Molecular and Phenotypic Changes in FLExDUX4 Mice.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by the aberrant expression of the double homeobox 4 (DUX4) gene. The FLExDUX4 mouse model carries an inverted human DUX4 transgene which has leaky DUX4 transgene expression at a very low level. No overt muscle pathology was reported before 16 weeks. The purpose of this study is to track and characterize the FLExDUX4 phenotypes for a longer period, up to one year old. In addition, transcriptomic changes in the muscles of 2-month-old mice were investigated using RNA-seq. The results showed that male FLExDUX4 mice developed more severe phenotypes and at a younger age in comparison to the female mice. These include lower body and muscle weight, and muscle weakness measured by grip strength measurements. Muscle pathological changes were observed at older ages, including fibrosis, decreased size of type IIa and IIx myofibers, and the development of aggregates containing TDP-43 in type IIb myofibers. Muscle transcriptomic data identified early molecular changes in biological pathways regulating circadian rhythm and adipogenesis. The study suggests a slow progressive change in molecular and muscle phenotypes in response to the low level of DUX4 expression in the FLExDUX4 mice.

Implicit processes enhance cognitive abilities in mild cognitive impairment.

Previous work has shown that older adults with typical age-related memory changes (i.e., without cognitive impairment) pick up irrelevant information implicitly, and unknowingly use that information when it becomes relevant to a later task. Here, we address the possibility that implicit processes play a similarly beneficial role in the cognitive abilities of individuals with amnestic mild cognitive impairment (aMCI). Twenty-two individuals with aMCI and 22 matched controls participated in a picture judgment task while instructed to ignore distractions in the form of word/non-word letter strings. Memory for the distracting words was later tested with a word-fragment completion task. Both groups showed a priming effect, that is, they were significantly more likely to solve fragments of previously presented than non-presented words. However, the aMCI group had significantly higher scores than the older adults without cognitive impairment, t(42) = 2.16, p < .05, Cohen's d = 0.67. Our findings suggest that individuals with aMCI can enhance their performance on an explicit cognitive task, in this case, word-fragment completion, if previously exposed to the relevant information implicitly, opening up possible interventions aimed at this population.

Beyond Placement of Pedicle Screws - New Applications for Robotics in Spine Surgery: A Multi-Surgeon, Single-Institution Experience.

Interest in robotic-assisted spine surgery has grown as surgeon comfort and technology has evolved to maximize benefits of time saving and precision. However, the Food and Drug Administration (FDA) has currently only approved robotics to assist in determining the ideal trajectory for pedicle screw placement after extensive research supporting its efficacy and efficiency. To be considered a durable and effective option, robotics need to expand beyond the indication of just placing pedicle screws. This article aims to illustrate a multi-surgeon, single-institution experience with unique applications of robotic technologies in spine surgery. We will explore accessing Kambin's Triangle in percutaneous transforaminal interbody fusion (percLIF), iliac fixation in metastatic cancer, and sacroiliac (SI) fusions. Each of these topics will be covered in depth with associated background information and subsequent discussion. We show that with proper understanding of its limitations, robots can help surgeons perform difficult surgeries in a safe manner.

Automated closed volume reduction process for apheresis stem cell grafts: From development to clinical implementation.

BACKGROUND: Collection of HPC by apheresis (HPC-A) can sometimes result in higher collection volumes, increasing the dimethyl sulfoxide (DMSO) volume infused into patients and the space requirements in liquid nitrogen freezers. Volume reduction prior to the addition of cryoprotectant is an efficient means to reduce the DMSO load infused into patients and to optimize freezer storage space. STUDY DESIGN AND METHODS: To implement a closed semi-automated volume reduction process, a method was developed to produce leukocyte-rich mock apheresis products using buffy coats derived from whole blood collections. The mock HPC products were then used to measure the efficiency and reliability of the semi-automated process over a range of volumes and cell concentrations. The resulting data was used to support the implementation of the process with concurrent monitoring. RESULTS: A closed, semi-automated volume reduction process resulted in recoveries of over 93% and 91% of white blood cells and CD34+ cells with no significant loss of product viability or potency. Mean doses of CD34+ and CFU infused per kilogram recipient body weight were 4.0 ± 1.1 × 106 /kg and 4.2 ± 1.7 × 105 /kg, resulting in no delays in median time to neutrophil and platelet engraftment, significant increase in adverse reaction or nonconformances. DISCUSSION: The effectiveness outcomes of the first Canadian experience in the implementation of a closed semi-automated volume reduction system in the processing of HPC-A products for autologous transplant have met the predetermined acceptance criteria, supporting its use in a stem cell manufacturing laboratory compliant with good manufacturing practice regulations.

Sacroiliac Joint Fusion Using Robotic Navigation: Technical Note and Case Series.

BACKGROUND: Patients undergoing sacroiliac (SI) fusion can oftentimes experience significant improvements in pain and quality of life. OBJECTIVE: To describe a novel application of robotic navigation to assist with minimally invasive SI joint fusion. METHODS: Patients undergoing stand-alone SI joint fusion with ExcelsiusGPS robotic navigation from July 2020 through June 2021 were retrospectively enrolled. Baseline demographic and perioperative variables including radiation exposure, postoperative pain scores, and narcotic requirements in the postanesthesia care unit (PACU) were recorded. Length of stay and any postoperative complications were also noted. RESULTS: A total of 10 patients (64.4 ± 8.2 years, body mass index 28.7 ± 4.8 kg/m2) met inclusion criteria. Seven patients (70.0%) were female, and there was a 6:4 split between left-sided and right-sided SI joint fusion. The total operative time was 54 ± 9 minutes, and the estimated blood loss was 21.0 ± 16.7 mL. The intraoperative radiation exposure was 13.7 ± 6.2 mGy, and there were no complications. The average pain score in PACU was 5.2 ± 1.0, and the average opioid administration in PACU was 27.6 ± 10.3 morphine equivalents. Length of stay was 0.4 ± 0.7 days, with 7 of 10 patients discharged on the same day as surgery. There were no readmissions. The average length of follow-up was 4.3 ± 2.5 months. At the last follow-up, patients reported an average of 73.1% ± 30.1% improvement in their preoperative pain. CONCLUSION: Robot-navigated SI joint fusion is a feasible and reproducible method for addressing refractory SI joint disease. Further investigation on clinical outcomes and long-term fusion rates is needed, as are studies comparing robot-navigated SI joint fusion with more traditional techniques.

Machine Learning to Predict Successful Opioid Dose Reduction or Stabilization After Spinal Cord Stimulation.

BACKGROUND: Spinal cord stimulation (SCS) effectively reduces opioid usage in some patients, but preoperatively, there is no objective measure to predict who will most benefit. OBJECTIVE: To predict successful reduction or stabilization of opioid usage after SCS using machine learning models we developed and to assess if deep learning provides a significant benefit over logistic regression (LR). METHODS: We used the IBM MarketScan national databases to identify patients undergoing SCS from 2010 to 2015. Our models predict surgical success as defined by opioid dose stability or reduction 1 year after SCS. We incorporated 30 predictors, primarily regarding medication patterns and comorbidities. Two machine learning algorithms were applied: LR with recursive feature elimination and deep neural networks (DNNs). To compare model performances, we used nested 5-fold cross-validation to calculate area under the receiver operating characteristic curve (AUROC). RESULTS: The final cohort included 7022 patients, of whom 66.9% had successful surgery. Our 5-variable LR performed comparably with the full 30-variable version (AUROC difference <0.01). The DNN and 5-variable LR models demonstrated similar AUROCs of 0.740 (95% CI, 0.727-0.753) and 0.737 (95% CI, 0.728-0.746) ( P = .25), respectively. The simplified model can be accessed at SurgicalML.com . CONCLUSION: We present the first machine learning-based models for predicting reduction or stabilization of opioid usage after SCS. The DNN and 5-variable LR models demonstrated comparable performances, with the latter revealing significant associations with patients' pre-SCS pharmacologic patterns. This simplified, interpretable LR model may augment patient and surgeon decision making regarding SCS.

Usability and Accessibility of the ArtontheBrain™ Virtual Recreation Activity for Older Adults With Low Vision Due to Age-Related Macular Degeneration.

Experiencing visual art can inspire, be an overall positive leisure activity, and has been linked to improved cognition, especially in older adults. Access to artwork in a museum environment can comprise a variety of barriers, including difficulties linked to its visual experience for persons that are visually impaired. The present study explored the barriers and facilitators experienced by 15 older adults (age 65 to 93) living with age-related macular degeneration when using an iPad to access ArtontheBrain™, a virtual art museum recreation experience created by members of this team. Using the Concurrent Think Aloud method, participants were asked to continuously comment on their experiences with the application while being audio/video recorded. Indeed, codes were determined by identifying frequently stated and emphasized ideas or behaviors of participants using the ArtontheBrain™ application. Transcripts underwent thematic analysis and indicated that the main access barriers were linked to control of the contrast, magnification, and the tactile interface on the tablet device. The learn and play activities as well as the text-to-speech feature were identified as facilitators for ArtontheBrain™ engagement. The present findings should also be considered in the larger context of application development, as this study provides insight pertaining to the needs of low vision individuals regarding usability and accessibility.

Neurocognitive Outcome Following Recovery from Severe Acute Respiratory Syndrome - Coronavirus-1 (SARS-CoV-1).

OBJECTIVE: Severe acute respiratory syndrome (SARS) is a highly contagious viral respiratory illness associated with hypoxia and dyspnea. Many of those who contracted and recovered from SARS during the 2002-2003 outbreak reported persistent physical, psychological, and cognitive difficulties. Here, we investigated the residual influences of SARS on cognition for a subset of healthcare professionals who recovered and were referred for neuropsychological evaluation through their workplace insurance. METHOD: Twenty-eight healthcare professionals were evaluated on neuropsychological and mood functioning approximately 1.5 years post-recovery from a severe respiratory illness. Test scores were compared with age-matched normative data, and correlations were examined between mood, self-report memory scales, subjective complaints (e.g., poor concentration, pain, fatigue), illness severity (i.e., length of hospitalization, oxygen use during hospital stay), and cognitive performance. RESULTS: Participants performed within age expectations on the majority of cognitive measures including overall memory ability. Although processing speed was generally within normal limits, 43% showed significant speed-accuracy trade-offs favoring accuracy over maintaining speed. Deficits were observed on measures of complex attention, such as working memory and the ability to sustain attention under conditions of distraction. Participants endorsed poorer memory ability than same-age peers on a meta-memory measure and mild to moderate depression and anxiety symptoms. Objective test performance was largely uncorrelated with self-reports, mood, or illness severity, except for moderate correlations between complex attention and participants' subjective ratings of Everyday Task-Oriented Memory. CONCLUSIONS: These findings demonstrate specific long-term cognitive deficits associated with SARS and provide further evidence of the cognitive effects of hypoxic illnesses.

Management of Acute Traumatic Spinal Cord Injury: A Review of the Literature.

Traumatic spinal cord injury (TSCI) is a debilitating disease that poses significant functional and economic burden on both the individual and societal levels. Prognosis is dependent on the extent of the spinal injury and the severity of neurological dysfunction. If not treated rapidly, patients with TSCI can suffer further secondary damage and experience escalating disability and complications. It is important to quickly assess the patient to identify the location and severity of injury to make a decision to pursue a surgical and/or conservative management. However, there are many conditions that factor into the management of TSCI patients, ranging from the initial presentation of the patient to long-term care for optimal recovery. Here, we provide a comprehensive review of the etiologies of spinal cord injury and the complications that may arise, and present an algorithm to aid in the management of TSCI.

ArtontheBrain: Results of a Pilot Project Among Long-Term Care Residents.

For long-term care (LTC) residents, multiple barriers impede access to formal museum-based participa-tory art programming. Capitalizing on available technologies may circumvent common barriers and improve quality of life for those older adults even in the presence of dementia. Targets: A convenience sample of 31 older adults was recruited from the population of residents in one LTC facility. Intervention: ArtontheBrain, a web-based program, engages participants in activities centered on visual artwork, enabling users to learn about artists through activities, such as puzzles, storytelling, and group discussions. Mechanisms of Action: Researchers hypothesized that engagement with ArtontheBrain would benefit perceived quality of life in the domains of meaningful activity engagement and personal relationships and secondarily, improvements in functional performance, mood state, and cognitive performance may occur. Outcomes: Application of a quality of life survey pre and post ArtontheBrain intervention revealed significant improvements within the individual subsample for two activity options: engagement in enjoyable activities on weekends and evenings and explore new skills and interests. Total scores for the personal relationship scale had significant improvements post-intervention for the individual and group subsamples. The individual subsample demonstrated improvement in cognitive performance, which worsened for the group subsample. Mood and functional ability worsened for the entire sample.[Research in Gerontological Nursing, 14(5), 235-243.].

The Impact of Earplugs and Eye Masks on Sleep Quality in Surgical ICU Patients at Risk for Frequent Awakenings.

OBJECTIVES: Sleep disturbances may contribute to the development of delirium, prolonged ICU stay, and increased mortality. There is conflicting data on the effectiveness of earplugs and eye masks for sleep promotion in the ICU. This study evaluates the impact of earplugs and eye masks on sleep quality in postoperative surgical ICU patients at risk for frequent awakenings. DESIGN: Prospective randomized controlled trial. SETTING: Surgical ICU within the University of Texas Southwestern Medical Center. PATIENTS: Adult, female patients admitted to the surgical ICU requiring hourly postoperative assessments following breast free flap surgery between February 2018 and October 2019. INTERVENTIONS: Patients were randomized into an intervention group or a control group. The intervention group received earplugs and eye masks in addition to standard postoperative care, whereas the control group received standard postoperative care. MEASUREMENTS AND MAIN RESULTS: The primary outcome was overall sleep quality assessed via the Richards-Campbell Sleep Questionnaire. Secondary outcomes of patient satisfaction and rates of ICU delirium were assessed with a modified version of the Family Satisfaction in the ICU survey and the Confusion Assessment Method for the ICU. After a planned interim analysis, the study was stopped early because prespecified criteria for significance were attained. Compared with the control group's average Richards-Campbell Sleep Questionnaire total score of 47.3 (95% CI, 40.8-53.8), the intervention group's average Richards-Campbell Sleep Questionnaire total score was significantly higher at 64.5 (95% CI, 58.3-70.7; p = 0.0007). There were no significant between-group differences for Confusion Assessment Method for the ICU scores or modified Family Satisfaction in the ICU survey scores. CONCLUSIONS: These results suggest that earplugs and eye masks are effective in improving sleep quality in ICU patients undergoing frequent assessments. The results strengthen the evidence for nonpharmacologic sleep-promoting adjuncts in the ICU.

Healthy and Ready to Learn: Prevalence and Correlates of School Readiness among United States Preschoolers.

OBJECTIVE: To assess the national and state prevalence of being "Healthy and Ready to Learn" (HRL) and associated sociodemographic, health, family and neighborhood factors. METHODS: Cross-sectional analysis of the 2016 National Survey of Children's Health, a nationally representative parent-reported survey administered by web and paper June 2016 to February 2017. Four domains were constructed from 18 items through confirmatory factor analyses: "Early Learning Skills", "Social-Emotional Development", "Self-Regulation", and "Physical Well-being and Motor Development." Each item and domain were scored according to age-specific standards as "On-Track", "Needs Support", and "At Risk" with overall HRL defined as "On-Track" in all domains for 7565 randomly selected children ages 3 to 5 years. RESULTS: In 2016, 42.2% of children ages 3 to 5 years were considered HRL with the proportion considered "On-Track" ranging from 58.4% for Early Learning Skills to 85.5% for Physical Well-being and Motor Development"; approximately 80% of children were considered "On-Track" in Social-Emotional Development and Self-Regulation, respectively. Sociodemographic differences were mostly non-significant in multivariable analyses. Health, family, and neighborhood factors (ie, special health care needs status/type, parental mental health, reading, singing and storytelling, screen time, adverse childhood experiences, and neighborhood amenities) were associated with HRL. HRL prevalence ranged from 25.5% (NV) to 58.7% (NY), but only 4 states were significantly different from the U.S. overall. CONCLUSIONS: Based on this pilot measure, only about 4 in 10 US children ages 3 to 5 years may be considered "Healthy and Ready to Learn." Improvement opportunities exist for multiple, modifiable factors to affect young children's readiness to start school.

Technology Use among Family Caregivers of People with Dementia.

This study explored family caregivers' use of technology to care for people with dementia living at home. Three questions were pursued: (1) what are the important, unmet needs of family caregivers, (2) how do they use technologies to assist in care tasks, and (3) what do health care providers know about caregivers' needs and technology use? Two comprehensive surveys were developed to answer these questions: one for family caregivers (n = 33), and one for health care providers (n = 60). Descriptive and quantitative analyses showed that caregivers' important, unmet needs were in the domains of information, formal services, and emotional support. Caregivers make limited use of technology but believe in its potential usefulness. Health care providers agree that technology is useful in dementia care; however, they underestimate caregivers' willingness to adopt technologies to communicate with providers. Findings prove caregiver willingness to use technology to support their care role and provide guidance regarding the caregiver needs that these technologies should address.

Accessible Virtual Arts Recreation for Wellbeing Promotion in Long-Term Care Residents.

The efficacy of a technology-driven visual arts recreation activity, delivered virtually, was evaluated for its potential to achieve positive impacts, similar to traditional arts-interventions, on wellbeing in long-term care residents. Thirty-one residents (average age 86.8 years; SD = 9.4) engaged with the arts-intervention for 30-minutes, twice weekly, for 6 weeks with either a partner or as part of a group. Wellbeing indicators included self-reported psychological and health-related wellness, and attention capacity. Binomial tests of postintervention change revealed a significant above-chance probability of improvement in one or more wellbeing indicators (p < .05). Postparticipation feedback survey scores were positive (p < .05). Cognitive status did not influence outcome; however, other participant characteristics such as younger age, higher openness-to-experience (personality trait), and lower baseline mood were significantly associated with positive response to the intervention (p < .05). Findings demonstrate technology may be an effective platform for promoting accessibility to beneficial arts-interventions for older adults.

Sex differences in cortisol and memory following acute social stress in amnestic mild cognitive impairment.

OBJECTIVE: Older adults with amnestic mild cognitive impairment (aMCI) develop Alzheimer's type dementia approximately 10 times faster annually than the normal population. Adrenal hormones are associated with aging and cognition. We investigated the relationship between acute stress, cortisol, and memory function in aMCI with an exploratory analysis of sex. METHOD: Salivary cortisol was sampled diurnally and during two test sessions, one session with the Trier Social Stress Test (TSST), to explore differences in the relationship between cortisol and memory function in age-normal cognition (NA) and aMCI. Participants with aMCI (n = 6 women, 9 men; mean age = 75) or similarly aged NA (n = 9 women, 7 men, mean age = 75) were given tests of episodic, associative, and spatial working memory with a psychosocial stressor (TSST) in the second session. RESULTS: The aMCI group performed worse on the memory tests than NA as expected, and males with aMCI had elevated cortisol levels on test days. Immediate episodic memory was enhanced by social stress in NA but not in the aMCI group, indicating that stress-induced alterations in memory are different in individuals with aMCI. High cortisol was associated with impaired performance on episodic memory in aMCI males only. Cortisol in Session 1 moderated the relationship with spatial working memory, whereby higher cortisol was associated with worse performance in NA, but better spatial working memory in aMCI. In addition, effects of aMCI on perceived anxiety in response to stress exposure were moderated by stress-induced cortisol in a sex-specific manner. CONCLUSIONS: We show effects of aMCI on Test Session cortisol levels and effects on perceived anxiety, and stress-induced impairments in memory in males with aMCI in our exploratory sample. Future studies should explore sex as a biological variable as our findings suggest that effects at the confluence of aMCI and stress can be obfuscated without sex as a consideration.

Episodic memory decline is associated with deficits in coherence of discourse.

This study investigates coherence of discourse in the production of autobiographical narratives by individuals with aMCI. Autobiographical interviews were analyzed to determine whether reduced episodic recall was related to deficits in discourse coherence. A coherence rating scale was used to evaluate relatedness of the autobiographical details produced by participants to the topic of discourse. Interviews were transcribed, segmented into details, and divided into sets of episodic, semantic, or supplementary information, which were subsequently analysed with the coherence rating scale. We predicted that the known episodic deficits observed in aMCI could also affect the retrieval of coherent episodic information. The results revealed deficits in coherence could be found in both episodic and semantic information in the aMCI group. These results suggest that the cognitive deficits experienced by individuals with aMCI may go beyond their known difficulty in recalling episodic details, as they also affect the controlled retrieval of both episodic and semantic information.

An Incidental Learning Method to Improve Face-Name Memory in Older Adults With Amnestic Mild Cognitive Impairment.

OBJECTIVE: Forgetting names is a common memory concern for people with amnestic mild cognitive impairment (aMCI) and is related to explicit memory deficits and pathological changes in the medial temporal lobes at the early stages of Alzheimer's disease (AD). In the current experiment, we tested a unique method to improve memory for face-name associations in people with aMCI involving incidental rehearsal of face-name pairs. METHOD: Older adults with aMCI and age- and education-matched controls learned 24 face-name pairs and were tested via immediate cued recall with faces as cues for associated names. During a 25- to 30-min retention interval, 10 of the face-name pairs reappeared as a quarter of the items on a seemingly unrelated 1-back task on faces, with the superimposed names irrelevant to the task. After the delay, surprise delayed cued recall and forced-choice associative recognition tests were administered for the face-name pairs. RESULTS: Both groups showed reduced forgetting of the names that repeated as distraction and enhanced recollection of these pairs. CONCLUSIONS: The results demonstrate that passive methods to prompt automatic retrieval of associations may hold promise as interventions for people with early signs of AD.

Preparing for COVID-19: rapid redeployment workshops for Senior Doctors.

This article was migrated. The article was marked as recommended. Background Restructuring secondary care provision for COVID-19 raised the possibility of redeployment of senior physicians. Increasing specialization meant that redeployment of non-acute or non-medical consultants to support the medical take was a source of anxiety. Objective We delivered focused refresher training for senior doctors. This study hoped to determine usefulness, feasibility and acceptability of delivering training in this new fashion. Methods Candidates undertook a half-day course of high-fidelity simulation, resuscitation, recognizing COVID-19, oxygen therapy, basic procedures, IT training, and PPE. The sessions were delivered by clinicians from across the medical and nursing hierarchy, with social distancing maintained throughout. All candidates were given an anonymous post-course evaluation. Results We received 307/360 evaluation forms. 98.7% of candidates agreed (31.1%) or strongly agreed (67.5%) that the course was beneficial. Candidates commented that they felt more confident, and less anxious, about redeployment to manage COVID-19 patients. Discussion The employment of Clinical Fellows in Medical Education without ties to service provision allowed them to focus on high volume, high quality training. The resultant redundancy in staffing proved useful in covering faculty sickness but also ensuring smooth running of the course. Freeing up the education team allowed simultaneous planning and adaptation of the sessions upskill 4 th and 5 th year medical students. Our simple course model with nimble staffing solutions could be reused in any future major incident. Conclusions Our experience demonstrates clear benefit in a cohort of juniors with educational interest. Lean working provides adaptability and resilience when training must be delivered rapidly.

Establishing a Developmentally Appropriate fMRI Paradigm Relevant to Presurgical Mapping of Memory in Children.

Functional magnetic resonance imaging (fMRI) is an established eloquent cortex mapping technique that is now an integral part of the pre-operative work-up in candidates for epilepsy surgery. Emerging evidence in adults with epilepsy suggests that material-specific fMRI paradigms can predict postoperative memory outcomes, however these paradigms are not suitable for children. In pediatric age, the use of memory fMRI paradigms designed for adults is complicated by the effect of developmental stages in cognitive maturation, the impairment experienced by some people with temporal lobe epilepsy (TLE) and the normal representation of memory function during development, which may differ from adults. We present a memory fMRI paradigm designed to activate mesial temporal lobe structures that is brief, independent of reading ability, and therefore a novel candidate for use in children. Data from 33 adults and 19 children (all healthy controls) show that the paradigm captures the expected leftward asymmetry of mesial temporal activation in adults. A more symmetrical pattern was observed in children, consistent with the progressive emergence of hemispheric specialisation across childhood. These data have important implications for the interpretation of presurgical memory fMRI in the pediatric setting. They also highlight the need to carefully consider the impact of cognitive development on fMRI tools used in clinical practice.