Neurosurg ; 178: 202-212.e2, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37543199

RESUMO

BACKGROUND: Despite higher rates of seizure freedom, a large proportion of patients with medically refractory seizures who could benefit from epilepsy surgery do not receive surgical treatment. This literature review describes the association of race and insurance status with epilepsy surgery access and outcomes. METHODS: Searches in Scopus and PubMed databases related to disparities in epilepsy surgery were conducted. The inclusion criteria consisted of data that could be used to compare epilepsy surgery patient access and outcomes by insurance or race in the United States. Two independent reviewers determined article eligibility. RESULTS: Of the 289 studies reviewed, 26 were included. Most of the studies were retrospective cohort studies (23 of 26) and national admissions database studies (13 of 26). Of the 17 studies that evaluated epilepsy surgery patient demographics, 11 showed that Black patients were less likely to receive surgery than were White patients or had an increased time to surgery from seizure onset. Nine studies showed that patients with private insurance were more likely to undergo epilepsy surgery and have shorter time to surgery compared with patients with public insurance. No significant association was found between the seizure recurrence rate after surgery with insurance or race. CONCLUSIONS: Black patients and patients with public insurance are receiving epilepsy surgery at lower rates after a prolonged waiting period compared with other patients with medically refractory epilepsy. These results are consistent across the current reported literature. Future efforts should focus on additional characterization and potential causes of these disparities to develop successful interventions.

9.
STAR Protoc ; 4(3): 102470, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37585295

RESUMO

Human stem-cell-derived organoids represent a promising substrate for transplantation-based neural repair. Here, we describe a protocol for transplanting forebrain organoids into an injured adult rat visual cortex. This protocol includes surgical details for craniectomy, aspiration injury, organoid transplantation, and cranioplasty. This platform represents a valuable tool for investigating the efficacy of organoids as structured grafts for neural repair. For complete details on the use and execution of this protocol, please refer to Jgamadze et al.1.


Assuntos
Prosencéfalo , Córtex Visual , Adulto , Humanos , Animais , Ratos , Craniotomia , Organoides , Células-Tronco , Córtex Visual/cirurgia
10.
Epilepsia ; 64(6): 1568-1581, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37013668

RESUMO

OBJECTIVE: Stereotactic laser amygdalohippocampotomy (SLAH) is an appealing option for patients with temporal lobe epilepsy, who often require intracranial monitoring to confirm mesial temporal seizure onset. However, given limited spatial sampling, it is possible that stereotactic electroencephalography (stereo-EEG) may miss seizure onset elsewhere. We hypothesized that stereo-EEG seizure onset patterns (SOPs) may differentiate between primary onset and secondary spread and predict postoperative seizure control. In this study, we characterized the 2-year outcomes of patients who underwent single-fiber SLAH after stereo-EEG and evaluated whether stereo-EEG SOPs predict postoperative seizure freedom. METHODS: This retrospective five-center study included patients with or without mesial temporal sclerosis (MTS) who underwent stereo-EEG followed by single-fiber SLAH between August 2014 and January 2022. Patients with causative hippocampal lesions apart from MTS or for whom the SLAH was considered palliative were excluded. An SOP catalogue was developed based on literature review. The dominant pattern for each patient was used for survival analysis. The primary outcome was 2-year Engel I classification or recurrent seizures before then, stratified by SOP category. RESULTS: Fifty-eight patients were included, with a mean follow-up duration of 39 ± 12 months after SLAH. Overall 1-, 2-, and 3-year Engel I seizure freedom probability was 54%, 36%, and 33%, respectively. Patients with SOPs, including low-voltage fast activity or low-frequency repetitive spiking, had a 46% 2-year seizure freedom probability, compared to 0% for patients with alpha or theta frequency repetitive spiking or theta or delta frequency rhythmic slowing (log-rank test, p = .00015). SIGNIFICANCE: Patients who underwent SLAH after stereo-EEG had a low probability of seizure freedom at 2 years, but SOPs successfully predicted seizure recurrence in a subset of patients. This study provides proof of concept that SOPs distinguish between hippocampal seizure onset and spread and supports using SOPs to improve selection of SLAH candidates.


Assuntos
Epilepsia do Lobo Temporal , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Epilepsia do Lobo Temporal/diagnóstico , Epilepsia do Lobo Temporal/cirurgia , Epilepsia do Lobo Temporal/complicações , Convulsões/diagnóstico , Convulsões/cirurgia , Convulsões/complicações , Eletroencefalografia , Lasers , Imageamento por Ressonância Magnética
11.
World Neurosurg ; 174: e144-e151, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36907269

RESUMO

OBJECTIVE: There are limited data evaluating the outcomes of attending neurosurgeons with different types of first assistants. This study considers a common neurosurgical procedure (single-level, posterior-only lumbar fusion surgery) and examines whether attending surgeons deliver equal patient outcomes, regardless of the type of first assistant (resident physician vs. nonphysician surgical assistant [NPSA]), among otherwise exact-matched patients. METHODS: The authors retrospectively analyzed 3395 adult patients undergoing single-level, posterior-only lumbar fusion at a single academic medical center. Primary outcomes included readmissions, emergency department visits, reoperation, and mortality within 30 and 90 days after surgery. Secondary outcome measures included discharge disposition, length of stay, and length of surgery. Coarsened exact matching was used to match patients on key demographics and baseline characteristics known to independently affect neurosurgical outcomes. RESULTS: Among exact-matched patients (n = 1402), there was no significant difference in adverse postsurgical events (readmission, emergency department visits, reoperation, or mortality) within 30 days or 90 days of the index operation between patients who had resident physicians and those who had NPSAs as first assistants. Patients who had resident physicians as first assistants demonstrated a longer length of stay (mean: 100.0 vs. 87.4 hours, P < 0.001) and a shorter duration of surgery (mean: 187.4 vs. 213.8 minutes, P < 0.001). There was no significant difference between the two groups in the percentage of patients discharged home. CONCLUSIONS: For single-level posterior spinal fusion, in the setting described, there are no differences in short-term patient outcomes delivered by attending surgeons assisted by resident physicians versus NPSAs.


Assuntos
Fusão Vertebral , Cirurgiões , Adulto , Humanos , Neurocirurgiões , Estudos Retrospectivos , Qualidade da Assistência à Saúde , Reoperação , Fusão Vertebral/efeitos adversos , Complicações Pós-Operatórias/etiologia , Vértebras Lombares/cirurgia
12.
bioRxiv ; 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-36824705

RESUMO

The human olfactory system has two discrete channels of sensory input, arising from olfactory epithelia housed in the left and right nostrils. Here, we asked whether primary olfactory cortex (piriform cortex, PC) encodes odor information arising from the two nostrils as integrated or distinct stimuli. We recorded intracranial EEG signals directly from PC while human subjects participated in an odor identification task where odors were delivered to the left, right, or both nostrils. We analyzed the time-course of odor-identity coding using machine learning approaches, and found that uni-nostril odor inputs to the ipsilateral nostril are encoded ~480 ms faster than odor inputs to the contralateral nostril on average. During naturalistic bi-nostril odor sampling, odor information emerged in two temporally segregated epochs with the first epoch corresponding to the ipsilateral and the second epoch corresponding to the contralateral odor representations. These findings reveal that PC maintains distinct representations of odor input from each nostril through temporal segregation, highlighting an olfactory coding scheme at the cortical level that can parse odor information across nostrils within the course of a single inhalation.

13.
J Nucl Med ; 64(6): 852-858, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36549916

RESUMO

Accurate differentiation between tumor progression (TP) and pseudoprogression remains a critical unmet need in neurooncology. 18F-fluciclovine is a widely available synthetic amino acid PET radiotracer. In this study, we aimed to assess the value of 18F-fluciclovine PET for differentiating pseudoprogression from TP in a prospective cohort of patients with suspected radiographic recurrence of glioblastoma. Methods: We enrolled 30 glioblastoma patients with radiographic progression after first-line chemoradiotherapy for whom surgical resection was planned. The patients underwent preoperative 18F-fluciclovine PET and MRI. The relative percentages of viable tumor and therapy-related changes observed in histopathology were quantified and categorized as TP (≥50% viable tumor), mixed TP (<50% and >10% viable tumor), or pseudoprogression (≤10% viable tumor). Results: Eighteen patients had TP, 4 had mixed TP, and 8 had pseudoprogression. Patients with TP/mixed TP had a significantly higher 40- to 50-min SUVmax (6.64 + 1.88 vs. 4.11 ± 1.52, P = 0.009) than patients with pseudoprogression. A 40- to 50-min SUVmax cutoff of 4.66 provided 90% sensitivity and 83% specificity for differentiation of TP/mixed TP from pseudoprogression (area under the curve [AUC], 0.86). A maximum relative cerebral blood volume cutoff of 3.672 provided 90% sensitivity and 71% specificity for differentiation of TP/mixed TP from pseudoprogression (AUC, 0.779). Combining a 40- to 50-min SUVmax cutoff of 4.66 and a maximum relative cerebral blood volume of 3.67 on MRI provided 100% sensitivity and 80% specificity for differentiating TP/mixed TP from pseudoprogression (AUC, 0.95). Conclusion: 18F-fluciclovine PET uptake can accurately differentiate pseudoprogression from TP in glioblastoma, with even greater accuracy when combined with multiparametric MRI. Given the wide availability of 18F-fluciclovine, larger, multicenter studies are warranted to determine whether amino acid PET with 18F-fluciclovine should be used in the routine posttreatment assessment of glioblastoma.


Assuntos
Glioblastoma , Humanos , Glioblastoma/diagnóstico por imagem , Glioblastoma/terapia , Glioblastoma/patologia , Estudos Prospectivos , Imageamento por Ressonância Magnética , Ácidos Carboxílicos , Tomografia por Emissão de Pósitrons , Aminoácidos
14.
Int J Mol Sci ; 23(22)2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36430464

RESUMO

Parkinson's disease (PD) affects 1-2% of people over 65, causing significant morbidity across a progressive disease course. The classic PD motor deficits are caused by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc), resulting in the loss of their long-distance axonal projections that modulate striatal output. While contemporary treatments temporarily alleviate symptoms of this disconnection, there is no approach able to replace the nigrostriatal pathway. We applied microtissue engineering techniques to create a living, implantable tissue-engineered nigrostriatal pathway (TE-NSP) that mimics the architecture and function of the native pathway. TE-NSPs comprise a discrete population of dopaminergic neurons extending long, bundled axonal tracts within the lumen of hydrogel micro-columns. Neurons were isolated from the ventral mesencephalon of transgenic rats selectively expressing the green fluorescent protein in dopaminergic neurons with subsequent fluorescent-activated cell sorting to enrich a population to 60% purity. The lumen extracellular matrix and growth factors were varied to optimize cytoarchitecture and neurite length, while immunocytochemistry and fast-scan cyclic voltammetry (FSCV) revealed that TE-NSP axons released dopamine and integrated with striatal neurons in vitro. Finally, TE-NSPs were implanted to span the nigrostriatal pathway in a rat PD model with a unilateral 6-hydroxydopamine SNpc lesion. Immunohistochemistry and FSCV established that transplanted TE-NSPs survived, maintained their axonal tract projections, extended dopaminergic neurites into host tissue, and released dopamine in the striatum. This work showed proof of concept that TE-NSPs can reconstruct the nigrostriatal pathway, providing motivation for future studies evaluating potential functional benefits and long-term durability of this strategy. This pathway reconstruction strategy may ultimately replace lost neuroarchitecture and alleviate the cause of motor symptoms for PD patients.


Assuntos
Doença de Parkinson , Ratos , Animais , Doença de Parkinson/patologia , Substância Negra/metabolismo , Dopamina/metabolismo , Axônios/metabolismo , Neurônios Dopaminérgicos/metabolismo
15.
Sci Adv ; 8(44): eabm3291, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36332027

RESUMO

Functional restoration following major peripheral nerve injury (PNI) is challenging, given slow axon growth rates and eventual regenerative pathway degradation in the absence of axons. We are developing tissue-engineered nerve grafts (TENGs) to simultaneously "bridge" missing nerve segments and "babysit" regenerative capacity by providing living axons to guide host axons and maintain the distal pathway. TENGs were biofabricated using porcine neurons and "stretch-grown" axon tracts. TENG neurons survived and elicited axon-facilitated axon regeneration to accelerate regrowth across both short (1 cm) and long (5 cm) segmental nerve defects in pigs. TENG axons also closely interacted with host Schwann cells to maintain proregenerative capacity. TENGs drove regeneration across 5-cm defects in both motor and mixed motor-sensory nerves, resulting in dense axon regeneration and electrophysiological recovery at levels similar to autograft repairs. This approach of accelerating axon regeneration while maintaining the pathway for long-distance regeneration may achieve recovery after currently unrepairable PNIs.

16.
Nature ; 607(7919): 527-533, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35794479

RESUMO

Immature dentate granule cells (imGCs) arising from adult hippocampal neurogenesis contribute to plasticity and unique brain functions in rodents1,2 and are dysregulated in multiple human neurological disorders3-5. Little is known about the molecular characteristics of adult human hippocampal imGCs, and even their existence is under debate1,6-8. Here we performed single-nucleus RNA sequencing aided by a validated machine learning-based analytic approach to identify imGCs and quantify their abundance in the human hippocampus at different stages across the lifespan. We identified common molecular hallmarks of human imGCs across the lifespan and observed age-dependent transcriptional dynamics in human imGCs that suggest changes in cellular functionality, niche interactions and disease relevance, that differ from those in mice9. We also found a decreased number of imGCs with altered gene expression in Alzheimer's disease. Finally, we demonstrated the capacity for neurogenesis in the adult human hippocampus with the presence of rare dentate granule cell fate-specific proliferating neural progenitors and with cultured surgical specimens. Together, our findings suggest the presence of a substantial number of imGCs in the adult human hippocampus via low-frequency de novo generation and protracted maturation, and our study reveals their molecular properties across the lifespan and in Alzheimer's disease.


Assuntos
Envelhecimento , Hipocampo , Longevidade , Neurogênese , Neurônios , Adulto , Envelhecimento/genética , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Proliferação de Células , Giro Denteado/citologia , Giro Denteado/patologia , Perfilação da Expressão Gênica , Hipocampo/citologia , Hipocampo/patologia , Humanos , Longevidade/genética , Aprendizado de Máquina , Camundongos , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/patologia , Neurogênese/genética , Neurônios/citologia , Neurônios/metabolismo , Neurônios/patologia , Reprodutibilidade dos Testes , Análise de Sequência de RNA , Análise de Célula Única , Transcrição Gênica
17.
World Neurosurg ; 163: e113-e123, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35314405

RESUMO

OBJECTIVES: Predicting patient needs for extended care after spinal fusion remains challenging. The Risk Assessment and Prediction Tool (RAPT) was externally developed to predict discharge disposition after nonspine orthopedic surgery but remains scarcely used in neurosurgery. The present study is the first to use coarsened exact matching-which incorporated patient characteristics known to independently affect outcomes-for 1:1 matching across a large population of single-level, posterior lumbar fusions, to isolate the predictive value of preoperative RAPT score on postoperative discharge disposition. METHODS: Preoperative RAPT scores were prospectively calculated for 1066 patients undergoing consecutive single-level, posterior-only lumbar fusion within a single, university healthcare system. The primary outcome was discharge disposition. Logistic regression was executed across all patients, evaluating the RAPT score as a continuous variable to predict home discharge. Subsequently, patients were retrospectively clustered into predicted risk cohorts-validated within prior orthopedic joint research-based on the RAPT score (Lowest, Intermediate, and Highest Risk). Coarsened exact matching was performed among predicted risk cohorts, and outcomes were compared between exact-matched groups. RESULTS: Among all patients, single-point increases in the RAPT score (i.e., decrease in predicted risk) were associated a 75% increased odds of home discharge (P < 0.001). Exact-matched analysis demonstrated increased odds of home discharge by 400% when comparing the Lowest versus Highest Risk cohorts (P = 0.004), by 750% when comparing the Intermediate versus Highest Risk cohorts (P < 0.001), and by 200% when comparing the Lowest versus Intermediate Risk cohorts (P < 0.001). CONCLUSIONS: The RAPT score, captured in preoperative evaluations, can be highly predictive of discharge disposition following single-level, posterior lumbar fusion.


Assuntos
Alta do Paciente , Fusão Vertebral , Humanos , Vértebras Lombares/cirurgia , Complicações Pós-Operatórias , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
19.
Sci Transl Med ; 13(612): eabf8629, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34550728

RESUMO

Soft bioelectronic interfaces for mapping and modulating excitable networks at high resolution and at large scale can enable paradigm-shifting diagnostics, monitoring, and treatment strategies. Yet, current technologies largely rely on materials and fabrication schemes that are expensive, do not scale, and critically limit the maximum attainable resolution and coverage. Solution processing is a cost-effective manufacturing alternative, but biocompatible conductive inks matching the performance of conventional metals are lacking. Here, we introduce MXtrodes, a class of soft, high-resolution, large-scale bioelectronic interfaces enabled by Ti3C2 MXene (a two-dimensional transition metal carbide nanomaterial) and scalable solution processing. We show that the electrochemical properties of MXtrodes exceed those of conventional materials and do not require conductive gels when used in epidermal electronics. Furthermore, we validate MXtrodes in applications ranging from mapping large-scale neuromuscular networks in humans to cortical neural recording and microstimulation in swine and rodent models. Last, we demonstrate that MXtrodes are compatible with standard clinical neuroimaging modalities.


Assuntos
Fenômenos Eletrofisiológicos , Eletrofisiologia
20.
Int J Spine Surg ; 15(4): 826-833, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34266938

RESUMO

BACKGROUND: We present a "Do-It-Yourself" method to build an affordable augmented reality heads-up display system (AR-HUD) capable of displaying intraoperative images. All components are commercially available products, which the surgeons may use in their own practice for educational and research purposes. METHODS: Moverio BT 35-E smart glasses were connected to operating room imaging modalities (ie, fluoroscopy and 3D navigation platforms) via a high-definition multimedia interface (HDMI) converter, allowing for continuous high-definition video transmission. The addition of an HDMI transmitter-receiver makes the AR-HUD system wireless. RESULTS: We used our AR-HUD system in 3 patients undergoing instrumented spinal fusion. AR-HUD projected fluoroscopy images onto the surgical field, eliminating shift of surgeon focus and procedure interruption, with only a 40- to 100-ms delay in transmission, which was not clinically impactful. CONCLUSIONS: An affordable AR-HUD capable of displaying real-time information into the surgeon's view can be easily designed, built, and tested in surgical practice. As wearable heads-up display technology continues to evolve rapidly, individual components presented here may be substituted to improve its functionality and usability. Surgeons are in a unique position to conduct clinical testing in the operating room environment to optimize the augmented reality system for surgical use.

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