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Methods have been developed for the stereocontrolled synthesis of bicyclic diaza [3.3.0] octane carboxylic acids as possible isosteres of piperazine 2S-carboxylic acid. In the first approach, l-pyroglutamic acid was functionalized adopting new as well as documented reaction sequences via Michael and aza-Michael reactions, leading to two of the four intended isosteres. An alternative shorter route relying on enolate chemistry starting with N-Pf 4-keto l-proline methyl ester led to two other isosteres. Calculated pKa values and density functional theory (DFT) calculations have provided some insights into the relative basicities of the nitrogen atoms in these diaza [3.3.0] octane carboxylic acids in relation to piperazine 2S-carboxylic acid.
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INTRODUCTION: The current approach to assessing bradykinesia in Parkinson's Disease relies on the Unified Parkinson's Disease Rating Scale (UPDRS), which is a numeric scale. Inertial sensors offer the ability to probe subcomponents of bradykinesia: motor speed, amplitude, and rhythm. Thus, we sought to investigate the differential effects of high-frequency compared to low-frequency subthalamic nucleus (STN) deep brain stimulation (DBS) on these quantified facets of bradykinesia. METHODS: We recruited advanced Parkinson's Disease subjects with a chronic bilateral subthalamic nucleus (STN) DBS implantation to a single-blind stimulation trial where each combination of medication state (OFF/ON), electrode contacts, and stimulation frequency (60 Hz/180 Hz) was assessed. The Kinesia One sensor system was used to measure upper limb bradykinesia. For each stimulation trial, subjects performed extremity motor tasks. Sensor data were recorded continuously. We identified STN DBS parameters that were associated with improved upper extremity bradykinesia symptoms using a mixed linear regression model. RESULTS: We recruited 22 subjects (6 females) for this study. The 180 Hz STN DBS (compared to the 60 Hz STN DBS) and dopaminergic medications improved all subcomponents of upper extremity bradykinesia (motor speed, amplitude, and rhythm). For the motor rhythm subcomponent of bradykinesia, ventral contacts yielded improved symptom improvement compared to dorsal contacts. CONCLUSION: The differential impact of high- and low-frequency STN DBS on the symptoms of bradykinesia may advise programming for these patients but warrants further investigation. Wearable sensors represent a valuable addition to the armamentarium that furthers our ability to conduct objective, quantitative clinical assessments.
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Estimulação Encefálica Profunda , Hipocinesia , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Doença de Parkinson/terapia , Doença de Parkinson/fisiopatologia , Estimulação Encefálica Profunda/métodos , Estimulação Encefálica Profunda/instrumentação , Hipocinesia/terapia , Hipocinesia/fisiopatologia , Núcleo Subtalâmico/fisiopatologia , Feminino , Masculino , Pessoa de Meia-Idade , IdosoRESUMO
INTRODUCTION: Directional deep brain stimulation (dDBS) has been suggested to have a similar therapeutic effect when compared with the traditional omnidirectional DBS, but with an improved therapeutic window that yields optimized clinical effect owing to the ability to better direct, or "steer," electric current. We present our single-center, retrospective analysis of our experience in the use of dDBS in patients with movement disorders and provide a review of the literature. MATERIALS AND METHODS: We identified all patients with Parkinson disease (PD) and essential tremor (ET) who received a dDBS system between 2018 and 2022 and retrospectively examined characteristics of their longitudinal treatment. A total of 70 leads were identified across 42 patients (28 PD, 14 ET). RESULTS: Three types of systems were implemented (single-segment activation, 45.2% of patients; multiple independent current control, 50.0%; and local field potential sensing-enabled, 4.7%). The subthalamic nucleus or globus pallidus internus was targeted in PD, and the ventral intermediate nucleus of the thalamus in ET. Across the entire cohort (n = 70 leads), at initial programming, 54.2% of leads (n = 38) were programmed using directional stimulation. At the most recent reprogramming, 58.6% of leads (n = 41) implemented directionality. In patients with PD, the average decrease in levodopa-equivalent daily dose at six months after implantation was 35.4% ± 39.2%. Despite the ability to steer current to relieve stimulation-induced side effects, ten leads in six patients required surgical revision owing to electrode malposition. CONCLUSIONS: We show wide adaptability and implementation of directional stimulation, adding to the growing compendium of real-world uses of dDBS therapy. We used directionality to improve clinical response in both patients with PD and patients with ET and found that its programming flexibility was used at high rates long after implantation and initial programming. In patients with PD, dDBS led to a significant reduction in dopaminergic medication, suggesting sustained clinical improvement. Nonetheless, accurate surgical placement remains necessary to ensure optimal clinical outcomes.
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Estimulação Encefálica Profunda , Tremor Essencial , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Estudos Retrospectivos , Estimulação Encefálica Profunda/efeitos adversos , Resultado do Tratamento , Doença de Parkinson/terapia , Tremor Essencial/terapiaRESUMO
PURPOSE: Management of patients with large brain metastases poses a clinical challenge, with poor local control and high risk of adverse radiation events when treated with single-fraction stereotactic radiosurgery (SF-SRS). Hypofractionated SRS (HF-SRS) may be considered, but clinical data remains limited, particularly with Gamma Knife (GK) radiosurgery. We report our experience with GK to deliver mask-based HF-SRS to brain metastases greater than 10 cc in volume and present our control and toxicity outcomes. METHODS: Patients who received hypofractionated GK radiosurgery (HF-GKRS) for the treatment of brain metastases greater than 10 cc between January 2017 and June 2022 were retrospectively identified. Local failure (LF) and adverse radiation events of CTCAE grade 2 or higher (ARE) were identified. Clinical, treatment, and radiological information was collected to identify parameters associated with clinical outcomes. RESULTS: Ninety lesions (in 78 patients) greater than 10 cc were identified. The median gross tumor volume was 16.0 cc (range 10.1-56.0 cc). Prior surgical resection was performed on 49 lesions (54.4%). Six- and 12-month LF rates were 7.3% and 17.6%; comparable ARE rates were 1.9% and 6.5%. In multivariate analysis, tumor volume larger than 33.5 cc (p = 0.029) and radioresistant histology (p = 0.047) were associated with increased risk of LF (p = 0.018). Target volume was not associated with increased risk of ARE (p = 0.511). CONCLUSIONS: We present our institutional experience treating large brain metastases using mask-based HF-GKRS, representing one of the largest studies implementing this platform and technique. Our LF and ARE compare favorably with the literature, suggesting that target volumes less than 33.5 cc demonstrate excellent control rates with low ARE. Further investigation is needed to optimize treatment technique for larger tumors.
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Neoplasias Encefálicas , Radiocirurgia , Humanos , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Estudos Retrospectivos , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Análise Multivariada , Resultado do TratamentoRESUMO
We report the synthesis of two novel azaperhydroazulene tropane-hederacine chimeras A and B, which contain an 8-azabicyclo[3.2.1]octane ring and a 7-azabicyclo[4.1.1]octane ring, respectively. The synthesis of both chimeras was achieved by epoxide ring opening and was governed by the stereochemistry of the hydroxy-epoxide unit. Finally, a density functional theory study was conducted to explain the regioselectivity of the cyclization and the importance of the stereochemistry of the hydroxyl group.
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BACKGROUND: Deep brain stimulation has become an established technology for the treatment of patients with a wide variety of conditions, including movement disorders, psychiatric disorders, epilepsy, and pain. Surgery for implantation of DBS devices has enhanced our understanding of human physiology, which in turn has led to advances in DBS technology. Our group has previously published on these advances, proposed future developments, and examined evolving indications for DBS. SUMMARY: The crucial roles of structural MR imaging pre-, intra-, and post-DBS procedure in target visualization and confirmation of targeting are described, with discussion of new MR sequences and higher field strength MRI enabling direct visualization of brain targets. The incorporation of functional and connectivity imaging in procedural workup and their contribution to anatomical modelling is reviewed. Various tools for targeting and implanting electrodes, including frame-based, frameless, and robot-assisted, are surveyed, and their pros and cons are described. Updates on brain atlases and various software used for planning target coordinates and trajectories are presented. The pros and cons of asleep versus awake surgery are discussed. The role and value of microelectrode recording and local field potentials are described, as well as the role of intraoperative stimulation. Technical aspects of novel electrode designs and implantable pulse generators are presented and compared.
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Neoplasias Encefálicas , Estimulação Encefálica Profunda , Doença de Parkinson , Humanos , Estimulação Encefálica Profunda/métodos , Doença de Parkinson/cirurgia , Vigília , Imageamento por Ressonância Magnética , Microeletrodos , Eletrodos ImplantadosRESUMO
Groundwater is the most abundant liquid freshwater on earth. Rapid urbanization in developing nations (like India) has led to increased groundwater withdrawal, adversely affecting the physicochemical characteristics. Ranchi district, Jharkhand, is a part of the smart city mission development plan of the government of India. Hence, to ensure safe and clean drinking water, it is necessary to assess groundwater quality and devise development plans. Seventeen physicochemical properties and metal(loid)s contents were analyzed to determine the groundwater quality. Various pollution indices such as water quality index (WQI), metal evaluation index (MI), heavy metal pollution index (HPI), and modified degree of contamination (mCd) are evaluated using arithmetic weighted value index and presented in a map using Arc GIS inverse distance weighting interpolation method. Chemometric analyses such as correlation, principal component, and cluster analysis were done to identify the source and determine the pollution state. A multiple linear regression model is employed to predict the impact of heavy metal and metalloid concentration on the WQI of the region. WQI shows that groundwater quality in Khelari (100.95) and Bundu (92.52) regions are highly degraded, whereas MI and HPI suggest that Ormanjhi (MI = 53.98) and Rahe (HPI = 109.20) are highly affected by metal contamination. The mCd suggests that Ormanjhi (97.15) has the highest degree of contamination. The contaminant sources were natural (geogenic processes) and anthropogenic (mining and industrial emissions). The high metal(loid)s concentration may soon result in groundwater quality degradation in the metal-affected regions.
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Água Subterrânea , Metais Pesados , Poluentes Químicos da Água , Monitoramento Ambiental/métodos , Poluentes Químicos da Água/análise , Metais Pesados/análise , Qualidade da Água , Água Subterrânea/química , Índia , Medição de RiscoRESUMO
PURPOSE: Terminated clinical trials are an inefficient use of financial, patient, and administrative resources. We reviewed ClinicalTrials.gov for completed and terminated clinical trials for glioblastoma multiforme (GBM) and compared reported characteristics of completed and terminated trials to identify factors associated with early trial termination. METHODS: ClinicalTrials.gov was queried to identify all completed and terminated GBM-related clinical trials. Trial characteristics were examined and the reason for trial termination was determined. Univariate analysis by Pearson's chi-square and a multivariate logistic regression were performed to identify independent predictors of early trial termination. RESULTS: We identified 886 completed and terminated GBM-related trials between 2003 and 2020. Of these, 175 (19.8%) were terminated prior to completion. The most common reason for termination was participant accrual difficulties, accounting for 63 (36.0%) terminated trials. Trial termination was associated with trials that reported a primary purpose of diagnosis relative to treatment (OR = 2.952, p = 0.001). CONCLUSION: Early termination of clinical trials investigating interventions for the treatment of GBM is associated with diagnostic trials relative to therapeutic trials. Patient accrual difficulties are the most commonly identified reason for early trial termination. Predictors of trial termination should be considered when designing GBM-related clinical trials to minimize the odds of early trial termination.
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Glioblastoma , Glioblastoma/terapia , Humanos , Modelos Logísticos , Projetos de PesquisaRESUMO
The progress of therapeutic neuromodulation greatly depends on improving stimulation parameters to most efficiently induce neuroplasticity effects. Intermittent θ-burst stimulation (iTBS), a form of electrical stimulation that mimics natural brain activity patterns, has proved to efficiently induce such effects in animal studies and rhythmic transcranial magnetic stimulation studies in humans. However, little is known about the potential neuroplasticity effects of iTBS applied through intracranial electrodes in humans. This study characterizes the physiological effects of intracranial iTBS in humans and compare them with α-frequency stimulation, another frequently used neuromodulatory pattern. We applied these two stimulation patterns to well-defined regions in the sensorimotor cortex, which elicited contralateral hand muscle contractions during clinical mapping, in patients with epilepsy implanted with intracranial electrodes. Treatment effects were evaluated using oscillatory coherence across areas connected to the treatment site, as defined with corticocortical-evoked potentials. Our results show that iTBS increases coherence in the ß-frequency band within the sensorimotor network indicating a potential neuroplasticity effect. The effect is specific to the sensorimotor system, the ß band, and the stimulation pattern and outlasted the stimulation period by â¼3 min. The effect occurred in four out of seven subjects depending on the buildup of the effect during iTBS treatment and other patterns of oscillatory activity related to ceiling effects within the ß band and to preexistent coherence within the α band. By characterizing the neurophysiological effects of iTBS within well-defined cortical networks, we hope to provide an electrophysiological framework that allows clinicians/researchers to optimize brain stimulation protocols which may have translational value.NEW & NOTEWORTHY θ-Burst stimulation (TBS) protocols in transcranial magnetic stimulation studies have shown improved treatment efficacy in a variety of neuropsychiatric disorders. The optimal protocol to induce neuroplasticity in invasive direct electrical stimulation approaches is not known. We report that intracranial TBS applied in human sensorimotor cortex increases local coherence of preexistent ß rhythms. The effect is specific to the stimulation frequency and the stimulated network and outlasts the stimulation period by â¼3 min.
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Ritmo beta/fisiologia , Terapia por Estimulação Elétrica , Estimulação Elétrica , Eletrocorticografia , Rede Nervosa/fisiologia , Plasticidade Neuronal/fisiologia , Córtex Sensório-Motor/fisiologia , Adulto , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Objective: This prospective, double-blind, randomized study aimed to compare the effects of dexmedetomidine and fentanyl on the latency and amplitude of transcranial motor evoked potentials (TcMEPs) under propofol-based total intravenous anaesthesia (TIVA) in spine surgery. Secondarily, intraoperative hemodynamics, total propofol consumption, recovery profile, and surgical field quality were compared. Methods: TcMEP amplitude and latency recordings of bilateral abductor pollicis brevis and abductor hallucis muscles posted for elective lumbar spine surgery under TcMEP monitoring randomly divided into two study groups. Throughout the surgery, TIVA was administered using intravenous propofol (100-150 µg kg-1 min-1) and dexmedetomidine (0.5-0.7 µg kg-1 h-1) in group D and intravenous propofol (100-150 µg kg-1 min-1) and fentanyl (1 µg kg-1 h-1) in group F. TcMEPs were recorded at various time points during the surgery. Immediately after extubation recovery from anaesthesia was noted. Additionally, hemodynamic parameters, total propofol consumption, and surgical field quality were assessed. Results: Latency and amplitude were comparable between the groups. Time to extubation was significantly longer in group D, but the mean (standard deviation) duration of stay in recovery was shorter in group D [47.55 (7.51) 95% confidence interval (CI) (44.863-50.237)] (P=0.046). Total propofol consumption was reduced in group D [220 (38) 95% CI (206.402-233.598)] (P=0.025) and surgical field condition was better in group D. Conclusions: Dexmedetomidine and fentanyl do not have any effect on TcMEP amplitude and latency. However, dexmedetomidine provides the additional advantage of reduced total propofol consumption, shorter stay in recovery, and better surgical field quality.
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The rise of antimicrobial resistance (AMR) has become a serious global health issue that kills millions of people each year globally. AMR developed in bacteria is difficult to treat and poses a challenge to clinicians. Bacteria develop resistance through a variety of processes, including biofilm growth, targeted area alterations, and therapeutic drug alteration, prolonging the period they remain within cells, where antibiotics are useless at therapeutic levels. This rise in resistance is linked to increased illness and death, highlighting the urgent need for effective solutions to combat this growing challenge. Nanoparticles (NPs) offer unique solutions for fighting AMR bacteria. Being smaller in size with a high surface area, enhancing interaction with bacteria makes the NPs strong antibacterial agents against various infections. In this review, we have discussed the epidemiology and mechanism of AMR development. Furthermore, the role of nanoparticles as antibacterial agents, and their role in drug delivery has been addressed. Additionally, the potential, challenges, toxicity, and future prospects of nanoparticles as antibacterial agents against AMR pathogens have been discussed. The research work discussed in this review links with Sustainable Development Goal 3 (SDG-3), which aims to ensure disease-free lives and promote well-being for all ages.
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The emergence and spread of antibiotic-resistant (AR) bacterial strains and biofilm-associated diseases have heightened concerns about exploring alternative bactericidal methods. The WHO estimates that at least 700 000 deaths yearly are attributable to antimicrobial resistance, and that number could increase to 10 million annual deaths by 2050 if appropriate measures are not taken. Therefore, the increasing threat of AR bacteria and biofilm-related infections has created an urgent demand for scientific research to identify novel antimicrobial therapies. Nanomaterials (NMs) have emerged as a promising alternative due to their unique physicochemical properties, and ongoing research holds great promise for developing effective NMs-based treatments for bacterial and viral infections. This review aims to provide an in-depth analysis of NMs based mechanisms combat bacterial infections, particularly those caused by acquired antibiotic resistance. Furthermore, this review examines NMs design features and attributes that can be optimized to enhance their efficacy as antimicrobial agents. In addition, plant-based NMs have emerged as promising alternatives to traditional antibiotics for treating multidrug-resistant bacterial infections due to their reduced toxicity compared to other NMs. The potential of plant mediated NMs for preventing AR is also discussed. Overall, this review emphasizes the importance of understanding the properties and mechanisms of NMs for the development of effective strategies against antibiotic-resistant bacteria.
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Introduction T-type fractures of the acetabulum are uncommon injuries, typically resulting in poorer long-term outcomes compared to other patterns of acetabular fractures. Our main purpose is to analyse the epidemiology, functional outcomes, and factors affecting the functional outcomes of patients with T-type acetabular fractures. Methods This prospective, single-centre study included 73 patients with T-type and T with posterior wall acetabular fractures. They underwent treatment with open reduction internal fixation using plating through the modified Stoppa, Kocher-Langenbeck (KL), or dual approach. The post-operative reduction was assessed according to Matta's criteria, and functional outcomes were evaluated using the modified Harris hip score. Results Between September 2017 and January 2023, 53 patients underwent surgery for T-type fractures (72.6%), and 20 patients were treated for T with posterior wall acetabular fractures (27.4%). The minimum follow-up period was one year, with a mean follow-up of 3.5 years. Anatomical reduction emerged as the major contributing factor towards good functional outcomes compared to satisfactory reduction according to Matta's criteria (P value: 0.006). Overall, 65 patients (89%) achieved excellent to good modified Harris hip scores, while eight patients (11%) obtained fair to poor scores. Patients with T-type fractures demonstrated better functional outcomes compared to T with posterior wall fractures (P value: 0.031). Conclusion Anatomical reduction, as assessed by Matta's reduction criteria, serves as a predictor of favourable functional outcomes. T with posterior wall fractures exhibit poor outcomes in comparison to T-type fractures. The surgical approach employed does not influence the reduction or the final functional outcome of the patient.
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Background: When applying lung-protective ventilation, fluid responsiveness cannot be predicted by pulse pressure variation (PPV) or stroke volume variation (SVV). Functional hemodynamic testing may help address this limitation. This study examined whether changes in dynamic indices such as PPV and SVV, induced by tidal volume challenge (TVC), can reliably predict fluid responsiveness in patients undergoing renal transplantation who receive lung-protective ventilation. Methods: This nonrandomized interventional study included renal transplant recipients with end-stage renal disease. Patients received ventilation with a 6 mL/kg tidal volume (TV), and the FloTrac system was attached for continuous hemodynamic monitoring. Participants were classified as responders or nonresponders based on whether fluid challenge increased the stroke volume index by more than 10%. Results: The analysis included 36 patients, of whom 19 (52.8%) were responders and 17 (47.2%) were nonresponders. Among responders, the mean ΔPPV6-8 (calculated as PPV at a TV of 8 mL/kg predicted body weight [PBW] minus that at 6 mL/kg PBW) was 3.32±0.75 and ΔSVV6-8 was 2.58±0.77, compared to 0.82±0.53 and 0.70±0.92 for nonresponders, respectively. ΔPPV6-8 exhibited an area under the curve (AUC) of 0.97 (95% confidence interval [CI], 0.93-1.00; P≤0.001), with an optimal cutoff value of 1.5, sensitivity of 94.7%, and specificity of 94.1%. ΔSVV6-8 displayed an AUC of 0.93 (95% CI, 0.84-1.00; P≤0.001) at the same cutoff value of 1.5, with a sensitivity of 94.7% and a specificity of 76.5%. Conclusions: TVC-induced changes in PPV and SVV are predictive of fluid responsiveness in renal transplant recipients who receive intraoperative lung-protective ventilation.
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Background: ABO-incompatible (ABOi) kidney transplantation poses significant challenges in achieving successful outcomes. This study aimed to investigate the impact of various interventions and techniques on improving the success rates of ABOi kidney transplantation. Methods: We conducted a retrospective observational analysis of patients who underwent ABOi kidney transplantation from November 2012 to March 2023. The study included a total of 105 patients. We collected and analyzed data on patient demographics, preoperative assessments, surgical details, and postoperative outcomes. Results: The mean ages of the donors and recipients were 50.52±10.32 and 36.63±11.61 years, respectively. The majority of recipients were male (81.9%), while most donors were female (89.5%). The most common blood group among recipients was O (69.5%), and among donors, it was B (46.7%). The median durations of chronic kidney disease and dialysis were 12 months (interquartile range [IQR], 7-28 months) and 6 months (IQR, 2-12 months), respectively. Baseline antibody titers (anti-A and anti-B) ranged from 64.0 to 256.0, while on the day of surgery, they were ≤8. Perioperative complications included hypotension (10.5%), acute tubular necrosis (5.7%), delayed graft function (3.8%), and reexploration (3.8%) due to hematoma. Conclusions: ABOi kidney transplantation is a viable option for recipients lacking available donors with an ABO-compatible match. Perioperative concerns, including hypoalbuminemia, heightened risk of infections, coagulopathies, aseptic precautions, and immunological surveillance, must be carefully addressed.
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OBJECTIVE: Burnout syndrome impacts one of two neurosurgeons and negatively impacts both the individual and institution. The impact of burnout on neurosurgeons may have increased due to the SARS-COV-2 pandemic. Characteristics of burnout may differ among neurosurgeons and non-neurosurgeon physicians, and this may better target wellness initiatives designed to alleviate burnout. METHODS: Validated burnout inventories (Maslach Burnout Inventory; MBI) were provided to physicians, including neurosurgeons, at a single, large academic institution. Rates of burnout and specific characteristics of burnout were compared. Free-response answers describing specific characteristics of burnout were also collected for neurosurgeons. RESULTS: A total of 294 physicians responded to the survey, including 40 neurosurgeons. The rate of burnout between neurosurgeons and non-neurosurgeons did not differ (39% vs 34%; p=0.631), but there were notable differences in the characteristics of burnout. Neurosurgery respondents were more likely to report depersonalization (p<0.001), and an additional 42.5% of neurosurgeon respondents reported a "period of hardship," which may lead to subsequent burnout. Neurosurgeons also more frequently reported higher feelings of personal accomplishment (p<0.001). Targeted wellness interventions specific to neurosurgeons may alleviate and prevent burnout. CONCLUSIONS: We show that although the rate of burnout does not differ for neurosurgeons, the characteristics of burnout may. This may represent the key to providing specialty-specific targeted interventions to alleviate burnout. Further, there is a significant proportion of neurosurgeons at risk for subsequent burnout for which additional importance must be placed to prevent progression to burnout.
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Background: Although deep brain stimulation (DBS) has established uses for patients with movement disorders and epilepsy, it is under consideration for a wide range of neurologic and neuropsychiatric conditions. Objective: To review successful and unsuccessful DBS clinical trials and identify factors associated with early trial termination. Methods: The ClinicalTrials.gov database was screened for all studies related to DBS. Information regarding condition of interest, study aim, trial design, trial success, and, if applicable, reason for failure was collected. Trials were compared and logistic regression was utilized to identify independent factors associated with trial termination. Results: Of 325 identified trials, 79.7% were successful and 20.3% unsuccessful. Patient recruitment, sponsor decision, and device issues were the most cited reasons for termination. 242 trials (74.5%) were interventional with 78.1% successful. There was a statistically significant difference between successful and unsuccessful trials in number of funding sources (p = 0.0375). NIH funding was associated with successful trials while utilization of other funding sources (academic institutions and community organizations) was associated with unsuccessful trials. 83 trials (25.5%) were observational with 84.0% successful; there were no statistically significant differences between successful and unsuccessful observational trials. Conclusion: One in five clinical trials for DBS were found to be unsuccessful, most commonly due to patient recruitment difficulties. The source of funding was the only factor associated with trial success. As DBS research continues to grow, understanding the current state of clinical trials will help design successful future studies, thereby minimizing futile expenditures of time, cost, and patient engagement.
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The discrete events of our narrative experience are organized by the neural substrate that underlies episodic memory. This narrative process is segmented into discrete units by event boundaries. This permits a replay process that acts to consolidate each event into a narrative memory. High frequency oscillations (HFOs) are a potential mechanism for synchronizing neural activity during these processes. Here, we use intracranial recordings from participants viewing and freely recalling a naturalistic stimulus. We show that hippocampal HFOs increase following event boundaries and that coincident hippocampal-cortical HFOs (co-HFOs) occur in cortical regions previously shown to underlie event segmentation (inferior parietal, precuneus, lateral occipital, inferior frontal cortices). We also show that event-specific patterns of co-HFOs that occur during event viewing re-occur following the subsequent three event boundaries (in decaying fashion) and also during recall. This is consistent with models that support replay as a mechanism for memory consolidation. Hence, HFOs may coordinate activity across brain regions serving widespread event segmentation, encode naturalistic memory, and bind representations to assemble memory of a coherent, continuous experience.
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BACKGROUND: Medical students are increasingly seeking out research opportunities to build their skills and network with future colleagues. Medical student-led conferences are an excellent endeavor to achieve this goal. METHODS: The American Association of Neurological Surgeons student chapter at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell designed an in-person medical student research symposium alongside the Northwell Health Department of Neurosurgery. Postconference feedback forms were sent out digitally to student attendees to evaluate event planning and execution and responses were given on a scale of 1-5 (5 being the highest score). RESULTS: In December 2023, the Northeast Medical Student Research Symposium was held with over 80 participants and 52 medical student presenters. Keynote speakers delivered lectures geared toward students interested in neurosurgery and neuroscience research, followed by an interactive poster board session and resident/attending networking dinner. After the conference, students affirmed that they learned more about neuroscience research after the event (mean: 4.3), were more inclined to attend other neuroscience research events in the future (mean: 4.7), and would attend this event if held next year (mean: 4.8). The poster sessions (mean: 4.75) and keynote lectures (mean: 5) were the highest rated events, while the resident/attending networking dinner (mean: 3.6) was a potential area for improvement. CONCLUSIONS: Regional in-person conferences are an excellent way to foster interest in neurosurgery and neuroscience research, network with like-minded peers, and prepare students for presentations at national meetings.