Independent Function Research Articles

Compensation training and lifestyle modifications to promote healthy aging in persons at risk for Alzheimer's disease: A digital application supported intervention

AbstractBackgroundThe protocol for ‘Brain Boosters’, a novel combined compensatory training and lifestyle modification intervention aimed at Alzheimer’s disease (AD) risk reduction is presented. Training in compensation will focus on a calendar and tracking system, organizational strategies, and goal setting, all aimed at supporting independent function. These same compensatory tools will be employed to facilitate adoption of lifestyle changes that support brain health (e.g., physical exercise, cognitive exercise, wellbeing exercise) through behavioral monitoring and feedback. A comprehensive suite of digital tools encapsulated in the Electronic Memory and Management Aid (EMMA), an easy to use, interactive application, will be used to facilitate behavioral change and enhance participant motivation. EMMA also allows collection of real‐time data to track intervention adherence and factors that influence adherence.MethodsTo capitalize on a critical window of opportunity to intervene, we will target cognitively normal older adults with subjective cognitive concerns (SCC), an established risk for AD and cognitive impairment. The trial will enroll 200 older adults with SCC who will be randomized to our digital application‐supported compensation training and lifestyle modification intervention or to an education only control group that will not use the EMMA app or be taught how to implement the educational material into their daily lives. Both intervention arms will be delivered in a group setting over 6 months, followed by 12 months of unsupervised follow‐up.ResultsSpecific aims of the project include to: 1) evaluate intervention efficacy on primary outcomes (global cognition and everyday function); secondary outcomes focus on indicators of well‐being, cognitive domains (memory and executive function), physical function, compensation, and health behaviors; 2) evaluate characteristics of treatment responders; 3) evaluate adherence and identify the effective components of the target intervention using a mixed‐method approach; and 4) design machine learning algorithms that use patterns of change in real‐time data metrics to identify incipient declines in treatment adherence and changes in health status.ConclusionsThe project is expected to expand understanding of factors that may impact adherence to and outcomes of a preventative intervention leading to optimization of a scalable intervention to reduce dementia risk applicable to diverse populations.

The two paralogous copies of the YoeB–YefM toxin–antitoxin module in Staphylococcus aureus differ in DNA binding and recognition patterns

Toxin–antitoxin (TA) systems are ubiquitous regulatory modules for bacterial growth and cell survival following stress. YefM–YoeB, the most prevalent type II TA system, is present in a variety of bacterial species. In Staphylococcus aureus, the YefM–YoeB system exists as two independent paralogous copies. Our previous research resolved crystal structures of the two oligomeric states (heterotetramer and heterohexamer–DNA ternary complex) of the first paralog as well as the molecular mechanism of transcriptional autoregulation of this module. However, structural details reflecting molecular diversity in both paralogs have been relatively unexplored. To understand the molecular mechanism of how Sa2YoeB and Sa2YefM regulate their own transcription and how each paralog functions independently, we solved a series of crystal structures of the Sa2YoeB–Sa2YefM. Our structural and biochemical data demonstrated that both paralogous copies adopt similar mechanisms of transcriptional autoregulation. In addition, structural analysis suggested that molecular diversity between the two paralogs might be reflected in the interaction profile of YefM and YoeB and the recognition pattern of promoter DNA by YefM. Interaction analysis revealed unique conformational and activating force effected by the interface between Sa2YoeB and Sa2YefM. In addition, the recognition pattern analysis demonstrated that residues Thr7 and Tyr14 of Sa2YefM specifically recognizes the flanking sequences (G and C) of the promoter DNA. Together, these results provide the structural insights into the molecular diversity and independent function of the paralogous copies of the YoeB–YefM TA system.

P.140: Impact of Successful Pancreas Transplantation on Patient Reported Hypoglycemia Outcomes

Introduction: Poorly controlled Type 1 Diabetes (T1D) is associated with increased HbA1c, increased severe hypoglycemia, decreased hypoglycemia awareness and diabetic ketoacidosis. These comorbidities and decreased quality of life are indications for Pancreas Transplantation (PT). Limited data are available about patient reported outcomes (PROs) related to Hypoglycemia after PT. Therefore, we prospectively studied these PROs over a year after PT in patients with T1D. Methods: Ten PT recipients were enrolled within a month after PT and completed 3 visits (V1, V2 & V3 at 4 weeks, 4 months and 1 year). At each visit, participants completed Hypoglycemia Fear Survey-II (HFS-II) and Clarke hypoglycemia unawareness survey. HFS-II is a 33-item questionnaire to measure behavior and worry subscales related to fear of hypoglycemia in patients with T1D. Behavior subscale (HFS-B) describes behaviors individual would engage in to avoid hypoglycemia or its consequences. Worry subscale (HFS-W) describes concerns related to hypoglycemia. Clarke questionnaire evaluates awareness of hypoglycemia based on responses to 8 questions, identifying awareness (A) or reduced awareness (R). The Clarke R score ranges from 0 to 7 with ≤ 2 indicating normal A, 3 as undetermined A and score ≥4 suggesting impaired awareness of hypoglycemia (IAH). We analyzed insulin independent and partial graft function on insulin separately. Statistical analysis was done using a linear mixed effects model. Results: Patients were 46.3 ± 14.3 years old, 9 F, duration of T1D 27.8 ± 15.8 years with 29.4 ± 18.3 days interval from PT. Laboratory results were HbA1c (%) 6.3, 5.4 and 5.4, fasting plasma glucose (mg/dL) 88.6, 104.8 and 91 and C-peptide (ng/ml) 4.6, 3.1 and 2.4 on V1, 2 & 3 respectively. In insulin independent participants (n=8), HFS-B showed almost every participant reported taking some behavioral measures over last 6 months to avoid hypoglycemia at V1. On V2, five participants took some behavioral measures and on V3 only one to avoid hypoglycemia (Table). HFS-W showed almost every participant had some concerns about low blood sugar at V1, five on V2 and none on V3. Two participants who had partial graft function around V2 engaged in behavior to avoid hypoglycemia on V1, 2 & 3, with a subsequent decreased behavioral engagement (p 0.1197) and concern to avoid hypoglycemia (p 0.1391) compared to V1. Clarke scoring showed indeterminate awareness at V1, improved significantly (p 00.0146) and attained normal hypoglycemia awareness over the year on V2 and V3 respectively (Table). Two participants who had partial graft failure reported IAH on all 3 visits (V1: V2:V3=5.0: 4.0: 4.0, p 0.5000). Conclusion: PT recipients reported reduced Fear of hypoglycemia and improved hypoglycemia awareness over a period of 1 year, even in patients with partial graft function. More studies would enable better assessment of these PROs and improve the field.

Germinal Center B Cells Derived from TET2-Mutated Clonal Hematopoiesis Provide a Microenviromental Niche for Tumor Cells in Angioimmunoblastic T-Cell Lymphoma

Germinal Center B Cells Derived from TET2-Mutated Clonal Hematopoiesis Provide a Microenviromental Niche for Tumor Cells in Angioimmunoblastic T-Cell Lymphoma

Doping Independent Work Function and Stable Band Gap of Spinel Ferrites with Tunable Plasmonic and Magnetic Properties.

Tuning optical or magnetic properties of nanoparticles, by addition of impurities, for specific applications is usually achieved at the cost of band gap and work function reduction. Additionally, conventional strategies to develop nanoparticles with a large band gap also encounter problems of phase separation and poor crystallinity at high alloying degree. Addressing the aforementioned trade-offs, here we report Ni-Zn nanoferrites with energy band gap (Eg) of ≈3.20 eV and a work function of ≈5.88 eV. While changes in the magnetoplasmonic properties of the Ni-Zn ferrite were successfully achieved with the incorporation of bismuth ions at different concentrations, there was no alteration of the band gap and work function in the developed Ni-Zn ferrite. This suggests that with the addition of minute impurities to ferrites, independent of their changes in the band gap and work function, one can tune their magnetic and optical properties, which is desired in a wide range of applications such as nanobiosensing, nanoparticle based catalysis, and renewable energy generation using nanotechnology.

A Catalytically Independent Function of Human DNA Polymerase Kappa Controls the Stability and Abundance of Checkpoint Kinase 1.

DNA polymerase kappa (Pol κ) has been well documented thus far for its specialized DNA synthesis activity during translesion replication, progression of replication forks through regions difficult to replicate, restart of stalled forks, and replication checkpoint efficiency. Pol κ is also required for the stabilization of stalled forks, although the mechanisms are poorly understood. In this study, we unveiled an unexpected role for Pol κ in controlling the stability and abundance of checkpoint kinase 1 (Chk1), an important actor for the replication checkpoint and fork stabilization. We found that loss of Pol κ decreased the Chk1 protein level in the nuclei of four human cell lines. Pol κ and not the other Y family polymerase members is required to maintain the Chk1 protein pool all along the cell cycle. We showed that Pol κ depletion affected the protein stability of Chk1 and protected it from proteasome degradation. Importantly, we also observed that the fork restart defects observed in Pol κ-depleted cells could be overcome by the reexpression of Chk1. Strikingly, this new function of Pol κ does not require its catalytic activity. We propose that Pol κ could contribute to the protection of stalled forks through Chk1 stability.

Driver, Collision and Meteorological Characteristics of Motor Vehicle Collisions among Road Trauma Survivors.

Road trauma remains a significant public health problem. We aimed to identify sub-groups of motor vehicle collisions in Victoria, Australia, and the association between collision characteristics and outcomes up to 24 months post-injury. Data were extracted from the Victorian State Trauma Registry for injured drivers aged ≥16 years, from 2010 to 2016, with a compensation claim who survived ≥12 months post-injury. People with intentional or severe head injury were excluded, resulting in 2735 cases. Latent class analysis was used to identify collision classes for driver fault and blood alcohol concentration (BAC), day and time of collision, weather conditions, single vs. multi-vehicle and regional vs. metropolitan injury location. Five classes were identified: (1) daytime multi-vehicle collisions, no other at fault; (2) daytime single-vehicle predominantly weekday collisions; (3) evening single-vehicle collisions, no other at fault, 36% with BAC ≥ 0.05; (4) sunrise or sunset weekday collisions; and (5) dusk and evening multi-vehicle in metropolitan areas with BAC < 0.05. Mixed linear and logistic regression analyses examined associations between collision class and return to work, health (EQ-5D-3L summary score) and independent function Glasgow Outcome Scale - Extended at 6, 12 and 24 months. After adjusting for demographic, health and injury characteristics, collision class was not associated with outcomes. Rather, risk of poor outcomes was associated with age, sex and socioeconomic disadvantage, education, pre-injury health and injury severity. People at risk of poor recovery may be identified from factors available during the hospital admission and may benefit from clinical assessment and targeted referrals and treatments.

Recognition of DNA Methylation Molecular Features for Diagnosis and Prognosis in Gastric Cancer.

Background: The management of gastric cancer (GC) still lacks tumor markers with high specificity and sensitivity. The goal of current research is to find effective diagnostic and prognostic markers and to clarify their related mechanisms. Methods: In this study, we integrated GC DNA methylation data from publicly available datasets obtained from TCGA and GEO databases, and applied random forest and LASSO analysis methods to screen reliable differential methylation sites (DMSs) for GC diagnosis. We constructed a diagnostic model of GC by logistic analysis and conducted verification and clinical correlation analysis. We screened credible prognostic DMSs through univariate Cox and LASSO analyses and verified a prognostic model of GC by multivariate Cox analysis. Independent prognostic and biological function analyses were performed for the prognostic risk score. We performed TP53 correlation analysis, mutation and prognosis analysis on eleven-DNA methylation driver gene (DMG), and constructed a multifactor regulatory network of key genes. Results: The five-DMS diagnostic model distinguished GC from normal samples, and diagnostic risk value was significantly correlated with grade and tumor location. The prediction accuracy of the eleven-DMS prognostic model was verified in both the training and validation datasets, indicating its certain potential for GC survival prediction. The survival rate of the high-risk group was significantly lower than that of the low-risk group. The prognostic risk score was an independent risk factor for the prognosis of GC, which was significantly correlated with N stage and tumor location, positively correlated with the VIM gene, and negatively correlated with the CDH1 gene. The expression of CHRNB2 decreased significantly in the TP53 mutation group of gastric cancer patients, and there were significant differences in CCDC69, RASSF2, CHRNB2, ARMC9, and RPN1 between the TP53 mutation group and the TP53 non-mutation group of gastric cancer patients. In addition, CEP290, UBXN8, KDM4A, RPN1 had high frequency mutations and the function of eleven-DMG mutation related genes in GC patients is widely enriched in multiple pathways. Conclusion: Combined, the five-DMS diagnostic and eleven-DMS prognostic GC models are important tools for accurate and individualized treatment. The study provides direction for exploring potential markers of GC.

A profile of adult patients with major burns admitted to a Level 1 Trauma Centre and their functional outcomes at discharge: A retrospective review

Background: Patients with major burns suffer with pain, which impacts their physical function during hospitalisation. Objectives: To describe the demographics, burn characteristics, clinical course, physical function, complications developed after major burns and to establish predictors of non-independent physical function at hospital discharge. Method: Records of all consecutive adult burn admissions to a Level 1 Trauma Centre between 2015 and 2017 were screened retrospectively against our study criteria, using the Trauma Bank Data Registry. Anonymised data from included records were captured on specifically designed data extraction forms. Descriptive statistics were used to summarise findings. A regression analysis was undertaken to establish predictors of non-independent function at discharge. Results: Males represented 87.7% ( n = 64) of included records ( n = 73). Median age was 38 (interquartile range [IQR]: 22). Thermal burns were most reported ( n = 47, 64.4%), followed by median total body surface area (TBSA) 31% and head and arms were most affected (60.3% and 71.2%). Injury severity was high with median intensive care unit (ICU) length of stay (LOS) of 17 (IQR: 34) and hospital LOS 44 (IQR: 31) days. Wound debridement was mostly performed ( n = 27, 36.9%) with limb oedema as a common complication ( n = 15, 21.7%). Muscle strength and functional performance improved throughout LOS. None of the variables identified were predictors of non-independent function at hospital discharge. Conclusion: Adults with major burns were predominantly male, in mid-life and sustained thermal injury with a high injury severity. Decreased range of motion (ROM) of affected areas, ‘fair’ muscle strength and independent function were recorded for most patients at hospital discharge. Clinical implications: These findings contribute to the limited body of evidence on the profile, clinical course and outcomes of South African adult burn patients.

Prediction of Potential Mutation of Chicken Coronavirus into Future Human Coronavirus Based on Spike S1 Glycoprotein Gene

The high mutation rates of the chicken coronavirus (IBV) cause economic threats to the poultry industry. However, the most dangerous situation is the likelihood of changing its sequences into human coronavirus (COVID-19-like virus). Therefore, in the present study we aimed to investigate the possibility of genetic mutation of IBV to COVID-19. Thus, the sequences of Spike (S1) Glycoprotein genes of both IBV and COVID-19 were aligned, analyzed and calculated to predict the possible changes that could happen in the sequences of S1. The results indicated that in the case of an independent function of probability of each cluster of S1 sequences, the potential mutation rate in the sequences of IBV to be as COVID-19 was equal to 1.87E-96. However, because the tendency for some sequence clusters of S1 gene was low or equal to zero, it is unattainable to mutate the chicken IBV into COVID-19 sequence. Furthermore, in case of the dependent function, the probability of assumed annual mutation to make IBV infectious for human may reach up to around 50% after about 260 years. As a conclusion, the mutating of chicken coronavirus into COVID-19-like virus is not impossible, but it might take a substantial period of time

A case series shows independent vestibular labyrinthine function after major surgical trauma to the human cochlea

BackgroundThe receptors for hearing and balance are housed together in the labyrinth of the inner ear and share the same fluids. Surgical damage to either receptor system was widely believed to cause certain permanent loss of the receptor function of the other. That principle, however, has been called into question because there have been anecdotal reports in individual patients of at least partial preservation of cochlear function after major surgical damage to the vestibular division and vice versa.MethodsWe performed specific objective vestibular function tests before and after surgical trauma (partial or subtotal cochlear removal) for treatment of intracochlear tumors in 27 consecutive patients in a tertiary referral center. Vestibular function was assessed by calorics (low-frequency response of the lateral semicircular canal), vestibulo-ocular reflex by video head impulse test (vHIT) of the three semicircular canals, cervical and ocular vestibular evoked myogenic potentials (cVEMP, saccule and oVEMP, utricle). Preoperative and postoperative distributions were compared with paired t-tests.ResultsHere we show that there was no significant difference between pre- and post-operative measures for all tests of the five vestibular organs, and that after major surgical cochlear trauma, the vestibular receptors continue to function independently.ConclusionsThese surprising observations have important implications for our understanding of the function and the surgery of the peripheral auditory and vestibular system in general and open up new possibilities for the development, construction and evaluation of neural interfaces for electrical or optical stimulation of the peripheral auditory and vestibular nervous system.

A systems analysis of the UK COVID 19 pandemic response: Part 2 - work as imagined vs work as done

Modelling complex sociotechnical systems to try to understand how observed behaviours emerge from a network of interacting, interdependent and interrelated functions is a major challenge. Woods et al (Branlat, 2010), have pointed out that it is difficult to find a satisfactory current methodology. They suggested that perhaps the Functional Resonance Analysis Methodology developed by Hollnagel (Hollnagel, 2012) could be an appropriate approach to try. In Part 1 this approach was employed to build an overall model of the UK’s COVID 19 response management system, which was constructed as a framework against which, a series of more detailed analyses of specific health care responses could be examined. This meant being conscious of the bigger picture of simultaneous activities and the dynamic emergence of unexpected developments. At that stage, it was of necessity a model of “work as imagined” from careful official and speculative media sources.Although, a full rigorous application will require a more authenticated, official (peer reviewed?), set of data, reports and evidence statements, which doubtless will be available eventually from the inevitable Public Inquiry, it seems a pity to delay gaining and applying any insights and adaptations from “work as (actually) done”, that have been observed to date. The recent select committee evidence from people at the heart of the system, (Committee, 2021), which may, or may not be corroborated later, nevertheless now provides a provisional database, which can be utilised to test whether the FRAM model can produce such insights from the actual performance of this highly complex system.This paper has thus attempted a trial run and has found that it can produce a plausible set of insights, which can explain how the system behaved in practice. With such a serious challenge to Government systems worldwide, in all their advisory, operation and decision-making functions, such insights although provisional, could usefully be incorporated and formalised in the current systems rather than waiting for inquiry endorsed recommendations to be formally considered perhaps some years into the future.The paper thus sets out a set of conclusions and recommendations, caveated by emphasising the lack of fully authenticated public domain data on which it is based. The main conclusion however is that the current system appears not to have included any of the functions which could have provided the adaptability and resilience required by fast moving emergencies, such as pandemics. The exception noted was the establishment of a parallel, independent vaccine development and delivery function and it is hoped that at least this lesson from the work as done could be recognised as providing the type of adaptability required and incorporated without delay.

Preprint Highlight: Pressure and curvature control of contact inhibition in epithelia growing under spherical confinement.

All living systems evolved molecular mechanisms to respond to their physical surroundings, such as by tuning cell cycle progression as well as transport of different cargo across intracellular compartments. However, it is difficult to determine if such responses are genetically programmed or purely resultant of physical forces. This study deploys a new confinement device that modulates chamber stiffness, curvature, and compression over epithelial tissue. Compression specifically regulated cell cycle progression, while increasing stiffness changed cell aspect ratio. The authors propose a new independent function of previous cooperative pathways that regulate long-range tissue scales (β-catenin) and local spatial changes (YAP/TAZ). This work represents a methodological advance in creating specific physical cues while measuring cellular processes, enabling many future studies combining other chemical and genetic perturbations..

Targeted tDCS Reduces the Expression of the Upper Limb Flexion Synergy in Chronic Hemiparetic Stroke

<h3>Research Objectives</h3> The emergence of abnormal movement synergies following a stroke presents a major limitation to the recovery of independent function(1). This study aims to explore a novel neuromodulatory technology based on a targeted tDCS(2-3) for reducing the upper limb flexion synergy post stroke. <h3>Design</h3> Randomized controlled trial. <h3>Setting</h3> Academic medical center. <h3>Participants</h3> Five adults (ages: 48-64 yrs. old) who suffered from a chronic hemiparetic stroke (Upper Extremity Fugl-Meyer score: 23-34) participated in this preliminary study. <h3>Interventions</h3> We collected electrical brain activity (EEG) and behavioral measures during a movement task before and after the TMS/EEG guided tDCS. The participants were seated on a Biodex rehabilitation chair and performed a shoulder abduction task at 30% of maximum effort with their paretic arm while they were receiving tactile electrical finger stimulation. TMS/EEG guided tDCS was applied using five small stimulation electrodes. Three participants received the anodal stimulation of tDCS that targeted the ipsilesional motor cortex and underlying corticospinal tracts, and two others received the cathodal stimulation inhibiting the contralesional somatosensory cortex. The anodal stimulation location was determined by TMS over the ipsilesional motor cortex(5). The cathodal stimulation location was determined by the somatosensory evoked potential over the contralesional somatosensory cortex(4). <h3>Main Outcome Measures</h3> We measured the shoulder abduction induced synergic elbow flexion torque as the main outcome measure to determine its expression. <h3>Results</h3> All tested participants showed a reduced expression of synergic elbow flexion after the targeted tDCS. <h3>Conclusions</h3> Our preliminary results suggested that facilitating the ipsilesional corticospinal tracts and inhibiting the contralesional sensory area in the brain, using the proposed tDCS technology, may help reducing motor impairments in chronic hemiparetic stroke. <h3>Author(s) Disclosures</h3> None

Distributed Robust Filtering over Sensor Networks with Quantized Measurement and Switching Topologies

This paper aims at exploring the theoretical research and distributed filtering design of state estimation for sensor networked systems with quantized measurement and switching topologies. In a sensor network, each sensor node has an independent static logarithmic quantizer function, and the quantized measurement is transmitted to the filtering network via the wireless network. In the corresponding filtering network, each local estimator achieves distributed consistent state estimation of the plant based on the local measurement and the neighboring shared information. In particular, the design of the distributed filter fully takes into account the fact that the communication links between the nodes are not fixed. That is, the communication topology has random switching, and such random switching behavior is described using Markov chains with partially unknown transition probabilities. A set of linear matrix inequalities gives the sufficient conditions for the existence of the distributed filter, while ensuring that the filter error system has the desired H∞ performance. Finally, two numerical simulations show the effectiveness of the design method.

Combination treatment with rituximab, low-dose cyclophosphamide and plasma exchange for severe antineutrophil cytoplasmic antibody-associated vasculitis

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis can present with life-threatening lung-kidney syndromes. However, many controlled treatment trials excluded patients with diffuse alveolar hemorrhage or severely impaired glomerular filtration rates, and so the optimum treatment in these cases is unclear. In this retrospective cohort study, we report the outcomes of 64 patients with life-threatening disease treated with a combination regimen of rituximab, low-dose intravenous cyclophosphamide, oral glucocorticoids, and plasma exchange. At entry, the median estimated glomerular filtration rate was 9 mL/min, 47% of patients required dialysis, and 52% had diffuse alveolar hemorrhage. All patients received a minimum of seven plasma exchanges, and the median cumulative doses of rituximab, cyclophosphamide, and glucocorticoid were 2, 3, and 2.6 g, respectively, at six months. A total of 94% of patients had achieved disease remission (version 3 Birmingham Vasculitis Activity Score of 0) at this time point, and 67% of patients who required dialysis recovered independent kidney function. During long-term follow-up (median duration 46 months), overall patient survival was 85%, and 69% of patients remained free from end-stage kidney disease, which compares favorably to a historic cohort with severe disease treated with a conventional induction regimen. Combination treatment was associated with prolonged B cell depletion and low rates of relapse; 87% of patients were in continuous remission at month 36. The serious infection rate during total follow-up was 0.28 infections/patient/year, suggesting that combination treatment is not associated with an enduring risk of infection. Thus, we suggest that combination immunosuppressive therapy may permit glucocorticoid avoidance and provide rapid and prolonged disease control in patients with severe ANCA-associated vasculitis.

Using the PODCI to Measure Motor Function and Parent Expectations in Children With Cerebral Palsy.

Involving parents in the evaluation of their child with cerebral palsy (CP) is associated with enhanced neurodevelopmental outcomes. The pediatric outcomes data collection instrument (PODCI) is a patient-reported outcome measure primarily used to assess motor function following orthopedic surgical intervention or for older children with more independent motor function. The PODCI expectations scale has infrequently been reported in previous studies. This study aims to determine the relationship between parent-reported motor performance using the PODCI and motor capacity assessed by pediatric therapists for young children with CP across all ability levels and to explore the use of the PODCI expectations scale for quantifying therapy-related parent expectations. This prospective cohort study included 108 participants with CP, 2 to 8years of age, gross motor function classification systems (GMFCS) levels I to V. Measures included the PODCI, gross motor function measure (GMFM), and GMFCS. There were moderate (r = 0.513) to large (r = 0.885) relationships between PODCI and GMFM scores. PODCI scores were significantly different across GMFCS levels. Weak, significant relationships (r = -0.28) were found between function expectations scores and measures of function. The PODCI, GMFM, and GMFCS provide different, but strongly related, information about the abilities of young children. The GMFM measures motor capacity. Parents report daily function and health-related quality of life for their child using the PODCI. Parent expectations for intervention outcomes may relate to a child's motor function. These study results are consistent with those for older children with greater independent mobility, indicating an opportunity for expanded use of the PODCI for measuring motor performance for younger children with CP across all ability levels. A strategy is provided for using the PODCI expectations scale to quantify parent therapy-related expectations in future research and clinical settings. Therapy-related expectations may relate to child outcomes.

Evaluation of a Novel Three-Dimensional Robotic Digital Microscope (Aeos) in Neurosurgery.

Simple SummaryCurrent literature debates the development and implementation of three-dimensional Exoscopes in the daily routine of neurosurgical practice. This study evaluates the grade of satisfaction and intraoperative handling of the novel Aesculap Aeos Three-Dimensional Robotic Digital Microscope used in a Neurosurgical Department in the daily practice in a larger series of neurosurgical procedures. Our evaluation of this modern microscope technology focuses on three central aspects of microsurgical procedures. First, the visualization of tumor tissue and its discernment from healthy tissue, which is of utmost importance during neurooncological procedures. Furthermore, the aspect of ergonomics and fatigue during long, repetitive surgical procedures have been shown to cause work-related musculoskeletal disorders. Finally, the implementation of novel three-dimensional microscopes may be a promising tool for surgical education. Improved image quality, superior ergonomic comfort for the surgeon and increased accessibility within the surgical field have been noted as major advantages to date.Objective: Current literature debates the role of newly developed three-dimensional (3D) Exoscopes in the daily routine of neurosurgical practice. So far, only a small number of cadaver lab studies or case reports have examined the novel Aesculap Aeos Three-Dimensional Robotic Digital Microscope. This study aims to evaluate the grade of satisfaction and intraoperative handling of this novel system in neurosurgery. Methods: Nineteen neurosurgical procedures (12 cranial, 6 spinal and 1 peripheral nerve) performed over 9 weeks using the Aeos were analyzed. Ten neurosurgeons of varying levels of training were included after undergoing device instruction and training. Following every surgery, a questionnaire consisting of 43 items concerning intraoperative handling was completed. The questionnaires were analyzed using descriptive statistics. Results: No intraoperative complications occurred. Surgical satisfaction was ranked high (78.95%). In total, 84.21% evaluated surgical ergonomics as satisfactory, while 78.95% of the surgeons would like to use this system frequently. Image quality, independent working zoom function and depth of field were perceived as suboptimal by several neurosurgeons. Conclusion: The use of Aeos is feasible and safe in microsurgical procedures, and surgical satisfaction was ranked high among most neurosurgeons in our study. The system might offer advanced ergonomic conditions in comparison to conventional ocular-based microscopes.

Pedicled fibular transfer for biologic knee extensor tendon reinsertion following proximal tibial resection in pediatric osteosarcoma: Long-term outcomes.

Proximal tibial sarcoma resections result in a reconstructive challenge, necessitating joint and extensor mechanism reconstruction. The gait and functional outcomes for children reconstructed with a combination of megaprosthesis and pedicled fibular flap for extensor mechanism reconstruction, are presented. Four patients, aged 11-18 years old, were available for comprehensive analysis. The proximal tibial osteosarcoma was resected, and the reconstructive technique involved a megaprosthesis for the knee joint, used in combination with a pedicled fibula flap as a biologic structure for reinsertion of the knee extensor mechanism. Outcomes were measured with three-dimensional gait analysis and patient questionnaires. Minor postoperative wound issues occurred in some patients, requiring debridement with skin grafting. One patient fractured their transferred fibula, requiring fixation. The follow up period ranged from 1.7 to 24 years postoperatively. The longevity and quality of reconstructions were strong, measured by both objective and patient-reported outcomes. All patients reported independent walking >500m in the Functional Mobility Scale and rated their walking as a nine or 10 (out of 10) on the Functional Assessment Questionnaire. Knee society scoring revealed overall satisfaction rate of 75-80%. No patients required gait aids. The gait profile analysis revealed effective gait patterns, with patterns deviating 5.4-7° from "typical gait." Deviations >6.5° are considered abnormal. The long-term results of combining a megaprosthesis with a pedicled fibula flap for extensor reinsertion, revealed a high level of independent function. The patients performed well, without the need for aids, and gait study evidence of minimal gait deviations.

Examining the Use of Electroencephalography for the Diagnosis of Alzheimer’s Disease and Mild Cognitive Impairment

Introduction: Alzheimer’s disease is a type of dementia characterized by a buildup of -amyloid plaques and neurofibrillary tangles. Prior to the development of Alzheimer’s disease, patients may experience mild cognitive impairment, characterized by a decline in cognitive abilities while maintaining independent function. Electroencephalography has shown promise as a clinical predictor of mild cognitive impairment. The purpose of this study is to review the existing literature on clinical biomarkers using resting-state electroencephalography or event-related potentials to differentiate Alzheimer’s disease or mild cognitive impairment from normal aging. Methods: A search of primary research articles was conducted in PubMed. Selected articles examined mild cognitive impairment and Alzheimer’s disease utilising electroencephalography, event-related potential data, and resting-state data. Reviews, conference abstracts, and studies without human controls were excluded. Results: Our search identified 100 and 125 records on resting-state and event-related potential data, respectively. The most common findings from resting-state studies included a reduction in alpha power, an increase in delta and theta power, a reduction in signal complexity, and differences in functional connectivity. The most common findings from event-related potential studies included reduction in P3 wave amplitude, as well as latency in both P3 and N2 waves. Discussion: Resting-state and event-related potential electroencephalography studies indicate distinct changes in oscillatory brain activity and waveform shape which indicate distinct differences in MCI or AD compared to HC which may be clinically relevant. Conclusion: There is evidence to support the use of certain electroencephalographic biomarkers for the diagnosis of Alzheimer’s disease or mild cognitive impairment. Future research should seek to examine how best to apply these findings in a clinical setting.