Neural correlates of motor imagery and execution in real-world dynamic behavior: evidence for similarities and differences.

A large body of evidence shows that motor imagery and action execution behaviors result from overlapping neural substrates, even in the absence of overt movement during motor imagery. To date it is unclear how neural activations in motor imagery and execution compare for naturalistic whole-body movements, such as walking. Neuroimaging studies have not directly compared imagery and execution during dynamic walking movements. Here we recorded brain activation with mobile EEG during walking compared to during imagery of walking, with mental counting as a control condition. We asked 24 healthy participants to either walk six steps on a path, imagine taking six steps, or mentally count from one to six. We found beta and alpha power modulation during motor imagery resembling action execution patterns; a correspondence not found performing the control task of mental counting. Neural overlap occurred early in the execution and imagery walking actions, suggesting activation of shared action representations. Remarkably, a distinctive walking-related beta rebound occurred both during action execution and imagery at the end of the action suggesting that, like actual walking, motor imagery involves resetting or inhibition of motor processes. However, we also found that motor imagery elicits a distinct pattern of more distributed beta activity, especially at the beginning of the task. These results indicate that motor imagery and execution of naturalistic walking involve shared motor-cognitive activations, but that motor imagery requires additional cortical resources.

Commit to your putting stroke: exploring the impact of quiet eye duration and neural activity on golf putting performance.

Introduction: There is a growing interest in characterizing the cognitive-motor processes that underlie superior performance in highly skilled athletes. The aim of this study was to explore neural markers of putting performance in highly skilled golfers by recording mobile EEG (electroencephalogram) during the pre-shot period. Methods: Twenty-eight right-handed participants (20 males) with a mean age of 24.2 years (± 6.4) and an average handicap of +1.7 (± 6.4) completed a testing session. Following the warm-up, participants completed 140 putts from a distance of 8ft (2.4m), with putts taken from 5 different positions. While putting, participants wore an eye tracker and a gel-based EEG system with 32 electrodes. Time and frequency domain features of the EEG signals were extracted to characterize Movement-Related Cortical Potentials (MRCP) and rhythmic modulations of neural activity in theta, alpha, sensorimotor and beta frequency bands associated with putting performance. Results: Eye-tracking data demonstrate that mean Quiet Eye durations are not a reliable marker of expertise as the same duration was found for both successful and unsuccessful putts. Following rigorous data processing data from 12 participants (8 males, mean age 21.6 years ± 5.4, average handicap +1.5 ± 4.4) were included in the EEG analysis. MRCP analysis revealed performance-based differences, with unsuccessful putts having a greater negative amplitude in comparison to successful putts. Time frequency analysis of the EEG data revealed that successful putts exhibit distinct neural activity profiles compared to unsuccessful ones. For successful putts, greater suppression of beta was present in the central region prior to the putt. By contrast, increased frontal theta power was present for unsuccessful putts immediately before the putt (consistent with hesitation and the need for motor plan adjustments prior to execution). Discussion: We propose that neural activity may provide plausible insights into the mechanisms behind why identical QE durations can lead to both success and failure. From an applied perspective, this study highlights the merits of a multi-measure approach to gain further insights into performance differences within highly skilled golfers. We discuss considerations for future research and solutions to address the challenges related to the complexities of collecting clean EEG signals within naturalistic sporting contexts.

Investigating the Brain Mechanisms of Externally Cued Sit-to-Stand Movement in Parkinson's Disease.

BACKGROUND: One of the more challenging daily-life actions for Parkinson's disease patients is starting to stand from a sitting position. Parkinson's disease patients are known to have difficulty with self-initiated movements and benefit from external cues. However, the brain processes underlying external cueing as an aid remain unknown. The advent of mobile electroencephalography (EEG) now enables the investigation of these processes in dynamic sit-to-stand movements. OBJECTIVE: To identify cortical correlates of the mechanisms underlying auditory cued sit-to-stand movement in Parkinson's disease. METHODS: Twenty-two Parkinson's disease patients and 24 healthy age-matched participants performed self-initiated and externally cued sit-to-stand movements while cortical activity was recorded through 32-channel mobile EEG. RESULTS: Overall impaired integration of sensory and motor information can be seen in the Parkinson's disease patients exhibiting less modulation in the θ band during movement compared to healthy age-matched controls. How Parkinson's disease patients use external cueing of sit-to-stand movements can be seen in larger high ß power over sensorimotor brain areas compared to healthy controls, signaling sensory integration supporting the maintenance of motor output. This appears to require changes in cognitive processing to update the motor plan, reflected in frontal θ power increases in Parkinson's disease patients when cued. CONCLUSION: These findings provide the first neural evidence for why and how cueing improves motor function in sit-to-stand movement in Parkinson's disease. The Parkinson's disease patients' neural correlates indicate that cueing induces greater activation of motor cortical areas supporting the maintenance of a more stable motor output, but involves the use of cognitive resources to update the motor plan. © 2024 International Parkinson and Movement Disorder Society.

Electrophysiologic and cardiovascular manifestations of Duchenne and Becker muscular dystrophies.

There have been significant advances in the diagnosis and management of the hereditary muscular disorders Duchenne and Becker muscular dystrophy (DMD and BMD). Cardiac electrophysiologic and cardiovascular involvement has long been important in the surveillance, care, and prognosis of patients with both BMD and DMD and is the leading cause of mortality in patients with DMD. With improved long-term prognosis, rhythm disorders and progressive cardiomyopathy with resultant heart failure are increasingly common. This review aimed to provide an overview to electrophysiologists and cardiologists of the cardiac electrophysiologic phenotypes and genetics of BMD and DMD and to highlight the recent discoveries that have advanced clinical course and management. A systematic review was performed of the diagnosis and management of DMD and BMD. The Cochrane Library, PubMed, MEDLINE, Europe PubMed Central, AMED, and Embase databases were accessed for available evidence. The research reported in this paper adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Evidence from randomized controlled trials and studies cited in expert consensus and practice guidelines are examined. Advanced imaging techniques and a spectrum of rhythm disorders associated with the progressive cardiomyopathy are presented. Early initiation of heart failure therapies, the role of cardiac implantable devices, and novel gene therapies approved for use with the potential to alter the disease course are discussed. When profound cardiac and cardiac electrophysiologic involvement is diagnosed and treated earlier, outcomes for DMD and BMD patients may be improved.

Left Atrial Appendage Closure: Therapy Overview and Future Perspective.

The left atrial appendage (LAA) has gained increasing attention in the field of cardiology as a potential site for intervention in patients with atrial fibrillation (AF) and an elevated risk of thromboembolic events. Left atrial appendage occlusion (LAAO) has emerged as a promising therapeutic strategy to mitigate the risk of stroke and systemic embolism, especially in individuals who are unsuitable candidates for long-term anticoagulation therapy. This review aims to provide a comprehensive analysis of the current state of LAAO, encompassing its anatomic considerations, procedural techniques, clinical outcomes, and future directions.

The Use of Biofluid Markers to Evaluate the Consequences of Sport-Related Subconcussive Head Impact Exposure: A Scoping Review.

BACKGROUND: Amidst growing concern about the safety of sport-related repetitive subconcussive head impacts (RSHI), biofluid markers may provide sensitive, informative, and practical assessment of the effects of RSHI exposure. OBJECTIVE: This scoping review aimed to systematically examine the extent, nature, and quality of available evidence from studies investigating the effects of RSHI on biofluid markers, to identify gaps and to formulate guidelines to inform future research. METHODS: PRISMA extension for Scoping Reviews guidelines were adhered to. The protocol was pre-registered through publication. MEDLINE, Scopus, SPORTDiscus, CINAHL, PsycINFO, Cochrane Library, OpenGrey, and two clinical trial registries were searched (until March 30, 2022) using descriptors for subconcussive head impacts, biomarkers, and contact sports. Included studies were assessed for risk of bias and quality. RESULTS: Seventy-nine research publications were included in the review. Forty-nine studies assessed the acute effects, 23 semi-acute and 26 long-term effects of RSHI exposure. The most studied sports were American football, boxing, and soccer, and the most investigated markers were (in descending order): S100 calcium-binding protein beta (S100B), tau, neurofilament light (NfL), glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), brain-derived neurotrophic factor (BDNF), phosphorylated tau (p-tau), ubiquitin C-terminal hydrolase L1 (UCH-L1), and hormones. High or moderate bias was found in most studies, and marker-specific conclusions were subject to heterogeneous and limited evidence. Although the evidence is weak, some biofluid markers-such as NfL-appeared to show promise. More markedly, S100B was found to be problematic when evaluating the effects of RSHI in sport. CONCLUSION: Considering the limitations of the evidence base revealed by this first review dedicated to systematically scoping the evidence of biofluid marker levels following RSHI exposure, the field is evidently still in its infancy. As a result, any recommendation and application is premature. Although some markers show promise for the assessment of brain health following RSHI exposure, future large standardized and better-controlled studies are needed to determine biofluid markers' utility.

Characterizing neurocognitive impairments in Parkinson's disease with mobile EEG when walking and stepping over obstacles.

The neural correlates that help us understand the challenges that Parkinson's patients face when negotiating their environment remain under-researched. This deficit in knowledge reflects the methodological constraints of traditional neuroimaging techniques, which include the need to remain still. As a result, much of our understanding of motor disorders is still based on animal models. Daily life challenges such as tripping and falling over obstacles represent one of the main causes of hospitalization for individuals with Parkinson's disease. Here, we report the neural correlates of naturalistic ambulatory obstacle avoidance in Parkinson's disease patients using mobile EEG. We examined 14 medicated patients with Parkinson's disease and 17 neurotypical control participants. Brain activity was recorded while participants walked freely, and while they walked and adjusted their gait to step over expected obstacles (preset adjustment) or unexpected obstacles (online adjustment) displayed on the floor. EEG analysis revealed attenuated cortical activity in Parkinson's patients compared to neurotypical participants in theta (4-7 Hz) and beta (13-35 Hz) frequency bands. The theta power increase when planning an online adjustment to step over unexpected obstacles was reduced in Parkinson's patients compared to neurotypical participants, indicating impaired proactive cognitive control of walking that updates the online action plan when unexpected changes occur in the environment. Impaired action planning processes were further evident in Parkinson's disease patients' diminished beta power suppression when preparing motor adaptation to step over obstacles, regardless of the expectation manipulation, compared to when walking freely. In addition, deficits in reactive control mechanisms in Parkinson's disease compared to neurotypical participants were evident from an attenuated beta rebound signal after crossing an obstacle. Reduced modulation in the theta frequency band in the resetting phase across conditions also suggests a deficit in the evaluation of action outcomes in Parkinson's disease. Taken together, the neural markers of cognitive control of walking observed in Parkinson's disease reveal a pervasive deficit of motor-cognitive control, involving impairments in the proactive and reactive strategies used to avoid obstacles while walking. As such, this study identified neural markers of the motor deficits in Parkinson's disease and revealed patients' difficulties in adapting movements both before and after avoiding obstacles in their path.

Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY.

Background: Patients with chronic lymphocytic leukemia (CLL) have a higher risk of developing other malignancies (OMs) compared to the general population. However, the impact of CLL-related risk factors and CLL-directed treatment is still unclear and represents the focus of this work. Methods: We conducted a retrospective international multicenter study to assess the incidence of OMs and detect potential risk factors in 19,705 patients with CLL, small lymphocytic lymphoma, or high-count CLL-like monoclonal B-cell lymphocytosis, diagnosed between 2000 and 2016. Data collection took place between October 2020 and March 2022. Findings: In 129,254 years of follow-up after CLL diagnosis, 3513 OMs were diagnosed (27.2 OMs/1000 person-years). The most common hematological OMs were Richter transformation, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Non-melanoma skin (NMSC) and prostate cancers were the most common solid tumors (STs).The only predictor for MDS and AML development was treatment with fludarabine and cyclophosphamide with/without rituximab (FC ± R) (OR = 3.7; 95% CI = 2.79-4.91; p < 0.001). STs were more frequent in males and patients with unmutated immunoglobulin heavy variable genes (OR = 1.77; 95% CI = 1.49-2.11; p < 0.001/OR = 1.89; 95% CI = 1.6-2.24; p < 0.001).CLL-directed treatment was associated with non-melanoma skin and prostate cancers (OR = 1.8; 95% CI = 1.36-2.41; p < 0.001/OR = 2.11; 95% CI = 1.12-3.97; p = 0.021). In contrast, breast cancers were more frequent in untreated patients (OR = 0.17; 95% CI = 0.08-0.33; p < 0.001).Patients with CLL and an OM had inferior overall survival (OS) than those without. AML and MDS conferred the worst OS (p < 0.001). Interpretation: OMs in CLL impact on OS. Treatment for CLL increased the risk for AML/MDS, prostate cancer, and NMSC. FCR was associated with increased risk for AML/MDS. Funding: AbbVie, and EU/EFPIAInnovative Medicines Initiative Joint Undertaking HARMONY grant n° 116026.

The evolving landscape of COVID-19 and post-COVID condition in patients with chronic lymphocytic leukemia: A study by ERIC, the European research initiative on CLL.

In this retrospective international multicenter study, we describe the clinical characteristics and outcomes of patients with chronic lymphocytic leukemia (CLL) and related disorders (small lymphocytic lymphoma and high-count monoclonal B lymphocytosis) infected by SARS-CoV-2, including the development of post-COVID condition. Data from 1540 patients with CLL infected by SARS-CoV-2 from January 2020 to May 2022 were included in the analysis and assigned to four phases based on cases disposition and SARS-CoV-2 variants emergence. Post-COVID condition was defined according to the WHO criteria. Patients infected during the most recent phases of the pandemic, though carrying a higher comorbidity burden, were less often hospitalized, rarely needed intensive care unit admission, or died compared to patients infected during the initial phases. The 4-month overall survival (OS) improved through the phases, from 68% to 83%, p = .0015. Age, comorbidity, CLL-directed treatment, but not vaccination status, emerged as risk factors for mortality. Among survivors, 6.65% patients had a reinfection, usually milder than the initial one, and 16.5% developed post-COVID condition. The latter was characterized by fatigue, dyspnea, lasting cough, and impaired concentration. Infection severity was the only risk factor for developing post-COVID. The median time to resolution of the post-COVID condition was 4.7 months. OS in patients with CLL improved during the different phases of the pandemic, likely due to the improvement of prophylactic and therapeutic measures against SARS-CoV-2 as well as the emergence of milder variants. However, mortality remained relevant and a significant number of patients developed post-COVID conditions, warranting further investigations.

Phosphorus adsorption and organic release from dried and thermally treated water treatment sludge.

The study investigated water treatment sludge (WTS) as a phosphorus (P) adsorbent and examined the release of organic matter during the P adsorption process. Previous studies indicated that WTS is an effective adsorbent for P but also releases organic matter, which may affect the organoleptic properties of treated water, but no study has characterised organic release and conducted an in-depth study on its behaviours. This study characterised the organic release during the P adsorption process from four different WTS samples. This study also offers results from a 60-day column experiment that indicate that WTS columns effectively removed the majority of P from the 2 mg/L feed solution. The total organic carbon (TOC) release was gradually reduced from 24.9 mg/L on day 1 to stable levels of 4.4 mg/L to 4.1 mg/L from day 22 onwards. After 60 days, when the organic matter was nearly exhausted, WTS columns were still effective in P adsorption from the solution. In addition, the thermal treatment of WTS at different temperatures was investigated to reduce TOC release and increase P adsorption. The results showed that thermal treatment not only minimized TOC release but also enhanced the P adsorption capacity of the sludge. In a 24-h batch experiment, WTS treated at 600 °C showed the highest P adsorption (1.7 mg/g) with negligible TOC release when compared to sludge treated at 500 °C WTS (1.2 mg/g), 700 °C WTS (1.5 mg/g) and dried WTS (0.75 mg/g). However, the release of inorganic compounds slightly increased after thermal treatment. Future studies could focus on determining whether the thermal processing of WTS which can enhance the WTS's adsorption to emerging pollutants like per- and poly-fluoroalkyl substances and other contaminants. The findings of this study could influence the management practices of water authorities and contribute to the water sector's sustainability objectives.

Metabolic Alterations in Multiple Myeloma: From Oncogenesis to Proteasome Inhibitor Resistance.

Despite significant improvements in treatment strategies over the past couple of decades, multiple myeloma (MM) remains an incurable disease due to the development of drug resistance. Metabolic reprogramming is a key feature of cancer cells, including MM, and acts to fuel increased proliferation, create a permissive tumour microenvironment, and promote drug resistance. This review presents an overview of the key metabolic adaptations that occur in MM pathogenesis and in the development of resistance to proteasome inhibitors, the backbone of current MM therapy, and considers the potential for therapeutic targeting of key metabolic pathways to improve outcomes.

Ocular pathology in aquarium fish with a focus on the Syngnathidae and Apogonidae families.

This study catalogued ocular pathology in fish histopathology submissions to a specialist diagnostic service and investigated associations with species and systemic disease, with a focus on species of conservation interest. Cross-tabulations and Fisher's exact tests were used to identify associations among the variables and results are reported as prevalence ratios (PRs) with 95% confidence intervals (CI). Of 12,488 reports reviewed, ocular histology examination was available for 4,572 submissions, in which histopathological ocular lesions were identified in 18% (813/4572). Most diagnoses (701/813; 87%) were in marine fish. Inflammatory conditions were most common (608/813; 75%), with identification of a bacterial aetiology in 42% (255/608) and a parasitic aetiology in 30% (183/608). Most bacterial infections were due to mycobacteriosis (153/255; 60%) and most parasitic infections were due to scuticociliatosis (114/184; 62%). The Syngnathidae, Centriscidae and Cichlidae families were each more likely than all other families combined to be diagnosed with ocular manifestations of mycobacteriosis (PRs = 2.6, 4.4 and 2.9, respectively, P <0.0001 for each). The Syngnathidae were also more likely to be diagnosed with ocular scuticociliatosis (PR = 1.9, P <0.0001). Fifty-four percent (39/72) of ocular mycobacteriosis and 38% (9/24) of gas bubble disease cases affected threatened or near threatened Syngnathidae species. The Apogonidae were more likely than any other family to have ocular iridovirus (PR = 10.3, 95% CI = 5.5-19.4, P <0.0001) and neoplasia (PR = 8.2, 95% CI = 4.2-16.3, P <0.0001). The endangered Banggai cardinalfish (Pterapogon kauderni) accounted for 13/15 ocular iridovirus and 16/18 mycobacteriosis cases in this family. All cases of neoplasia in the Apogonidae occurred in pajama cardinalfish (Sphaeramia nematoptera). These results should inform clinical diagnosis of ocular disease in aquarium fish and influence training for aquarists, highlighting ocular pathology as a potential early warning of systemic disease. The findings also have direct/indirect consequences for the welfare and conservation of some of these popular flagship fish species.

Subpalpebral lavage placement for remote topical administration of ocular medications in 12 dogs: A retrospective review and assessment of owner perception.

OBJECTIVE: The aim of this study was to describe the placement of subpalpebral lavage (SPL) systems in 12 dogs (15 eyes) intolerant of topical ocular medications to assess the suitability, complications encountered and owner perception of use. ANIMALS STUDIED: Retrospective review of dogs that underwent SPL placement for treatment of ocular disease at the Ophthalmology Department, University of Bristol Small Animal Hospital between 2017 and 2021. PROCEDURE(S): Data recorded included signalment, history, diagnosis, treatment, reason for SPL placement, uni- or bilateral placement, duration of placement, complications, and outcome. Owner perception was assessed using an online questionnaire. Statistical analysis included McNemar and Wilcoxon signed-ranks tests. RESULTS: Twelve dogs (15 eyes) underwent SPL placement. Eleven owners completed the online questionnaire. Corneal ulceration was the most common disease requiring SPL placement (n = 13/15 eyes, 86.7%). Most cases received multimodal topical therapy (n = 9/15 eyes, 60.0%) via SPL. Owners administered medication 6.63 times daily via SPL (range 1-16 applications/day). All dogs requiring ongoing topical medication (n = 8/12, 66.7%) were trained to accept direct administration during SPL treatment. Statistically significant improvements in medication compliance, ease of application, and reduced perceived risk of iatrogenic ocular injury were reported by owners (p-value = .001, .004, and .031 respectively). Minor complications were infrequently reported but an excellent outcome was achieved for all eyes. CONCLUSION: Subpalpebral lavage placement provides a practical and safe solution for the provision of frequent multimodal ocular medication when treating patients with a challenging temperament.

Teachers' emotions in the time of COVID: Thematic analysis of interview data reveals drivers of professional agency.

Purpose: We explored two complex phenomena associated with effective education. First, teachers' professional agency, the volitional actions they take in response to perceived opportunities, was examined to consider individual differences in its enactment. Second, "strong" emotions have been proposed as important in teaching and learning, and we wished to clarify which basic emotions might be involved, besides curiosity, which is a known emotional factor in engagement in teaching. We also explored how agency and basic emotions might be related. Approach: Thirteen teachers working in Scottish secondary schools were interviewed at the start of the covid pandemic in 2020 to discuss relevant feelings, thoughts and actions arising from unprecedented changes in their lives and professional practices. Thematic analysis was used to identify aspects of agentic behavior and basic emotions expressed. Findings: Teacher agency was expressed through adaptability, collective agency, constrained agency, and non-action. Four basic emotion percepts were identified, which we label as "CARE", "CURIOSITY", "COOPERATION", and "CHALLENGE". Originality: We extend the definition of agency to include volitional non-action as a response to opportunity. In contrast to prior research emphasizing emotions as an outcome of volitional behavior, we explore emotions preceding agency. We develop four theoretical propositions related to teacher emotions. (1) Four emotion percepts substantially influence teachers' voluntary motivated behavior. (2) The amount and proportion of emotions experienced varies between individual teachers. (3) The four percepts are experienced concurrently or in rapid succession in engaged teaching contexts. (4) Professional experience and specific situational factors also influence teachers' behavioral choices. For future consideration, we suggest that awareness of emotion percepts may encourage both teachers' engagement and their professional agency for the benefit of their pedagogical practice and outcomes for their students.

The neural response is heightened when watching a person approaching compared to walking away: Evidence for dynamic social neuroscience.

The action observation network has been proposed to play a key role in predicting the action intentions (or goals) of others, thereby facilitating social interaction. Key information when interacting with others is whether someone (an agent) is moving towards or away from us, indicating whether we are likely to interact with the person. In addition, to determine the nature of a social interaction, we also need to take into consideration the distance of the agent relative to us as the observer. How this kind of information is processed within the brain is unknown, at least in part because prior studies have not involved live whole-body motion. Consequently, here we recorded mobile EEG in 18 healthy participants, assessing the neural response to the modulation of direction (walking towards or away) and distance (near vs. far distance) during the observation of an agent walking. We evaluated whether cortical alpha and beta oscillations were modulated differently by direction and distance during action observation. We found that alpha was only modulated by distance, with a stronger decrease of power when the agent was further away from the observer, regardless of direction. Critically, by contrast, beta was found to be modulated by both distance and direction, with a stronger decrease of power when the agent was near and facing the participant (walking towards) compared to when they were near but viewed from the back (walking away). Analysis revealed differences in both the timing and distribution of alpha and beta oscillations. We argue that these data suggest a full understanding of action observation requires a new dynamic neuroscience, investigating actual interactions between real people, in real world environments.

Development of a Care Pathway for Atrial Fibrillation Patients in the Emergency Department.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and its prevalence is continuously increasing in the United States, leading to a progressive rise in the number of disease-related emergency department (ED) visits and hospitalizations. Although optimal long-term outpatient management for AF is well defined, the guidelines for optimal ED management of acute AF episodes is less clear. Studies have demonstrated that discharging patients with AF from the ED after acute stabilization is both safe and cost effective; however, the majority of these patients in the United States and in our institution are admitted to the hospital. To improve care of these patients, we established a multidisciplinary collaboration to develop an evidence-based systematic approach for the treatment and management of AF in the ED, that led to the creation of the University of California-Cardioversion, Anticoagulation, Rate Control, Expedited Follow-up/Education Atrial Fibrillation Pathway. Our pathway focuses on the acute stabilization of AF, adherence to best practices for anticoagulation, and reduction in unnecessary admissions through discharge from the ED with expedited outpatient follow-up whenever safe. A novel aspect of our pathway is that it is primarily driven by the ED physicians, while other published protocols primarily involve consulting cardiologists to guide management in the ED. Our protocol is very pertinent considering the current trend toward increased AF prevalence in the United States, coupled with a need for widespread implementation of strategies aimed at improving management of these patients while safely reducing hospital admissions and the economic burden of AF.

TP53 Mutations Identified Using NGS Comprise the Overwhelming Majority of TP53 Disruptions in CLL: Results From a Multicentre Study.

Limited data exists to show the correlation of (tumour protein 53) TP53 mutation detected by Next generation sequencing (NGS) and the presence/absence of deletions of 17p13 detected by FISH. The study which is the largest series to date includes 2332 CLL patients referred for analysis of del(17p) by FISH and TP53 mutations by NGS before treatment. Using a 10% variant allele frequency (VAF) threshold, cases were segregated into high burden mutations (≥10%) and low burden mutations (<10%). TP53 aberrations (17p [del(17p)] and/or TP53 mutation) were detected in 320/2332 patients (13.7%). Using NGS analysis, 429 TP53 mutations were identified in 303 patients (13%). Of these 238 (79%) and 65 (21%) were cases with high burden and low burden mutations respectively. In our cohort, 2012 cases did not demonstrate a TP53 aberration (86.3%). A total of 159 cases showed TP53 mutations in the absence of del(17p) (49/159 with low burden TP53 mutations) and 144 cases had both TP53 mutation and del(17p) (16/144 with low burden mutations). Only 17/2332 (0.7%) cases demonstrated del(17p) with no TP53 mutation. Validated NGS protocols should be used in clinical decision making to avoid missing low-burden TP53 mutations and can detect the vast majority of TP53 aberrations.

A prospective, masked, randomized, controlled superiority study comparing the incidence of corneal injury following general anesthesia in dogs with two methods of corneal protection.

OBJECTIVE: To compare the incidence of corneal injury during general anesthesia (GA) and the immediate post-operative period in eyes protected with topical ocular lubricant alone with eyes protected with topical lubricant followed by complete eyelid closure using tape. ANIMALS STUDIED: One hundred client-owned dogs (200 eyes) undergoing GA for MRI scan. METHODS: Patients had ocular lubricant applied to both eyes upon induction of anesthesia. One eye was taped closed immediately after induction for the duration of anesthesia using Strappal® tape (BSN medical™; treatment group), and the other eye was not taped (control group). Eyes were randomly allocated to a treatment group. Ophthalmic examination was performed before and after anesthesia; the examiner was masked to eye treatment groups. Corneal injury was defined as corneal ulceration or corneal erosion. A McNemar's test was used to compare the incidence of corneal injury between groups. A paired-samples t-test was used to compare Schirmer-1 tear test (STT-1) readings between groups. RESULTS: Sixteen eyes (8%) developed corneal erosion. No corneal ulceration occurred. There was no significant difference between incidence of corneal erosion between groups (p = .454). There was a significant decrease in STT-1 readings following GA in both groups (p < .001), with no significant difference in STT-1 between groups (p = .687). No adverse effects of taping the eye closed were observed. CONCLUSION: Taping the eyes closed during GA had no additional benefit to the lubrication protocol used in this study.

Implantation of a Dual-chamber Pacemaker in a Patient with Dextrocardia, Situs Inversus, and Sick Sinus Syndrome.

Situs inversus with dextrocardia is a rare congenital anomaly that presents a unique challenge for the consultant electrophysiologist. Implantation of cardiac device in these patients may be challenging owing to their individual cardiac and vascular anatomy. Consequently, adverse procedural outcomes are more common in this group and an informed pre- and intraoperative approach is critical. In this article, we present the relevant patient findings and implications for the electrophysiologist, including operative approaches. We then examine them in the context of an actual case, having implanted an intracardiac permanent pacemaker with a right-sided approach via the conventional method in a patient with dextrocardia situs inversus who had undergone multiple surgeries for structural heart disease.